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Nevin Manimala Statistics

Adipose tissue measurement in clinical research for obesity, type 2 diabetes and NAFLD/NASH

Endocrinol Diabetes Metab. 2022 Apr 6:e00335. doi: 10.1002/edm2.335. Online ahead of print.

ABSTRACT

INTRODUCTION: Excess body fat is linked to higher risks for metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CV), among other health conditions. However, it is not only the level but also the distribution of body fat that contributes to increased disease risks. For example, an increased level of abdominal fat, or visceral adipose tissue (VAT), is associated with a higher risk of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

METHODS: A review of the most relevant primary and secondary sources on body composition from the last 25 years was conducted. Relevant articles were identified using PUBMED and Google Scholar. Narrative synthesis was performed as statistical pooling was not possible due to the heterogeneous nature of the studies.

RESULTS: The body mass index (BMI) is commonly used as a proxy measure of body fatness. However, BMI does not reflect the level and distribution of body fat. Other anthropometric methods such as waist circumference measurement and waist-hip ratio, as well as methodologies like hydro densitometry, bioelectrical impedance, and isotope dilution are also limited in their ability to determine body fat distribution. Imaging techniques to define body composition have greatly improved performance over traditional approaches. Ultrasound (US), computed tomography (CT), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), are now commonly used in clinical research. Of these, MRI can provide the most accurate and high-resolution measure of body composition. In addition, MRI techniques are considered the best for the determination of fat at the organ level. On the other hand, imaging modalities require specialized, often expensive equipment and expert operation.

CONCLUSIONS: Anthropometric methods are suitable for rapid, high-volume screening of subjects but do not provide information on body fat distribution. Imaging techniques are more accurate but are expensive and do not lend themselves for high throughput. Therefore, successful trial strategies require a tiered approach in which subjects are first screened using anthropometric methods followed by more sophisticated modalities during the execution of the trial. This article provides a brief description of the most clinically relevant adipose tissue measurement techniques and discusses their value in obesity, diabetes, and NAFLD/NASH clinical research.

PMID:35388643 | DOI:10.1002/edm2.335

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Predicting breast cancer risk in a racially diverse, community-based sample of potentially high-risk women

Cancer Med. 2022 Apr 6. doi: 10.1002/cam4.4721. Online ahead of print.

ABSTRACT

BACKGROUND: Identifying women with high risk of breast cancer is necessary to study high-risk experiences and deliver risk-management care. Risk prediction models estimate individuals’ lifetime risk but have rarely been applied in community-based settings among women not yet receiving specialized care. Therefore, we aimed: (1) to apply three breast cancer risk prediction models (i.e., Gail, Claus, and IBIS) to a racially diverse, community-based sample of women, and (2) to assess risk prediction estimates using survey data.

METHODS: An online survey was administered to women who were determined by a screening instrument to have potentially high risk for breast cancer. Risk prediction models were applied using their self-reported family and medical history information. Inclusion in the high-risk subsample required ≥20% lifetime risk per ≥1 model. Descriptive statistics were used to compare the proportions of women identified as high risk by each model.

RESULTS: N = 1053 women were initially eligible and completed the survey. All women, except one, self-reported the information necessary to run at least one model; 90% had sufficient information for >1 model. The high-risk subsample included 717 women, of which 75% were identified by one model only; 96% were identified by IBIS, 3% by Claus, <1% by Gail. In the high-risk subsample, 20% were identified by two models and 3% by all three models.

CONCLUSIONS: Assessing breast cancer risk using self-reported data in a community-based sample was feasible. Different models identify substantially different groups of women who may be at high risk for breast cancer; use of multiple models may be beneficial for research and clinical care.

PMID:35388639 | DOI:10.1002/cam4.4721

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Controlled-release oral melatonin supplementation for hypertension and nocturnal hypertension: A systematic review and meta-analysis

J Clin Hypertens (Greenwich). 2022 Apr 7. doi: 10.1111/jch.14482. Online ahead of print.

