Bilateral Spontaneous Pneumothorax in a Child with Multisystem Inflammatory Syndrome Associated with COVID-19

Introduction: Spontaneous pneumothorax is a rare complication of coronavirus disease 2019 (COVID-19), primarily reported in adults. Pediatric cases with bilateral pneumothorax are much less reported. Case Presentation: We presented the case of a five-year-old previously healthy boy who developed persistent fever, abdominal pain, generalized maculopapular rash, and dyspnea before admission. His chest computed tomography (CT) showed a viral involvement pattern of pneumonia suggestive of COVID-19. Subsequently, he was confirmed with multisystem inflammatory syndrome in children (MIS-C). While he responded well to the therapies, on the fifth day of admission, he developed respiratory distress again. A chest roentgenogram showed bilateral spontaneous pneumothorax. Bilateral chest tubes were inserted, and his condition improved sig-nificantly after five days of admission to the intensive care unit. Two weeks later, he was discharged in good condition. Conclusion(s): Children with MIS-C associated with COVID-19 may develop primary spontaneous pneumothorax. Owing to the clinical picture overlapping with MIS-C associated with COVID-19, the timely diagnosis of pneumothorax may be challenging in such patients.Copyright © 2022, Author(s).

Boosting the Immune System with Vitamin D: Special Focus on Prevention of COVID-19 and Complications

In addition to the classical functions of the musculoskeletal system and calcium homeostasis, the function of vitamin D as an immune modulator is well established. The vitamin D receptors and enzymes that metabolize vitamin D are ubiquitously expressed in most cells in the body, including T and B lymphocytes, antigen-presenting cells, monocytes, macrophages and natural killer cells that trigger immune and antimicrobial responses. Many in vitro and in vivo studies revealed that vitamin D promotes tolerogenic immunological action and immune modulation. Vitamin D adequacy positively influences the expression and release of antimicrobial peptides, such as cathelicidin, defensin, and anti-inflammatory cytokines, and reduces the expression of proinflammatory cytokines. Evidence suggestss that vitamin D's protective immunogenic actions reduce the risk, complications, and death from COVID-19. On the contrary, vitamin D deficiency worsened the clinical outcomes of viral respiratory diseases and the COVID-19-related cytokine storm, acute respiratory distress syndrome, and death. The study revealed the need for more preclinical studies and focused on well-designed clinical trials with adequate sizes to understand the role of vitamin D on the pathophysiology of immune disorders and mechanisms of subduing microbial infections, including COVID-19.Copyright © 2023 Bentham Science Publishers.

Should Young Covid-19 Patients be Suplemented with Vitamin D?

It is well known that vitamin D's general immunomodulatory actions are helpful in viral infections and that a shortage is linked to a more serious prognosis for Covid-19. In this sistematic review, we examined the existing literature on evidence as to whether there is also link between vitamin D range levels in pediatric population and the outcome of the Covid-19 infection. We looked for studies that measured vitamin D blood concentrations and examined the effects of vitamin D supplementation in young infected patients. Vitamin D may decrease the risk of respiratory infections in a number of ways through its interactions with numerous cells, including by decreasing viral survival and replication, reducing the cytokine storm, raising angiotensin-converting enzyme 2 concentrations (ACE2) while not damaging the endothelial integrity. The incidence or severity of Covid-19 is linked with blood 25-hydroxyvitamin D concentrations, according to many observational studies. However experimental verification is still needed. Given their safety and broad therapeutic window, vitamin D supplements seem to be an effective way for individuals and doctors to prevent or treat Covid-19. Nonetheless, the outcomes of significant vitamin D randomized controlled trials are further needed.Copyright © 2022 Maria Nicolae et al., published by Sciendo.

Report of the Association Between Multisystem Inflammatory Syndrome and Severe Myocarditis

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusion(s): Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.Copyright © 2023, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

Prevention of vitamin D deficiency in children. The state of the problem in the world and in Ukraine.

