Search

Introduction: Phlyctenular keratoconjunctivitis is an inflammatory condition arising from a type IV hypersensitivity reaction, presenting with inflamed nodules on the conjunctiva and cornea. Scleritis is a severe ocular inflammation linked to systemic diseases, potentially vision threatening, and involving immune responses similar to phlyctenular keratoconjunctivitis. This case report discusses a patient with a history of herpes simplex virus (HSV)-2 infection who primarily developed phlyctenular conjunctivitis and later progressed to nodular scleritis., Case Presentation: A 66-year-old female presented with pain, redness, and a foreign body sensation in her left eye for 2 days. Initial treatment for epidemic keratoconjunctivitis with tobramycin-dexamethasone improved her symptoms. However, 3 weeks later, she developed a conjunctival phlyctenule. Diagnostic tests, including blood work and conjunctival swabs, were conducted. While most tests were negative, HSV-2 IgG was positive. The patient failed topical corticosteroid monotherapy; however, she responded to oral valacyclovir. Follow-up examinations showed significant improvement, with resolution of the conjunctival phlyctenule and nodular scleritis, and her best-corrected visual acuity returned to 20/20., Conclusion: This case highlights the importance of considering HSV-2 in atypical presentations of phlyctenular conjunctivitis and scleritis. The patient's response to antiviral therapy underscores the potential role of HSV-2 in such ocular inflammation. Thorough infectious workups and alternative treatment approaches are crucial in managing unconventional cases. Experimental treatments based on laboratory findings can be valuable for patients preferring conservative management, emphasizing the need for close follow-up and personalized care in ocular inflammatory diseases., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: To demonstrate the efficacy and safety of intravenous golimumab infusion in treating juvenile idiopathic arthritis-associated anterior uveitis., Methods: This study was a retrospective observation case series. Electronic records of patients diagnosed with juvenile idiopathic arthritis-associated anterior uveitis who received intravenous golimumab infusion were examined., Results: A total of 24 eyes of 13 patients were included in this study. During 12 months before starting intravenous golimumab, the median grade of anterior chamber reaction was 1 (range: 0.5-3), and the median number of flare-ups was 1 (1-3). During 12 months following the start of intravenous golimumab, the median grade of anterior chamber reaction was 0 (range: 0-1), and the median number of flare-ups was 0 (range: 0-1). Before starting intravenous golimumab, the average number of immunomodulatory agents was 2.6 ± 1.0 with a range of 2 to 5. The average age of patients at the time of starting intravenous golimumab was 13.69 ± 5.23 years (range between 5 and 22). A total of 11 (84.6%) patients responded to intravenous golimumab. The medication was discontinued in one patient due to ineffectiveness and in another patient due to the development of psoriasis as an adverse effect. Cystoid macular edema was present in six eyes of three patients which resolved in all six eyes after starting intravenous golimumab., Conclusion: Intravenous golimumab proves to be efficacious and safe for inducing and sustaining remission in JIA and JIA-associated uveitis. Nonetheless, further robust studies with larger sample sizes are needed to substantiate our findings.

Platelets play a critical role in blood clotting and the development of arterial blockages. Antiplatelet therapy is vital for preventing recurring events in conditions like coronary artery disease and strokes. However, there is a lack of comprehensive guidelines for using antiplatelet agents in elective neurosurgery. Continuing therapy during surgery poses a bleeding risk, while discontinuing it before surgery increases the risk of thrombosis. Discontinuation is recommended in neurosurgical settings but carries an elevated risk of ischemic events. Conversely, maintaining antithrombotic therapy may increase bleeding and the need for transfusions, leading to a poor prognosis. Artificial intelligence (AI) holds promise in making difficult decisions regarding antiplatelet therapy. This paper discusses current clinical guidelines and supported regimens for antiplatelet therapy in neurosurgery. It also explores methodologies like P2Y12 reaction units (PRU) monitoring and thromboelastography (TEG) mapping for monitoring the use of antiplatelet regimens as well as their limitations. The paper explores the potential of AI to overcome such limitations associated with PRU monitoring and TEG mapping. It highlights various studies in the field of cardiovascular and neuroendovascular surgery which use AI prediction models to forecast adverse outcomes such as ischemia and bleeding, offering assistance in decision-making for antiplatelet therapy. In addition, the use of AI to improve patient adherence to antiplatelet regimens is also considered. Overall, this research aims to provide insights into the use of antiplatelet therapy and the role of AI in optimizing treatment plans in neurosurgical settings.

