Search Results (53)

The hospital-at-home (HaH) model delivers hospital-level care to patients in their homes, with point-of-care ultrasonography (PoCUS) serving as a cornerstone diagnostic tool for respiratory illnesses such as pneumonia. This review—the third in a series—addresses the prognostic, synchronous, and potential overdiagnostic concerns of lung ultrasound (LUS) in managing pneumonia within HaH settings. LUS offers advantages of safety and repeatability, allowing clinicians to identify “red flag” sonographic findings that signal complicated or severe disease, including pleural line abnormalities, fluid bronchograms, absent Doppler perfusion, or poor diaphragmatic motion. Serial LUS examinations correlate closely with clinical recovery, showing progressive resolution of consolidations, B-lines, and pleural effusions, and thus provide a non-invasive method for monitoring therapeutic response. Compared with chest radiography, LUS demonstrates superior sensitivity in detecting pneumonia, pleural effusion, and interstitial syndromes across pediatric and adult populations. However, specificity may decline in tuberculosis-endemic or obese populations due to technical limitations and overlapping imaging patterns. Overdiagnosis remains a concern, as highly sensitive ultrasonography may identify minor or clinically irrelevant lesions, potentially leading to overtreatment. To mitigate this, PoCUS should be applied in parallel with conventional diagnostics and integrated into comprehensive clinical assessment. Standardized training, multi-zone scanning protocols, and structured image acquisition are recommended to improve reproducibility and inter-operator consistency. Full article

Tuberculosis (TB) has various clinical presentations; pulmonary TB (PTB) affects only the lungs, whereas extrapulmonary TB involves other organs, including pleural TB (PLTB). Immunological studies of patients with extrapulmonary TB primarily focus on the cellular Th1 response, which produces key cytokines, including IFN-γ, TNF, IL-12, and IL-6. TNF and IL-6 play functional roles in host resistance to Mycobacterium tuberculosis (Mtb) infection. Findings suggest that TNF facilitates macrophage containment of Mtb, whereas IL-6 increases macrophage apoptosis induced by Mtb. Studies of the human genome have identified single-nucleotide polymorphisms (SNPs) in genes encoding cytokines associated with TB susceptibility. This study aimed to assess the potential of the IL6-174G/C (rs1800795), TNF-308G/A (rs1800629), and TNF-238G/A (rs361525) SNPs as genetic biomarkers of susceptibility to PLTB in the Venezuelan mestizo population. A total of 269 individuals were included: 69 patients with PLTB and 200 healthy individuals. The IL6-174G/C, TNF-308G/A, and TNF-238G/A polymorphisms were determined by sequence-specific primer polymerase chain reaction (SSP-PCR). Results showed significantly higher frequencies of the G/C, G/A, and G/A genotypes in patients with PLTB (94.0%, 94.2%, and 83.3%) than in controls (40.0%, 19.0%, and 13.4%) for the IL6-174G/C, TNF-308G/A, and TNF-238G/A polymorphisms, respectively. Logistic regression analysis showed significant associations between the G/C, G/A, and G/A genotypes and susceptibility to PLTB. The IL6-174G/C, TNF-308G/A, and TNF-238G/A gene polymorphisms may serve as genetic biomarkers of susceptibility to PLTB in the Venezuelan mestizo population. Full article

