[Clinical features and influencing factors of long-term prognosis in patients with tuberculous meningitis].

Objective: To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM. Methods: Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression. Results: A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly (OR=1.06, P=0.048 ) , hyponatremia(OR=0.81,P=0.020), high protein level in cerebrospinal fluid (CSF) (OR=3.32,P=0.033), cerebral infarction(OR=10.50,P=0.040) and hydrocephalus(OR=8.51,P=0.049) were associated with poor prognosis in TBM patients. Conclusions: The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.

[The 469th case: multiple cutaneous abscesses, pelvic mass, and lung cavities].

A 28-year-old woman with multiple abscesses for 2 month and fever for 1 month was admitted in Peking Union Medical College Hospital. The skin abscesses gradually developed at skull, face, abdominal wall and pelvis. Laboratory examinations related to inflammatory reactions were strongly high including erythrocyte sedimentation rate 99 mm/1 h,C-reactive protein160.28 mg/L and ferritin 1 584 µg/L. Multiple nodules and cavities were detected in lungs. And vesico-cervical fistula was found during exploratory laparotomy. The pathological tests of abdominal tissues demonstrated necrosis and granuloma. Evidence of infectious diseases was not definite. Positive anti-proteinase 3 (PR3) antibody confirmed the diagnosis of granulomatosis with polyangiitis. After treated with glucocorticoid and immunosuppressants, the patient's symptoms improved remarkably. This case suggested that systemic vasculitis should be considered as a differential diagnosis of multiple abscesses which are not explained by infections.

[The 468th case: periodic fever, abdominal pain, small intestinal ulcers, NOD2 gene mutation].

Fever and abdominal pain are common symptoms and could be main manifestations in patients with autoinflammatory diseases. A 48-year-old female patient was admitted with recurrent fever and abdominal pain for 9 years. Serum level of inflammatory markers synchronously fluctuated with fever, and returned to normal when fever subsided. The periodic episodes of fever occurred every 1 to 4 months and failed to respond to empirical antibiotics. Whole exome sequencing showed heterozygous mutation of NOD2 gene q902k, leading to the final diagnosis of autoinflammatory disease. Corticosteroid and tripterygiumglycosides were effective for the disease remission.

[A clinical analysis of six patients with Brucella endocarditis and literature review].

Objective: To analyze the epidemiology and clinical characteristics of patients with Brucella endocarditis in order to improve the understanding and treatment of Brucella endocarditis. Methods: The clinical data including demographic characteristics, clinical features, laboratory data, echocardiography, treatment and clinical outcome of 6 patients with Brucella endocarditis were collected and analyzed. Results: In our database consisting of 211 brucellosis patients with positive blood culture, 6 patients (2.8%) with Brucella endocarditis were selected from May 2007 to December 2016 in Peking Union Medical College Hospital.The age range was 25-55 years, among whom 5 patients were men.The majority were farmers and all patients reported the history of closely contact with livestock.All of them had fever and 3 of them had arthralgia.Four patients had aortic involvement (4/6) and 2 of them presented with symptoms of left ventricular failure at admission.Blood culture of Brucella and serum agglutination test of Brucella were positive in all of them.Combined antibiotics treatments were given to all patients.Valve replacement surgery was performed in four patients, among them, three patients well recovered, one lost. Among all the patients, four were followed up continually and other two were lost. Conclusions:Brucella endocarditis has a predominance of aortic involvement and is prone to left ventricular failure.Early antibiotic treatment combined with valve-replacement surgery is effective to improve the prognosis.

Drug-drug interaction between valproic acid and meropenem: a retrospective analysis of electronic medical records from neurosurgery inpatients.

WHAT IS KNOWN AND OBJECTIVE: A series of studies have indicated that valproic acid (VPA) plasma concentration decreased rapidly when used concomitantly with carbapenem antibiotics, including meropenem (MEPM), imipenem and panipenem, which may increase the risk of seizure breakthrough. However, the cause for the change in VPA pharmacokinetics is unclear. A retrospective analysis of VPA therapeutic drug monitoring (TDM) records was performed to investigate this VPA pharmacokinetics drug-drug interaction. METHODS: Three hundred and eighty one VPA TDM records from the Department of Neurosurgery of Xiangya Hospital from January 2012 to December 2014 were collected. The VPA TDM records were categorized by VPA and MEPM daily dosages in grams/day (g/day). A comparison of VPA plasma levels among different groups was performed to investigate the change in VPA level in this drug interaction. RESULTS AND DISCUSSION: Remarkable decreases in VPA plasma level were observed when the drug was used concomitantly with MEPM in both 1.2 g/d and 1.6 g/d VPA groups (67·3 ± 4·6 µg/mL, n = 21 vs. 15·3 ± 1·9 µg/mL, n = 15, P < 0·001; 67·6 ± 1·2 µg/mL vs. 18·1 ± 2·6 µg/mL, n = 38, P < 0·001). No significant difference in VPA plasma concentrations was observed between the 1·2 g/day VPA + MEPM, 1·6 g/day VPA + MEPM and 2·0 g/day VPA + MEPM groups (15·3 ± 1·9 µg/mL, n = 15 vs. 18·1 ± 2·6 µg/mL, n = 38 vs. 9·0 ± 3·0 µg/mL, n = 7; P = 0·252). The decrease in VPA concentration was independent of MEPM daily dose (14·0 ± 5·1 µg/mL, n = 4 for high MEPM daily dose vs. 16·5 ± 1·9 µg/mL, n = 56 for low MEPM daily dose; P = 0·729). After discontinuation of MEPM for more than 7 days, VPA plasma concentration recovered to a value comparable to that before MPEM initiation (69·7 ± 4·2 µg/mL, n = 21 vs. 51·2 ± 8·1 µg/mL, n = 9; P = 0·48). WHAT IS NEW AND CONCLUSION: This is the first study using a large number of VPA TDM records to investigate the change in VPA levels caused by concomitant use of MEPM. Our results imply that the decrease in drug concentration cannot be reversed by increasing VPA dose. Moreover, MEPM daily dose did not influence the drop in VPA plasma level. At least 7 days are required for the recovery of VPA plasma concentration after discontinuation of MEPM.

