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Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.
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This proceedings contains 112 s that cover a wide range of topics related to microbiology. The s cover a wide range of topics related to microbiology, including new paradigms in a microbe-threatened world, the human-animal spillover of SARS-CoV-2 and its implications for public health, preparing for the next pandemic, antimicrobial resistance and the fight against it. Furthermore, tuberculosis, monkeypox, and their potential threat on a global scale are also discussed. The presentations also cover a variety of other topics, such as vaccines and vaccinations, COVID-19 vaccines, addressing vaccine hesitancy, key issues related to the COVID-19 healthcare system, regional support for outbreak preparedness, enhancing regional health security in Asia through genomic surveillance, the role of molecular diagnostic capacity in COVID-19 control, antimicrobial resistance in COVID-19 times, paediatric nosocomial infections, prescription ethics from a primary care perspective, the BCG vaccine and its relevance in the prevention of tuberculosis and beyond, tuberculosis as a forgotten pandemic, vector-borne diseases during COVID-19, the role of media advocacy in vector-borne diseases control and management, engaging communities in tackling vector-borne diseases, the way forward in managing mental health in the COVID-19 endemic phase, the spread of zoonotic diseases, and whole genome sequencing of SARS-CoV-2: clinical applications and experience.
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The explanations behind the wide spreadability of coronavirus sickness (COVID-19) are not known properly in this world. Several clinical investigations have indicated that the BCG antibody impacts on the immune system and human sicknesses which take part in the host system to such an extent that numerous types of viral diseases are extensively diminished or reduced. Subsequently, it was also observed in different studies that the recurrence and seriousness of numerous microbial or viral diseases, including COVID-19, will be lower in few countries where BCG Immunization programs are carried out. Few clinical investigations proposed by the epidemiological data have shown that the BCG antibody has a valuable impact in the treatment of COVID-19. So the BCG immunization may be found valuable in the coming months, particularly in the countries, where mass BCG immunization is done. Further thorough BCG immunization clinical trial is required to establish the above findings and its clinical significance. In future, this investigation will concentrate on the BCG vaccine and it may forestall the event of SARS-CoV-2 contamination and its succession in the large population.Copyright © 2021 Bentham Science Publishers.
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Introduction & Objectives: Patients with high risk non muscle invasive bladder cancer (NMIBC) who experience BCG failure have limited bladder preserving treatment options as radical cystectomy currently represents the standard therapeutical approach. Systematic immunotherapy (IO) has changed the landscape in advanced bladder cancer and is currently being investigated in NMIBC. Based on the hypothesis that intravesical administration will not be related with severe adverse events, we evaluated the role of intravesically administered durvalumab in NMIBC patients after BCG failure. Material(s) and Method(s): An open label, single-arm, multi-center, phase II clinical trial was conducted. A run-in phase had the objective to determine the maximum tolerated dose (MTD) of durvalumab and to exclude a detrimental effect on disease relapse by this strategy. Durvalumab was administered for a total of 6 instillations per patient at consecutive levels of 500, 750 and 1000 mg. Phase II has as primary end point the 1-year high-grade-relapse-free (HGRF)-rate. Secondary endpoints included toxicity, and high-grade progression-free rat at 1, 3 and 6 months after treatment. Result(s): Thirty patients were enrolled (run in phase: 9, phase II: 21). One patient withdrew consent prior to receiving study treatment, so 29 patients were included in efficacy and toxicity analyses. Mean age was 66.5 years. MTD of durvalumab was set at 1000 mg as no dose related toxicities (DLTs) occurred at any level studied. Three of 9 patients included in the run-in phase (33.3%) were tumor free one month after the last durvalumab instillation, therefore, the null hypothesis was rejected by the futility analysis. Western blot showed that durvalumab remained stable in urine during instillation. One patient died from Covid-19, 3 months after the last durvalumab administration. All patients concluded at least 1 year follow up. One-year HGRF rate was 34.6%. HGRF rates at 1, 3 and 6 months was 73%, 65.3% and 50% respectively. Five patients (17%) experienced a T2 or above disease relapse. Five out of the six patients who received 500mg or 750mg of durvalumab relapsed within 1 year. When efficacy analyses were restricted to patients receiving 1000mg of durvalumab, 1-year HGRF rate was 35%. Interestingly, 2 out of 2 patients with only CIS disease at baseline experienced a tumor complete response, which was durable and was maintained at least for a year. No severe adverse events were noted. The most common adverse event was Grade 1 hematuria. Conclusion(s): Intravesical IO using durvalumab was proved to be feasible with an excellent safety profile. Oncological results seem to be promising and comparable with other bladder preserving strategies in BCG failure with the advantage of a better safety profile. Further study of intravesical IO in high-risk patients with NMIBC after BCG failure is warranted.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Objective: Our goal was to elucidate a potential molecular link between the past and current tuberculosis vaccine Bacillus Calmette-Guerin (BCG;a live attenuated strain of Mycobacterium bovis) immunization policies and COVID-19. Method(s): Our sequence homology analyses have demonstrated that there is an intriguing level of sequence homology between a few of the BCG and Sars-CoV-2 proteins. Result(s): The data suggest that the BCG-specific memory B-cells that are preserved in BCG-vaccinated patients cross-recognize SARS-CoV-2 and that this cross-recognition may affect the virus proliferation and COVID-19 severity. Conclusion(s): Our results can stimulate the sharply focused follow-up experimental studies.Copyright © 2020 Bentham Science Publishers.