Background: The introduction of the “trace” category in the Xpert MTB/RIF Ultra assay has significantly improved the sensitivity of molecular tuberculosis diagnostics. While it enhances sensitivity, especially in paucibacillary and extrapulmonary cases, its specificity remains debatable, making its interpretation outside select populations a topic of clinical uncertainty. Objectives: This study evaluates the diagnostic and clinical significance of trace-positive results obtained with the Xpert MTB/RIF Ultra assay in the context of a high-incidence TB setting, examining their association with clinical, imaging, and microbiological findings. Methods: A retrospective analysis was conducted on 65 samples with trace-positive Xpert Ultra results, collected over a six-year period from 59 distinct patients in a general hospital in Romania. Correlations were assessed with microscopy, culture, clinical features, imaging, treatment initiation, and prior TB history. A composite reference standard was used for diagnostic accuracy evaluation. Results: Of the 65 trace-positive samples, 29 (44.6%) were culture-positive and 5 (7.7%) were smear-positive. A high proportion of patients, 56 (94.9%), presented with TB-compatible symptoms, and 47 (79.6% of those with imaging) had highly suggestive radiological findings. Based on the composite reference standard, 47 patients (79.7%) were ultimately diagnosed with active TB. Anti-TB treatment was initiated in 44 patients (74.5%). Trace positivity was observed across various specimen types, including sputum, pleural fluid, and cerebrospinal fluid. Conclusions: In high TB burden environments, trace-positive Xpert Ultra results frequently reflect true disease when interpreted within the appropriate clinical and imaging framework. Our findings indicate that, in regions with high tuberculosis incidence such as Romania, trace-positive Xpert Ultra results may contribute meaningfully to clinical decision-making when interpreted alongside clinical and radiological findings, in alignment with current WHO guidance. Full article

Hyaloserositis, also known as the icing sugar phenomenon, may be commonly observed during autopsies; however, it is not a well-documented topic with varying nomenclature and etiology, which can be generally defined as an organ being covered with a shiny, fibrous hyaline membrane. In our work, we present the case of a 71-year-old female patient with alcohol-induced liver cirrhosis and subsequent ascites and recurrent peritonitis. During the autopsy, a cirrhotic liver and an enlarged spleen were observed, both exhibiting features consistent with hyaloserositis, accompanied by acute fibrinopurulent peritonitis. Histological examination revealed the classical manifestation of hyaloserositis, further proven by Crossmon staining. The cause of death was concluded as hepatic encephalopathy. During our literature review, a total of seven cases were found. It must be emphasized that no publication describing hyaloserositis from the perspective of a pathologist was discovered. Regarding etiology, abdominal presentations were most commonly caused by serohepatic tuberculosis, while pleural manifestation was observed following trauma. Hyaloserositis may prove to be a diagnostic difficulty in imaging findings, as it can mimic malignancy; therefore, a scientific synthesis is necessary. Full article

Extrapulmonary tuberculosis (EPTB) remains diagnostically challenging due to its paucibacillary nature and variable presentation. Xpert and culture are limited in EPTB diagnosis due to sampling challenges, low sensitivity, and long turnaround times. This study evaluated the performance of the MPT64 antigen detection test for diagnosing EPTB, particularly tuberculous lymphadenitis (TBLN) and tuberculous pleuritis (TBP), in a high-TB, low-HIV setting. Conducted at Gulab-Devi Hospital, Lahore, Pakistan, this study evaluated the MPT64 test’s performance against conventional diagnostic methods, including culture, histopathology, and the Xpert MTB/RIF assay. Lymph node biopsies were collected, and cell blocks were made from aspirated pleural fluid from patients clinically presumed to have EPTB. Of 338 patients, 318 (94%) were diagnosed with EPTB. For TBLN, MPT64 demonstrated higher sensitivity (84%) than Xpert (48%); for TBP, the sensitivity was 51% versus 7%, respectively. Among histopathology-confirmed TBLN cases, MPT64 outperformed both culture and Xpert (85% vs. 58% and 47%). Due to the low number of non-TB cases, specificity could not be reliably assessed. The MPT64 test shows promise as a rapid, sensitive diagnostic tool for EPTB, particularly TBLN, in routine settings. While sensitivity is notably superior to Xpert, further studies are needed to evaluate its specificity and broader diagnostic utility. Full article

