Nevin Manimala

Ann Intensive Care. 2023 Sep 6;13(1):80. doi: 10.1186/s13613-023-01175-0.

ABSTRACT

AIMS: Impact of skin mottling has been poorly studied in patients admitted for cardiogenic shock. This study aimed to address this issue and identify determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all etiologies.

METHODS AND RESULTS: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October, 2016. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 660 had skin mottling assessed at admission (85.5%) with almost 39% of patients in cardiogenic shock presenting mottling. The need for invasive respiratory support was significantly higher in patients with mottling (50.2% vs. 30.1%, p < 0.001) and likewise for the need for renal replacement therapy (19.9% vs. 12.4%, p = 0.09). However, the need for mechanical circulatory support was similar in both groups. Patients with mottling at admission presented a higher length of stay (19 vs. 16 days, p = 0.033), a higher 30-day mortality rate (31% vs. 23.3%, p = 0.031), and also showed significantly higher mortality at 1-year (54% vs. 42%, p = 0.003). The subgroup of patients in whom mottling appeared during the first 24 h after admission had the worst prognosis at 30 days.

CONCLUSION: Skin mottling at admission in patients with cardiogenic shock was statistically associated with prolonged length of stay and poor outcomes. As a perfusion-targeted resuscitation parameter, mottling is a simple, clinical-based approach and may thus help to improve and guide immediate goal-directed therapy to improve cardiogenic shock patients’ outcomes.

PMID:37672139 | DOI:10.1186/s13613-023-01175-0

Brain. 2023 Sep 6:awad297. doi: 10.1093/brain/awad297. Online ahead of print.

ABSTRACT

Parkinson’s disease is an age-related neurodegenerative disorder with a higher incidence in males than females. The causes for this sex difference are unknown. Genome-wide association studies (GWAS) have identified 90 Parkinson’s disease risk loci, but the genetic studies have not found sex-specific differences in allele frequency on autosomal chromosomes or sex chromosomes. Genetic variants, however, could exert sex-specific effects on gene function and regulation of gene expression. To identify genetic loci that might have sex-specific effects, we studied pleiotropy between Parkinson’s disease and sex-specific traits. Summary statistics from GWASs were acquired from large-scale consortia for Parkinson’s disease (n cases=13 708; n controls=95 282), age at menarche (n=368 888 women) and age at menopause (n=69 360 women). We applied the conditional/conjunctional false discovery rate (FDR) method to identify shared loci between Parkinson’s disease and these sex-specific traits. Next, we investigated sex-specific gene expression differences in the superior frontal cortex of both neuropathologically healthy individuals and Parkinson’s disease patients (n cases=61; n controls=23). To provide biological insights to the genetic pleiotropy, we performed sex-specific expression quantitative trait locus (eQTL) analysis and sex-specific age-related differential expression analysis for genes mapped to Parkinson’s disease risk loci. Through conditional/conjunctional FDR analysis we found 11 loci shared between Parkinson’s disease and the sex-specific traits age at menarche and age at menopause. Gene-set and pathway analysis of the genes mapped to these loci highlighted the importance of the immune response in determining an increased disease incidence in the male population. Moreover, we highlighted a total of nine genes whose expression or age-related expression in the human brain is influenced by genetic variants in a sex-specific manner. With these analyses we demonstrated that the lack of clear sex-specific differences in allele frequencies for Parkinson’s disease loci does not exclude a genetic contribution to differences in disease incidence. Moreover, further studies are needed to elucidate the role that the candidate genes identified here could have in determining a higher incidence of Parkinson’s disease in the male population.

PMID:37671566 | DOI:10.1093/brain/awad297

J Cachexia Sarcopenia Muscle. 2023 Sep 6. doi: 10.1002/jcsm.13321. Online ahead of print.

ABSTRACT

In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.

PMID:37671529 | DOI:10.1002/jcsm.13321

J Glaucoma. 2023 Aug 17. doi: 10.1097/IJG.0000000000002293. Online ahead of print.

ABSTRACT

PRECIS: Primary trabeculectomy was safe and effective at lowering intraocular pressure in patients with primary open angle glaucoma and high myopia.

PURPOSE: To investigate the efficacy and safety of trabeculectomy in patients with glaucoma and high myopia.

