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.

OPPORTUNITIES FOR CORRECTION OF IMMUNOSUPPRESSION IN PATIENTS WITH COVID-19.

Here, we review thematic publications in available literature sources of the databases PubMed, Scopus, Web of Science, eLibrary, 49 of which were dated of the years 1997–2022. Analysis of such reports is aimed at assessing features of cytokine storm-induced hyperinflammatory reaction with signs of immunosuppression accompanied by pronounced lymphopenia and lowered count of CD4+T helpers during severe COVID-19. The prognostic factor for unfavorable prognosis was based on the marker of systemic inflammatory reaction correlating with the disease severity - the soluble IL-2 receptor as well as the neutrophil-to-lymphocyte ratio and the lymphocyte subset imbalance. An immunosuppressive therapy of severe forms of COVID-19, aimed at weakening the inflammatory response, exacerbates immune dysfunction by suppressing the T cell function, mainly due to Th1 lymphocytes involved in recognizing and eliminating intracellular pathogens particularly viruses. Upon that, cell-mediated immunity becomes compromised that relies on cytotoxic T-lymphocytes, natural killer cells and macrophages. Timely and targeted immunocorrection is required to prevent or reduce the immunosuppression that accompanies a severe disease course and leads to serious and prolonged complications, as well as to association of secondary infections. In fight against the cytokine storm, it is important not to miss a time point of developing immunosuppressive condition that transitions into immunoparalysis as follows from recent publications covering the tactics of treating immune-mediated complications of coronavirus infection. The review discusses opportunities for immunosuppressive therapy along with glucocorticosteroids and monoclonal antibodies blocking IL-6 or cognate receptors. Studies using mesenchymal stem cells (MSCs) to reduce systemic inflammatory response at COVID-19 are outlined in the review. The use of antigen-specific Treg and their combinations with antagonists of tumor necrosis factor-α (TNFα), interferon-γ (IFNγ) as well as low-dose IL-2 in patients with SARS-CoV-2 infection were analyzed. The prognostic perspectives for CAR-T cells and CAR-NK cells technology have been considered as novel therapeutic approaches aimed at “training” effector cells to recognize the surface SARS-CoV-2 virus spike-like (S) protein. The feasibility of a therapeutic approach is also emphasized by comparatively analyzed of efficacy of using IL-7 or IL-15 during lymphopenia in patients with COVID-19. Here, side effects complicating immunocorrection come to the fore. Critical evaluation of corrected immunosuppressive conditions in patients with COVID-19 in the post-COVID-19 period by using low-dose IL-2 therapy revealed its ability to repair cellular immune response. As a result, a low-dose IL-2 therapy is recommended as a cytokine replacement therapy in such patients with COVID-19 during hyper-to-hypo-inflammatory phase transition in immune response. (English) [ FROM AUTHOR] Обзор выполнен посредством поиска тематической информации среди доступных источников литературы в базах данных Pubmed, Scopus, Web of Science, eLibrary, 49 из которых (1997–2022 гг. издания) вошли в данный обзор. Анализ этих работ направлен на особенности индуцированной цитокиновым штормом гипервоспалительной реакции с признаками иммуносупрессии, сопровождающейся выраженной лимфопенией со снижением количества CD4+ Т-хелперов при тяжелом течении COVID-19. Прогностическим фактором неблагоприятного прогноза служит коррелирующий с тяжестью заболевания маркер системной воспалительной реакции - растворимый рецептор IL-2, а также соотношение нейтрофилов к лимфоцитам и дисбаланс субпопуляций лимфоцитов. Направленная на ослабление воспалительной реакции иммуносупрессивная терапия тяжелых форм COVID-19 усугубляет иммунную дисфункцию, подавляя Т-клеточный ответ, в основном, за счет Th1 лимфоцитов, участвующих в идентификации и элиминации внутриклеточных патогенов, в частности вирусов. При этом страдает клеточно-опосредованный иммунитет, который обеспечивают цитотоксические Т-лимфоциты, натуральные киллеры и макрофаги. Для предупреждения или ослабления иммуносупрессии, сопровождающей тяжелое течение и приводящей к серьезным и длительным осложнениям, а также к присоединению вторичных инфекций, необходима своевременная и адресная иммунокоррекция. Ð’ борьбе с цитокиновым штормом важно не упустить момент развития иммуносупрессивного состояния, переходящего в иммунопаралич, что следует из последних публикаций, освещающих тактику лечения иммуноопосредованных осложнений коронавирусной инфекции. Ð’ обзоре рассмотрены возможности иммуносупрессивной терапии, помимо глюкокортикостероидов и моноклональных антител, блокирующих IL-6 или его рецепторы. Приведены примеры работ с использованием мезенхимальных стволовых клеток (МСК) для снижения системной воспалительной реакции при COVID-19. Подвергнуто анализу применениеантиген-специфических Treg и их сочетаний с антагонистами фактора некроза опухолей α (TNFα), интерферона γ (IFNγ) и с низкими дозами IL-2 у пациентов с SARS-CoV-2-инфекцией. Прогностические перспективы технологии CAR-Т-клеток и CAR-NK-клеток рассмотрены в плане новых терапевтических подходов, нацеленных на «обучение» эффекторных ºÐ»ÐµÑ‚ок распознавать поверхностный шиповидный (S) белок вируса SARS-CoV-2. Целесообразностьиммунокоррегирующей терапии подчеркивается также сравнительным анализом эффективности IL-7 или IL-15 у пациентов с COVID-19 с иммуносупрессией. Критическая оценка коррекции иммуносупрессивных состояний у пациентов с COVID-19 в постковидный период с помощью низкодозной терапии препаратами IL-2 позволила выявить ее способность восстанавливать клеточный иммунный ответ. Ð’ результате в качестве заместительной цитокиновой терапии у этих пациентов, при переходе от гипервоспалительной к гиповоспалительной фазе иммунного ответа, может быть рекомендована низкодозная IL-2 терапия. (Russian) [ FROM AUTHOR] Copyright of Russian Journal of Infection & Immunity is the property of National Electronic-Information Consortium and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Thyroid storm in pregnancy: A case study

