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The endoplasmic reticulum (ER) forms an interconnected network of tubules stretching throughout the cell. Understanding how ER functionality relies on its structural organization is crucial for elucidating cellular vulnerability to ER perturbations, which have been implicated in several neuronal pathologies. One of the key functions of the ER is enabling Ca[Formula: see text] signaling by storing large quantities of this ion and releasing it into the cytoplasm in a spatiotemporally controlled manner. Through a combination of physical modeling and live-cell imaging, we demonstrate that alterations in ER shape significantly impact its ability to support efficient local Ca[Formula: see text] releases, due to hindered transport of luminal content within the ER. Our model reveals that rapid Ca[Formula: see text] release necessitates mobile luminal buffer proteins with moderate binding strength, moving through a well-connected network of ER tubules. These findings provide insight into the functional advantages of normal ER architecture, emphasizing its importance as a kinetically efficient intracellular Ca[Formula: see text] delivery system.
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Retículo Endoplásmico , Transducción de Señal , Retículo Endoplásmico/metabolismo , Neuronas/metabolismo , Calcio/metabolismo , Señalización del CalcioRESUMEN
HIV infection has been a severe global health burden, with millions living with the virus and continuing new infections each year. Antiretroviral therapy can effectively suppress HIV replication but requires strict lifelong adherence to daily oral medication regimens, which presents a significant challenge. Long-acting formulations of antiretroviral drugs administered infrequently have emerged as a promising strategy to improve treatment outcomes and adherence to HIV therapy and prevention. Long-acting injectable (LAI) formulations are designed to gradually release drugs over extended periods of weeks or months following a single injection. Critical advantages of LAIs over conventional oral dosage forms include less frequent dosing requirements, enhanced patient privacy, reduced stigma associated with daily pill regimens, and optimised pharmacokinetic/pharmacodynamic profiles. Several LAI antiretroviral products have recently gained regulatory approval, such as the integrase strand transfer inhibitor cabotegravir for HIV preexposure prophylaxis and the Cabotegravir/Rilpivirine combination for HIV treatment. A leading approach for developing long-acting antiretroviral depots involves encapsulating drug compounds in polymeric microspheres composed of biocompatible, biodegradable materials like poly (lactic-co-glycolic acid). These injectable depot formulations enable high drug loading with customisable extended-release kinetics controlled by the polymeric matrix. Compared to daily oral therapies, LAI antiretroviral formulations leveraging biodegradable polymeric microspheres offer notable benefits, including prolonged therapeutic effects, reduced dosing frequency for improved adherence, and the potential to kerb the initial HIV transmission event. The present manuscript aims to review the pathogenesis of the virus and its progression and propose therapeutic targets and long-acting drug delivery strategies that hold substantial promise for enhancing outcomes in HIV treatment and prevention.
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Fármacos Anti-VIH , Preparaciones de Acción Retardada , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacocinética , Inyecciones , Cumplimiento de la Medicación , Composición de Medicamentos , Piridonas , DicetopiperazinasRESUMEN
BACKGROUND: Mycophenolic acid is widely used to treat lupus nephritis (LN). However, it exhibits complex pharmacokinetics with large interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model and a 3-sample limited sampling strategy (LSS) to optimize therapeutic drug monitoring in Indian patients with LN. METHODS: Five blood samples from each LN patient treated with mycophenolic acid were collected at steady-state predose and 1, 2, 4, and 6 hours postdose. Demographic parameters were tested as covariates to explain interindividual variability. PopPK analysis was performed using Monolix and the stochastic approximation expectation-maximization algorithm. An LSS was derived from 500 simulated pharmacokinetic (PK) profiles using maximum a posteriori Bayesian estimation to estimate individual PK parameters and area under the curve (AUC). The LSS-calculated AUC was compared with the AUC calculated using the trapezoidal rule and all the simulated samples. RESULTS: A total of 51 patients were included in this study. Based on the 245 mycophenolic acid concentrations, a 1-compartmental model with double absorption using gamma distributions best fitted the data. None of the covariates improved the model significantly. The model was internally validated using diagnostic plots, prediction-corrected visual predictive checks, and bootstrapping. The best LSS included samples at 1, 2, and 4 hours postdose and exhibited good performances in an external dataset (root mean squared error, 21.9%; mean bias, -4.20%). CONCLUSIONS: The popPK model developed in this study adequately estimated the PK of mycophenolic acid in adult Indian patients with LN. This simple LSS can optimize TDM based on the AUC in routine practice.
