Objective: To describe opioid prescribing patterns following cesarean section before and after the New York State Department of Health (NYSDOH) mandated the Opioid Prescriber Training Program. Design: This is a retrospective cohort study. Setting: A single hospital institution in New York City, United States. Sample: 1,494 women hospitalized for cesarean section between July 2016 and August 2018. Methods: Chart review of patient records. Main Outcome Measures: Primary outcome was total amount of narcotic prescribed before and after the Opioid Prescriber Training. Secondary outcomes included outpatient opioid prescription habits by provider level, as well as outpatient opioid prescription patterns related to the amount of inpatient narcotic use, and patient, surgical, and hospital-specific factors. Results: There was a significant difference in narcotics prescribed before and after the training. The median dose of narcotic prescribed pre and post intervention was 150 morphine milligram equivalents (MME) which is equal to 20 pills of 5 mg of oxycodone. Pre-training, 41.1% of prescriptions amounted to >150 MME, compared with 21.3% post-training (p-value for association < 0.001). Post-training, all provider levels had reduced narcotic prescriptions in the category of >150 MME. Neither inpatient opioid use, patient demographic, surgical nor hospital factors affected opioid prescriber patterns. Conclusion: This suggests the NYSDOH mandated opioid training course had an effect on opioid prescribing patterns with the greatest impact noted in residents. Funding: None. Keywords: discharge prescriptions, obstetric narcotics, opioid training, post-cesarean narcotics.

Presented is a 62-year-old woman with poorly differentiated adenocarcinoma of the cecum with an ulcerative right breast metastasis. Although extramammary metastases to the breast are rare and difficult to diagnose, our multidisciplinary workup utilizing clinical history, radiographic, and pathologic findings allowed for accurate identification of tumor origin.

Dear Editor,SARS-CoV-2 (COVID-19) is responsible for the current global pandemic. At the date, no antivirals directed against the virus or effective vaccines are available. (1) It is essential to recognise the risk factors and components that may play a protective role. There is no clear evidence on the correlation between changes in the Renin-angiotensin system (RAS) by ACE-is, ARB or DRis and COVID-19 infection.(2) (3) (4) Randomised controlled trials are needed to verify the involvement of COVID-19 viral infection and chronic treatment with these drugs. A possible scientific hypothesis to investigate is the role of the neprilisin inhibitor Sacubitril in association with valsartan in the more severe stages of COVID-19 infection. The challenge to defeat the current pandemic poses several objectives, among them try to give added values to therapeutic solutions, in this direction the association sacubitril/valsartan has already demonstrated the therapeutic efficacy in the treatment of chronic symptomatic heart failure with reduced ejection fraction in several studies (5), indirectly the therapeutic benefits of cardiovascular type are also directed to a decrease in the risk of infection and complications from COVID-19. Furthermore, there is evidence of a significant increase in NT-proBNP in COVID-19 patients. (6) Studies show that higher NT-proBNP was an independent risk factor for death in patients with severe COVID-19, (7) moreover, NT-proBNP is associated with proinflammatory effects. (8) (9) Sacubitril through its mechanism of action increases neprylisin-degraded peptides, such as natriuretic peptides (NP), ANP and BNP, (10) evidence associates these peptides with anti antiflammatory, antihypertrophic and antifibrotic effects, recent evidence shows that IL-1𝛽 secretion is strongly inhibited by the BNP/NPR-1/cGMP axis to all molecular mechanisms closely controlling its production and release, NF-kB, ERK 1/2, and all elements of the NALP3/ASC/Caspase-1 inflammasomic cascade, and that NALP3 inflammatory inhibition is directly related to the deregulatory effect of BNP on the activation of NF-kB/ERK ½,(11) also the decrease of NT-proBNP by Sacubitril is known. Valsartan in association, by blocking the AT-1r receptor of ang II, decreases profibrotic and proinflammatory activity mediated by AT-1r, and indirectly increases the action of ang II on AT-2r with antifibrotic, antifibrotic effects. Based on the evidence and in relation to our generated hypothesis, we believe that a use of sacubitril/valsartan in the most severe stages of COVID-19 infection could have therapeutic efficacy, with anti-inflammatory and antifibrotic effects mediated by natriuretic peptides. Clinical studies are required to confirm this hypothesis.