The hospital-at-home (HaH) model delivers hospital-level acute care, including diagnostics, monitoring, and treatments, in a patient’s home. It is particularly effective for managing conditions such as pneumonia. Point-of-care ultrasonography (PoCUS) is a key diagnostic tool in the HaH model, and it often serves as a substitute for imaging-based diagnosis in the HaH setting. Both standard and handheld ultrasound equipment are suitable for lung ultrasound (LUS) evaluation. Curvelinear and linear probes are typically used. Patient positioning depends on their clinical condition and specific diagnostic protocols. To enhance sensitivity, we recommend using at least 10-point protocols supported by studies for pneumonia. Five essential LUS patterns should be identified, including A-line, multiple B-lines (alveolar-interstitial syndrome), confluent B-lines, subpleural consolidation, and consolidation with air bronchogram. Pleural effusion is common, and its internal echogenicity can indicate severity and the need for invasive procedures. The current evidence on various etiologies and types of pneumonia is limited, but LUS demonstrates good sensitivity in detecting abnormal sonographic patterns in atypical pneumonia, tuberculosis, and ventilator-associated pneumonia. Further LUS studies in the HaH setting are required to validate and generalize the findings. Full article

Background: Tuberculosis remains one of the biggest global public health problems today. The objective of this study was to evaluate the diagnostic methods, clinical outcomes, patient compliance, and mortality rates in patients diagnosed with extrarespiratory tuberculosis. Methods: 105 cases of extrarespiratory tuberculosis were analyzed over a five-year period (2018–2023). Data from medical records were reviewed and processed. Diagnostic methods included Ziehl–Nielsen staining, Löwenstein–Jensen cultures, GeneXpert, and histopathological analysis. Diagnosis was supplemented by a specialist organ examination and, in cases with concurrent pulmonary involvement, by a chest X-ray and sputum examination. For negative cases, a probabilistic diagnosis was made. Results: Most patients presented pleural TB (38%), osteo-articular TB (26.67%), and ganglionary TB (19%). Patients were mostly men (56.19%), in the 18–40 years-old category (40%), and lived in rural areas (61%). In total, 94.29% were newly diagnosed and most observed comorbidites were chronic smoking (11.37%), chronic lung diseases (10.20%), and malnutrition (9.02%). Moreover, 68% had a negative microscopic examination, while 55% had negative cultures on Löwenstein–Jensen. Conclusions: This study highlights the importance of a multi-modal approach to diagnosing extrarespiratory tuberculosis, especially in negative bacteriological and histopathological results. Imaging, combined with clinical and epidemiological data, is critical for a probabilistic diagnosis. GeneXpert proved useful in difficult cases. This study emphasizes the need for a comprehensive diagnostic strategy to effectively manage extrarespiratory tuberculosis. Full article

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The altered tumor microenvironment after tuberculosis infection appears to contribute to cancer progression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then, we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of the selected exosomal microRNAs. TPE-derived exosome treatment enhanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell invasion. Exosome-mediated transfer of the selected microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phosphorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p suppressed the promotion of lung cancer by TPE-derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TPE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer. Full article

Cystatin F (CstF) is a protease inhibitor of cysteine cathepsins, including those involved in activating the perforin/granzyme cytotoxic pathways. It is targeted at the endolysosomal pathway but can also be secreted to the extracellular milieu or endocytosed by bystander cells. CstF was shown to be significantly increased in tuberculous pleurisy, and during HIV coinfection, pleural fluids display high viral loads. In human macrophages, our previous results revealed a strong upregulation of CstF in phagocytes activated by interferon γ or after infection with Mycobacterium tuberculosis (Mtb). CstF manipulation using RNA silencing led to increased proteolytic activity of lysosomal cathepsins, improving Mtb intracellular killing. In the present work, we investigate the impact of CstF depletion in macrophages during the coinfection of Mtb-infected phagocytes with lymphocytes infected with HIV. The results indicate that decreasing the CstF released by phagocytes increases the major pro-granzyme convertase cathepsin C of cytotoxic immune cells from peripheral blood-derived lymphocytes. Consequently, an observed augmentation of the granzyme B cytolytic activity leads to a significant reduction in viral replication in HIV-infected CD4⁺ T-lymphocytes. Ultimately, this knowledge can be crucial for developing new therapeutic approaches to control both pathogens based on manipulating CstF. Full article