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OBJECTIVES: GMCSF+T-cells may be involved in pathogenesis of rheumatoid arthritis (RA), and polyfunctionality may be a marker of pathogenicity. Although, higher frequencies of CD4+GMCSF+ T-cells have been reported, there are no data on CD8+GMCSF+ T-cells or polyfunctionality.Our objective was to enumerate frequencies of CD8+GMCSF+ T cells in RA blood and synovial fluid (SF), and assess their polyfunctionality, memory phenotype and cytotoxic ability. METHODS: This study included RA patients (blood samples,in some with paired synovial fluid (SF)), healthy controls (HC) (blood) and SpA patients (SF). In some RA patients' blood was sampled twice, before and 16-24 weeks after methotrexate (MTX) treatment. After mononuclear cell isolation from blood and SF, ex-vivo stimulation using PMA/Ionomycin was done, and cells were stained (surface and intracellular after permeabilisation/fixation). Subsequently, frequencies of GMCSF+CD8+ and CD4+ T-cells, polyfunctionality (TNFα, IFNγ, IL-17), phenotype (memory) and perforin/granzyme expression were assessed by flowcytometry. RESULTS: There was no significant difference in frequencies of GMCSF+CD8+ (3.7, 4.1%, p=0.540) or GMCSF+CD4+ T-cells (4.5, 5.2%, p=0.450) inblood of RA and HC. However, there was significant enrichment of both CD8+GMCSF+ (5.8, 3.9%, p=0.0045) and CD4+GMCSF+ (8.5, 4.5%, p=0.0008) T-cells inSF compared to blood in RA patients. Polyfunctional triple cytokine positive TNFα+IFNγ+GMCSF+CD8+T-cells (81, 36%, p=0.049) and CD4+T-cells (48, 32%, p=0.010) was also higher in SF compared to blood in RA. CD8+ T cells showed higher frequency of effector-memory phenotype and granzyme-B expression in RA-SF. On longitudinal follow-up, blood CD4+GMCSF+ T-cells significantly declined (4.6, 2.9%, p=0.0014) post-MTX. CONCLUSIONS: We report a novel finding of enrichment of CD8+GMCSF+ in addition to CD4+GMCSF+ T-cells in RA-SF. These cells showed higher polyfunctionality for TNFα and IFNγ, and effector memory phenotype suggesting their involvement in RA pathogenesis.
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Artritis Reumatoide , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Interferón gamma , Líquido Sinovial , Factor de Necrosis Tumoral alfa , Humanos , Artritis Reumatoide/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Líquido Sinovial/inmunología , Líquido Sinovial/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Persona de Mediana Edad , Masculino , Femenino , Interferón gamma/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Estudios de Casos y Controles , Anciano , Fenotipo , Antirreumáticos/uso terapéutico , Memoria Inmunológica , Metotrexato/uso terapéutico , Granzimas/metabolismo , Interleucina-17/metabolismo , Perforina/metabolismo , Resultado del Tratamiento , Células T de Memoria/inmunología , Células T de Memoria/metabolismo , Citotoxicidad InmunológicaRESUMEN
Diabetes mellitus is a chronic and most prevalent metabolic disorder affecting 422 million the people worldwide and causing life-threatening associated conditions including disorders of kidney, heart, and nervous system as well as leg amputation and retinopathy. Steadily rising cases from the last few decades suggest the failure of currently available drugs in containment of this disease. α-Glucosidase is a potential target for effectively tackling this disease and attracting significant interest from medicinal chemists around the globe. Besides having a set of side effects, currently available α-glucosidase inhibitors (carbohydrate mimics) offer better tolerability, safety, and synergistic pharmacological outcomes with other antidiabetic drugs therefore medicinal chemists have working extensively over last three decades for developing alternative α-glucosidase inhibitors. The 1,2,3-Triazole nucleus is energetically used by various research groups around the globe for the development of α-glucosidase inhibitors posing it as an optimum scaffold in the field of antidiabetic drug development. This review is a systematic analysis of α-glucosidase inhibitors developed by employing 1,2,3-triazole scaffold with special focus on design strategies, structure-activity relationships, and mechanism of inhibitory effect. This article will act as lantern for medicinal chemists in developing of potent, safer, and effective α-glucosidase inhibitors with desired properties and improved therapeutic efficacy.
