Category: Nevin Manimala

Exp Clin Transplant. 2022 Jan 3. doi: 10.6002/ect.2021.0360. Online ahead of print.

ABSTRACT

OBJECTIVES: In this study, we investigated dynamic thiol-disulfide homeostasis as a new indicator of oxidative stress in lung transplant recipients. In addition, we compared dynamic thiol-disulfide homeostasis parameters according to transplant indication and time after transplant.

MATERIALS AND METHODS: This study had a single-center, observational, randomized design. In terms of transplant indications, lung transplant recipients were grouped as chronic obstructive pulmonary disease, interstitial lung disease, bronchiectasis, and other indications. To make comparisons based on time after transplant, lung transplant recipients were categorized into the following groups: >6 and ≤24 months, >24 and ≤48 months, >48 and ≤72 months, and >72 months. A fully automated spectrophotometric technique was used to measure dynamic thiol-disulfide homeostasis in fasting blood samples.

RESULTS: Our study included 34 lung transplant recipients and 36 healthy volunteers. Native thiol (P = .005) and total thiol levels (P = .06) were lower in lung transplant recipients. Disulfide levels were similar. Disulfide-to-native thiol (P = .027) and disulfide-to-total thiol ratios (P = .027) were significantly higher in lung transplant recipients. Native thiol-to-total thiol ratios were lower in lung transplant recipients (P = .027). When we examined patients according to transplant indication, no statistically significant differences were found in dynamic thiol-disulfide homeostasis parameters, except for total thiol and disulfide levels. We also found no significant differences when we examined dynamic thiol-disulfide homeostasis parameters according to time after transplant.

CONCLUSIONS: Thiol-related antioxidant activity is significantly reduced after lung transplant, regardless of indication and transplant time. Ensuring oxidative balance in lung transplant recipients with an antioxidant supplement regimen can prevent damage from oxidative stress.

PMID:34981712 | DOI:10.6002/ect.2021.0360

Int J Biostat. 2022 Jan 4. doi: 10.1515/ijb-2020-0073. Online ahead of print.

ABSTRACT

Effect modification occurs when the effect of a treatment on an outcome differsaccording to the level of some pre-treatment variable (the effect modifier). Assessing an effect modifier is not a straight-forward task even for a subject matter expert. In this paper, we propose a two-stageprocedure to automatically selecteffect modifying variables in a Marginal Structural Model (MSM) with a single time point exposure based on the two nuisance quantities (the conditionaloutcome expectation and propensity score). We highlight the performance of our proposal in a simulation study. Finally, to illustrate tractability of our proposed methods, we apply them to analyze a set of pregnancy data. We estimate the conditional expected difference in the counterfactual birth weight if all women were exposed to inhaled corticosteroids during pregnancy versus the counterfactual birthweight if all women were not, using data from asthma medications during pregnancy.

PMID:34981702 | DOI:10.1515/ijb-2020-0073

J Korean Med Sci. 2022 Jan 3;37(1):e1. doi: 10.3346/jkms.2022.37.e1.

ABSTRACT

BACKGROUND: The aim of this study was to estimate the 8-year prevalence and mortality statistics of autism spectrum disorder (ASD) according to birth year (2002-2012).

METHODS: We used the National Health Insurance Service database with 4,989,351 children born from 2002 to 2012 including 35,529 children diagnosed with ASD until 8 years of age. The 8-year cumulative prevalence of ASD was calculated annually (2010-2020) with 8 years of follow-up. The 8-year mortality was estimated using Cox models adjusted for sex, household income, area of residence, and year of birth.

