VISUAL OUTCOMES AFTER INTERNAL LIMITING MEMBRANE PEELING VERSUS FLAP IN THE CLOSURE OF FULL-THICKNESS MACULAR HOLES.

PURPOSE: To examine postoperative outcomes of internal limiting membrane peeling (ILMP) versus flap (ILMF) in the closure of full-thickness macular holes. METHODS: Retrospective chart review of patients who underwent pars plana vitrectomy and gas tamponade with ILMP or ILMF to close full-thickness macular hole at the Atrium Health Wake Forest Baptist from January 2012 to October 2022 with at least 3 months follow-up. Main outcome measures were type 1 primary full-thickness macular hole closure and postoperative best-corrected visual acuity in mean logMAR. RESULTS: One hundred thirty and 30 eyes underwent ILMP and ILMF, respectively. There were no significant differences in baseline characteristics between the groups. Ninety-six percent of ILMP eyes and 90% of ILMF eyes achieved primary hole closure ( P = 0.29). Among all eyes with primary hole closure, best-corrected visual acuity at 1 year was not different between the groups, but when stratified by lens status, it was superior in the ILMP versus ILMF group in pseudophakic eyes: the estimated least-squares mean best-corrected visual acuity (Snellen equivalent) (95% confidence interval) was 0.42 (20/50) (0.34, 0.49) in the ILMP group and 0.71 (20/100) (0.50, 0.92) in the ILMF group. CONCLUSION: Internal limiting membrane peeling and ILMF techniques yielded similarly high full-thickness macular hole closure rates. In pseudophakic eyes with primary hole closure, ILMF eyes had worse best-corrected visual acuity at 1 year.

False-Positive Rate for Suspected Drug-Related Deaths Following Full Autopsy.

ABSTRACT: The sharp increase in drug-related deaths has tempted medical examiner/coroner offices to perform external examinations with comprehensive toxicology testing instead of performing a standard autopsy. Compounding the problem of an increasing workload has been the decrease in available forensic pathologists. Opting for external examinations on suspected drug-related fatalities, however, is antithetical to current best practices. The purpose of this study was to review case files, autopsy reports, and toxicologic results of all deaths that were autopsied at the authors' facility and decide whether significant disease processes or injuries that would supersede the results of toxicologic testing and external examination findings alone were being missed.

Comparison of Two Techniques for Proximal Margin Analysis of Toe Amputations: A Retrospective Review.

Toe amputations are a common podiatric procedure for treatment of osteomyelitis. Whether or not the surgeon obtains a surgical cure, thus resolving the infection, can be difficult to assess. Obtaining a proximal bone margin can assist the treatment team in deciding the duration of postoperative antibiotics, need for reoperation, and postoperative care. The two senior surgeons use different methods to analyze proximal bone margins. The first surgeon obtains a microbiologic culture from the remaining bone, either at the proximal phalanx or metatarsal head, following the removal of the toe to be reviewed for osteomyelitis. Per the second surgeon's technique, the pathologist only analyzes the proximal aspect of the amputated toe for presence of osteomyelitis. Our goal is to analyze the reoperation and reamputation rates between the techniques in which the proximal margin specimens are obtained. A retrospective chart review was performed on all isolated toe or partial toe amputations from March 2017 to September 2022. There were 115 patients who met inclusion criteria. Reoperation and reamputation rates were analyzed for positive and negative infection margins from intraoperative cultures. Our study found an overall 28% reoperation rate and 26% reamputation rate for the negative margins group. In the positive proximal margin group, there was an overall 48% reoperation rate and 44% reamputation rate. Our analysis did not find a statistically significant difference between the reamputation rate in the negative margins group and the reamputation rate in the positive margins group. In conclusion, our study found that a positive proximal margin for osteomyelitis exhibited a nearly double reoperation and reamputation rate compared to patients with a negative margin, and that one margin analysis technique was not inferior to the other in regards to the need for additional surgeries.

Perioperative chemotherapy for resectable colorectal liver metastases: Analysis from the Colorectal Operative Liver Metastases International Collaborative (COLOMIC).

