The Pillar Effect of Large-Size Alkaline Ions on the Electrochemical Stability of Sodium Manganese Hexacyanoferrate for Sodium-Ion Batteries.

Sodium manganese hexacyanoferrate (NaMnHCF) is an attractive candidate as a cathode material for sodium-ion batteries due to its low cost and high energy density. However, its practical application is hindered by poor electrochemical stability caused by the Jahn-Teller effect of Mn and the unstable structure of NaMnHCF. Here, this paper aims to address this issue by introducing highly stable AMnHCF (where A = K, Rb, or Cs) through a facile method to composite with NaMnHCF. The findings reveal that all AMnHCFs have a "pillar effect" on the crystal structure of NaMnHCF. It is observed that the degree of pillar effect varies depending on the specific AMnHCF used. The less electrochemically inactive the alkaline ion is and the greater the degree of compositing with NaMnHCF, the more dramatic the pillar effect. KMnHCF shows limited pillar effect due to its rough composition with NaMnHCF and the loss of K+ upon (de)intercalation. RbMnHCF has lower electrochemical activity and can be better composited with NaMnHCF. On the other hand, CsMnHCF exhibits the strongest pillar effect due to the inactivation of Cs+ and the excellent coherent structure formed by CsMnHCF and NaMnHCF. This research provides a new perspective on stabilizing NaMnHCF with other alkaline elements.

Extensively Drug-Resistant Typhoidal Salmonellae: Are These Bugs Swarming Into Suburban and Rural Areas of Pakistan?

Background Typhoid is a serious public health concern with increasing antibiotic resistance. Early suspicion and choice of susceptible antibiotics are key to avoiding the morbidity and mortality associated with this disease. We have carried out this study to assess the antibiotic sensitivity of typhoidal salmonellae in Kharian, Pakistan. Materials and methods This cross-sectional study was carried out at Combined Military Hospital, Kharian, Pakistan, from January 2019 to September 2020. Blood culture specimens from patients clinically suspected of enteric fever were tested through the BacT/ALERT 3D automated blood culture system. Positive microbial growth was further identified by colony morphology, appropriate staining, biochemical testing, and Salmonella-specific grouping sera. Salmonella typhi and Salmonella paratyphi A-C were further analyzed for antimicrobial susceptibility using agar disc diffusion testing by the modified Kirby-Bauer technique. The Clinical and Laboratory Standards Institute (CLSI) guidelines (2018-2020) document M-100 was followed for antibiotic selection and assigning the sensitivity status of the isolates. Meropenem and azithromycin were additionally tested keeping in view the possibility of encountering isolates with extensive antimicrobial resistance. Results A total of 315 blood culture samples were received during the study period. Of these, 239 (75.9%) reported negative and 76 (24.1%) were positive. The mean age was 22.37 ± 12.39 years. There were 41 (53.9%) males and 35 (46.1%) females. Salmonella enterica (combined Salmonella typhi and Salmonella paratyphi A) was 100% sensitive to azithromycin, meropenem, and imipenem. Ampicillin and chloramphenicol have 28.9% sensitivity each. Ceftriaxone, co-trimoxazole, and ciprofloxacin revealed 64.5%, 23.7%, and 11.8% sensitivity, respectively. Among them, 11.84% of the isolates were pan-sensitive, 35.5% of the cultures were multidrug-resistant (MDR), and 35.5% of the cultures were extensively drug-resistant (XDR). Conclusion The study demonstrates that polyresistant typhoidal salmonellae are no more confined to a couple of outbreaks in large cities of Pakistan. It is the tip of the iceberg, and the balance has tilted toward difficult-to-treat typhoid and paratyphoid fevers all across the country owing to significant resistance to the commonly used antityphoid antibiotics (cephalosporins and fluoroquinolones). Azithromycin and carbapenems are offering the last line of defense against the rampant Salmonella typhi and Salmonella paratyphi.

Recent Development in Separators for High-Temperature Lithium-Ion Batteries.