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SETTING: Diagnosing osteoarticular tuberculosis (OATB) and detecting drug resistance is a challenge in an endemic country like India. OBJECTIVE: Truenat MTB Plus assay (TruPlus), a chip-based portable machine, was compared with GeneXpert Ultra (GxUltra) for diagnosing drug-resistant OATB. DESIGN: 115 synovial fluid and pus specimens [22 culture-positive confirmed, 58 culture-negative clinically-suspected, 35 non-TB controls] processed between 2017 and 2023 were subjected to TruPlus, GxUltra and multiplex-PCR for diagnosing OATB. They were further screened for rifampicin resistance using TruRif chip. The performance was evaluated against composite reference standard, phenotypic drug susceptibility testing and rpoB gene sequencing. RESULTS: TruPlus, GxUltra and MPCR detected 77.5 %, 71.25 %, and 83.75 %, cases of OATB, respectively. TruPlus detected five additional cases missed by GxUltra. The performance of TruPlus was comparable to GxUltra (p = 0.074) and to MPCR (p = 0.074), while performance of GxUltra was significantly inferior to MPCR (p = 0.004). The overall agreement with reference standard was substantial for TruPlus and MPCR and moderate for GxUltra. Both TruRif and GxUltra reported 4 cases as rifampicin resistant. CONCLUSION: TruPlus along with TruRif offers better sensitivity than GxUltra. Its compact and portable platform allows wider application in peripheral settings, thus making it a pragmatic solution for diagnosing OATB and its drug resistance.
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Mycobacterium tuberculosis , Tuberculosis Osteoarticular , Humanos , Rifampin/farmacología , Mycobacterium tuberculosis/genética , Pruebas de Sensibilidad Microbiana , Sensibilidad y Especificidad , Tuberculosis Osteoarticular/diagnóstico , Tuberculosis Osteoarticular/tratamiento farmacológico , Tuberculosis Osteoarticular/genética , Farmacorresistencia Bacteriana/genéticaRESUMEN
Diagnosis of TB at early stages of HIV infection may lead to timely intervention for improving patient outcome. Antibodies to Mycobacterium tuberculosis recombinant RpfB protein and two immunodominant peptides of Rpf B protein were evaluated in the sera of HIV +TB+, HIV+ and HIV- pulmonary TB patients by ELISA. Serum antibodies from 90 % and 65 % of HIV+TB+ patients reacted to recombinant RpfB protein and synthetic peptide RpfP1 respectively. Overall, this study shows that resuscitation promoting factor B elicits humoral antibody response in HIV+TB+ co-infected individuals and be proposed as a potential biomarker for diagnosis of HIV+TB+ patients, however further longitudinal follow up studies are warranted.
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Coinfección , Infecciones por VIH , Mycobacterium tuberculosis , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Formación de Anticuerpos , Péptidos , Ensayo de Inmunoadsorción Enzimática , Antígenos BacterianosRESUMEN
The present study investigates the potential of Arachis hypogaea skin-derived carbon nanospheres (CNSs) as an efficient adsorbent for the rapid removal of cationic dyes from aqueous solutions. The CNSs were synthesized through a facile, cost-effective, catalyst-free and environmentally friendly process, utilizing Arachis hypogaea skin waste as a precursor. This is the first reported study on the synthesis of mesoporous carbon nanospheres from Arachis hypogaea skin. The structural and morphological characteristics of the CNSs were confirmed by different nano-characterization techniques. The adsorption performance of the carbon nanospheres was evaluated through batch adsorption experiments using two cationic dyes-methylene blue (MB) and malachite green (MG). The effects of the initial dye concentration, contact time, adsorbent dosage, and pH were investigated to determine the optimal conditions for dye removal. The results revealed that the obtained CNSs exhibited remarkable adsorption capacity and rapid adsorption kinetics. Up to â¼98% removal efficiency was noted for both dyes in as little as 2 min for a 5 mg L-1 dye concentration, and the CNSs maintained their structural morphology even after adsorption. The adsorption data were fitted to various kinetic and isotherm models to gain insights into the adsorption mechanism and behaviour. The pseudo-second-order kinetic model and Redlich-Peterson model best described the experimental data, indicating multi-layer adsorption and chemisorption as the predominant adsorption mechanism. The maximum adsorption capacity was determined to be 1128.46 mg g-1 for MB and 387.6 mg g-1 for MG, highlighting the high affinity of the carbon nanospheres towards cationic dyes. Moreover, CNS reusability and stability were examined through desorption and regeneration experiments, which revealed sustained efficiency over 7 cycles. CNSs were immobilised in a membrane matrix and examined for adsorption, which demonstrated acceptable efficiency values and opened the door for further improvement.
