Tag: nevin manimala

Oncol Res Treat. 2022 Feb 16. doi: 10.1159/000522645. Online ahead of print.

ABSTRACT

Introduction The most common intracranial neoplasm diagnosed in adults are brain metastases (BrM). The benefit in terms of clinical control and toxicity for stereotactic radiotherapy (SRT)has been investigated for patients with low load of brain metastases. Aim of this single-institution experience was to investigate the best dose schedule for five-fraction stereotactic radiotherapy (FFSRT). Methods A retrospective analysis of patients treated for BrM with different dose schedules of FFSRT was performed. Local Control and clinical outcomes were evaluated with Magnetic resonance imaging (MRI) at 3, 6 and 9 months. Toxicity data were also collected. Results A total of 41 patients treated from November 2016 to September 2020 were enrolled in the analysis. Non Small Cell Lung cancer (51,2%) and breast cancer (24,3%) represented the most frequent primitive tumors. Treatment was performed on 5 consecutive days with prescribed dose ranging from 30 to 40 Gy, prescribed to the 95% isodose line that covered at least 98% of the GTV. Statistically significant differences (p=0.025) with higher LC control rates for dose schedules > 6Gy for fractions. Toxicity rates were not found to be higher than G1. Conclusion The results of this retrospective analysis suggest that FFSRT for BrM seems to be safe and feasible. Our results also underline that a total dose lower than 30 Gy in 5 fractions should not be used due to the expected minor LC.

PMID:35172322 | DOI:10.1159/000522645

Stat Med. 2022 Feb 16. doi: 10.1002/sim.9340. Online ahead of print.

ABSTRACT

Hepatitis B has been a well-documented risk factor of liver cancer and mortality. To what extent hepatitis B affects mortality through increasing liver cancer incidence is of research interest and remains to be studied. We formulate the research question as a hypothesis testing problem of causal mediation where both the mediator and the outcome are time-to-event variables. The problem is closely related to semicompeting risks because time to the intermediate event may be censored by an occurrence of the outcome. We propose two hypothesis testing methods: a weighted log-rank test (WLR) and an intersection-union test (IUT). A test statistic of the WLR is constructed by adapting a nonparametric estimator of the mediation effect; however, the test may be conservative regarding its Type I Error rate. To address this, we further propose the IUT, the test statistic of which is constructed under the composite null hypothesis. Asymptotic properties of the two tests are studied, showing that the IUT is a size α test with better statistical power than the WLR. The theoretical properties are supported by extensive simulation studies under finite samples. Applying the proposed methods to the motivating hepatitis study, both WLR and IUT provided strong evidence that hepatitis B had a significant mediation effect on mortality via liver cancer incidence.

PMID:35172384 | DOI:10.1002/sim.9340

Urol Int. 2022 Feb 16:1-5. doi: 10.1159/000522079. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVES: We report our experience with pediatric shock wave lithotripsy (SWL) using two types of lithotripters: Dornier HM3 (HM3) and Dornier Lithotripter SII (DLS).

STUDY DESIGN: We retrospectively reviewed the charts of children who underwent SWL between 2002 and 2016. Patients were divided into two groups based on the type of the lithotripter: during 2002-2009, we used the electrohydraulic HM3 lithotripter which was replaced in 2009 with the DLS electromagnetic lithotripter. Clinical and perioperative parameters were compared.

RESULTS: Our cohort included 107 children who underwent SWL. Average age was 11.5 ± 5.1 years. Average stone size was 10.6 ± 4.9 mm. HM3 was used in 38% of children and DLS2 in 62% (n = 41 and 66, respectively). There were no significant differences in age, gender, stone size, or location between the groups. The total SFR did not differ statistically between HM3 and DLS (83% vs. 74%, p = 0.35). SFR after one SWL was higher with the HM3 (78% vs. 62%, p = 0.093). Re-treatment rate was 22% and 17% (HM3 vs. DLS, p = 0.61). Complication rates were low, with renal colic being the most common (HM3 10%, DLS 20%, NS).

CONCLUSIONS: SWL in the pediatric population using the DLS showed good results with low complication rates that are equivalent to the gold standard HM3.

PMID:35172318 | DOI:10.1159/000522079

Neuroendocrinology. 2022 Feb 16. doi: 10.1159/000522643. Online ahead of print.

