Nevin Manimala

Sci China Life Sci. 2022 May 13. doi: 10.1007/s11427-022-2104-3. Online ahead of print.

ABSTRACT

Patients with hormone receptor (HR)-positive tumors breast cancer usually experience a relatively low pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Here, we derived a 10-microRNA risk score (10-miRNA RS)-based model with better performance in the prediction of pCR and validated its relation with the disease-free survival (DFS) in 755 HR-positive breast cancer patients (273, 265, and 217 in the training, internal, and external validation sets, respectively). This model, presented as a nomogram, included four parameters: the 10-miRNA RS found in our previous study, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and volume transfer constant (K^trans). Favorable calibration and discrimination of 10-miRNA RS-based model with areas under the curve (AUC) of 0.865, 0.811, and 0.804 were shown in the training, internal, and external validation sets, respectively. Patients who have higher nomogram score (>92.2) with NAC treatment would have longer DFS (hazard ratio=0.57; 95%CI: 0.39-0.83; P=0.004). In summary, our data showed the 10-miRNA RS-based model could precisely identify more patients who can attain pCR to NAC, which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HR-positive breast cancer.

PMID:35579777 | DOI:10.1007/s11427-022-2104-3

Int Ophthalmol. 2022 May 17. doi: 10.1007/s10792-022-02360-z. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the relationship between structure and function in moderate and advanced primary open-angle glaucoma (POAG) and to determine the accuracy of structure and vasculature for discriminating moderate from advanced POAG.

METHODS: In this cross-sectional study, 25 eyes with moderate and 40 eyes with advanced POAG were enrolled. All eyes underwent measurement of the thickness of circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (GCC), and optical coherence tomography angiography (OCTA) of the optic nerve head (ONH) and macula. Visual field (VF) was evaluated by Swedish interactive threshold algorithm and 24-2 and 10-2 patterns. The correlation between structure and vasculature and the mean deviation (MD) of the VFs was evaluated by a partial correlation coefficient. The area under the receiver operating characteristic curve (AUC) was applied for assessing the power of variables for discrimination moderate from advanced POAG.

RESULTS: Including all eyes, whole image vessel density (wiVD) of the ONH area, and vessel density (VD) in the inferior quadrant of perifovea were the parameters with significant correlation with the mean deviation (MD) of the VF 24-2 in OCTA of the ONH and macula (r = .649 and .397; p < .05). The greatest AUCs for discriminating moderate and advanced POAG belonged to VD of the inferior hemifield of ONH area (.886; 95% CI (.805, .967)), and VD in the inferior quadrant of perifovea (.833; 95% CI (.736, .930)) without statistically significant difference (.886 Versus .833; p = .601).

CONCLUSION: Among vascular parameters of the ONH area, wiVD had the strongest correlation with the MD of the VF 24-2 while VD of the inferior hemifield of the ONH area had the greatest AUC for discriminating moderate and advanced POAG. Vessel density in the inferior quadrant of perifovea had a significant correlation with the MD of VF 24-2 and also the greatest AUC for discriminating moderate and advanced POAG.

PMID:35579770 | DOI:10.1007/s10792-022-02360-z

J Echocardiogr. 2022 May 17. doi: 10.1007/s12574-022-00577-6. Online ahead of print.

ABSTRACT

BACKGROUND: The management of patients with asymptomatic significant aortic regurgitation (sAR) is often challenging and appropriate timing of aortic valve surgery remains controversial. Prognostic value of diastolic parameters has been demonstrated in several cardiac diseases. The aim of this study was to analyze the prognostic significance of the diastolic function evaluated by echocardiography, in asymptomatic patients with sAR.

METHODS: A total of 126 patients with asymptomatic sAR evaluated in the Heart Valve Clinic were retrospective included. Conventional echocardiographic systolic and diastolic function parameters were assessed. Left atrial (LA) auto-strain analysis was performed in a sub-group of 57 patients. A combined end-point of hospital admission due to heart failure, cardiovascular mortality, or aortic valve surgery was defined.

RESULTS: During a median follow-up of 34.1 (interquartile range 16.5-48.1) months, 25 (19.8%) patients reached the combined end-point. Univariate analysis showed that LV volumes, LV ejection fraction (LVEF), LV-GLS, E wave, E/e’ ratio, LA volume and LA reservoir strain (LASr) were significant predictors of events. Multivariate analysis that tested all classical echocardiographic variables statistically significant in the univariate model showed that LVEDV (HR = 1.02; 95% CI 1.01-1.03; p < 0.001) and E/e’ ratio (HR = 1.12; 95% CI 1.03-123; p = 0.01) were significant predictors of events. Kaplan-Meier curve, stratified by median value of LASr, showed that lower LASr values (less than median of 34%) were associated with higher rates of events (p = 0.013).

