Category: Nevin Manimala

Int J Lab Hematol. 2023 Dec 9. doi: 10.1111/ijlh.14213. Online ahead of print.

ABSTRACT

INTRODUCTION: Flow cytometry-based paroxysmal nocturnal hemoglobinuria (PNH) testing involves utilization of monoclonal antibodies against GPI-linked proteins and FLAER. The ability of FLAER to bind to a wide variety of GPI-linked structures and to be utilized across different leukocyte subsets is remarkable. We hypothesize that FLAER as a standalone reagent may be equally effective for detecting PNH clones. The present study intends to compare the results of a FLAER alone-based strategy to the recommended FLAER+GPI-linked protein-based approach for applicability in clinical settings.

METHODS: EDTA-anticoagulated blood samples from patients for PNH workup were tested for PNH by multiparametric flow cytometry. A conventional panel comprising gating markers (CD45 for WBC, CD15 for granulocytes, and CD64 for monocytes) and a combination of FLAER and GPI-linked markers, such as CD24 and CD14, henceforth referred to as the “routine panel,” was employed. Second, a “FLAER-only panel” comprising the gating markers and FLAER alone (excluding the GPI-linked markers CD24 and CD14) was set up. The samples were processed using the lyse-wash-stain-wash technique, and events were acquired on BC Navios Ex flow cytometer (Beckman Coulter, Inc., USA) and analyzed on Kaluza Software 2.1. The presence of a PNH clone was reported at a value of ≥0.01%.

RESULTS: A total of 209 patients were tested. Both panels found a PNH clone in 20.1% of patients (n = 42/209) with a 100% concordance rate. The PNH clone range for granulocytes was 0.01%-89.68%, and for monocyte was 0.04%-96.09% in the routine panel. The range in the FLAER-only panel for granulocytes was 0.01%-89.61%, and for monocytes, it was 0.01%-96.05%. Pearson correlation statistics revealed a significant correlation between the size of the PNH clone of granulocytes and monocytes among the two panels tested (granulocytes r = 0.9999, p < 0.0001, 95% CI = 0.9999 to 1.000; monocytes r = 0.9974, p < 0.0001, 95% CI = 0.9966-0.9980).

CONCLUSION: Based on our results, FLAER as a standalone marker is specific and sensitive for identifying PNH clones in granulocytes and monocytes, even for high-sensitivity PNH assay. The proposed “FLAER-only panel” panel is efficient and cost-effective for highly sensitive PNH testing in two different cell lineages, especially in resource-limited clinical settings.

PMID:38069562 | DOI:10.1111/ijlh.14213

Cancer Med. 2023 Dec 9. doi: 10.1002/cam4.6779. Online ahead of print.

ABSTRACT

BACKGROUND: Dexamethasone is important in the treatment for pediatric acute lymphoblastic leukemia (ALL) but induces muscle atrophy with negative consequences for muscle mass, muscle strength, and functional abilities. The aim of this study was to establish the effect of a dexamethasone course on sarcopenia and physical frailty in children with ALL, and to explore prognostic factors.

METHODS: Patients with ALL aged 3-18 years were included during maintenance therapy. Patients had a sarcopenia/frailty assessment on the first day of (T1) and on the day after (T2) a 5-day dexamethasone course. Sarcopenia was defined as low muscle strength in combination with low muscle mass. Prefrailty and frailty were defined as having two or ≥three of the following components, respectively: low muscle mass, low muscle strength, fatigue, slow walking speed, and low physical activity. Chi-squared and paired t-tests were used to assess differences between T1 and T2. Logistic regression models were estimated to explore patient- and therapy-related prognostic factors for frailty on T2.

RESULTS: We included 105 patients, 61% were boys. Median age was 5.3 years (range: 3-18.8). At T1, sarcopenia, prefrailty, and frailty were observed in respectively 2.8%, 23.5%, and 4.2% of patients. At T2, the amount of patients with frailty had increased to 17.7% (p = 0.002), whereas the number of patients with sarcopenia and prefrailty remained similar. Higher ASMM (odds ratio [OR]: 0.49, 95% CI: 0.28-0.83), stronger handgrip strength (OR: 0.41, 95% CI: 0.22-0.77) and more physical activity minutes per day (OR: 0.98, 95% CI: 0.96-0.99) decreased the risk of frailty at T2. Slower walking performance (OR: 2, 95% CI: 1.2-3.39) increased the risk. Fatigue levels at T1 were not associated with frailty at T2.

CONCLUSION: Physical frailty increased strikingly after a 5-days dexamethasone course in children with ALL. Children with poor physical state at start of the dexamethasone course were more likely to be frail after the course.

