Comparative performance analysis of mussel-inspired polydopamine, polynorepinephrine, and poly-α-methyl norepinephrine in electrochemical biosensors.

Polydopamine (PDA) has garnered significant interest for applications in biosensors, drug delivery, and tissue engineering. However, similar polycatecholamines like polynorepinephrine (PNE) with additional hydroxyl groups and poly-α-methylnorepinephrine (PAMN) with additional hydroxyl and methyl groups remain unexplored in the biosensing domain. This research introduces three innovative biosensing platforms composed of ternary nanocomposite based on reduced graphene oxide (RGO), gold nanoparticles (Au NPs), and three sister polycatecholamine compounds (PDA, PNE, and PAMN). The study compares and evaluates the performance of the three biosensing systems for the ultrasensitive detection of Mycobacterium tuberculosis (MTB). The formation of the nanocomposites was meticulously examined through UV-Visible, Raman, XRD, and FT-IR studies with FE-SEM and HR-TEM analysis. Cyclic voltammetry and differential pulse voltammetry measurements were also performed to determine the electrochemical characteristics of the modified electrodes. Electrochemical biosensing experiments reveal that the RGO-PDA-Au, RGO-PNE-Au, and RGO-PAMN-Au-based biosensors detected target DNA up to a broad detection range of 0.1 × 10-8 to 0.1 × 10-18 M, with a low detection limit (LOD) of 0.1 × 10-18, 0.1 × 10-16, and 0.1 × 10-17 M, respectively. The bioelectrodes were proved to be highly selective with excellent sensitivities of 3.62 × 10-4 mA M-1 (PDA), 7.08 × 10-4 mA M-1 (PNE), and 6.03 × 10-4 mA M-1 (PAMN). This study pioneers the exploration of two novel mussel-inspired polycatecholamines in biosensors, opening avenues for functional nanocoatings that could drive further advancements in this field.

Prevalence of vitamin D deficiency and the effect of vitamin D3 supplementation on response to anti-tuberculosis therapy in patients with extrapulmonary tuberculosis.

BACKGROUND: We aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course. METHODS: Serum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment. RESULTS: Serum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group. CONCLUSIONS: Vitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

Long-term outcomes of surgical reconstruction for post-tuberculosis tracheobronchial stenosis: a 7-year follow-up in a tuberculosis-endemic region.

Background: Surgical reconstruction is often necessary for severe tracheobronchial stenosis resulting from tuberculosis (TB). However, the long-term efficacy of this approach remains unclear. This study investigated the safety and long-term outcomes of surgery for severe post-TB tracheobronchial stenosis. Methods: We conducted a retrospective study of 48 patients with severe post-TB tracheobronchial stenosis who underwent surgical reconstruction between 2015 and 2018 in a TB-endemic region. Pre- and postoperative evaluations included Karnofsky performance status, modified Medical Research Council (mMRC) dyspnea scale, spirometry, chest computed tomography (CT) scan, and bronchoscopy. The primary outcome was intervention-requiring restenosis over the long term. Results: The mean patient age was 30.6±9.9 years, with 91.7% females. Airway fibrosis was the predominant lesion (93.8%), affecting the bronchi (93.8%) and trachea (6.2%). All the patients underwent resection and anastomosis, and 56.2% required lobectomy. Postoperative complications occurred in 13 patients (27.1%), with prolonged air leaks being the most prevalent (12.5%). All complications resolved with conservative management. Significant improvements in performance status, dyspnea, and lung function were observed postoperatively and sustained for over 5 years. Within a median follow-up of 69 months, five cases of intervention-requiring restenosis occurred within the first year. The freedom from restenosis rate was 90% from 1 year onwards. Conclusions: Surgical reconstruction is safe and effective in treating severe post-TB tracheobronchial stenosis. Larger studies are required to validate these findings.

Primary extrapulmonary tuberculosis diagnosis warrants extra-precautious pulmonary tuberculosis exclusion workup.