ABSTRACT

BACKGROUND: Family with sequence similarity 83, member A (FAM83A) has been reported to play an important role in cancer progression and metastasis. The purpose of this study was to clarify the role and mechanism of FAM83A in pancreatic neuroendocrine tumors (PanNETs).

METHODS: PanNET specimens and adjacent nontumor pancreatic tissues obtained from 68 patients who underwent curative surgery for PanNETs were assessed using immunochemical staining to identify FAM83A expression. The relationships between FAM83A expression, clinicopathological parameters and prognosis were statistically analyzed. PanNET cell lines were used to study the role of FAM83A in the progression and metastasis of PanNETs in vitro and in vivo.

RESULTS: FAM83A was overexpressed in PanNET specimens compared with adjacent nontumor tissues. Furthermore, FAM83A expression was closely associated with lymph node metastasis (P = 0.02), perineural invasion (P = 0.001), the WHO classification (P = 0.039), AJCC stage (P = 0.01) and shorter disease-free survival in patients with PanNETs (P < 0.001). Enforced expression of FAM83A effectively promoted PanNET cell proliferation, migration, invasion and growth both in vitro and in vivo, whereas FAM83A inhibition exerted the opposite effects. Subsequent mechanistic investigations revealed that FAM83A promoted the progression and metastasis of PanNETs by inducing epithelial-mesenchymal transition (EMT) via the PI3K/AKT and ERK pathways. More importantly, specific inhibition of either the AKT or ERK pathways partially rescued the effect of FAM83A overexpression on promoting PanNET progression and metastasis.

CONCLUSIONS: FAM83A plays an important role in the progression and metastasis of PanNET by inducing the EMT via the activation of the ERK and PI3K/AKT pathways and may serve as a valuable molecular target in PanNET treatment.

PMID:35172316 | DOI:10.1159/000522643

Neuroepidemiology. 2022 Feb 16. doi: 10.1159/000522611. Online ahead of print.

ABSTRACT

OBJECTIVE: Glioblastomas(GBM) are the most common primary CNS tumors. Epidemiologic studies have investigated the effect of demographics on patient survival, but the literature remains inconclusive.

METHODS: This study included all adult patients with intracranial GBMs reported in the SEER-9 population database (1975-2018). The sample consisted of 32746 unique entries. We forecast the annual GBM incidence in the US population through the year of 2060 using time series analysis with autoregressive moving averages. A survival analysis of the GBM-specific time to death was also performed. Multivariate Cox Proportional Hazards(PH) regression revealed frank violations of the PH assumption for multiple covariates. Parametric models best described the GBM population’s survival pattern; the results were compared to the semi-parametric analysis and the published literature.

RESULTS: We predicted an increasing GBM incidence, which demonstrated that by the year 2060, over 1800 cases will be reported annually in the SEER. All eight demographic variables were significant in the univariable analysis. The calendar year 2005 was the cutoff associated with an increased survival probability. A male survival benefit was eliminated in the year-adjusted Cox. The factors: infratentorial tumors, non-metropolitan areas, and White patient race were erroneously associated with survival in the multivariate Cox analysis. AFT lognormal regression was the best model to describe the survival pattern in our patient population, identifying age > 30 years old as a poor prognostic and patients > 70 years old as having the worst survival. Annual income > $75,000 and supratentorial tumors were good prognostics, while surgical intervention provided the strongest survival benefit.

CONCLUSIONS: Annual GBM incidence rates will continue to increase by almost 50% in the upcoming 30 years. Cox regression analysis should not be utilized for time-to-event predictions in GBM survival statistics. AFT lognormal distribution best describes the GBM specific survival pattern, and as an inherent population characteristic, it should be implemented by researchers for future studies. Surgical intervention provides the strongest survival benefit, while patient age > 70 years old is the worst prognostic. Based on our study, the demographics: gender, race, and county type should not be considered as meaningful prognostics when designing future trials.

PMID:35172317 | DOI:10.1159/000522611

Eur Addict Res. 2022 Feb 16:1-5. doi: 10.1159/000521614. Online ahead of print.

ABSTRACT

BACKGROUND: Fatal opioid overdose is a significant public health problem with increasing incidence in developed countries. This study aimed to describe demographic and service user characteristics of decedents of opioid overdose in Wales to identify possible targets for behaviour modification and life-saving interventions.