Covid-19 with its associated complications of overt disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS) and multi organ failure have collectively become the end point of disease course. This case series provides an insight on the fulminant disease course and the management challenges faced.

A 23-year-old gentleman came to Emergency Department with first episode of sudden collapse. He had a right pelvic Ewing's sarcoma surgically resected 6 years ago. MRI of the head demonstrated a lesion in right temporal lobe, extending into infratemporal fossa. He was referred to oncology for further management with chemotherapy.

Α 59-year-old female presented to our hospital with epigastric pain. A computed tomography scan of the abdomen revealed a foreign body in the head of pancreas. A laparoscopic surgery was performed and the foreign body was safely removed. The foreign body was identified as a 3-cm-long fish bone.

Background and Aim: Acute gastrointestinal system (A-GIS) hemorrhages are frequent. Anemia is frequently seen in these patients at the discharge from the hospital. The anemia prevalence and approach to the anemia in patients with A-GIS bleeding at the time of discharge and during 3 months’ follow-up has been evaluated in this study. Method: In this study 197 patients diagnosed A-GIS bleeding in our hospital between January 2017 –May 2018 have been evaluated retrospectively. Results: In 129 of these patients upper gastrointestinal endoscopy, in 3 of them enteroscopy, in 45 of them lower gastrointestinal endoscopy, in 8 of them both upper and lower gastrointestinal endoscopy, in 2 of them upper, middle and lower gastrointestinal endoscopies were applied and 10 patients didnt performed endoscopy. In 69 of these patients therapeutic endoscopic treatments were applied. The mean of the length of hospitalization was 10±13.84 day and 67% of patients had erythrocyte transfusion with a mean value of 3.5±5.89 units during hospitalization. The mean of hemoglobin rate was 9.85±1.67 g/dL at the time of discharge from the hospital. In 92.4 % of the patients (F 91.1%, M 93.2%; upper GI bleeding 93.9%, middle GI bleeding 100%, lower GI bleeding 86.8%) anemia was detected at the time of the discharge. In 9.7% of these patients, iron deficiency treatment were applied. 33% of all 197 patients were evaluated 3 months after discharge from the hospital and in 80 % of these patients had still ongoing anemia. Conclusion: Anemia frequency is high when the patients with A-GIS bleeding are discharged. Most patients are discharged without receiving a prescription for the anemia. In follow-up, control applications are inadequate and anemia persists in patients

Background: Epidemiological studies show that BCG vaccinated population seems to be more likely protected from COVID-19 infection, but WHO gave a stark warning on use of BCG vaccine without confirmed COVID-19 trials. The aim of this survey is to assess the ability and readiness to respond to viral infection by physicians who had been BCG vaccinated. Methods: After Ethical Committee authorization, professional orders were used to contact physicians with an online survey. Specialty, COVID-19 infection, and previous BCG vaccination were recorded. Statistical data analysis was performed. Results: 1906 medicals answered the questionnaire, (M=1068; F=838; mean age 50.7+/-13.3; >24<87 yrs), more than half (1062; 55.72 %) experienced BCG vaccination. Professional activity was recorded, and only 49 subjects (2.57%) of them was infected by SARS-CoV2. Among the group of infected people, asymptomatic form occurred in 12 subjects (24.5%); a pauci-symptomatic form in 24 subjects (49.0%); a severe form (pneumonia and/or respiratory distress) in 13 (26.5%). SARS-CoV2 infection rate was 2.17% (23/1062) in vaccinated group and 1.66 % (14/844) in unvaccinated group (p=0.359). Conclusion: Our experience does not confirm the possible protective role of BCG against COVID-19, pending ongoing controlled trials. Although recent epidemiological studies point out in BCG vaccinated population a lower prevalence of SARS-CoV2 infection, in our cohort of physicians no significant difference was found in terms of prevalence of COVID-19 infection. Our data underline the necessity to follow the WHO warning about indiscriminate use of BCG vaccine, until clear evidence of protection by BCG vaccination against COVID-19 is fully demonstrated.