PATIENT AND METHODS: Retrospective case control study. Glaucomatous patients with high myopia undergoing primary trabeculectomy surgery with at least one year of follow-up were compared to an age-matched control group without high myopia undergoing the same procedure. Surgical success was defined as: IOP ≤ 15 mm Hg with (qualified) or without (complete) antiglaucoma medications and at least 20% reduction from baseline IOP at the end of 48 months of follow-up.

RESULTS: We included a total of 90 eyes from 90 patients (45 eyes with high myopia and 45 controls). Within the 90 eyes, 70 eyes underwent trabeculectomy and 20 eyes underwent combined phacoemulsification and trabeculectomy. Although patients with high myopia had higher chances for failure (37% vs. 22%) compared to controls, the difference was not statistically significant (P=0.067). In the multivariable analysis, patients with African descent (P=0.043) and those with juvenile glaucoma (P=0.001) had more chances of failure, even after adjusting for myopia. There was no statistically significant difference between complication rates in both groups.

CONCLUSION: Trabeculectomy was effective in reducing IOP in patients with high myopia and glaucoma, without additional risk of complications compared to a control group.

PMID:37671507 | DOI:10.1097/IJG.0000000000002293

Br J Nutr. 2023 Sep 6:1-47. doi: 10.1017/S0007114523001861. Online ahead of print.

ABSTRACT

Prior meta-analytic investigations over a decade ago rather inconclusively indicated that conjugated linoleic acid (CLA) supplementation could improve anthropometric and body composition indices in the general adult population. More recent investigations have emerged, and an up-to-date systematic review and meta-analysis on this topic must be improved. Therefore, this investigation provides a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) on the impact of CLA supplementation on anthropometric and body composition (body mass [BM], boy mass index [BMI], waist circumference [WC], fat mass [FM], body fat percentage [BFP], and fat-free mass [FFM]) markers in adults. Online databases search, including PubMed, Scopus, the Cochrane Library, and Web of Science up to March 2022, were utilized to retrieve RCTs examining the effect of CLA supplementation on anthropometric and body composition markers in adults. Meta-analysis was carried out using a random-effects model. The I2 index was used as an index of statistical heterogeneity of RCTs. Among the initial 8351 studies identified from electronic databases search, 70 RCTs with 96 effect sizes involving 4159 participants were included for data analyses. The results of random-effects modeling demonstrated that CLA supplementation significantly reduced BM (WMD: -0.35, 95% CI: -0.54, -0.15, p<0.001), BMI (WMD: -0.15, 95% CI: -0.24, -0.06, p=0.001), WC (WMD: -0.62, 95% CI: -1.04, -0.20, p=0.004), FM (WMD: -0.44, 95% CI: -0.66, -0.23, p<0.001), BFP (WMD: -0.77 %, 95% CI: -1.09, -0.45, p<0.001), and increased FFM (WMD: 0.27, 95% CI: 0.09, 0.45, p=0.003). The high-quality subgroup showed that CLA supplementation fails to change FM and BFP. However, according to high-quality studies, CLA intake resulted in small but significant increases in FFM and decreases in BM and BMI. This meta-analysis study suggests that CLA supplementation may result in a small but significant improvement in anthropometric and body composition markers in an adult population. However, data from high-quality studies failed to show CLA’s body fat-lowering properties. Moreover, it should be noted that the weight loss properties of CLA were small and may not reach clinical importance.

PMID:37671495 | DOI:10.1017/S0007114523001861

J Magn Reson Imaging. 2023 Sep 6. doi: 10.1002/jmri.28943. Online ahead of print.

ABSTRACT

BACKGROUND: A referenced MRI-based classification associated with focused ultrasound ablation surgery (FUAS) outcomes is lacking in adenomyosis.

PURPOSE: To identify an MRI-based classification system for informing the FUAS outcomes.

STUDY TYPE: Retrospective.

POPULATION: Patients with FUAS for adenomyosis, were divided into a training set (N = 643; 355 with post-FUAS gonadotropin-releasing hormone/levonorgestrel, 288 without post-FUAS therapy) and an external validation set (N = 135; all without post-FUAS therapy).

FIELD STRENGTH/SEQUENCE: 1.5 T, turbo spin-echo T2-weighted imaging and single-shot echo-planar diffusion-weighted imaging sequences.