Lithium-ion batteries (LIBs) are promising energy storage devices for integrating renewable resources and high power applications, owing to their high energy density, light weight, high flexibility, slow self-discharge rate, high rate charging capability, and long battery life. LIBs work efficiently at ambient temperatures, however, at high-temperatures, they cause serious issues due to the thermal fluctuation inside batteries during operation. The separator is a key component of batteries and is crucial for the sustainability of LIBs at high-temperatures. The high thermal stability with minimum thermal shrinkage and robust mechanical strength are the prime requirements along with high porosity, ionic conductivity, and electrolyte uptake for highly efficient high-temperature LIBs. This Review deals with the recent studies and developments in separator technologies for high-temperature LIBs with respect to their structural layered formation. The recent progress in monolayer and multilayer separators along with the developed preparation methodologies is discussed in detail. Future challenges and directions toward the advancement in separator technology are also discussed for achieving remarkable performance of separators in a high-temperature environment.

Tyrosinase (TYR) gene sequencing and literature review reveals recurrent mutations and multiple population founder gene mutations as causative of oculocutaneous albinism (OCA) in Pakistani families.

PURPOSE: To investigate eight previously unreported Pakistani families with genetically undefined OCA for mutations in TYR. METHODS: Sanger sequencing of TYR has been performed in eight families with OCA phenotype. Mutation analysis was performed to establish the pathogenic role of novel mutation. Bioinformatics analysis was performed to predict the structural and functional impacts on protein due to the mutation. RESULTS: In this study, we identified six likely pathogenic variants of TYR (c.272 G>A, c.308 G>A, c.346C>T, c.715 C>T, c.832 C>T and c.1255 G>A), including one novel variant (c.308 G>A; p.Cys103Tyr), segregating as appropriate in each family. Cys103 lies in the highly conserved region of the tyrosinase enzyme, and p.Cys103Tyr is predicted to disturb enzymatic function via alteration of the configurational orientation of TYR leading to a more rigid polypeptide structure. We have also reviewed the mutation spectrum of TYR in Pakistani ethnicity. Published data on OCA families proposed that ~40% have been associated with genetic variations in the TYR gene. The mutations reported in this study have now been described with varying frequencies in Pakistani families, including very rare/unique mutations. CONCLUSION: A literature review of TYR gene mutations in Pakistani populations, combined with our genetic data, identified a number of gene mutations likely to represent regional ancestral founder mutations of relevance to Pakistani populations, in addition to sporadic and recurrent 'hotspot' mutations present repeatedly in other regions worldwide.

Carbon-Tungsten Disulfide Composite Bilayer Separator for High-Performance Lithium-Sulfur Batteries.

A bilayer separator based on cost-effective carbon-tungsten disulfide composite and commercial separators is developed in this work. The C-WS2 separator reduces the shuttling effect and increases the cycle life of the battery because of the excellent adsorption capability of polar WS2 to polysulfides. Furthermore, conductive carbon substantially enhances the ionic conductivity of (1 × 10-3 S cm-1). The cell with the C-WS2 separator delivers an excellent discharge capacity of 996 mA h g-1 at 1 C and retained at 416 mA h g-1 after runs over 1000 cycles with a 0.045% capacity decay per cycle. The work provides insights into high-capacity lithium-sulfur batteries with cost-effectiveness.

Nonsteroidal Anti-inflammatory Drugs and Endometrial Carcinoma Mortality and Recurrence.

Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients. Methods: Study subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained from medical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma-specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology. Results: Five hundred fifty endometrial carcinoma-specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR = 1.66, 95% CI = 1.21 to 2.30) increased endometrial carcinoma-specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR = 2.23, 95% CI = 1.19 to 4.18, two-sided P trend = .01). NSAID use was not associated with recurrence or endometrial carcinoma-specific mortality among women with type II tumors. Conclusions: In this study, use of NSAIDs was associated with increased endometrial carcinoma-specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted.

Surgical-pathological findings in type 1 and 2 endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study on GOG-210 protocol.

