Contemporary Diagnostics of Cardiac Sarcoidosis: The Importance of Multimodality Imaging.

Sarcoidosis is an inflammatory condition that can affect multiple organ systems and is characterized by the formation of non-caseating granulomas in various organs, including the heart. Due to suboptimal diagnostic rates, the true prevalence and incidence of cardiac sarcoidosis (CS) remain to be determined. In patients with suspected CS, an initial examination should include 12-lead ECG or ambulatory ECG monitoring, and echocardiography with the estimation of LV, RV function, and strain rate. In patients with confirmed extracardiac sarcoidosis and with high clinical suspicion for CS, sophisticated imaging modalities, including cardiac MRI and PET, are indicated. Typical inflammation patterns and myocardial scarring should pose a high suspicion for CS. In patients without diagnosed extracardiac sarcoidosis and high clinical suspicion, although with low diagnostic probability, an endomyocardial biopsy should be considered to establish the diagnosis of definite isolated cardiac sarcoidosis. Timely diagnosis enables the initiation of therapy and close monitoring of adverse cardiac events that can be life-threatening, including sudden cardiac death, ventricular tachycardia, high-degree AV block, and heart failure. Implementing biomarkers in correlation to cardiac imaging can determine the disease's severity and progression but can also be helpful in following the treatment response. The formation of larger global registries can be helpful in the identification of independent predictors of adverse clinical events and the development of specific diagnostic algorithms to reduce the overall risk of this serious condition.

The Correlation between Cardiac Magnetic Resonance Findings and Post-COVID-19: The Impact of Myocardial Injury on Quality of Life.

BACKGROUND: In the post-COVID-19 era, there is growing concern regarding its impact on cardiovascular health and the following effects on the overall quality of life of affected individuals. This research seeks to investigate cardiac magnetic resonance (CMR) findings following COVID-19 and their impact on the quality of life of affected individuals. METHODS: An observational, cross-sectional study was conducted in consecutive patients with persistent cardiovascular symptoms after COVID-19 who were referred to CMR due to suspected myocardial injury. In addition, patients completed a questionnaire about symptoms and the quality of life during the post-COVID-19 period. RESULTS: In this study, 85 patients were included. The study population consisted of patients with a mean age of 42.5 ± 13.4 years, predominantly women, who made up 69.4% of the study population, while men made up 30.6%. CMR findings showed non-ischemic myocardial injury in 78.8% of patients and myocardial edema in 14.1% of patients. Late pericardial enhancement was present in 40% of patients and pericardial effusion in 51.8% of patients. Pericardial effusion (p = 0.001) was more prevalent in patients who reported more pronounced symptoms in the post-COVID-19 period compared to the acute infection phase. Predictors of lower quality of life in the post-COVID-19 period were the presence of irregular heartbeat (p = 0.039), cardiovascular problems that last longer than 12 weeks (p = 0.018), and the presence of pericardial effusion (p = 0.037). CONCLUSION: Acute myocarditis was observed in a minority of patients after COVID-19, while non-ischemic LGE pattern and pericardial effusion were observed in the majority. Quality of life was worse during the post-COVID-19 period in patients with CMR abnormalities, primarily in patients with pericardial effusion. Also, irregular heartbeat, cardiovascular symptoms that last longer than 12 weeks, as well as pericardial effusion were independent predictors of lower quality of life during the post-COVID-19 period.

Influence of Thermal Treatment on the Chemical and Structural Properties of Geopolymer Gels Doped with Nd2O3 and Sm2O3.

In this research, the influence of the thermal treatment of geopolymer gels at 300 °C, 600 °C and 900 °C when incorporated with 5% rare earth elements (REEs) in the form of (GP-Sm) Sm2O3 and (GP-Nd) Nd2O3 was investigated. Changes in the chemical and structural properties of the geopolymer gels during thermal treatment for 1 h were monitored. Physico-chemical characterization was performed using the following methods: diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), scanning electron microscopy with energy dispersive spectrometry (SEM-EDS), and X-ray photoelectron spectroscopy (XPS). Besides the characterization of the fundamental properties, some practical macroscopic properties were analyzed as well: sorptivity, open porosity, and Archimedean density. The stretching vibrations of Nd-O-Si and Sm-O-Si were confirmed at a value of around 680 cm-1and an Nd-O-Si absorption band at a higher value, together with the most dominant band of Si-O stretching vibration similar for all the samples. No significant chemical changes occurred. Structural analysis showed that for GP-Nd, the largest pore diameter was obtained at 900 °C, while for GP-Sm, the largest pore diameter was obtained at 600 °C. EDS confirmed the amount of dopant to be about 5%. X-ray photoelectron spectroscopy showed that for GP-Nd, the ratio of Si and Al changed the most, while for GP-Sm, the ratio of Si and Al decreased with increasing temperature. The contributions of both dopants in the GP-gel structure remained almost unchanged and stable at high temperatures. The atomic percentages obtained by XPS analysis were in accordance with the expected trend; the amount of Si increased with the temperature, while the amount of Al decreased with increasing temperature. The sorptivity and open porosity showed the highest values at 600 °C, while the density of both geopolymers decreased linearly with increasing temperature.

Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review.

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.

Anti-MAPK Targeted Therapy for Ameloblastoma: Case Report with a Systematic Review.

Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in targeted therapy. We present a case of a 15-year-old girl with ameloblastoma successfully treated with targeted therapy and review the literature with this question: Is anti-MAPK targeted therapy safe and effective for treating ameloblastoma? This systematic review was registered in PROSPERO, adhered to PRISMA guidelines, and searched multiple databases up to December 2023, identifying 13 relevant studies out of 647 records, covering 23 patients treated with MAPK inhibitor therapies. The results were promising as nearly all patients showed a positive treatment response, with four achieving complete radiological remission and others showing substantial reductions in primary, recurrent, and metastatic ameloblastoma sizes. Side effects were mostly mild to moderate. This study presents anti-MAPK therapy as a significant shift from invasive surgical treatments, potentially enhancing life quality and clinical outcomes by offering a less invasive yet effective treatment alternative. This approach could signify a breakthrough in managing this challenging tumor, emphasizing the need for further research into molecular-targeted therapies.

Regression discontinuity design for the study of health effects of exposures acting early in life.

Regression discontinuity design (RDD) is a quasi-experimental approach to study the causal effect of an exposure on later outcomes by exploiting the discontinuity in the exposure probability at an assignment variable cut-off. With the intent of facilitating the use of RDD in the Developmental Origins of Health and Disease (DOHaD) research, we describe the main aspects of the study design and review the studies, assignment variables and exposures that have been investigated to identify short- and long-term health effects of early life exposures. We also provide a brief overview of some of the methodological considerations for the RDD identification using an example of a DOHaD study. An increasing number of studies investigating the effects of early life environmental stressors on health outcomes use RDD, mostly in the context of education, social and welfare policies, healthcare organization and insurance, and clinical management. Age and calendar time are the mostly used assignment variables to study the effects of various early life policies and programs, shock events and guidelines. Maternal and newborn characteristics, such as age, birth weight and gestational age are frequently used assignment variables to study the effects of the type of neonatal care, health insurance, and newborn benefits, while socioeconomic measures have been used to study the effects of social and welfare programs. RDD has advantages, including intuitive interpretation, and transparent and simple graphical representation. It provides valid causal estimates if the assumptions, relatively weak compared to other non-experimental study designs, are met. Its use to study health effects of exposures acting early in life has been limited to studies based on registries and administrative databases, while birth cohort data has not been exploited so far using this design. Local causal effect around the cut-off, difficulty in reaching high statistical power compared to other study designs, and the rarity of settings outside of policy and program evaluations hamper the widespread use of RDD in the DOHaD research. Still, the assignment variables' cut-offs for exposures applied in previous studies can be used, if appropriate, in other settings and with additional outcomes to address different research questions.

MR Imaging of Adverse Effects and Ocular Growth Decline after Selective Intra-Arterial Chemotherapy for Retinoblastoma.

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research.

Maternal antenatal mental health and its associations with perinatal outcomes and the use of healthcare services in children from the NINFEA birth cohort study.