ASSESSMENT: Five MRI-based adenomyosis classifications: classification 1 (C1) (diffuse, focal, and mild), C2 (intrinsic, extrinsic, intramural, and indeterminate), C3 (internal, adenomyomas, and external), C4 (six subtypes on areas [internal or external] and volumes [<1/3 or ≥2/3]), and C5 (internal [asymmetric or symmetric], external, intramural, full thickness [asymmetric or symmetric]) for FUAS outcomes (symptom relief and recurrence).

STATISTICAL TESTS: The optimal classification was significantly associated with the most subtypes of FUAS outcomes. Relating to the timing of recurrence was measured using Cox regression analysis and median recurrence time was estimated by a Kaplan-Meier curve. A P value <0.05 was considered statistically significant.

RESULTS: Dysmenorrhea relief and recurrence were only associated with C2 in training patients undergoing FUAS alone. Compared with other subtypes, the extrinsic subtype of C2 was significantly associated with dysmenorrhea recurrence in the FUAS group. Besides, the median dysmenorrhea recurrence time of extrinsic subtype was significantly shorter than that of other subtypes (42.0 months vs. 50.3 months). In the validation cohort, C2 was confirmed as the optimal system and its extrinsic subtype was confirmed to have a significantly shorter dysmenorrhea recurrence time than other subtypes.

DATA CONCLUSION: Classification 2 can inform dysmenorrhea relief and recurrence in patients with adenomyosis undergoing FAUS only. Itsextrinsic subtype was associated with an earlier onset of dysmenorrhea recurrence after treatment.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

PMID:37671487 | DOI:10.1002/jmri.28943

Hosp Pediatr. 2023 Sep 6:e2022007045. doi: 10.1542/hpeds.2022-007045. Online ahead of print.

ABSTRACT

OBJECTIVES: The American Academy of Pediatrics published a guideline in 2011 recommending against the routine use of voiding cystourethrogram (VCUG) in infants aged 2 to 24 months with first febrile urinary tract infection (UTI); however, the rates of VCUG for infants aged <2 months are unknown. The objective of this study was to determine the trend in VCUG performance during index hospitalization among infants aged 0 to 2 months with UTI.

METHODS: This retrospective cohort study included infants aged birth to 2 months hospitalized with a UTI from 2008 to 2019 across 38 institutions in the Pediatric Health Information System. Outcome measures included recurrent UTI within 1 year, vesicoureteral reflux diagnosis within 1 year and antiurinary reflux procedure performed within 2 years. Trends over time were compared between preguideline (2008-2011) and postguideline periods (2012-2019) using piecewise mixed-effects logistic regression.

RESULTS: The odds of VCUG decreased by 21% per year in the preguideline period (adjusted odds ratio, 0.79; 95% confidence interval, 0.77-0.81; P < .001) versus 20% (adjusted odds ratio, 0.80; 95% confidence interval, 0.77-0.83; P < .001) in the postguideline period. The preguideline and postguideline difference was not statistically significant (P = .60). There was no difference in the postguideline odds of UTI within 1 year (P = .07), whereas the odds of vesicoureteral reflux diagnosis (P < .001) and antiurinary reflux procedure performance (P < .001) decreased.

CONCLUSIONS: VCUG performance during hospitalization has declined over the past decade among young infants hospitalized with UTI. Further work is needed to determine the optimal approach to imaging in these young infants.

PMID:37671444 | DOI:10.1542/hpeds.2022-007045

Eur J Ophthalmol. 2023 Sep 6:11206721231199774. doi: 10.1177/11206721231199774. Online ahead of print.

ABSTRACT

PURPOSE: To determine if glaucoma medications are associated with pregnancy and/or postnatal complications.

METHODS: Multicenter descriptive survey. Subjects were female patients 18-45 years who were previously pregnant with a diagnosis of glaucoma or ocular hypertension prior to pregnancy. Chart review queried diagnosis, glaucoma severity, and race. Survey questions were asked for each pregnancy and queried pregnancy age, medications used, and pregnancy outcomes/complications.