CONCLUSION: In this population of asymptomatic patients with sAR and normal LV systolic function, baseline diastolic parameters were prognostic markers of cardiovascular events; among them, LASr played a significant predictor role.

PMID:35579751 | DOI:10.1007/s12574-022-00577-6

Mol Biol Rep. 2022 May 17. doi: 10.1007/s11033-022-07488-w. Online ahead of print.

ABSTRACT

BACKGROUND: Scab caused by Venturia inaequalis (Cke.) Wint. is the most important fungal disease of apple. Fungicide application is a widely practiced method of disease control. However, the use of chemicals is costintensive, tedious, and ecologically unsafe. The development of genetic resistance and the breeding of resistant cultivars is the most reliable and safest option. One such source of scab resistance happens to be the variety ‘Shireen’, released from SKUAST-Kashmir. However, to date, the nature of resistance and its genetic control have not been characterized. Objective This research aimed to elucidate the genetic basis of scab resistance in Shireen.

METHODS: Genetic mapping of quantitative trait loci (QTL) for resistance to apple scab disease was performed using an F1 cross developed between the susceptible cultivar ‘StarKrimson’ and the resistant cultivar ‘Shireen’. The population was evaluated for two consecutive years. Further, six candidate genes were analyzed via quantitative real-time PCR, to determine their expression level in response to the pathogen infestation.

RESULTS: Genotyping and disease phenotyping of populations led us to identify two quantitative trait loci (QTLs), namely qRVI.SS-LG2.2019 and qRVI.SS-LG8.2019 on chromosomes 2 and 8 with LOD-values of 7.67 and 4.99 respectively, and six potential CDGs for the polygenic resistance in ‘Shireen’. The genomic region corresponding to the mapped QTLs in LG 2 and LG 8 of ‘Shireen’ was examined for candidate genes possibly related to scab resistance using in silico analysis.

CONCLUSION: The QTLs mapped in the genetic background of Shireen are the novel QTLs and may be transferred to desirable genetic backgrounds and provide opportunities for isolation and cloning of genes apart from their utility to achieve durable resistance to scab.

PMID:35579736 | DOI:10.1007/s11033-022-07488-w

Diabetologia. 2022 May 17. doi: 10.1007/s00125-022-05715-4. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under review for marketing approval. Individual trials have assessed the clinical profile of tirzepatide vs different comparators. We conducted a systematic review and meta-analysis to assess the efficacy and safety of tirzepatide for type 2 diabetes.

METHODS: We searched PubMed, Embase, Cochrane and ClinicalTrials.gov up until 27 October 2021 for randomised controlled trials with a duration of at least 12 weeks that compared once-weekly tirzepatide 5, 10 or 15 mg with placebo or other glucose-lowering drugs in adults with type 2 diabetes irrespective of their background glucose-lowering treatment. The primary outcome was change in HbA_1c from baseline. Secondary efficacy outcomes included change in body weight, proportion of individuals reaching the HbA_1c target of <53 mmol/mol (<7.0%), ≤48 mmol/mol (≤6.5%) or <39 mmol/mol (<5.7%), and proportion of individuals with body weight loss of at least 5%, 10% or 15%. Safety outcomes included hypoglycaemia, gastrointestinal adverse events, treatment discontinuation due to adverse events, serious adverse events, and mortality. We used version 2 of the Cochrane risk-of-bias tool for randomised trials to assess risk of bias for the primary outcome.

RESULTS: Seven trials (6609 participants) were included. A dose-dependent superiority in lowering HbA_1c was evident with all three tirzepatide doses vs all comparators, with mean differences ranging from -17.71 mmol/mol (-1.62%) to -22.35 mmol/mol (-2.06%) vs placebo, -3.22 mmol/mol (-0.29%) to -10.06 mmol/mol (-0.92%) vs GLP-1 RAs, and -7.66 mmol/mol (-0.70%) to -12.02 mmol/mol (-1.09%) vs basal insulin regimens. Tirzepatide was more efficacious in reducing body weight; reductions vs GLP-1 RAs ranged from 1.68 kg with tirzepatide 5 mg to 7.16 kg with tirzepatide 15 mg. Incidence of hypoglycaemia with tirzepatide was similar vs placebo and lower vs basal insulin. Nausea was more frequent with tirzepatide vs placebo, especially with tirzepatide 15 mg (OR 5.60 [95% CI 3.12, 10.06]), associated with higher incidence of vomiting (OR 5.50 [95% CI 2.40, 12.59]) and diarrhoea (OR 3.31 [95% CI 1.40, 7.85]). Odds of gastrointestinal events were similar between tirzepatide and GLP-1 RAs, except for diarrhoea with tirzepatide 10 mg (OR 1.51 [95% CI 1.07, 2.15]). Tirzepatide 15 mg led to higher discontinuation rate of study medication due to adverse events regardless of comparator, while all tirzepatide doses were safe in terms of serious adverse events and mortality.

