A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival ind ineffectiveness of current treatments across central nervous locations and molecular subgroups. Tryggve Lundar MD, PhD1,2, Bernt Johan Due-Tønnessen MD,PhD1Radec Fric MD,PhD1Department of Neurosurgery, Oslo University Hospital1and University of Oslo2Correponding author:Tryggve LundarDepartment of NeurosurgeryOslo University HospitalPostboks 4950 Nydalen, Oslo, NorwayEmail: tryggve.lundar@gmail.comTotal word count: 474Short running title: GTR can improve outcome after relapse of pediatric ependymomaKey words: Pediatric ependymoma, relapse, repeat surgical resection (GTR)Number of tables: 0Number of figures: 0Letter to the EditorPediatr Blood CancerDear Editor,RE: Ritzmann TA, Rogers HA, Paine SML, Storer LCD, Jacques TS, Chapman RJ, Ellison D, Donson AM, Foreman NK, Grundy RG.A retrospective analysis of recurrent pediatric ependymoma reveals extremely poor survival ind ineffectiveness of current treatments across central nervous locations and molecular subgroups.Pediatr Blood Cancer 2020;67:e28426https://doi.org/10.1002/pbc.28426Congratulations to the authors with their detailed analysis of further management and outcome in pediatric patients who experience recurrence within a few years after initial treatment for ependymomas.Initial treatment for posterior fossa ependymomas (PFE) is maximal surgical resection (Gross total resection-GTR; if possible) followed by local radiotherapy or chemotherapy in small children. For supratentorial ependymomas (STE) GTR is also recommended (if possible) with or without postoperative radiotherapy.The management at relapses is, however, without consensus. The authors confirm the grave prognosis for these children. In the beginning of the discussion they state: Although primary surgery and irradiation reduced relapse risk variability in different intracranial locations, once a patient recurred these interventions gave, at best, short-term benefits, confirming the need for better therapies.This of course true – better therapies are urgently needed. They point to the lack of consensus regarding treatment at relapse, but recent guidelines have recommended the use of reirradiation and further surgery. In the conclusion they underline that recurrent pediatric ependymoma is highly aggressive with extremely poor outcome.This negative statement, is to some extent, in conflict with the results given under 3.5.2. At relapse: GTR at first relapse was associated with sustained improved EFS (25% vs 0% 10-year survival).This statement is in accord with Vinchon et al1 : Total resection is the only curative treatment for RIE (recurrent intracranial ependymoma) and is often possible, especially when the initial resection was total.How often GTR is within reach at local relapes may be a difficult matter. We have, however, observed several patients who underwent GTR after recurrence, and are tumor-free today after many years of further follow-up(up to 27 years) without any additional treatment2. We recognize that these patients are few compared to the majority of pediatric ependymoma patients who do not grow-up to be well functioning adults. It is, however, important for these small patients and their caretakers to have a hope for cure even after relapse. The role of GTR if possible may be under-communicated.Kind regardsTryggve LundarBernt Johan Due-TønnessenRadek Fric

Abstract Background: Marfan syndrome (MFS) is a connective tissue disorder that can lead to aortic disease, arrhythmias and heart failure. Many centers are reluctant to offer orthotopic heart transplantation (OHT) for patients with MFS with concurrent aortic disease due to complexity of the surgery and perceived inferior results when compared to patients without MFS. Methods: We present a case of a patient with MFS with previous Bentall procedure who underwent successful OHT, accompanied by a literature review on OHT performed for patients with MFS. Results and Conclusions: Patients with MFS who underwent OHT had no difference in mortality compared to patients without MFS. Even though OHT is technically more challenging when combined with concurrent intervention for aortic disease, it should be considered as a life-saving operation for patients with MFS.

