Tag: nevin manimala

Risk Manag Healthc Policy. 2023 Jul 26;16:1365-1376. doi: 10.2147/RMHP.S416592. eCollection 2023.

ABSTRACT

PURPOSE: Protein kinase B (PKB/AKT) has shown a high profile in the research of metabolic diseases. This research sought to determine whether the AKT1 gene’s single nucleotide polymorphisms (SNPs) and the risk of developing non-alcoholic fatty liver disease (NAFLD) were related.

PATIENTS AND METHODS: Recruited in this case-control study were 2693 subjects, including 815 with NAFLD and 1878 without NAFLD. Three SNPs of AKT1 (rs2494732, rs2494752 and rs1130233) were genotyped. To examine the correlation between SNPs and NAFLD susceptibility, logistic regression was performed.

RESULTS: After adjusting for sex, age, triglyceride and glucose, AKT1 rs2494732-C (all P < 0.05 in co-dominant model, dominant model and additive model) and rs2494752-G (P < 0.05 in co-dominant model) were linked to a lower risk of NAFLD. The combined effect of both SNPs on NAFLD risk was statistically significant, showing a dose dependence (P_trend = 0.010). Sex, body mass index, hypertension, hyperglycemia, hypertriglyceridemia, high-density lipoprotein-cholesterol, alanine aminotransferase, and beneficial alleles were all significant predictors of NAFLD risk (all P < 0.05). The prediction model achieved good discrimination, with an area under the receiver operating characteristic curve of 0.779. The Hosmer-Lemeshow test suggested an inadequate calibration of the model (χ² = 21.073, P = 0.007).

CONCLUSION: AKT1 rs2494732 and rs2494752 may be related to Chinese NAFLD susceptibility. The prediction model combining both SNPs with clinical factors displays a strong ability to discriminate NAFLD patients. Both SNPs may be exploited to design new models for early screening of NAFLD high-risk population.

PMID:37525829 | PMC:PMC10387243 | DOI:10.2147/RMHP.S416592

J Neurointerv Surg. 2023 Jul 31:jnis-2023-020531. doi: 10.1136/jnis-2023-020531. Online ahead of print.

ABSTRACT

BACKGROUND: Vessel perforation during thrombectomy is a severe complication and is hypothesized to be more frequent during medium vessel occlusion (MeVO) thrombectomy. The aim of this study was to compare the incidence and outcome of patients with perforation during MeVO and large vessel occlusion (LVO) thrombectomy and to report on the procedural steps that led to perforation.

METHODS: In this multicenter retrospective cohort study, data of consecutive patients with vessel perforation during thrombectomy between January 1, 2015 and September 30, 2022 were collected. The primary outcomes were independent functional outcome (ie, modified Rankin Scale 0-2) and all-cause mortality at 90 days. Binomial test, chi-squared test and t-test for unpaired samples were used for statistical analysis.

RESULTS: During 25 769 thrombectomies (5124 MeVO, 20 645 LVO) in 25 stroke centers, perforation occurred in 335 patients (1.3%; mean age 72 years, 62% female). Perforation occurred more often in MeVO thrombectomy (2.4%) than in LVO thrombectomy (1.0%, p<0.001). More MeVO than LVO patients with perforation achieved functional independence at 3 months (25.7% vs 10.9%, p=0.001). All-cause mortality did not differ between groups (overall 51.6%). Navigation beyond the occlusion and retraction of stent retriever/aspiration catheter were the two most common procedural steps that led to perforation.

CONCLUSIONS: In our cohort, perforation was approximately twice as frequent in MeVO than in LVO thrombectomy. Efforts to optimize the procedure may focus on navigation beyond the occlusion site and retraction of stent retriever/aspiration catheter. Further research is necessary in order to identify thrombectomy candidates at high risk of intraprocedural perforation and to provide data on the effectiveness of endovascular countermeasures.

PMID:37524518 | DOI:10.1136/jnis-2023-020531

Clin Implant Dent Relat Res. 2023 Jul 31. doi: 10.1111/cid.13254. Online ahead of print.