CONCLUSIONS/INTERPRETATION: A dose-dependent superiority on glycaemic efficacy and body weight reduction was evident with tirzepatide vs placebo, GLP-1 RAs and basal insulin. Tirzepatide did not increase the odds of hypoglycaemia but was associated with increased incidence of gastrointestinal adverse events. Study limitations include presence of statistical heterogeneity in the meta-analyses for change in HbA_1c and body weight, assessment of risk of bias solely for the primary outcome, and generalisation of findings mainly to individuals who are overweight or obese and already on metformin-based background therapy. PROSPERO registration no. CRD42021283449.

PMID:35579691 | DOI:10.1007/s00125-022-05715-4

JAMA. 2022 May 17;327(19):1875-1887. doi: 10.1001/jama.2022.5776.

ABSTRACT

IMPORTANCE: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear.

OBJECTIVE: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk.

DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019.

INTERVENTIONS: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455).

MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation.

RESULTS: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]).

CONCLUSIONS AND RELEVANCE: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year.

TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN57819173.

PMID:35579641 | DOI:10.1001/jama.2022.5776

JAMA. 2022 May 17;327(19):1910-1919. doi: 10.1001/jama.2022.6421.

ABSTRACT

IMPORTANCE: Patient-reported outcomes (PROs) can inform health care decisions, regulatory decisions, and health care policy. They also can be used for audit/benchmarking and monitoring symptoms to provide timely care tailored to individual needs. However, several ethical issues have been raised in relation to PRO use.

OBJECTIVE: To develop international, consensus-based, PRO-specific ethical guidelines for clinical research.

EVIDENCE REVIEW: The PRO ethics guidelines were developed following the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network’s guideline development framework. This included a systematic review of the ethical implications of PROs in clinical research. The databases MEDLINE (Ovid), Embase, AMED, and CINAHL were searched from inception until March 2020. The keywords patient reported outcome* and ethic* were used to search the databases. Two reviewers independently conducted title and abstract screening before full-text screening to determine eligibility. The review was supplemented by the SPIRIT-PRO Extension recommendations for trial protocol. Subsequently, a 2-round international Delphi process (n = 96 participants; May and August 2021) and a consensus meeting (n = 25 international participants; October 2021) were held. Prior to voting, consensus meeting participants were provided with a summary of the Delphi process results and information on whether the items aligned with existing ethical guidance.

FINDINGS: Twenty-three items were considered in the first round of the Delphi process: 6 relevant candidate items from the systematic review and 17 additional items drawn from the SPIRIT-PRO Extension. Ninety-six international participants voted on the relevant importance of each item for inclusion in ethical guidelines and 12 additional items were recommended for inclusion in round 2 of the Delphi (35 items in total). Fourteen items were recommended for inclusion at the consensus meeting (n = 25 participants). The final wording of the PRO ethical guidelines was agreed on by consensus meeting participants with input from 6 additional individuals. Included items focused on PRO-specific ethical issues relating to research rationale, objectives, eligibility requirements, PRO concepts and domains, PRO assessment schedules, sample size, PRO data monitoring, barriers to PRO completion, participant acceptability and burden, administration of PRO questionnaires for participants who are unable to self-report PRO data, input on PRO strategy by patient partners or members of the public, avoiding missing data, and dissemination plans.

CONCLUSIONS AND RELEVANCE: The PRO ethics guidelines provide recommendations for ethical issues that should be addressed in PRO clinical research. Addressing ethical issues of PRO clinical research has the potential to ensure high-quality PRO data while minimizing participant risk, burden, and harm and protecting participant and researcher welfare.

PMID:35579638 | DOI:10.1001/jama.2022.6421

Occup Ther Health Care. 2022 May 17:1-10. doi: 10.1080/07380577.2022.2076186. Online ahead of print.

