Covax-19/Spikogen: The first exclusively Australian-developed human vaccine in four decades

Introduction/Aim: The development of safe and effective vaccines is crucial to conquering the COVID-19 pandemic. Recombinant proteins represent the best understood and reliable approach to pandemic vaccine delivery with well-established safety;however, they face challenges in design, structural characterisation, manufacture, potency testing and ensuring adequate immunogenicity. Method(s): Our team used in silico structural modelling to design a vaccine based on a stabilised spike protein extracellular domain (ECD). The insect cell expressed recombinant spike ECD was formulated with Vaxine's proprietary Advax-CpG55.2 adjuvant. Result(s): The vaccine known as Covax-19 or SpikoGen induced high titers of antibody and memory T-cells which translated to protection against SARS-CoV-2 infection in hamsters, ferrets, and aged monkeys. Despite numerous challenges along the journey, clinical trials in Iran during a major wave of delta variant infection confirmed SpikoGen vaccine was 78% effective in reducing risk of severe disease and with no evidence of vaccine-associated thrombosis, myocarditis, or sudden death, receiving marketing approval under emergency use authorisation in Iran on 6 October 2021. This made it the first recombinant spike-protein vaccine in the world to be approved, and the first Australian-developed human vaccine to receive marketing approval in four decades. Since approval millions of doses have been administered and additional trials in Australia and Iran have confirmed its effectiveness as a booster to prevent waning immunity, as well as its safety and effectiveness in children from the age of 5 years. The ongoing Australian and overseas clinical trial program is focussed on gaining better understanding the effect of dosing intervals on vaccine immunogenicity, gathering additional data on use as a booster, and development of new variant formulations. Conclusion(s): Covax-19/Spikogen is safe and effective adjuvanted recombinant protein vaccine.

Novel Translational Animal Model Of Pediatric Viral Myocarditis

Myocarditis is a heart condition characterized by inflammation of cardiac myocytes. This inflammation is instigated by the activation of both the innate and acquired immune responses and is most often caused by viruses (flu, hand foot and mouth and COVID-19). Myocarditis may progress to dilated cardiomyopathy (DCM), a chronic heart condition in which fibrosis and remodeling weakens the ability of the heart to effectively pump. Myocarditis is a leading cause of sudden death in children and young adults. In this study, we investigated the progression and severity of myocarditis within the pediatric population as compared to an adult population. Prior to this study there were no mouse models for pediatric myocarditis but a large percent of patients with myocarditis are children. We utilized our knowledge from our adult mouse model of coxsackievirus B3 (CVB3) myocarditis to create a pediatric CVB3 myocarditis model in order to better understand the development of myocarditis in children. We hypothesized that myocarditis would have sex-specific differences in the manifestation and severity similar to the adult model but the mechanisms of disease would very between ages. We utilized 4-week-old male and female BALB/c mice to model pediatric myocarditis as compared to 8-week-old mice. Mice were be infected with heart-passaged CVB3 intraperitoneally (ip) on day (d) 0. Disease severity and progression was evaluated during acute myocarditis (d8-12 pi) and during DCM (d35pi). After anesthesia, body weight, heart weight and tibia length, blood, hearts, pancreas and spleens were harvested. Echocardiography was conducted on mice at the chronic DCM timepoint. We found that adult male and female mice develop myocarditis with male mice have more severe disease and progress to DCM as compared to female mice. The main immune cells and pathways involved in myocarditis severity were macrophages, complement and the inflammasome in male adult mice. This increase in disease was driven by testosterone and reduced by estrogen as seen utilizing gonadectomies. In the pediatric population we did not see as drastic of differences in sex hormone levels as the mice are pre-pubescent, this led to less dramatic sex differences in disease and altered immune mechanisms leading to disease in the pediatric population compared to the adults. We do see induction of myocarditis in both male and female pediatric mice compared to uninfected controls but severity in the pediatric population is less than adult population. Successful development of a pediatric translational mouse model of viral myocarditis will significantly impact the myocarditis field by allowing the ability to assess differences between pediatric and adult populations and develop targeted diagnostics and treatments.Copyright © 2022

