Patient experiences with outpatient opioid use disorder treatment before and during COVID-19: results from a survey of Medicaid members.

Background: Payers are increasingly interested in quality improvement for opioid use disorder (OUD) treatment, including incorporating patient experiences. Medicaid is the largest payer for OUD treatment, yet we know little about the treatment benefits Medicaid members report, how these vary across members, or changed with the COVID-19 pandemic.Objective: To examine Medicaid members' report of outpatient treatment benefits, employment, and housing outcomes before and during the pandemic.Methods: A representative sample of 1,032 Virginia Medicaid members (52% women) receiving OUD treatment completed a survey of treatment benefits, health status and social needs. A reported treatment benefit index was created based on seven self-reported items. Multivariable linear regression models, pooled and stratified by time (pre-COVID-19/COVID-19), assessed member characteristics associated with reported treatment benefit, employment and housing outcomes.Results: Members reported strong treatment benefit (mean: 21.8 [SD: 5.9] out of 28 points) and improvements in employment (2.4 [1.3] out of 5) and housing (2.8 [1.2] out of 5). After adjustment, mental distress (regression coefficient: -3.00 [95% CI:-3.97;-2.03]), polysubstance use (-1.25 [-1.99;-0.51]), and food insecurity (-1.00 [-1.71;-0.29]), were associated with decreased benefits from treatment. During COVID-19, justice-involved individuals reported decreased benefits (-2.17 [-3.54; -0.80]) compared to before the pandemic (-0.09 [-1.4-;1.24] p < .05).Conclusions: Medicaid members receiving outpatient OUD treatment reported positive treatment benefits, and housing and employment outcomes. However, those with comorbid health and social conditions often benefited the least. As payers move toward quality improvement and value-based purchasing initiatives, collecting and integrating patient reported outcomes into quality metrics is critical.

Advantages of Using 3D Spheroid Culture Systems in Toxicological and Pharmacological Assessment for Osteogenesis Research.

Bone differentiation is crucial for skeletal development and maintenance. Its dysfunction can cause various pathological conditions such as rickets, osteoporosis, osteogenesis imperfecta, or Paget's disease. Although traditional two-dimensional cell culture systems have contributed significantly to our understanding of bone biology, they fail to replicate the intricate biotic environment of bone tissue. Three-dimensional (3D) spheroid cell cultures have gained widespread popularity for addressing bone defects. This review highlights the advantages of employing 3D culture systems to investigate bone differentiation. It highlights their capacity to mimic the complex in vivo environment and crucial cellular interactions pivotal to bone homeostasis. The exploration of 3D culture models in bone research offers enhanced physiological relevance, improved predictive capabilities, and reduced reliance on animal models, which have contributed to the advancement of safer and more effective strategies for drug development. Studies have highlighted the transformative potential of 3D culture systems for expanding our understanding of bone biology and developing targeted therapeutic interventions for bone-related disorders. This review explores how 3D culture systems have demonstrated promise in unraveling the intricate mechanisms governing bone homeostasis and responses to pharmacological agents.

Temporal trends of failure-to-rescue following perioperative complications in vulvar cancer surgery in the United States.

OBJECTIVE: Failure-to-rescue, defined as mortality following a perioperative complication, is a perioperative quality indicator studied in various surgeries, but not in vulvar cancer surgery. The objective of this study was to assess failure-to-rescue in patients undergoing surgical therapy for vulvar cancer. METHODS: This cross-section study queried the National Inpatient Sample. The study population was 31,077 patients who had surgical therapy for vulvar cancer from 1/2001-9/2015. The main outcomes were (i) perioperative morbidity (29 indicators) and (ii) mortality following a perioperative complication during the index admission for vulvar surgery (failure-to-rescue), assessed with a multivariable binary logistic regression model. RESULTS: The cohort-level median age was 69 years, and 14,337 (46.1%) had medical comorbidity. Perioperative complications were reported in 4736 (15.2%) patients during the hospital admission for vulvar surgery. In multivariable analysis, patient factors including older age, medical comorbidity, and morbid obesity, and treatment factors with prior radiotherapy and radical vulvectomy were associated with perioperative complications (P < 0.05). The number of patients with morbid obesity, higher comorbidity index, and prior radiotherapy increased over time (P-trends < 0.001). Among 4736 patients who developed perioperative complications, 55 patients died during the hospital admission for vulvar surgery (failure-to-rescue rate, 1.2%). In multivariable analysis, cardiac arrest (adjusted-odds ratio [aOR] 27.25), sepsis or systemic inflammatory response syndrome (aOR 11.54), pneumonia (aOR 6.03), shock (aOR 4.37), and respiratory failure (aOR 3.10) were associated with failure-to-rescue (high-risk morbidities). There was an increasing trend of high-risk morbidities from 2.0% to 3.7% over time, but the failure-to-rescue from high-risk morbidities decreased from 9.1% to 2.8% (P-trend < 0.05). CONCLUSION: Vulvar cancer patients undergoing surgical treatment had increased comorbidity over time with an increase in high-risk complications. However, failure-to-rescue rate has decreased significantly.