Background Two studies examining the association between maternal diet inflammatory indices (DII) during pregnancy and offspring asthma and/or wheeze have shown either no effect, or increased risk. Neither study investigated a biological pathway for the association. We examined the association between maternal DII and risk of offspring asthma and/or wheeze, and sought to determine whether cord sera cytokines/chemokines might connect maternal DII with offspring risk. Methods Analysis included 1228 dyads in Healthy Start, a prospective prebirth cohort from Colorado. DII scores were computed for each mother based on repeated 24-hour dietary recalls during pregnancy. Child diagnosis of asthma and/or wheeze up to four years was obtained from electronic medical records. For a subset of participants, cord sera was analyzed for five cytokines and two chemokines. Results Unadjusted analyses showed positive association between maternal DII scores and child asthma and/or wheeze by 4 years (OR = 1.17; 95% CI: 1.07, 1.27), but the association was attenuated and no longer significant in adjusted models (OR = 1.13; 95% CI: 0.99, 1.28). There were no significant associations between cord sera cytokines/chemokines and child asthma and/or wheeze. There were no significant assocations between DII scores and any cytokine or chemokine measured. Conclusion Our study showed that the inflammatory profile of the maternal diet was not significantly associated with offspring asthma and/or wheeze or cord sera cytokines and chemokines. Although the maternal diet in pregnancy seems an obvious biological target for asthma and/or wheeze prevention, factors other than the inflammatory profile need to be investigated.

Headcut erosion is usually associated with the consumption and transformation of flow energy that occurs when runoff is used to transport sediment. Therefore, flow energy variations in the headcut erosion process are critical in the loess gully region of the Loess Plateau. The aim of this study was to clarify the effects of the flow discharge and slope gradient on flow energy and the response of the headcut erosion process in the gully region of the Loess Plateau. This study examined the headcut erosion process using slope gradients ranging from 1° to 7° in the upstream catchment area and downstream gully bed and inflow discharges ranging from 3.6 to 7.2 m3·h-1. The results showed that the slope gradient has a significant impact on the potential energy in the upstream catchment area; thus, changes in the slope gradients produced changes in the sediment yield. Moreover, the flow discharge significantly influenced not only the potential energy but also the kinetic energy in the upstream catchment area and downstream gully bed. The kinetic energy at the downstream gully bed was 0.03~0.16 J·s-1 lower than that in the upstream catchment area due to the flow drop at the gully head. Greater energy consumption occurred at the gully head than in the upstream catchment area and downstream gully bed, and the gully head contribution to the flow energy consumption was 44.30~64.29%, which increased with increasing flow discharge and decreasing slope gradient. The influence of the slope gradient on the sediment yield was more significant than that of the flow discharge, and a nonlinear regression equation was developed to estimate sediment the yield. The flow energy consumption was significantly correlated with the sediment yield. These findings could improve our understanding of the flow energy characteristics and headcut evolution process during headcut erosion.

OverviewStudents will begin by exploring how germs spread from person to person.  They will investigate how hand washing and social distancing are effective ways to stop the spread of germs.  Students will use the engineering design process to create a hands-free soap dispenser.VocabularyGermVirusSocial DistancingObjectivesStudents will learn how properly washing your hands and practicing social distancing are effective ways to stop the spread of germs.Students will learn how to create a hands-free soap dispenser using PVC piping, hot glue, and string.MaterialsA Little SPOT Stays Home: A Story about Viruses and Safe Distancing by Diane AlberEngineering Design NotebookBottle of SoapPVC PipingStringHot Glue (used only by the teacher)Yard StickLessonPart 1: Germs and Viruses Overview (10 minutes)Ask students to define germs and viruses.  Respond to ideas and definitions and discuss ways we can stop the spread of germs and viruses.Read A Little SPOT Stays Home: A Story about Viruses and Safe Distancing by Diane Alber.  Ask students what they learned about germs, viruses, and social distancing.  As a class, define these vocabulary words in the students' own words.  Write these definitions on an anchor chart and refer to them throughout the lesson.Part 2: Design and Build Your Own Hands-Free Soap Dispenser (45 minutes)After handing out the engineering design notebooks, students will first work on their own to plan and draw their designs for the soap dispensers.  Students will then get into groups of 4 and discuss their designs and decide on the best path forward.Hand out PVC piping, string, measuring stick, and bottle of soap to each group to be used in the prototype design.  Inform students that hot glue is available upon request; the teacher will apply it per the group's instructions.Students will work together to create their soap dispenser prototype.  This will include building with the PVC piping, string, bottle of soap, and hot glue.  Students will use the yard stick to measure.  Students will update their plans and designs in their engineering design notebooks.Once the prototypes are complete, the testing process will begin.  Most students will use the PVC piping to create a foot-operated soap dispenser.  Students will test their prototypes and evaluate the results.  Results will be recorded in the engineering design notebooks.Students will be given the opportunity improve and redesign their prototypes as needed.  They will be given another opportunity to test their designs and see if the improvements worked.Part 3: Whole-Class Discussion (5 minutes)Which designs worked?  Why is a hands-free soap dispenser design so important?  Will this design help in the stop of spreading germs?  What other ways can we stop the spreading of germs?HomeworkResearch the following questions to discuss in class.How many germs are on your hands at any given time?How long should you wash your hands?How many germs are killed by washing your hands?

