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Background & Aim: Amniotic fluid (AF)-derived EVs are currently under investigation for use as anti-inflammatory therapeutics in COVID-19 and COVID-19 long haulers. The dysregulation of the immune response induced by SARS-COV-2 is a key driver of both acute COVID-19 induced lung injury and long term COVID-19 sequela. There is a clear need to identify therapeutics that suppress excessive inflammation and reduce immune cell exhaustion to improve patient short term and long-term outcomes. Amniotic fluid (AF)- derived extracellular vesicles (EVs) have previously been shown to deliver anti-inflammatory and immune-modulatory signals to diverse cellular targets. We aimed to test if AF-EVs carry immune-suppressive molecules and can suppress T-cell immune activation and exhaustion in vitro. Methods, Results & Conclusion(s): The AF-EV biologic tested was derived from AF collected from consenting donors during planned, fullterm cesarean sections. AF was centrifuged and filtered to remove cellular debris and create a product containing AF-EVs and soluble extracellular components. Fluorescent EXODOT analysis was performed to demonstrate the presence of EV markers CD9, CD81, ALIX, and immune suppressive molecule PD-L1. T-cell activation/exhaustion was induced in vitro by treating human peripheral blood mononuclear cells with activation agent PHA for 3 days with the addition of AF-EVs or saline control. Immune activation/exhaustion was measured by flow cytometry to determine the expression of PD-1 on CD3+ T-cells. The AF-EV biologic was characterized to contain EVs with positive expression of CD9, CD81, ALIX, and PL-L1. T-cell activation/exhaustion was upregulated in response to PHA and was significantly reduced by 8% in AF-EV treated T-cells compared to saline control (77.7% vs 85.7%, respectively P<0.05). These findings demonstrate that AF-EVs do express PD-L1, a surface marker that has previously been demonstrated to contribute to exosome-mediated immunosuppression. Furthermore, we confirmed in vitro that AF-EVs suppress T-cell activation/ exhaustion in the presence of a T-cell activation agent. COVID-19 long haulers have been described to have upregulated and pro-longed immune activation and T-cell exhaustion, marked by an increase in PD1+ T-cells. Therefore, this finding serves as a starting point for the development of a potential mechanism of action that may describe AF-EV's therapeutic effect in COVID-19 long hauler patients.Copyright © 2023 International Society for Cell & Gene Therapy
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Background: Diarrhea was typical symptoms of the coronavirus disease 2019 (COVID-19). However, the underlying mechanism had not been fully understood. Aim(s): The study aimed to explore the mechanism of intestinal injury during COVID-19 in a coronavirus murine hepatitis virus strain 3 (MHV-3) induced acute mouse model. Method(s): MHV-3 induced acute infection Balb/cJ mice model was established. Intestine samples were collected at indicated time points as 0 h, 24 h, 48 h and 60 h post infection. The mRNA and protein expression of IL1b, TNFalpha, IL6, caspase 3 and cleaved caspase 3 were examined by real-time quantitative PCR (qPCR) and western blot respectively. The intestine injury and apoptosis were measured by HE staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Moreover, Z-DEVD-FMK (caspase 3 inhibitor) pre-treated MHV-3 infection mice model were established, in which the apoptosis of intestine was evaluated as well. Meanwhile, the murine intestinal cell MODE-K was infected by MHV-3 in vitro for evaluation of virus induced apoptosis. Result(s): Post MHV-3 infection, the histopathology of intestine tissue showed extraordinary injury with time dependence, as well as high level of TUNEL positivity. The mRNA levels of inflammatory cytokine IL1b, TNFalpha and IL6 were significantly increased. The protein expressions of caspase 3 and cleaved caspase 3 in the intestine was found significantly elevated from 24 to 48 h post MHV-3 infection. Z-DEVD-FMK pretreatment inhibited caspase 3 and cleaved caspase 3 expression and decreased TUNEL positivity. Meanwhile, alleviated gut injury and inhibited TNFalpha expression were observed. In vitro treated by MHV-3, intestinal cell line MODE-K showed nine-fold increase of apoptosis by comparison with saline treated ones. The expressions of apoptosis crucial protein caspase3 and cleaved caspase3 significantly elevated, as well as TNFalpha. Conclusion(s): Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis, which might shed light on the treatment of intestinal complications in COVID-19.