Two staged phase II clinical trial of Eribulin monotherapy in advanced or recurrent cervical cancer.

BACKGROUND: Eribulin a microtubule targeting agent and analog of Halichondrin B, a natural product isolated from marine sponge H. okadai, has proven clinical efficacy in metastatic pretreated breast cancer and liposarcoma. We conducted a 2-stage Phase II study of eribulin in patients with advanced/recurrent cervical cancer to examine its clinical activity and evaluate biomarkers for predictors of response. METHODS: Women with advanced/recurrent cervical cancer after ≤1 prior chemotherapy regimen, measurable disease and ECOG performance status ≤2 were treated with eribulin (1.4 mg/m2 IV day 1 and 8, every 21 days) with tumor assessments every 2 cycles. Primary endpoint was 6-month progression-free survival (PFS6); secondary were best overall response (RECISTv1.1), toxicity (CTCAEv4.03) and overall survival (OS). Exploratory endpoints were associations of biomarkers with clinical activity. Immunohistochemistry was performed on archival tumor samples. Overexpression was defined when both intensity and distribution scores were ≥ 2. RESULTS: 32 patients enrolled from 11/2012-5/2017. 29/32 patients had prior chemotherapy with cisplatin/paclitaxel/bevacizumab (n = 12) or cisplatin/gemcitabine (n = 12) as the most common regimens. 14 patients received prior paclitaxel. 1 (3%) had a complete response, 5 (16%) had a partial response and 13 (41%) had stable disease for ORR of 19% (95% CI 8, 37). Those who are paclitaxel naïve experienced the greatest benefit with a 29% ORR (95% CI 12, 54). Patients who received prior paclitaxel responded less favorably than those who did not (p = .002) and had a shorter PFS and OS. Grade 3/4 adverse events occurring in >10% of patients were anemia (n = 12, 38%), neutropenia (n = 7, 22%) and leukopenia (n = 6, 19%). Analysis of correlative predictors of response revealed that patients who did not overexpress ßII and BAX were significantly more likely to respond to e`ribulin. PFS was significantly shorter in patients with ßII and BAX overexpression, OS was significantly shorter in those with ßIII and BAX overexpression. These associations remained after multivariate analysis. CONCLUSIONS: Eribulin shows modest activity in patients with recurrent/advanced cervical cancer with a favorable toxicity profile. Prior paclitaxel exposure is associated with decreased eribulin response. ßII, ßIII tubulin subtypes and BAX are predictors of response and survival. Eribulin may be an option for women with paclitaxel-naïve recurrent/advanced cervical cancer.

Associations Between Patient-Reported Experiences with Opioid Use Disorder Treatment and Unmet Treatment Needs and Discontinuation Among Virginia Medicaid Members.

