Impact of Sodium Thiosulfate on Prevention of Nephrotoxicities in HIPEC: An Ancillary Evaluation of Cisplatin-Induced Toxicities in Ovarian Cancer.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary. METHODS: A prospective, nonrandomized, clinical trial evaluated safety outcomes of HIPEC with cisplatin 75 mg/m2 during cytoreductive surgery (CRS) in patients with EOC (n = 34) and endometrial cancer (n = 6). Twenty-one patients received no ST (nST), and 19 received ST. Adverse events (AEs) were reported according to CTCAE v.5.0. Serum creatinine (Cr) was collected preoperatively and postoperatively (Days 5-8). Progression-free survival (PFS) was followed. Normal peritoneum was biopsied before and after HIPEC for whole transcriptomic sequencing to identify RNAseq signatures correlating with AEs. RESULTS: Forty patients had HIPEC at the time of interval or secondary CRS. Renal toxicities in the nST group were 33% any grade AE and 9% grade 3 AEs. The ST group demonstrated no renal AEs. Median postoperative Cr in the nST group was 1.1 mg/dL and 0.5 mg/dL in the ST group (p = 0.0001). Median change in Cr from preoperative to postoperative levels were + 53% (nST) compared with - 9.6% (ST) (p = 0.003). PFS did not differ between the ST and nST groups in primary or recurrent EOC patients. Renal AEs were associated with downregulation of metabolic pathways and upregulation of immune pathways. CONCLUSIONS: ST significantly reduces acute renal toxicity associated with HIPEC with cisplatin in ovarian cancer patients. As nephrotoxicity is high in HIPEC with cisplatin, nephroprotective agents should be considered.

Primary hemiarthroplasty after unstable trochanteric fracture in elderly patients: mortality, readmission and reoperation.

BACKGROUND: Most unstable trochanteric fractures are treated with internal fixation and often with high complication rates. Hemiarthroplasty might be an alternative method in difficult condition, especially in unstable comminuted fracture in fragile bone. However, few have investigated the long-term outcomes after hemiarthroplasty for unstable trochanteric fracture. We conducted a population-based retrospective cohort study of trochanteric fracture after primary hemiarthroplasty using competing risk analysis on their long-term outcomes, including mortality, readmission and reoperation. METHODS: We studied a total of 2798 patients over 60 years old, with a mean age of 79 years, of which 68% are females and 67.23% have at least one comorbidity. They underwent a hemiarthroplasty for unstable trochanteric fracture during the period between January 1, 2000 and December 31, 2010 and were follow-up until the end of 2012, or death. Survival analysis and Cox model were used to characterize mortality. Competing risk analysis and Fine and Gray model were used to estimate the cumulative incidences of the first readmission and the first reoperation. RESULTS: The follow-up mortality rate for 1-year was 17.94%; 2-year, 29.76%; 5-year, 56.8%; and 10-year, 83.38%. The cumulative incidence of the first readmission was 16.4% for 1-year and 22.44% for 3-year. The cumulative incidence of the first reoperation was 13.87% for 1-year, 18.11% for 2-year, 25.79% for 5-year, and 38.24% for 10-year. Male gender, older age, higher Charlson Comorbidity Index (CCI) and lower insured amount were all risk factors for the overall mortality. Older age and higher CCI were risk factors for the first readmission. Older age was a protective factor for reoperation, which is likely due to the competing death. CONCLUSIONS: The mortality and revision rates after hemiarthroplasty for unstable trochanteric fracture are acceptable as a salvage procedure for this fragile sub-population.

Differential Inhibitory Configurations Segregate Frequency Selectivity in the Mouse Inferior Colliculus.

