Maternal prepregnancy weight as an independent risk factor for congenital heart defects: systematic review and meta-analysis stratified by cardiac defect subtypes and severity.

OBJECTIVES: To assess and quantify the association between pre-pregnancy maternal overweight and obesity, and the risk of congenital heart defects (CHDs) in offspring. METHODS: This systematic review and meta-analysis included searches of PubMed, Medline, Web of science, and Scopus up to April 20th, 2023. Risk estimates were abstracted or calculated for rising body mass index categories (overweight, obesity, moderate and severe obesity) compared to normal weight (reference). Fixed-effects or random-effects models were used to combine individual study risk estimates based on the degree of heterogeneity. Sensitivity analyses were conducted to weight pooled estimates for relevant moderators, particularly diabetes prior and during pregnancy. Subgroup analyses for specific congenital heart defects were conducted if there were at least two studies with accessible data. The findings were presented in two ways: as groups of defects, categorized using severity and topographic-functional criteria, and as individual defects. The certainty of the evidence for each effect estimate was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: Twenty studies for a total of 4,861,693 patients and 86,136 CHDs cases were included. The risk for CHDs progressively increases from moderate to severe obesity (pooled odds ratio (OR), respectively: 1.15, 95% confidence interval (CI), 1.11-1.20, and 1.39, 95% CI, 1.27-1.53). Sensitivity analysis indicated that this effect persists independently of maternal diabetes status before or during pregnancy. In subgroup analysis, obesity was associated with up to a 1.5-fold increase in the risk of severe CHDs (pooled OR, 1.48; 95% CI, 1.03-2.13). Specifically, severe obesity was found to be associated with an even higher risk, increasing up to 1.8 times for specific CHDs including tetralogy of Fallot (pooled OR, 1.72; 95% CI, 1.38-2.16), pulmonary valve stenosis (pooled OR, 1.79; 95% CI, 1.39-2.30), and atrial septal defects (pooled OR, 1.71; 95% CI, 1.48-1.97). CONCLUSIONS: Maternal weight emerged as a crucial modifiable risk factor for preventing CHDs, particularly the severe forms. Future research is needed to investigate whether weight management prior to pregnancy might serve as a preventive measure against CHDs. Additionally, for pregnant women with obesity, fetal echocardiography ought to be a routine diagnostic procedure. This article is protected by copyright. All rights reserved.

Prenatal diagnosis and postnatal outcome of Type-III vasa previa: systematic review of literature.

OBJECTIVE: Type-III vasa previa (VP) is a rare form of VP, not necessarily associated with other placental or vascular anomalies, in which aberrant vessels run from the placenta to the amniotic membranes, near the internal cervical os, before returning to the placenta. Early diagnosis of Type-III VP is important but technically challenging. The objective of this study was to gather the current available evidence on the perinatal diagnosis and outcome of Type-III VP. METHODS: A systematic review of the literature on the perinatal diagnosis of atypical Type-III VP was carried out in PubMed, MEDLINE and EMBASE accordingto PRISMA guidelines from inception to March 2023. Data extraction and tabulation were performed by two operators and checked by a third senior author. The quality of the included studies was evaluated using the National Institutes of Health tool for the quality assessment of case-series studies. Our local ultrasound database was searched for previously unreported recent cases. Characteristics of prenatally and postnatally diagnosed Type-III VP, including clinical features and perinatal outcomes, were summarized using descriptive statistics. RESULTS: Eighteen cases of Type-III VP were included, of which 16 were diagnosed prenatally (14 cases were retrieved from 10 publications and two were unpublished cases from our center) and two were diagnosed postnatally (retrieved from two publications). All prenatal cases were diagnosed on transvaginal ultrasound at a mean gestational age of 29 weeks (median, 31 weeks; range, 19-38 weeks). Conception was achieved with in-vitro fertilization in 4/16 (25.0%) cases. There were no prenatal symptoms in 15/18 (83.3%) cases, while in two (11.1%) cases there was vaginal bleeding and in one (5.6%) preterm labor occurred. In 15/18 (83.3%) cases, at least one placental abnormality was observed, including low-lying insertion (9/17), succenturiate or accessory lobe (1/17), velamentous cord insertion (3/18) and marginal insertion (9/18). All prenatally diagnosed cases were liveborn and were delivered by Cesarean section before rupture of membranes at a median gestational age of 35 weeks (range, 32-38 weeks) without neonatal complications. Emergency Cesarean section was performed in 2/16 (12.5%) cases with a prenatal diagnosis and 1/2 (50.0%) cases with a postnatal diagnosis (P = 0.179). Among those with data available, an Apgar score of ≤ 7 was observed in the prenatally vs postnatally diagnosed group in 5/13 vs 1/1 cases, respectively, at the 1-min evaluation and 3/13 vs 1/1 cases, respectively, at the 5-min evaluation. CONCLUSIONS: The prenatal diagnosis of Type-III VP is challenging, with few cases reported in the literature; however, it is crucial for minimizing the risk of adverse outcome by enabling early-term elective Cesarean delivery prior to rupture of membranes. Given that clinical manifestations and risk factors are non-specific, and that Type-III VP cannot be excluded when there is a normal cord insertion or a singular placental mass, systematic screening by transvaginal ultrasound in the general pregnant population is recommended, particularly in those with a low-lying or morphologically abnormal placenta and those who conceived using assisted reproductive technology. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Autonomic nervous system involvement in autoimmune encephalitis and paraneoplastic neurological syndromes.