The article presents current data on the prevalence of vitamin D deficiency and criteria for its deficiency in children in different countries. Vitamin D is recognized as one of the most important vitamins involved in many biochemical processes in the body. Its active metabolites play a key role in calcium absorption, bone mineralization and promote phosphate and magnesium metabolism. At the same time, in addition to affecting mineral metabolism, there is a wide range of conditions in which vitamin D also plays a preventive role. Vitamin D has been shown to play a vital role in innate immunity maintenance and is important in prevention of several diseases, including infections, autoimmune diseases, certain forms of cancer, type 1 and 2 diabetes, and cardiovascular diseases. Vitamin D is of particular importance for newborns and young children. This vitamin is involved in important physiological regulatory processes such as bone metabolism, lung development, maturation of the immune system and differentiation of the nervous system. Vitamin D deficiency increases risks of neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, and bronchopulmonary dysplasia. Adequate intake of vitamin D and calcium during childhood can reduce the risk of osteoporosis and other diseases associated with vitamin D deficiency in adults. Recently, vitamin D deficiency has shown to be a potential risk factor for COVID-19 propensity. It has been established that to date most scientific pediatric societies have recognized the need to prevent vitamin D deficiency in healthy children of all ages, but data on the dosage of vitamin D in its prophylactic use differ. Most scientific societies recommend an average of 400-600 IU per day of vitamin D for prophylactic purposes. The analysis of published data shows the need to follow a strategy based on an individual approach, taking into account physiological characteristics, individual requirements and lifestyle.Copyright © 2021 University of Tartu Press. All rights reserved.

Impact of La3+doping on temperature coefficient of resistivity and peak temperature of La x Ca0.89-xSr0.11MnO3 films prepared by sol-gel spin coating method

Herein, refined LaxCa0.89-xSr0.11MnO3 (LCSMO, x = 0.65, 0.68, 0.71 and 0.74) films were prepared through the sol-gel spin-coating. The influence of La3+ content on the structural properties of LCSMO films was investigated by X-ray diffraction and Atomic force microscope, demonstrating that LCSMO films can grow well on SrTiO3 (00l) substrate. Besides, X-ray photoemission spectroscopy verified the double exchange (DE) effect was weakened with La3+ dopant. The La3+ doping and interconnected grains boundaries (GBs) led to the weakening DE effect and GBs scattering, respectively. Due to superior GBs connectivity, the resistivity of LCSMO films was less than 7.1 x 10(-4) Omega.cm at low temperature of 100 K. Importantly, it is an effective control method to keep the temperature (T-k) corresponding to temperature coefficient of resistivity (TCR) at room temperature with Sr2+ content as constant in LCSMO films. At x = 0.71, the peak TCR value was found to be 8.84%/K and corresponding T-k was 283.15 K. These results are beneficial for advanced application of uncooling infrared bolometer.

Spectrum of Biochemical Alterations in Patients with Covid-19

Background and objective: Millions of people worldwide have died from COVID-19, which has caused the failure of the lungs and other organs. The research assessed biochemical anomalies in COVID-19 patients to comprehend the illness and its effect better. Study Design: Retrospective longitudinal cohort analysis Place of study: ABWA Medical College Faisalabad Methods: A total of 150 adult patients (n=150) who tested positive for COVID-19 via RT-PCR were included in the study. A Roche Diagnostics Cobas C501 used spectrophotometry to measure calcium, magnesium, phosphate, lactate dehydrogenase (LDH), urea, creatinine, ferritin, and chloride in the blood. A NOVA electrolytic analyzer used Ion-selective electrodes to measure sodium, chloride, potassium, and bicarbonate. Result(s): In the study, 33.6% of patients had elevated urea levels, and 22.4% had elevated creatinine levels. Furthermore, 88.8% of patients had elevated ferritin levels, and 93.5% had elevated LDH levels. After 44 weeks, there was a drop in sodium-containing electrolytes, with 9% of patients experiencing a decrease in sodium, 22.4% in potassium, 53.3% in bicarbonate, 48.6% in calcium, and 23.4% in phosphorus. These changes in electrolyte levels suggest a long-term trend in electrolyte depletion among the patient population. There was no significant difference in biochemical anomalies between age groups (p > 0.05). Conclusion(s): These results suggest that COVID-19 patients have lung illness and multi-organ involvement, which should be considered when managing these patients. These biochemical alterations warrant careful monitoring for organ failure by healthcare practitioners. More study is required to comprehend the processes causing these biochemical anomalies in COVID-19 patients.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Innovative Ingredients Fortified Nutrients Enriched Biscuits and Cookies: Quality and Sensory Analyses

