Tag: nevin manimala

J Hazard Mater. 2021 Aug 18;423(Pt A):126954. doi: 10.1016/j.jhazmat.2021.126954. Online ahead of print.

ABSTRACT

4-Aminobiphenyl (4-ABP) is a human bladder cancer carcinogen found in the manufacture of azo dyes and the composition of cigarette smoke in the environment. To determine whether low concentrations of 4-ABP induced or promote liver carcinogenesis and investigate the underlying mechanism, we have established the liver cell carcinogenesis model in human liver cell lines and zebrafish to evaluate liver cancer development associated with long-term exposure to low concentrations of 4-ABP. Results show that repeated 4-ABP exposure promoted cellular proliferation and migration via the involvement of ROS in Ras/MEK/ERK pathway in vitro. Also, 4-ABP (1, 10, and 100 nM) induces hepatocellular carcinoma (HCC) formation in HBx, Src (p53^-/-) transgenic zebrafish at four months of age and in wild-type zebrafish at seven months of age. In addition, we observed a correlation between the Ras-ERK pathway and 4-ABP-induced HCC in vitro and in vivo. Our finding suggests low concentrations of 4-ABP repeated exposure is a potential risk factor for liver cancer. To our knowledge, this is the first report on the promotion of liver carcinogenesis in human liver cells and zebrafish following 4-ABP exposure.

PMID:34474361 | DOI:10.1016/j.jhazmat.2021.126954

J Electrocardiol. 2021 Aug 30;69:6-14. doi: 10.1016/j.jelectrocard.2021.08.019. Online ahead of print.

ABSTRACT

This paper proposes a two-dimensional (2D) bidirectional long short-term memory generative adversarial network (GAN) to produce synthetic standard 12-lead ECGs corresponding to four types of signals-left ventricular hypertrophy (LVH), left branch bundle block (LBBB), acute myocardial infarction (ACUTMI), and Normal. It uses a fully automatic end-to-end process to generate and verify the synthetic ECGs that does not require any visual inspection. The proposed model is able to produce synthetic standard 12-lead ECG signals with success rates of 98% for LVH, 93% for LBBB, 79% for ACUTMI, and 59% for Normal. Statistical evaluation of the data confirms that the synthetic ECGs are not biased towards or overfitted to the training ECGs, and span a wide range of morphological features. This study demonstrates that it is feasible to use a 2D GAN to produce standard 12-lead ECGs suitable to augment artificially a diverse database of real ECGs, thus providing a possible solution to the demand for extensive ECG datasets.

PMID:34474312 | DOI:10.1016/j.jelectrocard.2021.08.019

Transplant Cell Ther. 2021 Aug 30:S2666-6367(21)01169-6. doi: 10.1016/j.jtct.2021.08.020. Online ahead of print.

ABSTRACT

INTRODUCTION: Each year more than 8,000 allogeneic stem cell transplantations (allo-SCT) are performed in the United States and approximately 30% of these patients are ≥60 years old. Allo-SCT cases have increased risk to develop human papillomavirus (HPV)-related precancer or second malignancy. It is important to evaluate HPV-related precancer or second malignancy among allo-SCT cases to develop or enhance screening and preventive practice guidelines to improve patients’ survival and quality of life.

OBJECTIVE: We estimated the cumulative incidence of HPV-related precancer or second malignancy in both male and female Medicare beneficiaries who received allo-SCT and compared it with non-SCT controls and non-cancer controls.

MATERIALS AND METHODS: This is a retrospective matched case control study. Hematologic cancer patients aged ≥18 years who received allo-SCT between 2002 and 2011 were matched 1:5 to non-SCT controls and to non-cancer controls by age, sex, race/ethnicity, and follow-up time. Proportions of HPV-related precancer or second malignancy were estimated and compared between cases and controls using Chi-square test and logistic regression. Kaplan-Meier cumulative incidences were estimated and compared using log rank tests.

RESULTS: We identified 700 allo-SCT cases (median age of 64 years and median follow-up time post-transplant of 4.3 years) matched with 3159 non-SCT controls and 3302 non-cancer controls. About 3.7% of allo-SCT cases developed HPV-related precancer or second malignancy post-transplant, compared with 1.9% in the non-SCT controls and 1.1% in the non-cancer controls. The odds ratio of developing HPV-related precancer or second malignancy of allo-SCT cases compared with non-SCT controls and non-cancer controls was 2.0 (95% confidence interval [CI]: 1.25-3.18) and 3.5 (95% CI: 2.1-5.8), respectively. Both allo-SCT cases and non-SCT controls had significantly higher proportions and odds in developing HPV-related precancer or second malignancy than non-cancer controls. The 5-year cumulative incidence in allo-SCT cases was 5% compared with 2.1% in non-SCT controls and 1.2% in non-cancer controls. The cumulative incidence of HPV-related precancer or second malignancy in the allo-SCT was statistically significantly higher than either of the two matched control groups, and non-SCT controls had a higher cumulative incidence of HPV-related precancer or second malignancy than that in non-cancer controls.