COVID-19 and the autonomic nervous system

Background: COVID-19 infection has been shown to have an adverse impact on the cardiovascular system. Cardiac injury, as indicated by elevated cardiac troponin and NT-proBNP levels have been confirmed in COVID-19 cases. There is still ambivalent data on the effect of left ventricular function. Cases of left ventricular impairment, persistent hypotension, acute myopericarditis, myocarditis, arrhythmia and heart failure have been reported in the short term, but there is a significant lacuna when it comes to medium and long-term follow-up of subjects previously infected with COVID-19. Purpose(s): To assess any residual myocardial and autonomic injury in subjects previously infected with COVID-19 at a median follow-up of 5 months. Method(s): A case-control study was performed. Cases were randomly selected subjects who were previously diagnosed with COVID-19 infection following nasopharyngeal swabbing. Controls were subjects who had not been found to be infected with COVID-19 following swabbing and were negative for COVID-19 IgG antibodies. All participants were submitted a standardised questionnaire regarding past medical history. Blood investigations were taken including NT-proBNP and troponin I levels. In addition, all participants underwent 24-hour ambulatory blood pressure monitoring (ABPM) and 24-hour ECG monitoring. The latter was used to assess both for underlying arrhythmias as well as heart rate variability (HRV), a measure of autonomic regulation of the heart. All data was analysed using SPSS version 23.0. Result(s): The study comprised 259 subjects, whereby cases included 174 participants while 75 subjects were age- and gender-matched controls. The study cohort was relatively young with a mean age of 46.1+/-13.8 years. The median follow-up was of approximately 5 months (median 173.5 days, IQR 129-193.25 days). There was no statistically significant difference between cases and controls with regards cardiovascular risk factors and underlying medical conditions. Likewise, there was no difference in blood investigations, including troponin I and NT-proBNP levels at 5-months followup. No difference was noted between the two groups in both awake and asleep blood pressure (BP) readings, as well as dipping BP status. No significant arrhythmias were noted in both groups on 24-hour ECG monitoring. However, when assessing for heart rate variability, it was shown that subjects who had been previously infected with COVID-19 exhibited lower root-mean square differences of successive R-R intervals (RMSSD), p=0.028. This indicates poor vagus nerve-mediated autonomic control of the heart. Conclusion(s): Subjects previously infected with COVID-19 exhibited lower HRV as exhibited by low RMSSD as compared to controls. Reduced HRV is a known biomarker for mortality and sudden death in cardiac disease. The possible long-term implications of reduced HRV in subjects previously infected with COVID-19 merits further investigation.

Patients with Myositis Contract Sars-Cov2 Infection: Two Different Cases

Background. Mortality risk of the COVID-19 is marked elevated in high-risk patients. In our series of 78 patients with inflammatory myopathies (IIM), we documented two patients who died after being infected with SARS-CoV2: we here describe our experience in these unfortunate cases. Case 1: A 45-years-old Caucasian man was diagnosed with PM in 2012 and was treated with prednisone (PDN) associated with intravenous (IVIg) and subcutaneous (SCIg) immunoglobulin. In January 2020, when in remission with a low-dose PDN, he performed a routine control, including a completely negative echocardiogram. In March 2020, he presented with fever and headache from occult SARS-CoV2 infection. Although myositis was in remission, and home treatment had given him with paracetamol and NSAIDs, after two days he had a sudden death. The cause was an acute myocardial ischemia in COVID-19 interstitial pneumonia revealed by autopsy investigation. Case 2: An 87-years-old Caucasian woman came to our attention with severeonset PM in 2017. She responded well at treatment with high-dose IVIg, PDN and methotrexate. In April 2020, she presented with SARS-CoV2 infection, who slowly complicated with an interstitial lung disease until the death due to respiratory failure 25 days after the COVID-19 infection. Conclusions. The two cases are opposite: the man, who had an acute thrombotic event during SARS-CoV2 infection, was in remission since 2012 and he did not have comorbidities. Unlikely, the woman, who had respiratory failure, was a high-risk patient due to old age, high cardiovascular risk, chronic obstructive pulmonary disease (COPD) and intraductal papillary mucinous neoplasms.