PMID:38069550 | DOI:10.1002/cam4.6779

Trop Med Int Health. 2023 Dec 8. doi: 10.1111/tmi.13958. Online ahead of print.

ABSTRACT

BACKGROUND: Uganda has one of the highest rates of cervical cancer in the world. Many women are diagnosed and treated with advanced stages of the disease. With only one facility offering comprehensive cervical cancer care in Uganda, many women are required to travel significant distances and spend time away from their homes to receive cervical cancer care. It is important to understand the burden of time away from home while attending treatment because it can inform the expansion of cervical cancer treatment programmes. The aim of this mixed-methods paper is to describe how the distance to cervical cancer treatment locations impacts women in Uganda.

METHODS: Women were recruited from 19 September, 2022, to 17 January, 2023, at the Uganda Cancer Institute (UCI) and the cancer clinic at Jinja Regional Referral Hospital (JRRF). Women were eligible for the study if they were (i) aged ≥18 years with a histopathologic diagnosis of cervical cancer; (ii) being treated at the UCI or JRRF for cervical cancer; and (iii) able to provide consent to participate in the study in English, Luganda, Lusoga, Luo, or Runyankole. All participants completed a quantitative survey and a selected group was sampled for semi-structured interviews. Data were analysed using the convergent parallel mixed-methods approach. Descriptive statistics were reported for the quantitative data and qualitative data using an inductive-deductive thematic analysis approach.

RESULTS: In all, 351 women participated in the quantitative section of the study and 24 in the qualitative. The quantitative and qualitative findings largely aligned and supported one another. Women reported travelling up to 14 h to receive treatment and 20% noted that they would spend three or more nights away from home during their current visit. Major themes of the qualitative include means of transportation, spending the night away from home, and financial factors.

CONCLUSION: Our findings show that travelling to obtain cervical cancer care can be a significant burden for women in Uganda. Approaches should be considered to reduce this burden such as additional satellite cervical cancer clinics or subsidised transportation options.

PMID:38069532 | DOI:10.1111/tmi.13958

Int Wound J. 2023 Dec 8. doi: 10.1111/iwj.14550. Online ahead of print.

ABSTRACT

Craniotomies are intricate neurosurgical procedures susceptible to post-operative complications, among which surgical site infections (SSIs) are particularly concerning. This study sought to elucidate the potential risk factors and pathogenetic characteristics associated with SSIs following craniotomy procedures in a clinical setting. A retrospective study was conducted from May 2020 to May 2023, examining patients subjected to elective or emergency craniotomies. The cohort underwent post-operative surveillance for SSIs, facilitating patient classification into SSI and Non-SSI groups based on infection occurrence. Data collection encapsulated demographic and clinical parameters, including American Society of Anesthesiologists (ASA) classifications, and operative factors. SSIs were diagnosed via an integrated approach combining clinical symptoms, microbiological culture findings and pertinent laboratory tests. A rigorous statistical methodology employing IBM’s SPSS version 27.0 was utilised for data analysis. In a univariate analysis, significant risk factors for post-craniotomy SSIs were identified, with patients aged over 60 displaying a pronounced susceptibility. Moreover, surgeries exceeding a duration of 4 h heightened infection risks. Elevated ASA grades denoted an increased prevalence of SSIs, as did emergency procedures and higher National Nosocomial Infections Surveillance scores. Multivariate analysis pinpointed epidural/subdural drainage as a protective measure against SSIs, whereas emergency surgeries, operative times beyond 4 h and subsequent surgeries within the hospital stay amplified infection risks. Notably, coagulase-negative Staphylococcus dominated the identified pathogens at 28.09%, followed by Escherichia coli (17.98%), Klebsiella pneumoniae (10.11%) and Staphylococcus aureus (11.24%), underscoring the need for diverse prophylactic measures. SSIs following craniotomies present a multifaceted challenge influenced by a confluence of patient-related, operative and post-operative determinants. Understanding these risk factors is paramount in refining surgical protocols and post-operative care strategies to mitigate SSI incidence.

PMID:38069518 | DOI:10.1111/iwj.14550

Diabetes Metab Res Rev. 2023 Dec 8:e3757. doi: 10.1002/dmrr.3757. Online ahead of print.

ABSTRACT

AIMS: To investigate the associations of baseline and longitudinal cardiovascular health (CVH) measured by ‘Life’s Essential 8’ (LE8) metrics with the risk of diabetes in Chinese people with normoglycaemia or prediabetes.

