[Retrospective analysis of 350 cases with dissection of lymph nodes posterior to right recurrent laryngeal nerve in endoscopic thyroidectomy through gasless axillary posterior approach].

Objective: To evaluated the safety and feasibility of dissection of lymph nodes posterior to right recurrent laryngeal nerve (ⅥB compartment) in endoscopic thyroidectomy through gasless axillary posterior approach. Methods: A total of 350 cases with right lobe papillary thyroid carcinoma (PTC) who underwent endoscopic lobectomy, isthmusectomy and central compartment neck dissection via gasless axillary posterior approach based at the Department of General Surgery, Nanfang Hospital, Southern Medical University from June 2020 to December 2022 were retrospectively analyzed. Summarize the clinical, pathological characteristics, and postoperative complications of the patients. SPSS 25.0 was used for statistical analysis of the data. Results: All 350 patients underwent endoscopic surgery successfully, with no conversion to open surgery. There were 303 females and 47 males, with an average age of (36.3±9.2) years. Of those, 287 patients were in pT1a stage, 62 in pT1b stage, and one patient in pT2 stage. There was no T3 or T4 stage patient. The mean numbers of yielded lymph nodes in right central compartment and ⅥB compartment were 8.11±4.65 (range, 1-31) and 2.62±1.86 (range, 1-12), respectively. ⅥB compartment metastasis was detected in 52 (14.86%) of 350 patients. The incidence of transient recurrent laryngeal nerve injury was 0.86%(3/350). Postoperative hematoma occurred in three patients (0.86%). Conclusion: The dissection of ⅥB compartment in endoscopic thyroidectomy through gasless axillary posterior approach is safe and feasible in selected PTC patients.

[Effects of ppk1 deletion on the drug susceptibility of uropathogenic Escherichia coli producing ESBLs].

To investigate the effect and the mechanism of ppk1 gene deletion on the drug susceptibility of uropathogenic Escherichia coli producing extended-spectrum beta-lactamases (ESBLs-UPEC). The study was an experimental study. From March to April 2021, a strain of ESBLs-UPEC (genotype was TEM combined with CTX-M-14) named as UE210113, was isolated from urine sample of the patient with urinary tract infection in the Laboratory Department of Guangzhou Eighth People's Hospital, meanwhile its ppk1 gene knock-out strain Δpk1 and complemented strain Δpk1-C were constructed by suicide plasmid homologous recombination technique, which was used to study the effect of ppk1 gene on ESBLs-UPEC drug sensitivity and its mechanism. The drug susceptibility of UE210113, Δpk1, and Δpk1-C were measured by Vitek2 Compact System and broth microdilution method. The quantitative expression of ESBLs, outer membrane protein and multidrug efflux systems encoding genes of UE210113, Δpk1 and Δpk1-C were performed by using qRT-PCR analysis. By using two independent sample Mann-Whitney U test, the drug susceptibility results showed that, compared with UE210113 strain, the sensitivities of Δpk1 to ceftazidime, cefepime, tobramycin, minocycline and cotrimoxazole were enhanced (Z=-2.121,P<0.05;Z=-2.236,P<0.05;Z=-2.236,P<0.05;Z=-2.121,P<0.05), and the drug susceptibility of Δpk1-C restored to the same as which of UE210113 (Z=0,P>0.05). The expression levels of ESBLs-enconding genes blaTEM and blaCTX-M-14 in Δpk1 were significantly down-regulated compared with UE210113, but the expression was not restored in Δpk1-C. The expression of outer membrane protein gene omp F in Δpk1 was significantly up-regulated, while the expression of omp A and omp C were down-regulated. The results showed that the expression of multidrug efflux systems encoding genes tol C, mdt A and mdtG were down-regulated in Δpk1 compared with UE210113. The expression of all of the outer membrane protein genes and the multidrug efflux systems genes were restored in Δpk1-C. In conclusion,the lost of ppk1 gene can affect the expression of the outer membrane protein and multidrug efflux systems encoding genes of ESBLs-UPEC, which increase the sensitivity of ESBLs-UPEC to various drugs.