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000)., Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch., Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes., Conclusions: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies., Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210])., Competing Interests: MC, ZD, DI, AA, MA, MC, KC, JC, BH, KK, MM, CP, SV, HW, AA, AA, SA, JA, PA, BB, AB, JC, Kd, AD, Jd, PD, CD, SD, ME, LF, DG, GG, MG, AG, CG, MG, RH, RH, YH, JH, OI, JI, JJ, CJ, DJ, JJ, GK, AK, AK, AK, SK, RK, RK, AL, ML, RL, SL, GM, TM, CM, AM, GN, SN, SN, TN, SN, EN, IO, SP, AP, FQ, FQ, SR, SR, DR, PR, RR, TR, JR, SS, SS, KS, MS, JS, JS, VS, JS, RS, SS, MS, AS, AS, KT, DT, AT, MT, MT, RT, NT, ST, KV, MV, BV, FW, JW, GD, SA, JK, DA, SB, KH No competing interests declared, NF NAF chairs the Wellcome Surveillance and Epidemiology of Drug Resistant Infections (SEDRIC) group, which has a focus on antimicrobial resistance. This could be perceived as relevant although not a direct conflict, IB IB has consulted to BlueDot and the NHL Players' Association, AP AJP is chair of the UK Department of Health and Social Care's (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) but does not take part in the JCVI COVID-19 committee. He was a member of WHO SAGE until 2022. AJPs employer, Oxford University has entered into a partnership with AstraZeneca for development of a COVID-19 vaccine. AJP has provided advice to Shionogi & Co., Ltd on development of a COVID19 vaccine, (© 2023, Carey et al.)

Porous liquids are an emerging class of microporous materials where intrinsic, stable porosity is imbued in a liquid material. Many porous liquids are prepared by dispersing porous solids in bulky solvents; these can be contrasted by the method of dissolving microporous molecules. We highlight the latter "Type II" porous liquids-which are stable thermodynamic solutions with demonstrable colligative properties. This feature significantly impacts the ultimate utility of the liquid for various end-use applications. We also describe a facile method for determining if a Type II porous liquid candidate is "porous" based on assessing the partial molar volume of the porous host molecule dissolved in the solvent by measuring the densities of candidate solutions. Conventional CO 2 isotherms confirm the porosity of the porous liquids and corroborate the facile density method., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objective: To assess the proportion of children, symptomatic for urinary tract infection (UTI), with urine culture showing single bacterial species >104 CFU/mL, and to compare patient and disease characteristics between children having low counts (from >104-105 CFU/mL) and those with counts >105 CFU/mL., Methods: Prospective observational study, enrolling symptomatic children aged 1 month to 12 years. Mid-stream clean-void or catheter collected urine were cultured. Children with single species >104 CFU/mL were scheduled for imaging studies, following age criteria of Indian Society of Pediatric Nephrology guidelines. The main outcome was proportion with single bacterial species >104 CFU/mL in urine culture., Results: Of 216 children (132 males) with median (IQR) age of 24 (12, 48) months, 38 (17.6%) showed single species growth >104 CFU/mL. Of these, 29 (13.4%) were diagnosed as UTI at cutoff >105 CFU/mL, and an additional 9 (4.2%) were found to have 'probable low-count UTI' (from >104 to 105 CFU/mL). One child in the latter group had bilateral hydroureteronephrosis, vesico-ureteral reflux and renal scarring. There was largely no difference in parameters between children with low counts and those with counts >105 CFU/mL., Conclusions: An additional proportion of symptomatic children with probable urinary tract infection and possible underlying urological abnormalities may be identified by lowering bacterial colony count cutoff to >104 CFU/mL, in clean-voided and catheter-based urine samples.

