Rotavirus trends and distribution of genotypes before and during COVID-19 pandemic era: Bangladesh, 2017-2021.

Rotavirus gastroenteritis is accountable for an estimated 128 500 deaths among children younger than 5 years worldwide, and the majority occur in low-income countries. Although the clinical trials of rotavirus vaccines in Bangladesh revealed a significant reduction of severe rotavirus disease by around 50%, the vaccines are not yet included in the routine immunization program. The present study was designed to provide data on rotavirus diarrhea with clinical profiles and genotypes before (2017-2019) and during the COVID-19 pandemic period (2020-2021). Fecal samples were collected from 2% of the diarrheal patients at icddr,b Dhaka hospital of all ages between January 2017 and December 2021 and were tested for VP6 rotavirus antigen using ELISA. The clinical manifestations such as fever, duration of diarrhea and hospitalization, number of stools, and dehydration and so on were collected from the surveillance database (n = 3127). Of the positive samples, 10% were randomly selected for genotyping using Sanger sequencing method. A total of 12 705 fecal samples were screened for rotavirus A antigen by enzyme immunoassay. Overall, 3369 (27%) were rotavirus antigen-positive, of whom children <2 years had the highest prevalence (88.6%). The risk of rotavirus A infection was 4.2 times higher in winter than in summer. Overall, G3P[8] was the most prominent genotype (45.3%), followed by G1P[8] (32.1%), G9P[8] (6.8%), and G2P[4] (6.1%). The other unusual combinations, such as G1P[4], G1P[6], G2P[6], G3P[4], G3P[6], and G9P[6], were also present. Genetic analysis on Bangladeshi strains revealed that the selection pressure (dN/dS) was estimated as <1. The number of hospital visits showed a 37% drop during the COVID-19 pandemic relative to the years before the pandemic. Conversely, there was a notable increase in the rate of rotavirus positivity during the pandemic (34%, p < 0.00) compared to the period before COVID-19 (23%). Among the various clinical symptoms, only the occurrence of watery stool significantly increased during the pandemic. The G2P[4] strain showed a sudden rise (19%) in 2020, which then declined in 2021. In the same year, G1P[8] was more prevalent than G3P[8] (40% vs. 38%, respectively). The remaining genotypes were negligible and did not exhibit much fluctuation. This study reveals that the rotavirus burden remained high during the COVID-19 prepandemic and pandemic in Bangladesh. Considering the lack of antigenic variations between the circulating and vaccine-targeted strains, integrating the vaccine into the national immunization program could reduce the prevalence of the disease, the number of hospitalizations, and the severity of cases.

Post-transplantation cyclophosphamide and cyclosporine A versus methotrexate and cyclosporine A for graft-versus-host disease prophylaxis after allogeneic peripheral stem cell transplantation in adult acute myeloid leukemia patients.

BACKGROUND: Different prophylactic protocols are available for preventing graft-versus-host disease (GVHD) after matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to compare the effectiveness of post-transplantation cyclophosphamide plus cyclosporine A (PT-CY/CSA) versus methotrexate plus CSA (MTX/CSA) as GVHD prophylaxis protocols in adult acute myeloid leukemia (AML) patients who received peripheral blood stem cells (PBSC) from fully matched donors. METHODS: The 1-year outcomes of 89 patients treated with PT-CY/CSA and 90 patients treated with MTX/CSA who had MSD allo-HCT for AML using unmanipulated mobilized PBSC were examined and compared. RESULTS: The cumulative incidence of acute GVHD at 100 days was considerably lower in the PT-CY/CSA group (4% vs 19.3%, p = 0.002), however there were no statistically significant difference in the cumulative incidence of chronic GVHD at 1-year (19.6% vs 37.4%, p = 0.053). Significant delays in neutrophil and platelet engraftments were reported in the PT-CY/CSA group (17 vs 12 days) and (13 vs 12 days), respectively (p < 0.001). The cumulative incidences of relapse (19.1% vs 13.7%, p = 0.470), overall survival (79.1% vs 77.3%, p = 0.986), non-relapse mortality (16.5% vs 16.8%, p = 0.837), and the GVHD and relapse-free survival (GRFS) (53.7% vs 46.6%, p = 0.478) did not differ statistically at 1-year. CONCLUSION: PT-CY/CSA demonstrated a significant decrease in the rate of acute GVHD. However, it was associated with engraftment delay.