Fermented rape pollen powder can alleviate benign prostatic hyperplasia in rats by reducing hormone content and changing gut microbiota.

Benign prostatic hyperplasia (BPH) can cause urethral compression, bladder stone formation, and renal function damage, which may endanger the life of patients. Therefore, we aimed to develop plant-based preparations for BPH treatment with no side effects. In this study, the Lactiplantibacillus plantarum 322Hp, Lactobacillus acidophilus 322Ha, and Limosilactobacillus reuteri 322Hr were used to ferment rape pollen. The fermented rape pollen was subsequently converted into fermented rape pollen powder (FRPP) through vacuum freeze-drying technology. After fermenting and drying, the bioactive substances and antioxidant capacity of FRPP were significantly higher than those of unfermented rapeseed pollen, and FRPP had a longer storage duration, which can be stored for over one year. To investigate the therapeutic effect of FRPP on BPH, a BPH rat model was established by hypodermic injection of testosterone propionate. The BPH rats were treated differently, with the model group receiving normal saline, the positive control group receiving finasteride, and the low, medium, and high dose FRPP group receiving FRPP at doses of 0.14 g/kg/d, 0.28 g/kg/d, and 0.56 g/kg/d, respectively. The results indicate that medium dose FRPP reduced the levels of hormone such as testosterone, dihydrotestosterone, and oestradiol in rats with BPH by about 32%, thus bringing the prostate tissue of BPH rats closer to normal. More importantly, medium dose FRPP treatment had a significant effect on the composition of gut microbiota in rats with BPH, increasing the levels of beneficial genera (such as Coprococcus and Jeotgalicoccus), and decreasing the levels of harmful pathogens (such as Turicibacter and Clostridiaceae_Clostridium) in the gut. This study showed that medium dose FRPP reduced the hormone level and regulated the unbalanced gut microbiota in BPH rats, thereby alleviating BPH.

Clinical epidemiology and outcome of HIV-associated talaromycosis in Guangdong, China, during 2011-2017.

OBJECTIVES: Talaromycosis is an invasive mycosis endemic to Southeast Asia. This study aimed to investigate the epidemiology, clinical features and prognostic factors of HIV-associated talaromycosis in Guangdong, China. METHODS: We retrospectively evaluated HIV patients hospitalized with histopathology- or culture-confirmed talaromycosis between 2011 and 2017. Factors associated with poor prognosis were identified using logistic regression. RESULTS: Overall, 1079 patients with HIV-associated talaromycosis were evaluated. Both the number and prevalence of talaromycosis among HIV admissions increased from 125 and 15.7% in 2011 to 253 and 18.8% in 2017, respectively, reflecting the increase in HIV admissions. Annual admissions peaked during the rainy season between March and August. Common clinical manifestations included fever (85.6%), peripheral lymphadenopathy (72.3%), respiratory symptoms (60.8%), weight loss (49.8%), skin lesions (44.5%) and gastrointestinal symptoms (44.3%). Common laboratory abnormalities were hypoalbuminaemia (98.6%), anaemia (95.6%), elevated aspartate aminotransferase level (AST) (76.9%), elevated alkaline phosphatase level (55.8%) and thrombocytopenia (53.7%). The median CD4 count was 9 cells/µL. Talaromyces marneffei was isolated from blood and bone marrow cultures of 66.6% and 74.5% of patients, respectively. The rate increased to 86.6% when both cultures were performed concurrently. At discharge, 14% of patients showed worsening conditions or died. Leucocytosis, thrombocytopenia, elevated AST, total bilirubin, creatinine and azole monotherapy independently predicted poor prognosis. CONCLUSIONS: The incidence of HIV-associated talaromycosis has increased in Guangdong with the high HIV burden in China. Skin lesions were seen in less than half of patients. Induction therapy with azole alone is associated with higher mortality. Findings from this study should help to improve treatment of the disease.

[Pathological diagnosis of lung cancer based on deep transfer learning].