Paratyphoid fever caused by S. Paratyphi A is endemic in parts of South Asia and Southeast Asia. The proportion of enteric fever cases caused by S. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study "Surveillance of Enteric Fever in India (SEFI)." In the study period (2017-2020), S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis highlights that the genome degradation events and gene acquisitions or losses are key molecular events in the evolution of new S. Paratyphi A lineages/sub-lineages. A total of 10 hypothetically disrupted coding sequences (HDCS) or pseudogenes-forming mutations possibly associated with the emergence of lineages were identified. The pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We have identified six characteristic missense mutations associated with lipopolysaccharide (LPS) biosynthesis genes of S. Paratyphi A, however, these mutations confer only a low structural impact and possibly have minimal impact on vaccine effectiveness. Since S. Paratyphi A is human-restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and monitoring by means of genomic surveillance would be constantly needed to avoid S. Paratyphi A serovar becoming a public health threat similar to the S. Typhi of today., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jacob et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: India is the highest TB burden country in the world with almost 27 lakh cases reported in 2019. Pediatric tuberculosis in India accounts for almost 31% of global TB burden. Despite such high mortality and morbidity in children, diagnosis of pulmonary TB in children still remains very challenging., Material and Methods: This cross-sectional study was conducted in a tertiary care hospital in Delhi, India. Children between 1 and 12 months with clinical suspicion of pulmonary tuberculosis who had not previously taken ATT were included. Early morning gastric aspirate samples were collected after overnight fasting, on two days. Both days sputum sample were subjected to sputum smear microscopy and one of the two samples was subjected to line probe assay (LPA), cartridge based nucleic acid amplification (CBNAAT) and mycobacterium growth in tube (MGIT-960)., Results: 84 children with pulmonary tuberculosis were enrolled. The most common presenting complaint was fever seen in 83 patients (98.8%). Only 17 (20.24%) were sputum smear positive by Ziehl- Neelsen (ZN) staining. LPA was positive in 47 (55.95%) samples and among these positive samples both INH and RIF resistance was detected in 2 (4.26%) samples. CBNAAT was positive in 53 patients (63%). Growth in liquid culture media (MGIT 960) was observed in 44 (52.38%) samples. Among 17 smear positive samples, LPA was detected in 14 (82.35%) samples and among 67 smear negative sample LPA was detected in 33 (49.25%) samples. LPA had 63.46% sensitivity, 100% specificity in detecting mycobacterium tuberculosis., Discussion: WHO's recommendation for using LPAs has been limited to culture isolates or smear-positive sputum specimens. New data has since been generated on the use of LPAs as newer versions of LPA have been developed over past few years. Previous studies conducted using LPA version 1.0 reported much lower detection rate of mycobacterium tuberculosis in smear negative specimens. With the availability of newer versions such as Hain GenoTypeMTBDRplusversion 2 and Nipro NTM + MDRTB detection kit 2, the diagnostic utility of LPA may be enhanced., Competing Interests: Conflict of interest The authors have none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Mucormycosis is a devastating opportunistic fungal infection resulting in significant mortality, especially in pediatric patients with predisposing risk factors., Materials & Methods: Biopsies and surgical specimens reported and proven as Mucormycosis in children under 12 years of age were retrieved from the records for three years (January 2018 to January 2021). Complete data, predisposing factors, treatment, and clinical outcome were recorded., Results: 15 cases were identified, ranging from 9 days to 5 years. The male-female ratio was 3:1; three children were preterm. Fourteen children were diagnosed with gastrointestinal Mucormycosis (14/15), and one had palatal and sinusoidal involvement. Abdominal pain with distention was the most typical complaint. On microscopy, biopsies and surgical specimens showed extensive liquefactive necrosis with broad aseptate fungal hyphae. An intraoperative diagnosis was rendered in two cases. All neonates underwent exploratory laparotomy with surgical debridement and were administered Liposomal Amphotericin B. However, only two neonates survived out of the fifteen cases, one with disease limited to the appendix and pouch colon. The others succumbed to the disease despite antifungal therapy and surgical debridement. Thus, the overall mortality in the current study was calculated to be 86%, with neonatal mortality of 75%., Conclusion: Gastrointestinal involvement is more common in neonates and infants with a male preponderance. The diagnosis relies on direct microscopy, histopathology, and fungal culture. Intraoperative tissue may be sent in all suspected cases for direct microscopic examination for rapid diagnosis and treatment., Competing Interests: None., (IJCEP Copyright © 2022.)