BACKGROUND: Many payers, including Medicaid, the largest payer of opioid use disorder (OUD) treatment, are pursuing treatment-related quality improvement initiatives. Yet, how patient-reported experiences with OUD treatment relate to patient-centered outcomes remains poorly understood. AIM: To examine associations between Medicaid members' OUD treatment experiences, outpatient treatment settings, demographic and social factors, and members' self-report of unmet needs during treatment and treatment discontinuation. METHODS: A sample of Virginia Medicaid members aged 21 years or older with OUD diagnoses who received outpatient OUD treatment completed a mail survey between January 2020 and August 2021 (n = 1042, weighted n = 9244). A treatment experience index was constructed from responses to four items from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) relating to feelings of involvement, safety, and respect and having treatment explained in an understandable way; two additional CAHPS items: "given options for treatment" and "able to refuse treatment" were also assessed. Weighted imputed logistic regressions tested adjusted associations between members' treatment experiences, demographic and social factors, and two outcomes capturing unmet needs during treatment and treatment discontinuation. RESULTS: More positive scores on the treatment experiences index were associated with lower adjusted odds of reporting unmet needs during treatment (aOR: 0.52, 95% CI: 0.41-0.66) and discontinuation (aOR: 0.63, 95% CI: 0.47-0.79). Respondents with serious psychological distress had higher odds of reporting unmet needs during treatment (aOR: 1.69 95% CI: 1.14-2.51) and discontinuation (aOR: 1.84, 95% CI: 1.21-2.82), as did individuals with housing insecurity (unmet needs: (aOR: 1.65, 95% CI: 1.11-2.44); treatment discontinuation: (aOR: 1.56, 95% CI: 1.04-2.36)). CONCLUSION: Using a first-of-its-kind survey of Medicaid members with OUD, we found that members who had more positive treatment experiences were less likely to report unmet treatment needs and discontinue treatment. Care approaches focused on improving patient experience are critical to delivering effective, high-quality OUD treatment.

Mental Health Service Utilization and Disparities in the U.S: Observation of the First Year into the COVID Pandemic.

This study examined mental health service utilization and disparities during the first year of COVID. We analyzed data from all adult respondents with any mental illness in the past year (n = 6967) in the 2020 National Survey on Drug Use and Health to evaluate if mental health service utilization differed by geographic areas, race/ethnicity, and age groups. Only 46% of individuals with any mental illness had received mental health treatment. Compared to non-Hispanic Whites, Asian and Hispanics were less likely to receive outpatient services and prescription medicine. Rural residents received less outpatient treatment compared to large metropolitan residents. No difference was found in telemedicine utilization across area types and race/ethnicity groups. Older individuals were less likely to utilize telemedicine services. Our findings highlighted continued mental health treatment disparities among race/ethnic minorities and other sub-populations during COVID. Targeted strategies are warranted to allow older populations to benefit from telemedicine.

Dietary fibre in hypertension and cardiovascular disease management: systematic review and meta-analyses.

BACKGROUND: Higher dietary fibre intakes are associated with a reduced risk of developing cardiovascular disease (CVD), and increasing intake has been shown to reduce blood pressure and other cardiometabolic risk factors. The extent to which dietary fibre can further reduce risk for those with CVD and treated with cardioprotective drugs has not been clearly established. We have examined the evidence for dietary fibre as adjunct therapy in those with CVD or hypertension. METHODS: Ovid MEDLINE, Embase, PubMed, and CENTRAL were searched to June 2021. Prospective observational studies reporting on fibre intakes and mortality in those with pre-existing CVD and controlled trials of increasing fibre intakes on cardiometabolic risk factors in those with CVD or hypertension were eligible. Outcomes were mortality (studies) and cardiometabolic risk factors (trials). Data synthesis was with random effects and dose response. Certainty of evidence was assessed using GRADE. RESULTS: Three prospective studies including 7469 adults with CVD, and 12 trials of 878 adults with CVD or hypertension were identified. Moderate certainty evidence indicates reduced all-cause mortality (relative risk, RR0.75 (95% confidence interval, CI 0.58-0.97)) when comparing higher with lower fibre intakes. Low certainty evidence from trials of adults with cardiovascular disease indicates increasing fibre intakes reduced total (mean difference, MD - 0.42 mmol/L (95%CI - 0.78 to - 0.05) and low-density lipoprotein (LDL) cholesterol (MD - 0.47mmol/L (95%CI - 0.85 to - 0.10)). High certainty evidence from trials of adults with hypertension indicates increasing fibre intakes reduces systolic (MD 4.3 mmHg (95% CI 2.2 to 5.8)) and diastolic blood pressure (MD 3.1 mmHg (95% CI 1.7 to 4.4)). Moderate and low certainty evidence indicated improvements in fasting blood glucose (MD 0.48 mmol/L (- 0.91 to - 0.05)) and LDL cholesterol (MD 0.29 mmol/L (95% CI 0.17 to 0.40)). Benefits were observed irrespective of cardioprotective drug use. CONCLUSIONS: These findings emphasise the likely benefits of promoting greater dietary fibre intakes for patients with CVD and hypertension. Further trials and cohort analyses in this area would increase confidence in these results.

