Nevin Manimala

Am J Prev Cardiol. 2024 Mar 28;18:100661. doi: 10.1016/j.ajpc.2024.100661. eCollection 2024 Jun.

ABSTRACT

OBJECTIVE: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort.

METHODS: Participants (n = 63,070; 67 % female; 18 % non-European) without prior CHD were followed from 2007 through 12/31/2022. The association between the PRS and incident CHD was assessed using Cox regression adjusting for genetic ancestry and risk factors. Event rates were estimated by categories of PCE and by low/intermediate/high genetic risk within PCE categories; risk discrimination and net reclassification improvement (NRI) were also assessed.

RESULTS: There were 3,289 incident CHD events during 14 years of follow-up. Adjusted hazard ratio (aHR) for incident CHD per 1 SD increase in PRS was 1.18 (95 % CI:1.14-1.22), and the aHR for the upper vs lower quintile of the PRS was 1.66 (95 % CI:1.49-1.86). The association was consistent in both sexes, in European participants compared with all minority groups combined and was strongest in the first 5 years of follow-up. The increase in the C-statistic was 0.004 (0.747 vs. 0.751; p < 0.0001); the NRI was 2.4 (0.9-3.8) for the entire cohort and 9.7 (7.5-12.0) for intermediate PCE risk individuals. After incorporating high genetic risk, a further 10 percent of participants at borderline/intermediate PCE risk would be candidates for statin therapy.

CONCLUSION: Inclusion of polygenic risk improved identification of primary prevention individuals who may benefit from more intensive risk factor modification.

PMID:38601895 | PMC:PMC11004687 | DOI:10.1016/j.ajpc.2024.100661

BMJ Paediatr Open. 2024 Apr 10;8(1):e002495. doi: 10.1136/bmjpo-2024-002495.

ABSTRACT

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren.

DESIGN: Phase 3 double-blind randomised placebo-controlled trial.

SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa.

PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline.

INTERVENTIONS: Oral vitamin D₃ (10 000 IU/week) versus placebo for 3 years.

MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy.

RESULTS: Mean serum 25-hydroxyvitamin D₃ concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass.

CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D₃ boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren.

TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.

PMID:38599800 | DOI:10.1136/bmjpo-2024-002495

JACC Cardiovasc Interv. 2024 Apr 8;17(7):874-886. doi: 10.1016/j.jcin.2024.02.012.

ABSTRACT

BACKGROUND: Adequate valve performance after surgical mitral valve repair with an annuloplasty ring is not always sustained over time. The risk of repeat mitral valve surgery may be high in these patients. Transcatheter mitral valve-in-ring (MViR) is emerging as an alternative for high-risk patients.

OBJECTIVES: The authors sought to assess contemporary outcomes of MViR using third-generation balloon-expandable aortic transcatheter heart valves.

METHODS: Patients who underwent MViR and were enrolled in the STDS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy) Registry between August 2015 and December 2022 were analyzed.

RESULTS: A total of 820 patients underwent MViR at 236 sites, mean age was 72.2 ± 10.4 years, 50.9% were female, mean STS score was 8.2% ± 6.9%, and most (78%) were in NYHA functional class III to IV. Mean left ventricular ejection fraction was 47.8% ± 14.2%, mean mitral gradient was 8.9 ± 7.0 mm Hg, and 75.5% had ≥ moderate mitral regurgitation. Access was transseptal in 93.9% with 88% technical success. All-cause mortality at 30 days was 8.3%, and at 1 year, 22.4%, with a reintervention rate of 9.1%. At 1-year follow-up, 75.6% were NYHA functional class I to II, Kansas City Cardiomyopathy Questionnaire score increased by 25.9 ± 29.1 points, mean mitral valve gradient was 8.4 ± 3.4 mm Hg, and 91.7% had ≤ mild mitral regurgitation.

CONCLUSIONS: MViR with third-generation balloon-expandable aortic transcatheter heart valves is associated with a significant reduction in mitral regurgitation and improvement in symptoms at 1 year, but with elevated valvular gradients and a high reintervention rate. MViR is a reasonable alternative for high-risk patients unable undergo surgery who have appropriate anatomy for the procedure. (STS/ACC TVT Registry Mitral Module [TMVR]; NCT02245763).

