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Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious BRCA1 and/or 2 mutations. Identifying patients with prostate cancer harboring these mutations may be challenging. Circulating cell-free DNA (cfDNA) provides an avenue for an easier detection of these mutations. Herein, we aimed to evaluate the concordance of BRCA mutations in the tumor tissue and cfDNA in patients with metastatic prostate cancer in the real-world setting., Methods: Somatic genomic profiling results were obtained from a clinical cohort of patients at our institution who had at least two samples tested. One of the samples needed to be from either primary or metastatic tissue. Concordance was adjusted to not include mutation types that the cfDNA platforms were not designed to detect., Results: The presence or absence of mutations in the BRCA gene was assessed in a total of 589 samples, including 327 cfDNA samples, from 260 patients with metastatic prostate cancer. The median time between the first test and any subsequent test was 22.8 (0.0-232) months. BRCA mutation was present in the patient's original prostate tissue in 23 samples (3.9%) of patients. The adjusted concordance between prostate tumor tissue and cfDNA was 97.9% [95% CI, 95.3-99.1%]. The adjusted concordance between metastatic samples and cfDNA was 93.5% [95% CI, 86.4-97.3%]. Of the patients who had a BRCA mutation detected in their prostate tissue, there was a 70% probability of detecting a BRCA mutation in the patient's cfDNA as well. For patients who did not have a detectable BRCA mutation in their primary prostate tissue, the probability of detecting a subsequent one later in the disease course was less than 0.9%., Conclusion: There is a high level of concordance between tissue and blood for BRCA mutations. Testing cfDNA can provide reliable information on BRCA mutational status and is a viable alternative to solid tissue sequencing when unavailable. The development of a new BRCA mutation later in the disease course is a rare event.

Introduction: Patients leaving against medical advice (AMA) are commonly encountered in hospital medicine. The problem is prevalent worldwide and across all fields of medicine. A retrospective study of 47,583 patients reported a 3.3% AMA rate in 2015., Objectives: In this retrospective study, we aimed (1) to study the demographic, clinical, and laboratory parameters of infective endocarditis (IE) patients leaving AMA. We also compared (2) the various risk factors and outcomes of these patients with IE patients who completed treatment., Results: A total of 111 patients diagnosed with IE were recruited for 36 months. Of the 74 patients with available details, 32 patients (29%) left AMA during their treatment. The mean age of patients leaving AMA was 39, and among those who left AMA, 66% were females. As compared with patients completing therapy, patients leaving AMA tend to have higher comorbidities, including injection drug use (68.1% versus 31.9%), prior IE (83.3% versus 16.7%), and chronic hepatitis C (72.4% versus 27.8%). Rates of consumption of substances of abuse were higher among those who left AMA. Patients leaving AMA also had higher psychiatric comorbidities (63% versus 37.5%), history of leaving AMA (70.5% versus 29.5%), and consumption of more than 2 substances of abuse. Morbidity was higher in patients leaving AMA. There was a statistically significant association between the development of distal embolus ( P < 0.001), the need for recurrent admissions ( P = 0.002), recurrent bacteremia ( P < 0.001), developing new embolus ( P < 0.001), and overall morbidity ( P = 0.002) among IE patients leaving AMA., Conclusions: Infective endocarditis patients leaving AMA tend to be younger females. These patients have prior comorbidities of injection drug use, prior IE, multiple psychiatric comorbidities, drug use, and multiple socioeconomic issues. Patients leaving AMA tend to develop further non-Central nervous system embolic events, recurrent bacteremia, and require frequent admissions. Morbidity in these patients was higher., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The bone health of patients with locally advanced and metastatic prostate cancer is at risk from treatment-related bone density loss and skeletal-related events from metastatic disease in bones. Evidence-based guidelines recommend using denosumab or zoledronic acid at bone metastasis-indicated dosages in the setting of castration-resistant prostate cancer with bone metastases and at the osteoporosis-indicated dosages in the hormone-sensitive setting in patients with a significant risk of fragility fracture. For the concerns of jaw osteonecrosis, a dental evaluation is recommended before starting bone-modifying agents. The literature review suggests a limited evidence-based practice for bone health with prostate cancer in the real world. Both under-treatment and inappropriate dosing of bone remodeling therapies place additional risks to bone health. An incomplete dental work up before starting bone-modifying agents increases the risk of jaw osteonecrosis. Methods: We created an algorithm-based clinical practice tool to minimize the deviation from evidence-based guidelines at our center and provide appropriate bone health care to our patients by ensuring indication-appropriate dosing and dental screening rates. This order set was incorporated into the electronic medical record system for ordering a bone remodeling agent for prostate cancer. The tool prompts the clinicians to follow the appropriate algorithm in a stepwise manner to ensure a pretreatment dental evaluation and use of the correct dosage of drugs. Results: We analyzed the data from Sept 2019 to April 2022 following the incorporation of this tool. 0/35 (0%) patients were placed on inappropriate bone modifying agent dosing, and dental health was addressed in every patient before initiating treatment. We compared the change in the practice of prescribing and noted a significant difference in the clinician’s practice while prescribing denosumab/zoledronic acid before and after implementation of this tool [incorrect dosing: 24/41 vs. 0/35 (p < 0.00001)]; and an improvement in pretreatment dental checkup before and after implementation of the tool was noted to be [missed dental evaluation:12/41 vs. 0/35 (p < 0.00001)]. Conclusion: We found that incorporating an evidence-based algorithm in the order set while prescribing bone remodeling agents significantly improved our institutional clinical practice of indication-appropriate dosing and dental screening rates, and facilitated high-quality, evidence-based care to our patients with prostate cancer.