Abstract Objectives Meralgia paresthetica is a very rare sensory mononeuropathy of the lateral femoral cutaneous nerve (LFCN). The purpose of this study was to evaluate the outcomes and compare the results of ultrasound-guided corticosteroid injection and ultrasound-guided alcohol neurolysis in the treatment of meralgia paresthetica. Methods We performed a retrospective clinical study of 26 patients with a diagnosis of marelgia paresthetica with a duration of ≥10 months. The patients were divided into 2 groups, with the Group 1 receiving ultrasound-guided local corticosteroid injection and Group 2 receiving ultrasound-guided alcohol neurolysis to the entrapment site of the LFCN. Results The mean age of the patients in Group 1 was 42.2 years and in Group 2 was 40.8 years. The mean follow-up period of Group 1 was 28.7 months and Group 2 was 28.4 months. At the end of the follow-up period 9 patients in Group 1 and 10 patients in Group 2 declared full pain relief and improvement in cutaneous sensitivity. Conclusion Once meralgia paresthetica has persisted corticosteroid injection and alcohol neurolysis are both effective methods. Although the recurrence rates are higher in corticosteroid injection, both treatment methods decreased the pain and improved the patients’ satisfaction and long-term curative effect.

Background Transesophageal echocardiography (TEE) is variably performed before atrial fibrillation (AF) ablation to evaluate left atrial appendage (LAA) thrombus. We describe our experience with transitioning to the pre-ablation cardiac computed tomography (CT) approach for the assessment of LAA thrombus during the COVID-19 pandemic. Methods We studied consecutive patients undergoing AF ablation at our center. The study cohort was divided into pre- vs. post-COVID groups. The pre-COVID cohort included ablations performed during 1 year before the COVID-19 pandemic; pre-ablation TEE was used routinely to evaluate LAA thrombus in high-risk patients. Post-COVID cohort included ablations performed during the 1 year after the COVID-19 pandemic; pre-ablation CT was performed in all patients, with TEE performed only in patients with LAA thrombus by CT imaging. The demographics, clinical history, imaging, and ablation characteristics, and peri-procedural cerebrovascular events (CVE) were recorded. Results A total of 637 patients (pre-COVID n=424, post-COVID n=213) were studied. The mean age was 65.6  10.1 years in the total cohort, and the majority were men. There was a significant increase in pre-ablation CT imaging from pre to post-COVID cohort (74.8 vs. 93.9%, p=<0.01), with a significant reduction in TEEs (34.6 vs. 3.7%, p=<0.01). One patient in the post-COVID cohort developed CVE following negative pre-ablation CT. However, the incidence of peri-procedural CVE between both cohorts remained statistically unchanged (0 vs. 0.4%, p=0.33). Conclusion Implementation of pre ablation CT-only imaging strategy with selective use of TEE for LAA thrombus evaluation is not associated with increased CVE risk during the COVID- 19 pandemic.

Background: The marked heterogeneity in CF disease complicates selection of those most likely to benefit from existing or emergent treatments. Objective: We aimed to predict progression of bronchiectasis in preschool children with CF. Methods: Using data collected up to three years of age, in the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort study, clinical information, chest computed tomography (CT) scores and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5-6. Results: Follow-up at 5-6 years was available in 171 children. Bronchiectasis prevalence at 5-6 was 134/171 (78%) and median bronchiectasis score 3 (range 0-12). The internally validated multivariate model retained eight independent predictors accounting for 37% (Adjusted R2) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% CI 6.3-27) with a positive and negative predictive values of 80% (95%CI 72%-86%) and 77% (95% CI 69%-83%) respectively. Conclusion: Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high-risk patient selection for interventional trials. The unexplained variability in disease progression at individual patient level remains high, limiting the use of this model as a clinical prediction tool.