Prognostic Value of a Classification System for Iliofemoral Stenting in Patients with Chronic Venous Obstruction.

OBJECTIVE: This retrospective, multicentre study aimed to assess the prognostic value of a proposed classification system for chronic venous obstruction (CVO) patients undergoing successful interventional procedures. METHODS: This study analysed data from 13 vascular centres, including 1 033 patients with CVO treated between 2015 - 2019. The patients were classified into five category types: 1 - non-thrombotic iliac vein lesion; 2 - CVO of iliac segment; 3 - CVO of iliofemoral segment above common femoral vein confluence; 4 - CVO of iliofemoral segment extending into the femoral vein (FV) or deep femoral vein (DFV); and 5 - CVO of iliofemoral segment involving both DFV and FV. Stent deployment, complications, and follow ups were evaluated. Univariate and multivariate analyses were performed to identify predictors of primary patency loss. RESULTS: Mean age of the patients was 44.0 ± 14.7 years, with 59.9% being women. A median of two stents were used for unilateral cases and five stents for bilateral cases. At 12 months of follow up, primary patency rates for types 1 - 5 were 94.9%, 90.3%, 80.8%, 60.6%, and 39.4%, respectively. These rates were strongly correlated with the extension of CVO and showed significant differences between each type. Univariate analysis identified predictors of primary patency loss as the type of CVO, history of deep vein thrombosis, and the total number of stents. In the multivariate analysis, the significant independent predictors of primary patency loss were the type of CVO and the total number of stents. CONCLUSION: The proposed anatomical classification of iliofemoral CVO will help to predict intervention outcomes and facilitate comparison of stent outcomes in future studies. However, further evaluation and validation in prospective studies are needed to confirm the utility of this classification.

Predictors of response to Radioactive Iodine Therapy in Intermediate and high risk patients with papillary thyroid carcinoma.

BACKGROUND: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored. METHODS: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans. RESULTS: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660-0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12-0.55), P < 0.001. CONCLUSION: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy.

Targeted analysis of Ubiquitin-Specific Peptidase (USP8) in a population of Iranian people with Cushing's disease and a systematic review of the literature.

OBJECTIVE: Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs. METHODS: Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases. RESULTS: In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas. CONCLUSION: Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.

The effect of climate changes on incidence of benign paroxysmal positional vertigo; a systematic review with meta-analysis of 16144 patients.

BACKGROUND: There were controversial findings in terms of the association between the incidence of Benign Paroxysmal Positional Vertigo (BPPV) and climate changes, so the current systematic review plus meta-analysis is designed to discover this possible relationship. METHODS: Web of science, PubMed, Scopus, Google Scholar, Embase, and Cochrane library were systematically searched up to August 2023. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Problem/Population, Intervention, Comparison, and Outcome (PICO) guidelines were used. Two authors independently reviewed the eligible articles and assessed the quality of them. RESULTS: In total, 15 studies including 16144 patients met the inclusion criteria. Ten studies reported the relation of BPPV to monthly mean temperature, 7 to monthly average humidity, 4 to monthly average rainfall, 6 to monthly sunlight time, and 2 to average solar radiation. The incidence of BPPV was associated significantly with atmospheric pressure (P: 0.003) and rainfall (P: 0.017). However, there was not any statistically significant correlation between incidence of BPPV and humidity, sunlight time, temperature, and solar radiation level (P > 0.05). CONCLUSIONS: The incidence of BPPV was higher in cold months of a year in both northern hemisphere and southern hemisphere countries. Although it can be because of negative correlation with temperature, the current meta-analysis did not find any statistically significant negative correlation with temperature. In addition, the incidence of BPPV was associated significantly with atmospheric pressure (positive correlation) and rainfall (negative correlation).

Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis.

BACKGROUND: Measures of insulin resistance (IR)/sensitivity (IS) are emerging tools to identify metabolic-associated fatty liver disease (MAFLD). However, the comprehensive assessment of the performance of various indicators is limited. Moreover, the utility of measures of IR/IS in detecting liver fibrosis remains unclear. AIMS: To evaluate the predictive ability of seventeen IR/IS and two beta cell function indices to identify MAFLD and liver fibrosis. METHODS: A cross-sectional study was conducted on individuals aged 25-75 years. Transient elastography was used to estimate liver stiffness and controlled attenuation parameter. The following measures were computed: homeostatic model assessment (HOMA/HOMA2) for IR, IS, and beta cell function; QUICKI; Bennett index; glucose/insulin; FIRI; McAuley index; Reynaud index; SPISE index; TyG; TyG-BMI; TyG-WC; TyG-WHtR; TG/HDL; and METS-IR. Subgroup analyses were performed according to age, gender, diabetes status, and body weight. RESULTS: A total of 644 individuals were included in our analysis. MAFLD and significant liver fibrosis were detected in 320 (49.7%) and 80 (12.4%) of the participants, respectively. All measures of IR/IS identified MAFLD and liver fibrosis. However, TyG-WC, TyG-BMI, and TyG-WHtR were the top three indicators that identified MAFLD. Measures that include insulin level in their mathematical calculation, namely, Raynaud index, HOMA-IR, HOMA 2-IR, FIRI, and QUICKI had the best performance in identifying liver fibrosis in the entire population, as well as among the study subgroups. CONCLUSIONS: TyG-WC, TyG-BMI, and TyG-WHtR were the best predictors of MAFLD. Insulin-based measures had better performances in the detection of advanced fibrosis. This was independent of age, gender, obesity, or diabetes status.

Trifocal versus extended depth of focus (EDOF) intraocular lenses after cataract extraction.

