Clinical Diagnostic Challenge in a Case of Disseminated Talaromyces marneffei Infection Misdiagnosed Initially as Pulmonary Tuberculosis: A Case Report and Literature Review.

This case reports a middle-aged male patient who was HIV-negative and initially misdiagnosed as pulmonary tuberculosis but was eventually diagnosed with disseminated Talaromyces marneffei (T. marneffei) infection by next-generation sequencing. The patient presented with respiratory symptoms, recurrent bone pain, and subcutaneous masses as the main symptoms. After one year of antifungal treatment, the symptoms improved obviously, but the symptoms recurred after two weeks of drug withdrawal, and the symptoms were relieved after re-administration of antifungal drugs again. This report highlights the need for the rapid evaluation of fungal infections with metagenomic next-generation sequencing (mNGS) in patients with an inadequate diagnostic basis for tuberculosis infection or a poor response to antituberculosis drugs. In addition, long-term follow-up is needed to observe disease recurrence in patients with disseminated T. marneffei infection.

Nine months of bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine chemotherapy for rifampicin/multidrug-resistant tuberculosis: a multicenter, randomized, open-label non-inferiority trial in China.

BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

A causal relationship between sarcopenia and cognitive impairment: A Mendelian randomization study.

OBJECTIVE: Sarcopenia and cognitive impairment often coexist in the elderly. In this study, we investigated the causal relationship between sarcopenia-related muscle characteristics and cognitive performance. METHODS: We used linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR) analyses to estimate genetic correlations and causal relationships between genetically predicted sarcopenia-related muscle traits and cognitive function, as well as cognitive function-based discovery samples and replicated samples. Estimated effect sizes were derived from a fixed-effects meta-analysis. RESULTS: Our univariate genome-wide association study (GWAS) meta-analysis indicated a causal relationship between appendicular lean mass (ALM) (ß = 0.049; 95% confidence interval (CI): 0.032-0.066, P < 0.001) and walking pace (ß = 0.349; 95% CI: 0.210-0.487, P < 0.001) with cognitive function, where a causal relationship existed between ALM in both male and female (ßALM-Male(M) = 0.060; 95% CI: 0.031-0.089, PALM-M < 0.001; ßALM-Female(F) = 0.045; 95% CI: 0.020-0.069, PALM-F < 0.001) with cognitive function. Low grip strength was not causally associated with cognitive function (ß = -0.045; 95% CI: -0.092 - -0.002, P = 0.062). A reverse causality GWAS meta-analysis showed a causal relationship between cognitive function and ALM (ß = 0.033; 95% CI: 0.018-0.048, P < 0.001) and walking pace (ß = 0.039; 95% CI: 0.033-0.051, P < 0.001), where ALM in both male and female showed a causality (ßALM-M = 0.041; 95% CI: 0.019-0.063, PALM-M < 0.001; ßALM-F = 0.034; 95% CI: 0.010-0.058, PALM-F = 0.005). Cognitive function was not causally related to low grip strength (ß = -0.024; 95% CI: -0.073-0.025, P = 0.344). Multivariable MR1 (MVMR1) analyses showed a significant causal relationship for ALM (ß = 0.077; 95% CI: 0.044-0.109, P = 0.000) and walking pace (ß = 0.579; 95% CI: 0.383-0.775, P = 0.000) and cognitive function. Multivariable MR2 (MVMR2) multivariate analysis showed that ALM causality remained (ß = 0.069; 95% CI: 0.033-0.106, P = 0.000), and walking pace (ß = 0.589; 95% CI: 0.372-0.806, P = 0.000). CONCLUSIONS: Bidirectional two-sample MR demonstrated that sarcopenia-related muscle characteristics and cognitive performance were positive causal genetic risk factors for each other, while a multivariable MR study demonstrated that low ALM and a slow walking pace were causally involved in reduced cognitive performance. This study suggests a causal relationship between sarcopenia and cognitive impairment in older adults and provide new ideas for prevention and treatment.

Hemifacial Spasm Associated With the Specific Offending Vein.