A 23-month-old girl born at 23 weeks' gestational age with a birth weight of 453 g and retinopathy of prematurity (ROP) stage 4A in 360° and plus disease in both eyes was treated in another institution with laser; her treatment was complicated with two cardiac arrests during the procedure. The patient was referred and treated at 31 weeks with repeated intravitreal bevacizumab injection in both eyes secondary to progressive ROP. Treatment with multiple anti-vascular endothelial growth factor (VEGF) therapy as monotherapy led to the resolution of a retinal detachment and full vascularization of the retina in both eyes. To the best of the authors' knowledge, this is the first description of a patient with stage 4A ROP treated solely with anti-VEGF after failed laser treatment that led to complete resolution of a retinal detachment without surgical intervention. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53:159-163.] .

Background: Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days., Methods: This is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is "definite or probable relapse" within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O'Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock's to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia., Discussion: This trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections., Trial Registration: Clinical Trials Registry India CTRI/2017/09/009743 . Registered on 13 September 2017., (© 2021. The Author(s).)

Background: There is a lack of evident data to explain the true scenario of age-specific enteric fever in India. The current study aimed to evaluate the burden and disease pattern of enteric fever among infants in a tertiary care pediatric hospital., Methods: A prospective laboratory-based surveillance was conducted from April 2018 to January 2020 at a children's hospital in North India, under the Surveillance for Enteric Fever in India study. The study included children <1 year of age in whom Salmonella serovar Typhi/Salmonella serovar Paratyphi grew in cultures from blood or sterile body fluid. The key outcome measures included disease spectrum and clinical presentation., Results: Of the 10 737 blood cultures from infants, 26 were positive for S. Typhi or S. Paratyphi. The majority of cases occurred in infants aged 6-12 months, with the youngest being 1 month old. Fever with abdominal pain and diarrhea were the common symptoms, with 46% of infants requiring inpatient care. All of the isolates were susceptible to ceftriaxone. Third-generation cephalosporins were used as the first-line therapy for hospitalized infants. The average duration of fever was 8.6 days. The overall case-fatality rate among infants with enteric fever was 7.4%., Conclusions: Enteric fever is a major contributor to disease and death among children. Robust surveillance studies are required to understand the true disease burden., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Lack of robust data on economic burden due to enteric fever in India has made decision making on typhoid vaccination a challenge. Surveillance for Enteric Fever network was established to address gaps in typhoid disease and economic burden., Methods: Patients hospitalized with blood culture-confirmed enteric fever and nontraumatic ileal perforation were identified at 14 hospitals. These sites represent urban referral hospitals (tier 3) and smaller hospitals in urban slums, remote rural, and tribal settings (tier 2). Cost of illness and productivity loss data from onset to 28 days after discharge from hospital were collected using a structured questionnaire. The direct and indirect costs of an illness episode were analyzed by type of setting., Results: In total, 274 patients from tier 2 surveillance, 891 patients from tier 3 surveillance, and 110 ileal perforation patients provided the cost of illness data. The mean direct cost of severe enteric fever was US$119.1 (95% confidence interval [CI], US$85.8-152.4) in tier 2 and US$405.7 (95% CI, 366.9-444.4) in tier 3; 16.9% of patients in tier 3 experienced catastrophic expenditure., Conclusions: The cost of treating enteric fever is considerable and likely to increase with emerging antimicrobial resistance. Equitable preventive strategies are urgently needed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Systematic studies to estimate the disease burden of typhoid and paratyphoid in India are limited. Therefore, a multicenter study on the