ABSTRACT

AIMS: This study evaluates patient-centered outcomes in patients undergoing full-arch rehabilitation, with immediate loading of implants. Using the Oral Health Impact Profile questionnaire pre-and post-treatment, it assesses the hypothesis that immediate full arch loading significantly improves quality of life.

METHODOLOGY: A dataset was defined as: 20 consecutive patients from a research database who had undergone IFAL surgery (maxilla, mandible, or both) and definitive restoration by a single clinician, and completed the OHIP-14 questionnaire prior to treatment and after restoration.

RESULTS: Pre (T₀ ) and post (T₁ ) treatment questionnaires were analyzed from 20 consecutive patients in whom a total of 160 implants were placed. The mean T₀ score was 26.7, and mean T₁ score 4.6. Differences were statistically significant (p = 0.00008). Greatest improvements were seen in psychological discomfort and disability, and pain. Worsening quality of life was shown by questions relating to speech in six patients and taste in three patients.

CONCLUSION: This study demonstrates that overall IFAL significantly improves tooth-related quality of life. It suggests reasons for patients to seek treatment while providing evidence to manage expectations, such as possible implications on speech, thus supporting informed consent of future patients in a primary care setting.

PMID:37524507 | DOI:10.1111/cid.13254

Int J Gynecol Cancer. 2023 Jul 31:ijgc-2023-004528. doi: 10.1136/ijgc-2023-004528. Online ahead of print.

ABSTRACT

OBJECTIVE: The implementation of a peri-operative care program based on enhanced recovery after surgery principles for minimally invasive gynecologic oncology surgery led to an improvement in same day discharge from 29% to 75% at our center. This study aimed to determine the program’s economic impact.

METHODS: Our initial enhanced recovery quality improvement program enrolled consecutive patients undergoing minimally invasive hysterectomy at a single center during a 12-month period and compared them to a pre-intervention cohort. The primary outcome was overall costs. The secondary outcomes were surgical and post-operative visit costs. The surgical visit costs included pre-operative and operating room, post-operative stay, pharmacy, and interventions costs. The 30-day post-operative visit costs included clinic and emergency room, and readmission costs. The costs for every visit were collected from the case-cost department and expressed in 2020 Canadian dollars (CAD).

RESULTS: A total of 96 and 101 patients were included in the pre- and post-intervention groups, respectively. The median total cost per patient for post-intervention was $7252 compared with $8381 pre-intervention (p=0.02), resulting in a $1129 cost reduction per patient. The total cost for the program implementation was $134 per patient for a total cost of $13 106. The median post-operative stay cost was $816 post-intervention compared with $1278 pre-intervention (p<0.05). Statistically significant savings for the post-intervention group were also found for operative visit, operating room costs, and pharmacy (p<0.05). On multivariate analysis, surgical approach was the only factor associated with operating room costs, whereas both surgical approach and group (pre- vs post-intervention) impacted the total and post-operative stay costs (p<0.05).

CONCLUSION: In addition to increasing the same day discharge rate after minimally invasive gynecologic oncology surgery, an enhanced recovery-based peri-operative care program led to significant reductions in cost.

PMID:37524497 | DOI:10.1136/ijgc-2023-004528

Int J Gynecol Cancer. 2023 Jul 31:ijgc-2023-004615. doi: 10.1136/ijgc-2023-004615. Online ahead of print.