BACKGROUND AND OBJECTIVES: Hemifacial spasm (HFS) caused by venous compression is a rare occurrence. Currently, there is no relevant research on the venous characteristics and potential pathogenic mechanisms causing venous HFS. Exploring the venous characteristics in venous-type HFS may reduce the likelihood of repeated surgery. METHODS: The authors presented 4 cases of HFS caused by veins of middle cerebellar peduncle (V. of Mid.Cer.Ped) successfully treated with microvascular decompression. RESULTS: Based on intraoperative observations and abnormal muscle response (AMR) monitoring, it was determined that V. of Mid.Cer.Ped were offending vessels in these patients. Moreover, veins crossed between the facial and vestibulocochlear nerves, and then surrounded the ventral aspect of the facial nerve root. Microvascular decompression for the offending vessel was successfully performed, and AMR disappeared for each patient. These patients were discharged without any complications and involuntary contractions or twitching of facial muscles. CONCLUSION: The study demonstrated that veins can indeed induce HFS. The characteristic of the V. of Mid.Cer.Ped that leads to HFS is that these veins traverse between the facial nerve and the vestibulocochlear nerve, and then surround the ventral aspect of the facial nerve root. The dynamic influence of cerebrospinal fluid leads to pulsatile impingement of the facial nerve on the vein, resulting in facial nerve bending and deformation at the location of the vein. Significantly, in the context of surgery, if it is noticed that the V. of Mid.Cer.Ped surrounds the ventral aspect of the facial nerve root and the facial nerve is compressed and deformed, when AMR disappears after decompression of the artery, it may be necessary to perform vein decompression.

Trigeminal neuralgia secondary to osteoma and vascular compression: illustrative case.

BACKGROUND: Trigeminal neuralgia (TN) is a common neurosurgical issue that has a detrimental impact on patients' quality of life. Osteoma at the petrous apex is a rare etiology of TN. Here, the authors present a case involving the co-occurrence of petrous osteoma and a vascular loop around the trigeminal nerve. Both exerted pressure or compression on the exit of the trigeminal nerve. OBSERVATIONS: A 46-year-old male presented with a 3-year history of persistent severe pain in the right side of his face. Magnetic resonance tomographic angiography of the trigeminal nerve revealed an abnormal signal in the right prepontine cistern, along with a vascular loop accompanying the right trigeminal nerve. A computed tomography scan of the skull indicated a nodular calcified density. The combined anterior transpetrosal approach for petrous osteoma and microvascular decompression (MVD) for the offending vessel were successfully performed. The patient was discharged without any complications or facial pain. LESSONS: Although extremely rare, TN simultaneously secondary to petrous osteoma and offending vessels should be considered in the diagnosis. In this case, the combined surgical removal of petrous osteoma and MVD for the offending vessels proved to be an effective treatment for TN secondary to osteoma and vascular compression.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Balloon compression, neuroendoscopy and electrophysiological monitoring-assisted retrosigmoid approach for resection of cholesteatoma in the cerebellopontine angle-Meckel's cave: a technical description.

We report a case of cholesteatoma that caused left facial pain with facial numbness. The tumour was located in the left cerebellopontine angle (CPA) and Meckel's cave. A balloon was first placed into Meckel's cave, and then, under electrophysiological monitoring, the tumour within the CPA cistern was resected via the retrosigmoid approach. The balloon was inflated in Meckel's cave to push the tumour out of Meckel's cave, and then, the tumour was completely removed under endoscopy. The symptoms, including pain and numbness, subsided after surgery.

Circ_0000253 promotes the progression of osteosarcoma via the miR-1236-3p/SP1 axis.

