Journal of Clinical Medicine

11 pages, 1528 KiB

Open AccessArticle

Sex Differences in Age-Related Physical Changes among Community-Dwelling Adults

by Takuhiro Okabe, Makoto Suzuki, Hiroshi Goto, Naoki Iso, Kilchoon Cho, Keisuke Hirata and Junichi Shimizu

J. Clin. Med. 2021, 10(20), 4800; https://doi.org/10.3390/jcm10204800 - 19 Oct 2021

Cited by 15 | Viewed by 3883

Abstract

The prevalence of physical functioning limitations is positively correlated with age in both men and women. However, whether the appearance of deterioration differs depending on physical function and sex remains unclear. This study aimed to clarify the modes of age-related changes in physical [...] Read more.

The prevalence of physical functioning limitations is positively correlated with age in both men and women. However, whether the appearance of deterioration differs depending on physical function and sex remains unclear. This study aimed to clarify the modes of age-related changes in physical function and sex differences in middle-aged and older adults. This study comprised 124 (46 men and 78 women) healthy adults aged 30 years or older and examined gender differences in physical function. The results of this study showed that one-leg standing time had the highest rate of age-related decline in both men and women, followed by knee extension strength, skeletal muscle mass, the 5 m walking test, and the timed up and go test. The sex-specific points showed a high rate of decline in trunk forward bending in men and a high rate of decline in forced expiratory volume (1 s) and gradual rate of decline in the bone area ratio in women. After middle age, it is desirable to start monitoring and training balance, muscle function, and walking. Men require early intervention for flexibility, and women require early intervention for respiratory function and continued intervention for bone mineral density. Full article

(This article belongs to the Section Epidemiology & Public Health)

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14 pages, 654 KiB

Open AccessArticle

Polish Nurses’ Attitude to e-Health Solutions and Self-Assessment of Their IT Competence

by Anna Bartosiewicz, Joanna Burzyńska and Paweł Januszewicz

J. Clin. Med. 2021, 10(20), 4799; https://doi.org/10.3390/jcm10204799 - 19 Oct 2021

Cited by 11 | Viewed by 3017

Abstract

In many countries, the implementation and dissemination of e-services for healthcare systems are important aspects of projects and strategies, as they contribute to significantly improving the access to such a system. The aim of the study is to analyze nurses’ opinions on the [...] Read more.

In many countries, the implementation and dissemination of e-services for healthcare systems are important aspects of projects and strategies, as they contribute to significantly improving the access to such a system. The aim of the study is to analyze nurses’ opinions on the application of the e-health solutions at work and the self-assessment of their IT competence. A linear stepwise regression allowed for the visualization of independent variables significantly influencing considerably the level of IT competency. Reduced IT competency was found in the group of nurses who rated the impact of the Internet and the new technologies as lower on the health care and general lives of modern people (β = 0.203; p < 0.0001), recommended e-health solutions to a lesser extent (β = 0.175; p < 0.0001), rated e-health solutions lower in relation to the patient (β = 0.149; p < 0.0001), and were older in age (β = 0.095; p = 0.0032). IT competence has become an indispensable requirement for nurses in fulfilling their professional roles. The quality of using new technologies in the work of nurses depends on their IT competence. Full article

(This article belongs to the Special Issue Ehealth, Telemedicine and AI in Clinical Medicine)

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17 pages, 1578 KiB

Open AccessArticle

Effect of Age on Innate and Adaptive Immunity in Hospitalized COVID-19 Patients

by Lamin B. Cham, Marie Høst Pahus, Kristoffer Grønhøj, Rikke Olesen, Hien Ngo, Ida Monrad, Mads Kjolby, Martin Tolstrup, Jesper Damsgaard Gunst and Ole S. Søgaard

J. Clin. Med. 2021, 10(20), 4798; https://doi.org/10.3390/jcm10204798 - 19 Oct 2021

Cited by 5 | Viewed by 3592

Abstract

An effective but balanced cellular and inflammatory immune response may limit the severity of coronavirus disease (COVID-19), whereas uncontrolled inflammation leads to disease progression. Older age is associated with higher risk of COVID-19 and a worse outcome, but the underlying immunological mechanisms for [...] Read more.

An effective but balanced cellular and inflammatory immune response may limit the severity of coronavirus disease (COVID-19), whereas uncontrolled inflammation leads to disease progression. Older age is associated with higher risk of COVID-19 and a worse outcome, but the underlying immunological mechanisms for this age-related difference are not clear. We investigated the impact of age on viral replication, inflammation, and innate and adaptive cellular immune responses in 205 hospitalized COVID-19 patients. During the early symptomatic phase of COVID-19, we found that patients above 65 years had significantly higher viral load, higher levels of proinflammatory markers, and inadequate mobilization and activation of monocytes, dendritic cells, natural killer cells, and CD8 T cells compared to those below 65 years. Our study points toward age-related deficiencies in the innate immune cellular response to SARS-CoV-2 as a potential cause of poorly controlled viral replication and inflammation during the early symptom phase and subsequent disease progression. Full article

(This article belongs to the Section Epidemiology & Public Health)

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Age is associated with increased SARS-CoV-2 viral load, inflammatory response, and delayed clinical recovery. Oropharyngeal swabs and serum sample of SARS-CoV-2 patients were analyzed for viral titer, biochemistry, IgG, and cytokine level. (a) Quantification of patients SARS-CoV-2 viral load by droplet PCR (ddPCR) from oropharyngeal swabs (n = 193). (b) Serum CRP and (c) serum ferritin level were determined using clinical-based biochemistry assay (n = 193). (d) Levels of SARS-CoV-2-specific IgG in serum (n = 193). (e) Cytokine profiling of serum IL-6 level (n = 89). Kaplan-Meier estimate of (f) time to clinical recovery and (g) time to intensive care unit or death. The data are shown as mean ± SEM. The statistical comparison of below 65 years (<65 years) vs. above 65 years (≥65 years) was performed using Student’s t-test (* p < 0.05, ** p < 0.01, **** p < 0.0001). Full article ">Figure 2
Elderly patients exhibited reduced monocyte activation and function. Flow cytometry analysis was performed on thawed PBMC from SARS-CoV-2 patients after an indicated timepoint of duration of symptom onset. Classical monocytes frequency and activation was analyzed. (a) Percentage of classical monocytes (% CD14+CD33+CD16− monocytes), mean fluorescence intensity (MFI) of (b) CD169, (c) CD47, (d) CD86, and (e) HLA-DR (n = 101). The data are shown as mean ± SEM. The statistical comparison of below 65 years (<65 years) vs. above 65 years (≥65 years) was performed using Student’s t-test (ns: not significant, * p <0.05, ** p < 0.01, *** p < 0.001). Full article ">Figure 3
Dendritic cell impairment in patients above 65 years. Analysis of dendritic cell proportion and cell surface activation in PBMC from SARS-CoV-2 patients after indicated duration of symptom onset. (a) Percentage of pDC (% CD303+CD123+CD11c− DCs). (b) Percentage of CD169 expressing pDCs. Mean fluorescence intensity (MFI) of (c) CD169 and (d) CD86 (n = 117). The data are shown as mean ± SEM. The statistical comparison of below 65 years (<65 years) vs. above 65 years (≥65 years) was performed using Student’s t-test (ns: not significant * p < 0.05). Full article ">Figure 4
Increased natural killer cell activation and IL-2 levels in younger patients. Natural killer cell response and cytokine level analysis from PBMC and serum, respectively. (a) Percentage of CD56bright NK cells. (b) Percentage of CD56dim NK cells. Mean fluorescence intensity (MFI) of (c) CD11b of CD56bright NK cells, (d) CD122 of CD56dim NK cells, (e) serum IL-2 level, and (f) percentage of NKG2a+Siglec7+ NK cells (n = 83). The data are shown as mean ± SEM. The statistical comparison of below 65 years (<65 years) vs. above 65 years (≥65 years) was performed using Student’s t-test (ns: not significant, * p < 0.05). Full article ">Figure 5
Reduced T cell activation in older COVID-19 patients. Cell surface staining of T cells response and cytokine level from PBMC and serum, respectively. (a) Percentage of CD8 T cells and (b) percentage of CD4 T cells from total CD3 T cells. (c) Percentage of CD69 expression on effector and memory CD8 T cells, (d) serum IFN-γ level, and (e) percentage of PD-1 expressing effector and memory CD8 T cells (n = 117). The data are shown as mean ± SEM. The statistical comparison of below 65 years (<65 years) vs. above 65 years (≥65 years) was performed using Student’s t-test (ns: not significant, * p < 0.05, ** p < 0.01). Full article ">

10 pages, 1342 KiB

Open AccessArticle

Plasma Neurofilament Light (NfL) in Patients Affected by Niemann–Pick Type C Disease (NPCD)

by Andrea Dardis, Eleonora Pavan, Martina Fabris, Rosalia Maria Da Riol, Annalisa Sechi, Agata Fiumara, Lucia Santoro, Maximiliano Ormazabal, Romina Milanic, Stefania Zampieri, Jessica Biasizzo and Maurizio Scarpa

J. Clin. Med. 2021, 10(20), 4796; https://doi.org/10.3390/jcm10204796 - 19 Oct 2021

Cited by 9 | Viewed by 2317

Abstract

(1) Background: Niemann–Pick type C disease (NPCD) is an autosomal recessive lysosomal storage disorder caused by mutations in the NPC1 or NPC2 genes. The clinical presentation is characterized by visceral and neurological involvement. Apart from a small group of patients presenting a severe [...] Read more.