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This article explores the use of phase change materials (PCMs) derived from waste, in energy storage systems. It emphasizes the potential of these PCMs in addressing concerns related to fossil fuel usage and environmental impact. This article also highlights the aspects of these PCMs including reduced reliance on renewable resources minimized greenhouse gas emissions and waste reduction. The study also discusses approaches such as integrating nanotechnology to enhance thermal conductivity and utilizing machine learning and deep learning techniques for predicting dynamic behavior. The article provides an overall view of research on biodegradable waste-based PCMs and how they can play a promising role in achieving energy-efficient and sustainable thermal storage systems. However, specific conclusions drawn from the presented results are not explicitly outlined, leaving room, for investigation and exploration in this evolving field. Artificial neural network (ANN) predictive models for thermal energy storage devices perform differently. With a 4% adjusted mean absolute error, the Gaussian radial basis function kernel Support Vector Regression (SVR) model captured heat-related charging and discharging issues. The ANN model predicted finned tube heat and heat flux better than the numerical model. SVM models outperformed ANN and ANFIS in some datasets. Material property predictions favored gradient boosting, but Linear Regression and SVR models performed better, emphasizing application- and dataset-specific model selection. These predictive models provide insights into the complex thermal performance of building structures, aiding in the design and operation of energy-efficient systems. Biodegradable waste-based PCMs' sustainability includes carbon footprint, waste reduction, biodegradability, and circular economy alignment. Nanotechnology, machine learning, and deep learning improve thermal conductivity and prediction. Circular economy principles include waste reduction and carbon footprint reduction. Specific results-based conclusions are not stated. Presenting a comprehensive overview of current research highlights biodegradable waste-based PCMs' potential for energy-efficient and sustainable thermal storage systems.
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ABSTRACT: Uterine fibroids are benign tumors originating from the smooth muscle cells of the myometrium seen in approximately 20%-50% of women of reproductive age. The Arg-Gly-Asp (RGD) binds to αvß3 integrin expressed on the surface of angiogenic blood vessels or tumor cells. 18 F-FDG PET/CT has been used to evaluate uterine fibroids, with moderate 18 F-FDG uptake. However, angiogenesis imaging in uterine fibroids has not been evaluated. The present case presents a rare finding of RGD uptake in the uterine fibroid on 68 Ga-DOTA-RGD-2 PET/CT in a patient who underwent angiogenesis imaging for left ankle joint pain and swelling.