RESULTS: Of the 473,494 children born in 2002, 2,467 (5.2 per 1,000 births) were diagnosed with ASD until 2010. The ASD prevalence was 2.6 times higher among boys (1,839; 7.4 per 1,000 boy births) than girls (628; 2.8 per 1,000 girl births). Of the 467,360 children born in 2012, 4,378 (9.4 per 1,000 births) were diagnosed with ASD until 2020. The ASD prevalence was 2.7 times higher among boys (3,246; 13.5 per 1,000 boy births) than girls (1,132; 5.0 per 1,000 girl births). The risk of all-cause mortality was higher among children with ASD than those without (hazard ratio [HR], 2.340; 95% confidence interval [CI], 2.063-2.654), which is substantially higher among girls (HR, 4.223; 95% CI, 3.472-5.135) than boys (HR, 1.774; 95% CI, 1.505-2.090).

CONCLUSION: The present study demonstrated that national-level prevalence and mortality statistics of ASD can be estimated effectively using claims data comprising newborns born each year and followed up for to the age of interest. Because this information is essential to establish evidence-based policies, health authorities need to consider producing epidemiological information of ASD continuously using the same methodology.

PMID:34981677 | DOI:10.3346/jkms.2022.37.e1

Mol Genet Genomic Med. 2022 Jan 3:e1864. doi: 10.1002/mgg3.1864. Online ahead of print.

ABSTRACT

BACKGROUND: In addition to patient-related systemic factors directing the immune response, the pathomechanisms of appendicitis (AP) might also include insufficient drainage leading to inflammation caused by decreased peristalsis. Genetic predisposition accounts for 30%-50% of AP. M. Hirschsprung (HSCR), also characterized by disturbed peristalsis, is associated with variants in the RET proto-oncogene. We thus hypothesized that RET variants contribute to the etiology of AP.

METHODS: DNA from paraffin-embedded appendices and clinical data of 264 children were analyzed for the RET c.135A>G variant (rs1800858, NC_000010.11:g.43100520A>G). In 46 patients with gangrenous or perforated AP (GAP), peripheral blood DNA was used for RET sequencing.

RESULTS: Germline mutations were found in 13% of GAP, whereas no RET mutations were found in controls besides the benign variant p.Tyr791Phe (NC_000010.11:g.43118460A>T). In GAP, the polymorphic G-allele in rs2435352 (NC_000010.11:g.43105241A>G) in intron 4 was underrepresented (p = 0.0317).

CONCLUSION: Our results suggest an impact of the RET proto-oncogene in the etiology of AP. Mutations were similar to patients with HSCR but no clinical features of HSCR were observed. The pathological phenotypes in both populations might thus represent a multigenic etiology including RET germline mutations with phenotypic heterogeneity and incomplete penetrance.

PMID:34981673 | DOI:10.1002/mgg3.1864

Clin Pharmacol Drug Dev. 2022 Jan 3. doi: 10.1002/cpdd.1064. Online ahead of print.

ABSTRACT

This study aimed to evaluate the bioequivalence of 2 amlodipine besylate tablet formulations, a generic formulation and an original formulation, and to investigate their pharmacokinetic and safety profiles. This study was designed as a randomized, open-label, single-dose, crossover, dual-period study and was divided into fasting and postprandial human bioequivalence trials. In the first trial after overnight fasting, 28 subjects were given 5-mg amlodipine besylate tablets via oral administration, and blood specimens were obtained up to 144 hours after dosing; another 28 subjects had a high-fat meal 1 hour before drug administration and proceeded the same as the fasting trial. Bioequivalence was evaluated using 90%CIs for the ratio test/reference of log area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration, log AUC from time 0 to infinity, and log peak concentration. The plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. The safety was assessed throughout the study. The results show that no significant differences were observed between the pharmacokinetic profiles of the test and reference amlodipine besylate tablets in the fasting and postprandial trials. The 90%CIs of the peak concentration, AUC from time 0 to the last quantifiable concentration and AUC from time 0 to infinity of amlodipine in the 2 trials were within the commonly accepted bioequivalence criteria of 80% to 125%. Compared with the pharmacokinetic parameters of the fasting and postprandial trials, food had no significant effect on exposure of amlodipine besylate. There was no significant difference in safety statistical results between the 2 groups. The results suggest that generic and original amlodipine besylate tablets are bioequivalent with similar safety profiles.

