Prevalence of frailty according to the Hospital Frailty Risk Score and related factors in older patients with acute coronary syndromes in Vietnam.

OBJECTIVES: (1) To investigate the prevalence of frailty defined by the Hospital Frailty Risk Score (HFRS), a new scale for assessing frailty, in older patients with acute coronary syndrome (ACS); (2) To identify associations between frailty and the prescriptions of cardiovascular medications, percutaneous coronary intervention (PCI) and in-hospital adverse outcomes. METHODS: An observational study was conducted in patients aged older than 60 years with ACS at Thong Nhat Hospital from August to December 2022. The Hospital Frailty Risk Score is retrospectively calculated for all participants based on ICD-10 codes, and those with HFRS scores ≥5 were defined as frail. Logistic regression models were applied to examine the relationship between frailty and the study outcomes. RESULTS: There were 511 participants in the study. The median age was 72.7, 60% were male and 29% were frail. Frailty was associated with lower odds of beta-blocker use at admission (OR .49 95% CI .25-.94), treatment with PCI during hospitalisation (OR .48, 95% CI .30-.75), but did not show an association with prescriptions of cardiovascular drugs at discharge. Frailty was significantly associated with increased odds of adverse outcomes, including major bleeding (OR 4.07, 95% CI1.73-9.54), hospital-acquired pneumonia (OR 2.55, 95% CI 1.20-5.42), all-cause in-hospital mortality (OR 3.14, 95% CI 1.37-7.20) and non-cardiovascular in-hospital mortality (OR 10.73, 95% CI 1.93-59.55). CONCLUSIONS: The HFRS was an effective tool for stratifying frailty and predicting adverse health outcomes in older patients with ACS. Further research is needed to compare the HFRS with other frailty assessment tools in this population.

Predicting EGFR Mutation Status in Non-Small Cell Lung Cancer Using Artificial Intelligence: A Systematic Review and Meta-Analysis.

RATIONALE AND OBJECTIVES: Recent advancements in artificial intelligence (AI) render a substantial promise for epidermal growth factor receptor (EGFR) mutation status prediction in non-small cell lung cancer (NSCLC). We aimed to evaluate the performance and quality of AI algorithms that use radiomics features in predicting EGFR mutation status in patient with NSCLC. MATERIALS AND METHODS: We searched PubMed (Medline), EMBASE, Web of Science, and IEEExplore for studies published up to February 28, 2022. Studies utilizing an AI algorithm (either conventional machine learning [cML] and deep learning [DL]) for predicting EGFR mutations in patients with NSLCL were included. We extracted binary diagnostic accuracy data and constructed a bivariate random-effects model to obtain pooled sensitivity, specificity, and 95% confidence interval. This study is registered with PROSPERO, CRD42021278738. RESULTS: Our search identified 460 studies, of which 42 were included. Thirty-five studies were included in the meta-analysis. The AI algorithms exhibited an overall area under the curve (AUC) value of 0.789 and pooled sensitivity and specificity levels of 72.2% and 73.3%, respectively. The DL algorithms outperformed cML in terms of AUC (0.822 vs. 0.775) and sensitivity (80.1% vs. 71.1%), but had lower specificity (70.0% vs. 73.8%, p-value < 0.001) compared to cML. Subgroup analysis revealed that the use of positron-emission tomography/computed tomography, additional clinical information, deep feature extraction, and manual segmentation can improve diagnostic performance. CONCLUSION: DL algorithms can serve as a novel method for increasing predictive accuracy and thus have considerable potential for use in predicting EGFR mutation status in patient with NSCLC. We also suggest that guidelines on using AI algorithms in medical image analysis should be developed with a focus on oncologic radiomics.

Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.