DISCUSSION: Allo-SCT cases were at increased risk of developing HPV-related precancer or second malignancy compared with non-SCT controls and non-cancer controls. Routine screening of HPV-related precancer or second malignancy in allo-SCT cases is needed to prevent HPV-related precancer or second malignancy.

PMID:34474166 | DOI:10.1016/j.jtct.2021.08.020

J Obstet Gynaecol Can. 2021 Aug 30:S1701-2163(21)00611-3. doi: 10.1016/j.jogc.2021.07.021. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare surgical and oncological outcomes in the treatment of endometrial cancer between laparotomy and minimally invasive surgery. The secondary objective was to determine which MIS approach was the most beneficial.

METHODS: This was a single-centre retrospective review of all endometrial cancer surgeries performed between November 1, 2012 and October 31, 2017 in a gynaecologic oncology unit of a university hospital. Descriptive statistics were used to compare histopathologic results and oncological outcomes, and Kaplan-Meier estimates were used to compare survival.

RESULTS: A total of 735 cases were reviewed. The majority of patients (77%) underwent either laparotomy (35%) or robotic-assisted hysterectomy (42%); the remaining patients underwent total laparoscopic hysterectomy (12%) or a laparoscopic-assisted vaginal hysterectomy (8.7%). There was a statistically significant overall survival benefit (P = 0.02), a shorter hospital stay (P < 0.0001), and fewer early surgical complications (<30 d; P = 0.0002), as well as a survival benefit in elderly patients (>70 y) in the robotic-assisted hysterectomy group (P = 0.043) than the laparotomy group. Operating time was shorter in the laparotomy group (P < 0.0001). Recurrence rates in stage 1 low-risk disease were similar between groups.

CONCLUSION: Minimally invasive surgical approaches, particularly robotic surgery, do not compromise oncologic outcomes, especially for early-stage low-risk disease. In addition, these approaches are associated with fewer early surgical complications and shorter hospital stay, with significantly more same-day discharges. Overall survival and survival in a subgroup of elderly patients were significantly better in the robotic-assisted hysterectomy group.

PMID:34474173 | DOI:10.1016/j.jogc.2021.07.021

Sex Med. 2021 Aug 30;9(5):100424. doi: 10.1016/j.esxm.2021.100424. Online ahead of print.

ABSTRACT

INTRODUCTION: The consequences of stroke on sexual life in stroke patients in need of specialized cognitive rehabilitation have been limited explored. A biopsychosocial perspective in post-stroke sexuality studies is warranted to capture the complex picture of stroke consequences and sexual life after stroke and sexual satisfaction is an important outcome measure when exploring such multifactorial associations.

AIM: To explore sexual satisfaction and associated biopsychosocial factors in stroke patients admitted to specialized cognitive rehabilitation.

METHODS: A cross-sectional study was performed including 91 consecutive stroke patients admitted to specialized cognitive rehabilitation. Data were collected from medical records and by face-to-face interviews using a structured interview guide and questionnaires. Descriptive and inferential statistics were applied.

MAIN OUTCOME MEASURES: A wide range of biopsychosocial variables including medical and sociodemographic characteristics, social support, sexual complaints, aspects of sexual life, psychological distress and life satisfaction were analyzed in relation to the main outcome “Satisfaction with sexual life.”

RESULTS: Only 33 % were satisfied with sexual life. Prevalence of sexual complaints was high, more frequent in women (84%) than in men (64%). Three-quarters were less sexually active than before stroke. Multivariable analyses showed that anxiety, sleep problems, manifested sexual complaint, decrease in sexual activity and fear of partner rejection were significantly associated with low odds of sexual satisfaction, while affectionate support and partnership satisfaction were significant for sexual satisfaction. When combined in a biopsychosocial multivariable model only fear of partner rejection (OR 0.07; 95 % CI: 0.01-0.42) and decrease in sexual activity (OR 0.11; 95 % CI: 0.02-0.58) showed significant contribution to sexual satisfaction.

CONCLUSION: The variety of predictors for sexual satisfaction indicates that therapeutic actions need to be individualized and points towards a broad assessment and interventional approach to meet the sexual rehabilitation needs of stroke patients with cognitive impairments in need of specialized rehabilitation. Vikan JK, Snekkevik H, Nilsson MI, et al. Sexual Satisfaction and Associated Biopsychosocial Factors in Stroke Patients Admitted to Specialized Cognitive Rehabilitation. Sex Med 2021;XX:XXXXXX.