Background: COVID-19 vaccination is one of the pivotal key tools against the ongoing pandemic, but its acceptance relies on efficacy and safety data among various populations, including patients with cancers. However, there is limited data on seroconversion rates, efficacy, and safety of the COVID-19 vaccine in patients with cancer. Breakthrough infections after vaccination have also been reported, which could further strengthen the refusal behavior of specific populations to be immunized. Our objective was to investigate the efficacy and safety of COVID-19 vaccination in real-world patients with advanced genitourinary cancers., Methods and Results: A retrospective study of the 738 patients with advanced metastatic genitourinary malignancy was conducted at our genitourinary oncology clinic from October 2020 to September 2021, out of which 462 patients (62.6%) were vaccinated. During the study period, two vaccinated, and six unvaccinated patients tested positive for SARS-CoV-2 (breakthrough infection rate: 0.4% vs. 2.2%, p = 0.027). Vaccine protection against infection was 81.8% (95% CI: 0.04-0.98). One vaccinated and 4 unvaccinated patients were hospitalized due to COVID-19 (0.2% vs. 1.4%, p = 0.048). Vaccine effectiveness in preventing hospitalization was 85.7% (95% CI: 0.02-1.33). Within one month of vaccination, 1.5% of patients (n = 7) had emergency visits, 0.8% (n = 4) were hospitalized for any reason, and of these, 3 (0.6%) experienced a delay in the receipt of their cancer therapy., Conclusion: In our hypothesis-generating data among patients with advanced genitourinary cancers, COVID-19 vaccination was efficacious and safe and was rarely associated with treatment disruptions. These data should help improve the acceptance of the COVID-19 vaccine in the general population and patients with cancer. The vaccine effectiveness in our patients is comparable with existing published data without cancer., Competing Interests: The authors declare the following conflict of interests: Dr. Neeraj Agarwal (lifetime disclosures): Consultancy to Astellas, Astra Zeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics. Research funding to Neeraj Agarwal's institution: Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Medivation, Merck, Nektar, New Link Genetics, Novartis, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. Dr. Umang Swami: Dr. Swami reports consultancy to Astellas, Exelixis and Seattle Genetics and research funding to institute from Janssen, Exelixis and Astellas/Seattle Genetics. Dr. Sumati Gupta: Dr. Sumati Gupta has received clinical trials support from Bristol Myers Squibb, Rexahn, Incyte, Novartis, LSK, Five Prime, Mirati, QED, Debiopharm, Merck, Pfizer, Astra Zeneca, Medimmune, Clovis, Immunocore, Seattle Genetics, Pfizer, LSK/Elevar therapeutics, Acrotech, Astra Zeneca, travel fund from QED and spouse has stock ownership in Salarius pharmaceutical. Dr. Benjamin Maughan: Roche/Genentech, Pfizer, AVEO Oncology, Janssen Oncology, Astellas, Bristol-Myers Squibb, Clovis, Tempu, Merck, Exelixis, Bayer Oncology, Peloton Therapeutics (C/A), Exelixis, Bavarian-Nordic, Clovis, Genentech, Bristol-Myers Squibb (FR– institutional)., (© 2022 Published by Elsevier Ltd.)

Introduction: Relugolix is the first oral gonadotrophin-releasing hormone (GnRH) receptor antagonist. Based on the phase III HERO trial results, relugolix received Food and Drug Administration approval for adult patients with advanced prostate cancer (PCa)., Areas Covered: We provide an overview of the preclinical and clinical development of relugolix and its role in the current treatment landscape of PCa., Expert Opinion: Relugolix leads to rapid inhibition of testicular production of testosterone and its rapid recovery upon discontinuation. In the HERO trial, relugolix was associated with a superior cardiovascular safety profile compared to GnRH agonists. These attributes make relugolix a promising therapy for patients with preexisting cardiovascular comorbidities, those pursuing intermittent androgen deprivation therapy, and those who desire rapid testosterone recovery during 'off-treatment' periods. In the HERO trial, very few patients received concomitant enzalutamide (n = 17, 2.7%) or docetaxel (n < 10, 1.3%). Safety of relugolix has not been established in combination with many androgen-receptor-axis targeted therapies (e.g. abiraterone, apalutamide), cabazitaxel, or lutetium Lu 177 vipivotide tetraxetan, which precludes its use in combination with these agents. In addition, being an oral drug, relugolix may also be associated with challenges of affordability, adherence, and compliance in this predominantly elderly population.