BACKGROUND: Atypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor prognostic conditions in several cancers. However, little is known about the role of RRM2 in ATRT. Uncovering the role of RRM2 in ATRT will further promote the development of feasible strategies and effective drugs to treat ATRT. METHODS: Expression of RRM2 was evaluated by molecular profiling analysis and was confirmed by IHC in both ATRT patients and PDX tissues. Follow-up in vitro studies used shRNA knockdown RRM2 in three different ATRT cells to elucidate the oncogenic role of RRM2. The efficacy of COH29, an RRM2 inhibitor, was assessed in vitro and in vivo. Western blot and RNA-sequencing were used to determine the mechanisms of RRM2 transcriptional activation in ATRT. RESULTS: RRM2 was found to be significantly overexpressed in multiple independent ATRT clinical cohorts through comprehensive bioinformatics and clinical data analysis in this study. The expression level of RRM2 was strongly correlated with poor survival rates in patients. In addition, we employed shRNAs to silence RRM2, which led to significantly decrease in ATRT colony formation, cell proliferation, and migration. In vitro experiments showed that treatment with COH29 resulted in similar but more pronounced inhibitory effect. Therefore, ATRT orthotopic mouse model was utilized to validate this finding, and COH29 treatment showed significant tumor growth suppression and prolong overall survival. Moreover, we provide evidence that COH29 treatment led to genomic instability, suppressed homologous recombinant DNA damage repair, and subsequently induced ATRT cell death through apoptosis in ATRT cells. CONCLUSIONS: Collectively, our study uncovers the oncogenic functions of RRM2 in ATRT cell lines, and highlights the therapeutic potential of targeting RRM2 in ATRT. The promising effect of COH29 on ATRT suggests its potential suitability for clinical trials as a novel therapeutic approach for ATRT.

Gamma Knife Radiosurgery for Spetzler-Martin Grade III Brain Arteriovenous Malformations.

BACKGROUND: Spetzler-Martin (SM) grade III arteriovenous malformations (AVMs) show angioarchitecture heterogeneity and lack a clearly defined treatment strategy. This study aims to evaluate outcomes after treatment of SM grade III AVMs with Gamma Knife radiosurgery (GKRS). METHODS: A single-institution retrospective analysis was conducted of 307 patients with SM grade III AVMs undergoing GKRS between October 2006 and December 2020 with follow-up times of at least 24 months. SM grade III AVMs were classified into 4 subtypes: IIIA (S1E1V1), IIIB (S2E0V1), subtype IIIC (S2E1V0), and IIID (S3E0V0). RESULTS: Over a median follow-up time of 50.3 months, complete AVM obliteration was achieved in 211 patients (68.7%). Complete obliteration rates in subtypes IIIA, IIIB, IIIC, and IIID were 80.8%, 55.4%, 53.4%, and 25.0%, respectively. Annual post-GKRS hemorrhage risk was 0.8%. Significant radiosurgery-induced imaging changes occurred in 7 patients (2.3%). Three variables were identified as predictors of obliteration in final forward stepwise regression models, including volume of AVM (B = -0.011; P < 0.001), age (B = -0.004; P = 0.024), and previous AVM hemorrhage (B = 0.187; P = 0.077). CONCLUSIONS: GKRS is a safe and effective treatment for SM grade III AVMs, particularly subtype IIIA (S1E1V1). AVM volume is the key predictor of post-GKRS obliteration.

Outcomes Following Penetrating Brain Injuries in Military Settings: A Systematic Review and Meta-Analysis.

OBJECTIVE: While neurosurgeons are experienced in treating penetrating brain injuries (PBIs) in civilian settings, much less is known about management and outcomes of PBIs in military settings. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Data extracted included surgical management, age, gender, location/type of injury, initial Glasgow Coma Scale (GCS) score, and outcomes. The primary outcomes were last reported Glasgow Outcome Score (GOS) and mortality. The secondary outcomes included central nervous system infections, seizures, and cerebrospinal fluid leak/fistula. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used for outcome analysis. RESULTS: Twelve studies with 1738 patients treated for PBIs in military settings were included. The weighted mean age was 27.8 years, 86.7% were male, and 64.3% underwent neurosurgical intervention. Most patients (64.3%) presented with a GCS score >8, while 31.0% presented in a coma (GCS score <8). Over a median last follow-up time of 9 months, 68.6% achieved a favorable (GOS = 4-5) outcome and 34.2% achieved a poor (GCS score = 1-3) outcome. The overall mortality was 18.0%. A meta-analysis was performed using 5 of 12 studies to evaluate the effect of the presenting GCS score on primary outcomes. Patients with an initial GCS score <8 had statistically significant lower odds of a favorable (GOS = 4-5) outcome (OR: 0.03; 95% CI: 0.00-0.19; P: 0.000) and higher odds of mortality (OR: 28.46; 95% CI: 8.62-94; P: 0.000) than patients with an initial GCS score >8. The pooled rates of central nervous system infection, seizures, and cerebrospinal fluid leak/fistula were 13.8%, 13.2%, and 5.4%, respectively. CONCLUSIONS: In this first systematic review and meta-analysis of outcomes following combat-related PBIs, a GCS score >8 at presentation was found to be an important predictor of a favorable GOS and decreased mortality.