Population-level uptake of neoadjuvant chemotherapy for stage IVB endometrial cancer.

OBJECTIVE: To examine population-level trends, characteristics, and outcomes of patients with stage IVB endometrial cancer who received neoadjuvant chemotherapy (NACT) prior to surgery. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was retrospectively queried by examining 5505 patients with stage IVB endometrial cancer from 2010 to 2018. Exposure allocation was per treatment: primary surgery followed by chemotherapy (n = 3052, 55.4%), NACT followed by surgery (n = 930, 16.9%), and chemotherapy alone (n = 1523, 27.7%). Main outcomes measured were (i) the trend of utilization of NACT and patient characteristics related to NACT assessed with multinomial regression analysis and (ii) overall survival (OS) assessed with multivariable Cox proportional hazards regression model. RESULTS: The number of patients receiving NACT prior to surgery increased from 11.6% to 21.7% whereas those undergoing primary surgery followed by chemotherapy decreased from 62.7% to 48.3% (P < 0.001). Increasing utilization of NACT remained independent in multivariable analysis (adjusted-odds ratio per one-year increments 1.11, 95% confidence interval [CI] 1.08-1.15). Increasing utilization of NACT was observed in several sub-cohorts including patients aged <65 years, ≥65 years, White, non-White, endometrioid, non-endometrioid, and cases with non-distant organ metastasis (P < 0.05). In a multivariable analysis, NACT followed by surgery and primary surgery followed by chemotherapy had comparable OS (median 25 versus 26 months, adjusted-hazard ratio [HR] 1.03, 95%CI 0.93-1.15). When examined for metastatic extent, NACT followed by surgery was associated with decreased OS compared to primary surgery followed by chemotherapy in the non-distant organ metastasis group (adjusted-HR 1.20, 95%CI 1.05-1.36) whereas it was associated with improved OS in the distant organ metastasis group (adjusted-HR 0.79, 95%CI 0.66-0.95). CONCLUSION: The treatment of stage IVB endometrial cancer is shifting from primary surgery to NACT in the United States.

Percutaneous/mini-laparotomy fetoscopic repair of open spina bifida: a novel surgical technique.

Open spina bifida is the most common congenital anomaly of the central nervous system compatible with life. Prenatal repair of open spina bifida via open maternal-fetal surgery has been shown to improve postnatal neurologic outcomes, including reducing the need for ventriculoperitoneal shunting and improving lower neuromotor function. Fetoscopic repair of open spina bifida minimizes the maternal risks while providing similar neurosurgical outcomes to the fetus. The following 2 fetoscopic techniques are currently in use: (1) the laparotomy-assisted approach, and (2) the percutaneous approach. The laparotomy-assisted fetoscopic technique appears to be associated with a lesser risk of preterm birth than the percutaneous approach. However, the percutaneous approach avoids laparotomy and uterine exteriorization and is associated with lesser anesthesia risk and improved maternal postsurgical recovery. The purpose of this article was to describe our experience with a modified surgical approach, which we call percutaneous/mini-laparotomy fetoscopy, in which access to the uterus for one of the ports is done via a mini-laparotomy, whereas the other ports are inserted percutaneously. This technique draws on the benefits of both the laparotomy-assisted and the percutaneous techniques while minimizing their drawbacks. This surgical approach may prove invaluable in the prenatal repair of open spina bifida and other complex fetal surgical procedures.

Side-to-end reanastomosis after low-anterior resection (STELAR): Outcomes, feasibility, and description of procedure performed by a gynecologic oncology service.