In developing countries, anti-D has been used in immune thrombocytopenia (ITP) as a cheaper alternative to human immunoglobulin. We aim to analyze the response and safety profile of anti-D in patients with severe ITP. A retrospective study was conducted at a tertiary care hospital in Northern India. Patients received a single intravenous infusion of 75 μg/kg anti-D. In total, 36 patients (20 females) were included in this study. The median duration from ITP diagnosis to anti-D therapy was 235 days (range 1-1613 days). Four (11.1%) patients received anti-D as an upfront treatment. The patients' platelet counts rose significantly by the end of day three and continued to be significantly high until day 30 of receiving anti-D (p ≤ 0.001). The overall response rate (ORR) by day seven was 88.89%. There was no effect of age, sex, duration of disease, prior therapy, and platelet count on the ORR. Patients were followed up for a median duration of 52 days (longest follow-up: 3080 days). Six (6/36, 16.67%) patients continued to be in remission till the last follow-up. The hemoglobin fall was statistically significant on day three and day seven (p < 0.001 and p = 0.001) and got normalized by day 30. We observed equally good ORR in mixed populations and different phases of ITP along with long-term sustained response. The study demonstrates a quick and high response rate along with good safety profile to anti-D in all forms of ITP., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There have been reports of increasing alcohol use and domestic violence among individuals with alcohol dependence syndrome during the COVID-19 pandemic. This study assessed the experiences of domestic violence, psychological distress, and coping mechanisms used by wives of individuals with alcohol dependence syndrome (PWADS) during the COVID-19 pandemic., Materials and Methods: This cross-sectional institutional-based study collected data from 50 participants using the consecutive sampling method. The following tools were utilized: Socio-demographic Questionnaire, Domestic Violence Questionnaire, the Kessler Psychological Distress Scale, and the Brief Cope., Results: The mean age of the spouses (PWADS) was 42 ± 8.20 years, with 42% (N = 21) being skilled workers. Sixty percent (N = 30) had been consuming alcohol for the past 10 years, and 50% (N = 25) had been undergoing treatment for 2-5 years. Among the study participants (wives of PWADS), the mean age was 40.70 ± 8.70 years, and 82% were housewives. They reported a significant increase in alcohol use and excessive spending by their husbands, which negatively affected the home environment. Domestic violence, in terms of psychological, physical, and sexual abuse, also significantly increased (p < .001) compared to before and during the lockdown. Forty-eight percent of the wives reported experiencing severe levels of psychological distress. They employed various coping strategies., Conclusion: The lived experiences of wives of individuals with alcohol dependence syndrome during the COVID-19 pandemic were challenging, as their husbands not only continued their regular alcohol consumption but also increased the amount and expenditure on alcohol. This had a detrimental effect on the home environment, worse than the situation before the lockdown. Targeted interventions are necessary to address these issues during the COVID-19 pandemic or similar situations., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

The use of immune checkpoint inhibitors (ICIs) is rapidly increasing as more combinations and clinical indications are approved in the field of genitourinary malignancies. Most immunotherapeutic agents being approved are for the treatment of renal cell carcinoma and bladder cancer, which mainly involve PD-1/PD-L1 and CTLA-4 pathways. There is an ongoing need for recognizing and treating immunotherapy-related autoimmune adverse effects (irAEs). This review aims to critically appraise the recent literature on the mechanism, common patterns, and treatment recommendations of irAEs in genitourinary malignancies. We review the epidemiology of these adverse effects as well as general treatment strategies. The underlying mechanisms will also be discussed. Diagnostic considerations including differential diagnosis are also included in this review.

Patients with infective endocarditis can have multiple neurological manifestations.  Cerebrovascular events (CVE) in patients with IE can be hemorrhagic or embolic.  Multiple factors are known to predispose to CVE and increased mortality in patients with IE.  In this study, we aimed to describe various outcomes among patients with IE and CVE.  We retrospectively analyzed 160 patients with definite IE.  Among these, patients with radiological evidence of CVE were included.  Clinical, radiological, echocardiographic details were obtained.  Outcome studied were the requirement of intensive care unit care, the requirement of mechanical ventilation, prolonged course of antibiotics, prolonged duration of hospital stay, the requirement of surgical intervention, and mortality.  In this study, 16 [10%] of patients with IE were identified to have a CVE.  The mean age of the patients was 55, and 87.5% of them were male.  25% of patients had prior IE.  IE involving left-sided valves were predominant, with the involvement of mitral valve reported in 62.5% of patients.  More than half of the patient's had details of magnetic resonance imaging (MRI) of the brain.  CVE were mostly ischemic, anterior circulation predominant, multiple, and bilateral.  In patients with IE and CVE morbidity including the requirement of ICU care, prolonged antibiotics course, and the requirement of surgical intervention contributed to increased duration of hospital stay.  In conclusion, CVE in patients with IE tends to present as multiple infarcts predominantly located over anterior circulation.  IE patients with CVE tend to have higher morbidity and mortality.

The rare earth elements being toxic in nature are being accumulated in water bodies as their industrial usage is growing exponentially, thus their efficient separation holds an immense significance. Herein, ligand functionalized metal organic framework (MOF), Phosphonomethyl iminodiacetic acid coordinated at Fe-BTC, was synthesized post-synthetically and incorporated subsequently in polyacrylonitrile polymer to prepare the composite beads via nonsolvent induced-phase-inversion technique for selective adsorption of La(III) from the wastewater in batch and dynamic column mode. XPS NMR, and FTIR were used to establish the interaction between functionalized ligand and unsaturated metal nodes of MOF. The adsorption capacity was 232.5 mg/g and 77.51 mg/g at 298 K of the functionalized MOF and composite beads respectively. Adsorption kinetics followed a pseudo-second order rate equation, and isotherm indicated the best fitting with Langmuir model. The dynamic behavior of the adsorption column packed with MOF/Polymer beads was fairly described by the Thomas model. The breakthrough time of 23.2 h could be attained with 12 cm of bed height and 10 ml/min of flow rate. These MOF/Polymer beads shown the selectivity of La over transitional metals were recycled over 5 times with about 15% loss of adsorption capacity. The findings provide suggestive insights of the potential use of functionalized MOF towards the separation of the rare earth element., (Copyright © 2021. Published by Elsevier B.V.)

