Tag: pubmed

Eur J Gastroenterol Hepatol. 2022 Jul 28. doi: 10.1097/MEG.0000000000002413. Online ahead of print.

ABSTRACT

INTRODUCTION: Liver transplantation (LT) is the only effective treatment for acute-on-chronic liver failure (ACLF), but it is limited by organ availability. This study aims to identify predictive factors of mortality for LT candidates based on parameters measured at the admission into the ICU.

METHODS: Sixty-four patients diagnosed with ACLF, admitted consecutively into ICU between 2015 and 2019, were retrospectively enrolled in the study. Data were assessed using univariate and multivariate regression analyses to identify risk factors for inhospital mortality and 1-year mortality.

RESULTS: A total of 67% of patients were diagnosed with ACLF grade 3, and 25 and 8% with grades 2 and 1. Thirty percent received LT with a 1-year mortality rate of 16%, whereas for nontransplanted patients it reached 90%. Clinical features were compared according to transplant eligibility. In the univariate analysis model, lung failure (HR, 3.01; 95% CI, 1.48-6.09; P = 0.002), high lactate levels (HR, 1.03; 95% CI, 1.02-1.04; P < 0.001) and CLIF-ACLF score (HR, 1.04; 95% CI, 1.01-1.09; P = 0.026) were independently correlated to increased inhospital mortality. LT reduced mortality risk (HR, 0.16; 95% CI, 0.04-0.72; P = 0.016).

CONCLUSION: Lung failure, CLIF-ACLF score and blood lactate levels at admission were the only statistically significant independent predictors of inhospital mortality, more accurate in determining transplant success than ACLF grade.

PMID:35913770 | DOI:10.1097/MEG.0000000000002413

JAMA Netw Open. 2022 Aug 1;5(8):e2224641. doi: 10.1001/jamanetworkopen.2022.24641.

ABSTRACT

IMPORTANCE: Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence.

OBJECTIVE: To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms.

DESIGN, SETTING, AND PARTICIPANTS: This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021).

MAIN OUTCOMES AND MEASURES: Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates.

RESULTS: Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = -5.45; 95% CI, -8.00 to -2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = -11.10; 95% CI, -13.63 to -8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = -6.14; 95% CI, -9.96 to -2.31; P = .002) and in participants with severe AUD (β = -6.26; 95% CI, -10.18 to -2.34; P = .002).

CONCLUSIONS AND RELEVANCE: This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.

PMID:35913741 | DOI:10.1001/jamanetworkopen.2022.24641

JAMA Neurol. 2022 Aug 1. doi: 10.1001/jamaneurol.2022.2030. Online ahead of print.

ABSTRACT

IMPORTANCE: Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder that leads to iron overload. Conflicting results from previous research has led some to believe the brain is spared the toxic effects of iron in HH.

OBJECTIVE: To test the association of the strongest genetic risk variant for HH on brainwide measures sensitive to iron deposition and the rates of movement disorders in a substantially larger sample than previous studies of its kind.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional retrospective study included participants from the UK Biobank, a population-based sample. Genotype, health record, and neuroimaging data were collected from January 2006 to May 2021. Data analysis was conducted from January 2021 to April 2022. Disorders tested included movement disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10], codes G20-G26), abnormalities of gait and mobility (ICD-10 codes R26), and other disorders of the nervous system (ICD-10 codes G90-G99).

EXPOSURES: Homozygosity for p.C282Y, the largest known genetic risk factor for HH.

MAIN OUTCOMES AND MEASURES: T2-weighted and T2* signal intensity from brain magnetic resonance imaging scans, measures sensitive to iron deposition, and clinical diagnosis of neurological disorders.

RESULTS: The total cohort consisted of 488 288 individuals (264 719 female; ages 49-87 years, largely northern European ancestry), 2889 of whom were p.C282Y homozygotes. The neuroimaging analysis consisted of 836 individuals: 165 p.C282Y homozygotes (99 female) and 671 matched controls (399 female). A total of 206 individuals were excluded from analysis due to withdrawal of consent. Neuroimaging analysis showed that p.C282Y homozygosity was associated with decreased T2-weighted and T2* signal intensity in subcortical motor structures (basal ganglia, thalamus, red nucleus, and cerebellum; Cohen d >1) consistent with substantial iron deposition. Across the whole UK Biobank (2889 p.C282Y homozygotes, 485 399 controls), we found a significantly increased prevalence for movement disorders in male homozygotes (OR, 1.80; 95% CI, 1.28-2.55; P = .001) but not female individuals (OR, 1.09; 95% CI, 0.70-1.73; P = .69). Among the 31 p.C282Y male homozygotes with a movement disorder, only 10 had a concurrent HH diagnosis.

CONCLUSIONS AND RELEVANCE: These findings indicate increased iron deposition in subcortical motor circuits in p.C282Y homozygotes and confirm an increased association with movement disorders in male homozygotes. Early treatment in HH effectively prevents the negative consequences of iron overload in the liver and heart. Our work suggests that screening for p.C282Y homozygosity in high-risk individuals also has the potential to reduce brain iron accumulation and to reduce the risk of movement disorders among male individuals who are homozygous for this mutation.