Objective: To establish an artificial intelligence (AI)-assisted diagnostic system for lung cancer via deep transfer learning. Methods: The researchers collected 519 lung pathologic slides from 2016 to 2019, covering various lung tissues, including normal tissues, adenocarcinoma, squamous cell carcinoma and small cell carcinoma, from the Beijing Chest Hospital, the Capital Medical University. The slides were digitized by scanner, and 316 slides were used as training set and 203 as the internal test set. The researchers labeled all the training slides by pathologists and establish a semantic segmentation model based on DeepLab v3 with ResNet-50 to detect lung cancers at the pixel level. To perform transfer learning, the researchers utilized the gastric cancer detection model to initialize the deep neural network parameters. The lung cancer detection convolutional neural network was further trained by fine-tuning of the labeled data. The deep learning model was tested by 203 slides in the internal test set and 1 081 slides obtained from TCIA database, named as the external test set. Results: The model trained with transfer learning showed substantial accuracy advantage against the one trained from scratch for the internal test set [area under curve (AUC) 0.988 vs. 0.971, Kappa 0.852 vs. 0.832]. For the external test set, the transferred model achieved an AUC of 0.968 and Kappa of 0.828, indicating superior generalization ability. By studying the predictions made by the model, the researchers obtained deeper understandings of the deep learning model. Conclusions: The lung cancer histopathological diagnostic system achieves higher accuracy and superior generalization ability. With the development of histopathological AI, the transfer learning can effectively train diagnosis models and shorten the learning period, and improve the model performance.

[Evaluation of the efficacy of cyclosporin A combined with recombined human thrombopoietin for treating patients with non-severe aplastic anemia].

Objectives: To compare the efficacy of cyclosporin A (CsA) alone and CsA combined with recombined human thrombopoietin (rhTPO) in patients with non-severe aplastic anemia (NSAA) . Methods: Data from 83 patients with NSAA between August 2014 and February 2019 were collected retrospectively. The study population included 35 men and 48 women, with a median age of 45 years (14-85 years) . Among them, 57 had been treated with CsA + rhTPO, TPO was administered at 15 000 U QD for 7 days, once a month for 3 months, and the other 26 patients with compatible baseline characters were treated with CsA alone. All the enrolled patients had been treated with CsA for at least 6 months and were followed up for at least 1 year. The efficacy and outcome were compared between the two groups. Results: Total 23 men and 34 women, with a median age of 46 years (14-85 years) were treated with CsA + rhTPO. The median duration of CsA treatment was 17 (8-28) months, and the patients were followed up for a median of 27 (12-45) months. Total 12 men and 14 women, with a median age of 40 years (20-64) were treated with CsA alone. The median duration of CsA treatment was 19 months (9-30 months) , and the median follow-up duration was 29 months (16-66 months) . There was no significant difference in the baseline characteristics of the two groups (P>0.05) . There was no significant difference in the CR and OR rates of the two groups at 1, 3, 6, 12, and 24 months of treatment (P>0.05) . The change in the platelet level for the CsA + rhTPO treated group after 1 month[8 (-12-86) ×10(9)/L vs. 3 (16-57) ×10(9)/L, P=0.029) , 3 months[24 (-6-102) ×10(9)/L vs. 7 (-9-76) ×10(9)/L, P=0.006], and 6 months[33.5 (-4-123) ×10(9)/L vs. 12.5 (-14-109) ×10(9)/L, P=0.048] of treatment was higher than that in the CsA alone group, while no significant difference was found between the two groups at other time points. There was no significant difference in the change in the megakaryocyte level between the two groups[3 (0-4) vs. 2 (0-5) , z=-0.868, P=0.385] after 6 months of treatment. Apart from 10.5% (6/57) of the patients in the CsA + rhTPO treated group who reported soreness at the injection site, there was no other significant difference between the two groups in terms of adverse effects. During the follow-up period, there were two cases of increasing paroxysmal nocturnal hemoglobinuria clone to over 10%, one in the CsA + rhTPO treated group, the other in the CsA alone group; and there was one case of progression to SAA in the CsA + rhTPO treated group; while no case of death or thromboembolic event (TEE) , fibrosis or reticulin proliferation, progression to myelodysplastic syndrome (MDS) , or acute myeloid leukemia was observed in either group. There was one case of progression to SAA in the CsA + rhTPO treated group but none in the CsA alone group. Conclusion: Compared to CsA alone, CsA + rhTPO treatment can accelerate the recovery of the platelet level with acceptable adverse effects.

