Journal of Clinical Medicine

12 pages, 1956 KiB

Open AccessReview

Post-Transplant Lymphoproliferative Disease (PTLD) after Allogeneic Hematopoietic Stem Cell Transplantation: Biology and Treatment Options

by Michele Clerico, Irene Dogliotti, Andrea Aroldi, Chiara Consoli, Luisa Giaccone, Benedetto Bruno and Federica Cavallo

J. Clin. Med. 2022, 11(24), 7542; https://doi.org/10.3390/jcm11247542 - 19 Dec 2022

Cited by 10 | Viewed by 2807

Abstract

Post-transplant lymphoproliferative disease (PTLD) is a serious complication occurring as a consequence of immunosuppression in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT) or solid organ transplantation (SOT). The majority of PTLD arises from B-cells, and Epstein–Barr virus (EBV) infection is present [...] Read more.

Post-transplant lymphoproliferative disease (PTLD) is a serious complication occurring as a consequence of immunosuppression in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT) or solid organ transplantation (SOT). The majority of PTLD arises from B-cells, and Epstein–Barr virus (EBV) infection is present in 60–80% of the cases, revealing the central role played by the latent infection in the pathogenesis of the disease. Therefore, EBV serological status is considered the most important risk factor associated with PTLDs, together with the depth of T-cell immunosuppression pre- and post-transplant. However, despite the advances in pathogenesis understanding and the introduction of novel treatment options, PTLD arising after alloHSCT remains a particularly challenging disease, and there is a need for consensus on how to treat rituximab-refractory cases. This review aims to explore the pathogenesis, risk factors, and treatment options of PTLD in the alloHSCT setting, finally focusing on adoptive immunotherapy options, namely EBV-specific cytotoxic T-lymphocytes (EBV-CTL) and chimeric antigen receptor T-cells (CAR T). Full article

(This article belongs to the Special Issue Hematopoietic Stem Cell Transplantation: Current Status and Future Research)

► Show Figures

Figure 1

11 pages, 980 KiB

Open AccessArticle

The Value of Delta Middle Cerebral Artery Peak Systolic Velocity for the Prediction of Twin Anemia-Polycythemia Sequence—Analysis of a Heterogenous Cohort of Monochorionic Twins

by Anthea de Sainte Fare, Ivonne Bedei, Aline Wolter, Johanna Schenk, Ellydda Widriani, Corinna Keil, Siegmund Koehler, Franz Bahlmann, Brigitte Strizek, Ulrich Gembruch, Christoph Berg and Roland Axt-Fliedner

J. Clin. Med. 2022, 11(24), 7541; https://doi.org/10.3390/jcm11247541 - 19 Dec 2022

Viewed by 1806

Abstract

Introduction: Twin anemia-polycythemia sequence (TAPS) is a complication in monochorionic-diamniotic (MCDA) twin pregnancies. This study analyzes whether the prenatal diagnosis using delta middle cerebral artery-peak systolic velocity (MCA-PSV) > 0.5 multiples of the median (MoM) (delta group) detects more TAPS cases than the [...] Read more.

Introduction: Twin anemia-polycythemia sequence (TAPS) is a complication in monochorionic-diamniotic (MCDA) twin pregnancies. This study analyzes whether the prenatal diagnosis using delta middle cerebral artery-peak systolic velocity (MCA-PSV) > 0.5 multiples of the median (MoM) (delta group) detects more TAPS cases than the guideline-based diagnosis using the MCA-PSV cut off levels of >1.5 and <1.0 MoM (cut-off group), in a heterogenous group of MCDA twins. Methods: A retrospective analysis of 348 live-born MCDA twin pregnancies from 2010 to 2021 with available information on MCA-PSV within one week before delivery and hemoglobin-values within 24 h postnatally were considered eligible. Results: Among postnatal confirmed twin pairs with TAPS, the cut-off group showed lower sensitivity than the delta group (33% vs. 82%). Specificity proved higher in the cut-off group with 97% than in the delta group at 86%. The risk that a TAPS is mistakenly not recognized prenatally is higher in the cut-off group than in the delta group (52% vs. 18%). Conclusions: Our data shows that delta MCA-PSV > 0.5 MoM detects more cases of TAPS, which would not have been diagnosed prenatally according to the current guidelines. In the collective examined in the present study, TAPS diagnostics using delta MCA-PSV proved to be a more robust method. Full article

(This article belongs to the Special Issue Update on Prenatal Diagnosis and Maternal Fetal Medicine)

► Show Figures

Figure 1

14 pages, 619 KiB

Open AccessArticle

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

by Yamile Zabana, Ignacio Marín-Jiménez, Iago Rodríguez-Lago, Isabel Vera, María Dolores Martín-Arranz, Iván Guerra, Javier P. Gisbert, Francisco Mesonero, Olga Benítez, Carlos Taxonera, Ángel Ponferrada-Díaz, Marta Piqueras, Alfredo J. Lucendo, Berta Caballol, Míriam Mañosa, Pilar Martínez-Montiel, Maia Bosca-Watts, Jordi Gordillo, Luis Bujanda, Noemí Manceñido, Teresa Martínez-Pérez, Alicia López, Cristina Rodríguez-Gutiérrez, Santiago García-López, Pablo Vega, Montserrat Rivero, Luigi Melcarne, María Calvo, Marisa Iborra, Manuel Barreiro de Acosta, Beatriz Sicilia, Jesús Barrio, José Lázaro Pérez Calle, David Busquets, Isabel Pérez-Martínez, Mercè Navarro-Llavat, Vicent Hernández, Federico Argüelles-Arias, Fernando Ramírez Esteso, Susana Meijide, Laura Ramos, Fernando Gomollón, Fernando Muñoz, Gerard Suris, Jone Ortiz de Zarate, José María Huguet, Jordina Llaó, Mariana Fe García-Sepulcre, Mónica Sierra, Miguel Durà, Sandra Estrecha, Ana Fuentes Coronel, Esther Hinojosa, Lorenzo Olivan, Eva Iglesias, Ana Gutiérrez, Pilar Varela, Núria Rull, Pau Gilabert, Alejandro Hernández-Camba, Alicia Brotons, Daniel Ginard, Eva Sesé, Daniel Carpio, Montserrat Aceituno, José Luis Cabriada, Yago González-Lama, Laura Jiménez, María Chaparro, Antonio López-San Román, Cristina Alba, Rocío Plaza-Santos, Raquel Mena, Sonsoles Tamarit-Sebastián, Elena Ricart, Margalida Calafat, Sonsoles Olivares, Pablo Navarro, Federico Bertoletti, Horacio Alonso-Galán, Ramón Pajares, Pablo Olcina, Pamela Manzano, Eugeni Domènech, Maria Esteve and on behalf of the ENEIDA Registry of GETECCU Show full author list Hide full author list

J. Clin. Med. 2022, 11(24), 7540; https://doi.org/10.3390/jcm11247540 - 19 Dec 2022

Cited by 2 | Viewed by 2835

Abstract

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide [...] Read more.

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case–control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March–July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3–5.9), occupational risk (OR: 2.9; 95%CI: 1.8–4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2–2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09–0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution. Full article

(This article belongs to the Special Issue Recent Advances in Inflammatory Bowel Diseases: From Diagnosis to Treatment)

► Show Figures

Figure 1

16 pages, 2276 KiB

Open AccessArticle

Dental and Occlusal Changes during Mandibular Advancement Device Therapy in Japanese Patients with Obstructive Sleep Apnea: Four Years Follow-Up

by Eri Ishida, Ryo Kunimatsu, Cynthia Concepcion Medina, Koji Iwai, Sayumi Miura, Yuji Tsuka and Kotaro Tanimoto

J. Clin. Med. 2022, 11(24), 7539; https://doi.org/10.3390/jcm11247539 - 19 Dec 2022

Cited by 2 | Viewed by 2212

Abstract

Dentoskeletal changes caused by the long-term use of mandibular advancement devices (MADs) for obstructive sleep apnea (OSA) have rarely been investigated in Japan. We assessed the long-term dentofacial morphological changes in 15 Japanese patients with OSA who used two-piece MADs for an average [...] Read more.

Dentoskeletal changes caused by the long-term use of mandibular advancement devices (MADs) for obstructive sleep apnea (OSA) have rarely been investigated in Japan. We assessed the long-term dentofacial morphological changes in 15 Japanese patients with OSA who used two-piece MADs for an average of 4 years. Lateral cephalography analyses were performed initially and 4 years later (T1). The dental assessment included overjet, overbite, upper anterior facial height, lower anterior facial height (LAFH), total anterior facial height (TAFH), and anterior facial height ratio. Dental casts were digitized and analyzed using a 3D scanner. Changes in the apnea hypopnea index (AHI) and other sleep-assessment indices were assessed using polysomnography and out-of-center sleep testing. Radiography revealed lingual inclination of the maxillary central incisors, labial inclination of the mandibular central incisors, clockwise rotation of the mandible, and an increase in the TAFH and LAFH at T1. In the dental cast analysis, the diameter width and palatal depth tended to decrease and increase, respectively. There was a significant decrease in the AHI and other sleep assessment indices after using the MADs for approximately 4 years. However, these findings do not provide a strong basis and should be interpreted cautiously. Future studies should have a larger sample size and should further investigate the long-term occlusal and dental changes caused by the original MADs in Japanese patients with OSA. Full article

(This article belongs to the Section Pulmonology)