OBJECTIVE: To report clinical and pathologic relationships with disease spread in endometrial cancer patients. METHODS: Surgical candidates with uterine cancer (adenocarcinoma or carcinosarcoma) who were eligible to participate in a surgical pathological study to create a clinically annotated tissue biorepository to support translational and clinical research studies. All patients were to undergo a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. From 2003-2007, open eligibility enrollment was conducted, and from 2007-2011, eligibility was restricted to enrich underrepresented patients or those at high risk. RESULTS: This report details clinical pathological relationships associated with extra uterine disease spread of 5866 evaluable patients including those with endometrioid histology as well as papillary serous, clear cell and carcinosarcoma histologies. Review of unrestricted enrollment was constructed in an effort to capture a cross-section population representative of endometrial cancers seen by the GOG participating members. Evaluation of this group of patients suggested the more natural incidence of different surgical pathological findings as well as demographic information. The addition of 2151 patients enrolled during the restricted time interval allowed a total of 1630 poor histotype patients available for further analysis. As expected, endometrioid (E) cancers represented the largest enrollment and particularly E grade 1 and 2 (G1 and 2) were more frequently confined to the uterus. Grade 3 (G3) endometrioid cancers as well as the poor histotype (papillary serous, clear cell and carcinosarcoma) had a much greater propensity for extant disease. CONCLUSIONS: This study confirms the previously reported surgical pathological findings for endometrioid cancers but in addition, using a large database of papillary serous, clear cell and carcinosarcoma, surgical pathological findings substantiate the categorization of poor histotypes for these cancers.

FGFR2 mutations are associated with poor outcomes in endometrioid endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study.

PURPOSE: Activating FGFR2 mutations have been identified in ~10% of endometrioid endometrial cancers (ECs). We have previously reported that mutations in FGFR2 are associated with shorter disease free survival (DFS) in stage I/II EC patients. Here we sought to validate the prognostic importance of FGFR2 mutations in a large, multi-institutional patient cohort. METHODS: Tumors were collected as part of the GOG 210 clinical trial "Molecular Staging of Endometrial Cancer" where samples underwent rigorous pathological review and had more than three years of detailed clinical follow-up. DNA was extracted and four exons encompassing the FGFR2 mutation hotspots were amplified and sequenced. RESULTS: Mutations were identified in 144 of the 973 endometrioid ECs, of which 125 were classified as known activating mutations and were included in the statistical analyses. Consistent with FGFR2 having an association with more aggressive disease, FGFR2 mutations were more common in patients initially diagnosed with stage III/IV EC (29/170;17%) versus stage I/II EC (96/803; 12%; p=0.07, Chi-square test). Additionally, incidence of progression (progressed, recurred or died from disease) was significantly more prevalent (32/125, 26%) among patients with FGFR2 mutation versus wild type (120/848, 14%; p<0.001, Chi-square test). Using Cox regression analysis adjusting for known prognostic factors, patients with FGFR2 mutation had significantly (p<0.025) shorter progression-free survival (PFS; HR 1.903; 95% CI 1.177-3.076) and endometrial cancer specific survival (ECS; HR 2.013; 95% CI 1.096-3.696). CONCLUSION: In summary, our findings suggest that clinical trials testing the efficacy of FGFR inhibitors in the adjuvant setting to prevent recurrence and death are warranted.

Paclitaxel, Carboplatin, and Bevacizumab in Advanced and Recurrent Endometrial Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the efficacy of adding bevacizumab to paclitaxel and carboplatin and as maintenance in a larger cohort of patients with advanced or recurrent endometrial carcinoma. METHODS: We retrospectively identified endometrial cancer patients treated with paclitaxel (175 mg/m per 3 hours), carboplatin (area under the curve, 5) and bevacizumab (15 mg/kg) and maintenance bevacizumab treated in a post-protocol treatment cohort and evaluated them with our previously published phase 2 trial of this regimen. RESULTS: Twenty-seven additional patients were identified; 19 received the regimen as first-line therapy, and 8 received the regimen as second-line therapy after prior paclitaxel and carboplatin. The 19 patients who received first-line therapy were analyzed alone and with the 15 patients enrolled on protocol. The 2 cohorts were similar with respect to risk factors. Overall survival curves were not statistically different between the protocol and the postprotocol patients (log-rank test; P > 0.1). Collectively, a total of 266 courses (median, 6 courses; range, 1-20 courses) of carboplatin, paclitaxel, and bevacizumab combination therapy and 305 courses (median, 16 courses; range, 0-45courses) of bevacizumab maintenance therapy were administered as first-line therapy. Collectively, the median progression-free survival was 20 months, and median overall survival was 56 months. Among 29 patients with measurable disease, the response rate was 82.8% (95% confidence interval, 69.0%-96.5%; 15 complete responses and 9 partial responses). Among the 8 patients who received paclitaxel and carboplatin and bevacizumab as second-line therapy after paclitaxel and carboplatin, the response rate was 87.5% (6 complete responses, 1 partial response). Their median progression-free survival and median overall survival were not reached after a median follow-up of 23.5 months. CONCLUSIONS: Although there are inherent limitations to small retrospective studies, this second analysis confirms the high response rate, progression-free survival, and overall survival in the bevacizumab, paclitaxel, and carboplatin regimen as first-line therapy in advanced and recurrent endometrial carcinoma.

