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Purpose: To determine whether multi-parametric magnetic resonance imaging (mpMRI) can reliably predict proximity of prostate cancer to the prostatic urethra in a contemporary series of men undergoing radical prostatectomy (RP) at two academic centers. Methods: Clinical characteristics of consecutive men undergoing pre-operative mpMRI prior to RP and whole-mount axial serial step-sectioned pathology examination at two academic centers between Jun 2016 and Oct 2018 were analyzed retrospectively. Every tumor was characterized by its pathologic minimum distance to the prostatic urethral lumen (pMDUL). Only the cancer closest to the urethra represented the prostatic urethral index lesion. The radiologic minimum distance of the index lesion to the prostatic urethral lumen was measured and noted as ≤ 5 mm versus > 5 mm. The sensitivity, specificity, positive and negative predicting values (PPV and NPV) and area under the receivers operating characteristics curve (AUC) were calculated for performance of mpMRI for predicting pMDUL ≤ 5 mm. Results: Of the 163 surgical specimens examined, 112 (69%) exhibited a pMDUL ≤ 5 mm. These men had significantly higher grade group (GG) and advanced pathological and clinical stage. The rates of high PI-RADS score and presence of gross extracapsular extension were also significantly greater for the group with pMDUL ≤ 5 mm. The AUC, sensitivity, specificity, PPV, and NPV were 0.641, 51.8, 76.5, 82.9, and 42.4%, respectively, for mpMRI to predict pMDUL < 5 mm. Conclusions: Nearly 70% of men undergoing RP present with tumor within 5 mm of the prostatic urethra. These tumors present higher risk characteristics, and mpMRI exhibited moderate performance and high PPV in their pre-operative detection. Physicians performing partial gland ablation should take these results into consideration during treatment selection and planning. [ABSTRACT FROM AUTHOR]

Due to an internal mistake during production the name of one of the co-authors, Aliasgar Moiyadi, was omitted from the original publication. With this Erratum the name of the co-author is included again and the original publication has been modified accordingly. SpringerNature apologizes for this and for any inconvenience associated therewith. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility, safety, and outcomes of an expedited One-Stop prostate cancer (PCa) diagnostic pathway. Patients and methods: We identified 370 consecutive patients who underwent multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound fusion prostate biopsy (MRI/TRUS-PBx) from our institutional review board-approved database. Patients were divided according to diagnostic pathway: One-Stop (n = 74), with mpMRI and same-day PBx, or Standard (n = 296), with mpMRI followed by a second visit for PBx. mpMRIs were performed and interpreted according to Prostate Imaging-Reporting and Data System (PI-RADS v2). Grade group ≥ 2 PCa defined clinically significant PCa (csPCa). Statistical significance was considered when p < 0.05. Results: Age (66 vs 66 years, p = 0.59) and PSA density (0.1 vs 0.1 ng/mL2, p = 0.26) were not different between One-Stop vs Standard pathway, respectively. One-Stop patients lived further away from the hospital than Standard patients (163 vs 31 km; p < 0.01), and experienced shorter time from mpMRI to PBx (0 vs 7 days; p < 0.01). The number (p = 0.56) and distribution of PI-RADS lesions (p = 0.67) were not different between the groups. All procedures were completed successfully with similar perioperative complications rate (p = 0.24). For patients with PI-RADS 3–5 lesions, the csPCa detection rate (49% vs 41%, p = 0.55) was similar for One-Stop vs Standard, respectively. The negative predictive value of mpMRI (PI-RADS 1–2) for csPCa was 78% for One-Stop vs 83% for Standard (p = 0.99). On multivariate analysis, age, prostate volume and PI-RADS score (p < 0.01), but not diagnostic pathway, predicted csPCa detection. Conclusion: A One-Stop PCa diagnostic pathway is feasible, safe, and provides similar outcomes in a shorter time compared to the Standard two-visit diagnostic pathway. [ABSTRACT FROM AUTHOR]

The delineation of the pathogenic interaction between the host skin immune responses and dermatophytes has remained indigent. The obscure enigma in host-dermatophyte immunopathogenic interactions is the T regulatory (Treg) and T-helper (Th) 17 cell role in maintaining immune homeostasis. We attempted to understand the regulation and recognition of lineage-specific response in chronic dermatophytic skin infection patients. The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell subpopulations in the peripheral circulation of thirty chronic dermatophytic skin infection patients and twenty healthy individuals was determined. The serum cytokine levels were estimated for disease correlation. The mean duration of the disease was 10.68 ± 8.72 months, with Trichophyton mentagrophytes complex as the major pathogen. Total serum IgE level of patients was significantly higher compared to healthy controls (305 ± 117 vs 98.53 ± 54.55 IU/ml; p < 0.01). Expression of Th17 and Treg cell markers on CD4+ T cells was significantly elevated in patients than controls (p < 0.05). Comparatively, serum interleukin (IL)-4 and interferon (IFN)-γ levels were increased, with low IL-10 levels in patients. Our data envisages a complex immune dysfunction in chronic dermatophytosis, arising either as a result of dermatophyte exposure or paradoxical precedence of disease establishment. Designing new treatment strategies and preventing recurrences are challenges for future research. • Th17 and Treg expression was elevated in dermatophytosis patients than controls. • Patient serum levels of IL-4 and IFN-γ were increased with decreased IL-10 levels. • A complex immune dysfunction was observed in patients of chronic dermatophytosis. [ABSTRACT FROM AUTHOR]