This editorial article takes an opportunity to apprehend the diagnostic challenges of primary gastrointestinal tuberculosis (an uncommon extrapulmonary tuberculosis condition) utilizing the recently published case report of a young male with prolonged gastrointestinal symptoms and weight loss who received intermittent anti-tubercular treatment and underwent operative interventions to relieve gastric outlet obstruction. The diagnosis chiefly relied on high-end examinations, like computed tomography scans and histopathological evaluation of post-operatively resected bowel tissue, which wasn't preceded by an all-inclusive stepwise primary pulmonary tuberculosis exclusion approach that usually begins with a detailed tuberculosis-pertinent history acquisition. Given the geographic locations where the patient had been (and/or treated), pivotal consideration of tuberculosis-associated endemicities in those regions, like human immunodeficiency virus (HIV) infection, might have improved the case description. The obtainment of HIV-relevant histories, like intravenous drug use and sexual practice, are good places to start. The sputum bacteriology also seems imperative to rule out atypical Mycobacterium species infection because of its clinico-radio-histopathological resemblance with pulmonary Mycobacterium tuberculosis. Altogether, this editorial aims to underscore that primary extrapulmonary tuberculosis diagnosis should comprise an elaborative, comprehensive, systematic, and stepwise primary pulmonary Mycobacterium tuberculosis exclusion workup.

A review of 280 nasopharyngeal tuberculosis cases and the effectiveness of antituberculosis treatments.

Objectives: Nasopharyngeal tuberculosis is a rare form of tuberculosis in which Mycobacterium tuberculosis infects the nasopharyngeal tissue. In this study, we analyzed key clinical features to prevent misdiagnosis and to raise awareness of the condition, while recommending suitable treatments. We also report a case of nasopharyngeal tuberculosis presenting with nasal congestion and intermittent ear fullness, contributing valuable educational insight for diagnosis. Methods: Demographic and clinical data from patients with nasopharyngeal tuberculosis were collected from PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials up to September 2022. In total, 280 patients from 69 studies were analyzed. Results: Reports indicate that the incidence of nasopharyngeal tuberculosis has doubled every decade, particularly in Asia. Most patients are female, presenting with granulomatous pathology and findings such as masses, lymphoid hyperplasia, polypoid formations, or swelling on endoscopic examination. Common symptoms include nasal obstruction, hearing impairment, sore throat, and dysphagia, usually accompanied by cervical lymphadenopathy. The mean duration from symptom onset to diagnosis is ∼2.88 months, and the average time from the start of treatment to resolution of symptoms is âˆ¼ 4.90 months. The antituberculosis treatment regimen and duration are significantly associated with the time to resolution (r = -0.648, p = 0.003 and r = 0.584, p = 0.028, respectively). Conclusion: These results suggest that an extended regimen of antituberculosis drugs may expedite symptom relief. However, there is a need for more standardized data on patient outcomes and treatment efficacy due to the current lack of comprehensive data.

Mycobacterium tuberculosis and host interactions in the manifestation of tuberculosis.

The final step of epigenetic processes is changing the gene expression in a new microenvironment in the body, such as neuroendocrine changes, active infections, oncogenes, or chemical agents. The case of tuberculosis (TB) is an outcome of Mycobacterium tuberculosis (M.tb) and host interaction in the manifestation of active and latent TB or clearance. This comprehensive review explains and interprets the epigenetics findings regarding gene expressions on the host-pathogen interactions in the development and progression of tuberculosis. This review introduces novel insights into the complicated host-pathogen interactions, discusses the challengeable results, and shows the gaps in the clear understanding of M.tb behavior. Focusing on the biological phenomena of host-pathogen interactions, the epigenetic changes, and their outcomes provides a promising future for developing effective TB immunotherapies when converting gene expression toward appropriate host immune responses gradually becomes attainable. Overall, this review may shed light on the dark sides of TB pathogenesis as a life-threatening disease. Therefore, it may support effective planning and implementation of epigenetics approaches for introducing proper therapies or effective vaccines.