(1) Background: Niemann–Pick type C disease (NPCD) is an autosomal recessive lysosomal storage disorder caused by mutations in the NPC1 or NPC2 genes. The clinical presentation is characterized by visceral and neurological involvement. Apart from a small group of patients presenting a severe perinatal form, all patients develop progressive and fatal neurological disease with an extremely variable age of onset. Different biomarkers have been identified; however, they poorly correlate with neurological disease. In this study we assessed the possible role of plasma NfL as a neurological disease-associated biomarker in NPCD. (2) Methods: Plasma NfL levels were measured in 75 healthy controls and 26 patients affected by NPCD (24 NPC1 and 2 NPC2; 39 samples). (3) Results: Plasma NfL levels in healthy controls correlated with age and were significantly lower in pediatric patients as compared to adult subjects (p = 0.0017). In both pediatric and adult NPCD patients, the plasma levels of NfL were significantly higher than in age-matched controls (p < 0.0001). Most importantly, plasma NfL levels in NPCD patients with neurological involvement were significantly higher than the levels found in patients free of neurological signs at the time of sampling, both in the pediatric and the adult group (p = 0.0076; p = 0.0032, respectively). Furthermore, in adults the NfL levels in non-neurological patients were comparable with those found in age-matched controls. No correlations between plasma NfL levels and NPCD patient age at sampling or plasma levels of cholestan 3β-5α-6β-triol were found. (4) Conclusions: These data suggest a promising role of plasma NfL as a possible neurological disease-associated biomarker in NPCD. Full article

(This article belongs to the Special Issue Management of Acute and Chronic Complications of Lysosomal Storage Diseases in Children and Adults: Current Practice and Future Opportunities)

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7 pages, 2512 KiB

Open AccessArticle

Update on Pulmonary Ossifications in the Differential Diagnosis of Solitary Pulmonary Nodules

by Jan F. Gielis, Lawek Berzenji, Vasiliki Siozopoulou, Marloes Luijks and Paul E. Y. Van Schil

J. Clin. Med. 2021, 10(20), 4795; https://doi.org/10.3390/jcm10204795 - 19 Oct 2021

Cited by 4 | Viewed by 1962

Abstract

Pulmonary ossifications have often been regarded as rare, post-mortem findings without any clinical significance. We have investigated the occurrence of pulmonary ossifications in patients undergoing thoracic procedures, and how this may affect the differential diagnosis of solitary pulmonary nodules. In addition, we have [...] Read more.

Pulmonary ossifications have often been regarded as rare, post-mortem findings without any clinical significance. We have investigated the occurrence of pulmonary ossifications in patients undergoing thoracic procedures, and how this may affect the differential diagnosis of solitary pulmonary nodules. In addition, we have performed a literature search on the occurrence and possible pathogenesis of these ossifications. From January 2008 until August 2019, we identified pulmonary ossifications in 34 patients who underwent elective pulmonary surgery. Pre-operative imaging was unable to differentiate these ossifications from solid tumors. A definitive diagnosis was made by an experienced pathologist (VS, ML). The PubMed database was researched in December 2019 with the search terms “pulmonary ossifications”; “heterotopic ossifications”; and “solitary pulmonary nodule”. In total, 27 patients were male, with a mean age of 63 ± 12 years (age 41 to 82 on diagnosis). All lesions were identified on thoracic CT and marked for resection by a multidisciplinary team. A total of 17 patients were diagnosed with malignancy concurrent with ossifications. There was a clear predilection for the right lower lobe (12 cases, 35.3%) and most ossifications had a nodular form (70.6%). We could not identify a clear association with any other pathology, either cancerous or non-cancerous in origin. Oncologic or pulmonary comorbidities did not influence patient survival. Pulmonary ossifications are not as seldom as thought and are not just a curiosity finding by pathologists. These formations may be mistaken for a malignant space-occupying lesion, both pre-and perioperatively, as they are indistinguishable in imaging. We propose these ossifications as an underestimated addition to the differential diagnosis of a solitary pulmonary nodule. Full article

(This article belongs to the Special Issue Minimally Invasive Approaches for Cardiovascular and Thoracic Surgery: The Current Status)

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10 pages, 962 KiB

Open AccessArticle

Recurrence of Gestational Diabetes Mellitus: To Assess Glucose Metabolism and Clinical Risk Factors at the Beginning of a Subsequent Pregnancy

by Grammata Kotzaeridi, Julia Blätter, Daniel Eppel, Ingo Rosicky, Veronica Falcone, Gabriela Adamczyk, Tina Linder, Gülen Yerlikaya-Schatten, Karen Weisshaupt, Wolfgang Henrich, Andrea Tura and Christian S. Göbl

J. Clin. Med. 2021, 10(20), 4794; https://doi.org/10.3390/jcm10204794 - 19 Oct 2021

Cited by 3 | Viewed by 1985

Abstract

Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing hyperglycemia in a subsequent pregnancy. This study aimed to assess parameters of glucose metabolism at the beginning of a subsequent pregnancy in women with a history of GDM. [...] Read more.

Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing hyperglycemia in a subsequent pregnancy. This study aimed to assess parameters of glucose metabolism at the beginning of a subsequent pregnancy in women with a history of GDM. This prospective cohort study included 706 women who had at least one previous pregnancy (120 with prior GDM and 586 without GDM history). All study participants received a broad risk evaluation and laboratory testing at the beginning of a subsequent pregnancy and were followed up until delivery to assess GDM status, risk factors for GDM recurrence, and pregnancy outcomes. Women with a history of GDM exhibited lower insulin sensitivity and subtle impairments in β-cell function associated with subclinical hyperglycemia already at the beginning of a subsequent pregnancy compared to women without GDM history. This was associated with a markedly increased risk for the later development of GDM (OR: 6.59, 95% CI 4.34 to 10.09, p < 0.001). Early gestational fasting glucose and HbA1c were identified as the most important predictors. Mothers with a history of GDM showed marked alterations in glucose metabolism at the beginning of a subsequent pregnancy, which explains the high prevalence of GDM recurrence in these women. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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27 pages, 1346 KiB

Open AccessReview

The Pathophysiology and Management of Hemorrhagic Shock in the Polytrauma Patient

by Alison Fecher, Anthony Stimpson, Lisa Ferrigno and Timothy H. Pohlman

J. Clin. Med. 2021, 10(20), 4793; https://doi.org/10.3390/jcm10204793 - 19 Oct 2021

Cited by 16 | Viewed by 10772

Abstract

The recognition and management of life-threatening hemorrhage in the polytrauma patient poses several challenges to prehospital rescue personnel and hospital providers. First, identification of acute blood loss and the magnitude of lost volume after torso injury may not be readily apparent in the [...] Read more.

The recognition and management of life-threatening hemorrhage in the polytrauma patient poses several challenges to prehospital rescue personnel and hospital providers. First, identification of acute blood loss and the magnitude of lost volume after torso injury may not be readily apparent in the field. Because of the expression of highly effective physiological mechanisms that compensate for a sudden decrease in circulatory volume, a polytrauma patient with a significant blood loss may appear normal during examination by first responders. Consequently, for every polytrauma victim with a significant mechanism of injury we assume substantial blood loss has occurred and life-threatening hemorrhage is progressing until we can prove the contrary. Second, a decision to begin damage control resuscitation (DCR), a costly, highly complex, and potentially dangerous intervention must often be reached with little time and without sufficient clinical information about the intended recipient. Whether to begin DCR in the prehospital phase remains controversial. Furthermore, DCR executed imperfectly has the potential to worsen serious derangements including acidosis, coagulopathy, and profound homeostatic imbalances that DCR is designed to correct. Additionally, transfusion of large amounts of homologous blood during DCR potentially disrupts immune and inflammatory systems, which may induce severe systemic autoinflammatory disease in the aftermath of DCR. Third, controversy remains over the composition of components that are transfused during DCR. For practical reasons, unmatched liquid plasma or freeze-dried plasma is transfused now more commonly than ABO-matched fresh frozen plasma. Low-titer type O whole blood may prove safer than red cell components, although maintaining an inventory of whole blood for possible massive transfusion during DCR creates significant challenges for blood banks. Lastly, as the primary principle of management of life-threatening hemorrhage is surgical or angiographic control of bleeding, DCR must not eclipse these definitive interventions. Full article

(This article belongs to the Special Issue Clinical Management and Challenges in Polytrauma)

