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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.
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Disparidades en Atención de Salud , Prolapso de Órgano Pélvico , Humanos , Hispánicos o Latinos , Complicaciones Intraoperatorias , Prolapso de Órgano Pélvico/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Estados Unidos/epidemiología , Estatus Socioeconómico Bajo , Negro o AfroamericanoRESUMEN
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.
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Cistadenocarcinoma Seroso , Neoplasias Uterinas , Línea Celular Tumoral , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Femenino , Humanos , Ftalazinas , Piperazinas , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Quinolinas , Receptor ErbB-2/metabolismo , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
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.
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COVID-19 , Gripe Humana , Neoplasias , COVID-19/epidemiología , Personal de Salud , Humanos , Gripe Humana/epidemiología , Neoplasias/epidemiología , Neoplasias/cirugía , Pandemias , Estudios RetrospectivosRESUMEN
Ovarian cancer remains the most lethal gynecologic malignancy. We analyzed the mutational landscape of 64 primary, 41 metastatic, and 17 recurrent fresh-frozen tumors from 77 patients along with matched normal DNA, by whole-exome sequencing (WES). We also sequenced 13 pairs of synchronous bilateral ovarian cancer (SBOC) to evaluate the evolutionary history. Lastly, to search for therapeutic targets, we evaluated the activity of the Bromodomain and Extra-Terminal motif (BET) inhibitor GS-626510 on primary tumors and xenografts harboring c-MYC amplifications. In line with previous studies, the large majority of germline and somatic mutations were found in BRCA1/2 (21%) and TP53 (86%) genes, respectively. Among mutations in known cancer driver genes, 77% were transmitted from primary tumors to metastatic tumors, and 80% from primary to recurrent tumors, indicating that driver mutations are commonly retained during ovarian cancer evolution. Importantly, the number, mutation spectra, and signatures in matched primary-metastatic tumors were extremely similar, suggesting transcoelomic metastases as an early dissemination process using preexisting metastatic ability rather than an evolution model. Similarly, comparison of SBOC showed extensive sharing of somatic mutations, unequivocally indicating a common ancestry in all cases. Among the 17 patients with matched tumors, four patients gained PIK3CA amplifications and two patients gained c-MYC amplifications in the recurrent tumors, with no loss of amplification or gain of deletions. Primary cell lines and xenografts derived from chemotherapy-resistant tumors demonstrated sensitivity to JQ1 and GS-626510 (P = 0.01), suggesting that oral BET inhibitors represent a class of personalized therapeutics in patients harboring recurrent/chemotherapy-resistant disease.
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Antineoplásicos/farmacología , Azepinas/farmacología , Mutación , Recurrencia Local de Neoplasia , Proteínas , Proteínas Proto-Oncogénicas c-myc , Triazoles/farmacología , Animales , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Femenino , Humanos , Ratones , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Neoplasias Ováricas , Proteínas/antagonistas & inhibidores , Proteínas/genética , Proteínas/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
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.
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COVID-19 , Internado y Residencia , Medios de Comunicación Sociales , COVID-19/epidemiología , Humanos , Pandemias , Estados Unidos/epidemiologíaRESUMEN
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.
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COVID-19 , Pandemias , Humanos , India , Reuniones Masivas , SARS-CoV-2 , Vigilancia de GuardiaRESUMEN
INTRODUCTION AND HYPOTHESIS: It is predicted that the number of women aged 80 years or older will more than triple by 2050. In the US, women have a 13% lifetime risk of undergoing pelvic organ prolapse surgery. Our aim was to compare the perioperative outcomes following various reconstructive approaches for apical prolapse surgery in the very elderly. METHODS: The National Surgical Quality Improvement Program database was used to identify women age ≥ 80 years of age who underwent reconstructive apical prolapse surgery from 2010 to 2017. Perioperative morbidity of vaginal colpopexy, minimally invasive sacrocolpopexy (MISC) and abdominal sacrocolpopexy (ASC) were compared. The primary outcome was the rate of composite serious complications. Univariate and multivariate logistic regression was used to identify independent predictors of serious complications. RESULTS: A total of 1012 patients were identified: vaginal (n = 792), MISC (n = 151) and ASC (n = 69). The composite serious complication rate was higher in the ASC group compared to vaginal/MISC groups (18.8% vs. 9.3% and 9.3%, p < 0.05). ASC had higher rates of blood transfusion, thromboembolism and reintubation. Life-threatening complications, readmission, pneumonia, stroke and 30-day mortality were lowest in the vaginal group. ASC (aOR 2.27), age > 85 years (aOR 1.98), operative time > 3 h (aOR 2.02), baseline dyspnea (aOR 2.17), "other race" (aOR 2.04), preoperative coagulopathy (aOR 2.92) and ASA (aOR 1.47) were associated with composite serious complications. CONCLUSION: ASC is associated with higher perioperative morbidity in the very elderly population. MISC and vaginal colpopexy have similar rates of composite serious complications; however, vaginal colpopexy is overall the safest approach in this population.