Diagnostic performance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in bronchoalveolar lavage fluid for pulmonary tuberculosis in HIV-infected patients.

Introduction: Pulmonary tuberculosis (PTB) remains a significant health concern, particularly in individuals infected with human immunodeficiency virus (HIV) who are more susceptible to developing active TB disease. Early and accurate diagnosis of TB is crucial for effective treatment and prevention of transmission. This study aims to evaluate the potential of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) analysis of bronchoalveolar lavage fluid (BALF) for diagnosis of suspected PTB in HIV-infected patients. Methods: This retrospective study recruited 60 HIV-infected patients with suspected PTB presenting with respiratory symptoms and abnormal chest radiographs between January 2022 and June 2023. BALF samples were collected and subjected to analysis using MALDI-TOF MS, GeneXpert, acid-fast bacilli (AFB) smear and culture. And their diagnostic performance was compared. Results: The sensitivity of MALDI⁃TOFMS for diagnosing PTB was 83.3 %, which was better than that of smear 11.9 %, culture 40.5 % or Xpert38.1 % (all p < 0.01). The area under the curve (AUC) value of MALDI⁃TOFMS was 0.889, which was better than that of smear 0.532, culture 0.675 or Xpert 0.690 (all p < 0.01). The katG315 and rpoB-RRDR 511 mutations were detected by the MALDI⁃TOFMS in two patients. Conclusion: Nucleotide MALDI-TOFMS has a good clinical performance for rapid diagnosis of PTB from BALF samples in HIV infected patients, and detects mutations of TB simultaneously.

Retrograde Transvenous Thoracic Duct Embolization for Tubercular Chylothorax.

This case study documents the clinical profile of a 27-year-old male patient who visited the medical facility two months ago with complaints of dry cough, fatigue, weight loss, and occasional fever. He had been treated for ascites and pleural effusion in the hospital before presentation and returned with an intercostal drain in place. A detailed examination revealed symptoms of respiratory disorders, including fluid in both lungs, fever, and dyspnea. His fluid levels showed multiple deviations from the normal range, according to the report's findings and lab test results. It was determined that the patient had chylothorax, which resulted from hemophagocytic lymphohistiocytosis (HLH) and abdominal tubercular lymphadenopathy. His anti-tubercular treatment (AKT4) was initiated, along with octreotide for his management. Initial management included non-invasive ventilator (NIV) support, intravenous antibiotics, nebulization, and an intercostal chest drain (ICD). Later, the patient underwent retrograde transvenous thoracic duct embolization (TDE) using N-butyl cyanoacrylate (NBCA) glue. The removal of the drainage tube and the patient's stable discharge were made possible through regular monitoring and collaboration between specialists.

Clinical, Radiological, and Etiological Aspects of Pachymeningitis: A Study of 24 Cases.

Introduction and importance Hypertrophic pachymeningitis (HP) is an uncommon disorder with varied etiological origins and heterogeneous clinical presentation. Establishing the etiological diagnosis poses a challenge, but prompt identification provides a treatment window, potentially leading to a reversal of symptoms. MRI is the reference examination, allowing not only the early diagnosis of pachymeningitis but also the assessment of its extent and importance, detection of possible complications, and suggestion of etiology. Case presentation We conducted a retrospective study involving 24 patients recruited over 5 years for who brain imaging had revealed the presence of pachymeningitis. The average age of the patients was 40 years, with a male-to-female ratio of 0.6. Clinical discussion Headache was present in 54.17% of patients. All the patients underwent MRI examinations utilizing different sequences, with subsequent Gadolinium injection showing localized and asymmetrical meningeal thickening in 13 cases, and diffuse in the rest. The cerebrospinal fluid study unveiled an inflammatory fluid characterized by a lymphocytic predominance and hyperproteinorrhea, noted in 50% of the patients. The histopathological analysis of a stereotactic biopsy conducted on an individual patient revealed non-diagnostic results. The etiological investigation was dominated by tuberculosis, which was detected in 33.3% of cases. Idiopathic origin was identified in 16.7% of patients. Conclusion Meningeal thickening is rare, and the multitude of potential causes makes the etiological investigation challenging unless they fall within the scope of secondary meningeal disorders; otherwise, a dural biopsy becomes necessary, and the prompt initiation of treatment, along with determining the etiology influences the prognosis.

