Uveal melanoma immunogenomics predict immunotherapy resistance and susceptibility.

Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but has limited efficacy against metastatic uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human uveal melanoma metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these metastases harbor tumor infiltrating lymphocytes with potent autologous tumor specificity, despite low mutational burden and resistance to prior immunotherapies. However, we observe strikingly low intratumoral T cell receptor clonality within the tumor microenvironment even after prior immunotherapies. To harness these quiescent tumor infiltrating lymphocytes, we develop a transcriptomic biomarker to enable in vivo identification and ex vivo liberation to counter their growth suppression. Finally, we demonstrate that adoptive transfer of these transcriptomically selected tumor infiltrating lymphocytes can promote tumor immunity in patients with metastatic uveal melanoma when other immunotherapies are incapable.

The Efficacy and Safety of Intravenous Colistin Plus Aerosolized Colistin Versus Intravenous Colistin Alone in Critically Ill Trauma Patients With Multi-Drug Resistant Gram-Negative Bacilli Infection.

BACKGROUND AND AIM: Gram-negative bacteria (GNB) with potential multiple drug resistance (MDR) have emerged as a major group of organisms causing ventilator-associated pneumonia (VAP). Higher concentrations are deposited directly in the lungs when antibiotics are given via inhalation, minimizing systemic side effects. This study aims to compare the efficacy and safety of intravenous plus aerosolized colistin versus intravenous (IV) colistin alone in critically ill trauma patients who reported MDR-GNB infection on endotracheal aspirate culture. METHODS: A hundred patients were recruited in the Intensive Care Unit, Trauma Centre, Institute of Medical Sciences, Banaras Hindu University, Varanasi, and randomly assigned to the control (n=50) group, which received IV colistin plus aerosolized colistin and the intervention group (n = 50), which received IV colistin alone. Changes in total leucocyte count (TLC), renal function test (RFT), endotracheal aspirate culture, 24-hour urine output, length of ICU stay, and 28-day ICU mortality were investigated. RESULTS: Patients receiving intravenous plus nebulized colistin therapy had a better outcome compared to IV colistin alone in terms of faster eradication of MDR-GNB infection. A rise in serum urea and creatinine levels was seen in both groups, which were significantly higher, along with a decrease in urine output in the group receiving intravenous colistin alone. No significant difference was observed in serum sodium and potassium levels in the RFT protocol, length of ICU stay, or 28-day ICU mortality. CONCLUSION: Intravenous nebulized colistin could be considered a better alternative therapy for VAP caused by multi-drug-resistant Gram-negative bacteria in the ICU in terms of faster microbiological cure and lesser nephrotoxicity.

Duloxetine in Reducing Catheter-Related Bladder Discomfort: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study.

OBJECTIVE: The excessive desire to void with discomfort in the supra-pubic region, which is experienced postoperatively by patients who underwent urinary catheterization, is known as catheter-related bladder discomfort. In this study, we evaluated duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, in preventing catheter-related bladder discomfort. MATERIAL AND METHODS: Around 64 adults (18-60 years), of either sex, with American Society of American Society of Anesthesiologists (ASA) physical status I and II, scheduled to undergo elective gastrointestinal carcinoma surgeries under general anesthesia were analyzed in the final assessment of 2 comparative groups C and D of 32 patients each. Group D received 1 ranitidine tablet of 150 mg and 1 duloxetine tablet of 60 mg, while group C patients received 2 tablets of ranitidine of 75 mg 2 hours prior to induction. A 16 F Foley catheter was used to catheterize bladder intra-operatively, and 10 mL of distilled water was used to fill the balloon. At 0, 1, 2, and 6 hours, the catheter-related bladder discomfort was evaluated, and categorized into none, mild, moderate, and severe. The study drug's adverse effects, if any, were reported. RESULTS: At all-time intervals, group D had lower incidence and severity of catheterrelated bladder discomfort than group C (P < .05). Compared to group C, patients in group D had a higher incidence of nausea, dizziness, and vomiting; nevertheless, the difference was statistically insignificant (P > .05). CONCLUSION: Duloxetine of 60 mg given orally 2 hours before induction decreases the incidence and severity of catheter-related bladder discomfort.

