Protocol for systematic review and meta-analysis on randomized clinical trials for direct oral anticoagulant in subjects with acute coronary syndrome

Background: Recently, direct oral anticoagulant (DOAC) has been projected for secondary prevention of recurrent ischemic events post-acute coronary syndrome (ACS). The addition of a DOAC to the antiplatelet regimen of subjects with the ACS is clinically practiced in candidates where compelling anticoagulation is indicated by high thromboembolic risk. The current evidence provides approved compelling indication for the DOAC, particularly for rivaroxaban which bears the strongest existing evidence. Objective: We intend to assess the role of DOAC in addition to single or dual antiplatelet therapy in subjects with ACS. We will compare the clinical characteristics and explore the efficacy and safety of the DOAC class members (apixaban, betrixaban, dabigatran, edoxaban and rivaroxaban) in terms of reduction in ischemic events in subjects with ACS (ST-segment elevation myocardial infarction [STEMI] or non–ST-segment elevation [NSTEMI]) or subjects who underwent percutaneous coronary intervention (PCI) and or ACS and coexisting atrial fibrillation (AF). Methods: Relevant data will be searched on known data-bases such as Embase, Google Scholar, the Cochrane Central, and PubMed. The trials included will be randomized controlled trials from 2009 to 2022. Subjects will be receiving DOAC for ACS were evaluated for inclusion. The extraction, synthesis, quality, and validity of data will follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The risk of bias tool, version 2.0 (Cochrane) will be used for risk of bias assessment. Data will be pooled using random-effects models. The primary outcome measure will be efficacy end point (composite of cardiovascular death, myocardial infarction, and stroke), while the safety outcome will be minor/major bleeding. (AU)

Mini review: The clinical avenues of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction

Background: Combined hydralazine-nitrate has an avenue in the management of subjects with heart failure with reduced ejection fraction. Exploring the pharmacotherapy in this context will facilitate the clinical utility of the combined therapy. Objective: The main objective of this mini-review was to evaluate the role of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction. Methods: We conducted a literature search on Google scholar, MEDLINE, and PubMed to identify the randomized clinical trials on combined hydralazine-nitrate, in subjects with heart failure with reduced ejection fraction. 2760 articles were returned initially out of which 10 trials were conforming to the inclusion criteria. However, three trails were the focus for the current mini-review. Key findings: The current mini-review lends support to the use of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction (HFrEF). The combination may offer subjects who have remained symptomatic with HFrEF despite optimum dosing of standard therapy. Black subjects with HFrEF have proved to benefit from combined hydralazine-nitrate. The combination (e.g. small dose of hydralazine 12.5-25 mg twice a day and isosorbide mononitrate 10 mg twice a day) may provide alternative clinical utility in subjects with contraindications (renal artery stenosis, creatinine clearance less than 30 mL/minute, sustained hyperkalemia) to the use of ACEinh, ARBs, and/or ARNI. Subjects with HFrEF on combined hydralazine-nitrate should be assessed and monitored for systolic BP (keep >120 mmHg) and subjects with chronic kidney disease (keep eGFR > 30 mL/min/1.73 m2). Hydralazine-nitrate was inferior to ACEinh (higher all-cause mortality and cardiovascular mortality. Conclusion: The current mini- review provides the key points to support the use of hydralazine-nitrate in subjects with heart failure with reduced ejection fraction. (AU)

LYRM7-associated mitochondrial complex III deficiency with non-cavitating leukoencephalopathy and stroke-like episodes.

Defects of respiratory chain complex III (CIII) result in characteristic but rare mitochondrial disorders associated with distinct neuroradiological findings. The underlying molecular defects affecting mitochondrial CIII assembly factors are few and yet to be identified. LYRM7 assembly factor is required for proper CIII assembly where it acts as a chaperone for the Rieske iron-sulfur (UQCRFS1) protein in the mitochondrial matrix and stabilizing it. We present here the seventeenth individual with LYRM7-associated mitochondrial leukoencephalopathy harboring a previously reported rare pathogenic homozygous LYRM 7 variant, c.2T>C, (p.Met1?). Like previously reported individuals, our 5-year-old male proband presented with recurrent metabolic and lactic acidosis, encephalopathy, and fatigue. Further, he has additional, previously unreported features, including an acute stroke like episode with bilateral central blindness and optic neuropathy, recurrent hyperglycemia and hypertension associated with metabolic crisis. However, he has no signs of psychomotor regression. He has been stable clinically with residual left-sided reduced visual acuity and amblyopia, and no more metabolic crises for 2-year-period while on the mitochondrial cocktail. Although the reported brain MRI findings in other affected individuals are homogenous, it is slightly different in our index, revealing evidence of bilateral almost symmetric multifocal periventricular T2 hyperintensities with hyperintensities of the optic nerves, optic chiasm, and corona radiata but with no cavitation or cystic changes. This report describes new clinical and radiological findings of LYRM7-associated disease. The report also summarizes the clinical and molecular data of previously reported individuals describing the full phenotypic spectrum.

