Statistics are critical in holding governments accountable for the well-being of citizens with di... more Statistics are critical in holding governments accountable for the well-being of citizens with disability. International initiatives are underway to improve the quality of disability statistics, but meaningful ID data is exceptionally rare. The status of ID data was evaluated in a review of 12 national statistical systems. Recurring data collection by national ministries was identified and the availability of measures of poverty, exclusion, and disadvantage was assessed. A total of 131 recurring systems coordinated by 50 different ministries were identified. The majority included general disability but less than 25% of the systems screened ID. Of these, few provided policy-relevant data. The scope of ID data was dismal at best, though a significant statistical infrastructure exists for the integration of ID data. Advocacy will be necessary. There is no optimal form of data monitoring, and decisions regarding priorities in purpose, targeted audiences, and the goals for surveillance must be resolved.
International Journal of Clinical and Experimental Medicine, Feb 1, 2008
Radiofrequency ablation (RFA) is gaining popularity for treating colorectal liver metastases by i... more Radiofrequency ablation (RFA) is gaining popularity for treating colorectal liver metastases by inducing image guided tumor hyperthermia. In order to reduce tumor recurrence, adjuvant therapies have been administered post-RFA. We hypothesized that tumor cells escaping RFA cytotoxicity by being in the sublethal zones of tumor might develop differential behavior toward cytotoxic drugs. Here, we used cultured human colorectal cancer cells to evaluate the interaction between heat treatment and chemotherapeutic agents. Human colon cancer cell lines HT29 and HCT116 were subjected to temperatures of 42° to 50°C for 15 min, in combination with 5-fluorouracil, oxaliplatin, or irinotecan at different sequences. Cytotoxicity was determined by MTT assay. The cell cycle progression was analyzed by flow cytometry with propidium iodide staining. The expression of several genes associated with drug sensitivity was quantitated by real-time RT-PCR before and after heat treatment. Either heat treatment at 45°C by simultaneous or pre-treatment with three different chemotherapeutic agents didn't affect the cytotoxicity of the combined treatment to HT29 and HCT116 cells, except for irinotecan treatment in HCT116 cells. However, when pre-exposure to 45°C, HCT116 cells, but not HT29 cells, developed resistance to these three drugs. In an analysis of cell cycle profile after the drug followed heat treatment, a longer delay in cell cycle progression in HCT116 cells was observed in comparison to HT29 cells. Furthermore, HCT116 and HT29 cells exhibited different expression profiles of several drug-related genes in response to heat treatment at 45°C. An observation of a differential response to the drug and heat treatment sequences between two human colon cancer cell lines suggests that tumor heterogeneity and selection of chemotherapeutic agents need to be under consideration in the clinical setting.
Pheochromocytomas are complex tumors that require a comprehensive, and systematic management plan... more Pheochromocytomas are complex tumors that require a comprehensive, and systematic management plan orchestrated by a multidisciplinary team. To achieve these ends, The Mount Sinai Adrenal Center hosted an interdisciplinary retreat where experts in adrenal disorders assembled with the aim of developing a clinical pathway for the management of pheochromocytomas. The result is a consensus for the diagnosis, peri-operative management, and post-operative management of pheochromocytoma with specific recommendations from our team of adrenal experts, as well as a review of the current literature. Our clinical pathway can be applied by other institutions directly or may serve as a guide for institution-specific management.
A number of histologic variants of well-differentiated papillary carcinoma have been found to be ... more A number of histologic variants of well-differentiated papillary carcinoma have been found to be associated with more aggressive tumor behavior. Tall cell, columnar cell, diffuse sclerosing, solid/trabecular, and insular variants of well-differentiated papillary thyroid cancer are all potentially more aggressive than conventional papillary thyroid cancer. When subjected to multivariate analysis, however, evidence that the histologic subtype of tumor is an independent predictor of outcome is weak. Rather, the aggressive variants tend to present with features recognized by other staging systems as associated with a worse prognosis, including higher histologic grade, extracapsular spread, large tumor size, and the presence of distant metastases. Prognosis is directly related to the presence of these features. The state of our knowledge is limited by the relatively small number of cases that have been studied. The presence of an aggressive variant of papillary carcinoma should alert the surgeon that he is dealing with a potentially aggressive tumor. Clinical treatment decisions should be based on the stage of the disease, influenced by the knowledge that the aggressive variants tend to be associated with higher risk factors. The surgeon must be prepared to perform at the first, or second stage, a total thyroidectomy, central compartment neck dissection, additional lymphadenectomy, and/or resection of invaded surrounding structures, and search for distant metastasis. Postoperative radioactive iodine should generally be administered for these variants as they will generally be intermediate to advanced tumors. The tall cell variant is often refractory to such treatment but may be susceptible to treatment targeted against BRAF mutation. External beam irradiation may be used in cases of incomplete resection.