Healthcare disparities and pelvic organ prolapse operative complications: a nationwide analysis.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to evaluate the differences in the incidence of peri-operative complications at the time of pelvic organ prolapse (POP) repair based on health care disparities such as race and socioeconomic status. METHODS: The National Inpatient Sample (NIS) database was queried using ICD-9/-10 codes for patients aged >18 years undergoing POP repair in 2008-2018. Demographic information, Elixhauser Comorbidity Index (ECI), insurance status, and peri-operative complications were extracted. Multivariate weighted logistic regression using the discharge weights from NIS were constructed on binary outcomes. Complications with at least 1% incidence were included in the analysis. RESULTS: A total of 172,483 POP repair patients were analyzed: 130,022 (75.4%) were white, 10,561 (6.1%) were Black, 21,915 (12.7%) were Hispanic, and 9,985 (5.8%) were of other races. Patients with Medicaid as well as Black, Hispanic, and other races had higher odds of developing postoperative complications such as urinary tract infections, sepsis, and acute renal failure (p value <0.001-0.02). These were also more common in smaller, rural hospitals and with patients with an annual income of $45,999 or less (p value <0.001-0.03). Black and Hispanic patients had lower odds of intraoperative complications such as hemorrhage (aOR 0.77, 95% CI 0.71-0.84; aOR 0.75, 95% CI 0.7-0.8 respectively) or abdominopelvic injury (aOR 0.86, 95% CI 0.81-0.92; aOR 0.93, 95% CI 0.79-0.88 respectively) compared with white patients. CONCLUSION: Nonwhite patients with lower socioeconomic status had increased postoperative complications and fewer intraoperative complications from POP surgery, whereas white patients with higher socioeconomic status had more intraoperative complications.

Ichthyosis uteri: A keratinizing squamous metaplasia of the endometrium with premalignant potential.

•Ichthyosis uteri is a rare condition describing extensive endometrial keratinization.•There may be an association with squamous cell carcinoma of the endometrium.•Endometrial extension of cervical malignancy may closely resemble ichthyosis.•A hysterectomy should be considered in patients who have completed childbearing.

Genome-wide gain-of-function screening characterized lncRNA regulators for tumor immune response.

The majority of lncRNAs' roles in tumor immunology remain elusive. This project performed a CRISPR activation screening of 9744 lncRNAs in melanoma cells cocultured with human CD8+ T cells. We identified 16 lncRNAs potentially regulating tumor immune response. Further integrative analysis using tumor immunogenomics data revealed that IL10RB-DT and LINC01198 are significantly correlated with tumor immune response and survival in melanoma and breast cancer. Specifically, IL10RB-DT suppresses CD8+ T cells activation via inhibiting IFN-γ-JAK-STAT1 signaling and antigen presentation in melanoma and breast cancer cells. On the other hand, LINC01198's up-regulation sensitizes the killing of tumor cells by CD8+ T cells. Mechanistically, LINC01198 interacts and activates NF-κB component p65 to trigger the type I and type II interferon responses in melanoma and breast cancer cells. Our study systematically characterized novel lncRNAs involved in tumor immune response.

Reservoir of Carbapenem-Resistant Acinetobacter baumannii in the Hospital Environment and Colonization Pressure: A Surveillance-Based Study in Indian Intensive Care Unit.