Acute Leukemia and Latent Tuberculosis Infection in Italy: Quantiferon-Tb Test Screening in a Low Tuberculosis Incidence Country.

Background: Identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low-incidence countries. However, it is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. According to guidelines, in TB non-endemic countries, no clear screening program is established at diagnosis for patients with acute leukemia (AL). The primary endpoint of this study was to establish the prevalence of LTBI in patients with a diagnosis of AL using QuantiFERON (QFT)-TB. Secondarily, radiological and clinical features driving the increased risk of LTBI were evaluated. Methods: QFT-TB screening was performed before induction or consolidation in all patients with AL (myeloid and lymphoid) treated at our Institution between October 2019 and August 2023. Results: We accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. All positive patients started prophylaxis with isoniazid 300 mg daily, while patients whose test was indeterminate did not receive any prophylaxis. Active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage if signs of any infection were detected. During the 46 months of observation, no patients developed TB reactivation. Conclusions: Despite the low sample size, 1/10 of our patients had prior TB exposure, hinting that LTBI could be more common than expected in Italy. This finding suggests implementing TB screening in the pre-treatment setting, particularly at a time when more active treatments are becoming available also for patients ineligible for intensive chemotherapy.

Physiologic medium renders human iPSC-derived macrophages permissive for M. tuberculosis by rewiring organelle function and metabolism.

In vitro studies are crucial for our understanding of the human macrophage immune functions. However, traditional in vitro culture media poorly reflect the metabolic composition of blood, potentially affecting the outcomes of these studies. Here, we analyzed the impact of a physiological medium on human induced pluripotent stem cell (iPSC)-derived macrophages (iPSDM) function. Macrophages cultured in a human plasma-like medium (HPLM) were more permissive to Mycobacterium tuberculosis (Mtb) replication and showed decreased lipid metabolism with increased metabolic polarization. Functionally, we discovered that HPLM-differentiated macrophages showed different metabolic organelle content and activity. Specifically, HPLM-differentiated macrophages displayed reduced lipid droplet and peroxisome content, increased lysosomal proteolytic activity, and increased mitochondrial activity and dynamics. Inhibiting or inducing lipid droplet formation revealed that lipid droplet content is a key factor influencing macrophage permissiveness to Mtb. These findings underscore the importance of using physiologically relevant media in vitro for accurately studying human macrophage function. IMPORTANCE: This work compellingly demonstrates that the choice of culture medium significantly influences M. tuberculosis replication outcomes, thus emphasizing the importance of employing physiologically relevant media for accurate in vitro host-pathogen interaction studies. We anticipate that our work will set a precedent for future research with clinical relevance, particularly in evaluating antibiotic efficacy and resistance in cellulo.

Apramycin has high in vitro activity against Mycobacterium tuberculosis.

Introduction. Aminoglycoside antibiotics such as amikacin and kanamycin are important components in the treatment of Mycobacterium tuberculosis (Mtb) infection. However, more and more clinical strains are found to be aminoglycoside antibiotic-resistant. Apramycin is another kind of aminoglycoside antibiotic that is commonly used to treat infections in animals.Hypothesis. Apramycin may have in vitro activity against Mtb.Aim. This study aims to evaluate the efficacy of apramycin against Mtb in vitro and determine its epidemiological cut-off (ECOFF) value.Methodology. One hundred Mtb isolates, including 17 pansusceptible and 83 drug-resistant tuberculosis (DR-TB) strains, were analysed for apramycin resistance using the MIC assay.Results. Apramycin exhibited significant inhibitory activity against Mtb clinical isolates, with an MIC50 of 0.5 µg ml-1 and an MIC90 of 1 µg ml-1. We determined the tentative ECOFF value as 1 µg ml-1 for apramycin. The resistant rates of multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains were 12.12 % (4/33), 20.69 % (6/29) and 66.67 % (14/21), respectively. The rrs gene A1401G is associated with apramycin resistance, as well as the cross-resistance between apramycin and other aminoglycosides.Conclusion. Apramycin shows high in vitro activity against the Mtb clinical isolates, especially the MDR-TB clinical isolates. This encouraging discovery calls for more research on the functions of apramycin in vivo and as a possible antibiotic for the treatment of drug-resistant TB.