► Show Figures

Figure 1

Figure 1
Flowchart illustrating the enrollment and the diagnosis procedure. OSA, obstructive sleep apnea; MAD, mandibular advancement device; TMJ, temporomandibular joint; PSG, polysomnography. Full article ">Figure 2
Design of the two-piece MAD used in this study. (A) lateral view and (B) upper and lower plates. MAD: mandibular advancement device. Full article ">Figure 3
Anatomical landmarks and points of reference. S: Center of sella turcica. N (nasion): Most anterior point of the frontonasal suture. Or (Orbitale): Lowest point on the average left and right inferior borders of the bony orbit. Po (Porion): Highest point on the superior surface of soft tissue of the external auditory meatus. ANS: Apex of the anterior nasal spine. PNS: Intersection between the nasal floor and the posterior contour of the maxilla. A: Most posterior point on the anterior contour of the upper alveolar process. B: Most posterior point on the anterior contour of the lower alveolar process. Me (menton): the lowest point on the symphysis of the mandible. Go (Gonion): Most posterior–inferior point on the convexity of the angle of the mandible. U1: maxillary central incisor. L1: mandibular central incisor. Full article ">Figure 4
Anatomical angles analyzed in this study. SNA: the angle between the S–N plane and the straight-line N–A. SNB: the angle between the S–N plane and the straight-line N–B. ANB: the angle between the straight-line N–A and N–B. MnP: mandibular plane according to Downs; the plane connecting through Go and Me. FH (Frankfort horizontal) plane: the plane that connects Po and Or. SN/MP: the angle created between the SN plane and the MnP plane. U1 to FH: the angle between the U1′s axis and FH plane. L1 to MnP: the angle between L1′s axis and MnP. Interincisal angle: measures the degree of procumbence of the incisor teeth. Full article ">Figure 5
Anatomical planes of reference. N–Me: the plane that connects N and Me. MxP: maxillary plane, the line through ANS and PNS. Overjet (OJ): the horizontal overlap of maxillary incisors over the mandibular incisors (mm). Overbite (OB): the vertical overlap of maxillary incisors over mandibular incisors (mm). UAFH (upper anterior facial height): linear measurement from Nasion to Anterior Nasal Spine (N–ANS). LAFH (Lower anterior facial height): linear measurement from Anterior Nasal Spine to Menton (ANS–Me). TAFH (total anterior facial height): linear measurement from Nasion to Menton (N–Me). Anterior facial height ratio: the ratio calculated between UAFH and LAFH (%). Full article ">Figure 6
Odontometric variables used in the dental casts analysis. (A) Crown arch width (4-4 CAW): measured width of the dental arch between the buccal cusps of the first permanent premolars. Crown arch width (6-6 CAW): measured width of the dental arch between the mesio-buccal cusps of the first permanent molars. (B) Basal arch width (4-4 BAW): measured width of the basal arch between the most concave points of the basal bone at the first permanent premolar area. (C) Palatal depth from occlusal plane (PDOC): the deepest point of the palate intersecting at a point perpendicular to the mid-palatal raphe and a line connecting the mesio-buccal cusps of the first permanent molars bilaterally. (D) Overjet and overbite, as defined in the previous section. Full article ">Figure 7
Longitudinal assessment with polysomnography (PSG) and out-of-center sleep testing (OCST). * p < 0.01. Full article ">

16 pages, 5110 KiB

Open AccessReview

Bedside Ultrasound for Hemodynamic Monitoring in Cardiac Intensive Care Unit

by Maria Concetta Pastore, Federica Ilardi, Andrea Stefanini, Giulia Elena Mandoli, Stefano Palermi, Francesco Bandera, Giovanni Benfari, Roberta Esposito, Matteo Lisi, Annalisa Pasquini, Ciro Santoro, Serafina Valente, Antonello D’Andrea and Matteo Cameli

J. Clin. Med. 2022, 11(24), 7538; https://doi.org/10.3390/jcm11247538 - 19 Dec 2022

Cited by 5 | Viewed by 3918

Abstract

Thanks to the advances in medical therapy and assist devices, the management of patients hospitalized in cardiac intensive care unit (CICU) is becoming increasingly challenging. In fact, Patients in the cardiac intensive care unit are frequently characterized by dynamic and variable diseases, which [...] Read more.

Thanks to the advances in medical therapy and assist devices, the management of patients hospitalized in cardiac intensive care unit (CICU) is becoming increasingly challenging. In fact, Patients in the cardiac intensive care unit are frequently characterized by dynamic and variable diseases, which may evolve into several clinical phenotypes based on underlying etiology and its complexity. Therefore, the use of noninvasive tools in order to provide a personalized approach to these patients, according to their phenotype, may help to optimize the therapeutic strategies towards the underlying etiology. Echocardiography is the most reliable and feasible bedside method to assess cardiac function repeatedly, assisting clinicians not only in characterizing hemodynamic disorders, but also in helping to guide interventions and monitor response to therapies. Beyond basic echocardiographic parameters, its application has been expanded with the introduction of new tools such as lung ultrasound (LUS), the Venous Excess UltraSound (VexUS) grading system, and the assessment of pulmonary hypertension, which is fundamental to guide oxygen therapy. The aim of this review is to provide an overview on the current knowledge about the pathophysiology and echocardiographic evaluation of perfusion and congestion in patients in CICU, and to provide practical indications for the use of echocardiography across clinical phenotypes and new applications in CICU. Full article

(This article belongs to the Special Issue The Development and Application of Echocardiography in Heart Disease)

► Show Figures

Figure 1

Figure 1
LVOT Velocity Time Integral (VTI), which is the distance the blood travels across the LVOT, calculated after tracing the LVOT pulsed−wave doppler. Full article ">Figure 2
Typical morphological appearance of the Doppler signal “dagger−shaped” and late peaking curve in left ventricular outflow tract obstruction. Full article ">Figure 3
Echocardiographic markers of congestion. (A) increased IVC inferior vena cava (IVC) diameter; (B) lung ultrasound showing vertical B-lines as a measure of interstitial oedema. Full article ">Figure 4
Echocardiographic markers of pulmonary hypertension (PH). (A) Increased peak tricuspid regurgitation velocity (TRV); (B) reduced right ventricular outflow tract (RVOT) acceleration time. Full article ">Figure 5
Normal findings and different grades of abnormal findings in venous ultrasound evaluation. Adapted from [<a href="#B39-jcm-11-07538" class="html-bibr">39</a>]. Full article ">Figure 6
A 4-chamber view of standard echocardiography in a patient with PH. As results of the increased afterload, RV wall hypertrophies and dilates, developing a spherical shape accompanied by increased RV wall stress, RV dysfunction and severe RA dilatation. Full article ">

13 pages, 832 KiB

Open AccessReview

Axial Spondyloarthritis: Reshape the Future—From the “2022 GISEA International Symposium”

by Fausto Salaffi, Cesare Siragusano, Alessandra Alciati, Giulia Cassone, Salvatore D’Angelo, Serena Guiducci, Ennio Giulio Favalli, Fabrizio Conti, Elisa Gremese, Florenzo Iannone, Roberto Caporali, Marco Sebastiani, Gian Franco Ferraccioli, Giovanni Lapadula and Fabiola Atzeni

J. Clin. Med. 2022, 11(24), 7537; https://doi.org/10.3390/jcm11247537 - 19 Dec 2022

Cited by 3 | Viewed by 2382

Abstract

The term “axial spondyloarthritis” (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an [...] Read more.

The term “axial spondyloarthritis” (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium. Full article

(This article belongs to the Section Immunology)

► Show Figures

Figure 1

10 pages, 1497 KiB

Open AccessArticle

Vagus Nerve Stimulation for Drug Resistant Epilepsy: Clinical Outcome, Adverse Events, and Potential Prognostic Factors in a Single Center Experience

by Ming Shan, Hongliang Mao, Hutao Xie, Yifei Gan, Delong Wu, Jian Song, Yutong Bai and Jianguo Zhang

J. Clin. Med. 2022, 11(24), 7536; https://doi.org/10.3390/jcm11247536 - 19 Dec 2022

Cited by 8 | Viewed by 1511

Abstract

Objective: Vagus nerve stimulation (VNS) has been used for adjunctive treatment in drug resistant epilepsy (DRE) for decades. Nevertheless, information is lacking on possible potential prognostic factors. Our study presents the efficacy and safety of VNS with a focus on prognostic factors in [...] Read more.

Objective: Vagus nerve stimulation (VNS) has been used for adjunctive treatment in drug resistant epilepsy (DRE) for decades. Nevertheless, information is lacking on possible potential prognostic factors. Our study presents the efficacy and safety of VNS with a focus on prognostic factors in 45 patients with DRE. Methods: We retrospectively evaluated the clinical outcome of 45 consecutive patients with DRE undergoing VNS implantation in The First Affiliated Hospital of Anhui Medical University between November 2016 and August 2021. Medical records were aggregated across all patient visits. Cox proportional hazards regression was used to estimate the prognostic factors. Results: Significant decrease in seizure frequency was observed after intermittent stimulation of the vagus nerve. According to the modified McHugh classification, 11 patients (24.4%) were Class I, 11 patients (24.4%) were Class II, four patients (8.9%) were Class III, 10 patients (22.2%) were Class IV, and nine patients (20.0%) were Class V. Notably, 22 patients (48.9%) were responders and four patients (8.9%) were seizure-free at the final follow-up. No significant prognostic factors were found in this cohort. Furthermore, 37 patients reported improved quality of life. Of the patients, 22 (48.9%) experienced adverse events after surgery; hoarseness, discomfort at the surgical site, and coughing were the most common. Conclusion: The results confirmed the efficacy and safety of VNS. No prognostic factors were identified. Full article

(This article belongs to the Section Clinical Neurology)

► Show Figures

Figure 1

9 pages, 266 KiB

Open AccessReview

Acne Vulgaris—Novel Treatment Options and Factors Affecting Therapy Adherence: A Narrative Review

by Aleksandra Tobiasz, Danuta Nowicka and Jacek C. Szepietowski

J. Clin. Med. 2022, 11(24), 7535; https://doi.org/10.3390/jcm11247535 - 19 Dec 2022

Cited by 11 | Viewed by 5522

Abstract

Acne vulgaris is an extremely common skin condition, affecting a large population of adolescents, but at the same time, remaining a quite common issue in the group of adult patients. Its complex pathogenesis includes increased sebum secretion, impaired follicular keratinization, colonization of sebaceous [...] Read more.

Acne vulgaris is an extremely common skin condition, affecting a large population of adolescents, but at the same time, remaining a quite common issue in the group of adult patients. Its complex pathogenesis includes increased sebum secretion, impaired follicular keratinization, colonization of sebaceous glands with Cutibacterium acne bacteria, and the development of inflammation in pilosebaceous units. Although there are many methods of treatment available targeting the mechanisms mentioned above, a large percentage of patients remain undertreated or non-compliant with treatment. Ineffective treatment results in the formation of acne scars, which has a major impact on the well-being and quality of life of the patients. The aim of this publication was a review of available evidence on widely used and novel methods of topical and systemic treatment of acne, additionally including current literature-based analysis of factors affecting patients’ compliance. The strengths and limitations of novel substances for treating acne were discussed. We conclude that an effective acne treatment remains a challenge. A better understanding of current treatment options and factors affecting patients’ compliance could be a helpful tool in choosing a proper treatment option. Full article

(This article belongs to the Special Issue New Insights on Acne, Rosacea, and Hidradenitis Suppurativa: Etiology and Treatment)

13 pages, 610 KiB

Open AccessArticle

An Evaluation of Serological Tests to Determine Postvaccinal Immunity to SARS-CoV-2 by mRNA Vaccines

by Graciela Iglesias García, Ángel Díaz Rodríguez, Beatriz Díaz Fernández, Carmela Cuello Estrada, Tania García Ferreiro, Noelia Crespo García and Jesús Seco-Calvo

J. Clin. Med. 2022, 11(24), 7534; https://doi.org/10.3390/jcm11247534 - 19 Dec 2022

Viewed by 1487

Abstract

Background: The duration of the protective efficacy of vaccines against SARS-CoV-2 is unknown. Thus, an evaluation of the clinical performance of available tests is required. Objectives: To evaluate the clinical performance of LFIA immunoassay compared to ELIA and CLIA immunoassays available in Europe [...] Read more.

