Fetal cardiac rhabdomyoma should trigger the awareness of potential coexisting tuberous sclerosis complex that can lead to a poor neurological outcome. This condition is not only uncommon but can be easily unrecognized prenatally in the absence of a meticulous neurosonogram and MRI. We emphasize that careful consideration of all prenatal facilities is needed to confirm the diagnosis of tuberous sclerosis complex as early as possible during pregnancy. Key words: cardiac rhabdomyoma; tuberous sclerosis; prenatal diagnosis

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Background: In terms of the pulmonary vein (PV), atrial fibrillation (AF) patients have a shorter effective refractory period (ERP) and a larger dispersion of the ERP than patients without AF. Although the frequency of AF from the superior vena cava (SVC) was the highest among non-PV foci, the characteristics of the ERP in the SVC (SVC-ERP) were unclear. The purpose of this study was to elucidate the relationship between SVC-ERP and the inducibility of AF after pulmonary vein isolation (PVI). Methods and Results: Consecutive 28 patients who underwent PVI were included. After successful PVI, the SVC-ERP was measured at three positions in SVC. Rapid electrical stimuli were delivered at the shortest SVC-ERP to induce AF. Patients in whom AF was induced were assigned to the SVC-induced group (SIG) and the remaining patients were the non-SVC-induced group (non-SIG). The size of the SVC sleeve was evaluated using three-dimensional electroanatomic mapping. The SIG had a significantly shorter average SVC-ERP (236.0±25.2 vs. 294.8±36.8 ms, p<0.001), while SVC-ERP dispersion was not significantly different (30.0±25.4 vs. 33.3±20.1 ms, p=0.56). Although the longer SVC diameter was significantly longer in the SIG (27.4±4.3 vs. 22.9±4.6 mm, p=0.03), the SVC-ERP was significantly associated with pacing inducibility of AF after adjustment for the longer SVC diameter (odds ratio: 0.96 [1-ms increments], p=0.01). Conclusions: The SIG had a shorter SVC-ERP, while the dispersion was not significantly different between the two groups. The SVC-ERP can be one of the mechanisms of arrhythmogenicity for AF originating from the SVC.

Background. To investigate safety and clinical efficacy of percutaneous closure of PFO under TEE guidance in patients with cryptogenic stroke (CS) and migraine, combined PFO and large right-to-left shunt（RLS）. Methods. From January 2018 to June 2021 in our hospital, 128 patients were treated by percutaneous PFO occlusion under TEE guidance in CS and migraine. Effective occlusion rate, complications, cerebral ischemia events, migraine relief, and hospitalization costs were analyzed. Postoperative follow-up were conducted. Results. All the 128 patients were successful in percutaneous PFO occlusion. The average operation time was 20~32 (25.6±4.2) min, the average hospitalization time was 2~3(2.8±0.4) d. There were 122 patients without RLS and 6 patients with medium residual RLS, with the sealing efficiency of 95.31% by TTE and right heart contrast echocardiography. 30 patients with migraine underwent percutaneous PFO occlusion, 24 patients relief after operation, with a relief rate of 80.0%. Postoperative follow-up was conducted for 1-36（28.8±3.6）months, and no follow-up was lost. 98 cases of CS with PFO underwent percutaneous blockade were followed up without cerebral embolism recurrence, 26 of 30 patients with migraine received significant remission of migraine, with remission rate of 86.66%. There were no serious adverse events. Conclusions. For patients with CS and migraine, combined PFO and large RLS, percutaneous PFO occlusion under the guidance of TEE has fewer complications and is safe and effective. It can prevent the recurrence of CS and treat migraine.