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Leiomioma , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Femenino , Fluorodesoxiglucosa F18 , Oligopéptidos/metabolismo , Leiomioma/diagnóstico por imagen , Integrina alfaVbeta3/metabolismoRESUMEN
Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) rarely coexist with systemic thrombotic microangiopathy (TMA).The TMA can be in the form of either hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). This review explores the clinical characteristics, histopathological findings, treatment options, and outcomes in patients presenting as AAV with coexisting HUS/TTP. Methods: We conducted a search on the PubMed database and additional searches from January 1998 to September 2022 using the following terms: "ANCA", "Antineutrophil cytoplasmic antibody", "thrombotic thrombocytopenic purpura", "TTP", "thrombotic microangiopathy", "haemolytic uremic syndrome", and "HUS". We excluded articles that described renal-limited TMA. Two authors independently reviewed the full texts and extracted all critical data from the included case reports. Finally, we included 15 cases for this review. Hematological remission and kidney recovery in the form of independence from dialysis was assessed. Results: The median age of the patients was 61 years and a majority of them were females (66.7%). Myeloperoxidase (MPO)-ANCA positivity (66.67%) was more common than proteinase 3 (PR3)-ANCA positivity (33.33%). All patients had laboratory parameters consistent with systemic TMA (HUS or TTP), and only six (out of 11) cases showed histological features of renal TMA. Ten had crescentic glomerulonephritis, and two had advanced degrees of chronicity in histology. Eighty-six percent of cases had hematological remission, and sixty percent of cases became dialysis-independent after treatment. Conclusion: In conclusion, kidney outcome was worse in patients who manifested both AAV and systemic TMA. A paucity of literature regarding this diagnostic quandary calls for avid reporting of such cases.
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Thyroid carcinoma is the most common malignancy of the endocrine system and accounts for nearly 1.5% of all new cancer cases in India. The incidence of thyroid cancers is on the rise secondary to multiple factors including the widespread use of radiological imaging. Surgery remains the cornerstone of treatment, and radioactive iodine therapy plays a pivotal role in differentiated thyroid cancer. Radiation therapy appears to be an underutilized treatment modality. In this review, we have summarized the role of radiation in the treatment of thyroid cancer.
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Adenocarcinoma , Neoplasias de la Tiroides , Humanos , Adenocarcinoma/radioterapia , Radioisótopos de Yodo , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/patologíaRESUMEN
ABSTRACT: Relapsing polychondritis (RP) is an uncommon autoimmune disease that causes inflammation of the cartilage and proteoglycan-rich structures, including the ear, nose, and airway. Paraneoplastic RP is a subset of RP that occurs in some individuals following the detection and treatment of certain types of cancers. FDG PET/CT helps with early diagnosis of RP, identifying inflammatory areas even in the absence of symptoms, and guiding the selection of appropriate biopsy sites. Here, we present a case of adenocarcinoma of the lung presenting with paraneoplastic symptoms of RP as initial presentation, and symptoms were resolved after 3 cycles of chemotherapy.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares , Policondritis Recurrente , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Policondritis Recurrente/diagnóstico por imagen , Policondritis Recurrente/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/complicaciones , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/complicaciones , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/complicaciones , Síndromes Paraneoplásicos/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Background: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Results: Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Conclusion: Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.
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Artritis Experimental , Artritis Reumatoide , Diclofenaco/análogos & derivados , Nanopartículas , Humanos , Ratas , Animales , Metotrexato , Ratas Wistar , Artritis Reumatoide/patología , Nanopartículas/química , Inflamación/tratamiento farmacológico , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Lípidos/químicaRESUMEN
HIV-infected individuals receiving regular antiretroviral therapy (ART) can present with a high viral load in cerebrospinal fluid (CSF) at times when it is suppressed in blood. This study presents data of HIV-infected patients who had undetectable or low plasma viral load in blood but presented with neurological signs and symptoms and were diagnosed to have CSF HIV viral escape. Records were reviewed for clinical manifestations, details of opportunistic or coinfection, and HIV viral copies in plasma and CSF at time of diagnosis of CSF escape. A total of 10,200 HIV-infected individuals were registered in HIV care till December 31, 2021. Nineteen individuals (14 virologically confirmed and 5 clinically) were diagnosed with high viral copies in CSF from June 2014 to December 2021. Mean age was 41.5 ± 9.2 (median, 39.5; range, 30-62) years. Average duration of antiretroviral treatment received at the time of diagnosis of CSF escape was 10.1 years. Median plasma HIV-viral copies were 2,469.8 (undetectable to 29,418) and in CSF were 12,773.7 (n = 14, range, 1,340-48,530) copies/mL. HIV viral copies in CSF were significantly higher than in plasma at the time of presentation (p = .003). ART regimen switch was done after identification of HIV CSF escape. Seventeen patients were alive with a regular follow-up of average 35 (range 7-66) months. All had documented clinical improvement with reversal of neurological impairment after ART switch. There was one death and one lost to follow-up. Early identification and timely intervention in CSF viral escape could revert severe neurological impairment and improves treatment outcome.
