Association between ultrasonography foetal anomalies and autism spectrum disorder.

Multiple pieces of evidence support the prenatal predisposition of autism spectrum disorder (ASD). Nevertheless, robust data about abnormalities in foetuses later developing into children diagnosed with ASD are lacking. Prenatal ultrasound is an excellent tool to study abnormal foetal development as it is frequently used to monitor foetal growth and identify foetal anomalies throughout pregnancy. We conducted a retrospective case-sibling-control study of children diagnosed with ASD (cases); their own typically developing, closest-in-age siblings (TDS); and typically developing children from the general population (TDP), matched by year of birth, sex and ethnicity to investigate the association between ultrasonography foetal anomalies and ASD. The case group was drawn from all children diagnosed with ASD enrolled at the National Autism Research Center of Israel. Foetal ultrasound data from the foetal anatomy survey were obtained from prenatal ultrasound clinics of Clalit Health Services in southern Israel. The study comprised 659 children: 229 ASD, 201 TDS and 229 TDP. Ultrasonography foetal anomalies were found in 29.3% of ASD cases versus only 15.9% and 9.6% in the TDS and TDP groups [adjusted odds ratio (aOR) = 2.23, 95% confidence interval (CI) = 1.32-3.78, and aOR = 3.50, 95%CI = 2.07-5.91, respectively]. Multiple co-occurring ultrasonography foetal anomalies were significantly more prevalent among ASD cases. Ultrasonography foetal anomalies in the urinary system, heart, and head and brain were the most significantly associated with ASD diagnosis (aORUrinary = 2.08, 95%CI = 0.96-4.50 and aORUrinary = 2.90, 95%CI = 1.41-5.95; aORHeart = 3.72, 95%CI = 1.50-9.24 and aORHeart = 8.67, 95%CI = 2.62-28.63; and aORHead&Brain = 1.96, 95%CI = 0.72-5.30 and aORHead&Brain = 4.67, 95%CI = 1.34-16.24; versus TDS and TDP, respectively). ASD females had significantly more ultrasonography foetal anomalies than ASD males (43.1% versus 25.3%, P = 0.013) and a higher prevalence of multiple co-occurring ultrasonography foetal anomalies (15.7% versus 4.5%, P = 0.011). No sex differences were seen among TDS and TDP controls. ASD foetuses were characterized by a narrower head and a relatively wider ocular-distance versus TDP foetuses (ORBPD = 0.81, 95%CI = 0.70-0.94, and aOROcular distance = 1.29, 95%CI = 1.06-1.57). Ultrasonography foetal anomalies were associated with more severe ASD symptoms. Our findings shed important light on the multiorgan foetal anomalies associated with ASD.

Reversibility of precapillary pulmonary hypertension and outcomes after heart transplantation bridged with left ventricular assist devices: Insight from the United Network for Organ Sharing.

BACKGROUND: In light of the updated lowered threshold for diagnosing pulmonary hypertension (PH), the reversibility of precapillary PH with left ventricular assist device (LVAD) and the associated post-heart transplantation (HT) outcomes remain unclear. METHODS: Using data from the United Network for Organ Sharing database, we aimed to investigate predictors of persistent precapillary PH in HT recipients bridged with LVAD and examine the interrelated post-HT survival using the updated pulmonary vascular resistance (PVR) cutoff of >2 Wood units for precapillary PH. RESULTS: Among 2169 HT recipients bridged with LVAD, 1299 had PVR >2 at baseline; 551 (42.4%) of whom normalized their PVR ≤2 and 748 (57.6%) remained with elevated PVR >2 after LVAD implantation. Female sex (adjusted odds ratio [aOR]; 2.22, 95% confidence interval [CI], 1.61-3.07; P < .001) and inotrope treatment at listing (aOR, 1.31; 95% CI, 1.03-1.66; P = .028) were associated with persistently elevated PVR after LVAD. Conversely, longer duration of LVAD support (aOR, 0.74; 95% CI, 0.65-0.84; P < .001) and use of HeartMate II (aOR, 0.74; CI, 0.59-0.93; P = .011) were found to be protective against persistently elevated PVR after LVAD. Persistently elevated PVR >2 after LVAD was associated with increased risk of death compared with those who normalized their PVR (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.01-1.57; P = .037). However, the normalized PVR post-LVAD group had comparable survival with those with PVR ≤2 at baseline (aHR, 0.76; 95% CI, 0.57-1.02; P = .07). CONCLUSIONS: Many recipients of HT bridged with LVAD remain with PVR >2 after LVAD implantation, which is associated with increased risk of death after HT compared with patients with normalized PVR after LVAD.

