Category: Statistics

Biochem Genet. 2023 Dec 16. doi: 10.1007/s10528-023-10608-1. Online ahead of print.

ABSTRACT

Beclin 1 protein encoded by the BECN1 gene plays a critical role in the autophagy pathway which is utilized by the Hepatitis B virus (HBV) for its replication. HBV is known for the subversion of the host’s autophagy process for its multiplication. The aim of this study was to determine the role of BECN1 intronic variants in HBV susceptibility. Intronic region variant rs9890617 was analyzed using Human splicing finder v3.1 and was found to alter splicing signals. A total of 712 individuals (494 HBV infected and 218 healthy controls) were recruited in the study and genotyped by applying Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Statistical analysis revealed that the mutant allele T of rs9890617 was significantly associated with the overall disease risk in the allelic model (OR 1.41; 95%CI 1.00-1.99, p = 0.04). On stratifying the data based on the different stages of HBV infection, the mutant genotype showed a significant association with the chronic group in allelic (OR 1.62; 95%CI 1.11-2.39, p = 0.01), dominant (OR 1.64; 95%CI 1.07-2.52, p = 0.02), and co-dominant (OR 1.55; 95%CI 1.00-2.40, p = 0.04) models. Overall, this is the first study regarding beclin 1 variant rs9890617 and we found a significant association of the mutant T allele with the genetic predisposition to HBV infection.

PMID:38103127 | DOI:10.1007/s10528-023-10608-1

Biochem Genet. 2023 Dec 16. doi: 10.1007/s10528-023-10600-9. Online ahead of print.

ABSTRACT

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterized by autoantibody production and organ involvement. The role of toll-like receptor-7 in SLE is well established. Although genetic variations in the TLR-7 gene have been associated with an increased risk of developing SLE, the findings are not consistent. We performed a meta-analysis of previously published articles on four important single nucleotide polymorphisms in the TLR-7 gene (rs3853839, rs179008, rs179019, and rs179010) to reach a valid conclusion. Various literature databases, including PubMed, Science Direct, and Scopus, were scoured for eligible reports until May 10, 2023. GPower software v.3 was used to assess the power of individual reports included in the meta-analysis. Comprehensive Meta-analysis v3 software was used to perform all statistics. The publication biases in each genetic comparison model were investigated using funnel plots and Egger’s regression test. To test heterogeneity, Cochrane Q statistics, probability value and I² were used. Considering the predefined inclusion and exclusion criteria, the current study included a total of 10 eligible studies that included 15,472 SLE cases and 16,721 healthy controls. The meta-analysis revealed a significant association between TLR7 polymorphisms (rs179019 and rs179010) and susceptibility to SLE development. Other TLR7 polymorphisms (rs3853839 and rs179008), on the other hand, showed no significant association. Furthermore, the trial sequential analysis identified the need for additional case control studies for TLR-7 polymorphisms (rs3853839, rs179008, and rs179019) other than the rs179010 polymorphism. TLR7 variants for rs179010 and rs179019 are risk factor for the development of SLE. Further investigations are required to reach a valid conclusion.

PMID:38103124 | DOI:10.1007/s10528-023-10600-9

Clin Transl Oncol. 2023 Dec 16. doi: 10.1007/s12094-023-03359-3. Online ahead of print.

ABSTRACT

BACKGROUND: Small cell lung cancer (SCLC) is an extremely malignant subtype of lung cancer because of its high potential for metastases. Cardiac invasion of SCLC is a serious concern that may lead to systemic embolism or tract obstruction. It has aroused much concern that cardiovascular comorbidities may significantly affect the survival of SCLC patients and their treatment decisions.

METHODS: We consecutively recruited 772 small cell lung cancer (SCLC) patients between January 2011 and December 2018 from 4 cancer specialty hospitals in China. Only newly diagnosed primary cancer inpatients were included. Univariable and multivariable adjusted Cox proportional hazard models were conducted to evaluate the risk factors associated with mortality. Hazard ratios (HRs) for mortality and corresponding 95% confidence intervals (95% CIs) were calculated.

RESULTS: The prevalence of cardiovascular diseases (CVDs) was 34.6% in all SCLC patients. Log-rank analysis presented statistically significant differences in median survival time (MST) between patients with CVD and without CVD in all SCLC patients (9.0 months vs. 15.0 months, P = 0.005) and patients with chemotherapy only (12.0 months vs. 18.0 months, P = 0.048). Pericardial effusion (HR 1.671, 95% CI 1.082-2.580, P = 0.021) and heart failure (HR 1.752, 95% CI 1.290-2.379, P < 0.001) were independent risk factors associated with mortality in all SCLC patients. VTE is related to poorer prognosis in patients with chemotherapy only (HR 5.558, 95% CI 1.335-23.135, P = 0.018) and chemoradiotherapy (HR 3.057, 95% CI 1.270-7.539, P = 0.013).