The endemicity of Acinetobacter baumannii in intensive care units (ICUs) is a serious concern. We studied the reservoirs of A. baumannii in the ICU and their effects on colonization pressure and transmission. A prospective surveillance (6 months) was conducted. Screening culture (rectal and axillary) swabs were collected within 48 hours admission and in 120 hours. Surveillance cultures from patients' surroundings, health care workers (HCWs), and hospital sewage were collected. A. baumannii was identified by phenotypic and genotypic methods. Carbapenem resistance and insertion sequence element were detected. Typing was done by repetitive extragenic palindromic-polymerase chain reaction and multilocus sequence typing. Colonization pressure was calculated and compared with environment colonizers. Of the 87 patients, 21.83% (19) were colonized with A. baumannii, 73.68% (14/19) were imported, and 26.31% (5/19) acquired carriers. Axilla was the commonest site. From the environment (15), bed rails 33.33% (5/15) and suction tubes 26.66% (4/15) were the common sites. HCWs showed 7.5% (3/40) carriage. Carbapenem resistance with blaOXA-51, blaOXA-23, and ISAba1 were 91.89% (34/37). Strong correlation between colonization pressures and environmental colonizers was seen (r2 = 0.719, p = 0.032). Carbapenem and polymyxin B were (p ≤ 0.05) significant exposures. Sequence type 623 was the predominant cluster with isolates from carriers, HCWs, and environment. Colonization pressure of carbapenem-resistant A. baumannii depends on their presence in the hospital. Hands of HCWs were an important vehicle for transmission. Infection control measure should consider reducing the environmental reservoir.

Efficacy of phenytoin for 7 days versus 21 days as prophylactic anticonvulsant in traumatic brain injury patients - A comparative study.

Background: Post traumatic seizures (PTS) are very common after traumatic brain injury and occur more common in severe form of injury. Prophylactic treatment with phenytoin has been found to be effective however till now no uniform internationally agreed guideline is available for the duration of anticonvulsant prophylaxis for traumatic brain injury patients. Methods: 100 patients of either sex between age group of 18-65 years who have suffered intracranial injury identified by CT scan, admitted in Trauma ICU were enrolled in this prospective randomized single blinded clinical study. Group 1 (n = 50) received 7 days prophylactic anticonvulsant therapy with phenytoin and Group 2 (n = 50) received for 21 days. The primary end point was the occurrence of seizures, which were classified as early (occurring from time of drug loading to day 7) or late (occurring on day 8 or later after loading of drug). Patients were also assessed for the possible adverse side effects of phenytoin. Result: Out of 100 patients, 90 completed the study successfully as 5 patients from each group expired during the duration of the study. On comparing the frequency of seizure from 1st to 7th day after loading dose of phenytoin between two groups, out of 45 patient, 2 (4.4%) developed seizure in group 1 and 3 (6.7%) developed seizure in group 2 and found to be statistically insignificant (P = 0.645). On comparing the frequency of seizure from 1st to 21st day after loading dose of phenytoin between two groups, out of 45 patient, 4 (8.9%) developed seizure in groups 1 and 3 (11.1%) developed seizure in group 2 and found to be statistically insignificant (P = 0.725). Conclusion: A 21-day prophylactic anticonvulsant therapy with phenytoin was not more effective than a 7-day prophylactic therapy with phenytoin to reduce the frequency of seizure in a TBI patient in trauma ICU and was also associated with more adverse side effects that were insignificant.

Cancer surgery during COVID increased the patient mortality and the transmission risk to healthcare workers: results from a retrospective cohort study (NCT05240378).

BACKGROUND: India encountered two waves of COVID-19 pandemic with variability in its characteristics and severity. Concerns were raised over the safety of treatment, and higher morbidity was predicted for oncological surgery. The present study was conducted to evaluate and compare the rate of morbidity and mortality in patients undergoing curative surgery for cancer before and during the COVID-19 pandemic. METHOD: The prospectively obtained clinical data of 1576 patients treated between April 2019 and May 2021 was reviewed; of these, 959 patients were operated before COVID-19 and 617 during the pandemic. The data on complications, deaths, confirmed or suspected COVID-19 cases, and COVID-19 infection among health workers (HCW) was extracted. RESULTS: A 35% fall in number of surgeries was seen during the COVID period; significant fall was seen in genital and esophageal cancer. There was no difference in postoperative complication; however, the postoperative mortality was significantly higher. A total of 71 patients had COVID-19, of which 62 were preoperative and 9 postoperative, while 30/38 healthcare workers contracted COVID-19, of which 7 had the infection twice and 3 were infected after two doses of vaccination; there was no mortality in healthcare workers. CONCLUSION: The present study demonstrates higher mortality rates after surgery in cancer patients, with no significant change in morbidity rates. A substantial proportion of HCWs were also infected though there was no mortality among this group. The results suggest higher mortality in cancer patients despite following the guidelines and protocols.