Background: The duration of the protective efficacy of vaccines against SARS-CoV-2 is unknown. Thus, an evaluation of the clinical performance of available tests is required. Objectives: To evaluate the clinical performance of LFIA immunoassay compared to ELIA and CLIA immunoassays available in Europe for the detection of IgG antibodies generated by mRNA vaccines against SARS-CoV-2. Methods: Two automated immunoassays (the EUROIMMUN anti-SARS-CoV-2 IgG S1 ELISA and the LIAISON de Diasorin anti-SARS-CoV-2 IgG S1/S2 test) and a lateral flow immunoassay (the Livzon LFIA anti-SARS-CoV-2 IgG S test) were tested. We analyzed 300 samples distributed in three groups: 100 subjects aged over 18 years and under 45 years, 100 subjects aged between 45 and 65 years, and 100 subjects aged over 65 years. The samples were collected before vaccination; at 21 days; and then at 1, 2, 3, and 6 months after vaccination. The sensitivity, specificity, positive predictive value, negative predictive value, positive probability quotient, negative probability quotient, and concordance (kappa index) were calculated for each serological test. Results: The maximum sensitivity values for IgG were 98.7%, 98.1%, and 97.8% for the EUROIMMUN ELISA, Abbott CLIA, and Livzon LFIA tests, respectively, and the maximum specificity values for IgG were 99.4%, 99.9%%, and 98.4% for the ELISA, CLIA, and LFIA tests, respectively, at the third month after vaccination, representing a decrease in the antibody levels after the sixth month. The best agreement was observed between the ELISA and CLIA tests at 100% (k = 1.00). The agreement between the ELIA, CLIA, and LFIA tests was 99% (k = 0.964) at the second and third month after vaccination. Seroconversion was faster and more durable in the younger age groups. Conclusion: Our study examined the equivalent and homogeneous clinical performance for IgG of three immunoassays after vaccination and found LFIA to be the most cost-effective, reliable, and accurate for routine use in population seroconversion and seroprevalence studies. Full article

(This article belongs to the Section Immunology)

► Show Figures

Figure 1

16 pages, 4421 KiB

Open AccessArticle

Next in Surgical Data Science: Autonomous Non-Technical Skill Assessment in Minimally Invasive Surgery Training

by Renáta Nagyné Elek and Tamás Haidegger

J. Clin. Med. 2022, 11(24), 7533; https://doi.org/10.3390/jcm11247533 - 19 Dec 2022

Cited by 5 | Viewed by 2562

Abstract

Background: It is well understood that surgical skills largely define patient outcomes both in Minimally Invasive Surgery (MIS) and Robot-Assisted MIS (RAMIS). Non-technical surgical skills, including stress and distraction resilience, decision-making and situation awareness also contribute significantly. Autonomous, technologically supported objective skill assessment [...] Read more.

Background: It is well understood that surgical skills largely define patient outcomes both in Minimally Invasive Surgery (MIS) and Robot-Assisted MIS (RAMIS). Non-technical surgical skills, including stress and distraction resilience, decision-making and situation awareness also contribute significantly. Autonomous, technologically supported objective skill assessment can be efficient tools to improve patient outcomes without the need to involve expert surgeon reviewers. However, autonomous non-technical skill assessments are unstandardized and open for more research. Recently, Surgical Data Science (SDS) has become able to improve the quality of interventional healthcare with big data and data processing techniques (capture, organization, analysis and modeling of data). SDS techniques can also help to achieve autonomous non-technical surgical skill assessments. Methods: An MIS training experiment is introduced to autonomously assess non-technical skills and to analyse the workload based on sensory data (video image and force) and a self-rating questionnaire (SURG-TLX). A sensorized surgical skill training phantom and adjacent training workflow were designed to simulate a complicated Laparoscopic Cholecystectomy task; the dissection of the cholecyst’s peritonial layer and the safe clip application on the cystic artery in an uncomfortable environment. A total of 20 training sessions were recorded from 7 subjects (3 non-medicals, 2 residents, 1 expert surgeon and 1 expert MIS surgeon). Workload and learning curves were studied via SURG-TLX. For autonomous non-technical skill assessment, video image data with tracked instruments based on Channel and Spatial Reliability Tracker (CSRT) and force data were utilized. An autonomous time series classification was achieved by a Fully Convolutional Neural Network (FCN), where the class labels were provided by SURG-TLX. Results: With unpaired t-tests, significant differences were found between the two groups (medical professionals and control) in certain workload components (mental demands, physical demands, and situational stress,

p < 0.0001

, 95% confidence interval,

p < 0.05

for task complexity). With paired t-tests, the learning curves of the trials were also studied; the task complexity resulted in a significant difference between the first and the second trials. Autonomous non-technical skill classification was based on the FCN by applying the tool trajectories and force data as input. This resulted in a high accuracy (85%) on temporal demands classification based on the z component of the used forces and 75% accuracy for classifying mental demands/situational stress with the x component of the used forces validated with Leave One Out Cross-Validation. Conclusions: Non-technical skills and workload components can be classified autonomously based on measured training data. SDS can be effective via automated non-technical skill assessment. Full article

(This article belongs to the Special Issue Advances in Robot-Assisted Minimally Invasive Surgery)

► Show Figures

Figure 1

Figure 1
Surgical skills in MIS and RAMIS are built on technical skills, non-technical skills and managing the workload. These segments are directly influencing each other. Surgical skill training and assessment can affect the skills of the surgeon, which derive patient outcomes. Full article ">Figure 2
Laparoscopic Cholecystectomy (LC) anatomy and the proposed phantom; (a) Laparoscopic Cholecystectomy surgical scene, after the exploration of the Calot’s triangle, which is a critical task in patient safety; (b) Anatomy of the gallbladder and its environment; (c) Surgical phantom created for LC with the peritoneum, gallbladder and the cystic artery, which provides the option for abrupt bleeding, intending to mimic a stressful surgical situation. Full article ">Figure 3
Proposed workflow of the MIS experiment; (a) Grasping the outer layer (representing the parietal peritoneum) with a dissector; (b) Cutting the outer layer with a pair of scissors; (c) Blunt dissection; (d) Cutting; (e) Removing the covering layer; (f) Abrupt bleeding; (g) Localize the bleeding source, change the tool(s) to the clipper; (h) Clipping the blood vessel considering the direction of the blood flow. Full article ">Figure 4
Experimental environment; (a) MIS box trainer with the components of the experiment–phantom and sensors, such as the camera and the force-gauging system); (b) Camera image streamed for the operators during the training and recorded for data processing. Full article ">Figure 5
Autonomous non-technical surgical skill assessment method workflow based on sensory data with FCN multivariate time series classification. Full article ">Figure 6
SURG-TLX values (0–20) of medical professionals from first to third trials (first column) and novices (second column). Asterisk (*) notes if the first task (dissecting the cholecyst) was successful. Full article ">Figure 7
Surgical training environment and phantom validation (applicability for laparoscopy training, similarity of motions, anatomical similarity, simulation of stress) based only on medical professionals’ evaluation. The environment was assessed as good for applicability, very good for movement similarity, acceptable for anatomical similarity and moderate for stress simulation. Full article ">

15 pages, 1690 KiB

Open AccessSystematic Review

Platelet-Rich Plasma in Chronic Wound Management: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

by Fanni Adél Meznerics, Péter Fehérvári, Fanni Dembrovszky, Kata Dorottya Kovács, Lajos Vince Kemény, Dezső Csupor, Péter Hegyi and András Bánvölgyi

J. Clin. Med. 2022, 11(24), 7532; https://doi.org/10.3390/jcm11247532 - 19 Dec 2022

Cited by 18 | Viewed by 3763

Abstract

Background: Chronic wounds place a heavy burden on the healthcare system due to the prolonged, continuous need for human resources for wound management. Our aim was to investigate the therapeutic effects of platelet-rich plasma on the treatment of chronic wounds. Methods: The systematic [...] Read more.

Background: Chronic wounds place a heavy burden on the healthcare system due to the prolonged, continuous need for human resources for wound management. Our aim was to investigate the therapeutic effects of platelet-rich plasma on the treatment of chronic wounds. Methods: The systematic literature search was performed in four databases. Randomized clinical trials reporting on patients with chronic wounds treated with platelet-rich plasma (PRP) were included, comparing PRP with conventional ulcer therapy. We pooled the data using the random effects model. Our primary outcome was the change in wound size. Results: Our systematic search provided 2688 articles, and we identified 48 eligible studies after the selection and citation search. Thirty-three study groups of 29 RCTs with a total of 2198 wounds showed that the odds for complete closure were significantly higher in the PRP group than in the control group (OR = 5.32; CI: 3.37; 8.40; I² = 58%). Conclusions: PRP is a safe and effective modality to enhance wound healing. By implementing it in clinical practice, platelet-rich plasma could become a widely used, valuable tool as it could not only improve patients’ quality of life but also decrease the healthcare burden of wound management. Full article

(This article belongs to the Special Issue Wound Healing and Plastic Surgery: Challenges and Innovations)

► Show Figures

Figure 1

10 pages, 560 KiB

Open AccessArticle

Next-Generation Sequencing of a Large Gene Panel for Outcome Prediction of Bariatric Surgery in Patients with Severe Obesity

by Gabriele Bonetti, Kristjana Dhuli, Maria Rachele Ceccarini, Jurgen Kaftalli, Michele Samaja, Vincenza Precone, Stefano Cecchin, Paolo Enrico Maltese, Giulia Guerri, Giuseppe Marceddu, Tommaso Beccari, Barbara Aquilanti, Valeria Velluti, Giuseppina Matera, Marco Perrone, Amerigo Iaconelli, Francesca Colombo, Francesco Greco, Marco Raffaelli, Mahmut Cerkez Ergoren and Matteo Bertelli Show full author list Hide full author list

J. Clin. Med. 2022, 11(24), 7531; https://doi.org/10.3390/jcm11247531 - 19 Dec 2022

Cited by 5 | Viewed by 1775

Abstract

Obesity is a chronic disease in which abnormal deposition of fat threatens health, leading to diabetes, cardiovascular diseases, cancer, and other chronic illnesses. According to the WHO, 19.8% of the adult population in Italy is obese, and the prevalence is higher among men. [...] Read more.