Background: Three-dimensional reconstruction technology is used to measure the volume of the descending aorta and to evaluate the characteristics of the remodeling of the descending aorta with different lengths after frozen elephant trunk (FET) treatment of acute type A aortic dissection (ATAAD). Methods: Three-dimensional reconstruction of the computed tomography angiography (CTA) of 48 cases ATAAD patients preoperatively and 1-3 months postoperatively was performed to measure the total volume of the aorta lumen model, descending aorta lumen volume, abdominal arterial lumen volume, as well as the true lumen (TL) and false lumen (FL) of each segment. The postoperative volumetric ratio was subtracted from the preoperative volumetric ratio, and the final distinction was made according to our remodeling classification criteria. Result: There were 13 (76.47%) positive remodeling cases, 9 (42.86%) stable remodeling cases, and 2 (20.00%) negative remodeling cases in the long FET group. In the short FET group, there were 4 (23.53%) positive remodeling cases, 12 (57.14%) stable remodeling cases, and 8 (80.00%) negative remodeling cases. As shown above, the data was obtained from the volumetric measurement and the morphological analysis of the three-dimensional reconstruction model. Conclusion: According to our classification criteria, long FET can promote the positive remodeling of the descending aorta, and it is meaningful for three-dimensional reconstruction to be used in volume measurement and morphological research.

Background: The largest age group among children and adolescents referred for lung transplantation for cystic fibrosis (CF) have been those who in the pubertal or post pubertal age range. However, over 100 younger patients with CF have undergone lung transplantation over the last three decades in the USA. Methods: We performed a retrospective review of our experience with 18 children with CF who underwent lung transplantation in our center before the age of 11 years. Results: Notable findings were a high prevalence of methicillin-resistant Staphylococcus aureus, a high prevalence of diabetes mellitus and an impressive prevalence of consolidated lobar or whole lung disease. Post-transplant outcomes, however, were comparable to those older than 10 years of age in our center. Conclusions: In an era of increasingly effective medications modifying the natural history of CF, identification of risk factors for early severe lung disease in CF remains relevant and potentially more important for effective intervention in order to extend life.

The hydroclimatology of Northern South America responds to strongly-coupled dynamics of oceanic and terrestrial surface-atmosphere exchange, as moisture evaporated from these sources interact to produce continental rainfall. However, the relative contributions of these two source types through the annual cycle have been described only in modeling studies, with no observational tools used to corroborate these predictions. The use of isotopic techniques to study moisture sources has been common in assessing changes in the water cycle and in climate dynamics, as isotopes allow tracking the connection between evaporation, transpiration, and precipitation, as well as the influence of large scale hydroclimatic phenomena, such as the seasonal Inter Tropical Convergence Zone migration. We characterize the isotopic composition of moisture sources becoming precipitation in the Andes and Caribbean regions of Colombia, using stable isotopes data (δ18O, δ2H) from the Global Network of Isotopes in Precipitation (1971-2016) and contrasting it with moisture trajectory tracking from the FLEXPART model, using input from ERA-Interim reanalysis to compute the relative contribution of oceanic and terrestrial sources through the annual cycle. Our results indicate that most precipitation in the region comes from terrestrial sources including recycling (>30 % for all months), Orinoco (up to 28 % monthly for April), and the northern Amazon (up to 17 % monthly for June, July, and August); followed by oceanic sources including the Tropical South Pacific (up to 30 % monthly in October, November, December) and Tropical North Atlantic (up to 30 % monthly for January). These outcomes highlight the utility of combining stable isotopes in precipitation and modeling techniques to discriminate terrestrial and oceanic sources of precipitation. Further, our results highlight the need to assess the hydrological consequences of land cover change in South America, particularly in a country like Colombia where water, food and energy security all depend directly on precipitation. .

The impact of rising global temperatures on survival and reproduction is putting many species at risk of extinction. In particular, it has recently been shown that thermal effects on reproduction, especially limits to male fertility, can underpin species distributions in insects. However, the physiological factors influencing fertility at high temperatures are poorly understood. Key factors that affect somatic thermal tolerance such as hardening, the ability to phenotypically increase thermal tolerance after a mild heat shock, and the differential impact of temperature on different life stages, are largely unexplored for thermal fertility tolerance. Here, we examine the impact of high temperatures on male fertility in the cosmopolitan fruit fly Drosophila virilis. We first determined whether temperature stress at either the pupal or adult life-history stage impacts fertility. We then tested the capacity for heat-hardening to mitigate heat-induced sterility. We found that thermal stress reduces fertility in different ways in pupae and adults. Pupal heat stress delays sexual maturity, whereas males heated as adults can reproduce initially following heat stress, but lose the ability to produce offspring. We also found evidence that while heat-hardening in D. virilis can improve high temperature survival, there is no significant protective impact of this same hardening treatment on fertility. These results suggest that males may be unable to prevent the costs of high temperature stress on fertility through heat-hardening which limits a species' ability to quickly and effectively reduce fertility loss in the face of short-term high temperature events.