Global suffering from COVID-19 has necessitated augmenting the immunity systems of humans through consumption of macro-micro-nutrients and antioxidant-enriched fortified foods. In this article, fortifications of popular bakery products, viz. biscuits, cookies, have been reviewed, encompassing the novel fortifying ingredients and innovative methods employed with an emphasis on the overall enrichment in the final product quality. A few notable features concerning novel fortified biscuit and fortified cookie have been decisively summarized. Wheat flour blended with 40% sesame-cake flour resulted in a fortified biscuit possessing higher protein (16.6%), crude fat (16.95%), and dietary fiber (8.2%) with acceptable sensory characteristics. About 9% toting up of chicken-eggshell dried-powder could result in high Ca content in biscuits with customary changes in texture and sensory properties. A remarkable 5% addition of bee pollen to wheat flour appreciably improved the nutrient compositions (carbohydrate 65.18%, protein 7.32%, and total dietary-fiber 1.47%) along with high polyphenol and antioxidant potentials. Notably, mixing fish fillet protein concentrate with wheat flour could yield enhanced nutritional content (protein 14.63-19.52%, fat 16.2-16.5%), as well as augmented amino acids. Remarkably, wheat flour fortified with fermented jack bean flour resulted in an overall fortified biscuit with substantial carbohydrate, crude protein, fat, fiber, ash, and appreciable macro-micro mineral contents and sensory characteristics. Innovative fortified cookies were made by blending wheat flour or Brewer's spent grain flour with one or more ingredients, e.g. full fat soya, mushroom, cardamom powder, moringa leaves, coconut, sweet potato flour rendering amplified values of nutrients, superior physical properties, increased mineral and flavonoid contents and organoleptic qualities.Copyright © 2023 Bentham Science Publishers.

Analyses of kidney biomarkers in patients with sars-cov-2 (Covid-19)

The new coronavirus was first reported in China and caused a widespread global outbreak of pneumonia that spread rapidly across this country and many other countries. Acute kidney injury is one of the important complications of COVID-19, which has been shown in some cases. Exploring the diagnostic features of biomarkers of kidney function in COVID-19 patients may lead to better patient management. We collected laboratory data from 206 people with confirmed COVID-19 disease and evaluated their renal biomarkers, Blood Urea Nitrogen (BUN), and creatinine. The age range of the patients was almost 62 years old. The mean age in the dead patients and recovered patients was 71 and 54 years old, respectively. The average LDH value was 755 U/L, and creatine phosphokinase (CPK) was 267 U/L in the patients. The average BUN was 59.1 U/L, and creatinine was 1.5 U/L in COVID-2019 patients. Among all 193 patients, laboratory results revealed that 163 (85.4%) patients had an elevated BUN level. Based on creatinine levels for total patients, laboratory results revealed that 49 (25.4%) patients had an elevated value. The average BUN value in dead patients was 85 mg/dL, while in recovered patients was 40.5 mg/dL (P<0.0001). Also, the average creatinine level in dead patients was 1.86 mg/dL, while in recovered patients was 1.24 mg/dL (P=0.0004). Inflammation following COVID-19 disease causes kidney damage and elevated urea and creatinine levels, which may increase the risk of death in these patients.Copyright © 2023 Tehran University of Medical Sciences.

Relationship of Atherosclerotic Plaque Structure with the History of COVID-19 in Patients Undergoing Coronary Computed Tomographic Angiography.

Although there is no sign of reinfection, individuals who have a history of coronavirus disease 2019 (COVID-19) may experience prolonged chest discomfort and shortness of breath on exertion. This study aimed to examine the relationship between atherosclerotic coronary plaque structure and COVID-19. This retrospective cohort comprised 1269 consecutive patients who had coronary computed tomographic angiography (CCTA) for suspected coronary artery disease (CAD) between July 2020 and April 2021. The type of atherosclerotic plaque was the primary outcome. Secondary outcomes included the severity of coronary stenosis as determined via the Coronary Artery Disease-Reporting and Data System (CAD-RADS) classification and the coronary artery calcium (CAC) score. To reveal the relationship between the history of COVID-19 and the extent and severity of CAD, propensity score analysis and further multivariate logistic regression analysis were performed. The median age of the study population was 52 years, with 53.5% being male. COVID-19 was present in 337 individuals. The median duration from COVID-19 diagnosis to CCTA extraction was 245 days. The presence of atherosclerotic soft plaque (OR: 2.05, 95% confidence interval [CI]: 1.32-3.11, P = 0.001), mixed plaque (OR: 2.48, 95% CI: 1.39-4.43, P = 0.001), and high-risk plaque (OR: 2.75, 95% CI: 1.98-3.84, P < 0.001) was shown to be linked with the history of COVID-19 on the conditional multivariate regression analysis of the propensity-matched population. However, no statistically significant association was found between the history of COVID-19 and the severity of coronary stenosis based on CAD-RADS and CAC score. We found that the history of COVID-19 might be associated with coronary atherosclerosis assessed via CCTA.

