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Nevin Manimala Statistics

A Propensity Score-Weighted Analysis of Short-Term Corticosteroid Therapy for Refractory Pain Following Spontaneous Subarachnoid Hemorrhage

Neurocrit Care. 2024 Nov 19. doi: 10.1007/s12028-024-02165-1. Online ahead of print.

ABSTRACT

BACKGROUND: Corticosteroids are prescribed for refractory headache in patients with spontaneous subarachnoid hemorrhage (SAH) despite limited supporting evidence. We hypothesized that a short course of corticosteroids would reduce pain.

METHODS: We reviewed all patients who received corticosteroids for refractory headache following spontaneous SAH within our institutional database. Pain was measured by a numeric rating scale (NRS) every 2 h. The primary outcome was maximum daily NRS score; secondary outcomes were the mean daily NRS score and daily opioid consumption. Propensity scores were developed using potential predictors of corticosteroid use, including age, sex, pretreatment 24-h pain burden, and the number of analgesics being used to control pain. Inverse probability treatment weighting (IPTW) was used to balance baseline covariate distributions between patients receiving corticosteroids and control patients. Generalized estimating equations were used to analyze longitudinal NRS scores and oral morphine equivalents based on the weighted cohort.

RESULTS: A total of 213 patients were included. The mean age was 55 (SD 13) years, and 141 of 213 (66%) were female. Of 213 patients, 195 (92%) had a low clinical grade (i.e., Hunt-Hess grades 1-3). Seventy patients were prescribed corticosteroids on postbleed day 5 (SD 3.3) on average, with an average of 26 (SD 10) mg of dexamethasone over 48 h. Patients receiving corticosteroids and controls were well balanced on baseline predictors of treatment status. After IPTW, we found that corticosteroid therapy reduced the daily maximum pain NRS score by 0.59 (SE = 0.39, p = 0.12), 0.96 (SE = 0.42, p = 0.02), and 0.91 (SE = 0.46, p = 0.048) on days 1-3, respectively, after adjusting for control effects. The mean daily pain NRS score and daily opioid use were nonsignificantly reduced in the 3 days following corticosteroid initiation after adjusting for control effects.

CONCLUSIONS: Short-term corticosteroids only slightly reduced maximum pain severity after spontaneous SAH. Other analgesic strategies are required to manage refractory pain in this population.

PMID:39562388 | DOI:10.1007/s12028-024-02165-1

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Neuroimaging Markers of Brain Reserve and Associations with Delirium in Patients with Intracerebral Hemorrhage

Neurocrit Care. 2024 Nov 19. doi: 10.1007/s12028-024-02148-2. Online ahead of print.

ABSTRACT

BACKGROUND: Delirium occurs frequently in patients with stroke, but the role of preexisting neural substrates in delirium pathogenesis remains unclear. We sought to explore associations between acute and chronic neural substrates of delirium in patients with intracerebral hemorrhage (ICH).

METHODS: Using data from a single-center ICH registry, we identified consecutive patients with acute nontraumatic ICH and available magnetic resonance imaging scans. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria were used to classify each patient as delirious or nondelirious during their hospitalization. Magnetic resonance imaging scans were processed and analyzed using semiautomated software, with volumetric measurement of acute ICH volume as well as white matter hyperintensity volume (WMHV) and gray and white matter volumes from the contralateral hemisphere. We tested associations between WMHV and incident delirium using multivariable regression models, and then determined the predictive accuracy of these neuroimaging models via area under the curve (AUC) analysis.

RESULTS: Of 139 patients in our cohort (mean [standard deviation] age 67.3 [17.3] years, 53% male), 58 (42%) patients experienced delirium. In our primary analyses, WMHV was significantly associated with delirium after adjusting for ICH features (odds ratio 1.56 per 10 cm3, 95% confidence interval 1.13-2.13), and this association was strengthened after further adjustment for segmented brain volume in patients with high-resolution scans (odds ratio 1.89 per 10 cm3, 95% confidence interval 1.24-2.86). Neuroimaging-based models predicted delirium with high accuracy (AUC 0.81), especially in patients with Glasgow Coma Scale score > 13 (AUC 0.85) and smaller ICH (AUC 0.91).