BACKGROUND: Chemotherapy has been increasingly combined with surgery as multimodality treatment for resectable colorectal-liver metastases (CLM). There is paucity of clinical data addressing optimal timing of chemotherapy relative to surgery. We examined outcomes of patients undergoing hepatectomy for resectable CLM. METHODS: Seven hundred and eighteen patients treated with hepatectomy for CLM were analyzed from five hepatobiliary institutions between 2000 and 2018. Overall survival (OS) was measured from time of hepatectomy for patients receiving: surgery alone, neoadjuvant, adjuvant, and neoadjuvant-plus-adjuvant (perioperative) chemotherapy. Kaplan-Meier analysis was performed to detect differences in OS between treatment groups. Single- and multi-variable analysis with Cox proportional hazards were run for OS between groups. RESULTS: One hundred and thirty-seven patients (19.08%) received surgery, 104 (14.48%) received neoadjuvant-only, 214 (29.81%) received adjuvant-only, and 263 (36.63%) received perioperative chemotherapy; with median OS of 48.20, 46.83, 56.27, and 49.93 months, respectively. No differences in median OS were seen between groups on Kaplan-Meier analysis. No significant difference in Charlson-Deyo comorbidity status was seen between groups (p = 0.853), while significant difference was seen in maximum tumor size (p = 0.0023). On multivariate analysis, adjuvant (p = 0.010) and perioperative (p = 0.020) chemotherapy were independently associated with OS compared to surgery alone. DISCUSSION: Despite group differences, chemotherapy after surgery was independently associated with improved OS in CLM.

Long-term transmural drainage of pancreatic fluid collections with double pigtail stents following lumen-apposing metal stent placement improves recurrence-free survival in disconnected pancreatic duct syndrome.

OBJECTIVES: Disconnected pancreatic duct syndrome (DPDS) is the most common cause of pancreatic fluid collection (PFC) recurrence. While long-term transmural drainage with plastic stents is the preferred endoscopic approach, there is a paucity of literature on patients undergoing initial drainage with lumen-apposing metal stents (LAMS). We describe our experience managing patients with DPDS. METHODS: A retrospective review of a prospectively maintained database (November 2015-September 2020) was performed looking at clinical outcomes and overall survival for patients undergoing endoscopic management of PFCs using LAMS. The primary outcome was to assess recurrence-free survival in PFC patients with DPDS managed with or without double pigtail stents (DPS) replacement after LAMS removal. RESULTS: Of 96 patients with PFCs, 48 with DPDS were included in the study. The median follow-up was 20.1 months. LAMS replacement with DPS was successful in 21/48 (43.8%) patients. Recurrence was seen in 1/21 (5%) patients with DPS replacement and 10/27 (37%) without DPS replacement. In multivariable models, a longer duration of LAMS placement was negatively associated with successful DPS replacement (odds ratio 1.33, 95% confidence interval [CI] 1.11, 1.59, P = 0.0019) and successful LAMS replacement with DPS in patients with DPDS improved recurrence-free survival (hazard ratio 0.09, 95% CI 0.01, 0.83, P = 0.033). CONCLUSION: In patients with PFCs and DPDS, early replacement of LAMS with DPS improves the likelihood of successful long-term transmural drainage and decreases recurrences.

Effect of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy on Quality of Life in Patients with Peritoneal Mesothelioma.

INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is an accepted treatment for peritoneal mesothelioma. In this study, we evaluated QOL after HIPEC for peritoneal mesothelioma. METHODS: This was a prospective study performed after HIPEC for peritoneal mesothelioma between 2002 and 2015. Patients completed QOL surveys, including the Short Form-36 (SF-36), Functional Assessment of Cancer Therapy + Colon (FACT-C), Brief Pain Inventory (BPI), and Center for Epidemiologic Studies Depression Scale (CES-D) preoperatively and at 3, 6, 12, and 24 months postoperatively. RESULTS: Overall, 46 patients underwent HIPEC for peritoneal mesothelioma and completed QOL surveys. Mean age was 52.8 ± 13.8 years and 52% were male. Good preoperative functional status was 70%. Median survival was 3.4 years, and 1, 3, and 5-year survivals were 77.4, 55.2, and 36.5%, respectively. CES-D score decreased at 3 months postoperatively, but increased at 24 months (p = 0.014); SF-36 physical functioning scale decreased at 3 months but returned to baseline at 12 months (p = 0.0045); and the general health scale decreased at 3 months, then improved by 6 months (p = 0.0034). Emotional well-being (p = 0.0051), role limitations due to emotional problems (p = 0.0006), social functioning (p = 0.0022), BPI (p = 0.025), least pain (p = 0.045), and worst pain (p < 0.0001) improved. FACT-C physical well-being decreased at 3 months but returned to baseline at 6 months (p = 0.020), and total FACT-C score improved at 6 months (p = 0.052). CONCLUSION: QOL returned to baseline or improved from baseline between 3 months and 1 year following surgery. Despite the risks associated with this operation, patients may tolerate HIPEC well and have good overall QOL postoperatively.