PMID:38599690 | DOI:10.1016/j.jcin.2024.02.012

RMD Open. 2024 Apr 10;10(2):e003816. doi: 10.1136/rmdopen-2023-003816.

ABSTRACT

OBJECTIVE: We sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60-64 years from the Medical Research Council National Survey of Health and Development, a nationally representative British birth cohort.

METHODS: Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at age 20 years. 10 modes of variation in hip shape (HM1-10), described by statistical shape models, were previously ascertained from DXA images taken at ages 60-64 years. Associations between (1) height at each age; (2) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity; and (3) height gain during specific periods of childhood and adolescence, and HM1-10 were tested.

RESULTS: Faster growth velocity was associated with a wider, flatter femoral head and neck, as described by positive scores for HM6 (regression coefficient 0.014; 95% CI 0.08 to 0.019; p<0.001) and HM7 (regression coefficient 0.07; 95% CI 0.002 to 0.013; p=0.009), and negative scores for HM10 (regression coefficient -0.006; 95% CI -0.011 to 0.00, p=0.04) and HM2 (males only, regression coefficient -0.017; 95% CI -0.026 to -0.09; p<0.001). Similar associations were observed with greater height size and later height tempo. Examination of height gains during specific periods of childhood and adolescence identified those during the adolescence period as being most consistently associated.

CONCLUSION: Our analyses suggest that individual growth patterns, particularly in the adolescent period, are associated with modest variations in hip shape at 60-64 years, which are consistent with features seen in osteoarthritis.

PMID:38599656 | DOI:10.1136/rmdopen-2023-003816

RMD Open. 2024 Apr 10;10(2):e003666. doi: 10.1136/rmdopen-2023-003666.

ABSTRACT

OBJECTIVE: Primary Sjögren’s syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva.

METHODS: Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls.

RESULTS: Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

PMID:38599651 | DOI:10.1136/rmdopen-2023-003666

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024 Apr 8;59:335-342. doi: 10.3760/cma.j.cn115330-20231114-00207. Online ahead of print.

ABSTRACT

Objective: To explore the effectiveness and safety of programmed death 1(PD-1) inhibitory combined with chemotherapy as a neoadjuvant therapy for locally advanced resectable oral squamous cell carcinoma. Methods: This study was a randomized controlled phase Ⅱ trial. Patients recruited from Tianjin Medical University Cancer Institute and Hospital from July 2021 to February 2023 were randomly divided into two groups in a 1∶1 ratio: the experimental group (Toripalimab combined with albumin paclitaxel and cisplatin) and the control group (albumin paclitaxel and cisplatin); patients in both groups underwent three cycles of neoadjuvant therapy. After completion of neoadjuvant therapy, patients were evaluated and subsequent surgical treatment was performed. According to the completion of treatment, the analysis was conducted on both the full analysis set and the protocol set. The effectiveness and safety of treatments were evaluated. SPSS 20.0 software was used for statistical analysis. Results: A total of 41 cases with oral cancer were enrolled, including 26 males and 15 females, aged between 34 and 74 years old. There were 23 cases in the experimental group and 18 cases in the control group. A total of 23 cases completed neoadjuvant therapy and surgery according to the protocol. Experimental group and control group showed respectively the complete response rates of 1/19 and 0/17, the partial response rates of 13/19 and 8/17, the stage-down rates of 4/19 and 3/17, the pathologic complete response rate of 8/14 and 2/9, with no statistically significant differences in individual rates between two groups (P>0.05). The major pathological response rate of 13/14 in experimental group was higher than that of 2/9 in control group (P<0.05). The incidence of grade 3-4 adverse reactions related to treatment was low in both groups (4/23 vs. 3/18, χ²=0.13, P=0.72), and the most common serious adverse reactions in the experimental group were granulocyte deficiency and electrolyte disorder. There were no adverse reactions that affected subsequent surgical treatment or caused death, and the safety and tolerability were good. The median follow-up time was 15 months, and the one-year disease-free survival rate of the experimental group was higher than that of control group (92.86% vs. 77.78%, χ²=0.62, P=0.42), with a relative decrease of 87% in the risk of disease progression or death (P=0.029). For patients with programmed death-ligand 1(PD-L1) protein expression combined positive score≥20, the experimental group showed higher major pathological response rate than control group (5/5 vs. 0/4, P=0.03). Conclusion: The neoadjuvant therapy of immunotherapy combined with chemotherapy can improve the pathological remission of oral squamous cell carcinoma and the long-term survival benefits and the prognosis of patients.