Introduction: Non-tuberculous mycobacterial (NTM) disease is an underdiagnosed condition that usually manifests as pulmonary infection. Extrapulmonary manifestations are rare and can be easily overlooked or misdiagnosed as tuberculosis or malignancy. Case report: Herein, we present four cases of extrapulmonary NTM disease in immunocompetent patients. Patient 1 had bone marrow suppression secondary to NTM infection. Patient 2 was diagnosed with Mycobacterium abscessus meningitis, brain abscess and arachnoiditis. Patient 3 had pleural effusion, and fluid cytology revealed Mycobacterium fortuitum. Patient 4 was a 30-year-old male with cervical lymphadenopathy due to NTM. Two patients (case 2 and case 4) were initially diagnosed with tuberculosis but showed no response to anti-tubercular drugs. One patient (case 3) died within seven days of initiation of treatment. The rest of the patients (cases 1 and 2) showed clinical improvement with antimicrobial therapy for NTM species. Case 4 responded well to surgical excision without the need for antibiotics. Conclusions: Clinicians should be vigilant about the possibility of NTM disease. Early diagnosis is vital to prevent poor outcomes, particularly in the setting of disseminated infections. Full article

Background: Lung ultrasound (LUS) is a tool of growing interest in Rheumatoid Arthritis (RA) oligo- symptomatic ILD to avoid. Objective: We aimed to evaluate (i) the prevalence of pleural (PLUS) and parenchymal (PAUS) abnormalities in LUS in the RA population and their possible correlation to biomarkers; (ii) the predictivity of gender, smoking habits, previous infections (past COVID-19 tuberculosis), and treatments; (iii) the differences in LUS between sexes. Methods: We collected the data of 155 (15 early and 140 late) RA patients with mild respiratory symptoms, evaluating PLUS and PAUS, in fourteen lung areas and also summing the scores (LUS-T). Results: Only 13/155 (8.4%) were completely negative; LUS correlated to age (all parameters p 0.0001), rheumatoid factor IgM (PLUS p 0.0006, PAUS p 0.02, LUS-T p 0.001) and ACPA (p 0.001, 0.006, 0.001, respectively), and PLUS also correlated to IL6 (p 0.02). The male gender was predictive of all LUS evaluations (p 0.001, 0.05, 0.001, respectively), which were higher than in women (p 0.001, 0.01, 0.001, respectively). Other potential risk factors were independent, except biological treatments, which showed a low predictivity to PLUS (p < 0.05). Conclusions: We can conclude that LUS is a useful technique in RA low respiratory symptoms and correlates with age, the most important RA biomarkers, and male sex. Full article

This article aims to detect lung cavitations using lung ultrasound (LUS) in a cohort of patients with pulmonary tuberculosis (TB) and correlate the findings with chest computed tomography (CT) and chest X-ray (CXR) to obtain LUS diagnostic sensitivity. Patients with suspected TB were enrolled after being evaluated with CXR and chest CT. A blinded radiologist performed LUS within 3 days after admission at the Infectious Diseases Department. Finally, 82 patients were enrolled in this study. Bronchoalveolar lavage (BAL) confirmed TB in 58/82 (71%). Chest CT showed pulmonary cavitations in 38/82 (43.6%; 32 TB patients and 6 non-TB ones), LUS in 15/82 (18.3%; 11 TB patients and 4 non-TB ones) and CXR in 27/82 (33%; 23 TB patients and 4 non-TB ones). Twelve patients with multiple cavitations were detected with CT and only one with LUS. LUS sensitivity was 39.5%, specificity 100%, PPV 100% and NPV 65.7%. CXR sensitivity was 68.4% and specificity 97.8%. No false positive cases were found. LUS sensitivity was rather low, as many cavitated consolidations did not reach the pleural surface. Aerated cavitations could be detected with LUS with relative confidence, highlighting a thin air crescent sign towards the pleural surface within a hypoechoic area of consolidation, easily distinguishable from a dynamic or static air bronchogram. Full article