BACKGROUND: Cataract, defined as an opacity of the lens in one or both eyes, is the leading cause of blindness worldwide. Cataract may initially be treated with new spectacles, but often surgery is required, which involves removing the cataract and placing a new artificial lens, usually made from hydrophobic acrylic. Recent advancements in intraocular lens (IOL) technology have led to the emergence of a diverse array of implantable lenses that aim to minimise spectacle dependence at all distances (near, intermediate, and distance). To assess the relative merits of these lenses, measurements of visual acuity are needed. Visual acuity is a measurement of the sharpness of vision at a distance of 6 metres (or 20 feet). Normal vision is 6/6 (or 20/20). The Jaegar eye card is used to measure near visual acuity. J1 is the smallest text and J2 is considered equivalent to 6/6 (or 20/20) for near vision. OBJECTIVES: To compare visual outcomes after implantation of trifocal intraocular lenses (IOLs) to those of extended depth of focus (EDOF) IOLs. To produce a brief economic commentary summarising recent economic evaluations that compare trifocal IOLs with EDOF IOLs. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, and three trial registries on 15 June 2022. For our economic evaluation, we also searched MEDLINE and Embase using economic search filters to 15 June 2022, and the NHS Economic Evaluation Database (EED) from 1968 up to and including 31 December 2014. We did not use any date or language restrictions in the electronic searches. SELECTION CRITERIA: We included studies comparing trifocal and EDOF IOLs in adults undergoing cataract surgery. We did not include studies involving people receiving IOLs for correction of refractive error alone (or refractive lens exchange in the absence of cataract). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Two review authors working independently selected studies for inclusion and extracted data from the reports. We assessed the risk of bias in the studies, and we assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included five studies that compared trifocal and EDOF lenses in people undergoing cataract surgery. Three trifocal lenses (AcrySof IQ PanOptix, ATLISA Tri 839MP, FineVision Micro F) and one EDOF lens (TECNIS Symfony ZXR00) were evaluated. The studies took place in Europe and North America. Follow-up ranged from three to six months. Of the 239 enroled participants, 233 (466 eyes) completed follow-up and were included in the analyses. The mean age of participants was 68.2 years, and 64% of participants were female. In general, the risk of bias in the studies was unclear as methods for random sequence generation and allocation concealment were poorly reported, and we judged one study to be at high risk of performance and detection bias. We assessed the certainty of the evidence for all outcomes as low, downgrading for the risk of bias and for imprecision. In two studies involving a total of 254 people, there was little or no difference between trifocal and EDOF lenses for uncorrected and corrected distance visual acuity worse than 6/6. Sixty per cent of participants in both groups had uncorrected distance visual acuity worse than 6/6 (risk ratio (RR) 1.06, 95% confidence intervals (CI) 0.88 to 1.27). Thirty-one per cent of the trifocal group and 38% of the EDOF group had corrected distance visual acuity worse than 6/6 (RR 1.04, 95% CI 0.78 to 1.39). In one study of 60 people, there were fewer cases of uncorrected near visual acuity worse than J2 in the trifocal group (3%) compared with the EDOF group (30%) (RR 0.08, 95% CI 0.01 to 0.65). In two studies, participants were asked about spectacle independence using subjective questionnaires. There was no evidence of either lens type being superior. One further study of 60 participants reported, "overall, 90% of patients achieved spectacle independence", but did not categorise this by lens type. All studies included postoperative patient-reported visual function, which was measured using different questionnaires. Irrespective of the questionnaire used, both types of lenses scored well, and there was little evidence of any important differences between them. Two studies included patient-reported ocular aberrations (glare and halos). The outcomes were reported in different ways and could not be pooled; individually, these studies were too small to detect meaningful differences in glare and halos between groups. One study reported no surgical complications. Three studies did not mention surgical complications. One study reported YAG capsulotomy for posterior capsular opacification (PCO) in one participant (one eye) in each group. One study reported no PCO. Two studies did not report PCO. One study reported that three participants (one trifocal and two EDOF) underwent laser-assisted subepithelial keratectomy (LASEK) to correct residual myopic refractive error or astigmatism. One study reported a subset of participants who were considering laser enhancement at the end of the study period (nine trifocal and two EDOF). Two studies did not report laser enhancement rates. No economic evaluation studies were identified for inclusion in this review. AUTHORS' CONCLUSIONS: Distance visual acuity after cataract surgery may be similar whether the lenses implanted are trifocal IOLs or EDOF (TECNIS Symfony) IOLs. People receiving trifocal IOLs may achieve better near vision and may be less dependent on spectacles for near vision. Both lenses were reported to have adverse subjective visual phenomena, such as glare and halos, with no meaningful difference detected between lenses.

Improving diabetic retinopathy screening at the point of care: integrating telemedicine to overcome current challenges.

OBJECTIVE: To investigate the utility of point of care screening of diabetic retinopathy (DR) and the impact of a telemedicine program to overcome current challenges. METHODS: This was a retrospective study on people with type 2 diabetes mellitus (T2DM) who were screened for DR using the single-field non-mydriatic fundus photography at the point of care during routine follow-up visits at endocrinology clinic. Retinal images were uploaded and sent to a retina specialist for review. Reports indicating retinopathy status and the need for direct retinal examination were transmitted back to the endocrinology clinic. All patients were informed about DR status and, if needed, referred to the retina specialist for direct retinal examination. RESULTS: Of the 1159 individuals screened for DR, 417 persons (35.98%) were screen-positive and referred to the retina specialist for direct retinal examination. A total of 121 individuals (29.01%) underwent direct retinal examination by the specialist. Diabetes macular edema (DME) was detected in 12.1%. In addition, non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were detected in 53.4% and 2.6% of the patients, respectively. CONCLUSION: Integrating DR screening program at the point of care at the secondary care services improves the rate of DR screening as well as detection of sight threatening retinopathy and provides the opportunity for timely intervention in order to prevent advanced retinopathy in people with T2DM.