RORγt+Foxp3+ regulatory T (Treg) cells, known as T regulatory 17 cells (Tr17 cells), are a novel subset of Treg cells, which have the potential to regulate the development of experimental autoimmune encephalomyelitis (EAE) thorough a specific repression of T helper 17 (Th17) cell mediated inflammation. However, the function of Tr17 cells the development of other autoimmune diseases such as autoimmune arthritis remains unclear. Collagen induced arthritis (CIA) was found to be prolonged in Foxp3creRORγtfl/fl mice, in which Tr17 cells were deleted, compared with Foxp3wtRORγtfl/fl mice. Tr17 cells were significantly increased in ankle joints compared with draining lymph nodes after the onset of arthritis. CC chemokine receptor 6 (CCR6) was up-regulated on Tr17 cells compared to RORγt negative Treg cells. CD25, cytotoxic T-lymphocyte antigen 4 (CTLA-4), glucocorticoid-induced TNF-receptor (GITR), and inducible T-cell co-stimulator (ICOS) expression was also up-regulated on Tr17 cells compared to RORγt negative Treg cells. IL-10-producing cells and Blimp-1+ cells were increased in Tr17 cells compared to RORγt-Treg cells. Tr17-enriched Treg cells significantly suppressed proliferation of conventional T cells compared with CCR6-Treg cells. Tr17 cells increased during the clinical course of CIA and accumulated in inflamed joints. These cells expressed CD25, CTLA4, GITR, and ICOS molecules and up-regulated Blimp-1 and over-produced IL-10. Moreover, CCR6+ Treg cells significantly suppressed cell proliferation. Taken together, it appears that Tr17 cells play a crucial role in the regulation of autoimmune arthritis.

Background: Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung disease in children born prematurely. There is little information about the epidemiology and severity of BPD places with high altitude. This study aimed to evaluate the frequency of BPD severity levels and the associated risk factors with severity in a cohort of preterm newborns ≤34 weeks of gestational age born in Rionegro, Colombia Materials and methods: We carried out a retrospective analytical cohort of preterm newborns without major malformations from Rionegro, Colombia between 2011-2018 admitted to neonatal intensive unit at high altitude (2200m above sea level). The main outcomes were the incidence and severity of bronchopulmonary dysplasia. Results: The bronchopulmonary dysplasia incidence was 25.7% (95% CI, 21.6-29.9). Bronchopulmonary dysplasia was moderate in 62.1% of patients and severe in 26.7%. The most frequent complications were sepsis (62.1%), hyaline membrane disease (59.5%), and pneumonia (26.7%). After modeling regression analysis, and force in the model the variable gestational age at birth, the final variables associated with BPD severity levels were: duration of oxygen therapy and pulmonary hypertension. Conclusion: The incidence of BPD was higher and similar to cities with higher altitudes. In our population, the variables associated with BPD severity levels were: duration of oxygen therapy and pulmonary hypertension. It is necessary to increase the awareness of risk factors, the effect of clinical practices, and early recognition of bronchopulmonary dysplasia to reduce morbidity in patients with this pathology.

Salt stress affects stomatal behavior and photosynthesis, by a combination of osmotic and ionic components, but it is unknown how these components affect photosynthesis dynamics under fluctuating light. Tomato (Solanum lycopersicum) plants were grown using a reference nutrient solution (Control, EC: 2.3 dS m-1), the reference containing extra macronutrients (only osmotic effect; EC: 12.6 dS m-1), or the reference containing an additional 100 mM NaCl (osmotic and ionic effects; EC: 12.8 dS m-1). Steady-state and dynamic photosynthesis along with leaf biochemistry were characterized throughout leaf development. Osmotic effects resulted in increased leaf chlorophyll content per unit leaf area, induced stomatal closure along with rapid stomatal responses to changes in light intensity, and limited dynamic but not steady-state photosynthesis. Ionic effects were barely observed in plant growth and dynamic photosynthesis, but led to a reduction in leaf chlorophyll content and photosynthetic capacity in old leaves. Steady-state and dynamic photosynthesis traits decreased with leaf age, due to increases in stomatal and non-stomatal limitations. With increasing leaf age, rates of light-triggered stomatal movement decreased across treatments, which is more strongly for stomatal opening rather than closure. We conclude that osmotic effect strongly impacts dynamic stomatal and photosynthetic behavior under salt stress.