Rate of Mesh Erosion After Sacrocolpopexy With Concurrent Supracervical Compared With Total Hysterectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the effect of concomitant supracervical hysterectomy compared with total hysterectomy during abdominal sacrocolpopexy on the rate of mesh erosion by performing a systematic review and meta-analysis of the existing literature. DATA SOURCES: From database inception through January 2022, we explored MEDLINE, Web of Science, EMBASE, CINAHL, ClinicalTrials.gov , and Cochrane Central Register of Controlled Trials. Studies comparing the rate of mesh erosion in women undergoing abdominal sacrocolpopexy who had concomitant supracervical hysterectomy compared with total hysterectomy were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers separately ascertained studies, obtained data, and gauged study quality. The rate of mesh erosion was compared, and odds ratios (ORs) with 95% CIs were estimated. TABULATION, INTEGRATION, AND RESULTS: Nineteen studies with 10,572 women who underwent abdominal sacrocolpopexy were identified, including 4,285 women in the supracervical group and 6,287 women in the total hysterectomy group. The overall mean postprocedure follow-up time was 30.7±15.1 months (median 12.4, range 1.5-44.2). The median (95% CI) point prevalence of mesh erosion was 0.36% (0-1.9%) in women who had supracervical hysterectomy compared with 3.8% (1.8-8.7%) in women who had total hysterectomy. The overall rate of mesh erosion in women who had supracervical hysterectomy was lower compared with women who had total hysterectomy (pooled OR 0.26, 95% CI 0.18-0.38, I 2 0%). CONCLUSION: In women with symptomatic apical pelvic organ prolapse who undergo abdominal sacrocolpopexy with concomitant hysterectomy, supracervical hysterectomy is associated with a lower risk of mesh erosion compared with total hysterectomy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022301862.

Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu.

INTRODUCTION: Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer with a poor prognosis. Approximately 30% of USC overexpress HER2/neu, a recognized target for trastuzumab in advanced/recurrent HER2/neu-positive USC. We evaluated the efficacy of the pan-c-erb inhibitor neratinib and the poly (ADP-ribose)-polymerase (PARP) inhibitor olaparib as single agents and in combination against USC cell lines and xenografts. METHODS: In-vitro cell-viability assays with olaparib, neratinib, and olaparib/neratinib were assessed using flow-cytometry based assays against a panel of USC cell lines with high and low HER2/neu expression. Homologous recombination deficiency (HRD) signatures were evaluated as described by Alexandrov et al. (Nature;2020;578:94-101) while downstream signaling affected by neratinib/olaparib exposure was assessed with immunoblotting. Efficacy of single- versus dual-agent inhibition was evaluated in-vivo using two USC-xenografts with 3+ HER2/neu expression. RESULTS: Neratinib was more potent than olaparib in suppression of in-vitro growth of HER2/neu 3+ cell lines (ARK1: p = 0.0047; ARK2: p = 0.0428) while no difference was noted against HER2/neu 1+ tumors (ARK4). Importantly, the combination of olaparib with neratinib synergistically improved tumor suppression compared to either single-agent in vitro. USC cells exposed to olaparib upregulated HER2/neu expression, while neratinib treatment increased PARP activity (ARK1: p < 0.0001; ARK2: p < 0.0001). Single-agent neratinib transiently inhibited in vivo growth of USC xenografts harboring HER2/neu gene amplification (ARK1: p < 0.05; ARK2: p < 0.05). In contrast, the combination of the two inhibitors caused a stronger and durable growth inhibition in both USC xenografts (ARK1: p < 0.05; ARK2: p < 0.05). CONCLUSION: The combination of olaparib and neratinib is active and synergistic against primary HER2/neu + USC. This combination may represent a novel therapeutic option for USC patients with HER2/neu+, homologous recombination-proficient tumors resistant to chemotherapy.