Utility of PET/CT to Evaluate Retroperitoneal Lymph Node Metastasis in High-Risk Endometrial Cancer: Results of ACRIN 6671/GOG 0233 Trial.

Purpose To assess the diagnostic accuracy of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with diagnostic contrast material-enhanced computed tomography (CT) in detecting lymph node (LN) metastasis in high-risk endometrial cancer. Materials and Methods This prospective multicenter HIPAA-compliant study had institutional review board approval, and all participants gave written informed consent. Data were accrued between January 2010 and June 2013. Patients underwent PET/CT and pelvic and abdominal lymphadenectomy. Two hundred seven of 215 enrolled patients had PET/CT and pathologic examination results for the abdomen and pelvis. Mean patient age was 62.7 years ± 9.6 (standard deviation). Data in all 23 patients with a positive abdominal examination and in 26 randomly selected patients with a negative abdominal examination were used for this central reader study. Seven independent blinded readers reviewed diagnostic CT and PET/CT results in different sessions 1 month apart. Accuracy was calculated at the participant level, correlating abdominal (right and left para-aortic and common iliac) and pelvic (right and left external iliac and obturator) LN regions with pathologic results, respecting laterality. Reader-average sensitivities, specificities, and areas under the receiver operating characteristic curve (AUCs) of PET/CT and diagnostic CT were compared. Power calculation was for sensitivity and specificity in the abdomen. Results Sensitivities of PET/CT versus diagnostic CT for the detection of LN metastasis were 0.65 (95% confidence interval [CI]: 0.57, 0.72) versus 0.50 (95% CI: 0.43, 0.58) (P = .01) in the abdomen and 0.65 (95% CI: 0.57, 0.72) versus 0.48 (95% CI: 0.41, 0.56) (P = .004) in the pelvis. Corresponding specificities were 0.88 (95% CI: 0.83, 0.92) versus 0.93 (95% CI: 0.89, 0.96) (P = .11) and 0.93 (95% CI: 0.86, 0.96) versus 0.89 (95% CI: 0.82, 0.94) (P = .27), and AUCs were 0.78 (95% CI: 0.66, 0.89) versus 0.74 (95% CI: 0.63, 0.86) (P = .39) and 0.82 (95% CI: 0.71, 0.92) versus 0.73 (95% CI: 0.63, 0.84) (P = .02). Conclusion FDG PET/CT has satisfactory diagnostic accuracy in the detection of abdominal LN metastasis in high-risk endometrial cancer. Compared with diagnostic CT alone, addition of PET to diagnostic CT significantly increased sensitivity in both the abdomen and pelvis while maintaining high specificity. © RSNA, 2017 Online supplemental material is available for this article.

Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study.

