COVID-19 related pneumonia overlaps with ACS, one of the most common acute presentations in SCD patients.We present a case of 22-year-old SCD patient presented to the emergency department with mild respiratory symptoms turned out to be COVID-19 positive and received red blood cell exchange to avoid the possibility of deterioration.

An 80 year old woman underwent vitrectomy for recurrent uveitis, demonstrating lymphocytic vitreous fluid. Less than a month later skin biopsy confirmed the diagnosis of extranodal NK/T cell lymphoma. Chemotherapy with SMILE (steroid - dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) was poorly tolerated despite reduced doses, while pembrolizumab was ineffective.

TAR syndrome is a rare congenital disorder whose genetic bases have remained unclear for many years. It has now been understood that the disease is caused by the compound inheritance of a rare null allele (usually the 1q21.1 deletion) and a low-frequency hypomorphic noncoding single nucleotide polymorphism (SNP) in RBM8A gene. Nevertheless, only a limited set of variants has been identified so far. A recent report of Boussion et al. described four novel RBM8A noncoding SNPs (i.e., 1) c.205 + 3_205 + 6del, 2) c.206 − 13C>A, 3) c. − 19G>T, and 4) c.*6C>G) increasing the mutational spectrum of TAR syndrome. Here, based on the recently published manuscript by Boussion et al., we report data regarding an additional African TAR patient carrying the 1q21.1q21.2 deletion in trans with the 3’UTR (c.*6C>G) variant. Present data further confirm the pathogenic role of this hypomorphic SNP and highlights its relevance in the African population, leading to advice geneticists to directly search for the c.*6C>G variant in African patients affected by TAR syndrome and carrying the 1q21.1 deletion, shortening the diagnostic time window.

We report the clinical and laboratory coagulation characteristics of 27 pediatric and young adult patients (2 months to 21 years) treated for symptomatic COVID-19 at a children’s hospital in the Bronx, New York between March 1 and May 31, 2020. D-Dimer was > 0.5 ug/mL (upper limit of normal) in 25 (93%) patients at admission; 11 (41%) developed peak D-Dimer > 5 ug/mL during admission. Seven (26%) patients developed venous thromboembolism: three with deep vein thrombosis and four with pulmonary embolism. Requirement of increased ventilatory support was a risk factor for thrombosis (p=0.006). Three of eight (38%) patients on prophylactic anticoagulation developed thrombosis, however no patients developed VTE on low molecular weight heparin prophylaxis titrated to anti-Xa level. Manifestation of COVID-19 disease was severe or critical in 16 (59%) patients. Four (15%) patients died of COVID-19 complications: all had comorbidities. Elevated D-dimer and increased VTE rate were observed in this young cohort, particularly in those with severe respiratory complications suggesting thrombotic coagulopathy. More data is needed to guide thromboprophylaxis in this age group.

A document by Xiaoting Song. Click on the document to view its contents.

The frantic search for a cure or prophylactic treatment of COVID-19 has unfortunately led to a dropping of the guard of many medical specialists resulting in widespread adoption of unproven treatment modalities. The recent article regarding the inconsistent physician attitudes towards hydroxychloroquine paints a depressing picture of the actual practices during the so-called era of evidence-based medicine. On this backdrop, we comment on how Romania (where this survey took place) has imposed some of the most severe lockdown measures in Europe, including the forced hospitalization of all confirmed with SARS-CoV-2 infection. Additionally, a therapeutic guideline was written into law, endorsing concomitant use of several drugs with unproven antiviral efficiency. This unprecedented situation has resulted in the sometimes indiscriminate prescription of off-label drugs, with a non-negligible risk of adverse reactions, especially in fragile patients with coexisting conditions. In light of the experience accrued in a COVID-19 dedicated unit, the authors discuss the importance of avoiding polypharmacy and administering all antiviral drugs within the confines of rigorously conducted clinical trials.

Background: Non-invasive ventilation (NIV) is a first-line therapy for sleep-related breathing disorders and chronic respiratory insufficiency. Evidence about predictors that may impact long-term NIV outcomes, however, is scarce. The aim of this study is to determine demographic, clinical, and technology-related predictors of long-term NIV outcomes. Methods: A ten-year multi-centred retrospective review of children started on long-term continuous or bilevel positive airway pressure (CPAP, BPAP) in Alberta. Demographic, technology-related, and longitudinal clinical data was collected. Long-term outcomes examined included ongoing NIV use, discontinuation due to improvement in underlying condition, switch to invasive mechanical ventilation (IMV) or death, patient/family therapy declination, transfer of services, and hospital admissions. Results: 622 children were included. Both younger age and CPAP use predicted higher likelihood for NIV discontinuation due to improvement in underlying conditions. Children with upper airway disorders or bronchopulmonary dysplasia were less likely to require NIV continuation while presence of central nervous system (CNS) disorders resulted in higher likelihood of hospitalizations and switch to IMV or death. The presence of obesity/metabolic syndrome and early NIV-associated complications predicted higher risk for NIV declination. Children with more co-morbidities or use of additional therapies required more hospitalizations and the latter also predicted higher risk to be switched to IMV or death. Conclusions: Demographic, clinical data, and NIV type impact long-term NIV outcomes and need to be considered during the initial discussions about therapy expectations with families. Knowledge of factors that may impact long-term NIV outcomes might help to better monitor at-risk patients and minimize adverse outcomes.

