Clinical Prediction Models in Neurocritical Care: An Overview of the Literature and Example Application to Prediction of Hospital Mortality in Traumatic Brain Injury.

Clinical prediction models serve as valuable instruments for assessing the risk of crucial outcomes and facilitating decision-making in clinical settings. Constructing these models requires nuanced analytical decisions and expertise informed by the current statistical literature. Access and thorough understanding of such literature may be limited for neurocritical care physicians, which may hinder the interpretation of existing predictive models. The present emphasis is on narrowing this knowledge gap by providing neurocritical care specialists with methodological guidance for interpreting predictive models in neurocritical care. Presented are the statistical learning principles integral to constructing a model predicting hospital mortality (nonsurvival during hospitalization) in patients with moderate and severe blunt traumatic brain injury using components of the IMPACT-Core model. Discussion encompasses critical elements such as model flexibility, hyperparameter selection, data imbalance, cross-validation, model assessment (discrimination and calibration), prediction instability, and probability thresholds. The intricate interplay among these components, the data set, and the clincal context of neurocritical care is elaborated. Leveraging this comprehensive exploration of statistical learning can enhance comprehension of articles encompassing model generation, tailored clinical care, and, ultimately, better interpretation and clinical applicability of predictive models.

Comparative Analysis of Clinical Severity and Outcomes in Penetrating Versus Blunt Traumatic Brain Injury Propensity Matched Cohorts.

Traumatic brain injury (TBI) is a global health challenge; however, penetrating brain injury (PBI) remains under-represented in evidence-based knowledge and research efforts. This study utilized data from the Trauma Quality Improvement Program (TQIP) of the National Trauma Data Bank (NTDB) to investigate outcomes of PBI as compared with clinical-severity-matched non-penetrating or blunt TBI. A total of 1765 patients with PBI were 1:1 propensity score-matched for clinical severity with blunt TBI patients. The intent of PBI was self-inflicted in 34.1% of the cases, and the mechanism was firearm-inflicted in 89.1%. Mortality was found to be significantly more common in PBI than in the severity- matched TBI cohort (33.9% vs. 14.3 %, p < 0.001) as was unfavorable outcome. Mortality was mediated by withdrawal of life-sustaining therapies (WOLST) 30% of the time, and WOLST occurred earlier (median 3 days vs. 6 days, p < 0.001) in PBI. Increased rate of mortality was observed with a Glasgow Coma Scale (GCS) of <11 in PBI as compared with <7 in blunt TBI. In conclusion, PBI patients exhibited higher mortality rates and unfavorable outcomes; one third of excess mortality was mediated by WOLST. The study also brings into question the applicability of the conventional TBI classification, based on GCS, in PBI. We emphasize the need to address the observed disparities and better understand the distinctive characteristics and mechanisms underlying PBI outcomes to improve patient care and reduce mortality.

Is vitamin D deficiency associated with retinopathy in type 2 diabetes mellitus? A case-control study.

BACKGROUND AND AIMS: This study aimed to determine the associations between vitamin D deficiency and diabetic retinopathy (DR) progression risk in type 2 diabetes mellitus (T2DM) patients. METHODS: This is a case-control study that enrolled 201 diabetic retinopathy (DR) patients as case and 201 T2DM without DR as a control. Demographic variables were obtained during an interview using a questionnaire, furthermore, anthropometric measures were evaluated based on the standard protocol. In addition, biochemical indices including 25-hydroxyvitamin D, fasting blood glucose (FBG), insulin, Glycosylated hemoglobin (HbA1c), total cholesterol (TC), LDL-C, HDL-C, and triglyceride (TG) were assessed for all of the participants. Multivariate logistic regression was performed to estimate the relationship between vitamin D and retinopathy. RESULTS: Based on the statistical analysis of age, sex, and BMI there was no significant difference between the two groups, while the mean concentration of 25-hydroxyvitamin D substantially was lower in case group in comparison with the control group (14.46 VS. 19.88). Furthermore, low levels of vitamin D are associated with DR and consequently proliferative diabetic retinopathy (PDR) in patients with T2DM. CONCLUSION: Totally based on the results of the present study vitamin D deficiency increased the risk of RD in patients with T2DM, also in case of deficiency of this nutrient, retinopathy may develop into PDR type.

Comparative Effectiveness of Early Neurosurgical Intervention in Civilian Penetrating Brain Injury Management.

BACKGROUND AND OBJECTIVES: To compare the outcomes of early vs no-neurosurgical intervention in civilians with penetrating brain injury (PBI). METHODS: We collected data from the National Trauma Data Bank for PBI between 2017 and 2019. A total of 10 607 cases were identified; 1276 cases met the following criteria: age 16-60 years, an intensive care unit (ICU) length of stay (LOS) of >2 days, a Glasgow Coma Scale of 3-12, and at least one reactive pupil on presentation. Patients with withdrawal of life-sustaining treatments within 72 hours were excluded, leaving 1231 patients for analysis. Neurosurgical intervention was defined as an open-approach cranial procedure involving release, drainage, or extirpation of brain matter performed within 24 hours. Outcomes of interest were mortality, withdrawal of life-sustaining treatments, ICU LOS, and dispositional outcome. RESULTS: The target population was 1231 patients (84.4% male; median [IQR] age, 29 [18] years); 267 (21.7%) died, and 364 (29.6%) had a neurosurgical intervention within the first 24 hours. 1:1 matching yielded 704 patients (352 in each arm). In the matched cohort (mortality 22.6%), 64 patients who received surgery (18.2%) died compared with 95 (27%) in the nonsurgical group. Survival was more likely in the surgical group (odds ratio [OR] 1.66, CI 1.16-2.38, P < .01; number needed to treat 11). Dispositional outcome was not different. Overlap propensity score-weighted analysis (1231 patients) resulted in higher odds of survival in the surgical group (OR 1.8, CI 1.16-2.80, P < .01). The E-value for the OR calculated from the matched data set was 2.83. Early neurosurgical intervention was associated with longer ICU LOS (median 12 days [7.0, 19.0 IQR] vs 8 days [4.0, 15.0 IQR], P < .05). CONCLUSION: Management including early neurosurgical intervention is associated with decreased mortality and increased ICU LOS in matched cohorts of PBI.

