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Nevin Manimala Statistics

Experimenting with ASL-based arterialized cerebral blood volume as a novel imaging biomarker in grading glial neoplasms

Neuroradiol J. 2023 Aug 7:19714009231193163. doi: 10.1177/19714009231193163. Online ahead of print.

ABSTRACT

BACKGROUND: Perfusion imaging is one of the methods used to grade glial neoplasms, and in this study we evaluated the role of ASL perfusion in grading brain glioma.

PURPOSE: The aim is to evaluate the role of arterialized cerebral blood volume (aCBV) of multi-delay ASL perfusion for grading glial neoplasm.

MATERIALS AND METHODS: This study is a prospective observational study of 56 patients with glial neoplasms of the brain who underwent surgery, and only cases with positive diagnosis of glioma are included to evaluate the novel diagnostic parameter.

RESULTS: In the study, ASL-derived normalized aCBV (naCBV) and T2*DSC-derived normalized CBV (nCBV) are showing very high correlation (Pearson’s correlation coefficient value of 0.94) in grading glial neoplasms. naCBV and nCBF are also showing very high correlation (Pearson’s correlation coefficient value of 0.876). The study also provides cutoff values for differentiating LGG from HGG for normalized aCBV(naCBV) of ASL, normalized CBV (nCBV), and normalized nCBF derived from T2* DCS as 1.12, 1.254, and 1.31, respectively. ASL-derived aCBV also shows better diagnostic accuracy than ASL-derived CBF.

CONCLUSION: This study is one of its kind to the best of our knowledge where multi-delay ASL perfusion-derived aCBV is used as a novel imaging biomarker for grading glial neoplasms, and it has shown high statistical correlation with T2* DSC-derived perfusion parameters.

PMID:37548164 | DOI:10.1177/19714009231193163

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Association of Dental Diseases and Oral Hygiene Care With the Risk of Heart Failure in Patients With Type 2 Diabetes: A Nationwide Cohort Study

J Am Heart Assoc. 2023 Aug 7:e029207. doi: 10.1161/JAHA.122.029207. Online ahead of print.

ABSTRACT

Background To evaluate the association of dental diseases and oral hygiene care with incidence of heart failure (HF) among patients with type 2 diabetes. Methods and Results This study included 173 927 patients with type 2 diabetes aged ≥40 years, who underwent Korean National Health Insurance Service health examinations in 2008 and were followed up until the end of 2017. Hazard ratios (HRs) and 95% CIs for HF were estimated using multivariable Cox proportional hazards regression analysis. During a median follow-up of 9.3 years, 1.94% of participants developed HF. An increased number of missing teeth was associated with a higher risk of HF (P<0.001). HRs of HF increased among individuals with ≥15 missing teeth (HR, 1.37 [95% CI, 1.14-1.64]) compared with those without missing teeth. Decreased risk of HF was observed in individuals with ≥1 time/year of professional dental cleaning (HR, 0.93 [95% CI, 0.87-0.99]) and in those with ≥2 times/d of toothbrushing (HR, 0.90 [95% CI, 0.82-0.98]) compared with those without these practices. While combined presence of missing teeth and periodontal disease (P=0.004) or dental caries (P=0.007) increased HF risk, combined oral hygiene care was associated with further HF risk reduction (P=0.024). Better oral hygiene care was associated with decreased HF risk, even as the number of missing teeth increased (P<0.001). Conclusions Among patients with type 2 diabetes, dental diseases and oral hygiene care are important determinants of HF development. Dental disease management and good oral care may prevent HF in patients with type 2 diabetes.

PMID:37548156 | DOI:10.1161/JAHA.122.029207

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Epidemic history and evolution of an emerging threat of international concern, the severe acute respiratory syndrome coronavirus 2

J Med Virol. 2023 Aug;95(8):e29012. doi: 10.1002/jmv.29012.

ABSTRACT

This comprehensive review focuses on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact as the cause of the COVID-19 pandemic. Its objective is to provide a cohesive overview of the epidemic history and evolutionary aspects of the virus, with a particular emphasis on its emergence, global spread, and implications for public health. The review delves into the timelines and key milestones of SARS-CoV-2’s epidemiological progression, shedding light on the challenges encountered during early containment efforts and subsequent waves of transmission. Understanding the evolutionary dynamics of the virus is crucial in monitoring its potential for adaptation and future outbreaks. Genetic characterization of SARS-CoV-2 is discussed, with a focus on the emergence of new variants and their implications for transmissibility, severity, and immune evasion. The review highlights the important role of genomic surveillance in tracking viral mutations linked to establishing public health interventions. By analyzing the origins, global spread, and genetic evolution of SARS-CoV-2, valuable insights can be gained for the development of effective control measures, improvement of pandemic preparedness, and addressing future emerging infectious diseases of international concern.