METHODS: A retrospective cross-sectional analysis was conducted of a census sample of opioid overdose-related deaths recorded between January 01, 2012, and October 11, 2018, in Wales. UK Office for National Statistics, Welsh Demographic Service, and National Health Service datasets were linked deterministically. Decedents’ circumstances of death, demographic characteristics, residency, and health service use were characterized over 3 years prior to fatal overdose using descriptive statistics.

RESULTS: In total, 638 people died of opioid overdose in Wales between January 01, 2012, and October 11, 2018, with an incidence rate of 3.04 per 100,000 people per year. Decedents were predominantly male (73%) and middle aged (median age 50 years). Fatal overdoses predominantly occurred in the community (93%) secondary to heroin (30%) or oxycodone derivative use (34%). In the 3 years prior to death, decedents changed address frequently (53%) but rarely moved far geographically. The majority of decedents had recently visited the emergency department (83%) or were admitted to the hospital (64%) prior to death. Only a minority had visited specialist drug services (32%).

CONCLUSIONS: Deaths from opioid overdose typically occur in middle-aged men living peripatetic lifestyles. Victims infrequently visit specialist drug services but often attend emergency medical services. Emergency department-based interventions may therefore be important in prevention of opioid overdose fatalities in the community.

PMID:35172309 | DOI:10.1159/000521614

Nanotechnology. 2022 Feb 16. doi: 10.1088/1361-6528/ac55d2. Online ahead of print.

ABSTRACT

Chemical vapor deposition (CVD)-grown monolayer (ML) molybdenum disulfide (MoS2) is a promising material for next-generation integrated electronic systems due to its capability of high-throughput synthesis and compatibility with wafer-scale fabrication. Several studies have described the importance of Schottky barriers in analyzing the transport properties and electrical characteristics of MoS2 field-effect-transistors (FETs) with metal contacts. However, the analysis is typically limited to single devices constructed from exfoliated flakes and should be verified for large-area fabrication methods. In this paper, CVD-grown ML MoS2 was utilized to fabricate large-area (1 cm x 1 cm) FET arrays. Two different types of metal contacts (i.e., Cr/Au and Ti/Au) were used to analyze the temperature-dependent electrical characteristics of ML MoS2 FETs and their corresponding Schottky barrier characteristics. Statistical analysis provides new insight about the properties of metal contacts on CVD-grown MoS2 compared to exfoliated samples. Reduced Schottky barrier heights (SBH) are obtained compared to exfoliated flakes, attributed to a defect-induced enhancement in metallization of CVD-grown samples. Moreover, the dependence of SBH on metal work function indicates a reduction in Fermi level pinning (FLP) compared to exfoliated flakes, moving towards the Schottky-Mott limit. Optical characterization reveals higher defect concentrations in CVD-grown samples supporting a defect-induced metallization enhancement effect consistent with the electrical SBH experiments.

PMID:35172287 | DOI:10.1088/1361-6528/ac55d2

Med Princ Pract. 2022 Feb 16. doi: 10.1159/000522626. Online ahead of print.

ABSTRACT

OBJECTIVE: While SARS-CoV-2 primarily affects lung tissue, it may cause direct or indirect damage to the cardiovascular system and permanent damage may occur. Arterial stiffness is an early indicator of cardiovascular disease risk. The aim of our study was to establish the potential effects of SARS-CoV-2 on the vascular system evaluated by transthoracic echocardiographic (TTE) examination.

SUBJECTS AND METHODS: This study compared arterial stiffness between the survivors of COVID-19 and those without a history of COVID-19 infection. The difference in aortic diameter was examined using echocardiography.

RESULTS: The study included 50 patients who survived COVID-19 in the last 3 to 6 months and 50 age- and gender-matched healthy volunteers. In surviving COVID-19 patients, aortic diastolic diameter in cm ([3.1±0.2] vs. [2.9±0.1], p < 0.001), pulse pressure ([43.02±14.05] vs [35.74±9.86], p = 0.004), aortic distensibility ([5.61±3.57] vs [8.31±3.82], p < 0.001), aortic strain ([10.56±4.91] vs [13.88±5.86], p = 0.003), pulse pressure/stroke volume index ([1.25±0.47] vs [0.98±0.28], p = 0.001) and aortic stiffness index ([2.82±0.47] vs [2.46±0.45], p < 0.001) were statistically significant compared to the control group.