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Background: There is still no specific treatment strategy for COVID-19 other than supportive management. The potential biological benefits of ozone therapy include reduced tissue hypoxia, decreased hypercoagulability, modulated immune function by inhibiting inflammatory mediators, improved phagocytic function, and impaired viral replication. This study aimed to evaluate the effect of intravenous ozonated normal saline on patients with severe COVID-19 disease. Method(s): In this study, a single centralized randomized clinical trial was conducted on 80 hospitalized patients with severe COVID-19. The patients were selected by random allocation method and divided into two groups A and B. In group A (control group), patients were given standard drug treatment, and in group B (intervention group), patients received ozonated normal saline in addition to the standard drug treatment. In the intervention group, 400 mL of normal saline was weighed by 40 mug/ kg of body weight and was injected into patients within 15 to 30 minutes (80 to 120 drops per minute). This process was done daily every morning for a week. Primary and secondary outcomes of the disease included changes in the following items: length of hospital stay, inflammatory markers including C-reactive protein (CRP), clinical recovery, arterial blood oxygen status, improvement of blood disorders such as leukopenia and leukocytosis, duration of ventilator attachment, and rapid clearance of lung lesions on CT scans. The need for intensive care unit (ICU) hospitalization, the length of ICU stay, and the mortality rate in patients of the two groups was compared. Result(s): According to the results of the initial outcome variable analysis, the probability of discharge of patients who received the normal ozonated saline intervention was 33% higher than patients who did not receive this intervention;however, this relationship was not statistically significant (HR = 0.67, 95%, CI = 0.42-1.06, P value = 0.089). The chance of ICU hospitalization in patients of the intervention group was three times more than that of the comparison group, but this relationship was not significant (odds ratio = 4.4 95% CI = 1.32-14.50, P value = 0.016). The use of ozonated normal saline was found to increase the risk of death by 1.5 times but this relationship was not statistically significant (odds ratio = 1.5, 95% CI = .24-9.75, P value = 0.646). Ozonated normal saline had a significant effect on changes in respiration rate (in the intervention group the number of breaths was decreased) and the erythrocyte sedimentation rate (in the intervention group the erythrocyte sedimentation rate was increased);however, it had no significant effect on other indicators. Conclusion(s): The present study showed that ozone therapy in hospitalized patients with severe COVID-19 could help improve some primary and secondary outcomes of the disease. Governments and health policymakers should make ozone therapy an available care service so that the need for advanced treatment facilities decreases;consequently, this measure may improve patient safety, prevent lung tissue destruction, and control cytokine storms in patients. Additionally, health decision-makers need to aim for the effective clinical improvement of patients, especially severe ones, and the reduction of their mortality. However, further large-scale multicenter studies with larger sample sizes considering drug side effects and other variables influencing the clinical course of COVID-19 can provide more information on the effectiveness and importance of ozone therapy.Copyright © 2023 The Author(s);Published by Kerman University of Medical Sciences.
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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.