PMID:34981666 | DOI:10.1002/cpdd.1064

CNS Neurosci Ther. 2022 Jan 3. doi: 10.1111/cns.13786. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the factors influencing enlarged perivascular space (EPVS) characteristics at the onset of acute ischemic stroke (AIS), and whether the PVS characteristics can predict later post-stroke epilepsy (PSE).

METHODS: A total of 312 patients with AIS were identified, of whom 58/312 (18.6%) developed PSE. Twenty healthy participants were included as the control group. The number of PVS in the basal ganglia (BG), centrum semiovale (CS), and midbrain (MB) was manually calculated on T₂ -weighted MRI. The scores and asymmetry index (AI) of EPVS in each region were compared among the enrolled participants. Other potential risk factors for PSE were also analyzed, including NIHSS at admission and stroke etiologies.

RESULTS: The EPVS scores were significantly higher in the bilateral BG and CS of AIS patients compared to those of the control group (both p < 0.01). No statistical differences in EPVS scores in BG, CS, and MB were obtained between the PSE group and the nonepilepsy AIS group (all p > 0.01). However, markedly different AI scores in CS were found between the PSE group and the nonepilepsy AIS group (p = 0.004). Multivariable analysis showed that high asymmetry index of EPVS (AI≥0.2) in CS was an independent predictor for PSE (OR = 3.7, 95% confidence interval 1.5-9.1, p = 0.004).

CONCLUSIONS: Asymmetric distribution of EPVS in CS may be an independent risk factor and a novel imaging biomarker for the development of PSE. Further studies to understand the mechanisms of this association and confirmation with larger patient populations are warranted.

PMID:34981639 | DOI:10.1111/cns.13786

ESC Heart Fail. 2022 Jan 3. doi: 10.1002/ehf2.13797. Online ahead of print.

ABSTRACT

AIMS: Contemporary heart failure (HF) classification based on left ventricular (LV) ejection fraction is limited for comprehensive assessment of LV function. We aimed to validate the feasibility of the contraction-relaxation coupling index (CRC) as a novel predictor for clinical outcomes in patients with acute HF.

METHODS AND RESULTS: A total of 3266 consecutive patients (median age: 74 years, 53% male) with acute HF were included. CRC was defined as the ratio of end-diastolic elastance (LV end-diastolic pressure/stroke volume) to end-systolic elastance (LV end-systolic pressure/end-systolic volume). The risk for 1 year composite endpoint of all-cause mortality or hospitalization for HF (primary outcome) was compared after group categorization using CRC tertiles (Tertile 1: CRC ≤ 0.17, Tertile 2: 0.17 < CRC ≤ 0.40, and Tertile 3: 0.40 < CRC). The median CRC was 0.3 and the median LVEF was 42%. After adjustment for clinical and echocardiographic covariates, CRC was an independent predictor for the primary outcome (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.47-2.07 in Tertile 3 and HR: 1.21, 95% CI: 1.02-1.44 in Tertile 2 when compared with Tertile 1; HR: 1.23, 95% CI: 1.14-1.33 per one-standard deviation increment in CRC). The risk model with CRC showed better performance in outcome discrimination than the model with LVEF (c-statistic 0.701 vs. 0.699, P for difference <0.001). Patients with higher CRC demonstrated better effectiveness of neurohormonal blockade for the primary outcome compared with those with lower CRC (HR: 0.38, 95% CI: 0.29-0.50 in Tertile 3 and HR: 0.67, 95% CI: 0.52-0.89 in Tertile 1).

CONCLUSIONS: CRC provides an independent value for outcome prediction in patients with acute HF. CRC would be a sensitive indicator for prognostic risk stratification and for predicting treatment response to the neurohormonal blockade.

PMID:34981649 | DOI:10.1002/ehf2.13797

Microsc Res Tech. 2022 Jan 4. doi: 10.1002/jemt.24039. Online ahead of print.