In autoimmune neurological diseases, the autonomic nervous system can be the primary target of autoimmunity (e.g. autoimmune autonomic ganglionopathy), or, more frequently, be damaged together with other areas of the nervous system (e.g. Guillain-Barré syndrome). Patients with autoimmune encephalitis and paraneoplastic neurological syndromes (PNS) often develop dysautonomia; however, the frequency and spectrum of autonomic signs and symptoms remain ill defined except for those scenarios in which dysautonomia is a core feature of the disease. Such is the case of Lambert-Eaton myasthenic syndrome, Morvan syndrome or anti-NMDAR encephalitis; in the latter, patients with dysautonomia have been reported to carry a more severe disease and to retain higher disability than those without autonomic dysfunction. Likewise, the presence of autonomic involvement indicates a higher risk of death due to neurological cause in patients with anti-Hu PNS. However, in anti-Hu and other PNS, as well as in the context of immune checkpoint inhibitors' toxicities, the characterization of autonomic involvement is frequently overshadowed by the severity of other neurological symptoms and signs. When evaluated with tests specific for autonomic function, patients with autoimmune encephalitis or PNS usually show a more widespread autonomic involvement than clinically suggested, which may reflect a potential gap of care when it comes to diagnosing dysautonomia. This review aims to revise the autonomic involvement in patients with autoimmune encephalitis and PNS, using for that purpose an antibody-based approach. We also discuss and provide general recommendations for the evaluation and management of dysautonomia in these patients.

Advances in treatments of patients with classical and emergent neurological toxicities of anticancer agents.

The neurotoxicity associated to the anticancer treatments has received a growing body of interest in the recent years. The development of innovating therapies over the last 20years has led to the emergence of new toxicities. Their diagnosis and management can be challenging in the clinical practice and further research is warranted to improve the understanding of their pathogenic mechanisms. Conventional treatments as radiation therapy and chemotherapy are associated to well-known and under exploration emerging central nervous system (CNS) and peripheral nervous system (PNS) toxicities. The identification of the risk factors and a better understanding of their pathogeny through a "bench to bedside and back again" approach, are the first steps towards the development of toxicity mitigation strategies. New imaging techniques and biological explorations are invaluable for their diagnosis. Immunotherapies have changed the cancer treatment paradigm from tumor cell centered to immune modulation towards an efficient anticancer immune response. The use of the immune checkpoints inhibitors (ICI) and CAR-T cells (chimeric antigen receptor) lead to an increase in the incidence of immune-mediated toxicities and new challenges in the neurological patient's management. The neurological ICI related adverse events (n-irAE) are rare but potentially severe and may present with both CNS and PNS involvement. The most frequent and well characterized, from a clinical and biological standpoint, are the PNS phenotypes: myositis and polyradiculoneuropathy, but the knowledge on CNS phenotypes and their treatments is expanding. The n-irAE management requires a good balance between dampening the autoimmune toxicity without impairing the anticancer immunity. The adoptive cell therapies as CAR-T cells, a promising anticancer strategy, trigger cellular activation and massive production of proinflammatory cytokines inducing frequent and sometime severe toxicity known as cytokine release syndrome and immune effector cell-associated neurologic syndrome. Their management requires a close partnership between oncologist-hematologists, neurologists, and intensivists. The oncological patient's management requires a multidisciplinary clinical team (oncologist, neurologist and paramedical) as well as a research team leading towards a better understanding and a better management of the neurological toxicities.