Health-Related Quality of Life After Cytoreductive Surgery/HIPEC for Mucinous Appendiceal Cancer: Results of a Multicenter Randomized Trial Comparing Oxaliplatin and Mitomycin.

BACKGROUND: This study evaluated health-related quality of life (HRQOL) using patient-reported outcomes in subjects with mucinous appendiceal neoplasms who underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as part of a randomized trial comparing mitomycin with oxaliplatin. METHODS: In this prospective multicenter study, 121 mucinous appendiceal cancer patients, with evidence of peritoneal dissemination who underwent CRS, were randomized to receive mitomycin (divided 40 mg) or oxaliplatin (200 mg/m2) for HIPEC. The Functional Assessment of Cancer Therapy Neurotoxicity (FACT-G/NTX) questionnaire was utilized to assess HRQOL. The Trial Outcome Index (TOI) is a summary index responsive to changes in physical/functional outcomes. Repeated measures mixed models with an unstructured variance matrix were applied to assess changes in HRQOL longitudinally. RESULTS: Baseline questionnaire compliance was 95.9%. Baseline physical well-being (PWB) was independently associated with overall survival (hazard ratio 0.79, 95% confidence interval 0.66-0.96; p = 0.017). The TOI was significantly lower in the mitomycin group compared with the oxaliplatin arm at 12 weeks (p = 0.044; score difference 6.35) and 24 weeks after surgery (p = 0.049; score difference 5.61). At 12 weeks after surgery, declines from baseline were significant in the TOI (p = 0.004; score decline 8.99), PWB (p < 0.001; score decline 2.83), and FWB (p < 0.001; score decline 3.42) in the mitomycin group but not the oxaliplatin group. CONCLUSIONS: Compared with mitomycin, HIPEC perfusion with oxaliplatin results in significantly better physical and functional outcomes. With similar survival outcomes and complication rates, oxaliplatin should be considered as the chemoperfusion agent of choice in mucinous appendiceal cancer patients undergoing CRS/HIPEC.

Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial.

INTRODUCTION: The effect of intensive blood pressure control upon erectile function in men with hypertension, but without diabetes, is largely unknown. AIM: To examine the effects of intensive systolic blood pressure (SBP) lowering on erectile function in a multiethnic clinical trial of men with hypertension. METHODS: We performed subgroup analyses from the Systolic Blood Pressure Intervention Trial ([SPRINT]; ClinicalTrials.gov: NCT120602, in a sample of 1255 men aged 50 years or older with hypertension and increased cardiovascular disease risk. Participants were randomly assigned to an intensive treatment group (SBP goal of <120 mmHg) or a standard treatment group (SBP goal of <140 mmHg). MAIN OUTCOME MEASURE: The main outcome measure was change in erectile function from baseline, using the 5-item International Index of Erectile Function (IIEF-5) total score, and erectile dysfunction ([ED]; defined as IIEF-5 score ≤21) after a median follow-up of 3 years. RESULTS: At baseline, roughly two-thirds (66.1%) of the sample had self-reported ED. At 48 months after randomization, we determined that the effects of more intensive blood pressure lowering were significantly moderated by race-ethnicity (p for interaction = 0.0016), prompting separate analyses stratified by race-ethnicity. In non-Hispanic whites, participants in the intensive treatment group reported slightly, but significantly better change in the IIEF-5 score than those in the standard treatment group (mean difference = 0.67; 95% CI = 0.03, 1.32; P = 0.041). In non-Hispanic blacks, participants in the intensive group reported slightly worse change in the IIEF-5 score than those in the standard group (mean difference = -1.17; 95% CI = -1.92, -0.41; P = 0.0025). However, in non-Hispanic whites and non-Hispanic blacks, further adjustment for the baseline IIEF-5 score resulted in nonsignificant differences (P > 0.05) according to the treatment group. In Hispanic/other participants, there were no significant differences in change in the IIEF-5 score between the two treatment groups (P = 0.40). In a subgroup of 280 participants who did not report ED at baseline, the incidence of ED did not differ in the two treatment groups (P = 0.53) and was without interaction by race-ethnicity. CLINICAL IMPLICATIONS: The effect of intensive treatment of blood pressure on erectile function was very small overall and likely not of great clinical magnitude. STRENGTH & LIMITATIONS: Although this study included a validated measure of erectile function, testosterone, other androgen, and estrogen levels were not assessed. CONCLUSION: In a sample of male patients at high risk for cardiovascular events but without diabetes, targeting a SBP of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in statistically significant effects on erectile function that differed in accordance with race-ethnicity, although the clinical importance of the differences may be of small magnitude. Foy CG, Newman JC, Russell GB, et al. Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial. J Sex Med 2020;17:238-248.