Receptive fields and tuning curves of sensory neurons represent the neural substrates that allow animals to efficiently detect and distinguish external stimuli. They are progressively refined to create diverse sensitivity and selectivity for neurons along ascending central pathways. However, the neural circuitry mechanisms have not been directly determined for such fundamental qualities in relation to sensory neurons' functional organizations, because of the technical difficulty of correlating neurons' input and output. Here, we obtained spike outputs and synaptic inputs from the same neurons within characteristically defined neural ensembles, to determine the synaptic mechanisms driving their diverse frequency selectivity in the mouse inferior colliculus. We find that the synaptic strength and timing of excitatory and inhibitory inputs are configured differently and independently within individual neurons' receptive fields, which segregate sensitive and selective neurons and endow neural populations with broad receptive fields and sharp frequency tuning. By computationally modeling spike outputs from integrating synaptic inputs and comparing them with real spike responses of the same neurons, we show that space-clamping errors did not qualitatively affect the estimation of spike responses derived from synaptic currents in in vivo voltage-clamp recordings. These data suggest that heterogeneous inhibitory circuits coexist locally for a parallel but differentiated representation of incoming signals.SIGNIFICANCE STATEMENT Sensitivity and selectivity are functional qualities of sensory systems to facilitate animals' survival. There is little direct evidence for the synaptic basis of neurons' functional variance within neural ensembles. Here we adopted a novel framework to fill such a long-standing gap by uniting population activities with single cells' spike outputs and their synaptic inputs. Furthermore, the effects of space-clamping errors on subcortical synaptic currents were evaluated in vivo, by comparing recorded spike responses and simulated spike outputs from computationally integrating synaptic inputs. Our study illustrated that the synaptic strength and timing of inhibition relative to excitation can be configured differently for neurons within a defined neural ensemble, to segregate their selectivity. It provides new insights into coexisting heterogeneous local circuits.

Cc2d1a Loss of Function Disrupts Functional and Morphological Development in Forebrain Neurons Leading to Cognitive and Social Deficits.

Loss-of-function (LOF) mutations in CC2D1A cause a spectrum of neurodevelopmental disorders, including intellectual disability, autism spectrum disorder, and seizures, identifying a critical role for this gene in cognitive and social development. CC2D1A regulates intracellular signaling processes that are critical for neuronal function, but previous attempts to model the human LOF phenotypes have been prevented by perinatal lethality in Cc2d1a-deficient mice. To overcome this challenge, we generated a floxed Cc2d1a allele for conditional removal of Cc2d1a in the brain using Cre recombinase. While removal of Cc2d1a in neuronal progenitors using Cre expressed from the Nestin promoter still causes death at birth, conditional postnatal removal of Cc2d1a in the forebrain via calcium/calmodulin-dependent protein kinase II-alpha (CamKIIa) promoter-driven Cre generates animals that are viable and fertile with grossly normal anatomy. Analysis of neuronal morphology identified abnormal cortical dendrite organization and a reduction in dendritic spine density. These animals display deficits in neuronal plasticity and in spatial learning and memory that are accompanied by reduced sociability, hyperactivity, anxiety, and excessive grooming. Cc2d1a conditional knockout mice therefore recapitulate features of both cognitive and social impairment caused by human CC2D1A mutation, and represent a model that could provide much needed insights into the developmental mechanisms underlying nonsyndromic neurodevelopmental disorders.

Factors Predicting Use of Neoadjuvant Chemotherapy Compared With Primary Debulking Surgery in Advanced Stage Ovarian Cancer-A National Cancer Database Study.

OBJECTIVES: We performed a patterns-of-care study to characterize the types of patients with epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT) versus primary debulking surgery (PDS) using the National Cancer Database (NCDB). METHODS: We identified patients with stages IIIC and IV EOC in the NCDB diagnosed from 2003 to 2011. Patients who received chemotherapy (CT) prior to surgery were classified as receiving NACT; if surgery preceded CT, then it was classified as PDS. Data collected from the NCDB included demographics, medical comorbidity index, cancer characteristics and treatment, and hospital characteristics. Univariate and multivariable analyses were performed using χ test, logistic regression, log-rank test, and Cox proportional hazards modeling as indicated. Statistical significance was set at P < 0.05. RESULTS: A total of 62,727 patients with stages IIIC and IV EOC were identified. The sequence of surgery and CT was identified, of which 6922 (11%) had NACT and 31,280 (50%) had PDS. Neoadjuvant CT was more frequently done in stage IV than stage IIIC (13% vs 9%), and its use markedly increased over time. Variables associated with increased likelihood of NACT use were as follows: age older than 50 years and those with higher comorbidities, stage IV, and higher-grade EOC. Neoadjuvant CT use was also associated with hospitals that were adherent to the National Comprehensive Cancer Network guidelines, high-volume facilities, those in the Midwest and West, and academic centers. CONCLUSIONS: Evidence suggests that patients with greater adverse risk factors are more likely to receive NACT instead of PDS. Use of NACT has significantly increased over the study period, especially in patients with stage IV ovarian cancer.