PMID:35913729 | DOI:10.1001/jamaneurol.2022.2030

Anesth Analg. 2022 Aug 1:ANE.0000000000006162. doi: 10.1213/ANE.0000000000006162. Online ahead of print.

ABSTRACT

BACKGROUND: Lumbar erector spinae plane block (ESPB) has been proposed to relieve pain after total hip replacement (THR), but high-quality evidence is scarce.

METHODS: This double-blinded (patient and assessor) randomized clinical trial, performed in 2 tertiary centers in Hong Kong, recruited patients undergoing primary unilateral THR under general anesthesia (GA) who received either single-shot ESPB at L1 (treatment arm) or no block (control arm). Patients were followed up on the first day postoperatively. We hypothesized that compared to no block, a single-shot lumbar ESPB at L1 would reduce postoperative fentanyl use and postoperative pain scores. Primary outcomes were intravenous fentanyl use at 12 and 24 hours postoperatively, along with pain intensity in numeric rating scale (0-10) at rest and upon movement on the first day postoperatively. Per-protocol analysis was performed. Mann-Whitney U test was used to compare the outcomes between both groups, and median difference was derived from the Hodges-Lehmann estimator.

RESULTS: Seventy-one patients were randomized (n = 36 in treatment arm, n = 35 in control arm). The median amount of fentanyl consumed at 12 hours postoperatively was 210 (quartiles, 140.5-363) μg for the ESPB group and 165 (quartiles, 77.5-330.5) μg for the control group, while at 24 hours postoperatively, it was 409 (quartiles, 221-636.5) μg for the former and 349 (quartiles, 114-626.5) μg for the latter. The median differences in fentanyl consumption 12 and 24 hours postoperatively were 39 μg (95% confidence interval [CI], -40 to 116; P = .463) and 41 μg, respectively (95% CI, -83.5 to 199.5; P = .474), which were statistically insignificant. The median pain score at rest was 3 for both the ESPB group (quartiles, 0-5) and the control group (quartiles, 0-4.5), while upon movement, it was 7 for both the former (quartiles, 6-8) and the latter (quartiles, 4.5-8.5). The median difference in pain scores between both groups was 0 at rest (95% CI, -1 to 1; P = .890) and upon movement (95% CI, -1 to 1; P = .509).

CONCLUSIONS: This trial did not demonstrate that ESPB at L1 improved analgesia following THR.

PMID:35913722 | DOI:10.1213/ANE.0000000000006162

Ophthalmol Ther. 2022 Aug 1. doi: 10.1007/s40123-022-00549-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Ophthalmic surgery is assumed to be safe, but some operations require general anaesthesia which is associated with a number of potential complications. In addition, adverse cardiovascular symptoms, such as severe slowing of the heart rate and, in some cases, cardiac arrest may occur due to the surgical technique. The aim of this study was to determine whether it is possible to predict the occurrence of oculocardiac reflex (OCR) based on heart rate variability (HRV) analysis for autonomic nervous system (ANS) activity assessment measured prior to the induction of anaesthesia and immediately before eyeball traction.

METHODS: Fifty-two adults of both sexes (age range 18-65 years) with American Society of Anesthesiologists (ASA) physical status class 1 and 2 were enrolled in this study. All patients had underwent episcleral buckling under general anaesthesia. High-frequency (HF) changes in HRV are thought to reflect parasympathetic impulse transmission, whereas low-frequency (LF) changes reflect both sympathetic and parasympathetic activity. However, in practice, LF changes can be considered to reflect sympathetic changes. Thus, the LF/HF ratio reflects the actual balance between sympathetic and parasympathetic activity. Based on that, frequency domain HRV parameters from 5-min Holter electrocardiogram recordings before anaesthesia induction and before eyeball traction were used for the analysis. The statistical analysis also included patient age, sex, ASA status and preanaesthesia and premanoeuvre heart rate and blood pressure.

RESULTS: Data from 42 patients were analysed. Oculocardiac reflex was observed in 32 patients (76.2%). No difference was found in the analysed parameters between patients with and without oculocardiac reflex. There was no relationship between the incidence of the OCR and the analysed parameters.

CONCLUSION: The prediction of OCR based on initial ANS tone was not possible, and the initial heart rate, blood pressure, age, sex, and ASA status were not helpful for the identification of patients at risk of this reflex.

TRIAL REGISTRATION: ClinicalTrials.gov identifier no.: NCT01714362.

PMID:35913657 | DOI:10.1007/s40123-022-00549-0

Target Oncol. 2022 Aug 1. doi: 10.1007/s11523-022-00901-1. Online ahead of print.

ABSTRACT

BACKGROUND: Both randomized controlled trials (RCTs) and real-world evidence (RWE) studies provide results regarding the efficacy and toxicity of checkpoint inhibitors in cancer patients. The results from these two sources are considered complementary but whether they are comparable remains unknown.

OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of checkpoint inhibitors between RCTs and RWE studies in patients with advanced non-small cell lung cancer (NSCLC) or melanoma.