Efficacy of Estradiol Cream for Venipuncture Pain in Obese Female Patients: A Pilot Study.

INTRODUCTION: Venipuncture is often a painful procedure causing significant anxiety, distress, and psychological consequences. We evaluated the efficacy of estradiol cream and compared it with a eutectic mixture of local anesthetics (EMLA) cream for alleviation of venipuncture pain and to make cannulation easy in female obese patients. MATERIALS AND METHODS: The clearance from the Institutional Ethical Committee as well as prior written and informed consent were obtained from the participants. A total of 105 obese female adult patients aged between 25 and 64 years belonging to the American Society of Anesthesiologists (ASA) physical status I and II with body mass index (BMI) > 30 kg/m2 were included in our study. The study participants were randomly allocated into three groups: In group I, a placebo cream was applied; in group II, estradiol cream was applied, and in group III, EMLA cream was applied. Any abnormal sensation at the site of application of the cream was noted and followed up at 0, 2, and 6 hours for the same. The primary outcome was the measurement of the severity of the pain experienced during venipuncture using the visual analog scale (VAS). Ease of cannulation was our secondary outcome. VAS was compared with the Z test. Statistical Package for the Social Sciences (SPSS) v16.0 software (SPSS Inc., Chicago) was used for statistical analysis. A p-value of <0.05 was considered statistically significant. RESULT: The final analysis was carried out on 25 patients in group I, 27 patients in group II, and 33 patients in group III. There was no significant improvement in the ease of cannulation in group II when compared to group I. The mean VAS was similar in group I and group II, whereas it was significantly reduced in group III (p < 0.05). CONCLUSION: EMLA cream was found to significantly reduce the pain of venipuncture in comparison to placebo and estradiol cream. There is no beneficial effect of estradiol cream in reducing the pain from venipuncture or in ease of cannulation compared to placebo.

Health Care Disparities in Surgical Management of Pelvic Organ Prolapse: A Contemporary Nationwide Analysis.

OBJECTIVES: Our objective was to compare the rate of native tissue repair (NTR) versus sacrocolpopexy (SCP) and reconstructive (RECON) versus obliterative repair (OBR) for the treatment of pelvic organ prolapse (POP), evaluating for health care disparities based on race, socioeconomic, and geographic factors. METHODS: The National Inpatient Sample database was queried for patients older than 18 years undergoing POP surgery from 2008 to 2018. Baseline demographics, comorbidity index, socioeconomic, and hospital variables were extracted. The weighted t test, Wilcoxon test, and χ2 test were used to compare the rate of (1) NTR versus SCP and (2) RECON vs OBR. Multivariate weighted logistic regression was used to compare while controlling for confounders. Reference groups were White race, Medicare patients, northeast region, small hospital size, and rural location. RESULTS: Of 71,262 patients, 67,382 (94.6%) underwent RECON. Patients undergoing OBR were older and had a higher comorbidity score. Multivariate analysis showed the following: (1) Black, Hispanic, and other races; (2) Medicaid patients; (3) patients at urban teaching hospitals are less likely to receive RECON. Patients in the midwest were more likely to receive RECON. Among 68,401 patients, 23,808 (34.8%), and 44,593 (65.19%) underwent SCP and NTR, respectively. Hysterectomy was more common in the NTR group. Multivariate analysis showed the following:(1) Black, Hispanic, and "other" races; (2) uninsured and Medicaid patients; (3) patients in the midwest, south, and west were at higher odds of receiving NTR. Patients in large and urban hospitals were less likely to undergo NTR. CONCLUSIONS: Racial, socioeconomic, and geographic disparities exist in surgical management for POP warranting further study to seek to eliminate these disparities.

COVID-19 and its effect on Instagram adoption by #OBGYN residency programs.