BACKGROUND AND OBJECTIVES: Low anterior rectosigmoid resection for a gynecologic disease is usually performed in concert with other procedures and can result in significant morbidity should anastomotic complication occur. This study examined surgical outcomes of side-to-end reanastomosis after low anterior resection (STELAR) performed by gynecologic oncology service. METHODS: This is a case series examining consecutive patients who underwent STELAR for gynecologic indications by a single gynecologic oncology group from 2009 to 2018. Prospectively collected institutional surgical database was searched for STELAR, and standard descriptive statistics were used to describe intraoperative and postoperative complications specific to reanastomosis. RESULTS: A total of 69 women underwent STELAR, with median age and body mass index of 54 years and 24 kg/m2 , respectively. 63.8% of patients had ovarian cancer and 84.4% had stage III-IV disease. The median estimated blood loss was 875 ml. Four (5.8%) women underwent protective loop colostomy at the time of STELAR. Postoperatively, there was 1 (1.4%) case of abscess formation within 30 days and 1 (1.4%) case of anastomotic leak 5 weeks after STELAR that required reoperation and diversion. No cases of fistula were clinically identified. CONCLUSION: Side-to-end reanastomosis may be a safe and feasible procedure to accomplish low rectosigmoid anastomosis in women with gynecologic disease.

Decline of Tuberculosis Burden in Vietnam Measured by Consecutive National Surveys, 2007-2017.

Vietnam, a high tuberculosis (TB) burden country, conducted national TB prevalence surveys in 2007 and 2017. In both surveys participants were screened by using a questionnaire and chest radiograph; sputum samples were then collected to test for Mycobacterium tuberculosis by smear microscopy and Löwenstein-Jensen culture. Culture-positive, smear-positive, and smear-negative TB cases were defined by laboratory results, and the prevalence of tuberculosis was compared between the 2 surveys. The results showed prevalence of culture-positive TB decreased by 37% (95% CI 11.5%-55.4%), from 199 (95% CI 160-248) cases/100,000 adults in 2007 to 125 (95% CI 98-159) cases/100,000 adults in 2017. Prevalence of smear-positive TB dropped by 53% (95% CI 27.0%-69.7%), from 99 (95% CI 78-125) cases/100,000 adults to 46 (95% CI 32-68) cases/100,000 adults; smear-negative TB showed no substantial decrease. Replacing microscopy with molecular methods for primary diagnostics might enhance diagnosis of pulmonary TB cases and further lower TB burden.

In Situ Formation of Mixed-Dimensional Surface Passivation Layers in Perovskite Solar Cells with Dual-Isomer Alkylammonium Cations.

Dimensional engineering of perovskite solar cells has attracted significant research attention recently because of the potential to improve both device performance and stability. Here, a novel 2D passivation scheme for 3D perovskite solar cells is demonstrated using a mixed cation composition of 2D perovskite based on two different isomers of butylammonium iodide. The dual-cation 2D perovskite outperforms its single cation 2D counterparts in surface passivation quality, resulting in devices with an impressive open-circuit voltage of 1.21 V for a perovskite composition with an optical bandgap of ≈1.6 eV, and a champion efficiency of 23.27%. Using a combination of surface elemental analysis and valence electron spectra decomposition, it is shown that an in situ interaction between the 2D perovskite precursor and the 3D active layer results in surface intermixing of 3D and 2D perovskite phases, providing an effective combination of defect passivation and enhanced charge transfer, despite the semi-insulating nature of the 2D perovskite phase. The demonstration of the synergistic interaction of multiple organic spacer cations in a 2D passivation layer offers new opportunities for further enhancement of device performance with mixed dimensional perovskite solar cells.

Dietary fibre intake in childhood or adolescence and subsequent health outcomes: A systematic review of prospective observational studies.

AIM: To determine whether higher fibre intakes during childhood or adolescence effect a broad range of intermediate markers of cardiometabolic risk or other health related issues. MATERIALS AND METHODS: We used online searches up to January 2020 and manual searches to identify prospective observational studies reporting on childhood or adolescent intakes of dietary fibre, vegetables, fruit and refined or whole grains. Outcomes measured later in life were body weight, blood lipids, blood pressure, glycaemia, bone health, cognition, growth and bowel habits. Potential age-specific ranges for dietary fibre were extrapolated from published adult data. RESULTS: We identified 45 publications reporting on 44 354 participants from 30 cohort studies. Mean age at dietary assessment varied from 1 to 19.3 years. Follow-up duration varied from 4 months to 27 years. Although well-conducted studies reported improvements in body weight, blood lipids and glycaemia, the diverse nature of studies precluded meta analysis. The quality of evidence was very low to low given the limited data available per outcome and the inability to synthesize results from multiple studies. Potential dietary fibre intake begins at 13-16 g a day for 2-year-olds and increases until the age of 10 years, when values are comparable with an adult range of 25-30 g a day. CONCLUSIONS: Given the inconsistency in findings from cohort studies other than an absence of detrimental effects, it seems appropriate that recommendations regarding childhood fibre intake are extrapolated from relevant adult data.