Background: Spindle Cell Carcinoma (SpCC) is a rare type of squamous cell carcinoma (SCC) with prominent malignant spindle cell component. This unique biphasic feature on histopathological examination makes its diagnosis problematic. Detection of p63 antigens in SpCC can be helpful however its expression in variousb proliferating soft tissue lesions demands for better marker., Methods: In this study, histopathologically diagnosed SpCC of head and neck region were considered as cases, and 22 soft tissue sarcomas, reactive lesions and spindle cell lesions of the body were taken as controls. Immunohistochemistry (IHC) was done using Anti-p63 and p40 clone and the results were compared. CK was done for negative cases to prove their epithelial origin. P. value < 0.05 considered statistically significant., Results: Among 22 cases of SpCC, 19 cases showed positive immunoreactivity to p63, and 18 cases for p40. IHC of controls showed no immunoreactivity in any of the sarcomas, reactive lesions or spindle cell lesions. The sensitivity of p63 is 86% while that of p40 is 82%. Specificity of both the markers was 100% CONCLUSION: Though p63 is a slightly (4%) more sensitive marker than p40, percentage of cell positivity for p40 is higher compared to p63. Both of these markers are 100% specific for SpCC., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

The emergence of colistin-carbapenem-resistant Klebsiella pneumoniae (CCR-Kp) in bloodstream infection results in high mortality, and virulence factor contributes further to the difficulty of treatment. A total of 158 carbapenem-resistant K. pneumoniae (CRKP) isolates causing bloodstream infection were collected from three Indian tertiary care hospitals during the 9-month study period, of which 27 isolates exhibited resistance to both colistin and carbapenem antibiotics. In this study, all the strains were characterized for antimicrobial resistance, virulence factors and capsular serotypes that facilitate the development of colistin and carbapenem-resistant K.pneumoniae (CCR-Kp) in bloodstream infection. Fourteen isolates displayed extremely drug resistance (XDR), susceptible only to tigecycline, and the remaining 13 isolates displayed multidrug resistance (MDR). The gene prevalence analysis for CCR-Kp isolates showed the predominance of bla KPC (81.48%) followed by bla NDM (62.96%), bla VIM (37.03%) and bla IMP (18.51%) genes. The distribution of virulence genes was found to be fimH (81.48%) , wabG (59.25%) , mrkD (55.56%) , entB (48.15%) , irp1 (33.33%) , and rmpA (18.52%). The capsular serotypes K1, K2, K5 and K54 have been identified in 16 isolates. The absence of plasmid-mediated colistin resistance ( mcr ) genes implies the involvement of other mechanisms. The ERIC and (GTG) 5 molecular typing methods detected 18 and 22 distinct clustering patterns among the CCR-Kp isolates, respectively. A strong correlation between ERIC and (GTG)5 genotyping method was established with antimicrobial resistance patterns and virulence determinants at P  < 0.05, while no correlation was found with capsular serotyping. Similar virulence and resistance typing among the isolates suggest hospital-acquired infection in a health care setup. These outcomes will advance our awareness of CCR-Kp outbreaks associated with tertiary care hospitals and help forecast their occurrence in the near future., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-03056-4., Competing Interests: Conflict of interestThe authors declare that they have a conflict of interest., (© King Abdulaziz City for Science and Technology 2021.)

Background: Blood group has been stated to be one of the risk factors associated with viral diseases like dengue, hepatitis virus, Norwalk virus and even the coronavirus associated with 2003 severe acute respiratory syndrome (SARS) outbreak. In addition, anti-A antibodies in experimental models have been shown to inhibit the interaction between coronavirus and angiotensin converting enzyme (ACE) receptor of the host target cell, the major receptor involved in viral pathogenesis. Thus, several workers propose an association between ABO blood type and coronavirus disease- 2019 (COVID-19) disease in many previous studies. The present study was undertaken in the Eastern part of India in line with these authors to study the association of ABO blood group of patients with COVID susceptibility and severity., Methods: This is a retrospective study over a period of 6 months from June 2020 to November 2020 where patients who underwent quantitative real-time polymerase chain reaction (qRT-PCR) test for SARS-COV2 and having a recorded patient blood group type were considered. The qRT-PCR positive admitted cases were considered as cases, and qRT-PCR negative cases were considered as controls. Data were entered in Microsoft Excel format and analyzed by statistical method to obtain association., Results: Consecutively obtained 5000 qRT-PCR positive patients (cases) and 11,700 (controls) were included in the present study. The mean age of cases was higher (54.24 vs. 34. 67) than the controls. Among the cases, the highest number (2379; 47.6%) of samples belonged to A blood group followed by B (1278; 25.6%) while among the control group O blood group had the highest prevalence (4215; 36%). Blood group A had a higher odd of testing positive (Odds ratio-2.552; CI 2.381-2.734; p  < 0.0001) than all other blood groups. A blood group is also associated with higher risk of ICU admission (Odds ratio- 1.699; 95% CI 1.515-1.905) and 65.3% of this group is also associated with high viral load which gives an indication of higher disease severity., Conclusion: Blood group A is associated with an increased susceptibility to COVID 19 infection than other blood groups. Cases of this blood group are also associated with more critical care needs and a higher viral load on testing., Competing Interests: Competing interestsThe authors declare that they have no competing interest., (© The Author(s) 2022.)

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel antidiabetic agents with overwhelming cardiorenal protection. Recent trials focusing on the nephroprotective role of SGLT2i have underscored its success as a phenomenal agent in halting the progression of kidney disease in patients with and without Type 2 diabetes mellitus. Multitudes of pleiotropic effects on tubules have raised hopes for reasonable nephroprotection beyond the purview of the hyperglycemic milieu., Area Covered: This review summarizes various animal and human data as evidence for the utility of SGLT2i in non-diabetic chronic kidney disease (CKD). Web-based medical database entries were searched. On the premise of existing evidence, we have discussed mechanisms likely contributing to nephroprotection by SGLT2i in patients with non-diabetic CKD., Expert Opinion: Further elucidation of mechanisms of nephroprotection offered by SGLT2i is required to extend its use as a nephroprotective agent. The use of non-traditional markers of kidney damage in future studies would improve the evaluation of their role in attenuating CKD progression. Emerging animal data support the early use of SGLT2i in states of modest proteinuria for superior outcomes. Future long-term trials in patients should aim to address the time of intervention with SGLT2i during the natural disease course of CKD for best outcomes.

