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.

Variations in Quinolinic Acid Levels in Tuberculosis Patients with Diabetes Comorbidity: A Pilot Prospective Cohort Study.

Objective: We aimed to investigate dysregulated metabolic pathways and identify diagnostic and therapeutic targets in patients with tuberculosis-diabetes (TB-DM). Methods: In our prospective cohort study, plasma samples were collected from healthy individuals, diabetic (DM) patients, untreated TB-only (TB-0)/TB-DM patients (TB-DM-0), and cured TB (TB-6)/TB-DM patients (TB-DM-6) to measure the levels of amino acids, fatty acids, and other metabolites in plasma using high-throughput targeted quantification methods. Results: Significantly different biological processes and biomarkers were identified in DM, TB-DM-0, and TB-DM-6 patients. Moreover, quinolinic acid (QA) showed excellent predictive accuracy for distinguishing between DM patients and TB-DM-0 patients, with an AUC of 1 (95% CI 1-1). When differentiating between TB-DM-0 patients and TB-DM-6 patients, the AUC was 0.9297 (95% CI 0.8460-1). Compared to those in DM patients, the QA levels were significantly elevated in TB-DM-0 patients and decreased significantly after antituberculosis treatment. We simultaneously compared healthy controls and untreated tuberculosis patients and detected an increase in the level of QA in the plasma of tuberculosis patients, which decreased following treatment. Conclusion: These findings improve the current understanding of tuberculosis treatment in patients with diabetes. QA may serve as an ideal diagnostic biomarker for TB-DM patients and contribute to the development of more effective treatments.

Deep Amplicon Sequencing Reveals Culture Selection of Mycobacterium Tuberculosis by Clinical Samples.

The commonly-used drug susceptibility testing (DST) relies on bacterial culture and faces shortcomings such as long turnaround time and clone/subclone selection. We developed a targeted deep amplification sequencing (DAS) method directly applied to clinical specimens. In this DAS panel, we examined 941 drug-resistant mutations associated with 20 anti-tuberculosis drugs with an initial amount of 4 pg DNA and reduced clinical testing time from 20 days to two days. A prospective study was conducted using 115 clinical specimens mainly with Xpert® Mycobacterium tuberculosis/rifampicin (Xpert MTB/RIF) assay positive to evaluate drug-resistant mutation detection. DAS was performed on culture-free specimens, while culture-dependent isolates were used for phenotypic DST, DAS, and whole-genome sequencing (WGS). For in silico molecular DST, our result based on DAS panel revealed the similar accuracy to three published reports based on WGS. For 82 isolates, application of DAS showed better sensitivity (93.03% vs. 92.16%), specificity (96.10% vs. 95.02%), and accuracy (91.33% vs. 90.62%) than Mykrobe software using WGS. Compared to culture-dependent WGS, culture-free DAS provides a full picture of sequence variation at population level, exhibiting in detail the gain-and-loss variants caused by bacterial culture. Our study performs a systematic verification of the advantages of DAS in clinical applications and comprehensively illustrates the discrepancy in Mycobacterium tuberculosis before and after culture.

Myriocin enhances the clearance of M. tuberculosis by macrophages through the activation of PLIN2.

Myriocin is an inhibitor of de novo synthesis of sphingolipids and ceramides. In this research, we showed myriocin could significantly reduce Mtb burden and histopathological inflammation in mice. However, the underlying mechanism remains unclear. RNA-seq analysis revealed a significant increase in gene expression of PLIN2/CD36/CERT1 after myriocin treatment. The reduced bactericidal burden was only reversed after silencing the lipid droplets (LDs) surface protein PLIN2. This suggests that myriocin enhances the ability of macrophages to clear Mtb depending on the PLIN2 gene, which is part of the PPARγ pathway. Indeed, we observed a significant increase in the number of LDs following myriocin treatment.IMPORTANCEMycobacterium tuberculosis has the ability to reprogram host cell lipid metabolism and alter the antimicrobial functions of infected macrophages. The sphingolipids, such as ceramides, are the primary host lipids utilized by the bacteria, making the sphingomyelinase/ceramide system critical in Mtb infections. Surprisingly, the antimicrobial effect of myriocin was found to be independent of its role in reducing ceramides, but instead, it depends on the lipid droplets surface protein PLIN2. Our findings provide a novel mechanism for how myriocin enhances Mtb clearance in macrophages.

A blood-based 3-gene signature score for therapeutic monitoring in patients with pulmonary tuberculosis.