OBJECTIVE: Circular RNAs (circRNAs) play important roles in modulating tumour progression. This study investigated the role of circ_0000253 in osteosarcoma (OS). METHODS: We downloaded the chip dataset GSE140256 from the Gene Expression Omnibus database and the circRNAs differentially expressed in OS tissue and normal tissue samples were analysed. Quantitative real-time PCR (qRT-PCR) was carried out to examine circ_0000253 expression in OS tissues and cells. Cell counting kit-8, BrdU and flow cytometry assays were performed to verify the effects of circ_0000253 on OS cell growth and apoptosis. Bioinformatics analysis was conducted to predict, and RNA immunoprecipitation assay and dual-luciferase reporter gene assay were performed to verify the targeted relationships of miR-1236-3p with circ_0000253 and Sp1 transcription factor (SP1) mRNA 3'UTR. The effects of miR-1236-3p and circ_0000253 on SP1 expression in OS cells were detected through Western blot. KEY FINDINGS: Circ_0000253 was upregulated in OS tissues and cell lines. Circ_0000253 overexpression facilitated OS cell growth and suppressed apoptosis, whereas knocking down circ_0000253 inhibited OS cell growth and facilitated apoptosis. Circ_0000253 targeted miR-1236-3p directly and negatively modulated its expression. SP1 was miR-1236-3p's target gene and positively regulated by circ_0000253. CONCLUSION: Circ_0000253 promotes OS cell proliferation and suppresses cell apoptosis via regulating the miR-1236-3p/SP1 molecular axis.

Prediction of Higher Ki-67 Index in Pituitary Adenomas by Pre- and Intra-Operative Clinical Characteristics.

Objective: The Ki-67 index is an indicator of the active proliferation and aggressive behavior of pituitary adenomas (PAs). Appropriate pre- and intra-operatives of the Ki-67 index can help surgeons develop better and more personalized treatment strategies for patients with PAs. This study aimed to investigate the influence factors for predicting the Ki-67 index in PAs. Methods: Data of 178 patients with PAs confirmed by pathology were retrospectively analyzed. According to the Ki-67 index, the patients were divided into the Ki-67 < 3% and Ki-67 ≥ 3% cohorts. Patient data, including age, sex, postoperative immunohistochemical pituitary hormone positive index, Knosp grade, tumor breaking through the sellar floor, rich blood supply to the tumor, tumor located inside the sella, erosion of the dorsum sellae bone, and pituitary-specific transcription factor, were collected. A univariate logistic analysis was used to evaluate the influence factors for a high Ki-67 index. Multiple regression and receiver operating characteristic (ROC) curve were used to analyze the factors with p < 0.05. The mutant status of Ki-67 index was predicted by nomogram. Results: Multivariate regression analysis showed that rich blood supply to the tumor and erosion of the dorsum sellae bone were independent risk factors for the Ki-67 proliferation index. The ROC curves demonstrated that age, rich blood supply to the tumor, and erosion of the dorsum sellae bone can predict the occurrence of a high Ki-67 index. Together, the three risk factors provide a stronger ability to predict the Ki-67 index. The nomogram was developed and validated. Conclusion: Age, rich blood supply to the tumor, and erosion of the dorsum sellae bone are influencing factors for predicting the Ki-67 index. Suitable nomogram prediction models were developed and validated, and there is potential for personalized treatment for PA patients.

Using TBAg/PHA Ratio for Monitoring TB Treatment: A Prospective Multicenter Study.

The way to monitor tuberculosis (TB) treatment is extremely lacking in clinical practice. The aim of the study is to assess the role of the TBAg/PHA ratio in the treatment monitoring of TB. TB patients were followed up for 6 months and serial T-SPOT.TB (T-SPOT) assays were performed. In patients with successful treatment outcomes, the ESAT-6 sfc, CFP-10 sfc, and TBAg/PHA ratio all showed a decreased trend after the initiation of treatment. Conversely, PHA sfc showed an increased trend after 2 months of treatment. However, these indicators had moderate performance in distinguishing between before and after 6 months of treatment, and the AUC ranged from 0.702 to 0.839. Notably, the TBAg/PHA ratio in patients without risk factors was of important value in differentiation between before and after treatment. The optimal AUC of TBAg/PHA ratio reached up to 0.890. Patients with unsuccessful treatment outcomes showed persistently high levels of TBAg/PHA ratio. The TBAg/PHA ratio in patients after 6 months of treatment showed a certain potential in distinguishing between patients with successful and unsuccessful treatment outcomes. A further calculation of the TBAg/PHA ratio in T-SPOT assay has potential value in the treatment monitoring of TB, but further confirmation is needed.

JKAP serves as a potential biomarker for the evaluation of inflammatory condition, disease activity, and treatment response to TNF inhibitor in ankylosing spondylitis patients.