Obesity is a chronic disease in which abnormal deposition of fat threatens health, leading to diabetes, cardiovascular diseases, cancer, and other chronic illnesses. According to the WHO, 19.8% of the adult population in Italy is obese, and the prevalence is higher among men. It is important to know the predisposition of an individual to become obese and to respond to bariatric surgery, the most up-to-date treatment for severe obesity. To this purpose, we developed an NGS gene panel, comprising 72 diagnostic genes and 244 candidate genes, and we sequenced 247 adult obese Italian patients. Eleven deleterious variants in 9 diagnostic genes and 17 deleterious variants in 11 candidate genes were identified. Interestingly, mutations were found in several genes correlated to the Bardet–Biedl syndrome. Then, 25 patients were clinically followed to evaluate their response to bariatric surgery. After a 12-month follow-up, the patients that carried deleterious variants in diagnostic or candidate genes had a reduced weight loss, as compared to the other patients. The NGS-based panel, including diagnostic and candidate genes used in this study, could play a role in evaluating, diagnosing, and managing obese individuals, and may help in predicting the outcome of bariatric surgery. Full article

(This article belongs to the Special Issue Obesity and Bariatric/Metabolic Surgery: Risks, Outcomes, Prognosis, and Development Trends)

► Show Figures

Figure 1

15 pages, 4540 KiB

Open AccessArticle

Incidence, Risk Factors, and Outcomes of Symptomatic Bone Cement Displacement following Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fracture: A Single Center Study

by Junbo Qi, Yuanyu Hu, Zhongwei Yang, Yanlei Dong, Xin Zhang, Guojin Hou, Yang Lv, Yan Guo, Fang Zhou, Bingchuan Liu and Yun Tian

J. Clin. Med. 2022, 11(24), 7530; https://doi.org/10.3390/jcm11247530 - 19 Dec 2022

Cited by 10 | Viewed by 2181

Abstract

Study design: Retrospective. Background: Symptomatic bone cement displacement (BCD) is a rare complication following percutaneous kyphoplasty (PKP) interventions for osteoporotic vertebral compression fracture (OVCF). This study aimed to investigate the incidence and the outcomes of symptomatic BCD comprehensively and identify its risk factors. [...] Read more.

Study design: Retrospective. Background: Symptomatic bone cement displacement (BCD) is a rare complication following percutaneous kyphoplasty (PKP) interventions for osteoporotic vertebral compression fracture (OVCF). This study aimed to investigate the incidence and the outcomes of symptomatic BCD comprehensively and identify its risk factors. Methods: The clinical data of patients treated with PKP for OVCF between January 2012 and December 2020 were extracted. Patients who developed BCD following PKP during follow-up were divided into the symptomatic and asymptomatic groups. Patients who did not develop BCD were assigned to the control group. Univariate and multiple logistic regression analyses were used to compare the three clinical groups’ features to assess the independent risk factors for the symptomatic and asymptomatic groups. Results: A total of 896 patients were enrolled. Twenty-one patients (2.3%) were identified as having symptomatic BCD following PKP for OVCF, and 35 (3.9%) developed asymptomatic BCD. Compared with the control group, the symptomatic and asymptomatic groups had a higher incidence of anterior leakage, intravertebral vacuum cleft (IVC) signs, and a lower cement distribution score. The symptomatic group had a lower relative cross-sectional area (rCSA) of the paraspinal muscle (PSM), higher PSM fatty degeneration, and higher kyphotic angle (at the last follow-up) than the asymptomatic and control groups. For outcomes, the symptomatic group had a higher VAS/ODI score and a higher incidence of new vertebral fractures compared with the asymptomatic and control groups. Anterior leakage (OR: 1.737, 95% CI: 1.215–3.300), the IVC sign (OR: 3.361, 95% CI: 1.605–13.036), the cement distribution score (OR: 0.476, 95% CI: 0.225–0.904), PSM rCSA (OR: 0.953, 95% CI: 0.917–0.992), and PSM fatty degeneration (OR: 1.061, 95% CI: 1.005–1.119) were identified as independent risk factors for the symptomatic group. Anterior leakage (OR: 1.839, 95% CI: 1.206–2.803), the IVC sign (OR: 2.936, 95% CI: 1.174–9.018), and cement distribution score (OR: 0.632, 95% CI: 0.295–0.858) were independent risk factors for the asymptomatic group. Conclusion: The incidence of symptomatic BCD is 2.3% in patients treated with PKP. Anterior leakage, the IVC sign, and the distribution score were independent risk factors for BCD, and paraspinal muscle degeneration was a specific risk factor for symptomatic BCD. Symptomatic BCD can lead to poor outcomes. Full article

(This article belongs to the Special Issue Orthopedic Surgery in Elderly Patients: Past, Present, and Future)

► Show Figures

Figure 1

Figure 1
The flowchart of the study. OVCF = osteoporotic vertebral compression fracture, PKP = percutaneous kyphoplasty, DXA = dual-energy X-ray absorptiometry, CT = computed tomography, MRI = magnetic resonance imaging, BCD = bone cement displacement, and VAS = Visual Analogue Scale. Full article ">Figure 2
(A) The patient showed well-located bone cement, and the distance between the cement’s anterior edge and the anterior wall of the vertebral body was 1.75 mm before discharge. (B) The patient showed that the distance was 7.16 mm at follow-up. By taking the anterior wall of the vertebral body as a reference, the movement of the anterior edge of bone cement was 8.91 mm, and the patient met the criteria for radiographic diagnosis of BCD. Full article ">Figure 3
Measurement of vertebral collapse and kyphosis. Vertebral collapse (%) was measured as follows: [(a + c)/2 − b]/ [(a + c)/2] × 100. The kyphosis Cobb was measured by using the Cobb method. a = upper vertebral height, b = affected vertebral height, c = lower vertebral height. Full article ">Figure 4
The tCSA of PSM was measured by drawing the outline of the fascial–muscle boundary using the ROI at the level of the inferior vertebral endplate of L4 on axial T2-weighted MRI. Measurement of fCSA of PSM was performed using a threshold method. tCSA = total cross-sectional area, PSM = paraspinal muscle, ROI = region of interest, and fCSA = functional cross-sectional area. Full article ">Figure 5
(A,B) A 74-year-old male patient with OVCF at T12. Anteroposterior and lateral images were taken after PKP, and the bone cement distribution score was calculated as 4 + 4 + 2 = 10. (C,D) A 77-year-old female patient with OVCF at T12. The bone cement distribution score was calculated as 2 + 2 + 1 = 5. Full article ">Figure 6
The proportion of fractured levels in the symptomatic, asymptomatic, and control groups. Full article ">

14 pages, 1308 KiB

Open AccessArticle

Nomogram for Early Prediction of Outcome in Coma Patients with Severe Traumatic Brain Injury Receiving Right Median Nerve Electrical Stimulation Treatment

by Chao Zhang, Wen-Dong You, Xu-Xu Xu, Qian Zhou and Xiao-Feng Yang

J. Clin. Med. 2022, 11(24), 7529; https://doi.org/10.3390/jcm11247529 - 19 Dec 2022

Cited by 1 | Viewed by 2110

Abstract

Background: Accurate outcome prediction can serve to approach, quantify and categorize severe traumatic brain injury (TBI) coma patients for right median electrical stimulation (RMNS) treatment, which can support rehabilitation plans. As a proof of concept for individual risk prediction, we created a novel [...] Read more.

Background: Accurate outcome prediction can serve to approach, quantify and categorize severe traumatic brain injury (TBI) coma patients for right median electrical stimulation (RMNS) treatment, which can support rehabilitation plans. As a proof of concept for individual risk prediction, we created a novel nomogram model combining amplitude-integrated electroencephalography (AEEG) and clinically relevant parameters. Methods: This study retrospective collected and analyzed a total of 228 coma patients after severe TBI in two medical centers. According to the extended Glasgow Outcome Scale (GOSE), patients were divided into a good outcome (GOSE 3–8) or a poor outcome (GOSE 1–2) group. Their clinical and biochemical indicators, together with EEG features, were explored retrospectively. The risk factors connected to the outcome of coma patients receiving RMNS treatment were identified using Cox proportional hazards regression. The discriminative capability and calibration of the model to forecast outcome were assessed by C statistics, calibration plots, and Kaplan-Meier curves on a personalized nomogram forecasting model. Results: The study included 228 patients who received RMNS treatment for long-term coma after a severe TBI. The median age was 40 years, and 57.8% (132 of 228) of the patients were male. 67.0% (77 of 115) of coma patients in the high-risk group experienced a poor outcome after one year and the comparative data merely was 30.1% (34 of 113) in low-risk group patients. The following variables were integrated into the forecasting of outcome using the backward stepwise selection of Akaike information criterion: age, Glasgow Coma Scale (GCS) at admission, EEG reactivity (normal, absence, or the stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs)), and AEEG background pattern (A mode, B mode, or C mode). The C statistics revealed that the nomograms’ discriminative potential and calibration demonstrated good predictive ability (0.71). Conclusion: Our findings show that the nomogram model using AEEG parameters has the potential to predict outcomes in severe TBI coma patients receiving RMNS treatment. The model could classify patients into prognostic groups and worked well in internal validation. Full article

(This article belongs to the Topic Advances in Neurocritical Care)

► Show Figures

Figure 1

Figure 1
Recruitment flow chart of patients. Abbreviations: TBI, traumatic brain injury; RMNS, right median electrical stimulation. Full article ">Figure 2
Nomogram Predicting Outcome in TBI Coma Patients After Receiving RMNS treatment. The nomogram to predict a good outcome was created based on four independent prognostic factors (see the Model Specifications and Predictors of good outcome subsection of the Methods section). Abbreviations: GCS, Glasgow Coma Scale; AEEG, amplitude-integrated electroencephalography. Full article ">Figure 3
Kaplan-Meier Curves Demonstrating Poor Outcome in TBI Coma Patients After Receiving RMNS Treatment According to Dichotomy of Predicted Outcome. p values are by the log-rank test. Full article ">Figure 4
Calibration Plot Comparing Predicted and Actual Good Outcome Probabilities at 1-year Follow-up cross represents the result of each point corrected by hierarchical Kaplan-Meier’ after the word ‘bootstrap-corrected estimates’ in the annotation of <a href="#jcm-11-07529-f001" class="html-fig">Figure 1</a>. The calibration plot for predicting a 1-year good outcome with 40 samples is presented. The gray line signifies best fit; circles show nomogram-predicted probabilities; crunode represents bootstrap-corrected estimates, and error bars stand for 95% confidence intervals for these estimates. Full article ">

8 pages, 237 KiB

Open AccessArticle

Increased Frequency of Hand Hygiene and Other Infection Prevention Practices Correlates with Reduced Surgical Wound Infection Rates in Spinal Surgery during the COVID-19 Pandemic

by Andrea Perna, Francesco Maruccia, Franco Lucio Gorgoglione, Felice Barletta, Raffaele Vitiello, Luca Proietti, Francesco Ciro Tamburrelli and Domenico Alessandro Santagada

J. Clin. Med. 2022, 11(24), 7528; https://doi.org/10.3390/jcm11247528 - 19 Dec 2022

Cited by 3 | Viewed by 1962

Abstract

Background: Due to the COVID-19 pandemic outbreak, many changes were done in the hospital practice, and new guidelines were issued in order to contain the infection spread. One of the most common measures is represented by a correct and frequent hand washing. Recently, [...] Read more.