OBJECTIVES: Instagram (IG) is becoming one of the larger resource tools within medicine. Since the onset of the COVID-19 pandemic, it is becoming important for programs to improve virtual presence and outreach. We evaluated the adoption of IG by OB/GYN residency programs in the United States and aimed to see if highly ranked programs had higher utilization rates. METHODS: IG presence and engagement metrics were extracted for all ACGME accredited OB/GYN programs. Doximity residency navigator tool was used to obtain nationwide program rankings, and statistical analysis was performed to prove any significant correlation. Mann-Whitney U test, Cochran-Armitage test and Analysis of variance were used for analysis. IRB exemption was obtained. RESULTS: Seventy percent of programs (202/287) have IG presence, with the majority creating presence after the COVID pandemic began (115/202; 57%). Seventy-two percent (83/115) of these programs created their IG account once virtual interviews were announced. The top 25% of programs, as ranked on Doximity, have a higher number of posts, followers and likes when compared to the rest of the programs. CONCLUSIONS: The COVID-19 pandemic has led to increased adoption of IG by residency programs. Highly ranked and reputed programs have higher rates of activity, popularity, and engagement on IG.

Extensive outbreak of colistin resistant, carbapenemase (blaOXA-48, blaNDM) producing Klebsiella pneumoniae in a large tertiary care hospital, India.

BACKGROUND: Extensive drug resistance in Klebsiella pneumoniae (K. pneumoniae) causing major outbreaks in large hospitals is an emerging challenge. We describe a near fatal outbreak of colistin resistant, carbapenem resistant K. pneumoniae (CRKp) producing metallo beta-lactamases (blaNDM) and blaOXA-48 in the neonatal intensive care unit (NICU) at the background of a larger outbreak involving multiple parts of the hospital and the challenges in its containment. METHODS: Following identification of an outbreak due to colistin resistant CRKp between April to June 2017 in the NICU, a thorough surveillance of similar cases and the hospital environment was performed to trace the source. All the isolated K. pneumoniae were tested for susceptibility to standard antibiotics by disc diffusion and microbroth dilution methods. Molecular detection of extended spectrum beta lactamases (ESBLs) and carbapenemases (classes A, B, D) genes was done. Enterobacterial repetitive intergenic consensus (ERIC) PCR and multi-locus sequence typing (MLST) was done to determine the genetic relatedness of the isolates. Characteristics of different sequence types were statistically compared (Student's t-test). RESULTS: A total of 45 K. pneumoniae isolates were studied from NICU (14 cases of neonatal sepsis), ICU (18 cases), other wards (7 cases) along with 6 isolates from hospital environment and human colonizers. The primary case was identified in the ICU. All the K. pneumoniae from NICU and 94.4% from the ICU were colistin resistant CRKp. Majority (59.37% and 56.25%) harbored blaSHV/blaCTXM and blaOXA-48 genes, respectively. Two distinct sequence types ST5235 and ST5313 were noted with colistin resistance, distribution within the NICU and mortality as significant attributes of ST5235 (p < 0.05). The outbreak was contained with strengthening of the infection control practices and unintended short duration closure of the hospital. CONCLUSION: Large hospital outbreaks with considerable mortality can be caused by non-dominant clones of colistin resistant CRKp harboring blaOXA-48 and blaNDM carbapenemases in endemic regions. The exact global impact of these sequence types should be further studied to prevent future fatal outbreaks.

Applying Human-Centered Design Principles to Digital Syndromic Surveillance at a Mass Gathering in India: Viewpoint.

In the wake of the COVID-19 pandemic, digital health tools have been deployed by governments around the world to advance clinical and population health objectives. Few interventions have been successful or have achieved sustainability or scale. In India, government agencies are proposing sweeping changes to India's digital health architecture. Underpinning these initiatives is the assumption that mobile health solutions will find near universal acceptance and uptake, though the observed reticence of clinicians to use electronic health records suggests otherwise. In this practice article, we describe our experience with implementing a digital surveillance tool at a large mass gathering, attended by nearly 30 million people. Deployed with limited resources and in a dynamic chaotic setting, the adherence to human-centered design principles resulted in near universal adoption and high end-user satisfaction. Through this use case, we share generalizable lessons in the importance of contextual relevance, stakeholder participation, customizability, and rapid iteration, while designing digital health tools for individuals or populations.

