A Comparative Factor Analysis and New Magnetic Resonance Imaging Scoring System for Differentiating Pyogenic Versus Tuberculous Spondylodiscitis.

OBJECTIVE: This study aimed to compare and analyze differences in clinical and magnetic resonance imaging (MRI) findings between tuberculous spondylodiscitis (TbS) and pyogenic spondylodiscitis (PyS), and to develop and validate a simplified multiparameter MRIbased scoring system for differentiating TbS from PyS. METHODS: We compared predisposing factors in 190 patients: 123 with TbS and 67 with PyS, confirmed by laboratory tests, culture, or pathology. Data encompassing patient demographics, clinical characteristics, laboratory results, and MRI findings were collected between 2015 and 2020. Data were analyzed using logistic regression methods, and selected coefficients were transformed into an MRI-based scoring system. Internal validation was performed using bootstrapping method. RESULTS: Univariate analysis revealed that the significant risk factors associated with TbS included thoracic lesions, vertebral destruction > 50%, intraosseous abscess, thin-walled abscess, well-defined paravertebral abscess, subligamentous spreading, and epidural abscess. Multivariate analysis revealed that only thoracic lesions, absence of epidural phlegmon, subligamentous spreading, intraosseous abscesses, well-defined paravertebral abscesses, epidural abscesses, and absence of facet joint arthritis were independent predictive factors for TbS (all p < 0.05). These potential predictors were used to derive an MRI scoring system. Total scores ≥ 14/29 points significantly predicted the probability of TbS, with a sensitivity of 97.58%, specificity of 92.54%, and an area under the curve of 0.96 (95% confidence interval, 125.40-3,257.95). CONCLUSION: This simplified MRI-based scoring system for differentiating TbS from PyS helps guide appropriate treatment when the causative organism is not identified.

Calcific pericarditis strangling the heart, an answer to unexplained heart failurediagnostic modalities.

Pericardial calcification is often found incidentally from imaging studies and may be a clue to constrictive pericarditis. Constrictive pericarditis often mimics other causes of heart failure, pulmonary, or liver disease, making it hard to diagnose. Tuberculosis is the most common infectious aetiology of Constrictive Pericarditis. Living in developing countries, such as Indonesia, should warn us of the possibility of tuberculous constrictive pericarditis as a differential diagnosis of unexplained heart failure. The presented case came with complaints of shortness of breath, especially on exertion for five years, which worsened in the last 6 months. The past history of pulmonary Tuberculosis with the Cardiac CT findings confirmed the diagnosis of Constrictive Pericarditis.

Clinical and genomic features of Mycobacterium avium complex: a multi-national European study.

BACKGROUND: The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated. METHODS: Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort. RESULTS: Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04-0.28, p < 0.001 and OR 0.11 95% CI 0.02-0.4, p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%). CONCLUSIONS: This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.

Successful Treatment of Intractable Tuberculous Peritonitis in a Woman with Chronic Kidney Allograft Dysfunction Using Contezolid Containing Regimen.

Tuberculosis(TB) is a serious infection that affects transplant recipients, particularly in high TB burden countries. Clinical presentation of these patients is atypical, and the care and management are frequently tricky as multi-drug interaction and intolerable adverse effects. Contezolid, a novel oxazolidinone antibacterial agent, had been demonstrated to be effective for TB in vitro and had been shown in some clinical cases with a more favorable safety profile than linezolid, the first-generation oxazolidinone, which had a commonly seen myelosuppression and neuropathy. Additionally, Contezolid has a unique metabolic mechanism that leads to less drug interaction. Here, we report a case of multi-system TB in a transplant recipient with chronic kidney allograft dysfunction. She was intolerant to most first and second-line anti-TB drugs and repeatedly developed ascites and nocturnal low-grade fever. She finally achieved good efficacy and safety results after enhanced anti-TB treatment with the addition of contezolid. Given the increased risk of TB in patients with organ transplantation and multi-drug interaction in patients with severe comorbidities, further clinical studies are needed to investigate the application and appropriate dosage of contezolid in patients with active TB.