Extraovarian primary peritoneal carcinoma (EOPPC) is a rare tumour of the peritoneum that shares many features with serous ovarian carcinoma because of a common embryological origin. We report a case of EOPPC presenting with a malignant pleural effusion. https://bit.ly/3GMuKgL., Competing Interests: Conflict of interest: J. Mendonca has nothing to disclose. Conflict of interest: V. Acharya has nothing to disclose. Conflict of interest: S. D'Souza has nothing to disclose. Conflict of interest: K.K. Sahu has nothing to disclose. Conflict of interest: S. Kamath has nothing to disclose. Conflict of interest: J.R. Kini has nothing to disclose., (Copyright ©ERS 2022.)

Background: Clostridioides difficile infection (CDI) is a considerable healthcare burden, and now identified as the leading cause of acquired diarrheal illness in patients receiving antibiotics. Patients with malignancies are more prone to acquire CDI, owing to their frequent exposure to risk factors., Objective: This study aims to investigate the factors affecting the outcome of Clostridioides Difficile Infection in patients with solid tumors at our community healthcare center., Methods: This is a retrospective study that included a total of 59 patients with solid tumors who were hospitalized for Clostridioides difficile infection., Results: The median age of the study population was 79 years with 39 males and 20 females. The patients had a diagnosis of a malignancy involving the following sites: prostate (25), lung (19), colon (7), bladder (4), breast (3), and renal (1). There were 52 cases of first time and 7 cases of recurrent CDI admissions. 40 patients were detected to have CDI at presentation while 19 patients were diagnosed with CDI after admission. CDI was categorized as follows: non-severe (29), severe (28), and very severe (2). There were 33 patients on chemotherapy and 20 patients undergoing radiotherapy. Twenty-seven patients had a recent history of cancer care-related procedures or interventions. Twenty-nine patients were from either a rehabilitation center or a long-term nursing care facility. There were 39 recent hospitalizations with 29 patients receiving antibiotics. Almost half of the patients were on proton pump inhibitors (29) and 12 were on steroids (20.3%) at the time of developing CDI. Patients with a high-risk qSOFA score of 2 or more (p-value = 0.008) or a high white blood cell count of >15 × 10 9 /L (p-value = 0.016) at the time of admission were found to have higher in-hospital mortality. Critical care data suggested that 9 patients required intensive care, 7 patients required vasopressor support, and 6 needed mechanical ventilation. Patients were treated with either vancomycin alone (13), or metronidazole alone (25), or combination therapy with vancomycin + metronidazole (21). The median duration of hospital stay was 6 days with 11 fatalities (18.64%)., Conclusions: CDI causes significant morbidity in patients with malignancies. A high qSOFA score and leukocytosis are significantly associated with high morbidity and thus should be used to prioritize and intensify inpatient care of these patients., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

Background: Cardiovascular complications of the coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), have been documented both in the acute phase and in convalescence. One such complication is the formation of the left ventricular (LV) thrombus. There is a lack of clarity regarding the incidence, risk factors, and management of this complication., Aim: The aim of the study is to identify the clinical presentation, risk factors and outcome of COVID-19 patients with left ventricular thrombus (LVT)., Methods: A literature search was conducted to identify all case reports of COVID-19 with LVT in PubMed/Medline, Embase, Web of Science, and Google Scholar., Results: Among the 65 patients identified, 60 had LVT, either at admission, or during the acute phase of the illness. Six patients with mild symptoms during the acute phase of viral illness had only the COVID-19 antibody test positivity at the time LV thrombus was detected. Few of the patients (23.1%) had no comorbidities. The mean age of the patients was 52.8 years, and the youngest patient was 4 years old. This suggests that LVT formation can occur in young COVID-19 patients with no co-morbid conditions. Most of the patients (69.2%) had more than one site of thrombosis. A mortality rate of 23.1% was observed in our review, and ST-elevation myocardial infarction (STEMI) was diagnosed in 33.3% of those who died., Conclusions: A high degree of suspicion for LVT must be maintained in patients with known cardiac disease and those with new-onset arterial or venous thromboembolism, and such patients may benefit from a screening echocardiography at admission., Relevance for Patients: The patients with preexisting cardiovascular disease must take added precautions to prevent acquiring COVID-19 infection as there is a higher risk of developing LV thrombus. In patients who develop LVT in COVID-19, mortality rate is higher., Competing Interests: The authors have no conflicts of interest to declare., (Copyright: © Whioce Publishing Pte. Ltd.)