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STUDY DESIGN: Systematic literature review and meta-analysis. OBJECTIVES: Predicting patient risk of intraoperative neuromonitoring (IONM) alerts preoperatively can aid patient counselling and surgical planning. Sielatycki et al established an axial-MRI-based spinal cord classification system to predict risk of IONM alerts in scoliosis correction surgery. We aim to systematically review the literature on operative and radiologic factors associated with IONM alerts, including a novel spinal cord classification. METHODS: A systematic review and meta-analysis was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines. A literature search identifying all observational studies comparing patients with and without IONM alerts was conducted. Suitable studies were included. Patient demographics, radiological measures and operative factors were collected. RESULTS: 11 studies were included including 3040 patients. Relative to type 3 cords, type 1 (OR = .03, CI = .01-.08, P < .00001), type 2 (OR = .08, CI = .03, P <.00001) and all non-type 3 cords (OR = .05, CI = .02-.16, P < .00001) were associated with significantly lower odds of IONM alerts. Significant radiographic measures for IONM alerts included coronal Cobb angle (MD = 10.66, CI = 5.77-15.56, P < .00001), sagittal Cobb angle (MD = 9.27, CI = 3.28-14.73, P = .0009), sagittal deformity angle ratio (SDAR) (MD = 2.76, CI = 1.57-3.96, P < .00001) and total deformity angle ratio (TDAR) (MD = 3.44, CI = 2.27-4.462, P < .00001). Clinically, estimated blood loss (MD = 274.13, CI = -240.03-788.28, P = .30), operation duration (MD = 50.79, CI = 20.58-81.00, P = .0010), number of levels fused (MD = .92, CI = .43-1.41, P = .0002) and number of vertebral levels resected (MD = .43, CI = .01-.84, P = .05) were significantly greater in IONM alert patients. CONCLUSIONS: This study highlights the relationship of operative and radiologic factors with IONM alerts.
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INTRODUCTION: Surface mold brachytherapy (SMBT) is an established treatment modality in skin cancer, especially in accessible areas, and has shown comparable outcomes to surgery. We have presented our results for the skin tumor treatment with SMBT treated with high-dose-rate (HDR) brachytherapy in terms of clinical outcomes and toxicity at our institute. MATERIALS AND METHODS: In this retrospective analysis, 15 patients with skin cancer were treated with customized tube-based SMBT at our institute between January 2019 and July 2021. The patients were treated using HDR-brachytherapy using Iridium-192. The median dose was 40 Gy in 10 fractions. The dosimetric parameters were assessed, and patients were followed up as per the institutional protocol. All patients underwent individualized CT-based planning. Skin toxicity was assessed using the Dermatology Life Quality Index (DLQI). RESULTS: With the majority of the patients being male, the median age was 59 years and the most common site affected was the face (8/15; 53.3%). Among the 15 cases, five were squamous cell carcinoma, nine were basal cell carcinoma, and a single case of sebaceous cell carcinoma. The median depth of invasion was 4 mm, and the median catheter-to-surface distance was 1 mm. The complete response rate among the 10 definitive cases was 90% and partial response in one case. The treatment was well-tolerated with no grade 3-5 toxicities. The median V95% and V90% were 94.8% and 97.1%, respectively. The mean coverage index (C.I.), dose non-uniformity ratio (DNR), and overdose volume index (ODI) were 0.97, 0.13, and 0.05, respectively. After a median follow-up of 12 months, none of the patients had recurrence. On assessment of DLQI, the scores were found to be significant in association with the tumor size and tumor site with scores favoring <2 cm and non-exposed area lesions. CONCLUSION: SMBT is a safe and effective treatment modality for skin tumors providing excellent response and cosmetic outcomes. It is well-tolerated and a non-invasive option for elderly patients with comorbidities and lesions in inoperable areas.