To investigate the associations between maternal mental health disorders before and during pregnancy and perinatal outcomes and child healthcare utilization between 6 and 18 months of age. Among the 6814 mother-child pairs from the Italian Internet-based NINFEA birth cohort, maternal depression, anxiety, and sleep disorders diagnosed by a physician before and during pregnancy were assessed through self-reported questionnaires completed during pregnancy and 6 months after delivery. Perinatal outcomes (preterm birth, birth weight, small for gestational age, congenital anomalies, and neonatal intensive care unit (NICU)) and children's healthcare utilization (emergency department (ED) visits, hospitalizations, and outpatient visits) were reported by mothers at 6 and 18 months postpartum. We used regression models adjusted for maternal age, education, parity, country of birth, region of delivery, and household income. Maternal mental health disorders were not associated with perinatal outcomes, except for depression, which increased the risk of offspring admission to NICU, and anxiety disorders during pregnancy, which were associated with preterm birth and lower birth weight. Children born to mothers with depression/anxiety disorders before pregnancy, compared to children of mothers without these disorders, had an increased odds of a visit to ED for any reason (odds ratio (ORadj) = 1.26, 95% confidence interval (CI): 1.02-1.54), of an ED visit resulting in hospitalization (ORadj = 1.75, 95%CI: 1.27-2.42), and of planned hospital admissions (ORadj = 1.55, 95%CI: 1.01-2.40). These associations with healthcare utilization were similar for mental disorders also during pregnancy. The association pattern of maternal sleep disorders with perinatal outcomes and child healthcare utilization resembled that of maternal depression and/or anxiety disorders with these outcomes.   Conclusion: Antenatal maternal mental health is a potential risk factor for child-health outcomes and healthcare use. Early maternal mental health interventions may help to promote child health and reduce healthcare costs. What is Known: • Poor maternal mental health affects pregnancy outcomes and child health, and children of mothers with mental health conditions tend to have increased healtcare utilization. • Parents with poor mental health often face challenges in caring for their children and have less parenting self-efficacy, which could potentially lead to frequent medical consultations for minor health issues. What is New: • Maternal pre-pregnancy mental disorders were not associated with preterm birth, low birth weight, SGA, and congenital anomalies, except for depression, which increased the risk of offspring admission to NICU. Anxiety disorders during pregnancy were associated with lower birth weight and an increased odds of preterm birth. • Maternal depression and/or anxiety and sleep disorders, both before and during pregnancy, were associated with an increase in children's healthcare utilization between 6 and 18 months of life.

Immunostimulatory and Antibacterial Effects of Cannabis sativa L. Leaves on Broilers.

The aim of this study was to evaluate the effect of dried Cannabis sativa L. leaves as a phytogenic mixture added to broiler feed on CD4+ and CD8+ T lymphocyte subpopulations, Newcastle disease virus (NDV) antibody titres, and the presence of E. coli in faecal samples. The study was conducted on 100 male Ross 308 broilers, divided into four groups of 25 broilers, for a 42-day research period. The groups were housed separately in boxes on a litter of softwood shavings and were fed starter mixture from day 1 to day 21 and finisher mixture from day 22 to day 42. Industrial hemp (C. sativa) was grown in the Crkvina area, Croatia (latitude: 45°18'46.8″ N; longitude: 15°31'30″ E). The hemp leaves were manually separated, sun-dried, and ground to a powder. The mixture offered to the control group did not contain cannabis leaves, whereas the three experimental groups received mixtures containing mixed cannabis leaves in a quantity of 10 g/kg, 20 g/kg, or 30 g/kg (E_10, E_20, and E_30, respectively). The mean NDV antibody level was uniform in all study groups until post-vaccination day 14 and increased comparably with time. The percentage of CD4+ and CD8+ lymphocytes in the peripheral blood subpopulation showed statistically significant differences (p < 0.001) in the E_20 group as compared with the control group and both the E_10 and E_30 groups throughout the study period. As the broiler age increased, the CD4+-to-CD8+ ratios also increased and were statistically significant (p < 0.0001) on day 42 in all experimental groups as compared to the control group. Comparing the control group with the experimental groups indicated that the bacterial count was lower in broiler groups having received feed with the addition of 20 g/kg and 30 g/kg C. sativa leaves. In conclusion, the C. sativa leaves were found to elicit a favourable immunomodulatory effect on cell-mediated and humoral immune responses in broilers via increased CD4+ and CD8+ lymphocyte subpopulations and higher CD4+:CD8+ cell ratios, thus indicating enhanced immune function capacity. In addition, C. sativa leaves may have complementary effects on the broiler post-vaccination immune response, increase broilers' resistance to infectious diseases, reduce the effect of stress associated with vaccination, and improve broiler health and welfare.

Socioeconomic position, family context, and child cognitive development.