PMID:38599641 | DOI:10.3760/cma.j.cn115330-20231114-00207

J Neurol Surg A Cent Eur Neurosurg. 2024 Apr 10. doi: 10.1055/s-0043-1771267. Online ahead of print.

ABSTRACT

BACKGROUND: Quality of life (QoL) may be affected due to various reasons such as low back or leg pains with accompanying neurologic problems. Lumbar disk surgery is one of the most common performed surgeries to relieve those symptoms. Various anesthetic techniques can be used safely to perform lumbar disk surgeries. Properties that make an anesthetic technique good are mainly the quick onset and returning of the effects. This large retrospective study with patients who have undergone lumbar disk surgery under spinal anesthesia aims to evaluate the perioperative and postoperative parameters of the spinal anesthesia and review the literature.

METHODS: Cases operated under spinal anesthesia between January 2017 and December 2020 were investigated, and 617 patients who underwent simple lumbar disk surgery were included in the study. Demographic characteristics and American Society of Anesthesiologists (ASA) physical status of the patients were recorded. Visual analog scale (VAS) and QoLscores were obtained before and after the operation.

RESULTS: There were 282 (45.7%) male and 335 (54.3%) female patients with a mean age of 39.48 ± 16.71 years (range: 18-58 years) at symptom onset. The mean operating time was 46.3 minutes (range: 22-68 minutes). Average blood loss was 85 mL (range: 55-125 mL). All the patients were mobilized 6 to 12 hours after surgery. In our patient group, there were both high- and normal-risk groups in terms of the ASA physical status. During the clinical follow-up, a statistically significant improvement was found for the VAS and QoL scores (p < 0.05).

CONCLUSIONS: In this large retrospective study, our results have confirmed that spinal anesthesia is at least comparable to general anesthesia and even superior to it in some aspects.

PMID:38599624 | DOI:10.1055/s-0043-1771267

Facial Plast Surg. 2024 Apr 10. doi: 10.1055/a-2302-9456. Online ahead of print.

ABSTRACT

The apparent lack of quadrangular cartilage in Black African noses is commonly observed both from a radiological and clinical point of view. To the best of our knowledge only a few research papers has been conducted on the facial proportions and structural anatomy of black people of Southern and Eastern Africa. The aim of this retrospective comparative study is a radiological assessment of the total amount of septal quadrangular cartilage by measuring its area in sagittal CT views, in two selected Black South African (SA) and Caucasian (CA) samples and the comparison with the literature in our hands. Statistical analysis was conducted, Categorical variables are showed as frequencies and percentages, while continuous variables as means and standard deviations (SD). Normal distribution of variables was verified using the Shapiro-Wilk test or by means of skewness and kurtosis values. Differences among unpaired groups were evaluated using the independent Student’s t test for normally distributed data (complemented by the Cohen’s d to show the effect size with the following cut-off: d=0.2, “small” effect size; d=0.5, “medium” effect size; d=0.8, “large” effect size) and Mann-Whitney U test in case of no normal distribution. Statistical significance was defined as p < 0.05 setting the α-error probability at 5%. This study shows that on average there is a 30% more cartilage available in caucasian compared to Black African noses and confirms the apparent lack of quadrangular cartilage and in Black African noses which is commonly observed in surgery. The need for an adequate amount of autologous septal cartilage makes cartilage availability a major concern before surgery and being able to pre-operative accurately measure the amount of septal cartilage that is available to be harvested for other grafts in the surgery is essential.