Neurological adverse events of immune checkpoint inhibitors: An update of clinical presentations, diagnosis, and management.

The use of immune checkpoint inhibitors (ICIs) has represented a major advance in cancer treatment. By enhancing endogenous immune responses to destroy cancer cells, ICIs can cause immune-related adverse events (irAEs), with possible involvement of any organ system. IrAEs are frequent, particularly those involving the skin or the endocrine system, and usually completely reversible after temporary immunosuppression, while neurological irAEs (n-irAEs) are relatively rare, often severe, and they carry a considerable risk of mortality and long-term disability. They usually affect the peripheral nervous system, mainly manifesting as myositis, polyradiculoneuropathy, or cranial neuropathy, and, less frequently, involve the central nervous system, causing encephalitis, meningitis, or myelitis. Although somehow reminiscent of the disorders that neurologists are familiar to deal with in their daily practice, n-irAEs are characterized by distinctive features from their idiopathic counterparts; for instance, myositis may have a predominant oculo-bulbar involvement reminiscent of myasthenia gravis and frequently associates with myocarditis; peripheral neuropathy, although often resembling Guillain-Barré syndrome, usually responds to corticosteroids. Remarkably, several associations between the neurological phenotype and the type of ICIs or the type of cancer have emerged in the last few years, and the growing administration of ICIs in patients with neuroendocrine cancers has led to an increased number of reports of paraneoplastic neurological syndromes (triggered or worsened by ICIs). This review aims to update current knowledge regarding the clinical presentation of n-irAEs. We also discuss the essential parts of the diagnostic approach, and we provide general recommendations for the management of these disorders.

Reference ranges of uterine artery pulsatility index from first to third trimester based on serial Doppler measurements: longitudinal cohort study.

OBJECTIVE: To provide gestational-age (GA)-specific reference ranges for mean uterine artery (UtA) pulsatility index (PI) based on longitudinal data assessment throughout pregnancy. METHODS: This was a prospective longitudinal cohort study of singleton low-risk pregnancies with adequate health and nutritional status at the time of enrolment and without fetal anomaly, receiving prenatal care between January 2018 and July 2021 at the Maternal Fetal Medicine Unit of IRCCS San Raffaele Scientific Institute, Milan, Italy. Women were recruited at ≤ 12 + 6 weeks' gestation and underwent serial standardized ultrasound monitoring, including UtA-PI measurement, by experienced certified operators until delivery. Association of UtA-PI with GA was modeled with fractional polynomial regression. Equations for mean ± SD of the estimated curves were calculated, as well as GA-specific reference charts of centiles for UtA-PI from 10 + 0 to 39 + 0 gestational weeks. RESULTS: We included 476 healthy, low-risk pregnant women and a total of 2045 ultrasound scans (median, 4 (range, 3-9) per patient) were available for analysis. Mean UtA-PI was 1.84 ± 0.55, 1.07 ± 0.38 and 0.78 ± 0.23 in the first, second and third trimesters of pregnancy, respectively. Goodness-of-fit assessment revealed that second-degree smoothing was the most accurate fractional polynomial for describing the course of UtA-PI throughout gestation; therefore, it was modeled in a multilevel framework for the construction of UtA-PI curves. We observed a rapid and substantial decrease in mean UtA-PI before 16 weeks, with subsequent smoother decrement of the slope and more stable values from 20 until 39 weeks. The 3rd , 5th , 10th , 25th , 50th , 75th , 90th , 95th and 97th centiles according to GA for UtA-PI are provided, as well as equations to allow calculation of any value as a centile. CONCLUSIONS: UtA-PI shows a progressive non-linear decrease throughout pregnancy. The new reference ranges for GA-specific mean UtA-PI constructed using rigorous methodology may have a better performance compared with previous models for screening for placenta-associated diseases in the early stages of pregnancy and for evaluating the potential risk for pregnancy-induced hypertension and/or small-for-gestational age later in pregnancy. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound diagnosis of placental and umbilical cord anomalies in singleton pregnancies resulting from in-vitro fertilization.