Purpose: To describe the epidemiological profile and clinical characteristics of ocular and periocular tumors in patients presenting to three tertiary care referral centers in North and Central India., Methods: Hospital-based consortium study., Settings and Design: Retrospective, descriptive, observational study., Results: A total of 3184 patients were diagnosed with 3557 ocular and periocular tumors over 11 years from 2010 to 2021. Of these, 2395 (67.33%) were benign, 84 (2.36%) were premalignant, and 1078 (30.30%) were malignant. The most common location was the ocular surface (n = 1294, 37.09%), followed by the eyelid (n = 1185, 33.97%), intraocular (n = 624, 17.88%), and orbit (n = 454, 13.01%). The most common tumors were retinoblastoma (n = 483, 13.57%), ocular surface squamous neoplasia (OSSN) (n = 301, 8.46%), and dermoid cyst (n = 167, 4.69%). In the pediatric age group, retinoblastoma was the most common tumor (n = 483, 13.57%), while in adults, it was OSSN (n = 301, 8.46%). The stage at presentation for malignant tumors was divided into in-situ (57.14%), local spread (8.16%), and metastasis (32.83%). For specific tumor locations, the stages were 78.83%, 17.51%, and 2.18%, respectively, for eyelid tumors; 51.76%, 27.05%, and 17.64%, respectively, for orbital tumors; 88.37%, 5.81%, and 5.19%, respectively for ocular surface tumors; and 35.71%, 14.15%, and 50.28%, respectively, for intraocular tumors., Conclusions: Identifying the epidemiological characteristics of ocular and periocular tumors will aid in early diagnosis and timely intervention. Intraocular tumors showed delayed diagnosis, advanced stages at presentation, and required patients to travel longer distances for treatment, indicating the need for strengthened diagnostic and treatment facilities to improve access to care., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Salmonella enterica subspecies enterica serovar Abortusequi (S. Abortusequi) is a leading cause of abortion in equines that hinders the rapid growth of equine industry. S. Abortusequi infection in equids has re-emerged over last ten years. In the present study, S. Abortusequi was isolated and characterized from donkeys during an abortion storm in the southern peninsular region of India. Further, whole genome sequencing and phylogenomic analysis revealed that the present isolate was clustered among S. Abortusequi clade. The core genome MLST (cgMLST) analysis based on hierarchical clustering and single nucleotide polymorphism (SNP) core-genome dendrogram of the present isolate against 10 S. Abortusequi isolates revealed that the present isolate established a distinct clade compared to all previously reported isolates. A comparison of cgMLST and SNP analyses revealed the same clustering concordance between isolates. In addition, comparative genomics and phylogenetic analysis was carried out with six S. Abortusequi serovars showed a higher number of core genes than accessory genes. Further, comparative analysis of phenotype and genotype antimicrobial resistance revealed a concordance of 32% and discordance of 68% respectively., (© 2024. The Author(s).)

Objectives: Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a life-threatening infection with limited treatment options. This is the first meta-analysis of recently published data to compare the clinical outcomes of ceftazidime-avibactam (CAZ-AVI) with other antimicrobial agents in treating MDR-PA infections., Design: Systematic review and meta-analysis., Data Sources: PubMed, Embase and the Cochrane Library have been systematically reviewed, for publications in the English language, from database inception to July 2023., Eligibility Criteria for Selecting Studies: Studies comparing CAZ-AVI outcomes with other antimicrobial agents were included. In-hospital mortality & 30-day mortality were assessed as the main outcomes., Data Extraction and Synthesis: Literature screening, data extraction, and the quality evaluation of studies were conducted by two researchers independently, with disagreements resolved by another researcher. The Newcastle-Ottawa Scale was used to assess the bias risk for the included studies. Review Manager V.5.4 was employed for the meta-analysis., Results: The meta-analysis included four retrospective studies, enrolling 1934 patients. The CAZ-AVI group demonstrated significantly lower in-hospital mortality (risk ratio (RR) = 0.60, 95% CI:0.37-0.97, I2 = 74%, p = 0.04) in three studies with 1444 patients and lower 30-day mortality, in 438 patients from three studies (RR = 0.54, 95% CI:0.28-1.05, I2 = 67%, p = 0.07). No significant difference in clinical success, microbiological success, length of hospital, and ICU stay was observed., Conclusions: This meta-analysis demonstrated that CAZ-AVI treatment significantly lowered in-hospital mortality compared with other antimicrobial agents in MDR-PA infections. However, the analysis only included a few observational studies and high-quality, randomized controlled trials are needed to investigate further the scope of CAZ-AVI in MDR-PA  infections., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To assess the utility of pig head model as an oculoplastic surgical training tool., Methods: Fresh pig head was availed for surgical workshop for entropion correction, eyelid margin repair, and evisceration with implant for oculoplastic surgery-naïve participants. Skill improvement, surgical understanding, and performance of the participants were evaluated both subjectively and objectively by trained oculoplastic surgeons. Subjective assessment was done by a standardized questionnaire based on Likert scale shared with the participants post training. Objective evaluation was done by the faculty based on a three-point scale and a competency-based surgical assessment rubric., Results: There were 18 surgery-naïve participants in the workshop which comprised ophthalmology residents and comprehensive ophthalmologists. About 88.88% of the participants were able to perform the lid margin and sub-tarsal dissection in entropion surgery. While performing lid tear repair, 94.44% were correctly able to identify the grey line and anterior and posterior lamellae. About 83.33% of the participants were able to place an implant in the scleral shell or intraconal space. About 83.33% of the participants noted that texture and tissue maneuvering were similar to the human eye while performing surgical steps. About 94.44% of the participants reported better understanding, development of skill and additional confidence after training. The median score on objective assessment was 3. The performance on real patients resulted in a median score of 4 for entropion correction., Conclusion: Porcine orbital dissection is an available, affordable, and useful tool for oculoplastic surgical training. Training on porcine model can improve anatomical understanding, clinical judgement, and surgical efficiency in trainees.