Heart failure with improved ejection fraction: patient characteristics, clinical outcomes and predictors for improvement.

Background: Heart failure with improved ejection fraction (HFimpEF) is a recently recognized entity presenting a diagnostic and therapeutic challenge. Our aim was to characterize the profile of HFimpEF patients and evaluate predictors for EF lack of improvement among heart failure with reduced ejection fraction (HFrEF) patients. Methods: We included ambulatory HFrEF patients (EF≤40%) between January 1, 2015, and September 1, 2022, with two consecutive echocardiography exams at least 6 months apart. HFimpEF was defined as improved EF from ≤40%->40% and by ≥10%. Results: A total of 567 HFrEF patients (72% male, 54.3 ± 14.4 years old) were analyzed. Patients without EF improvement were more likely to be male, had more comorbidities, ischemic cardiomyopathy (ICMP), markers of adverse cardiac remodeling (lower EF and higher left and right ventricular diameters) and presence of late gadolinium enhancement (LGE) in MRI (P < 0.05 for all). In a multivariate analysis, male sex, ICMP, lower EF, larger ventricular size and LGE remained independent predictors for lack of EF improvement. A prediction model for lack of EF improvement including LVEF, LV diameter, diastolic blood pressure and ischemic etiology exhibited an area under the ROC curve of 0.77 (95% CI 0.73-0.81; P < 0.001). HFimpEF patients had better prognosis with lower hospitalizations and mortality rates. Guideline directed medical therapy (GDMT) were associated with improved outcomes in both groups regardless of EF improvement. Conclusions: Lack of improvement in EF among HFrEF patients may be predicted by HF etiology and imaging parameters of adverse cardiac remodeling, and is associated with worse prognosis. GDMT were associated with improved outcomes in both HFimpEF and HFrEF patients.

Admission of kidney patients to a closed staff nephrology department results in a better short-term survival.

BACKGROUND: The outcome of patients with chronic kidney disease (CKD) and acute kidney injury (AKI) is often dismal and measures to ameliorate their course are scarce. When admitted to the hospital, kidney patients are often hospitalized in general Medicine wards rather than in a specialized Nephrology department. In the current study, we compared the outcome of two cohorts of kidney patients (CKD and AKI) admitted either to general open-staff (with rotating physicians) Medicine wards or to a closed-staff (non-rotating Nephrologists) Nephrology ward. METHODS: In this population-based retrospective cohort study, we enrolled 352 CKD patients and 382 AKI patients admitted to either Nephrology or General Medicine wards. Short-term (< = 90 days) and long-term (>90 days) outcomes were recorded for survival, renal outcomes, cardiovascular outcomes, and dialysis complications. Multivariate analysis was performed using logistic regression and negative binomial regression adjusting to potential sociodemographic confounders as well as to a propensity score based on the association of all medical background variables to the admitted ward, to mitigate the potential admittance bias to each ward. RESULTS: One hundred and seventy-one CKD patients (48.6%) were admitted to the Nephrology ward and 181 (51.4%) were admitted to general Medicine wards. For AKI, 180 (47.1%) and 202 (52.9%) were admitted to Nephrology and general Medicine wards, respectively. Baseline age, comorbidities and the degree of renal dysfunction differed between the groups. Using propensity score analysis, a significantly reduced mortality rate was observed for kidney patients admitted to the Nephrology ward vs. general Medicine in short term mortality (but not long-term mortality) among both CKD patients admitted (OR = 0.28, CI = 0.14-0.58, p = 0.001), and AKI patients (or = 0.25, CI = 0.12-0.48, p< 0.001). Nephrology ward admission resulted in higher rates of renal replacement therapy (RRT), both during the first hospitalization and thereafter. CONCLUSIONS: Thus, a simple measure of admission to a specialized Nephrology department may improve kidney patient outcome, thereby potentially affecting future health care planning.

Worldwide Prevalence and Clinical Characteristics of RAS Mutations in Head and Neck Cancer: A Systematic Review and Meta-Analysis.