Knowledge and Awareness of Dental Practitioners About the Utilization of Endocrown in Post-endodontic Management.

BACKGROUND: The objective of this study was to evaluate the knowledge, and awareness of dentists in Ha'il, Kingdom of Saudi Arabia, regarding the use of endocrown as post-endodontic restorations, utilizing an online questionnaire. METHODS: A cross-sectional study was carried out among dental practitioners working in Ha'il, Kingdom of Saudi Arabia. Dentists who practice in the Ha'il were included in the current study. The survey study involved a sample size of 245 participants. The researchers employed the snowball sampling technique in this investigation. The validated, closed-ended questionnaires were disseminated to the entire sample of selected dental practitioners using electronic mail. The initial section of the survey encompassed inquiries pertaining to the demographic characteristics of the participants, encompassing variables such as gender, years of professional experience, and workplace. The subsequent section of the survey focused on assessing the participants' knowledge and opinions regarding the endocrown technique. The Chi-square test was employed to assess the associations between categorical variables. RESULTS: The most of participants 228 (93.1%) had knowledge about endocrown and 94 (38.4%) of them received information from their educational institutions. Among the responses of the participants, 232 (94.7%) expressed their preference for utilizing endocrown restorations specifically for molar teeth. Moreover, 183 (74.7%) of respondents indicated that the endocrown is preferred when there is a restricted amount of inter-arch space available. A majority of respondents 152 (62.0%) indicated that the ferrule does not exert any influence on the endocrown. A majority of participants 135 (55.1%) expressed a preference for utilizing lithium disilicate ceramic in the fabrication of endocrown. The most of participants 209 (85.3%) opted to use resin cement for the purpose of cementation. The characteristics of gender, experience, and working place were found to have a significant relationship with the knowledge of the participants about endocrown (p <0.05). CONCLUSIONS: The study participants need to enhance their knowledge and awareness pertaining to the utilization of endocrowns as a post-endodontic treatment.

A genetic association study of glutamine-encoding DNA sequence structures, somatic CAG expansion, and DNA repair gene variants, with Huntington disease clinical outcomes.

BACKGROUND: Huntington disease (HD) is caused by an unstable CAG/CAA repeat expansion encoding a toxic polyglutamine tract. Here, we tested the hypotheses that HD outcomes are impacted by somatic expansion of, and polymorphisms within, the HTT CAG/CAA glutamine-encoding repeat, and DNA repair genes. METHODS: The sequence of the glutamine-encoding repeat and the proportion of somatic CAG expansions in blood DNA from participants inheriting 40 to 50 CAG repeats within the TRACK-HD and Enroll-HD cohorts were determined using high-throughput ultra-deep-sequencing. Candidate gene polymorphisms were genotyped using kompetitive allele-specific PCR (KASP). Genotypic associations were assessed using time-to-event and regression analyses. FINDINGS: Using data from 203 TRACK-HD and 531 Enroll-HD participants, we show that individuals with higher blood DNA somatic CAG repeat expansion scores have worse HD outcomes: a one-unit increase in somatic expansion score was associated with a Cox hazard ratio for motor onset of 3·05 (95% CI = 1·94 to 4·80, p = 1·3 × 10-6). We also show that individual-specific somatic expansion scores are associated with variants in FAN1 (pFDR = 4·8 × 10-6), MLH3 (pFDR = 8·0 × 10-4), MLH1 (pFDR = 0·004) and MSH3 (pFDR = 0·009). We also show that HD outcomes are best predicted by the number of pure CAGs rather than total encoded-glutamines. INTERPRETATION: These data establish pure CAG length, rather than encoded-glutamine, as the key inherited determinant of downstream pathophysiology. These findings have implications for HD diagnostics, and support somatic expansion as a mechanistic link for genetic modifiers of clinical outcomes, a driver of disease, and potential therapeutic target in HD and related repeat expansion disorders. FUNDING: CHDI Foundation.