Background: Cryptococcosis is an invasive, opportunistic fungal infection seen especially in human immunodeficiency virus (HIV) infected patients. Cryptococcal meningitis (CM) is the second leading cause of mortality in HIV patients. We report a case of disseminated cryptococcosis presenting with altered mental status in a newly diagnosed HIV infection., Methods and Results: A 50-year-old with a short history of altered mental sensorium and a history of low-grade fever and weight loss for few months presented at a tertiary care hospital in North India. He was detected positive for HIV-1. Cryptococcal antigen (CRAG) was positive in Cerebrospinal fluid (CSF), and negative in serum. The fungal culture in CSF was sterile while the fungal blood culture grew Cryptococcus neoformans. The patient was treated with single high-dose Liposomal Amphotericin B (LAmB) therapy followed by Fluconazole and Flucytosine for the next two weeks followed by fluconazole daily for consolidation and maintenance therapy. Antiretroviral therapy (ART) was started 4 weeks after induction therapy. After 6 months, the patient is doing fine., Conclusion: Single dose LAmB along with the backbone of fluconazole and flucytosine appears promising in disseminated cryptococcal infection in HIV-infected individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Platelet count and its associated indices like mean platelet volume (MPV) and platelet distribution width (PDW) are cost-effective biomarkers that are easily accessible and have a potent role in the diagnosis and management of thrombocytopenia. Since anaemia and thrombocytopenia often go together in pregnancy, it is advisable to utilise these indices for feto-maternal benefit., Material and Methods: The study was conducted in the Department of Obstetrics and Gynaecology at a tertiary care centre in New Delhi from July 2022 to December 2023 wherein pregnant women of age 18-40 years, period of gestation >28 weeks with thrombocytopenia or abnormal platelet indices were enrolled. Women with pancytopenia, bone marrow suppression or past or current SARS-CoV-2 positive status were excluded., Results: A total of 150 women were enrolled in the study. The mean age of study population was 25.33 ± 2.90 (range 19-34) years. Subjects were divided into three groups - Group A (mild thrombocytopenia) 24.6%, Group B (moderate thrombocytopenia) 64.6% and Group C (severe thrombocytopenia) 10.6% based on thrombocytopenia severity. Analysing the risk factors, Group C was found to have a significantly higher number of patients with anaemia (p=<0.001), fever (p=0.031), abnormal liquor volumes (p=0.004) and need for blood and platelet transfusion (p=0.077). On correlation of thrombocytopenia with abnormal platelet indices, it was observed that manual platelet count (MPC) and MPV were indirectly correlated (p=0.027). PDW was found to be directly associated with severe thrombocytopenia and indirectly associated with moderate thrombocytopenia.  Conclusion: Thrombocytopenia in pregnancy is directly correlated to factors like maternal fever and anaemia, fetal growth restriction, abnormal liquor, blood products and platelet transfusions. It was also concluded that platelet indices like PDW and MPV play an important role in predicting the feto-maternal outcome and hence timely interventions can be done to improve the same., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mushahary et al.)

Background Objectives: Early warning systems (EWS) involve serial observations (track) with criteria (trigger) to timely identify patients at risk of complications. Carle designed a statistically based clinically modified obstetric early warning score (Carle's OEWS). This study evaluated Carle's OEWS and its individual components for predicting admission to the obstetric critical care unit (OCCU). Maternal near-miss and maternal mortality were the secondary outcomes., Methods: A prospective observational study was conducted among 1250 pregnant women with a period of gestation ≥28 week admitted in the labour wards of a tertiary centre over 18 months. The physiological parameters of OEWS were recorded and aggregate score was calculated at admission and at regular intervals thereafter, till discharge or OCCU admission., Results: The area under receiver operating characteristic (ROC) curve of OEWS was 0.975 for predicting OCCU admission, 0.971 for near-miss, and 0.996 for predicting maternal mortality and was significant for all outcomes. All individual parameters, except diastolic blood pressure, had a significant relative risk for predicting OCCU requirement., Interpretation Conclusions: Carle's OEWS is a useful screening tool for predicting obstetric OCCU admission and can be routinely used in labour wards to ensure timely intervention., (Copyright © 2023 Copyright: © 2023 Indian Journal of Medical Research.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide and declared a Public Health Emergency by the World Health Organization (WHO) on January 30, 2020. Albeit, unprecedented efforts have been made from the scientific community to understand the pathophysiology of COVID-19 disease, the host immune and inflammatory responses are not explored well in the Indian population. Continuous arrival of new variants fascinated the scientists to understand the host immune processes and to eradicate this deadly virus. The aim of this study was to see the helper and cellular host immune responses including memory and activated cell subsets of COVID-19 patients admitted to the intensive care unit (ICU) at different time intervals during the treatment. PBMCs separated from nine patients with SARS-CoV-2 infection were incubated with fluorescent conjugated antibodies and acquired on flow cytometer machine to analyze the T and B cell subsets. The results in COVID-19 patients versus healthy volunteers were as follows: elevated helper T cells (57.4% vs 44.9%); low cytotoxic T cells (42.8% vs 55.6%), and activated T (17.7% vs 21.2%) subsets. Both, TREG (40.15% vs 51.7%) and TH17 (13.2% vs 24.6%) responses were substantially decreased and high expression of TREG markers was observed in these patients compared with controls., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Introduction: Renal cell carcinoma (RCC) is primarily managed by surgery with the use of systemic targeted therapy in a metastatic setting. Newer targeted therapeutic options are evolving; Eph-ephrin is a potential new pathway. The therapeutic potential of targeting the EphB4-EphrinB2 pathway has been demonstrated in many solid tumors; however, its expression in RCC has only been evaluated in a few studies with limited cases. We herein determine the immunohistochemical expression of EphrinB2 in RCC., Methods: A tissue microarray comprising 110 cases of different histological subtypes of RCC and 10 normal kidney tissues were stained with monoclonal anti-EphrinB2 antibody (Abcam, AB201512). The tumor and endothelial cells expressing the EphrinB2 were examined and its expression was correlated with sex, histological subtypes, and tumor nodes metastasis (TNM) stage., Results: Twenty cases of urothelial carcinoma and two unsatisfactory conventional clear cell RCC cases were excluded, and EphrinB2 expression was interpreted in the remaining 88 tumors. EphrinB2 was expressed in 42 out of 88 tumors (47.7%) and was negative in the normal renal parenchyma. There was a statistically significant difference in the expression of EphrinB2 in males (55%) and females (32%). However, no such difference of expression was noted for the histological subtypes and the stages. Half (51%) of Stage 1 ( n = 30) and Stage 2 ( n = 11) tumors showed EphrinB2 positivity., Conclusions: EphrinB2 is expressed in approximately half of RCC cases. EphrinB2 expression in the early stage cancer might indicate its induction as an early event., Competing Interests: Conflicts of interest: David Quinn: Honoraria from Dendreon, Bayer, Astellas, Janssen, Sanofi, Clovis, AstraZeneca, Celgene, Mundipharma; Parkash Gill: Equity in Vasgene Therapeutics Inc; Chhavi Gupta, Akash Pramod Sali, Binyun Ma, Alexandra Jackovich, Sarmad Sadeghi, Inderbir Gill: Nothing to Disclose., (Copyright: © 2023 Indian Journal of Urology.)