CONCLUSIONS: Chronic white matter disease is independently associated with delirium in patients with acute ICH, and neuroimaging biomarkers may have utility in predicting delirium occurrence.

PMID:39562387 | DOI:10.1007/s12028-024-02148-2

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Hydrochemical assessment of groundwater utilizing statistical analysis, integrated geochemical methods, and EWQI: a case study of Laiwu region, North China

Environ Monit Assess. 2024 Nov 19;196(12):1222. doi: 10.1007/s10661-024-13359-7.

ABSTRACT

The investigation of groundwater quality and hydrochemical assessment holds immense significance in safeguarding and ensuring the rational utilization of groundwater resources. This study utilizes groundwater sampling and testing data from the Laiwu region (LWR), encompassing both dry and wet seasons, to delve into the hydrochemical characteristics, ion sources, and overall groundwater quality. The research findings indicate that the groundwater in LWR exhibits weak alkalinity, with the dominant ions being Ca2+ followed by Mg2+, Na+, and K+, and HCO3, SO42-, NO3, Cl, and F. The average total dissolved solids (TDS) concentrations during the dry and wet seasons are recorded as 683 mg/L and 679 mg/L, respectively, classifying LWR’s groundwater primarily as hard-fresh water. The spatial pattern of TDS concentration in LWR displays consistency throughout both the dry and wet seasons, with relatively low TDS levels observed in the northern and southeastern regions and higher concentrations in the lower reaches of the Dawen River and nearby Gangcheng. Predominantly, Ca2+, Mg2+, and HCO3 ions in groundwater originate from the dissolution of calcite and dolomite, with the hydrogeochemical process of carbonate rock weathering involving the presence of sulfuric acid. It is noteworthy that human activities significantly impact the chemical composition of groundwater in LWR. Notably, during the dry and wet seasons, the average concentration of NO3 in groundwater is 102.81 and 106.61 mg/L respectively, and the analysis shows that agricultural practice is the main source. Furthermore, the calculated average values of the entropy water quality index (EWQI) during those seasons are 58.44 and 57.24, respectively. The EWQI shows good to moderate water quality in most areas, except for a few poor-quality spots in the west. It is worth mentioning that LWR’s groundwater is deemed suitable for agricultural irrigation. These research findings provide valuable insights and serve as a significant reference for the rational development and sustainable utilization of groundwater resources in the LWR region.

PMID:39562385 | DOI:10.1007/s10661-024-13359-7

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Hematological profile and erythrocyte osmotic fragility of free-living yellow-footed tortoise Chelonoidis denticulatus (Linnaeus, 1766)

Vet Res Commun. 2024 Nov 20;49(1):19. doi: 10.1007/s11259-024-10585-9.

ABSTRACT

The yellow-footed tortoise (Chelonoidis denticulatus, Linnaeus, 1766) is among the most consumed chelonian species in the Amazon region, raising concerns about its conservation status. Furthermore, few studies have been carried out on the parameters of physiological normality of this species in free-living conditions, making it difficult to assess the impact of environmental changes on the physiology of the group. The erythrocyte osmotic fragility (EOF) test is a biomarker of environmental changes that cause membrane damage, decreasing erythrocyte resistance to osmotic stress. However, the physiology of the species is still poorly understood, and the reference ranges for hematological parameters and EOF is unknown for most species in natural conditions. Understanding the reference intervals of the physiological parameters of these animals have fundamental importance to assess when a population is under the effect of environmental stressors, such as xenobiotics, as well as to provide comparative parameters in clinical analyzes for the species. The lack of information on normal EOF values ​​makes it difficult to assess the effects of environmental and clinical changes on the physiology of the species. This study aimed to establish reference intervals for hematological parameters and EOF analysis for C. denticulatus, using thirty tortoises (n = 15 males and n = 15 females). The t-test and Mann-Whitney test were used to compare the hematological parameters between sexes, while the Kruskal-Wallis test was used in the EOF analysis, and the reference range was calculated for males and females together. No statistical differences were found in hematological values between sexes, nor in the hemolysis profile in the EOF analysis, demonstrating that in this population, these parameters of C. denticulatus are similar between sexes during the sampling period. According to the results of this study, we can consider the erythrocytes of these animals osmotically resistant, reflecting the stability of the cell membrane. This study reports for the first time hematological values and EOF analysis for the species C. denticulatus in the wild in a region of the far western Brazilian Amazon.