Mortality, readmission, and reoperation after hip fracture in nonagenarians.

BACKGROUND: Osteoporotic hip fractures are associated with high mortality and morbidity in people of advanced age; however, few studies have investigated the complication rates in nonagenarians. In this study, we applied a competing risk analysis to estimate the mortality, readmission, and reoperation rates after surgery for hip fracture among nonagenarians. METHODS: A total of 11,184 nonagenarians (aged ≥ 90) who received surgery for hip fracture during the period 1 January 1997 and 31 December 2010 were selected from Taiwan's National Health Insurance (NHI) database. Nonagenarians were followed up until the end of 2012, death, or the date they left the NHI program. Cumulative mortality was estimated using the Kaplan-Meier analysis and risk factors for mortality were investigated using a Cox proportional hazards model. Competing risk analysis was used to estimate cumulative incidence rates and to assess the risk factors for reoperation and readmission. RESULTS: The mortality rates were 29.5% at 1 year, 45.0% at 2 years and 78.1% at 5 years. The cumulative incidence rates of reoperation were 7.3% at 1 year, 9.2% at 2 years and 11.6% at 5 years whereas those of readmission were 18.9% at 1 month and 24.1% at 3 months. Significant risk factors for death included age, male gender, trochanteric fracture, and higher Charlson comorbidity index (CCI) whereas those for reoperation were age, cervical fracture and higher CCI. Furthermore, age, male gender, and higher CCI were risk factors for readmission. CONCLUSIONS: The overall 2-years mortality rate among nonagenarians in Taiwan was around 45%, the 2-years reoperation rate was around 9% and the 90-days medical complication rate was around 24%. High complication rates are associated with increased risk for death. Postoperative care to prevent medical complications is likely the most effective strategy to reduce mortality rates among nonagenarians with hip fracture.

Disparities in treatment and survival for women with endometrial cancer: A contemporary national cancer database registry analysis.

PURPOSE: The study aim was to identify contemporary socioeconomic, racial, ethnic, and facility-related factors associated with stage at diagnosis, receipt of cancer treatment, and survival in women with endometrial cancer (EC). PATIENTS AND METHODS: Women diagnosed with EC between 1998 and 2010 were identified from the National Cancer Database. Variables associated with the outcomes of interest were assessed using multivariable Cox proportional hazards and logistic regression. RESULTS: Among 228,511 women identified, the percentage of blacks with stage IIIC/IV disease at diagnosis was nearly twice that of non-Hispanic whites (17.8% vs 9.8%; P<0.001). Patients with advanced disease who were insured with Medicare were less likely to receive standard-of-care postoperative radiotherapy and/or chemotherapy than those with private insurance (odds ratio: OR 0.80, P<0.001), as were those residing in the South (reference) in comparison to the Northeast, Atlantic, Great Lakes, and Midwest regions (OR 1.3-1.7, all P<0.001). Those residing in the Mountain region were even less likely to receive appropriate treatment (OR 0.7, P<0.001). Five-year stage IIIC/IV survival was 42.8% for non-Hispanic whites vs 24.6% for blacks (hazard ratio 1.3, P<0.001). Other factors associated with inferior 5-year survival included payer status (not insured, Medicaid, Medicare, vs private, ORs 1.2-1.3, all P<0.01), and treatment at low-volume centers (<5 vs ≥30cases/year, HR 1.3, P<0.001). CONCLUSIONS AND RELEVANCE: Socioeconomic, geographic and facility-related factors predict advanced endometrial cancer stage, failure to receive cancer care, and shorter survival. Black women had especially poor survival. Nationwide standardization and concentration of treatment at high-volume centers may improve outcomes.

Refusal of Recommended Chemotherapy for Ovarian Cancer: Risk Factors and Outcomes; a National Cancer Data Base Study.