Background: The evidence of acupuncture for in vitro fertilization (IVF) remains debatable. Objectives: To evaluate the efficacy of acupuncture on embryo transfer in women undergoing IVF. Search Strategy: PubMed, MEDLINE, Web of Science, EMBASE, CENTRAL, Wanfang, Chinese National Knowledge Infrastructure, VIP were searched up to 6 September 2021. Selection Criteria: Randomized controlled trials (RCTs) of acupuncture evaluating IVF’s effects were included. Data Collection and Analysis: Clinical pregnancy rate (CPR) and live birth rate (LBR) were quantitatively summarized by the random-effect model. Variations in pooled estimates were examined by subgroup analyses and I2 was measured to quantify statistical heterogeneity. Main Results: Forty-nine eligible RCTs representing 9422 women undergoing IVF for pregnant success were identified. Pooled CPR and LBR showed a significant difference between acupuncture and control groups (odds ratio [OR]=1.65, 95% confidence interval [CI]: 1.45 to 1.88; OR=1.34, 95% CI: 1.08 to 1.66). Subgroup analysis showed a benefit of traditional acupuncture for women aged < 35 years (CPR: OR=1.57, 95% CI: 1.23 to 2.03; LBR: OR=1.34, 95% CI:1.23 to 1.48), treatment with  3 sessions (CPR: OR=2.37, 95% CI: 1.46 to 3.85; LBR: OR=1.99, 95% CI:1.52 to 2.60), and lower baseline control group rates of CPR (CPR: OR=2.14, 95% CI: 1.22 to 2.13; LBR: OR=2.23, 95% CI:1.07 to 4.62). Heterogeneity across studies were found (CPR: I2=47.4, p <0.001; LBR: I2=62.9, p <0.001). Conclusions: Although benefits of acupuncture in CPR and LBR among IVF women existed, no robust associations were found and which might be limited by the heterogeneity of current evidence

The present study is aimed at validation of notch stress/ strain estimation schemes such as classical Neuber, Hoffmann-Seeger and recently developed Ince-Glinka method for Nuclear piping material (low C-Mn steel). The study has considered different constraints, loading conditions, various hole sizes to accommodate strain gradient variations and equivalent peak strains. The notch stress field evaluated using these schemes is compared with corresponding stress using elastic-plastic Finite Element (FE) analyses. The comparisons have brought out that the Hoffmann-Seeger scheme results in reasonably accurate assessment of stress localization nearly for all constraint geometries, loadings and strain gradients. However, the classical Neuber scheme is more suitable for low constraint geometries and intermediate constraint geometries whereas it results in under-estimation of maximum principal stress for high constraint geometries, thereby leading to over-prediction of fatigue life. Further, the suitability of energy equivalence equations of Ince-Glinka model for individual stress components, has been reviewed.

Objective: Predictors for post-operative reverse remodeling in patients with severe aortic regurgitation (AR) and reduced left ventricular ejection fraction (LVEF) are unknown. We performed low-dose dobutamine stress echocardiography (DSE) in patients with severe AR and reduced LVEF to evaluate the relationship between contractile reserve (CR) and reverse remodeling after surgery. Methods: In 31 patients with chronic severe AR and reduced LVEF (LVEF < 50%), we performed pre-operative DSE, assessed CR and examined whether changes in preoperative DSE were associated with improvement of post-operative LVEF after aortic valve surgery. Results: The pre-operative echocardiographic findings were as follows: left ventricular (LV) end-diastolic dimension: 67 ± 10 mm, LV end-systolic dimension: 52 ± 13 mm and LVEF: 42% ± 8%. All patients underwent aortic valve surgery. Patients with pre-operative LVEF of >45% exhibited a significant increase in LVEF; however, patients with pre-operative LVEF of <45% showed no significant change. When we examined the results of DSE performed in patients with pre-operative LVEF of <45%, ΔLVEF of ≥6% (with CR) during DSE was related to an improvement in post-operative LVEF; ΔLVEF of ≥6% during DSE predicted an improvement in post-operative LVEF, with a sensitivity and specificity of 80% and 85%, respectively. Conclusions: DSE may be a helpful tool for predicting post-operative reverse remodeling in patients with severe AR and moderately reduced LVEF.