Gamma Knife Radiosurgery for Brain Arteriovenous Malformations: A 15-Year Single-Center Experience in Southern Vietnam.

BACKGROUND: In the present study, we aimed to identify the obliteration outcomes, complications, and predictors in gamma knife radiosurgery (GKRS) treatment of brain arteriovenous malformations (AVMs) at a tertiary center in a developing country in a 15-year experience. METHODS: We retrospectively reviewed the clinical data and GKRS procedures of patients who had undergone GKRS from 2006 to 2011 (cohort 1) and from 2011 to 2020 (cohort 2) at Cho Ray Hospital, Vietnam. The exclusion criteria included patients with <24 months of follow-up without obliteration or AVM-related hemorrhage during the study period. RESULTS: A total of 870 patients were included in the final analysis. The patients in cohort 1 had had significantly smaller AVMs (8.4 ± 11.6 cm3 vs. 11.2 ± 12.8 cm3; P < 0.001), and the AVMs were less frequently located in eloquent locations (46.6% vs. 65.5%; P < 0.001) than in cohort 2. The mean follow-up time was 49.6 ± 22.6 months (range, 5.9-102.6). The overall AVM obliteration rate was 66.6%. Cohort 1 had a significantly higher rate of complete obliteration compared with cohort 2 (81.0% vs. 55.1%; P < 0.001). The post-GKRS annual hemorrhage risk was 1.0%. Significant radiosurgery-induced brain edema and radiosurgery-induced cyst formation was reported in 24 (2.6%) and 4 (0.5%) patients in cohorts 1 and 2, respectively. Using multivariate analysis, we identified prior AVM hemorrhage (hazard ratio [HR], 1.430; 95% confidence interval [CI], 1.182-1.729), a higher margin dose (HR, 1.136; 95% CI, 1.086-1.188), a noneloquent location (HR, 0.765; 95% CI, 0.647-0.905), and smaller AVM volume (HR, 0.982; 95% CI, 0.968-0.997) as predictive factors for obliteration. CONCLUSIONS: GKRS is a safe and effective treatment of brain AVMs. The lack of prior AVM hemorrhage, an eloquent location, and higher AVM were unfavorable predictors for post-GKRS obliteration.

Overview of medical malpractice in neurosurgery.

Annually, 20% of all practicing neurosurgeons in the United States are faced with medical malpractice litigation. The average indemnity paid in a closed neurosurgical civil claim is $439,146, the highest of all medical specialties. The majority of claims result from dissatisfaction following spinal surgery, although claims after cranial surgery tend to be costlier. On a societal scale, the increasing prevalence of medical malpractice claims is a catalyst for the practice of defensive medicine, resulting in record-level healthcare costs. Outside of the obvious financial strains, malpractice claims have also been linked to professional disenchantment and career changes for afflicted physicians. Unfortunately, neurosurgical residents receive minimal practical education regarding these matters and are often unprepared and vulnerable to these setbacks in the earlier stages of their careers. In this article, the authors aim to provide neurosurgical residents and junior attendings with an introductory guide to the fundamentals of medical malpractice lawsuits and the implications for neurosurgeons as an adjunct to more formal residency education.