Surveillance of Enteric Fever in India was carried out to estimate the incidence, clinical presentation, and antimicrobial resistance (AMR) trend. The data presented here represent the national burden of AMR in Salmonella Typhi and Salmonella Paratyphi A., Methods: Antimicrobial susceptibility testing was performed for S. Typhi and S. Paratyphi A (n = 2373) isolates collected prospectively during a 2-year period from November 2017 to January 2020., Results: Of 2373 Salmonella isolates, 2032 (85.6%) were identified as S. Typhi and 341 (14.4%) were S. Paratyphi A. Approximately 2% of S. Typhi were multidrug-resistant (MDR), whereas all 341 (100%) of S. Paratyphi A isolates were sensitive to the first-line antimicrobials. Among 98% of ciprofloxacin nonsusceptible isolates, resistance (minimum inhibitory concentration [MIC] >0.5 µg/mL) was higher in S. Typhi (37%) compared with S. Paratyphi A (20%). Azithromycin susceptibility was 99.9% and 100% with a mean MIC of 4.98 μg/mL for S. Typhi and 7.39 μg/mL for S. Paratyphi A respectively. Ceftriaxone was the only agent that retained 100% susceptibility. Moreover, beta-lactam/beta-lactamase inhibitors showed potent in vitro activity against the study isolates., Conclusions: Data obtained from this systematic surveillance study confirms the declining trend of MDR Salmonella isolates from India. The higher prevalence of ciprofloxacin nonsusceptibility enforces to limit its use and adhere to the judicious usage of azithromycin and ceftriaxone for enteric fever management., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Ileal perforation occurs in about 1% of enteric fevers as a complication, with a case fatality risk (CFR) of 20%-30% in the early 1990s that decreased to 15.4% in 2011 in South East Asia. We report nontraumatic ileal perforations and its associated CFR from a 2-year prospective enteric fever surveillance across India., Methods: The Surveillance for Enteric Fever in India (SEFI) project established a multitiered surveillance system for enteric fever between December 2017 and March 2020. Nontraumatic ileal perforations were surveilled at 8 tertiary care and 6 secondary care hospitals and classified according to etiology., Results: Of the 158 nontraumatic ileal perforation cases identified,126 were consented and enrolled. Enteric fever (34.7%), tuberculosis (19.0%), malignancy (5.8%), and perforation of Meckel diverticulum (4.9%) were the common etiology. In those with enteric fever ileal perforation, the CFR was 7.1%., Conclusions: Enteric fever remains the most common cause of nontraumatic ileal perforation in India, followed by tuberculosis. Better modalities of establishing etiology are required to classify the illness, and frame management guidelines and preventive measures. CFR data are critical for comprehensive disease burden estimation and policymaking., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB are serious threats to global TB control. Molecular tests like GenoType MTBDRplus has revolutionized MDR-TB diagnosis by rapid detection of resistance, leading to early and appropriate management of DR-TB. Information about common mutations imparting resistance to RIF and INH, helps in understanding the disease epidemiology in various regions. The study was conducted to determine the genetic mutation in drug resistant tuberculosis in children less than 12 years with pulmonary or extrapulmonary tuberculosis., Materials/methods: Retrospective analysis was done over a period of 54 months from January 2015 to June 2019 to study the resistance pattern and mutations present in DR-TB in children less than 12 years with suspected pulmonary or extrapulmonary tuberculosis using Hain's GenoType MTBDRplus VER 2.0., Results: Over a period of 54 months, samples from 3461 patients with suspected TB were received for MGIT culture, out of which, 347 were positive for Mycobacterium tuberculosis. 250 of these 347 isolated were tested for drug resistance by Hain's GenoType MTBDRplus VER 2.0.61.1% were sensitive to isoniazid and rifampicin while 15.2% were DR-TB (38 out of 250). Out of these 38, 22 were MDR TB, 13 were isoniazid monoresistant (34.2%) and 3 were rifampicin monoresistant. The most common genotypic resistance for rifampicin was absence of rpoB WT8 band and presence of rpoB MUT 3 band (88%). 