Socioeconomic position (SEP) may have different effects on cognitive development and family context could play a role in this association. This work aimed to analyse the role of socioeconomic positions, measured via various indicators collected longitudinally, in cognitive development at 7-11 years of age, evaluating the role of family context as a potential mediator. The study sample included 394 and 382 children from the INMA Gipuzkoa and Valencia cohorts, respectively. SEP indicators were assessed during pregnancy (family social class, parental education, employment, and disposable income) and at 7 (Gipuzkoa) and 11 (Valencia) years of age (At Risk of Poverty or Social Exclusion (AROPE)). Family context and cognitive development were measured with the Haezi-Etxadi Family Assessment Scale 7-11 (HEFAS 7-11) and Raven's Coloured Progressive Matrices (Raven's CPM), respectively. Linear regression models were developed to assess the relationships between (a) SEP-family context, (b) SEP-cognitive development, and (c) family context-cognitive development, adjusting for a priori-selected confounders. Simple and multiple mediation analyses were performed to explore the role of family context in the SEP-cognitive development relationship. Lower SEP was related with a lower cognitive score, this association being particularly robust for family social class. SEP indicators were related to subscales of family context, in particular those regarding cognitive stimulation, parental stress, and parenting. A relationship was also found between these three subscales and child cognitive development, mediating the effect of family social class on child cognition by 5.2, 5.5, and 10.8%, respectively, and 12.0% jointly.    Conclusion: Both family SEP and context contribute to a child's cognitive development. Equalising policies and positive parenting programmes could contribute to improving cognitive development in children. What is Known: • Parental social class, education, and employment status have been widely employed to measure socioeconomic position. What is New: • This work focuses on standard measurements of socioeconomic position but also other economic indicators such as the EHII and AROPE, and their effect on child cognitive development and family context. • Promotion of cognitive and linguistic development, parental stress and conflict, and parental profile fostering child development mediated the effect of family social class on cognitive development.

Transporting results in an observational epidemiology setting: purposes, methods, and applied example.

In the medical domain, substantial effort has been invested in generating internally valid estimates in experimental as well as observational studies, but limited effort has been made in testing generalizability, or external validity. Testing the external validity of scientific findings is nevertheless crucial for the application of knowledge across populations. In particular, transporting estimates obtained from observational studies requires the combination of methods for causal inference and methods to transport the effect estimates in order to minimize biases inherent to observational studies and to account for differences between the study and target populations. In this paper, the conceptual framework and assumptions behind transporting results from a population-based study population to a target population is described in an observational setting. An applied example to life-course epidemiology, where internal validity was constructed for illustrative purposes, is shown by using the targeted maximum likelihood estimator.

When the second comes first- rhabdomyosarcoma preceding heritable retinoblastoma- a case report.

BACKGROUND: Retinoblastoma (rb) is the most frequent intraocular tumor, accounting for 3% of all childhood cancers. Heritable rb survivors are germline carriers for an RB1 mutation and have a lifelong risk to develop non-ocular second primary tumors (SPTs) involving multiple other organs like the bones, soft tissues, or skin. These SPTs usually become manifest several years succeeding the diagnosis of rb. In our instance, however, a non-ocular SPT presented prior to the diagnosis of heritable rb. CASE PRESENTATION: We report a rare case of a monozygotic twin who presented with primary rhabdomyosarcoma (RMS) preceding the manifestation of heritable rb. The rb was diagnosed when the child developed strabismus while already on therapy for the RMS. The child underwent therapy for both as per defined treatment protocols. The rb regressed well on treatment, but the RMS relapsed and the child developed multiple refractory metastatic foci and succumbed to his disease. CONCLUSIONS: Non-ocular SPTs like sarcomas are usually known to manifest in heritable rb survivors with a lag of two to three decades (earlier if exposure to radiation is present) from the presentation of the rb. However, in our case, this seemed to be reversed with the RMS being manifest at an unusual early age and the rb being diagnosed at a later point in time.

Association of child neurodevelopmental or behavioural problems with maternal unemployment in a population-based birth cohort.