Introduction: Burnout is often misconstrued for stress, whereas it is one of the consequences of stress when not managed prosperously. Stress leads to apprehensiveness, loss of energy, and the primary damage is physical. Whereas, burnout is characterized by disengagement where emotions are blunted thus fostering helplessness and hopelessness leading to detachment and despondence, loss of motivation and ideals with the primary damage being emotional., Objectives: To find out the prevalence and severity of stress and burnout among bank officers in Meerut District and to find the correlation between the two parameters., Methods: Banks were selected by simple random sampling through computer random table method for our study. Further, officer grade bank employees were approached for data collection. A prevalidated seven-point Likert scale Shriom-Melamed Burnout Questionnaire was used for the assessment of burnout. Data were analyzed using appropriate statistical tests by EPI Info and Microsoft Excel 2013., Result: 19.7% bank officers have pathological burnout followed by 55.1% of bank officers who are at the brink of developing burnout. Severe stress was found only among 7.9% bank officers, whereas burnout was present in 19.4%. A positive correlation was found between stress and burnout., Conclusion: It was found that stress and job burnout are linked but do not entirely overlap, with individuals having a high risk of job burnout experiencing only moderate stress. Therefore, perceived stress cannot be taken as the only indicator of risk of burnout., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Occupational and Environmental Medicine.)

Dermatophytosis is a common superficial fungal infection of the skin and its appendages caused by dermatophytes. Recent times have witnessed a dynamic evolution of dermatophytes driven by their ecology, reproduction, pathogenicity and host immune response, influenced by population migration and socioeconomic status. Dermatophytes establish infection following successful adherence of arthroconidia to the surface of keratinized tissues. The proteolytic enzymes released during adherence and invasion not only ascertain their survival but also allow the persistence of infection in the host. While the cutaneous immune surveillance mechanism, after antigen exposure and presentation, leads to activation of T lymphocytes and subsequent clonal expansion generating effector T cells that differentially polarize to a predominant Th17 response, the response fails to eliminate the pathogen despite the presence of high levels of IFN-γ. In chronic dermatophytosis, antigens are a constant source of stimulus promoting a dysregulated Th17 response causing inflammation. The host-derived iTreg response fails to counterbalance the inflammation and instead polarizes to Th17 lineage, aggravating the chronicity of the infection. Increasing antifungal resistance and recalcitrant dermatophytosis has impeded the overall clinical remission. Human genetic research has the potential to generate knowledge to explore new therapeutic targets. The review focuses on understanding specific virulence factors involved in pathogenesis and defining the role of dysregulated host immune response against chronic dermatophytic infections for future management strategies., (Copyright © 2022 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Mycobacterium abscessus (MAB) is an emerging pathogen that leads to chronic lung infections. To date, the global population structure of non-cystic fibrosis (CF) MAB and evolutionary patterns of drug resistance emergence have not been investigated. Here we construct a global dataset of 1,279 MAB whole genomes from CF or non-CF patients. We utilize whole genome analysis to assess relatedness, phylogeography, and drug resistance evolution. MAB isolates from CF and non-CF hosts are interspersed throughout the phylogeny, such that the majority of dominant circulating clones include isolates from both populations, indicating that global spread of MAB clones is not sequestered to CF contexts. We identify a large clade of M. abscessus harboring the erm(41) T28C mutation, predicted to confer macrolide susceptibility in this otherwise macrolide-resistant species. Identification of multiple evolutionary events within this clade, consistent with regain of wild type, intrinsic macrolide resistance, underscores the critical importance of macrolides in MAB., (© 2021. The Author(s).)