Effects of COVID-19 infection on ECG parameters in outpatients

Objective: Covid-19 infection has been declared as a pandemic disease by the World Health Organization (WHO) and has been associated with increased morbidity and mortality. More than 400 million people diagnosed with the disease has been reported until February 2022 [1]. Covid-19 infection mostly progresses with lung involvement and pneumonia, however, its effects on the cardiovascular system are also well-known. Studies have reported that Covid 19 infection can trigger cardiac events such as acute myocardial damage, acute myocarditis, acute coronary syndrome (ACS), ventricular arrhythmias, cardiogenic shock, and cardiac arrest [2]. Electrocardiogram (ECG) is an important tool to diagnose cardiac involvement. QTc interval, QT dispersion, Tp-e interval, Tp-e/QTc ratio are defined as ventricular repolarization parameters and these parameters are associated with increased risk of ventricular arrhythmia [3,4]. In our study, we aimed to evaluate to predict ventricular arrhythmia by ECG in Covid-19 patients. Method(s): Our study is a single-center, cross-sectional study. Patients diagnosed with Covid-19 in our center between July and October 2020 were included. 408 patients with positive SARS-CoV2 PCR test were detected and the ECGs of the patients were recorded at admission and 15 days after symptomatic recovery. After the exclusion criteria, remained 91 patients were analyzed. Conduction parameters (PR and QRS durations) and repolarization parameters (QTc interval, QT dispersion, Tp-e interval and Tp-e/QTc ratio) were evaluated in 12-lead ECG recordings. Result(s): Ninety-one patients with Covid-19 infection were included. The group were consisted of 47 male (52%) and 44 female (48%). The mean age was 50.4 years. As a result of the statistical analysis, no significant difference was observed between the groups in terms of PR interval (142.2+/-21.4 ms vs. 140.1+/-19.0 ms;p=0.312). QRS duration was found significantly higher during active infection (91.4+/-12.2 ms vs. 88.8+/-10.9 ms;p=0.022). The mean QTc duration was detected longer in the first ECG, but no statistically significant difference was observed between the two groups (426.1+/-23.6 ms vs. 422.5+/-26.2 ms;p=0.237). QT dispersion (35.2+/-7.3 ms vs. 27.7+/-7.8 ms;p<0.001), Tp-e interval (86.7+/-10.1 ms vs. 76.1+/-9.9 ms;p<0.001) and Tp-e/QTc ratio (0.204+/-0.026 vs 0.180+/-0.025;p<0.001) were found significantly higher during active infection Conclusion(s): In our study, QRS complex, QT dispersion, Tp-e interval, Tpe/ QTc ratio were significantly higher during active infection. We considered these parameters as a contributor of the increased mortality by inducing ventricular arrhythmia and sudden death in Covid-19 patients during active infection.

Long-term safety of 3 years of ozanimod in moderately to severely active ulcerative colitis: an interim analysis of the True North open-label extension