PURPOSE: The clinicopathologic significance of mismatch repair (MMR) defects in endometrioid endometrial cancer (EEC) has not been definitively established. We undertook tumor typing to classify MMR defects to determine if MMR status is prognostic or predictive. METHODS: Primary EECs from NRG/GOG0210 patients were assessed for microsatellite instability (MSI), MLH1 methylation, and MMR protein expression. Each tumor was assigned to one of four MMR classes: normal, epigenetic defect, probable mutation (MMR defect not attributable to MLH1 methylation), or MSI-low. The relationships between MMR classes and clinicopathologic variables were assessed using contingency table tests and Cox proportional hazard models. RESULTS: A total of 1,024 tumors were assigned to MMR classes. Epigenetic and probable mutations in MMR were significantly associated with higher grade and more frequent lymphovascular space invasion. Epigenetic defects were more common in patients with higher International Federation of Gynecology and Obstetrics stage. Overall, there were no differences in outcomes. Progression-free survival was, however, worse for women whose tumors had epigenetic MMR defects compared with the MMR normal group (hazard ratio, 1.37; P < .05; 95% CI, 1.00 to 1.86). An exploratory analysis of interaction between MMR status and adjuvant therapy showed a trend toward improved progression-free survival for probable MMR mutation cases. CONCLUSION: MMR defects in EECs are associated with a number of well-established poor prognostic indicators. Women with tumors that had MMR defects were likely to have higher-grade cancers and more frequent lymphovascular space invasion. Surprisingly, outcomes in these patients were similar to patients with MMR normal tumors, suggesting that MMR defects may counteract the effects of negative prognostic factors. Altered immune surveillance of MMR-deficient tumors, and other host/tumor interactions, is likely to determine outcomes for patients with MMR-deficient tumors.

Utility of PET-CT to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer: Results of ACRIN6671/GOG0233 trial.

OBJECTIVE: To assess if FDG PET combined with diagnostic CT improves diagnostic CT accuracy to detect lymph node (LN) metastasis in advanced cervical cancer. METHODS: A prospective HIPAA compliant ACRIN/GOG multicenter trial was conducted. Patients underwent concurrent diagnostic contrast-enhanced CT (DCT) and PET and pelvic/abdominal lymphadenectomy. Seven independent blinded readers reviewed PET-DCT and DCT one-month apart. Reference standard was surgically removed LN pathology. Accuracy values were calculated at participant level, correlating abdominal (right and left para-aortic/common iliac) and pelvic (right and left external iliac/obturator) LN regions with pathology, respecting laterality. Reader average sensitivities/specificities of PET-DCT vs. DCT were compared with generalized linear mixed models, and AUCs with Obuchowski's method. RESULTS: One hundred fifty-three patients had PET-DCT and pathology. Forty-three of 153 patients had metastasis to abdominal LNs. Sample size calculation required review of the first 40 abdominal positive and 40 randomly selected abdominal negative studies. Patients were 24 to 74years (48.9±10.6) old. Mean sensitivities of PET-DCT/DCT for detection of LN metastasis in abdomen were 0.50 (CI: 0.44, 0.56) and 0.42 (CI: 0.36, 0.48) (p=0.052) and in pelvis 0.83 (CI: 0.78, 0.87) and 0.79 (CI: 0.73, 0.83) (p=0.15). Corresponding specificities were 0.85 (CI: 0.80, 0.89) and 0.89 (CI: 0.84, 0.92) (p=0.21) and 0.63 (CI: 0.54, 0.70) and 0.62 (CI: 0.53, 0.69) (p=0.83). Mean AUC values were 0.70 (CI: 0.61, 0.79) and 0.68 (CI: 0.59, 0.77) (p=0.43) and 0.80 (CI: 0.71, 0.88) and 0.76 (CI: 0.67, 0.85) (p=0.21) respectively. CONCLUSION: Addition of PET to DCT resulted in statistically borderline increase in sensitivity to detect LN metastasis in abdomen in advanced cervical cancer.

Expression Patterns of the Wnt Pathway Inhibitors Dickkopf3 and Secreted Frizzled-Related Proteins 1 and 4 in Endometrial Endometrioid Adenocarcinoma: An NRG Oncology/Gynecologic Oncology Group Study.