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Prolapso de Órgano Pélvico , Procedimientos de Cirugía Plástica , Anciano , Anciano de 80 o más Años , Femenino , Procedimientos Quirúrgicos Ginecológicos , Humanos , Prolapso de Órgano Pélvico/cirugía , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: Various biomarkers are used for predicting outcome from sepsis and septic shock but single value doesn't give clear-cut picture. Changing trends of serum lactate and red cell distribution width (RDW) gives more accurate information of patient outcome. So, aim of this prospective observational study was to identify the correlation, for initial and changing trend of blood lactate level and RDW, with 28-day mortality in sepsis and septic shock. MATERIAL AND METHODS: Patient who fulfills the criteria of sepsis and septic shock, according to the consensus conference published in 2016, were included in this study. All patients were resuscitated and managed according to institutional protocol for sepsis and septic shock. Serum lactate and RDW was obtained from arterial blood gas and complete blood count, respectively. Serum lactate and RDW were recorded at 0 h, 6 h, 24 h, day 2, day 3, day 7, week 2, and week 3. Mean between two groups were compared with student t-test. Pearson and Spearman correlation coefficient was used for establishing correlation between two continuous data. P value < 0.05 indicates significant difference between two groups. RESULTS: There is positive correlation between serum lactate and RDW at all-time point in non-survival group while negative correlation was found in survival group except on day1 and 2. CONCLUSION: Changing trends of serum lactate and RDW can be used as a prognostic marker in patient of sepsis and septic shock.
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OBJECTIVE: Aberrant expression of HER2/neu and PIK3CA gene products secondary to amplification/mutations are common in high-grade-serous-endometrial (USC) and ovarian-cancers (HGSOC). Because scant information is currently available in the literature on the potential negative effect of PIK3CA mutations on the activity of afatinib, in this study we evaluate for the first time the role of oncogenic PIK3CA mutations as a potential mechanism of resistance to afatinib in HGSOC and USC overexpressing HER2/neu. METHODS: We used six whole-exome-sequenced primary HGSOC/USC cell-lines and three xenografts overexpressing HER2/neu and harboring mutated or wild-type PIK3CA/PIK3R1 genes to evaluate the role of PI3K-mutations as potential mechanism of resistance to afatinib, an FDA-approved pan-c-erb-inhibitor in clinical trials in USC. Primary-USC harboring wild-type-PIK3CA gene was transfected with plasmids encoding oncogenic PIK3CA-mutations (H1047R/E545K). The effect of afatinib on HER2/PI3K/AKT/mTOR pathway was evaluated by immunoblotting. RESULTS: We found PI3K wild-type cell-lines to be significantly more sensitive (lower IC50) than PI3K-mutated cell-lines pâ¯=â¯0.004). In vivo, xenografts of primary cell-line USC-ARK2, transfected with the PIK3CA-H1047R or E545K hotspot-mutations, exhibited significantly more rapid tumor growth when treated with afatinib, compared to mice harboring ARK2-tumors transfected with wild-type-PIK3CA (pâ¯=â¯0.041 and 0.001, respectively). By western-blot, afatinib effectively reduced total and phospho-HER2 proteins in all cell-lines. However, H1047R/E545K-PIK3CA-transfected-ARK2-cells demonstrated a greater compensatory increase in phosphorylated-AKT proteins after afatinib exposure when compared to controls ARK2. CONCLUSIONS: Oncogenic PI3K mutations may represent a major mechanism of resistance to afatinib. Combinations of c-erb with PIK3CA, AKT or mTOR inhibitors may be necessary to more efficiently block the PIK3CA/AKT/mTOR pathway.