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(A) OHD curve which relates the saturation of Hgb (y-axis) to the degree of partial pressure of oxygen to which Hgb is exposed (x-axis). The pO2 that saturates ½ of Hgb is referred to as p50, which in this example p50 = 27 mmHg. The p50 is the conventional measure of affinity of Hgb for oxygen. The lower the p50 the higher the affinity of Hgb for oxygen. The ‘steep’ portion of the oxyHgb dissociation curve is in the range of pO2 that exists in systemic capillaries (thus a small decrease in systemic capillary pO2 can result in the release of large amounts of oxygen for diffusion to, and uptake by cells). As shown in the figure, several factors increase the affinity of Hgb for oxygen (leftward shift; ↓p50) or decrease affinity (rightward shift; ↑p50). Biochemically, H+ is a heterotropic allosteric inhibitor of Hgb, whereas O2 is a homeotropic allosteric activator of Hgb. (B) Hypothermia and acidosis have opposing effects on p50. Lower temperature shifts the curve to the left increasing Hgb affinity for oxygen and decreasing offloading in capillaries; low pH (increase in H+) decreases the affinity of Hgb for oxygen (Bohr effect) increasing oxygen availability to reverse anaerobic metabolism. A trauma patient may be, and often is hypothermic and acidotic (and coagulopathic). Whether there is a significant change in p50 can be calculated using the Hill–Langmuir equation. (C): Hypothetical oxygen transport variables of a normal subject (Temp = 37 °C; p50 = 25 mmHg) and a subject with hypothermia (Temp = 31 °C; p50 = 20 mmHg), before and after compensation. The p50 at 31 °C and pH = 7.4 is calculated using the Hill–Langmuir equation. A venous blood gas is obtained through a Swan Catheter introducer (7.5Fr) with the tip in the superior vena cava reveals in the hypothermic subject, central venous oxygen saturation (ScvO2) = 85%. This reflects the fact that hypothermia increases the affinity of Hgb for oxygen, shifting the Hgb dissociation curve to the left. A ScvO2 of 85% would imply only 15% of the delivered 1000 mL of oxygen (DO2) prior to compensation is being offloaded, which is approximately 150 mL/min, well below VO2 (250 mL/min). The hypothermic patient can compensate by increasing cardiac output and hence DO2. Assume that stroke volume is unchanged (although a well-known consequence of tachycardia is a reduction in stroke volume), and cardiac output increases by an increase in heart rate (HR) from 72 beats/min to 120 beats/min (a 40% increase in HR causing a substantial increase in myocardial oxygen demand). Full article ">Figure 2
DO2 CRIT defines shock. As DO2 (solid black line) decreases secondary to a fall in cardiac output, drop in Hgb concentration, or both, O2ER (solid grey line) increases to maintain VO2 constant until extraction is maximized. At this point, designated as DO2 CRIT (also referred to as the anaerobic threshold), VO2 begins to decrease with further decreases in DO2. When DO2 > DO2 CRIT t, VO2 is flow-independent; when DO2 < DO2 CRIT, VO2 becomes flow-dependent. In addition, DO2 CRIT is associated with the onset of lactate formation and accumulation. Thus, shock can be defined conceptually as the presence of DO2 less than DO2 CRIT, producing a reduction in VO2. Normal DO2 = 800 mL O2/min/m2; normal VO2 = 200 mL O2/min/m2; normal O2ER = 25%. Full article ">Figure 3
Pathways of plasminogen activation and inhibition. Plasminogen is synthesized by and released from the liver. To be activated to plasmin, plasminogen initially binds to lysine residues exposed on fibrin. The generation of plasmin from its precursor, plasminogen is achieved by the plasminogen activators, tissue-type type plasminogen activator (tPA), and urokinase (not depicted). Protien C, once activated by thrombin bound to thrombomodulin blocks PAI-1, the major inhibitor of tPA; therefore thrombin, through activated protein C, can promote fibrinolysis. However, thrombin-thrombimodulin interactions can also inhibit fibrinolysis through activation of TAFI (thrombin-activatable fibrinolysis inhibitor). Plasmin once formed can also cleave plasma prekallikrein (Fletcher factor) and Hageman factor (FXII) and in turn plasminogen can be activated to plasmin by these proteases. Furthermore, plasmin, can activate the complement factors, C5 and C3, while on the other hand, it can itself be inhibited by the C1-inhibitor, thereby providing a natural means to regulate this process. Excessive plasmin formation can result in hyperfibrinolysis, which increases the risk of bleeding. Tranexamic acid (TXA) blocks lysine-dependent interactions and therefore inhibits binding of plasminogen to and transfusion requirements. Plasminogen receptors located on the surface of immune cells also contain C-terminal lysine the surface of fibrin and misfolded proteins. Plasmin also activates other substrates with pro-inflammatory potential including TGF-β, a neurotrophic agent brain-derived neurotropic factor, and other proteases like the matrix metalloproteinases. Full article ">Figure 4
Thromboelastography (TEG®). (A) Schematic presentation of different viscoelastic tracings reflecting states of the coagulation system compared with normal. (B) Basic viscoelastic tracing with measured parameters and limits of normal for thromboelastography, correlated with different elements of the coagulation system (R = reaction time, K = clot formation time, angle, MA = maximum amplitude, Ly30 = percent clot lysis 30 m after MA). Viscoelastic k-time and angle correlate to some degree with fibrinogen concentration. However, the agreement between these parameters and fibrinogen levels determined by standard von Clauss assay is not sufficiently strong to be useful clinically. To overcome this limitation with TEG, the specific contributions of fibrinogen and platelets to clot strength can be determined with additional reagents (TEG; Functional Fibrinogen [Haemonetics Corp, Niles, IL, USA]). Using TEG, additional measures of clot strength can be computed. Coagulation index (CI; black arrow) is derived from R, k-time, angle, and MA, with a CI >+3.0 suggesting a hypercoagulable state and CI <−3.0 suggesting coagulopathy. The shear elastic module strength, designated G, is a computer-generated quantity that reflects an integrated measure of clot strength. Conceptually, G is considered the most informative parameter of clot strength because it reflects the contributions of the enzymatic and platelet components of hemostasis. Abbreviations: rTEG, rapid thromboelastography; DIC, disseminated intravascular coagulation; EPL, estimated percent lysis; FFP, fresh frozen plasma; Cryo, cryoprecipitate; Plts, platelets; TXA, tranexamic acid. Full article ">

25 pages, 999 KiB

Open AccessReview

Glycation and Glycosylation in Cardiovascular Remodeling: Focus on Advanced Glycation End Products and O-Linked Glycosylations as Glucose-Related Pathogenetic Factors and Disease Markers

by Elena Dozio, Luca Massaccesi and Massimiliano Marco Corsi Romanelli

J. Clin. Med. 2021, 10(20), 4792; https://doi.org/10.3390/jcm10204792 - 19 Oct 2021

Cited by 16 | Viewed by 3468

Abstract

Glycation and glycosylation are non-enzymatic and enzymatic reactions, respectively, of glucose, glucose metabolites, and other reducing sugars with different substrates, such as proteins, lipids, and nucleic acids. Increased availability of glucose is a recognized risk factor for the onset and progression of diabetes-mellitus-associated [...] Read more.

Glycation and glycosylation are non-enzymatic and enzymatic reactions, respectively, of glucose, glucose metabolites, and other reducing sugars with different substrates, such as proteins, lipids, and nucleic acids. Increased availability of glucose is a recognized risk factor for the onset and progression of diabetes-mellitus-associated disorders, among which cardiovascular diseases have a great impact on patient mortality. Both advanced glycation end products, the result of non-enzymatic glycation of substrates, and O-linked-N-Acetylglucosaminylation, a glycosylation reaction that is controlled by O-N-AcetylGlucosamine (GlcNAc) transferase (OGT) and O-GlcNAcase (OGA), have been shown to play a role in cardiovascular remodeling. In this review, we aim (1) to summarize the most recent data regarding the role of glycation and O-linked-N-Acetylglucosaminylation as glucose-related pathogenetic factors and disease markers in cardiovascular remodeling, and (2) to discuss potential common mechanisms linking these pathways to the dysregulation and/or loss of function of different biomolecules involved in this field. Full article

(This article belongs to the Special Issue Cardiovascular Remodeling in Metabolic Disorders)

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Metabolic disorders, advanced glycation end products (AGE), and cardiovascular remodeling. Obesity, diabetes mellitus, and metabolic syndrome may induce cardiovascular remodeling both directly, by inducing side effects due to the increased levels of AGE, reactive oxygen species (ROS), and inflammation, and indirectly, by promoting other disorders such as atherosclerosis, myocardial infarct, heart failure, atrial fibrillation, and kidney and liver diseases. The high levels of AGE, ROS, and inflammatory mediators that characterize these pathologies can, in turn, play additional roles in promoting cardiovascular remodeling. Full article ">Figure 2
The Hexosamine Biosynthetic Pathway (HBP) and dynamic interplay between O-GlcNAc and O-phosphate. Once in the cells, glucose is enzymatically metabolized by Hexokinase (HK) to Glucose-6-Phosphate (Glc-6-P), which is then converted by Glc-6-P isomerase (GPI) into Glc-6-P to Fructose-6-phosphate (Fruc-6-P). About 3–5% of Fruc-6-P is metabolized to Glucosamine-6-phosphate (GlcN-6-P) by Glutamine Fructose-6-phosphate AmidoTransferase (GFAT). Glucosamine-6-Phosphate N-Acetyltransferase 1 (GNPNAT1) utilizes acetyl-CoA to convert GlcN-6-P into N-Acetylglucosamine-6-Phosphate (GlcNAc-6-P), which is then converted by Phospho-Acetyl Glucosamine Mutase 1 (AGM1) into N-acetylglucosamine-1-phosphate (GlcNAc-1-P). By utilizing Uridine Triphosphate (UTP), UDP-N-Acetylglucosamine Pyrophosphorylase (UAP) converts GlcNAc-1-P to Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). O-GlcNac modification and phosphorylation are reciprocal events because the site of attachment is the same or is adjacent to Ser/Thr residues. Two highly conserved enzymes mediate the addition and removal of the UDP-GlcNAc: OGlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. Full article ">Figure 3
Pathological effects of O-GlcNAcylation on Sarco/endoplasmic reticulum Ca2+-Atpase (SERCA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII). High levels of protein O-GlcNAcylation strongly reduce SERCA activity leading to impaired myocardial relaxation and/or augmented risk of arrhythmia onset. Conversely, O-GlcNAcylation of CaMKII (at Ser 280) leads to CaMKII activation with consequent alteration in myocardial relaxation and onset of atrial fibrillation. Full article ">

14 pages, 888 KiB

Open AccessReview

Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target

by Sonsoles Piera-Velazquez and Sergio A. Jimenez

J. Clin. Med. 2021, 10(20), 4791; https://doi.org/10.3390/jcm10204791 - 19 Oct 2021

Cited by 31 | Viewed by 5366

Abstract

Numerous clinical and research investigations conducted during the last two decades have implicated excessive oxidative stress caused by high levels of reactive oxygen species (ROS) in the development of the severe and frequently progressive fibrotic process in Systemic Sclerosis (SSc). The role of [...] Read more.

Numerous clinical and research investigations conducted during the last two decades have implicated excessive oxidative stress caused by high levels of reactive oxygen species (ROS) in the development of the severe and frequently progressive fibrotic process in Systemic Sclerosis (SSc). The role of excessive oxidative stress in SSc pathogenesis has been supported by the demonstration of increased levels of numerous biomarkers, indicative of cellular and molecular oxidative damage in serum, plasma, and other biological fluids from SSc patients, and by the demonstration of elevated production of ROS by various cell types involved in the SSc fibrotic process. However, the precise mechanisms mediating oxidative stress development in SSc and its pathogenetic effects have not been fully elucidated. The participation of the NADPH oxidase NOX4, has been suggested and experimentally supported by the demonstration that SSc dermal fibroblasts display constitutively increased NOX4 expression and that reduction or abrogation of NOX4 effects decreased ROS production and the expression of genes encoding fibrotic proteins. Furthermore, NOX4-stimulated ROS production may be involved in the development of certain endothelial and vascular abnormalities and may even participate in the generation of SSc-specific autoantibodies. Collectively, these observations suggest NOX4 as a novel therapeutic target for SSc. Full article

(This article belongs to the Special Issue Systemic Sclerosis—Pathogenesis and Emerging Therapies)

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10 pages, 894 KiB

Open AccessArticle

Long-Term Influence of Paraspinal Muscle Quantity in Adolescent Idiopathic Scoliosis Following Deformity Correction by Posterior Approach

by Hong Jin Kim, Jae Hyuk Yang, Dong-Gune Chang, Se-Il Suk, Seung Woo Suh, Yunjin Nam, Sang-Il Kim and Kwang-Sup Song

J. Clin. Med. 2021, 10(20), 4790; https://doi.org/10.3390/jcm10204790 - 19 Oct 2021

Cited by 7 | Viewed by 2150

Abstract

Pedicle screw instrumentation (PSI) through posterior approach has been the mainstay of deformity correction for adolescent idiopathic scoliosis (AIS). However, changes in the quantity of paraspinal muscles after AIS surgery has remained largely unknown. The aim of this study was to investigate long-term [...] Read more.