OBJECTIVE: To assess the validity of Xpert Tuberculosis Fingerstick score for monitoring treatment response and analyze factors influencing its performance. METHODS: 122 adults with pulmonary tuberculosis were recruited and stratified into three cohorts: Diabetic-drug-susceptible-TB (DM-TB), Non-diabetic-drug-susceptible-TB (NDM-TB) and Non-diabetic Multidrug-resistant TB (MDR-TB). Fingerstick blood specimens were tested at treatment initiation (M0) and the end of the first (M1), second (M2), and sixth month (M6) to generate a TB-score. RESULTS: The TB-score in all participants yielded an AUC of 0.707 (95% CI: 0.579-0.834) at M2 when its performance was evaluated against sputum culture conversion. In all non-diabetes patients, the AUC reached 0.88 (95% CI: 0.756-1.000) with an optimal cut-off value of 1.95 at which sensitivity was 90.0% (95% CI: 59.6-98.2%) and specificity was 81.3% (95% CI: 70.0-88.9%). The mean TB score was higher in patients with low bacterial loads (n = 31) than those with high bacterial loads (n = 91) at M0, M1, M2, and M6, and was higher in non-cavitary patients (n = 71) than those with cavitary lesions (n = 51) at M0, M1, and M2. CONCLUSION: Xpert TB-score shows promising predictive value for culture conversion in non-diabetic TB patients. Sputum bacterial load and lung cavitation status have an influence on the value of TB score.

Evaluation of Sulfasalazine as an Adjunctive Therapy in Treating Pulmonary Pre-XDR-TB: Efficacy, Safety, and Treatment Implication.

Background: The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB. Methods: A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment. Results: Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures. Conclusion: Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective.

The association between type 2 diabetes and pulmonary cavitation revealed among IGRA-positive tuberculosis patients.

The co-occurrence of tuberculosis (TB) and diabetes mellitus (DM) presents a significant obstacle to TB eradication. Pulmonary cavitation can occur in severe cases of TB, particularly in patients with DM. From 1 May 2014 through 30 June 2019, we conducted a cross-sectional study of 1,658 smear- or culture-confirmed pulmonary TB (PTB) patients at the Second Department of Pulmonary Medicine and Tuberculosis, Shenzhen, China. A total of 861 participants who satisfied the criteria (chest CT scan for cavitation, interferon-gamma release assay (IGRA), diagnosis of diabetes mellitus), with the median age of 36.7 years, 63.6% of male, 79.7% IGRA positive, 13.8% with diabetes, and 40.8% with pulmonary cavitation, were included in the study. The association between diabetes and pulmonary cavitation was confirmed in these TB patients (adjusted OR, 2.54; 95% CI, 1.66-3.94; p < 0.001). No associations were observed between diabetes and IGRA, as well as between lung cavitary and IGRA. Based on the criteria of IGRA+/-, pulmonary cavitation+/-, and DM+/-, the further analysis with univariate and multivariate logistic regression were conducted in six subgroups. The significant association between diabetes and pulmonary cavitation was further confirmed in the IGRA+ subgroup (adjusted OR, 3.07; 95% CI, 1.86-5.16; p < 0.001) but not observed in IGRA- individuals. This observation suggests that different immunological mechanisms of pulmonary cavitary/DM may be employed in IGRA+ TB patients from IGRA- TB patients.

Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR].

INTRODUCTION: The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs). METHODS: Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients' treatment regimens are initially based on drug resistance profiles and patient's preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions. DISCUSSION: Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations. TRAIL REGISTRATION: Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021.

Selecting an appropriate all-oral short-course regimen for patients with multidrug-resistant or pre-extensive drug-resistant tuberculosis in China: A multicenter prospective cohort study.