Background: The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod in UC. This analysis evaluated the cumulative long-term safety of ozanimod in these studies, which included pts with up to ~3 years of treatment exposure. Method(s): In TN, pts were randomised to once-daily ozanimod 0.92 mg or placebo, or to open-label ozanimod for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo in the maintenance period through Week 52. TN pts were eligible to enrol in the OLE and receive ozanimod if they did not achieve clinical response at the end of induction (Week 10), lost response during maintenance, or completed maintenance at Week 52. This interim analysis of the TN OLE (data cutoff: 10 January 2022) included all pts who entered the OLE from TN (n=823). Safety was monitored from the first dose of ozanimod in TN and throughout the subsequent OLE. Exposureadjusted incidence rates per 100 patient-years (PY) were calculated. Result(s): The average age of TN OLE study participants was 41.7 years (+/-13.6), 41% were female, 62% had left-sided UC disease, and 35% had prior exposure to tumor necrosis factor inhibitors. Total PY exposure to ozanimod was 2219 years (mean [SD] exposure = 2.7 [1.6]). The most frequent treatment-emergent adverse events (TEAEs) reported through OLE Week 94 (up to 146 weeks of continuous treatment) are listed in the Table. Most TEAEs were nonserious;TEAEs leading to discontinuation were uncommon. Bradycardia was reported in 3 pts (0.4%;EAIR 0.1/100 PY;2 in TN and 1 in OLE;no pts were discontinued from treatment). Macular edema was reported in 2 (0.2%;EAIR 0.1/100 PY) pts. Reductions in ALC were common (470 [57.1%] had ALC < 500 cells/mm3), as previously described, but ALC reductions were not associated with the occurrence of TEAEs. Malignancies were uncommon (n=13 [1.6%];EAIR 0.6/100 PY), and included 6 basal cell carcinomas and 3 colorectal neoplasms. Two deaths were reported: 1 due to COVID-19 and 1 sudden death. Investigators deemed both to be unrelated to treatment. Ozanimod was not associated with an increased risk of ischemic heart disease or thromboembolic events. Conclusion(s): Long-term exposure to ozanimod for up to 3 years was well tolerated in pts with moderately to severely active UC. No new safety signals were observed with long-term ozanimod use in UC (2219 PY exposure). Safety findings are consistent with previous reports from the UC and multiple sclerosis development programs (>16,512 PY exposure). (Table Presented).

Phospholamban Mutation Leading to Recurrent Short-Coupled Polymorphic Ventricular Tachycardia and Fibrillation in Patient without Apparent Structural Heart Disease

Background Phospholamban (PLN), an inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, is a regulator of Ca2+ release during excitation-contraction coupling. We present a case of recurrent polymorphic ventricular tachycardia (PMVT)/ventricular fibrillation (VF) due to a PLN mutation. Case 38 year-old male presents after resuscitation following VF arrest. An ICD was implanted. Seven years later, he presented with VF storm requiring ventricular assist device support and he underwent catheter ablation of PVC triggers of VF arising from the moderator band. Because he had an ECG that was concerning for early repolarization syndrome, he was placed on quinidine and metoprolol. After an episode of VT in 2020 in the setting of COVID infection, whole genome sequencing was obtained and identified a pathogenic PLN mutation. PLN L39Ter has been associated with dilated and hypertrophic cardiomyopathy as well as sudden death. The patient has a history of normal left ventricular function and wall thickness by echocardiography. Decision-making Given the involvement of PLN on SR handling of Ca2+, flecainide may be a more effective therapy for the treatment of PMVT/VF in this patient. Conclusion PLN mutations have been associated with cardiomyopathies. This case illustrates a patient with the pathogenic PLN L39X variant with short-coupled PMVT with no imaging evidence of structural heart disease. Whether a more targeted therapy such as flecainide may be more effective in this patient remains to be determined. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

A case of fatal multi-organ inflammation following COVID-19 vaccination.

A 14-year-old Japanese girl died unexpectedly 2 days after receiving the third dose of the BNT1262b2 mRNA COVID-19 vaccine. Autopsy findings showed congestive edema of the lungs, T-cell lymphocytic and macrophage infiltration in the lungs, pericardium, and myocardium of the left atria and left ventricle, liver, kidneys, stomach, duodenum, bladder, and diaphragm. Since there was no preceding infection, allergy, or drug toxicity exposure, the patient was diagnosed with post-vaccination pneumonia, myopericarditis, hepatitis, nephritis, gastroenteritis, cystitis, and myositis. Although neither type of inflammation is fatal by itself, arrhythmia is reported to be the most common cause of death in patients with atrial myopericarditis. In the present case, arrhythmia of atrial origin was assumed as the cause of cardiac failure and death. In sudden post-vaccination deaths, aggressive autopsy systemic search and histological examination involving extensive sectioning of the heart, including the atrium, are indispensable.

Case report: Otitis media with subsequent mastoiditis and cerebral herniation in a patient with Arnold chiari malformation.

