Category: Nevin Manimala

Alzheimers Res Ther. 2022 Jul 27;14(1):105. doi: 10.1186/s13195-022-01048-x.

ABSTRACT

BACKGROUND: The ability of ¹⁸F-PI-2620 PET to measure the spatial distribution of tau pathology in Alzheimer’s disease (AD) has been demonstrated in previous studies. The objective of this work was to evaluate tau deposition using ¹⁸F-PI-2620 PET in beta-amyloid positive subjects with a diagnosis of mild cognitive impairment (MCI) or mild AD dementia and characterize it with respect to amyloid deposition, cerebrospinal fluid (CSF) assessment, hippocampal volume, and cognition.

METHODS: Subjects with a diagnosis of MCI due to AD or mild AD dementia and a visually amyloid-positive ¹⁸F-florbetaben PET scan (n=74, 76 ± 7 years, 38 females) underwent a baseline ¹⁸F-PI-2620 PET, T1-weighted magnetic resonance imaging (MRI), CSF assessment (Aβ42/Aβ40 ratio, p-tau, t-tau) (n=22) and several cognitive tests. A 1-year follow-up ¹⁸F-PI-2620 PET scans and cognitive assessments were done in 15 subjects.

RESULTS: Percentage of visually tau-positive scans increased with amyloid-beta deposition measured in ¹⁸F-florbetaben Centiloids (CL) (7.7% (<36 CL), 80% (>83 CL)). ¹⁸F-PI-2620 standardized uptake value ratio (SUVR) was correlated with increased ¹⁸F-florbetaben CL in several regions of interest. Elevated ¹⁸F-PI-2620 SUVR (fusiform gyrus) was associated to high CSF p-tau and t-tau (p=0.0006 and p=0.01, respectively). Low hippocampal volume was associated with increased tau load at baseline (p=0.006 (mesial temporal); p=0.01 (fusiform gyrus)). Significant increases in tau SUVR were observed after 12 months, particularly in the mesial temporal cortex, fusiform gyrus, and inferior temporal cortex (p=0.04, p=0.047, p=0.02, respectively). However, no statistically significant increase in amyloid-beta load was measured over the observation time. The MMSE (Recall score), ADAS-Cog14 (Word recognition score), and CBB (One-card learning score) showed the strongest association with tau deposition at baseline.

CONCLUSIONS: The findings support the hypothesis that ¹⁸F-PI-2620 PET imaging of neuropathologic tau deposits may reflect underlying neurodegeneration in AD with significant correlations with hippocampal volume, CSF biomarkers, and amyloid-beta load. Furthermore, quantifiable increases in ¹⁸F-PI-2620 SUVR over a 12-month period in regions with early tau deposition are consistent with the hypothesis that cortical tau is associated with cognitive impairment. This study supports the utility of ¹⁸F-PI-2620 PET to assess tau deposits in an early AD population. Quantifiable tau load and its corresponding increase in early AD cases could be a relevant target engagement marker in clinical trials of anti-amyloid and anti-tau agents.

TRIAL REGISTRATION: Data used in this manuscript belong to a tau PET imaging sub-study of the elenbecestat MissionAD Phase 3 program registered in ClinicalTrials.gov ( NCT02956486 ; NCT03036280 ).

PMID:35897078 | DOI:10.1186/s13195-022-01048-x

Crit Care. 2022 Jul 27;26(1):228. doi: 10.1186/s13054-022-04079-w.

ABSTRACT

BACKGROUND: While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as ‘mild’, ‘moderate’ or ‘severe’ based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights.

METHODS: We developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation (< 24 h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset (N = 1,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation.

RESULTS: Six stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with ‘moderate’ TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with ‘severe’ GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both p < 0.001).

CONCLUSIONS: Six stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care. Trial registration The core study was registered with ClinicalTrials.gov, number NCT02210221 , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).

PMID:35897070 | DOI:10.1186/s13054-022-04079-w

Ital J Pediatr. 2022 Jul 27;48(1):127. doi: 10.1186/s13052-022-01317-3.