OBJECTIVE: To identify risk factors associated with refusal of recommended chemotherapy and its impact on patients with epithelial ovarian cancer (EOC). METHODS: We identified patients in the National Cancer Data Base diagnosed with EOC from January 1998 to December 2011. Patients who refused chemotherapy were identified and compared with those who received recommended, multiagent chemotherapy. Univariate and multivariable analyses were performed using chi-square test with Bonferroni correction, binary logistic regression, log-rank test, and Cox proportional hazards modeling. The threshold for statistical significance was set at a P value of less than 0.05. RESULTS: From a cohort of 147,713 eligible patients, 2,707 refused chemotherapy. These patients were compared with 92,212 patients who received recommended multiagent chemotherapy. Older age, more medical comorbidities, not having insurance, and later year of diagnosis were directly and significantly associated with chemotherapy refusal when analyzed using multivariable logistic regression. In addition, lower-than-expected facility adherence to NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer, treatment at low-volume center, lower grade, and higher stage were all significantly and independently associated with chemotherapy refusal. Median overall survival of patients who received multiagent chemotherapy was significantly longer than that of those who refused chemotherapy (43 vs 4.8 months; P<.0005). After controlling for known patient, facility, and disease prognostic factors, chemotherapy refusal is significantly associated with increased risk of death. CONCLUSIONS: Refusal of recommended chemotherapy carries significant risk of early death from ovarian cancer. Our data demonstrate that the decision to refuse chemotherapy is multifactorial and, in addition to unalterable factors (eg, stage/grade, age), involves factors that can be changed, including facility type and payor. Efforts at addressing these discrepancies in care can improve compliance with chemotherapy recommendations in the NCCN Guidelines for Ovarian Cancer and outcomes.

Balance or imbalance: inhibitory circuits for direction selectivity in the auditory system.

The auditory system detects and processes dynamic sound information transmitted in the environment. Other than the basic acoustic parameters, such as frequency, amplitude and phase, the time-varying changes of these parameters must also be encoded in our brain. Frequency-modulated (FM) sound is socially and environmentally significant, and the direction of FM sweeps is essential for animal communication and human speech. Many auditory neurons selectively respond to the directional change of such FM signals. In the past half century, our knowledge of auditory representation and processing has been updated frequently, due to technological advancement. Recently, in vivo whole-cell voltage clamp recordings have been applied to different brain regions in sensory systems. These recordings illustrate the synaptic mechanisms underlying basic sensory information processing and provide profound insights toward our understanding of neural circuits for complex signal analysis. In this review, we summarize the major findings of direction selectivity at several key auditory regions and emphasize on the recent discoveries on the synaptic mechanisms for direction selectivity in the auditory system. We conclude this review by describing promising technical developments in dissecting neural circuits and future directions in the study of complex sound analysis.

Incidence and excess mortality of hip fracture in young adults: a nationwide population-based cohort study.

BACKGROUND: This study assessed the incidence and excess mortality of hip fractures among inpatients aged 20-40 years in a nationwide population database in Taiwan. METHODS: Subjects were selected from Taiwan's National Health Insurance Research Database for the period 2001-2008 and were followed up until the end of 2010. A total of 4,523 subjects were admitted for the first time with primary diagnosis of hip fracture and treated with operation. RESULTS: The overall annual incidence, mortality, and standardized mortality ratio (SMR) decreased from 7.68 to 7.23 per 100,000, from 1.37 % to 0.94 %, and from 9.06 to 6.71, respectively, from 2001 to 2008. The 1-year, 2-year, 3-year, 5-year, and 10-year mortality rates were 1.28 %, 2.44 %, 3.54 %, 5.32 %, and 10.50 %, respectively for the whole cohort. The 1-year, 2-year, 3-year, 5-year, and 10-year SMRs were 8.33, 7.59, 7.28, 6.39, and 5.82, respectively, for the whole cohort. Risk factors for overall death were male gender, trochanteric fracture, hemiarthroplasty, and higher Charlson comorbidity index (CCI) scores. CONCLUSIONS: The high SMRs found in the present study suggest that young adults with former hip fracture should be closely followed up to prevent early mortality.