Background: Due to the COVID-19 pandemic outbreak, many changes were done in the hospital practice, and new guidelines were issued in order to contain the infection spread. One of the most common measures is represented by a correct and frequent hand washing. Recently, an association between increased adherence to hand hygiene (HH) protocols and reduction in hospital infections was documented however no studies about the surgical wound infection rate were reported in the Literature. Methods: The present study represents a multicentric retrospective epidemiological study. The HH compliance rate was recorded through direct observations by trained nurses, 24 h a day. The primary outcome was HH compliance rate. The association of HH with spinal surgical wound infections was the secondary outcome. Results: We reported a compliance to HH practices during the pandemic period of 85.2% compared with 57% observed during 2019. Our analysis showed an overall surgical wound infection reduction of 66.6% during the hospital stay in the pandemic period. Conclusion: Hand hygiene has always been considered one of the most effective, reproducible and low-cost weapons to deal with hospital infections. The good health habits acquired during the COVID-19 pandemic should be maintained even after the virus is eradicated. Full article

(This article belongs to the Special Issue Orthopedics and Coronavirus: Analyzing the Past to Face the Present and to Prevent the Future)

10 pages, 6045 KiB

Open AccessArticle

Characteristics of Hearing Loss in Patients with Systemic Lupus Erythematosus

by Huixian Chen, Fan Wang, Ye Yang, Bingzhu Hua, Hong Wang, Jie Chen and Xuebing Feng

J. Clin. Med. 2022, 11(24), 7527; https://doi.org/10.3390/jcm11247527 - 19 Dec 2022

Cited by 1 | Viewed by 2117

Abstract

Objective: To investigate the clinical characteristics of hearing loss (HL) in patients with systemic lupus erythematosus (SLE) and its related factors. Methods: Ninety-one hospitalized SLE patients and thirty healthy controls were enrolled. All subjects completed pure tone audiometry (PTA), extended high frequency audiometry [...] Read more.

Objective: To investigate the clinical characteristics of hearing loss (HL) in patients with systemic lupus erythematosus (SLE) and its related factors. Methods: Ninety-one hospitalized SLE patients and thirty healthy controls were enrolled. All subjects completed pure tone audiometry (PTA), extended high frequency audiometry (EHFA) and distortion product otoacoustic emission (DPOAE) to assess hearing function. SLE patients were divided into two groups according to the presence or absence of HL, and the risk factors of HL were determined by multivariate logistic regression. Results: The incidence of HL was 27.47% in SLE patients, significantly higher than in the control group (3.3%) and most cases were mild-to-moderate, bilateral and predominantly sensorineural. Compared with the control group, the hearing thresholds of SLE patients increased significantly in the middle and high frequencies starting from 2000 Hz. Even though the PTA test results were normal, the EHFA test results showed significant differences in hearing impairment between SLE patients and normal controls. For patients with abnormal PTA results, the signal-to-noise ratio (SNR) in DPOAE was markedly reduced, and the pass rate was also decreased. The Systemic Lupus International Collaborating Clinics Damage Index (SDI, OR 9.13) and secondary Sjögren’s syndrome (sSS, OR 8.20) were identified as independent associated factors for HL, and there was no difference in PTA and EHFA at all frequencies between hydroxychloroquine users and non-users. Conclusions: HL is not rare in SLE patients, and EHFA can help identify early hearing impairment. Having a high SDI score and secondary Sjögren’s syndrome may predict the presence of HL in SLE. Full article

(This article belongs to the Special Issue Lupus and Scleroderma: New Aspects and Considerations)

► Show Figures

Figure 1

Figure 1
Comparison of pure tone audiometry and extended high frequency audiometry thresholds from 250 to 16,000 Hz frequencies between 91 SLE patients and 30 healthy controls. Data are presented as mean ± SEM and the mean values at each hearing frequency are linked by the trend line. * p < 0.05, ** p < 0.01, *** p < 0.001 by t-test. Full article ">Figure 2
Comparison of extended high frequency audiometry thresholds at 9000 to 16,000 Hz between SLE patients (38 ears) and controls (16 ears) with normal pure tone audiometry thresholds. Data are presented as median and interquartile range, and the median values at each hearing frequency are linked by the trend line. * p < 0.05 by Mann–Whitney U Test. Full article ">Figure 3
Association of DPOAE results with PTA. (A) SNR values in the ears of SLE patients with and without normal PTA at different frequencies. The dashed line indicates normal SNR value (6 dB). Data are presented as mean ± SEM and the mean values at each F2 frequency are linked by the trend line. p < 0.05 by t-test. (B) Percentages of valid DPOAE in the ears of SLE patients with and without normal PTA at different frequencies. p < 0.05 by chi-squared test. DPOAE: distortion product otoacoustic emission; PTA: pure tone audiometry; SNR: signal-to-noise ratio. Full article ">Figure 4
Hearing thresholds at different frequencies in SLE patients. (A,B) Comparison of hearing thresholds in SLE patients with SDI ≥ 2 (n = 28) and <2 (n = 63) in the left or right ear. (C,D) Comparison of hearing thresholds in SLE patients with (n = 16) and without sSS (n = 75) in the left or right ear. Data are presented as mean ± SEM and the mean values at each hearing frequency are linked by the trend line. * p < 0.05, ** p < 0.01 by t-test. SDI: Systemic Lupus International Collaborating Clinics/ACR damage index, sSS: secondary Sjögren’s syndrome. Full article ">

18 pages, 1900 KiB

Open AccessArticle

Ileal Bile Acid Transporter Blockers for Cholestatic Liver Disease in Pediatric Patients with Alagille Syndrome: A Systematic Review and Meta-Analysis

by Hafiza Sidra tul Muntaha, Mubashar Munir, Syeda Haleema Sajid, Zouina Sarfraz, Azza Sarfraz, Karla Robles-Velasco, Muzna Sarfraz, Miguel Felix and Ivan Cherrez-Ojeda

J. Clin. Med. 2022, 11(24), 7526; https://doi.org/10.3390/jcm11247526 - 19 Dec 2022

Cited by 5 | Viewed by 2529

Abstract

Alagille syndrome (ALGS) is a rare, debilitating inheritable disease that is associated with refractory pruritus due to chronic cholestasis. The following systemic review and meta-analysis presents the latest evidence for ileal bile acid transport (IBAT) blockers in AGLS patients in order to improve [...] Read more.

Alagille syndrome (ALGS) is a rare, debilitating inheritable disease that is associated with refractory pruritus due to chronic cholestasis. The following systemic review and meta-analysis presents the latest evidence for ileal bile acid transport (IBAT) blockers in AGLS patients in order to improve their efficacy. This study adhered to PRISMA 2020 Statement guidelines. A systematic search of PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane library was conducted from inception until 23 October 2022. A combination of the following keywords was used: Alagille syndrome, therapeutics, treatment, therapy. Meta-analytical outcomes included effect directions of end-line changes in serum bile acids (sBAs), Itch Scale scores (ItchRO), Multidimensional Fatigue Scale scores, pediatric quality of life (QL), alanine aminotransferase (ALT), and total bilirubin. A total of 94 patients across four trials were enrolled and received maralixibat, odevixibat, or a placebo. There was a significant reduction in ItchRO scores by 1.8 points, as well as in sBAs by 75.8 μmol/L. Both the Multidimensional Fatigue Scale and Pediatric QL scale were also improved by 11.4 and 8.3 points, respectively. However, ALT levels were raised by 40 U/L. The efficacy of IBAT inhibitors across current trials was noted. Future trials may focus on the optimization of dosing regimens, considering gastrointestinal side effects and drug-induced ALT elevation in AGLS patients. Full article

(This article belongs to the Special Issue Recent Advances in Liver Transplantation and Adjacent Therapies)

► Show Figures

Figure 1

11 pages, 1574 KiB

Open AccessArticle

Analysis of ProP1 Gene in a Cohort of Tunisian Patients with Congenital Combined Pituitary Hormone Deficiency

by Mariam Moalla, Mouna Mnif-Feki, Wajdi Safi, Nadia Charfi, Nabila Mejdoub-Rekik, Mohamed Abid, Faten Hadj Kacem and Hassen Hadj Kacem

J. Clin. Med. 2022, 11(24), 7525; https://doi.org/10.3390/jcm11247525 - 19 Dec 2022

Cited by 2 | Viewed by 1355

Abstract

Background: Non-syndromic combined pituitary hormone deficiency (CPHD) occurs due to defects in transcription factors that govern early pituitary development and the specification of hormone-producing cells. The most common mutations are in the Prophet of Pit-1 (ProP1) gene. This work aims to [...] Read more.

Background: Non-syndromic combined pituitary hormone deficiency (CPHD) occurs due to defects in transcription factors that govern early pituitary development and the specification of hormone-producing cells. The most common mutations are in the Prophet of Pit-1 (ProP1) gene. This work aims to (1) report findings of genetic analyses of Tunisian patients with non-syndromic CPHD and (2) describe their phenotype patterns and their evolution through life. Methods: Fifteen patients from twelve unrelated families with variable clinical phenotypes were included after excluding autoimmune and acquired forms of non-syndromic CPHD. Detailed pedigree charts and auxological, hormonal, radiological, and therapeutic details were recorded. Sanger sequencing was performed, and sequences were analyzed with a specific focus on coding and splice site regions of the ProP1 gene. Retained variants were classified using several in silico pathogenicity prediction tools and the VarSome platform. Results: We identified the common p.Arg73Cys mutation in seven patients from four unrelated pedigrees. We found a novel homozygous mutation (c.340C>T) in one sporadic case. This mutation generates a truncated ProP1 protein, predicted to be non-functional, lacking the last 112 codons (p.(Gln114Ter)). We confirmed by polymerase chain reaction (PCR) the absence of large exon deletions or insertions in the remaining sporadic patients (7/8). Conclusions: We report two mutations {one newly identified [p.(Gln114Ter)] and one previously reported (p.Arg73Cys)} in five unrelated Tunisian families with non-syndromic CPHD. This work is of clinical importance as it reports the high frequency of the p.Arg73Cys mutation in Tunisian CPHD families. Our study also illuminated the involvement of novel gene(s) in the emergence of non-syndromic CPHD. Full article

(This article belongs to the Section Endocrinology & Metabolism)

► Show Figures

Figure 1

Figure 1
Pedigree of the studied families. The generations within the family are indicated by roman numerals. Squares and circles represent male and female, respectively. Normal individuals are shown as clear symbol, whereas the affected individuals are shown as filled symbol. Patients F3-II.2, F4-V.1 and F4-V.3 consult in private clinics and refuse hormonal assessment and genetic testing. Full article ">Figure 2
Mutation analysis of the ProP1 gene in familial cases. Electropherogram analysis of ProP1 gene in affected and unaffected individuals. The c.217C>T mutation in exon 2 resulted in substitution of the arginine by cysteine at amino acid position 73. Mutated nucleotide on the chromatographs is in bold, underlined and depicted with an arrow. Amino acid substitution is indicated in red. Full article ">Figure 3
Mutation analysis of the ProP1 gene in sporadic case. (A) Pedigree of the S1 sporadic case. (B) Electropherogram analysis of ProP1 gene in the family. The c.340C>T mutation in exon 2 resulted in truncated protein lacking the last 112 codons [p.(Gln114Ter)]. Mutated nucleotide on the chromatographs is in bold, underlined and depicted with an arrow. Amino acid substitution is indicated in red. Full article ">Figure 4
Location of ProP1 mutations reported so far. Mutations found in our cohort are highlighted. Exons are represented by shaded boxes. Exons, introns, and untranslated regions (5′ and 3′UTRs) are not drawn to scale. Full article ">

9 pages, 238 KiB

Open AccessArticle

Association of Chronic Kidney Disease with Prior Tinnitus: A Case–Control Study

by Shih-Han Hung, Sudha Xirasagar, Yen-Fu Cheng, Nai-Wen Kuo and Herng-Ching Lin

J. Clin. Med. 2022, 11(24), 7524; https://doi.org/10.3390/jcm11247524 - 19 Dec 2022

Cited by 1 | Viewed by 1410

Abstract

This population-based, case–control study aims to explore the relationship between prior tinnitus and the occurrence of chronic kidney disease (CKD) using a nationwide, population-based cohort study. We used data from the Taiwan National Health Insurance Research Database to explore the association of CKD [...] Read more.