Molecular and Morphological Diversity of Heterodesmus Brady and Its Phylogenetic Position within Cypridinidae (Ostracoda).

Ostracod genus Heterodesmus Brady, 1866 is known thus far to contain only three species: H. adamsii Brady, 1866; H. apriculus Hiruta, 1992; and H. naviformis (Poulsen, 1962). This genus has been recorded from the Sea of Japan, and the coastal areas of Thailand and Vietnam. The main generic character is the presence of antero-dorsal and postero-dorsal tube-like processes on the rostrum on both valves. The three species mostly differ in the shell lateral projections. Their relationship and the position of Heterodesmus within family Cypridinidae are poorly understood, partly due to the lack of publication of DNA data so far. We study Heterodesmus collected from several localities in the Northwest Pacific, namely Tsushima and Iki Islands in Japan and Maemul Island in Korea. Besides morphological characters, we also use two mitochondrial markers (16S rRNA and mtCOI) and three nuclear regions (18S rRNA, 28S rRNA, and internal transcribed spacer - ITS) in the samples to detect the biodiversity of this genus. Our phylogenetic tree based on molecular data coupled with morphology reveals the presence of two species, H. adamsii and H. apriculus. We report on their morphological variability, molecular diversity, and phylogenetic position within Cypridinidae based on 16S, 28S and 18S rRNAs, and provide a taxonomic key for all living genera of this family. For the first time, we give an overview of the intrageneric and intrafamily DNA distances of the above markers for the entire subclass Myodocopa.

Twin-Twin Transfusion Syndrome Complicated by Proximate Placental Cord Insertion Sites: Endoscopic Clip-Assisted Laser Occlusion.

INTRODUCTION: Severe twin-twin transfusion syndrome (TTTS) with a large vascular communication between proximate placental cord insertion sites is a therapeutic dilemma because laser ablation may cause thermal injury to the cord roots and subsequent fetal demise. CASE PRESENTATION: Stage IV TTTS with placental cord insertion sites 1.3 cm apart and with an intervening large arterio-arterial (AA) anastomosis presented for treatment. The application of endoclips onto the large AA anastomosis between the cord roots allowed for successful laser occlusion using minimal energy. Both the donor and recipient twins were alive and well at 6 months of age. CONCLUSION: Endoscopic clip-assisted laser occlusion of a placental vessel is technically feasible and may be a useful therapeutic option in select cases.

Extent of pelvic lymphadenectomy and use of adjuvant vaginal brachytherapy for early-stage endometrial cancer.

OBJECTIVE: To examine trends of adjuvant radiotherapy choice and to examine associations between pelvic lymphadenectomy and radiotherapy choice for women with early-stage endometrial cancer. METHODS: The Surveillance, Epidemiology, and End Results Program was used to identify surgically treated stage I-II endometrial cancer between 1983 and 2012 (type 1 n=79,474, and type 2 n=25,020). Piecewise linear regression models were used to examine temporal trends of intracavitary brachytherapy (ICBT) and whole pelvic radiotherapy (WPRT) use, pelvic lymphadenectomy rate, and sampled node counts. Multivariable binary logistic regression models were used to identify independent predictors for ICBT use. RESULTS: There was a significant increase in ICBT use and decrease in WPRT use during the study period. ICBT use exceeded WPRT use in 2003 for type 1 stage IA, and in 2007 for type 1 stage IB and type 2 stage IA diseases. In addition, number of sampled pelvic nodes significantly increased over time in type 1-2 stage I-II diseases (mean, 7.0-12.7 in 1988 to 15.2-17.6 in 2012, all P<0.001). On multivariable analysis, extent of sampled pelvic nodes was significantly associated with ICBT use for type 1 cancer: adjusted-odds ratios for 1-10 and >10 nodes versus no lymphadenectomy in stage IA (1.38/2.40), IB (2.75/6.32), and II (1.36/2.91) diseases. Similar trends were observed for type 2 cancer: adjusted-odds ratios for stage IA (1.69/3.73), IB (2.25/5.65), and II (1.36/2.19) diseases. CONCLUSION: Our results suggest that surgeons and radiation oncologists are evaluating the extent of pelvic lymphadenectomy when counseling women with early-stage endometrial cancer for adjuvant radiotherapy.