Prevalence of anemia and its associated factors among patients with type 2 diabetes mellitus in a referral diabetic clinic in the north of Iran.

BACKGROUND: PURPOSE: This study intended to investigate the prevalence of anemia and its associated factors among patients with type 2 diabetes mellitus (T2DM) in Gorgan, Iran. METHODS: This cross-sectional study was conducted on 415 (109 men) patients with T2DM referred to the referral diabetes clinic of Sayad Shirazi Hospital in Gorgan in 2021. Demographic information, anthropometric indices, past medical history,  and some laboratory data on cell counts, serum blood glucose, HbA1c, creatinine, lipid/iron profiles, and urinary albumin were collected. The univariable and multivariable logistic regression analysis was applied to compute odds ratios (ORs) and 95% confidence intervals (CI) for potential associated factors, using SPSS version 21. The multivariable Model was adjusted for obesity, Hb A1c, T2DM duration, using glucose-lowering drugs (GLDs), chronic kidney disease (CKD), albuminuria, hypertriglyceridemia, and hypercholesterolemia.  RESULTS: The prevalence of anemia was 21.5% [95%CI: 17.6-25.7] among our total participants. The corresponding values for men and women were 20.2 (13.1-29.0) and 21.9 (17.4-27.0), respectively.The adjusted model revealed that obesity (OR, 1.94 [95% CI, 1.17-3.23]), T2DM duration for more than five years (OR, 3.12 [1.78-5.47]), albuminuria (OR, 6.37 [3.13-10.91]), chronic kidney disease (OR, 4.30 [ 2.83-7.29]) and hypertriglyceridemia (OR, 1.72 [ 1.21-2.77]) were significantly associated with prevalent anemia among patients with T2DM. Moreover, using insulin separately or in combination with oral GLDs associated positively with the prevalence of anemia with ORs of 2.60 [1.42-6.42] and 1.87 [1.30-4.37] , respectively. CONCLUSION: Anemia had a high prevalence among patients with T2DM in the north of Iran (about 22%), which is associated with obesity, hypertriglyceridemia, duration of T2DM, and diabetic kidney disease.

Involvement of heat shock proteins and parkin/α-synuclein axis in Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurological diseases, next only to Alzheimer's disease (AD) in terms of prevalence. It afflicts about 2-3% of individuals over 65 years old. The etiology of PD is unknown and several environmental and genetic factors are involved. From a pathological point of view, PD is characterized by the loss of dopaminergic neurons in the substantia nigra, which causes the abnormal accumulation of α-synuclein (α-syn) (a component of Lewy bodies), which subsequently interact with heat shock proteins (HSPs), leading to apoptosis. Apoptosis is a vital pathway for establishing homeostasis in body tissues, which is regulated by pro-apoptotic and anti-apoptotic factors. Recent findings have shown that HSPs, especially HSP27 and HSP70, play a pivotal role in regulating apoptosis by influencing the factors involved in the apoptosis pathway. Moreover, it has been reported that the expression of these HSPs in the nervous system is high. Apart from this finding, investigations have suggested that HSP27 and HSP70 (related to parkin) show a potent protective and anti-apoptotic impact against the damaging outcomes of mutant α-syn toxicity to nerve cells. Therefore, in this study, we aimed to investigate the relationship between these HSPs and apoptosis in patients with PD.

AMPK signaling in diabetes mellitus, insulin resistance and diabetic complications: A pre-clinical and clinical investigation.

Diabetes mellitus (DM) is considered as a main challenge in both developing and developed countries, as lifestyle has changed and its management seems to be vital. Type I and type II diabetes are the main kinds and they result in hyperglycemia in patients and related complications. The gene expression alteration can lead to development of DM and related complications. The AMP-activated protein kinase (AMPK) is an energy sensor with aberrant expression in various diseases including cancer, cardiovascular diseases and DM. The present review focuses on understanding AMPK role in DM. Inducing AMPK signaling promotes glucose in DM that is of importance for ameliorating hyperglycemia. Further investigation reveals the role of AMPK signaling in enhancing insulin sensitivity for treatment of diabetic patients. Furthermore, AMPK upregulation inhibits stress and cell death in ß cells that is of importance for preventing type I diabetes development. The clinical studies on diabetic patients have shown the role of AMPK signaling in improving diabetic complications such as brain disorders. Furthermore, AMPK can improve neuropathy, nephropathy, liver diseases and reproductive alterations occurring during DM. For exerting such protective impacts, AMPK signaling interacts with other molecular pathways such as PGC-1α, PI3K/Akt, NOX4 and NF-κB among others. Therefore, providing therapeutics based on AMPK targeting can be beneficial for amelioration of DM.