Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to 1 or more antituberculosis drugs is an increasingly common clinical problem, although the impact on outcome is uncertain. METHODS: We performed a prospective study of 180 Vietnamese adults admitted consecutively for TBM. M. tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and was tested for susceptibility to first-line antituberculosis drugs. Presenting clinical features, time to CSF bacterial clearance, clinical response to treatment, and 9-month morbidity and mortality were compared between adults infected with susceptible and those infected with drug-resistant organisms. RESULTS: Of 180 isolates, 72 (40.0%) were resistant to at least 1 antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and rifampicin. Isoniazid and/or streptomycin resistance was associated with slower CSF bacterial clearance but not with any differences in clinical response or outcome. Combined isoniazid and rifampicin resistance was strongly predictive of death (relative risk of death, 11.63 [95% confidence interval, 5.21-26.32]) and was independently associated with human immunodeficiency virus infection. CONCLUSIONS: Isoniazid and/or streptomycin resistance probably has no detrimental effect on the outcome of TBM when patients are treated with first-line antituberculosis drugs, but combined isoniazid and rifampicin resistance is strongly predictive of death.     

Chemokines and Antimicrobial Peptides Have a cag-Dependent Early Response to Helicobacter pylori Infection in Primary Human Gastric Epithelial Cells

Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection.     

Cardioprotection by clopidogrel in acute ST-elevated myocardial infarction patients: a retrospective analysis

Antiplatelet agents have been extensively used in acute coronary syndromes and improve clinical outcome in STEMI patients. Previous experimental studies of the impact of antiplatelet agents on infarct size have been equivoqual. We questioned whether clopidogrel might reduce infarct size in STEMI patients, independently of any antithrombotic effect, by activating a post-conditioning-like myocardial protection. We retrospectively analyzed three recent controlled, randomized, proof of concept clinical trials aimed at determining whether PCI post-conditioning might attenuated infarct size in STEMI. We addressed whether clopidogrel (300-600?mg before angioplasty) might have influenced infarct size using a multivariable linear regression analysis with infarct size as the continuous outcome variable and age, clopidogrel and GP IIb/IIIa inhibitors, post-conditioning, area at risk, ischemia time, coronary thrombectomy and final TIMI flow, as covariates. In this population of 88 STEMI patients, ischemic post-conditioning and clopidogrel administration were the only two therapeutic independent predictors of the final infarct size as determined by cardiac enzymes release (p?=?0.005 and p?相似文献   

Polarity Independent Effects of Cerebellar tDCS on Short Term Ankle Visuomotor Learning

BackgroundTranscranial direct current stimulation (tDCS), an emerging technique of noninvasive brain stimulation, has shown to produce beneficial neural effects in consequence with improvements in motor behavior. There are not many studies examining the use of tDCS for lower limb motor control and learning. Most studies using tDCS for facilitating lower limb motor coordination have applied tDCS to the lower limb motor cortex (M1). As the cerebellum is also critically involved in movement control, it is important to dissociate the effect of tDCS on the cerebellum and M1 with respect to lower limb motor control before we begin the application of tDCS as a neuromodulatory tool.Objective/HypothesisThe purpose of this study was to determine the effects of cerebellar vs. motor cortical tDCS on short term ankle visuomotor learning in healthy individuals.MethodsEight healthy individuals practiced a skilled ankle motor tracking task while receiving either facilitatory anodal tDCS to cerebellum, inhibitory cathodal tDCS to cerebellum, facilitatory anodal tDCS to M1, inhibitory cathodal tDCS to M1 or sham stimulation. Pre- and post-measures of changes in cortical excitability of the tibialis anterior muscle and measures of tracking accuracy were assessed.ResultsAnodal cerebellar, cathodal cerebellar, and anodal M1 stimulation improved target-tracking accuracy of the ankle. This was not dependent on the observed changes in motor cortical excitability of the tibialis anterior muscle.Conclusion(s)Polarity independent effects of tDCS on cerebellum were observed. The present study shows that modulation effects of tDCS can occur because of changes in the cerebellum, a structure implicated in several forms of motor learning, providing an additional way in which tDCS can be used to improve motor coordination.     