INTRODUCTION: placental anomalies can affect fetal and maternal outcome due to severe maternal hemorrhage potentially resulting in hysterectomy and cord accident including abruption that can determine fetal damage or death. The aims of our study are to determine if the rate of placental and umbilical cord anomalies are more common in IVF singleton pregnancies compared to spontaneous pregnancies; to evaluate the role of ultrasound in screening for these anomalies and to investigate if oocyte donor fertilization is an additional risk factor for the development of these anomalies. METHODS: this was a prospective cohort study involving two tertiary centers. Patients with a singleton pregnancy conceived with IVF and patients presenting with a spontaneous conception were recruited between 1st May 2019 to 31st March 2021. A total of 634 pregnancies were enrolled in the study. All patients underwent similar antenatal care, which included ultrasound examinations at 11-14, 19-22 and 33-35 weeks. Ultrasound findings of placental and/or umbilical cord abnormalities were recorded using the same protocol for both groups and confirmed after birth. RESULTS: IVF pregnancies had a significantly higher risk of low-lying placenta, placenta previa, bilobed placenta and velamentous cord insertion (VCI) compared with spontaneous pregnancies. In the heterologous subgroup there was a significant increased incidence of placenta accreta spectrum (PAS) disorders than in spontaneous pregnancies. All these anomalies were identified prenatally on ultrasound imaging and confirmed at birth. DISCUSSION: IVF pregnancies in general and those resulting from donor oocyte in particular are at higher risk of placental and umbilical cord abnormalities compared to spontaneous pregnancies. These anomalies can be diagnosed accurately at the mid-trimester detailed fetal anomaly scan and our findings support the need for a targeted ultrasound screening of these anomalies in IVF pregnancies.

Comparative Benefits and Risks Associated with Currently Authorized COVID-19 Vaccines.

This article provides a systematic assessment of the efficacy, risks, and methodological quality of evidence from five major publicly available vaccine trials. Results from Pfizer-BioNTech mRNA, Moderna-US NIH mRN-1273, AstraZeneca-Oxford ChAdOx1 nCov-19, Gamaleya GamCovidVac (Sputnik V), and Ad26.COV2.S Johnson & Johnson vaccines were included. Extracted benefits and risks data from each trial were summarized using the GRADE approach denoting the overall certainty of evidence along with relative and absolute effects. Relative risk reduction across all five vaccine trials ranged from 45% to 96%. Absolute risk reduction in symptomatic COVID-19 ranged from 6 to 17 per 1000 across trials. None of the vaccines were associated with a significant increase in serious adverse events compared to placebo. The overall certainty of evidence varied from low to moderate. All five vaccines are effective and safe, but suggest room for improvement in the conduct of large-scale vaccine trials. Certainty of evidence was downrated due to risk of bias, which can be mitigated by improving transparency and thoroughness in conduct and reporting of outcomes.

Family Needs After Traumatic Brain Injury: A VA TBI Model Systems Study.

OBJECTIVE: To describe the self-reported needs of family caregivers of service members and veterans (SMVs) who sustained a traumatic brain injury (TBI) and to identify predictors of the unmet family caregiver needs. SETTING: Five Department of Veterans Affairs (VA) Polytrauma Rehabilitation Centers (PRCs). PARTICIPANTS: Family caregivers of SMVs enrolled in the VA PRC TBI Model Systems (TBIMS) national database who were within their first 5 years post-TBI ( n = 427). DESIGN: Observational study. MAIN OUTCOME MEASURE: The Family Needs Questionnaire-Revised (FNQ-R) was completed by each SMV's designated caregiver. ANALYSES: Descriptive analyses were conducted on the FNQ-R responses at the item, domain, and total score levels. Unadjusted univariable and adjusted multivariable regression models were fitted to identify predictors of total unmet needs and unmet family need domains. RESULTS: FNQ-R item-level and domain-level descriptive results indicated that health information was the most frequently met need domain. In contrast, emotional and instrumental support domains were the least often met. On average, family caregivers reported that 59.2% of the 37 FNQ-R needs were met at the time of the follow-up assessment. Regression models indicated that both the number of SMV-perceived environmental barriers and whether the SMV received mental health treatment within the past year predicted the number of unmet FNQ-R needs. SMV-reported environmental barriers predicted increased unmet needs in all 6 family caregiver domains, and SMV mental health treatment in the past year predicted more unmet family caregiver emotional support, community support, and professional support needs. CONCLUSIONS: The current findings can be used to inform policy and programming for VA and Department of Defense to proactively address the specific needs of families and caregivers experienced in the first 5 years post-TBI.

