Category: Nevin Manimala

Metab Syndr Relat Disord. 2022 May 9. doi: 10.1089/met.2022.0006. Online ahead of print.

ABSTRACT

Background: Nonalcoholic fatty liver disease (NAFLD) constitutes a significant cause of deaths, liver transplantations, and economic costs worldwide. Despite extended research, investigations on the role of erythrocytes are scarce. Red blood cells from experimental animals and human patients with NAFLD present phosphatidylserine exposure, which is then recognized by Kupffer cells. This event leads to erythrophagocytosis and amplification of inflammation through iron disposition. In addition, it has been shown that erythrocytes from NAFLD patients release the chemokine monocyte chemoattractant protein-1 (MCP1), leading to increased tumor necrosis factor alpha release from macrophages RAW 264.7. However, erythrophagocytosis can also be caused by reduced CD47 levels. Moreover, increased MCP1 release could be either signal-induced or caused by higher MCP1 levels on the erythrocyte membrane. Finally, erythrocyte efferocytosis could provide additional inflammatory metabolites. Methods: In this study, we measured the erythrocyte membrane levels of CD47 and MCP1 by enzyme-linked immunosorbent assay, and cholesterol and sphingosine with thin-layer chromatography. Eighteen patients (8 men and 10 women, aged 56.7 ± 11.5 years) and 14 healthy controls (7 men and 7 women, aged 39.3 ± 15.6 years) participated in our study. Results: The erythrocyte CD47 levels were decreased in the erythrocyte membranes of NAFLD patients (844 ± 409 pg/mL) compared with healthy controls (2969 ± 1936 pg/mL) with P = 0.012. Levels of MCP1 increased in NAFLD patients (389 ± 255 pg/mL) compared with healthy controls (230 ± 117 pg/mL) with P = 0.0274, but low statistical power. Moreover, in erythrocyte membranes, there was a statistically significant accumulation of sphingosine and cholesterol in NAFLD patients compared with healthy controls. Conclusions: Our results imply that erythrocytes release chemotactic “find me” signals (MCP1) while containing reduced “do not eat me” signals (CD47). These molecules can lead to erythrophagocytosis. Next, increased “goodbye” signals (sphingosine and cholesterol) could augment inflammation by metabolic reprogramming.

PMID:35532955 | DOI:10.1089/met.2022.0006

JAMA Pediatr. 2022 May 9. doi: 10.1001/jamapediatrics.2022.1153. Online ahead of print.

ABSTRACT

IMPORTANCE: The establishment and renovation of supermarkets may promote healthy diet practices among youth by increasing retail infrastructure for fresh foods.

OBJECTIVE: To estimate the association between the Food Retail Expansion to Support Health (FRESH) program and the weight status of children and adolescents.

DESIGN, SETTING, AND PARTICIPANTS: Using a difference-in-differences (DiD) design and including 12 months before and after a FRESH supermarket opened, data were analyzed for residentially stable public school students in kindergarten through 12th grade with objectively measured height and weight data from the academic years 2009 through 2016. Of the 8 FRESH-subsidized supermarkets in residential neighborhoods in New York City, New York, 5 were new and 3 were renovation projects between December 2011 and June 2014. Data were analyzed from June 2021 to January 2022.

INTERVENTIONS: The treatment group included students who resided within 0.50 miles of a FRESH-subsidized supermarket and had at least 1 body mass index (BMI) measurement within 12 months before and 3 to 12 months after the month a FRESH supermarket opened (n = 22 712 student-year observations). A 2-stage matching-weighting approach was used to construct a control group of students who resided more than 0.50 miles from a FRESH supermarket in a FRESH-eligible area (n = 86 744 student-year observations).

MAIN OUTCOMES AND MEASURES: BMI z score was calculated using objectively measured height and weight data from FITNESSGRAM, an annual, school-based, standardized fitness assessment of every New York City public school student. Obesity was defined as 95th percentile or greater of the BMI z score using Centers for Disease Control and Prevention growth charts.