Evaluation of concordance of new QuantiFERON-TB Gold Plus platforms for Mycobacterium tuberculosis infection diagnosis in a prospective cohort of household contacts.

Interferon-gamma (IFN-γ) release assays play a pivotal role in tuberculosis infection (TBI) diagnosis, with QuantiFERON-TB Gold Plus-an enzyme-linked immunosorbent assay (ELISA)-among the most widely utilized. Newer QuantiFERON-TB platforms with shorter turnaround times were recently released. We aimed to evaluate these platforms' agreement in the diagnosis of TBI. Blood samples from a prospective cohort of tuberculosis household contacts were collected at baseline and after 12 weeks of follow-up, and tested with LIAISON, an automated chemiluminescence immunoassay (CLIA) system, QIAreach, a lateral flow (QFT-LF) semi-automated immunoassay, and the ELISA QuantiFERON-TB Gold Plus platform. Test concordances were analyzed. ELISA vs CLIA overall agreement was 83.3% for all tested samples (120/144) [Cohen's kappa coefficient (κ): 0.66 (95% CI: 0.54-0.77)]. Samples positive with CLIA provided consistently higher IFN-γ levels than with ELISA (P < 0.001). Twenty-four (16.7%) discordant pairs were obtained, all CLIA-positive/ELISA-negative: 15 (62.5%) had CLIA IFN-γ levels within borderline values (0.35-0.99 IU/mL) and 9 (37.5%) >0.99 IU/mL. QFT-LF showed only 76.4% (68/89) overall agreement with ELISA [κ: 0.53 (95% CI: 0.37-0.68)] with 21 (23.6%) discordant results obtained, all QFT-LF-positive/ELISA-negative. Overall concordance between ELISA and CLIA platforms was substantial, and only moderate between ELISA and QFT-LF. The CLIA platform yielded higher IFN-γ levels than ELISA, leading to an almost 17% higher positivity rate. The techniques do not seem interchangeable, and validation against other gold standards, such as microbiologically-confirmed tuberculosis disease, is required to determine whether these cases represent true new infections or whether CLIA necessitates a higher cutoff. IMPORTANCE: Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis that affects over 10 million people annually, with over 2 billion people carrying an asymptomatic tuberculosis infection (TBI) worldwide. Currently, TBI diagnosis includes tuberculin skin test and the blood-based interferon-gamma (IFN-γ) release assays, with Qiagen QuantiFERON-TB Gold Plus (QFT) being among those most widely utilized. We evaluated Qiagen's newer QFT platforms commercially available in a prospective cohort of tuberculosis contacts. A substantial agreement was obtained between the current QFT-enzyme-linked immunosorbent assay (ELISA) and the new QFT-chemiluminescence immunoassay (CLIA) platform, although QFT-CLIA provided higher concentrations of IFN-γ, leading to a 16.6% higher positivity rate. We highlight that both platforms may not be directly interchangeable and that further validation is required.

Beyond the diagnosis of drug-resistant Tuberculosis in Norway: patients' experiences before, during and after treatment.