Targeted Next Generation Sequencing (tNGS) for detection of drug-resistant tuberculous meningitis: Is this sequencing technology ready for prime time?

PURPOSE: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB). Difficulty in diagnosing the condition along with other factors, increases its potential for high morbidity and mortality. Targeted Next Generation Sequencing (tNGS) generates high quality sequence read depths, enabling the identification of low-frequency alleles linked to Drug resistance (DR). The paucibacillary nature of tuberculous meningitis is a challenge for making a definitive diagnosis. METHODS: tNGS was performed on 20 cerebrospinal fluid (CSF) samples where, MGIT has shown Positive MTB Cultures. We simultaneously performed pyrosequencing (PSQ) and phenotypic Drug susceptibility testing (pDST) for these 20 samples. RESULTS: Sequencing results (from tNGS and PSQ) were compared with reference standards i.e. pDST. tNGS detected MTB in 7/20 (35%) CSF samples whereas, PSQ detected MTB in 17/20 (85%). CONCLUSION: Although tNGS has ability to detect minority variants along with detection of additional targets than PSQ, PSQ remains the diagnostic choice in our tertiary lab.

Incidence and clinical significance of non-tuberculous mycobacteria among migrants in Denmark: a nationwide register-based cohort study from 1991 through 2021.

BACKGROUND: There is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark. METHOD: Nationwide register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance. RESULTS: 433 migrants had a positive NTM culture, resulting in an overall incidence rate (IR) of 3.7 (95%CI 3.3-4.0) per 100,000 migrants. Overall NTM IRs for definite disease were 1.0 (95%CI 0.9-1.2), possible disease 1.0 (95%CI 0.8-1.2), and isolation 1.7 (95%CI 1.4-1.9) per 100,000 migrants. Migrants had considerably higher age- and sex-adjusted NTM IRs of positive cultures (incidence rate ratio [IRR]=2.1, 95%CI 1.9-2.3, p<0.001), possible disease (IRR=2.4, 95%CI 2.0-3.0, p<0.001), and isolation (IRR=4.6, 95%CI 3.9-5.4, p<0.001) compared to Danish-born, but not of definite disease (IRR=1.1, 95%CI 0.9-1.3, p=0.562). IRs of migrants with positive NTM cultures did not increase over time (-0.8%/year, p=0.133). CONCLUSIONS: Migrants have a higher, but stable, burden of NTM compared with Danish-born. The higher rates likely reflect that more specimens are examined for M. tuberculosis. Also, microbiologically classified definite NTM disease is not substantially more common among migrants.

Efficacy of cartridge-based nucleic acid amplification test (CBNAAT) in comparison with line probe assay and liquid culture in the evaluation of tubercular lymph node abscess.

Background: Tuberculosis (TB) remains the number one cause of adult deaths by a curable infectious disease. Mycobacterium tuberculosis bacilli (MTB) is the most common causative organism isolated from mycobacterial lymphadenitis. Accurate and speedy diagnosis is required, especially in paucibacillary extrapulmonary TB. In this study, we compared the efficacy of CBNAAT with line probe assay and liquid culture in the evaluation of tubercular lymph node abscesses. Materials and Methods: This is a hospital-based observational cross-sectional study conducted at Gandhi Medical College and Hospital, Secunderabad, TS, in patients who presented with lymph node abscesses over a period of 18 months after obtaining clearance from the ethics committee and obtaining informed consent. Each sample was evaluated and analyzed in association with the clinical findings, AFB staining, CBNAAT, LPA, and AFB culture, and the results were compared. Results: Fifty patients with TB lymph node abscess diagnosed through FNAC were included in the present study. AFB smear was positive in 29 samples, CBNAAT was positive in 43 samples, LPA was positive in 44 samples, and liquid culture was positive in 39 samples. CBNAAT could detect TB in 16 smear-negative cases, 10 liquid culture-negative cases, and one LPA-negative case. In our study, CBNAAT was more effective in diagnosing TB lymph node abscess than AFB smear. No significant results were obtained when comparing CBNAAT with LPA and liquid culture. Conclusion: This study demonstrates excellent diagnostic accuracy of the Xpert MTB/RIF test in patients with tuberculous lymphadenitis, with a sensitivity of 86%, specificity of 83.33%, negative predictive value of 95.56%, and positive predictive value of 58.82%. Thus, it can be a rule in testing for lymph node TB. These efforts will contribute to the attainment of the TB elimination goal.