CONCLUSIONS: Comprehensive management of CVD comorbidities is of vital importance for the long-term prognosis of SCLC patients.

PMID:38103121 | DOI:10.1007/s12094-023-03359-3

Dig Dis Sci. 2023 Dec 16. doi: 10.1007/s10620-023-08207-6. Online ahead of print.

ABSTRACT

BACKGROUND: Emergency presentation (EP) of cancer, a new cancer diagnosis made following an emergency department (ED) visit, is associated with worse patient outcomes and greater organizational stress on healthcare systems. Pancreatic cancer has the highest rate of EPs among European studies but remains understudied in the U.S.

AIMS: To evaluate the association between pancreatic cancer EPs and cancer stage, treatment, and survival.

METHODS: We conducted a retrospective cohort study among patients with pancreatic adenocarcinoma diagnosed from 2007 to 2019 at a tertiary-care Veterans Affairs medical center. Electronic health records were reviewed to identify EP cases, defined as a new pancreatic cancer diagnosis made within 30 days of an ED visit where cancer was suspected. We used multivariate logistic regression models and Cox proportional hazards models to examine the associations between EPs and cancer stage, treatment, and survival.

RESULTS: Of 243 pancreatic cancer patients, 66.7% had EPs. There was no difference in stage by EP status. However, patients diagnosed through EPs were 72% less likely to receive cancer treatment compared to non-emergency presenters (adjusted OR 0.28; 95% CI 0.13-0.57). Patients with EPs also had a 73% higher mortality risk (adjusted HR 1.73; 95% CI 1.29-2.34). This difference in mortality remained statistically significant after adjusting for cancer stage and receipt of cancer treatment (adjusted HR 1.47; 95% CI 1.09-1.99).

CONCLUSIONS: Pancreatic cancer EPs are common and independently associated with lower treatment rates and survival. Enhanced understanding of process breakdowns that lead to EPs can help identify care gaps and inform future quality improvement efforts.

PMID:38103105 | DOI:10.1007/s10620-023-08207-6

Heart Vessels. 2023 Dec 16. doi: 10.1007/s00380-023-02343-9. Online ahead of print.

ABSTRACT

Recently, a once-daily dose of edoxaban (15-mg) has been approved for stroke prevention in non-valvular atrial fibrillation (NVAF) patients aged ≥ 80 years, in whom standard oral anticoagulants are not recommended because of high bleeding risk (HBR), based on the ELDERCARE-AF trial. However, information regarding the characteristics and clinical outcomes among such patients is limited. Thus, this study aimed to clarify the characteristics and event rates in elderly patients with NVAF and HBR defined by the ELDERCARE-AF criteria. Of the 7406 NVAF outpatients included in the J-RHYTHM Registry, 60 patients with creatinine clearance (CrCl) < 15 mL/min were excluded. The remaining 7346 patients (age, 69.7 ± 9.9 years; men, 70.9%; warfarin use, 78.7%) were divided into three groups: Group 1, aged < 80 years (n = 6165); Group 2, aged ≥ 80 years without HBR (n = 584); and Group 3, aged ≥ 80 years with HBR (at least one of the followings; CrCl, 15-30 mL/min, history of bleeding, body weight ≤ 45 kg, and antiplatelet use) (n = 597, eligible for 15-mg edoxaban). Patients in Group 3 had a higher prevalence of comorbidities, and therefore, both higher thromboembolic and bleeding risk scores than in the other groups. During the 2-year follow-up period, the incidence rates (per 100 person-years) of thromboembolism in Groups 1, 2, and 3 were 0.7, 1.5, and 2.1 (P < 0.001), major hemorrhage, 0.8, 1.2, and 2.0 (P < 0.001), and all-cause death, 0.8, 2.6, and 4.6 (P < 0.001), respectively. Adjusted hazard ratios of Group 3 were 1.64 (95% confidence interval 0.89-3.04, P = 0.116) for thromboembolism, 1.53 (0.85-2.72, P = 0.154) for major hemorrhage, and 1.84 (1.19-2.85, P = 0.006) for all-cause death compared with Group 1. The NVAF Patients aged ≥ 80 years with HBR defined by the ELDERCARE-AF criteria were certainly at a higher adverse event risk, especially for all-cause death. Clinical trial registration: The J-RHYTHM Registry is registered in the University Hospital Medicine Information Network (UMIN) Clinical Trials Registry (unique identifier: UMIN000001569) http://www.umin.ac.jp/ctr/ .