Single Marital Status and Infectious Mortality in Women With Cervical Cancer in the United States.

OBJECTIVE: Unmarried status including single marital status is associated with increased mortality in women bearing malignancy. Infectious disease weights a significant proportion of mortality in patients with malignancy. Here, we examined an association of single marital status and infectious mortality in cervical cancer. METHODS: This is a retrospective observational study examining 86,555 women with invasive cervical cancer identified in the Surveillance, Epidemiology, and End Results Program between 1973 and 2013. Characteristics of 18,324 single women were compared with 38,713 married women in multivariable binary logistic regression models. Propensity score matching was performed to examine cumulative risk of all-cause and infectious mortality between the 2 groups. RESULTS: Single marital status was significantly associated with young age, black/Hispanic ethnicity, Western US residents, uninsured status, high-grade tumor, squamous histology, and advanced-stage disease on multivariable analysis (all, P < 0.05). In a prematched model, single marital status was significantly associated with increased cumulative risk of all-cause mortality (5-year rate: 32.9% vs 29.7%, P < 0.001) and infectious mortality (0.5% vs 0.3%, P < 0.001) compared with the married status. After propensity score matching, single marital status remained an independent prognostic factor for increased cumulative risk of all-cause mortality (adjusted hazards ratio [HR], 1.15; 95% confidence interval [CI], 1.11-1.20; P < 0.001) and those of infectious mortality on multivariable analysis (adjusted HR, 1.71; 95% CI, 1.27-2.32; P < 0.001). In a sensitivity analysis for stage I disease, single marital status remained significantly increased risk of infectious mortality after propensity score matching (adjusted HR, 2.24; 95% CI, 1.34-3.73; P = 0.002). CONCLUSIONS: Single marital status was associated with increased infectious mortality in women with invasive cervical cancer.

Safety and feasibility of fasting in combination with platinum-based chemotherapy.

BACKGROUND: Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. METHODS: 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. RESULTS: The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. CONCLUSION: Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. TRIAL REGISTRATION: NCT00936364 , registered propectively on July 9, 2009.

Endoplasmic reticulum stress in complex atypical hyperplasia as a possible predictor of occult carcinoma and progestin response.

Glucose-regulated protein (GRP)-78, the key regulator of endoplasmic reticulum (ER) stress, is associated with endometrial cancer (EC) development and progression. However, its role in the continuum from complex atypical hyperplasia (CAH) to EC is unknown and the focus of this study. METHODS: 252 formalin-fixed, paraffin-embedded endometrial biopsies from patients with CAH diagnosed between 2003 and 2011 were evaluated for GRP78 expression by immunohistochemistry. Expression was also evaluated in subsequent biopsies from those patients treated with progestins. Differences in GRP78 expression were assessed using standard statistical methods. RESULTS: GRP78 expression was undetectable in 45(18%) patients with CAH, while 120(48%) CAH cases showed moderate/strong expression. Among women who ultimately underwent hysterectomy for CAH (n=134), 54(40%) had occult EC while 57(43%) had persistent CAH. Those with occult EC upon hysterectomy had significantly stronger GRP78 expression than those who did not have occult EC (p=0.007). Greater GRP78 expression within CAH remained independently associated with the presence of an occult EC (p=0.017). Thirty-four of 54 (63%) patients with occult EC had moderate/strong GRP78 expression compared to 36 of 80 (45%) patients with persistent CAH, benign or non-atypical hyperplastic endometrium. In those treated with progestins, samples with persistent CAH and EC were more likely to have high levels of GRP78 expression in the initial biopsies than those who responded (p=0.014). CONCLUSIONS: Increased GRP78 expression in untreated CAH correlates with the presence of an occult EC. In addition, CAH specimens with greater GRP78 expression may identify patients who are less likely to respond to progestin therapy.