BACKGROUND: This study aims to explore the varied experiences of patients with drug-resistant tuberculosis in Norway. The study emphasizes challenges and implications of being diagnosed with drug-resistant tuberculosis, including the impact on psychosocial health during the diagnosis, disease, treatment, isolation and recovery phases. Norway is a low endemic country of tuberculosis. Most patients are immigrants, and some of them have recently arrived in the country. Patients undergoing treatment for drug-resistant tuberculosis endure prolonged and demanding treatment that could affect their psychosocial health. METHODS: This qualitative study conducted 16 in-depth interviews with individuals aged 18 years and above who were diagnosed with drug-resistant tuberculosis. All participants completed the treatment between 2008 and 2020. Fourteen participants were immigrants, and eight of them had resided in Norway for less than four years before diagnosis. Data analysis followed the six-phase reflexive thematic analysis framework, focusing on identifying patterns in participants' experiences, thoughts, expectations and attitudes. RESULTS: The narratives of the participants highlighted the complexities of navigating the diagnosis of drug-resistant tuberculosis, treatment, side effects and life after treatment. Immigrants encountered additional challenges, including language barriers and adapting to new social environments. All participants reported experiencing physical health issues that additionally affected their mental health and social activity. Several participants had a delayed or prolonged diagnosis that complicated their disease trajectory. Participants with suspected or confirmed contagious pulmonary tuberculosis underwent hospital isolation for periods ranging from weeks to six months. The participants reported mental health issues, social isolation and stigma, however few were offered follow-up by a psychologist. Many participants had persistent problems at the time of the interviews. Three main themes emerged from the analysis: Delayed and prolonged diagnosis; Psychosocial impact of isolation during treatment; The life after tuberculosis. CONCLUSION: This study highlights the enduring impact of drug-resistant tuberculosis on patients and the significance of timely diagnosis, psychosocial support and post-treatment follow-up. The participants universally faced serious implications of the disease, including stigma and isolation. Participants who experienced delayed diagnosis, reflected on missed early intervention opportunities. We recommend further research in low endemic countries to evaluate the international and local recommendations on psychosocial support.

A Novel Inflammatory Indicator for Tuberculosis-Associated Obstructive Pulmonary Disease (TOPD): The Systemic Inflammatory Response Index (SIRI).

Background: The development of chronic obstructive pulmonary disease (COPD) following tuberculosis (TB) is known as tuberculosis-associated obstructive pulmonary disease (TOPD). This study aimed to explore the predictive value of inflammatory indicators for TOPD in TB patients. Methods: Data for this cross-sectional study were collected between January 2014 and January 2022 at Wuhan Jinyintan Hospital. The ratio of inflammatory indicators, including Systemic Inflammatory Response Index (SIRI), C-reactive protein-to-lymphocyte ratio (CLR), eosinophil count-to-lymphocyte count ratio (ELR), were calculated. Univariate and multivariate logistic regression analyses were conducted to explore the association between the ratio of inflammatory indicators and TOPD. Furthermore, the relationship between the ratio of inflammatory indicators and TOPD was investigated using propensity score matching (PSM) and receiver operating characteristic (ROC) curve analysis was performed to evaluate their predictive value for TOPD. Results: The present study included a total of 737 patients, of whom 83 participants (11.26%) had TOPD. Sixty-nine TOPD patients and 69 non-TOPD (NTOPD) patients were successfully matched. Univariate and multivariable logistics regression analysis, conducted before and after PSM, revealed that SIRI was independently significantly associated with an increased risk of TOPD. The area under curve (AUC) of SIRI were 0.702 and 0.668 before and after PSM, respectively. Additionally, patients were stratified into four different groups based on SIRI quartiles for further analysis. The prevalence of TOPD in TB patients showed an increase with higher SIRI values, both before and after PSM. Conclusion: Levels of inflammatory indicators were higher in TOPD patients when compared to NTOPD patients. SIRI may be a simple and useful inflammatory index for assessing TOPD, and TB patients with higher values of SIRI are more likely to be high-risk group for TOPD.

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.

Acupuncture as adjunctive treatment for linezolid-induced peripheral neuropathy: a case series report.