In the current paper, we present the most generalized variant of the Hilfer derivative so-called (k, Ψ)-Hilfer fractional derivative operator. The (k, Ψ)-Riemann-Liouville and (k, Ψ)-Caputo fractional derivatives are obtained as special case of (k, Ψ)-Hilfer fractional derivative. We demonstrate a few properties of (k, Ψ)-Riemann-Liouville fractional integral and derivative that expected to build up the calculus of (k, Ψ)-Hilfer fractional derivative operator. We present some significant outcomes about (k, Ψ)-Hilfer fractional derivative operator that require to derive the equivalent fractional integral equation to nonlinear (k, Ψ)-Hilfer fractional differential equation. We prove the existence and uniqueness for the solution of nonlinear (k, Ψ)-Hilfer fractional differential equation. In the conclusion section, we list the various k-fractional derivatives that are specific cases of (k, Ψ)-Hilfer fractional derivative.

Background: The benefits of perioperative mechanical circulatory support (MCS) in cardiac surgery patients are still uncertain. This study aims to review early outcomes of perioperative temporary MCS using the Impella device in cardiac surgery patients. Methods: Retrospective, single center analysis in cardiac surgery patients presenting with cardiogenic shock (CS) in whom Impella was used for perioperative temporary MCS, whether as single device therapy or as left ventricular (LV) venting strategy for concomitant extra corporeal membrane oxygenation (ECPELLA). Study outcomes were 30-day mortality and occurrence of complication composite outcome. Results: Between 2016 and 2019, a total of 33 consecutive patients were supported with Impella [single-device therapy in 19 (57.6%) patients and ECPELLA in 14 (42.4%) patients]. The 30-day mortality of Impella-alone and ECPELLA groups was 15.8% and 50.0% (P=0.03).The 30-day mortality according to pre-, intra- and postoperative implantation was 12.5%, 60.0% and 28.6% (P=0.04), and it was significantly lower in those patients in whom a left ventricular assist device was implanted in comparison to all other surgical procedures (P<0.01). The complication composite outcome occurred more frequently after axillary implantation in comparison to femoral Impella (P=0.05) due to higher stroke rates (P=0.03). Bleeding requiring surgical re-exploration was more frequent in the ECPELLA than in the Impella-alone group [1 (3.0%) vs 5 (15.1%);P=0.03]. Conclusions: Temporary MCS with Impella is associated with high complication and mortality rates. However, preoperative use of Impella as single-device temporary MCS is associated with lower mortality rates and is a reasonable alternative as bridge-to-decision strategy for acutely decompensated patients.

Background: Octogenarians are being increasingly referred for coronary artery bypass grafting (CABG). However, there is a paucity of studies reporting impact of choice of surgical revascularization strategy on in-hospital mortality and mid-term survival of octogenarians. We evaluated our institutional experience to determine the impact of off-pump and on-pump CABG on in-hospital mortality and mid-term survival of octogenarians. Methods: We retrospectively analysed prospectively collected data from the Patients Analysis and Tracking System database (Dendrite Clinical Systems, Oxford, UK) for all isolated first-time CABG procedures with at least 2 grafts performed at our institution from January 2000 to September 2017. Over the study period, 566 octogenarians underwent either off-pump (N = 374) or on-pump CABG (N = 192). Short-term outcomes including in-hospital mortality as well as mid-term survival was compared for the two groups. Results: The two groups had similar preoperative demographics and mean number of distal anastomoses (off-pump: 2.7 ± 0.6 [median 3] vs on-pump: 2.7 ± 0.3 [median 3]; P=0.6). However, more bilateral internal mammary artery grafts were performed in the off-pump cohort compared to on-pump cohort (117 [31.3%] vs 22 [11.5%]; P <0.001). In-hospital mortality for the entire cohort was 5.7% with significantly fewer deaths in the off-pump cohort (4.3% vs 8.3%; P=0.04). The remaining in-hospital outcomes were similar. Kaplan-Meier survival at 1 year (89.7% vs 82.9%; P=0.048) and 5 year (71.1% vs 61.3%; P=0.038) was significantly better for the off-pump cohort. Conclusion: Octogenarians experience lower in-hospital mortality and improved mid-term survival after off-pump CABG compared to on-pump CABG.

A document by Andrea Amabile. Click on the document to view its contents.