Impact of Hypocalcemia on the Prognosis of Patients with Acute Myocarditis.

Acute viral myocarditis is a serious complication of viral infectious diseases, including coronavirus disease 2019 (COVID-19). To better understand the pathogenesis of acute viral myocarditis, we retrospectively analyzed the incidence and prognostic significance of hypocalcemia among patients with acute myocarditis, most of whom were considered to have acute viral myocarditis. We retrospectively reviewed the demographic and clinical data of patients with clinically confirmed acute myocarditis treated in our hospital over a 13-year period from 2006 to 2019, including laboratory results, cardiac imaging findings, and clinical outcomes. These data were compared between lower, middle, and higher calcium groups depending on the minimum calcium level measured during hospitalization. Among the 288 patients with acute myocarditis included, the hypocalcemia group (lower calcium group) had poorer clinical and laboratory results, received more medications and device support, and experienced poorer outcomes, including heart failure, arrhythmias, and death. Specifically, the left ventricular ejection fraction was significantly lower, and the length of hospital stay was significantly longer in the hypocalcemia group than in the other two groups. Furthermore, the incidence rates of atrioventricular block, ventricular tachycardia/ventricular fibrillation, cardiogenic shock, and mortality were significantly higher in the hypocalcemia group. Multivariate Cox regression analysis identified hypocalcemia as an independent risk factor for 30-day mortality in patients with acute myocarditis. In conclusion, the clinical evidence provided by the present study indicates that hypocalcemia is a risk factor for poorer outcomes in patients with acute myocarditis that should be considered carefully in the diagnosis and treatment of these patients.

Applications of advances in mRNA-based platforms as therapeutics and diagnostics in reproductive technologies.

The recent COVID-19 pandemic led to many drastic changes in not only society, law, economics, but also in science and medicine, marking for the first time when drug regulatory authorities cleared for use mRNA-based vaccines in the fight against this outbreak. However, while indeed representing a novel application of such technology in the context of vaccination medicine, introducing RNA into cells to produce resultant molecules (proteins, antibodies, etc.) is not a novel principle. It has been common practice to introduce/inject mRNA into oocytes and embryos to inhibit, induce, and identify several factors in a research context, while such aspects have also been proposed as potential therapeutic and diagnostic applications to combat infertility in humans. Herein, we describe key areas where mRNA-based platforms have thus far represented potential areas of clinical applications, describing the advantages and limitations of such applications. Finally, we also discuss how recent advances in mRNA-based platforms, driven by the recent pandemic, may stand to benefit the treatment of infertility in humans. We also present brief future directions as to how we could utilise recent and current advancements to enhance RNA therapeutics within reproductive biology, specifically with relation to oocyte and embryo delivery.

Acute Pancreatitis Following a Lower Extremity Angioplasty

Introduction: Acute pancreatitis affects a significant population globally. Usual etiologies are gallstones, alcohol, hypertriglyceridemia, medications;less frequent are trauma, hypercalcemia, infections, toxins, ischemia, anatomic anomalies, vasculitis, and idiopathic. Pancreatitis post coronary intervention is an uncommon cause with only 19 published cases in the last two decades. Being cognizant of this etiology is important given the increasing number of patients undergoing angiography. Case Description/Methods: An 81-year-old female with hypertension, diabetes, peripheral arterial disease, prior cholecystectomy underwent left lower extremity angioplasty at an outside center. Within a few hours, she started having severe epigastric pain radiating to her back, nausea, vomiting and loose bloody stool. She presented to the emergency department 24 hours after symptom onset. Epigastric tenderness was present on exam. Labs revealed leukocytosis (24,450/muL), elevated lipase (1410 U/L), elevated creatinine (1.3 mg/dL), lactate (3.1 mmol/L), calcium 9.4 mg/dL and triglycerides 161 mg/dL. Incidentally, found to be positive for COVID-19. Normal common bile duct diameter seen on sonogram. CT angiogram of the abdomen/pelvis showed acute pancreatitis, duodenal and central small bowel enteritis (Figure). She was not on any medications known to cause pancreatitis and denied alcohol use. Patient improved with analgesics and intravenous fluids. She had no recurrence of bloody stools and hemoglobin remained stable. On day 4, she was able to tolerate a regular diet, and leukocyte count and creatinine normalized. Patient did not have any COVID respiratory symptoms, and was discharged. Discussion(s): Given the temporal association to angioplasty and no other identifiable cause, acute pancreatitis was presumed to be due to the contrast used during angioplasty. Other possibilities included cholesterol embolism but no peripheral signs of cholesterol embolism were seen. Patient was an asymptomatic COVID-19 case. Although, there are case series of pancreatitis due to COVID, those were found in very sick symptomatic patients. On review of literature, cholesterol embolism was identified as a definite cause only on autopsy or laparotomy (Table). Other possible mechanisms are: high viscosity of the contrast media leading to ischemia and necrosis, contrast causing NF-kB activation followed by epithelial damage, and vasospasm. Pancreatitis after coronary angiography is rare, nonetheless, an important differential especially if there is a temporal relationship.

