TB and interstitial lung disease: a systematic review and meta-analysis.

To determine the frequency of TB among patients with interstitial lung diseases (ILDs).We performed a comprehensive search in the PubMed/Medline, EMBASE and Scopus databases up to 1 August 2023 of studies reporting on the prevalence of TB among patients with ILDs.Twelve studies comprising 3,817 patients with ILD were found: the pooled prevalence of TB among ILD patients was 11.0% (95% CI 5.4-21.0). In the subgroup analysis, the TB rate among patients with silicosis and idiopathic pulmonary fibrosis (IPF) was respectively 35.6% (95% CI 32.6-38.8) and 4.4% (95% CI 3.6-5.3) (P = 0.00). The frequency of TB among ILD patients was higher in high TB burden countries than in low/intermediate-burden countries: 26.3%, 95% CI 17.7-37.3 vs. 4.9%, 95% CI 3.3-7.2; P = 0.00.This study shows the frequency of TB among ILD patients. The meta-analysis reveals a significantly increased prevalence of TB among ILD patients with silicosis compared to IPF, and among individuals in high TB burden countries than in those with low/intermediate burden. The study results can help physicians and policymakers make efficient decisions for prompt screening and anti-TB treatment initiation in ILD patients..

Factors influencing delayed discharge after day-surgery laparoscopic cholecystectomy: the DeDiLaCo study protocol.

OBJECTIVE: Laparoscopic cholecystectomy (LC) is the gold standard for most benign gallbladder diseases. Early discharge (<24 hours) has the same outcomes as longer (>24 hours) hospital stay. Nevertheless, the rate of delayed discharge >24 hours range from 4.6% to 37%. The primary endpoint of this Italian nationwide study is to analyze the prevalence of patients undergoing elective LC who experienced a delayed discharge >24 hours and identify potential limiting factors of early discharge. Results from these analyses will be used to select patients who can be safely discharged on the same day after surgery. Secondary endpoints will be to evaluate the patient's quality of life (QoL), assess the direct health costs associated with late discharge, and quantify the patient's involvement in the treatment process. PATIENTS AND METHODS: This prospective, observational study was conducted following a resident-led model and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. All patients were treated according to the local hospital protocol and received routine care as standard therapy. RESULTS: We expected to obtain the enrollment of at least 500 patients based on an assumed difference in discharge delay between the reference and the recruitable population of 6% and the identification of factors related to discharge failure within 24 h. Early discharge after LC leads to advantages both in terms of clinical outcomes and quality of life of the patient, and it is highly effective in terms of health costs and shortening the waiting list. However, clinical reality differs from the results of randomized studies by a complex series of non-objectionable real-world data influencing treatment plans. Therefore, we expected to identify independent predictors and factors of failure of early discharge. CONCLUSIONS: Clinical reality often differs from randomized trial results. In Italy, the vast majority of delayed discharges after LC may not be related to surgery and can be prevented both with logistical reorganization and with a readjustment of the trust reimbursement policies.

Silicosis and tuberculosis: A systematic review and meta-analysis.

INTRODUCTION: Silicosis mostly happens in workers with high silica exposure and may accompany the development of various diseases like tuberculosis, cancer, or autoimmune diseases. The term silico-tuberculosis describes a condition in which an individual is affected by both silicosis and tuberculosis at the same time. This systematic review and meta-analysis study was conducted to evaluate the risk of tuberculosis in silicosis patients and individuals exposed to silica dust. METHODS: We performed a systematic search for relevant studies up to 6 September 2022 using PubMed/ Medline, and Embase with the following keywords in titles or abstracts: "silicosis" OR "silicoses" OR "pneumoconiosis" OR "pneumoconioses" AND "tuberculosis". Cohort and case-control studies containing relevant and original information about tuberculosis infection in silicosis patients were included for further analysis. Pooled estimates and 95% confidence intervals (CI) for the relative risk of tuberculosis in individuals with silicosis compared to those without; these were evaluated using the random effects model due to the estimated heterogeneity of the true effect sizes. RESULTS: Out of 5352 potentially relevant articles, 7 studies were eligible for systematic review, of which 4 cohort studies were included for meta-analysis. The total population of all studies was 5884, and 90.63% were male. The mean age of participants was 47.7 years. Our meta-analysis revealed a pooled risk ratio of 1.35 (95%CI 1.18-1.53, I 2: 94.30%) which means an increased risk of silicosis patients and silica-exposed individuals to tuberculosis infection. CONCLUSION: Silicosis and silica dust exposure increase the risk of tuberculosis. Therefore, we suggest that individuals with long-time silica exposure, like mine workers, be routinely considered for both silicosis and tuberculosis screening programs.

Infections in lung transplanted patients: A review.

Lung transplantation can improve the survival of patients with severe chronic pulmonary disorders. However, the short- and long-term risk of infections can increase morbidity and mortality rates. A non-systematic review was performed to provide the most updated information on pathogen, host, and environment-related factors associated with the occurrence of bacterial, fungal, and viral infections as well as the most appropriate therapeutic options. Bacterial infections account for about 50% of all infectious diseases in lung transplanted patients, while viruses represent the second cause of infection accounting for one third of all infections. Almost 10% of patients develop invasive fungal infections during the first year after lung transplant. Pre-transplantation comorbidities, disruption of physical barriers during the surgery, and exposure to nosocomial pathogens during the hospital stay are directly associated with the occurrence of life-threatening infections. Empiric antimicrobial treatment after the assessment of individual risk factors, local epidemiology of drug-resistant pathogens and possible drug-drug interactions can improve the clinical outcomes.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Bronchoscopic sampling techniques in the era of technological bronchoscopy.

Flexible bronchoscopy is a key diagnostic and therapeutic tool. New endoscopes and technologically advanced navigational modalities have been recently introduced on the market and in clinical practice, mainly for the diagnosis of mediastinal lymph adenopathies and peripheral lung nodules. Bronchoscopic sampling tools have not changed significantly in the last three decades, with the sole exception of cryobiopsy. We carried out a non-systematic, narrative literature review aimed at summarizing the scientific evidence on the main indications/contraindications, diagnostic yield, and safety of the available bronchoscopic sampling techniques. Performance of bronchoalveolar lavage, bronchial washing, brushing, forceps biopsy, cryobiopsy and needle aspiration techniques are described, focusing on indications and diagnostic accuracy in the work-up of endobronchial lesions, peripheral pulmonary abnormalities, interstitial lung diseases, and/or hilar-mediastinal lymph adenopathies. Main factors affecting the diagnostic yield and the navigational methods are evaluated. Preliminary data on the utility of the newest sampling techniques (i.e., new needles, triple cytology needle brush, core biopsy system, and cautery-assisted transbronchial forceps biopsy) are shown. TAKE HOME MESSAGE: A deep knowledge of bronchoscopic sampling techniques is crucial in the era of technological bronchoscopy for an optimal management of respiratory diseases.

Efficiency of desensitizing materials in xerostomic patients with head and neck cancer: a comparative clinical study.

OBJECTIVES: To assess the clinical effectiveness of four desensitizing materials in patients who are xerostomic due to radiotherapy for head and neck cancer (HNC) in comparison to a healthy group with normal salivation. METHODS AND MATERIALS: The study was conducted as a split-mouth randomized clinical trial. Forty HNC patients (group A) and 46 healthy patients (group B) suffering from dentin hypersensitivity (DH) were included. Salivary flow was determined through a scialometric test. Hypersensitivity was assessed with air stimulus and tactile stimulus. The materials used as desensitizing agents were Vertise Flow, Universal Dentin Sealant, Clearfil Protect Bond, and Flor-Opal Varnish. The response was recorded before application of the materials, immediately after, and at 1 week, 4 weeks, and 12 weeks. RESULTS: Salivary flow rates in groups A/B were 0.15/0.53 mL/min (unstimulated) and 0.54/1.27 mL/min (stimulated), respectively. In group A, 100 hypersensitive teeth were included. Application of the desensitizing agents significantly decreased the hypersensitivity immediately and throughout the 4-week follow-up (p < 0.001). However, after the 12-week timepoint, a loss of efficacy was detected in all agents (p = 0.131). In group B, 116 hypersensitive teeth were included. The materials performed a more stable action, although a loss of effectiveness was detected at 12-week control (p = 0.297). CONCLUSION: The efficiency of the desensitizing agents after the first application was similar in both groups. In the radiated group, this effect lasted for shorter periods than in healthy controls. CLINICAL RELEVANCE: HNC patients with hyposalivation may be a new risk group for DH.

Tuberculosis and latent tuberculous infection screening of migrants in Europe: comparative analysis of policies, surveillance systems and results.

Migration patterns into and within Europe have changed over the last decade. In 2015, European Union (EU) countries received over 1.2 million asylum requests, more than double the number registered in the previous year. This review compares the published literature on policies for tuberculosis (TB) and latent tuberculous infection (LTBI) screening in EU and European Free Trade Association (EFTA) countries with the existing TB/LTBI screening programmes for migrants in 11 EU/EFTA countries based on a survey of policy and surveillance systems. In addition, we provide a systematic review of the literature on the yield of screening migrants for active TB and LTBI in Europe. Published studies provide limited information about screening coverage and the yield of screening evaluations in EU/EFTA countries. Furthermore, countries use different screening strategies and settings, and different definitions for coverage and yield of screening for active TB and LTBI. We recommend harmonising case definitions, reporting standards and policies for TB/LTBI screening. To achieve TB elimination targets, a European platform for multi-country data collection and analysis, sharing of countries' policies and practices, and harmonisation of migrant screening strategies is needed.

Clinical research in the treatment of tuberculosis: current status and future prospects.

To supplement previous state-of-art reviews on anti-tuberculosis treatment and to pave the way forward with reference to the current status, we systematically reviewed published literature on clinical research on tuberculosis (TB) over the past decade in the treatment of drug-susceptible and multidrug-resistant TB (MDR-TB), with a focus on drugs, dosing factors and regimens. Our review was restricted to Phase II/III clinical trials, cohort and case-control studies, and systematic reviews of clinical studies. TB programmatic and patient behavioural factors, non-TB drugs, adjunctive surgery, new vaccines, immunotherapy, antiretroviral therapy and management of latent tuberculous infection are outside the scope of this review. An algorithm was used to systematically search PubMed for relevant articles published in English from 1 January 2005 to 31 December 2014. Articles without evaluated factors (drugs, dosing factors and regimens) or comparative analysis of specified anti-tuberculosis treatment outcomes were excluded. Of the 399 articles initially identified, 294 were excluded. The main findings of the remaining 105 articles are described under two categories: presumed drug-susceptible TB and MDR-TB. Fifty-nine articles included under drug-susceptible TB were divided into 12 subcategories: isoniazid, rifampicin, pyrazinamide, fluoroquinolones, fixed-dose combination drugs, dosing frequency, treatment phases, treatment duration, experimental regimens for pulmonary (surrogate markers vs. clinical outcomes) and extra-pulmonary TB. Forty-nine articles included under MDR-TB were divided into seven subcategories: fluoroquinolones, pyrazinamide, second-line injectable drugs, World Health Organization Group 4 and Group 5 drugs, MDR-TB regimens and novel drugs. Clinical research in the last decade and ongoing trials might furnish new paradigms for improving the treatment of this recalcitrant ancient disease.

Thiophene-based compounds as fluorescent tags to study mesenchymal stem cell uptake and release of taxanes.

Human mesenchymal stem cells (hMSC) are multipotent cells that display the unique ability to home and engraft in tumor stroma. This remarkable tumor tropic property has generated a great deal of interest in many clinical settings. Recently, we showed that hMSC represent an excellent base for cell-mediated anticancer therapy since they are able to internalize paclitaxel (PTX) and to release it in an amount sufficient to inhibit tumor cell proliferation. In order to shed light on the dynamics of drug uptake and release, in the present paper we describe the synthesis of two novel thiophene-based fluorophore-paclitaxel conjugates, namely PTX-F32 and PTX-F35, as tools for in vitro drug tracking. We aimed to study the ability of these novel derivatives to be efficiently internalized by hMSC and, in a properly engineered coculture assay, to be released in the medium and taken up by tumor cells. In order to ensure better stability of the conjugates toward enzymatic hydrolysis, the selected oligothiophenes were connected to the taxol core at the C7 position through a carbamate linkage between PTX and the diamino linker. Antiproliferative experiments on both tumor cells and stromal cells clearly indicate that, in good correlation with the parent compound, cells are sensitive to nanomolar concentrations of the fluorescent conjugates. Moreover, in the coculture assay we were able to monitor, by fluorescence microscopy, PTX-F32 trafficking from hMSC toward glioblastoma U87 tumor cells. Our work paves the way for novel possibilities to perform extensive and high quality fluorescence-based analysis in order to better understand the cellular mechanisms involved in drug trafficking, such as microvescicle/exosome mediated release, in hMSC vehicle cells.

Mesenchymal stem cells as delivery vehicle of porphyrin loaded nanoparticles: effective photoinduced in vitro killing of osteosarcoma.

Mesenchymal stem cells (MSC) have the unique ability to home and engraft in tumor stroma. These features render them potentially a very useful tool as targeted delivery vehicles which can deliver therapeutic drugs to the tumor stroma. In the present study, we investigate whether fluorescent core-shell PMMA nanoparticles (FNPs) post-loaded with a photosensitizer, namely meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) and uploaded by MSC could trigger osteosarcoma (OS) cell death in vitro upon specific photoactivation. In co-culture studies we demonstrate using laser confocal microscopy and time lapse imaging, that only after laser irradiation MSC loaded with photosensitizer-coated fluorescent NPs (TPPS@FNPs) undergo cell death and release reactive oxygen species (ROS) which are sufficient to trigger cell death of all OS cells in the culture. These results encourage further studies aimed at proving the efficacy of this novel tri-component system for PDT applications.

Impact of a Mycobacterium tuberculosis-specific interferon-γ release assay in bronchoalveolar lavage fluid for a rapid diagnosis of tuberculosis.

OBJECTIVES: Evaluation of different methods for an initial treatment decision in individuals with suspected pulmonary tuberculosis. BACKGROUND: Recently, important advances regarding the diagnosis of pulmonary tuberculosis have been introduced, which influence the decision to initiate anti-tuberculosis treatment. METHODS: To evaluate the impact of different methods for the presumed diagnosis of tuberculosis, individuals with suspected tuberculosis were prospectively enrolled following a specific algorithm including initial smear microscopy and Mycobacterium tuberculosis-specific nucleic acid amplification (NAAT) from sputum. In cases of negative initial test results, tuberculin skin testing, bronchoscopy with transbronchial biopsies and interferon-γ release assays (IGRAs) in peripheral blood and bronchoalveolar lavage (BAL) fluid were performed. RESULTS: Amongst 135 individuals with suspected tuberculosis, 42 had tuberculosis, 10 had nontuberculous mycobacteria pulmonary infection/colonization (one had both tuberculosis and nontuberculous mycobacteria pulmonary infection/colonization) and 84 had an alternative final diagnosis. The sensitivity and specificity were 41% and 99% [positive likelihood ratio (LR+) = 40] for sputum microscopy and 31% and 98% (LR+) = 16) for BAL nucleic acid amplification, respectively. In patients with acid-fast bacilli smear-negative tuberculosis (25/42, 59.5%), M. tuberculosis-specific BAL fluid IGRA was 92% sensitive and 87% specific (LR+) = 7) for the diagnosis of tuberculosis. CONCLUSION: None of the microbiological or immunological methods that aim to provide a rapid diagnosis of tuberculosis whilst waiting the confirmation of the M. tuberculosis culture results is on its own accurate enough to diagnose or exclude pulmonary tuberculosis. Negative sputum microscopy and M. tuberculosis-specific NAAT results should prompt bronchoscopy including BAL for M. tuberculosis-specific IGRA in individuals with suspected pulmonary tuberculosis.

The best on infections: update from the 2010 ERS Congress.

Respiratory tract infections and tuberculosis are among the leading reasons for seeking medical care. In this report the most recent advances in the field of clinical research and basic sciences of respiratory infections and tuberculosis are presented through the analysis of some of the best abstracts presented at the 20th European Respiratory Society Congress in Barcelona, Spain and their subsequent publications in major journals. The role of viruses in chronic obstructive pulmonary disease exacerbations, the importance of new biomarkers in the management and risk assessment of lower respiratory tract infections, new modalities of treatment of respiratory infections as well as new tools for the diagnosis of latent and active tuberculosis in special subgroups of patients (children and immunocompromised individuals), and the new epidemiological threat of multidrug-resistant and extensively drug-resistant tuberculosis cases are discussed.

Tuberculosis and noncommunicable diseases: neglected links and missed opportunities.

Globally, the incidence of tuberculosis (TB) is declining very slowly, and the noncommunicable disease (NCD) burden for many countries is steadily increasing. Several NCDs, such as diabetes mellitus, alcohol use disorders and smoking-related conditions, are responsible for a significant proportion of TB cases globally, and in the European region, represent a larger attributable fraction for TB disease than HIV. Concrete steps are needed to address NCDs and their risk factors. We reviewed published studies involving TB and NCDs, and present a review and discussion of how they are linked, the implications for case detection and management, and how prevention efforts may be strengthened by integration of services. These NCDs put patients at increased risk for developing TB and at risk for poor treatment outcomes. However, they also present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for both TB and NCDs. Hastening the global decline in TB incidence may be assisted by strengthening these types of activities.

The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement.

Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-γ release assays or, as an alternative in individuals without a history of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-γ release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.

Development of a standardised multidrug-resistant/extensively drug-resistant tuberculosis assessment and monitoring tool.

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) threaten global TB control. The MDR/XDR-TB Assessment and Monitoring Tool was developed to standardise evaluations of country capacity to prevent, diagnose and treat MDR/XDR-TB and identify program gaps. It provides data to guide national plans, generates baseline data to measure progress, provides information for Green Light Committee (GLC) and Global Fund to Fight AIDS, Tuberculosis and Malaria applications, guides technical assistance and informs donor investment. In field testing, the tool scoring system performed equally well in high- and low-prevalence settings. This GLC-endorsed tool supports global efforts to contain MDR/XDR-TB and is useful in developing national MDR/XDR-TB control strategies.

[Smoking habit and behaviour among health professionals]. / Indagine conoscitiva sull'abitudine al fumo del personale sanitario.

The study reports the results of a survey by questionnaire on the health staff's smoking habits in the Hospital-University Complex of Sassari. Thirty-one percent are smokers: 35.5% among nurses, 21.4% among doctors and 40.4% among service staff. Daily smokers are 87.2% and 46% smoke 10 or more cigarettes per day. The great part of the sample thinks that it has to participate in tobacco control programs, although 6.0% of doctors disagree. Multiple correspondence analysis showed different profiles on attitudes and smoking habits among health staff components. Among no-smokers, nurses, technicians and service staff are not favorable to the tobacco control campaigns thinking they should not be a role model to others. Among smokers, service staff and some physicians showed a similar profile; moreover, they smoke in front of patients. These results indicate that the smoking attitude of some health staff components might be a "negative" model to which refer and it might interfere with tobacco control programs.