PMID:37548148 | DOI:10.1002/jmv.29012

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Topical ropivacaine hydrochloride 0.5% and lidocaine hydrochloride 2% significantly reduce corneal sensitivity without short-term negative side effects in horses

Vet Ophthalmol. 2023 Aug 7. doi: 10.1111/vop.13137. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate corneal sensitivity and acute side effects following application of ropivacaine hydrochloride 0.5% and lidocaine hydrochloride 2% on the healthy equine cornea.

ANIMALS STUDIED: Eight healthy adult horses.

PROCEDURE: A randomized, masked, crossover study design was utilized. Baseline Semiquantitative Preclinical Ocular Toxicology (SPOT) scores and corneal touch thresholds (CTT) using a Cochet-Bonnet esthesiometer were recorded and measured, respectively, for eight healthy adult horses before medication application. Commercially available eyewash was used as a negative control. Ropivacaine hydrochloride 0.5% or lidocaine hydrochloride 2% solution was sprayed on a randomly selected eye, and the contralateral eye received eyewash. CTT was measured in both eyes at 1, 5, 15, 25, 35, 45, 55, 65, and 75 min post-application. Post-application SPOT scores were recorded immediately following the trial. Linear mixed model statistical analyses (mean ± standard error) were performed (p < .05).

RESULTS: Mean eyewash CTT (3.41 cm ± 0.464) was significantly different from ropivacaine-treated (1.44 cm ± 0.562) (p = .008) and lidocaine-treated eyes (1.75 cm ± 0.562) (p = .024); CTT was not significantly different between drug groups (p = .88). Time to maximum anesthesia was not significantly different between ropivacaine (13.25 min ± 3.353) and lidocaine (16.25 min ± 3.353) (p = .40). No side effects were appreciated as confirmed by SPOT.

CONCLUSIONS: Ropivacaine and lidocaine similarly decreased corneal sensitivity when applied topically without clinically evident short-term ocular side effects. Lidocaine may be preferable in clinical settings due to its large, multi-use vials and similar effects to ropivacaine.

PMID:37548143 | DOI:10.1111/vop.13137

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The effect of neoadjuvant chemotherapy on surgical site wound infection after immediate breast reconstruction in patients with breast cancer: A meta-analysis

Int Wound J. 2023 Aug 7. doi: 10.1111/iwj.14337. Online ahead of print.

ABSTRACT

Using a meta-analysis approach, we conducted a comprehensive evaluation of the effect of neoadjuvant chemotherapy (NACT) on the incidence of surgical site wound infection during immediate breast reconstruction (IBR) following breast cancer. The aim was to provide evidence-based support for the prevention of wound surgical site infection during IBR after breast cancer surgery. Relevant literature on the effects of NACT on IBR in patients with breast cancer published up until May 2023, was retrieved from various databases, including PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang databases, and China Biology Medicine Database. Two researchers performed the literature screening, data collection, and quality assessment of the included studies independently. The meta-analysis was conducted using Stata version 17.0. Fourteen studies involving 3401 patients (599 in the intervention group and 2802 in the control group) were included in the analysis. The incidence of surgical site infection in the NACT group was higher than that in the control group, but the difference between the two groups was not statistically significant (7.17% vs. 4.85%, odds ratio: 1.02, 95% confidence interval: 0.70-1.50, p = 0.902). These findings suggest that NACT does not increase the risk of surgical site infection during IBR. However, owing to the variation in sample size and literature quality among the included studies, randomised controlled trials are needed to confirm the safety of IBR in patients receiving neoadjuvant chemotherapy.

PMID:37548134 | DOI:10.1111/iwj.14337

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Contemporary epidemiological data of Rift Valley fever virus in humans, mosquitoes and other animal species in Africa: A systematic review and meta-analysis

Vet Med Sci. 2023 Aug 7. doi: 10.1002/vms3.1238. Online ahead of print.