Impact of adjuvant chemotherapy with radiation for node-positive vulvar cancer: A National Cancer Data Base (NCDB) analysis.

BACKGROUND: For node-positive vulvar cancer, adjuvant radiotherapy has an established benefit, whereas the impact of chemotherapy is unknown. A National Cancer Data Base (NCDB) analysis was conducted to determine patterns of care and evaluate the survival impact of adjuvant chemotherapy. METHODS: The NCDB was queried for vulvar cancer patients diagnosed from 1998-2011 who underwent extirpative surgery with confirmed inguinal nodal involvement treated with adjuvant radiotherapy. Patients with inadequate follow-up or non-squamous histologies were excluded. Chi-square test, logistic regression analysis, log-rank test and multivariable Cox proportional regression modeling with adjustment using propensity score with inverse probability of treatment weights (IPTW) were conducted to establish factors associated with utilization and survival. RESULTS: A total of 1797 patients were identified: 26.3% received adjuvant chemotherapy and 76.6% had 1-3 involved lymph nodes. Adoption of adjuvant chemotherapy significantly increased over time, from 10.8% in 1998 to 41.0% in 2006 (p<0.001). Lower utilization was seen in older patients, Northeast or Southern facilities, and patients with more extensive nodal dissection, whereas greater number of involved nodes, stage IVA disease and positive surgical margins led to a higher probability of receiving chemotherapy. Unadjusted median survival without and with adjuvant chemotherapy was 29.7months and 44.0months (p=0.001). On IPTW-adjusted Cox proportional regression modeling, delivery of adjuvant chemotherapy resulted in a 38% reduction in the risk of death (HR 0.62, 95% CI 0.48-0.79, p<0.001). CONCLUSION: In a large population-based analysis, adjuvant chemotherapy resulted in a significant reduction in mortality risk for node-positive vulvar cancer patients who received adjuvant radiotherapy.

Mortality and complications after hip fracture among elderly patients undergoing hemodialysis.

BACKGROUND: Osteoporotic hip fractures cause high mortality and morbidity in elderly adults. Compared to the general population, subjects with end-stage renal disease and hemodialysis often develop mineral bone disorders and have a higher risk for hip fractures. METHODS: We conducted a matched cohort study design and used competing risk analysis to estimate the cumulative incidence of the complication rate. Subjects aged greater than 60 years with hip fracture were selected from Taiwan's National Health Insurance Research Database covering a period from 1997 to 2007, and these subjects were followed up until 2009. We used the Kaplan-Meier method to estimate the overall survival and used the log-rank test and multiple Cox proportional hazards model to explore the risk factors for survival. The cumulative incidence of the first complication was estimated using competing risk analysis. RESULTS: Among hemodialysis subjects, the three-month, one-year, two-year and five-year mortality rates were 17.3 %, 37.2 %, 51.5 %, and 80.5 %, respectively; the one-year and five-year cumulative incidences of the first surgical complication were 14.2 % and 20.6 %, respectively; and the three-month cumulative incidence of the first medical complication was 24.1 %. Hemodialysis subjects presented a 2.32 times (95 % CI: 2.16-2.49) higher hazard ratio of overall death, 1.15 times (95 % CI: 1.01-1.30) higher sub-hazard ratio (sub-HR) of surgical complications, and 1.35 times (95 % CI: 1.21-1.52) higher sub-HR of the first medical complication than non-hemodialysis controls. CONCLUSIONS: The overall mortality and complication rates of hemodialysis subjects after surgery for hip fracture were significantly higher than those of non-hemodialysis subjects. Further prospective studies which include important risk factors are necessary to more precisely quantify the adjusted effect of hemodialysis.

Outcomes after fixation for undisplaced femoral neck fracture compared to hemiarthroplasty for displaced femoral neck fracture among the elderly.