Hepatic arterial infusion chemotherapy for colorectal liver metastases revisited.

BACKGROUND: Recent reports indicate improved survival in patients undergoing surgical treatment for colorectal liver metastases (CRLM) with hepatic arterial infusion (HAI) pump chemotherapy compared to surgery alone. METHODS: Patients who underwent resection and/or ablation of CRLM between 1996 and 2016 were included from a single-institution prospectively maintained database. Proportional hazards regression analysis was performed to determine predictors of overall survival (OS) and 3:1 propensity score analysis (PSA). RESULTS: Of 349 patients included, 36 had HAI pumps placed (HAI group) and 313 did not (no-HAI group). There was no difference in primary tumor grade (p = 0.24), ECOG status (p = 0.44), tumor number (p = 0.1), tumor size (p = 0.56), margin status (p = 0.76) between the two groups. Median overall survival was 44.7months vs 37.1months for the HAI versus no-HAI group (p = 0.01). Cox proportional hazards regression analysis demonstrated positive margin status (HR:2.47,p < 0.0001), HAI therapy (HR:0.56,p = 0.02), preoperative chemotherapy (HR:0.69,p = 0.02) and tumor diameter (HR:1.07,p = 0.005) as predictors of OS. In 3:1 PSA, 32 HAI subjects were matched with 87 non-HAI subjects balancing all covariates. Median OS was 42.4 months versus 35.6 months for the HAI versus no-HAI group (p = 0.03). CONCLUSION: Surgical treatment of CRLM combined with HAI chemotherapy is associated with improved OS compared to surgery alone. Further study of this treatment approach is indicated.

Temporal trends in fluid management with incremental hemodialysis
.

BACKGROUND: Incremental hemodialysis (HD) is seldom prescribed in the United States. This study describes longitudinal changes in volume management in patients with incident end-stage kidney disease (ESKD) initiated on bi-weekly (twice a week) HD, later converted to thrice-weekly HD. MATERIALS AND METHODS: 23 patients (mean age 65.6 years, 48% male, and 30% black) were included. Repeated measurement analysis of regression was used to test for differences in interdialytic weight gain (IDWG) and ultrafiltration rate (UFR) over three dialysis periods: the first 3 months of bi-weekly HD, the last 3 months of bi-weekly HD, and the first 3 months of thrice-weekly HD. RESULTS: The mean transition time to thrice-weekly HD was 332.9 days. Compared to the first 3 months of HD, the IDWG and UFR increased by 0.6 kg and 2.2 mL/kg/h in the last 3 months of bi-weekly HD (p = 0.02 and 0.009, respectively) and by 0.7 kg and 2.1 mL/kg/h in the first 3 months of thrice-weekly HD (p = 0.002). The average proportion of patients with IDWG > 5.7% of the dry weight was 0% in the first 3 months of bi-weekly HD, 12% in the last 3 months of bi-weekly HD, and 4% in the first 3 months of thrice-weekly HD; while the average proportion of patients with UFR > 10 mL/kg/h was 16%, 39%, and 25%, respectively. CONCLUSION: Fluid management in incident-ESKD patients receiving bi-weekly HD deteriorates prior to conversion to thrice-weekly HD. Further studies are needed to optimize the prescription of incremental HD.