OBJECTIVES: Long, ineffective, and toxic regimens hinder the treatment of patients with multidrug-resistant tuberculosis (MDR-TB) and pre-extensive drug-resistant tuberculosis (pre-XDR-TB). METHODS: We conducted a multicenter cohort study to prospectively evaluate the safety and efficacy of three 9-month, all-oral, 5-drug regimens. Regimen A (bedaquiline [Bdq]+linezolid [Lzd]+moxifloxacin [Mfx]+cycloserine [Cs]+pyrazinamide [Pza]) and Regimen B (Lzd+Mfx+Cs+clofazimine [Cfz]+Pza) were used to treat MDR-TB patients (Groups A and B, respectively, assigned according to the patient's treatment preference), while Regimen C (Bdq+Lzd+Cs+Cfz+Pza) was used to treat pre-XDR-TB patients (Group C). The primary endpoint was the occurrence of an unfavorable outcome within 12 months of treatment completion, regardless of regimen. RESULTS: A total of 104 patients (34 in Group A, 46 in Group B, and 24 in Group C), with a median age of 35.5 (29.0-54.0) years, were included in the analysis population. At 12 months after treatment completion, five patients were deemed non-assessable. Of the remaining 99 participants, seven (7.1%) had an unfavorable outcome (including two deaths from any cause, four with treatment failure, and one loss to follow-up) and 92 (92.9%) had a favorable outcome. Culture conversion was achieved in 82.5% (80/97) of participants at month 2 and in 97.9% (94/97) of participants at month 6. Adverse events (AEs) resulting in drug adjustment occurred in 69.2% (72/104) of participants, mainly due to Lzd and Pza use. A QT interval prolongation of ≥ 500 ms occurred in 5.8% (6/104) of participants. CONCLUSION: The primary outcome of the three tailored, 9-month, all-oral, 5-drug regimens was satisfactory in the vast majority of MDR-TB and pre-XDR-TB patients, with manageable and reversible AEs.

The interaction of macrophages and CD8 T cells in bronchoalveolar lavage fluid is associated with latent tuberculosis infection.

Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune responses. However, the immune mechanisms that govern the progression from LTBI to TB remain poorly defined in humans. Here, we profiled the lung immune cell populations within the bronchoalveolar lavage fluid (BALF) from patients with LTBI or TB using single-cell RNA sequencing (scRNA-seq). We found that Mtb infection substantially changed the immune cell compartments in the BALF, especially for the three subsets of macrophages, monocyte macrophage (MM)-CCL23, MM-FCN1, and MM-SPP1, which were found to be associated with the disease status of TB infection. Notably, MM-CCL23 cells derived from monocytes after stimulation with Mtb were characterized by high levels of chemokine (CCL23 and CXCL5) production and might serve as a marker for Mtb infection. The MM-CCL23 population mainly recruited CD8-CCR6 T cells through CCL20/CCR6, which was a prominent feature associated with protection immunity in LTBI. This study improves our understanding of the lung immune landscape during Mtb infection, which may inform future vaccine design for protective immunity.

Pharmacokinetics of Antituberculosis Drugs in Plasma and Cerebrospinal Fluid in a Patient with Pre-Extensive Drug Resistant Tuberculosis Meningitis.

Drug-resistant tuberculous meningitis (TBM) is the most devastating and critical form of extrapulmonary tuberculosis. Here, we present a case of a 45-year-old male with pre-extensive drug-resistant tuberculosis meningitis (pre-XDR-TBM). He underwent emergency surgery for the long-tunneled external ventricular drainage (LTEVD). Molecular test and phenotypic drug sensitivity test (DST) of Mycobacterium tuberculosis in cerebrospinal fluid (CSF) showed that the isolate was resistant to both rifampin and fluoroquinolones. An anti-tuberculous regimen of isoniazid, pyrazinamide, cycloserine, moxifloxacin, clofazimine, and linezolid was tailored accordingly. We monitored the drug concentration in his plasma and CSF before (at 0-hour) and after anti-TB drugs administration (at 1-hour, 2-hour, 6-hour, and 12-hour) on 10th day after treatment initiation. We hope to provide reference values of drug exposures in plasma and CSF for patients with pre-XDR-TBM.

A cross-sectional study: a breathomics based pulmonary tuberculosis detection method.

BACKGROUND: Diagnostics for pulmonary tuberculosis (PTB) are usually inaccurate, expensive, or complicated. The breathomics-based method may be an attractive option for fast and noninvasive PTB detection. METHOD: Exhaled breath samples were collected from 518 PTB patients and 887 controls and tested on the real-time high-pressure photon ionization time-of-flight mass spectrometer. Machine learning algorithms were employed for breathomics analysis and PTB detection mode, whose performance was evaluated in 430 blinded clinical patients. RESULTS: The breathomics-based PTB detection model achieved an accuracy of 92.6%, a sensitivity of 91.7%, a specificity of 93.0%, and an AUC of 0.975 in the blinded test set (n = 430). Age, sex, and anti-tuberculosis treatment does not significantly impact PTB detection performance. In distinguishing PTB from other pulmonary diseases (n = 182), the VOC modes also achieve good performance with an accuracy of 91.2%, a sensitivity of 91.7%, a specificity of 88.0%, and an AUC of 0.961. CONCLUSIONS: The simple and noninvasive breathomics-based PTB detection method was demonstrated with high sensitivity and specificity, potentially valuable for clinical PTB screening and diagnosis.

Detecting latent tuberculosis infection with a breath test using mass spectrometer: A pilot cross-sectional study.