84.6% of the INH monoresistant isolates showed high level isoniazid resistant. All these isolates showed presence of katG MUT 1 band. On comparing Hain's GenoType MTBDRplus VER 2.0 with Xpert MTB/Rif Assay, most common mutation for rifampicin resistance at S531L which can be detected by Xpert MTB/Rif Assay (probe E). However, two cases with rifampicin resistance had mutation in codon region 509-513 and 513-519 which could be missed by Xpert MTB/Rif Assay., Conclusions: We cannot solely rely on Xpert MTB/Rif Assay for detection of drug resistance due to the risk of missing the isoniazid monoresistance. GenoType MTBDRplus has revolutionized MDR-TB diagnosis by substantially reducing turn around time and leading to early management of DR-TB cases., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2021 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Significance: This case report highlights the merits of using fine needle aspiration biopsy to obtain gene expression profiling of individual choroidal melanomas when more than one tumor arises in the same eye. It is also the first such case to document laser ablation therapy as the primary treatment., Purpose: This report describes a case of two primary choroidal melanomas with different genetic profiles in the same eye., Case Report: An 80-year-old man presented to the office with a neoplasm of uncertain behavior in the left eye. The patient's visual acuity and IOP in the left eye, respectively, at the time of his first visit to the office were 20/25 and 8 mmHg. A dilated fundus examination revealed that there were two choroidal lesions in the left eye. The macular lesion was classified as type 1A, and the ciliochoroidal lesion was classified as type 1B. The patient underwent a vitrectomy of the left eye, followed by endolaser ablation of the tumors. The patient was also injected with bevacizumab. To date, the patient is free of known metastasis. Most recently, his visual acuity and IOP in the left eye were 20/30 and 14 mmHg, respectively., Conclusions: Although rare, multiple melanomas in the same eye may have differing genetic profiles, which may alter prognosis and management, depending on the class of tumor detected., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Streptococcus pneumoniae is the major cause of childhood pneumonia and related deaths in India. Widespread use of erythromycin for the treatment of pneumonia has led to the emergence of erythromycin resistance. Despite this increase in erythromycin resistance, there are very little data on resistance determinants from India. Hence, we aimed to perform the molecular characterization of erythromycin-resistant invasive pneumococcal isolates in India. In this study, 250 erythromycin-resistant invasive isolates obtained from four Indian hospitals between 2014 and 2019 were included. The isolates were reconfirmed by standard CDC protocols, followed by detection of erm(B), mef(A/E) genes, and screening for mutations in 23S rRNA, ribosomal proteins L4 and L22. Among the 250 erythromycin-resistant isolates, 46% (n = 114) and 35% (n = 87) carried the mef(A/E) gene and erm(B) gene, respectively; both genes were present in 8% (n = 20) of the isolates and 12% (n = 29) of the studied strains did not bear any of them. The major mutations associated with erythromycin resistance in 23S rRNA, such as A2060C, A2061G, and C2613G, were absent. The predominant serotypes were 19F, 14, 23F, 6A, 6B, 19A, and 9V. The major clonal complexes were CC320, followed by CC230 and CC63. The predominant gene was mef(A/E), and most of the serotypes were PCV13 (54%). This study contributes to the baseline understanding of the erythromycin resistance determinants associated with the serotypes and sequence types (ST) of Indian invasive S. pneumoniae., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: India is among the nations reporting substantial healthcare burden linked to pneumococcal infections. Nafithromycin is a novel lactone ketolide antibiotic, which recently entered Phase 3 development in India for the indication of community-acquired bacterial pneumonia (CABP)., Objectives: To assess the in vitro activity of nafithromycin against serotyped invasive and non-invasive Streptococcus pneumoniae isolates, collected from nine medical centres across India., Methods: A total of 534 isolates of S. pneumoniae were collected during 2015-20 and serotyped as per CDC protocol. A subset of erythromycin-non-susceptible S. pneumoniae ( n =  200) was screened for the presence of erm (B) and mef (A/E) genes. A subset of MDR isolates ( n =  54) were also subjected to MLST. The MICs of antibiotics were determined