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Background: Ecological studies showed that countries with national Bacillus Calmette-Guerin (BCG) vaccination programs for tuberculosis prevention reported lower incidences of severe and fatal COVID-19 than countries without such programs. Several studies have demonstrated that the BCG vaccine can induce long-term trained Immunity in bone marrow progenitor cells. In this study, we tried to evaluate the relationship between tuberculin skin test results, BCG scar, and COVID-19 outcomes among patients with confirmed COVID-19. Material(s) and Method(s): This was a cross-sectional study. Cases included 160 patients with confirmed COVID-19 in Zahedan hospitals (southeast Iran) in 2020, selected by convenient sampling. PPD test was performed for all patients through the intradermal technique. Collected data included demographic information, underlying conditions, PPD test results, and COVID-19 outcome. Analysis was conducted utilizing ANOVA, chi2 test, and multivariate analysis (logistic regression). Result(s): The univariate analysis showed a positive relationship between older age, having underlying diseases, and positive tuberculin skin test results with the outcome of COVID-19. We also found a lower frequency of BCG scar among patients with death outcomes than recovered ones. In the multivariate analysis by logistic regression through the backward method, only age and underlying diseases remained predictors of death. Conclusion(s): Tuberculin test results might be dependent on age and underlying conditions. Our study did not show relationship between BCG vaccine and mortality in COVID-19 patients. Further investigations in different settings are required to reveal the efficacy of the BCG vaccine in preventing this devastating disease.Copyright © 2022 NRITLD, National Research Institute of Tuberculosis and Lung Disease, Iran.
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Introduction: The COVID19 pandemic has changed the way of life all over the world, many diseases have started to reactivate and reappear. Tuberculosis (TB) can be among them despite the existence of effective measures and programs to control it. The aim of study was to establish patients' knowledge of TB at the time of the COVID19 pandemic. Method(s): The prospective study included patients with respiratory diseases who were interviewed (questionnaire with 27 questions) at the Institute of Pulmonary Diseases of Vojvodina (Serbia) in the period September-December 2021. Result(s): A total of 600 patients in two groups were surveyed (300 outpatient-AMB;300 in-hospital-HOS). Almost all patients in both groups knew that TB was a contagious disease (562, 93.6%, p=0.735);a curable disease (521, AMB-240, 80.0%, HOS-281, 93.7%, p=0.052). Less than 50% said bacteria was the causative agent (273 patients, AMB-149 patients, 49%, HOS-124, 41.3%, p=0.041). The 3/4 patients in both groups (521 patients, p=0.590) responded that cough was a way of transmission. Nearly 30% of all patients are unaware of the existence of TB vaccine (BCG), while 1/3 of patients believe that the vaccine cannot helps (204 patients, AMB-141, 47%, HOS-63, 21%, p=0.014). Conclusion(s): Patients showed mediocre knowledge of TB, especially with reference to TB immunization measures. The probable reason lies in the various informations in the media about immunization against COVID19 and the consequent rejection of the success of immunization against TB. It is necessary to intensify the education of the population about the positive effects of all types of immunization in order to prevent the disease.