ABSTRACT

Placenta accreta spectrum encompasses cases where the placenta is morbidly adherent to the myometrium. Placenta percreta, the most severe form of placenta accreta spectrum (grade 3E), occurs when the placenta invades through the myometrium and possibly into surrounding structures next to the uterine corpus. Maternal morbidity of placenta percreta is high, including severe maternal morbidity in 82.1% and mortality in 1.4% in the recent nationwide U.S. statistics. Although cesarean hysterectomy is commonly performed for patients with placenta accreta spectrum, conservative management is becoming more popular because of reduced morbidity in select cases. Treatment of grade 3E disease involving the urinary bladder, uterine cervix, or parametria is surgically complicated due to the location of the invasive placenta deep in the maternal pelvis. Cesarean hysterectomy in this setting has the potential for catastrophic hemorrhage and significant damage to surrounding organs. We propose a step-by-step schema to evaluate cases of grade 3E disease and determine whether immediate hysterectomy or conservative management, including planned delayed hysterectomy, is the most appropriate treatment option. The approach includes evaluation in the antenatal period with ultrasound and magnetic resonance imaging to determine suspicion for placenta previa percreta with surrounding organ involvement, planned cesarean delivery with a multidisciplinary team including experienced pelvic surgeons such as a gynecologic oncologist, intra-operative assessment including gross surgical field exposure and examination, cystoscopy, and consideration of careful intra-operative transvaginal ultrasound to determine the extent of placental invasion into surrounding organs. This evaluation helps decide the safety of primary cesarean hysterectomy. If safely resectable, additional considerations include intra-operative use of uterine artery embolization combined with tranexamic acid injection in cases at high risk for pelvic hemorrhage and uretinary stent placement. Availability of resuscitative endovascular balloon occlusion of the aorta is ideal. If safe resection is concerned, conservative management including planned delayed hysterectomy at around 4 weeks from cesarean delivery in stable patients is recommended.

PMID:37524496 | DOI:10.1136/ijgc-2023-004615

Genome Res. 2023 Jul 31:gr.277491.122. doi: 10.1101/gr.277491.122. Online ahead of print.

ABSTRACT

Accurately measuring biological age is crucial for improving healthcare for the elderly population. However, the complexity of aging biology poses challenges in how to robustly estimate aging and in how to interpret the biological significance of the traits used for estimation. Here we present SCALE, a statistical pipeline that quantifies biological aging in different tissues using explainable features learned from literature and single-cell transcriptomic data. Applying SCALE to the “Mouse Aging Cell Atlas” (Tabula Muris Senis) data, we identified tissue-level transcriptomic aging programs for over 20 murine tissues and created a multi-tissue resource of mouse quantitative aging-associated genes. We observe that SCALE correlates well with other age indicators, such as the accumulation of somatic mutations, and can distinguish subtle differences in aging even in cells of the same chronological age. We further compared SCALE with other transcriptomic and methylation ‘clocks’ in data of aging muscle stem cells, Alzheimer’s disease, and heterochronic parabiosis. Our results confirm that SCALE is more generalizable and reliable in assessing biological aging in aging-related diseases and rejuvenating interventions. Overall, SCALE represents a valuable advancement in our ability to measure aging accurately, robustly, and interpretably in single cells.

PMID:37524436 | DOI:10.1101/gr.277491.122

Thorax. 2023 Jul 31:thorax-2022-219925. doi: 10.1136/thorax-2022-219925. Online ahead of print.

ABSTRACT

INTRODUCTION: Readmission rates following hospital admission with community-acquired pneumonia (CAP) have increased in the UK over the past decade. The aim of this work was to describe the cohort of patients with emergency 30-day readmission following hospitalisation for CAP in England and explore the reasons for this.

METHODS: A retrospective analysis of cases from the British Thoracic Society national adult CAP audit admitted to hospitals in England with CAP between 1 December 2018 and 31 January 2019 was performed. Cases were linked with corresponding patient level data from Hospital Episode statistics, providing data on the primary diagnosis treated during readmission and mortality. Analyses were performed describing the cohort of patients readmitted within 30 days, reasons for readmission and comparing those readmitted and primarily treated for pneumonia with other diagnoses.

RESULTS: Of 8136 cases who survived an index admission with CAP, 1304 (15.7%) were readmitted as an emergency within 30 days of discharge. The main problems treated on readmission were pneumonia in 516 (39.6%) patients and other respiratory disorders in 284 (21.8%). Readmission with pneumonia compared with all other diagnoses was associated with significant inpatient mortality (15.9% vs 6.5%; aOR 2.76, 95% CI 1.86 to 4.09, p<0.001). A diagnosis of hospital-acquired infection was more frequent in readmissions treated for pneumonia than other diagnoses (22.1% vs 3.9%, p<0.001).

CONCLUSION: Pneumonia is the most common condition treated on readmission following hospitalisation with CAP and carries a higher mortality than both the index admission or readmission due to other diagnoses. Strategies to reduce readmissions due to pneumonia are required.