BACKGROUND: This study compared the rates of mortality, medical complication, and reoperation after fixation surgery for displaced femoral neck fracture with those after hemiarthroplasty surgery for undisplaced femoral neck fracture using competing risk analysis in inpatients aged 60 years and above from a population database in Taiwan. METHODS: We identified 13,772 subjects who underwent fixation for undisplaced cervical fracture and 13,772 matched controls who underwent hemiarthroplasty for displaced cervical fracture from 1998 to 2007, and followed them up until the end of 2009. The outcomes of patients who received internal fixation for undisplaced fracture and those of patients who received hemiarthroplasty for displaced fracture were compared. RESULTS: The 3-month, 2-year, and 10-year mortality rates were 4.9%, 22.1%, and 67.1% for fixation, and 5.6%, 23.8%, and 71.0% for hemiarthroplasty, respectively. The 3-month, 2-year, and 10-year cumulative incidence rates of the first reoperation were 7.4%, 18.1%, and 27.7% for fixation and 6.3%, 12.0%, and 22.3% for hemiarthroplasty, respectively. The 3-month cumulative incidence rates of the first medical complication were 14.4% for fixation and 15.4% for hemiarthroplasty, respectively. Hemiarthroplasty had a 1.09 times (95% CI: 1.05-1.12) higher hazard ratio for overall death than fixation. However, fixation had a 1.36 times (95% CI: 1.29-1.43) higher subdistribution hazard ratio for first reoperation than hemiarthroplasty after adjusting for gender, age, and comorbidities. CONCLUSIONS: The short-term overall mortality and medical complication rate of fixation for undisplaced fracture were slightly lower than those of hemiarthroplasty for displaced fracture. However, the short-term cumulative incidence of first reoperation after fixation was significantly higher than that for hemiarthroplasty. Further prospective studies or clinical trials based on the competing risk model, and which include important risk factors, are necessary to quantify the adjusted effects more precisely.

Comparison of two minimally invasive approaches to endometrial cancer staging: a single-surgeon experience.

OBJECTIVE: To compare the clinical outcomes of endometrial cancer staging procedures performed by a single surgeon utilizing traditional and robotic-assisted laparoscopic techniques. STUDY DESIGN: A retrospective review of minimally invasive endometrial cancer staging performed by a single surgeon. RESULTS: There were no significant differences in operative time, blood loss, surgical complications, or length of hospitalization between laparoscopic (n = 45) and robotic-assisted (n = 77) procedures. On multivariable analysis controlling for surgical chronology, robotic assistance was independently associated with a significantly greater number of lymph nodes (23 vs. 19, p < 0.05; beta 0.163, p < 0.05). When comparing the first chronologic half of robotic-assisted surgeries to the second half, the latter had shorter operative time (208 vs. 246 min, p = 0.01) and a greater number of lymph nodes (27 vs. 19, p = 0.001). Finally, compared to the laparoscopic cases, the second half of robotic-assisted cases had a greater number of total (27 vs. 19, p < 0.001) and pelvic (23 vs. 17, p < 0.001) lymph nodes harvested. CONCLUSION: There was a learning curve associated with robotic-assisted laparoscopic endometrial cancer staging, with decreased operative time and increased lymph node yield over time. In our study population, robotic assistance was independently associated with a greater lymph node harvest with no increase in operative time or perioperative complications.

Adoption and impact of concurrent chemoradiation therapy for vaginal cancer: a National Cancer Data Base (NCDB) study.

BACKGROUND: Vaginal cancer is an uncommon entity for which concurrent chemoradiation (CCRT) may be used based on small retrospective series and extrapolation from cervical cancer. We explored the adoption rate of CCRT and determined its impact on survival. METHODS: Patients entered into the National Cancer Data Base (NCDB) diagnosed with vaginal cancer from 1998 to 2011 who received definitive radiation therapy were included. Univariate/multivariable exploratory analyses of factors associated with CCRT were performed. Log-rank test and Cox proportional hazards modeling identified the contribution of CCRT on survival. RESULTS: Of the 13,689 patients identified, 8222 (60.1%) received radiation therapy. Of these, 3932 (47.8%) received CCRT and its use increased from 20.8% to 59.1% (1998-2011). Of the 23 patient, disease, facility, and treatment factors, 13 were significantly associated with patient outcomes and were entered into a binary logistic regression model. This evaluation revealed that younger age, larger tumor size, later year of diagnosis, higher facility volume, squamous histology, and higher stage (in order of increasing association) are independently associated with CCRT use. Median overall survival is longer with CCRT compared to radiation alone (56.2 vs. 41.2 months, p<0.0005). On multivariable analysis, younger age, higher facility volume, squamous histology, lower comorbidity score, CCRT, brachytherapy utilization and lower stage (in order of increasing association) are independently prognostic of improved survival. CONCLUSIONS: Use of CCRT for patients with vaginal cancer has increased and is associated with a significant improvement in survival in this large, national cohort. CCRT should be integrated into treatment guidelines for vaginal cancer.

