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Background and objectiveQuantifying exposure to drugs for personalized dose adjustment is of critical importance in patients with tuberculosis who may be at risk of treatment failure or toxicity due to individual variability in pharmacokinetics. Traditionally, serum or plasma samples have been used for drug monitoring, which only poses collection and logistical challenges in high-tuberculosis burden/low-resourced areas. Less invasive and lower cost tests using alternative biomatrices other than serum or plasma may improve the feasibility of therapeutic drug monitoring.MethodsA systematic review was conducted to include studies reporting anti-tuberculosis drug concentration measurements in dried blood spots, urine, saliva, and hair. Reports were screened to include study design, population, analytical methods, relevant pharmacokinetic parameters, and risk of bias.ResultsA total of 75 reports encompassing all four biomatrices were included. Dried blood spots reduced the sample volume requirement and cut shipping costs whereas simpler laboratory methods to test the presence of drug in urine can allow point-of-care testing in high-burden settings. Minimal pre-processing requirements with saliva samples may further increase acceptability for laboratory staff. Multi-analyte panels have been tested in hair with the capacity to test a wide range of drugs and some of their metabolites.ConclusionsReported data were mostly from small-scale studies and alternative biomatrices need to be qualified in large and diverse populations for the demonstration of feasibility in operational settings. High-quality interventional studies will improve the uptake of alternative biomatrices in guidelines and accelerate implementation in programmatic tuberculosis treatment.

Objectives: Diffuse large B-cell lymphoma (DLBCL) is a morphologically and molecularly diversified disease with aggressive biological behavior. The double expression of MYC/BCL2 proteins portends a poorer prognosis. This study aims to evaluate the frequency, describe the clinicopathological features of the double-expressor phenotype of DLBCL in primary nodal (PN) versus primary extranodal (PEN) sites, and investigate their associations. Materials and Methods: A total of 48 patients with the double-expressor phenotype of lymphoma (DEPL) in a tertiary care hospital were included over three years. Clinicopathological parameters and associations were investigated based on the primary site. Statistical Analysis: Data were documented and analyzed using appropriate statistical tests. Results: The incidence of DEPL in our study was 28.7%. The median age of all DEPL patients was 56 years, with a predominance of men (69%). DEPL cases were further subcategorized as PN-DEPL (n = 33) and PEN-DEPL (n =15). Males were affected almost equally in both groups. More PN-DEPL patients exhibited B symptoms (82%), elevated lactate dehydrogenase (LDH) levels (73%), III/IV stage disease (71%), and maximum revised international prognostic index (R-IPI) score (64%) compared to PEN-DEPL patients. On the other hand, bone marrow (BM) involvement (87%), activated B-cell-type phenotype (80%), pathologic stage I/II (67%), and Ki67 index >90% (93%) were more common in PEN-DEPL patients. Conclusions: Significant differences were observed between PN-DEPL and PEN-DEPL in terms of B symptoms, LDH levels, stage at presentation, BM involvement, pathological subtype, Ki67 index, and R-IPI score. This study provides an estimate of the burden of this aggressive entity and encourages further prognostic studies and therapeutic trials. [ABSTRACT FROM AUTHOR]

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm comprising perivascular epithelioid cells that express myomelanocytic immunophenotype, while stain negative for epithelial markers. We describe a case of prostatic PEComa in a 55-year-old man, who had one month history of frequent urination, hesitancy, and sensation of incomplete voiding. Radiological imaging disclosed prostatomegaly. Despite the medical treatment offered, episodes of urinary retention persisted. Subsequently, he underwent endoscopic transurethral resection of the prostate, histology showed tumor arranged in nests surrounded by thin delicate vessels. The tumor cells were epithelioid with abundant clear-to-eosinophilic cytoplasm, round nuclei, and inconspicuous nucleoli. Bizarre multinucleated giant cells, conspicuous mitosis and focal necrosis were evident. On immunohistochemistry, the tumor cells were diffusely positive for Human Melanoma Black (HMB45) and smooth muscle actin, negative for anti-cytokeratin monoclonal antibodies (AE1/AE3), Homeobox protein (NKX3.1), GATA Binding Protein 3 (GATA3), synaptophysin, Transcription Factor Binding to Immunoglobulin Heavy Constant Mu (IGHM) Enhancer 3 (TFE3), desmin, and SRY (sex determining region Y) -Box Transcription Factor 10 (SOX10). This uncommon case illustrates our diagnostic ordeal with a brief discussion on its nosology and a comprehensive literature review. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis ( Mtb ) is a major threat to global health and is responsible for over one million deaths each year. To stem the tide of cases and maximize opportunities for early interventions, there is an urgent need for affordable and simple means of tuberculosis diagnosis in under-resourced areas. We sought to develop a CRISPR-based isothermal assay coupled with a compatible, straightforward sample processing technique for point-of-care use. Here, we combine Recombinase Polymerase Amplification (RPA) with Cas13a and Cas12a, to create two parallelised one-pot assays that detect two conserved elements of Mtb ( IS6110 and IS1081 ) and an internal control targeting human DNA. These assays were shown to be compatible with lateral flow and can be readily lyophilized. Our finalized assay exhibited sensitivity over a wide range of bacterial loads (10 5 to 10 2 CFU/mL) in sputum. The limit of detection (LoD) of the assay was determined to be 69.0 (51.0 - 86.9) CFU/mL for Mtb strain H37Rv spiked in sputum and 80.5 (59.4 - 101.6) CFU/mL for M. bovis BCG. Our assay showed no cross reactivity against a wide range of bacterial/fungal isolates. Clinical tests on 13 blinded sputum samples revealed 100% (6/6) sensitivity and 100% (7/7) specificity compared to culture. Our assay exhibited comparable sensitivity in clinical samples to the microbiological gold standard, TB culture, and to the nucleic acid state-of-the-art, GeneXpert MTB/RIF Ultra. This technology streamlines TB diagnosis from sample extraction to assay readout in a rapid and robust format, making it the first test to combine amplification and detection while being compatible with both lateral flow and lyophilization.