RESULTS: The treatment group in the analytic sample had 11 356 students (22 712 student-year observations), and the control group had 43 372 students (86 744 student-year observations). The students were predominately Black (18.8%) and Hispanic and Latino (68.5%) and eligible for free or reduced-priced lunch (84.6%). There was a significant decrease in BMI z score among students who resided within 0.50 miles of a FRESH supermarket (vs control group students) in the 3- to 12-month follow-up period (DiD, -0.04; 95% CI, -0.06 to -0.02). This was true for those exposed to supermarkets that were either new (DiD, -0.07; 95% CI, -0.11 to -0.03) or renovated (DiD, -0.03; 95% CI, -0.06 to -0.01). A statistically significant decrease was also observed in the likelihood of obesity (DiD, -0.01; 95% CI, -0.02 to -0.002).

CONCLUSIONS AND RELEVANCE: Government-subsidized supermarkets may contribute to a small decrease in obesity risk among children residing near those supermarkets, if part of a comprehensive policy approach.

PMID:35532919 | DOI:10.1001/jamapediatrics.2022.1153

JAMA Intern Med. 2022 May 9. doi: 10.1001/jamainternmed.2022.1657. Online ahead of print.

ABSTRACT

IMPORTANCE: Recent guidelines recommend a systolic blood pressure (BP) goal of less than 150 mm Hg or even 130 mm Hg for adults aged 60 years or older. However, harms from intensive BP treatments occur immediately (eg, syncope, fall), and benefits for cardiovascular event reduction emerge over time. Therefore, harms with low chance of benefit need to be clearer, particularly for those with limited life expectancy.

OBJECTIVE: To estimate the time needed to potentially derive clinical benefit from intensive BP treatment in patients 60 years and older.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis included individual patient data from published randomized clinical trials with 27 414 patients 60 years or older with hypertension. Patient-level survival data were reconstructed when the original data were not available. Published trials were identified by searching PubMed until October 15, 2021.

EXPOSURES: Intensive BP lowering vs standard BP lowering with the treat-to-target design.

MAIN OUTCOMES AND MEASURES: Major adverse cardiovascular event (MACE) defined by each trial, which was broadly similar with all trials including myocardial infarction, stroke, and cardiovascular mortality.

RESULTS: Six trials (original data from 2 trials and reconstructed data from 4 trials) with 27 414 participants (mean age, 70 years; 56.3% were women) were included in the analysis. Intensive BP treatment with a systolic BP target below 140 mm Hg was significantly associated with a 21% reduction in MACE (hazard ratio, 0.79; 95% CI, 0.71-0.88; P < .001). On average, 9.1 (95% CI, 4.0-20.6) months were needed to prevent 1 MACE per 500 patients with the intensive BP treatment (absolute risk reduction [ARR], 0.002). Likewise, 19.1 (95% CI, 10.9-34.2) and 34.4 (95% CI, 22.7-59.8) months were estimated to avoid 1 MACE per 200 (ARR, 0.005) and 100 (ARR, 0.01) patients, respectively.

CONCLUSIONS AND RELEVANCE: In this analysis, findings suggest that for patients 60 years and older with hypertension, intensive BP treatment may be appropriate for some adults with a life expectancy of greater than 3 years but may not be suitable for those with less than 1 year.

PMID:35532917 | DOI:10.1001/jamainternmed.2022.1657

JAMA Pediatr. 2022 May 9. doi: 10.1001/jamapediatrics.2022.1159. Online ahead of print.

NO ABSTRACT

PMID:35532906 | DOI:10.1001/jamapediatrics.2022.1159

Clin Pharmacol Drug Dev. 2022 May 9. doi: 10.1002/cpdd.1111. Online ahead of print.

