Background H3G34‐mutant diffuse hemispheric glioma (DHG) is recognized as a new, distinct entity in the latest World Health Organization classification for central nervous system tumors and is associated with a particularly aggressive course. The authors performed a systematic review and pooled analysis to investigate the frequency of genetic events in these tumors and to determine whether these events were associated with survival trends. Methods Two electronic databases were accessed to search for relevant data. Included criteria were studies that had individual patient data on H3.3 G34‐mutant gliomas. To analyze the impact of genetic events on overall survival, Kaplan‐Meier analysis and Cox regression models were used, and corresponding hazard ratios and 95% confidence intervals were computed. Results In total, 20 studies with 257 H3G34‐mutant DHGs were included for integrated analyses. The H3 glycine‐to‐valine (H3G34V) mutation showed a significantly worse prognosis than the glycine‐to‐arginine (H3G34R) mutation (median overall survival, 9.9 vs 14.8 months; hazard ratio, 3.040; 95% confidence interval, 1.208‐7.651; P = .018), and this result remained statistically significant in the multivariate Cox regression model. Among H3G34 DHGs, TP53 mutation was the most common genetic alteration (94.9%), followed by ATRX alterations (87.5%), MGMT methylation (79.5%), and PDGFRA alterations (33.2%). The presence of PDGFRA amplification or EGFR amplification conferred poor survival. After adjusting for age and sex, these alterations were still independent indicators for adverse outcomes. Conclusions The authors highlight the important role of molecular stratification of H3G34 DHGs, which may help refine our understanding of the natural history of this group of malignant tumors.

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OBJECTIVE The prognostic significance and genetic characteristics of H3 K27M–mutant diffuse midline gliomas (DMGs) in different anatomical locations requires further clarification. In this study, the authors integrated published data to investigate the differences between brainstem, thalamic, and spinal cord tumors. METHODS PubMed and Web of Science databases were used to search for eligible articles. Studies were included if they provided individual patient data of H3 K27M–mutant DMGs with available tumor locations. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to investigate the survival of each subgroup. RESULTS Eight hundred four tumors were identified, including 467, 228, and 109 in the brainstem, thalamus, and spine, respectively. Brainstem tumors were primarily observed in young children, while patients with thalamic and spinal cord tumors afflicted older patients. The Ki-67 labeling index was highest in brainstem tumors. Compared to patients with brainstem tumors, those with thalamic (HR 0.573, 95% CI 0.463–0.709; p < 0.001) and spinal cord lesions (HR 0.460, 95% CI 0.341–0.621; p < 0.001) had a significantly better survival. When patients were stratified by age groups, superior overall survival (OS) of thalamic tumors was observed in comparison to brainstem tumors in young children and adolescents, whereas adult tumors had uniform OS regardless of anatomical sites. Genetically, mutations in HIST1H3B/C (H3.1) and ACVR1 genes were mostly detected in brainstem tumors, whereas spinal cord tumors were characterized by a higher incidence of mutations in the TERT promoter. CONCLUSIONS This study demonstrated that H3 K27M–mutant DMGs have distinct clinical characteristics, prognoses, and molecular profiles in different anatomical locations.

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Background Emphysematous pyelonephritis (EP) is a severe necrotizing infection of the renal parenchyma which is associated with significant case mortality. We sought to identify the incidence and predictive risk factors associated with EP mortality. Methods Two electronic databases, PubMed and Web of Science, were searched from their inception until June 06, 2021 for relevant articles. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. A meta-analysis has been reported in line with PRISMA 2020 and AMSTAR Guidelines. Results Of the 1080 retrieved abstracts, 79 underwent full-text review and 45 studies were included in the final analysis, comprising a total cohort of 1303 patients and 177 mortalities. The pooled prevalence of mortality among the patients with EP disease was 13%. Our analysis found a significantly decreasing trend in mortality rates, an increasing trend in minimally invasive intervention and decreasing trends in emergency nephrectomy in the EP studies from 1985 to 2020. Significant risk factors that were associated with a negative impact on survival of EP patients included sepsis (OR = 15.99), shock (OR = 15.57), disturbance of consciousness (OR = 12.11), thrombocytopenia (OR 7.85), acute renal failure (OR = 5.41), Wan classification I (OR = 4.57), emergency nephrectomy (OR = 3.73), Huang-Tseng classification III-IV (OR = 2.4) and medical management alone (OR = 2.04). Female sex (OR = 0.52) and minimally invasive intervention (OR = 0.47) (percutaneous nephrostomy or ureteral stent placement) were associated with decreased mortality rates. Conclusions Our study results demonstrated several significant risk factors that could help guide treatment to reduce the mortality risk of EP patients. Clinically, early treatment with a combination of minimally invasive intervention and appropriate medical management may be protective for reducing mortality risk in EP patients.