PMID:38103100 | DOI:10.1007/s00380-023-02343-9

Arch Orthop Trauma Surg. 2023 Dec 16. doi: 10.1007/s00402-023-05164-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Previous studies have shown that intra-articular hip injections prior to hip arthroscopy (HA) can be a helpful diagnostic tool. However, local anesthetic and corticosteroid injections can be chondrotoxic and corticosteroid injections have been shown to increase the risk of infection during subsequent surgical intervention. The purpose of this study was to evaluate whether preoperative injections adversely affect outcomes of HA using a national database.

MATERIALS AND METHODS: The TriNetX database was retrospectively queried. Patients undergoing HA for femoroacetabular impingement with at least 1 year of claims runout were included in the analysis. Patients were grouped by whether they had a hip injection within 1 year prior to HA. The rates of repeat HA, total hip arthroplasty (THA), infection, osteonecrosis, and new onset hip OA at 1- and 5-years postoperatively were compared between groups. Statistical significance was assessed at α = 0.05.

RESULTS: 6511 HA patients with previous injection and 1178 HA patients without previous injection were included. Patients with a previous injection were overall younger (32.3 vs. 34.7 years, p < 0.001), more likely to be female (69 vs. 48%, p < 0.001) and had a higher BMI (26.3 vs. 25.7 kg/m², p = 0.043). At 1 and 5-years postoperatively, patients with any injection were 1.43 (p < 0.001) and 1.89 (p < 0.001) times more likely to undergo repeat HA, respectively. At 1 and 5-years postoperatively, patients who underwent a corticosteroid injection were 2.29 (p < 0.001) and 1.89 (p < 0.001) times more likely to undergo repeat HA than patients with local anesthetic injection only and 1.56 (p < 0.001) and 2.08 (p < 0.001) times more likely to undergo repeat HA than patients with no injection.

CONCLUSIONS: Intraarticular hip injections prior to hip arthroscopy, particularly corticosteroid injections, are associated with increased risk of repeat hip arthroscopy at 1 and 5 years. Additional studies are needed to elucidate this risk.

PMID:38103052 | DOI:10.1007/s00402-023-05164-7

Angiology. 2023 Dec 16:33197231215240. doi: 10.1177/00033197231215240. Online ahead of print.

ABSTRACT

The objective of this study is to evaluate the effect of preoperative embolization on carotid body tumor resection. A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Scopus, and Web of Science were screened for studies published between 2010 and 2022. Primary outcomes investigated were intraoperative blood loss, operative time, length of hospital stay, and perioperative complications such as transient ischemic attack (TIA)/stroke, vascular injury, and cranial nerve injury (CNI). A random effects model was used in cases where study heterogeneity was high. Overall, 25 studies were included in the systematic review, involving 1649 patients: 23 studies were eligible for meta-analysis. The incidence of vascular injury was significantly less in the preoperative embolization group (odds ratio (OR) = 0.60; 95% CI: 0.42-0.84; P = .003). There was no statistically significant difference between the two groups regarding intraoperative blood loss, operative time, length of hospital stay, incidence of TIA/stroke, and CNI. Subgroup analyses did not demonstrate significant difference between Shamblin I, II, and III subgroups regarding operative time. This meta-analysis found preoperative embolization to be significantly beneficial in reducing incidence of vascular injury.

PMID:38103038 | DOI:10.1177/00033197231215240

Global Spine J. 2023 Dec 16:21925682231222903. doi: 10.1177/21925682231222903. Online ahead of print.

ABSTRACT

BACKGROUND CONTEXT: Several studies have shown that factors such as insurance type and patient income are associated with different readmission rates following certain orthopaedic procedures. The literature, however, remains sparse with regard to these demographic characteristics and their associations to perioperative lumbar spine fusion outcomes.

PURPOSE: The purpose of this study was to assess the associations between hospital type, insurance type, and patient median income to both 30-day complication and readmission rates following lumbar spine fusion.

PATIENT SAMPLE: Patients who underwent primary lumbar spine fusion (n = 596,568) from 2010-2016 were queried from the National Readmissions Database (NRD).

OUTCOME MEASURES: Incidence of 30-day complication and readmission rates.

METHODS: All relevant diagnoses and procedures were identified using International Classification of Disease, 9th and 10th Edition (ICD-9, 10) codes. Hospital types were categorized as metropolitan non-teaching (n = 212,131), metropolitan teaching (n = 364,752), and rural (n = 19,685). Insurance types included: Medicare (n = 213,534), Medicaid (n = 78,520), private insurance (n = 196,648), and out-of-pocket (n = 45,025). Patient income was divided into the following quartiles: Q1 (n = 112,083), Q2 (n = 145,755), Q3 (n = 156,276), and Q4 (n = 147,289), wherein quartile 1 corresponded to lower income ranges and quartile 4 to higher ranges. Statistical analysis was conducted in R. Kruskal-Wallis tests with Dunn’s pairwise comparisons were performed to analyze differences in 30-day readmission and complication rates in patients who underwent lumbar spine fusion. Complications analyzed included infection, wound injury, hematoma, neurological injury, thromboembolic event, and hardware failure.