Aim: To compare the demographical profile, indications, efficacy, and contributors to adverse outcome following administration of 4F-PCC in patients on warfarin with supratherapeutic INR., Methodology: Retrospective cross-sectional study was performed in a community based teaching hospital. All patients 18 years and older on warfarin with supratherapeutic INR, who had received 4F-PCC between January 2014 and December 2018 were eligible and included in the study., Results: 44 patients were included in the analysis. The mean age of the patients was 79.5 years. The male to female ratio was 1:1. Patients were on warfarin for atrial fibrillation, thromboembolism in 79.5% (N-35), and 20.5% (N-9) respectively. Indications for use of 4F-PCC were active bleeding in 93% (N-41) of patients. The common sites of bleeding were gastrointestinal, intracranial, and musculoskeletal which were seen in 54.5% (N-24), 29.5% (N-13) and 6.8% (N-3) respectively. The median number of doses of 4F-PCC administered was 1 per patient. The mean dose administered was 2,883u. Clinical improvement was documented in 84% (N-37) of patients. Mortality was seen in 16% (N-7) of patients. BMI greater than 30, anemia, hypotension, presence of intracranial bleed, the requirement of blood products, and mechanical ventilation were associated with higher odds for mortality. Hypotension and requirement of mechanical ventilation were statistically significant., Conclusion: 4F-PCC continues to be an effective agent in the rapid reversal of warfarin therapy in patients with supratherapeutic INR presenting with major bleeding events. Most patients have clinical improvement with a single, weight-adjusted dose.

Virus infections can cause tissue damage in many ways. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a cause of the current COVID-19 pandemic, has been extensively studied so far to investigate its pathophysiology and evaluate its impact on the metabolic system of human cells. This has given a lead to study the role of 2-deoxy-D-glucose (2DG) against COVID-19 disease. We hereby would like to briefly discuss the concept and rationale behind the use of 2DG COVID-19., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Family Medicine and Primary Care.)

Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Immune Thrombocytopenia (ITP) is characterized by low platelet counts. Splenectomy has been in practice for the treatment of ITP since the early 20th century. We aimed to analyze the data of ITP patients from our hospital who underwent splenectomy and further present the long-term outcome and safety profile in these patients., Method: This study was a single-center, registry based study conducted at a tertiary care hospital in Northern India. Patients aged 18 years or more, who underwent splenectomy after at least one line of therapy, were included in the study. The primary outcome was the overall response rate (ORR) at one month after splenectomy. Secondary outcomes were sustained response, relapse-free survival, factors affecting the ORR, and adverse events after splenectomy., Results: Forty-five patients of ITP were included in the study. Thirty-six patients underwent splenectomy in the first half (2001-2010), of the study period. The median age of the patients was 38 (19-56) years. The median duration from diagnosis to splenectomy was 1.76 (0.47-2.58) years. The median number of therapy received before splenectomy was 3 (1-6). The overall response rate (ORR) post-splenectomy at day 30 was 89.2% with 61.8% complete response (CR). The ORR was 88.5% at 1-year, with 48.8% CR. The relapse-free survival (RFS) at 5-years was 57.38% (95% Confidence Interval 40.59-71.02%), There was no effect of duration of disease, age, gender, and prior therapy received, on the ORR at one-month. At one year, the platelet response was significantly better in patients who had a CR at one-month than patients who had a partial response at one month. The relapse-free survival was better in patients who achieved CR after 1-month of splenectomy. During the median follow-up of 5.02 (1 month-20 years) years, there were five cases of overwhelming post-splenectomy infection (OPSI). There was no recorded incidence of perioperative mortality, deep vein thrombosis, or mesenteric thrombosis., Discussion: Despite the variation in outcome from different studies, splenectomy gives the best possible long-term treatment-free remission amongst all the available second-line agents. It is also, one of the most financially affordable therapies. Despite advantages, the number of ITP patients undergoing splenectomy has been on the decline and largely attributable to the newer and more effective second-line therapies. There is no pre-surgery variable predicting the ORR after splenectomy., Conclusion: Splenectomy in ITP offers a long-term sustained response at an economical cost., Competing Interests: None., (AJBR Copyright © 2021.)

Introduction: Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30-66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML., Method: This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included., Result: A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12-71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days ( p  = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 ( p  = 0.063). Thirteen patients (23.63%) died during the study period., Discussion: Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections., Conclusion: Infections continues to be a major cause of morbidity and mortality among AML patients., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Immune thrombocytopenia (ITP) is a relapsing-remitting disease often requiring more than one line of therapy. Rituximab is a recommended second-line therapy, but the real-world data on its efficacy and safety from resource constraint settings is limited. We aimed to analyze the safety and efficacy of rituximab in ITP. This is a single-center, retrospective study. This study was conducted at a tertiary care hospital in Northern India from 2005 to 2019. On audit of medical records, all patients of ITP (n-513) who had received rituximab (n-81) were screened for inclusion. Patients whose response assessment was not possible were excluded. Finally, 66 patients were analyzed using statistical packages of Python v3.7. The cumulative incidence of overall response on day 20 was 30.61%, and day 30 was 51.72%. The median time to response was 28 day (range 21-51 day). Cumulative incidence of complete response was 16.67%, and partial response 37.88%. After a median follow-up of 789 day (range 181-5260 day), the cumulative incidence of relapse was 30.32%, 36.12%, and 56.57% at 1, 2, and 5 years respectively. There was no effect of age, sex, duration of disease, lines of therapy received, and platelet count on either cumulative incidence of overall response or relapse. ANA positivity was significantly related to the better cumulative incidence of overall response ( p  = 0.012), but not with relapse. Infusion-related reactions were the commonest adverse event noted (n-4, grade ≥ 3 CTCAEv4). Rituximab and its generic version are safe and effective second line agent in ITP with a good overall response and sustained response., Competing Interests: Conflict of InterestThere is no conflict of interest between the authors., (© Indian Society of Hematology and Blood Transfusion 2021.)