OBJECTIVE: The aim of the study was to determine the differential expression patterns of the wingless-type (Wnt) pathway inhibitors Dkk3 (Dickkopf 3), SFRP1 (secreted frizzled-related protein 1), and SFRP4 in normal müllerian tissue and endometrial endometrioid adenocarcinoma specimens. METHODS: Messenger RNA (mRNA) and protein levels of the Wnt pathway inhibitors Dkk3, SFRP1, and SFRP4 were evaluated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. A total of 87 human tissue specimens were obtained from 60 women who participated in Gynecologic Oncology Group protocol 210. Twenty-seven normal müllerian tissues, 32 early-stage, and 28 advanced-stage endometrial endometrioid cancer specimens were analyzed. RESULTS: Median age for this cohort was 60 years, with median body mass index of 32 kg/m. There was a difference in Dkk3 protein expression between normal müllerian tissues and primary endometrial endometrioid adenocarcinoma samples (P = 0.05). There was down-regulation of Dkk3, SFRP1, and SFRP4 mRNA expression in patients with high-grade disease (P = 0.08, 0.06, and 0.05, respectfully). Furthermore, a decrease in SFRP1 and SFPR4 mRNA expression was noted in patients with a diagnosis of locoregional and distant disease recurrence. Lastly, a trend toward decreased progression-free survival in patients with low Dkk3, SFRP1, and SFRP4 mRNA expression levels was noted. CONCLUSIONS: Wnt pathway inhibitor (Dkk3, sFRP1, and/or sFRP4) expression was down-regulated in patients with high-grade disease and was associated with locoregional and distant disease recurrence. Despite sample size (power) limitations, these results support previous preclinical studies and may suggest a therapeutic role for Wnt signaling in endometrial cancer.

Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study.

PURPOSE: The best screening practice for Lynch syndrome (LS) in endometrial cancer (EC) remains unknown. We sought to determine whether tumor microsatellite instability (MSI) typing along with immunohistochemistry (IHC) and MLH1 methylation analysis can help identify women with LS. PATIENTS AND METHODS: ECs from GOG210 patients were assessed for MSI, MLH1 methylation, and mismatch repair (MMR) protein expression. Each tumor was classified as having normal MMR, defective MMR associated with MLH1 methylation, or probable MMR mutation (ie, defective MMR but no methylation). Cancer family history and demographic and clinical features were compared for the three groups. Lynch mutation testing was performed for a subset of women. RESULTS: Analysis of 1,002 ECs suggested possible MMR mutation in 11.8% of tumors. The number of patients with a family history suggestive of LS was highest among women whose tumors were classified as probable MMR mutation (P = .001). Lynch mutations were identified in 41% of patient cases classified as probable mutation (21 of 51 tested). One of the MSH6 Lynch mutations was identified in a patient whose tumor had intact MSH6 expression. Age at diagnosis was younger for mutation carriers than noncarriers (54.3 v 62.3 years; P < .01), with five carriers diagnosed at age > 60 years. CONCLUSION: Combined MSI, methylation, and IHC analysis may prove useful in Lynch screening in EC. Twenty-four percent of mutation carriers presented with ECs at age > 60 years, and one carrier had an MSI-positive tumor with no IHC defect. Restricting Lynch testing to women diagnosed at age < 60 years or to women with IHC defects could result in missing a substantial fraction of genetic disease.

Associations between etiologic factors and mortality after endometrial cancer diagnosis: the NRG Oncology/Gynecologic Oncology Group 210 trial.

BACKGROUND: Few studies have analyzed relationships between risk factors for endometrial cancer, especially with regard to aggressive (non-endometrioid) histologic subtypes, and prognosis. We examined these relationships in the prospective NRG Oncology/Gynecologic Oncology Group 210 trial. METHODS: Prior to surgery, participants completed a questionnaire assessing risk factors for gynecologic cancers. Pathology data were derived from clinical reports and central review. We used the Fine and Gray subdistribution hazards model to estimate subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations between etiologic factors and cause-specific subhazards in the presence of competing risks. These models were stratified by tumor subtype and adjusted for stage and socioeconomic status indicators. RESULTS: Median follow-up was 60months after enrollment (range: 1day-118months). Among 4609 participants, a total of 854 deaths occurred, of which, 582 deaths were attributed to endometrial carcinoma. Among low-grade endometrioid cases, endometrial carcinoma-specific subhazards were significantly associated with age at diagnosis (HR=1.04, 95% CI=1.01-1.06 per year, P-trend) and BMI (class II obesity vs. normal BMI: HR=2.29, 95% CI=1.06-4.98, P-trend=0.01). Among high-grade endometrioid cases, endometrial carcinoma-specific subhazards were associated with age at diagnosis (HR=1.05, 95% CI=1.02-1.07 per year, P-trend<0.001). Among non-endometrioid cases, endometrial carcinoma-specific subhazards were associated with parity relative to nulliparity among serous (HR=0.55, 95% CI=0.36-0.82) and carcinosarcoma cases (HR=2.01, 95% CI=1.00-4.05). DISCUSSION: Several endometrial carcinoma risk factors are associated with prognosis, which occurs in a tumor-subtype specific context. If confirmed, these results would suggest that factors beyond histopathologic features and stage are related to prognosis. ClinicalTrials.gov Identifier: NCT00340808.

