Valproic acid induced aplastic crisis and Stevens-Johnson syndrome in a single pediatric patient.

Valproic acid (VPA) is a commonly used antiepileptic drug (AED). Aplastic crisis is defined as acute arrest of hematopoiesis. Stevens-Johnson syndrome (SJS) is a fatal cutaneous adverse drug reaction. We herein report a rare case of aplastic crisis and SJS in a single pediatric patient that were probably caused by VPA. A 2-year-old girl was involved in a car accident. She was diagnosed with skull fractures, cerebral contusions, pulmonary contusions, and fractures of the left iliac bone by computed tomography. VPA was administered as prophylaxis for post-traumatic epilepsy. From day 13, she developed repeated high fevers, and multiple antibiotics were ineffective; she was then transferred to our pediatric intensive care unit. After transfer, she developed liver function impairment, decreased peripheral blood cell counts, and skin damage. After withdrawal of the VPA and administration of prednisone, intravenous immunoglobulin, local skin care, and nutritional support, her body temperature normalized and her hematopoietic function and skin lesions successively resolved. She was transferred out of the pediatric intensive care unit on day 56 and discharged on day 70. At the 6-month follow-up, a blood examination was normal, and repeat computed tomography revealed multiple softening foci of the bilateral brain and less subdural effusion than before. To our knowledge, no report to date has described aplastic crisis and SJS in a single patient. The purpose of this paper is to increase clinicians' knowledge in the treatment of adverse drug reactions (ADRs) and emphasize the importance of standardized application and strict monitoring of VPA in patients with post-traumatic brain trauma.

Intrahepatic Cholestasis of Pregnancy Increases Inflammatory Susceptibility in Neonatal Offspring by Modulating Gut Microbiota.

Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that is characterized by increased bile acid levels in maternal serum. Studies have shown that cholestatic pregnancy can result in long-term metabolic disturbances in the offspring. However, how ICP shapes the offspring's immunity and predisposition to inflammatory disorders at an early stage is unknown. In this study, we investigated the effect of maternal cholestasis on neonatal offspring metabolism and immune function. We compared 71 neonates with ICP mothers and 63 neonates with healthy mothers and found that the incidence of jaundice and infection was significantly higher in ICP offspring. Maternal serum total bile acid level was associated with blood cell counts in full-term ICP offspring. In animal experiments, a compensatory activation of hepatic and ileal farnesoid X receptor (FXR) and altered gut microbiota in the first week were found in ICP offspring. We also investigated lipopolysaccharide (LPS)-induced inflammatory responses in neonatal rats and found that ICP offspring were more susceptible to inflammation. To understand the correlation between congenital abnormal FXR activation and tissue immunity dysregulation, we assessed the effects of the FXR agonist GW4064 and FXR antagonist E/Z-GS in ICP offspring after LPS exposure. The expression of several pro-inflammatory cytokines significantly decreased after treatment with E/Z-GS but increased after treatment with GW4064. Treatment with the probiotic Lactobacillus rhamnosus LRX01 that inhibits FXR expression in the ileum reduced susceptibility to LPS exposure in ICP offspring. The current study indicated that cholestatic pregnancy may increase the susceptibility of the offspring to inflammation by altering bile acid metabolism and gut microbiota at an early stage. We suggest that supplementation with Lactobacillus rhamnosus LRX01, which inhibits FXR expression in the ileum, may improve intestinal immunity in ICP offspring.

Anti-Osteoporosis Medications Associated with Decreased Mortality after Hip Fracture.

OBJECTIVE: To study the effect of anti-osteoporosis therapies on mortality after hip fracture. METHODS: This retrospective study was carried out in the Second Affiliated Hospital of Fujian Medical University and enrolled 690 patients 50 years of age and older who were admitted with hip fractures between 2010 and 2015. The patients were followed in 2017: 690 patients aged was from 50 to 103 years. There were 456 women and 234 men. There were 335 patients with fractures of the femoral neck and 355 patients with intertrochanteric fractures of the femur. There were 444 (64.35%) patients who also had internal diseases. The Charlson comorbidity index was 0-6. The anti-osteoporosis medications were classified into no anti-osteoporosis medication, calcium + vitamin D supplementations, non-bisphosphonate medication, and bisphosphonate medication. The physicians followed the patients or family members by personal visit and telephone. Multivariable Cox regression analyses were done with known risk factors for mortality of hip fracture, such as gender, age, number of combined internal diseases, fracture type, place of residence, and Charlson comorbidity index, to show which anti-osteoporosis medications had significant effects on mortality after adjustment for these variables. RESULTS: Out of 690 patients with hip fractures, 149 patients received no anti-osteoporosis medication, 63 patients received calcium +vitamin D supplementations, 398 patients received non-bisphosphonate medication, and 80 patients received bisphosphonate medication. The patients were followed between 7 months and 52 months, with the average of 28.53 ± 9.75 months. A total of 166 patients died during the follow-up period. Of 166 deaths, 43 occurred within 3 months, 65 within 6 months, and 99 within 1 year after the hip fracture. In this study, fracture type, place of residence, and Charlson comorbidity index were not associated with the mortality, and the male gender, age > 75 years, and ≥ 2 combined internal diseases were the independent factors for deaths post-hip fracture. The cumulative mortality was 36.24% in the patients receiving no anti-osteoporosis medication. The hazard ratio for mortality after hip fracture with bisphosphonate medication, non-bisphosphonate medication, and calcium/vitamin D supplementation was 0.355 (95% CI, 0.194-0.648), 0.492 (95% CI, 0.347-0.699) and 0.616 (95% CI, 0.341-1.114), respectively, as compared with no anti-osteoporosis group. Bisphosphonate and non-bisphosphonate medications for osteoporosis were significantly associated with the reduction of cumulative mortality post-hip fracture (P < 0.01). CONCLUSIONS: Bisphosphonate and non-bisphosphonate medications for osteoporosis were significantly associated with decreased mortality after fragility hip fracture.