by the reference agar-dilution method (CLSI). Susceptibilities of the comparators were interpreted as per CLSI criteria., Results: Fifty-nine distinct serotypes were identified among the 534 isolates. Among erythromycin-non-susceptible isolates, erm (B) and mef (A/E) genes were found in 49% and 59% strains respectively, while MLST showed clonal diversity. Azithromycin (67.6% non-susceptible) and clindamycin (31.8% non-susceptible) showed limited activity. Penicillin (for non-meningitis) or quinolone non-susceptibility was low (<11% and <6%, respectively). Nafithromycin showed potent activity with MIC 50 and MIC 90 of 0.015-0.03 and 0.06 mg/L, respectively, regardless of the macrolide resistance mechanisms., Conclusions: Indian pneumococcal isolates show poor susceptibilities to macrolides, in concordance with the global trend. Nafithromycin overcomes erm as well as mef -mediated macrolide resistance mechanisms expressed individually or concurrently in S. pneumoniae . This study supports continued clinical development of nafithromycin for pneumococcal infections including CABP., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Bacille Calmette-Guerin (BCG) vaccine is administered worldwide to neonates and considered safe. Serious complications like disseminated BCGosis are extremely rare occurrences (<1 per million vaccinations). A 6 months male was brought to paediatric outpatient department with fever and swelling over the dorsum of the left hand for 5 days. On examination, he was febrile and had hepatosplenomegaly. X-ray of the hand showed lytic lesions in the first and second metacarpals. Provisional clinical diagnosis included Langerhans cell histiocytosis, congenital syphilis, and haematological malignancy. Fine Needle Aspiration Cytology (FNAC) was done from the swelling and showed diffuse sheets of histiocytes with both intracellular and extracellular rod-shaped unstained structures along with inflammatory cells. These ghost images stained positive with ZN stain. A cytological diagnosis of atypical mycobacteria vs leprosy was made. Child was revisited and found to have an active BCG scar. Further investigations showed low serum IgM and positive AFB culture. These bacilli were confirmed by GenoType MTBDR plus test as Mycobacterium bovis. Despite Antitubercular therapy, the patient succumbed to death. This case highlights the variable clinical presentation of BCGosis. Its occurrence may unmask any underlying immunodeficiency. If unfamiliar with the above cytological features and in absence of routinely performed special stains, the cytopathologist may miss these notorious organisms and treat such cases like suppurative lesions. To conclude, an early and definitive diagnosis of BCGosis can be established on FNAC which would ensure timely management and better outcome in this highly lethal entity., (© 2019 Wiley Periodicals, Inc.)

Introduction To evaluate the implementation and dosimetric outcomes of magnetic resonance imaging (MRI) planning for improved target and normal tissue definition for the treatment of prostate cancer with high-dose-rate brachytherapy (HDRBT). Methods From August 2015 to October 2017, 137 unique patients with newly diagnosed localized prostate cancer underwent a total of 174 outpatient brachytherapy procedures using MRI-based treatment planning. Patients receiving brachytherapy as monotherapy underwent two separate procedures while those receiving brachytherapy as a boost after external beam radiation therapy underwent a single procedure. The target volume was defined as the prostate +/- seminal vesicles as clinically appropriate without any additional margin. Pre-treatment dose-volume histogram (DVH) goals to the target were: D90≥95%, V90≥95%, V100≥90%, V150≤30%, V200≤15%. DVH goals to organs-at-risk (OARs): urethra D.01cc ≤115%, bladder D1cc ≤75%, rectum D1cc ≤75%, neurovascular bundle D0.1cc ≤100%, penile bulb D1cc ≤100%. Procedure times were recorded at each step of the procedure, from catheter insertion to removal. Results The median target volume was 45.9 cc, the median volume receiving the prescription dose was 53.0 cc, and the median selectivity index was 0.9. The median values for target dosimetry were as follows: D90=99.9%, V90=95.7%, V100=90.1%, V150=28.1%, V200=10.5%. The median values for OAR dosimetry were: urethra D.01cc=114.3%, bladder D1cc=68.3%, rectum D1cc=51.8%, left neurovascular bundle D0.1cc=86.8%, right neurovascular bundle D0.1cc=88.5%, penile bulb D1cc=31.7%. The