Hereditary papillary renal cell carcinoma (HPRCC) is a rare inherited renal cancer syndrome characterized by bilateral and multifocal papillary type 1 renal tumors (PRCC1). Activating germline pathogenic variants of MET gene were identified in HPRCC families. We reviewed the medical and molecular records of a large French series of 158 patients screened for MET oncogenic variants (153 index-cases and five relatives). MET pathogenic variant rate was 10.4% (16/153) with 37.5% among patients with familial PRCC1 and 3.3% among patients with sporadic PRCC1 presentation. The phenotype in MET mutated cases was characteristic as PRCC1 tumors were mainly bilateral (82.3%) and multifocal (85.8%). Histologically, six out of seven patients with MET germline pathogenic variant harboured biphasic squamoid alveolar PRCC. Genetic screening identified in four index-cases a novel missense pathogenic variant within the tyrosine kinase domain: MET c.3389T>C, p.(Leu1130Ser). Functional assay confirmed its oncogenic effect with a constitutive phosphorylation of ERK protein and an abnormal focus formation induced. The genotype-phenotype correlation between MET pathogenic variants and PRCC1 presentation should encourage to widen the screening, especially toward non-familial PRCC1. This precise phenotype also constitutes a strong argument for the classification of novel missense variants within the tyrosine kinase domain when functional assays aren’t accessible.

In this paper, we consider the following p-Laplacian equation      −∆pu + |u|p−2u − λu = µ|u|q−2u + |u|p∗−2u, in RN, u > 0, ∫ RNu2dx = a2, where a,µ > 0, −∆pu = div(|∇u|p−2∇u),1 < p < N, λ ∈ R is an unknown parameter that appears as a Lagrange multiplier, p < q

Non recurrent laryngeal nerve (NRLN) is an extremely rare entity constantly associated with an aberrant right subclavian artery also called arteria lusoria. Knowing this association can help predicting a NRLN preoperatively and thus to prevent its injury. We present two patients in whome this association was proven.

Background: Data on influenza incidence during pregnancy in China are limited. Methods: From October 2015–September 2018, we conducted active surveillance for acute respiratory illness (ARI) among women during pregnancy. Nurses conducted twice weekly phone and text message follow-up upon enrollment until delivery to identify new episodes of ARI. Nasal and throat swabs were collected ≤10 days from illness onset to detect influenza. Results: In total, we enrolled 18,724 pregnant women median aged 28yo, 37% in first trimester, 48% in second trimester and 15% in third trimester, with 7 self-reported vaccination during pregnancy. In the 18-week epidemic period during October 2015–September 2016, influenza incidence was 0.7/100 person-months (95% CI:0.5–0.9). In the 29-week epidemic during October 2016–September 2017, influenza incidence was 1.0/100 person-months (95% CI:0.8–1.2). In the 11-week epidemic period during October 2017–September 2018, influenza incidence was 2.1/100 person-months (95% CI:1.9–2.4). Influenza incidence was similar by trimester. More than half of the total influenza illnesses had no elevated temperature and cough. Most influenza-associated ARIs were mild, and <5.1% required hospitalization. Conclusions: Influenza illness in all trimesters of pregnancy was common. These data may help inform decisions regarding the use of influenza vaccine to prevent influenza during pregnancy.

While there are several public repositories of biological sequence variation data and associated annotations, there is little open-source tooling designed specifically for the upkeep of local collections of variant data. Many clinics curate and maintain such local collections and are burdened by frequent changes in the representation of those variants and evolving interpretations of clinical significance. A dictionary of genetic variants from the Huntsman Cancer Institute was analyzed over a period of two years and used to inform the development of LocalVar. This tool is institution-agnostic and uses publicly available ClinVar files to provide the following functionality: auto-complete search bar to pre-empt duplicate entries; single or bulk new variant record entry; auto-detection and merge suggestions for duplicate variant records; auto-detection and merge suggestions for variant records with HGVS expressions that are marked as synonyms in ClinVar; asynchronous suggestion of HGVS expression or variant interpretation updates; history tracking of additions, merges, updates, or other manual edits made to variant records; and the easy export of the collection (.csv), edit history (.json), or HGVS synonym bins (.json).