Introduction: Inadequately treated maternal hyperthyroidism increases the risk of severe preeclampsia, heart failure, and thyroid storm. Thyroid storm is a life-threatening endocrine emergency characterized by multiple organ failure due to severe thyrotoxicosis. A storm can be triggered by precipitating events such as trauma, surgery, infection, delivery;even pregnancy itself. Case Description: A 35-year-old lady presented to the emergency department with complete miscarriage. She had underlying hyperthyroidism for six years but defaulted her follow-ups and medications since the beginning of the Covid-19 pandemic. She complained of palpitations despite minimal vaginal blood loss. ECG showed sinus tachycardia with a heart rate of 190 beats per minute. Her hemoglobin level was stable, but thyroid function test showed hyperthyroidism with raised free T4 (60 pmol/L) and low TSH (< 0.01 mIU/L). Her Burch-Wartofsky score was 35, implying an impending thyroid storm. IV Verapamil was given immediately and her heart rate improved to 140-150 bpm. She was transferred to a high dependency ward for close monitoring and started on oral Propylthiouracil and Propranolol. Regrettably, when she began to improve, she requested for discharge against medical advice. Discussion: The diagnosis of thyroid storm is clinical, with laboratory tests consistent with overt hyperthyroidism. Clinical scoring systems such as the Burch-Wartofsky Score helps to confirm diagnosis and triage disease severity. Treatment is multimodal using medications (thioamides, iodide, beta-blockers, corticosteroids, antipyretics), oxygen, volume resuscitation, and correction of electrolyte imbalance. A high index of suspicion, rapid recognition, prompt treatment and intensive monitoring are key elements of management.

New diagnosis of Graves' disease during SARS-CoV-2 infection. A further trigger of hyperthyroidism?

Background: Graves' disease is an autoimmune disorder which represents the most common cause of hyperthyroidism. It is often triggered by an acute event, such as infections. SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2), expressed mostly in the lungs but also in several endocrine organs like thyroid. Description of the Case: We report a case of a 49-years-old woman admitted to our Unit due to fever, tachycardia and worsening dyspnea. Nasopharyngeal swab test resulted positive for SARS-CoV-2 (PCR). Blood sample test for D-dimer resulted increased (1272 ug/l, normal value <500), and bilateral subsegmental embolism was found on CTAngiography. She reported palpitations, insomnia and weight loss in the past days. Past medical history included euthyroid nodular thyroid disease, hypertension and obesity. Laboratory tests revealed hyperthyroidism with positive thyroid antibodies with TSH<0.05 mU/l, FT4 32 ng/l and FT3 5.9 ng/l (normal value 8-17 and 2-4, respectively), and elevated AbTPO 137 KU/l (<34) and AbTSH-r 2.4 U/l (<2). Thyroid ultrasound showed an enlarged gland with heterogeneous echotexture and hyperechoic nodules;an hypervascular pattern with elevated peak systolic velocity in inferior thyroid artery (50-69 cm/s) was found at colorDoppler. A diagnosis of Graves' disease was established and treatment with thiamazole was started, achieving normal heart rate control and recovery of symptoms. Conclusions: In the absence of a clear trigger for our patient's thyroid storm, we suggest SARS-CoV-2 infection, in addition to CT iodinate contrast medium, might precipitate or worsen a latent Graves' disease.