PCI is Not Predictive of Survival After Complete CRS/HIPEC in Peritoneal Dissemination from High-Grade Appendiceal Primaries.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option in patients with carcinomatosis from high-grade appendiceal (HGA) primaries. It is unknown if there is a Peritoneal Carcinomatosis Index (PCI) upper limit above which a complete CRS/HIPEC does not assure long-term survival. METHODS: Retrospective analysis from three centers was performed. The PCI was used to grade volume of of disease. Survival in relation to PCI was studied on patients with complete cytoreduction. RESULTS: Overall, 521 HGA patients underwent CRS/HIPEC from 1993 to 2015, with complete CRS being achieved in 50% (260/622). Mean PCI was 14.8 (standard deviation 8.7, range 0-36). Median survival for the complete CRS cohort was 6.1 years, while 5- and 10-year survival was 51.7% (standard error [SE] 4.6) and 36.1% (SE 6.3), respectively. Arbitrary cut-off PCI limits with 5-point splits (p = 0.63) were not predictive of a detrimental effect on survival as long as a complete CRS was achieved. A linear effect of the PCI on survival (p = 0.62) was not observed, and single-point PCI cohort splits within a PCI range of < 5 to > 10 were not predictive of survival for complete CRS patients. The PCI correlated with the ability to achieve a complete CRS, with a mean PCI of 14.7 (8.7) for completeness of cytoreduction (CC)0, 22.3 (7.8) for CC1 and 26.1 (9.5) for CC2/3 resections (p = 0.0001, hazard ratio 1.12, 95% confidence interval 1.09), with an HR of 1.15 for each 1-unit increase in the PCI score. Only 21% of the cohort achieved a complete CRS with a PCI ≥ 21. CONCLUSIONS: The PCI correlates with the ability to achieve a complete CRS in carcinomatosis from HGA. PCI is not associated with survival as long as a complete CRS can be achieved.

Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has dramatically improved the survival of patients with epithelioid peritoneal mesothelioma. It is unknown if CRS/HIPEC is indicated for the more aggressive biphasic mesothelioma variant. METHODS: A retrospective analysis of the Peritoneal Surface Oncology Group International (PSOGI) registry including data from 33 centers was performed. Survival was reviewed based on mesothelioma type, completion of cytoreduction, and volume of disease. RESULTS: Overall, 484 of 1165 (41.5%) CRS/HIPEC procedures with complete CC0 and CC1 cytoreductions were analyzed; 450 (93%) procedures were performed for epithelioid mesotheliomas, while 34 (7%) were performed for biphasic mesotheliomas. For patients with CC0 resection, 5-year survival was 64.5 and 50.2% (median 7.8 and 6.8 years; p = 0.015) for epithelioid and biphasic mesotheliomas, respectively, while inclusion of CC1 resections in the analysis resulted in inferior 5-year survival of 62.9% and 41.6% (median 7.8 and 2.8 years; p = 0.0012), respectively. Incomplete CC2 resections for biphasic primaries resulted in a median survival of 4.3 months. Univariate analysis of the biphasic cohort indicated Peritoneal Cancer Index (PCI; p = 0.015), CC status of resection (p < 0.0001), and Ki67 (p = 0.04) as predictors of survival. Systemic chemotherapy before (p = 0.55) or after (p = 0.7) CRS/HIPEC did not influence survival. In multivariate analysis, only PCI (p = 0.03) and CC (p = 0.04) remained significant. CONCLUSIONS: Long-term survival is achievable in patients with low-volume biphasic mesothelioma after complete macroscopic cytoreduction. Biphasic peritoneal mesotheliomas should not be considered as an absolute contraindication for CRS/HIPEC if there is low-volume disease and if complete cytoreduction can be achieved.

Preclinical medical student observations associated with later professionalism concerns.

