Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

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.

5th International Conference on Tropical Medicine and Infectious Diseases 2022 (ICTMID 2022), Ipoh, Malaysia, 23-25 August 2022

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.

Corrigendum: The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections.

[This corrects the article DOI: 10.3389/fimmu.2023.980711.].

Coronavirus infection and organizational changes in the clinical process in patients with non-muscle-invasive bladder carcinoma.

The spread of the aggressive disease caused by the novel respiratory syndrome coronavirus-2 (SARS-CoV-2) has had an impact not only on the health and psyche of people, but also on the state of health systems in different countries, by complicating the treatment and diagnostic process. These changes have affected patients with cancers to a greater extent. The diagnosis, treatment, and follow-up of patients are of particular scientific and practical interest when working in conditions of special anti-epidemic control. Objective. To assess the possibility of reducing the frequency of hospitalization of patients with non-muscle-invasive bladder carcinoma (NMIBC) during the Covid-19 period. Subjects and methods. Sixty-four patients with urinary tract malignancy, including 19 (29.7%) patients with low-and high-risk re-current NMIBC, were followed up in two clinics (Saint Petersburg, Russia) in March to October 2020. All the patients were oper-ated on;the patients at high risk for recurrence received a cycle of adjuvant BCG therapy. Methods for cytological examination of urine sediment and the biomarkers UBC and Cyfra 21-1 were used for special laboratory diagnosis;the server stations of both clinics were applied for telehealth consultations (TCs). Results. TCs were used to reduce hospitalization rates: after TCs, all the patients reported a reduction in transport costs and recovery time after hospitalization. TCs could protect the followed-up patients against COVID-19 infection, by observing the rules of clinical examination, and achieve maximum individualization of treatment. The authors refused to perform diagnostic operations for low-risk NMIBC and to use laboratory tests using urinary biomarkers. At the place of their residence, outpatients underwent urinalysis for several indicators, transmitting the result to the clinic's servers or through a monitoring system. Inpatient treatment was used only in cases of gross hematuria or after recording abnormal laboratory test results. Control cystoscopy detected no re-current tumor. Conclusion. During the spread of COVID-19, the periods of endoscopic examinations and control diagnostic operations can be post-poned, by replacing face-to-face consultations with TC monitoring. Outpatient laboratory and radiation examinations are indicat-ed in patients with new-onset gross hematuria or after combination treatment. Repeated operations, including diagnostic ones, should be performed in the case of multiple NMIBCs or after incomplete excision of the primary tumor.Copyright © 2021.

NF-Heart: A Near-field Non-contact Continuous User Authentication System via Ballistocardiogram

The increasingly remote workforce resulting from the global coronavirus pandemic has caused unprecedented cybersecurity concerns to organizations. Considerable evidence has shown that one-pass authentication fails to meet security needs when the workforce work from home. The recent advent of continuous authentication (CA) has shown the potential to solve this predicament. In this paper, we propose NF-Heart, a physiological-based CA system utilizing a ballistocardiogram (BCG). The key insight is that the BCG measures the body's micro-movements produced by the recoil force of the body in reaction to the cardiac ejection of blood, and we can infer cardiac biometrics from BCG signals. To measure BCG, we deploy a lightweight accelerometer on an office chair, turning the common chair into a smart continuous identity "scanner". We design multiple stages of signal processing to decompose and transform the distorted BCG signals so that the effects of motion artifacts and dynamic variations are eliminated. User-specific fiducial features are then extracted from the processed BCG signals for authentication. We conduct comprehensive experiments on 105 subjects in terms of verification accuracy, security, robustness, and long-term availability. The results demonstrate that NF-Heart achieves a mean balanced accuracy of 96.45% and a median equal error rate of 3.83% for CA. The proposed signal processing pipeline is effective in addressing various practical disturbances.