Seed germination is a physiological process regulated by multiple factors. Abscisic acid (ABA) can inhibit seed germination to improve seedling survival under conditions of abiotic stress, and this process is often regulated by light signals. Constitutive Photomorphogenic 1 (COP1) is an upstream core repressor of light signals, and is involved in several ABA responses. Here, we demonstrate that COP1 is a negative regulator of the ABA-mediated inhibition of seed germination. Disruption of COP1 enhanced Arabidopsis seed sensitivity to ABA and increased ROS levels. In seeds, ABA induced the translocation of COP1 to the cytoplasm, resulting in enhanced ABA-induced ROS levels. Genetic evidence indicated that HY5 and ABI5 act downstream of COP1 in the ABA-mediated inhibition of seed germination. ABA-induced COP1 cytoplasmic localization increased HY5 and ABI5 protein levels in the nucleus, leading to increased expression of ABI5 target genes and ROS levels in seeds. Together, our results reveal that ABA-induced cytoplasmic translocation of COP1 activates the HY5-ABI5 pathway to promote the expression of ABA-responsive genes and the accumulation of ROS during ABA-mediated inhibition of seed germination. These findings enhance the role of COP1 in the ABA signal transduction pathway.

In this work, we study the Watson-type integral transforms for the convolutions related to the Hartley and Fourier transformations. We establish necessary and sufficient conditions for these operators to be unitary in the L 2 (R) space and get their inverse represented in the conjugate symmetric form. Furthermore, we also formulated the Plancherel-type theorem for the aforementioned operators and prove a sequence of functions that converge to the original function in the defined L 2 (R) norm. Next, we study the boundedness of the operators (T k ). Besides, showing the obtained results, we demonstrate how to use it to solve the class of integro-differential equations of Barbashin type, the differential equations, and the system of differential equations. And there are numerical examples given to illustrate these.

M-protein (PAM) largely contributes to the pathogenesis of Pattern D Group A Streptococcus pyogenes (GAS). However, the mechanism of complex formation is unknown. In a system consisting of a Class II PAM from Pattern D GAS isolate NS88.2 (PAMNS88.2), with one K2hPg binding a-repeat in its A-domain, we employed biophysical techniques to analyze the mechanism of the K2hPg/PAMNS88.2 interaction. We show that apo-PAMNS88.2 is a coiled-coil homodimer (M.Wt. ~80 kDa) at 4°C - 25°C, and is monomeric (M.Wt. ~40 kDa) at 37°C, demonstrating a temperature-dependent dissociation of PAMNS88.2 over a narrow temperature range. PAMNS88.2 displayed a single tight binding site for K2hPg at 4°C, which progressively increased at 25°C through 37°C. We isolated the K2hPg/PAMNS88.2 complexes at 4°C, 25°C, and 37°C and found molecular weights of ~50 kDa at each temperature, corresponding to a 1:1 (m:m) K2hPg/PAMNS88.2 monomer complex. hPg activation experiments by streptokinase demonstrated that the hPg/PAMNS88.2 monomer complexes are fully functional. The data show that PAM dimers dissociate into functional monomers at physiological temperatures or when presented with the active hPg module (K2hPg) showing that PAM is a functional monomer at 37°C.

A combination of next-generation sequencing technologies and mate-pair libraries of large insert sizes is used as a standard method to generate genome assemblies with high contiguity. The third-generation sequencing techniques also are used to improve the quality of assembled genomes. However, both mate-pair libraries and the third-generation libraries require high-molecular-weight DNA, making the use of these libraries inappropriate for samples with only degraded DNA. An in silico method that generates mate-pair libraries using a reference genome was devised for the task of assembling target genomes. Although the contiguity and completeness of assembled genomes were significantly improved by this method, a high level of errors manifested in the assembly, further to which the methods for using reference genomes were not optimized. Here, we tested different strategies for using reference genomes to generate in silico mate-pairs. The results showed that using a closely related reference genome from the same genus was more effective than using divergent references. Conservation of in silico mate-pairs by comparing two references and using those to guide genome assembly reduced the number of misassemblies (18.6% – 46.1%) and increased the contiguity of assembled genomes (9.7% – 70.7%), while maintaining gene completeness at a level that was either similar or marginally lower than that obtained via the current method. Finally, we compared the optimized method with another reference-guided assembler, RaGOO. We found that RaGOO produced longer scaffolds (17.8 Mbp vs 3.0 Mbp), but resulted in a much higher misassembly rate (85.68%) than our optimized in silico mate-pair method.