We present the case of a 13-year-old boy who unexpectedly needed to be resuscitated at home after an assumed uncomplicated otitis media. Imaging at our clinic showed mastoiditis and a cystoid mass in the left cerebellopontine angle compressing the brainstem, as well as an Arnold-Chiari-Malformation. Both the laboratory examination of cerebrospinal fluid (CSF) and surgical biopsy with pathological evaluation of the mastoid supported the inflammatory etiology of the mass. Microbiologically, Streptococcus intermedius was detected in the blood culture and CSF. Due to brain death, which most likely already existed preclinically, the organs were released for donation during the course. Our case demonstrates a very rare lethal complication of acute otitis media on the basis of a cerebral malformation and emphasizes the need to stay alert when patients complain of symptoms after assumed resolution.

Sudden death due to diffuse metastatic melanoma - a case report

Undiagnosed metastatic malignancy at autopsy is an uncommon finding in the younger age groups. Melanoma, however, is a common malignancy and early diagnosis is important for long term survival. We present a case of widely disseminated metastatic melanoma in a young Caucasian male, in his forties. He died suddenly and unexpectedly on his way to the hospital for ongoing lower back pain. The deceased had a three-month history of persistent back pain and ongoing purulent discharge from a wound on his arm. There was no history of neoplasia and the deceased had not been physically seen by a doctor due to the COVID-19 pandemic. On internal examination macroscopic tumour deposits were seen diffusely in the skin, muscle, bone, heart, lungs, and other major organs. Microscopic deposits of melanoma were seen in the brain and conduction system of the heart. We review the complications of metastatic melanoma as a cause of death and emphasise the importance of direct clinical care of patients during an ongoing pandemic. Copyright © 2022

Unmasked type I electrocardiographic pattern of Brugada syndrome after SARS COV-2 (COVID 19) vaccine shot: Is there any relationship with the suspected increased risk of sudden death?

The vaccination used for the prevention of COVID-19 could unmask patients with hidden Brugada syndrome even without febrile episodes. We described a case of unmasking or Brugada syndrome in a female patient after vaccination for COVID-19. A possible relationship with sudden death events requires further study. In people with known Brugada syndrome or in their relatives, we recommend serial electrocardiographic monitoring after the administration of the vaccination dose. Copyright © 2022 Heart, Vessels and Transplantation.

Pulmonary thromboembolism associated with coronavirus infection: A possible correlation-case series

We present a case series of patients with pulmonary embolism of unknown etiology who did not have any risk factors. According to the findings, the most likely cause of the pulmonary embolism was undiagnosed, asymptomatic, or mild Corona Virus disease-2019 (COVID-19) infections in the recent past. In the current post-pandemic era, where there has been a surge of sudden unexplained deaths and pulmonary embolism cases, this case series emphasizes the importance of pulmonary embolism evaluation in patients seeking medical care for dyspnea. Physicians should be aware of the possibility of pulmonary embolism as a late complication in patients with mild, asymptomatic, or undiagnosed COVID-19 infection. Copyright © the Author(s), 2022.

Sudden Death with Dual Organ Pathologies–An Autopsy-based Case Report

Sudden death due to cardiac cause is considered as a major health problem worldwide accounting for 15–20% of all deaths and cardiomyopathies account for 10–15% of the cases.According to the 2016 WHO classification, angiomatous meningioma is a rare subtype of meningioma classified as Grade I. It is an aggressive variety with a fair prognosis, with typical symptoms including headache and seizures. We present a case of a 60-year-old man brought to the morgue for autopsy with a history of progressive left-sided weakness and headache for several months with no prior diagnosis or treatment for the same because of current pandemic of COVID-19.On conducting medicolegal autopsy significant pathologies in heart and brain were found which could have contributed to the cause of death.