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Braquiterapia , Dosificación Radioterapéutica , Neoplasias Cutáneas , Humanos , Braquiterapia/efectos adversos , Braquiterapia/métodos , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/patología , Femenino , Estudios Retrospectivos , Anciano , Adulto , Radioisótopos de Iridio/uso terapéutico , Resultado del Tratamiento , Planificación de la Radioterapia Asistida por Computador/métodos , Carcinoma Basocelular/radioterapia , Carcinoma Basocelular/patología , Estudios de Seguimiento , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Calidad de VidaRESUMEN
SETTING AND OBJECTIVE: To develop and evaluate newer molecular tests that identify drug resistance according to contemporary definitions in Tuberculous meningitis (TBM), the most severe form of EPTB. DESIGN: 93 cerebrospinal fluid (CSF) specimens [41 culture-positive and 52 culture-negative], were subjected to Truenat MTB Plus assay along with chips for rifampicin, isoniazid, fluoroquinolones and bedaquiline resistance. The performance was compared against phenotypic drug susceptibility testing (pDST), Line probe assay (LPA) and gene sequencing. RESULTS: Against pDST, Truenat chips had a sensitivity and specificity of 100%; 94.47%, 100%; 94.47%, 100%; 97.14% and 100%; 100%, respectively for rifampicin, isoniazid, fluoroquinolones and bedaquiline. Against LPA, all Truenat chips detected resistant isolates with 100% sensitivity; but 2 cases each of false-rifampicin and false-isoniazid resistance and 1 case of false-fluoroquinolone resistance was reported. Truenat drug chips gave indeterminate results in â¼25% cases, which were excluded. All cases reported indeterminate were found to be susceptible by pDST/LPA. CONCLUSION: The strategic drug resistance chips of Truenat Plus assay can contribute greatly to TB elimination by providing rapid and reliable detection of drug resistance pattern in TBM. Cases reported indeterminate require confirmation by other phenotypic and genotypic methods.
Asunto(s)
Antituberculosos , Farmacorresistencia Bacteriana Múltiple , Tuberculosis Extensivamente Resistente a Drogas , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Tuberculosis Meníngea , Humanos , Tuberculosis Meníngea/microbiología , Tuberculosis Meníngea/diagnóstico , Tuberculosis Meníngea/tratamiento farmacológico , Tuberculosis Meníngea/líquido cefalorraquídeo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Fenotipo , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Valor Predictivo de las Pruebas , Rifampin/farmacología , Técnicas de Diagnóstico Molecular/métodos , Diarilquinolinas/uso terapéutico , Diarilquinolinas/farmacología , Isoniazida/farmacologíaRESUMEN
BACKGROUND: Esophageal cancer has a poor survival outcome with 5-year OS at 16.7% despite treatment. Some inflammation-based prognostic indicators like the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been previously studied as potential biomarker for predicting outcome in esophageal cancer. Recently, platelet-to-albumin ratio (PAR) has been reported as a promising prognostic factor in gastrointestinal malignancies. METHODS: We performed a retrospective analysis of prospectively treated patients of carcinoma esophagus to evaluate the prognostic significance of inflammation-based prognostic indicators-neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and a composite inflammation-nutrition index: platelet-to-albumin ratio (PAR) in esophageal cancer. Based on previous studies, the optimal cut-off value of PAR was kept at 5.7 × 10^9, and 2.62 for NLR. RESULTS: A total of 71 patients of locally advanced esophageal cancer treated between 2019 and 2022, with either neoadjuvant or definitive chemoradiotherapy, were included. Median follow-up time was 19 months [range: 7-44 months]. Median OS and PFS in our study cohort were 11.3 months [range: 7-23 months] and 7.8 months [range: 3-17 months], respectively. In univariate analysis, lower PAR was found to be significantly correlated with shorter survival time (HR = 2.41; 1.3-4.76; p = 0.047). There was no association found between the OS and the NLR [HR = 1.09; 0.95-1.26; p = 0.222]. Univariate and multivariate linear and logistic regressions found no association between V15, V10, V5, or V2 of spleen and nadir lymphocyte count or between Dmax or Dmean and nadir lymphocyte counts. CONCLUSION: Present analysis found a trend toward an inverse association between PAR and OS. PAR, in the not-so-distant future, may evolve as a novel, convenient, and inexpensive prognostic indicator in esophageal cancer.