Impact of facility volume on therapy and survival for locally advanced cervical cancer.

OBJECTIVE: Chemosensitizing radiation with brachytherapy is standard of care for treatment of locally advanced cervical cancer, an increasingly rare disease. Treatment facility volume has been correlated with outcome in many diseases. Treatment outcome and likelihood of receiving standard therapy in locally advanced cervical cancer based on facility volume were examined using a large national cancer database. METHODS: The National Cancer Data Base was queried for patients with stage IIB - IIIB cervical cancer from 1/1998 through 12/2010. Facility volumes were tallied. Overall survival was estimated using Kaplan-Meier method. Univariate and multivariable analyses were performed to determine variables affecting survival, receiving standard therapy, and total duration of radiotherapy. RESULTS: We identified a total of 27,660 patients who were treated at 1361 facilities. Thirty of the facilities (2.2%) treated the highest quartile volume of patients (>9.4 patients annually) while 1072 facilities (78.8%) treated <2.4 patients annually. The median age of patients was 53, the majority were Caucasian, treated in a metropolitan area, and of squamous cell histology. Median survival of patients treated at lowest- and highest-volume centers were 42.3 months (95% CI 39.8-44.8) and 53.8 months (50.1-57.5), respectively (p < 0.001). The proportions of patients receiving brachytherapy and chemotherapy were 54.8% and 79.9%, respectively. On multivariable analysis, higher facility volume independently predicted improved survival (p = 0.022), increased likelihood of receiving brachytherapy (p < 0.0005) and chemotherapy (p = 0.013), and shorter time to radiotherapy completion (p < 0.0005). CONCLUSIONS: Patients with locally advanced cervical cancer treated at high volume centers are more likely to receive standard therapy, complete therapy sooner, and experience better survival.

Mortality and complications of hip fracture in young adults: a nationwide population-based cohort study.

BACKGROUND: This study assessed the mortality and complications of hip fractures using in-patients aged 20-40 years from a nationwide population database in Taiwan. METHODS: Subjects were selected from Taiwan's National Health Insurance Research Database for the period 2000-2008, and these subjects were followed up until the end of 2010. A total of 5,079 (3,879 male and 1,200 female) subjects were admitted for the first time with primary diagnosis of hip fracture and treated with operation. We calculated the long-term overall survival rate and complication-free rate. We also assessed the risk factors for mortality and complications. RESULTS: The 1-month, 3-month, 6-month, 1-year, 2-year, 5-year, and 10-year complication-free rates were 98.3%, 96.2%, 94.5%, 86.8%, 80.4%, 75.3%, and 73.5% for the entire cohort, respectively. The 10-year survival rates were 93.3%, 91.8%, and 94.5% for total cases, trochanteric fracture, and cervical fracture, respectively. The 10-year complication-free rates were 73.5%, 80.5%, and 67.3% for total cases, trochanteric fracture, and cervical fracture, respectively. The risk factors for overall death were male, older age, and greater number of Charlson comorbidity index (CCI) comorbidities. The risk factors for complication were cervical fracture, and greater number of CCI comorbidities. Complications resulted in 42.83% of patients receiving internal fixation implants or prothesis removal and 2.01% underwent conversion to revision arthroplasty during follow-up. CONCLUSIONS: The overall 10-year survival rate in hip fracture patients aged 20-40 years in Taiwan was over 90%. The 10-year complication-free rates were around 70%. Preventing the occurrence of severe complications after hip fracture among young adults is an important public health issue that warrants greater attention.

Robotic HIPEC with use of a vaginal GelPoint®.