OBJECTIVE: This study aimed to evaluate the value of JKAP as a biomarker in estimating treatment response to TNF inhibitor in AS patients. METHODS: Totally, 63 AS patents who planned to receive adalimumab (TNF inhibitor) treatment were enrolled. Baseline JKAP level was determined in serum samples. All patients received 40 mg adalimumab every two weeks for 12 weeks. At W2, W4, W8, and W12, ASAS40 response rates were evaluated. RESULTS: JKAP was negatively correlated with CRP (P = 0.032), BASDAI score (P = 0.021), BASFI score (P = 0.045), ASDASCRP score (P = 0.038), TNF-α (P = 0.031), IL-6 (P = 0.025) and IL-17A (P = 0.022). The ASAS40 response rates were 17.5%, 31.7%, 44.4% and 55.5% at W2, W4, W8 and W12, respectively. Baseline JKAP level was lower in patients with ASAS40 response than those without ASAS40 response (25.8 (13.2-42.7) pg/mL vs. 47.3 (26.7-71.2) pg/mL, P = 0.003). Multivariate logistic regression disclosed that JKAP level (P = 0.049) and CRP level (P = 0.014) independently correlated with ASAS40 response; further analyses disclosed that they exhibited acceptable to good ability in distinguishing patients with ASAS40 response from those without ASAS40 response. CONCLUSION: JKAP serves as a potential biomarker for evaluation of inflammatory condition, disease activity, especially for assessing treatment response to TNF inhibitor in AS patients.

Epidemiology of concurrent extrapulmonary tuberculosis in inpatients with extrapulmonary tuberculosis lesions in China: a large-scale observational multi-centre investigation.

AIMS: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. METHODS: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. RESULTS: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25-34 years (87.50%). CONCLUSIONS: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.

Long noncoding RNA intersectin 1-2 gradually declines during adalimumab treatment, and its reduction correlates with treatment efficacy in patients with ankylosing spondylitis.

Previous studies show that long noncoding RNA intersectin 1-2 (lnc-ITSN1-2) promotes the inflammation process and serves as a potential biomarker in autoimmune diseases, except for ankylosing spondylitis (AS). Therefore, this study aimed to explore the correlation of baseline lnc-ITSN1-2 expression with disease risk and activity of AS, and to investigate its longitudinal change with treatment response to a tumour necrosis factor alpha (TNFα) inhibitor in patients with AS. In total, 63 patients with AS receiving 12-week adalimumab treatment were included and their baseline clinical features were collected. Lnc-ITSN1-2 expression in peripheral blood mononuclear cells (PBMC) of patients with AS was detected by reverse transcription quantitative polymerase chain reaction. Meanwhile, Assessment in Spondyloarthritis International Society (ASAS) 40 response was evaluated at week 2 (W2), W4, W8, and W12. According to the ASAS40 response status at W12, patients with AS were classified into responders and non-responders. PBMC lnc-ITSN1-2 expression was also determined in healthy controls (N = 60). Lnc-ITSN1-2 expression was elevated in patients with AS compared to controls (P < 0.001). Baseline lnc-ITSN1-2 expression was positively associated with C-reaction protein (CRP) (P = 0.021), interleukin (IL)-1ß (P = 0.020), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score (P = 0.040), and Ankylosing Spondylitis Disease Activity score with C-reactive protein (ASDASCRP) (P = 0.045) in patients with AS. Furthermore, lnc-ITSN1-2 expression declined during the treatment with adalimumab (P < 0.001). Notably, this reduction was more obvious in responders than non-responders. In conclusion, declined lnc-ITSN1-2 expression during the TNFα inhibitor treatment correlates with good treatment efficacy in patients with AS, suggesting its clinical value for AS management.

High irisin and low BDNF levels in aqueous humor of high myopia.