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The proceedings contain 63 papers. The topics discussed include: a retrospective study to optimize post-anesthetic recovery time after ambulatory lower limb orthopedic procedures at a tertiary care hospital in Canada;a virtual airway evaluation as good as the real thing?;airway management during in hospital cardiac arrest by a consultant led airway management team during the COVID-19 pandemic: a prospective and retrospective quality assurance project;prevention of cautery induced airway fire using saline filled endotracheal tube cuffs: a study in a trachea airway fire model;smart phone assisted retrograde illumination versus conventional laryngoscope illumination for orotracheal intubation: a prospective comparative trial;time to single lung isolation in massive pulmonary hemorrhage simulation using a novel bronchial blocker and traditional techniques;cannabinoid type 2 receptor activation ameliorates acute lung injury induced systemic inflammation;bleeding in patients with end-stage liver disease undergoing liver transplantation and fibrinogen level: a cohort study;endovascular Vena Cavae occlusion in right anterior mini-thoracoscopic approach for tricuspid valve in patients with previous cardiac surgery;and mesenchymal stem cell extracellular vesicles as a novel, regenerative nanotherapeutic for myocardial infarction: a preclinical systematic review.
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Background: An emerging finding about COVID-19 is its effect on nutrition and weight loss. The COVID-19 symptoms of fatigue, altered taste or smell, and lack of appetite are well known. But COVID-19 may have a more profound effect on clinical nutrition status. Two recent studies have identified that approximately one-third of ambulatory COVID-19 patients are at risk of experiencing weight loss >= 5% (Anker, et al;di Filippo, et al). The case study presented here discusses home start total parenteral nutrition (TPN) in a patient recently diagnosed with COVID-19 at high risk for refeeding syndrome. Method(s): N/A Results: Case Study: A 92-year-old patient was diagnosed with COVID-19 on June 8, 2022. Over the next week, she was hospitalized twice to manage symptoms of acute mental status changes, lethargy, aphasia, hypotension, and loss of appetite. The patient received nirmatrelvir/ritonavir, remdesivir, and bebtelovimab to treat COVID-19 at different times between June 9, 2022, and June 18, 2022. She remained COVID positive and continued to deteriorate clinically. On June 20, 2022, the patient began receiving 24/7 homecare, including intravenous (IV) fluids of dextrose 5% in normal saline (D5NS) 1000 mL daily for three days. She continued to experience loss of appetite and had no bowel movement for 3 days. On June 23, 2022, she was referred to this specialty infusion provider to initiate TPN therapy in the home setting. The patient's BMI was 18.2 kg/m2. Lab results revealed potassium 3.0 mmol/L, phosphate 1.6 mg/dL, and magnesium 1.6 mg/dL. High risk of refeeding syndrome was identified by the level of hypophosphatemia and hypokalemia. The specialty infusion provider's registered dietitian recommended to discontinue D5NS and begin NS with added potassium, phosphate, and magnesium. Thiamine 200mg daily was added to prevent Wernicke's encephalopathy. The patient's clinical status and lab values were monitored closely each day until her electrolyte levels stabilized (Table 1). Home TPN therapy was initiated on June 28, 2022, with <10% dextrose and 50% calorie requirement with 85% protein and 1.0 g/kg lipids. Three-day calorie count and nutrition education were performed four days post TPN initiation. Oral intake met only 25% of estimated needs. Over several days, theTPN formula was gradually increased to goal calories and the infusion cycle was slowly decreased. The following week, the patient's oral intake improved to 60%-75% of estimated needs. Her constipation resolved, and she showed improvement in functional status and mobility. Her appetite drastically improved when the TPN was cycled. Another three-day calorie count was performed when TPN calories reached goals. Oral intake demonstrated 100% estimated calorie and protein needs. TPN therapy was ultimately discontinued on July 14, 2022. As of September 30, 2022, the patient has stabilized at her pre-COVID weight of 45 kg with full recovery of appetite, function, and cognition. Discussion(s): The ASPEN Consensus Recommendations for Refeeding Syndrome (da Silva, et al) describe the repletion of electrolyte levels before introducing calories to prevent end-organ damage associated with refeeding syndrome (respiratory muscle dysfunction, decreased cardiac contractility, cardiac arrhythmias, and encephalopathy). Conclusion(s): This case study highlights the successful initiation of home TPN therapy in a patient at high risk of refeeding syndrome post COVID-19 infection. Although home start TPN and the risk of refeeding syndrome are not new concepts, they must be considered in the setting of COVID-19. Given the effects COVID-19 has on taste, smell, and appetite and the recent finding that one-third of patients with COVID infection may experience weight loss of >= 5%, nutrition support and patient education are vital components of overall patient care. (Figure Presented).