Antimicrobial resistance (AMR) is an emerging public health problem in modern times and the current COVID-19 pandemic has further exaggerated this problem. Due to bacterial co-infection in COVID-19 cases, an irrational consumption of antibiotics has occurred during the pandemic. This study aimed to observe the COVID-19 patients hospitalized from 1 March 2019 to 31 December 2020 and to evaluate the AMR pattern of bacterial agents isolated. This was a single-center study comprising 494 bacterial isolates (blood and urine) that were obtained from patients with SARS-CoV-2 admitted to the ICU and investigated in the Department of Microbiology of a tertiary care hospital in Delhi, India. Out of the total bacterial isolates, 55.46% were gram negative and 44.53% were gram positive pathogens. Of the blood samples processed, the most common isolates were CoNS (Coagulase Negative Staphylococcus ) and Staphylococcus aureus . Amongst the urinary isolates, most common pathogens were Escherichia coli and Staphylococcus aureus . A total of 60% MRSA was observed in urine and blood isolates. Up to 40% increase in AMR was observed amongst these isolates obtained during COVID-19 period compared to pre-COVID-19 times. The overuse of antibiotics gave abundant opportunity for the bacterial pathogens to gradually develop mechanisms and to acquire resistance. Since the dynamics of SARS-COV-2 are unpredictable, a compromise on hospital antibiotic policy may ultimately escalate the burden of drug resistant pathogens in hospitals. A shortage of trained staff during COVID-19 pandemic renders it impossible to maintain these records in places where the entire hospital staff is struggling to save lives. This study highlights the extensive rise in the use of antibiotics for respiratory illness due to COVID-19 compared to antibiotic use prior to COVID-19 in ICUs. The regular prescription audit followed by a constant surveillance of hospital infection control practices by the dedicated teams and training of clinicians can improve the quality of medications in the long run and help to fight the menace of AMR.

Purpose: We evaluated the prostate cancer and clinically significant prostate cancer detection on systematic biopsy (SB), target biopsy (TB) alone and combined SB and TB in men with Prostate Imaging Reporting and Data System™ (PI-RADS™) 5 lesion., Materials and Methods: From a prospectively maintained prostate biopsy database, we identified consecutive patients with PI-RADS 5 lesion on multiparametric magnetic resonance imaging. The patients underwent multiparametric magnetic resonance imaging followed by transrectal TB of PI-RADS 5 lesion and 12-core SB. The prostate cancer and clinically significant prostate cancer (Grade Group, GG ≥2) detection on SB, TB and SB+TB were determined for all men and accordingly to prostate specific antigen density. Statistic significant was set a p <0.05., Results: Overall, 112 patients met inclusion criteria. The detection rate of prostate cancer for SB, TB and SB+TB was 89%, 93% and 95%, respectively, and for clinically significant prostate cancer it was 72%, 81% and 85%, respectively. SB added 2% prostate cancer and 4% clinically significant prostate cancer detection to TB. A total of 78 patients had prostate specific antigen density >0.15 ng/ml 2 , and the detection rate of PCa for SB, TB and SB+TB was 92%, 97% and 97%, respectively, and for clinically significant prostate cancer it was 79%, 91% and 95%, respectively. In this population, if SB was omitted, 0 prostate cancer and only 4% (3) of clinically significant prostate cancer would be missed. The clinically significant prostate cancer detection rate improved with increased prostate specific antigen density for SB (p=0.01), TB (p <0.0001) and combined SB+TB (p=0.002)., Conclusions: In patients with PI-RADS 5 on multiparametric magnetic resonance imaging and prostate specific antigen density >0.15 ng/ml 2 , SB marginally increases clinically significant prostate cancer detection, but not overall prostate cancer detection in comparison to TB alone. Systematic biopsy did not affect patients' management and can be omitted on this population.

Purpose: The purpose is to highlight the primary intracranial (meningeal-based) occurrence of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET)., Methods: This report is a collation of clinicopathological features of eight cases of molecularly and clinicoradiologically confirmed primary (non-metastatic) intracranial (non-osseous) meningeal ES/PNET., Results: The age range was 1 to 33 years with a median age of 9 years. Male to female ratio was 0.6:1. All patients were diagnosed on the debulking surgical material (gross total resection, 2 cases; subtotal resection, 6 cases) and showed primitive embryonal histomorphology with diffuse membranous CD99 immunoexpression and EWSR1 gene rearrangement by fluorescence in situ hybridization. Seven of them showed a typical FISH pattern of split signals with break-apart probe, while one showed an unusual signal pattern of loss of green signals. EFT-2001 adjuvant protocol was followed along with focal radiotherapy (RT) in all cases (except case 8, full course of chemotherapy could not be completed). Two cases had local recurrence-one of them died of disease recurrence before the administration of further treatment., Conclusion: This series adds non-osseous intracranial site to the list of uncommon sites of occurrence for ES/PNET and more importantly emphasizes the need to be considered in a differential list of primary intracranial primitive embryonal tumors before embarking as primary central nervous system (CNS) embryonal tumor, NOS.

Background: Prostate cancer is managed by surgery, androgen deprivation and cytotoxic chemotherapy. Targeted therapy is emerging as an important pillar in cancer therapeutics, however, efficacy in prostate cancer has been limited. Eph-ephrin is a novel pathway that is upregulated in prostate cancer and promotes the initiation and progression of cancer. The aim of this study was to determine the immunohistochemical expression of ephrinB2 in prostate adenocarcinoma., Methods: A tissue microarray comprising of prostate adenocarcinoma of different grade groups was stained with a monoclonal anti-ephrinB2 antibody (Abcam, AB201512). The tumor and endothelial cells expressing the ephrinB2 positivity were noted. The statistical analysis was performed to determine the difference in expression based on grade groups and the TNM stage., Results: EphrinB2 was expressed in 40 out of 72 cases (55.5 %) of prostate adenocarcinoma and was predominantly negative in the normal prostatic tissue. There was no significant difference in the expression of ephrinB2 in various grade groups (p = 0.7) or stages (p = 0.6)., Conclusions: EphrinB2 is expressed in a significant number of prostate adenocarcinoma regardless of grade and stage. Hence, there is a potential to target this molecule in the low-grade tumors with localized disease as well as high grade, high volume tumors with metastatic disease., Competing Interests: Declaration of Competing Interest David Quinn: Honoraria from Dendreon, Bayer, Astellas, Janssen, Sanofi, Clovis, AstraZeneca, Celgene, Mundipharma Parkash Gill: Equity in Vasgene Therapeutics Inc. Chhavi Gupta, Akash Sali, Binyun Ma, Alexandra Jackovich, Sarmad Sadeghi, Inderbir Gill: Nothing to Disclose., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