Just Keep Swimming...Just Keep Swimming

History: We present a 15-year-old right hand dominant high school swimmer with no significant past medical history, who complains of right elbow pain along the distal biceps' tendon for a 2 months. Pain was insidious in onset, sharp, intermittent, and described as a 0 to 6 out of 10. The patient has been swimming more frequently over the last few months to prepare for competition and noticed progressive pain with swimming. He went on vacation and then was diagnosed with a COVID-19 infection and took an additional 2 weeks off due to fatigue. He returned to sport without re-integration and increased his swimming intensity to 1 to 2 hours daily, which worsened his pain. Performing the butterfly and breaststroke provoke symptoms and cessation of activity reduces the pain. Denies pain at rest. He took Advil which did not reduce his pain. Denies acute trauma, prior injuries, or paresthesias. Physical Exam: Inspection of right elbow: no swelling or signs of discoloration. Palpation: Tenderness at the distal biceps tendon but can hook the tendon without pain. No shoulder or wrist tenderness. Active Range of Motion: Elbow extension 0 degrees, elbow flexion 130 degrees, supination and pronation normal. Normal shoulder and wrist ROM. Muscle strength: 5/5 grip, wrist extension, and wrist flexion. Pain elicited with resisted elbow flexion at the distal humerus. Maneuvers: pain with distal humerus squeeze. Negative Maudsley and negative Cozen test. Differential Diagnosis: 36. Distal Biceps Tendonitis/Tear 37. Stress Reaction of the Distal Humerus 38. Medial Epicondyle Apophysitis 39. Capitellar Osteochondritis Dissecans 40. Radiocapitellar Plica Syndrome Test Results: x-ray right elbow: AP and Lateral views indicate no abnormalities to the bones, alignment, or soft tissue structures. MRI right elbow No IVCON: Biceps tendon intact. There is periosteal edema and endosteal aspect marrow edema along the medial aspect of the distal diaphysis and metaphysis of the humerus. Several small foci of increased cortical signal. No fractures, joint effusion, or chondral defects. Findings comparable to Fredrickson grade 4a distal humerus diametaphysis stress injury. Final Diagnosis: Right Elbow Supracondylar Grade 4a Stress Reaction. Discussion(s): Actives that involve repetitive motion are susceptible to overuse injuries. Cases of upper extremity stress reactions in swimmers have been documented along the inferior angle of the scapula, upper ribs, and olecranon. Stress reactions along the distal humerus in swimmers is not well documented. This pathology has been seen in baseball players, cricket bowlers, and tennis players. In swimming, the butterfly technique requires significant endurance and athletic strength. During a sprint, fast synchronized upper extremity revolutions occurring up to 60 cycles perminute counterforcewater surface area friction leading to excessive loading forces even at 50 meter distances. Outcome(s): The patient was withheld from upper body work outs and swimming for 6 weeks. VitaminDand Calcium levels were drawn revealing a normal calcium level (10.2), but a vitamin D level of 28.1. Patient was started on 600 IU of Vitamin D and 1300 mg of Calcium daily. The patient started a return to swim program and returned to full competition at 7 months post presentation. Follow-Up: At 6 weeks, started an upper extremity low impact non-aquatic physical therapy program. Then a slow progressive return to swimming was initiated at 50% effort for 4 weeks. At 10 weeks, a return to sport plan including 200 m all strokes except butterfly, progressed to 250 m at week 2, 300 m at week 3, and 350 m at week 4. Finally, initiated speed work in =0 to 100 m increments and elbow loading workouts.