ABSTRACT

Oral melatonin is a potential alternative treatment for hypertension and nocturnal hypertension. However, high-quality and relevant meta-analyses are lacking. This meta-analysis aimed to investigate whether oral melatonin supplementation reduces daytime/asleep blood pressure and cardiovascular risk, improves sleep quality, and is well-tolerated compared with placebo. Relevant articles were searched in multiple databases, including MEDLINE, EMBASE, CINAHL Complete, and the Cochrane Library, from their inception to June 2021. The included studies were randomized controlled trials recruiting patients with hypertension, using oral melatonin as the sole intervention, and investigating its effect on blood pressure. The mean out-of-office (including 24-h, daytime, and asleep) systolic and diastolic blood pressures, sleep quality, and side effects were compared between the melatonin and placebo arms using pairwise random-effect meta-analyses. A risk of bias assessment was performed using the Cochrane risk-of-bias tool. Four studies were included in the analysis and only one study was considered to have a low risk of bias. No study reported on cardiovascular risk or outcomes. Only controlled-release melatonin (not an immediate-release preparation) reduced asleep systolic blood pressure by 3.57 mm Hg (95% confidence interval: -7.88 to .73; I2 = 0%). It also reduced asleep and awake diastolic blood pressure, but these differences were not statistically significant. Melatonin improves sleep efficacy and total sleep time and is safe and well-tolerated. Due to the limited number of high-quality trials, the quality of evidence was low to very low. Therefore, adequately powered randomized controlled trials on melatonin are warranted.

PMID:35388609 | DOI:10.1111/jch.14482

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From fibre to function: are we accurately representing muscle architecture and performance?

Biol Rev Camb Philos Soc. 2022 Apr 7. doi: 10.1111/brv.12856. Online ahead of print.

ABSTRACT

The size and arrangement of fibres play a determinate role in the kinetic and energetic performance of muscles. Extrapolations between fibre architecture and performance underpin our understanding of how muscles function and how they are adapted to power specific motions within and across species. Here we provide a synopsis of how this ‘fibre to function’ paradigm has been applied to understand muscle design, performance and adaptation in animals. Our review highlights the widespread application of the fibre to function paradigm across a diverse breadth of biological disciplines but also reveals a potential and highly prevalent limitation running through past studies. Specifically, we find that quantification of muscle architectural properties is almost universally based on an extremely small number of fibre measurements. Despite the volume of research into muscle properties, across a diverse breadth of research disciplines, the fundamental assumption that a small proportion of fibre measurements can accurately represent the architectural properties of a muscle has never been quantitatively tested. Subsequently, we use a combination of medical imaging, statistical analysis, and physics-based computer simulation to address this issue for the first time. By combining diffusion tensor imaging (DTI) and deterministic fibre tractography we generated a large number of fibre measurements (>3000) rapidly for individual human lower limb muscles. Through statistical subsampling simulations of these measurements, we demonstrate that analysing a small number of fibres (n < 25) typically used in previous studies may lead to extremely large errors in the characterisation of overall muscle architectural properties such as mean fibre length and physiological cross-sectional area. Through dynamic musculoskeletal simulations of human walking and jumping, we demonstrate that recovered errors in fibre architecture characterisation have significant implications for quantitative predictions of in-vivo dynamics and muscle fibre function within a species. Furthermore, by applying data-subsampling simulations to comparisons of muscle function in humans and chimpanzees, we demonstrate that error magnitudes significantly impact both qualitative and quantitative assessment of muscle specialisation, potentially generating highly erroneous conclusions about the absolute and relative adaption of muscles across species and evolutionary transitions. Our findings have profound implications for how a broad diversity of research fields quantify muscle architecture and interpret muscle function.