PURPOSE: To estimate associations between suspected or diagnosed neurodevelopmental or behavioural problems in 7-year-old children and maternal unemployment at child age 7 and 10, in a Portuguese birth cohort. METHODS: We evaluated 5754 mothers and their children of the population-based birth cohort Generation XXI in Porto, Portugal. Data on suspected and diagnosed child neurodevelopmental and behavioural problems (exposures)-learning, attention and language problems, externalising behaviours, developmental delay, autism spectrum disorders, and other neurodevelopmental problems-were retrieved at 7 years of age by interviewing caregivers. Maternal employment status (outcome) was collected at the 7- and 10-year follow-up waves. Robust Poisson regression models were used to estimate associations. RESULTS: After adjustment for maternal and household characteristics, women were more likely to be unemployed at child age 10 if the child had, up to age 7, any of the following suspected problems: an autism spectrum disorder (PR = 1.73; 95% CI 1.07, 2.79), developmental delay (PR = 1.58; 95% CI 1.20, 2.06), externalising behaviours (PR = 1.29; 95% CI 1.11, 1.50) or learning problems (PR = 1.26; 95% CI 1.07, 1.48). When the exposure was restricted to clinically diagnosed disorders, the magnitude of associations remained similar but estimates were less precise. Associations with unemployment were stronger at child age 10 (prospective analyses), than at child age 7 (cross-sectional). CONCLUSION: Having a child with learning, developmental or behavioural problems, or an autism spectrum disorder up to age 7 was associated with maternal unemployment three years later, even in a less affluent European economy where the dual-earner family structure is often necessary to make ends meet.

Acetamiprid's degradation products and mechanism: Part II - Inert atmosphere and charge storage.

Reuse and/or recycling of spent adsorbents is taking a central role in modern thinking and catalyzed carbonization is the way forward. Herein we explore the carbonization of adsorbed acetamiprid, in an inert atmosphere, as a way of recycling and producing nitrogen-rich carbon material for potential use in supercapacitors. Added value material and the reuse of the adsorbent were achieved by carbonization at 700 °C under argon. The formation of a nitrogen-doped carbon layer as an active material on the adsorbent, bonded through a C-Si linkage, has been conclusively verified through elemental composition quantification using XPS and EDX measurements. Two-stage catalytic decomposition and condensation of the adsorbed pesticide is followed by TGA and TPD-MS. Attained carbon-based materials give stable Faradaic capacitance with a slight dependency on the number of adsorbing cycles. Capacitance calculated with respect to the adlayer carbon material reaches values as high as 610 F g-1. Galvanostatic Charge/Discharge measurement confirmed the stability of explored materials with a slight increase in capacitance over 1000 cycles. The presented results envisage electroactive materials preparation from environmental pollutants, adding value to spent adsorbents.

Gender- and Age-Related Differences of Ocular Biometric Parameters in Patients Undergoing Cataract Surgery in Bosnia and Herzegovina.

Purpose: The aim of the study is to determine the distribution and mutual relationship of ocular biometric parameters, as well as to evaluate gender- and age-related differences in patients undergoing cataract surgery in Bosnia and Herzegovina. Materials and Methods: It was a retrospective cross-sectional study of consecutive patients who underwent cataract surgery between January 2017 and December 2021 in a tertiary care clinic. All biometric measurements were performed using the optical biometer OA-2000 (Tomey, Nagoya, Japan). Results: The study evaluated 1278 eyes from 1278 consecutive cataract patients. The average age of all included patients was 69.4 ± 9.98 (range 40-96). A total of 672 eyes (52.58%) were from females. The mean axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and mean keratometry were 23.46 ± 1.18 mm, 3.17 ± 0.40 mm, 4.54 ± 0.48 mm, and 43.42 ± 1.55D, respectively. Corneal astigmatism of ≥1D, >2D and >3D was found in 33.4%, 7.8% and 2.5% patients, respectively. Females were found to have shorter AL (p < 0.0001), shallower ACD (p < 0.0001) and steeper corneas (p < 0.0001). In both genders, AL, ACD and with the rule astigmatism showed a decreasing trend (p = 0.0001), while keratometry, the average cylinder, and against the rule astigmatism showed an increasing trend (p = 0.0001) with increasing age. Furthermore, in both genders, there was an increasing trend in ACD (p = 0.0001), and a decreasing trend in keratometry (p = 0.0001) and LT (p = 0.0001) with increasing AL. Conclusions: This study provides useful reference data on ocular biometry for cataract surgeons in Bosnia and Herzegovina. Female patients tend to have steeper corneas, shorter AL and shallower AC than males, and these differences are independent of age or AL.

Accuracy of biomicroscopy, ultrasonography and spectral-domain OCT in detection of complete posterior vitreous detachment.