Pseudopropionibacterium propionicum (P.p.) is an anaerobic, Gram-positive, branching beaded rod that is a component of the human microbiome. An infection of the thoracic cavity with P.p. can mimic tuberculosis (TB), nocardiosis, and malignancy. We present a case of a 77-year-old male who presented with dyspnea and a productive cough who was initially misdiagnosed with TB based on positive acid-fast staining of a pleural biopsy specimen and an elevated adenosine deaminase level of the pleural fluid. He was then diagnosed with nocardiosis based on the Gram stain of his pleural fluid that showed a Gram-positive beaded and branching rod. The pleural fluid specimen was culture-negative, but the diagnosis of thoracic P.p. infection was determined with next-generation sequencing (NGS). The patient was initially treated with imipenem and minocycline, then ceftriaxone and minocycline, and later changed to minocycline only. This report shows the utility of NGS in making a microbiological diagnosis when other techniques either failed to provide a result (culture) or gave misleading information (histopathologic exam, pleural fluid adenosine deaminase determination, and organism morphology on Gram stain). Full article

Tuberculosis (TB) is a worldwide burden whose total control and eradication remains a challenge due to factors including false positive/negative diagnoses associated with the poor sensitivity of the current diagnostics in immune-compromised and post-vaccinated individuals. As these factors complicate both diagnosis and treatment, the early diagnosis of TB is of pivotal importance towards reaching the universal vision of a TB-free world. Here, an aptasensor for signaling an interferon gamma (IFN-γ) TB biomarker at low levels is reported. The aptasensor was assembled through gold–thiol interactions between poly(3,4-propylenedioxythiophene), gold nanoparticles, and a thiol-modified DNA aptamer specific to IFN-γ. The aptasensor sensitively detected IFN-γ in spiked pleural fluid samples with a detection limit of 0.09 pg/mL within a linear range from 0.2 pg/mL to 1.2 pg/mL. The good performance of the reported aptasensor indicates that it holds the potential for application in the early diagnosis of, in addition to TB, various diseases associated with IFN-γ release in clinical samples. Full article

Early diagnosis of pulmonary tuberculosis (PTB) is pivotal for achieving effective tuberculosis (TB) control. This study aimed to assess the effectiveness of nanopore sequencing of sputum, bronchoalveolar lavage fluid (BALF), and pleural fluid samples for achieving early PTB diagnosis and provided head-to-head comparisons of nanopore sequencing results versus results obtained using smear, culture, and Xpert MTB/RIF assays. Patients admitted from October 2021 to April 2023 were screened for PTB using diagnostic imaging and electronic medical records. A total of 172 patients (129 PTB, 43 non-TB patients) were included in the final analysis after the exclusion of patients who did not meet the study’s inclusion criteria. PTB-positive rates were determined for each assay, and then, assay diagnostic efficacies were compared. The positive MTB-detection rates obtained using nanopore sequencing were 86.8% for all samples, 62.3% for BALF, and 84.6% for pleural fluid, all of which were significantly higher than the corresponding rates obtained using the other three assays. The overall sensitivity rates, specificity rates, and area under the curve (AUC) values obtained from smear testing were 5.4%, 95.3%, and 0.504, respectively, as compared to the respective results obtained via culture (18.6%, 100.0%, and 0.593), Xpert MTB/RIF (26.4%, 97.7%, and 0.620), and nanopore sequencing (85.3%, 95.4%, and 0.903). The diagnostic efficacy of nanopore sequencing surpassed the diagnostic efficacies of smear, culture, and Xpert MTB/RIF assays. Thus, nanopore sequencing holds promise as an alternative to Xpert MTB/RIF for early PTB detection, particularly for the testing of BALF and pleural fluid samples. Full article