Efficiency and input congestion of major marine transport companies in the world

The marine transport companies have been experiencing intense competition with the supply increasing faster than the demand, making most of them face input congestion. This paper applies the input congestion data envelopment analysis (DEA) model proposed by Tone and Sahoo (2004) to compute efficiency scores and input congestions of 159 major marine transport companies in the world during 2010-2019. The inputs include em-ployees, total assets, and capital whereas the output is net sales. The base year for monetary values is 2010. It is found that the annual ratios of input-congested marine companies are between 20.9% and 65.7%, indicating that input congestion is not an unusual phenomenon among these companies. This paper also applies a BCG-like analysis to consider inefficiency and input congestion at the same time. The Mann-Whitney U test shows that most of the marine transport companies in Asia, Europe, and the Americas face both inefficiency and input congestion problems during the data period. This analysis is able to provide the implications for shipping companies to conduct more precise and efficient resource allocation and coordination in the post Covid-19 era.

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination

The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial effects of BCG are stronger amongst children who develop a BCG scar. Within an international randomised trial (‘BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers';BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination in healthcare workers. Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2–0.9), BCG revaccination (OR 1.7, 95%CI 1.3–2.0), female sex (OR 2.0, 95%CI 1.7–2.4), older age (OR 0.4, 95%CI 0.4–0.5) and study country (Brazil OR 1.6, 95%CI 1.3–2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (2242/2341, 96%) did not regret having the vaccine due to scar development. Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.

This work was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number P50NS108676 and Moore Foundation

The increasingly remote workforce resulting from the global coronavirus pandemic has caused unprecedented cybersecurity concerns to organizations. Considerable evidence has shown that one-pass authentication fails to meet security needs when the workforce work from home. The recent advent of continuous authentication (CA) has shown the potential to solve this predicament. In this paper, we propose NF-Heart, a physiological-based CA system utilizing a ballistocardiogram (BCG). The key insight is that the BCG measures the body's micro-movements produced by the recoil force of the body in reaction to the cardiac ejection of blood, and we can infer cardiac biometrics from BCG signals. To measure BCG, we deploy a lightweight accelerometer on an office chair, turning the common chair into a smart continuous identity "scanner". We design multiple stages of signal processing to decompose and transform the distorted BCG signals so that the effects of motion artifacts and dynamic variations are eliminated. User-specific fiducial features are then extracted from the processed BCG signals for authentication. We conduct comprehensive experiments on 105 subjects in terms of verification accuracy, security, robustness, and long-term availability. The results demonstrate that NF-Heart achieves a mean balanced accuracy of 96.45% and a median equal error rate of 3.83% for CA. The proposed signal processing pipeline is effective in addressing various practical disturbances. © 2023 ACM.

Reactivation of BCG vaccination scars after mRNA -SARS- CoV2 -vaccine and SARS-CoV2 infection: Two case reports

Case report Purpose: To report two cases of reactivation of BCG vaccination scars, the first after mRNA -SARS- CoV2 -vaccine and the second after SARS-CoV2 infection. Case 1: A 33 year-old woman, a nursing assistant, was referred with erythema and swelling of her BCG vaccination scar 24 hours after receiving her second dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) and, 10 months later, after receiving her third dose with the mRNA-1273 (Moderna) vaccine. Case 2: A 60 year-old woman, a medical doctor, was referred with erythema and swelling of her two BCG vaccination scars (one administered at birth and the second one at the age of 10), 12 days after testing positive for SARS-CoV2 associated with homolateral supraclavicular and axillary adenopathy's . In both cases, total IgE values and D-dimer were normal and symptoms resolved spontaneously within 7 days, without further treatment. Discussion(s): Bacillus Calmette-Guerin (BCG) local scar inflammatory reactions have been described with Kawasaki disease in children, with other viral infections such as measles and human herpesvirus type 6 (HHV6) infection and following influenza vaccination. The relationship between the BCG vaccine and SARS-CoV2 remains unclear. Even in mid-2020 and during the first years of the pandemic, it was proposed that the BCG vaccine could be protective against SARS-CoV2 infection. Several studies were launched to evaluate this hypothesis, with no conclusive results in this regard. Along the last two years, some cases of reactivation of BCG vaccination scars have been reported after vaccination with mRNA -SARS- CoV2 -vaccines. To our knowledge, this is the first reported case of reactivation of BCG vaccination scars after SARS-CoV2 infection. Conclusion(s): We report the first case of BCG vaccine scar inflammation as a local reaction following SARS-CoV2 infection. The reactivation of BCG vaccine scar after receiving mRNA vaccines and after SARS-CoV2 infection might have been caused by an immunological reaction due to a cross reactivity phenomenon between BCG and SARS-CoV2. The immunological and clinical implication of this reaction needs to be further studied. Clinicians need to be aware of this local reaction to SARS-CoV2 vaccines and infection. (Figure Presented).