Competing Interests: None

Objectives: Neutrophil-lymphocyte ratio (NLR), as an indicator of heightened systemic inflammatory response, predicts increased disease burden and poor oncological outcomes in urothelial carcinoma (UC). The study was undertaken with an aim to evaluate the association of NLR with clinicopathological variables and survival outcomes., Methods: A total of 80 patients of UC were enrolled in the current retrospective study. Pre-operative NLR (within one month prior to the procedure), patient age, sex, tumour grade, pathological stage, recurrence free survival (RFS), progression free survival (PFS) and cancer specific survival (CSS) were recorded. We chose a cut-off value of 2.7 for NLR and patients were divide into two groups (NLR <2.7 and ≥2.7)., Results: NLR ≥2.7 was significantly associated with advanced tumour stage (p=0.001), but not with tumour grade (p=0.116). Progression (p=0.032) and death rates (p=0.026) were high in patients with NLR ≥2.7. Mean RFS (p=0.03), PFS (p=0.04) and CSS (p=0.04) were reduced in patients with NLR ≥2.7. On univariate analysis, NLR ≥2.7 predicted worse RFS (HR=2.928, p=0.007), PFS (HR=3.180, p=0.006) and CSS (HR=3.109, p=0.016). However, it was not an independent predictor of outcomes on multivariate analysis., Conclusions: Tumour stage and grade are the only independent predictors of RFS, PFS and CSS. High NLR at a cut-off value of ≥2.7 is associated with advanced pathological stage, but does not have an independent predictive value for RFS, PFS and CSS., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Immune thrombocytopenia (ITP) is a benign hematological disorder characterized by low platelet counts in peripheral blood and spectrum of various bleeding manifestations. Azathioprine is one of the effective, readily available, and affordable immunosupressants available for ITP management in developing countries. We aimed to study the efficacy and long-term safety profile of our patients with ITP who were treated with azathioprine., Method: This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India. The patients who had received at least one line of therapy before receiving azathioprine were included in this study. All patients received oral azathioprine at a dose of 1 mg/kg/day (50 mg or 100 mg tablet formulations were used), which was increased up to 2 mg/kg/day depending upon the response and adverse effects., Result: Sixty-three patients were analyzed. Their median age was 28 years (range 15-68); 29/63 patients (46.03%) were females. The median duration from diagnosis to azathioprine initiation was 539 days (323 days-980.5 days). The patients included in the study had received a median of 3 (range 1-6) prior lines of therapies; 38/63 patients (60.32%) had received ≥3 prior therapies. Six patients (9.5%) had relapsed after splenectomy, and 16 patients (25.4%) had relapsed after receiving rituximab. The mean baseline platelet count was 10000/μL. The median time to response was 95 days (90 days-not reached) and the cumulative overall response rate (complete and partial response) at day 90 was 38.1%. Only one patient achieved complete response with azathioprine in our study. The cumulative rate of relapse at five years was 21.2%. Twenty-six patients stopped azathioprine after achieving some response (CR/PR) with Azathioprine for a median duration of 1067.5 days (range: 236 days-2465 days). They were followed up for a median of 870 days (range: 392 days-1928 days), and twelve of them relapsed. Twenty-six patients (26/63, 41.27%) reported one or more adverse events while on azathioprine. Leucopenia was the most frequent adverse event, followed by anemia and hepatobiliary laboratory abnormalities. Serious adverse events (grade ≥3 CTCAEv4) were noted in three patients (4.7%). One patient succumbed to severe sepsis multiorgan dysfunction while being on treatment., Conclusion: We conclude that azathioprine has a good response rate in chronic ITP patients. It is well-tolerated with minimal and manageable side effects., Competing Interests: None., (AJBR Copyright © 2021.)

We read with great interest the article by D'Ettorre et al. on workplace safety and violence against healthcare workers in emergency medicine recently published in your esteemed journal. Authors address one of the critical issues faced in healthcare industry today. We wish to complement the article with some additional thoughts.  As authors try to find remedies to minimize workplace violence against the healthcare providers by optimizing number of night shifts and adopting constant forward-rotating shift schedules, we need to augment this effort by continual effort to improve education and sensitivity amongst the colleagues to be able to emotionally support each other. An important aspect to this is to also provide religious and spiritual support to the healthcare staff (and patients) upon request. Evidence supports improvement in overall well-being and a protective benefit against burnout with religious and spiritual beliefs in healthcare providers. As quite aptly pointed out by other seasoned authors; based on decades of experience, commonality of common sense has been a declining asset in our current set up of medical practice, whether it has a component moral decline associated with it remains debatable. Daily physician care by the physicians themselves and peers is an aspect that needs to be highlighted and inculcated in our medical practice. This aspect of psychological safety (in addition to physical safety) in work place of practicing physicians is rarely discussed and the results are tangible, indicated by high burnout rates and poor sense of accomplishment. To make matters worse we often shy away from open discussions regarding the issue.

For the last few months, various geographical regions and health sectors have been facing challenges posed by the current COVID-19 pandemic. COVID-19 has led to significant disruption in the normal functioning of potentially life-saving therapies of hematopoietic cell transplant and chimeric antigen receptor therapy. As transplant physicians are gaining more information and experience regarding the undertaking of these complex procedures during the ongoing COVID-19 pandemic, we believe it is important to discuss the challenges faced, prognostic risk factors, and outcomes of COVID-19 in post-hematopoietic stem cell transplantation patients based on the available real-world data., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Background: Immune thrombocytopenia (ITP) is a heterogeneous acquired disorder characterized by isolated thrombocytopenia whose exact pathogenesis is not yet clear. Depending upon the presence or absence of an underlying treatable cause, ITP can be categorized as primary or secondary. Primary ITP is a diagnosis of exclusion and there is no gold standard test for its confirmation. Recent drug intake, infections, lymphoproliferative disorders, and connective tissue disorders should be ruled out before labeling a patient as primary ITP., Area Covered: This review summarizes a comprehensive update on the diagnostic and therapeutic modalities for ITP. We reviewed the literature using GOOGLE SCHOLAR, PUBMED and ClinicalTrial.gov databases as needed to support the evidence. We searched the literature using the following keywords: 'immune thrombocytopenia,' 'idiopathic thrombocytopenic purpura,' 'thrombocytopenia,' 'immune thrombocytopenic purpura,' and 'isolated thrombocytopenia'., Expert Opinion: We believe that more detailed studies are required to understand the exact pathophysiology behind ITP. The first-line drugs like corticosteroids have both short-term and long-term adverse effects. This brings the need to explore effective alternative medications and to reconsider their role in ITP treatment algorithm if guidelines can be modified based on new studies.

