Tag: nevin manimala

Invest Ophthalmol Vis Sci. 2023 Jun 1;64(7):12. doi: 10.1167/iovs.64.7.12.

ABSTRACT

INTRODUCTION: Keratoconus (KC) is an ocular disorder with a multifactorial origin. Transcriptomic analyses (RNA-seq) revealed deregulations of coding (mRNA) and non-coding RNAs (ncRNAs) in KC, suggesting that mRNA-ncRNA co-regulations can promote the onset of KC. The present study investigates the modulation of RNA editing mediated by the adenosine deaminase acting on dsRNA (ADAR) enzyme in KC.

MATERIALS: The level of ADAR-mediated RNA editing in KC and healthy corneas were determined by two indexes in two different sequencing datasets. REDIportal was used to localize known editing sites, whereas new putative sites were de novo identified in the most extended dataset only and their possible impact was evaluated. Western Blot analysis was used to measure the level of ADAR1 in the cornea from independent samples.

RESULTS: KC was characterized by a statistically significant lower RNA-editing level compared to controls, resulting in a lower editing frequency, and less edited bases. The distribution of the editing sites along the human genome showed considerable differences between groups, particularly relevant in the chromosome 12 regions encoding for Keratin type II cluster. A total of 32 recoding sites were characterized, 17 representing novel sites. JUP, KRT17, KRT76, and KRT79 were edited with higher frequencies in KC than in controls, whereas BLCAP, COG3, KRT1, KRT75, and RRNAD1 were less edited. Both gene expression and protein levels of ADAR1 appeared not regulated between diseased and controls.

CONCLUSIONS: Our findings demonstrated an altered RNA-editing in KC possibly linked to the peculiar cellular conditions. The functional implications should be further investigated.

PMID:37279397 | DOI:10.1167/iovs.64.7.12

Chin Med J (Engl). 2023 Jun 7. doi: 10.1097/CM9.0000000000002631. Online ahead of print.

ABSTRACT

BACKGROUND: As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment.

METHODS: Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses.

RESULTS: In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70-0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80-1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03-1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25-0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69-0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67-0.92, P = 0.002).

CONCLUSIONS: The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.

PMID:37279392 | DOI:10.1097/CM9.0000000000002631

Issues Ment Health Nurs. 2023 Jun 6:1-8. doi: 10.1080/01612840.2023.2212768. Online ahead of print.

ABSTRACT

Although it is not mandatory for systematic review and meta-analysis studies, protocol registration is essential in the prevention of biases. This study aims to investigate the protocol registration status and reporting of systematic reviews and meta-analyses published in psychiatric nursing journals. This descriptive study’s data were obtained by scanning the 10 mental health and psychiatric nursing journals in which the studies of psychiatric nurses were most frequently published and by examining the systematic reviews and meta-analyses published between 2012-2022. A total of 177 completed studies have been reviewed. It was determined that 18.6% of the examined systematic reviews and meta-analyses had a protocol registration. Almost all (96.9%) of the registered studies were registered with PROSPERO, and 72.7% were registered prospectively. It was determined that the registration status of the studies changed statistically according to the country where the studies’ authors were located. When the published studies were examined, it was determined that approximately one out of every five studies were registered. With the prospective registration of systematic reviews, biases could be prevented, and evidence-based interventions can be made based on the knowledge obtained.

PMID:37279384 | DOI:10.1080/01612840.2023.2212768

Chin Med J (Engl). 2023 Jun 7. doi: 10.1097/CM9.0000000000002639. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between the elevation of cardiac troponin and the increase of mortality and hospitalization rate in patients with heart failure with reduced ejection fraction is clear. This study investigated the association between the extent of elevated levels of high-sensitivity cardiac troponin I (hs-cTnI) and the prognosis in heart failure with preserved ejection fraction patients.

METHODS: A retrospective cohort study consecutively enrolled 470 patients with heart failure with preserved ejection fraction from September 2014 to August 2017. According to the level of hs-cTnI, the patients were divided into the elevated level group (hs-cTnI >0.034 ng/mL in male and hs-cTnI >0.016 ng/mL in female) and the normal level group. All of the patients were followed up once every 6 months. Adverse cardiovascular events were cardiogenic death and heart failure hospitalization.

RESULTS: The mean follow-up period was 36.2 ± 7.9 months. There was a statistically significant higher in cardiogenic mortality (18.6% [26/140] vs. 1.5% [5/330], P <0.001) and heart failure (HF) hospitalization rate (74.3% [104/140] vs. 43.6% [144/330], P <0.001) in the elevated level group. The Cox regression analysis showed that the elevated level of hs-cTnI was a predictor of cardiogenic death (hazard ratio [HR]: 5.578, 95% confidence interval [CI]: 2.995-10.386, P <0.001) and HF hospitalization (HR: 3.254, 95% CI: 2.698-3.923, P <0.001). The receiver operating characteristic curve demonstrated that a sensitivity of 72.6% and specificity of 88.8% for correct prediction of adverse cardiovascular events when a level of hs-cTnI of 0.1305 ng/mL in male and a sensitivity of 70.6% and specificity of 90.2% when a level of hs-cTnI of 0.0755 ng/mL in female were used as the cut-off value.