RESULTS: 30-day readmission was significantly higher in metropolitan teaching hospitals compared to metropolitan non-teaching hospitals and rural hospitals (P < .05). Patients from metropolitan teaching hospitals had significantly higher rates of infection (P < .001), wound injury (P < .001), hematoma (P = .018), and hardware failure (P < .002) compared to those treated at metropolitan non-teaching hospitals. Privately insured patients were significantly less likely to be readmitted at 30 days than those paying with Medicare or Medicaid (P < .01). Patients with private insurance also experienced significantly lower rates of hematoma formation than Medicare beneficiaries and out-of-pocket payers (P < .01), postoperative wound injury compared to Medicaid patients and out-of-pocket payers (P < .005), and infection compared to all other groups (P < .001). Patients in Quartile 4 experienced significantly greater rates of hematoma formation compared to those in Quartiles 1 and 2 and were more likely to experience a thromboembolic event compared to all other groups.

CONCLUSION: Patients undergoing lumbar spine fusion at metropolitan non-teaching hospitals and paying with private insurance had significantly lower 30-day readmission rates than their counterparts. Complications within 30 days following lumbar spine fusion were significantly higher in patients treated at metropolitan teaching hospitals and in Medicare and Medicaid beneficiaries. Aside from a few exceptions, however, patient income was generally not associated with differential complication rates.

PMID:38103012 | DOI:10.1177/21925682231222903

Biom J. 2023 Dec 16:e2300177. doi: 10.1002/bimj.202300177. Online ahead of print.

ABSTRACT

Online testing procedures assume that hypotheses are observed in sequence, and allow the significance thresholds for upcoming tests to depend on the test statistics observed so far. Some of the most popular online methods include alpha investing, LORD++, and SAFFRON. These three methods have been shown to provide online control of the “modified” false discovery rate (mFDR) under a condition known as CS. However, to our knowledge, LORD++ and SAFFRON have only been shown to control the traditional false discovery rate (FDR) under an independence condition on the test statistics. Our work bolsters these results by showing that SAFFRON and LORD++ additionally ensure online control of the FDR under a “local” form of nonnegative dependence. Further, FDR control is maintained under certain types of adaptive stopping rules, such as stopping after a certain number of rejections have been observed. Because alpha investing can be recovered as a special case of the SAFFRON framework, our results immediately apply to alpha investing as well. In the process of deriving these results, we also formally characterize how the conditional super-uniformity assumption implicitly limits the allowed p-value dependencies. This implicit limitation is important not only to our proposed FDR result, but also to many existing mFDR results.

PMID:38102999 | DOI:10.1002/bimj.202300177

FASEB J. 2024 Jan;38(1):e23375. doi: 10.1096/fj.202201709RRRR.

ABSTRACT

BACKGROUND: Elevated IL-21 expression which can effectively induce Th17 cell differentiation has been implicated in the pathogenesis of psoriasis, but its role in angiogenesis remains poorly understood.

METHODS: PASI and PSI score assessment was applied to evaluate the severity of psoriatic lesions. The expression of IL-21, IL-21 receptor (IL-21R), CD31, VEGFA, MMP-9, and ICAM-1 in skin was determined by immunohistochemistry or quantitative real-time polymerase chain reaction. The serum level of IL-21 was measured by enzyme-linked immunosorbent assay (ELISA). Then, their correlation was analyzed statistically. Human umbilical vein endothelial cells (HUVECs) cocultured with conditional medium from normal human epidermal keratinocytes (NHEKs) were treated with IL-21 and/or M5 cocktail (mixture of IL-1α, IL-17A, IL-22, TNF-α, and oncostatin M). The migration and tube formation of HUVECs were detected, and the levels of VEGFA, MMP-9, and ICAM-1 in NHEKs were measured by Western blotting or ELISA.

RESULTS: Increased IL-21 and IL-21R expression was observed in psoriatic sera or skin specimens, with IL-21R mainly locating in keratinocytes and IL-21 in immune cells. Pearson analysis showed significantly positive correlation between IL-21/IL-21R and erythema scores/microvessel density in psoriatic lesions. Moreover, the expression of proangiogenic genes, VEGFA, ICAM-1, and MMP-9 was upregulated in skins of psoriasis. Additionally, in M5 microenvironment, migration and tube formation could be magnified in HUVECs using IL-21 pre-treated NHEK medium. Mechanically, the co-stimulation of IL-21 and M5 to NEHKs increased the expression of ICAM-1.

CONCLUSION: IL-21 could regulate keratinocytes to secrete ICAM-1, thereby promoting angiogenesis in psoriasis.

PMID:38102968 | DOI:10.1096/fj.202201709RRRR