Prevalence and predictors of NTM in presumed/confirmed drug-resistant TB.

INTRODUCTION: Non-tuberculous mycobacteria (NTM) are increasingly isolated in individuals with presumed/confirmed pulmonary TB. We aimed to estimate the prevalence and species distribution of NTM among presumed/confirmed drug-resistant TB (DR-TB) individuals and determine NTM isolation predictors. METHODS: Sputum samples collected for DR-TB diagnosis and follow-up from 2012 to 2021 in Ghana were retrospectively analysed. Samples were subjected to sputum smear microscopy (SSM) and mycobacterial culture. The MPT64 assay was performed on positive cultures to distinguish between Mycobacterium tuberculosis complex MTBc and NTM. NTM isolates were re-cultured for species identification using GenoType® Mycobacterium CM/AS line-probe assay, polymerase chain reaction, and Sanger sequencing targeting 16S rRNA and rpoB genes. MTBc isolates identified by GenoType underwent spoligotyping. A logistic regression model was used to identify the predictors of NTM isolation. RESULTS: Of the 2,492 samples, 839 (33.7%) tested culture-positive for mycobacteria, with 257 (30.6%) presumed to be NTM. Of these, 53 (23.6%) were identified at the species level, with a predominance of M. intracellulare (66.0%). MPT64 testing missed 18 (3%) MTBc isolates. Logistic regression showed increased odds of NTM isolation in follow-up samples (aOR 2.41, 95% CI 1.46-3.99). NTM species were isolated from 46 patients, with four classified as NTM pulmonary disease. CONCLUSION: Enhancing our understanding of local NTM epidemiology and improving local diagnostic capabilities can optimise patient management strategies and outcomes.

INTRODUCTION: Les mycobactéries non tuberculeuses (NTM) sont de plus en plus souvent isolées chez les personnes atteintes de TB pulmonaire présumée/confirmée (DR-TB). Notre étude visait à évaluer la fréquence et la répartition des différentes espèces de NTM chez les personnes atteintes de TB pharmacorésistante, ainsi qu'à identifier les facteurs prédictifs de l'isolement de ces NTM. MÉTHODES: Les échantillons d'expectorations collectés entre 2012 et 2021 au Ghana pour le diagnostic et le suivi de la DR-TB ont été analysés rétrospectivement. Les échantillons ont subi une microscopie du frottis d'expectoration (SSM) et une culture mycobactérienne. Le test MPT64 a été réalisé sur les cultures positives pour différencier le complexe Mycobacterium tuberculosis (MTBc) et les NTM. Les isolats de NTM ont été soumis à une nouvelle culture pour identification des espèces à l'aide du test par sondes en ligne GenoType® Mycobacterium CM/AS, de l'amplification en chaîne par polymérase et du séquençage de Sanger ciblant les gènes 16S rRNA et rpoB. Les isolats de MTBc identifiés par GenoType ont été soumis à un spoligotypage. Un modèle de régression logistique a été utilisé pour identifier les facteurs prédictifs de l'isolement des NTM. RÉSULTATS: Parmi les 2 492 échantillons analysés, 839 (33,7%) ont été testés positifs à la culture de mycobactéries, dont 257 (30,6%) étaient présumés être des NTM. Parmi ces échantillons, 53 (23,6%) ont été identifiés au niveau de l'espèce, avec une prédominance de M. intracellulare (66,0%). Le test MPT64 a échoué à détecter 18 (3%) isolats de MTBc. L'analyse de régression logistique a révélé une probabilité accrue d'isolement de MNT dans les échantillons de suivi (aOR 2,41 ; IC à 95% 1,46­3,99). Des espèces de NTM ont été isolées chez 46 patients, dont quatre ont été classés dans la catégorie des maladies pulmonaires à NTM. CONCLUSION: Une connaissance approfondie de l'épidémiologie locale des NTM et le renforcement des compétences de diagnostic au niveau local peuvent améliorer les stratégies de prise en charge des patients et les résultats obtenus.