Traumatic atlantoaxial rotatory fixation in adults: a systematic review of published cases.

Atlantoaxial rotatory fixation (AARF) in adults is a rare and clinically challenging condition characterized by a spectrum of etiological factors, predominantly attributed to traumatic and inflammatory pathologies within the craniovertebral region. Trauma is the most frequently identified cause within the adult population, with the first case report published in 1907. This study aims to conduct a systematic review that addresses the clinical presentations and management strategies relating to traumatic atlantoaxial rotatory fixation in adults. A comprehensive search of the PubMed database was executed, adhering to the PRISMA guidelines. The inclusion criteria encompassed case reports and series documenting AARF cases in individuals aged 18 and above, spanning database inception to July 2022. Studies not published in the English language were excluded. A total of 61 articles reporting cases of AARF in the adult population were included in the study. The mean age of affected individuals was 36.1 years (± 15.6), with a distribution of 46% females and 54% males. Predominant mechanisms of injury included motor vehicle accidents and falls, constituting 38% and 22% of cases, respectively. Among the classification systems employed, Fielding and Hawkins type I accounted for the majority at 63%, followed by type II at 10%, and type III at 4%. Conservative management was used for treatment in 65% of acute (65%) cases and 29% of chronic cases. Traumatic AARF is a rare phenomenon in the adult population, is more common in younger adults, and does not often present with neurologic deficits. Patients diagnosed acutely are more likely to be successfully treated with conservative management, while patients diagnosed chronically are less likely to be reduced with conservatively and often require surgical treatment. Surgery should be considered for patients with irreducible dislocations, ligamentous injuries, unstable associated fractures, and persistent pain resistant to conservative management.

Targeted FT-NIR and SERS Detection of Breast Cancer HER-II Biomarkers in Blood Serum Using PCB-Based Plasmonic Active Nanostructured Thin Film Label-Free Immunosensor Immobilized with Directional GNU-Conjugated Antibody.

This work describes our recent PCB-based plasmonic nanostructured platform patent (US 11,828,747B2) for the detection of biomarkers in breast cancer serum (BCS). A 50 nm thin gold film (TGF) was immersion-coated on PCB (i.e., PCB-TGF) and immobilized covalently with gold nanourchin (GNU) via a 1,6-Hexanedithiol (HDT) linkage to produce a plasmonic activated nanostructured thin film (PANTF) platform. A label-free SERS immunosensor was fabricated by conjugating the platform with monoclonal HER-II antibodies (mAb) in a directional orientation via adipic acid dihydrazide (ADH) to provide higher accessibility to overexpressed HER-II biomarkers (i.e., 2+ (early), 3+ (locally advanced), and positive (meta) in BCS. An enhancement factor (EF) of 0.3 × 105 was achieved for PANTF using Rhodamine (R6G), and the morphology was studied by scanning electron microscopy (SEM) and atomic force microscope (AFM). UV-vis spectroscopy showed the peaks at 222, 231, and 213 nm corresponding to ADH, mAb, and HER-II biomarkers, respectively. The functionalization and conjugation were investigated by Fourier Transform Near Infrared (FT-NIR) where the most dominant overlapped spectra of 2+, 3+, and Pos correspond to OH-combination of carbohydrate, RNH2 1st overtone, and aromatic CH 1st overtone of mAb, respectively. SERS data were filtered using the filtfilt filter from scipy.signals, baseline corrected using the Improved Asymmetric Least Squares (isals) function from the pybaselines.Whittaker library. The results showed the common peaks at 867, 1312, 2894, 3026, and 3258 cm-1 corresponding to glycine, alanine ν (C-N-C) assigned to the symmetric C-N-C stretch mode; tryptophan and α helix; C-H antisymmetric and symmetric stretching; NH3+ in amino acids; and N-H stretch primary amide, respectively, with the intensity of Pos > 3+ > 2+. This trend is justifiable considering the stage of each sample. Principal Component Analysis (PCA) and Linear Discrimination Analysis (LDA) were employed for the statistical analysis of data.