PATIENTS AND METHODS: Two electronic databases were searched to identify eligible studies, either RCTs or RWE studies, investigating the efficacy or toxicity of checkpoint inhibitors given for indications that were approved by the European Medicines Agency (EMA) at the date of the last search. A meta-analysis was performed and the pooled estimates of objective response rates (ORR), progression-free survival (PFS), overall survival (OS), and toxicity and treatment discontinuation between RCTs and RWE studies were compared.

RESULTS: In total, 43 RWE studies and 15 RCTs were eligible, with adequate data for pooled estimates for immunotherapy indications regarding NSCLC and melanoma. No statistically significant or clinically meaningful differences in terms of pooled PFS, OS, or rates of treatment discontinuation due to toxicity between RCTs and RWE studies were observed. In some indications, a higher rate of response rates and lower rate of toxicity in favor of RWE was observed.

CONCLUSION: In patients with melanoma or NSCLC, the clinical value of checkpoint inhibitors is evident in both RCTs and real-world settings. Some differences in response or toxicity rates in favor of RWE mainly reflects the inherent difficulties in evaluating these outcomes in RWE studies.

PMID:35913645 | DOI:10.1007/s11523-022-00901-1

Am J Sports Med. 2022 Aug;50(10):2595-2597. doi: 10.1177/03635465221113347.

NO ABSTRACT

PMID:35913617 | DOI:10.1177/03635465221113347

J Math Biol. 2022 Aug 1;85(2):17. doi: 10.1007/s00285-022-01780-w.

ABSTRACT

We considered an SIS functional partial differential model cooperated with spatial heterogeneity and lag effect of media impact. The wellposedness including existence and uniqueness of the solution was proved. We defined the basic reproduction number and investigated the threshold dynamics of the model, and discussed the asymptotic behavior and monotonicity of the basic reproduction number associated with the diffusion rate. The local and global Hopf bifurcation at the endemic steady state was investigated theoretically and numerically. There exists numerical cases showing that the larger the number of basic reproduction number, the smaller the final epidemic size. The meaningful conclusion generalizes the previous conclusion of ordinary differential equation.

PMID:35913603 | DOI:10.1007/s00285-022-01780-w

J Mol Evol. 2022 Aug 1. doi: 10.1007/s00239-022-10065-1. Online ahead of print.

ABSTRACT

When a dispensable gene is duplicated (referred to the ancestral dispensability denoted by O⁺), genetic buffering and duplicate compensation together maintain the duplicate redundancy, whereas duplicate compensation is the only mechanism when an essential gene is duplicated (referred to the ancestral essentiality denoted by O^–). To investigate these evolutionary scenarios of genetic robustness, I formulated a simple mixture model for analyzing duplicate pairs with one of the following states: double dispensable (DD), semi-dispensable (one dispensable one essential, DE), or double essential (EE). This model was applied to the yeast duplicate pairs from a whole-genome duplication (WGD) occurred about 100 million years ago (mya), and the mouse duplicate pairs from a WGD occurred about more than 500 mya. Both case studies revealed that the proportion of essentiality for those duplicates with ancestral essentiality [P_E(O^–)] was much higher than that for those with ancestral dispensability [P_E(O⁺)]. While it was negligible in the yeast duplicate pairs, P_E(O⁺) (about 20%) was shown statistically significant in the mouse duplicate pairs. These findings, together, support the hypothesis that both sub-functionalization and neo-functionalization may play some roles after gene duplication, though the former may be much faster than the later.

PMID:35913597 | DOI:10.1007/s00239-022-10065-1

Mycotoxin Res. 2022 Aug 1. doi: 10.1007/s12550-022-00466-y. Online ahead of print.

ABSTRACT

Alternariol (AOH) is one of the toxins of Alternaria, and it has been widely detected in a variety of foods. It has been reported to be cytotoxic, dermally toxic, genotoxic, and potentially carcinogenic in vitro. However, in vivo toxicity data are lacking. This study used a novel in vivo 28-day multi-endpoint (Pig-a assay + micronucleus test + comet assay) genotoxicity evaluation system to evaluate the general toxicity and genotoxicity of AOH. A total of 42 male Sprague-Dawley rats were randomly distributed into three AOH-treated groups (5.51, 10.03, and 22.05 µg/kg bw), one AOH high-dose recovery group (AOH-HR, 22.05 µg/kg bw), one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw), and two vehicle control groups (corn oil and PBS). Treatments were administered by oral gavage for 28 consecutive days. Histopathological lesions were observed in the liver, kidney, and spleen in all AOH-treated groups. No statistical difference was found in each genotoxicity index within 28 days in the AOH-treated groups compared with those in the corn oil group. On day 42, in the AOH-HR group, the rate of Pig-a mutant phenotype reticulocytes (RET^CD59-) significantly increased. On day 56, both RET^CD59- and the rate of Pig-a mutant phenotype erythrocytes (RBC^CD59-) were significantly reduced. These findings indicated that AOH might cumulatively induce genetic mutations.

PMID:35913592 | DOI:10.1007/s12550-022-00466-y