Background: Wheeze-associated disorders are common in childhood, associated with considerable morbidity, if not detected and treated. Under diagnosis of asthma remains a problem, especially in resource-limited settings. Methods: We used a validated school-based screening questionnaire to detect children likely to have asthma. Children with positive screening were referred to the Pulmonology Department for clinical review and lung function testing. We compared asthma-like symptoms, activity limitation, school absence and health service utilization before and after in those diagnosed with, and treated for asthma. Results: 6400 children, from a potential population of 70,000 were screened between 2010 and 2016, with 900 (14.1%) screening positive. Lung function data were available from 578 (64.2%) children (5.7 to 6.5 years old). Asthma was confirmed in 549 children; 438 were treated with short acting bronchodilator alone and 111 with inhaled corticosteroids. Asthma control improved in 58% of children, with fewer daytime [mean 4.7 (SD1.9), vs 11.1 (0.6) days per week, p<0.001] and nocturnal [4.3 (1.1) vs 0.89 (0.5) days per month, p<0.001] symptoms. Activity improved and fewer school days were lost due to asthma [12.8 (3.0) vs 1.9 (0.9) days in past 3 months, p<0.001] in over 50% of children. Emergency department visits were reduced [1.8 (0.7) vs 0.3 (0.2) visits in past 3 months, p<0.001] in over 80% of children. Conclusions: Asthma under diagnosis remains a problem in Argentina. Our school-based assessment is an effective tool for detecting children with undiagnosed asthma. Instituting effective asthma treatment in these children reduces symptoms and improves control.

Periodic breathing is indicative of immaturity of respiratory control and is well recognized within the normal limits in both full term and premature infants but unusual beyond infancy and at high altitude. We would like to focus on the importance of recognizing and scoring the pattern of periodic breathing in older children both clinically and in the sleep laboratory as an abnormal breathing pattern that should draw the attention of the treating physician into the possibility of hindbrain malformation or other significant pathology. Despite that sleep disordered breathing including central and obstructive apneas with or without hypoventilation are well reported as a manifestation of Chiari type I malformation, scoring periodic breathing pattern beyond infancy has not been an area of focus.

Objectives: The early diagnosis of pertussis is a public health issue, and there is a lack of sufficient lab testing. sTREM-1 has been found to be a potential specific marker for infectious diseases. This study aimed to evaluate the early diagnostic value of serum sTREM-1 to pertussis in infants. Methods: In patients with suspected pertussis, various potential indicators were evaluated, including serum sTREM-1, white blood cells, serum C reactive protein, and serum procalcitonin. Multiplex PCR of nasopharyngeal secretion was employed to identify B. pertussis, and bacterial cultures and viral antigen detection were performed. Cases in which the pathogen and various indicators were present were considered as pertussis. Cases were divided into two groups, the pertussis and non-pertussis groups, and then the indicator results were analyzed. Results: Seventy-eight infants with pertussis and 42 infants without pertussis were analyzed; there were no significant differences in terms of sex, age, onset time, feeding patterns, and location of residence. The difference in serum sTREM-1 levels between the pertussis group (238.99±71.95 pg/ml) and non-pertussis group (104.04±49.38 pg/ml) was statistically significant (t = 10.8482, P<0.05). Serum sTREM-1 had an AUC of 0.930, cutoff value of 142.5 pg/ml, sensitivity of 85.9%, and specificity of 83.3% (95% CI: 0.886–0.973, P<0.05). Lymphocyte proportion had an AUC of 0.871; however, white blood cells, C reactive protein, and procalcitonin had AUC values below 0.7. Conclusion: The detection of serum sTREM-1 may be useful for the early diagnosis of pertussis.

