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.

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.

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.

Hyperthermic Intraperitoneal Chemotherapy-Induced Molecular Changes in Humans Validate Preclinical Data in Ovarian Cancer.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) confers a survival benefit in epithelial ovarian cancer (EOC) and in preclinical models. However, the molecular changes induced by HIPEC have not been corroborated in humans. PATIENTS AND METHODS: A feasibility trial evaluated clinical and safety outcomes of HIPEC with cisplatin during optimal cytoreductive surgery (CRS) in patients with EOC diagnosed with stage III, IV, or recurrent EOC. Pre- and post-HIPEC biopsies were comprehensively profiled with genomic and transcriptomic sequencing to identify mutational and RNAseq signatures correlating with response; the tumor microenvironment was profiled to identify potential immune biomarkers; and transcriptional signatures of tumors and normal samples before and after HIPEC were compared to investigate HIPEC-induced acute transcriptional changes. RESULTS: Thirty-five patients had HIPEC at the time of optimal CRS; all patients had optimal CRS. The median progression-free survival (PFS) was 24.7 months for primary patients and 22.4 for recurrent patients. There were no grade 4 or 5 adverse events. Anemia was the most common grade 3 adverse event (43%). Hierarchical cluster analyses identified distinct transcriptomic signatures of good versus poor responders to HIPEC correlating with a PFS of 29.9 versus 7.3 months, respectively. Among good responders, significant HIPEC-induced molecular changes included immune pathway upregulation and DNA repair pathway downregulation. Within cancer islands, % programmed cell death protein 1 expression in CD8+ T cells significantly increased after HIPEC. An exceptional responder (PFS 58 months) demonstrated the highest programmed cell death protein 1 increase. Heat shock proteins comprised the top differentially upregulated genes in HIPEC-treated tumors. CONCLUSION: Distinct transcriptomic signatures identify responders to HIPEC, and preclinical model findings are confirmed for the first time in a human cohort.

Synergistic therapeutic effect of low-dose bevacizumab with cisplatin-based chemotherapy for advanced or recurrent cervical cancer.

BACKGROUND: Cisplatin-based chemotherapy (CBC) is highly efficacious for advanced cervical cancer; its efficacy can be enhanced by combining with 15 mg/kg (standard dose) bevacizumab (BEV). However, this standard dose is associated with various adverse events (AEs). Therefore, in this retrospective study, we analyzed the survival outcomes and AEs in patients with advanced or recurrent cervical cancer treated with CBC in combination with BEV 7.5 mg/kg. METHODS: Registered patient data were retrieved between October 2014 and September 2019, and 64 patients with advanced or recurrent cervical cancer treated with CBC + BEV (n = 21) or CBC alone (n = 43) were analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were the frequency and severity of AEs. The Cox proportional-hazards model was applied to explore prognostic factors associated with PFS and OS. RESULTS: The 1-, 2-, and 3-year PFS rates (95% CI) were 36.24% (22.0-50.5), 20.7% (9.8-34.2), and 17.7% (7.7-31.1) for the CBC group; and 71.4% (47.1-86.0), 51.0% (27.9-70.1), and 51.0% (27.9-70.1) for the CBC + BEV group, respectively. The 1-, 2-, and 3-year OS rates were 62.6% (46.4-75.18), 32.4% (18.8-46.9), and 23.2% (11.2-37.6) for the CBC group; and 85.7% (61.9-95.1), 66.6% (42.5-82.5), and 55.5% (27.1-76.7) for the CBC + BEV group, respectively. The CBC + BEV group presented higher PFS and OS rates, p = 0.003 and p = 0.005, respectively. Proteinuria (6 vs 9, p = 0.025) and hypertension (0 vs 10, p < 0.001) were less common, but anemia was more common in the CBC group (35 vs 11, p = 0.021). CONCLUSION: Overall, CBC + BEV significantly improved the PFS and OS compared with CBC alone. CBC + BEV also prevents severe AEs and hence is an efficacious and safe therapeutic option.

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.

Lower rates of mortality, readmission and reoperation in patients receiving acupuncture after hip fracture: a population-based analysis.