ABSTRACT

Abrocitinib is a selective Janus kinase 1 inhibitor for the treatment of moderate to severe atopic dermatitis (AD). To assess the relationship between abrocitinib plasma concentrations and heart rate (HR)-corrected QT (QTc) and HR and calculate the effect of abrocitinib on these parameters at supratherapeutic concentrations, 36 healthy volunteers received single doses of abrocitinib 600 mg, placebo, and moxifloxacin 400 mg in a 3-period crossover study. The relationship between change from baseline in Fridericia-corrected QTc (∆QTcF) values and abrocitinib plasma concentrations was modeled using a prespecified linear mixed-effects model. The 90%CIs for time-matched placebo-corrected ∆QTcF (∆∆QTcF) were calculated from model parameter estimates and assessed against the regulatory threshold (10 millisecond) at the predicted supratherapeutic concentration in patients with atopic dermatitis (2156 ng/mL). Mean (90%CI) time-matched placebo-corrected change from baseline in HR (∆∆HR) was calculated similarly. At the supratherapeutic concentration, mean (90%CI) estimates for ∆∆QTcF and ∆∆HR were 6.00 (4.52-7.49) milliseconds and 6.51 (5.23-7.80) bpm, respectively. Despite a concentration-dependent effect on ∆QTcF and ∆HR, with statistically significant slopes (90%CI) of 0.0026 (0.0018-0.0035) milliseconds/(ng/mL) and 0.0031 (0.0024-0.0038) bpm/(ng/mL), respectively, abrocitinib does not have a clinically significant effect on QTc interval or HR at supratherapeutic exposures.

PMID:35532896 | DOI:10.1002/cpdd.1111

Ann Hematol. 2022 May 9. doi: 10.1007/s00277-022-04836-5. Online ahead of print.

ABSTRACT

Immune thrombocytopenia (ITP) patients are at risk developing to systemic lupus erythematosus (SLE) in the future. Our study attempted to explore the potential risk factors for the development from ITP to SLE in Chinese children by statistical analysis. This study was a retrospective case-control study. Patients diagnosed with ITP and developed to SLE after the diagnosis of ITP were defined as the case group. The control group consisted of children with ITP but without developing to SLE was recruited with a ratio of 1:2. Besides univariable analysis, multivariable logistic regression was built to evaluate the potential risk factors. A total of 150 children was included with 50 in the case group and 100 in the control group. Median developing time from ITP to SLE was 34.5 [IQR 12.5, 58.75] months. ANA was found significantly different between the two groups in our study in the univariable analysis but not in the multivariable analysis (OR = 4.50, 95% CI 0.97 to 21.01). Age diagnosed ITP was positively associated with SLE (OR = 1.07 every 5 years, 95% CI 1.01 to 1.15) with alert point at 8 years old (sensitivity 0.82, specificity 0.60). A lower level of complement was also positively associated with SLE (OR = 8.33, 95% CI 1.62 to 42.91). A minimum 3-year of close follow-up for pediatric ITP patients was recommended to monitor the risk for developing SLE. Older age and hypocomplementemia were potential risk factors for the development from ITP to SLE.

PMID:35532821 | DOI:10.1007/s00277-022-04836-5

Hepatol Int. 2022 May 9. doi: 10.1007/s12072-022-10343-6. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies.

METHODS: PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm).

RESULTS: Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted.

CONCLUSION: ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment.

PROTOCOL REGISTRATION: This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/ ).

PMID:35532861 | DOI:10.1007/s12072-022-10343-6

Arch Orthop Trauma Surg. 2022 May 9. doi: 10.1007/s00402-022-04460-y. Online ahead of print.

ABSTRACT

INTRODUCTION: This study investigated the anatomic feasibility of a new surgical therapy option for radial head arthrosis using an autologous vascularized bone graft of the second metatarsal and proximal fibula to recreate the proximal radiohumeral joint.

MATERIALS AND METHODS: Upper and lower extremities of eleven body donors were evaluated using CT prior to anatomic dissection. Several distinct anatomic parameters were measured on the ipsi- and contralateral radial and fibular head and the second metatarsal base: bone diameter, articular surface diameter, head height, metaphyseal (neck) diameter, articular surface radius, total articular surface area, and angulation of the articular surfaces (facet). Each dissection phase was photographed in a standardized fashion and all measurements were repeated by direct caliper-measurements.

RESULTS: When comparing the proximal radius and fibula to search for anatomic similarities, similar values were found in the maximum articular surface diameter and minimum and maximum measures of the neck diameter. Comparing the proximal radius and the second metatarsal, statistically similar values were found in the maximum neck diameter performing direct measurements and CT evaluation, the maximum head diameter in CT evaluation and the articular facet angulation.

CONCLUSIONS: Neither the proximal fibula nor the base of the second metatarsal are ideal bone grafts for replacement of the head of the radius. The base of the second metatarsal might be a bit more suitable as a potential donor since the angulation of the proximal articular facet is similar to that of the radius.