Objectives. We sought to evaluate the ability of left atrial strain and derived index to discriminate patients with HFpEF from individuals with risk factors of HFpEF. Methods and results. A total of n=389 patients with risk factors for HFpEF finally was prospectively enrolled into the study, 51 of them were diagnosed with HFpEF by ESC diagnostic criteria. 55 patients were undergone left ventricular catheterization, 35 of them with LVEDP elevated. Left atrial strain was measured in all patients. Compared patients without HFpEF, LASr and LASr/(E/e’) was lower in HFpEF; E/LASr, LAVi/LASr and LVMI/LASrwas higher in patients with HFpEF. After adjusted for hypertension, diabetes, chronic kidney disease, LVEF and NT-proBNP, multivariate logistic regression analyses showed that LASr and derived indexes(E/LASr, LASr/(E/e’), LAVi/LASr and LVMI/LASr) were still the predictors of HFpEF in their respective models. LASr had good diagnostic accuracy for HFpEF. Of the left atrial strain derived parameters, LVMI/LASr was the best discriminatory ability for HFpEF (AUC 0.796, cutoff value 5.2, specificity 82%, sensitivity 73%). LASr, LASr/(E/e’), LAVi/LASr and LVMI/LASr with higher AUC was superior to conventional echocardiographic measures of diagnosing HFpEF. LASr and derived indexes were incorporated into the ESC diagnostic criteria, LASr-HFA-PEF score system (AUC=0.804) had a higher detection rate of LVEDP≥16mmHg than the HFA-PEF score system (AUC=0.781). Conclusion. LASr and derived indexes with good accuracy beyond conventional echocardiographic parameters discriminate HFpEF from patients with risk factors of HFpEF. LASr and derived indexes incorporated into the ESC diagnostic criteria will improve the diagnostic efficiency.

Objective: To identify the association between cervical length (CL) and gestational age at birth. Design: Prospective cohort study. Setting: Seventeen Brazilian reference hospitals. Population: A cohort of 3139 asymptomatic singleton pregnant women who participated in the screening phase of a Brazilian multicenter randomized controlled trial (P5 trial). Methods: Transvaginal ultrasound (TVU) to measure CL was performed from 18 to 22+6 weeks. Women with CL ≤ 30 mm received vaginal progesterone (200 mg/day) until 36 weeks’ gestation. Main Outcome Measures: Area under receive operating characteristic curve (AUC), sensitivity, specificity, Kaplan-Meier curves for preterm birth (PTB), number needed to screen (NNS). Results: CL ≤25mm was associated with extremely severe, severe, moderate and late PTB, whereas a CL 25–30mm was directly associated with late sPTB. The AUC to predict sPTB<28 weeks was 0.82 and for sPTB<34 weeks was 0.67. Almost half of the sPTB occurred in nulliparous women and CL ≤30mm was associated with sPTB <37 weeks (OR = 7.84; 95%CI = 5.5–11.1). The NNS to detect one sPTB <34 weeks in women with CL ≤25mm is 121 and 248 screening tests are necessary to prevent one sPTB <34 weeks using vaginal progesterone prophylaxis. Conclusions: CL measured by TVU is associated with sPTB <34 weeks. Women with CL ≤30mm are at increased risk for late sPTB. Funding: Bill & Melinda Gates Foundation [OPP1107597], the Brazilian Ministry of Health, and the Brazilian National Council for Scientific and Technological Development (CNPq) [401615/20138]. Keywords: cervical length; number needed to screen; preterm birth; short cervix.