BACKGROUND: The pathogenesis of myopia remains unclear. Both genetic and environmental factors play a role in the disease progression. Reasons including reduced physical activity (PA) and low-grade intraocular inflammation may be involved in the development of myopia. OBJECTIVES: To analyze the levels of irisin, brain-derived neurotrophic factor (BDNF) and other intraocular cytokines in aqueous humor of high myopia patients, and to evaluate the roles of PA and inflammation in developing myopia. MATERIAL AND METHODS: We collected aqueous humor samples from patients with axial length (AL) over 26 mm (n = 35) or shorter than 25 mm (n = 38) during cataract extraction surgery. Samples were assayed using the enzyme-linked immunosorbent assay (ELISA) kit for irisin and a multiplex immunoassay kit for BDNF, interleukin (IL)-6, IL-8 and IL-10, and tumor necrosis factor alpha (TNF-α). RESULTS: Irisin levels in the aqueous samples of the highly myopic eyes were significantly higher than in the control group (p = 0.027). The BDNF levels of the highly myopic group were significantly lower than in the control group (p = 0.043). Median level of leukemia inhibitory factor (LIF) for highly myopic group (2.035 pg/mL) was statistically significantly higher than in the control group (0.750 pg/mL) (U = 210.5, Z = -4.495, p < 0.001). Interleukin 1 receptor antagonist (IL-1ra) level in the aqueous samples of the highly myopic group was significantly lower than in the shorter AL group (p = 0.049). Interleukin 6, IL-8 and IL-10 levels were not significantly different between the 2 groups (p = 0.501, p = 0.059 and p = 0.192, respectively). Tumor necrosis factor α levels could only be detected in 30 samples and median levels in the 2 groups were not statistically significantly different (U = 99, Z = -0.482, p = 0.650). No correlation was found between IL-6, IL-8, IL-10 and TNF-α, and the AL (p > 0.05). Irisin was positively correlated with AL (p = 0.028, r = 0.287). The BDNF was negatively correlated with AL (p = 0.040, r = -0.246). Interleukin 1ra was negatively correlated with AL (p = 0.038, r = -0.276). There was also a correlation between LIF and AL (p < 0.001, r = 0.486). CONCLUSIONS: Higher irisin level in high myopia group opens a new direction to discover the relationship between PA and myopia. The decreased BDNF in high myopia group probably demonstrates the connection between myopia and neurodegenerative disease.

Efficacy of Internal Neurolysis for Trigeminal Neuralgia without Vascular Compression.

BACKGROUND AND OBJECTIVE: Trigeminal neuralgia is a common neurologic disease that seriously impacts a patient's quality of life. We retrospectively investigated the efficacy and safety of internal neurolysis (nerve combing) for trigeminal neuralgia without vascular compression. PATIENTS AND METHODS: This study was a retrospective review of all patients with trigeminal neuralgia who were admitted between January 2014 and February 2019. A subgroup of 36 patients had no vascular compression at surgery and underwent internal neurolysis. Chart review and postoperative follow-up were performed to assess the overall outcomes of internal neurolysis. RESULTS: Thirty-six patients were identified, with a mean age of 44.89 ± 7.90 (rang: 31-65) years and a disease duration of 5.19 ± 2.61 years. The immediate postoperative pain relief (Barrow Neurological Institute [BNI] pain score of I or II) rate was 100%. The medium- to long-term pain relief rate was 91.7%. Three patients experienced recurrence. Facial numbness was the primary postoperative complication. Four patients with a score of III on the BNI numbness scale immediately after surgery had marked improvement at 6 months. No serious complications occurred. CONCLUSION: Internal neurolysis is a safe and effective treatment for trigeminal neuralgia without vascular compression or clear responsible vessels.

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients.