ABSTRACT

Research has demonstrated the Head Control Scale to have almost perfect inter-rater reliability when utilized by experienced clinicians. This study examines if further clinical experience or additional training is required to use the scale for assessment of head control in a reliable and effective manner. First and second year physical and occupational therapy students were shown five videotaped subjects of varying ages and abilities in four positions (supine, prone, supported sitting, and pull to sit). Students then utilized each subscale of the HCS to rate every subject on the rating scale in each of the positions. When utilizing the kappa coefficient statistic, the inter-rater reliability among student participants was “almost perfect” on each of the subscales. Thus, the Head Control Scale was found to be reliable with no significant difference in interrater reliability when used by clinicians or students suggesting that additional training or expertise is not required to reliably use this scale in clinical practice.

PMID:35579614 | DOI:10.1080/07380577.2022.2076186

Transpl Infect Dis. 2022 May 17. doi: 10.1111/tid.13849. Online ahead of print.

ABSTRACT

BACKGROUND: Liver transplantation (LT) is considered the only treatment for patients with end-stage liver disease and, despite its incredible impacts on the patients’ health status, places them in an immunocompromised state in which opportunistic infection would find a way to present. Latent Tuberculosis Infection (LTBI) is the most common form of TB and can be diagnosed through Tuberculin Skin Test (TST) or Interferon-Gamma Release Assays (IGRA). LT recipients are at significant risk of TB activation. There is no strict guideline to approaching these cases though, in most centers, Isoniazid (INH) would be prescribed prophylactically. INH is a hepatotoxic medication and can have adverse effects on the transplanted liver. There is no consensus on this issue; therefore, we aimed to survey the potential hepatotoxic effects of INH among LT recipients in Shiraz, Iran.

METHODS: A retrospective cohort study was conducted among LT candidates and recipients at Abu Ali Sina Organ Transplantation Center between 1993 and 2019. All the cases underwent TST and chest X-ray to detect LTBI. All the LTBI were treated with INH from six to nine months and followed by the level of liver enzymes for quick detection of hepatotoxicity. A control group was selected among LT recipients and matched for age, gender, MELD score, and donor age.

RESULTS: Among 4895 medical records reviewed, 55 (1.12%) cases had LTBI. Neither INH-related hepatotoxicity, nor signs and symptoms that were suspicious to TB reactivation were reported. Overall, three deaths were reported, two because of myocardial infarction and one due to pneumonia. Ten patients (18.2%) experienced acute rejection as confirmed with pathology and responded to methylprednisolone. Aspartate aminotransferase (AST) was diminished from pre-LT time to the first time after transplantation; after that, it showed a steady pattern. Meanwhile, Alanine transaminase (ALT) was constant before and one stage later and decreased after that. Statistical analyses only showed significant changes in the total bilirubin titer between the case and control groups.

CONCLUSION: This survey showed prophylactic management of LTBI with INH in LT candidates and recipients was associated with no hepatotoxicity or related death. It seems INH prophylaxis is safe in LT settings and can efficiently prevent TB activation; however, careful monitoring for adverse effects and liver enzymes elevation is highly recommended. This article is protected by copyright. All rights reserved.

PMID:35579604 | DOI:10.1111/tid.13849

Syst Rev. 2022 May 16;11(1):96. doi: 10.1186/s13643-022-01976-7.

ABSTRACT

BACKGROUND: Art therapy is a form of complementary therapy to treat a wide variety of health problems. Existing studies examining the effects of art therapy differ substantially regarding content and setting of the intervention, as well as their included populations, outcomes, and methodology. The aim of this review is to evaluate the overall effectiveness of active visual art therapy, used across different treatment indications and settings, on various patient outcomes.

METHODS: We will include randomised controlled studies with an active art therapy intervention, defined as any form of creative expression involving a medium (such as paint etc.) to be actively applied or shaped by the patient in an artistic or expressive form, compared to any type of control. Any treatment indication and patient group will be included. A systematic literature search of the Cochrane Library, EMBASE (via Ovid), MEDLINE (via Ovid), CINAHL, ERIC, APA PsycArticles, APA PsycInfo, and PSYNDEX (all via EBSCOHost), ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform (ICTRP) will be conducted. Psychological, cognitive, somatic and economic outcomes will be used. Based on the number, quality and outcome heterogeneity of the selected studies, a meta-analysis might be conducted, or the data synthesis will be performed narratively only. Heterogeneity will be assessed by calculating the p-value for the chi² test and the I² statistic. Subgroup analyses and meta-regressions are planned.

DISCUSSION: This systematic review will provide a concise overview of current knowledge of the effectiveness of art therapy. Results have the potential to (1) inform existing treatment guidelines and clinical practice decisions, (2) provide insights to the therapy’s mechanism of change, and (3) generate hypothesis that can serve as a starting point for future randomised controlled studies.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42021233272.

PMID:35578277 | DOI:10.1186/s13643-022-01976-7