Background: The COVID-19 pandemic has highlighted the need for targeted local interventions given substantial heterogeneity within cities and counties. Publicly available case data are typically aggregated to the city or county level to protect patient privacy, but more granular data are necessary to identify and act upon community-level risk factors that can change over time. Methods: Individual COVID-19 case and mortality data from Massachusetts were geocoded to residential addresses and aggregated into two time periods: “Phase 1” (March–June 2020) and “Phase 2” (September 2020–February 2021). Institutional cases associated with long-term care facilities, prisons, or homeless shelters were identified using address data and modeled separately. Census tract sociodemographic and occupational predictors were drawn from the 2015-2019 American Community Survey. We used mixed-effects negative binomial regression to estimate incidence rate ratios (IRRs), accounting for town-level spatial autocorrelation. Results: Case incidence was elevated in census tracts with higher proportions of Black and Latinx residents, with larger associations in Phase 1 than Phase 2. Case incidence associated with proportion of essential workers was similarly elevated in both Phases. Mortality IRRs had differing patterns from case IRRs, decreasing less substantially between Phases for Black and Latinx populations and increasing between Phases for proportion of essential workers. Mortality models excluding institutional cases yielded stronger associations for age, race/ethnicity, and essential worker status. Conclusions: Geocoded home address data can allow for nuanced analyses of community disease patterns, identification of high-risk subgroups, and exclusion of institutional cases to comprehensively reflect community risk.

Litter decomposition is a critical component of the ecological nutritional transformation process. It is particularly important to investigate characteristics and interactions of bacterial communities in litter decomposition in heavy metal polluted degrade areas, which will help clarify driving mechanisms of organic matter and nutrient cycling in mining areas that harbor contaminated soil. Imperata cylindrical was the dominant plant species in the degrade area investigated; thus, we selected this species as research object. Here we explore bacterial community characteristics and key microbial groups as well as driving factors of litter decomposition using in-situ litter decomposition experiments. The nutrient content of I. cylindrica decreased, while the litter pH status increased as decomposition progressed in one of the three sub-dams investigated (i.e., S516). Proteobacteria and Actinobacteriota were the dominant bacterial phyla during the different litter decomposition stages. Moreover, the role of Friedmanniella was critical in sustaining both structure and function of the bacterial community during the early decomposition stage. Quadrisphaera became the dominant species as litter decomposition progressed. Litter properties and enzyme activities both had significant effects on litter bacterial community characteristics, whose driving factors varied during different restoration stages. The bacterial community dynamics of litter were affected primarily by litter properties during the decomposition process. Furthermore, the most crucial factors that impacted bacterial litter structure were pH and copper content. Findings will help to deepen our understanding of litter decomposition mechanisms in degraded ecosystems, while also providing a scientific basis for improving effectiveness of material circulation and nutrient transformation in degrade ecosystems.

What can be seen from the case report by Verzelloni et al. has a double value, beyond the case itself. First of all, the use of platelet aggregation assessment tests, such as TEG-PM, allows clinicians to verify the exact timing between the suspension of thienopyridines and the possibility of surgery without further temporal delays and is also able to favor the evolution of ischemic problems or hemodynamic instability not easily treatable. It therefore allows clinicians to optimize the bleeding / thrombosis matching. Secondly, the use of point of care methodologies for the evaluation of platelet aggregation allows us to evaluate the adequacy of the anti-aggregation, facilitating, where resistance or percentages of anti-aggregation are lower than expected, modification of the therapeutic regimen.

Accurate runoff simulation is of great importance to understand watershed hydrologic cycle process, effective utilize water resources and respond flood disaster. Hydrologic model is one of the main tools for runoff simulation research and the continuous improvement in Machine Learning offers powerful tools for modeling of hydrologic process. This research took the runoff process of the Atsuma River basin in Hokkaido from 2015 to 2019 as object, proposed a special machine learning framework: Long-and Short-term Time-series Network (LSTNet) for runoff simulation, discussed the accuracy for runoff simulation of LSTNet model with (multivariate LSTNet Model) or without (univariate LSTNet Model) meteorological factors and Soil and Water Assessment Tool (SWAT) model respectively, analyzed the model selection for runoff simulation under different data conditions in the basin. The Nash-Sutcliffe efficiency coefficients (NSE) of the runoff simulation results in the validation (test) period were 0.633 (SWAT model), 0.643 (multivariate LSTNet model), and 0.716 (univariate LSTNet model) respectively. The results show that the accuracies of the two models for runoff simulation in the Atsuma River basin are all very high. SWAT model has prominent advantages in runoff simulation and shortcomings. LSTNet model shows great advantages and potential in runoff simulation. In summary, when target basin’ s data is accurate and complete, the accuracy of SWAT model in runoff simulation is high and stable. When the target basin lacks data or the quality of data is poor, LSTNet model can realize high-precision runoff simulation only based on the measured runoff data, which has a strong application.