This population-based, case–control study aims to explore the relationship between prior tinnitus and the occurrence of chronic kidney disease (CKD) using a nationwide, population-based cohort study. We used data from the Taiwan National Health Insurance Research Database to explore the association of CKD with tinnitus. We identified 15,314 patients aged ≥40 years old with a first-time diagnosis of CKD as the cases. We used propensity-scored matching to select 45,942 controls (1:3 ratio). We performed multivariate logistic regression to estimate the odds ratio (OR) of a prior tinnitus diagnosis among the CKD group vs. the control group. Analysis showed that 770 (1.26%) out of the 61,256 sampled patients had previously diagnosed tinnitus. Chi-square testing revealed a significant difference in the rate of previously diagnosed tinnitus between cases and controls (3.86% vs. 0.93%, p < 0.001). Univariate logistic regression analysis showed an OR of prior tinnitus for cases of 10.249 (95% confidence interval (CI): (8.662~12.126)) relative to controls. In adjusted analysis, cases were more likely than controls to have a prior diagnosis of tinnitus (OR = 10.970, 95% CI = 9.255~13.004, p < 0.001) after adjusting for age, sex, monthly income, geographic location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and autoimmune disease. Our study shows that CKD patients have a higher likelihood of having suffered from tinnitus before CKD was diagnosed, but we have no data suggesting that tinnitus is a predictor of subsequent CKD. Patients diagnosed with tinnitus may benefit from proactive measures to prevent CKD and detect it early through lifestyle modifications and regular renal function examinations, regardless of CKD-related symptoms. Full article

(This article belongs to the Section Otolaryngology)

29 pages, 2237 KiB

Open AccessReview

Recent and Future Strategies to Overcome Resistance to Targeted Therapies and Immunotherapies in Metastatic Colorectal Cancer

by Giulia Dazio, Samantha Epistolio, Milo Frattini and Piercarlo Saletti

J. Clin. Med. 2022, 11(24), 7523; https://doi.org/10.3390/jcm11247523 - 19 Dec 2022

Cited by 2 | Viewed by 2478

Abstract

Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide, and 20% of patients with CRC present at diagnosis with metastases. The treatment of metastatic CRC is based on a fluoropyrimidine-based chemotherapy plus additional agents such as oxaliplatin and irinotecan. [...] Read more.

Colorectal cancer (CRC) is the third most common cause of cancer-related deaths worldwide, and 20% of patients with CRC present at diagnosis with metastases. The treatment of metastatic CRC is based on a fluoropyrimidine-based chemotherapy plus additional agents such as oxaliplatin and irinotecan. To date, on the basis of the molecular background, targeted therapies (e.g., monoclonal antibodies against epidermal growth factor receptor or inhibiting angiogenesis) are administered to improve the treatment of metastatic CRC. In addition, more recently, immunological agents emerged as effective in patients with a defective mismatch repair system. The administration of targeted therapies and immunotherapy lead to a significant increase in the survival of patients; however these drugs do not always prove effective. In most cases the lack of effectiveness is due to the development of primary resistance, either a resistance-inducing factor is already present before treatment or resistance is acquired when it occurs after treatment initiation. In this review we describe the most relevant targeted therapies and immunotherapies and expand on the reasons for resistance to the different approved or under development targeted drugs. Then we showed the possible mechanisms and drugs that may lead to overcoming the primary or acquired resistance in metastatic CRC. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

► Show Figures

Figure 1

12 pages, 671 KiB

Open AccessArticle

Incidence and Severity of Community- and Hospital-Acquired Hyponatremia in Pediatrics

by J. M. Rius-Peris, P. Tambe, M. Chilet Sáez, M. Requena, E. Prada and J. Mateo

J. Clin. Med. 2022, 11(24), 7522; https://doi.org/10.3390/jcm11247522 - 19 Dec 2022

Cited by 2 | Viewed by 1387

Abstract

Hyponatremia is the most common electrolyte disturbance in hospitalized children, with a reported incidence of 15–30%, but its overall incidence and severity are not well known. The objective of our study was to determine the incidence, severity, and associated risk factors of community- [...] Read more.

Hyponatremia is the most common electrolyte disturbance in hospitalized children, with a reported incidence of 15–30%, but its overall incidence and severity are not well known. The objective of our study was to determine the incidence, severity, and associated risk factors of community- and hospital-acquired hyponatremia on a general pediatric ward. Data of 5550 children admitted from June 2012 to December 2019 on plasma sodium and discharge diagnosis were analyzed by logistic regression model. Clinically relevant diagnostic groups were created. Hyponatremia was classified as mild, moderate, and severe. The incidence of community- and hospital-acquired hyponatremia was 15.8% and 1.4%, respectively. Most of the cases were mild (90.8%) to moderate (8.6%), with only two cases of severe community-acquired hyponatremia. There were no clinical complications in any of the hyponatremic children. Age and diagnosis at discharge were principal factors significantly correlated with hyponatremia. Community-acquired hyponatremia is more common than hospital-acquired hyponatremia in clinical practice. Severe cases of both types are rare. Children from 2 to 11 years of age presenting with infections, cardiovascular disorders, and gastrointestinal disorders are at risk of developing hyponatremia. Full article

(This article belongs to the Section Nephrology & Urology)

► Show Figures

Figure 1

12 pages, 562 KiB

Open AccessReview

Therapeutic Exercise Interventions through Telerehabilitation in Patients with Post COVID-19 Symptoms: A Systematic Review

by Carlos Bernal-Utrera, Gines Montero-Almagro, Ernesto Anarte-Lazo, Juan Jose Gonzalez-Gerez, Cleofas Rodriguez-Blanco and Manuel Saavedra-Hernandez

J. Clin. Med. 2022, 11(24), 7521; https://doi.org/10.3390/jcm11247521 - 19 Dec 2022

Cited by 17 | Viewed by 2276

Abstract

The worldwide incidence of COVID-19 has generated a pandemic of sequelae. These sequelae require multidisciplinary rehabilitative work to address the multisystemic symptoms that patients will present with now and in the future. The aim of the present systematic review is to analyze the [...] Read more.

The worldwide incidence of COVID-19 has generated a pandemic of sequelae. These sequelae require multidisciplinary rehabilitative work to address the multisystemic symptoms that patients will present with now and in the future. The aim of the present systematic review is to analyze the current situation of telerehabilitation in patients with COVID-19 sequelae and its effectiveness. Searches were conducted on the following databases: PubMed, Scopus, PEDro, and Web of Science (WOS). There was no complete homogeneity among the five selected articles, so we differentiated two clinical subgroups for the clustering of outcome measures: (group one) patients with post-discharge symptoms and (group two) patients with permanent symptoms or “long COVID-19” defined as persistent symptoms > 2 months. For group one, post-discharge sequelae, improvements were obtained in cardiovascular parameters, and physical test studies in group two presented very favorable results in all the cardiorespiratory measures and physical tests evaluated. Telerehabilitation through therapeutic exercise based on mixed protocols of aerobic, respiratory, and low-load strength exercises appear to be an effective and safe strategy for the recovery of short- and long-term post-COVID-19 sequelae. Full article

(This article belongs to the Special Issue Long COVID: Current Approaches and Clinical Challenges in Treatment and Rehabilitation)

► Show Figures

Figure 1

14 pages, 886 KiB

Open AccessArticle

The Safety of Chemotherapy for Ovarian Malignancy during Pregnancy

by Naidong Xing, Lihui Wang, Xinlei Sui, Chunru Zhao, Yan Huang and Jin Peng

J. Clin. Med. 2022, 11(24), 7520; https://doi.org/10.3390/jcm11247520 - 19 Dec 2022

Cited by 1 | Viewed by 1697

Abstract

Background: Data on epidemiologic features, treatments and outcomes in women diagnosed with ovarian malignancy during pregnancy are very sparse due to its low incidence. The goal of our study was to summarize the epidemiologic characteristics of pregnant women complicated with ovarian malignancy and [...] Read more.

Background: Data on epidemiologic features, treatments and outcomes in women diagnosed with ovarian malignancy during pregnancy are very sparse due to its low incidence. The goal of our study was to summarize the epidemiologic characteristics of pregnant women complicated with ovarian malignancy and investigate the safety and efficacy of chemotherapy during pregnancy. Methods: We retrospectively analyzed the clinicopathological data of eight patients suffering from ovarian malignancy during pregnancy in our institution from June 2011 to July 2021. Furthermore, a systematic literature search was conducted in PubMed up to 1 September 2021, which identified 92 cases with ovarian malignancy during pregnancy eligible for the analysis. Therefore, we collected the data of 100 pregnant patients complicated with ovarian malignancy, including clinical demographics, tumor characteristics, treatment interventions and outcomes. Results: In total, 100 pregnant patients complicated with ovarian malignancy were investigated and classified into three groups: 34 cases in the epithelial ovarian cancer (EOC) group, 38 cases in the germ cell tumors (GCTs) group and 28 cases in the sex cord-stromal tumors (SCSTs) group. The onset age of pregnant patients with epithelial ovarian cancer was significantly higher than that of other patients. Pelvic mass and abdominal pain were the common clinical presentations of pregnant patients with ovarian malignancy. For distinguishing epithelial ovarian cancer during pregnancy, the area under the curve (AUC) of CA-125 was 0.718 with an optimal cutoff value of 58.2 U/mL. Moreover, 53 patients underwent surgery during pregnancy, the majority of whom underwent unilateral adnexectomy in the second trimester. Furthermore, 43 patients received chemotherapy during pregnancy, and 28 delivered completely healthy newborns at birth; 13 neonates showed transient abnormalities without further complications; and 2 died during the neonatal period. Conclusions: Our study reveals the safety of chemotherapy for ovarian malignancy during pregnancy. However, large-sample prospective studies are still needed to further explore the safety of chemotherapy in pregnant patients with malignancy to choose the appropriate chemotherapy regimen and achieve the maximum benefit for patients. Full article

(This article belongs to the Section Obstetrics & Gynecology)

► Show Figures

Figure 1

22 pages, 4029 KiB

Open AccessArticle

New Insights Regarding Hemin Inhibition of the Purified Rat Brain 2-Oxoglutarate Carrier and Relationships with Mitochondrial Dysfunction

by Daniela Valeria Miniero, Nicola Gambacorta, Anna Spagnoletta, Vincenzo Tragni, Stefano Loizzo, Orazio Nicolotti, Ciro Leonardo Pierri and Annalisa De Palma

J. Clin. Med. 2022, 11(24), 7519; https://doi.org/10.3390/jcm11247519 - 19 Dec 2022

Viewed by 1806

Abstract

A kinetic analysis of the transport assays on the purified rat brain 2-oxoglutarate/malate carrier (OGC) was performed starting from our recent results reporting about a competitive inhibitory behavior of hemin, a physiological porphyrin derivative, on the OGC reconstituted in an active form into [...] Read more.