Mycobacterium tuberculosis (M.tb) infects a quarter of the world's population and may progress to active tuberculosis (ATB). There is no gold standard for diagnosing latent tuberculosis infection (LTBI). Some immunodiagnostic tests are recommended to detect LTBI but can not distinguish ATB from LTBI. The breath test is useful for diagnosing ATB compared to healthy subjects but was never studied for LTBI. This proof-of-concept study (Chinese Clinical Trials Registry number: ChiCTR2200058346) was the first to explore a novel, rapid, and simple LTBI detection method via breath test on high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). The case group of LTBI subjects (n = 185) and the control group (n = 250), which included ATB subgroup (n = 121) and healthy control (HC) subgroup (n = 129), were enrolled. The LTBI detection model indicated that a breath test via HPPI-TOFMS could distinguish LTBI from the control with a sensitivity of 80.0% (95% CI: 67.6%, 92.4%) and a specificity of 80.8% (95% CI: 71.8%, 89.9%). Nevertheless, further intensive studies with a larger sample size are required for clinical application.

Pediatric isoniazid-resistant tuberculosis of the bone marrow manifesting as hemophagocytic syndrome: A case report.

Hemophagocytic syndrome (HPS) is a critical syndrome of ineffective hyperinflammatory immune response resulting in infiltration of lymphocytes and histiocytes in various organs. Causes can be hereditary or due to malignancy, autoimmune disease, or infection. HPS due to Mycobacterium tuberculosis is rare as only a handful of cases are reported, and they are mostly associated with severe disseminated tuberculosis (TB). We reported a 9-year-old boy with tuberculosis of the bone marrow accompanied with hemophagocytic syndrome. The patient presented with manifestation of HPS and had no respiratory symptoms or risk factors for TB but was later diagnosed of isoniazid-resistant TB in the bone marrow. He had a good outcome after receiving anti-TB drugs and corticosteroids on time. This case highlights that bone marrow might be a shelter for Mycobacterium tuberculosis. Concurrent testing for drug susceptibility in TB cases with an uncommon manifestation is recommended even for first episodes. Early diagnosis and etiological confirmation of the infection origin and appropriate treatment are essential to improve survival in this otherwise life-threatening condition.

[Expert consensus on diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases].

Rheumatic diseases, a typical kind of autoimmune disease, are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, which often leads to immune dysfunction in patients and increases the risk of activation of latent tuberculosis infection. To regulate the screening, diagnosis, and prophylactic treatment of latent tuberculosis infection in patients with rheumatic diseases, reduce the risk of developing active tuberculosis and improve the prognosis, Peking University Shenzhen Hospital, Shenzhen Third People's Hospital and Peking Union Medical College Hospital jointly organized domestic experts in the field of rheumatology and tuberculosis to establish the expert consensus on the diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases. This consensus focuses on epidemiology, the importance of screening, screening methods, and prophylactic anti-tuberculosis treatment strategies for latent tuberculosis infection combined with rheumatic diseases.

Sleep quality and influencing factors and correlation with T-lymphocyte subpopulation counts in patients with pulmonary tuberculosis: a cross-sectional study.

BACKGROUND: Patients diagnosed with pulmonary tuberculosis (TB) have poor sleep quality due to multiple factors. We aimed to assess the sleep status and related factors of TB patients in Shenzhen, China. METHODS: A questionnaire survey was conducted on 461 TB patients hospitalized at Shenzhen Third People's Hospital from March 2021 to January 2022, and sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). RESULTS: A total of 459 valid questionnaires were collected, and 238 of the 459 TB patients had general or poor sleep quality (PSQI > 5). Patients' gender, marriage, nutritional screening score, family atmosphere, fear of discrimination, fear of interactions, and the impact of the disease on their work life had significant effects on sleep quality (P < 0.05); PSQI scores of TB patients were negatively correlated with lymphocyte counts (r = - 0.296, P < 0.01), T-lymphocyte counts (r = - 0.293, P < 0.01), helper T lymphocyte counts (r = - 0.283, P < 0.01), killer T lymphocyte counts (r = - 0.182, P < 0.05), and were positively correlated with depression scores (r = 0.424, P < 0.01). Multivariable logistic regression analysis showed that male (OR = 1.64,95% CI 1.11-2.42, P < 0.05), unmarried (OR = 1.57, 95% CI 1.02-2.42, P < 0.05), NRS score grade 3(OR = 5.35, 95% CI 2.08-15.73, P < 0.01), general family atmosphere (OR = 2.23, 95% CI 1.07-4.93, P < 0.05), and the disease affecting work (OR = 1.66, 95% CI 1.11-2.50, P < 0.05) were factors influencing poor sleep quality. CONCLUSION: Most TB patients had varying degrees of sleep disturbance, which may be affected by their gender, marriage, family atmosphere, nutritional status, the effect of the disease on work life, and, depression, as well as lower absolute T-lymphocyte subpopulation counts. Appropriate interventions should be implemented to improve their sleep quality, when treating or caring for such patients.