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Introduction: Prior to colonoscopy, it is well understood that patients must undergo bowel cleansing. Based on the type of laxative, colonoscopy preparations fall into two categories - polymer-based formulas (PEG) and saline-based formulas (NaP). Both types of bowel preparations are deemed to be relatively safe and part of routine practice. However, we describe the rare case of an ulcerative colitis (UC) flare due to the bowel preparation formula. Case Description/Methods: A 29-year-old female with diagnosis of UC, presently in clinical and biochemical remission on oral mesalamine, contracted COVID-19 and had reactivation of UC symptoms. After being on budesonide tablets and rectal foam for two months, patient achieved clinical remission, and a surveillance colonoscopy was performed which revealed normal colon and terminal ileum except mild congestion in the cecum (Figure A). Pathology revealed unremarkable mucosa in the entire colon except for chronic active colitis in the cecum. Immediately following this colonoscopy, the patient started to experience another severe UC flare requiring hospitalization. The patient's laboratory work-up was normal except for an elevated fecal calprotectin (1710). Stool infectious work-up was negative and the patient denied any NSAID or antibiotic use. The patient underwent a repeat colonoscopy which revealed severe Mayo 3 pancolitis (Figure B) in comparison to a stable colonoscopy a few weeks prior. It was revealed that for her initial colonoscopy, she had used SUPREP bowel prep kit. On prior colonoscopies she had used MiraLAX bowel prep with no adverse effects. During hospitalization, the patient was started on biologic therapy with good effect. Discussion(s): There are no clear guidelines on appropriate bowel preparation formula for the inflammatory bowel disease (IBD) population. Sufficient literature exists to confirm that NaP can irritate the intestinal mucosal wall. Moreover, numerous animal experiments have employed dextran sodium sulfate for chemical induction of intestinal inflammation to mimic UC flares in humans [1]. Thus, it can be surmised that because SUPREP ingredients contain sodium sulfate, the potential for UC flare is higher. It is pertinent for practitioners to be aware of the possible rare adverse effects of saline-based formulas, especially when treating the IBD population.
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The COVID-19 outbreak has fashioned to severe threat to each and every individual in social and economic aspects in the country. This required improved wisdom to know how it is different and dominant, to diagnose and determine effective vaccines to avoid the transmission of these deadly causative agents. From this review, the probable property of these deadly transmissible viruses is related to that of SARS-CoV-2 as a fright zone of viruses. It also provides some sparks about effective and accurate diagnosis and treatment strategies. The effective management and control of panic zone of virus (PZV) and SARS-CoV-2 are more important to reduce the pandemic situation.Copyright © 2023 Inderscience Enterprises Ltd.
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Background: Acute sinusitis is not an uncommon disease that manifests with inflammation of the mucosal lining of the paranasal sinuses. It has varied etiologies including viral, bacterial, fungal, and allergic. Anatomical variations, trauma, auto-immunity, diabetes mellitus, and dental procedures are predisposing factors. With the wide variation in the etiological factors, the management could be tricky. This study is quite relevant with the advent of the relentlessly persisting COVID-19 pandemic which affects the upper respiratory tract as well. Method(s): This is a descriptive hospital-based prospective study conducted at the Khartoum ENT Teaching Hospital, Ibnsina Teaching Hospital, Omdurman Military Hospital, and Omdurman Teaching Hospital in Khartoum State in the period from March 2020 to February 2021. The study included all patients 18 years and older diagnosed with acute sinusitis. The data was collected by a well-structured questionnaire designed to meet the objectives of the study and analyzed using SPSS 20. Any COVID-19 suspect is excluded from the study. Result(s): The total number of patients was 109;of them, 59 (54.1%) were females and 50 (45.9%) were males, and the female to male ratio was 1.18:1. One hundred seven (98.2%) patients received medical treatment and two patients (1.8%) did take the medications. Eighty-one patients (74.3%) were cured with medical treatment and only 28 patients (25.7%) needed surgical intervention. The age group from 25 to 40 years old was the most affected, accounting for 68 patients (62.4%), and the above 60 years old (3.7%) was the least affected group. Conclusion(s): Acute sinusitis is not an uncommon disease, if addressed properly and timely is medically treatable in most cases apart from complicated cases. This study shows that the active working ages (25-40) were the most affected. Few patients needed surgery (FESS). Negligence could result in complications. Diseases like COVID-19 affect the upper respiratory tract, and there is a similarity in symptoms, and in the advent of the COVID-19 pandemic nowadays, differentiation is of paramount importance.Copyright © 2022, The Author(s).