PMID:35388613 | DOI:10.1111/brv.12856

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A randomized prospective study of low-dose isotretinoin alone and combination with salicylic acid and mandelic peel against acne tarda

J Cosmet Dermatol. 2022 Apr 7. doi: 10.1111/jocd.14973. Online ahead of print.

ABSTRACT

BACKGROUND: Acne tarda (AT) is typically known as adult acne and most preferably affected 25-45 age groups. Used isotretinoid mono-therapy is not effective and also produces side effects from long treatment.

AIM: The present study assesses the effectiveness of combined treatment of oral isotretinoid with topical chemical peeling (20% salicylic and 10% mandelic acid known as SM peeling) by a comparative double-blind randomized single-center interventional open-label study.

MATERIALS AND METHODS: A total fifty-eight participants AT outpatients (25-45 age-groups) attending for diagnosis in two groups and effectiveness of proposed combined treatments were determined at baseline and follow-up within 4weeks interval. Briefly group A (n=28) received 0.5 mg/kg of oral isotretinoin once daily for sixteen weeks and group B (n=30) received the same oral dose, addition with SM peeling every four weeks interval for sixteen weeks. After four weeks, treatment efficacy was assessed based on Michelson’s acne severity index (MASI) and visual analog scale (VAS), further validated using statistical tools.

RESULTS: Based on MASI and VAS scores, combined treatment was significantly effective than the monotherapy. The pre- and post-treatment analyses of response to scarring, inflammatory components at baseline and at the end of treatment were also statistically significant with p>0.008.

CONCLUSION: The above investigation revealed that the combination of oral isotretinoin with SM peeling was highly effective and could be used as newer therapy against AT without any serious side effects.

PMID:35388606 | DOI:10.1111/jocd.14973

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Prognostic value of tumor-stroma ratio in oral carcinoma: role of cancer associated fibroblasts

Oral Dis. 2022 Apr 7. doi: 10.1111/odi.14203. Online ahead of print.

ABSTRACT

OBJECTIVE: Tumor-stroma Ratio(TSR) is a promising parameter representing the abundance of the stroma which has been validated in many solid tumors. However, it is still not clear which part of stroma mainly contribute to the prognostic value of TSR. The aim of this study is to confirm the prognostic value of TSR in a large cohort of oral squamous cell carcinoma (OSCC) and further demonstrated that cancer associated fibroblasts (CAFs)-stroma ratio (CSR) contributed to the prognostic value of TSR.

MATERIALS AND METHODS: TSR was evaluated on hematoxylin and eosin-stained tissue samples from 581 patients with OSCC, which divides patients into high (>50%) and low (<50%) stroma. Then, CSR was estimated on immunohistochemical staining slides of 100 patients selected from 581patients.

RESULTS: In multivariate analysis, TSR was identified as an independent prognostic factor for disease-free survival (DFS) (P < 0.001) and oral cancer-specific survival (OCSS) (P < 0.001). The interaction term reached statistical significance for histological grade for DFS and OCSS separately. Furthermore, the high-stroma group had a higher CSR than the low-stroma group.

CONCLUSION: The prognostic value of TSR is validated in OSCC particularly in moderate and high differentiation. And CSR palys its part in the prognosis of TSR.

PMID:35388593 | DOI:10.1111/odi.14203

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Learning Curve of Total Hip Arthroplasty in Direct Anterior Approach without Requiring Corrective Osteotomy for Hip Dysplasia

Orthop Surg. 2022 Apr 7. doi: 10.1111/os.13231. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the learning curve of total hip arthroplasty in direct anterior approach (DA-THA) without requiring corrective osteotomy for patients with unilateral developmental dysplasia of the hip (DDH) through the evaluation of clinical and radiographic results.