ABSTRACT

To compare the clinical application value of positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) in the diagnosis of cervical cancer lymph node metastasis. We searched PubMed and other databases for the studies comparing the use of PET-CT and MRI for the diagnosis of cervical cancer lymph node metastasis up to January 20, 2021. We strictly followed the inclusion and exclusion criteria to screen the literature and extract the data. Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool was used for quality evaluation of included studies, and Revman 5.3 and Stata 15.0 software were used for evaluating heterogeneity, synthesize sensitivity (SEN), specificity (SPE), positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the curve (AUC) and comparing the pretest and posttest probabilities. Finally, 11 studies were included for meta-analysis. The synthesized results indicated that the SEN value of PET-CT was 0.65 (0.60 ~ 0.69) and SPE was 0.93 (0.91 ~ 0.94), and the SEN value of MRI was 0.58 (0.54 ~ 0.63) and SPE was 0.91 (0.90 ~ 0.92). AUC of PET-CT was 0.824, which was significantly higher than that of MRI (AUC = 0.702; p < .05). The subgroup analysis showed that the AUC value of the study based on study design and use of blinding methods was not statistically significant (all p > .05). There was no obvious publication bias in the synthesized analysis of the diagnostic value of PET-CT and MRI (all p > .05). HIGHLIGHTS: To compare positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) in diagnosis of cervical cancer lymph node metastasis. Synthesize sensitivity value of PET-CT was comparable with that of MRI. Area under the curve of PET-CT was significantly higher than that of MRI. There was no obvious publication bias in synthesized analysis.

PMID:34981608 | DOI:10.1002/jemt.24039

Congenit Anom (Kyoto). 2022 Jan 3. doi: 10.1111/cga.12456. Online ahead of print.

ABSTRACT

To evaluate the safety of triptan use during pregnancy in a Japanese population, we descriptively analyzed the data on pregnancy and fetal outcomes from 128 pregnant women using triptans for migraine treatment at two Japanese facilities that provided counseling on drug exposure in pregnancy between 2001 and 2017. The risks of miscarriage, low birth weight, and preterm birth were similar to those reported in the demographic statistics in Japan. The incidence proportion of malformation was also within the baseline risk range. Accumulated data suggest that exposure to triptans during pregnancy does not clearly increase the risk of negative pregnancy and fetal outcomes. This finding can help reduce anxiety in pregnant women with migraines who are taking triptans.

PMID:34981573 | DOI:10.1111/cga.12456

J Obstet Gynaecol Res. 2022 Jan 3. doi: 10.1111/jog.15142. Online ahead of print.

ABSTRACT

AIM: Frozen-thawed embryo transfer (FET) has gained popularity as an assistive reproductive technology despite its increased risk of large-for-gestational-age offspring. This study aimed to analyze the effect of FET on fetal development, particularly the growth rate and estimated fetal weight (EFW) throughout pregnancy.

METHODS: This was a single-center, retrospective study that examined 97 patients with FET conception and 477 patients with natural conception (NC) who underwent labor and delivery at our clinic between December 2015 and June 2019. Crown-rump length (CRL) in the first trimester and EFW measurements in the second and third trimesters were obtained from transabdominal ultrasound records. Birthweight was adjusted for sex, parity, and gestational age. Regression coefficients of CRL, EFW, and birthweight were compared between the FET and NC groups to examine the growth rate. Multiple regression analysis was performed to determine the relationship between birth size and baseline characteristics.

RESULTS: The growth rate was higher in the first trimester in the FET group than in the NC group (difference: 0.19 mm/day, p = 0.018). CRL, EFW, and adjusted birthweight were higher in the FET group than in the NC group throughout pregnancy. The factors associated with the development of larger offspring through FET than through NC were advanced maternal age, primiparity, cesarean section delivery, and high birthweight.

CONCLUSIONS: Throughout pregnancy, FET resulted in a larger offspring than in NC, with accelerated growth observed only during the first trimester. Thus, FET highly affects early fetal development.

PMID:34981599 | DOI:10.1111/jog.15142