Pedicle screw instrumentation (PSI) through posterior approach has been the mainstay of deformity correction for adolescent idiopathic scoliosis (AIS). However, changes in the quantity of paraspinal muscles after AIS surgery has remained largely unknown. The aim of this study was to investigate long-term follow-up changes in paraspinal muscle volume in AIS surgery via a posterior approach. Forty-two AIS patients who underwent deformity correction by posterior approach were analyzed through a longitudinal assessment of a cross-sectional area (CSA) in paraspinal muscles with a minimum five-year follow-up. The CSA were measured using axial computed tomography images at the level of the upper endplate L4 by manual tracing. The last follow-up CSA ratio of the psoas major muscle (124.5%) was significantly increased compared to the preoperative CSA ratio (122.0%) (p < 0.005). The last follow-up CSA ratio of the multifidus and erector spine muscles significantly decreased compared to the preoperative CSA ratio (all p < 0.005). The CSA ratio of the erector spine muscle was correlated with the CSA ratio of the psoas major (correlation coefficient = 0.546, p < 0.001). Therefore, minimizing the injury to the erector spine muscle is imperative to maintaining psoas major muscle development in AIS surgery by posterior approach. Full article

(This article belongs to the Special Issue Advances on Scoliogeny, Diagnosis and Management of Scoliosis and Spinal Disorders)

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12 pages, 824 KiB

Open AccessReview

The Development of Electronic Health and Artificial Intelligence in Surgery after the SARS-CoV-2 Pandemic—A Scoping Review

by Stephanie Taha-Mehlitz, Ahmad Hendie and Anas Taha

J. Clin. Med. 2021, 10(20), 4789; https://doi.org/10.3390/jcm10204789 - 19 Oct 2021

Cited by 3 | Viewed by 2319

Abstract

Background: SARS-CoV-2 has significantly transformed the healthcare environment, and it has triggered the development of electronic health and artificial intelligence mechanisms, for instance. In this overview, we concentrated on enhancing the two concepts in surgery after the pandemic, and we examined the factors [...] Read more.

Background: SARS-CoV-2 has significantly transformed the healthcare environment, and it has triggered the development of electronic health and artificial intelligence mechanisms, for instance. In this overview, we concentrated on enhancing the two concepts in surgery after the pandemic, and we examined the factors on a global scale. Objective: The primary goal of this scoping review is to elaborate on how surgeons have used eHealth and AI before; during; and after the current global pandemic. More specifically, this review focuses on the empowerment of the concepts of electronic health and artificial intelligence after the pandemic; which mainly depend on the efforts of countries to advance the notions of surgery. Design: The use of an online search engine was the most applied method. The publication years of all the studies included in the study ranged from 2013 to 2021. Out of the reviewed studies; forty-four qualified for inclusion in the review. Discussion: We evaluated the prevalence of the concepts in different continents such as the United States; Europe; Asia; the Middle East; and Africa. Our research reveals that the success of eHealth and artificial intelligence adoption primarily depends on the efforts of countries to advance the notions in surgery. Conclusions: The study’s primary limitation is insufficient information on eHealth and artificial intelligence concepts; particularly in developing nations. Future research should focus on establishing methods of handling eHealth and AI challenges around confidentiality and data security. Full article

(This article belongs to the Special Issue Ehealth, Telemedicine and AI in Clinical Medicine)

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14 pages, 1230 KiB

Open AccessArticle

Lack of Association between Serum Interleukin-23 and Interleukin-27 Levels and Disease Activity in Patients with Active Systemic Lupus Erythematosus

by Katarzyna Pawlak-Buś, Wiktor Schmidt and Piotr Leszczyński

J. Clin. Med. 2021, 10(20), 4788; https://doi.org/10.3390/jcm10204788 - 19 Oct 2021

Cited by 3 | Viewed by 2144

Abstract

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of multiple autoantibodies, resulting in tissue and organ damage. Recent studies have revealed that interleukin-23 (IL-23) and interleukin-27 (IL-27) may be therapeutically relevant in selected SLE manifestations. This study [...] Read more.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by the production of multiple autoantibodies, resulting in tissue and organ damage. Recent studies have revealed that interleukin-23 (IL-23) and interleukin-27 (IL-27) may be therapeutically relevant in selected SLE manifestations. This study aimed to identify associations between serum IL-27 and IL-23 levels and disease activity in Polish patients with different manifestations of SLE: neuropsychiatric lupus (NPSLE), and lupus nephritis (LN). Associations between interleukin levels and oligo-specific antibodies against double-stranded DNA (dsDNA), dose of glucocorticoids, and type of treatment were also analyzed. An enzyme-linked immunosorbent assay was used to assess anti-dsDNA antibodies and analyze the serum concentration of IL-27 and IL-23 from 72 patients aged 19–74 years with confirmed active SLE. Disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2-K). No significant correlations between interleukin levels and SLEDAI score, anti-dsDNA, corticosteroid dose, or type of treatment were noted. Patients with NPSLE and LN presented the highest median scores of SLEDAI. Full article

(This article belongs to the Special Issue Systemic Lupus Erythematosus: Pathogenesis, Diagnosis and Treatment)

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12 pages, 1378 KiB

Open AccessArticle

Minimally Invasive Surgery and Surgical Volume-Specific Survival and Perioperative Outcome: Unmet Need for Evidence in Gynecologic Malignancy

by Shinya Matsuzaki, Maximilian Klar, Erica J. Chang, Satoko Matsuzaki, Michihide Maeda, Renee H. Zhang, Lynda D. Roman and Koji Matsuo

J. Clin. Med. 2021, 10(20), 4787; https://doi.org/10.3390/jcm10204787 - 19 Oct 2021

Cited by 6 | Viewed by 1797

Abstract

This study examined the effect of hospital surgical volume on oncologic outcomes in minimally invasive surgery (MIS) for gynecologic malignancies. The objectives were to assess survival outcomes related to hospital surgical volume and to evaluate perioperative outcomes and examine non-gynecologic malignancies. Literature available [...] Read more.

This study examined the effect of hospital surgical volume on oncologic outcomes in minimally invasive surgery (MIS) for gynecologic malignancies. The objectives were to assess survival outcomes related to hospital surgical volume and to evaluate perioperative outcomes and examine non-gynecologic malignancies. Literature available from the PubMed, Scopus, and the Cochrane Library databases were systematically reviewed. All surgical procedures including gynecologic surgery with hospital surgical volume information were eligible for analysis. Twenty-three studies met the inclusion criteria, and nine gastro-intestinal studies, seven genitourinary studies, four gynecological studies, two hepatobiliary studies, and one thoracic study were reviewed. Of those, 11 showed a positive volume–outcome association for perioperative outcomes. A study on MIS for ovarian cancer reported lower surgical morbidity in high-volume centers. Two studies were on endometrial cancer, of which one showed lower treatment costs in high-volume centers and the other showed no association with perioperative morbidity. Another study examined robotic-assisted radical hysterectomy for cervical cancer and found no volume–outcome association for surgical morbidity. There were no gynecologic studies examining the association between hospital surgical volume and oncologic outcomes in MIS. The volume–outcome association for oncologic outcome in gynecologic MIS is understudied. This lack of evidence calls for further studies to address this knowledge gap. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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Selection schema for the systematic review of the literature. Full article ">Figure 2
Association between annual hospital surgical cases and volume–outcome. The association between the hospital annual cases of minimally invasive surgery and perioperative outcomes is shown. The median number of annual cases was 37.5. Red indicates the observed volume–outcome association. Green indicates that the volume–outcome association was inconsistent. Blue indicates that the volume–outcome association was not observed. Abbreviations: USA, United States of America; Rad Hyst, radical hysterectomy; oophorec, oophorectomy; lobec, lobectomy; esophag, esophagectomy; PD, pancreaticoduodenectomy; nephrec, nephrectomy; gastrec, gastrectomy; hyst, hysterectomy; colec, colectomy; and Rad Pros, radical prostatectomy. Full article ">Figure 3
Association between the study period and volume–outcome. Studies from United States are included in this figure. * Mixed with conventional laparoscopic surgery. ** Cases with conventional laparoscopic surgery were excluded from this analysis. Red shapes and lines: the volume–outcome association for perioperative outcomes was observed. Blue shapes and lines: the volume–outcome association was not observed. Abbreviations: FDA Robotic, The Food and Drug Administration approval for robotic-assisted minimally invasive surgery; Robotic, robotic surgery; GI, gastrointestinal; HPB, hepato–pancreato–biliary, GU, genitourinary; GYN, gynecology; PD, pancreaticoduodenectomy; Esophag, esophagectomy; Rad Pros, radical prostatectomy; and Rad Hyst, radical hysterectomy. Full article ">

22 pages, 414 KiB

Open AccessReview

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview

by Undine-Sophie Deumer, Angelica Varesi, Valentina Floris, Gabriele Savioli, Elisa Mantovani, Paulina López-Carrasco, Gian Marco Rosati, Sakshi Prasad and Giovanni Ricevuti