The present study was aimed at evaluating clinicopathologic and immunohistochemical (IHC) features of 300 rhabdomyosarcomas (RMSs), including differential IHC expression and prognostic value of myogenin and MyoD1 across various subtypes of RMSs. IHC expression of myogenin and MyoD1 was graded on the basis of percentage of tumor cells displaying positive intranuclear immunostaining i.e. grade 1 (1-25%); grade 2 (26-50%); grade 3 (51-76%) and grade 4 (76-100%).Clinical follow-up was available in 238 (79.3%) patients. Various clinicopathologic parameters were correlated with 3-year disease free survival (DFS) and overall survival (OS). There were 140 cases (46.7%) of alveolar RMS (ARMS), 90 of embryonal RMS (ERMS) (30%), 61 (20.3%) of spindle cell/sclerosing RMS and 9 cases (3%) of pleomorphic RMS. Most cases, barring pleomorphic RMSs, occurred in the first two decades (228 cases) (76%), frequently in males, in the head and neck region (126) (42%). By immunohistochemistry, desmin was positive in 292/299 (97.6%) tumors; myogenin in 238/267 (89.1%) and MyoD1 in 192/266 (72.2%) tumors. High myogenin expression (in ≥51% positive tumor cells) was significantly associated with ARMSs (95/121, 78.5%), as compared to other subtypes (48/117, 41%) (p value < 0.001). High MyoD1 expression (≥51% tumor cells) was seen in more cases of pure sclerosing, combined with spindle cell/sclerosing RMSs (10/10, 100%), as compared to the other subtypes (91/141, 67.4%) (p = 0.032). There was no significant difference between high myogenin expression and clinical outcomes. Patients without metastasis and harbouring tumors, measuring ≤5 cm showed a significant increase in OS, with p values = 0.01 and <0.001, respectively. ARMS was the most frequent subtype. There was a significant association between high myogenin expression and ARMSs and high MyoD1 expression and spindle cell/sclerosing RMSs. High myogenin expression did not correlate with clinical outcomes. Patients with smaller sized tumors and without metastasis had significantly better clinical outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Onychomycosis refers to fungal infection of the nail and is commonly caused by dermatophytes, while yeasts and non-dermatophytic molds (NDM) are increasingly recognized as pathogens in nail infections. The present study was done to delineate molecular epidemiology of Fusarium onychomycosis in India. Five hundred nail samples of Indian patients clinically suspected of onychomycosis were subjected to direct microscopy and fungal culture. Representative Fusarium isolates were further identified to species level by multi-locus sequencing for internal transcribed spacer, translation elongation factor 1 alpha (tef1-α) and RNA polymerase II subunit (rpb2) regions (primer pairs: ITS1/ITS4, EF1/EF2, 5f2/7cr, respectively). These representative strains were also tested for in vitro antifungal susceptibility by the broth microdilution method. Members of the genus Fusarium proved to be the most common NDM responsible for onychomycosis. The Fusarium spp. responsible for onychomycosis belonged to the Fusarium solani species complex (F. keratoplasticum and F. falciforme) and Fusarium fujikuroi species complex (F. proliferatum, F. acutatum and F. sacchari). Antifungal susceptibility results indicated that amphotericin B was the most effective antifungal across all isolates (MIC ranging 0.5-2 mg/L), followed by voriconazole (MIC ranging 1-8 µg/ml). However, a large variation was shown in susceptibility to posaconazole (MIC ranging 0.5 to >16 µg/ml). To conclude, we identified different Fusarium spp. responsible for onychomycosis in India with variation within species in susceptibility to antifungal agents, showing that fusariosis requires correct and prompt diagnosis as well as antifungal susceptibility testing.

The immunology of onychomycosis is poorly understood. Th1 and Th17 are the principal effector cells responsible for protective immunity against fungi, while it is assumed that Th2 responses are associated with deleterious effects. The study was conducted to appraise the role of interleukin-6 (IL-6), transforming growth factor β (TGF-β) and immunoglobulin E (IgE) in onychomycosis patients and to study skin reactivity to trichophytin antigen in them. Serum samples of 60 cases of chronic onychomycosis and 30 healthy controls were assayed for serum IgE, IL-6 and TGF-β levels using specific immunoassay kits; 0.01 ml of trichophytin antigen, Candida antigen and phosphate-buffered saline using separate syringes were injected intradermal at three independent sites of the forearm in cases and controls. Serum IL-6 levels were significantly lower in cases as compared to controls, while serum TGF-β levels in both cases and controls were comparable. Serum IgE levels in cases were significantly higher when compared with controls. Thirty-eight patients showed immediate hypersensitivity response to trichophytin antigen, while none showed delayed hypersensitivity reaction to trichophytin antigen. Constant fungal antigenic stimuli induce a state of anergy as indicated by low serum IL-6 levels and the absence of delayed hypersensitivity reaction to trichophytin antigen in cases, leading to chronicity of infection. High total IgE may indicate a high probability of prior fungal sensitization.

Chronic otitis media is persistent and insidious disease. It is one of the most common bacterial infections in the field of otolaryngology having significant economic and individual repercussion. Medical management of chronic suppurative otitis media (CSOM) for dry ear is essential before surgical treatment. The objective is to consider the most appropriate medical treatment modalities for patients of CSOM. To assess results of acetic acid irrigation and topical and systemic antibiotic in CSOM and consider, the most appropriate medical management. This study was conducted prospectively from Nov 2011 to Sep 2013 in 100 patients of CSOM (tubotympanic type). Patient included in the present study were divided in two groups. In one group patients were treated with aural toilet and irrigation with acetic acid and in other group patients were treated with topical and systemic antibiotic. After a follow up period of 3 months duration results were assessed on the basis of absence of discharge, healing of perforation and status of middle ear. Otorrhoea resolution in group treated with acetic acid was 84 % and healing of perforation was noted in 26 % while failure rate of 16 % was noted. In group treated with topical and systemic antibiotic 58 % of patient shows otorrhoea resolution, 14 % achieve healing of perforation and 32 % had failure. Medical management of CSOM without Cholesteatoma by frequent aural cleaning and irrigation using dilute acetic acid can be more desirable choice as compared to the topical and oral antibiotics.