As the temperatures are projected to increase across the world due to global warming, heat stress (HS) is a major concern for all crop plants. We report here, a time-series transcriptome analysis of one Pigeonpea cultivar (Cajanus cajan) and two Crop Wild Relatives (CWRs), Cajanus acutifolius and Cajanus scarabaeoides under heat stress (HS) at 42±2ºC. A total of 9521, 12447, 5282 transcripts were identified to be differentially expressed in C. cajan, C. acutifolius and C. scarabaeoides respectively. In this study, we also examined alternative splicing (AS) during HS and revealed that a significant number of DEGs undergo AS in a species-specific pattern. Both transcriptome and qRT-PCR analysis showed that the HS caused the down-regulation of photosynthetically important genes such as Curvature Thylakoid protein, RuBisCO small chain, and NDH complex subunit; fatty acid modulating genes and up-regulation of defense mechanisms such as expression of HSPs and anti-oxidant enzymes in all Cajanus species. The results of histochemical assay showed higher lipid peroxidation in C. acutifolius inferring the presence of high quantity of PUFA in the plasma membrane which might have led to severe damage of membrane-bound organelles like chloroplast during HS, coupled by high electrolyte leakage during HS.

To the Editor,Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multisystem and often debilitating disorder of unknown etiology. (1) It is a complicated disease characterized by at least six months (in pediatrics 3 months) of extreme fatigue that is not alleviated by rest and a group of other symptoms that are constant for a period of time. (1)Post-exertional malaise (PEM) and delayed recovery are core symptoms and the most useful when making a diagnosis. (2) PEM involves a constellation of substantially disabling signs and symptoms that occur in response to physical, mental, emotional, and spiritual over-exertion. (2) The diagnosis of CFS/ME relies on the typical clinical presentation and the exclusion of other causes of fatigue. Up until now there was no test to confirm the diagnosis of CFS/ME. The two-day cardiopulmonary exercise testing (CPET) is becoming a new diagnostic method that can be used in case of suspicion of CFS/ME in attempt to evaluate presence of PEM. (4) This test, used in centres for patients with CFS/ME, has not yet published any data in pediatrics to support its use.We present a case of a 13-year-old patient with chronic debilitating fatigue who meets the criteria for CFS/ME. The patient was examined in detail by a pediatrician (anamnestic unclear cause, resting tachycardia in the physical examination, laboratory tests within normal limits), endocrinologist (normal hormonal profile for a given age, Tanner stage 3), infectologist (serology for typical viruses negative), psychologist (normal cognitive functions). For a history of resting tachycardia, the patient was examined by a cardiologist where no cardiogenic cause of fatigue was demonstrated, sinus tachycardia was present, and the patient was recommended head-up-tilt test, which showed the presence of postural orthostatic tachycardia. Due to the idiopathic nature of the difficulties and the excluded secondary cause, a two-day protocol examination by cardiopulmonary exercise testing was indicated. Written consent was taken and documented. Before the examination, we performed resting spirometry (physiological findings), resting ECG (sinus tachycardia) and a shortened Schellong test with a tachycardic response to orthostasis immediately after standing up and after 3 minutes of standing. Subsequently, standard CPET using treadmill (Itam, Poland) with individualized protocol with progressive increase in workload until exhaustion and breath-by-breath analysis of exhaled gases (Geratherm, Germany) was performed. On the first day, basal values were determined, the patient subjectively tolerated the examination well, the exercise ended prematurely due to subjective fatigue and a feeling of lack of