J. Clin. Med. 2021, 10(20), 4786; https://doi.org/10.3390/jcm10204786 - 19 Oct 2021

Cited by 55 | Viewed by 12130

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as “brain fog”. These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods [...] Read more.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic systemic disease that manifests via various symptoms such as chronic fatigue, post-exertional malaise, and cognitive impairment described as “brain fog”. These symptoms often prevent patients from keeping up their pre-disease onset lifestyle, as extended periods of physical or mental activity become almost impossible. However, the disease presents heterogeneously with varying severity across patients. Therefore, consensus criteria have been designed to provide a diagnosis based on symptoms. To date, no biomarker-based tests or diagnoses are available, since the molecular changes observed also largely differ from patient to patient. In this review, we discuss the infectious, genetic, and hormonal components that may be involved in CFS pathogenesis, we scrutinize the role of gut microbiota in disease progression, we highlight the potential of non-coding RNA (ncRNA) for the development of diagnostic tools and briefly mention the possibility of SARS-CoV-2 infection causing CFS. Full article

(This article belongs to the Special Issue Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment)

24 pages, 1094 KiB

Open AccessReview

Shared Care and Virtual Clinics for Glaucoma in a Hospital Setting

by Anne-Sophie Simons, Julie Vercauteren, João Barbosa-Breda and Ingeborg Stalmans

J. Clin. Med. 2021, 10(20), 4785; https://doi.org/10.3390/jcm10204785 - 19 Oct 2021

Cited by 6 | Viewed by 2484

Abstract

Glaucoma patients require lifelong management, and the prevalence of glaucoma is expected to increase, resulting in capacity problems in many hospital eye departments. New models of care delivery are needed to offer requisite capacity. This review evaluates two alternative schemes for glaucoma care [...] Read more.

Glaucoma patients require lifelong management, and the prevalence of glaucoma is expected to increase, resulting in capacity problems in many hospital eye departments. New models of care delivery are needed to offer requisite capacity. This review evaluates two alternative schemes for glaucoma care within a hospital, i.e., shared care (SC) and virtual clinics (VCs), whereby non-medical staff are entrusted with more responsibilities, and compares these schemes with the “traditional” ophthalmologist-led outpatient service (standard care). A literature search was conducted in three large bibliographic databases (PubMed, Embase, and Trip), and the abstracts from the prior five annual meetings of the Association for Research in Vision and Ophthalmology were consulted. Twenty-nine were included in the review (14 on SC and 15 on VCs). Patients with low risk of vision loss were considered suitable for these approaches. Among the non-medical staff, optometrists were the most frequently involved. The quality of both schemes was good and improved with the non-medical staff being trained in glaucoma care. No evidence was found on patients feeling disadvantaged by the lack of a doctor visit. Both schemes increased the hospital’s efficiency. Both SC and VCs are promising approaches to tackle the upcoming capacity problems of hospital-based glaucoma care. Full article

(This article belongs to the Special Issue Going for Gaps in Glaucoma)

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13 pages, 288 KiB

Open AccessReview

Fertility-Sparing Treatment of Patients with Endometrial Cancer: A Review of the Literature

by Umberto Leone Roberti Maggiore, Rola Khamisy-Farah, Nicola Luigi Bragazzi, Giorgio Bogani, Fabio Martinelli, Salvatore Lopez, Valentina Chiappa, Mauro Signorelli, Antonino Ditto and Francesco Raspagliesi

J. Clin. Med. 2021, 10(20), 4784; https://doi.org/10.3390/jcm10204784 - 19 Oct 2021

Cited by 17 | Viewed by 4102

Abstract

Endometrial cancer (EC) is currently the most common malignancy of the female genital tract in developed countries. Although it is more common in postmenopausal women, it may affect up to 25% in the premenopausal age and 3–5% under the age of 40 years. [...] Read more.

Endometrial cancer (EC) is currently the most common malignancy of the female genital tract in developed countries. Although it is more common in postmenopausal women, it may affect up to 25% in the premenopausal age and 3–5% under the age of 40 years. Furthermore, in the last decades a significant shift to pregnancy at older maternal ages, particularly in resource-rich countries, has been observed. Therefore, in this scenario fertility-sparing alternatives should be discussed with patients affected by EC. This study summarizes available literature on fertility-sparing management of patients affected by EC, focusing on the oncologic and reproductive outcomes. A systematic computerized search of the literature was performed in two electronic databases (PubMed and MEDLINE) in order to identify relevant articles to be included for the purpose of this systematic review. On the basis of available evidence, fertility-sparing alternatives are oral progestins alone or in combination with other drugs, levonorgestrel intrauterine system and hysteroscopic resection in association with progestin therapies. These strategies seem feasible and safe for young patients with G1 endometrioid EC limited to the endometrium. However, there is a lack of high-quality evidence on the efficacy and safety of fertility-sparing treatments and future well-designed studies are required. Full article

(This article belongs to the Special Issue Clinical Advances on Endometrial Cancer)

15 pages, 1937 KiB

Open AccessArticle

Incidence and Practice of Early Prone Positioning in Invasively Ventilated COVID-19 Patients—Insights from the PRoVENT-COVID Observational Study

by Willemke Stilma, David M. P. van Meenen, Christel M. A. Valk, Hendrik de Bruin, Frederique Paulus, Ary Serpa Neto, Marcus J. Schultz and on behalf of the PRoVENT-COVID Collaborative Group

J. Clin. Med. 2021, 10(20), 4783; https://doi.org/10.3390/jcm10204783 - 19 Oct 2021

Cited by 20 | Viewed by 4554

Abstract

We describe the incidence and practice of prone positioning and determined the association of use of prone positioning with outcomes in invasively ventilated patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) in a national, multicenter observational study, performed [...] Read more.

We describe the incidence and practice of prone positioning and determined the association of use of prone positioning with outcomes in invasively ventilated patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) in a national, multicenter observational study, performed at 22 intensive care units in the Netherlands. Patients were categorized into 4 groups, based on indication for and actual use of prone positioning. The primary outcome was 28-day mortality. Secondary endpoints were 90-day mortality, and ICU and hospital length of stay. In 734 patients, prone positioning was indicated in 60%—the incidence of prone positioning was higher in patients with an indication than in patients without an indication for prone positioning (77 vs. 48%, p = 0.001). Patients were left in the prone position for median 15.0 (10.5–21.0) hours per full calendar day—the duration was longer in patients with an indication than in patients without an indication for prone positioning (16.0 (11.0–23.0) vs. 14.0 (10.0–19.0) hours, p < 0.001). Ventilator settings and ventilation parameters were not different between the four groups, except for FiO₂ which was higher in patients having an indication for and actually receiving prone positioning. Our data showed no difference in mortality at day 28 between the 4 groups (HR no indication, no prone vs. no indication, prone vs. indication, no prone vs. indication, prone: 1.05 (0.76–1.45) vs. 0.88 (0.62–1.26) vs. 1.15 (0.80–1.54) vs. 0.96 (0.73–1.26) (p = 0.08)). Factors associated with the use of prone positioning were ARDS severity and FiO₂. The findings of this study are that prone positioning is often used in COVID-19 patients, even in patients that have no indication for this intervention. Sessions of prone positioning lasted long. Use of prone positioning may affect outcomes. Full article

(This article belongs to the Section Intensive Care)

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Flow chart of patient inclusion. Full article ">Figure 2
Cumulative distribution duration of prone positioning per day. Duration of prone positioning session for each patient on day 0 to day 3. Full article ">Figure 3
Cumulative distribution of ventilatory parameters on day 0. Levels of tidal volume, PEEP, driving pressure and compliance for each patient on day 0. Full article ">Figure 4
Cumulative distribution of parameters of gas exchange on day 0. Levels of P/F ratio FiO2, PO2 and PCO2 for each patient on day 0. Full article ">Figure 5
Outcomes. Patient outcomes for the groups of patients with an indication for prone positioning, on the left panel patients are displayed that did not receive prone positioning; on the right panel patients are displayed that did receive prone positioning. HR’s for outcomes were (no indication, no prone vs. no indication, prone vs. indication, no prone vs. indication, prone). 28-day mortality: 1.05 (0.76–1.45) vs. 0.88 (0.62–1.26) vs. 1.15 (0.80–1.54) vs. 0.96 (0.73–1.26) (p = 0.08); 90-day mortality: 0.93 (0.67–1.27) vs. 0.89 (0.64–1.24) vs. 1.19 (0.88–1.62) vs. 0.99 (0.76–1.28) (p = 0.02); ICU discharge: 1.28 (1.02–1.61) vs. 1.03 (0.80–1.33) vs. 0.88 (0.69–1.12) vs. 0.89 (0.74–1.08) (p = 0.02); Hospital discharge: 1.25 (0.99–1.58) vs. 1.07 (0.83–1.39) vs. 0.88 (0.69–1.13) vs. (0.89 (0.73–1.08) (p = 0.01); HR’s for outcomes in the groups with an indication were (indication, no prone vs. indication, prone); 28-day mortality: 1.30 (0.82–2.07 vs. 0.76 (0.48–1.21) (p = 0.25); 90-day mortality: 1.41 (0.93–2.14) vs. 0.70 (0.46–1.07) (p = 0.10); ICU discharge: 0.77 (0.52–1.14) vs. 1.29 (0.87–1.91) (p = 0.93); Hospital discharge: 0.78 (0.52–1.18) vs. 1.26 (0.84–1.90) (p = 0.70). Full article ">

20 pages, 26967 KiB

Open AccessReview

Heart Failure in Patients with Arrhythmogenic Cardiomyopathy

by Shi Chen, Liang Chen, Firat Duru and Shengshou Hu

J. Clin. Med. 2021, 10(20), 4782; https://doi.org/10.3390/jcm10204782 - 19 Oct 2021

Cited by 6 | Viewed by 3225

Abstract

Arrhythmogenic cardiomyopathy (ACM) is a rare inherited cardiomyopathy characterized as fibro-fatty replacement, and a common cause for sudden cardiac death in young athletes. Development of heart failure (HF) has been an under-recognized complication of ACM for a long time. The current clinical management [...] Read more.