Greater estimated fetal weight and birth weight in IVF/ICSI pregnancy after frozen-thawed vs fresh blastocyst transfer: prospective cohort study with novel unified modeling methodology.

OBJECTIVE: To compare, using a unified approach, standardized estimated fetal weight (EFW) trajectories from the second trimester to birth and birth-weight (BW) measurements in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies obtained after frozen-thawed vs fresh blastocyst transfer (BT). METHODS: This was a secondary analysis of a prospective longitudinal cohort study performed at the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, Italy, from January 2016 to December 2020. Eligible for inclusion were singleton viable gestations conceived by autologous IVF/ICSI conception after fresh or frozen-thawed BT that underwent standard fetal biometry assessment at 19-41 weeks and had BW measurements available. All ultrasound assessments were performed by operators blinded to the employment of cryopreservation. Patients with twin gestation, significant pregestational disease, miscarriage, major fetal abnormalities and use of other types of medically assisted reproduction techniques were excluded. EFW and BW Z-scores and their trajectories were analyzed using general linear models (GLM) and logistic regression with a unified modeling methodology based on the Fetal Medicine Foundation fetal and neonatal population weight charts, adjusting for major confounders. Differences between prenatal EFW and postnatal BW centiles in the two groups were assessed and compared using contingency tables, χ2 test and conversion of prenatal to postnatal centiles. RESULTS: A total of 631 IVF/ICSI pregnancies were considered, comprising 263 conceived following fresh BT and 368 after frozen-thawed BT. A total of 1795 EFW observations were available (n = 715 in fresh BT group and n = 1080 in frozen-thawed BT group; median of three observations per patient). EFW and BW < 10th centile were significantly more frequent in the fresh than in the frozen-thawed BT group (P = 0.003 and P < 0.001, respectively). EFW and BW > 90th centile were significantly more frequent in the frozen-thawed vs fresh BT group (P = 0.034 and P = 0.002, respectively). GLM showed significantly decreasing EFW Z-scores with advancing gestational age (GA) in both groups. The effect of GA was assumed to be equal in the two study groups, as no significant interaction effect was found. Smoothed mean EFW Z-scores from 19 weeks of gestation to term and smoothed mean BW Z-scores were both significantly higher in the frozen-thawed compared with the fresh BT group (EFW Z-score, 0.70 ± 1.29 vs 0.28 ± 1.43; P < 0.001; BW Z-score, 0.04 ± 1.08 vs -0.31 ± 1.28; P < 0.001). Mean smoothed EFW Z-score values in the frozen-thawed vs fresh BT groups were 1.01 ± 0.12 vs 0.60 ± 0.08 at 19-27 weeks, 0.36 ± 0.07 vs -0.06 ± 0.04 at 28-35 weeks and -0.66 ± 0.01 vs -0.88 ± 0.02 at 36-41 weeks. Mean smoothed BW Z-score values in the frozen-thawed vs fresh BT groups were -0.80 ± 0.14 vs -1.20 ± 0.10 at 28-35 weeks and 0.22 ± 0.16 vs -0.24 ± 0.14 at 36-41 weeks. Assessment of EFW and BW concordance showed a significantly greater rate of postnatal confirmation of prenatally predicted small-for-gestational age (SGA) < 10th centile in the fresh compared with the frozen-thawed BT group (P < 0.001), whereas the rate of postnatal confirmation of large-for-gestational age (LGA) > 90th centile was significantly higher in the frozen-thawed vs the fresh BT group (P < 0.001). Logistic regression analysis showed that the smoothed rate of EFW < 3rd centile was about 6-fold higher in the fresh vs frozen-thawed BT group (P < 0.001), whereas the smoothed rates of EFW 90th -97th centile and > 97th centile were nearly double in the frozen-thawed compared with the fresh BT group (P < 0.05 and P < 0.001, respectively). CONCLUSIONS: Robust novel unified prenatal-postnatal modeling in IVF/ICSI pregnancies after frozen-thawed or fresh BT from 19 weeks of gestation to birth showed non-divergent growth trajectories, with higher EFW and BW Z-scores in the frozen-thawed vs fresh BT group. The mean EFW Z-scores in both IVF/ICSI groups were greater than those expected for natural conceptions, being highest in the midtrimester and decreasing with advancing gestation in both groups, becoming negative after 32 weeks in the fresh and after 35 weeks in the frozen-thawed BT group. Mean BW Z-scores were negative in both groups, with lower values in preterm fetuses, and increased with advancing gestation, becoming positive at term in the frozen-thawed BT group. IVF/ICSI conceptions from frozen-thawed as compared to fresh BT presented increased rate of LGA and reduced rate of SGA both prenatally and postnatally. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Perception of Medical Student Mistreatment: Does Specialty Matter?