PMID:38599617 | DOI:10.1055/a-2302-9456

J Knee Surg. 2024 Apr 10. doi: 10.1055/s-0044-1786007. Online ahead of print.

ABSTRACT

This study aimed to test and compare the biomechanical properties of three tibial fixation methods of anterior cruciate ligament (ACL) tendon grafts under cyclic load and load-to-failure testing in the bovine proximal tibiae, comprising (1) staple fixation alone, (2) interference screw fixation alone, and (3) interference screw fixation with a supplementary staple. Twenty-four bovine tibiae used in the study were divided into three groups (eight proximal tibiae in each group) based on tibial fixation methods of ACL tendon grafts: group A (a spiked ligament staple alone), group B (a cannulated interference screw alone), and group C (a cannulated interference screw with a supplementary staple). Each graft fixation was exposed to cyclic loading conditions. Significant differences were determined in failure load among the three groups (p = 0.008). The mean failure load was significantly higher in group B (717.04 ± 218.51 N) than in group A (308.03 ± 17.22 N) (p = 0.006). No significant differences were observed among the groups regarding axial stiffness (p = 0.442). Cyclic displacement differed significantly among the three groups (p = 0.005). In pairwise comparisons, the mean cyclic displacement was significantly higher in group A (8.22 ± 3.24 mm) compared with group C (1.49 ± 0.41 mm) (p = 0.005). Failure displacement varied considerably among the groups (p = 0.037). Although group B (15.53 ± 6.43 mm) exhibited a greater mean failure displacement than both group A (4.9 ± 0.75 mm) and group C (8.84 ± 4.65 mm), these differences did not reach statistical significance (p = 0.602 and p = 0.329, respectively). Interference screw fixation alone and supplementary staple fixation have biomechanically similar characteristics in terms of initial strength and stiffness of tibial ACL soft tissue graft fixation. Regardless of staple use, an interference screw with the same diameter as the tibial tunnel can ensure sufficient tensile strength in tibial ACL graft fixation.

PMID:38599605 | DOI:10.1055/s-0044-1786007

Cancer Rep (Hoboken). 2024 Apr;7(4):e1978. doi: 10.1002/cnr2.1978.

ABSTRACT

BACKGROUND AND AIMS: Oncogenesis and tumor development have been related to oxidative stress (OS). The potential diagnostic utility of OS genes in hepatocellular carcinoma (HCC), however, remains uncertain. As a result, this work aimed to create a novel OS related-genes signature that could be used to predict the survival of HCC patients and to screen OS related-genes drugs that might be used for HCC treatment.

METHODS: We used The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database to acquire mRNA expression profiles and clinical data for this research and the GeneCards database to obtain OS related-genes. Following that, biological functions from Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on differentially expressed OS-related genes (DEOSGs). Subsequently, the prognostic risk signature was constructed based on DEOSGs from the TCGA data that were screened by using univariate cox analysis, and the Least Absolute Shrinkage and Selection Operator (LASSO) regression, and multivariate cox analysis. At the same time, we developed a prognostic nomogram of HCC patients based on risk signature and clinical-pathological characteristics. The GEO data was used for validation. We used the receiver operating characteristic (ROC) curve, calibration curves, and Kaplan-Meier (KM) survival curves to examine the prediction value of the risk signature and nomogram. Finally, we screened the differentially expressed OS genes related drugs.

RESULTS: We were able to recognize 9 OS genes linked to HCC prognosis. In addition, the KM curve revealed a statistically significant difference in overall survival (OS) between the high-risk and low-risk groups. The area under the curve (AUC) shows the independent prognostic value of the risk signature model. Meanwhile, the ROC curves and calibration curves show the strong prognostic power of the nomogram. The top three drugs with negative ratings were ZM-336372, lestaurtinib, and flunisolide, all of which inversely regulate different OS gene expressions.

CONCLUSION: Our findings indicate that OS related-genes have a favorable prognostic value for HCC, which sheds new light on the relationship between oxidative stress and HCC, and suggests potential therapeutic strategies for HCC patients.

PMID:38599581 | DOI:10.1002/cnr2.1978