ACUTE MYOPERICARDITIS COMPLICATED WITH CARDIAC TAMPONADE IN COVID-19

CASE: 68yo Caucasian female with no significant cardiac history presented with worsening dyspnea and fatigue started around 7 days ago. She denied having any travel or known history of tuberculosis or any other autoimmune conditions. COVID RT-PCR test was positive on the day soon after admission. Initial vitals include SpO2 of 96% on 2L, BP 118/72 mmHg and HR in 110s/min Sinus. EKG revealed sinus tachycardia with non-specific ST-T changes. Labs showed c-reactive protein 2.0 mg/dl, ferritin 1061 ng/ml, LDH 300 EnzU/L;cardiac markers-troponin 212-261 ng/L and proBNP of 11,497 pg/mL. ECHO showed EF of 30-45% with global hypokinesis, and circumferential pericardial effusion with fibrinous strands. Within 48 hours, the patient sustained cardiac arrest with recurrent hemodynamically unstable tachyarrhythmia requiring multiple cardioversions. Repeat Bedside ECHO revealed larger effusion compared to prior, worrisome for cardiac tamponade. Emergent pericardiocentesis yielded 200ml of serous fluid improving the hemodynamics in form of improved SBP to 140mmHg from 70mmHg. Although this improvement appeared promising, it was only transient with rapid decline. Her ferritin levels went up 10-fold correlating with the worsening status. Her pressor requirement gradually worsened to the point of requiring IMPELLA, intercepting the initiation of RRT for acute renal failure. Unfortunately, with higher risk of poor outcome, the family opted to respect the patient's wishes and further care was withdrawn. IMPACT/DISCUSSION: As of January 2022, there have been close to 300 million confirmed COVID-19 cases all over the world. This ongoing pandemic disease, although primarily occur as respiratory illness, the florid symptoms with increasing mortality are due to its systemic inflammatory response causing multiorgan failure. Hence the symptoms can be anywhere from mild febrile illness to sudden death. As such, Cardiac involvement in form of Myo-pericarditis is less recognized in such scenario and often underestimated. The onset can vary as the primary presenting symptom to late presentation following respiratory course. While the association of pericarditis with COVID has been documented, the global presentation as Myo-pericarditis is still less known. Our case depicts one such occurrence where cardiac presentation is the key finding having led to poor prognosis more than the lung damage. The management is still the same using NSAIDs / Colchicine like any other type of pericarditis. If there were signs of cardiac tamponade, pericardiocentesis is warranted. In some cases, especially in the setting of recurrent effusions, pericardial window will be useful. CONCLUSION: Myo-pericarditis in COVID-19 can predispose to life threatening arrhythmias which would increase mortality. With the cytokine storm and inflammatory response associated with COVID being the primary offender, it can be challenging to treat them as any other type as the treatment should also focus on removal of inciting factors simultaneously.

On the issue of post COVID-19 condition in patients with rheumatic diseases

Actual problems of rheumatology include the possibility of developing a wide range of long-term consequences of COVID-19, so-called post-COVID syndrome (PCS). The results of our own research are presented, during which among 45 patients over 18 years with rheumatic diseases (RD) PCS was detected in 20% cases: 6 of them had ANCA-associated vasculitis (AAV) and one each for rheumatoid arthritis, juvenile arthritis and osteoarthritis. In AAV cases PCS was more severe and varied than in other RD: lung lesions according to computed tomography (up to the damage 75% of the lung parenchyma), skin and nervous (Guillain – Barré syndrome) lesions, myalgias, arthralgias were present. In most patients PCS ended in recovery, sudden death occurred only in the patient with AAV. The frequency of RD’s relapses in patients with PCS was 9%. Relapses were not noted in AAV, against the background of anti-B cell therapy with rituximab. Our own results and literature data indicate that patients with RD after COVID-19 need careful continuous monitoring to detect long-term complications of coronavirus infection and early diagnosis of relapses of the underlying disease.