air. On the second day, under the same conditions, the CPET was repeated, during which the patient also terminated the exercise prematurely but a half minute later than on the first day (exercise duration 6:32 min vs. 7:00 min; peak work rate 3,26W/kg vs. 3,68W/kg; peak VO2 34,5 ml/kg/min vs. 36,5 ml/kg/min). Using this methodology, patient did not meet diagnostic criteria for PEM and subsequently CFS/ME (decrease in monitored values on the second day of the examinations). In both days, during exercise, a bizarre pattern of respiration with malposition of the respiratory act to the large airways was observed by observing the flow-volume loop. Analysis of the respiratory pattern identified an erratic respiratory pattern (figure 1A) with low resting ETCO2 (26mmHg) and tachypnoea at maximal workload with dominant ventilation of dead space (figure 1B, 1C, 1G). The consequence of this pattern of respiration is a chronic state of hypocapnia and respiratory alkalosis, which is metabolically compensated in the patient. Fatigue and increased heart rate are expected clinical manifestations. Respiratory rehabilitation was recommended to the patient in order to fixate the correct breathing patterns (diaphragmatic breathing) and psychological guidance. The patient was subsequently retested 3 months after the start of physiotherapy and psychotherapy at the request of the parents. Retesting showed significant improvements in the monitored parameters (figure 1G) as well as in the clinical condition of the patient. The patient’s overall fitness increased, an adequate resting respiratory pattern was present (figure 1D), normal resting ETCO2 (36mmHg), ventilatory efficiency was adjusted (figure 1F, 1G), and the patient reported a subjective increase in energy. Prior to the examination, we performed a Schellong test on the patient, in which there were no signs of postural orthostatic tachycardia.Dysfunctional breathing (DB) is a condition of the airways characterized by an irregular breathing pattern and changes in the airways that cannot be attributed to a specific diagnosis and that causes respiratory and non-respiratory problems. (3) It is not a disease process, but rather changes in respiratory patterns that disrupt normal respiratory processes. However, DB can coexist with diseases such as bronchial asthma or heart disease. The main symptom is shortness of breath or air hunger, associated with non-respiratory symptoms such as dizziness, palpitations, cervical spine pain or fatigue. (5) It also plays a role in chronic fatigue, neck and back pain, fibromyalgia, and some aspects of anxiety and depression. (5)The most common type of DB is hyperventilation syndrome, which is defined as respiration exceeding metabolic requirements, reducing blood carbon dioxide concentrations below normal values. (3) This changes the pH of the blood, increases the alkalinity and thus triggers a number of adaptive changes that cause symptoms. These conditions are non-somatic in nature and their treatment consists of respiratory rehabilitation by various techniques (diaphragmatic breathing, Feldenkrais method, Buteyko method, Pilates) and psychotherapy in order to control impulsive changes in the respiratory pattern in various situations. (5)CPET confirmed the presence of DB in the patient based on the low resting value of ETCO2, the presence of a chaotic pattern of respiration during resting and exercise with the presence of tachypnoea (with very low ventilatory efficiency) in maximal exertion. Diagnosis of DB using CPET is one of the methods of DB diagnostics. Proper respiratory rehabilitation and psychological guidance resulted in the patient fixing the respiratory pattern and subsequently eliminating the primary cause of the examination - chronic fatigue. Patients with CFS/ME are a common pediatric problem. The current possibilities of diagnostics are enriched by the possibility of performing CPET which can be a benefit in differential diagnostics as well as in confirming the diagnosis.