Patients with advanced stage ovarian cancers commonly undergo hyperthermic intraperitoneal chemotherapy (HIPEC) following interval debulking via exploratory laparotomy. This video demonstrates the feasibility of HIPEC delivery via a minimally invasive approach with the use of a vaginal GelPoint® port. This video demonstrates a 56-year-old patient with Stage 3 bilateral fallopian tube cancer who underwent 3 cycles of neoadjuvant chemotherapy with cisplatin and paclitaxel. Prior to administration of HIPEC the patient underwent an uncomplicated robotic assisted radical hysterectomy, bilateral salpingo-oopherectomy and infracolic omentectomy. Additionally, the falciform ligament was transected. The vaginal cuff was then used for placement of the GelPoint® port. The inflow and outflow cannulas were placed at the level of the liver and pelvis robotically. To minimize risk of inadvertent spillage, robotic obturators were replaced. Prior to administration of HIPEC, 4 L of warm saline was administered. An additional safety check was performed with no areas of leak. Cisplatin was administered for 90 min followed by sodium thiosulfate and 3 L of normal saline. Confirmation of no residual fluid was noted laparoscopically. The patient was discharged 2 days postoperatively without postoperative complications. In this video we demonstrated the innovative technique of performing HIPEC via a minimally invasive approach, that typically requires an open procedure. With the use of a vaginal Gelpoint® we were able to safely administer intraperitoneal chemotherapy without risk to our patient. We were also able to minimize their length of hospital stay and expedite postoperative recovery. Further implementation of this technique may improve hospital resource allocation.

Long-Term Use of Immunosuppressive Agents Increased the Risk of Fractures in Patients with Autoimmune Diseases: An 18-Year Population-Based Cohort Study.

The risk of fractures is higher in patients with autoimmune diseases, but it is not clear whether the use of immunosuppressive agents can further increase this risk. To investigate this issue, a retrospective study was conducted using data from Taiwan's National Health Insurance Research Database. Patients diagnosed with autoimmune diseases between 2000 and 2014, including psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, were included in the study. A control group of patients without autoimmune diseases was selected from the same database during the same period. Patients with autoimmune diseases were divided into two sub-cohorts based on their use of immunosuppressive agents. This study found the risk of fractures was 1.14 times higher in patients with autoimmune diseases than in those without. Moreover, we found that patients in the immunosuppressant sub-cohort had a higher risk of fractures compared to those in the non-immunosuppressant sub-cohort. The adjusted sub-distribution hazard ratio for shoulder fractures was 1.27 (95% CI = 1.01-1.58), for spine fractures was 1.43 (95% CI = 1.26-1.62), for wrist fractures was 0.95 (95% CI = 0.75-1.22), and for hip fractures was 1.67 (95% CI = 1.38-2.03). In conclusion, the long-term use of immunosuppressive agents in patients with autoimmune diseases may increase the risk of fractures.

Pretreatment Radiologically Enlarged Lymph Nodes as a Significant Prognostic Factor in Clinical Stage IIB Cervical Cancer: Evidence from a Taiwanese Tertiary Care Center in Reaching Consensus.

The incidence of lymph node (LN) involvement and its prognostic value based on radiological imaging in stage IIB cervical cancer (CC) remains unclear, and evidence regarding oncological outcomes of patients with stage IIB CC with LN metastases is limited. In this study we retrospectively reviewed the incidence and prognostic significance of pretreatment radiologic LN status in 72 patients with clinical stage IIB CC (FIGO 2009), with or without radiologic evidence of LN enlargement. An enlarged LN was defined as a diameter > 10 mm on CT/MRI. Progression-free survival (PFS) and overall survival (OS) were assessed. Radiologic LN enlargement of >10 mm was observed in 45.8% of patients with stage IIB CC. PFS (p = 0.0088) and OS rates (p = 0.0032) were significantly poorer in the LN group (n = 33) than in the non-LN group (n = 39). Univariate Cox analysis revealed that LN > 10 mm contributed to a higher rate of recurrence and mortality. In conclusion, nearly half of the patients with clinical stage IIB CC had enlarged LNs (>10 mm) identified during pretreatment radiologic evaluation, which negatively impacted prognosis. Our findings highlight the need to incorporate CT- or MRI-based LN assessment before treatment for stage IIB CC.