Objective Long-term respiratory consequences of bronchopulmonary dysplasia (BPD) in preterm infants born in the post-surfactant era (“new” BPD) remain partially unknown. The present study aimed to evaluate respiratory outcomes of “new” BPD in adolescents who were born preterm. Methods This multicenter, cross-sectional study included 286 adolescents born between 2003 and 2005 (mean age: 14.2 years); among them, 184 and 102 were born extremely preterm (EP) (< 28 weeks’ gestation) and moderate-late preterm (32 to < 37 weeks’ gestation), respectively. Among EP adolescents, 92 had BPD, and 92 did not. All participants underwent lung function tests, skin prick testing, and questionnaires on asthma symptoms and quality of life. Results EP adolescents with BPD had significantly lower forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25%–75% of FVC than other included adolescents. FEV1/FVC ratios were below the lower limit of normal (z-score < −1.645) in 30.4% of EP adolescents with BPD, 13.0% of EP adolescents without BPD, and 11.8% of adolescents who were born moderate-late preterm. Bronchodilator response and air-trapping were significantly higher in BPD adolescents than in other adolescents. Diffusion capacity was significantly lower in EP adolescents than in moderate-late preterm adolescents. Asthma symptoms and quality of life scores were similar among groups. Conclusion EP adolescents with “new” BPD had poorer pulmonary function than EP adolescents without BPD or moderate-late preterm adolescents. Further studies are needed to determine whether “new” BPD is associated with early-onset chronic obstructive pulmonary disease in adulthood.

This study presents the results of a long-term paired catchment experiment in south central Chile (mean annual precipitation = 2,500 mm, 5% falling in summer, mean annual temperature = 10 °C) in which fast-growing plantations of exotic Eucalyptus spp. were clearcut and replaced with native temperate rainforest species as part of an ecological restoration project. Precipitation, streamflow, and vegetation were measured starting in 2006 in four small (3 to 5 ha) catchments with Eucalyptus globulus plantations and native riparian buffers in the Valdivian Coastal Reserve. In 2011, the 12-yr-old Eucalyptus plantations were harvested in three catchments, and the clearcut area was planted with native trees (Nothofagus dombeyi), and diverse native forest species regenerated vigorously. In the restoration period (2011 to 2019), annual streamflow increased in average by 21 – 73% compared to the 2006-2010 pre-treatment period, and as much as 100% in wet years and by more than 150% in fall and summer of some years. Streamflow was 50 to 100% lower than before treatment in two dry summers (2014-2015. Base flow increased by 28 to 87% during the restoration period (2011 to 2019) compared to the pre-treatment period, and remained elevated in later years despite low summer precipitation. Streamflow increases persisted through the first decade of restoration. Overall, these findings indicate that removal of Eucalyptus plantations immediately increased streamflow, and native forest restoration gradually restored deep soil moisture reservoirs that sustain base flow during dry periods, and these flows showed steady positive values in the last three years contributing to water provision ecosystem services. The results of this study are relevant to efforts to restore native forest ecosystems on land currently intensively managed fast-growing forest plantations. They also provide useful information to inform policy and decision-making related to options for climate change mitigation under a drying trend in South-central Chile. To our knowledge this study is the first to test streamflow response to native forest restoration in former fast-growing Eucalyptus forest plantations.

In this study, we introduce datasets that include both hydrological and meteorological records at the Nučice experimental catchment (0.53 km2) which is representative for an intensively farmed landscape in the Czech Republic. The Nučice experimental catchment was established in 2011 for the observation of rainfall-runoff processes, soil erosion processes, and water balance of a cultivated landscape. The average altitude is 401 m a.s.l., the mean land slope is 3.9%, and the climate is humid continental (mean annual temperature 7.9 °C, annual precipitation 630 mm). The catchment is drained by an artificially straightened stream and consists of three fields covering over 95 % of the area which are managed by two different farmers. The typical crops are winter wheat, rapeseed, and alfalfa. The installed equipment includes a standard meteorological station, several rain gauges distributed across the basin, and an H-flume that monitors stream discharge, water turbidity, and basic water quality indicators. Additionally, the groundwater level and soil water content at various depths near the stream are recorded. Recently, large-scale soil moisture monitoring efforts have been introduced with the installation of two cosmic-ray soil moisture sensors. The datasets consist of measured precipitation, air temperature, stream discharge, and soil moisture and are available online for public use. The cross seasonal, open access runoff generation datasets at this small-scale agricultural catchment will benefit not only hydrologists but also local farmers.