One of the most significant complication of thyroid surgery is injury of the recurrent laryngeal ... more One of the most significant complication of thyroid surgery is injury of the recurrent laryngeal nerve. Injury of the external branch of the superior laryngeal nerve is a less obvious but occasionally significant problem. Recently, neuromonitoring during thyroidectomy has received considerable attention because of literature encouraging its use, but there is no consensus about its advantages and utility. A critical assessment of the literature on neuromonitoring was conducted in order to define its effectiveness, safety, cost-effectiveness and medical-legal impact. Available data does not show results superior to those obtained by traditional anatomical methods of nerve identification during thyroid surgery. Data about cost-effectiveness is scarce. The literature shows inconsistencies in methodology, patient selection and randomization in various published studies which may confound the conclusions of individual investigations. The current recommendation for use in "high risk" patients should be assessed because definition heterogeneity makes identification of these patients difficult. As routine use of neuromonitoring varies according to geography, its use should not be considered to be the standard of care.
Secondary and tertiary hyperparathyroidism (HPT) develop in patients with renal failure due to a ... more Secondary and tertiary hyperparathyroidism (HPT) develop in patients with renal failure due to a variety of mechanisms including increased phosphorus and fibroblast growth factor 23 (FGF23), and decreased calcium and 1,25-dihydroxy vitamin D levels. Patients present with various bone disorders, cardiovascular disease, and typical laboratory abnormalities. Medical treatment consists of controlling hyperphosphatemia, vitamin D/analog and calcium administration, and calcimimetic agents. Improved medical therapies have led to a decrease in the use of parathyroidectomy (PTX). The surgical indications include parathyroid hormone (PTH) levels >800 pg/ml associated with hypercalcemia and/or hyperphosphatemia despite medical therapy. Other indications include calciphylaxis, fractures, bone pain or pruritis. Transplant recipients often show decreased PTH, calcium and phosphorus levels, but some will have persistent HPT. Evidence suggests that PTX may cause deterioration in renal graft function in the short-term calling into the question the indications for PTX in these patients. Pre-operative imaging is only occasionally helpful except in re-operative PTX. Operative approaches include subtotal PTX, total PTX with or without autotransplantation, and possible thymectomy. Each approach has its proponents, advantages and disadvantages which are discussed. Intraoperative PTH monitoring has a high positive predictive value of cure but a poor negative predictive value and therefore is of limited utility. Hypocalcemia is the most common complication requiring aggressive calcium administration. Benefits of surgery may include improved survival, bone mineral density and alleviation of symptoms.
Neuromonitoring in thyroid surgery has been employed to make nerve identification easier and decr... more Neuromonitoring in thyroid surgery has been employed to make nerve identification easier and decrease the rates of laryngeal nerve injuries. Several individual randomized controlled trials (RCTs) have been published, which did not identify statistical differences in the rates of recurrent laryngeal nerve (RLN) or external branch of the superior laryngeal nerve (EBSLN) injuries. The objective of this report is to perform meta-analysis of the combined results of individual studies to measure the frequency of RLN and EBSLN injuries in patients who underwent thyroidectomy with routine neuromonitoring in comparison with common practice of search and identification. RCTs comparing routine neuromonitoring versus no use in patients who underwent elective partial or total thyroidectomy were evaluated. Outcomes measured were temporary and definitive palsy of the RLN and EBSLN. A systematic review and meta-analysis was done using random effects model. GRADE was used to classify quality of evidence. Six studies with 1,602 patients and 3,064 nerves at risk were identified. Methodological quality assessment showed high risk of bias in most items. Funnel plot did not reveal publication bias. The risk difference for temporary RLN palsy, definitive RLN palsy, temporary EBSLN palsy, and definitive EBSLN palsy were -2% (95% confidence interval -5.1 to 1); 0% (-1 to 1); -9% (-15 to -2) and -1% (-4 to 2), respectively. Quality was rated low or very low in most outcomes due to methodological flaws. Meta-analysis did not demonstrate a statistically significant decrease in the risk of temporary or definitive RLN injury and definitive EBSLN injury with the use of neuromonitoring. The neuromonitoring group had a statistically significant decrease in the risk of temporary EBSLN injury.