Arrhythmogenic cardiomyopathy (ACM) is a rare inherited cardiomyopathy characterized as fibro-fatty replacement, and a common cause for sudden cardiac death in young athletes. Development of heart failure (HF) has been an under-recognized complication of ACM for a long time. The current clinical management guidelines for HF in ACM progression have nowadays been updated. Thus, a comprehensive review for this great achievement in our understanding of HF in ACM is necessary. In this review, we aim to describe the research progress on epidemiology, clinical characteristics, risk stratification and therapeutics of HF in ACM. Full article

(This article belongs to the Section Cardiology)

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The incidence of heart transplantation/death reported from the ACM registry in different countries worldwide. Full article ">Figure 2
Heart failure progression in classical ACM. Full article ">Figure 3
The CMR and ECG characteristics of ACM HF patients. (A) The CMR image of ACM HF patient; (B) the ECG of ACM HF patient. (Adapted with permission from Liang et al. [<a href="#B42-jcm-10-04782" class="html-bibr">42</a>]). CMR, cardiac magnetic resonance; ECG, electrocardiogram; ACM, arrhythmogenic cardiomyopathy; HF, heart failure. Full article ">Figure 4
The diagnostic criteria of imaging and ECG in the 2010 Revised Task Force Criteria. 2D, two dimensional; RV, right ventricular; PLAX, parasternal long-axis; RVOT, RV outflow tract; PSAX, parasternal short-axis; BSA, body surface area; CMR, cardiac MRI; EDV, end-diastolic volume; RVEF, right ventricular ejection fraction; RBBB, right bundle branch block; SAECG, signal-averaged ECG; VT, ventricular tachycardia; LBBB, left bundle branch block; PVC, premature ventricular complex. Full article ">Figure 5
Plasma biomarker application in ACM. Full article ">Figure 6
The gross morphology and histopathological characteristics of ARVC HF patients. (A) The explanted heart from ARVC patient; (B) the diagram of sampling position; (C) Masson staining of six representative sections. (Adapted with permission from Liang et al. [<a href="#B42-jcm-10-04782" class="html-bibr">42</a>]). LVAW, anterior wall of left ventricular (LV); LVLW, lateral wall of LV; LVIW, inferior wall of LV; IVS, interventricular septum; RVAW, anterior wall of right ventricle (RV); RVIW, inferior wall of RV. Full article ">Figure 7
Risk factors of heart failure in ACM. Full article ">Figure 8
Prevention and management of heart failure in ACM. ICD, implantable cardioverter-defibrillators; ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin II receptor blockers; RV, right ventricular; CRT, cardiac resynchronization therapy. Full article ">

11 pages, 711 KiB

Open AccessArticle

Retinopathy of Prematurity and Hearing Impairment in Infants Born with Very-Low-Birth-Weight: Analysis of a Korean Neonatal Network Database

by Chang Myeon Song, Ja-Hye Ahn, Jae Kyoon Hwang, Chang-Ryul Kim, Mi Jung Kim, Kyeong Mi Lee, Hyun Ju Lee and Seong Joon Ahn

J. Clin. Med. 2021, 10(20), 4781; https://doi.org/10.3390/jcm10204781 - 19 Oct 2021

Cited by 1 | Viewed by 1699

Abstract

Background: To investigate hearing impairment and its association with retinopathy of prematurity (ROP) among children born with very low birth weight (VLBW, birth weight < 1500 g). Methods: This prospective registry study included 7940 VLBW infants who underwent both ophthalmic (ROP) and hearing [...] Read more.

Background: To investigate hearing impairment and its association with retinopathy of prematurity (ROP) among children born with very low birth weight (VLBW, birth weight < 1500 g). Methods: This prospective registry study included 7940 VLBW infants who underwent both ophthalmic (ROP) and hearing screening at the 70 participating centers of the Korean Neonatal Network. Hearing screening was performed using auditory brainstem response and/or automated otoacoustic emission testing. Hearing impairment, defined as a unilateral or bilateral hearing threshold of ≥40 dB on the auditory brainstem response threshold (ABR-T) test, was evaluated and compared between children with and without ROP at the corrected ages of 18 months and 3 years. Results: The frequency of infants who did not undergo hearing screening at near-term ages was higher in the ROP group than in the no-ROP group (18.2% vs. 12.0%, p < 0.001), and the prevalence of hearing impairment at 18 months was higher in the ROP group than in the no-ROP group (3.5% vs. 2.2%, p = 0.043). The prevalence of deafness was higher in children with ROP than those without ROP (0.4% vs. 0.1%, p = 0.049). There were significant differences in hearing impairment among the stages of ROP (p < 0.001). However, multivariate analyses and propensity score matching showed no significant association between ROP and hearing impairment at 18 months and 3 years after adjusting for prematurity-related variables (all p > 0.05). Conclusions: Among infants born with VLBW, hearing impairment was more common in those with ROP than in those without ROP at 18 months of age. However, there was no significant independent association between hearing impairment and ROP. Full article

(This article belongs to the Section Ophthalmology)

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10 pages, 534 KiB

Open AccessArticle

Clinical Analysis of the Diagnostic Accuracy and Time of Execution of a Transillumination Caries Detection Method Compared to Bitewing Radiographs

by Gian Andrea Pelliccioni, Maria Rosaria Antonella Gatto, Silvia Bolognesi, Daniele Dal Fiume, Maicon Sebold and Lorenzo Breschi

J. Clin. Med. 2021, 10(20), 4780; https://doi.org/10.3390/jcm10204780 - 19 Oct 2021

Cited by 2 | Viewed by 2289

Abstract

Purposes: this clinical study evaluated the accuracy and execution time of a digital imaging fiber-optic transillumination (DIFOTI) technique for the detection of approximal caries in posterior teeth compared to intra-oral examination associated with bitewing radiographs. Methods: one hundred patients were selected and submitted [...] Read more.

Purposes: this clinical study evaluated the accuracy and execution time of a digital imaging fiber-optic transillumination (DIFOTI) technique for the detection of approximal caries in posterior teeth compared to intra-oral examination associated with bitewing radiographs. Methods: one hundred patients were selected and submitted to clinical inspection and bitewing radiographs. The outcomes of this process were converted into scores, according to the International Caries Detection and Assessment System (ICDAS): 0—sound tooth; 1, 2, and 3—carious lesion confined within enamel; 4, 5, and 6—dentin carious lesion. Subsequently, an independent investigator acquired digital images of the same teeth using a DIFOTI device (DIAGNOcam, Kavo Dental), which were also converted into ICDAS scores. The time required for executing diagnostic procedures was measured. The clinical sensitivity and specificity of DIFOTI were analyzed by receiver operating characteristic (ROC) curves. The time necessary to perform the diagnostic methods was evaluated by Mann–Whitney U (alfa = 0.05). Results: the overall test accuracy for the DIFOTI-based device ranged from 0.717 to 0.815 (area under the ROC curve) with p < 0.0001 for all ICDAS scores. Bitewing radiographs took almost twice the time required by DIFOTI (p < 0.001). Conclusions: the DIFOTI-based device DIAGNOcam provided accurate detection of approximal caries in posterior teeth, even at early stages. The technique employed for transillumination caries diagnosis by the same device took less time than conventional bitewing radiographs. Clinical Relevance: transillumination devices, such as DIAGNOcam, can be accurately used for caries diagnosis in approximal surfaces of posterior teeth, demanding less clinical time and without radiation-related risks. Full article

(This article belongs to the Topic State-of-the-Art Dentistry and Oral Health)

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14 pages, 1499 KiB

Open AccessArticle

Developing a Prediction Model for 7-Year and 10-Year All-Cause Mortality Risk in Type 2 Diabetes Using a Hospital-Based Prospective Cohort Study

by Sherry Yueh-Hsia Chiu, Ying Isabel Chen, Juifen Rachel Lu, Soh-Ching Ng and Chih-Hung Chen

J. Clin. Med. 2021, 10(20), 4779; https://doi.org/10.3390/jcm10204779 - 18 Oct 2021

Cited by 5 | Viewed by 1857

Abstract

Leveraging easily accessible data from hospitals to identify high-risk mortality rates for clinical diabetes care adjustment is a convenient method for the future of precision healthcare. We aimed to develop risk prediction models for all-cause mortality based on 7-year and 10-year follow-ups for [...] Read more.

Leveraging easily accessible data from hospitals to identify high-risk mortality rates for clinical diabetes care adjustment is a convenient method for the future of precision healthcare. We aimed to develop risk prediction models for all-cause mortality based on 7-year and 10-year follow-ups for type 2 diabetes. A total of Taiwanese subjects aged ≥18 with outpatient data were ascertained during 2007–2013 and followed up to the end of 2016 using a hospital-based prospective cohort. Both traditional model selection with stepwise approach and LASSO method were conducted for parsimonious models’ selection and comparison. Multivariable Cox regression was performed for selected variables, and a time-dependent ROC curve with an integrated AUC and cumulative mortality by risk score levels was employed to evaluate the time-related predictive performance. The prediction model, which was composed of eight influential variables (age, sex, history of cancers, history of hypertension, antihyperlipidemic drug use, HbA1c level, creatinine level, and the LDL /HDL ratio), was the same for the 7-year and 10-year models. Harrell’s C-statistic was 0.7955 and 0.7775, and the integrated AUCs were 0.8136 and 0.8045 for the 7-year and 10-year models, respectively. The predictive performance of the AUCs was consistent with time. Our study developed and validated all-cause mortality prediction models with 7-year and 10-year follow-ups that were composed of the same contributing factors, though the model with 10-year follow-up had slightly greater risk coefficients. Both prediction models were consistent with time. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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13 pages, 280 KiB

Open AccessArticle

Spinal Cord Signal Change on Magnetic Resonance Imaging May Predict Worse Clinical In- and Outpatient Outcomes in Patients with Spinal Cord Injury: A Prospective Multicenter Study in 459 Patients

by Thorsten Jentzsch, David W. Cadotte, Jefferson R. Wilson, Fan Jiang, Jetan H. Badhiwala, Muhammad A. Akbar, Brett Rocos, Robert G. Grossman, Bizhan Aarabi, James S. Harrop and Michael G. Fehlings

J. Clin. Med. 2021, 10(20), 4778; https://doi.org/10.3390/jcm10204778 - 18 Oct 2021

Cited by 11 | Viewed by 2843

Abstract

Prognostic factors for clinical outcome after spinal cord (SC) injury (SCI) are limited but important in patient management and education. There is a lack of evidence regarding magnetic resonance imaging (MRI) and clinical outcomes in SCI patients. Therefore, we aimed to investigate whether [...] Read more.