CONCLUSION: Significant elevation of hs-cTnI (≥0.1305 ng/mL in male and ≥0.0755 ng/mL in female) is an effective indicator of the increased risk of cardiogenic death and HF hospitalization in heart failure with preserved ejection fraction patients.

PMID:37279378 | DOI:10.1097/CM9.0000000000002639

Discov Oncol. 2023 Jun 6;14(1):90. doi: 10.1007/s12672-023-00678-3.

ABSTRACT

PURPOSE: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide.

METHODS: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m², daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety.

RESULTS: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively.

CONCLUSIONS: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

PMID:37278858 | DOI:10.1007/s12672-023-00678-3

Wien Klin Wochenschr. 2023 Jun 6. doi: 10.1007/s00508-023-02222-3. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of the present study was to determine the demographic, epidemiological and clinical characteristics of adult patients with tetanus in Slovenia between 2006 and 2021, as well as to determine the therapeutic approaches which have been successfully used in the intensive care unit (ICU) of the Infectious Diseases Department in the University Medical Centre Ljubljana (UMC).

METHODS: We included all adult patients who were treated for tetanus in the ICU of the Department of Infectious Diseases Ljubljana between January 1st, 2006, and December 31th, 2021, in the retrospective study. Available epidemiological and clinical characteristics were reviewed from the medical documentation.

RESULTS: There were 31 patients included in the study, four (12.9%) males and 27 (87.1%) females. The vast majority of patients required mechanical ventilation (MV) (87.1%) which lasted (± SD) on average 35.4 ± 16.0 days. Autonomic dysfunction was present in 29 (93.5%) patients and was statistically significantly associated with shorter disease evolution (p = 0.005) and presence of healthcare-associated infection (p = 0.020). During the hospitalization, 27 (87.1%) patients acquired at least one healthcare-associated infection, most commonly ventilator-associated pneumonia. The average length of stay in the ICU (± SD) was 42.5 ± 21.3 days. With increasing age, MV lasted statistically significantly longer (p = 0.001), length of stay was longer (p = 0.015), and healthcare-associated infections occurred (p = 0.003) more frequently. Four patients (12.9%) died.

CONCLUSIONS: Although the tetanus incidence rate in Slovenia is high in comparison to other European countries on average, our therapeutic approach resulted in a good survival rate and low mortality.

PMID:37278856 | DOI:10.1007/s00508-023-02222-3

Eur Radiol. 2023 Jun 6. doi: 10.1007/s00330-023-09805-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the utility of ultrafast dynamic-contrast-enhanced (DCE) MRI in visualization and quantitative characterization of pregnancy-associated breast cancer (PABC) and its differentiation from background-parenchymal-enhancement (BPE) among lactating patients.

MATERIALS AND METHODS: Twenty-nine lactating participants, including 10 PABC patients and 19 healthy controls, were scanned on 3-T MRI using a conventional DCE protocol interleaved with a golden-angle radial sparse parallel (GRASP) ultrafast sequence for the initial phase. The timing of the visualization of PABC lesions was compared to lactational BPE. Contrast-noise ratio (CNR) was compared between the ultrafast and conventional DCE sequences. The differences in each group’s ultrafast-derived kinetic parameters including maximal slope (MS), time to enhancement (TTE), and area under the curve (AUC) were statistically examined using the Mann-Whitney test and receiver operator characteristic (ROC) curve analysis.

RESULTS: On ultrafast MRI, breast cancer lesions enhanced earlier than BPE (p < 0.0001), enabling breast cancer visualization freed from lactation BPE. A higher CNR was found for ultrafast acquisitions vs. conventional DCE (p < 0.05). Significant differences in AUC, MS, and TTE values were found between the tumor and BPE (p < 0.05), with ROC-derived AUC of 0.86 ± 0.06, 0.82 ± 0.07, and 0.68 ± 0.08, respectively. The BPE grades of the lactating PABC patients were reduced as compared with the healthy lactating controls (p < 0.005).

CONCLUSION: Ultrafast DCE MRI allows BPE-free visualization of lesions, improved tumor conspicuity, and kinetic quantification of breast cancer during lactation. Implementation of this method may assist in the utilization of breast MRI for lactating patients.

CLINICAL RELEVANCE: The ultrafast sequence appears to be superior to conventional DCE MRI in the challenging evaluation of the lactating breast. Thus, supporting its possible utilization in the setting of high-risk screening during lactation and the diagnostic workup of PABC.