Assessing the prognostic role of ATR mutation in endometrioid endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study.

OBJECTIVE: We sought to validate the clinicopathologic implications and prognostic significance of ATR (ataxia telangiectasia mutated and Rad3-related) mutation in patients with endometrioid endometrial cancer and defective DNA mismatch repair enrolled in a cooperative group molecular staging study of endometrial cancer. METHODS: After pathology review, only endometrioid tumors with high neoplastic cellularity (≥70%) and high quality DNA for molecular analyses were included. MSI (microsatellite instability) typing was performed and the target sequence in exon 10 of ATR was evaluated by direct sequencing in all MSI-high tumors. Associations between ATR mutations and clinicopathologic variables were assessed using contingency table tests. Differences in overall survival (OS) and disease-free survival (DFS) were evaluated by univariate analyses and multivariable Cox proportional hazard models. RESULTS: A total of 475 eligible cases were identified. Of 368 MSI+ cases, the sequence of interest could be successfully genotyped in 357 cases. ATR mutations were exclusively identified in 46 tumors with high level microsatellite instability (MSI+) (12.9%, p<0.001) and were associated with higher tumor grade (p=0.001). ATR mutations were not associated with OS (HR 1.16; 95% CI, 0.58-2.32; p=0.68) or DFS (HR 0.61; 95% CI, 0.25-1.50; p=0.28). CONCLUSION: Truncating mutations in exon 10 of ATR occur exclusively in tumors with evidence of defective DNA mismatch repair. We were not able to confirm the prognostic value of these mutations in patients with endometrioid endometrial cancer.

MICROBIOLOGICAL PATTERN OF VENTILATOR ASSOCIATED PNEUMONIA.

BACKGROUND: Ventilator associated pneumonia (VAP) is an important and common complication of mechanically ventilated patients. It is the leading cause of morbidity and mortality in Intensive Care Units (ICU) worldwide. The aim of study was to determine the pattern of bacteria involved in VAP in intensive care unit of Jinnah hospital Lahore. METHODS: It was descriptive case series study, conducted over a period of one year on mechanically ventilated 50 patients. American Thoracic Society (ATS) guidelines recommend quantitative/semi-quantitative culture of endotracheal aspirates (ETA) or bronchoscopic aspirates/washing from the infected lung segments for the diagnosis of VAP. Hence this study was conducted to identify the types of bacteria involved in VAP in our ICU. Patients enrolled were clinically and radiologically suspected VAP, admitted in the ICU of Jinnah Hospital/Allama Iqbal Medical College (AIMC) Lahore. Bronchial washings were taken with the help of Fiber optic bronchoscope. Wherever bronchoscopy was not possible, subglottic secretions were collected with the help of sterilized catheter and sucker. Collected samples were sent to the Pathology laboratory of AIMC for aerobic culture and sensitivity. RESULTS: Major pathogenic bacteria isolated were Gram negative (74%). Among this group E. coli, Pseudomonas, Klebsiella and Acinetobacter were the commonest organisms. Gram positive bacteria were 20%, Staphylococcus aureus (MRSA) and beta-haemolyticus streptococci were the major isolate. In 4% cases mixed growth and in 2% cases no growth was reported. CONCLUSION: Major pathogenic organisms of VAP in our ICU are Gram negative bacteria. The Bacteriological culture of endobroncheal aspirates is helpful in the diagnosis and management of VAP. Emperic antibiotic therapy for VAP should cover Gram negative organisms.

Frequency and antimicrobial susceptibility pattern of acinetobacter species isolated from pus and pus swab specimens.