Statistics are critical in holding governments accountable for the well-being of citizens with di... more Statistics are critical in holding governments accountable for the well-being of citizens with disability. International initiatives are underway to improve the quality of disability statistics, but meaningful ID data is exceptionally rare. The status of ID data was evaluated in a review of 12 national statistical systems. Recurring data collection by national ministries was identified and the availability of measures of poverty, exclusion, and disadvantage was assessed. A total of 131 recurring systems coordinated by 50 different ministries were identified. The majority included general disability but less than 25% of the systems screened ID. Of these, few provided policy-relevant data. The scope of ID data was dismal at best, though a significant statistical infrastructure exists for the integration of ID data. Advocacy will be necessary. There is no optimal form of data monitoring, and decisions regarding priorities in purpose, targeted audiences, and the goals for surveillance must be resolved.
International Journal of Clinical and Experimental Medicine, Feb 1, 2008
Radiofrequency ablation (RFA) is gaining popularity for treating colorectal liver metastases by i... more Radiofrequency ablation (RFA) is gaining popularity for treating colorectal liver metastases by inducing image guided tumor hyperthermia. In order to reduce tumor recurrence, adjuvant therapies have been administered post-RFA. We hypothesized that tumor cells escaping RFA cytotoxicity by being in the sublethal zones of tumor might develop differential behavior toward cytotoxic drugs. Here, we used cultured human colorectal cancer cells to evaluate the interaction between heat treatment and chemotherapeutic agents. Human colon cancer cell lines HT29 and HCT116 were subjected to temperatures of 42° to 50°C for 15 min, in combination with 5-fluorouracil, oxaliplatin, or irinotecan at different sequences. Cytotoxicity was determined by MTT assay. The cell cycle progression was analyzed by flow cytometry with propidium iodide staining. The expression of several genes associated with drug sensitivity was quantitated by real-time RT-PCR before and after heat treatment. Either heat treatment at 45°C by simultaneous or pre-treatment with three different chemotherapeutic agents didn't affect the cytotoxicity of the combined treatment to HT29 and HCT116 cells, except for irinotecan treatment in HCT116 cells. However, when pre-exposure to 45°C, HCT116 cells, but not HT29 cells, developed resistance to these three drugs. In an analysis of cell cycle profile after the drug followed heat treatment, a longer delay in cell cycle progression in HCT116 cells was observed in comparison to HT29 cells. Furthermore, HCT116 and HT29 cells exhibited different expression profiles of several drug-related genes in response to heat treatment at 45°C. An observation of a differential response to the drug and heat treatment sequences between two human colon cancer cell lines suggests that tumor heterogeneity and selection of chemotherapeutic agents need to be under consideration in the clinical setting.
Pheochromocytomas are complex tumors that require a comprehensive, and systematic management plan... more Pheochromocytomas are complex tumors that require a comprehensive, and systematic management plan orchestrated by a multidisciplinary team. To achieve these ends, The Mount Sinai Adrenal Center hosted an interdisciplinary retreat where experts in adrenal disorders assembled with the aim of developing a clinical pathway for the management of pheochromocytomas. The result is a consensus for the diagnosis, peri-operative management, and post-operative management of pheochromocytoma with specific recommendations from our team of adrenal experts, as well as a review of the current literature. Our clinical pathway can be applied by other institutions directly or may serve as a guide for institution-specific management.
A number of histologic variants of well-differentiated papillary carcinoma have been found to be ... more A number of histologic variants of well-differentiated papillary carcinoma have been found to be associated with more aggressive tumor behavior. Tall cell, columnar cell, diffuse sclerosing, solid/trabecular, and insular variants of well-differentiated papillary thyroid cancer are all potentially more aggressive than conventional papillary thyroid cancer. When subjected to multivariate analysis, however, evidence that the histologic subtype of tumor is an independent predictor of outcome is weak. Rather, the aggressive variants tend to present with features recognized by other staging systems as associated with a worse prognosis, including higher histologic grade, extracapsular spread, large tumor size, and the presence of distant metastases. Prognosis is directly related to the presence of these features. The state of our knowledge is limited by the relatively small number of cases that have been studied. The presence of an aggressive variant of papillary carcinoma should alert the surgeon that he is dealing with a potentially aggressive tumor. Clinical treatment decisions should be based on the stage of the disease, influenced by the knowledge that the aggressive variants tend to be associated with higher risk factors. The surgeon must be prepared to perform at the first, or second stage, a total thyroidectomy, central compartment neck dissection, additional lymphadenectomy, and/or resection of invaded surrounding structures, and search for distant metastasis. Postoperative radioactive iodine should generally be administered for these variants as they will generally be intermediate to advanced tumors. The tall cell variant is often refractory to such treatment but may be susceptible to treatment targeted against BRAF mutation. External beam irradiation may be used in cases of incomplete resection.