Prognostic factors for clinical outcome after spinal cord (SC) injury (SCI) are limited but important in patient management and education. There is a lack of evidence regarding magnetic resonance imaging (MRI) and clinical outcomes in SCI patients. Therefore, we aimed to investigate whether baseline MRI features predicted the clinical course of the disease. This study is an ancillary to the prospective North American Clinical Trials Network (NACTN) registry. Patients were enrolled from 2005–2017. MRI within 72 h of injury and a minimum follow-up of one year were available for 459 patients. Patients with American Spinal Injury Association impairment scale (AIS) E were excluded. Patients were grouped into those with (n = 354) versus without (n = 105) SC signal change on MRI T2-weighted images. Logistic regression analysis adjusted for commonly known a priori confounders (age and baseline AIS). Main outcomes and measures: The primary outcome was any adverse event. Secondary outcomes were AIS at the baseline and final follow-up, length of hospital stay (LOS), and mortality. A regression model adjusted for age and baseline AIS. Patients with intrinsic SC signal change were younger (46.0 (interquartile range (IQR) 29.0 vs. 50.0 (IQR 20.5) years, p = 0.039). There were no significant differences in the other baseline variables, gender, body mass index, comorbidities, and injury location. There were more adverse events in patients with SC signal change (230 (65.0%) vs. 47 (44.8%), p < 0.001; odds ratio (OR) = 2.09 (95% confidence interval (CI) 1.31–3.35), p = 0.002). The most common adverse event was cardiopulmonary (186 (40.5%)). Patients were less likely to be in the AIS D category with SC signal change at baseline (OR = 0.45 (95% CI 0.28–0.72), p = 0.001) and in the AIS D or E category at the final follow-up (OR = 0.36 (95% CI 0.16–0.82), p = 0.015). The length of stay was longer in patients with SC signal change (13.0 (IQR 17.0) vs. 11.0 (IQR 14.0), p = 0.049). There was no difference between the groups in mortality (11 (3.2%) vs. 4 (3.9%)). MRI SC signal change may predict adverse events and overall LOS in the SCI population. If present, patients are more likely to have a worse baseline clinical presentation (i.e., AIS) and in- or outpatient clinical outcome after one year. Patients with SC signal change may benefit from earlier, more aggressive treatment strategies and need to be educated about an unfavorable prognosis. Full article

(This article belongs to the Special Issue Management of Degenerative Cervical Myelopathy and Spinal Cord Injury)

13 pages, 1172 KiB

Open AccessArticle

Assessing Cognitive Function in Neuromuscular Diseases: A Pilot Study in a Sample of Children and Adolescents

by Rossella D’Alessandro, Neftj Ragusa, Martina Vacchetti, Enrica Rolle, Francesca Rossi, Chiara Brusa, Chiara Davico, Benedetto Vitiello, Tiziana Mongini and Federica S. Ricci

J. Clin. Med. 2021, 10(20), 4777; https://doi.org/10.3390/jcm10204777 - 18 Oct 2021

Cited by 6 | Viewed by 2479

Abstract

Central nervous system (CNS) involvement has been variously studied in pediatric neuromuscular disorders (NMDs). The primary goal of this study was to assess cognitive functioning in NMDs, and secondary aims were to investigate possible associations of cognitive impairment with motor impairment, neurodevelopmental delay, [...] Read more.

Central nervous system (CNS) involvement has been variously studied in pediatric neuromuscular disorders (NMDs). The primary goal of this study was to assess cognitive functioning in NMDs, and secondary aims were to investigate possible associations of cognitive impairment with motor impairment, neurodevelopmental delay, and genotype. This was a cross-sectional study of 43 pediatric patients, affected by six NMDs. Myotonic dystrophy type 1 (DM1) and glycogen storage disease type 2 (GSD2) patients had a delay on the Bayley-III scales. On Wechsler scales, DMD and DM1 patients showed lower FSIQ scores, with an intellectual disability (ID) in 27% and 50%, respectively. FSIQ was normal in Becker muscular dystrophy (BMD), GSD2, and hereditary motor sensory neuropathy (HMSN) patients, while higher individual scores were found in the spinal muscular atrophy (SMA) group. In the DM1 cohort, lower FSIQ correlated with worse motor performance (ρ = 0.84, p < 0.05), and delayed speech acquisition was associated with ID (p = 0.048), with worse cognitive impairment in the congenital than in the infantile form (p = 0.04). This study provides further evidence of CNS in some NMDs and reinforces the need to include cognitive assessment in protocols of care of selected pediatric NMDs. Full article

(This article belongs to the Special Issue Feature Papers in Clinical Psychology)

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20 pages, 766 KiB

Open AccessReview

Is Irritable Bowel Syndrome Considered as Comorbidity in Clinical Trials of Physical Therapy Interventions in Fibromyalgia? A Scoping Review

by Paula Mª Rodríguez-Castillejo, César Fernández-de-las-Peñas, Francisco Alburquerque-Sendín and Daiana P. Rodrigues-de-Souza

J. Clin. Med. 2021, 10(20), 4776; https://doi.org/10.3390/jcm10204776 - 18 Oct 2021

Cited by 1 | Viewed by 2607

Abstract

Evidence supports the presence of comorbid conditions, e.g., irritable bowel syndrome (IBS), in individuals with fibromyalgia (FM). Physical therapy plays an essential role in the treatment of FM; however, it is not currently known whether the IBS comorbidity is considered in the selection [...] Read more.

Evidence supports the presence of comorbid conditions, e.g., irritable bowel syndrome (IBS), in individuals with fibromyalgia (FM). Physical therapy plays an essential role in the treatment of FM; however, it is not currently known whether the IBS comorbidity is considered in the selection criteria for clinical trials evaluating physiotherapy in FM. Thus, the aim of the review was to identify whether the presence of IBS was considered in the selection criteria for study subjects for those clinical trials that have been highly cited or published in the high-impact journals investigating the effects of physical therapy in FM. A literature search in the Web of Science database for clinical trials that were highly cited or published in high-impact journals, i.e., first second quartile (Q1) of any category of the Journal Citation Report (JCR), investigating the effects of physical therapy in FM was conducted. The methodological quality of the selected trials was assessed with the Physiotherapy Evidence Database (PEDro) scale. Authors, affiliations, number of citations, objectives, sex/gender, age, and eligibility criteria of each article were extracted and analyzed independently by two authors. From a total of the 412 identified articles, 20 and 61 clinical trials were included according to the citation criterion or JCR criterion, respectively. The PEDro score ranged from 2 to 8 (mean: 5.9, SD: 0.1). The comorbidity between FM and IBS was not considered within the eligibility criteria of the participants in any of the clinical trials. The improvement of the eligibility criteria is required in clinical trials on physical therapy that include FM patients to avoid selection bias. Full article

(This article belongs to the Special Issue Physiotherapy in Muscle Pain: Current Updates from Theory to Clinical Practice)

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9 pages, 497 KiB

Open AccessArticle

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Health in Patients with Type 2 Diabetes Mellitus

by Dong-Hwa Lee, Kyong Young Kim, Min Young Yoo, Hansol Moon, Eu Jeong Ku, Tae Keun Oh and Hyun Jeong Jeon

J. Clin. Med. 2021, 10(20), 4775; https://doi.org/10.3390/jcm10204775 - 18 Oct 2021

Cited by 6 | Viewed by 1648

Abstract

Patients with type 2 diabetes (T2DM) have a higher risk of bone fracture even when bone mineral density (BMD) values are normal. The trabecular bone score (TBS) was recently developed and used for evaluating bone strength in various diseases. We investigated the effect [...] Read more.

Patients with type 2 diabetes (T2DM) have a higher risk of bone fracture even when bone mineral density (BMD) values are normal. The trabecular bone score (TBS) was recently developed and used for evaluating bone strength in various diseases. We investigated the effect of DPP-4 inhibitors on bone health using TBS in patients with T2DM. This was a single-center, retrospective case-control study of 200 patients with T2DM. Patients were divided into two groups according to whether they were administered a DPP-4 inhibitor (DPP-4 inhibitor group vs. control group). Parameters related to bone health, including BMD, TBS, and serum markers of calcium homeostasis, were assessed at baseline and after one year of treatment. We found TBS values increased in the DPP-4 group and decreased in the control, indicating a significant difference in delta change between them. The BMD increased in both groups, with no significant differences in delta change between the two groups observed. Serum calcium and 25-hydroxy vitamin D3 increased only in the DPP-4 inhibitor group, while other glycemic parameters did not show significant differences between the two groups. Treatment with DPP-4 inhibitors was associated with favorable effects on bone health evaluated by TBS in patients with T2DM. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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10 pages, 6564 KiB

Open AccessArticle

Clinical Efficacy of Ruxolitinib in Patients with Myelofibrosis: A Nationwide Population-Based Study in Korea

by Byung-Hyun Lee, Hyemi Moon, Jae-Eun Chae, Ka-Won Kang, Byung-Soo Kim, Juneyoung Lee and Yong Park

J. Clin. Med. 2021, 10(20), 4774; https://doi.org/10.3390/jcm10204774 - 18 Oct 2021

Cited by 2 | Viewed by 1896

Abstract

Previous studies have reported the survival benefit after ruxolitinib treatment in patients with myelofibrosis (MF). However, population-based data of its efficacy are limited. We analyzed the effects of ruxolitinib in MF patients with data from the Korean National Health Insurance Database. In total, [...] Read more.