Objective: Evaluate the effectiveness of short interfering RNA against Bax (Bax siRNA) as a treatment for tumor necrosis factor α (TNFα)-induced auditory hair cell (HC) loss in rat organ of Corti (OC) explants., Study Design: Basic science., Setting: Basic science laboratory, University of Miami Ear Institute., Methods: Organ of Corti explants dissected from 3-day-old rats were cultured in control media, TNFα, and TNFα + Bax siRNA at 0, 48, and 72 hours in vitro. Real-time polymerase chain reaction, enzyme-linked immunosorbent assay, HC viability studies, immunofluorescence, and confocal microscopy were performed. Analysis of variance with post hoc testing was used with P < .05 considered significant., Results: The TNFα-damaged explants demonstrated significant decreases in viable HCs in the basal turn with corresponding increased levels of Bax gene and protein expression, compared with control explant levels. The levels of viable HCs and Bax gene and protein expression in TNFα + Bax siRNA-treated explants approached levels measured in control explants. Immunolocalization studies showed increased Bax protein expression in basal turn HCs in TNFα-treated explants, whereas control explants and TNFα + Bax siRNA-treated explants had low levels of Bax expression., Conclusion: TNFα initiates the programmed cell death of auditory HCs in OC explants through upregulation of proapoptotic Bax gene and protein expression. Bax siRNA blocks TNFα-induced apoptosis of HCs by decreasing the TNFα-induced levels of Bax mRNA and protein expression in treated explants. Bax siRNA is an effective treatment for TNFα-induced ototoxicity in OC explants in vitro and has great potential to be a therapeutic agent against trauma/inflammation-induced hearing loss.

Purpose: To model the kinetics of penetration of fluorescein across the cornea from the endothelial surface., Methods: Rabbit corneas mounted in vitro were exposed to fluorescein at their endothelial surface. Trans-corneal fluorescence were acquired periodically for 6 h using a custom-built confocal microfluorometer. The profiles were then employed to fit a kinetic model for calculation of permeability and diffusion coefficients across the cellular layers and stroma, respectively., Results: At the endothelium-stroma and stroma-epithelium interfaces, the fluorescence profile exhibited sudden jumps. In each case, the fluorescence was higher at the stroma, indicating reduced partitioning of the dye into the lipid-rich cellular layers. The stroma did not swell significantly until 180 min of perfusion. The fluorescence profiles reached a pseudo-steady state at ~6 h. A transport model, which included convective and diffusive fluxes into the stroma, showed a good fit to the trans-corneal profiles at different time points. The estimated permeability coefficients for the cellular layers were close to the values reported previously, but the diffusion coefficient of fluorescein in the stroma was found to be smaller than the values obtained previously using Ussing chambers., Conclusions: The penetration of fluorescein could be modeled accurately by a combination of diffusion and convection.

Hypothesis: Mannitol has otoprotective effects against tumor necrosis factor (TNF) α-induced auditory hair cell (HC) loss., Background: Mannitol has been demonstrated to possess cytoprotective effects in several organ systems. Its protective effect on postischemic hearing loss has also been shown. Mannitol's otoprotective mechanism and site of action are at present unknown., Materials and Methods: Organ of Corti (OC) explants were dissected from 3 day-old rat pups. The safety (nonototoxicity) of mannitol was assessed at 4 different concentrations (1-100 mM). Three experimental arms were designed including: a control group, TNFα group, and TNFα + mannitol group. Cell viability was determined by counts of fluorescein isothiocyanate (FITC) phalloidin stained HC. Immunofluorescence assay of phospho-c-Jun and the proapoptotic mediators, cleaved caspase-3, apoptosis inducing factor (AIF), and endonuclease G (Endo G) were performed., Results: Analysis of HC density confirmed the safety of mannitol at concentration ranges of 1 to 100 mM. The ototoxic effect of TNFα was demonstrated (p < 0.05). The otoprotective effect of 100 mM mannitol in TNFα-challenged OC explants was also demonstrated (p < 0.001). Mannitol treatment reduced the high levels of phospho-c-Jun observed in the TNFα-challenged group. AIF cluster formation and EndoG translocation into the nuclei of HCs were also reduced by mannitol treatment., Conclusion: Mannitol significantly reduces the ototoxic effects of TNFα against auditory HC's potentially by inhibiting c-Jun N terminal kinase (JNK) activation pathway and AIF, EndoG nuclear translocation. This local otoprotective effect may have therapeutic implications in inner ear surgery, for example, cochlear implants, protection of residual hearing, as well as implications for postischemic inner ear insults.

The cochlear implant (CI) is the first effective treatment for deafness and severe losses in hearing. As such, the CI is now widely regarded as one of the great advances in modern medicine. This article reviews the key events and discoveries that led up to the current CI systems, and we review and present some among the many possibilities for further improvements in device design and performance. The past achievements include: (1) development of reliable devices that can be used over the lifetime of a patient; (2) development of arrays of implanted electrodes that can stimulate more than one site in the cochlea; and (3) progressive and large improvements in sound processing strategies for CIs. In addition, cooperation between research organizations and companies greatly accelerated the widespread availability and use of safe and effective devices. Possibilities for the future include: (1) use of otoprotective drugs; (2) further improvements in electrode designs and placements; (3) further improvements in sound processing strategies; (4) use of stem cells to replace lost sensory hair cells and neural structures in the cochlea; (5) gene therapy; (6) further reductions in the trauma caused by insertions of electrodes and other manipulations during implant surgeries; and (7) optical rather electrical stimulation of the auditory nerve. Each of these possibilities is the subject of active research. Although great progress has been made to date in the development of the CI, including the first substantial restoration of a human sense, much more progress seems likely and certainly would not be a surprise., (Copyright © 2012 Wiley Periodicals, Inc.)