Dear Editor in ChiefWe read with interest “The outcome of pregnancy in women with cystic fibrosis: a UK population based descriptive study1.”  We thank the authors for this timely paper which highlights the growing need for robust clinical data capture for Cystic Fibrosis maternal and infant health.This is a rapidly expanding area of interest as the landscape of CF care is changing dramatically, particularly in the era of CFTR modulation. Clinical teams caring for people living with CF are increasingly being asked about pregnancy and potential risks to mothers and their babies. As the authors highlight data on pregnancy in CF historically has mainly been small case series from single sites carried out before CFTR modulators were widely available. The guidelines referenced are somewhat dated as the authors allude to.The authors describe the strength of the data collection in the form of the UK OSS. However, over the 24 month period only 71 cases are collected. The authors also reference around 30 -40 women with CF being pregnant per year in the UK.* We suspect that there are a significant proportion of missing cases within this study suggested by an interrogation of the UK CF Registry data. The UK CF Registry has been sponsored and hosted by the CF Trust since 2007. CF clinical care teams enter data at every specialist centre and clinic across the UK, with over 99% of people with CF consenting to their data being submitted. Data from the UK CF Registry over the time period reported by this study revealed 64, 71 and 58 women having babies in 2015, 2016 and 2017 respectively. Although it is not possible to exactly match the dates (March 2015 to February 2017) described within this study to the CF registry data it is likely that there were considerably more than 71 cases in a two year period. **There remain queries regarding the clinical details of those women reported in this study. Eight of the 71 (11%) had no underlying CFTR mutation available and 51% were reported as pancreatic sufficient which is much higher than would be expected from a cohort of adults with CF in the UK. For 15 of the women included in the case series, lung function is not described.One of the main conclusions of the paper is that gestational age is highly correlated with FEV1. We find the presentation of this misleading as this is most likely the case because women with poorer lung function had pre-term caesareans or had labour induced earlier. Although this doesn’t change the correlation it may mean that it is due to the intervention.There is an ongoing UK Government funded project, CF Prosper, looking at pregnancies in women with CF using UK CF Registry and US CF Foundation registry data from 2003 to current (https://cfprosper.yolasite.com). We expect to be able to report on over 1000 pregnancies and help to delineate predictive factors for successful pregnancies and examine subsequent maternal disease trajectory after starting a family. Using the largest dataset yet available we also hope to develop a decision-making tool in conjunction with women living with CF and their clinical care teams to enable women with CF to make more informed choices regarding pregnancy and starting a family.Yours faithfully,Jamie Duckers, Cardiff and Vale University Health Board, UKDaniela Schlueter, Liverpool University, UKRhiannon Phillips, Cardiff Metropolitan University, UKRebecca Cosgriff, Cystic Fibrosis Trust, UKEsan Oluwaseun, Liverpool University, UKShantini Paranjothy, Aberdeen University, UKDeni Williams, Cardiff Metropolitan University, UKRachel Norman Cardiff and Vale University Health Board, UKDavid Taylor Robinson, Liverpool University, UKSiobhan Carr, Royal Brompton Hospital, London UK1) Ashcroft A, Chapman SJ, Mackillop L. The outcome of pregnancy in women with cystic fibrosis: a UK population-based descriptive study. BJOG. 2020 Jul 19. doi: 10.1111/1471-0528.16423. Epub ahead of print. PMID: 32683738.*There appears to be an error in the referencing numbering within the article as no reference 13 exists**Details on how to request data from the UK CF Registry are available via www.cysticfibrosis.org.uk/registry