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Safe, effective, and accessible vaccines are urgently needed to end tuberculosis (TB) by 2030. The 6th Global Forum on TB Vaccines, convened virtually 22–25 February 2022, was hosted by Toulouse, France, under the high patronage of President Emmanuel Macron, and the patronages of Minister for Solidarity and Health, Olivier Véran, and Minister for Higher Education, Research and Innovation, Frédérique Vidal. The theme for the meeting, "New horizons for TB vaccines”, reflected the changing landscape in which TB vaccine research and development (R&D) is being conducted: TB vaccines advancing into late-stage clinical trials and toward licensure, innovative research toward diversifying the TB vaccine pipeline and developing the next generation of candidates, increasing political, civil society, and community support for TB vaccines, and the ongoing COVID-19 pandemic. In this report, we summarize key themes and findings from the meeting, highlighting progress and gaps in the TB vaccine field.
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SARS-CoV-2 has affected essentially all countries worldwide and caused millions of people to become infected and die. Therefore, it is extremely valuable to investigate new approaches to stop the most scarring ongoing pandemic. BCG vaccine has been proposed that it could reduce the rate of new COVID cases and limit the severity of infection since TB and COVID-19 have similar dominant effects, such as cytokine storm and improper immune response. This review aimed to focus on the latest literature data on trained immunity as well as the possible cross protection effect of BCG vaccine against COVID-19. The first immune response to BCG vaccines has started with the stimulation of adaptive immune response and establishment of the immunological memory of antigen-specific T and B cells to target infectious agents. In the past years, innate immune response was thought to be not having the talent to adapt and "learn” from previous exposure to a pathogen. Trained immunity is conceivable as 'de facto' innate immune system memory. Some researches argue that there is a strong relationship between BCG immunization and COVID-19 although some are against this argument. Based on the data obtained from different research studies and ongoing clinical trials, there is still no evidence that BCG vaccine is effective against COVID-19. Besides assumptions, knowns and unknowns, the clinical efficiency of BCG vaccine against SARS-CoV-2 should be validated by accurate scientific clinical reports in different age groups to understand the potential benefits of BCG vaccine to limit COVID-19 incidence and mortality.
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Introduction: Google Trends is an online metadata platform that measures the relative search volume of every topic in online search engines. In medical settings, this behavior has been associated with active changes in people's perceptions and search for healthcare. This study aimed to evaluate the online search patterns of Portuguese extra-program and risk-based vaccination. Method(s): Analysis of the relative search volume was performed for extra-program and risk-based vaccines, in every Portuguese district between 2006 and 2021. Relative search volume was represented between 0 and 100 (highest interest in the query). Result(s): Rotavirus vaccine was consistently the most searched, followed by BCG and flu, the last of which, with abnormal peaks of search in November 2009 and October 2020. We registered a significant increase in the search for every vaccine in the last 5 years (p < 0.01). Particularly, during the COVID-19 pandemic, a more abrupt increase was registered for the flu vaccine, but most importantly for BCG (3,0[69,9] vs. 9,0[528,0]). Lisboa and Porto are the only Portuguese districts where percentual research is spread across all types of vaccines. On the other hand, in Portalegre, 84% of total searches correspond to BCG. Discussion and Conclusion(s): The recent increase in the interest in vaccination may translate into the investment of health professionals in primary prevention measures. However, the mediatic impact of pandemics is not neglectable. Health professionals must fight misinformation as it may have happened with the increasing interest in BCG, probably due to the protective association proposed with the infection by SARS-CoV-2. Copyright © 2022 The Author(s). Published by S. Karger AG, Basel.
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Mycobacterium tuberculosis causes the disease tuberculosis and affects a third of the world's population. The recent COVID-19 pandemic exacerbated the situation with a projected 27% increase in tuberculosis related deaths. M. tuberculosis has an elaborate cell wall consisting of peptidoglycan, arabinogalactan and mycolic acids which shield the bacilli from the toxic bactericidal milieu within phagocytes. Amongst, the numerous glycosyltransferase enzymes involved in mycobacterial cell wall biosynthesis, arabinofuranosyltransferase C (aftC) is responsible for the branching of the arabinan domain in both arabinogalactan and lipoarabinomannan. Using Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) we have generated aftC knockdowns in Mycobacterium bovis BCG and demonstrated the generation of a truncated, immunogenic lipoarabinomannan within its cell envelope. The aftC depleted BCG mutants were unable to form characteristic mycobacterial pellicular biofilms and elicit a potent immunostimulatory phenotype compared to wild type M. bovis BCG in a THP1 cell line. This study paves the way to further explore novel BCG mutants as promising vaccine boosters in preventing pulmonary tuberculosis.