LEVEL OF EVIDENCE: Level IV, anatomic study.

PMID:35532813 | DOI:10.1007/s00402-022-04460-y

Z Rheumatol. 2022 May 9. doi: 10.1007/s00393-022-01209-1. Online ahead of print.

ABSTRACT

INTRODUCTION: The concept of complex multimodal rheumatologic treatment (CMRT) has been established for several years in German rheumatologic departments and aims at a multifaceted therapeutic approach to patients with rheumatic diseases. Objective of this study was to examine the therapeutic effect of CMRT in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in an acute rheumatology center.

METHODS: The treatment success of CMRT was evaluated by epidemiologic data, patient questionnaires on visual analog scales (VAS) regarding morning stiffness, pain and disease activity (DA), as well as clinical scores (Disease Activity Score 28 [DAS28], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Bath Ankylosing Spondylitis Functional Index [BASFI]), laboratory inflammation markers (CRP, erythrocyte sedimentation rate) and medication in three visits: visit 1 = begin of CMRT; visit 2 = end of CMRT; visit 3 = 3 months after CMRT.

RESULTS: In this study 162 patients from the Rheumatology Center, Rhineland-Palatinate, Germany (96 (59.3%) RA, 30 (18.8%) AS, 36 (22.2%) PsA) were recruited. Statistical examinations revealed a significant improvement of VAS(DA) (visit 2 versus visit 1: RA: p = 0.02, AS: p < 0.001, PsA: p < 0.001), morning stiffness (RA: p < 0.001, AS: p = 0.03, PsA: p < 0.001) and patient reported pain (all; p < 0.001) in the context of CMRT. In the RA and AS subgroups improvements of DAS28 and BASDAI could also be observed (visit 2 versus visit 1: both; p < 0.001). Moreover, significant improvement of patient reported outcomes could be observed 3 months after CMRT regarding VAS(DA) (RA: p = 0.02 und AS: p = 0.03, morning stiffness (PsA: p = 0.02) and patient reported pain (RA: p = 0.01)). Interestingly, subgroup analyses showed that the therapeutic benefit was independent of the concomitant pharmacotherapy.

CONCLUSION: The results of this study suggest a therapeutic benefit for patients being treated by CMRT and highlight the high value of this therapeutic concept in patients with systemic-inflammatory rheumatic diseases.

PMID:35532799 | DOI:10.1007/s00393-022-01209-1

J Neurol. 2022 May 9. doi: 10.1007/s00415-022-11161-4. Online ahead of print.

ABSTRACT

OBJECTIVE: Higher body mass index (BMI) during early life is thought to be a causal risk factor for multiple sclerosis (MS). We used longitudinal Mendelian randomisation (MR) to determine whether there is a critical window during which BMI influences MS risk.

METHODS: Summary statistics for childhood BMI (n ~ 28,000 children) and for MS susceptibility were obtained from recent large genome-wide association studies (GWAS) (n = 14,802 MS, 26,703 controls). We generated exposure instruments for BMI during four non-overlapping age epochs (< 3 months, 3 months-1.5 years, 2-5 years, and 7-8 years) and performed MR using the inverse variance weighted method with standard sensitivity analyses. Multivariable MR was used to account for effects mediated via later-life BMI.

RESULTS: For all age epochs other than birth, genetically determined higher BMI was associated with an increased liability to MS: Birth [Odds Ratio (OR) 0.81, 95% Confidence Interval (CI) 0.50-1.31, Number of Single-Nucleotide Polymorphisms (N_SNPs) = 7, p = 0.39], Infancy (OR 1.18, 95% CI 1.04-1.33, N_SNPs = 18, p = 0.01), Early childhood (OR 1.31, 95% CI 1.03-1.66, N_SNPs = 4, p = 0.03), Later childhood (OR 1.34, 95% CI 1.08-1.66, N_SNPs = 4, p = 0.01). Multivariable MR suggested that these effects may be mediated by effects on adult BMI.

CONCLUSION: We provide evidence using MR that genetically determined higher BMI during early life is associated with increased MS risk. This effect may be driven by shared genetic architecture with later-life BMI.

PMID:35532785 | DOI:10.1007/s00415-022-11161-4