median time from catheter insertion to end of HDRBT delivery was four hours 14 minutes (range 2:56-9:08); total treatment package time was five hours 32 minutes (range 3:31-9:45). Conclusion Routine MRI-based treatment planning is feasible for the delivery of HDRBT for prostate cancer. We met stringent dosimetric criteria despite more objective target and normal tissue definition with MRI imaging. Treatment package time remains reasonable. We have adopted MRI as our standard imaging modality for HDRBT for prostate cancer., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this work was to compare dose distributions between two radiosurgery modalities, single-isocenter volumetric modulated arc therapy (VMAT), and GammaKnife Perfexion (GK), in the treatment of a large number (≥7) of brain metastases. Twelve patients with 103 brain metastases were analyzed. The median number of targets per patient was 8 (range: 7-14). GK plans were compared to noncoplanar VMAT plans using both 6-MV flattening filter-free (FFF) and 10-MV FFF modes. Parameters analyzed included radiation therapy oncology group conformity index (CI), 12, 6, and 3 Gy isodose volumes (V12 Gy, V6 Gy, V3 Gy), mean and maximum hippocampal dose, and maximum skin dose. There were statistically significant differences in CI (2.5 ± 1.6 vs 1.6 ± 0.8 and 1.7 ± 0.9, P < 0.001, P < 0.001), V12 Gy (2.8 ± 6.1 cc vs 3.0 ± 5.2 cc and 3.1 ± 5.4 cc, P = 0.003, P < 0.001), and V3 Gy (323.0 ± 294.8 cc vs, 880.1 ± 369.1 cc and 937.9 ±  vs 361.9 cc, P = 0.005, P = 0.001) between GK versus both 6-MV FFF and 10-MV FFF. No significant differences existed for maximum hippocampal or skin doses. In conclusion, highly optimized VMAT produced improved conformity at the expense of a higher V12 Gy and V3 Gy volume when compared with highly optimized GK., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: We report clinical outcomes in patients treated with neoadjuvant endocrine therapy (NET) versus neoadjuvant cytotoxic chemotherapy (NCT) in a cohort of postmenopausal women with ER+, HER2- breast cancer., Materials and Methods: We retrospectively reviewed 140 patients treated between May 1998 and September 2010 and collected patient, disease, and treatment characteristics, response to neoadjuvant therapy, and clinical outcome., Results: The median age was 59.5 years. Stage group: stage I 2.2%, stage II 26.8%, stage III 71%, the median tumor size 6 cm (range, 1.5 to 19 cm). Fifty-seven (40.7%) received NET and 83 (59.3%) NCT. One patient (1.8%) in the NET group and 7 (8.4%) in the NCT group had a pathologic complete response (P=0.142). The median follow-up was 48.1 months. Five-year cumulative incidence of locoregional recurrence (LRR) among the entire cohort was 4.1% (95% confidence interval [CI]: 1.5, 8.9), and any recurrence 25.3% (95% CI: 17.6, 33.6). There was no difference in cumulative incidence of LRR or overall recurrence between NET and NCT. On multivariate analysis adjusting for receipt of chemotherapy, presenting stage, and positive lymph nodes, the use of adjuvant radiation therapy was associated with decreased risk of LRR (hazard ratio [HR]=0.24, P=0.035), and ypN2 status with higher risk of LRR (HR=4.91, P=0.032). When the same multivariate model was fitted for any recurrence outcome, only ypN2 status was a significant predictor of overall recurrence (HR=3.02, P=0.005)., Conclusions: We have demonstrated equivalent locoregional and overall outcomes in patients receiving NET versus NCT in a cohort of postmenopausal women with locally advanced ER+HER2-tumors.

Leptospirosis has been recognised as an emerging global public health problem. The aim of our study was to explore the epidemiological and clinical pattern of disease occurrence in suspected cases and to search for any existing co-infections. Ours was a retrospective study in patients with acute febrile illness in north India over a period of three years (April 2011 to June 2014). Serological diagnosis of leptospirosis was made using the PanBio IgM ELISA kit. Using modified Faine's criteria, presumptive and possible diagnosis was made in 57% and 34% cases, respectively. Most of the affected population was resident in north and central India. Nineteen patients showed co-infection with other common pathogens prevailing locally. There is a need to increase awareness and understand the local sero-epidemiological pattern of leptospirosis so that timely preventive and curative action may be taken by healthcare authorities.