Cool Your Jets Bro

History: Twenty-two year old male basic trainee was brought to the ED after collapsing during a routine ruck march. At mile 8/12, soldier was noted to develop an unsteady gate and had witnessed loss of consciousness. A rectal core temperature was obtained and noted to be >107degreeF. Cooling initiated with ice sheets and EMS was activated. On arrival to the ED, patient demonstrated confusion and persistently elevated core temperatures despite ice sheeting, chilled saline and cold water bladder lavage. Cooling measures were discontinued after patient achieved euthermia in the ED;however, his temperatures subsequently spiked>103degreeF. Given rebound hyperthermia, an endovascular cooling (EVC) device was placed in the right femoral vein and patient was transferred to the ICU. Multiple attempts to place EVC device on standby were unsuccessful with subsequent rebound hyperthermia. Prolonged cooling was required. Physical Exam: VS: HR 121, BP 85/68, RR 22 SpO2 100% RA, Temp 102.4degreeF Gen: young adult male, NAD, shivering, A&Ox2 (person and place only) HEENT: Scleral anicteric, conjunctiva non-injected, moist mucus membranes Neck: Supple, no LAD Chest: CTAB, no wheezes/rales/rhonchi CV: tachycardia, regular rhythm, normal S1, S2 without murmurs, rubs, gallops ABD: NABS, soft/non-distended, no guarding or rebound EXT: No LE edema, tenderness SKIN: blisters with broad erythematous bases on bilateral heels Neuro: CN II-XII grossly intact, 5/5 strength in all extremities. Differential Diagnosis: 216. Septic Shock 217. Hypothalamic Stroke 218. Exertional Heat Stroke (EHS) 219. Neuroleptic Malignant Syndrome 220. Thyroid Storm Test Results: CBC: 18.2>14.5/40.6<167 CMP: 128/3.5 88/1831/2.7<104, AST 264, ALT 80, Ca 8.8 Lactate: 7.1 CK: 11 460 Myoglobin: 18 017 TSH: 3.16 CXR: No acute cardiopulmonary process Blood Cx: negative x2 CSF Cx: Negative COVID/Influenza/EBV: Negative Brain MRI: wnl. Final Diagnosis: Exertional Heat Stroke. Discussion(s): No EVC protocols exist for the management of EHS or rebound/refractory hyperthermia. As a result, the protocol used for this patient was adapted from post-cardiac arrest cooling protocols. It is unclear if this adapted protocol contributed to his delayed cooling and rebound hyperthermia as it was not intended for this patient demographic/ pathophysiology. Furthermore, despite initiating empiric antibiotics upon admission, delayed recognition and tailored therapy for his bilateral ankle cellulitis may have contributed to the difficulty in achieving euthermia. In summary, more research needs to be done to evaluate and develop an EVC protocol for EHS. Outcome(s): Euthermia was achieved and maintained after 36 hours of continuous EVC, at which point it was discontinued. His CK, AST/ALT, creatinine and sodium down-trended after discontinuation of EVC. Patient's antibiotics were transitioned to an oral formulation for treatment of ankle cellulitis and he was prepared for discharge. He was discharged with regular follow-up with the Fort Benning Heat Clinic. Follow-Up: After discharge, patient had regularly scheduled visits with the Fort Benning Heat Clinic. His typical lab markers for exertional heat stroke were regularly monitored. He had continued resolution of his Rhabdomyolysis, acute kidney injury and hyponatremia with typical treatment. Soldier returned to duty after 10 weeks of close monitoring and rehabilitation.

Esophageal Mucosal Calcinosis: A Rare Site of Calcium Deposition in End-Stage Renal Disease