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 15% of all newly diagnosed ALL in children and adolescents and is associated with worse outcomes compared to pre-B ALL. We aimed to decrease T-ALL relapses by intensifying our regimen. Methods: Patients with T-ALL were treated using two different regimens; before September 2014, patients were treated per St. Jude Total XV protocol; subsequently, a major change was adopted by adding two intensive blocks: FLAG and Re-Intensification (fludarabine, dexamethasone, cytarabine, etoposide and asparaginase). Cranial radiation was limited to patients with WBC >=100k/µl at diagnosis and/or patients with CNS2/CNS3 status. Results: Between June 2005 and April 2020, a total of 100 patients (76 males) were treated and followed for a median of 70 months (range, 14-181 months). Median age at diagnosis was 9 years (range,0.5-17.8 years). Forty-eight patients were diagnosed after September 2014 and received the augmented regimen; their median follow up was 46 months (range,14-74 months). The 5-yr-EFS estimates for patients who received the augmented regimen vs. standard regimen were 87%±4.9% vs 67%±6.8% (p=0.03); and the 5-yr-OS estimates were 87%±5.1% vs. 71%±6.3% (p=0.06) respectively. Treatment related mortality (TRM) were reported in 2 patients treated using our standard regimen but none for patients who received the augmented regimen. Conclusions: We implemented a novel approach with early intensification added to a backbone of modified St. Jude Total-XV regimen for patients with T-ALL that resulted in improved outcome with no treatment related mortality.

Corticosteroids and L-asparaginase used in the treatment of pediatric acute lymphoblastic leukemia (ALL) results in Drug induced Diabetes Mellitus (DIDM). Literature on the management of DIDM among children with ALL is sparse and the diagnostic criteria for pediatric diabetes should be carefully applied considering the acute and transient nature of DIDM during ALL therapy. Insulin remains the standard of care for DIDM management and the choice of Insulin regimen (standalone Neutral Protamine Hagedorn (NPH) or basal bolus) should be based on the type and dose of steroids used for ALL and the pattern of hyperglycemia. A modest glycemic control (140-180 mg/dl) to achieve euglycemia and prevent hypoglycemia would be the general approach. This review is intended to suggest a evidence based practical guidance in the diagnosis and management of DIDM during pediatric ALL therapy.

Background and aims: The COVID-19 pandemic caused a dramatic shift in the provision of cardiac surgical services in the United Kingdom (UK) with all elective surgery suspended. We sought to explore referral patterns, changes in clinical decision making and resource allocation to adult cardiac surgical services in the UK during the first wave of the pandemic. Methods: Data from 11 UK centres on referrals and available health resources (operating theatre and bed capacity) for urgent or emergency adult cardiac surgery between the 1st March 2020 and the 1st August 2020 was collated, and securely transferred to the lead centre for analysis. Results: 1113 patients were referred for cardiac surgery over the study period. Following UK lockdown in March 2020 the number of referrals initially fell to 39% of pre-lockdown levels before recovering to 211% of that seen prior to the pandemic. A change in treatment strategies was observed with a trend towards deferring surgery entirely or favouring less invasive, non-surgical treatments. At the peak of the pandemic in April 2020, theatre availability and bed capacity fell to 26% and 54% of pre-lockdown levels, respectively. Provision for emergency surgery was maintained throughout at 1 to 2 emergency lists per unit weekly. Conclusion: During the first wave of the UK COVID-19 pandemic cardiac surgical operative activity dropped acutely before increasing over the next four months. Despite this drop, provision for emergency surgery was retained throughout. In the event of further waves of COVID-19 pandemic, maintaining essential cardiac surgical services should be prioritised.