METHOD: From December 2015 to January 2021, we retrospectively evaluated a surgeon’s first 100 patients with unilateral hip dysplasia (Crowe I-III) who underwent DA-THA. All procedures were performed by a fellowship-trained joint surgeon. Cementless hemispheric porous-coated acetabular cups and tapered cementless stems were used in all hips. The radiographic data, including leg length, the height of the center of rotation, femoral head offset, the cup anteversion and inclination angle, were measured. The cumulative sum analysis (CUSUM) and risk-adjusted cumulative sum analysis (RA-CUSUM) were used to determine the learning curve of DA-THA for each patient’s operation time. By analyzing the operation time, complication rate, postoperative length of hospitalization and creatine kinase (before surgery and the third day after surgery), estimated blood loss, Harris score, radiographic data were compared between the different stages of the learning curve.

RESULTS: The mean follow-up time was 35.45 ± 16.82 months. The CUSUM method obtained the maximum turning point of the curve at 43 cases, which divided the learning curve into Learning Period and Mastery Period. The CUSUM learning curve was best modeled as a cubic curve with the equation: CUSUM (min) = 0.001x3 – 0.495x2 + 33.60x – 10.00, which had a higher R2 value of 0.967. The pre-operative data, creatine kinase, estimated blood loss and postoperative Harris scores of the two stages were not statistically significant (P > 0.05). The mean operation time was 118 min in the Learning Period and 87 min in the Mastery Period. Statistically significant differences were detected in the operation time (P < 0.001), postoperative length of hospitalization(P = 0.024), and postoperative leg length discrepancy (P = 0.012) between the two stages. The overall complication rates were 27.9% in the Learning Period and 12.3% in the Mastery Period (p = 0.049). The overall outliers of radiographic data were 34 cases in the Learning Period and 31 cases in the Mastery Period (79.07% vs 54.39%, P = 0.010).

CONCLUSIONS: The DA-THA is a valuable alternative to achieve satisfactory clinical results for mild-to-moderate DDH patients. Furthermore, accurate analysis of the learning curve of DA-THA for hip dysplasia by the CUSUM method showed that the surgeons need to finish about 43 cases to master the technique.

PMID:35388599 | DOI:10.1111/os.13231

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Post-dialysis recovery time in ESRD patients receiving more frequent hemodialysis in skilled nursing facilities

Hemodial Int. 2022 Apr 6. doi: 10.1111/hdi.13012. Online ahead of print.

ABSTRACT

INTRODUCTION: Post-dialysis recovery time (DRT) has an important relationship to quality of life and survival, as identified in studies of ESRD patients on conventional dialysis. ESRD patients are often discharged from hospitals to skilled nursing facilities (SNFs) where on-site treatment using home hemodialysis technology is increasingly offered, but nothing is known about DRT in this patient population.

METHODS: From November 4, 2019 to June 11, 2021, within a dialysis organization providing service across 12 states and 154 SNFs, patients receiving in-SNF, more frequent dialysis (MFD) (modeled to deliver 14 treatment hours minimum per week and stdKt/V ≥2.0) were asked to describe their post-dialysis recovery time following their previous treatment, within predefined categoric choices: 0-½, ½-1, 1-2, 2-4, 4-8, 8-12 h, by next morning, or not even by next morning. Patients reporting DRT following at least one full-week treatment opportunity were included in a mixed model logistic regression of rapid recovery (DRT ≤2 h).

FINDINGS: Two thousand three hundred and nine patients met the statistical modeling inclusion criteria, providing DRT on 108,876 dialysis sessions, while receiving mean (SD) 4.3 (0.96) weekly dialysis treatments. 2118 (92%) reported DRT ≤2 h. Results appeared biologically plausible, as lower odds of rapid DRT were observed for patients who were older, missed their previous treatment, or experienced intradialytic hypotension. Greater odds of rapid DRT were observed in patients receiving five dialyses in the previous week or having 160-179 mmHg pre-hemodialysis systolic blood pressure. Rapid recovery was associated with reduced mortality or hospitalization.