Aim Rapidly changing climate is likely to modify the spatial distribution of both flora and fauna. Land use change continues to alter the availability and quality of habitat and further intensifies the effects of climate change on wildlife species. We used an ensemble modelling approach to predict changes in habitat suitability for an iconic wildlife species, greater one-horned rhinoceros due to the combined effects of climate and land use changes. Location Nepal. Methods We compiled an extensive database on current rhinoceros distribution and selected nine ecologically meaningful environmental variables for developing ensemble models of habitat suitability using seven different species distribution modelling techniques in the BIOMOD2 R package; and we did this under current climatic conditions and then projected them onto two possible climate scenarios (SSP1-2.6 and SSp5-8.5) and two different time frames (2050 and 2070). Results Out of seven algorithms, random forest performed the best, and four environmental variables — distance from grasslands, distance from wetlands, annual precipitation, and slope, contributed the most in the model. The ensemble model estimated the current suitable habitat of rhinoceros to be 1,875 km2, about 1.3% of the total area of Nepal. The future habitat suitability under the lowest and highest emission scenarios was estimated to be: (1) 1,637 km2 and 1,417 km2 in 2050; and (2) 1,562 km2 and 1,301 km2 in 2070, respectively. Main conclusions Our results suggest that nearly one-third of the current rhinoceros habitat would become unsuitable within a period of 50 years, with the predicted declines being influenced to a greater degree by climatic changes than land use changes. We have recommended several measures to moderate these impacts, including relocation of the proposed Nijgad International Airport given that a considerable portion of potential rhinoceros habitat will be lost if the airport is constructed on the currently proposed site.

Objectives: e-MEDRESP is a novel web-based tool that provides easily interpretable information on patient adherence to asthma/chronic obstructive pulmonary disease medications, using pharmacy claims data. This study investigated the feasibility of implementing e-MEDRESP in primary care. Materials and Methods: In this 16-month prospective cohort study, e-MEDRESP was integrated into electronic medical records. Nineteen family physicians and 346 of their patients were enrolled. Counters embedded in the tool tracked physician use during the follow-up. Patient/physician satisfaction with e-MEDRESP was evaluated though telephone interviews and online questionnaires. The capacity of e-MEDRESP to improve adherence was explored using a pre–post analysis. Results: Overall, 252 patients had at least one medical visit during follow-up. e-MEDRESP was consulted by 15 (79%) physicians for 85 (34%) patients during clinic visits. Seventy-three patients participated in telephone interviews; 84% reported discussing their medication use with their physician; 33% viewed their e-MEDRESP report and indicated that it was easy to interpret. The physicians reported that the tool facilitated their evaluation of their patients’ medication adherence (mean ± standard deviation rating: 4.8 ± 0.7, on a 5-point Likert scale). Although the pre–post analysis did not reveal improved adherence in the overall cohort, adherence improved significantly in patients whose adherence level was <80% and patients prescribed inhaled corticosteroids (26.9% [95% CI 14.3%–39.3%]) or long-acting muscarinic agents (26.4% [95% CI 12.4%–40.2%]). Conclusions: e-MEDRESP was successfully integrated in clinical practice. It could serve as a powerful tool to help physicians monitor their patients’ medication adherence.

Abstract The T.O.HO. scoring system was developed to predict stone-free status after flexible ureterenoscopy (fURS) lithotripsy applied for ureter and renal stones. This study aimed to perform the external validation of the T.O.HO. score in the Turkish population and propose a modification for this system. Material Methods Patients who underwent fURS for kidney and ureteral stones between January 2017 and January 2020 were retrospectively analyzed. The patient and stone characteristics and perioperative findings were noted. The T.O.HO. score was externally validated and compared with the STONE score. Stone-free parameters were evaluated with the multivariate analysis. Based on the results of this analysis, the T.O.HO. score was modified and internally validated. Results A total of 621 patients were included in the study. The stone-free rate was determined as 79.8% (496/621) after fURS. The regression analysis showed that stone area had better predictive power than stone diameter (p=0.025). Lower pole (reference), middle pole [odds ratio (OR)=0.492 p=0.016] and middle ureteral (OR=0.227, p=0.024) localizations, stone density (OR=1.001, p<0.001), and stone volume (OR = 1.008, p <0.001) were determined as independent predictive markers for stone-free status. Based on the effect size of the stone surface area in the nomogram, stone volume was divided into five categories, at 1-point intervals. The AUC values of the T.O.HO., STONE, and modified T.O.HO. score in predicting stone-free status were calculated as 0.758, 0.634, and 0.821, respectively. The modified T.O.HO. created by adding stone volume was statistically significantly superior to the original version (ROC curve comparison, p < 0.001). Conclusion The T.O.HO. score effectively predicted stone-free status after fURS. However, Modified T.O.HO. SS showed the best predictive performance compared with original T.O.HO. SS.