The ongoing COVID-19 pandemic is the most trending and talked topic across the World. From its point of origin in Wuhan, China to clinical laboratory at NIH, a mere six-month-old SARS-CoV-2 virus is keeping the clinicians, and scientists busy at various fronts. However, COVID-19 is an emerging and evolving disease and each day brings in more data, new figures, and findings from the field of clinical practice. The role of hematologists has been increasingly recognized during the current pandemic because of several reasons. Most important of them are the characteristic hematological findings of COVID-19 patients that also have prognostic implications and that were not seen in other viral infections. The treatment of hematological complications in COVID-19 patients is very challenging given the critical care setting. There are interim and limited guidelines thus far due to the novelty of the disease. As this remains to be a quite fluid situation, all the appropriate medical societies including the major hematology bodies are proposing initial and interim guidelines (e.g. ASH guideline). This puts a hematologist on consult service in a dubious position where, he/she must tailor the recommendations on case to case basis. The purpose of this review is to provide the background context about the impact of COVID-19 on the blood system and to summarize the current interim guidelines to manage the associated hematological issues in COVID-19 infection., (Copyright © 2020. Published by Elsevier Ltd.)

Coronavirus disease-2019 (COVID-19) is a rapidly evolving health crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is a novel disease entity and we are in a learning phase with regards to the pathogenesis, disease manifestations, and therapeutics. In addition to the primary lung injury, many patients especially the ones with moderate to severe COVID-19 display evidence of endothelial damage, complement activation, which leads to a pro-coagulable state. While there are still missing links in our understanding, the interplay of endothelium, complement system activation, and immune response to the SARS-CoV-2 virus is a surprisingly major factor in COVID-19 pathogenesis. One could envision COVID-19 becoming a novel hematological syndrome. This review is to discuss the available literature with regards to the involvement of the complement system, and coagulation cascade and their interaction with endothelium.

The objective of this study is to compare game-based digital therapeutic device and other DHI like (smartphone apps, wearable technologies) for ADHD with the current pharmacological and behavior therapy. The FDA has approved a game-based digital therapeutic device - EndeavorRx, for the treatment of ADHD in pediatric patients belonging to the age group of 8-12 years old. This has been primarily recommended for the treatment of inattentive or combined-type ADHD who have demonstrated an attention issue. This is the first game-based therapeutic device to be approved by the FDA for any type of condition. According to the FDA, this has been shown to improve attention which is measured by computer-based testing. Objective: The objective of this study is to compare a game-based digital therapeutic device and other DHI (smartphone apps, wearable technologies) with the current pharmacological and behavior therapy used in the treatment of ADHD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Antidepressants are well known to exert their role via upregulation of brain derived neurotrophic factor (BDNF). BDNF has been reported to exerts its neuroprotective effect in rodent and primate models as well as in patients of Alzheimer's disease (AD). The aim of our study was to evaluate the effect of protriptyline (PRT), a tricyclic antidepressant, in streptozotocin (STZ)- induced rat model of AD. Total 10 µl of STZ was injected into each ventricle (1 mg/kg). PRT (10 mg/kg, i.p.) treatment was started 3-day post STZ administration and continued till 21 days. We found that STZ treatment significantly increased pTau, Aβ42 and BACE-1 expression, oxidative stress and neurodegeneration in hippocampus and cortex of adult rats. STZ induced impairment in spatial learning and retention memory was associated with increased NFκB and reduced CREB and BDNF expression in cortex and hippocampus. Interestingly, PRT treatment significantly reduced pTau, Aβ42 and BACE-1 levels, neurodegeneration, oxidative stress and glial activation, contributing to the improved spatial learning and retention memory in STZ treated rats. Moreover, PRT treatment significantly improved p-ERK/ERK ratio and enhanced BDNF and CREB levels by reducing NFκB and GFAP expression in STZ treated rats. Our data suggest that impaired NFκB and CREB signaling potentially contribute in AD pathogenesis by elevating oxidative stress and neuroinflammation mediated neurodegeneration. Our study has established protriptyline as a multi target molecule in pre-clinical model of AD and further investigations on PRT like molecules could pave way for further development of effective new treatments in neurodegenerative disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Esophageal perforation is a fatal entity if not diagnosed in a timely fashion. Once diagnosed, it requires collaborative effort of team of doctors including radiologists, thoracic surgeons and general surgeons. We share hereby our experience with esophageal perforation and successful outcome.

The current pandemic due to coronavirus disease 2019 (COVID-19) has posed an unprecedented challenge for the medical communities, various countries worldwide, and their citizens. Severe acute respiratory syndrome coronavirus 2 has been studied for its various pathophysiological pathways and mechanisms through which it causes COVID-19. In this study, we discussed the immunological impact of COVID-19 on the hematological system, platelets, and red blood cells., (© 2020 Wiley Periodicals LLC.)