PURPOSE: Professionalism is a core physician competency and identifying students at risk for poor professional development early in their careers may allow for mentoring. This study identified indicators in the preclinical years associated with later professionalism concerns. METHODS: A retrospective analysis of observable indicators in the preclinical and clinical years was conducted using two classes of students (n = 226). Relationships between five potential indicators of poor professionalism in the preclinical years and observations related to professional concerns in the clinical years were analyzed. RESULTS: Fifty-three medical students were identified with at least one preclinical indicator and one professionalism concern during the clinical years. Two observable preclinical indicators were significantly correlated with unprofessional conduct during the clinical years: Three or more absences from attendance-required sessions (odds ratio 4.47; p=.006) and negative peer assessment (odds ratio 3.35; p=.049). CONCLUSIONS: We identified two significant observable preclinical indicators associated with later professionalism concerns: excessive absences and negative peer assessments. Early recognition of students at risk for future professionalism struggles would provide an opportunity for proactive professional development prior to the clinical years, when students' permanent records may be affected. Peer assessment, coupled with attention to frequent absences, may be a method to provide early recognition.

Conditional Survival After Cytoreductive Surgery with Heated Intraperitoneal Chemotherapy for Low- and High-Grade Appendiceal Primaries.

INTRODUCTION: Survival of patients after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy for appendiceal neoplasms is projected by conventional overall survival (OS) curves that do not address the survival time a patient has already accrued. We sought to study the conditional survival (CS) after CRS, contingent on patients surviving a fixed duration of time after surgery. METHODS: A retrospective analysis of 493 appendiceal cancer patients from a prospective database was performed. OS was calculated for patients who achieved a complete CRS. CS was estimated based on Kaplan-Meier curves to determine what the patient's long-term survival (3-, 5-, 7-, or 10-year) would be if they were alive at 1, 2, or 3 years from surgery. RESULTS: OS at 5 and 10 years for 137 low-grade patients with complete resections was 83.3 and 74.2 %, respectively. For low-grade patients still alive at 3 years, 5- and 10-year CS was 93.4 and 83.2 %, respectively. For the 35 high-grade patients with complete CRS who survived to 3 years, CS at 10 years was 41.7 %, while their 10-year conventional OS was 24.6 %. CONCLUSIONS: Conventional analysis underestimates OS due to unpredictable variations in tumor biology. When adjusted for time already elapsed since surgery, improvements in survival estimates are more pronounced with high-grade tumors. CS outcomes can be used in determining the optimal frequency of long-term follow-up of these patients.

Peritoneal surface disease (PSD) from appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): overview of 481 cases.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) used to treat peritoneal surface disease (PSD) from appendiceal cancer have shown variability in survival outcomes. The primary goal of this study was to determine predictors of surgical morbidity and overall survival. The secondary goal was to describe the impact of nodal status on survival after CRS/HIPEC for PSD from low-grade appendiceal (LGA) and high-grade appendiceal (HGA) primary lesions. METHODS: A retrospective analysis of 1,069 procedures from a prospective database was performed. Patient characteristics, tumor grade, nodal status, performance status, resection status, morbidity, mortality, and survival were reviewed. RESULTS: The study identified 481 CRS/HIPEC procedures: 317 (77.3 %) for LGA and 93 (22.7 %) for HGA lesions. The median follow-up period was 44.4 months, and the 30-day major morbidity and mortality rates were respectively 27.8 and 2.7 %. Major morbidity was jointly predicted by incomplete cytoreduction (p = 0.0037), involved nodes (p < 0.0001), and comorbidities (p = 0.003). Multivariate negative predictors of survival included positive nodal status (p = 0.003), incomplete cytoreduction (p < 0.0001), and preoperative chemotherapy (p = 0.04) in LGA patients and incomplete cytoreduction (p = 0.0003) and preoperative chemotherapy (p = 0.0064) in HGA patients. After complete cytoreduction, median survival was worse for patients with positive nodes than for those with negative nodes in LGA (85 months vs not reached [82 % alive at 90 months]; p = 0.002) and HGA (30 vs 153 months; p < 0.0001). CONCLUSIONS: Positive nodes are associated with decreased survival not only for HGA patients but also for LGA patients even after complete cytoreduction. Nodal status further stratifies histologic grade as a prognostic indicator of survival. Patients with node-negative HGA primary lesions who receive a complete cytoreduction may experience survival comparable with that for LGA patients.