Role of early foldscopy (microscopy) of endotracheal tube aspirates in deciding restricted empirical therapy in ventilated patients.

PURPOSE: Prevention of healthcare-associated infections (HAI) like ventilator associated pneumonia (VAP) is particularly challenging especially in resource limited settings. Complex microbial interactions between patients and health care workers (HCWs) further complicate the situation, requiring a holistic approach for successful management. To bridge the gap between laboratory and intensive care unit (ICU) this study was conducted to find the role of hand-held microscope 'Foldscope' in restricting empirical therapy in intubated patients. METHODS: A total of 75 endotracheal aspirates (ETA) were collected from intubated patients in the ICU with (group 1) and without (group 2) VAP. For group 2, those with less than 48 â€‹h ventilation and with endotracheal tube (ETT) in situ were considered. Presence of biomass was detected through foldscope and ETA samples were processed for quantitative gram staining (QGS), semi-quantitative and quantitative culture. Phenotypic and genotypic characterization of Acinetobacter baumannii, the commonest isolate, was done and findings were statistically analysed. RESULTS: Biomass was present as seen through a foldscope in 45 cases (90%) in group 1 and 17 cases (68%) in group 2. In both the groups, A. baumannii was the most common isolate. Biomass production, significant QGS and culture was significantly more in group 1 (p â€‹< â€‹0.05). However, carbapenem resistant A. baumannii (CRAB) was comparably present in both the groups thus showing limited role of empirical carbapenem therapy. CONCLUSIONS: Early assessment of biomass in mechanically ventilated patients could provide guidance for empirical antibiotic therapy. Foldscope proved to be an excellent tool for restricting empirical therapy and driving antimicrobial stewardship in low resource settings.

Susceptibility profile of bla OXA-23 and metallo-ß-lactamases co-harbouring isolates of carbapenem resistant Acinetobacter baumannii (CRAB) against standard drugs and combinations.

Background: The rapid emergence of carbapenem resistant Acinetobacter baumannii (CRAB) has resulted in an alarming situation worldwide. Realizing the dearth of literature on susceptibility of CRAB in genetic context in the developing region, this study was performed to determine the susceptibility profile against standard drugs/combinations and the association of in-vitro drug synergy with the prevalent molecular determinants. Methods and findings: A total of 356 clinical isolates of A. baumannii were studied. Confirmation of the isolates was done by amplifying recA and ITS region genes. Susceptibility against standard drugs was tested by Kirby Bauer disc diffusion. Minimum inhibitory concentration (MIC), MIC50 and MIC90 values against imipenem, meropenem, doripenem, ampicillin/sulbactam, minocycline, amikacin, polymyxin B, colistin and tigecycline was tested as per guidelines. Genes encoding enzymes classes A (bla GES, bla IMI/NMC-A, bla SME, bla KPC), B (bla IMP, bla VIM, bla NDM) and D (bla OXA-51, bla OXA-23 and bla OXA-58) were detected by multiplex polymerase chain reaction. Synergy against meropenem-sulbactam and meropenem-colistin combinations was done by checkerboard MIC method. Correlation of drug synergy and carbapenemase encoding genes was statistically analyzed. Results: Of the total, resistance above 90% was noted against gentamicin, ciprofloxacin, levofloxacin, ceftazidime, cefepime, ceftriaxone, cotrimoxazole and piperacillin/tazobactam. By MIC, resistance rates from highest to lowest was seen against imipenem 89.04% (n=317), amikacin 80.33% (n=286), meropenem 79.49% (n=283), doripenem 77.80% (n=277), ampicillin/sulbactam 71.62% (n=255), tigecycline 55.61% (n=198), minocycline 14.04% (n=50), polymyxin B 10.11% (n=36), and colistin 2.52% (n=9). CRAB was 317 (89.04%), 81.46% (n=290) were multidrug resistant and 13.48% (n=48) were extensively drug resistant. All the CRAB isolates harboured bla OXA-51 gene (100%) and 94% (n=298) bla OXA-23 gene. The bla IMP gene was most prevalent 70.03% (n=222) followed by bla NDM, 59.62% (n=189). Majority (87.69%, 278) were co-producers of classes D and B carbapenemases, bla OXA-23 with bla IMP and bla NDM being the commonest. Synergy with meropenem-sulbactam and meropenem-colistin was 47% and 57% respectively. Reduced synergy (p= <0.0001) was noted for those harbouring bla OXA-51+blaOXA-23with bla NDM gene alone or co-producers. Conclusion: Presence of bla NDM gene was a significant cause of synergy loss in meropenem-sulbactam and meropenem-colistin. In bla NDM endemic regions, tigecycline, minocycline and polymyxins could be viable options against CRAB isolates with more than one carbapenemase encoding genes.