Effects of sarcopenia, hypoalbuminemia, and laparoscopic surgery on postoperative complications in elderly patients with colorectal cancer: A prospective study.

With the increasing number of elderly patients, the risk of diseases such as colorectal cancer (CRC) has increased. The objective of this prospective study was to explore the effects of sarcopenia, hypoalbuminemia, and laparoscopic surgery on postoperative complications among elderly patients who recently underwent colorectal surgery. Patients aged over 65 years who underwent surgery for CRC at the First Affiliated Hospital of Wenzhou Medical University were considered for this study. The demographical and clinical characteristics of these patients, as well as postoperative complications, were prospectively analyzed. The patients were divided into two groups depending on the diagnosis of sarcopenia, and the clinical variables corresponding to the two groups were compared. Further, the risk factors associated with postoperative complications were evaluated using univariate analysis and multivariate logistic regression analysis. A total of 360 patients fulfilled the inclusion criteria. Incidences of postoperative complications in the sarcopenia and non-sarcopenia groups were at 38.3% and 27.3%, respectively. In addition, sarcopenia (p=0.029) and hypoalbuminemia (p=0.010) were identified as independent risk factors, while laparoscopic surgery (p=0.023) was identified as a protective factor for postoperative complications. However, laparoscopic surgery was a protective factor for postoperative complications in the colon group only (p=0.001). Sarcopenia and hypoalbuminemia are independent risk factors that influence the probability of developing complications following CRC surgery. Laparoscopic surgery is a protective factor for postoperative complications of CRC patients, particularly colon cancer patients.

Effect of chlorhexidine bathing on colonization or infection with Acinetobacter baumannii: a systematic review and meta-analysis.

Healthcare-associated infections (HAIs) caused by multi-drug-resistant Gram-negative bacteria (MDRGNB) have increased prevalence in intensive care units (ICUs). A common strategy to prevent HAIs is bathing patients with chlorhexidine gluconate (CHG). However, the effectiveness of CHG bathing against multidrug-resistant Acinetobacter baumannii (MDRAB) is still controversial. The aim of this study was to perform a systematic review and meta-analysis of the effectiveness of CHG bathing on Acinetobacter baumannii colonization and infection in the ICU setting. A systematic literature search of PubMed, EMBASE, Web of Science and CINAHL was performed from inception through to June 2018. Randomized controlled trials (RCTs), pre-post studies, or interrupted time series (ITS) studies were included. The numbers of patients with/without colonization or infection of A. baumannii in the experimental or control groups were extracted from each study. Quality assessment was performed by the related instruments of National Institute of Health. Pooled risk ratios (RRs) were calculated using the random-effects model. One RCT and 12 pre-post or ITS studies comprising 18,217 patients were included, of which 8069 were in the CHG bathing arm and 9051 in the control arm. CHG bathing was associated with a reduced colonization of A. baumannii (RR, 0.66; 95% confidence interval: 0.57-0.77; P<0.001). Chlorhexidine at 4% showed a better effect than 2% chlorhexidine (meta-regression P=0.044). CHG bathing was associated with a non-significant reduction of infection (pooled RR 0.41, 95% CI: 0.13-1.25). This study suggests that CHG bathing significantly reduces colonization of A. baumannii in the ICU setting. However, more trials are needed to confirm whether CHG bathing can reduce infections with A. baumannii.

Elevated hepatic MDR3/ABCB4 is directly mediated by MiR-378a-5p in human obstructive cholestasis.