Abstract.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a rescue strategy for non-responders to conventional CPR (CCPR) in cardiac arrest. Definitive guidelines for ECPR deployment do not exist. Prior studies suggest that arrest rhythm and cardiac origin of arrest may be variables used to assess candidacy for ECPR. Aim: To describe a single center experience with ECPR and to assess associations between survival and physician-adjudicated origin of arrest and arrest rhythm. Methods: A retrospective review of all patients who underwent ECPR at a quaternary care center over a 7-year period was performed. Demographic and clinical characteristics were extracted from the medical record and used to adjudicate origin of cardiac arrest, etiology, rhythm, survival, and outcomes. Univariate analysis was performed to determine association of patient and arrest characteristics with survival. Results: Between 2010 and 2017, 47 cardiac arrest patients were initiated on extracorporeal membrane oxygenation (ECMO) at the time of active CPR. ECPR patient survival to hospital discharge was 25.5% (n=12). Twenty-six patients died on ECMO (55.3%) while 9 patients (19.1%) survived decannulation but died prior to discharge. Neither physician-adjudicated arrest rhythm nor underlying origin were significantly associated with survival to discharge, either alone or in combination. Younger age and arresting in the emergency department were significantly associated with survival. Nearly all survivors experienced myocardial recovery and left the hospital with a good neurological status. Conclusions: Arrest rhythm and etiology may be insufficient predictors of survival in ECPR utilization. Further studies are needed to determine evidenced based criteria for ECPR deployment.

Although most autoimmune diseases are considered to be CD4 T-cell or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab that is used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities, notably multiple sclerosis, where ofatumumab is in late stage development and ocrelizumab is approved for use. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of multiple sclerosis and COVID-19, it was hypothesised that whilst B-cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B-cell subset inhibition that controls multiple sclerosis and other autoimmunities, would not influence innate and CD8 T-cell responses, which are central to SARS-CoV-2 elimination, nor the hyper-coagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority (mortality rate n=~5/392) of SARS-CoV-2 infected, CD20-depleted people with multiple sclerosis have recovered. However, protective neutralising-antibody and vaccination responses are predicted to be blunted, until naïve B-cells repopulate, based on B-cell repopulation-kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose-interruption to maintain inflammatory disease control in MS and other autoimmune diseases, whilst allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available.

he genus Telestes comprises primarily freshwater fishes distributed mostly in the Mediterranean area. Recent investigation of the evolutionary history of this genus revealed that it originated in southern Europe, where the most ancient Telestes species are still present. Isolation of rivers in the karstic region facilitated allopatric speciation resulting in a high number of Telestes species and a great portion of endemics in freshwaters of Croatia and Bosnia and Herzegovina. Most of the endemic Telestes species have very small distribution areas, inhabiting a single river or few water bodies in a single karstic field, making them extremely vulnerable to all anthropogenic changes. In order to contribute to practical conservation of the endemic Telestes species through design of conservational measures that are likely to be the most effective in ensuring future viability and undisturbed evolutionary course of those species, we have investigated their population genetic structure and estimated their viabilities. Population viability analyses were carried out based on the current state of populations and their habitats, as well as recognized threats. Several scenarios included also potential threats. Our results show that invasive species pose the most dangerous threats to the future survival of the endemic Telestes species. Contrary to previous opinions that a reduced genetic diversity is characteristic for small populations, high intraspecific genetic diversity was revealed inside most of the investigated species, which might enable most of the populations to cope with future changes and mitigate negative effects.

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus. Data about clinical characteristics, genetics, access to diagnosis and treatment were collected from 2010 by the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in Minsk. A questionnaire about attacks, prophylactic (LTP) and on-demand therapy (ODT) was administered to patients. We identified 64 C1-INH-HAE patients belonging to 26 families, 27 (42.2%) of which were diagnosed in the last 3 years. The estimated minimal prevalence was 1:148000. Median age at diagnosis was 29 years, with diagnostic delay of 19 years. Thirty-eight patients answered a questionnaire about therapy. Twenty-seven patients underwent ODT: 9 (33.3%) with appropriate treatments, and 18 (66.7%) with inappropriate treatments. Nine patients used LTP with attenuated androgens and eleven recovered spontaneously. Thirty-two patients answered a questionnaire about attacks and triggers: 368 angioedema attacks were reported, with an average of 10 attacks per year. We found 24 different SERPING1 variants: 9 missenses, 6 in splice sites, 6 small deletions, 2 nonsense, 1 large deletion; 7 have not been previously described. De novo variants were found in 11 patients. C1-INH-HAE diagnosis and management in Belarus is improved as seen from the high number of new diagnosis in the last 3 years. Next steps will be to reduce the diagnostic delay and to promote the LTP and OTD.