PURPOSE: Medical student mistreatment is pervasive, yet whether all physicians have a shared understanding of the problem is unclear. The authors presented professionally designed trigger videos to physicians from 6 different specialties to determine if they perceive mistreatment and its severity similarly. METHOD: From October 2016 to August 2018, resident and attending physicians from 10 U.S. medical schools viewed 5 trigger videos showing behaviors that could be perceived as mistreatment. They completed a survey exploring their perceptions. The authors compared perceptions of mistreatment across specialties and, for each scenario, evaluated the relationship between specialty and perception of mistreatment. RESULTS: Six-hundred fifty resident and attending physicians participated. There were statistically significant differences in perception of mistreatment across specialties for 3 of the 5 scenarios: aggressive questioning (range, 74.1%-91.2%), negative feedback (range, 25.4%-63.7%), and assignment of inappropriate tasks (range, 5.5%-25.5%) (P ≤ .001, for all). After adjusting for gender, race, professional role, and prior mistreatment, physicians in surgery viewed 3 scenarios (aggressive questioning, negative feedback, and inappropriate tasks) as less likely to represent mistreatment compared with internal medicine physicians. Physicians from obstetrics-gynecology and "other" specialties perceived less mistreatment in 2 scenarios (aggressive questioning and negative feedback), while family physicians perceived more mistreatment in 1 scenario (negative feedback) compared with internal medicine physicians. The mean severity of perceived mistreatment on a 1 to 7 scale (7 most serious) also varied statistically significantly across the specialties for 3 scenarios: aggressive questioning (range, 4.4-5.4; P < .001), ethnic insensitivity (range, 5.1-6.1; P = .001), and sexual harassment (range, 5.5-6.3; P = .004). CONCLUSIONS: Specialty was associated with differences in the perception of mistreatment and rating of its severity. Further investigation is needed to understand why these perceptions of mistreatment vary among specialties and how to address these differences.

Giga-voxel multidimensional fluorescence imaging combining single-pixel detection and data fusion.

Time-resolved fluorescence imaging is a key tool in biomedical applications, as it allows to non-invasively obtain functional and structural information. However, the big amount of collected data introduces challenges in both acquisition speed and processing needs. Here, we introduce a novel technique that allows to acquire a giga-voxel 4D hypercube in a fast manner while measuring only 0.03% of the dataset. The system combines two single-pixel cameras and a conventional 2D array detector working in parallel. Data fusion techniques are introduced to combine the individual 2D and 3D projections acquired by each sensor in the final high-resolution 4D hypercube, which can be used to identify different fluorophore species by their spectral and temporal signatures.

Enhanced diffuse optical tomographic reconstruction using concurrent ultrasound information.

Multimodal imaging is an active branch of research as it has the potential to improve common medical imaging techniques. Diffuse optical tomography (DOT) is an example of a low resolution, functional imaging modality that typically has very low resolution due to the ill-posedness of its underlying inverse problem. Combining the functional information of DOT with a high resolution structural imaging modality has been studied widely. In particular, the combination of DOT with ultrasound (US) could serve as a useful tool for clinicians for the formulation of accurate diagnosis of breast lesions. In this paper, we propose a novel method for US-guided DOT reconstruction using a portable time-domain measurement system. B-mode US imaging is used to retrieve morphological information on the probed tissues by means of a semi-automatical segmentation procedure based on active contour fitting. A two-dimensional to three-dimensional extrapolation procedure, based on the concept of distance transform, is then applied to generate a three-dimensional edge-weighting prior for the regularization of DOT. The reconstruction procedure has been tested on experimental data obtained on specifically designed dual-modality silicon phantoms. Results show a substantial quantification improvement upon the application of the implemented technique. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

Transient plasma cell dyscrasia in COVID-19 patients linked to IL-6 triggering.