PMID:39562384 | DOI:10.1007/s11259-024-10585-9

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Biomarkers of systemic treatment response: MR images of intratumoral fat deposition in colorectal liver metastases (CRLM) after chemotherapy

Int J Colorectal Dis. 2024 Nov 20;39(1):185. doi: 10.1007/s00384-024-04762-0.

ABSTRACT

PURPOSE: Colorectal cancer cells containing mobile lipids are said to be an early indicator of chemotherapy effects. The objective of the study was to examine the frequency and clinical relevance of intratumoral fat deposition in colorectal liver metastases (CRLM) post-chemotherapy using dual-echo chemical shift gradient-echo magnetic resonance imaging (MRI).

METHODS: A retrospective analysis of 98 patients with CRLM diagnosed between 2017 and 2022 (69 M, mean age 62.87 ± 10.73 years old) who had an MRI after chemotherapy was performed. On dual-echo chemical shift gradient-echo MRI, intratumoral fat deposition of CRLM was evaluated. A signal intensity drop of ≥ 12% in opposed-phase images vs. in-phase images indicated intratumoral fat. After chemotherapy, the presence of fat deposition was correlated with patients’ overall survival.

RESULTS: Before and after chemotherapy, 0 (0%) and 29 (29.59%) patients exhibited intratumoral fat. The number of CRLM ranged from 1 to 25 with a median of 3 and a mean size of 32.58 ± 22.95 mm. The groups had statistically different survival times. Overall survival was shorter for patients with intratumoral fat deposition in CRLM (32 months (24-60, 95% CI)) than for patients without fat deposition in CRLM (48 months (36-NA, 95% CI)).

CONCLUSION: In our group, nearly 30% of CRLM patients exhibited intratumoral fat after chemotherapy. Patients with intratumoral fat deposition in CRLM have a shorter overall survival time. The presence of fat in CRLM correlates with a poor long-term prognosis.

PMID:39562379 | DOI:10.1007/s00384-024-04762-0

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A Data Driven Strategy for Implementation of Singlicate Analysis in Ligand Binding Assays Used for the Determination of Anti-drug Antibodies to a Multidomain Biotherapeutic

AAPS J. 2024 Nov 19;27(1):1. doi: 10.1208/s12248-024-00984-w.

ABSTRACT

A stepwise, data-driven approach for Anti-Drug Antibodies (ADA) singlicate assays has been developed to evaluate the feasibility of singlicate ligand binding assay (LBA) method development, qualification and validation to support our clinical programs. With initial precision runs in method validation and subsequent statistical analysis to directly compare duplicate and singlicate formats, our results indicated no meaningful difference in assay precision between duplicate and singlicate. Consequently, the rest of the ADA method validation proceeded with singlicate analysis yielding acceptable validation results. The validated ADA assay in singlicate has been employed to support a Phase I study. The appropriateness of singlicate analyses is further supported by Signal-to-Noise (S/N) data from the three tiers of the confirmatory positive samples, which showed strong correlation in S/N values.

PMID:39562377 | DOI:10.1208/s12248-024-00984-w

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Efficacy and safety of stereotactic radiosurgery with gamma knife machine in patients with essential tremor: a systematic review and single-arm meta-analysis

Neurosurg Rev. 2024 Nov 20;47(1):862. doi: 10.1007/s10143-024-03094-5.