OBJECTIVE: The function of MDR3 is important in bile acid transport. The miRNAs can suppress the expression of gene through combining mRNA of target gene. The regulation about MDR3 mediated by FXR or PPARα in cholestasis is clear, but the mechanism through miRNA is hardly reported. We aimed to find out the miRNA, which could suppress MDR3 expression and the significance of this connection in cholestasis. PATIENTS AND METHODS: We measured hsa-miR-378a-5p expression level in liver tissues from 20 patients with cholestasis and 15 patients without cholestasis by quantitative PCR. We also tested the level of clinical features of the same group. HepG2 cell lines were performed experiments to discover the connection between hsa-miR-378a-5p and MDR3, including transient transfection, RNA and protein extraction, qPCR, Western blotting and luciferase reporter assay. RESULTS: A significant decrease of miR-378a-5p was observed in obstructive cholestasis patient liver tissues compared to control group. We also find that the miR-378a-5p expression is correlated to several clinical features, which are important biomarkers in cholestatic liver injury. Then we predicted that MDR3 may be the target gene of miR-378a-5p through miRanda v3.3a. We programed the transient transfection of mimics and inhibitor on HepG2 cell lines, and detected the mRNA and protein expression of MRP2, MRP3 and MDR3. The results suggested that miR-378a-5p could negatively regulate MDR3 expression in both mRNA and protein expression level, and this regulation is specific. We didn't find same regulation in MRP2 and MRP3. Dual luciferase assays proved this regulation is mediated by a direct binding between miR-378a-5p and CDS of MDR3. CONCLUSIONS: We found that hsa-miR-378a-5p expression was down-regulated in cholestatic liver tissues, compared to control liver tissues. Transient transfection and luciferase reporter assay in HepG2 cell lines results suggest that hsa-miR-378a-5p can directly combine MDR3 mRNA and suppress MDR3 protein expression. The down-regulated hsa-miR-378a-5p may cause a protective alteration through up-regulating MDR3 expression in cholestasis.

[Recent studies on the signaling pathways implicated myopia].

Myopia has emerged as one of the major health issues in China given its increasingly high prevalence. It is generally accepted that myopia is the result of a complex interaction of environmental exposures and genetic predisposition. Many studies have indicated that abnormal visual stimulation regulates retinal neurotransmitters and growth factors to release resulting in scleral remodeling and axial elongation through signaling pathway transduction. It has been reported that the signaling pathways play important roles in the elongation of axial length and development of myopia. In this study, we reviewed several important signaling pathways implicated myopia.(Chin J Ophthalmol, 2019, 55:148-152).

Incidence and risk factors of osteomyelitis in adult and pediatric systemic lupus erythematosus: a nationwide, population-based cohort study.

OBJECTIVE: The objective of this paper is to investigate the incidence rate, risk factors and outcome of osteomyelitis among patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: We conducted a cohort study using data for patients enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. Patients with SLE and age- and sex-matched controls without SLE were enrolled. Primary endpoint was the first occurrence of osteomyelitis. Risks of osteomyelitis in SLE patients were analyzed with Cox proportional hazards regression models, including age, sex, comorbidities and medications. RESULTS: Among 24,705 SLE patients (88.4% women, mean age 35.8 years) with a median follow-up of 9.1 years, 386 patients had osteomyelitis. The incidence rate ratio (IRR) of osteomyelitis in the SLE group vs the control group was 8.52 (95% confidence interval (CI) 7.24-10.05). The SLE group had higher incidence rates of osteomyelitis than the control group, especially in pediatric subgroups (IRR 41.1 95% CI 18.57-107.35). Compared to controls, SLE patients experienced osteomyelitis at a younger age (42.3 vs 58.1 years) but did not have an increased risk of mortality (hazard ratio 0.7; 95% CI 0.21-2.38). Age >60 years, male gender, malignancy within five years, prior bone fracture and higher daily prednisolone dose (>7.5 mg) cumulatively for >180 days increased risk for osteomyelitis. CONCLUSIONS: SLE patients have a higher IRR of osteomyelitis than controls. Pediatric and elder SLE patients, patients with a history of bone fracture, malignancy within five years and higher-dose glucocorticoid use have a higher risk of osteomyelitis and should be carefully monitored.

External validation of a modified trauma and injury severity score model in major trauma injury.