ABSTRACT: The T-SPOT.TB assay detects cellular immune responses to 2 core Mycobacterium tuberculosis antigens, early secreted antigenic target of 6-kDa protein (ESAT-6) and culture filtrate protein-10 (CFP-10). T-SPOT.TB has been recently used for auxiliary diagnosis of active pulmonary tuberculosis (PTB). However, testing can produce inconsistent results due to differential PTB patient immune responses to these antigens, prompting us to identify factors underlying inconsistent results.Data were retrospectively analyzed from 1225 confirmed PTB patients who underwent T-SPOT.TB testing at 5 specialized tuberculosis hospitals in China between December 2012 and November 2015. Numbers of spot-forming cells (SFCs) reflecting T cell responses to ESAT-6 and CFP-10 antigens were recorded then analyzed via multivariable logistic regression to reveal factors underlying discordant T cell responses to these antigens.The agreement rate of 84.98% (82.85%-86.94%) between PTB patient ESAT-6 and CFP-10 responses demonstrated high concordance. Additionally, positivity rates were higher for ESAT-6 than for CFP-10 (84.8% vs 80.7%, P < .001), with ESAT-6 and CFP-10 microwell SFC numbers for each single positive group not differing significantly (P > .99), while spot numbers of the single positive group were lower than numbers for the double positive group (P < .001). Elderly patients (aged ≥66 years) and patients receiving retreatment were most likely to have discordance results.ESAT-6 promoted significantly more positive T-SPOT.TB results than did CFP-10 in PTB patients. Advanced age and retreatment status were correlated with discordant ESAT-6 and CFP-10 results. Assessment of factors underlying discordance may lead to improved PTB diagnosis using T-SPOT.TB.

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

BACKGROUND: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). METHODS: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. RESULTS: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. CONCLUSIONS: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

[Strategies for monitoring 24-hour intraocular pressure curve: 41 cases of prospective clinical study].

OBJECTIVE: To investigate accuracy of the currently used strategies for intraocular pressure measurements for reflecting actual 24-hour intraocular pressure fluctuations. METHODS: From September, 2018 to January, 2019, the patients with a suspected diagnosis of primary open angle glaucoma at our hospital were prospectively enrolled to receive 24-hour intraocular pressure monitoring using a Goldmann tonometer. With the intraocular pressure measurements at 0:00, 2:00, 5:00, 7:00, 8:00, 10:00, 11:00, 14:00, 16:00, 18:00, 20:00, and 22:00 as the gold standard (strategy 1), we compared the measurements taken at 5:00, 7:00, 10:00, 14:00, 18:00, and 22:00 (strategy 2) and at 8:00, 11:00, 14:00, and 16:00 (strategy 3) for their accuracy in reflecting 24-h intraocular pressure fluctuations. RESULTS: A total of 41 patients (82 eyes) were enrolled in this study. The peak intraocular pressures measured using the 3 strategies were 21.09±4.15 mmHg, 20.54±4.10 mmHg, and 19.91±4.38 mmHg, respectively, showing significant differences among them (P < 0.05). The trough intraocular pressures measured by the 3 strategies were also significantly different (13.93±3.38 mmHg, 14.63±3.49 mmHg, and 15.46±3.63 mmHg, respectively; P < 0.05). The co-occurrence of the peak intraocular pressure was 74.39% between strategies 1 and 2 and 43.90% between strategies 1 and 3. The sensitivity of strategies 2 and 3 for detecting 24-h intraocular pressure fluctuations was 55.56% and 36.11%, respectively. CONCLUSIONS: For suspected cases of glaucoma, intraocular pressure measurements at 4 and 6 time points of a day can not precisely reflect the actual range of intraocular pressure fluctuations, and may lead to a missed diagnosis of glaucoma.

Efficacy of and risk factors for percutaneous balloon compression for trigeminal neuralgia in elderly patients.

OBJECTIVE: To investigate the efficacy and safety of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia in elderly patients. Methods: We retrospectively analysed data of 105 elderly patients with primary trigeminal neuralgia who were over 70 years and underwent percutaneous balloon compression using anatomic positioning and imaging guidance from January 2019 to November 2019. Results: The immediate cure rate of pain in this group of patients was 97.1% (Barrow Neurological Institute (BNI) pain scores: class I and II; numbness score: class II). Postoperative keratitis was reported in 1 patient, masticatory muscle weakness and muscle atrophy in 1 patient, herpes labialis in 8 patients and lacunar infarction in 2 patients. Facial numbness and decreased sensation occurred in patients with significant pain relief. No serious complications were reported. There was no statistically significant difference in efficacy between the short compression and long compression time groups. Conclusion: PBC is a safe and effective approach to treat trigeminal neuralgia.

The prevalence and risks of major comorbidities among inpatients with pulmonary tuberculosis in China from a gender and age perspective: a large-scale multicenter observational study.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.