Upregulation of Protein Synthesis and Proteasome Degradation Confers Sensitivity to Proteasome Inhibitor Bortezomib in Myc-Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid rhabdoid tumors (ATRTs) are among the most malignant brain tumors in early childhood and remain incurable. Myc-ATRT is driven by the Myc oncogene, which directly controls the intracellular protein synthesis rate. Proteasome inhibitor bortezomib (BTZ) was approved by the Food and Drug Administration as a primary treatment for multiple myeloma. This study aimed to determine whether the upregulation of protein synthesis and proteasome degradation in Myc-ATRTs increases tumor cell sensitivity to BTZ. We performed differential gene expression and gene set enrichment analysis on matched primary and recurrent patient-derived xenograft (PDX) samples from an infant with ATRT. Concomitant upregulation of the Myc pathway, protein synthesis and proteasome degradation were identified in recurrent ATRTs. Additionally, we found the proteasome-encoding genes were highly expressed in ATRTs compared with in normal brain tissues, correlated with the malignancy of tumor cells and were essential for tumor cell survival. BTZ inhibited proliferation and induced apoptosis through the accumulation of p53 in three human Myc-ATRT cell lines (PDX-derived tumor cell line Re1-P6, BT-12 and CHLA-266). Furthermore, BTZ inhibited tumor growth and prolonged survival in Myc-ATRT orthotopic xenograft mice. Our findings suggest that BTZ may be a promising targeted therapy for Myc-ATRTs.

Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan.

In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). In this study, we aimed to identify a molecular-clinical correlation and somatic mutation for exploring risk-adapted treatment, drug targets, and potential genetic predisposition. In total, 52 frozen tumor tissues of childhood MBs were collected. RNA sequencing (RNA-Seq) and DNA methylation array data were generated. Molecular subgrouping and clinical correlation analysis were performed. An adjusted Heidelberg risk stratification scheme was defined for updated clinical risk stratification. We selected 51 genes for somatic variant calling using RNA-Seq data. Relevant clinical findings were defined. Potential drug targets and genetic predispositions were explored. Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The adjusted Heidelberg scheme showed its applicability. Potential drug targets were detected in the pathways of DNA damage response. Among the 10 patients with SHH MBs analyzed using whole exome sequencing studies, five patients exhibited potential genetic predispositions and four patients had relevant germline mutations. The findings of this study provide valuable information for updated risk adapted treatment and personalized care of childhood MBs in our cohort series and in Taiwan.

Neurosurgical Oncology in Vietnam.

BACKGROUND: In conjunction with Vietnam's unparalleled economic growth over the past 20 years, our scope of neurosurgical interventions has considerably diversified throughout this time period. METHODS: Although still appreciably limited, healthcare resources and infrastructure have expanded and shifted the focus within neurosurgery at Ho Chi Minh City's Cho Ray Hospital from head trauma (which remains highly prevalent) to an equal proportion of elective cases for vascular lesions, tumors, and degenerative spine disease. Arguably the most significant progress throughout the new millennium has been achieved in the realm of neurosurgical oncology. RESULTS: About 1000 craniotomies are performed annually for brain tumors at our institution, most of which are for lower-grade lesions that result in excellent surgical outcomes. We continue to strive to improve the standard of care for patients with malignant brain tumors, as the first multidisciplinary neuro-oncology care team was founded recently in 2016. CONCLUSIONS: This article is the first in the English neurosurgical literature to report on the current state and outcomes of neuro-oncology in Vietnam, as we highlight our experiences in caring for patients with brain tumors at Cho Ray Hospital.

Inside Vietnam's Largest Neurosurgery Department.

Cho Ray Hospital is the premier tertiary care center in Ho Chi Minh City, Vietnam's most populous city. The neurosurgical department was founded in 1958 and is currently one of the busiest in the world. Last year the department was responsible for more than 10,000 neurosurgical operations, excluding neuroendovascular cases. Most of the elective cases are craniotomies for complex lesions such as aneurysms, arteriovenous malformations, skull base tumors, gliomas, and meningiomas. Although the neurosurgeons within the department are technically gifted, doing more with less predominates as the mantra at Cho Ray Hospital. The necessity to minimize costs and the scarcity of resources creates many unique circumstances, some of which lag decades behind the rest of the world. Nonetheless, the progress and trajectory of the department has been impressive as the neurosurgical care provided to the Vietnamese public continues to improve. This article describes the current state and future direction of The Department of Neurological Surgery at Cho Ray Hospital.