ABSTRACT

According to the latest version of the Diagnostic and Statistical Manual of Mental Disorders, somatic symptom and related disorders (SSRDs) are defined as psychopathological manifestations characterized by physical signs not attributable to organic pathology. Their incidence has grown dramatically over the past few decades, and treatment is challenging. Besides other interventions on the child and the family, physiotherapy is considered an integral part of the treatment, although there is no evidence for its efficacy.The study aimed to review the available proof on the effectiveness of physiotherapy in children and adolescents with SSRDs. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, including 1999 to 2021. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different study designs. The scientific bibliography on the subject was minimal and had poor methodological quality. The choice of outcome indicators and the scales to measure them varied from study to study and were not standardized, making comparison and meta-analysis challenging.Conclusion: According to the available evidence, it is impossible to answer the review question regarding the effectiveness of physiotherapy in children and adolescents with SSRDs. It is necessary to improve the methodological quality of the studies. Definition of standard rehabilitation treatments, identification of appropriate result indicators, and adoption of standardized evaluation scales are needed.

PMID:35897067 | DOI:10.1186/s13052-022-01317-3

BMC Endocr Disord. 2022 Jul 27;22(1):193. doi: 10.1186/s12902-022-01107-2.

ABSTRACT

BACKGROUND: In our previous published study, we demonstrated that a qualitatively assessed elevation in deltoid muscle echogenicity on ultrasound was both sensitive for and a strong predictor of a type 2 diabetes (T2DM) diagnosis. This study aims to evaluate if a sonographic quantitative assessment of the deltoid muscle can be used to detect T2DM.

METHODS: Deltoid muscle ultrasound images from 124 patients were stored: 31 obese T2DM, 31 non-obese T2DM, 31 obese non-T2DM and 31 non-obese non-T2DM. Images were independently reviewed by 3 musculoskeletal radiologists, blinded to the patient’s category. Each measured the grayscale pixel intensity of the deltoid muscle and humeral cortex to calculate a muscle/bone ratio for each patient. Following a 3-week delay, the 3 radiologists independently repeated measurements on a randomly selected 40 subjects. Ratios, age, gender, race, body mass index, insulin usage and hemoglobin A_1c were analyzed. The difference among the 4 groups was compared using analysis of variance or chi-square tests. Both univariate and multivariate linear mixed models were performed. Multivariate mixed-effects regression models were used, adjusting for demographic and clinical variables. Post hoc comparisons were done with Bonferroni adjustments to identify any differences between groups. The sample size achieved 90% power. Sensitivity and specificity were calculated based on set threshold ratios. Both intra- and inter-radiologist variability or agreement were assessed.

RESULTS: A statistically significant difference in muscle/bone ratios between the groups was identified with the average ratios as follows: obese T2DM, 0.54 (P < 0.001); non-obese T2DM, 0.48 (P < 0.001); obese non-T2DM, 0.42 (P = 0.03); and non-obese non-T2DM, 0.35. There was excellent inter-observer agreement (intraclass correlation coefficient 0.87) and excellent intra-observer agreements (intraclass correlation coefficient 0.92, 0.95 and 0.94). Using threshold ratios, the sensitivity for detecting T2DM was 80% (95% CI 67% to 88%) with a specificity of 63% (95% CI 50% to 75%).

CONCLUSIONS: The sonographic quantitative assessment of the deltoid muscle by ultrasound is sensitive and accurate for the detection of T2DM. Following further studies, this process could translate into a dedicated, simple and noninvasive screening method to detect T2DM with the prospects of identifying even a fraction of the undiagnosed persons worldwide. This could prove especially beneficial in screening of underserved and underrepresented communities.

PMID:35897066 | DOI:10.1186/s12902-022-01107-2

Arthroplasty. 2022 Jul 27;4(1):34. doi: 10.1186/s42836-022-00129-4.

ABSTRACT

BACKGROUND: Recent studies show an increase in the prevalence of iron deficiency anemia (IDA) worldwide and a concomitant rise in the number of revision total knee arthroplasty (RTKA). The literature evaluating the association between IDA and perioperative outcomes following RTKA are limited. Therefore, the purpose of this study was to determine whether IDA patients undergoing RTKA have higher rates of (1) in-hospital lengths of stay (LOS), (2) complications; and (3) costs.