Introduction: Calciphylaxis, otherwise known as calcium uremic arteriolopathy, is defined as calcium deposition around blood vessels in skin and fat tissue which occurs in 1-4% of patients with end-stage renal disease (ESRD). Calcium deposition in the esophagus is extremely rare;to date, there have been only 4 cases reported worldwide. We report the fifth case of esophageal mucosal calcinosis occurring in a young male with ESRD. Case Description/Methods: A 37-year-old Thai man with ESRD on peritoneal dialysis since 2005 presented with generalized weakness and odynophagia due to oral ulcers, resulting in poor PO intake. He denied drinking alcohol, illicit drug use, or smoking. On exam his abdomen was soft, non-distended, non-tender, without any guarding. Past medical history included hypertension and COVID-19 in January 2022. Laboratory tests revealed neutropenia and pancytopenia, hyperphosphatemia, and hypocalcemia. EGD revealed distal esophageal esophagitis and hemorrhagic erosive gastropathy. Biopsy showed ulcerative esophagitis with dystrophic calcification, consistent with esophageal mucosal calcinosis .No intestinal metaplasia was noted. Immunohistochemistry was negative for CMV, HSV1, and HSV2. The patient was treated with pantoprazole 40mg IV every 12 hours, Magic Mouthwash 5ml qid, and Carafate 10mg qid. He was transferred to a cancer center where he had a bone marrow biopsy formed which was negative. His symptoms resolved and the patient was discharged to home (Figure). Discussion(s): Esophageal mucosal calcinosis is extremely rare. It is due to a combination of factors involving acidosis and the phenotypic differentiation (and apoptosis) of vascular smooth muscle cells (VSMC) into chondrocytes or osteoblast-like cells. These changes, along with the passive accumulation of calcium and phosphate, induce calcification. Acidosis is well-known to promote inflammation of the arterial walls, releasing cytokines that induce vascular calcification. The benefits of treatment with sodium thiosulfate remain unclear. An ample collection of cases should help devise standardized treatment options and establish management guidelines for this condition.

Nirmatrelvir/ritonavir - A New Culprit of Acute Pancreatitis

Introduction: Nirmatrelvir/ritonavir is a new medication approved for the treatment of COVID-19 infection. It prevents viral replication by inhibiting the SARS-CoV-2 main protease. While mild adverse effects were described, including dysgeusia, diarrhea, hypertension and myalgia1, there were no reported cases of pancreatitis. Case Description/Methods: An 81-year-old female with a past medical history of hypertension and COPD presented to the hospital complaining of abdominal pain and nausea for one day. She had no history of alcohol, tobacco or marijuana use, recent travel, or trauma. Her medications included lisinopril and prednisone, and she had completed a 5-day course of nirmatrelvir/ritonavir for the treatment of COVID-19 infection 2 days prior to presentation. On abdominal exam, she had left upper and lower quadrant tenderness. Blood tests revealed an amylase of 1333 U/L, lipase of 3779 U/L, triglycerides of 297 mg/dL and calcium of 8.7 mg/dL. CT scan revealed an indurated pancreatic body and tail with peripancreatic fluid along the paracolic gutter. Ultrasound of the abdomen and MRCP did not reveal any acute findings. IgG subclasses 1-4 were normal. Discussion(s): According to the revised Atlanta criteria, the patient had clinical findings consistent with acute pancreatitis. Common causes such as gallstone, alcohol, autoimmune and hypertriglyceridemiainduced pancreatitis were ruled out. There were no masses or structural abnormalities on imaging that might have explained her diagnosis. There have been at least 2 reported cases of lisinopril and prednisone induced pancreatitis, however according to Badalov et al.2 both of these medications are class III drugs that lack any rechallenge in the literature. Moreover, the patient had been taking these medications for many years, making them an unlikely cause of the presenting diagnosis. There are no reports of nirmatrelvir/ritonavir associated pancreatitis or known pharmacologic interaction with her home medications, and a meta-analysis conducted by Babajide et al. revealed no association between acute pancreatitis and COVID-19 infection (3). Given the negative findings stated above and the recent initiation of a new medication, nirmatrelvir/ritonavir was the likely cause of acute pancreatitis.