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Despite controversy over the protective effect of the BCG (Bacille Calmette-Guérin) vaccine in preventing pulmonary tuberculosis (TB) in adults, it has been used worldwide since 1921. Although the first reports in the 1930s had noted a remarkable decrease in child mortality after BCG immunization, this could not be explained solely by a decrease in mortality from TB. These observations gave rise to the suggestion of nonspecific beneficial effects of BCG vaccination, beyond the desired protection against M. tuberculosis. The existence of an innate immunity-training mechanism based on epigenetic changes was demonstrated several years ago. The emergence of the pandemic caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in 2019 revived the debate about whether the BCG vaccine can affect the immune response against the virus or other unrelated pathogens. Due to the mortality of the coronavirus disease (COVID-19), it is important to verify each factor that may have a potential protective value against the severe course of COVID-19, complications, and death. This paper reviews the results of numerous retrospective studies and prospective trials which shed light on the potential of a century-old vaccine to mitigate the pandemic impact of the new virus. It should be noted, however, that although there are numerous studies intending to verify the hypothesis that the BCG vaccine may have a beneficial effect on COVID-19, there is no definitive evidence on the efficacy of the BCG vaccine against SARS-CoV-2.
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Background: The Covid-19 pandemic risks disruption to diagnosis and treatment of Tuberculosis (TB) globally, jeopardising the 2035 eradication target. Between 1990-2010 40.9% of contacts did not complete Tuberculosis (TB) contact screening in Birmingham, UK. Understanding screening outcome success is urgently needed to guide future resource allocation. Aim: To evaluate changes made to TB screening since 2010. To identify predictors of contact screening non-completion, and of screening outcomes. Methods: A retrospective cohort analysis of all index and contact patients in Birmingham between 2011-2020, with separation of Covid-19 data, and stratification of contacts by Pulmonary TB (PTB) or Extra-Pulmonary TB (EPTB) index infection. Univariate and multiple logistic regression models were used to identify predictors of screening completion and clinical outcome. Results: 3,255 index cases and 27,820 contacts were identified. Screening non-completion has improved from 40.9% of contacts to 25% since 2010. Contacts were less likely to complete screening if they were >65 years (P=0.001) had no BCG (P<0.001), were male (P<0.001 PTB, P=0.02 EPTB), had had TB themselves (P<0.001 PTB, P=0.025 EPTB), were a close contact (P<0.001), or were from the Indian subcontinent (PTB only, P=0.019). Contacts were significantly more likely to require treatment for TB if they were born outside the UK (P<0.001), were <65 years (P<0.001 PTB, P=0.01 EPTB), if they were male, close contacts, or of Black ethnicity (all P=0.001, PTB only). Conclusions: Changes to contact screening since 2010 have substantially improved screening completion rates. Significant predictors of screening non-completion exist, which warrant further investigation and targeted screening support.
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Background: Multisystem Infammatory Syndrome in Children (MISC) is a hyper-infammatory state with similarities to Kawasaki Disease, 4 to 6 weeks after Covid-19 infection1. Literature describes a 11:1 Relative Risk for Asian children versus Caucasians2. Since the start of the pandemic, 17,699 children under 12 years were infected with Covid-193. Objectives: To describe presentation and short term outcomes, for a cohort of children with MIS-C at the sole Children's Hospital in Singapore. Methods: Demographic and clinical/lab data were collected from children diagnosed with MIS-C accrording to the WHO criteria4 at KK Woman's and Children's Hospital, Singapore. Nonparametric descriptive statistics were used to describe and analyse data. Results: Eleven patients were diagnosed with MIS-C between October 2021 and Jan 2022. Seven (64%) were male and 4 (36%) were Chinese, with median age at presentation was 8.08 years (IQR 4.54-9.79). All patients had positive COVID-19 serology at the time of diagnosis. Median duration of fever prior to diagnosis was 5 days (IQR 4-5);Nine (82%) had gastrointestinal symptoms and median number of Kawasaki Disease (KD) features were 2 (IQR 2-3.5);common manifestations were conjunctivitis (90%), red lips (55%) and rash (36%). Of note, 8 (70%) patients had KD type peeling on follow-up. No BCGitis was found during acute phase. Seven (64%) were admitted to higher dependency care. Table 1, all patient received IVIG and IV steroids;6 (55%) as pulse (30mg/kg/day) therapy. Patient 8, additionally received Anakinra. Median duration of admission was 6 days (IQR 5-13). One patient developed complications post therapy and was re-admitted to hospital for hematochezia. Treatment involved stopping Enoxaparin and Prednisone. Aspirin was resumed as soon as bleeding ceased. Laboratory characteristics and outcomes are denoted in Table 1. All patients had a monophasic course during the median of 10 weeks (IQR 8-11.5) of follow-up. Conclusion: 1.Asian prevalence of MIS-C is not as high as that reported from the West. Similarities in presentation as to age and gender were noted. 2.Most of our MIS-c patients developed periungual peeling at follow up, similarly to Kawasaki Disease. 3.Different from our typical KD population, no BCG site infammation was found.