Automated synthesis of 68Ga/177Lu-PSMA on the Trasis miniAllinOne

Prostate-specific membrane antigen (PSMA)-based radioligands for positron emission tomography (PET)/computed tomography (CT) studies represent the gold standard for detection of recurrent prostate cancer (PCa). [⁶⁸Ga]PSMA-HBED-CC is a PET radiotracer suitable for detection of PCa, and its clinical use has become widespread over the last few years. In this contribution, we detail our GMP-compliant production of [⁶⁸Ga]PSMA-HBED-CC using the Trasis miniAllinOne radiosynthesizer and report synthetic and clinical data for the first 100 productions of 2019. Additionally, we detail our efforts towards a GMP-compliant production of the radiotherapeutic [¹⁷⁷Lu]PSMA-I&T using the same synthesis module. PSMA-based radioligand therapy (RLT) offers a possible future treatment in cases of metastatic castration-resistant PCa, and GMP-compliant routine production methods are therefore called for. This report highlights how PSMA-based agents for theranostic purposes can be conveniently produced at a single radiochemistry Good Manufacturing Practice (GMP) site, thereby facilitating optimized detection and treatment of PCa.     

WHO's Service Availability and Readiness Assessment of primary health care services of commune health centers in a rural district of Northern Vietnam

The objective of this study was to assess the availability and readiness of the primary health care (PHC) services of commune health centers (CHCs) in Quoc Oai, a rural district of Northern Vietnam based on the World Health Organization's Service Availability and Readiness Assessment (SARA) tool. The study was done in 2 steps. First, the heads of the 21 CHCs of Quoc Oai district were interviewed using SARA, a quantitative survey, and the responses were then validated by direct observations of each facility. The results showed that although the average number of health staffs in each CHC met the national standards (at least 5 staffs per CHC), its allocation within each CHC was not properly met because some CHCs had only 2 health staffs. Several health equipment and facilities were not fully available in many CHCs, and although the majority of the PHC services were available at the CHCs, their readiness remained limited. Several significant correlates between the availability of health care workers and the availability of the facilities and the PHC services were observed, suggesting that they depend upon and affect one another in the health system. Using the SARA‐based inventory, the study helps health managers and policy makers to prioritize efforts and allocate resources more appropriately. To be effective, attention should be given to how to make facilities, services, and human resources for health ready for PHC activities—more investment and support from the system (from higher to lower level) and the government.     

Single-Port Laparoscopic Repair of Perforated Duodenal Ulcers

Background

Laparoscopic single-port surgery has widely been introduced for the treatment of various abdominal conditions. But controversies still exist regarding its potential advantages and risks, especially for emergency surgery. The aim of this study was to evaluate the results of a single-port laparoscopic repair using straight laparoscopic instruments for the treatment of perforated duodenal ulcers.

Methods

A prospective consecutive case series was conducted including all patients with a perforated duodenal ulcer who underwent a laparoscopic single-port repair at a single institution from January 2012 to June 2018. The operation was performed through a single port using conventional straight laparoscopic instruments and intra-corporeal knot tying techniques.

Results

Out of 75 patients, simple closure of the perforation without omental patch was accomplished in 96% of cases. Conversion to an open operation was required in one patient (1.3%) due to a posterior duodenal perforation, and additional trocar placement was needed in another patient (1.3%). The mean incision length was 2.0 ± 0.2 cm. The mean operation time was 63.0 ± 26.6 min. Meantime a nasogastric tube remained in place was 2.9 ± 0.8 days. Mean duration of analgesic use was 2.8 ± 0.8 days. The rate of postoperative complications was 2.7%, including two patients with wound infections. There were no instances of intestinal leak or abscess. The postoperative hospital stay was 5.7 ± 1.2 days.

Conclusion

Laparoscopic single-port repair using conventional straight laparoscopic instruments with intra-corporeal knot tying technique was safe and feasible for patients with perforated duodenal ulcers with low risk factors. This method offers results comparable to those expected with the standard multiport laparoscopic approach with the addition of improved cosmetic outcomes.