An unusual clonal gammopathy was reported in COVID-19 patient but whether this anomaly is related or not to the disease has not yet been clarified. To this aim, we selected a cohort of 35 COVID-19 patients swab positive and investigated serological levels of IL-6, immune response to major viral antigens and electrophoretic profile. Elevated levels of IL-6 were accompanied by a significative humoral response to viral Spike protein, revealing an altered electrophoretic profile in the gamma region. We can conclude that elevated levels of IL-6 triggers humoral response inducing a transient plasma cell dyscrasia in severe COVID-19 patients.

Changes on soundscapes reveal impacts of wildfires in the fauna of a Brazilian savanna.

Wildfire is a natural process in Brazilian savannas, but human activities alter fire regimes and threaten biodiversity. In this study, we used an ecoacoustics approach to assess fauna responses and recovery after wildfire in a Brazilian savanna. Six passive acoustic monitoring devices were used to record soundscapes before and after a wildfire a at burned and non-burned sites for one year and one month (September 2012 to September 2013). Power Spectral Density and the Acoustic Complexity Index were used to track biophony. Before the fire, the two sites had similar biophonic patterns (PSD: T = 1136, Z = 1.52, P = 0.12; ACI: T = 1117, Z = 1.10, P = 0.26) and soniferous species richness (Site 1 = 52 and Site 2 = 49). However, in the first two sessions of recordings after the fire, biophony became higher at the burned site during the day (PSD: T = 211 and 233; Z = 4.13 and 6.41; ACI: T = 120 and 469, Z = 5.14 and 7.07; all P < 0.00). During the night, biophony was usually higher at the non-burned site until May 2013 (PSD: T = 0 to 453; Z = 3.30 to 5.90; ACI: T = 333 to 491, Z = 3.80 to 4.93; all P < 0.00). Biophony became similar (P = 0.17 to 0.38) at the two sites or higher (P = 0.00 to 0.01) at the burned site from July to September 2013 (PSD: T = 55 to 1167; Z = 1.35 to 6.89; ACI: T = 719 to 1365, Z = 0.87 to 3.04). After the fire, a reduction of soniferous species at the burned site was observed for insects and bats. Both biophonic activity and soniferous species showed a tendency to recover one year after the fire, but there were still less species in September 2013 (non-burned = 43 and burned = 37) when compared to September 2012 at both sites (Site 1 = 52 and Site 2 = 49). Our results showed that changes in the natural regimes of fire can negatively impact the biodiversity and reinforce the need for monitoring protocols and inspection of wildfires.

High dose brachytherapy with non sealed 188Re (rhenium) resin in patients with non-melanoma skin cancers (NMSCs): single center preliminary results.

BACKGROUND AND AIM: High dose brachytherapy using a non sealed 188Re-resin (Rhenium-SCT®, Oncobeta® GmbH, Munich, Germany) is a treatment option for non-melanoma skin cancer (NMSC). The aim of this prospective study was to assess the efficacy and the safety of a single application of Rhenium-SCT® in NMSC. MATERIALS AND METHOD: Fifty consecutive patients (15F, 35 M, range of age 56-97, mean 81) showing 60 histologically proven NMSCs were enrolled and treated with the Rhenium-SCT® between October 2017 and January 2020. Lesions were located on the face, ears, nose or scalp (n = 46), extremities (n = 9), and trunk (n = 5). Mean surface areas were 7.0 cm2 (1-36 cm2), mean thickness invasion was 1.1 mm (0.2-2.5 mm), and mean treatment time was 79 min (21-85 min). Superficial, mean, and target absorbed dose were 185 Gy, 63 Gy, and 31 Gy respectively. Patients were followed-up at 14, 30, 60, 90, and 180 days posttreatment, when dermoscopy and biopsy were performed. Mean follow-up was 20 months (range 3-33 months). Early skin toxicity was classified according to Common Terminology Criteria for Adverse Events (CTCAE). Cosmetic results were evaluated after at least 12 months according to Radiation Therapy Oncology Group (RTOG) scale. RESULTS: At 6 months follow-up, histology and dermoscopy were available for 54/60 lesions, of which 53/54 (98%) completely responded. One patient showed a 1-cm2 residual lesion that was subsequently surgically excised. Twelve months after treatment, 41/41 evaluable lesions were free from relapse. Twenty four months after treatment, 23/24 evaluable lesions were free of relapse. In 56/60 lesions early side effects, resolving within 32 days were classified as grades 1-2 (CTCAE). In the remaining 4/60 lesions, these findings were classified as grade 3 (CTCAE) and lasted up to 8-12 weeks but all resolved within 90 days. After at least 12 months (12-33 months), cosmetic results were excellent (30 lesions) or good (11 lesions). CONCLUSION: High dose brachytherapy with Rhenium-SCT® is a noninvasive, reasonably safe, easy to perform, effective and well-tolerated approach to treat NMSCs, and it seems to be a useful alternative option when surgery or radiation therapy are difficult to perform or not recommended. In our population 98% of the treated lesions resolved completely after a single application and only one relapsed after 2 years. Larger patients' population and longer follow-up are needed to confirm these preliminary data and to find the optimal dose to administer in order to achieve complete response without significant side effects.