PMID:37524392 | DOI:10.1136/thorax-2022-219925

Annu Rev Pharmacol Toxicol. 2023 Jul 31. doi: 10.1146/annurev-pharmtox-022823-113946. Online ahead of print.

ABSTRACT

Here we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-Ras^G12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-Ras^G12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding growth of insensitive cell clones, and proliferation. Statistics confirm the expectation that most resistance-related mutations are in cis, pointing to the high probability of cooperative, same-allele effects. In addition to targeted Ras inhibitors and drug combinations, bifunctional molecules and innovative tri-complex inhibitors to target Ras mutants are also under development. Since the identities and potential contributions of preexisting and evolving mutations are unknown, selecting a pharmacologic combination is taxing. Collectively, our broad review outlines considerations and provides new insights to pharmacology and resistance. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:37524384 | DOI:10.1146/annurev-pharmtox-022823-113946

J Periodontal Implant Sci. 2023 Jun 27. doi: 10.5051/jpis.2204320216. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to investigate the relationships between gingival thickness (GT) and keratinized gingiva width (KGW), papilla height (PH), and crown ratio (CR) by employing transgingival probing and an intraoral scanner (IOS).

METHODS: This cross-sectional study examined 360 maxillary anterior teeth from 60 patients. GT was assessed using transgingival probing with an endodontic spreader. KGW, CR, and PH were measured using an IOS. One-way analysis of variance, the Student’s t-test, and Spearman correlation coefficients were employed for statistical analysis.

RESULTS: Higher GT was significantly associated with thinner KGW in the central region (P=0.019). There was no statistically significant difference in GT between teeth (P=0.06). PH was lower in lateral teeth than in canines (P=0.047), with a PH of 2.99 mm in lateral teeth. The KGW was narrower in canines than in central teeth (P=0.007). A moderate correlation was observed between KGW and PH in the central region (P=0.01), while a weak negative correlation was found between KGW and CR (P=0.043).

CONCLUSIONS: A moderate negative correlation was found between GT and KGW, as well as between PH and KGW in central teeth. In contrast, a weak negative correlation existed between CR and KGW. The PH (2.99 mm) was lower in lateral teeth than in canines. The traditional paradigm, which suggests a positive correlation between KGW and GT, was re-evaluated by measuring KGW using an IOS.

PMID:37524382 | DOI:10.5051/jpis.2204320216

J Periodontal Implant Sci. 2023 Jun 12. doi: 10.5051/jpis.2204360218. Online ahead of print.

ABSTRACT

PURPOSE: The inflammatory response due to inflammatory cytokines, bacterial pathogens, and the altered lipoprotein metabolism in patients with periodontitis indicates that infection with periodontal anaerobic bacteria may influence atherogenesis in vitro and in vivo. We aimed to explore the effect of periodontitis concerning clinical and ultrasound markers of early atherosclerosis.

METHODS: In this case-control study, a total of 30 systemically healthy adults (15 with periodontitis and 15 without periodontitis) over 40 years of age were studied. Periodontitis was determined by measuring the clinical attachment level (CAL) and radiographic bone loss (RBL). Conventional cardiovascular risk factors, including body mass index, serum levels of total cholesterol (TCH), triglycerides (TG), and high-density and low-density lipoprotein (HDL and LDL, respectively) cholesterol were evaluated. Carotid artery intima-media thickness (IMT) was measured using ultrasonography.

RESULTS: The mean values of the CAL and carotid IMT were 5.02±0.9 mm and 0.084±0.01 cm vs. 1.6±0.61 mm and 0.072±0.02 cm in the periodontitis and healthy groups, respectively, reflecting statistically significant differences (P=0.001 and P=0.037, respectively). There were statistically significant differences in the serum levels of TCH, TG, and LDL between the 2 groups (P=0.017). The CAL and RBL were positively associated with carotid IMT and serum cholesterol levels, except for HDL, whereas tooth loss was not associated with any markers (P<0.05). Compared to the healthy group, participants with periodontitis exhibited 2.09 times higher odds (95% confidence interval, 1.22-3.59) of having subclinical atherosclerosis.

CONCLUSIONS: The presence of periodontitis increased the risk of atherosclerosis.

PMID:37524377 | DOI:10.5051/jpis.2204360218