Carle's obstetric early warning score as a screening tool for critical care admission.

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.

EphrinB2: Expression of a novel potential target in renal cell carcinoma.

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.

Systematic Biopsy of the Prostate can Be Omitted in Men with PI-RADS™ 5 and Prostate Specific Antigen Density Greater than 15.

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/ml2, 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/ml2, 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.

MRI predicts prostatic urethral involvement in men undergoing radical prostatectomy: implications for cryo-ablation of localized prostate cancer.

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.

Primary intracranial Ewing sarcoma/ peripheral primitive neuroectodermal tumor, an entity of unacquaintance: a series of 8 cases.

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.

The interplay among Th17 and T regulatory cells in the immune dysregulation of chronic dermatophytic infection.

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.

One-Stop MRI and MRI/transrectal ultrasound fusion-guided biopsy: an expedited pathway for prostate cancer diagnosis.

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.

Clinicopathologic features of 300 rhabdomyosarcomas with emphasis upon differential expression of skeletal muscle specific markers in the various subtypes: A single institutional experience.

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.

Possible Role of Trichophytin Antigen in Inducing Impaired Immunological Clearance of Fungus in Onychomycosis.

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 ß (TGF-ß) 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-ß 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-ß 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.

Genotyping and In Vitro Antifungal Susceptibility Testing of Fusarium Isolates from Onychomycosis in India.

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.

Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling.

Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca(2+) imaging. Both types of neurons responded consistently with robust intracellular Ca(2+) ([Ca(2+)]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25-1 pps). Radiant exposures of ∼637 mJ/cm(2) resulted in continual neuronal activation. Temperature or [Ca(2+)] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca(2+) involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na(+), K(+), and Ca(2+) plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca(2+) cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca(2+)]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca(2+) release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses.

HIV-associated disseminated cryptococcosis-An unusual clinical and diagnostic picture with successful cure by single dose liposomal amphotericin B treatment.

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.

Feto-Maternal Outcome in Pregnancy With Thrombocytopenia and Abnormal Platelet Indices.

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.

Job Burnout and Perceived Stress among Bank Officers of Meerut: A Cross Sectional Study.

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.

Fibro-Osseus Pseudotumor of the Digit: A Case Report and Review of Literature.

Introduction: Bony subungual growths arising on the digital tip are uncommon. Among these, subungual exostosis is a common cause. Case Presentation: We describe a 35-year-old-male patient with a rare occurrence of a fibro-osseus pseudotumor of the digit. It presents with reactive intramembranous ossification, with no continuity with the distal phalanx, helping differentiate it from a subungual exostosis. The patient presented with an asymptomatic subungual growth, lifting up the nail plate distally causing onycholysis. The characteristic clinical, radiological, and histopathological features of the case are described, which helped confirm the diagnosis. Conclusion: Cases with fibro-osseus pseudotumor of the digit reported in literature are reviewed comprehensively. The factors helping differentiate this from the other bony tumors affecting the distal phalanx, including subungual exostosis, myositis ossificans, and osteosarcoma are also highlighted.