Prospective longitudinal cohort study of uterine arteries Doppler in singleton pregnancies obtained by IVF/ICSI with oocyte donation or natural conception.

STUDY QUESTION: Do uterine arteries Doppler studies show different pulsatility index (UtA-PI) measurements in IVF/ICSI pregnancies with oocyte donation (OD) as compared to natural conceptions? SUMMARY ANSWER: In IVF/ICSI pregnancies with OD, UtA-PI is reduced by an average of about 40% as compared to pregnancies with natural conception. WHAT IS KNOWN ALREADY: OD pregnancies present worse pregnancy outcomes as compared to natural conception, particularly for increased incidence of pre-eclampsia (PE). Recent evidence shows that IVF/ICSI pregnancies with frozen blastocyst transfer also present higher prevalence of PE and 15% lower UtA-PI as compared to pregnancies after fresh blastocyst transfers. STUDY DESIGN, SIZE, DURATION: Prospective, longitudinal matched cohort study performed in the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, between 2013 and 2018. The analysis is based on 584 Doppler observations collected from 296 women with different method of conception (OD n = 122; natural conception n = 174). PARTICIPANTS/MATERIALS, SETTING, METHODS: IVF/ICSI viable singleton pregnancies with OD and natural conception control pregnancies matched for BMI and smoking, performing repeated UtA-PI measurements at 11-34 weeks. Miscarriages, abnormalities, twins, significant maternal diseases and other types of ARTs were excluded. Log mean left-right UtA-PI was used for analysis with linear mixed model (LMM) and correction for significant confounders. Pregnancy outcome was also analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: Participants after OD were older and more frequently nulliparous (mean age: OD 43.4, 95% CI from 42.3 to 44.6; natural conception 35.1, 95% CI from 34.5 to 35.7; P-value < 0.001; nulliparous: OD 96.6%; natural conception 56.2%; P-value < 0.001). Mean pulsatility index was lower in OD (UtA-PI: natural conception 1.22; 95% CI from 1.11 to 1.28; OD 1.04; 95% CI from 0.96 to 1.12; P-value < 0.001). A significant effect of parity, gestational age (GA) modeled with a cubic polynomial and BMI was described in the LMM. The mean Log UtA-PI was on average 37% lower in OD as compared to natural conception pregnancies at LMM (P-value < 0.001). We also found a significant interaction between longitudinal UtA-PI Doppler and GA. Therefore, at 11 weeks' gestation the Log UtA-PI was 42% lower and, at 34 weeks, the differences reduced to 32%. GA at delivery and birth weight were statistically lower in OD group; however, birthweight centile was not statistically different. Preeclampsia was 11-fold more common in the OD group (0.6% and 6.6%, P-value = 0.003). No other significant difference in pregnancy outcome was shown in the study groups (gestational diabetes mellitus, small or large for GA). LIMITATIONS, REASONS FOR CAUTION: It was not possible to properly match for maternal age and to blind the assessment given the major differences between cohorts; however, we did not find significant within-groups effects related to maternal age. Future research is needed to reassess outcomes and correct them for maternal characteristics (e.g. cardiovascular function). WIDER IMPLICATIONS OF THE FINDINGS: This finding reproduces our previous discovery of lower UtA-PI in frozen as compared to fresh blastocyst transfer. The vast majority of OD is obtained by the use of cryopreservation. We speculate that increased uterine perfusion may be the physiological response to compensate dysfunctions both in the mother and in the placenta. STUDY FUNDING/COMPETING INTEREST(S): This is a non-funded study. The authors do not declare competing interest. TRIAL REGISTRATION NUMBER: N/A.