One of the most significant complication of thyroid surgery is injury of the recurrent laryngeal ... more One of the most significant complication of thyroid surgery is injury of the recurrent laryngeal nerve. Injury of the external branch of the superior laryngeal nerve is a less obvious but occasionally significant problem. Recently, neuromonitoring during thyroidectomy has received considerable attention because of literature encouraging its use, but there is no consensus about its advantages and utility. A critical assessment of the literature on neuromonitoring was conducted in order to define its effectiveness, safety, cost-effectiveness and medical-legal impact. Available data does not show results superior to those obtained by traditional anatomical methods of nerve identification during thyroid surgery. Data about cost-effectiveness is scarce. The literature shows inconsistencies in methodology, patient selection and randomization in various published studies which may confound the conclusions of individual investigations. The current recommendation for use in "high risk" patients should be assessed because definition heterogeneity makes identification of these patients difficult. As routine use of neuromonitoring varies according to geography, its use should not be considered to be the standard of care.
Secondary and tertiary hyperparathyroidism (HPT) develop in patients with renal failure due to a ... more Secondary and tertiary hyperparathyroidism (HPT) develop in patients with renal failure due to a variety of mechanisms including increased phosphorus and fibroblast growth factor 23 (FGF23), and decreased calcium and 1,25-dihydroxy vitamin D levels. Patients present with various bone disorders, cardiovascular disease, and typical laboratory abnormalities. Medical treatment consists of controlling hyperphosphatemia, vitamin D/analog and calcium administration, and calcimimetic agents. Improved medical therapies have led to a decrease in the use of parathyroidectomy (PTX). The surgical indications include parathyroid hormone (PTH) levels >800 pg/ml associated with hypercalcemia and/or hyperphosphatemia despite medical therapy. Other indications include calciphylaxis, fractures, bone pain or pruritis. Transplant recipients often show decreased PTH, calcium and phosphorus levels, but some will have persistent HPT. Evidence suggests that PTX may cause deterioration in renal graft function in the short-term calling into the question the indications for PTX in these patients. Pre-operative imaging is only occasionally helpful except in re-operative PTX. Operative approaches include subtotal PTX, total PTX with or without autotransplantation, and possible thymectomy. Each approach has its proponents, advantages and disadvantages which are discussed. Intraoperative PTH monitoring has a high positive predictive value of cure but a poor negative predictive value and therefore is of limited utility. Hypocalcemia is the most common complication requiring aggressive calcium administration. Benefits of surgery may include improved survival, bone mineral density and alleviation of symptoms.
Neuromonitoring in thyroid surgery has been employed to make nerve identification easier and decr... more Neuromonitoring in thyroid surgery has been employed to make nerve identification easier and decrease the rates of laryngeal nerve injuries. Several individual randomized controlled trials (RCTs) have been published, which did not identify statistical differences in the rates of recurrent laryngeal nerve (RLN) or external branch of the superior laryngeal nerve (EBSLN) injuries. The objective of this report is to perform meta-analysis of the combined results of individual studies to measure the frequency of RLN and EBSLN injuries in patients who underwent thyroidectomy with routine neuromonitoring in comparison with common practice of search and identification. RCTs comparing routine neuromonitoring versus no use in patients who underwent elective partial or total thyroidectomy were evaluated. Outcomes measured were temporary and definitive palsy of the RLN and EBSLN. A systematic review and meta-analysis was done using random effects model. GRADE was used to classify quality of evidence. Six studies with 1,602 patients and 3,064 nerves at risk were identified. Methodological quality assessment showed high risk of bias in most items. Funnel plot did not reveal publication bias. The risk difference for temporary RLN palsy, definitive RLN palsy, temporary EBSLN palsy, and definitive EBSLN palsy were -2% (95% confidence interval -5.1 to 1); 0% (-1 to 1); -9% (-15 to -2) and -1% (-4 to 2), respectively. Quality was rated low or very low in most outcomes due to methodological flaws. Meta-analysis did not demonstrate a statistically significant decrease in the risk of temporary or definitive RLN injury and definitive EBSLN injury with the use of neuromonitoring. The neuromonitoring group had a statistically significant decrease in the risk of temporary EBSLN injury.
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