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.

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 (aOR_Urinary = 2.08, 95%CI = 0.96–4.50 and aOR_Urinary = 2.90, 95%CI = 1.41–5.95; aOR_Heart = 3.72, 95%CI = 1.50–9.24 and aOR_Heart = 8.67, 95%CI = 2.62–28.63; and aOR_Head&Brain = 1.96, 95%CI = 0.72–5.30 and aOR_Head&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 (OR_BPD = 0.81, 95%CI = 0.70–0.94, and aOR_{Ocular 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.

Background & Objectives: To explore the potential association between positive ANA serology and all-cause mortality in a large cohort of patients, including those with and without rheumatological conditions and other immune-related diseases. Material and Methods: A retrospective cohort study analyzed all-cause mortality among 205,862 patients from Clalit Health Services (CHS), Israel’s largest health maintenance organization (HMO). We compared patients aged 18 and older with positive ANA serology (n = 102,931) to an equal number of ANA-negative controls (n = 102,931). Multivariable Cox regression models were used to assess hazard ratios (HR) for mortality, adjusting for demographic and clinical factors. Results: ANA positivity was strongly associated with increased mortality (adjusted HR [aHR] 4.62; 95% CI 4.5–4.7, p < 0.001). Significant predictors of mortality included male gender (39.2% vs. 24.4%, p < 0.001), older age at testing (72.4 ± 13.0 vs. 50.1 ± 17.3 years, p < 0.001), and Jewish ethnicity (89.6% vs. 83.2%, p < 0.001). Certain ANA patterns, such as mitochondrial (and dense fine speckled (DFS-AC2)), were highly predictive of mortality, with aHRs of 36.14 (95% CI 29.78–43.85) and 29.77 (95% CI 26.58–33.34), respectively. ANA-positive patients with comorbid rheumatological immune-related disorders (RIRDs) demonstrated a higher survival rate compared to those without such a condition (aHR 0.9, 95% CI 0.86–0.95, p < 0.001). This finding remained significant after adjusting for several parameters, including age. Conclusions: ANA positivity is associated with increased all-cause mortality, particularly in individuals without rheumatologic disorders, after adjusting for confounders such as age. This may indicate occult malignancies, cardiovascular pathology, or chronic inflammatory states, necessitating more vigilant surveillance

Despite evidence for prenatal onset of abnormal head growth in children with autism spectrum disorder (ASD), fetal ultrasound studies in ASD are limited and controversial. We conducted a longitudinal matched case-sibling-control study on fetal ultrasound biometric measures from 174 ASD children, their own typically developed siblings (TDS; n=178) and other population-based typically developed children (TDP; n=176). During second trimester, ASD and TDS fetuses had significantly smaller biparietal diameter (BPD) than TDP fetuses (aOR _zBPD =0.685, 95%CI=0.527-0.890 and aOR _zBPD =0.587, 95%CI=0.459-0.751, respectively). Interestingly, sex had a significant effect on head growth with males having larger heads than females within and across groups. Also, males and females with ASD showed different head shapes which were inversely correlated with ASD severity across different gestation periods. 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.