METHODS: Using International Classification of Disease, Ninth Revision (ICD-9) and Current Procedural Terminology (CPT), a retrospective query was performed from January 1^st, 2005 to March 31^st, 2014. The inclusion criteria consisted of those patients who have IDA undergoing RTKA. Study group patients were 1:5 ratio matched to a comparison cohort by age, sex, and various comorbidities: coronary artery disease, chronic obstructive pulmonary disease, diabetes mellitus, hyperlipidemia, hypertension, obesity, and tobacco use, yielding a total of 106,534 patients within the study (n = 17,784) and control (n = 88,750) cohorts. Outcomes assessed included: in-hospital LOS, costs of care, and medical complications. Multivariate Logistic regression analyses were used to calculate the odds-ratios (OR) and respective 95% confidence intervals (95%CI). Welch’s t-tests were used to compare in-hospital LOS and costs of care. Following Bonferroni-correction, a P-value less than 0.001 was considered statistically significant.

RESULTS: IDA patients undergoing RTKA were found to have significantly higher in-hospital LOS (4-days vs. 3-days, P < 0.0001). Additionally, IDA patients were found to have significantly higher odds (OR) of medical complications (OR: 5.29, P < 0.0001) such as: pneumonia (OR: 6.86, P < 0.0001), respiratory failures (OR: 5.95, P < 0.0001), myocardial infarctions (OR: 4.31, P < 0.0001) and other complications. Furthermore, IDA patients incurred significantly higher day of surgery ($16,976.01 vs. $14,515.81, P < 0.0001) and 90-day costs ($22,548.71 vs. $16,819.15, P < 0.0001).

CONCLUSION: The study demonstrated IDA patients undergoing RTKA have higher rates of in-hospital LOS, costs of care, and medical complications. Orthopedic surgeons and other healthcare professionals can use this information to adequately educate these patients of the potential complications following their procedure.

PMID:35897041 | DOI:10.1186/s42836-022-00129-4

World J Surg Oncol. 2022 Jul 28;20(1):242. doi: 10.1186/s12957-022-02695-y.

ABSTRACT

BACKGROUND: This study aimed to investigate the predictive values of serum biomarkers including absolute eosinophil count (AEC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) with respect to immune-related adverse events (irAEs) during anti-PD-1/PD-L1 inhibitor treatment in patients with advanced malignant tumors.

METHODS: We retrospectively analyzed 95 patients with advanced cancer who were treated with anti-PD-1/PD-L1 inhibitors from January 1, 2017, to May 1, 2020, in our cancer center. We then analyzed associations between irAEs and anti-PD-1/PD-L1 inhibitor responses and evaluated the predictive values of serum biomarkers with respect to the risk of irAEs.

RESULTS: The incidence of irAEs was 55.8%. There were no statistically significant differences between the irAEs and no-irAEs groups in an objective response rate (ORR) or disease control rate (DCR). However, landmark analysis showed that the irAEs group had better survival after 120 days following the initiation of anti-PD-1/PD-L1 inhibitor treatment, compared with the no-irAEs group. The incidences of irAEs were greater in the high-AEC and low-NLR groups than in the low-AEC and high-NLR groups. Univariate logistic analysis showed that low NLR, ECOG performance status (0-1), and high AEC were risk factors for irAEs. Multivariate logistic analysis showed that high AEC and good ECOG performance status were independent predictors for irAEs.

CONCLUSIONS: irAEs may be associated with a survival benefit. Baseline AEC is a strong predictor of irAEs in patients undergoing treatment with anti-PD-1/PD-L1 inhibitors.

PMID:35897018 | DOI:10.1186/s12957-022-02695-y

BMC Psychiatry. 2022 Jul 27;22(1):504. doi: 10.1186/s12888-022-04159-9.

ABSTRACT

PURPOSE: The aim of this study was to evaluate the association of marital status with cognitive function and to examine the potential effect modifiers in Chinese hypertensive populations.