RESULTS: 114 pregnancies of 56 patients (mean 2.0 pregnancies per patient) were included. Three pregnancies with therapeutic abortion were excluded from further analysis. Mean age during pregnancy was 29.1 ± 5.7 years. Of the 111 pregnancies, 20 (18.0%) used no medications and 91 (82.0%) used at least one medication. Medications were topical carbonic anhydrase inhibitors (n = 45), beta-blockers (n = 55), alpha-agonists (n = 56), and prostaglandin analogues (n = 28). Outcomes were: preterm contractions/labour (6.3%), miscarriage (4.5%), stillbirth (4.5%), induction of labour (11.9%), emergency/unplanned caesarean delivery (13.9%), neonatal intensive care unit (NICU) stay (15.8%), congenital anomalies (8.1%), and low birth weight (10.9%). Fisher exact test assessed outcome associations with individual agents, use of any agent, and different number of agents. Alpha-agonist use was associated with NICU stay: 25.5% rate (p = 0.012) in alpha-agonist use. Most of the alpha-agonist use NICU stays occurred in pregnancies with third trimester use. All other associations were not statistically significant.

CONCLUSIONS: The data from this survey suggest an overall favourable safety profile for topical glaucoma medications in pregnancy, but further investigation is needed. Caution should be employed regarding third trimester alpha-agonist use owing to association with NICU stay.

PMID:37671417 | DOI:10.1177/11206721231199774

Asian Cardiovasc Thorac Ann. 2023 Sep 6:2184923231197872. doi: 10.1177/02184923231197872. Online ahead of print.

ABSTRACT

INTRODUCTION: The feasibility and standardization of coronary artery bypass grafting (CABG) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and unstable angina (UA) remain topics of ongoing debate. In this study, feasibility and early-term outcomes of CABG in patients with NSTE-ACS and UA were discussed.

METHODS: This study enrolled 79 patients who underwent on-pump CABG with complete revascularization between January 2020 and May 2022. the survival rates analyzed using Kaplan Meier test with log rank test. The p value of statistical significance was taken as below 0.05.

RESULTS: Preoperatively, the patients had a mean age of 60.9 years and a BMI of 28.0. The medical history included hypertension (50.6%), peripheral arterial disease and atrial fibrillation (12.7%), and other comorbidities such as COPD (22.8%) and type 2 diabetes mellitus (44.3%). Intraoperatively, the mean distal anastomosis count was 3.4, with average cardiopulmonary bypass and aortic cross-clamp times of 84.0 and 49.0 min, respectively. Early-term outcomes revealed low rates of mortality (2.5%) and complications such as myocardial infarction (1.3%), acute kidney injury (5.1%) and transient ischemic attack (5.1%). Post-discharge outcomes demonstrated low cardiac and all-cause mortality rates (2.5% and 3.8%, respectively) and a high overall survival rate (93.7%) at 12-month follow-up.

CONCLUSION: This study demonstrated the feasibility and positive outcomes of complete surgical revascularization in patients with UA and NSTE-ACS. It showed no graft occlusion or stroke, low complication rates and promising survival outcomes. Further research is needed for confirmation and to establish the procedure’s efficacy and safety in this patient population.

PMID:37671414 | DOI:10.1177/02184923231197872

Cleft Palate Craniofac J. 2023 Sep 6:10556656231198945. doi: 10.1177/10556656231198945. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop risk prediction models for preterm birth among infants with orofacial clefts.

DESIGN: Data from the Texas Birth Defects Registry for infants with orofacial clefts born between 1999-2014 were used to develop preterm birth predictive models. Logistic regression was used to consider maternal and infant characteristics, and internal validation of the final model was performed using bootstrapping methods. The area under the curve (AUC) statistic was generated to assess model performance, and separate predictive models were built and validated for infants with cleft lip and cleft palate alone. Several secondary analyses were conducted among subgroups of interest.

SETTING: State-wide, population-based Registry data.

PATIENTS/PARTICIPANTS: 6774 infants with orofacial clefts born in Texas between 1999-2014.

MAIN OUTCOME MEASURE(S): Preterm birth among infants with orofacial clefts.

RESULTS: The final predictive model performed modestly, with an optimism-corrected AUC of 0.67 among all infants with orofacial clefts. The optimism-corrected models for cleft lip (with or without cleft palate) and cleft palate alone had similar predictive capability, with AUCs of 0.66 and 0.67, respectively. Secondary analyses had similar results, but the model among infants with delivery prior to 32 weeks demonstrated higher optimism-corrected predictive capability (AUC = 0.74).

CONCLUSIONS: This study provides a first step towards predicting preterm birth risk among infants with orofacial clefts. Identifying pregnancies affected by orofacial clefts at the highest risk for preterm birth may lead to new avenues for improving outcomes among these infants.

PMID:37671412 | DOI:10.1177/10556656231198945