OBJECTIVE: To evaluate the frequency and antimicrobial susceptibility pattern of Acinetobacter species isolated from pus and pus swab specimens at a tertiary care setting. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from July 2008 to July 2012. METHODOLOGY: Data regarding positive culture and antimicrobial sensitivity pattern was retrieved from the pus and pus swab culture records of the Microbiology Department, AFIP, Rawalpindi. Only those pus and pus swab specimens which yielded the growth of Acinetobacterspecies were included in the study. RESULTS: Out of 2781, 1848 were of pure pus while 933 were pus swab specimens. Out of 2538 culture positive isolates, 276 (10.9%) were identified as Acinetobacterspecies. Among 276 Acinetobacterspp., 245 (88.8%) were Acinetobacter baumannii and 31 (11.2%) were Acinetobacterjohnsonii. Male/female ratio of the affected patients was 5.6:1. Doxycycline was the most sensitive antibiotic to which 45% of the tested isolates were sensitive. Sensitivity to all other antimicrobials was 15% or less. CONCLUSION: About 11% of soft tissue and wound infections are caused by Acinetobacterspecies in our set up particularly in male. Doxycycline was the most sensitive antibiotic. Sensitivity to all other antimicrobials was 15% or less. In vitro sensitivity to carbapenems is very low.

Batchwise dyeing of bamboo cellulose fabric with reactive dye using ultrasonic energy.

Bamboo is a regenerated cellulose fiber usually dyed with reactive dyes. This paper presents results of the batchwise dyeing of bamboo fabric with reactive dyes by ultrasonic (US) and conventional (CN) dyeing methods. The study was focused at comparing the two methods for dyeing results, chemicals, temperature and time, and effluent quality. Two widely used dyes, CI Reactive Black 5 (bis-sulphatoethylsulphone) and CI Reactive Red 147 (difluorochloropyrimidine) were used in the study. The US dyeing method produced around 5-6% higher color yield (K/S) in comparison to the CN dyeing method. A significant savings in terms of fixation temperature (10°C) and time (15 min), and amounts of salt (10 g/L) and alkali (0.5-1% on mass of fiber) was realized. Moreover, the dyeing effluent showed considerable reductions in the total dissolved solids content (minimum around 29%) and in the chemical oxygen demand (minimum around 13%) for the US dyebath in comparison to the CN dyebath. The analysis of colorfastness tests demonstrated similar results by US and CN dyeing methods. A microscopic examination on the field emission scanning electron microscope revealed that the US energy did not alter the surface morphology of the bamboo fibers. It was concluded that the US dyeing of bamboo fabric produces better dyeing results and is a more economical and environmentally sustainable method as compared to CN dyeing method.

Cationic starch (Q-TAC) pre-treatment of cotton fabric: influence on dyeing with reactive dye.

Reactive dyes require high concentrations of an electrolyte to improve dye-fiber interaction, leading to the discharge of harmful effluent. One approach to reduce this unsafe release is treatment of the cotton fabric with cationic chemical reagents. This paper reports on the treatment of cotton fabric with cationic starch (Q-TAC), a commercial product, by batchwise method and pad batch method for the first time prior to reactive dyeing process. Furthermore,three commercial reactive dyes, based on monochloro triazine, vinyl sulfone and monochlorotriazine + vinyl sulfonechemistry, was applied on the cotton fabrics by continuous (pad-dry-cure) method. The treated cotton fabric by batchwise method produced 70% higher color yield (K/S) and 20% enhanced dye fixation (%F) than the untreated cotton fabric. X-ray photoelectron spectrometer (XPS) analysis revealed the presence of N1s peaks in the treated cotton fabrics. The crystallinity of treated cotton fabrics was reduced in comparison to untreated cotton fabric as revealed by wide angle X-ray diffraction (WAXD) measurements. Field Emission Scanning Electron Microscopy (FE-SEM) showed that the surface of treated cotton fabrics was rougher than untreated cotton fabric due to the deposition of cationic starch. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrum confirmed the existence of quaternary ammonium groups, N(+)(CH3)3, in the treated cotton fabrics. The analysis of color fastness tests demonstrated good to excellent ratings for treated cotton fabrics. In this way, cationic starch treatment of cotton fabric before reactive dyeing process has been proven potentially a more environmentally sustainable method than conventional dyeing method.