Quantitative correlation of colony forming units of Acinetobacter baumannii obtained from endotracheal tube aspirate culture with clinical pulmonary infection score.

BACKGROUND AND AIMS: Ventilator-associated pneumonia (VAP) is the most common healthcare-associated infection in adult critical care units. The reason behind the different levels of severity and the outcome in different individuals is not established yet.Co-morbidities and age may be a valid reason.In an attempt to find out the reason behind the different levels of severity of VAP in different individuals, we conducted a studywith the primary objective being to assess the quantitative correlation between the colony forming units (CFU) of Acinetobacter baumannii in the endotracheal tube aspirate and the Clinical Pulmonary Infection Score (CPIS) in mechanically ventilated patients without co-morbidities. The secondary objective was to see whether the severity of VAP depends on the number of CFU(>105/ml). METHODS: This observational study was conducted in a 27-bedded intensive care unit of a tertiary care hospital in northern India. Endotracheal tube aspirate was collected from patients with suspected VAP.A total of 81 patients without any prior co-morbidity and having Acinetobacter baumannii in their endotracheal tube aspirate were included in the study group. Quantification of Acinetobacter baumannii was done by counting CFU.The CPIS was calculated for all Acinetobacter baumannii positive patients. Correlation between CFU of Acinetobacter baumannii and CPIS was assessed using Spearman's Rho correlation coefficient. RESULTS: Among 81 patients having Acinetobacter baumannii infection, only 61.9% had a CPIS >4. There was an insignificant correlation between the quantity of CFUs of Acinetobacter baumannii and CPIS (P value = 0.784). CONCLUSION: Number of CFU >105/ml in an endotracheal tube aspirate culture bears no relation to the severity of VAP as predicted by the CPIS.

Neonatal and maternal outcomes among twin pregnancies stratified by mode of conception in the United States.

OBJECTIVE: To compare neonatal and maternal outcomes among twin pregnancies conceived as a result of different types of fertility treatments with those of spontaneously conceived twin pregnancies. DESIGN: Retrospective Cohort. SETTING: Population-based analysis. PATIENT(S): Population-based analysis of twin pregnancies in the United States based on their mode of conception using the natality data from the National Center for Health Statistics from the Centers for Disease Control and Prevention (from January 2015 through December 2017). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Adverse neonatal and maternal outcomes. RESULT(S): The overall prevalence of early adverse maternal outcomes and medical complications and obstetric complications including the risk of unplanned hysterectomy, intensive care unit admission, maternal blood transfusion, and perineal laceration were significantly higher in the fertility treatment group (including both ovulation induction/intrauterine insemination and assisted reproductive technology groups) compared with those of the spontaneous conception group, even after adjusting for several potential confounders. The risk of adverse composite neonatal outcomes was slightly lower in the spontaneous conception live twin birth group even after adjustment for several potential confounders. CONCLUSION(S): The rate of maternal and neonatal morbidity in twins conceived via different fertility treatments was slightly increased compared with those of twins conceived spontaneously. Because the absolute risks of maternal and neonatal morbidity were low, overall reassurance regarding these outcomes can be provided to the patients undergoing all types of fertility treatments.