In light of the development of RAS inhibitors, a reliable assessment of the prevalence of RAS mutations and their correlation with the clinical features of patients with HNC is crucially needed. This meta-analysis compiles the findings of 149 studies with over 8500 HNC patients and assesses the global prevalence of mutations in the HRAS, KRAS and NRAS genes. The available data were stratified according to geographical region, clinical features, and tumor characteristics, including human papillomavirus (HPV) infection status and tumor stage. In addition, the distribution of codon substitutions in each RAS gene was assessed. The estimated mutation rate is highest for HRAS (7%), followed by KRAS (2.89%) and NRAS (2.20%). HRAS prevalence in South Asia (15.28%) is twice as high as the global estimate. HRAS mutations are more prevalent in oral cavity and salivary gland tumors. In contrast, KRAS mutations are found more frequently in sinonasal tumors, and NRAS mutations are found chiefly in tumors of the nasopharynx. OR analyses show a significant association between HRAS mutations and a high tumor stage (OR=3.63). In addition, there is a significant association between HPV-positive status and KRAS mutations (OR=2.09). This study highlights RAS as a potential therapeutic target in certain subsets of HNC patients.

Tumor-Treating Fields for the treatment of glioblastoma: a systematic review and meta-analysis.

BACKGROUND: Tumor-Treating Fields (TTFields) is an emerging treatment modality for glioblastoma (GBM). Studies have shown a good safety profile alongside improved efficacy in newly diagnosed GBM (ndGBM), while a less clear effect was shown for recurrent GBM (rGBM). Despite regulatory support, sectors of the neuro-oncology community have been reluctant to accept it as part of the standard treatment protocol. To establish an objective understanding of TTFields' mechanism of action, safety, efficacy, and economical implications, we conducted a systematic literature review and meta-analysis. METHODS: A systematic search was conducted in PubMed, Scopus, and Cochrane databases. Twenty studies met the pre-defined inclusion criteria, incorporating 1636 patients (542 ndGBM and 1094 rGBM), and 11 558 patients (6403 ndGBM and 5155 rGBM) analyzed for the clinical outcomes and safety endpoints, respectively. RESULTS: This study demonstrated improved clinical efficacy and a good safety profile of TTFields. For ndGBM, pooled median overall survival (OS) and progression-free survival (PFS) were 21.7 (95%CI = 19.6-23.8) and 7.2 (95%CI = 6.1-8.2) months, respectively. For rGBM, pooled median OS and PFS were 10.3 (95%CI = 8.3-12.8) and 5.7 (95%CI = 2.8-10) months, respectively. Compliance of ≥75% was associated with an improved OS and the predominant adverse events were dermatologic, with a pooled prevalence of 38.4% (95%CI = 32.3-44.9). Preclinical studies demonstrated TTFields' diverse molecular mechanism of action, its potential synergistic efficacy, and suggest possible benefits for certain populations. CONCLUSIONS: This study supports the use of TTFields for GBM, alongside the standard-of-care treatment protocol, and provides a practical summary, discussing the current clinical and preclinical aspects of the treatment and their implication on the disease course.

Association Between Abnormal Fetal Head Growth and Autism Spectrum Disorder.

OBJECTIVE: Despite evidence for the prenatal onset of abnormal head growth in children with autism spectrum disorder (ASD), studies on fetal ultrasound data in ASD are limited and controversial. METHOD: We conducted a longitudinal matched case-sibling-control study on prenatal ultrasound biometric measures of children with ASD, and 2 control groups: (1) their own typically developed sibling (TDS) and (2) typically developed population (TDP). The cohort comprised 528 children (72.7% male), 174 with ASD, 178 TDS, and 176 TDP. RESULTS: During the second trimester, ASD and TDS fetuses had significantly smaller biparietal diameter (BPD) than TDP fetuses (adjusted odds ratio for the z score of BPD [aORzBPD] = 0.685, 95% CI = 0.527-0.890, and aORzBPD = 0.587, 95% CI = 0.459-0.751, respectively). However, these differences became statistically indistinguishable in the third trimester. Interestingly, head biometric measures varied by sex, with male fetuses having larger heads than female fetuses within and across groups. A linear mixed-effect model assessing the effects of sex and group assignment on fetal longitudinal head growth indicated faster BPD growth in TDS versus both ASD and TDP in male fetuses (ß = 0.084 and ß = 0.100 respectively; p < .001) but not in female fetuses, suggesting an ASD-sex interaction in head growth during gestation. Finally, fetal head growth showed conflicting correlations with ASD severity in male and female children across different gestation periods, thus further supporting the sex effect on the association between fetal head growth and ASD. CONCLUSION: Our findings suggest that abnormal fetal head growth is a familial trait of ASD, which is modulated by sex and is associated with the severity of the disorder. Thus, it could serve as an early biomarker for ASD.