Predicting cerebral infarction in tuberculous meningitis and its prognostic significance.

Aim: Tuberculous meningitis (TBM) often causes cerebral infarction, but its predictive factors are not well understood. Methods: Patients aged ≥13 years admitted with TBM were enrolled prospectively. Cerebral infarction was diagnosed using magnetic resonance imaging. Results: Of 186 patients, 80 (43%) had infarction. Most infarctions were multiple and located in the cortical areas, basal ganglia and subcortical regions. Independent predictors of infarction at admission included high blood pressure, short illness duration, low Glasgow coma scale and hydrocephalus. Neuroimaging inflammation signs, cerebrospinal fluid analysis abnormalities and pre-existing cardiovascular risks did not predict infarction. In-hospital mortality was higher in TBM with infarction, particularly in those with advanced TBM (stage 3). Conclusion: Baseline parameters of raised intracranial pressure predict cerebral infarction in TBM.

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Cutaneous infection due to Mycobacterium marinum: A series of four cases from Kerala, India.

Mycobacterium marinum is a non-tuberculous mycobacterium which can be found in naturally occurring, non-chlorinated water sources and is a known pathogen that affects fish. In humans, M. marinum typically results in cutaneous lesions, it can occasionally lead to more invasive disorders. We discuss four cases of M. marinum-related cutaneous infections examined in a tertiary care facility. We want to draw attention to the challenges of accurately diagnosing this infection, stress the significance of having a high level of clinical suspicion in order to identify it, and discuss the available treatment choices.

Too much ado about data: Continuous remote monitoring of water temperatures, circulation and throughput can assist in the reduction of hospital-associated waterborne infections.

BACKGROUND: National and international guidance provides advice on maintenance and management of water systems in healthcare buildings, however, healthcare-associated waterborne infections (HAWI) are increasing. This narrative review identifies parameters critical to water quality in healthcare buildings and assesses if remote sensor monitoring can deliver safe water systems thus reducing HAWI. METHOD: A narrative review was performed using the following search terms 1) consistent water temperature AND waterborne pathogen control OR nosocomial infection 2) water throughput AND waterborne pathogen control OR nosocomial infection 3) remote monitoring of in-premise water systems AND continuous surveillance for temperature OR throughput OR flow OR use. Databases employed were PubMed, CDSR (Clinical Study Data Request) and DARE (Database of Abstracts of Reviews of Effects) from Jan 2013 - Mar 2024. FINDINGS: Single ensuite-patient rooms, expansion of wash-hand basins, widespread glove use, alcohol gel and wipes have increased water system stagnancy resulting in amplification of waterborne pathogens and transmission risk of Legionella, Pseudomonas and Non-Tuberculous Mycobacteria. Manual monitoring does not represent temperatures across large complex water systems. This review deems that multiple point continuous remote sensor monitoring is effective at identifying redundant and low use outlets, hydraulic imbalance and inconsistent temperature delivery across in-premise water systems. CONCLUSION: As remote monitoring becomes more common there will be greater recognition of failures in temperature control, hydraulics and balancing in water systems and there remains much to learn as we adopt this developing technology within our hospitals.