DISCUSSION: SNF dialysis patients receiving 5x per week MFD report rapid recovery time ≤2 h in 92% of dialyses despite advanced age, frailty, and comorbidities. Future studies will assess the practical ramifications of rapid DRT perception/experience on nursing home rehabilitation programs, which could impact patient health beyond the nursing home stay.

PMID:35388580 | DOI:10.1111/hdi.13012

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Preliminary mechanism in fetal alloimmune thrombocytopenia associated with anti-HPA 15b antibodies

J Obstet Gynaecol Res. 2022 Apr 6. doi: 10.1111/jog.15257. Online ahead of print.

ABSTRACT

OBJECTIVE: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disease that can cause fetal hydrops, a rare but life-threatening condition in which abnormal amounts of fluid accumulate in one or two areas of the fetus’s body. A case of FNAIT with fetal hydrops caused by anti-HPA-15b antibodies was involved in this study, as we investigated whether or not anti-HPA-15b antibodies can induce endothelial angiogenesis and apoptosis.

METHODS: The monoclonal antibody immobilization of platelet antigens assay (MAIPA) was used to identify anti-HPA-15b antibodies. The three groups in Tube formation and apoptosis assays were the PBS group, the AB serum IgG group, and the anti-HPA-15b serum IgG group, all reacted with HPA-15bb HUVEC.

RESULTS: The presence of anti-HPA-15b antibodies was found in this case by MAIPA assay. The OD values are 0.33 and 0.21, reacted with HPA-15bb and HPA-15ab platelets, respectively (cutoff OD value = 0.2). Quantitative analysis revealed that the length of capillary-like tube induced by anti-HPA-15b antibodies was significantly decreased over that of AB serum IgG (*p = 0.0005), but weaker than when incubated with thrombin (**p = 0.0009). The apoptosis results show a significantly increased number of apoptotic endothelial cells in the anti-HPA-15b antibody IgG group when compared with the PBS and AB serum IgG groups (*p < 0.0001, **p < 0.0001). In addition, there is no statistical difference between the PBS and AB serum groups.

CONCLUSION: Anti-HPA-15b antibodies can inhibit angiogenesis and induce apoptosis. This may associate with hydrops fetalis (HF), or fetal hydrops of FNAIT.

PMID:35388576 | DOI:10.1111/jog.15257

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Does cerebrospinal fluid pulsation affect DWI thermometry? A study in healthy volunteers

NMR Biomed. 2022 Apr 6. doi: 10.1002/nbm.4738. Online ahead of print.

ABSTRACT

PURPOSE: Diffusion-weighted imaging (DWI)-based thermometry offers potential as a non-invasive method for measuring temperatures deep inside the human brain. However, DWI might be influenced by the pulsatile flow of cerebrospinal fluid (CSF). This study aimed to investigate the influence of such pulsations on DWI thermometry in healthy individuals.

MATERIALS AND METHODS: A total of 104 participants (50 men, 54 women; mean (± standard deviation) age, 44.2 ± 14.3 years; range 21-69 years) were investigated. DWI-based brain temperature (TDWI ) was acquired at three speeds (maximum and minimum speeds of ascending flow and random timing at the cerebral aqueduct) of CSF pulsation using a 3.0-T magnetic resonance imaging scanner. Magnetic resonance spectroscopy (MRS)-based temperature (TMRS ) at the thalamus was also obtained as a reference standard for brain temperature. The three different CSF pulsatile flows were monitored by heart rate during the scan. The difference between reference temperature and brain temperature (ΔT = TDWI – TMRS ) along with the three CSF speeds were statistically compared using Student’s matched pair t-test.

RESULTS: No significant difference in ΔT was evident among CSF speeds (P > 0.05). No significant linear correlation between ΔT and CSF flow speed at the cerebral aqueduct was observed.

CONCLUSION: Using DWI thermometry with clinical acquisition settings, which utilizes mean values within thresholds, no effect of CSF pulsation speed was observed in the estimation of ΔT.

PMID:35388508 | DOI:10.1002/nbm.4738