ABSTRACT

Essential tremor (ET) is identified as the most prevalent movement disorder, primarily characterized by tremors in both upper extremities. The spectrum of surgical options for ET includes gamma knife radiosurgery (GKRS) and other stereotactic radiosurgery (SRS) modalities. Despite the limitations of these options, SRS is deemed an essential and indispensable approach. Our research aimed to assess the safety and efficacy of SRS, such as GKRS, on tremor control and the spectrum of associated adverse events in the treatment of ET, also focusing on long term outcomes of the procedure. We systematically conducted an extensive search across esteemed databases, which included PubMed, Cochrane Library, Embase, and Web of Science. We included studies involving individuals diagnosed with ET who had undergone GRKS treatment. A proportional rate was used to evaluate the outcomes in a 95% confidence interval. We included 12 studies comprising 414 patients. The treatment success rate with SRS was 86.6% (95% CI: 72.4-100%). Conversely, the overall failure rate was 13.4% (95% CI: 0.00 to 27.6%). Notably, post-procedure complications were observed in 9.7% of patients (95% CI: 5.8-13.6%). A meta-analysis of five studies revealed a statistically significant reduction of tremor from the FTM scale after treatment with GKRS (MD -2.1; 95% CI -2.5 to -1.6; p < 0.01; I² = 81%). A meta-analysis of eight studies revealed a statistically significant reduction in writing tremor from the FTM scale after treatment with GKRS (MD -1.7; 95% CI -2.3 to -1.2; p < 0.01; I² = 93%). A meta-analysis of six studies revealed a statistically significant reduction in drawing tremor from the FTM scale after treatment with GKRS (MD -1.9; 95% CI -2.5 to -1.4; p < 0.01; I² = 80%). Finally, a meta-analysis of three studies revealed a statistically significant reduction in drinking tremor from the FTM scale after treatment with GKRS (MD -1.6; 95% CI -1.9 to -1.3; p < 0.01; I² = 11%). Our findings show a high success rate and low failure of GKRS for ET. Thus, GKRS is a seemingly effective and safe option for managing these patients. The importance of this research lies in its contribution to the evolving landscape of radiosurgery, providing a robust basis for the clinical application of GKRS.

PMID:39562373 | DOI:10.1007/s10143-024-03094-5

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Machine learning approach in canine mammary tumour classification using rapid evaporative ionization mass spectrometry

Anal Bioanal Chem. 2024 Nov 19. doi: 10.1007/s00216-024-05656-4. Online ahead of print.

ABSTRACT

Rapid evaporative ionization mass spectrometry (REIMS) coupled with a monopolar handpiece used for surgical resection and combined with chemometrics has been previously explored by our research group (Mangraviti et al. in Int J Mol Sci 23(18):10562, 2022) to identify several mammary gland pathologies. Here, the increased sample size allowed the construction of three statistical models to distinguish between benign and malignant canine mammary tumours (CMTs), facilitating a more in-depth investigation of changes in cellular metabolic phenotype during neoplastic transformation and biological behaviour. The results demonstrate that REIMS is effective in identifying neoplastic tissues with an accuracy of 97%, with differences in MS spectra characterized by the relative abundance of phospholipids compared to triglycerides more commonly identified in normal mammary glands. The increased rate of phospholipid synthesis represents an informative feature for tumour recognition, with phosphatidylcholine and phosphatidylethanolamine, the two major phospholipid species identified here together with sphingolipids, playing a crucial role in carcinogenesis. REIMS technology allowed the classification of different histotypes of benign CMTs with an accuracy score of 95%, distinguishing them from normal glands based on the increase in sphingolipids, glycolipids, phospholipids, and arachidonic acid, demonstrating the close association between cancer and inflammation. Finally, dysregulation of fatty acid metabolism with increased signalling for saturated, mono- and polyunsaturated fatty acids characterized the metabolic phenotype of neoplastic cells and their malignant transformation, supporting the increased formation of new organelles for cell division. Further investigations on a more significant number of tumour histotypes will allow for the creation of a more extensive database and lay the basis for how understanding metabolic alterations in the tumour microenvironment can improve surgical precision.

PMID:39562368 | DOI:10.1007/s00216-024-05656-4

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Left-sided portal hypertension: what an interventional radiologist can offer?

Eur Radiol. 2024 Nov 19. doi: 10.1007/s00330-024-11196-3. Online ahead of print.