ABSTRACT

Rift Valley fever (RVF) is a severe zoonotic mosquito-borne disease that represents an important threat to human and animal health, with major public health and socioeconomic impacts. This disease is endemic throughout many African countries and the Arabian Peninsula. This systematic review with meta-analysis was conducted to determine the RVF prevalence in humans, mosquitoes and other animal species in Africa. The review also provides contemporary data on RVF case fatality rate (CFR) in humans. In this systematic review with meta-analysis, a comprehensive literature search was conducted on the PubMed, Embase, Web of Science and Global Index Medicus databases from January 2000 to June 2022 to identify relevant studies. Pooled CFR and prevalence estimates were calculated using the random-effects model. Subgroup analysis and sensitivity analysis were performed, and the I2 -statistic was used to investigate a potential source of heterogeneity. A total of 205 articles were included in the final analysis. The overall RVF CFR in humans was found to be 27.5% [95% CI = 8.0-52.5]. The overall pooled prevalence was 7.8% [95% CI = 6.2-9.6] in humans and 9.3% [95% CI = 8.1-10.6] in animals, respectively. The RVF prevalence in individual mosquitoes ranged from 0.0% to 25%. Subgroup analysis showed substantial heterogeneity with respect to geographical regions and human categories. The study shows that there is a correspondingly similar prevalence of RVF in human and animals; however, human CFR is much higher than the observed prevalence. The lack of a surveillance programme and the fact that this virus has subclinical circulation in animals and humans could explain these observations. The implementation of a One Health approach for RVF surveillance and control would be of great interest for human and animal health.

PMID:37548116 | DOI:10.1002/vms3.1238

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Gadolinium Retention and Nephrotoxicity in a Mouse Model of Acute Ischemic Stroke: Linear Versus Macrocyclic Agents

J Magn Reson Imaging. 2023 Aug 7. doi: 10.1002/jmri.28931. Online ahead of print.

ABSTRACT

BACKGROUND: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used for acute ischemic stroke (AIS) patients. GBCAs or AIS alone may cause the adverse effects on kidney tissue, respectively. However, whether GBCAs and AIS would generate a synergistic negative effect remains undefined.

PURPOSE: To evaluate synergistic negative effects of AIS and GBCAs on renal tissues in a mouse model of AIS, and to compare the differences of these negative effects between linear and macrocyclic GBCAs.

STUDY TYPE: Animal study.

ANIMAL MODEL: Seventy-two healthy mice underwent transient middle cerebral artery occlusion (tMCAO) and sham operation to establish AIS and sham model (N = 36/model). 5.0 mmol/kg GBCAs (gadopentetate or gadobutrol) or 250 μL saline were performed at 4.5 hours and 1 day after model establishing (N = 12/group).

ASSESSMENT: Inductively coupled plasma mass spectrometry (ICP-MS) was performed to detect Gd concentrations. Serum biochemical analyzer was performed to measure the serum creatinine (Scr), uric acid (UA), and blood urea nitrogen (BUN). Pathological staining was performed to observe tubular injury, cell apoptosis, mesangial hyperplasia, and interstitial fibrosis.

STATISTICAL TESTS: Two-way analysis of variances with post hoc Sidak’s tests and independent-samples t-tests were performed. A P-value <0.05 was considered statistically significant.

RESULTS: AIS groups showed higher Gd concentration than sham group on day 1 p.i. regardless of gadopentetate or gadobutrol used. Increased total Gd concentration was also found in AIS + gadopentetate group compared with the sham group on day 28 p.i. Significantly higher rates for renal dysfunction, higher tubular injury scores, and higher numbers of apoptotic cells on days 1 or 28 p.i. were found for AIS mice injected with GBCA. AIS + gadopentetate group displayed more severe renal damage than the AIS + gadobutrol group.

DATA CONCLUSION: AIS and GBCAs may cause increased total Gd accumulation and nephrotoxicity in a mouse, especially linear GBCAs were used.

LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

PMID:37548106 | DOI:10.1002/jmri.28931

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Causal discovery analysis: A promising tool in advancing precision medicine for eating disorders

Int J Eat Disord. 2023 Aug 7. doi: 10.1002/eat.24040. Online ahead of print.

ABSTRACT

OBJECTIVE: Precision medicine (i.e., individually tailored treatments) represents an optimal goal for treating complex psychiatric disorders, including eating disorders. Within the eating disorders field, most treatment development efforts have been limited in their ability to identify individual-level models of eating disorder psychopathology and to develop and apply an individually tailored treatment for a given individual’s personalized model of psychopathology. In addition, research is still needed to identify causal relationships within a given individual’s model of eating disorder psychopathology. Addressing this limitation of the current state of precision medicine-related research in the field will allow us to progress toward advancing research and practice for eating disorders treatment.