KEY POINTS: • Differences in the enhancement slope of cancer relative to BPE allowed the optimal visualization of PABC lesions on mid-acquisitions of ultrafast DCE, in which the tumor enhanced prior to the background parenchyma. • The conspicuity of PABC lesions on top of the lactation-related BPE was increased using an ultrafast sequence as compared with conventional DCE MRI. • Ultrafast-derived maps provided further characterization and parametric contrast between PABC lesions and lactation-related BPE.

PMID:37278853 | DOI:10.1007/s00330-023-09805-8

Matern Child Health J. 2023 Jun 6. doi: 10.1007/s10995-023-03727-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Home visitor well-being is integral to delivering effective home visiting services and a core component of successful home visiting program implementation. While burnout (BO), compassion fatigue (CF), and compassion satisfaction (CS) have been studied extensively in physicians, nurses, and other health providers, little is known about the correlates of these phenomena in home visitors.

METHODS: This cross-sectional study examined demographic characteristics (age, race, gender), health and personal experiences (anxiety, physical health, and adverse childhood experiences), and job-related factors (caseload, role certainty, job satisfaction) as correlates of BO, CF and CS among a sample of 75 home visitors employed across six MIECHV-funded agencies in New York State. Descriptive statistics were used to characterize our sample; linear regressions were employed to investigate correlates with outcomes of interest.

RESULTS: Anxiety was significantly and positively associated with BO (β = 2.5, p < 0.01) and CF (β = 3.08, p < 0.01). Overall job satisfaction was significantly and inversely associated with BO only (β = -0.11, p < 0.001). Participants who identified as white were less likely to report higher levels of CS relative to non-white counterparts (β = -4.65, p = 0.014). Examinations of specific aspects of job satisfaction revealed significant associations between satisfaction with workplace operating conditions, nature of the work, and contingent rewards and select outcomes of interest.

DISCUSSION: Prioritizing preventive measures that target correlates of BO and CF, such as higher levels of anxiety and lower levels of job satisfaction – particularly operating conditions – may improve workforce well-being, continuity of service delivery, and ultimately quality of care provided to clients.

PMID:37278846 | DOI:10.1007/s10995-023-03727-z

Int J Comput Assist Radiol Surg. 2023 Jun 6. doi: 10.1007/s11548-023-02963-6. Online ahead of print.

ABSTRACT

PURPOSE: This work uses deep learning algorithms to provide automated feedback on the suture with intracorporeal knot exercise in the fundamentals of laparoscopic surgery simulator. Different metrics were designed to provide informative feedback to the user on how to complete the task more efficiently. The automation of the feedback will allow students to practice at any time without the supervision of experts.

METHODS: Five residents and five senior surgeons participated in the study. Object detection, image classification, and semantic segmentation deep learning algorithms were used to collect statistics on the practitioner’s performance. Three task-specific metrics were defined. The metrics refer to the way the practitioner holds the needle before the insertion to the Penrose drain, and the amount of movement of the Penrose drain during the needle’s insertion.

RESULTS: Good agreement between the human labeling and the different algorithms’ performance and metric values was achieved. The difference between the scores of the senior surgeons and the surgical residents was statistically significant for one of the metrics.

CONCLUSION: We developed a system that provides performance metrics of the intracorporeal suture exercise. These metrics can help surgical residents practice independently and receive informative feedback on how they entered the needle into the Penrose.

PMID:37278834 | DOI:10.1007/s11548-023-02963-6

Z Rheumatol. 2023 Jun 6. doi: 10.1007/s00393-023-01374-x. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to assess the relative efficacy and safety of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and azathioprine (AZA) as maintenance therapies for lupus nephritis.

METHODS: Randomized controlled trials (RCTs) examining the efficacy and safety of CNI, MMF, and AZA as maintenance therapies in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine the direct and indirect evidence from RCTs.

RESULTS: Ten RCTs comprising 884 patients were included in the study. Although the difference was not statistically significant, MMF showed a trend toward a lower relapse rate compared with AZA (odds ratio [OR] 0.72, 95% credible interval [CrI] 0.45-1.22). Similarly, tacrolimus showed a trend toward a lower relapse rate compared with AZA (OR 0.85, 95% CrI 0.34-2.00). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that MMF had the highest probability of being the best treatment based on the relapse rate, followed by CNI and AZA. The incidence of leukopenia in the MMF and CNI groups was significantly lower than that in the AZA group (OR 0.12, 95% CrI 0.04-0.34; OR 0.16, 95% CrI 0.04-0.50; respectively). Fewer patients with infections were observed in the MMF group than in the AZA group, although the difference was not statistically significant. The analysis of withdrawals due to adverse events showed a similar pattern.

CONCLUSION: Lower relapse rates combined with a more favorable safety profile suggest that CNI and MMF are superior to AZA as maintenance treatments in lupus nephritis patients.

PMID:37278824 | DOI:10.1007/s00393-023-01374-x