BACKGROUND: The establishment of an accurate prognostic model in major trauma patients is important mainly because this group of patients will benefit the most. Clinical prediction models must be validated internally and externally on a regular basis to ensure the prediction is accurate and current. This study aims to externally validate two prediction models, the Trauma and Injury Severity Score model developed using the Major Trauma Outcome Study in North America (MTOS-TRISS model), and the NTrD-TRISS model, which is a refined MTOS-TRISS model with coefficients derived from the Malaysian National Trauma Database (NTrD), by regarding mortality as the outcome measurement. METHOD: This retrospective study included patients with major trauma injuries reported to a trauma centre of Hospital Sultanah Aminah over a 6-year period from 2011 and 2017. Model validation was examined using the measures of discrimination and calibration. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC) and 95% confidence interval (CI). The Hosmer-Lemeshow (H-L) goodness-of-fit test was used to examine calibration capabilities. The predictive validity of both MTOS-TRISS and NTrD-TRISS models were further evaluated by incorporating parameters such as the New Injury Severity Scale and the Injury Severity Score. RESULTS: Total patients of 3788 (3434 blunt and 354 penetrating injuries) with average age of 37 years (standard deviation of 16 years) were included in this study. All MTOS-TRISS and NTrD-TRISS models examined in this study showed adequate discriminative ability with AUCs ranged from 0.86 to 0.89 for patients with blunt trauma mechanism and 0.89 to 0.99 for patients with penetrating trauma mechanism. The H-L goodness-of-fit test indicated the NTrD-TRISS model calibrated as good as the MTOS-TRISS model for patients with blunt trauma mechanism. CONCLUSION: For patients with blunt trauma mechanism, both the MTOS-TRISS and NTrD-TRISS models showed good discrimination and calibration performances. Discrimination performance for the NTrD-TRISS model was revealed to be as good as the MTOS-TRISS model specifically for patients with penetrating trauma mechanism. Overall, this validation study has ascertained the discrimination and calibration performances of the NTrD-TRISS model to be as good as the MTOS-TRISS model particularly for patients with blunt trauma mechanism.

Invasive aspergillosis in patients with systemic lupus erythematosus: a retrospective study on clinical characteristics and risk factors for mortality.

Objective The objective of this paper is to analyze the clinical features, outcomes, mortality risk factors, and all-cause mortalities of invasive aspergillosis (IA) in patients with systemic lupus erythematosus (SLE). Methods Medical records were reviewed to identify SLE patients with IA from January 2006 to June 2017, at Taipei Veterans General Hospital, Taiwan. A total of 6714 SLE patients were included. Clinical/laboratory parameters and treatment outcomes were analyzed. Results Four patients (19.0%) had definite and 17 had probable (81.0%) IA. Seven patients (33.3%) survived and 14 died (66.7%). Concurrently, there were 19 pneumonias (90.5%), 17 cases of other infections (81.0%), eight bacteremia (38.1%), nine cytomegalovirus (CMV, 42.7%) and six Candida (28.6%) infections. In all 55 blood cultures, 38 (69.1%) yielded gram-negative bacilli, of which carbapenem-resistant A. baumannii accounted for eight (21.1%); 17 (30.9%) yielded gram-positive cocci, of which methicillin-resistant S. aureus accounted for six (35.3%); and vancomycin-resistant Enterococcus accounted for four (23.5%). Daily steroid dose ≥ 20 mg (hazard ratio (HR) 2.00), recent pulse steroid therapy (HR 2.80), azathioprine (HR 2.00), rituximab (HR 2.00), plasmapheresis (HR 2.00), acute respiratory distress syndrome (HR 2.00), concurrent infections (HR 5.667) and CMV viremia (HR 1.75) were higher in the fatality group. All p values were less than 0.05. Septic shock ( n = 7, 50% in the fatality group) is the most common cause of mortality. Conclusions High daily steroid dosing, recent pulse steroid therapy, azathioprine, rituximab, concurrent infections, and CMV viremia were mortality risk factors for IA in SLE.

[Spatial-temporal analysis of enterovirus infection in Macao Special Administrative Region, China, 2011-2016].