BACKGROUND: Studies on the effects of acupuncture on mortality and complication rates in hip fracture patients are limited by small sample size and short follow-up time. We aimed to assess the associations of acupuncture use with mortality, readmission and reoperation rates in hip fracture patients using a longitudinal population-based database. METHODS: A retrospective matched cohort study was conducted using data for the years 1996-2012 from Taiwan's National Health Insurance Research Database. Hip fracture patients were divided into an acupuncture group consisting of 292 subjects who received at least 6 acupuncture treatments within 183 days of hip fracture, and a propensity score matched "no acupuncture" group of 876 subjects who did not receive any acupuncture treatment and who functioned as controls. The two groups were compared using survival analysis and competing risk analysis. RESULTS: Compared to non-treated subjects, subjects treated with acupuncture had a lower risk of overall death (hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.24-0.73, p = 0.002), a lower risk of readmission due to medical complications (subdistribution HR (sHR): 0.64, 95% CI: 0.44-0.93, p = 0.019) and a lower risk of reoperation due to surgical complications (sHR: 0.62, 95% CI: 0.40-0.96, p = 0.034). CONCLUSION: This is the first study to suggest that postoperative acupuncture in hip fracture patients is associated with significantly lower mortality, readmission and reoperation rates compared with those of matched controls.

Fat distribution may predict intra- or extra-capsular hip fracture in geriatric patients after falling.

INTRODUCTION: Hip fractures can be divided into intra-capsular and extra-capsular fracture based on fracture location; these two types of fracture have different pathogeneses, treatments and prognoses. Many factors influence the patterns of hip fractures, including the injury mechanism, areal bone mineral density and the geometry of the hip. However, the relationship between body composition and hip fracture pattern has not yet been discussed. In this investigation, an analysis of the body compositions of geriatric patients with hip fractures were conducted to identify differences between fat and muscle distributions between patients with intra- and extra-capsular hip fractures. MATERIAL AND METHODS: From December 2017 to February 2019, 139 patients with a hip fracture were prospectively enrolled in this study. The groups of patients that were diagnosed as having intra- and extra-capsular hip fractures were compared in terms of patient demographics, pre-operative laboratory data, bone mineral density (BMD) and body composition including muscle and fat distributions obtained using dual-energy X-ray absorptiometry (DXA) . RESULTS: Eighty-six and 53 patients were diagnosed with intra-capsular and extra-capsular hip fractures, respectively. A significantly higher serum glucose level, a lower hemoglobin level, a lower T-score level in the proximal femur region, a lower T-score of all parts of interest, and a lower percentage fat content on the region of bilateral proximal hips (gynoid region) and in the lower limb region, were observed in patients with an extra-capsular hip fracture than in those with an intra-capsular hip fracture. However, with all confounding factors controlled for, only the T-score at the proximal femur, percentage fat content in the region of bilateral proximal hips and the ratio of android fat content to gynoid fat content (A/G ratio) are the most relevant factors in predicting the patterns of hip fracture in geriatric patients after falling. CONCLUSION: This work demonstrates that lower fat content in the region of bilateral proximal hips and a lower BMD on the proximal femur may predict greater vulnerability of geriatric patients to extra-capsular rather than intra-capsular hip fracture after a falling accident.

Radical Hysterectomy After Neoadjuvant Chemotherapy for Locally Bulky-Size Cervical Cancer: A Retrospective Comparative Analysis between the Robotic and Abdominal Approaches.

Radical hysterectomy (RH) is the standard treatment for early stage cervical cancer, but the surgical approach for locally bulky-size cervical cancer (LBS-CC) is still unclear. We retrospectively compared the outcomes of women with LBS-CC treated with neoadjuvant chemotherapy (NACT) and subsequent RH between the robotic (R-RH) and abdominal approaches (A-RH). Between 2012 and 2014, 39 women with LBS-CC FIGO (International Federation of Gynecology and Obstetrics) stage IB2-IIB were treated with NACT-R-RH (n = 18) or NACT-A-RH (n = 21). Surgical parameters and prognosis were compared. Patient characteristics were not significantly different between the groups, but the NACT-R-RH group had significantly more patients with FIGO stage IIB disease, received multi-agent-based NACT, and had a lower percentage of deep stromal invasion than the NACT-A-RH group. After NACT-R-RH, surgical parameters were better, but survival outcomes, such as disease-free survival (DFS) and overall survival (OS), were significantly worse. On multivariate analysis, FIGO stage IIB contributed to worse DFS (p = 0.003) and worse OS (p = 0.012) in the NACT-A-RH group. Women with LBS-CC treated with NACT-R-RH have better perioperative outcomes but poorer survival outcomes compared with those treated with NACT-A-RH. Thus, patients with FIGO stage IIB LBS-CC disease might not be suitable for surgery after multi-agent-based NACT.