BACKGROUND: To evaluate the accuracy of preoperative biomicroscopy (BM), ultrasonography (US), and spectral domain optical coherence tomography (SD-OCT) to determine complete posterior vitreous detachment (PVD) confirmed by intraoperative findings of triamcinolone acetonide-assisted pars plana vitrectomy (PPV). METHODS: This prospective study included all consecutive patients admitted for surgical treatment of the epiretinal membrane (ERM) and macular hole (MH). The presence of complete PVD was determined one day before PPV using BM, US, SD-OCT. The preoperative findings were compared to the PVD status determined during PPV. RESULTS: A total of 123 eyes from 123 patients were included in the study. Indications for PPV included ERM in 57 (46.3%), full thickness macular hole in 57 (46.3%) and lamellar macular hole in 9 (7.3%) patients. Complete PVD during PPV was observed in 18 (31.6%; 95%CI:18.7-49.9) patients with ERM and 13 (19.7%; 95%CI:10.4-33.7) patients with MH. The sensitivity of preoperative BM, US, SD-OCT was 48.4% (95%CI:30.2-66.9), 61.3% (95%CI:42.2-78.2) and 54.8% (95%CI:36.0-72.7) respectively. The specificity of preoperative BM, US, SD-OCT was 81.5% (95%CI:72.1-88.9), 90.2% (95%CI:82.2-95.4) and 85.9% (95%CI:77.0-92.3) respectively. With a prevalence of 25.2% of PVD in our sample the positive predictive value of preoperative BM, US, SD-OCT was 46.9% (95%CI:29.1-65.3), 67.9% (95%CI:47.6-84.1) and 56.7% (95%CI:37.4-74.5) respectively. CONCLUSION: Preoperative BM, US, and SD-OCT showed relatively low sensitivity but also good specificity in assessing complete PVD. A combination of all three diagnostic methods can provide a good assessment of the vitreoretinal interface state.

Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

Risk factors for overweight and obesity after childhood acute lymphoblastic leukemia in North America and Switzerland: A comparison of two cohort studies.

BACKGROUND: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors. METHODS: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25-29.9 kg/m2 ) and obesity (≥30 kg/m2 ) using multinomial regression. RESULTS: We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27-32 vs. 24%, 21-29; obesity: 29%, 27-32 vs. 7%, 5-10] and siblings (overweight: 30%, 27-32 vs. 25%, 22-29; obesity: 24%, 22-26 vs. 6%, 4-8). Survivors in North America [odds ratio (OR) = 1.24, 1.01-1.53] and Switzerland (1.27, 0.74-2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7-9.0); male (1.7, 1.3-2.3); attained age (≥45 years: 5.1, 2.4-10.8); Non-Hispanic Black (3.4, 1.6-7.0); low household income (2.3, 1.4-3.5); young age at diagnosis (1.6, 1.1-2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0-1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts. CONCLUSIONS: Although treatment-related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials.

CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (123/131I-mIBG) in vitro and in vivo: a promising candidate for advancing theranostics in neuroendocrine tumors.

BACKGROUND: Neuroblastoma (NB) and pheochromocytoma/paraganglioma (PHEO/PGL) are neuroendocrine tumors. Imaging of these neoplasms is performed by scintigraphy after injection of radiolabeled meta-iodobenzylguanidine (mIBG), a norepinephrine analog taken up by tumoral cells through monoamine transporters. The pharmacological induction of these transporters is a promising approach to improve the imaging and therapy (theranostics) of these tumors. METHODS: Transporters involved in mIBG internalization were identified by using transfected Human Embryonic Kidney (HEK) cells. Histone deacetylase inhibitors (HDACi) and inhibitors of the PI3K/AKT/mTOR pathway were tested in cell lines to study their effect on mIBG internalization. Studies in xenografted mice were performed to assess the effect of the most promising HDACi on 123I-mIBG uptake. RESULTS: Transfected HEK cells demonstrated that the norepinephrine and dopamine transporter (NET and DAT) avidly internalizes mIBG. Sodium-4-phenylbutyrate (an HDACi), CUDC-907 (a dual HDACi and PI3K inhibitor), BGT226 (a PI3K inhibitor) and VS-5584 and rapamycin (two inhibitors of mTOR) increased mIBG internalization in a neuroblastoma cell line (IGR-NB8) by 2.9-, 2.1-, 2.5-, 1.5- and 1.3-fold, respectively, compared with untreated cells. CUDC-907 also increased mIBG internalization in two other NB cell lines and in one PHEO cell line. We demonstrated that mIBG internalization occurs primarily through the NET. In xenografted mice with IGR-NB8 cells, oral treatment with 5 mg/kg of CUDC-907 increased the tumor uptake of 123I-mIBG by 2.3- and 1.9-fold at 4 and 24 h post-injection, respectively, compared to the untreated group. CONCLUSIONS: Upregulation of the NET by CUDC-907 lead to a better internalization of mIBG in vitro and in vivo.