Analysis of risk factors for long-term mortality in patients with stage II and III tuberculous meningitis.

OBJECTIVE: To investigate risk factors associated with long-term mortality in patients with stage II and III tuberculous meningitis (TBM). METHODS: This retrospective analysis examined patients who were first diagnosed with stage II and III TBM at West China Hospital of Sichuan University between January 1, 2018 and October 1, 2019. Patients were followed via telephone and categorized into survival and mortality groups based on 4-year outcomes. Multivariate logistic regression identified independent risk factors for long-term mortality in stage II and III TBM. RESULTS: In total, 178 patients were included, comprising 108 (60.7%) males and 36 (20.2%) non-survivors. Mean age was 36 ± 17 years. Compared to survivors, non-survivors demonstrated significantly higher age, heart rate, diastolic blood pressure, blood glucose, rates of headache, neurological deficits, cognitive dysfunction, impaired consciousness, hydrocephalus, and basal meningeal inflammation. This group also exhibited significantly lower Glasgow Coma Scale (GCS) scores, blood potassium, albumin, and cerebrospinal fluid chloride. Multivariate analysis revealed age (OR 1.042; 95% CI 1.015-1.070; P = 0.002), GCS score (OR 0.693; 95% CI 0.589-0.814; P < 0.001), neurological deficits (OR 5.204; 95% CI 2.056-13.174; P < 0.001), and hydrocephalus (OR 2.680; 95% CI 1.081-6.643; P = 0.033) as independent mortality risk factors. The ROC curve area under age was 0.613 (95% CI 0.506-0.720; P = 0.036) and 0.721 (95% CI 0.615-0.826; P < 0.001) under GCS score. CONCLUSION: Advanced age, reduced GCS scores, neurological deficits, and hydrocephalus were identified as independent risk factors for mortality in stage II and III TBM patients.

Applications and advances in molecular diagnostics: revolutionizing non-tuberculous mycobacteria species and subspecies identification.

Non-tuberculous mycobacteria (NTM) infections pose a significant public health challenge worldwide, affecting individuals across a wide spectrum of immune statuses. Recent epidemiological studies indicate rising incidence rates in both immunocompromised and immunocompetent populations, underscoring the need for enhanced diagnostic and therapeutic approaches. NTM infections often present with symptoms similar to those of tuberculosis, yet with less specificity, increasing the risk of misdiagnosis and potentially adverse outcomes for patients. Consequently, rapid and accurate identification of the pathogen is crucial for precise diagnosis and treatment. Traditional detection methods, notably microbiological culture, are hampered by lengthy incubation periods and a limited capacity to differentiate closely related NTM subtypes, thereby delaying diagnosis and the initiation of targeted therapies. Emerging diagnostic technologies offer new possibilities for the swift detection and accurate identification of NTM infections, playing a critical role in early diagnosis and providing more accurate and comprehensive information. This review delineates the current molecular methodologies for NTM species and subspecies identification. We critically assess the limitations and challenges inherent in these technologies for diagnosing NTM and explore potential future directions for their advancement. It aims to provide valuable insights into advancing the application of molecular diagnostic techniques in NTM infection identification.

Rifabutin central nervous system concentrations in a rabbit model of tuberculous meningitis.

Tuberculous meningitis (TBM) has a high mortality, possibly due to suboptimal therapy. Drug exposure data of antituberculosis agents in the central nervous system (CNS) are required to develop more effective regimens. Rifabutin is a rifamycin equivalently potent to rifampin in human pulmonary tuberculosis. Here, we show that human-equivalent doses of rifabutin achieved potentially therapeutic exposure in relevant CNS tissues in a rabbit model of TBM, supporting further evaluation in clinical trials.

Disease spectrum and prognostic factors in patients treated for tuberculous meningitis in Shaanxi province, China.