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Afatinib/farmacología , Fosfatidilinositol 3-Quinasa Clase I/genética , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/genética , Adulto , Anciano , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase I/biosíntesis , Fosfatidilinositol 3-Quinasa Clase Ia , Resistencia a Antineoplásicos/genética , Femenino , Neoplasias de los Genitales Femeninos/enzimología , Neoplasias de los Genitales Femeninos/genética , Humanos , Ratones , Ratones SCID , Persona de Mediana Edad , Mutación , Fosfatidilinositol 3-Quinasas/biosíntesis , Inhibidores de Proteínas Quinasas/farmacología , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Objective To describe the scenario of academic tweeting and utilization of Twitter by editorial board members of the leading journal in obstetrics and gynecology. Methods The Twitter presence of an editorial board members of obstetrics and gynecology journal with an impact factor greater than 4 was determined. Details of their Twitter activity, year of graduation from medical school and gender were analyzed. Median SparkScore™, an online influence measure, of journals was compared to the highest impact factor journals in medicine (New England Journal of Medicine, The Lancet, The British Medical Journal and Journal of the American Medical Association). Results In the six highest impact factor journals in obstetrics and gynecology, 92 of 240 (38.3%) editorial board members had an active Twitter account. The Twitter presence of editorial members of Obstetrics and Gynecology was statistically less when compared to all other journals (P < 0.01). The median number of tweets in the last 24 h and 7 days were 0. Median SparkScore™ for the highest impact factor obstetrics and gynecology journals (24) were lower compared to the highest impact journals in medicine (66) (P = 0.03). Conclusion Editorial board members of the six highest impact factor journals in obstetrics and gynecology are not capitalizing on the dynamic nature of Twitter and its instant convenient access from our smartphones to further academia, when compared to specialties in medicine. There is a need for increased adoption of Twitter among physician leaders in the specialty.
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Ginecología/estadística & datos numéricos , Obstetricia/estadística & datos numéricos , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Medios de Comunicación Sociales/estadística & datos numéricosRESUMEN
INTRODUCTION: Since the majority of patients are diagnosed at an advanced stage, ovarian cancer remains the most lethal gynecologic malignancy. There is no single biomarker with the sensitivity and specificity required for effective cancer screening; therefore, we investigated a panel of novel biomarkers for the early detection of high-grade serous ovarian carcinoma. METHODS: Twelve serum biomarkers with high differential gene expression and validated antibodies were selected: IL-1Ra, IL-6, Dkk-1, uPA, E-CAD, ErbB2, SLPI, HE4, CA125, LCN2, MSLN, and OPN. They were tested using Simple Plex™, a multi-analyte immunoassay platform, in samples collected from 172 patients who were either healthy, had benign gynecologic pathologies, or had high-grade serous ovarian adenocarcinomas. The receiver operating characteristic (ROC) curve, ROC area under the curve (AUC), and standard error (SE) of the AUC were obtained. Univariate ROC analyses and multivariate ROC analyses with the combination of multiple biomarkers were performed. RESULTS: The 4-marker panel consisting of CA125, HE4, E-CAD, and IL-6 had the highest ROC AUC. When evaluated for the ability to distinguish early stage ovarian cancer from a non-cancer control, not only did this 4-marker panel (AUC=0.961) performed better than CA 125 alone (AUC=0.851; P=0.0150) and HE4 alone (AUC=0.870; P=0.0220), but also performed significantly better than the 2- marker combination of CA125+HE4 (AUC=0.922; P=0.0278). The 4-marker panel had the highest average sensitivity under the region of its ROC curve corresponding to specificity ranging from 100% down to ~95%. CONCLUSION: The four-marker panel, CA125, HE4, E-CAD, and IL-6, shows potential in detecting serous ovarian cancer at earlier stages. Additional validation studies using the biomarker combination in ovarian cancer patients are warranted.
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Biomarcadores de Tumor/metabolismo , Cistadenocarcinoma Seroso/diagnóstico , Neoplasias Ováricas/diagnóstico , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patología , Femenino , Expresión Génica , Humanos , Mesotelina , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Curva ROCRESUMEN
BACKGROUND AND AIMS: Poorly managed acute postoperative pain may result in prolonged morbidity. Various pharmacotherapies have targeted this, but research on an ideal preemptive analgesic continues, taking into account drug-related side effects. Considering the better tolerability profile of tapentadol, we assessed its role as a preemptive analgesic in the reduction of postoperative analgesic requirements, after laparoscopic cholecystectomy. MATERIAL AND METHODS: In a prospective-double-blinded fashion, sixty patients posted for above surgery, were randomized to receive tablet tapentadol 75 mg (Group A) or starch tablets (Group B) orally, an hour before induction of general anesthesia. Perioperative analgesic requirement, time to first analgesia, pain, and sedation score were compared for first 24 h during the postoperative period and analyzed by one-way analysis of variance test. A P < 0.05 was considered significant. RESULTS: Sixty patients were analyzed. The perioperative analgesic requirement was significantly lower in Group A. Verbal numerical score was significantly lower in Group A at the time point, immediately after shifting the patient to the postanesthesia care unit. Ramsay sedation scores were similar between the groups. No major side effects were observed except for nausea and vomiting in 26 cases (10 in Group A, 16 in Group B). CONCLUSION: Single preemptive oral dose of tapentadol (75 mg) is effective in reducing perioperative analgesic requirements and acute postoperative pain, without added side effects. It could be an appropriate preemptive analgesic, subjected to future trials concentrating upon its dose-response effects.