MATERIALS AND METHODS: A total 86,149 participants without diabetes were enroled from the Kailuan study and were stratified by baseline glycaemic status (normoglycaemia or prediabetes). Cardiovascular health score ranged from 0 to 100 points was categorised into low (0-49), middle (50-79), and high (80-100) CVH status. Cox regressions were used to assess the associations of baseline and time-updated CVH status with incident diabetes in the overall cohort and across baseline glycaemic statuses.

RESULTS: During a median follow-up of 12.94 (interquartile rage: 12.48-13.16) years, we identified 13,097 (15.20%) cases of incident diabetes. Baseline and time-updated high CVH status was associated with a lower risk of diabetes, the corresponding hazard ratio (HR) versus low CVH status was 0.27 (95% confidence interval [CI], 0.23-0.31) and 0.26 (95% CI, 0.23-0.30) in the overall cohort, respectively. Additionally, the effect of high CVH on diabetes was more prominent in participants with normoglycaemia than those with prediabetes (P < 0.0001), with an HR of 0.26 (95% CI, 0.22-0.31) versus 0.50 (95% CI, 0.41-0.62) for baseline CVH, and 0.25 (95% CI, 0.21-0.30) versus 0.39 (95% CI, 0.32-0.48) for time-updated CVH.

CONCLUSIONS: Elevated baseline and longitudinal CVH score assessed by LE8 metrics is associated with a lower risk of subsequent diabetes, especially in normoglycaemic adults.

PMID:38069514 | DOI:10.1002/dmrr.3757

Photodermatol Photoimmunol Photomed. 2023 Dec 8. doi: 10.1111/phpp.12937. Online ahead of print.

ABSTRACT

BACKGROUND: Long wavelength ultraviolet-A1 in combination with visible light induces hyperpigmentation, particularly in dark-skin phototypes. This study evaluated the efficacy of four sunscreen formulations in protecting against VL + UVA1 (370-700 nm).

METHODS: The test products (A-D) were applied to the back of 12 volunteers, then irradiated with 320 J/cm² VL + UVA1 (3.5% UVA1 [370-400 nm]). Immediately after irradiation, and at Days 1, 7, and 14, erythema and pigmentation were assessed by investigator global assessment (IGA), colorimetry (Δa* and ΔITA) and diffuse reflectance spectroscopy (DRS)-measured relative dyschromia (area under the curve AUC). Control areas were irradiated without sunscreen.

RESULTS: Product D, containing titanium dioxide 11%, iron oxides 1%, and antioxidants, provided the highest and most consistent protection. Compared with unprotected irradiated control, it had statistically significantly less erythema on IGA, DRS (Δoxyhemoglobin), and colorimetry (Δa*) at Day 0; less pigmentation on IGA at all time points, on DRS (relative dyschromia) at Days 7 and 14, and on colorimetry (ΔITA) at Day 0. Product B, containing zinc oxide 12% plus organic UV filters, iron oxides 4%, and antioxidants, also showed some efficacy.

CONCLUSION: Of the sunscreens tested, the tinted products provided better protection against VL + UVA1 than the non-tinted products. Since the product with 1% iron oxides was superior to the product with 4% iron oxides, further studies are needed to evaluate whether iron oxide content correlates with better protection.

PMID:38069506 | DOI:10.1111/phpp.12937

J Atten Disord. 2023 Dec 8:10870547231215516. doi: 10.1177/10870547231215516. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate social cognition and empathy properties in children among Disruptive Mood Dysregulation Disorder (DMDD) + Attention and Hyperactivity Disorder(ADHD); ADHD and healthy controls from Türkiye.

METHODS: Twenty-two children with DMDD were compared to matched 30 children with ADHD and 60 healthy controls. We administered Affective Reactivity Index (ARI), KaSi Empathy Scale, Kiddie-SADS, and Reading Mind in the Eyes Test (RMET) to evaluate Theory of Mind skills to all study participants.

RESULTS: DMDD + ADHD group had lower performance in ToM skills and empathy than in two groups. The ARI scores were found to be statistically significantly higher in the DMDD group than in two groups. It was also found that ARI, empathy, and ToM scores were significantly related in children with DMDD + ADHD.

CONCLUSION: These results might be important to understand the difficulties in social functioning and interpersonal relationship in children with DMDD and ADHD. Children with DMDD may attend specific therapeutic programs which include specific techniques in social cognition, emotion regulation, and irritability.

PMID:38069496 | DOI:10.1177/10870547231215516

Physiother Res Int. 2023 Dec 8:e2064. doi: 10.1002/pri.2064. Online ahead of print.

ABSTRACT

BACKGROUND: Within the current context of implementation of an Advanced Practice Grade, the Irish Society of Chartered Physiotherapists commissioned a survey of physiotherapy manager opinions regarding the role of Advanced Practice Physiotherapists.