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China. Methods: A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as "confirmed," "probable," or "possible" TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome-assessed using the modified Barthel disability index-were recorded and compared. Findings: A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 "not TBM." Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298-11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372-10.761), age > 60 years (OR = 3.566; 95%CI: 1.022-12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027-5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score ≥ 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138-135.758) and a higher TBM score (≥15, OR = 8.437; 95%CI: 1.328-53.585) were most strongly associated with death. Conclusion: TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

Polypropylene Mesh Infection From Surgical Site Infections Caused by Mycobacterium fortuitum.

This report highlights two cases of surgical site infections (SSIs) caused by Mycobacterium fortuitum (Mf) following abdominal mesh implantation. The first case involved an 83-year-old male experiencing non-healing erythema and wounds post-operation, which persisted despite multiple treatments, until effective management was achieved with targeted antibiotics after Mf identification. The second case concerned a female patient with a gynecological postoperative hernia, where Mf was quickly detected following SSI onset three weeks after surgery. Prompt mesh removal and appropriate antibiotic treatment led to a rapid and full recovery. These cases emphasize the importance of early detection and intervention in managing Mf infections effectively, illustrating how the timing of diagnosis can significantly influence treatment outcomes.

Clinical spectrum and relevance of Mycobacterium malmoense: Systematic review and meta-analysis of 859 patients.

INTRODUCTION: The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this study, we aimed to analyse all published clinical data of patients with M. malmoense isolation to investigate the clinical spectrum, relevance, and outcomes of infections with this uncommon mycobacterium. METHODS: A systematic review of PubMed, Web of Science, Embase, and Scopus was performed to identify all clinical data about M. malmoense. Random effects meta-analyses of proportions were calculated for clinical relevance, treatment success, and mortality, as well as for other clinical characteristics. A logistic regression analysis, investigating predictors of mortality, as well as Kaplan-Meier survival analyses, were performed. RESULTS: One hundred and eighty eight patients with individual data from 112 articles and 671 patients with pooled data from 12 articles were included in the meta-analyses. Of patients with individual data, pulmonary infection was the most common manifestation (n = 106/188, 56.4%). One third (n = 61/188, 32.4%) suffered from isolated extra-pulmonary and 21/188 (11.2%) from disseminated disease. In 288 patients with pooled data and pulmonary affection, clinical relevance was high with 68% (95% CI 44-85%) of patients fulfilling criteria for clinical disease. Macrolide and rifamycin-containing regimens were associated with improved survival (adjusted OR 0.12, 95% CI 0.03-0.42, p = 0.002, and 0.23, 95% CI 0.04-0.86, p = 0.03, for lethal events, respectively). CONCLUSION: In this study, we provide a detailed clinical description of M. malmoense infections. The pathogen is of high clinical relevance for the individual patient with more than 2 out of 3 patients having relevant disease and >40% of manifestations being extra-pulmonary or disseminated. Macrolide and rifamycin-containing regimens are associated with improved survival.

Medical Causes of Hospitalisation among Patients with Bronchiectasis: A Nationwide Study in Japan.

PURPOSE: Although the international guidelines for managing bronchiectasis are centred on preventing the exacerbation of bronchiectasis, the medical causes of admissions to hospital among patients with bronchiectasis have not been fully investigated. METHODS: This study targeted patients with bronchiectasis who were admitted to hospitals between April 2018 and March 2020 using the national inpatient database in Japan. The causes of hospitalisation and types of antibiotics used for hospitalised patients were recorded. RESULTS: In total, 21,300 hospitalisations of 16,723 patients with bronchiectasis were analysed. The most common cause was respiratory diseases in 15,145 (71.1%) admissions, including bacterial pneumonia and the exacerbation of bronchiectasis in 6238 (41.2%) and 3151 (20.8%), respectively. Antipseudomonal antibiotics were used in approximately 60% of patients with bacterial pneumonia who were administered antibiotic treatments and in approximately 50% of patients with the exacerbation of bronchiectasis. CONCLUSIONS: Bacterial pneumonia was the most frequent cause of hospitalisation, followed by the exacerbation of bronchiectasis, among patients with bronchiectasis. Physicians need to focus on the prevention of bacterial pneumonia in addition to the exacerbation of bronchiectasis in patients with bronchiectasis.

Nebulized hypertonic saline and positive expiratory pressure device use in patients with bronchiectasis: Analysis from the United States Bronchiectasis and NTM research registry.

BACKGROUND: Nebulized Hypertonic saline (HS) and positive expiratory pressure device (PEP) are often used in patients with bronchiectasis. We sought to describe the clinical characteristics in patients using HS and PEP, utilizing a large national database registry. METHODS: Data from the US Bronchiectasis and NTM Research Registry were used in this study. Patients with a diagnosis of bronchiectasis were included. Eligible patients were assigned to one of four mutually exclusive groups: HS only, PEP only, HS & PEP, or no airway clearance or mucoactive agent. Descriptive statistics were computed for the overall study population and stratified by the four groups. One-way ANOVA and chi-square tests were used to test the difference in the means in continuous variables and the association between categorical variables (respectively) across the four groups. RESULTS: A total of 2195 patients were included. Of those with bronchiectasis and a productive cough, a greater number of patients utilized HS only vs PEP only (17.5 % vs 9.1 %, p < 0.001). Similar association was found in those with Pseudomonas aeruginosa (22.3 % HS only vs 6.5 % PEP only, p < 0.001). There was a higher number of patients who used HS and PEP therapy in combination vs PEP therapy alone (25.0 % vs 9.1 %, p = 0.002), in those with a productive cough. CONCLUSIONS: In patients with bronchiectasis and a productive cough or Pseudomonas aeruginosa, HS is used more often than PEP alone. There is a need for further analysis to compare these two modalities and explore the factors influencing their utilization.

Diagnostic value and safety of medical thoracoscopy in undiagnosed pleural effusions-a prospective observational cohort study.

Background: With the need for "actionable histology" in the current era of targeted cancer treatment, and the increasing practice of upfront thoracoscopy (without a prior diagnostic thoracentesis) or a "biopsy first" approach in suspected malignant pleural effusions (MPEs), we sought to prospectively evaluate the diagnostic accuracy, including full molecular profiling of cancer, and safety of medical thoracoscopy (MT) at a tertiary referral hospital. Methods: Patients with MT performed for an undiagnosed pleural effusion between January 2020 and December 2022 were included in this observational cohort study. All procedures were performed with a semirigid thoracoscope under conscious sedation. Clinical outcomes and adverse events were recorded prospectively. Results: We evaluated 141 patients, with a mean age of 67±12 years. Talc poudrage was performed in 67 (47.5%) patients with a median of 2 [interquartile range (IQR), 1-4] hospitalisation days after MT. Upfront thoracoscopy was performed in approximately half (55.3%) of patients. The overall diagnostic accuracy of MT was 95.7% in our cohort. A final diagnosis of cancer was made in 116 (82.3%) patients, with lung (67.2%) and breast cancer (8.6%) the most common. The diagnostic sensitivity of MT for malignancy was 94.8%, and molecular profiling of relevant cancer types for oncogenic mutations was achieved in all patients with malignancy seen on histopathology. The most common non-malignant diagnosis was tuberculous pleuritis in 14 patients (9.9%). Major complications occurred in 3 (2.1%) patients. Two patients had re-expansion pulmonary edema that resolved with low flow oxygen supplementation in the general ward, and one patient required intensive care unit admission for cardiac tamponade from a malignant pericardial effusion. There were no cases of mortality, bleeding complications or persistent air leaks. Conclusions: MT is a well-tolerated and effective option for the evaluation of undiagnosed pleural effusions. With expanding utility and expertise with MT and other pleural interventions, the challenge for respiratory physicians is integrating these into expeditious diagnostic and effective therapeutic pathways, individualised to patients' needs.