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergic disorder with a well-characterised clinical phenotype, but limited understanding of factors associated with food cross-reactivity, severity and tolerance. Methods: A retrospective cohort study spanning 20 years on children with acute FPIES from a single paediatric tertiary centre in New South Wales, Australia focusing on identifying food trigger co-associations and factors associated with reaction severity, multiple trigger FPIES and/or tolerance was performed. Results: 169 individuals with 329 recorded FPIES episodes between 1997 and 2017 were included. 49% were male. The median age at first FPIES reaction was 5 months and median age at diagnosis was 9 months. 73% experienced at least one severe FPIES reaction. Rice (45%), cow’s milk (30%), soy (13%) were the most common triggers. FPIES to rice or cow’s milk were strongly associated with increased odds of having multiple trigger FPIES. Associations between causative foods were seen with rice/oats, cow’s milk/soy, and fish/shellfish. No factors were associated with increased risk of severe reactions. Infants with rice and grains FPIES outgrew their reactions at an earlier age, compared to those with fish FPIES. Conclusions: Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergic disorder with a well-characterised clinical phenotype, but limited understanding of factors associated with food cross-reactivity, severity and tolerance. Methods: A retrospective cohort study spanning 20 years on children with acute FPIES from a single paediatric tertiary centre in New South Wales, Australia focusing on identifying food trigger co-associations and factors associated with reaction severity, multiple trigger FPIES and/or tolerance was performed. Results: 169 individuals with 329 recorded FPIES episodes between 1997 and 2017 were included. 49% were male. The median age at first FPIES reaction was 5 months and median age at diagnosis was 9 months. 73% experienced at least one severe FPIES reaction. Rice (45%), cow’s milk (30%), soy (13%) were the most common triggers. FPIES to rice or cow’s milk were strongly associated with increased odds of having multiple trigger FPIES. The odds of having multiple food FPIES and severe reactions were slightly decreased with vaginal delivery. No factors were associated with increased risk of severe reactions. Infants with rice and grains FPIES outgrew their reactions at an earlier age, compared to those with fish FPIES. Conclusions: Rice remains the most common trigger for FPIES in this region with co-associations between rice/oats and cow’s milk/soy observed. The co-associations among food groups suggest that taxonomically related foods share similar protein structure and trigger similar mechanisms of antigen recognition. Vaginal delivery appears to have a mild protective effect on the development of multiple FPIES and severe reactions.

Background: Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define the better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children’s Oncology Group (COG). Methods: We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised IVADo (ifosfamide, vincristine, dactinomycin, doxorubicin), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531 it consisted on either VAC (vincristine, dactinomycin, cyclophosphamide) or VAC alternating with VI (vincristine, irinotecan). Local treatment was similar in both protocols. Results: The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced IRS Group and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95%CI=39-59) and 44% (95%CI=30-58), and overall survival (OS), 51% (95%CI=41-61) and 53.6% (95%CI=40-68), in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those FOXO1-negative (49.3% vs 73%, p=0.034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those FOXO1-negative. Conclusions: The outcome of patients with ARMS N1 was similar using different schemas of chemotherapy. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that this subgroup may benefit from the EpSSG strategy which included maintenance chemotherapy.

Hand and foot syndrome (HFS) is a toxic dermatologic reaction to chemotherapy, commonly described with capecitabine, 5fluouracile, vinorelbine, and cytarabine. Taxanes are less likely to induce HFS, and very few cases reported paclitaxel-induced HFS. We report a serious case of HFS induced by paclitaxel in a breast cancer female.

Background: Mediastinal cystic teratoma is a rare diagnosis in adolescence from low-income setting. Pleural effusion often mislead to infection and delay resection. We report a case from high burden tuberculosis country and analyze data from the literature. Methods: Clinical record of an adolescent patient from the Democratic Republic of Congo

Background: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is a progressive autosomal recessive disorder characterized by cachexia, gastrointestinal (GI) dysmotility, ptosis, peripheral neuropathy and brain MRI white matter changes. Bi-allelic TYMP mutations lead to deficient thymidine phosphorylase (TP) activity, toxic accumulation of plasma nucleosides (thymidine and deoxyuridine), nucleotide pool imbalances and mtDNA instability. Death is mainly due to GI complications: intestinal perforation, peritonitis, and/or liver failure. Based on our previous observations in 3 patients with MNGIE, that platelet infusions resulted in a transient 40% reduction of plasma nucleoside levels, in 2005 we performed the first HSCT worldwide as a life-long source of TP in a patient with MNGIE. Procedure: HSCT was performed in a total of six patients with MNGIE. The multiple factors involved in the prognosis of this cohort were analyzed and compared to the literature experience. Results: Cell source was bone marrow in five patients and peripheral stem cells in one, all from fully HLA-matched related donors, including four who were TYMP mutation carriers. Four of six (66%) survived compared to the 37% survival rate in the literature. Reduced intensity conditioning regimen contributed to secondary graft failure in 2 patients. 15 years post-HSCT the first transplanted patient is seemingly cured. Severe GI symptoms pre-transplantation were mostly irreversible and a poor prognostic factor. Conclusions: Allogenic HSCT could constitute a curative therapeutic option for carefully selected, young, pre-symptomatic or mildly affected patients. Timing, donor selection and optimal conditioning protocol are major determinants of outcome. HSCT is inadvisable in patients with advanced MNGIE disease.

We also aimed to present our experience about the diagnosis and treatment of our cesarean scar choriocarcinoma case whose tumor was chemoresistant and recurred in four months.

1.7% of myeloproliferative neoplasms are associated with autoimmune conditions. Association of myasthenia gravis (MG) with chronic myeloid leukemia is reported, but its association with polycythemia vera (PV) has never been reported. We report two patients who had MG and PV with JAK2V617F mutation. Both had splenomegaly but no thymoma.