A kinetic analysis of the transport assays on the purified rat brain 2-oxoglutarate/malate carrier (OGC) was performed starting from our recent results reporting about a competitive inhibitory behavior of hemin, a physiological porphyrin derivative, on the OGC reconstituted in an active form into proteoliposomes. The newly provided transport data and the elaboration of the kinetic equations show evidence that hemin exerts a mechanism of partially competitive inhibition, coupled with the formation of a ternary complex hemin-carrier substrate, when hemin targets the OGC from the matrix face. A possible interpretation of the provided kinetic analysis, which is supported by computational studies, could indicate the existence of a binding region responsible for the inhibition of the OGC and supposedly involved in the regulation of OGC activity. The proposed regulatory binding site is located on OGC mitochondrial matrix loops, where hemin could establish specific interactions with residues involved in the substrate recognition and/or conformational changes responsible for the translocation of mitochondrial carrier substrates. The regulatory binding site would be placed about 6 Å below the substrate binding site of the OGC, facing the mitochondrial matrix, and would allow the simultaneous binding of hemin and 2-oxoglutarate or malate to different regions of the carrier. Overall, the presented experimental and computational analyses help to shed light on the possible existence of the hemin-carrier substrate ternary complex, confirming the ability of the OGC to bind porphyrin derivatives, and in particular hemin, with possible consequences for the mitochondrial redox state mediated by the malate/aspartate shuttle led by the mitochondrial carriers OGC and AGC. Full article

(This article belongs to the Section Endocrinology & Metabolism)

► Show Figures

Figure 1

12 pages, 1888 KiB

Open AccessArticle

Hypokalemia Duration in the First Year Associated with Subsequent Peritoneal Dialysis-Associated Peritonitis: A Multicenter Retrospective Cohort Study

by Zhihao Huo, Qianqian Zhuo, Shaoxin Zhong, Fang Wang, Chao Xie, Nirong Gong, Xiaohong Zhong, Zhixiu Yi, Yaozhong Kong, Dehui Liu, Xianrui Dou, Guobao Wang and Jun Ai

J. Clin. Med. 2022, 11(24), 7518; https://doi.org/10.3390/jcm11247518 - 19 Dec 2022

Cited by 2 | Viewed by 1484

Abstract

Background: The association of hypokalemia (LK) with peritoneal dialysis-associated peritonitis (PDAP) risk remains uncertain. Here, we calculated LK duration in the first PD year and evaluated its association with PDAP. Methods: A multicenter, retrospective, incident cohort study of 1633 participants was conducted from [...] Read more.

Background: The association of hypokalemia (LK) with peritoneal dialysis-associated peritonitis (PDAP) risk remains uncertain. Here, we calculated LK duration in the first PD year and evaluated its association with PDAP. Methods: A multicenter, retrospective, incident cohort study of 1633 participants was conducted from January 2008 to October 2020 in China. The duration of LK and severe hypokalemia (SLK) was calculated as the total number of months that a patient’s serum potassium (SK) level was less than 3.5 or 3.0 mEq/L during the first PD year. The study outcome was the risk of subsequent PDAP started in the second year and later. Cox proportional hazards models and competing risk models were used to assess the association. Results: The subsequent PDAP occurred in 420 (25.7%) participants during a median of 28 months of follow-up. Overall, LK duration in the first year was positively associated with a subsequent PDAP risk (per 3-month increments, adjusted HR, 1.13; 95%CI: 1.05–1.23). After categorization, patients with LK duration longer than 6 months had the highest adjusted HR of 1.53 (p = 0.005 vs. those without LK) for subsequent PDAP risk. A similar trend was also found for SLK duration. In a competing risk model, a similar trend was also observed. None of the variables, including demographic and PD characteristics, diabetes history, and several clinical measurements, significantly modified this association. The causative organisms of PDAP were similar to those previously reported. Conclusions: PD patients with longer LK duration in the first year had a higher subsequent PDAP risk. Full article

(This article belongs to the Special Issue Management of Treatment and Prognosis in Acute Kidney Injury Patients)

► Show Figures

Figure 1

Figure 1
Flowchart of the participants in the current analysis. Notes: Baseline measurement of serum potassium was collected before PD initiation. Hypokalemia duration was calculated in the first PD year. The endpoint of the study was subsequent PDAP, which was followed up starting from the second year. Abbreviations: PD, peritoneal dialysis; CAPD, continuous ambulatory peritoneal dialysis; HD, hemodialysis; PDAP, peritoneal dialysis-associated peritonitis. Full article ">Figure 2
Kaplan–Meier curves for the cumulative hazard of subsequent PDAP. Notes: The follow-up time for subsequent PDAP started in the second year. Group differences were compared by log-rank tests. Abbreviations: PDAP, peritoneal dialysis-associated peritonitis; LK, hypokalemia. Full article ">Figure 3
Association of LK duration in the first PD Year with subsequent PDAP risk in various subgroups. Notes: a If not stratified, adjusted for age, gender, BMI, education level, smoking, diabetes, CVD history, RASi medications, RRF loss (with or without, in the first year), baseline potassium, and the mean values of dialysate GLUC, total weekly Kt/V score, serum albumin, serum creatinine and serum phosphorus in the first PD year. b,c The mean values of total Kt/V score and ALB in the first PD year were used. Abbreviations: LK, hypokalemia; PD, peritoneal dialysis; PDAP, peritoneal dialysis-associated peritonitis; HR, hazards ratio; CI, confidence interval; BMI, body mass index; CVD cardiovascular disease; RRF, residual renal function; ALB, albumin; RASi, renin–angiotensin system inhibitor; GLUC, dialysate glucose concentration. Full article ">Figure 4
Distribution of causative organisms in PD patients with and without LK. Notes: Comparisons of causative organisms in patients with LK (left) and without LK (right) in the first PD year. LK here was defined as at least one episode in the first PD year. CNS includes S epidermidis, S hominis, S capitis, S warneri, and S hemolyticus. Abbreviations: PD, peritoneal dialysis; LK, hypokalemia; CNS, coagulase-negative Staphylococcus; spp., species. Full article ">

13 pages, 871 KiB

Open AccessArticle

Impact of Time-To-Surgery on the Prognosis of Patients with T1 Renal Cell Carcinoma: Implications for the COVID-19 Pandemic

by Wei Ou, Changxuan Wang, Hiocheng Un, Shengjie Guo, Han Xiao, Bin Huang, Bin Li, Jiahao Lei, Jinhuan Wei, Sui Peng, Junhang Luo, Zongren Wang and Lingwu Chen

J. Clin. Med. 2022, 11(24), 7517; https://doi.org/10.3390/jcm11247517 - 19 Dec 2022

Cited by 1 | Viewed by 1762

Abstract

Background: During the COVID-19 pandemic, elective surgery has to undergo longer wait times, including nephrectomy for T1 renal cell carcinoma (RCC). This study aimed to investigate the time-to-surgery (TTS) of Chinese T1 RCC patients and its influencing factors, and to illustrate the impact [...] Read more.

Background: During the COVID-19 pandemic, elective surgery has to undergo longer wait times, including nephrectomy for T1 renal cell carcinoma (RCC). This study aimed to investigate the time-to-surgery (TTS) of Chinese T1 RCC patients and its influencing factors, and to illustrate the impact of TTS on the prognosis of T1 RCC. Methods: We retrospectively enrolled 762 Chinese patients with pathological T1 RCC that underwent nephrectomy. To discover the impact of TTS on survival outcomes, we explored the possible delay intervals by week using the Kaplan-Meier method and Log-rank test. Cox proportional hazard models with inverse probability-treatment weighting (IPTW) were used to assess the association between TTS and disease-free survival (DFS) and overall survival (OS). Results: The median TTS of T1 RCC patients was 15 days. The Charlson comorbidity index, the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score, and the maximal tumor diameter on presentation were independent influencing factors for TTS. The cut-off point of TTS was selected as 5 weeks according to the Log-rank analysis. For T1a RCC, patients with TTS > 5 weeks had similar DFS (HR = 2.39; 95% CI, 0.82–6.94; p = 0.109) and OS (HR = 1.28; 95% CI, 0.23–7.16; p = 0.779) compared to patients with TTS ≤ 5 weeks. For T1b RCC, patients with TTS > 5 weeks had shorter DFS (HR = 2.90; 95% CI = 1.46–5.75; p = 0.002) and OS (HR = 2.49, 95% CI = 1.09–5.70; p = 0.030) than patients with TTS ≤ 5 weeks. Conclusions: Prolonged TTS had no impact on the prognosis of T1a RCC while surgery delayed for over 5 weeks may lead to worse survival in T1b RCC. Full article

(This article belongs to the Section Nephrology & Urology)

► Show Figures

Figure 1

16 pages, 895 KiB

Open AccessReview

Prevention and Treatment of Grade C Postoperative Pancreatic Fistula

by Chengzhi Xiang, Yonghua Chen, Xubao Liu, Zhenjiang Zheng, Haoqi Zhang and Chunlu Tan

J. Clin. Med. 2022, 11(24), 7516; https://doi.org/10.3390/jcm11247516 - 19 Dec 2022

Cited by 5 | Viewed by 5244

Abstract

Postoperative pancreatic fistula (POPF) is a troublesome complication after pancreatic surgeries, and grade C POPF is the most serious situation among pancreatic fistulas. At present, the incidence of grade C POPF varies from less than 1% to greater than 9%, with an extremely [...] Read more.