PMID:34474266 | DOI:10.1016/j.esxm.2021.100424

Transplant Cell Ther. 2021 Aug 30:S2666-6367(21)01170-2. doi: 10.1016/j.jtct.2021.08.021. Online ahead of print.

ABSTRACT

BACKGROUND: Acute graft-versus-host disease (GVHD) is a major cause of mortality in patients receiving hematopoietic cell transplantation (HCT) for hematologic malignancies. The skin is the most commonly involved organ in GVHD. Elafin, a protease inhibitor overexpressed in inflamed epidermis, was previously identified as a diagnostic biomarker of skin GVHD. However, this finding was restricted to a subset of patients with isolated skin GVHD. The main driver of nonrelapse mortality (NRM) in HCT patients is GI GVHD. Two biomarkers, Regenerating islet-derived 3a (REG3a) and Suppressor of tumorigenesis 2 (ST2), have been validated as biomarkers of GI GVHD that predict long-term outcomes in patients treated for GVHD. We undertook this study to determine the utility of elafin as a prognostic biomarker in the general population of acute GVHD patients in whom GVHD may develop in multiple organs.

OBJECTIVE: To analyze serum elafin concentrations as a predictive biomarker of acute GVHD outcomes and to compare it to ST2 and REG3a in a large group of patients treated at multiple centers.

STUDY DESIGN: 526 patients who received corticosteroid treatment for skin GVHD and who had not been previously studied were analyzed from the Mount Sinai Acute GVHD International Consortium (MAGIC). Serum concentrations of elafin, ST2 and REG3a were measured for all patients using ELISA. Patients were divided randomly into equal training and validation sets and a competing risk regression model was developed to model 6-month NRM using elafin concentration in the training set. Additional models were developed using concentrations of ST2 and REG3a, or the combination of all three biomarkers as predictors. ROC curves were constructed using the validation set to evaluate the predictive accuracy of each model and to stratify patients into high- and low-risk biomarker groups. The cumulative incidence of 6-month NRM, overall survival, and four-week treatment response were compared between risk groups.

RESULTS: Patients in the low-risk elafin group unexpectedly demonstrated a higher incidence of 6-month NRM, although this difference was not statistically significant (17% vs. 11%, P=0.19). Overall survival at 6 months (68% vs. 68%, P>0.99) and four-week response (78% vs. 78%, P=0.98) were similar in the low- and high-risk elafin groups. The area under the receiver operating curve (AUROC) for elafin was 0.55 whereas it was 0.75 for the combination of ST2 and REG3a. The addition of elafin to the other two biomarkers did not improve the AUROC.

CONCLUSION: Serum elafin concentrations measured at the initiation of systemic treatment for acute GVHD do not predict 6-month NRM, overall survival, or treatment response in a multicenter population of patients treated systemically for acute GVHD. As seen in previous studies, serum concentrations of the GI GVHD biomarkers ST2 and REG3a were significant predictors of NRM and the addition of elafin levels did not improve their accuracy. These results underscore the importance of GI disease in driving NRM in patients who develop acute GVHD.

PMID:34474163 | DOI:10.1016/j.jtct.2021.08.021

Ann Vasc Surg. 2021 Aug 30:S0890-5096(21)00560-4. doi: 10.1016/j.avsg.2021.06.018. Online ahead of print.

ABSTRACT

BACKGROUND: The UK has one of the highest rates of recreational drug use and consequent deaths in Europe. Scotland is the “Drugs death capital of Europe.” Intravenous drug use can result in limb- and life-threatening pathology. This study aimed to characterise limb-related admissions associated with intravenous drug use, outcomes and healthcare expenditure.

METHODS: Retrospective data collection between December 2011-August 2018. Patients were identified through discharge codes. Admission details were extracted from electronic records and a database compiled. Statistical analyses were performed using Statistical Package for the Social Science, p<0.05 denoted significance.

RESULTS: There were 558 admissions for 330 patients (1-9 admissions/patient), mean age 37 years (+/-7.6 SD) and 196 (59.2%; 319 admissions, 57.2%) were male. 348 (62.4%) admissions were to surgical specialties, predominantly Vascular Surgery (247). Including onward referrals, Vascular ultimately managed 54.8% of admissions. Patients presented with multiple pathologies: 249 groin abscesses; 38 other abscesses; 74 pseudoaneurysms; 102 necrotising soft tissue infections (NSTI); 85 cellulitis; 138 DVTs; 28 infected DVTs and 70 other diagnoses. 277 admissions (220 patients) required operations, with 361 procedures performed (1-7 operations/admission). There were 24 major limb amputations and 74 arterial ligations. 11 amputations were due to NSTI and 13 followed ligation (17.6% of ligations). During follow-up 50 (15.2%) patients died, of which six (12%) had amputations (OR 3.2, 95% CI 1.04-9.61, p=0.043). Cumulative cost of acute care was £4,783,241.