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination.

The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial off-target effects of BCG are proposed to be stronger amongst children who develop a BCG scar. Within an international randomised trial ('BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers'; BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination . Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2-0.9), BCG revaccination (OR 1.7, 95%CI 1.3-2.0), female sex (OR 2.0, 95%CI 1.7-2.4), older age (OR 0.4, 95%CI 0.4-0.5) and study country (Brazil OR 1.6, 95%CI 1.3-2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (96%) did not regret having the vaccine. Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.

Interruption of BCG Therapy for NMIBC During COVID-19 Crisis, Dilemma in Its Continuation: a Review of Available Evidence and Suggested Management Strategies.

The COVID-19 disease, caused by SARS-CoV-2 virus, has been one of the worst pandemics ever to hit the human mankind. Undoubtedly the start of the second wave of COVID-19 has literally ripped apart the hearts of millions of people. Cancer patients have been left of the beaten track to their fate, with no access to treatments. Intravesical BCG instillation is the standard of care for patients with non-muscle invasive bladder cancer (NMIBC). Several patients were in the middle of their treatment regimen when this pandemic struck. As slowly the word is recuperating from concussion effect of this pandemic and routine health services are being restored, uro-oncologist will face a unique scenario with respect to intravesical BCG therapy i.e., whether to restart the course of BCG therapy or to continue course from where it was interrupted. There are no studies in literature to directly answer this peculiar question and to resolve this dilemma. So, we in this review article propose to explore the literature for the most appropriate therapeutic regimen for these patients with interruption of intravesical BCG therapy. We plan to divide the patients with interruption to BCG therapy into the following three groups:Group 1: Patients who had interruption during the induction period.Group 2: Patients who completed the induction course but maintenance course could not be started.Group 3: Patients who had interruption during maintenance phase of BCG therapy. We will compile the recent recommendations by NCCN, AUA, and EAU for the administration of intravesical BCG in non-muscle invasive bladder cancer. We herein want to review the literature to propose the most appropriate strategy, its safety profile for these subsets of patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01742-8.

The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection.

Background: The cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection. Methods: Sixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models. Results: Data suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively. Conclusion: This pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens.

Previous BCG vaccination is associated with less severe clinical progression of COVID-19.

BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

An Observational Study on the Early Stages of the Covid-19 Pandemic in Pakistan

Bachground: The coronavirus disease 2019 (COVID-19) pandemic, which started on February 26, 2020 in city of karachi, spread quickly throughout Pakistan. Material(s) and Method(s): The design of this study was a observational study design and this study was conducted at king Edward medical University Lahore. More than 6,200 persons were afflicted by the illness in the first seven weeks, and there were more than 111 documented fatalities. Many problems arise if we contrast the COVID-19 tragedies in Pakistan with those in nations like China, Iran, and the European Union. The geography of the nation, poverty, poor literacy rates, environmental circumstances, sanitary conditions, and dietary habits are only a few of the difficulties we face in containing this epidemic. Although there are terrible circumstances in each of these areas, Pakistan's COVID-19 epidemic was slower than that of other developing nations. Result(s): The impact of COVID-19 appears to be lessened by Pakistan's humid hot temperature, early reaction to COVID-19, population immune system, BCG vaccination, and the proportion of young individuals. In this essay, we explore the COVID-19 pandemic outbreak in China, Iran, and Pakistan and present its day-to-day changes. We outline the COVID-19 structure and how it compares to SARS-COV and SARS-COV2. The use of Remdesivir (an adenosine analogue used against RNA viruses), Chloroquine (a widely used anti-malarial drug), convalescent plasma, neutralising antibodies targeting the ACE-2 receptor, and an ACE-2-like molecule that might bind to the S protein of the coronavirus are also covered in terms of treatment options and their drawbacks. Also covered are the effects of COVID-19 on Pakistan's economy and government relief measures. Conclusion(s): In conclusion, it may be said that the support systems in place may not be sufficient to stop the spread of the virus. Even with the meagre assistance offered, it is weaker for rural places where the virus's effects may be severe than in the nation's cities. Further research is required as the epidemic develops to better understand governmental efforts to contain the virus and its effects across the nation.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Impact of BCG Vaccine Against the Pandemic of Corona (COVID-19): A Review

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.

Major Drugs Used in COVID-19 Treatment: Molecular Mechanisms, Vali-dation and Current Progress in Trials

Background: Currently, the present world is facing a new deadly challenge from a pandemic disease called COVID-19, which is caused by a coronavirus named SARS-CoV-2. To date, no drug or vaccine can treat COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This review article discussed and compared those drugs which are running ahead in COVID-19 treatments. Method(s): We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press releases of WHO, NIH and FDA for articles related to COVID-19 and reviewed them. Result(s): Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin, corticosteroids and interferons have been found effective to some extent, and partially approved by FDA and WHO to treat COVID-19 at different levels. However, some of these drugs have been disapproved later, although clinical trials are going on. In parallel, plasma therapy has been found fruitful to some extent too, and a number of vaccine trials are going on. Conclusion(s): This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how drugs could act on this virus with the comparative discussion on progress and drawbacks of major drugs used till date, which might be beneficial for choosing therapies against COVID-19 in different countries.Copyright © 2022 Bentham Science Publishers.

Intravesical administration of durvalumab to patients with high risk non muscle invasive bladder cancer after BCG failure. A phase II trial by the Hellenic GU Cancer Group

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.

Online Search Patterns about Vaccination: A National Study

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).

Reactivation of Tuberculosis and COVID-19 in Pediatric Patients

Objective Mycobacterium tuberculosis is an immobile aerobic bacillus that causes tuberculosis (TB) disease. We aimed to evaluate the association between coronavirus disease 2019 (COVID-19), COVID-19-related drugs, TB reactivation, and TB incidence during the pandemic. Methods Eight patients who were diagnosed as having TB in Meram Medical Faculty, Necmettin Erbakan University between March 1, 2020, and December 31, 2021, at the beginning of the pandemic, were enrolled in this study. The presence of COVID-19 infection was confirmed using COVID-19 antibody tests and the patients' COVID-19 history. We evaluated the demographic data, laboratory findings, imaging tests, and pathology results of all patients. Results We checked all our patients with TB using COVID-19 antibodies (immunoglobulin [Ig]G + IgM) or polymerase chain reaction. Seven of the eight patients were female (87.5%). The median age was 16 years. Family screening of all patients was negative, and they had bacillus Calmette-Guerin vaccine scars. Two patients had chronic diseases. One was diagnosed as having primary ciliary dyskinesia in our department (patient no. 8) and the second was under follow-up by the rheumatology department with a diagnosis of juvenile idiopathic rheumatoid arthritis. Conclusion There has been an increase in the incidence of TB in children, especially in adolescents, during the pandemic period. This may be due to the pathogenic structure of the COVID-19 virus with an unknown mechanism. In addition, lifestyle changes and changes in health care policies during the pandemic may have caused this. Further research should be performed on this topic.Copyright © 2023 Authors. All rights reserved.