Prevalence of methylenetetrahydrofolate reductase C677T and its association with arterial and venous thrombosis in the Chinese population.

Moderate hyperhomocysteinaemia (MHH) is associated with arterial and venous thrombosis. A main genetic defect related to MHH is a C to T substitution at nucleotide 677 of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. A prothrombin 20210A mutation was recently identified as a risk factor for arterial and venous thrombosis. However, studies on the prevalence of mutant MTHFR C677T and prothrombin G20210A and their association with thrombosis were controversial and seldom reported in the Chinese population. We investigated the prevalence of MTHFR C677T and prothrombin G20210A genotypes by polymerase chain reaction (PCR) followed by restriction enzyme digestion in 420 Chinese subjects: 53 with deep venous thrombosis (DVT); 145 with cerebrovascular disease [115 cerebral infarction, 30 cerebral haemorrhage (CH)]; 100 with coronary artery disease (CAD); and 122 control subjects. The prevalence of the mutated MTHFR 677TT genotype and the 677T allele in normal controls was 12.3% and 30.7% respectively, similar to that in Caucasians and Japanese. The mutant 677T homozygotes and alleles were more frequent in patients with DVT than in controls (18.9% vs. 12.3%, 0.01 < P < 0. 025; 48.1% vs. 30.7%, P < 0.005). The relative risk of DVT among the carriers of 677TT and 677T were significantly increased [odds ratios: 3.4, 95% confidence interval (CI) 1.3-9.5, and 3.6, 95% CI 1. 7-7.7, respectively). The mutant MTHFR heterozygous 677C/T carriers were increased in patients with cerebral infarction compared with controls (53.9% vs. 36.9%, 0.01 < P < 0.025). Relative risk of cerebral infarction was 0.96 (95% CI 0.4-2.3) for 677TT homozygotes and 1.99 (95% CI 1.2-3.4) for 677C/T heterozygotes. However, the distribution of the MTHFR TT genotype was less frequent in patients with CAD with coronary artery stenosis of > 50% than in controls (2. 8% vs. 12.3%, 0.025 < P < 0.05). Relative risk of CAD was not increased among the carriers of 677TT and 677T (odds ratios: 0.2, 95% CI 0-1.1, and 0.97, 95% CI 0.5-1.8, respectively). There were no differences in the distribution of the MTHFR genotypes among CH, CAD with coronary artery stenosis of < 50% and controls. The prothrombin 20210A mutation was not found in any patients or controls. These results demonstrated that MTHFR 677T was associated with DVT and cerebral infarction but was less associated with CAD in the Chinese population.

Influence of selective decontamination of the digestive tract on cell-mediated immune function and bacteria/endotoxin translocation in thermally injured rats.

OBJECTIVE: To determine the influence of pretreatment with selective decontamination of the digestive tract (SDD) on systemic immunosuppression, and the relationship between bacteria/endotoxin translocation and abnormalities of immune function in thermally injured rats. DESIGN, MATERIALS, AND METHODS: Animals were subjected to a 40% full-thickness scald injury, and divided into SDD-treated and control groups. The treatment group received SDD (polymyxin E, tobramycin, and 5-flucytosine) by gavage twice daily for 3 days before the experiment and continued for 5 days after thermal injury. The control group was given the same amount of water. The parameters reflecting cell-mediated immunity, including splenocyte proliferation in response to mitogens, interleukin 2 (IL-2) production, and lymphocyte subpopulation, were measured before injury and 1 and 5 days after burn, respectively. MEASUREMENTS AND MAIN RESULTS: Thermal injury resulted in marked reduction in splenocyte proliferative response to T-cell mitogens, IL-2 production, and T-helper/suppressor cells (CD4/CD8) ratio. Prophylactic treatment with SDD significantly decreased the incidences of bacterial translocation and endotoxemia, prevented suppressive mitogenic response and inadequate IL-2 production (p < 0.05-0.01) but did not affect the abnormal ratio of CD4 to CD8 T lymphocytes in blood (p > 0.05). CONCLUSIONS: These results suggest that bacteria/endotoxin translocation from the gut appears to be involved in cell-mediated immune dysfunction as a consequence of thermal injury. Pretreatment with SDD might attenuate postburn immunosuppression by preventing translocation events.