CONCLUSION: Limb-related sequalae of intravenous drug use represents a substantial surgical workload, especially for Vascular. These are complex, high-risk patients with poor outcomes and high healthcare costs.

PMID:34474130 | DOI:10.1016/j.avsg.2021.06.018

J Shoulder Elbow Surg. 2021 Aug 30:S1058-2746(21)00643-1. doi: 10.1016/j.jse.2021.07.027. Online ahead of print.

ABSTRACT

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has proven to be a highly effective treatment for rotator cuff deficient conditions and other end-stage shoulder pathologies. With value-based care emerging, identifying predictive factors of outcomes are of great interest. Although preoperative opioid use has been shown to predict inferior outcomes after anatomic total shoulder arthroplasty and rotator cuff repair, there is a paucity of data regarding its effect on outcomes after RTSA. We analyzed a series of RTSAs to determine the influence of preoperative opioid use on clinical and radiographic outcomes at a minimum of 2 years follow-up.

METHODS: A retrospective review of primary RTSA patient data revealed 264 patients with at least 2 years of clinical and radiographic follow-up. Patients were classified as preoperative opioid users (71 patients) if they had taken narcotic pain medication for a minimum of 3 months prior to surgery or opioid-naive (193 patients) at the time of surgery. Assessments included preoperative and postoperative visual analog pain scores (VAS), American Shoulder and Elbow Surgeons (ASES) scores, strength, range of motion (ROM), complications, and revisions. Radiographs were analyzed for signs of loosening or mechanical failure. Mann-Whitney U and Fisher exact tests were used for comparisons between groups. Statistical significance was set at p < 0.05.

RESULTS: The mean patient age was 69.9 years, and the mean follow-up time was 2.8 years. Opioid users were significantly younger (66.1 vs. 70.7 years, p < 0.001) at time of surgery and had significantly higher preoperative rates of mood disorders, chronic pain disorders, and disability status (all p < 0.05). Postoperatively, opioid users had inferior VAS (2.59 vs 1.25, p < 0.001), ASES scores (63.2 vs 75.2, p < 0.001), active forward elevation (p < 0.001), and internal and external rotational shoulder strength (all p < 0.05) than opioid-naïve patients. Periprosthetic radiolucency (8.45% vs 2.07%, p = 0.026) and subsequent revision arthroplasty (14.1% vs 4.66%, p = 0.014) occurred more frequently in opioid users than opioid-naïve patients. Both groups improved from baseline preoperatively to most recent follow-up in terms of functional outcomes and pain.

CONCLUSION: Preoperative opioid use portended markedly inferior clinical outcomes in patients undergoing RTSA. Additionally, opioid users had significantly increased rates of periprosthetic radiolucency and revisions. Preoperative opioid use appears to be a significant marker for adverse outcomes after RTSA.

PMID:34474138 | DOI:10.1016/j.jse.2021.07.027

Pharmacol Res. 2021 Aug 30:105863. doi: 10.1016/j.phrs.2021.105863. Online ahead of print.

NO ABSTRACT

PMID:34474101 | DOI:10.1016/j.phrs.2021.105863

Int J Biostat. 2021 Sep 2. doi: 10.1515/ijb-2020-0046. Online ahead of print.

ABSTRACT

Interrupted time series (ITS) design is commonly used to evaluate the impact of interventions in healthcare settings. Segmented regression (SR) is the most commonly used statistical method and has been shown to be useful in practical applications involving ITS designs. Nevertheless, SR is prone to aggregation bias, which leads to imprecision and loss of power to detect clinically meaningful differences. The objective of this article is to present a weighted SR method, where variability across patients within the healthcare facility and across time points is incorporated through weights. We present the methodological framework, provide optimal weights associated with data at each time point and discuss relevant statistical inference. We conduct extensive simulations to evaluate performance of our method and provide comparative analysis with the traditional SR using established performance criteria such as bias, mean square error and statistical power. Illustrations using real data is also provided. In most simulation scenarios considered, the weighted SR method produced estimators that are uniformly more precise and relatively less biased compared to the traditional SR. The weighted approach also associated with higher statistical power in the scenarios considered. The performance difference is much larger for data with high variability across patients within healthcare facilities. The weighted method proposed here allows us to account for the heterogeneity in the patient population, leading to increased accuracy and power across all scenarios. We recommend researchers to carefully design their studies and determine their sample size by incorporating heterogeneity in the patient population.

PMID:34473922 | DOI:10.1515/ijb-2020-0046