Properties of OSA-esterified insoluble fraction of Persian gum and its application in dairy cream.

BACKGROUND: In the present study, the insoluble fraction of Persian gum (IFPG) was modified with octenyl succinic anhydride (OSA) and its various properties were assessed. In addition, the effect of OSA-IFPG on the rheological and textural properties of dairy cream was investigated. RESULTS: Suitable conditions for achieving a degree of substitution (DS) of 0.023 were found at pH 9, IFPG concentration 4 wt%, OSA concentration 10 wt% and a temperature of 40 °C, within 120 min. The carbonyl group attachment in OSA-IFPG was also confirmed via Fourier transform infrared and H-nuclear magnetic resonance spectroscopy (1 H-NMR). While the X-ray diffraction test indicated no significant changes in the structure of the IFPG after modification with OSA, esterification increased the negative charge density, decreased thermal decomposition temperature and increased the emulsifying capacity to 100%, which was obtained for the first time. The use of OSA-modified IFPG in creams augmented the complex viscosity, loss and storage modulus, while also demonstrating the creation of a pseudo-gel network. The hardness and adhesiveness of the texture increased, which can be explained by the formation of a compact structure and reduced particle size. CONCLUSION: Overall, OSA-IFPG with hydrophilic and hydrophobic sections may function as an emulsifier and be recommended as a safe source of hydrocolloids for emulsion stability. It can also provide a positive physical structure when added to dairy cream, even if the fat concentration is lower than usual. © 2023 Society of Chemical Industry.

Outcomes in progressive systemic sclerosis treated with autologous hematopoietic stem cell transplantation compared with combination therapy.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive systemic sclerosis (SSc) compared with cyclophosphamide. Cyclophosphamide, however, does not provide a long-term benefit in SSc. The combination of mycophenolate mofetil (MMF) and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab. METHODS: Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease > 25% or an FVC increase > 10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death. RESULTS: Twenty-one SSc patients in the combination therapy group were compared with sixteen in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (p= 0.7). The hazard ratio for EFS at 24 months favored the combination group (HR = 0.09, P= 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months. CONCLUSION: MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months.

Potential metabolic biomarkers of critical limb ischemia in people with type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a significant risk factor for the development of critical limb ischemia (CLI), the most advanced stage of peripheral arterial disease. The concurrent existence of T2DM and CLI often leads to adverse outcomes, namely limb amputation. OBJECTIVE: To identify biomarkers for improving the screening of CLI in high-risk people with T2DM. METHODS: We investigated metabolome profiles in serum samples of 113 T2DM people with CLI (n = 23, G2) and without CLI (n = 45, G0: no lower limb stenosis (LLS) and n = 45, G1: LLS < 50%), using hydrogen nuclear magnetic resonance (1H NMR) approach. Principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to analyze 1H NMR data. RESULTS: Twenty potential metabolites that could discriminate people with T2DM and CLI (G2) from non-CLI patients without LLS (G0) were determined in serum samples. The correct percent of classification for the PLS-DA model for the test set samples was 85% (n = 20) and 100% (n = 5) for G0 and G2 groups, respectively. Non-CLI patients with LLS < 50% (G1) were projected on the PCA abstract space built using 20 discriminatory metabolites. Eleven people with T2DM and LLS < 50% were prospectively followed, and their ankle-brachial index (ABI) was measured after 4 years. A promising agreement existed between the PCA model's predictions and those obtained by ABI values. CONCLUSION: The findings suggest that confirmation of blood potential metabolic biomarkers as a complement to ABI for screening of CLI in a large group of high-risk people with T2DM is needed.

Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study.

BACKGROUND: People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population. METHODS: People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012-2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership. RESULTS: The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: 'substance related' (24.9%), 'atopic' (24.2%), 'pure affective' (30.4%), 'cardiovascular' (14.1%), and 'complex multimorbidity' (6.4%). Patients had on average 7-9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the 'pure affective'. Compared to the largest cluster ('pure affective'), the 'substance related' and the 'atopic' clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98-1.00) and 0.96 (0.95-0.97) respectively], and the 'cardiovascular' and 'complex multimorbidity' clusters were older (ORs 1.09 (1.07-1.10) and 1.16 (1.14-1.18) respectively). The 'substance related' cluster was more likely to be White, the 'cardiovascular' cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10-2.79), and both more likely to have schizophrenia, compared to other clusters. CONCLUSION: The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.

Effect of Empagliflozin and Pioglitazone on left ventricular function in patients with type two diabetes and nonalcoholic fatty liver disease without established cardiovascular disease: a randomized single-blind clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease. METHODS: This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM). RESULTS: In this study, GLS improved by 1.56 ± 2.34% (P < 0.01) in the pioglitazone group and 1.06 ± 1.83% (P < 0.01) in the empagliflozin group without a significant difference between the two groups (P = 0.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r = - 0.311, P = 0.007. LSM in the pioglitazone and empagliflozin group [(-0.73 ± 1.59) and (-1.11 ± 1.33)] kpa (P < 0.01) decreased significantly. It was without substantial difference between the two groups (P = 0.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22 + 35.02 dB/m vs. -25.67 + 41.50 dB/m, P = 0.01. CONCLUSION: Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations. TRIAL REGISTRATION: This trial was registered in the Iranian Registry of Clinical Trials (IRCT): "A Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease" IRCT20190122042450N5, 29 November 2020. https://www.irct.ir/search/result?query=IRCT20190122042450N5 .

Non-alcoholic fatty liver disease and compromised endothelial function in people with type 2 diabetes.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) frequently coexists with type 2 diabetes mellitus (T2DM) and synergistically contributes to the development of atherosclerosis. Flow-mediated dilation (FMD) is a commonly used noninvasive test for assessing endothelial function. The main objective of this study was to explore FMD in patients with T2DM with and without NAFLD. METHODS: In this cross-sectional study, conducted on people with T2DM, NAFLD was defined as controlled attenuation parameter (CAP) score > 302 dB/m. Endothelial dysfunction was detected when arterial FMD of brachial artery was equal or less than 0.7%. Regression analyses were applied to assess factors associated with impaired FMD. RESULT: A total of 147 patients (72 with NAFLD and 75 without NAFLD) were included in the final analysis. Patients with NAFLD were more likely to develop FMD ≤ 7% (77.8% vs. 58.7%, P = 0.01). In multivariate analysis, NAFLD (OR = 2.581, 95% CI (1.18-5.62), P = 0.017) and hypertension (HTN) (OR = 3.114, 95% CI (1.31-7.35), P = 0.010) were associated with an increased risk of impaired FMD. However, female sex was associated with a decreased risk of impaired FMD (OR = 0.371, 95% CI (0.15-0.87), P = 0.024). CONCLUSION: NAFLD is associated with endothelial dysfunction in people with T2DM. This risk is comparable with the risk imposed by HTN, highlighting the importance of screening and management of NAFLD in these patients.

Attainment of NICE blood pressure targets among older people with newly diagnosed hypertension: nationwide linked electronic health records cohort study.