This review covers the most recent clinical and surgical advances made in the development and application of cochlear implants (CIs). In recent years, dramatic progress has been made in both clinical and basic science aspect of cochlear implantation. Today's modern CI uses multi-channel electrodes with highly miniaturized powerful digital processing chips. This review article describes the function of various components of the modern multi-channel CIs. A selection of the most recent clinical and surgical innovations is presented. This includes the preliminary results with electro-acoustic stimulation or hybrid devices and ongoing basic science research that is focused on the preservation of residual hearing post-implantation. The result of an original device that uses a binaural stimulation mode with a single implanted receiver/stimulator is also presented. The benefit and surgical design of a temporalis pocket technique for the implant's receiver stimulator is discussed. Advances in biomedical engineering and surgical innovations that lead to an increasingly favorable clinical outcome and to an expansion of the indication of CI surgery are presented and discussed., (Copyright © 2012 Wiley Periodicals, Inc.)

This study presents a novel in vitro model of electrode insertion trauma-induced hair cell (HC) damage and loss and its application for testing the efficacy of otoprotective drugs. In the cochlear implant (CI) procedure as a treatment for profound deafness, an electrode array is surgically inserted to provide electrical stimulation to the auditory nerve. Mechanical trauma from insertion of a CI electrode into the scala tympani can lead to inflammation and a high level of oxidative stress, which can initiate the apoptosis of auditory HCs and intracochlear fibrosis. HC apoptosis and intracochlear fibrosis are thought to be causes of poor CI functional outcomes. In order to gain insight into the molecular mechanisms that initiate HC apoptosis and scala tympani fibrosis following electrode insertion trauma (EIT), and the otoprotective effects of dexamethasone (DXM) observed in previous studies, an in vitro model of EIT was designed. Here we present and characterize a novel, reproducible in vitro model for the study of cellular and molecular events that occur following an EIT procedure. Cochleae from 3-day-old rats were subjected to a cochleostomy and were then divided into three groups: (1) control, (2) EIT, and (3) EIT + DXM (20 μg/mL). In Groups 2 and 3, a 0.28-mm diameter monofilament fishing line was introduced through the small cochleostomy located next to the round window area, allowing for an insertion of between 110° and 150°. HC counts, gene expression for pro-inflammatory cytokines (i.e., TNFα and IL-1β), pro-inflammatory inducible enzymes (i.e., iNOS and COX-2) and growth factors (i.e., TGFβ1, TGFβ3 and CTGF), oxidative stress (i.e., CellROX), and analyses of apoptosis pathways (i.e., caspase-3, apoptosis induced factor and Endonuclease G) were carried out on all explants at different time points. The results of this EIT in vitro model show the initiation of wound healing in which an inflammatory response is followed by a proliferative-fibrosis phase. Moreover, DXM treatment of EIT explants inhibited the inflammatory response and promoted a nonscarring wound healing process. The novel in vitro model described here will improve our understanding of mechanisms underlying CI insertion trauma and protective strategies such as DXM treatment., (Copyright © 2012 Wiley Periodicals, Inc.)

Dry eyes are treated by instillation of eye drops of cyclosporine A emulsion or by punctal plug insertion in canaliculus to block tear drainage. This paper focuses on a novel approach of developing a punctal plug that can also release cyclosporine A to provide a dual mechanism for treating dry eyes. The punctal plug consists of a cylindrical hydroxy ethyl methacrylate core containing drug microparticles surrounded by an impermeable silicone shell that covers about 50% of the core, with the uncovered part directed towards the eyes. The geometry of this design is significantly different from those in patent literature, which are mostly designed to be rods. Plugs release cyclosporine A for a period of about 3 months at zero-order at a rate of about 3 μg/day. The in vivo release rates are expected to be about half of this value. A mathematical model is presented that provides an accurate estimate of the release without any fitting parameter. Pharmacokinetic models are also developed for drug delivered through Restasis® and punctal plugs, and based on these models the release rate of about 1.5 μg/day may be therapeutically effective. The predictions of the ocular pharmacokinetic model are in reasonable agreement with reported measurements in humans., (Copyright © 2010 Elsevier B.V. All rights reserved.)

This paper focuses on exploring the mechanism of cyclosporine A transport in hydroxyethyl methacrylate (HEMA) rods to develop conjunctival inserts for extended ocular delivery. Cylindrical conjunctival HEMA inserts were prepared by thermal polymerization in presence of drug at high loadings to create rods containing particles of drug dispersed in the matrix. The drug release rates were measured to explore the effect of length, drug loading, crosslinking, and mixing in the release medium. Also microstructure of the inserts was characterized by SEM imaging. The inserts release the drug for a period of about a month at therapeutic rates. The rates of drug release are zero order and independent of drug loading and crosslinking for certain period of time. These effects were shown to arise due to a mass-transfer boundary layer in the fluid and a mathematical model was developed by coupling mass transfer in the insert with that in the boundary layer in the surrounding fluid. The model with diffusivity in the insert and boundary layer thickness as parameters fits the experimental data and explains all trends in release kinetics. The fitted diffusivity is about twice that obtained by direct measurements, which agreed well with the value obtained by using the Brinkman's equation but only after accounting for drug binding to the polymer., (Copyright 2010 Elsevier Inc. All rights reserved.)