Trajectories of Posttraumatic Growth and Associated Characteristics in Women with Breast Cancer.

BACKGROUND: Cancer survivors may experience posttraumatic growth (PTG), positive psychological changes resulting from highly stressful events; however, the longitudinal course of PTG is poorly understood. PURPOSE: The purpose of the present study was to determine trajectories of PTG in breast cancer survivors and associated characteristics. METHODS: Women (N = 653) participating in a longitudinal observational study completed questionnaires within 8 months of breast cancer diagnosis and 6, 12, and 18 months later. Group-based modeling identified PTG trajectories. Chi-square tests and ANOVA detected group differences in demographic, medical, and psychosocial variables. RESULTS: Six trajectory groups emerged. Three were stable at different levels of PTG, two increased modestly, and one increased substantially over time. Trajectory groups differed by age, race, receipt of chemotherapy, illness intrusiveness, depressive symptoms, active-adaptive coping, and social support. CONCLUSIONS: This first examination of PTG trajectories in US cancer survivors elucidates heterogeneity in longitudinal patterns of PTG. Future research should determine whether other samples exhibit similar trajectories and whether various PTG trajectories predict mental and physical health outcomes.

Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia.

BACKGROUND: Hyperkalemia is a potentially life-threatening condition that is common in kidney disease patients. Insulin is used to treat hyperkalemia, but may cause hypoglycemia, especially in kidney disease when insulin may be metabolized more slowly. OBJECTIVE: We compared the rates of hypoglycemia in patients with low estimated glomerular filtration rate (eGFR) using high versus low doses of insulin for hyperkalemia to determine if lower doses of insulin would decrease the incidence of hypoglycemia. METHODS: This was a retrospective study of hospitalized patients receiving intravenous insulin for hyperkalemia during a 6-month period. Patients with low eGFR were analyzed based on how much insulin they received: high dose (10 units, n = 78) versus low dose (5 units, n = 71). Postdose nadir blood glucose values were examined for up to 8 hours after the dose. The percentage of hypoglycemia (blood glucose ≤70 mg/dl) and a subset of severe hypoglycemia (blood glucose <50 mg/dl) were then reported for each dose group. RESULTS: A total of 149 doses were identified in patients with low eGFR. The rates of hypoglycemia were 16.7% and 19.7% (P = 0.79), respectively, among high-dose (n = 78) and low-dose (n = 71) groups. Rates of severe hypoglycemia were 8.9% and 7.0%, respectively (P = 0.90). More than 28% of hypoglycemic episodes with high doses occurred after 4 hours (median = 2.5 hours) compared with 14.3% with low doses (median = 2.38 hours). CONCLUSION: There was no difference in the rate of hypoglycemia or severe hypoglycemia between high or low doses of insulin in patients with low eGFR. We recommend monitoring up to 6 hours after insulin use in hyperkalemia.

Detection of diabetic nephropathy from advanced glycation endproducts (AGEs) differs in plasma and urine, and is dependent on the method of preparation.

Increased advanced glycation endproducts (AGEs) and oxidation products (OPs) have been proposed as pathogenic for diabetic nephropathy (DN). We investigated the relationship between AGEs and OPs measured in different plasma and urine preparations, and progression of DN in 103 young, normoalbuminuric, normotensive participants with type 1 diabetes in the Natural History of Diabetic Nephropathy Study. The primary endpoint was electron microscopy-measured change in glomerular basement membrane (GBM) width from baseline to 5 years; change in mesangial fractional volume was a secondary endpoint. Fast progressors (FP) were defined as the upper quartile (n = 24) of rate of GBM thickening; slow progressors (SP) were the remainder (n = 79). Four AGEs [3-deoxyglucosone and methylglyoxal hydroimidazolones (DG3H1, MGH1) and carboxymethyl and ethyl lysine (CML, CEL)], and two oxidation products methionine sulfoxide and aminoadipic acid were measured by liquid chromatography, triple quadrupole mass spectrometry. Measurements were done on 10 K plasma filtrates and plasma proteolytic digests (PPD) at year 5, and at four time points over 5 years for urinary 10 K filtrates. Urinary filtrate CEL levels were significantly higher in FP, but not after adjustment for HbA1c, sex, and duration of diabetes. MGHI, CEL, and CML plasma filtrate levels were significantly higher in FP relative to SP (p < 0.05). In PPD, only MGHI showed borderline significantly higher levels in FP relative to SP (p = 0.067), while no other product showed correlation. AGE and OP measurements were not correlated with mesangial expansion. In plasma filtrates, HbA1c at year 5 accounted for 4.7 % of the variation in GBM width. The proportion of variation in GBM width was increased to 11.6 % when MGHI, CEL, and CML were added to the model (6.9 % increase).