Previous studies have reported the survival benefit after ruxolitinib treatment in patients with myelofibrosis (MF). However, population-based data of its efficacy are limited. We analyzed the effects of ruxolitinib in MF patients with data from the Korean National Health Insurance Database. In total, 1199 patients diagnosed with MF from January 2011 to December 2017 were identified, of which 731 were included in this study. Patients who received ruxolitinib (n = 224) were matched with those who did not receive the drug (n = 507) using the 1:1 greedy algorithm. Propensity scores were formulated using five variables: age, sex, previous history of arterial/venous thrombosis, and red blood cell (RBC) or platelet (PLT) transfusion dependence at the time of diagnosis. Cox regression analysis for overall survival (OS) revealed that ruxolitinib treatment (hazard ratio (HR), 0.67; p = 0.017) was significantly related to superior survival. In the multivariable analysis for OS, older age (HR, 1.07; p < 0.001), male sex (HR, 1.94; p = 0.021), and RBC (HR, 3.72; p < 0.001) or PLT (HR, 9.58; p = 0.001) transfusion dependence were significantly associated with poor survival, although type of MF did not significantly affect survival. Considering evidence supporting these results remains weak, further studies on the efficacy of ruxolitinib in other populations are needed. Full article

(This article belongs to the Section Orthopedics)

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13 pages, 1810 KiB

Open AccessArticle

Influence of Pharyngeal Anaesthesia on Post-Bronchoscopic Coughing: A Prospective, Single Blinded, Multicentre Trial

by Maik Häntschel, Mariella Zahn-Paulsen, Ahmed Ehab, Michael Böckeler, Werner Spengler, Richard A. Lewis, Hubert Hautmann and Jürgen Hetzel

J. Clin. Med. 2021, 10(20), 4773; https://doi.org/10.3390/jcm10204773 - 18 Oct 2021

Cited by 1 | Viewed by 1575

Abstract

Background: Local anaesthesia of the pharynx (LAP) was introduced in the era of rigid bronchoscopy (which was initially a conscious procedure under local anaesthetic), and continued into the era of flexible bronchoscopy (FB) in order to facilitate introduction of the FB. LAP reduces [...] Read more.

Background: Local anaesthesia of the pharynx (LAP) was introduced in the era of rigid bronchoscopy (which was initially a conscious procedure under local anaesthetic), and continued into the era of flexible bronchoscopy (FB) in order to facilitate introduction of the FB. LAP reduces cough and gagging reflex, but its post-procedural effect is unclear. This prospective multicentre trial evaluated the effect of LAP on coughing intensity/time and patient comfort after FB, and the feasibility of FB under propofol sedation alone, without LAP. Material and methods: FB was performed in 74 consecutive patients under sedation with propofol, either alone (35 patients, 47.3%) or with additional LAP (39 patients, 52.7%). A primary endpoint of post-procedural coughing duration in the first 10 min after awakening was evaluated. A secondary endpoint was the cough frequency, quality and development of coughing in the same period during the 10 min post-procedure. Finally, the ease of undertaking the FB and the patient’s tolerance and safety were evaluated from the point of view of the investigator, the assistant technician and the patient. Results: We observed a trend to a shorter cumulative coughing time of 48.6 s in the group without LAP compared to 82.8 s in the group receiving LAP within the first 10 min after the procedure, although this difference was not significant (p = 0.24). There was no significant difference in the cough frequency, quality, peri-procedural complication rate, nor patient tolerance or safety. FB, including any additional procedure, could be performed equally well with or without LAP in both groups. Conclusions: Our study suggests that undertaking FB under deep sedation without LAP does to affect post-procedural cough duration and frequency. However, further prospective randomised controlled trials are needed to further support this finding. Full article

(This article belongs to the Special Issue Interventional Pulmonology: A New World)

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Figure 1
Cumulative cough duration in seconds during the observation interval of 10 min immediately after extubation. Each dot represents the cough duration of a single patient in seconds. S1 (+LAP)—Standard 1 with local anaesthesia of the pharynx, S2 (−LAP)—Standard 2 without local anaesthesia of the pharynx. Full article ">Figure 2
Development of median cumulative cough duration in 2-min intervals during the 10 min recording time. Median cumulative cough duration is shown in seconds for both Standards (S1 (+LAP)—red columns, S2 (−LAP)—green columns) for the respective intervals. Full article ">Figure 3
Cumulative cough duration in seconds during the ten minute post-procedural observation period with regard to patient age. Shown data cumulate both groups (S1 and S2, independent of application of LAP) with one dot for each patient. Full article ">Figure A1
(A)—Example for single coughs. One cough or multiple coughs with a total duration < 1.0 s; (B)—Example for cough clusters. It shows numerous subsequent forced exhalations (interval between each subsequent forced exhalations of less than one second, but with a total duration of more than one second). A cough cluster starts with the first forced exhalations and ending with the last forced exhalation. Full article ">Figure A2
Study population. S1—Standard 1 with LAP, S2—Standard 2 without LAP. Full article ">Figure A3
Box plots show median and quantiles for absolute number of single coughs (A), cough clusters (B) and the sum of both (C) for each patient during the 10-min evaluation interval, separately for both standards (S1 (+LAP)—Standard 1 with local anaesthesia of the pharynx; S2 (−LAP)—Standard 2 without local anaesthesia of the pharynx). Full article ">Figure A4
(A–C) Postinterventional complaints—coughing (A), gagging (B) and dyspnea (C). (A) Assessment of patient’s coughing, semi-quantified on a 5-step scale by the patient himself, the investigator (doctor) and the assistant technician in the recovery room. The scale ranged from 0 (no—light colour) to 4 (maximum—dark colour) for S1 (+LAP) as red columns and for S2 (−LAP) as green columns. (B) Assessment of patient’s gagging, semi-quantified on a 5-step scale by the patient himself, the investigator (doctor) and the assistant technician in the recovery room. The scale ranged from 0 (no—light colour) to 4 (maximum—dark colour) for S1 (+LAP) as red columns and for S2 (−LAP) as green columns. (C) Assessment of patient’s dyspnea, semi-quantified on a 5-step scale by the patient himself and the assistant technician in the recovery room. The scale ranged from 0 (no—light colour) to 4 (maximum—dark colour) for S1 (+LAP) as red columns and for S2 (−LAP) as green columns. n.s.—not significant. Full article ">

11 pages, 924 KiB

Open AccessReview

The Role of Microbial Factors in Prostate Cancer Development—An Up-to-Date Review

by Karolina Garbas, Piotr Zapała, Łukasz Zapała and Piotr Radziszewski

J. Clin. Med. 2021, 10(20), 4772; https://doi.org/10.3390/jcm10204772 - 18 Oct 2021

Cited by 8 | Viewed by 3562

Abstract

Up-to-date studies emphasize the role of human urinary and intestinal microbiome in maintaining urogenital health. Both microbial flora and sexually transmitted pathogens may affect metabolic or immune mechanisms and consequently promote or inhibit prostate carcinogenesis. Hereby, we review the most current evidence regarding [...] Read more.

Up-to-date studies emphasize the role of human urinary and intestinal microbiome in maintaining urogenital health. Both microbial flora and sexually transmitted pathogens may affect metabolic or immune mechanisms and consequently promote or inhibit prostate carcinogenesis. Hereby, we review the most current evidence regarding the microbial factors and their link to prostate cancer. We conducted a literature search up to December 2020. The microbial impact on prostate cancer initiation and progression is complex. The proposed mechanisms of action include induction of chronic inflammatory microenvironment (Propionibacterium spp., sexually-transmitted pathogens) and direct dysregulation of cell cycle (Helicobacter pylori, Kaposi’s sarcoma-associated herpesvirus- KSHV, human papilloma virus 18- HPV18). Suppression of immune cell expression and downregulating immune-associated genes are also observed (Gardnerella vaginalis). Additionally, the impact of the gut microbiome proved relevant in promoting tumorigenesis (Bacteroides massiliensis). Nevertheless, certain microbes appear to possess anti-tumor properties (Listeria monocytogenes, Pseudomonas spp.), such as triggering a robust immune response and apoptotic cancer cell death. The role of microbial factors in prostate cancer development is an emerging field that merits further studies. In the future, translating microbial research into clinical action may prove helpful in predicting diagnosis and potential outcomes of the disease. Full article

(This article belongs to the Section Nephrology & Urology)

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3 pages, 174 KiB

Open AccessEditorial

Update on Male Infertility

by Erlisa Bardhi and Panagiotis Drakopoulos

J. Clin. Med. 2021, 10(20), 4771; https://doi.org/10.3390/jcm10204771 - 18 Oct 2021

Cited by 4 | Viewed by 1901

Abstract

Infertility, defined as the failure to conceive after one year of regular intercourse without the use of contraception, in women less than 35 years of age remains a unique medical condition, as it involves a couple rather than a single individual [...] Full article

(This article belongs to the Special Issue Updates in Male Infertility)

19 pages, 649 KiB

Open AccessReview

The Person’s Care Requires a Sex and Gender Approach

by Ilaria Campesi, Andrea Montella, Giuseppe Seghieri and Flavia Franconi

J. Clin. Med. 2021, 10(20), 4770; https://doi.org/10.3390/jcm10204770 - 18 Oct 2021

Cited by 13 | Viewed by 2686

Abstract

There is an urgent need to optimize pharmacology therapy with a consideration of high interindividual variability and economic costs. A sex–gender approach (which considers men, women, and people of diverse gender identities) and the assessment of differences in sex and gender promote global [...] Read more.

There is an urgent need to optimize pharmacology therapy with a consideration of high interindividual variability and economic costs. A sex–gender approach (which considers men, women, and people of diverse gender identities) and the assessment of differences in sex and gender promote global health, avoiding systematic errors that generate results with low validity. Care for people should consider the single individual and his or her past and present life experiences, as well as his or her relationship with care providers. Therefore, intersectoral and interdisciplinary studies are urgently required. It is desirable to create teams made up of men and women to meet the needs of both. Finally, it is also necessary to build an alliance among regulatory and ethic authorities, statistics, informatics, the healthcare system and providers, researchers, the pharmaceutical and diagnostic industries, decision makers, and patients to overcome the gender gap in medicine and to take real care of a person in an appropriate manner. Full article

(This article belongs to the Special Issue Gender Medicine: Pharmacometabolomics and Personalized Medicine)

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