Although vitiligo is a multifactorial skin disease, accumulating data have strongly indicated that melanocytes are ultimately destroyed by a cascade of autoimmune responses. Contrast to widely accepted T cell-based cellular immunity, the role of B cell-based humoral immunity in vitiligo remains elusive. The present study investigated the changes of distributions and fucntions of circulating B cells and Tfh cells in patients with active non-segmental vitiligo. Compared with HC, the antibody secreting B cells in circulation were statistically increased along with high positive ratio of melanocyte specific antibodies in sera of patients. Meanwhile, the proportion of circulating Tfh cells was significantly elevated concomitant with increased Tfh17 cells and reduced Tfh2 subgroup as well as unchanged Tfh1 cells. The levels of IL-10 and IgM were greatly decreased while no statistical changes were found in IL-21, total IgG, IgE and IgA concentrations in sera of patients. Besides, vitiligo-derived circulating Tfh cells presented enhancement in inducing IgG production. Our study shed light on B cell-based humoral immunity in the pathogenesis of vitiligo and indicated that altered Tfh cells favored the differentiation of antibody secreting B cells and production of melanocyte-specific autoantibodies that may contribute to further progression of vitiligo.

Immune response variations could define successful resistance to Hepatitis C Virus (HCV) infection. Toll-like receptors (TLR)-3 are innate detectors of dsRNA viruses while bacterial and viral unmethylated CpG motifs are recognized by TLR9. We previously reported that TLR3.rs3775290 “CC” genotype was associated with HCV chronicity, while TLR9 gene played no major role in this infection. This study identified the role of TLR3.rs3775290 (c.1377C/T), TLR9.rs5743836 (-1237T→C) and TLR9.rs352140 (G2848A) gene polymorphisms in predicting the outcome of HCV-specific cell-mediated immunity (CMI) among Egyptian healthcare workers (HCWs) and patients. We enrolled 546 subjects (409 HCWs and 137 patients) divided into four groups. Group1: 265 seronegative, aviraemic subjects; group2: 25 seronegative, viraemic subjects; group3: 87 subjects with spontaneously resolved HCV infection; and group4: 169 chronic HCV HCWs and patients. All subjects were genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis for the TLR3.rs3775290, TLR9.rs5743836 and TLR9.rs352140 SNPs. We, also, quantified HCV-specific CMI in 265 HCWs distributed among the four groups using an interferon gamma (IFN-γ) enzyme-linked immunospot (ELISpot) assay in response to nine HCV genotype 4a overlapping 15mer peptide pools covering the whole viral genome. No statistically significant difference was found between CMI responding subjects with different HCV states and TLR3.rs3775290 genotype or TLR9.rs352140. However, there was a significant relationship between the outcome of the HCV-specific CMI and the TLR9.rs5743836 genotype among the responding subjects (p=0.005) and the chronic HCV patients (p=0.044). In conclusion, TLR9.rs5743836 SNP; but not TLR3.rs3775290 or TLR9.rs352140 genotypes; could predict the outcome of HCV-specific CMI responses among genotype-4-infected Egyptians.

To understand the current situation of canine parvovirus (CPV) epidemic strains in Jilin Province and to analyze the molecular biological characteristics and genetic evolution of the epidemic strains, 44 fecal or intestinal tissue samples detected by canine parvovirus test strips in Changchun and Liaoyuan City, Jilin Province, from February 2018 to November 2019 were collected for cloning, sequencing and genetic evolution analysis of the gene encoding the virus structural protein VP2. The results showed that 44 of the 44 samples were CPV-2 positive by PCR, among which CPV-2c was the dominant variant (70.4%). In addition, new-CPV-2a (18.2%), new-CPV-2b (9.1%) and CPV-2 (2.3%) also existed. This is the highest frequency of CPV-2c subtypes observed in canine populations in Jilin Province so far. In addition to the substitutions of Ala5Gly, Phe267Tyr, Tyr324Ile, and Gln370Arg in the VP2 protein, a novel variant with an Arg481Lys mutation was observed in a CPV-2c strain. Hence, there is a subsequent need for further and extensive epidemiological investigation and eventual adaptation of current vaccines.