METHODS: A total of 9,525 adult Chinese hypertensive patients were enrolled in this cross-sectional study. Cognitive function, as the dependent variable in our study, was assessed by the Chinese version of the Mini-Mental State Examination (MMSE). We adjusted for potential confounding factors in multiple linear regression models to examine the relationship of marital status with cognitive function. In addition, we divided the population according to sex to explore whether there were sex-specific differences.

RESULTS: Among the 9,525 study participants, the mean (SD) age for men was 63.5 (10.3) years, and the mean MMSE score was 24.9 ± 5.0, whereas for women, the mean (SD) age was 63.8 (9.3) years, and the mean MMSE score was 19.4 ± 6.4. Unmarried persons had lower scores on the MMSE and lower subscores in each of the cognitive domains. A stronger correlation between marital status and a lower MMSE score was statistically significant in men (unmarried men: β = -1.55; 95% CI: -1.89, -1.21) but not women (unmarried women: β = -0.22; 95% CI: -0.56, 0.12; p interaction = 0.006). Compared to men who were widowed or divorced, never married men were more likely to have lower MMSE scores (β = -2.30, 95% CI -3.10,-1.50; p < 0.001).

CONCLUSIONS: Our study demonstrated that being unmarried is an extremely important but neglected social risk factor for cognitive function. Sex was a strong effect modifier: being unmarried was correlated with a higher risk of cognitive decline than being married in Chinese hypertensive men, especially among older men, but this correlation was not observed among women. Moreover, never married men showed poorer cognitive function than those who were divorced or widowed.

PMID:35897015 | DOI:10.1186/s12888-022-04159-9

BMC Neurol. 2022 Jul 27;22(1):280. doi: 10.1186/s12883-022-02808-w.

ABSTRACT

BACKGROUND AND PURPOSE: The recanalization rate after intravenous thrombolysis (IVT) is not enough and there is still the possibility of re-occlusion. We aim to investigate the effectiveness and safety of infusing tirofiban after IVT.

METHODS: We performed a prospective controlled study of 60 patients with acute non-cardiogenic ischemic stroke who were hospitalized in Yantai Yuhuangding Hospital from January 2018 to December 2019. The patients were divided into 2 groups: those who received tirofiban for 24 h after IVT (rt-PA + T group) and those who did not receive postprocedural intravenous tirofiban (rt-PA group). The rt-PA + T group received low-dose rt-PA (0.6 mg/kg). The rt-PA group received standard dose rt-PA (0.9 mg/kg). The main outcome measure were safety, included the symptomatic intracranial hemorrhage (sICH), any ICH, severe systemic bleeding, and mortality. The secondary outcome measure is curative efficacy which were evaluated by the 7d-NIHSS score and functional outcomes at 90 days. During hospitalization, the deterioration of neurological function was recorded.

RESULTS: All patients completed the follow-up with complete data, there were 30 patients in each of groups. The general characteristics between the two group patients had no statistically significant differences. Compared with the rt-PA + T group and the rt-PA group, in terms of safety, the rates of the sICH, severe systemic bleeding, and mortality in both groups were 0, and there was no statistically significant difference in the rates of any ICH between the two groups (10.0% vs. 3.3%, P = 0.306). In terms of efficacy, the rate of the early neurological deterioration events (END) was no statistical significance (0 vs. 6.6%, P = 0.246). There was no significant difference in the NIHSS score between the two groups before the IVT, and also at 24 h, however, the 7d-NIHSS score was lower in the rt-PA + T group compared with the rt-PA group (2.33 ± 1.85 vs. 4.80 ± 4.02, P = 0.004). At 90 days, 83.3% of patients in the rt-PA + T group had favorable functional outcomes compared with 60.0% of patients in the rt-PA group (P = 0.045).

CONCLUSIONS: Low-dose rt-PA combined with tirofiban in acute non-cardiogenic ischemic stroke did not increase the risk of ICH, and mortality, and it was associated with neurological improvement.