CONCLUSION: SARS-CoV-2 may cause reduced or impaired aortic elasticity parameters linked to impaired arterial wall function in COVID-19 survivors compared with controls.

PMID:35172305 | DOI:10.1159/000522626

Eur J Cancer. 2022 Feb 13;164:39-51. doi: 10.1016/j.ejca.2021.12.030. Online ahead of print.

ABSTRACT

BACKGROUND: Biomarkers for cyclin-dependent kinase 4/6 inhibitors, such as palbociclib, for patients with hormone receptor-positive/HER2-negative metastatic breast cancer are lacking. Thymidine kinase is a proliferation marker downstream of the cyclin-dependent kinase 4/6 pathway. We prospectively investigated the prognostic role of serum thymidine kinase activity (sTKa), in patients treated with Palbociclib + fulvestrant.

PATIENTS AND METHODS: PYTHIA was a phase II, single-arm, multicentre, trial that enrolled 124 post-menopausal women with endocrine-resistant hormone receptor-positive/HER2-negative metastatic breast cancer. Serum samples were collected pre-treatment (pre-trt; n = 122), at day 15 of cycle 1 (D15; n = 108), during the one week-off palbociclib before initiating cycle 2 (D28; n = 108) and at end of treatment (n = 76). sTKa was determined centrally using Divitum®, a refined ELISA-based assay with a limit of detection of 20 Divitum Units (Du)/L. The primary study endpoint was progression-free survival, assessed for its association with pre- and on-treatment sTKa.

RESULTS: Data from 122 women were analysed. Pre-treatment sTKa was not associated with clinical characteristics and moderately correlated with tissue Ki-67. Palbociclib + fulvestrant markedly suppressed sTKa levels at D15, with 83% of patients recording levels below limit of detection. At D28, sTKa showed a rebound in 60% of patients. At each timepoint, higher sTKa was associated with shorter progression-free survival (each p < 0.001), with the strongest effect at D15.

CONCLUSIONS: STKa is an independent prognostic biomarker in patients treated with palbociclib. High pre-treatment sTKa and its incomplete suppression during treatment may identify patients with poorer prognosis and primary resistance. This warrants validation in prospective comparative trials. CLINICALTRIALS.

GOV IDENTIFIER: NCT02536742; EudraCT 2014-005387-15.

PMID:35172272 | DOI:10.1016/j.ejca.2021.12.030

Infect Dis Now. 2022 Feb 13:S2666-9919(22)00030-6. doi: 10.1016/j.idnow.2022.01.007. Online ahead of print.

ABSTRACT

OBJECTIVES: While the World Health Organization has recommended preoperative washing with plain or antimicrobial soap for surgical site infection (SSI) prevention, it has not formulated recommendations on use of chlorhexidine gluconate (CHG)-impregnated cloths. The purpose of this systematic review was to evaluate the benefit of preoperative bathing with CHG-cloths on SSI incidence.

PATIENTS AND METHODS: Publications were searched on Medline, CENTRAL, Web of Science, Clinical Trial between 01/01/1990 and 30/06/2018. Randomized controlled trials (RCT), quasi-randomized, case-control and cohort studies on patients with surgery (Population) having preoperative bathing with CHG-cloths (Intervention) or antiseptic soap, plain soap, placebo, no washing, no instruction (Comparator) were included. The main outcome was SSI occurrence. The results were synthetized using the Odds-Ratio (OR) and 95% confidence interval [95%CI]. Study quality was assessed using the Cochrane and Newcastle-Ottawa tools and evidence quality with the GRADE method. Statistics were calculated on RevMan5.3.

RESULTS: All in all, 1108 publications were identified and 3 were included in the meta-analysis. OR of the 2 cohort studies was 0.25 [95%CI: 0.13-0.50] for use of CHG-cloths the evening and the morning before intervention versus non-compliance with preoperative washing. OR of the RCT was 0.12 [95%CI: 0.02-1.00] for use of CHG-cloths the evening and the morning before intervention versus a shower with antibacterial soap the evening before the intervention. Study quality was moderate.

CONCLUSIONS: While the available studies show a benefit for CHG-cloths on SSI occurrence in orthopaedic surgery, there is no comparison with usual practices. Further studies are needed to confirm the benefit of CHG-cloths for preoperative washing.

PMID:35172215 | DOI:10.1016/j.idnow.2022.01.007