METHOD: We present a novel set of analytic tools, causal discovery analysis (CDA) methods, which can facilitate increasingly fine-grained, person-specific models of causal relations among cognitive, behavioral, and affective symptoms.

RESULTS: CDA can advance the identification of an individual’s causal model that maintains that individuals’ eating disorder psychopathology.

DISCUSSION: In the current article, we (1) introduce CDA methods as a set of promising analytic tools for developing precision medicine methods for eating disorders including the potential strengths and weaknesses of CDA, (2) provide recommendations for future studies utilizing this approach, and (3) outline the potential clinical implications of using CDA to generate personalized models of eating disorder psychopathology.

PUBLIC SIGNIFICANCE STATEMENT: CDA provides a novel statistical approach for identifying causal relationships among variables of interest for a given individual. Person-specific causal models may offer a promising approach to individualized treatment planning and inform future personalized treatment development efforts for eating disorders.

PMID:37548100 | DOI:10.1002/eat.24040

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Alkaline phosphatase to treat ischemia reperfusion injury in living-donor kidney transplantation – APhIRI I feasibility pilot study

Br J Clin Pharmacol. 2023 Aug 7. doi: 10.1111/bcp.15871. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of kidney transplantation. This study aimed to evaluate the safety and feasibility of peri-procedural AP administration in living donor kidney transplantation.

EXPERIMENTAL APPROACH: In this double blind, randomized, placebo-controlled, single-center pilot study, all eligible recipients of living donor kidneys were asked to give informed consent. AP (bRESCAP) or a placebo was administered intravenously over 24 hours after the transplantation procedure. The primary outcome – graft function at one year – was represented by iohexol measured glomerular filtration rate (mGFR). Serum and urine biomarkers within seven days after surgery were used as surrogate markers of kidney function and injury.

KEY RESULTS: Eleven patients were enrolled of whom five were treated with bRESCAP and six with placebo. After one year, mGFR was not different between groups. No specific adverse events were observed in the bRESCAP group. Urine expression of injury biomarkers CCL14, NGAL and Cystatin C was lower in the bRESCAP group at day seven. This was statistically significant.

CONCLUSION AND IMPLICATIONS: This study illustrates that bRESCAP treatment is feasible in kidney transplantation, might have a dampening effect on IRI induced renal inflammation, and raises no safety concerns. Future research will evaluate the effects of bRESCAP treatment in donation after circulatory death kidney transplantation where IRI is more pronounced.

PMID:37548047 | DOI:10.1111/bcp.15871

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Severity of GNAO1-related disorder correlates with changes in G-protein function

Ann Neurol. 2023 Aug 7. doi: 10.1002/ana.26758. Online ahead of print.

ABSTRACT

OBJECTIVE: GNAO1-related disorders (OMIM #615473 and #617493), caused by variants in the GNAO1 gene, are characterized by developmental delay or intellectual disability, hypotonia, movement disorders, and epilepsy. Neither a genotype-phenotype correlation nor a clear severity score have been established for this disorder. The objective of this prospective and retrospective observational study was to develop a severity score for GNAO1-related disorders and to delineate the correlation between the underlying molecular mechanisms and clinical severity.

METHODS: Sixteen individuals with GNAO1-related disorders harboring 12 distinct missense variants, including four novel variants (p.K46R, p.T48I, p.R209P, and p.L235P) were examined with repeated clinical assessments, video-EEG monitoring, and brain MRI. The molecular pathology of each variant was delineated using a molecular deconvoluting platform.

RESULTS: The patients displayed a wide variability in the severity of their symptoms. This heterogeneity was well represented in the GNAO1-related disorders severity score, with a broad range of results. Patients with the same variant had comparable severity scores, indicating that differences in disease profiles are not due to inter-patient variability but rather to unique disease mechanisms. Moreover, we found a significant correlation between clinical severity scores and molecular mechanisms.

INTERPRETATION: The clinical score proposed here provides further insight into the correlation between pathophysiology and phenotypic severity in GNAO1-related disorders. We found that each variant has a unique profile of clinical phenotypes and pathological molecular mechanisms. These findings will contribute to better understanding GNAO1-related disorders. Additionally, the severity score will facilitate standardization of patients categorization and assessment of response to therapies in development. This article is protected by copyright. All rights reserved.

PMID:37548038 | DOI:10.1002/ana.26758