BACKGROUND: it is not known if clinical practice reflects guideline recommendations for the management of hypertension in older people and whether guideline adherence varies according to overall health status. AIMS: to describe the proportion of older people attaining National Institute for Health and Care Excellence (NICE) guideline blood pressure targets within 1 year of hypertension diagnosis and determine predictors of target attainment. METHODS: a nationwide cohort study of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 years newly diagnosed with hypertension between 1st June 2011 and 1st June 2016. The primary outcome was attainment of NICE guideline blood pressure targets as measured by the latest blood pressure recording up to 1 year after diagnosis. Predictors of target attainment were investigated using logistic regression. RESULTS: there were 26,392 patients (55% women, median age 71 [IQR 68-77] years) included, of which 13,939 (52.8%) attained a target blood pressure within a median follow-up of 9 months. Success in attaining target blood pressure was associated with a history of atrial fibrillation (OR 1.26, 95% CI 1.11, 1.43), heart failure (OR 1.25, 95% CI 1.06, 1.49) and myocardial infarction (OR 1.20, 95% CI 1.10, 1.32), all compared to no history of each, respectively. Care home residence, the severity of frailty, and increasing co-morbidity were not associated with target attainment following adjustment for confounder variables. CONCLUSIONS: blood pressure remains insufficiently controlled 1 year after diagnosis in nearly half of older people with newly diagnosed hypertension, but target attainment appears unrelated to baseline frailty, multi-morbidity or care home residence.

Physical multimorbidity, depressive symptoms, and social participation in adults over 50 years of age: findings from the English Longitudinal Study of Ageing.

OBJECTIVES: The aim of the current study was to identify specific patterns of physical multimorbidity and examine how these patterns associated with changes in social participation over time. METHODS: We used latent class analysis to identify clusters of physical multimorbidity in 11,391 older adults. Mixed effects regression models were used to assess associations between physical multimorbidity clusters and changes in social participation over 15 years. RESULTS: Four clusters of physical multimorbidity were identified. All physical multimorbidity clusters were associated with a reduction in cultural engagement (e.g. visits to theatre, cinema, museums) over time, with the strongest association seen in the complex/multisystem cluster (ß = -0.26, 95% CI = -0.38 to -0.15). Similar results emerged for leisure activities. Adjusting for depressive symptoms fully attenuated some associations. All physical multimorbidity clusters were associated with an increase in civic participation over time. CONCLUSIONS: Physical multimorbidity reduced some aspects of social participation over time, with specific combinations of conditions having increased risk of reductions.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2021.2017847.

Comparison of Different Antiviral Regimens in the Treatment of Patients with Severe COVID-19: A Retrospective Cohort.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disorders, with disease severity ranging from asymptomatic to critical manifestations. The current retrospective study compared the efficacies of different antiviral regimens used in patients suffering from severe COVID-19 disease from 19 January 2020 to December 2021 in a single center in Saudi Arabia. In total, 188 patients were enrolled in the current study, including 158 patients treated with different antiviral regimens, and 30 who did not receive any antiviral treatment. Different antiviral regimens, including favipiravir, remdesivir, oseltamivir, favipiravir/remdesivir, and favipiravir/oseltamivir were adopted. The effects of using different antivirals and antibiotics on the survival rate were evaluated, as well as the presence of comorbidities. Among all severely affected patients, 39/188 (20.7%) survived. Both age and comorbidities, including diabetes and hypertension, were significantly correlated with high case fatality following SARS-CoV-2 infection. Remdesivir alone and the combination of favipiravir and remdesivir increased the survival rate. Surprisingly, both imipenem and linezolid helped in the deterioration of disease outcome in the patients. A negative correlation was detected between increased mortality and the use of favipiravir and the use of either imipenem or linezolid. Among the compared antiviral regimens used in the treatment of severe COVID-19, remdesivir was found to be an effective antiviral that reduces COVID-19 case fatality. Antibiotic treatment using imipenem and/or linezolid should be carefully re-evaluated.