Population Pharmacokinetic Modeling of Bedaquiline among Multidrug-Resistant Pulmonary Tuberculosis Patients from China.

Bedaquiline has been widely used as a part of combination dosage regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients with limited options. Although the effectiveness and safety of bedaquiline have been demonstrated in clinical trials, limited studies have investigated the significant pharmacokinetics and the impact of genotype on bedaquiline disposition. Here, we developed a population pharmacokinetic model of bedaquiline to describe the concentration-time data from Chinese adult patients diagnosed with MDR-TB. A total of 246 observations were collected from 99 subjects receiving the standard recommended dosage. Bedaquiline disposition was well described by a one-compartment model with first-order absorption. Covariate modeling identified that gamma-glutamyl transferase (GGT) and the single-nucleotide polymorphism (SNP) rs319952 in the AGBL4 gene were significantly associated with the apparent clearance of bedaquiline. The clearance (CL/F) was found to be 1.4 L/h lower for subjects with allele GG in SNP rs319952 than for subjects with alleles AG and AA and to decrease by 30% with a doubling in GGT. The model-based simulations were designed to assess the impact of GGT/SNP rs319952 on bedaquiline exposure and showed that patients with genotype GG in SNP rs319952 and GGT ranging from 10 to 50 U/L achieved the targeted maximum serum concentration at steady state (Cmax,ss). However, when GGT was increased to 100 U/L, Cmax,ss was 1.68-fold higher than the highest concentration pursued. The model developed provides the consideration of genetic polymorphism and hepatic function for bedaquiline dosage in MDR-TB adult patients.

Case report: Significant relief of linezolid-induced peripheral neuropathy in a pre-XDR-TB case after acupuncture treatment.

The revised WHO guidelines on multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) include linezolid in the core drug group. Common adverse events of prolonged linezolid use are bone marrow suppression and peripheral neuropathy (PN). Available measures against linezolid-induced PN (LIPN) often have insignificant effects, leading to linezolid discontinuation and a decline in the success rate of MDR/RR-TB treatment. Acupuncture treatment is a symptomatic treatment measure from traditional Chinese medicine (TCM) to relieve pain with overall very low evidence and has never been reported in LIPN. The pilot use of acupuncture in a pre-extensively drug-resistant (XDR)-TB (a more severe form of MDR/RR-TB) patient exhibited significant improvements in LIPN and thus maintained linezolid in the regimen for a longer period.

A feasibility study of Covid-19 detection using breath analysis by high-pressure photon ionization time-of-flight mass spectrometry.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a tremendous threat to global health. polymerase chain reaction (PCR) and antigen testing have played a prominent role in the detection of SARS-CoV-2-infected individuals and disease control. An efficient, reliable detection tool is still urgently needed to halt the global COVID-19 pandemic. Recently, the food and drug administration (FDA) emergency approved volatile organic component (VOC) as an alternative test for COVID-19 detection. In this case-control study, we prospectively and consecutively recruited 95 confirmed COVID-19 patients and 106 healthy controls in the designated hospital for treatment of COVID-19 patients in Shenzhen, China. Exhaled breath samples were collected and stored in customized bags and then detected by high-pressure photon ionization time-of-flight mass spectrometry for VOCs. Machine learning algorithms were employed for COVID-19 detection model construction. Participants were randomly assigned in a 5:2:3 ratio to the training, validation, and blinded test sets. The sensitivity (SEN), specificity (SPE), and other general metrics were employed for the VOCs based COVID-19 detection model performance evaluation. The VOCs based COVID-19 detection model achieved good performance, with a SEN of 92.2% (95% CI: 83.8%, 95.6%), a SPE of 86.1% (95% CI: 74.8%, 97.4%) on blinded test set. Five potential VOC ions related to COVID-19 infection were discovered, which are significantly different between COVID-19 infected patients and controls. This study evaluated a simple, fast, non-invasive VOCs-based COVID-19 detection method and demonstrated that it has good sensitivity and specificity in distinguishing COVID-19 infected patients from controls. It has great potential for fast and accurate COVID-19 detection.