Chronic Chilblain Like Lesions Associated with the Covid-19 Pandemic

Background/Aims We report the features of chronic chilblain-like digital lesions newly presenting since the start of the covid-19 pandemic. Comparison with primary perniosis and acrocyanosis, reveals a unique phenotype which appears to be a long-covid phenomenon. Methods The case records of 26 patients with new onset persistent chilblain-like lesions presenting to the Rheumatology service of St George's University Hospital, London between Autumn 2020 and Spring 2022 were reviewed. Demographic and clinical features, serology, imaging, treatment response and outcome up to Summer 2022 were collated retrospectively. Results Chilblain-like lesions first occurred between September and March;2019/ 2020 6 cases, 2020/2021 18 cases and 2021/2022 2 cases. Mean age 35.4 (17-60) years, 88% female, 85% white, all non-smokers. Median body mass index (BMI) 20.2, range 17.0 - 33.2. BMI underweight (<18.5) in 27%. All cases reported new red-purple-blue colour changes of the fingers, some with pain, swelling and pruritis, affecting both hands in 12, one hand in 6, and both hands and feet in 8 cases. There was a past history of cold sensitivity or primary Raynaud's in 54%. Covid was confirmed in 3 cases, 2 - 8 months prior to onset of chilblain-like symptoms. Possible covid, unconfirmed, was suspected in 5 cases, 1 - 11 months earlier. Affected digits appeared diffusely erythro-cyanotic in 81%, with blotchy discrete maculo-papular erythematous lesions in 42%, some with both features. Involvement was asymmetric in 54%, thumbs spared in 69%. Complement was low in 50% (8/16), ANA positive in 26% (6/23). MRI of hands showed phalangeal bone marrow oedema in keeping with osteitis in 4 of 7 cases. More severe signs and symptoms were associated with low BMI, low C3/4 and a past history of cold sensitivity or Raynauds. Cold avoidance strategies were sufficient for 58%. Pain prompted a trial of NSAIDs, aspirin, nitrates, calcium channel blockers, hydroxychloroquine, oral or topical corticosteroid or topical tacrolimus in 42%. In general, these were minimally effective or not tolerated. 4 severe cases received sildenafil or tadalafil, effective in 2. In 27% complete remission occurred during the first summer season after symptoms commenced, median duration 6 (range 2 - 10) months. In the remaining 19 cases, chilblain-like symptoms returned or worsened in the subsequent second winter period, with 6 of 19 entering remission the following summer. For the remaining 13 persistent cases the total duration of symptoms spans more than a year, and in four cases more than 2 years. Conclusion This series illustrates a distinct chronic chilblain-like condition. Features similar to primary perniosis include female predominance, middle age, pruritic painful blotchy lesions, asymmetry and low BMI. Features in keeping with acrocyanosis include chronicity, extensive diffuse erythro-cyanotic discoloration, relative improvement in warm weather and lack of association with smoking.

Unwinding mechanism of SARS-CoV helicase (nsp13) in the presence of Ca2+, elucidated by biochemical and single-molecular studies.

The recent outbreak of COVID-19 has created a serious health crisis with fatFal infectious viral diseases, such as Severe Acute Respiratory Syndrome (SARS). The nsp13, a helicase of coronaviruses is an essential element for viral replication that unwinds secondary structures of DNA and RNA, and is thus considered a major therapeutic target for treatment. The replication of coronaviruses and other retroviruses occurs in the cytoplasm of infected cells, in association with viral replication organelles, called virus-induced cytosolic double-membrane vesicles (DMVs). In addition, an increase in cytosolic Ca2+ concentration accelerates viral replication. However, the molecular mechanism of nsp13 in the presence of Ca2+ is not well understood. In this study, we applied biochemical methods and single-molecule techniques to demonstrate how nsp13 achieves its unwinding activity while performing ATP hydrolysis in the presence of Ca2+. Our study found that nsp13 could efficiently unwind double stranded (ds) DNA under physiological concentration of Ca2+ of cytosolic DMVs. These findings provide new insights into the properties of nsp13 in the range of calcium in cytosolic DMVs.

Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices.

The cardiotoxicity risk of hydroxychloroquine (HCQ) and azithromycin (AZM) has been the subject of intensive research triggered by safety concerns in COVID-19 patients. HCQ and AZM have been associated with QT interval prolongation and drug-induced arrhythmias, however other cardiotoxicity mechanisms remain largely unexplored. Our group has pioneered the living heart slice preparation, an ex-vivo platform that maintains native cardiac tissue architecture and physiological electrical and contractile properties. Here, we evaluated the cardiotoxic effect of HCQ and AZM applied alone or in combination on cardiac contractility by measuring contractile force and contraction kinetics in heart slices prepared from porcine hearts. Our results show that clinically relevant concentrations of HCQ monotherapy (1-10 µM) reduced contractile force and contraction kinetics in porcine slices in a dose-dependent manner. However, AZM monotherapy decreased contractile force and contraction kinetics only at higher concentrations (30 µM). Combination of HCQ and AZM induced a dose-dependent effect similar to HCQ alone. Furthermore, pre-treating porcine heart slices with the L-type calcium channel agonist Bay K8644 prevented the effect of both drugs, while administration of Bay K8644 after drugs interventions largely reversed the effects, suggesting a mechanism involving inhibition of L-type calcium channels. These findings indicate that HCQ and AZM alter cardiac function beyond QT prolongation with significant contractile dysfunction in intact cardiac tissue. Our porcine heart slices provide a powerful platform to investigate mechanisms of drug cardiotoxicity.