Objective: To understand the spatial-temporal distribution of enterovirus infection in Macao Special Administrative Region, China, from 2011 to 2016. Methods: The incidence data of enterovirus infections in child care settings and primary schools in Macao during this period, which were confirmed by the Health Bureau, were used for the spatial-temporal analysis. Bernoulli model was used as probability model. Software SPSS 20.0 was used for descriptive statistics of the study cases, and software SaTScan 9.4.4 was used for spatial and temporal scanning. Finally, software Google Earth was used for visualization of geographical information. Results: A total of 330 enterovirus infection events were reported in Macao from 2011 to 2016. The infection event number was highest in 2014 (101, 30.6%), the infections mainly occurred during May to June. A case clustering area with a radius of 0.7 km (high rates) was observed in northeast of Macao from 2011 to 2013 (log likelihood rate=13.4, P<0.001, RR=1.4). Conclusion: The annual prevention of enterovirus infection and related health education should be started in February and March in Macao, and the key area is the northeast of Macao island.

Susceptibility profile of echinocandins, azoles and amphotericin B against yeast phase of Talaromyces marneffei isolated from HIV-infected patients in Guangdong, China.

Talaromyces marneffei (T. marneffei) can cause talaromycosis, a fatal systemic mycosis, in patients with AIDS. With the increasing number of talaromycosis cases in Guangdong, China, we aimed to investigate the susceptibility of 189 T. marneffei clinical strains to eight antifungal agents, including three echinocandins (anidulafungin, micafungin, and caspofungin), four azoles (posaconazole, itraconazole, voriconazole, and fluconazole), and amphotericin B, with determining minimal inhibition concentrations (MIC) by Sensititre YeastOne™ YO10 assay in the yeast phase. The MICs of anidulafungin, micafungin, caspofungin, posaconazole, itraconazole, voriconazole, fluconazole, and amphotericin B were 2 to > 8 µg/ml, >8 µg/ml, 2 to > 8 µg/ml, ≤ 0.008 to 0.06 µg/ml, ≤ 0.015 to 0.03 µg/ml, ≤ 0.008 to 0.06 µg/ml, 1 to 32 µg/ml, and ≤ 0.12 to 1 µg/ml, respectively. The MICs of all echinocandins were very high, while the MICs of posaconazole, itraconazole, and voriconazole, as well as amphotericin B were comparatively low. Notably, fluconazole was found to have a higher MIC than other azoles, and exhibited particularly weak activity against some isolates with MICs over 8 µg/ml. Our data in vitro support the use of amphotericin B, itraconazole, voriconazole, and posaconazole in management of talaromycosis and suggest potential resistance to fluconazole.

Reliability and validity of the English and Malay versions of the Driving and Riding Questionnaire: a pilot study amongst older car drivers and motorcycle riders.

OBJECTIVES: This study aimed to examine the reliability and validity of the English and Malay versions of the Driving and Riding Questionnaire. STUDY DESIGN: An observational study with a mix-method approach by utilising both questionnaire and short debriefing interviews. METHODS: Forward and backward translations of the original questionnaire were performed. The translated questionnaire was assessed for clarity by a multidisciplinary research team, translators, and several Malay native speakers. A total of 24 subjects participated in the pilot study. Reliability (Cronbach's alpha) and validity (content validity) of the original and translated questionnaires were examined. RESULTS: The English and Malay versions of the Driving and Riding Questionnaire were found to be reliable tools in measuring driving behaviours amongst older drivers and riders, with Cronbach's alpha of 0.9158 and 0.8919, respectively. For content validity, the questionnaires were critically reviewed in terms of relevance, clarity, simplicity, and ambiguity. The feedback obtained from participants addressed various aspects of the questionnaire related to the improvement of wordings used and inclusion of visual guide to enhance the understanding of the items in the questionnaire. This feedback was incorporated into the final versions of the English and Malay questionnaires. CONCLUSION: The findings of this study demonstrated both the English and Malay versions of the Driving and Riding Questionnaire to be valid and reliable.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Risk of infective endocarditis in patients with systemic lupus erythematosus in Taiwan: a nationwide population-based study.

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the control cohort. By contrast, the older systemic lupus erythematosus cohort had lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox multivariate proportional hazards analysis revealed heart disease (hazard ratio = 5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034), receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001), and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001) were independent risk factors for infective endocarditis in systemic lupus erythematosus patients. Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.