Postoperative pancreatic fistula (POPF) is a troublesome complication after pancreatic surgeries, and grade C POPF is the most serious situation among pancreatic fistulas. At present, the incidence of grade C POPF varies from less than 1% to greater than 9%, with an extremely high postoperative mortality rate of 25.7%. The patients with grade C POPF finally undergo surgery with a poor prognosis after various failed conservative treatments. Although various surgical and perioperative attempts have been made to reduce the incidence of grade C POPF, the rates of this costly complication have not been significantly diminished. Hearteningly, several related studies have found that intra-abdominal infection from intestinal flora could promote the development of grade C POPF, which would help physicians to better prevent this complication. In this review, we briefly introduced the definition and relevant risk factors for grade C POPF. Moreover, this review discusses the two main pathways, direct intestinal juice spillover and bacterial translocation, by which intestinal microbes enter the abdominal cavity. Based on the abovementioned theory, we summarize the operation techniques and perioperative management of grade C POPF and discuss novel methods and surgical treatments to reverse this dilemma. Full article

(This article belongs to the Special Issue Updates on Prevention and Management of Pancreatic Surgery Complications)

► Show Figures

Figure 1

13 pages, 1964 KiB

Open AccessReview

Unraveling Pathophysiology of Takotsubo Syndrome: The Emerging Role of the Oxidative Stress’s Systemic Status

by Nicola Viceconte, Greta Petrella, Francesco Pelliccia, Gaetano Tanzilli and Daniel Oscar Cicero

J. Clin. Med. 2022, 11(24), 7515; https://doi.org/10.3390/jcm11247515 - 19 Dec 2022

Cited by 4 | Viewed by 1783

Abstract

Takotsubo Syndrome (TTS) is usually triggered by emotional or physical stressors, thus suggesting that an increased sympathetic activity, leading to myocardial perfusion abnormalities and ventricular dysfunction, plays a major pathogenetic role. However, it remains to be elucidated why severe emotional and physical stress [...] Read more.

Takotsubo Syndrome (TTS) is usually triggered by emotional or physical stressors, thus suggesting that an increased sympathetic activity, leading to myocardial perfusion abnormalities and ventricular dysfunction, plays a major pathogenetic role. However, it remains to be elucidated why severe emotional and physical stress might trigger TTS in certain individuals but not others. Clinical research has been focused mainly on mechanisms underlying the activation of the sympathetic nervous system and the occurrence of myocardial ischemia in TTS. However, scientific evidence shows that additional factors might play a pathophysiologic role in the condition’s occurrence. In this regard, a significant contribution arrived from metabolomics studies that followed the systemic response to TTS. Specifically, preliminary data clearly show that there is an interplay between inflammation, genetics, and oxidative status which might explain susceptibility to the condition. This review aims to sum up the established pathogenetic factors underlying TTS and to appraise emerging mechanisms, with particular emphasis on oxidative status, which might better explain susceptibility to the condition. Full article

(This article belongs to the Section Cardiology)

► Show Figures

Figure 1

Figure 1
Key pathogenetic aspects in Takotsubo syndrome. The interplay between triggers, pathogenetic factors, mechanisms of cardiac injury, and clinical consequences. ANS indicates autonomic nervous system; CNS, central nervous system; LV, left ventricular; and MVo2, myocardial oxygen consumption. (Reprinted with permission from Aimo A et al. Int J Cardiol. 2021, 333, 45–50). Full article ">Figure 2
The pyramid of life and the omics sciences. Full article ">Figure 3
The four layers that make up metabolomics research: from studying metabolites to trying to understand pathological states. Full article ">Figure 4
Differences in metabolite levels and ratios between CTRL and TTS. Boxes denote IQR, lines denote the median, whiskers denote the 5th and 95th percentile, and x denotes the average. * p < 0.05, ** p < 0.01. Abbreviation used: AcAc: acetoacetate; 3HB: 3-hydroxybutyrate; ALCAR: acetyl-L-carnitine; 2HB: 2-hydroxybutyrate; CAR: L-carnitine; Ala: alanine; Arg: arginine; His: histidine; Met: methionine; Glu: glutamate; Phe: phenylalanine; Tyr: tyrosine. (Reprinted with permission from Vanni D et al. Antioxidants (Basel). 2021, 10, 1982). Full article ">Figure 5
Linear correlation between acetoacetate/3-hydroxybutyrate ratio (AcAc/3HB) (A) and total amino acid concentration (B) with LVEF%. Green dots: controls; blue dots: TTS. (Reprinted with permission from Vanni D et al. Antioxidants (Basel). 2021, 10, 1982). Full article ">Figure 6
Summary of alteration observed in TTS patients related to oxidative stress. Abbreviation used: AcAc: acetoacetate; 3HB: 3-hydroxybutyrate; ALCAR: acetyl-L-carnitine; 2HB: hydroxybutyrate; ALCAR: acetyl-L-carnitine; CAR: L-carnitine; Ala: alanine; Arg: arginine; His: histidine; Met: methionine; Glu: glutamate; Phe: phenylalanine; Tyr: tyrosine. 2KB: _£HB: 3-ketobutyrate; 2-KG: 2-ketoglutarate; ALT: alanine aminotransferase; Pyr: Pyruvate. (Reprinted with permission from Vanni D et al. Antioxidants (Basel). 2021, 10, 1982). Full article ">

15 pages, 2135 KiB

Open AccessArticle

Prognostic Value of Systemic Immune-Inflammation Index (SII) in Patients with Glioblastoma: A Comprehensive Study Based on Meta-Analysis and Retrospective Single-Center Analysis

by Chao Yang, Bo-Wen Hu, Feng Tang, Qing Zhang, Wei Quan, Jie Wang, Ze-Fen Wang, Yi-Rong Li and Zhi-Qiang Li

J. Clin. Med. 2022, 11(24), 7514; https://doi.org/10.3390/jcm11247514 - 19 Dec 2022

Cited by 10 | Viewed by 2013

Abstract

Inflammation is related to cancer. The systemic immune-inflammation index (SII) has been linked to the prognosis of many types of cancer. The present study aimed to determine the prognostic value of the SII in glioblastoma (GBM) patients based on meta-analysis and single-center retrospective [...] Read more.

Inflammation is related to cancer. The systemic immune-inflammation index (SII) has been linked to the prognosis of many types of cancer. The present study aimed to determine the prognostic value of the SII in glioblastoma (GBM) patients based on meta-analysis and single-center retrospective analysis. Relevant publications published before 1 October 2022 were identified by searching PubMed, EMBASE, Cochrane Library databases, and Web of Science. Moreover, 208 GBM patients from Zhongnan Hospital were incorporated. Kaplan–Meier and Cox regression analyses determined the prognostic significance of inflammatory markers. By combining these indicators, we developed scoring systems. Nomograms were also built by incorporating independent variables. The accuracies of nomograms were evaluated by Harrell’s concordance index (c-index) and the calibration curve. According to meta-analysis, an elevated SII predicted the worst overall survival (OS) (Hazard ratio [HR] = 1.87, p < 0.001). Furthermore, a higher SII (>510.8) (HR = 1.782, p = 0.007) also predicted a poorer outcome in a retrospective cohort. The scoring systems of SII-NLR (neutrophil-to-lymphocyte ratio) showed the best predictive power for OS. The nomogram without MGMT (c-index = 0.843) exhibited a similar accuracy to that with MGMT (c-index = 0.848). A pre-treatment SII is independently associated with OS in GBM. A nomogram integrating the SII-NLR score may facilitate a comprehensive survival evaluation independent of molecular tests in GBM. Full article

(This article belongs to the Topic Inflammation in Neuro-Oncological Diseases and in Neuro-Vascular Diseases)

► Show Figures

Figure 1

Figure 1
Pooled hazard ratio (HR) and 95% confidence intervals (CIs) of SII for OS in glioblastoma patients (A) and detection of publication bias for meta-analysis of survival outcomes based on typical funnel plot (B) and Begg’s funnel plot (C). The references of Lv et al. (2019), Topkan et al. (2020), Yilmaz et al. (2021), Shi et al. (2022) and Pasqualetti et al. (2022) were [<a href="#B20-jcm-11-07514" class="html-bibr">20</a>,<a href="#B21-jcm-11-07514" class="html-bibr">21</a>,<a href="#B22-jcm-11-07514" class="html-bibr">22</a>,<a href="#B23-jcm-11-07514" class="html-bibr">23</a>,<a href="#B26-jcm-11-07514" class="html-bibr">26</a>]. Full article ">Figure 2
Kaplan–Meier survival curves of glioblastoma patients based on the cutoff values of SII (A), NLR (B), PLR (C), and LMR (D). Full article ">Figure 3
Kaplan–Meier survival curves of glioblastoma patients based on SII-NLR score (A), SII-PLR score (B), NLR-PLR score (C) and SII-NLR-PLR score (D). Full article ">Figure 4
Time-dependent ROC curve analysis of SII-NLR score (A), SII-PLR score (B), and NLR-PLR score (C) for predicting OS at one-year and two-year survival rate in patients with GBM. Full article ">Figure 5
Nomogram and calibration curve. In the nomogram (A) and (C) ((A) the nomogram including MGMT; (C) the nomogram without MGMT), each variable was assigned a different score as shown on the largest scale, and the total score for all variables yielded a numerical prediction of two-year survival, with higher scores leading to a worse prognosis. In the calibration curve (B) and (D) ((B) calibration of nomogram A; (D) calibration of nomogram C), the grey line represents the ideal prediction, and the blue line represents the performance of the nomogram. Full article ">

6 pages, 2046 KiB

Open AccessBrief Report

Biventricular Arrhythmogenic Cardiomyopathy Associated with a Novel Heterozygous Plakophilin-2 Early Truncating Variant

by Tolga Çimen, Verena C. Wilzeck, Giulia Montrasio, Nicole R. Bonetti, Argelia Medeiros-Domingo, Christian Grebmer, Christian M. Matter, Felix C. Tanner, Robert Manka, Corinna B. Brunckhorst, Firat Duru and Ardan M. Saguner

J. Clin. Med. 2022, 11(24), 7513; https://doi.org/10.3390/jcm11247513 - 19 Dec 2022

Viewed by 1410

Abstract

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a hereditary condition that can cause sudden cardiac death in young, frequently athletic individuals under the age of 35 due to malignant arrhythmias. Competitive and endurance exercise may hasten the onset and progression of ARVC, leading to [...] Read more.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a hereditary condition that can cause sudden cardiac death in young, frequently athletic individuals under the age of 35 due to malignant arrhythmias. Competitive and endurance exercise may hasten the onset and progression of ARVC, leading to right ventricular dysfunction and potentially fatal ventricular arrhythmias earlier in life. In this article, we present a novel, pathogenic, early truncating heterozygous variant in the PKP2 gene that causes biventricular arrhythmogenic cardiomyopathy and affects a family, of which the only member with the positive phenotype is a competitive endurance athlete. Full article

(This article belongs to the Special Issue Advances in Cardiac Electrophysiology and Pacing)

► Show Figures

Figure 1

Journal Menu

Journal Browser

J. Clin. Med., Volume 11, Issue 24 (December-2 2022) – 291 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI