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Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes. We conducted a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase from January 1, 2005, through April 3, 2023. Included studies reported WHO treatment outcomes, or adaptions hereof, for pre-extensively and/or extensively drug-resistant tuberculosis patients according to the 2006 WHO definition. Eligible studies included cohorts of at least 10 adults (aged>18 years) that were not pregnant. Using a random-effects model, we calculated pooled proportions of treatment outcomes and performed sensitivity and subgroup analyses. PROSPERO registration number: CRD42022340961. Among 5056 studies reviewed, we identified 94 studies from 26 countries, involving 10,223 extensively drug-resistant tuberculosis patients. The pooled proportion of successful treatment outcomes was 44.2% (95%CI: 38.3–50.3). Sensitivity analyses consistently produced similar estimates. A slight improvement in treatment outcomes was observed after 2013. Furthermore, 25 studies reported outcomes for 3564 individuals with pre-extensively drug-resistant tuberculosis, of which 63.3% achieved successful treatment (95%CI: 43.1–72.5). Globally, the success rate of extensively drug-resistant tuberculosis treatment is 44.2%, far below the WHO's target rate of 75%. These results may serve as a reference for future studies assessing extensively drug-resistant tuberculosis treatment outcomes under the 2021 definition treated with better treatment regimens available. Comprehensive surveillance data of extensively drug-resistant tuberculosis outcomes from the whole world are desirable to monitor treatment progress. [ABSTRACT FROM AUTHOR]

• Baricitinib, an anti-JAK1/JAK2, reduces cytokine release and SARS-Co-V2 entry. • In a retrospective multicenter study baricitinib reduces COVID-19 mortality rate. • Baricitinib reduces intensive care unit admissions of COVID-19 pneumonia. • Baricitinb reduces SARS-CoV-2 viral burden detected by nasopharyngeal swab. • Baricitinib used for 2 weeks was not associated with serious adverse events. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Estimated 2017 tuberculosis (TB) incidence is 10 million and mainly depends on the reservoir of individuals with latent TB infection (LTBI). QuantiferonⓇ-TB Gold in-Tube (QFT-GIT) is one of the tests used for LTBI detection. Since 2015 a new version, QuantiferonⓇ-TB Gold Plus (QFT-Plus) is available.Objectives: To perform a systematic review and meta-analysis to assess the diagnostic accuracy for TB of QFT-Plus compared to QFT-GIT.Methods: PubMed and Scopus were used to detect records related to predefined strings from 2015 to 2018. Full text articles dealing with the sensitivity and/or specificity of the QFT-Plus vs. QFT-GIT for active-TB and LTBI detection were analyzed. Scientific quality and risk of bias were assessed using QADAS-2.Results: We selected 15 articles. Studies were mainly observational and cross-sectional, performed in 8 countries. Sample size differed in the TB group (27 to 164) compared to LTBI group (29 to 1031). Pooled sensitivity of QFT-Plus for active-TB was 0.94 (0.91 and 0.95 for TB1 and TB2, respectively), whereas pooled specificity for healthy status was 0.96. Pooled sensitivity and specificity for LTBI was 0.91 and 0.95, respectively.Conclusions: We show that QFT-Plus is more sensitive compared to QFT-GIT for detecting M. tuberculosis infection, mainly due to TB2 responses. [ABSTRACT FROM AUTHOR]

Aim: To describe the phenotypic and genotypic profiles of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains isolated from patients with invasive infections at an Italian university hospital in order to assess the epidemiological trend.Methods: An observational prospective study was undertaken at the University Hospital of Sassari, Italy to detect KPC-Kp strains in patients with invasive bacteraemia. Isolates were identified phenotypically; carbapenemase production was assessed using phenotypic and genotypic methods. Sequencing of blaKPC genes, pulsed-field gel electrophoresis and multi-locus sequence typing were performed.Results: During the period 2015-2017, 46 cases of invasive infection with K. pneumoniae were recorded. Two-thirds (67.4%) of the patients were male, and the mean age was 69.4 years. Most patients had at least one comorbidity (56.5%) and/or had been hospitalized previously (70.5%), 81.8% had current or recent medical device use, and 85.4% had recent antibiotic exposure. The mortality rate was 52.3%. A multi-drug-resistant pattern (including carbapenems, fluoroquinolones, third-/fourth-generation cephalosporins) was shown for all K. pneumoniae isolates. KPC-3 and -2 were produced by all strains. The most common sequence types were 512 (91.3%) and 101 (8.7%), grouped into three clusters (A, A1 and B).Conclusions: A high incidence of KPC-Kp in patients with invasive infections was recorded at an Italian university hospital compared with the incidence measured before 2015. This study confirmed the importance of the KPC-3 carbapenemase variant, as reported by other Italian studies. High mortality and comorbidity rates appear to be associated with KPC-Kp infection. [ABSTRACT FROM AUTHOR]

Background Reprocessing of endoscopes is key to preventing cross-infection after colonoscopy. Culture-based methods are recommended for monitoring, but alternative and rapid approaches are needed to improve surveillance and reduce turnover times. A molecular strategy based on detection of residual traces from gut microbiota was developed and tested using a multicenter survey. Methods A simplified sampling and DNA extraction protocol using nylon-tipped flocked swabs was optimized. A multiplex real-time polymerase chain reaction (PCR) test was developed that targeted 6 bacteria genes that were amplified in 3 mixes. The method was validated by interlaboratory tests involving 5 reference laboratories. Colonoscopy devices (n = 111) were sampled in 10 Italian hospitals. Culture-based microbiology and metagenomic tests were performed to verify PCR data. Results The sampling method was easily applied in all 10 endoscopy units and the optimized DNA extraction and amplification protocol was successfully performed by all of the involved laboratories. This PCR-based method allowed identification of both contaminated (n = 59) and fully reprocessed endoscopes (n = 52) with high sensibility (98%) and specificity (98%), within 3-4 hours, in contrast to the 24-72 hours needed for a classic microbiology test. Results were confirmed by next-generation sequencing and classic microbiology. Conclusions A novel approach for monitoring reprocessing of colonoscopy devices was developed and successfully applied in a multicenter survey. The general principle of tracing biological fluids through microflora DNA amplification was successfully applied and may represent a promising approach for hospital hygiene. [ABSTRACT FROM AUTHOR]

Summary In spite of the recent introduction of two new drugs (delamanid and bedaquiline) and a few repurposed compounds to treat multidrug-resistant and extensively drug-resistant tuberculosis (MDR- and XDR-TB), clinicians are facing increasing problems in designing effective regimens in severe cases. Recently a 9 to 12-month regimen (known as the ‘Bangladesh regimen’) proved to be effective in treating MDR-TB cases. It included an initial phase of 4 to 6 months of kanamycin, moxifloxacin, prothionamide, clofazimine, pyrazinamide, high-dose isoniazid, and ethambutol, followed by 5 months of moxifloxacin, clofazimine, pyrazinamide, and ethambutol. However, recent evidence from Europe and Latin America identified prevalences of resistance to the first-line drugs in this regimen (ethambutol and pyrazinamide) exceeding 60%, and of prothionamide exceeding 50%. Furthermore, the proportions of resistance to the two most important pillars of the regimen – quinolones and kanamycin – were higher than 40%. Overall, only 14 out of 348 adult patients (4.0%) were susceptible to all of the drugs composing the regimen, and were therefore potentially suitable for the ‘shorter regimen’. A shorter, cheaper, and well-tolerated MDR-TB regimen is likely to impact the number of patients treated and improve adherence if prescribed to the right patients through the systematic use of rapid MTBDRsl testing. [ABSTRACT FROM AUTHOR]

Summary Background Childhood vaccination with Mycobacterium bovis Bacille Calmette-Guérin (BCG) reduces the risk of infection with Mycobacterium tuberculosis and the risk of severe forms of tuberculosis in children. The protection of adults from pulmonary tuberculosis is doubtful. This study evaluated the effect of the vaccination on the growth of M. tuberculosis human bronchoalveolar mononuclear cells (BALMC). Methods Healthy, adult healthcare workers who were regularly exposed to M. tuberculosis , household tuberculosis contacts, and cured tuberculosis patients were recruited in a multicentre study conducted in Germany. BALMC were co-cultured with different strains of M. tuberculosis in growth inhibition assays (MGIAs). Results MGIAs on BALMC were conducted in 90 contact persons (known vaccination status, n = 75) and 62 former tuberculosis patients (known status, n = 22). Growth rates for M. tuberculosis H37Rv in BALMC were independent of the vaccination status, both in healthy contacts and in cured tuberculosis patients. This finding was validated in growth inhibition assays using two different Haarlem M. tuberculosis outbreak strains. Subgroup analyses based on the Interferon-gamma release assay status found no impact of the vaccination on mycobacterial growth. Conclusions This study suggests that M. bovis BCG vaccination does not alter the anti-mycobacterial capacity of BALMC as assessed in ex-vivo growth inhibition assays. [ABSTRACT FROM AUTHOR]

Summary In this article we describe the key role of tuberculosis (TB) treatment, the challenges (mainly the emergence of drug resistance), and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM) is discussed in detail. Treatment success in multidrug-resistant (MDR) TB cases is low (62%, with 7% failing or relapsing and 9% dying) and in extensively drug-resistant (XDR) TB cases is even lower (40%, with 22% failing or relapsing and 15% dying). The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB) and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world. [ABSTRACT FROM AUTHOR]

A large number of people worldwide grapple with Major Depressive Disorder (MDD), and a significant portion of them confront resistance to conventional antidepressant treatments. Esketamine, an innovative intervention, has garnered attention due to its rapid-acting antidepressant effects. This meta-analysis aimed to evaluate the efficacy and safety of esketamine in individuals with MDD and Treatment-Resistant Depression (TRD). We performed an extensive search of electronic databases, including PubMed, EMBASE, and Cochrane Library, covering the period from inception to January 15, 2024, to identify clinical trials investigating the efficacy, safety, and tolerability of esketamine in individuals with MDD and TRD. Meta-analyses were conducted using a random-effect model, with the risk ratio (RR) chosen as the effect size. After screening, nine studies met inclusion criteria comprising 1752 patients. Esketamine dosages varied from 28 to 84 mg, administered intranasally in conjunction with an oral antidepressant. Intranasal esketamine exhibited significantly higher remission rates compared to the placebo (RR = 1.371, 95% CI: 1.194 to 1.574, p < 0.0001). Subgroup analysis revealed that the 84 mg and flexible doses were particularly effective. Moreover, intranasal esketamine demonstrated higher response rates compared to the placebo (RR = 1.274, 95% CI: 1.108 to 1.465, p-value = 0.001). Although adverse events were common in the esketamine group, they were generally tolerable. Intranasal esketamine demonstrated effectiveness in reducing scores among patients with MDD and TRD. The drug exhibited both safety and tolerability. However, further research is warranted to investigate its long-term effects and efficacy in specific patient subgroups. [ABSTRACT FROM AUTHOR]

• The study of chemical composition of psammoma bodies in thyroid cancer is performed. • The main component found by IR analysis is amorphous carbonated calcium phosphate. • Using XRF, ICP and EDX imaging the elements detected are Ca, P, Na, Mg, Fe and Zn. Recently the knowledge of chemical composition of pathological mineralizations is an important topic extensively studied because it could give more in-depth information to understand pathologies themselves and to improve prevention methods. In this work, psammoma bodies (PBs) microcalcifications in thyroid cancer tissue are investigated by different and complementary analytical methods as: micro-Fourier transformed spectroscopy, X-ray fluorescence spectroscopy, Inductively Coupled plasma Optical Emission Spectroscopy (ICP-OES) and scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy imaging (EDX). For the first time the micro-FTIR analysis of the only inorganic phase isolated from PBs was reported. Signals of the recorded spectrum showed that the main component of the calcifications is the amorphous carbonated calcium phosphate, and the IR spectrum of thyroid PBs is strongly consistent with that of PBs in human ovarian tumors. The XRF and the ICP analysis detected also the presence of iron ad zinc in thyroid PBs. These results are validated by scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy imaging (EDX) carried out on tissue samples of the papillary thyroid carcinoma. By these analytical methods magnesium and sodium were detected within PBs while the presence of iron was confirmed by the Perls test. Summarizing the results of applied analytical methods, the main detected elements within the thyroid psammoma bodies are Ca, P, Mg, Na, Fe and Zn. Magnesium and sodium are found in malignant breast cancer microcalcifications, thus they seem correlated to neoplastic transformation. The Fe and Zn elements could give information about the origin of these pathological microcalcifications. [ABSTRACT FROM AUTHOR]

The management of multidrug-resistant tuberculosis (TB) is associated with low treatment success, high mortality and failure rates. New drugs and novel short-therapeutic regimens have only recently helped overcome these obstacles. We carried out a narrative literature review aimed at summarizing the scientific evidence on the recent therapeutic advances in the field of drug-resistant TB. Experimental and observational studies on novel (i.e. bedaquiline, delamanid, pretomanid) drugs and novel regimens and the main pharmacological characteristics of the newest compounds are described. We also highlight the main scientific evidence on therapeutic strategies complementary to standard chemotherapy (i.e. new approaches to drug delivery, host-directed therapy, surgery, new collapse therapy, rehabilitation, and palliative care). • The clinical management of DR-TB cases is associated with lower treatment success, higher mortality and failure rates. • New and repurposed drug options have helped improve the therapeutic approach for drug-resistant tuberculosis. • Studies on safe, effective, all-oral, short-course therapeutic regimens have started to provide new anti-TB products. • New oral compounds in trial phase 2 have a potential future role in MDR-TB treatment. • Therapeutic strategies complementary to standard chemotherapy might be useful in difficult MDR-TB. [ABSTRACT FROM AUTHOR]

• Tuberculosis is an important clinical and public health issue worldwide. • Old TB therapies aimed to improve hygiene conditions, strengthen immune system, achieve the rest of the affected lungs. • New options based on old therapies have been explored: their potential implementation may be useful for drug resistant TB. Tuberculosis (TB) is an important clinical and public health issue worldwide. Despite improved treatment success rates following the introduction of antibiotics in daily clinical practice, the expected decline in incidence has been hampered by HIV epidemics and multi- and extensively drug-resistant TB. During the pre-antibiotic era, TB therapies were mainly based on improving hygiene conditions, strengthening the immune system, and targeting the rest of the affected lungs with invasive techniques. Detailed knowledge of old non-pharmacological therapies might support physicians and researchers in the identification of new solutions for difficult-to-treat patients. We performed a narrative literature review on the main old therapeutic options prescribed for patients with TB. The main recommendations and contraindications of sanatorium therapies (i.e., bed rest, fresh air, sunlight) and pulmonary collapse techniques are reviewed, evaluating their physiological basis and their impact on patient outcomes. We report studies describing new interventional pulmonary and surgical techniques and assess new perspectives based on old medical and surgical treatments, whose potential implementation could help complicated patients. [ABSTRACT FROM AUTHOR]

The estimated number of people deprived of liberty is increasing, with 11.55 million incarcerated globally in 2021. Transmission of Mycobacterium tuberculosis strains is facilitated in over-crowded, poorly ventilated settings, such as jails and penitentiaries. Moreover, inmates may show individual risk factors for the development of tuberculosis disease. Treatment regimens for latent tuberculosis infection (LTBI) may require up to 9 months of drug exposure and are characterized by adverse events (AE) and low completion rates. To describe current scientific evidence on feasibility, acceptability, and completion rate of LTBI treatment in prison or correctional institutes. Articles were retrieved from MEDLINE/PubMed, no time restriction was applied. Human retrospective and prospective studies published on LTBI treatment in incarcerated populations were included. Bias assessment plots and Egger weighted regression test were used to determine the risk of bias. Absolute and relative frequencies were assessed for qualitative data. Pooled proportion of included study groups and 95% confidence interval estimates, weighted for sample sizes, were illustrated in forest plots. I2 indicator association were used for true variability and overall variation. Fixed and random-effects models were chosen depending on the estimated between-study heterogeneity. Of the 11 selected studies, only 1 was conducted in a high tuberculosis incidence country. Overall, completion rates ranged from 26% to 100% across the included studies. Reason for the discontinuation of treatment were transfer to other facilities, release, or loss to follow-up (range, 0–74%), incidence of AEs (range, 0–18%), and refusal or withdrawal from treatment (range, 0–16%). Implementation of short-course regimens in prisons should be considered given the low incidence of AEs observed; however, inmates consistently refused to complete LTBI treatment, thus underlining the need for improvement in retention in care. [ABSTRACT FROM AUTHOR]

• The impact of COVID-19 on tuberculosis (TB) services is not fully understood. • 2019 vs 2020 data on TB incidence and mortality were collected in 11 countries. • Fewer TB (new cases/recurrences) and drug-resistant TB were notified in 2020. • More TB-related deaths were observed in 2020. • Urgent prevention and management measures are needed in the post-acute COVID phase. Although evidence is growing on the overall impact of the COVID-19 pandemic on tuberculosis (TB) services, global studies based on national data are needed to better quantify the extent of the impact and the countries' preparedness to tackle the two diseases. The aim of this study was to compare the number of people with new diagnoses or recurrence of TB disease, the number of drug-resistant (DR)-TB, and the number of TB deaths in 2020 vs 2019 in 11 countries in Europe, Northern America, and Australia. TB managers or directors of national reference centers of the selected countries provided the agreed-upon variables through a validated questionnaire on a monthly basis. A descriptive analysis compared the incidence of TB and DR-TB and mortality of the pre-COVID-19 year (2019) vs the first year of the COVID-19 pandemic (2020). Comparing 2020 vs 2019, lower number of TB cases (new diagnosis or recurrence) was notified in all countries (except USA-Virginia and Australia), and fewer DR-TB notifications (apart from France, Portugal, and Spain). The deaths among TB cases were higher in 2020 compared to 2019 in most countries with three countries (France, The Netherlands, USA-Virginia) reporting minimal TB-related mortality. A comprehensive evaluation of medium-term impact of COVID-19 on TB services would benefit from similar studies in multiple settings and from global availability of treatment outcome data from TB/COVID-19 co-infected patients. [ABSTRACT FROM AUTHOR]

The aim of the present systematic review and meta-analysis was to compare native tissue repair (NTR) against transvaginal mesh augmentation for the repair of anterior vaginal prolapse. A total of 2289 articles were found but only 27 (24.8 %) were included in the review. Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were followed to guide the process of the systematic review and meta-analysis. The quality of the observational studies was evaluated according to the Scottish Intercollegiate Guidelines Network, whereas the quality of randomized control trials (RCT) was assessed by the Cochrane risk-of-bias scale. The mesh repair intervention was associated with a higher anatomical cure rate in comparison with NTR repair when the follow-up was ≤24 months [pooled risk difference (95 % CI): -0.18 % (-0.22 %; 0.13 %); p-value: <0.0001; I2: 36.0 %]. Studies reporting anatomical failure had similar findings [pooled risk difference (95 % CI): 0.17 % (0.01 %; 0.33 %); p-value: 0.03; I2: 88.6 %]. No differences in the risk of re-operation were observed between NTR repair and mesh augmentation. Pooled risk differences in the incidence of post-surgical and late complications were higher for the mesh repair intervention [-0.05 % (95 % CI: -0.10 %; 0.00 %) p-value: 0.05; I2: 68.3 %] [-0.05 % (95 % CI: -0.14 %; 0.03 %) p-value: 0.25; I2: 82.0 %]. Women who underwent mesh repair reported greater satisfaction than women who underwent NTR [pooled risk difference (95 % CI): -0.07 % (-0.16 %; 0.02 %); p-value: 0.15; I2: 65.3 %]. In conclusion, mesh repair surgery had higher anatomical cure and satisfaction rates, with no differences in re-operation rate, but had higher post-surgical and late complications in comparison with NTR. [ABSTRACT FROM AUTHOR]