Doctors With Borders: The Impact Of International Travel Bans on Timorese Citizens Awaiting Cardiac Intervention

Background: In Timor-Leste, cardiac interventions and surgical procedures are largely provided by the East Timor Hearts Fund. Since March 2020, no Timorese patients have been able to travel to Australia for humanitarian cardiac procedures. Methods: We describe patients awaiting cardiac intervention as of March 2020, documenting their outcomes eighteen months later in August 2021. Contact with healthcare facilities (the national hospital, local clinics or online telehealth) was identified. Major adverse cardiac events (MACE;death, heart failure admission or stroke) were documented and demographic characteristics compared between patients experiencing MACE versus those remaining symptomatically stable. Results: In March 2020, 35 patients were waitlisted for cardiac intervention (68.6% female, mean age 26.8 ± 9.4 yrs). Eighteen months later, 9 (25.7%) patients experienced definite MACE, comprising 3 sudden deaths and 14 admissions for decompensated heart failure. A further 10 patients (28.6%) had newly-disconnected phone numbers, implying possible additional deaths. 15 patients attended online telehealth clinics;7 (46.7%) had deteriorating NYHA scores. 14 patients (40.0%) were symptomatically stable. Patients experiencing MACE had been waitlisted a median of 30 months by August 2021 compared to 22 months for stable patients. Conclusions: At least one-quarter and possibly over half of a humanitarian charity’s patient list died or developed severe heart failure following eighteen months’ delay to cardiac intervention during international border closures from COVID-19. Patients attending online telehealth clinics reported high rates of morbidity and deteriorating symptoms. Abrupt border closures leaving a country without access to humanitarian surgery highlight the vulnerabilities of short-term medical mission models.

A rare case of cardiomyopaty: a case report

A 46-years old Egyptian man was admitted to our department because of the onset of worsening dyspnea. In his clinical history were present: hypothyroidism, obesity, hyperuricemia, hypertension and recent Sars-Cov2 infection. Bilateral pleuric effusion was suspected during physical examination and confirmed by chest CT. Blood data showed mild macrocytic anemia, increased levels of creatinine, transaminases, pro-BNP (3574 pg/ml cut-off 0-125) and D-dimer. Multiple molecular swabs for research of Sars-Cov2 were negative. ECG showed sinus rhythm and non specific atypia of repolarization. An eco-fast was performed at bedside and revelead left ventricular dilatation and severe systolic disfunction due to diffuse hypokinesia (EF 30%). Diuretic therapy was set up with improvement of the clinical status. In order to exclude ischaemic genesis of the cardiopathy a coronary angiography was performed without evidence of obstructive lesions. An echocardiogram was repeated and it showed a parietal ipertrabeculation of the left ventricle. This aspect was suggestive of non-compact myocardium, a rare disease due to the arrest of the myocardial maturation process during fetal development, leading to the persistence of embryonic structures in the heart muscle. Genetic inheritance arises in 30-50% of patients and are involved genes that generally seem to encode sarcomeric or cytoskeletal proteins.Cardiac MRI is planned in order to have further confirmation of our diagnostic hypothesis. In the meantime wearable defibrillator was prescribed for the prevention of sudden death.

Unchanged Fatality Rate on Austrian Ski Slopes during the COVID-19 Lockdown.

Fatalities on ski slopes are very rare, with about one death per one million skier days. Whether the fatality rate is affected by substantial changes in the number of skier days and potentially associated alterations in the structure of the skier population is unknown. Thus, we compared the fatality rate on Austrian ski slopes in the winter season of 2020/21, when skiing activities were dramatically restricted during the COVID-19 lockdown, with those of the previous winter seasons. As a consequence of COVID-19 measures, the number of skier days dropped from over 50 million in previous years to 9.2 million skier days in the winter season of 2020/21. Still, the fatality rate (6.5 deaths/10 million skier days) was not different when compared to any of the seasons from 2011/12 to 2019/20. Despite the lack of international skiers and the reduction in skier days by more than 80%, the fatality rate remained surprisingly unchanged. The weather and snowfall conditions were on average comparable to those of previous winters, and, except for nationality, the composition of the skier population appears to have remained relatively unaltered. In conclusion, the fatality rate during downhill skiing is low and the absolute fatality numbers are primarily a function of the number of skier days.

Sudden death due to fulminant lymphocytic myocarditis with atypical prodromal symptoms.

Diagnosis of myocarditis is complex because it is not always preceded by clear symptoms. We report the case of a woman who died suddenly. Autopsy and histopathological investigations revealed a lymphocytic myocarditis. Clinical history showed the patient went to the hospital some days before for joint pain and low-grade fever.