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Introduction: Human steroid 5α-reductase 2 (SRD5A2) coded by SRD5A2 gene is an enzyme that catalyzes the reduction of testosterone to dihydrotestosterone. Dutasteride, an SRD5A2 inhibitor, is a widely used antiandrogen for the treatment of benign prostate hyperplasia. Multiple variations have been identified in the SRD5Ar gene. Some of these variations may affect the efficacy and safety of SRD5A2 inhibitors. Dutasteride has also been investigated for intermediate and high-risk nonmuscle- invasive urothelial bladder cancer treatment with the combination of BCG (Bacillus Calmette-Guerin). Objectives: The study aims to evaluate the potential impact of V89L (rs523349) and A49T (rs9282858) variations on the SRD5A2 gene on dutasteride efficacy and safety in bladder cancer patients that have been enrolled in Phase 2 clinical trial entitled 'Efficacy and safety of a 5-alpha reductase inhibitor, dutasteride, added to Bacillus Calmette Guerin (BCG) immunotherapy in the prevention of recurrence and progression of intermediate and high risk non-muscle invasive bladder cancer: A single-arm, Phase 2 clinical trial' Methods: Twenty-one patients on BCG and dutasteride in the Phase 2 clinical trial were included in the study. Genomic DNA was obtained from whole blood samples, and evaluation of V89L (rs523349) (G>C) and A49T (rs9282858) (C>T) variations on the SRD5A2 gene was performed by using TaqMan SNP Genotyping Assay. The severity of the adverse events was graded by the United States National Cancer Institute- Common Terminology Criteria for Adverse Events 5.0. The causality assessment of adverse drug reactions was performed using Liverpool Causality Assessment Tool, Naranjo Algorithm, and World Health Organization-Uppsala Drug Monitoring Centre Causality Assessment System. The response to dutasteride was evaluated as the presence of bladder cancer recurrence. The Chi-Square test was used for testing the relationship between categorical variables. P values of <0.05 were considered significant. Results: All patients were homozygous GG for V89L variation on the SRD5A2 gene. Regarding the A49T variation, only one patient was homozygous CC, 8 patients were homozygous TT and 12 patients were heterozygous TC. One of the 8 patients (%12) was homozygous TT and 3 of 12 patients (%25) were heterozygous TC had bladder cancer recurrence. There was no statistically significant difference between bladder cancer recurrence and A49T variation (p=0.803). None of the adverse events were associated with dutasteride treatment whereas some of the adverse events, mostly urinary tract infections, were associated with the BCG. Other adverse events were upper respiratory tract infections, COVID-19, abdominal pain, vomiting, and loss of appetite. Serious adverse events were coronary artery disease, dyspnea, hypotension, and urethral stricture. None of the serious adverse events were associated with dutasteride or BCG treatment. Conclusion: Neither V89L nor A49T variation on the SRD5A2 gene was found to be associated with the efficacy and safety of dutasteride in medium and high-risk bladder cancer patients. Further studies of these variations with larger sample sizes and/or healthy control groups may lead to a better understanding of the impact of these variations on the efficacy and safety of dutasteride.