TRIAL REGISTRATION: The trial has been registered at the ChiCTR and identified as ChiCTR1800014666 (28/01/2018).

PMID:35897006 | DOI:10.1186/s12883-022-02808-w

BMC Pregnancy Childbirth. 2022 Jul 27;22(1):601. doi: 10.1186/s12884-022-04933-3.

ABSTRACT

BACKGROUND: Postnatal care (PNC) services are an essential intervention for improving maternal and child health. In Ethiopia, PNC service has been poorly implemented, despite the governments and partners’ attempt to improve maternal and child health service utilization. Moreover, many literatures identified that women with no education are significantly underutilized the PNC services. Thus, this study aimed to assess the PNC service uptake among women at high risk for underutilization of PNC services and to identify the individual and community level determinants of PNC services uptake in Ethiopia using the positive deviance approach.

METHODS: Data from the Ethiopia Demographic and Health Survey 2016 were used. A total of 2417 deviant women (women with no education) were identified through a two-stage stratified sampling technique and included in this analysis. A multilevel mixed-effect binary logistic regression analysis was computed to identify the individual and community-level determinants of PNC services uptake among deviant women. In the final model, a p-value of less than 0.05 and adjusted odds ratio (AOR) with 95% confidence interval (CI) were used to declare statistically significant determinants of PNC services uptake.

RESULTS: In this analysis, the uptake of PNC service among deviant women was 5.8% [95% CI: 4.9-6.8]. Working in the agriculture (AOR = 2.15, 95% CI: 1.13-3.52), being Orthodox religion follower (AOR = 2.56, 95% CI: 1.42-4.57), living in the highest wealth quantile (AOR = 2.22, 95% CI: 1.25-3.91) were the individual level determinants, whereas residing in the city administration (AOR: 3.17, 95% CI: 1.15-8.71), and living closer to health facility (AOR: 1.57, 95% CI: 1.03-2.39) were the community level determinants.

CONCLUSION: The study highlighted a better PNC service uptake among deviant women who are working in the agriculture, follows orthodox religion, lives in highest household wealth status, resides in city administration, and living closer to the health facility. The positive deviance approach provides evidences for health policy makers and program implementers to improve health behavior in specific target population, and ultimately to bring better maternal and child health outcomes, despite acknowledged adverse risk profile. Such strategy and knowledge could facilitate targeted efforts aimed at achieving national goals of maternal and newborn mortality reduction in the country.

PMID:35897004 | DOI:10.1186/s12884-022-04933-3

BMC Neurol. 2022 Jul 27;22(1):279. doi: 10.1186/s12883-022-02793-0.

ABSTRACT

BACKGROUND: While several studies investigated the epidemiology and burden of stroke in the North Africa and Middle East region, no study has comprehensively evaluated the age-standardized attributable burden to all stroke subtypes and their risk factors yet.

OBJECTIVE: The aim of the present study is to explore the regional distribution of the burden of stroke, including ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage, and the attributable burden to its risk factors in 2019 among the 21 countries of North Africa and Middle East super-region.

METHODS: The data of the Global Burden of Disease Study (GBD) 2019 on stroke incidence, prevalence, death, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs) rates, and attributed deaths, DALYs, YLLs, and YLDs to stroke risk factors were used for the present study.

RESULTS: The age-standardized deaths, DALYs, and YLLs rates were diminished statistically significant by 27.8, 32.0, and 35.1% from 1990 to 2019, respectively. Attributed deaths, DALYs, and YLLs to stroke risk factors, including high systolic blood pressure, high body-mass index, and high fasting plasma glucose shrank statistically significant by 24.9, 25.8, and 28.8%, respectively.

CONCLUSION: While the age-standardized stroke burden has reduced during these 30 years, it is still a concerning issue due to its increased burden in all-age numbers. Well-developed primary prevention, timely diagnosis and management of the stroke and its risk factors might be appreciated for further decreasing the burden of stroke and its risk factors and reaching Sustainable Development Goal 3.4 target for reducing premature mortality from non-communicable diseases.

PMID:35896999 | DOI:10.1186/s12883-022-02793-0