Molecular determinants of susceptibility to oncolytic vesicular stomatitis virus in pancreatic adenocarcinoma.

BACKGROUND: M protein mutant vesicular stomatitis virus (M51R-VSV) has oncolytic properties against many cancers. However, some cancer cells are resistant to M51R-VSV. Herein, we evaluate the molecular determinants of vesicular stomatitis virus (VSV) resistance in pancreatic adenocarcinoma cells. METHODS: Cell viability and the effect of ß-interferon (IFN) were analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Gene expression was evaluated via microarray analysis. Cell infectability was measured by flow cytometry. Xenografts were established in athymic nude mice and treated with intratumoral M51R-VSV. RESULTS: Four of five pancreatic cancer cell lines were sensitive to M51R-VSV, whereas Panc 03.27 cells remained resistant (81 ± 3% viability 72 h after single-cycle infection). Comparing sensitive MiaPaCa2 cells with resistant Panc 03.27 cells, significant differences in gene expression were found relating to IFN signaling (P = 2 × 10(-5)), viral entry (P = 3 × 10(-4)), and endocytosis (P = 7 × 10(-4)). MiaPaCa2 cells permitted high levels of VSV infection, whereas Panc 03.27 cells were capable of resisting VSV cell entry even at high multiplicities of infection. Extrinsic ß-IFN overcame apparent defects in IFN-mediated pathways in MiaPaCa2 cells conferring VSV resistance. In contrast, ß-IFN decreased cell viability in Panc 3.27 cells, suggesting intact antiviral mechanisms. VSV-treated xenografts exhibited reduced tumor growth relative to controls in both MiaPaCa2 (1423 ± 345% versus 164 ± 136%; P < 0.001) and Panc 3.27 (979 ± 153% versus 50 ± 56%; P = 0.002) tumors. Significant lymphocytic infiltration was seen in M51R-VSV-treated Panc 03.27 xenografts. CONCLUSIONS: Inhibition of VSV endocytosis and intact IFN-mediated defenses are responsible for M51R-VSV resistance in pancreatic adenocarcinoma cells. M51R-VSV treatment appears to induce antitumor cellular immunity in vivo, which may expand its clinical efficacy.

Impact of health insurance education program on health care professional students: An interventional study.

In the complex landscape of health care, the relationship between medical practice and health insurance is increasingly crucial for effective care delivery. This paper emphasises the importance of integrating health insurance education into medical training, focusing on its impact on patient outcomes, health care accessibility, and system sustainability. It posits that health care providers with a comprehensive understanding of health insurance can offer more informed, efficient care by adeptly navigating coverage complexities. The study utilised a pretest-post-test design with a yearlong health insurance education curriculum at Wake Forest University School of Medicine. Student participants from various medical programmes self-assessed their knowledge and comfort across 13 health insurance topics before and after the intervention. The curriculum included workshops and a capstone project, emphasising real-life patient insurance challenges. Results show statistically significant improvements in 13 participants' understanding of health insurance concepts, highlighting the curriculum's effectiveness. The findings advocate for the inclusion of health insurance education in medical curricula. Such knowledge is vital in systems with diverse insurance models, like the United States, where understanding insurance intricacies is key to patient care. The study's limitations, such as a small sample size and reliance on self-reported data, suggest the need for further research with more participants and objective measures. In conclusion, incorporating health insurance education into medical training is essential for preparing health care professionals to navigate insurance complexities, make informed treatment decisions, and guide patients effectively. This approach fosters well-rounded professionals capable of managing both medical and financial aspects of patient care, leading to more equitable and efficient health care delivery. Future research should explore the long-term effects of this education on clinical practice and patient outcomes, particularly its impact on health care costs and patient satisfaction.