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Objective: Colombia has an expanded program of immunization of >22 biologics mainly for younger than 6 years old. We aimed to estimate vaccination coverage in children under 6 years old in San Jacinto (Bolivar), in a post-conflict and COVID-19 pandemic scenario. Methods: We conducted a cross-sectional survey from October to November of 2021, in a Caribbean municipality of Colombia (24,910 population) mostly affected by the armed conflict. A two-stage cluster sampling was used with a precision of 5.5% and a design effect of 2, considering a non-response rate of 20%. We collected data on immunization record cards and other basic sociodemographic information from surveys of caregivers of children. Absolute and timely-vaccine coverages adjusted by age were estimated. Data analysis was performed in Stata 13. Results: Out of 187 surveyed children, 159 (85.3%) had vaccination card. BCG (tuberculosis) vaccine had the greater coverage (99,3%), followed by Hb, pentavalent, and polio (>98%). All biologics showed absolute coverages greater than 90%, except for yellow fever (82.6%) and 5-year boosters (70% for MMR [measles, mumps, rubella] booster and 73% for polio and DPT booster). Age-appropriate timely vaccination coverages were lower than absolutes for all biologics. BCG and hepatitis B had coverages of 97% and initial doses of pentavalent, pneumococcal, polio, MMR, and first and second doses of rotavirus reported coverages greater than 91%. Second and third or booster dosages of pentavalent, polio, pneumococcal and booster of DPT, polio, and MMR had coverages between 70-80%. Lowest timely vaccination coverage were yellow fever (2.3%) and influenza (42.8% for first and 26.5% for second dosage). Conclusion: Although most vaccination coverages were greater than 90%, probably the mobility restrictions due to the pandemic severely impacted the timing of vaccination. Other plausible reasons are the timely flow of vaccines (opportunity in administration and vaccine shortages).
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INTRODUCTION AND OBJECTIVE: Patients with non-muscleinvasive bladder cancer (NMIBC) that recurs after treatment with intravesical Bacillus Calmette-Guerin (BCG) must weigh the risk of progression of bladder cancer and loss of a window of potential cure with medical therapy against the risk of morbidity and loss of quality of life (QOL) with radical cystectomy. The CISTO Study (NCT03933826) is a pragmatic, prospective observational cohort study comparing medical therapy (i.e., intravesical therapy or systemic immunotherapy) with radical cystectomy for recurrent highrisk NMIBC. Here we report on the design and progress of the CISTO Study. METHODS: 900 patients with recurrent high-risk NMIBC that has failed first-line BCG and who have chosen to undergo standard of care treatment will be enrolled. Patient stakeholders helped determine the primary outcome: 12-month patient-reported QOL using the EORTC QLQ-C30. Secondary outcomes include urinary and sexual function, decisional regret, financial distress, healthcare utilization, return to work/normal activities, progression, and recurrence-free, metastasis-free, and overall survival. Participants will be followed for up to 3 years. RESULTS: Enrollment is active at 32 sites across the US, including 23 university-based centers and 9 community sites. As of November 1, 2021, 173 participants have been enrolled, 104 of whom chose medical therapy and 69 of whom chose radical cystectomy. The completion rate for the primary outcome of QOL at 12 months is 94% (15 out of 16 participants to date). The inclusion of electronic consent and collection of PROs allowed recruitment and follow-up to continue remotely during the COVID-19 pandemic. Significant pandemic-related challenges have included slow study start-up at sites, staffing, periods of suspension, and delays in patients obtaining care. Strategies to address these challenges include improved methods for onboarding and training sites, all-site communication, confirming study eligibility, ing EHR data, and remote monitoring while adhering to the highest study standards. CONCLUSIONS: The CISTO Study will compare patient reported outcomes for those undergoing medical therapy with radical cystectomy for recurrent high-risk NMIBC. The CISTO Study has the potential to fill critical evidence gaps and provide for personalized, patient-centered care.
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INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic has impacted various clinical and research processes in urologic care. As part of a pragmatic clinical trial in bladder cancer, we collected information regarding the impact of COVID-19 at participating sites, which provides insight into how the pandemic has imposed constraints on clinical bladder cancer care and research. METHODS: Starting in May 2020, we distributed a monthly survey to sites participating in CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer, NCT0393382). The survey included questions about interruptions in routine clinical bladder cancer care, specifically assessing elective surgery restrictions, impact on radical cystectomy, TURBT, office cystoscopies, intravesical therapy, and intravesical bacillus Calmette- Guerin (BCG) supply. We report survey responses for sites that responded to > 50% of the monthly surveys from May 2020 to October 2021. RESULTS: From May 2020 through October 2021, 21 sites (66%) had > 50% monthly response rate. The time periods of greatest limitations on bladder cancer procedures (Figure 1) were May-July 2020, Dec-Jan 2020/2021, and Sept-Oct 2021, corresponding to the peak waves of COVID-19 infections. Elective surgery was most affected, with limitations or holds in those time periods at up to 76%, 38%, and 28% of CISTO sites, respectively. Most of the restrictions involved surgeries that required inpatient stays, potential intensive care unit admission, and staffing shortages. 9 sites (28%) experienced transient BCG shortages during the survey period. CONCLUSIONS: Clinical activity was most limited during the initial COVID-19 surge in Spring/Summer 2020. Despite higher COVID- 19 infection rates in subsequent waves, bladder cancer clinical activity has been maintained at CISTO sites throughout the COVID pandemic. Periodic BCG shortages continue to affect bladder cancer care across the US. (Figure Presented).