OBJECTIVES: The aim of this survey was to explore the views of physiotherapist managers in relation to the characteristics, role, competencies and management of Advanced Practice Physiotherapists (APPs) in Ireland.

METHODS: Physiotherapist managers based in primary and secondary care settings in Ireland were invited to participate in a survey on Advanced Practice. Quantitative data from a custom designed online survey was analysed with descriptive statistics and qualitative data from open-ended survey questions were analysed using thematic analysis.

RESULTS: The response rate to the survey was 32% (24/75). On average, respondents thought that 54% (range: 15%-80%) of an APPs time should be spent in clinical practice and between 17% and 20% variously on managerial and leadership, teaching and education and research and development duties. Four themes were identified from the surveys’ open-ended questions related to the description of APP: ‘Extended scope ‘Advanced clinical training, knowledge, and decision-making’, ‘Autonomy, independence and responsibility’, and ‘Wider roles’.

CONCLUSION: Irish physiotherapist managers recognised the extended scope of practice, expertise and multiple roles characteristic of APPs. They indicated the need for legislative changes and clarity around governance.

PMID:38069448 | DOI:10.1002/pri.2064

Int J Mol Sci. 2023 Dec 4;24(23):17090. doi: 10.3390/ijms242317090.

ABSTRACT

(1) Background: Previous studies have enriched high-density lipoproteins (HDL) using cholesteryl esters in rabbits with a three-quarter reduction in functional renal mass, suggesting that the kidneys participate in the cholesterol homeostasis of these lipoproteins. However, the possible role of the kidneys in lipoprotein metabolism is still controversial. To understand the role of the kidneys in regulating the HDL lipid content, we determined the turnover of HDL-cholesteryl esters in rabbits with a three-quarter renal mass reduction. (2) Methods: HDL subclass characterization was conducted, and the kinetics of plasma HDL-cholesteryl esters, labeled with tritium, were studied in rabbits with a 75% reduction in functional renal mass (Ntx). (3) Results: The reduced renal mass triggered the enrichment of cholesterol, specifically cholesteryl esters, in HDL subclasses. The exchange of cholesteryl esters between HDL and apo B-containing lipoproteins (VLDL/LDL) was not significantly modified in Ntx rabbits. Moreover, the cholesteryl esters of HDL and VLDL/LDL fluxes from the plasmatic compartment tended to decrease, but they only reached statistical significance when both fluxes were added to the Nxt group. Accordingly, the fractional catabolic rate (FCR) of the HDL-cholesteryl esters was lower in Ntx rabbits, concomitantly with its accumulation in HDL subclasses, probably because of the reduced mass of renal cells requiring this lipid from lipoproteins.

PMID:38069414 | DOI:10.3390/ijms242317090

Int J Mol Sci. 2023 Nov 29;24(23):16928. doi: 10.3390/ijms242316928.

ABSTRACT

Thinning of the sclera happens in myopia eyes owing to extracellular matrix (ECM) remodeling, but the initiators of the ECM remodeling in myopia are mainly unknown. The matrix metalloproteinase (MMPs) and tissue inhibitors of matrix metalloproteinase (TIMPs) regulate the homeostasis of the ECM. However, genetic studies of the MMPs and TIMPs in the occurrence of myopia are poor and limited. This study systematically investigated the association between twenty-nine genes of the TIMPs and MMPs families and early-onset high myopia (eoHM) based on whole exome sequencing data. Two TIMP4 heterozygous loss-of-function (LoF) variants, c.528C>A in six patients and c.234_235insAA in one patient, were statistically enriched in 928 eoHM probands compared to that in 5469 non-high myopia control (p = 3.7 × 10^-5) and that in the general population (p = 2.78 × 10^-9). Consequently, the Timp4 gene editing rat was further evaluated to explore the possible role of Timp4 on ocular and myopia development. A series of ocular morphology abnormalities in a dose-dependent manner (Timp4^-/- < Timp4^+/- < Timp4^+/+) were observed in a rat model, including the decline in the retinal thickness, the elongation in the axial length, more vulnerable to the form deprivation model, morphology changes in sclera collagen bundles, and the decrease in collagen contents of the sclera and retina. Electroretinogram revealed that the b-wave amplitudes of Timp4 defect rats were significantly reduced, consistent with the shorter length of the bipolar axons detected by HE and IF staining. Heterozygous LoF variants in the TIMP4 are associated with early onset high myopia, and the Timp4 defect disturbs ocular development by influencing the morphology and function of the ocular tissue.

PMID:38069250 | DOI:10.3390/ijms242316928