Aim: To investigate acute effects of add-on therapy with the sodium glucose co‐transporter 2 inhibitor tofogliflozin to dipeptidyl peptidase (DPP)-4 inhibitors on 24-hour glucose profile and glycemic variability evaluated by continuous glucose monitoring (CGM) in patients with type 2 diabetes. Patients and methods: We studied 17 patients with type 2 diabetes who were hospitalized for glycemic control. CGM was performed for 7 consecutive days in the last week of hospitalization. Tofogliflozin 20 mg/day was started on day 4 after initiating CGM and was administered to 10 patients receiving DPP-4 inhibitors and 7 patients not receiving DPP-4 inhibitors. We compared several CGM parameters between day 2 to 3 (ie, before treatment with tofogliflozin) and day 5 to 6 (ie, after starting treatment with tofogliflozin). Results: After starting treatment with tofogliflozin, mean 24-hour glucose and postprandial glucose after each meal were significantly decreased in both groups of patients. Time in range (ie, at a glucose level of 70-180 mg/dL) was significantly increased in both groups. The standard deviation of 24-hour glucose and mean amplitude of glycemic excursions, 2 indexes of glycemic variability, were significantly decreased in patients receiving DPP-4 inhibitors but were unchanged in those not receiving these drugs. Conclusions: Add-on therapy with tofogliflozin to DPP-4 inhibitors acutely reduces 24-hour glucose levels and improves glycemic variability in patients with type 2 diabetes.

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Introduction: Early prediction of return of spontaneous circulation (ROSC) for cardiac arrest (CA) patients is a major challenge. This study’s goal was to investigate the value of the carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels as a predictive marker for ROSC and prognostic marker for patients who achieve ROSC. Methods: A total of 241 adult patients (109 female, 132 male) diagnosed as non-traumatic CA were included in the study. The patients were divided into two groups based on whether they achieved ROSC. Complete blood count parameters, routine biochemistry measurements, coagulation parameters, and blood gas analysis, and cardiac markers values were compared between the groups. Results: COHb levels were significantly lower in the non-ROSC group (0.71 ± 0.57%) than in the ROSC group (0.95 ± 0.76%) and in the non-survival group (0.78 ± 0.53%) compared to the survivor group (1.45 ± 1.31%) (p =0.002, 0.022 respectively). There was no significant difference between the ROSC and non-ROSC groups and survivor group and non-survivor groups in terms of MetHb levels (p = 0.769 and 0.668, respectively). Conclusions: COHb levels in the blood gas analysis at the time of admission could be used as a predictive marker for ROSC and prognostic marker for the patients who achieved ROSC.

Structural variants (SVs) are large rearrangements (> 50 bp) within the genome that impact gene function and the content and structure of chromosomes. As a result, SVs are a significant source of functional genomic variation, i.e. variation at genomic regions underpinning phenotype differences, that can have large effects on individual and population fitness. While there are increasing opportunities to investigate functional genomic variation in threatened species via single nucleotide polymorphism (SNP) datasets, SVs remain understudied despite their potential influence on fitness traits of conservation interest. In this future-focused Opinion, we contend that characterizing SVs offers the conservation genomics community an exciting opportunity to complement SNP-based approaches to enhance species recovery. We also leverage the existing literature–predominantly in human health, agriculture and eco-evolutionary biology–to identify approaches for readily characterizing SVs and consider how integrating these into the conservation genomics toolbox may transform the way we manage some of the world’s most threatened species.