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The purpose of this research is to provide evidence-based natural therapies and foods that will enhance the immune system to fight the virus SARS CoV-2 and cancer. Minority populations that include Black African Americans and Hispanics are experiencing higher mortality rates due to both socioeconomic and lifestyle factors in the US and globally. Successful lessons learned from controlling previous 1918 pandemic flu will be discussed. Hypotheses: We hypothesize that targeting lifestyle factors such as diet, exercise, and hydrothermal therapy that enhance the immune system can effectively control and reduce the risk to COVID-19 disease and cancer simultaneously. The target cells for the SARS CoV-2 virus contain the ACE2 and TMPRSS2 receptors which serve as portals of entry. They are expressed throughout the body including the nose, lungs, heart, bladder, pancreas, kidneys and brain found on the epithelial and vascular tissue cells of these organs. Covid-19 affects multiple organs in the body and disrupts the innate immune system, especially the natural killer cells, monocytes, and neutrophils. Studies have shown that countries where BCG was used have less than 10% of COVID-19 cases and countries that do not use the BCG vaccine such as the US and Italy had high cases. It was also seen that people who had higher natural killer cell activity had 100% survival rates. Enhancing the innate immune system through natural therapies has shown to enhance immune cells to fight COVID-19 as well as cancer and destroy it. Methodology: Our research is exploratory and is based on recently published literature on COVID-19 diseases. The following databases were searched: CINAHL, Web of Science, PubMed, EBSCOHost, Google Scholar, Academic Search Complete, AccessMedicine, MedlinePlus, Nutrition Care Manuel, JSTOR and Publons. Results: During the Spanish flu pandemic death rates of those who received the best medical care was 6.7% compared with those who received hydrotherapy at 1.34%. Hydrotherapy will increase the body temperature and stimulate the activity of the immune cells, which can kill the viruses. Increasing the body temperature to 39.5 degrees centigrade was shown to kill the virus. Following the hot water bath with cold treatment was shown to be even more effective. Many foods have been found to enhance the immune system and to fight the flu virus. Foods such as blueberries, garlic, and probiotics were shown to improve natural killer activity. Vitamin C, Vitamin D, Zinc, and selenium play a role in immunity. Foods rich in antioxidants such as kale, blueberries, red bell peppers, and all citrus fruits also help enhance the immune system. During the 1918 flu pandemic that received hydrotherapy and other natural remedies, out of the 120 students and staff exposed, there were 90 patients, none very sick, and there were no deaths. Natural remedies used in the Spanish flu pandemic and should be instituted to help enhance immunity and lessen the deadly impact of COVID-19 cancer patients.
ABSTRACT
A national epidemiological research project was carried out to define the dynamics affecting the epidemiology of bovine tuberculosis (bTB) infection in Turkey and to identify the risk factors. Official veterinarian (OV) and breeder original questionnaires were produced separately as part of this study to collect thorough data regarding the disease from the field. The number of questionnaires that needed to be filled out was decided by 95% confidence interval (CI) and 5% margin of error. The findings of 371 OV and 317 breeder questionnaires completed online across the country were analyzed. In addition, 28 outbreaks determined by random method were visited. To observe regional differences and field conditions, the opinions of OVs who monitored the disease and breeders were compiled. It was observed that the data obtained from both questionnaires was largely compatible. The main factors in the epidemiology of bTB infection were found to be effective fight, development of state policy, providing adequate financing, animal purchase, ear tagging and records, animal traders, animal markets, animal movements, conditional slaughtering, slaughterhouses, postmortem inspection, premise conditions, socio-economic impact, evaluation of raw milk, disease-free premises, compensation payments, and quarantine processes.