ABSTRACT

Left-sided portal hypertension (LPH) refers to increased splenic venous pressure caused by splenic vein stenosis or occlusion. Pancreatitis is the leading cause of LPH. Typically, LPH remains asymptomatic, but it can lead to life-threatening hemorrhage from ruptured fundal varices in about 10% of patients. Further, it may be complicated by hypersplenism. Interventional radiology plays an essential role in LPH patients with failed endoscopic treatment. Variceal embolization is an effective salvage measure in bleeding gastric varices, but it carries a risk of recurrence and worsening of hypersplenism. Considering the pathophysiology, splenic vein recanalization (SVR) appears to be the best treatment; nevertheless, its lower technical success rate limits its utility only to a subgroup of LPH patients. Partial splenic embolization (PSE), a non-surgical alternative to splenectomy, reduces the splenic volume and venous outflow, thereby lowering variceal pressure. PSE is technically easier, which may explain its widespread use. Nonetheless, PSE can be complicated by life-threatening sepsis and portal vein thrombosis. Despite all attempts, some LPH patients eventually require a splenectomy. Importantly, the choice of therapy requires multidisciplinary discussion and is often influenced by availability, expertise, and clinical context. This article discusses various interventional strategies for managing LPH with the available evidence. KEY POINTS: Question Pressure within the main portal vein is normal in left-sided portal hypertension; thus, transjugular intrahepatic portosystemic shunt is ineffective. Findings Splenic vein stent placement can restore hepatopetal splenic blood flow and decompress splenic venous pressure. Clinical relevance Partial splenic embolization (PSE) is the most widely used interventional approach to manage left-sided portal hypertension-related complications.

PMID:39562367 | DOI:10.1007/s00330-024-11196-3

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Screening for Fabry disease in patients with hypertrophic cardiomyopathy using cardiac magnetic resonance imaging

Eur Radiol. 2024 Nov 19. doi: 10.1007/s00330-024-11203-7. Online ahead of print.

ABSTRACT

BACKGROUND: Fabry disease (FD) usually mimics hypertrophic cardiomyopathy (HCM). Decreased native T1 mapping and a unique late gadolinium enhancement (LGE) pattern by cardiac magnetic resonance (CMR) imaging are specific imaging markers for FD.

PURPOSE: Explore the performance of multiparametric CMR imaging in screening for FD in patients with a HCM phenotype.

MATERIALS AND METHODS: A prospective cohort of 602 patients with a HCM phenotype was assessed from April 2012 to December 2022. Participants underwent CMR imaging and genetic testing. FD diagnosis was according to genetic testing and enzyme-activity test of α-galactosidase A. Multiparameter CMR imaging included cardiac function, native T1 mapping, extracellular volume (ECV), T2 mapping, LGE, and myocardial strains. Diagnostic performance of CMR parameters in identifying FD from HCM was done by analysis of receiver operating characteristic (ROC) curves.

RESULTS: FD prevalence was 1.8% (11 cases) in this cohort with HCM. Native T1 mapping was significantly lower in FD compared with HCM (FD vs. HCM: native T1 mapping: 1174.08 ± 60.60 vs. 1293.94 ± 55.86, p < 0.001). Ventricular function, mass, ventricular wall thickness, and strains did not show significant differences between the two groups. Binary logistic regression and analysis of ROC curves demonstrated myocardial native T1 mapping of the left ventricular basal slice had the best performance in screening for FD in patients with a HCM phenotype (cutoff: 1216 ms; AUC: 0.947; sensitivity: 91%; specificity: 90%).

CONCLUSION: Native T1 mapping is the best parameter for screening FD in a Chinese population with a HCM phenotype.

KEY POINTS: Question The prevalence of Fabry Disease (FD) in the study population is unknown and the efficacy of cardiac MRI (CMR) parameter screening for FD needs validating. Findings We report the prevalence of FD among a Chinese hypertrophic cardiomyopathy (HCM) cohort and found T1 mapping is the best CMR parameter for screening FD. Clinical relevance Native T1 mapping is the best CMR parameter for screening FD in the HCM cohort, providing an effective method for rapid screening of FD in clinic, which may help identify patients for early treatment of FD.

PMID:39562366 | DOI:10.1007/s00330-024-11203-7