Protective effects and network analysis of natural compounds obtained from Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae against RANKL-induced osteoclastogenesis in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoporosis is one of the most common bone diseases; it is characterized by bone loss and is a risk factor for hip fracture. Chinese herbal medicines (CHMs) and their related natural compounds have been used for treating many diseases, including bone diseases, since ancient times in China and are regarded as a cost-effective complementary therapy. AIM OF THE STUDY: The goal of this study was to investigate the osteoprotective mechanisms of these three Chinese herbs and their related natural compounds. The effects of CHMs and related natural compounds on RANKL-induced osteoclastogenesis in vitro were investigated. MATERIALS AND METHODS: A network pharmacology method was applied to study CHM-related natural compounds and their osteoporosis targets. In addition, their effect on RANKL-induced osteoclastogenesis in RAW264.7 cells was also investigated in vitro. RESULTS: Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae exhibited protective effects against mortality in hip fracture patients. Furthermore, these three herbs inhibited RANKL-induced TRAP activities and reduced the expression of bone resorption-related genes in RAW264.7 cells. Network analysis of natural compound (ingredient)-target interactions identified 11 natural compounds. Signal pathway analyses suggested that these compounds may target cytokine-cytokine receptor interactions, including RANKL-induced osteoclastogenesis. Five novel natural compounds exhibited reduced RANKL-induced TRAP activities and bone resorption-related gene expression. CONCLUSION: The clinically used CHMs, Radix dipsaci, Eucommiae cortex, and Rhizoma drynariae, and natural compounds obtained from them may suppress RANKL-induced osteoclastogenesis in vitro.

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.

Effects of Chinese Herbal Medicines on the Risk of Overall Mortality, Readmission, and Reoperation in Hip Fracture Patients.

Hip fracture is a major public health concern, with high incidence rates in the elderly worldwide. Hip fractures are associated with increased medical costs, patient dependency on families, and higher rates of morbidity and mortality. Chinese herbal medicine (CHM) is typically characterized as cost-effective and suitable for long-term use with few side effects. To better understand the effects of CHM on hip fracture patients, we utilized a population-based database to investigate the demographic characteristics, cumulative incidence of overall mortality, readmission, reoperation, and patterns of CHM prescription. We found that CHM usage was associated with a lower risk of overall mortality [P = 0.0009; adjusted hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.30-0.73], readmission (P = 0.0345; adjusted HR: 0.67, 95% CI: 0.46-0.97), and reoperation (P = 0.0009; adjusted HR: 0.57, 95% CI: 0.40-0.79) after adjustment for age, type of hip fracture, surgical treatment type, and comorbidities. We also identified the herbal formulas, single herbs, and prescription patterns for the treatment of hip fracture by using association rule mining and network analysis. For hip fracture patients, the most common CHM coprescription pattern was Du-Zhong (DZ) → Xu-Duan (XD), followed by Du-Huo-Ji-Sheng-Tang (DHJST) → Shu-Jing-Huo-Xue-Tang (SJHXT), and Gu-Sui-Bu (GSB) → Xu-Duan (XD). Furthermore, XD was the core prescription, and DZ, GSB, SJHXT, and DHJST were important prescriptions located in cluster 1 of the prescription patterns. This study provides evidence for clinical CHM use as an adjunctive therapy that offers benefits to hip fracture patients.

Text analytics approach to extract course improvement suggestions from students' feedback.

In academic institutions, it is normal practice that at the end of each term, students are required to complete a questionnaire that is designed to gather students' perceptions of the instructor and their learning experience in the course. Students' feedback includes numerical answers to Likert scale questions and textual comments to open-ended questions. Within the textual comments given by the students are embedded suggestions. A suggestion can be explicit or implicit. Any suggestion provides useful pointers on how the instructor can further enhance the student learning experience. However, it is tedious to manually go through all the qualitative comments and extract the suggestions. In this paper, we provide an automated solution for extracting the explicit suggestions from the students' qualitative feedback comments. The implemented solution leverages existing text mining and data visualization techniques. It comprises three stages, namely data pre-processing, explicit suggestions extraction and visualization. We evaluated our solution using student feedback comments from seven undergraduate core courses taught at the School of Information Systems, Singapore Management University. We compared rule-based methods and statistical classifiers for extracting and summarizing the explicit suggestions. Based on our experiments, the decision tree (C5.0) works the best for extracting the suggestions from students' qualitative feedback.

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.

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.

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.

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.

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.