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BACKGROUND AND AIMS: Postsurgical pain is the leading complaint after laparoscopic cholecystectomy that may delay the postoperative recovery and hence we undertook a prospective randomized trial to analyze the role of flupirtine as a preemptive analgesic for postoperative pain relief in patients undergoing above surgery. MATERIAL AND METHODS: A total of 66 cases were randomly assigned to two groups to receive capsule flupirtine (200 mg) or capsule vitamin B complex administered orally, 2 h before the laparoscopic cholecystectomy surgery. Time to first analgesic requirement, assessment of postoperative pain in terms of visual analog score, and analgesic requirement postoperatively were measured as a primary outcome. RESULTS: Time to first analgesic requirement was significantly prolonged in the flupirtine group as compared with the placebo group. There was significant pain reduction in early postoperative period (up to 4 h), but no changes occurred thereafter. Total analgesic requirement (including rescue analgesia) and side-effects were comparable between the groups except for higher sedation in flupirtine group. CONCLUSIONS: Flupirtine is effective as a preemptive analgesic in providing adequate pain relief during the immediate postoperative period after laparoscopic cholecystectomy surgery. However, continuation of drug therapy postoperatively could possibly delineate its optimal analgesic profile more profoundly.
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IMPORTANCE: Despite growing popularity in medicine, data on large language models in urogynecology are lacking. OBJECTIVE: The aim of this study was to compare the performance of ChatGPT-3.5, GPT-4, and Bard on the American Urogynecologic Society self-assessment examination. STUDY DESIGN: The examination features 185 questions with a passing score of 80. We tested 3 models-ChatGPT-3.5, GPT-4, and Bard on every question. Dedicated accounts enabled controlled comparisons. Questions with prompts were inputted into each model's interface, and responses were evaluated for correctness, logical reasoning behind answer choice, and sourcing. Data on subcategory, question type, correctness rate, question difficulty, and reference quality were noted. The Fisher exact or χ2 test was used for statistical analysis. RESULTS: Out of 185 questions, GPT-4 answered 61.6% questions correctly compared with 54.6% for GPT-3.5 and 42.7% for Bard. GPT-4 answered all questions, whereas GPT-3.5 and Bard declined to answer 4 and 25 questions, respectively. All models demonstrated logical reasoning in their correct responses. Performance of all large language models was inversely proportional to the difficulty level of the questions. Bard referenced sources 97.5% of the time, more often than GPT-4 (83.3%) and GPT-3.5 (39%). GPT-3.5 cited books and websites, whereas GPT-4 and Bard additionally cited journal articles and society guidelines. Median journal impact factor and number of citations were 3.6 with 20 citations for GPT-4 and 2.6 with 25 citations for Bard. CONCLUSIONS: Although GPT-4 outperformed GPT-3.5 and Bard, none of the models achieved a passing score. Clinicians should use language models cautiously in patient care scenarios until more evidence emerges.
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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.
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Melanoma , Neoplasias Cutáneas , Neoplasias de la Úvea , Humanos , Melanoma/genética , Melanoma/terapia , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/terapia , Linfocitos Infiltrantes de Tumor , Inmunoterapia , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Reduction of postoperative nausea and vomiting (PONV) continues to be a major challenge in perioperative care in spite of introduction of newer antiemetics with better efficacy and safety profiles. Therefore, we evaluated the additive effect of oral midazolam and clonidine for PONV prophylaxis in granisetron premedicated patients undergoing laparoscopic cholecystectomy. MATERIALS AND METHODS: In a prospective, randomized fashion, 120 selected cases were randomized into three groups: I, II or III to receive a tablet of midazolam (15 mg, n = 36), clonidine (150 mcg, n = 40), or glucose as placebo (5 g, n = 44) orally, 1 h before anesthesia. Occurrence of PONV along with need for rescue antiemetic during the first postoperative day was compared between groups as a primary outcome. RESULTS: Episodes of PONV reduced significantly in Group II (15%) as compared to group I and III (22.2%, 59%) at various time points during the period of observation (P = 0.002). Need for rescue antiemetic was significantly lower in group I (13.88%) and II (5%) as compared to group III (52.27%, P < 0.001). CONCLUSION: Oral clonidine is better adjuvant for PONV prophylaxis, as compared to midazolam, in granisetron premedicated patients undergoing laparoscopic cholecystectomy.
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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.
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â¢Ichthyosis uteri is a rare condition describing extensive endometrial keratinization.â¢There may be an association with squamous cell carcinoma of the endometrium.â¢Endometrial extension of cervical malignancy may closely resemble ichthyosis.â¢A hysterectomy should be considered in patients who have completed childbearing.
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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.
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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.