Background: The treatment of multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains challenging due to the limited availability of effective drugs. Linezolid has emerged as a promising therapeutic option for these cases. However, its long-term use can lead to complications such as peripheral and optic neuropathies. Acupuncture, a cornerstone of traditional Chinese medicine, has been shown to be effective in the treatment of peripheral neuropathy (PN). This study examines the potential benefits of acupuncture in the treatment of linezolid-induced peripheral neuropathy (LIPN). Methods: Four patients, aged 27 to 60 years, diagnosed with LIPN, underwent daily acupuncture treatments. The main endpoint was to assess the efficacy of acupuncture in reducing neuropathic pain associated with LIPN in patients. This was primarily measured using changes in the Short Form McGill Pain Questionnaire (SF-MPQ) scores before and after acupuncture treatment. Results: Three of the patients experienced significant symptom remission, while one experienced marginal improvement. Treatments ranged from 7 to 18 sessions. Specifically, the first patient reported substantial relief with a score reduction from 33 to 13; the second patient observed minimal change; the third patient's score decreased dramatically from 10 to 2 after eight sessions; the last patient had a score reduction from 21 to 12 after five sessions, but did not continue treatment for a second assessment. Conclusion: Acupuncture is a promising therapeutic approach for LIPN. However, larger and more thorough studies are needed to determine its full potential.

A public health development intervention between acceptability and feasibility: descriptive-interpretive discussion of an example.

Introduction: the National Tuberculosis Control Program (NTP) in Cameroon participated between 2016 and 2018 in a multi-country operational study of the Union against Tuberculosis and Lung Disease (The UNION) aiming at demonstrating the efficiency and feasibility of systematic tuberculosis preventive treatment (TPT) with 3 months of an isoniazid/rifampicin (3RH) combination in under-five child contacts of bacilliferous TB patients. Cameroon was one of the participating countries of the study. Despite the promising results communicated following this study, the coverage of TPT with 3RH in Cameroon remains low. We explored the intervention under aspects of acceptability and perceived feasibility. Methods: key participants and stakeholders in this descriptive interpretative study in Cameroon were interviewed in five focus groups or individually (31 individuals). The Focus Group Discussion (FGD) and interview transcripts were analysed for different components of acceptability using a theoretical framework and the results discussed confronting them with the main objective of the study, i.e. demonstrating feasibility. Results: the children's parents expressed overall positive feelings about and acceptance of the intervention, emphasizing the unexpected empathy shown by the health staff. The involved field staff, too, showed unreserved acceptance. On the other hand, managers at the intermediate and central levels showed scepticism as to the process of initiation of the study as well as to its feasibility in the given context, neglecting aspects of resources necessary for a scaling-up and of prioritisation. Conclusion: the adoption of a public health strategy, also internationally recognized as an effective and efficient intervention, requires more than the demonstration of its acceptability or feasibility during the term of a showcase project introduced by an external development partner. Adoption is conditioned by adoption and circumspect planning involving at each stage the stakeholders on all levels of the program.

Mycobacterium tuberculosis Biofilms: Immune Responses, Role in TB Pathology, and Potential Treatment.

Tuberculosis (TB) is a major public health problem worldwide, and the burden of drug-resistant TB is rapidly increasing. Although there are literatures about the Mtb biofilms, their impact on immune responses has not yet been summarized. This review article provides recent knowledge on Mycobacterium tuberculosis (Mtb) biofilm-immunity interactions, their importance in pulmonary TB pathology, and immune-based therapy targeting Mtb biofilms. Pellicle/biofilm formation in Mtb contributes to drug resistance, persistence, chronicity, surface attachment, transfer of resistance genes, and modulation of the immune response, including reduced complement activation, changes in the expression of antigenic proteins, enhanced activation of T-lymphocytes, elevated local IFNγ+ T cells, and strong antibody production. The combination of anti-TB drugs and anti-biofilm agents has recently become an effective strategy to improve TB treatment. Additionally, immune-targeted therapy and biofilm-based vaccines are crucial for TB prevention.