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Background: Despite renal impairment (RI) being a risk factor for severe COVID-19, there are no approved antiviral treatment options for patients with severely impaired kidney function (eGFR less than 30 mL/min/1.73 m2 or kidney failure) in the US. At the time remdesivir (RDV) was initially approved for the treatment of COVID-19, the impact of renal impairment (RI) on pharmacokinetics (PK) of RDV, its metabolites, and the excipient, sulfobutylether beta-cyclodextrin sodium (SBECD), was not known. Method(s): Here, we report the PK data supporting dosing of RDV in COVID-19 patients with severely impaired kidney function. PK samples for RDV and metabolites (GS-704277, GS-441524) were collected in the Phase 3 REDPINE study in hospitalized COVID-19 patients with severely impaired kidney function. Participants in this double-blind study were randomized 2:1 to intravenous (IV) remdesivir (200 mg on Day 1, then 100 mg daily up to Day 5) or IV saline as placebo-to-match. SBECD PK was analyzed in a phase 1 study in non-COVID-19 participants with normal kidney function, mild and moderate RI who received 100 mg dose of remdesivir (containing 3000 mg SBECD). The population PK analysis included observations from healthy and COVID-19 patients with full range of renal function across all adult studies. Result(s): Geometric mean exposures (AUCtau) observed in REDPINE Study as compared to PINETREE Study increased up to 553% for the GS-441524 metabolite (dependent on renal elimination) and to a lesser degree GS-704277 (294%, minor renal elimination) and RDV (78.9%;an increase explained by factors other than renal function, namely, hospitalization and body weight) (Table 1). The increased PK exposures were not associated with new safety signals in this study (n=163 remdesivir, n=80 placebo). Population PK analysis identified baseline eGFR as a significant covariate for GS-704277 and GS-441524 clearance, but not for RDV itself. SBECD PK was characterized by short half-life (t1/2) (1.6 hours in normal renal function to 3.8 hours in moderate RI) and fast plasma clearance (7.9 L/h in normal renal function). Analysis of SBECD in severe RI (REDPINE) is ongoing, but accumulation is not expected based on its observed short plasma t1/2. Conclusion(s): Given the observed PK and the absence of any new safety signals associated with increased metabolite levels in patients with severely impaired kidney function, no dose adjustment is recommended for RDV in COVID-19 patients with eGFR < 30 mL/min/1.73 m2, regardless of the need for dialysis.
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Purpose of study Since mid-April 2020 in Europe and North America, clusters of pediatric cases with a newly described severe systemic inflammatory response with shock have appeared. Patients had persistent fevers >38.5 C, hypotension, features of myocardial dysfunction, coagulopathy, gastrointestinal symptoms, rash, and elevated inflammatory markers without other causes of infection. The World Health Organization, Centers for Disease Control, and Royal College of Paediatrics associated these symptoms with SARS-CoV-2 as multisystem inflammatory syndrome in children (MIS-C). Cardiac manifestations include coronary artery aneurysms, left ventricular systolic dysfunction evidenced by elevation of troponin-T (TnT) and pro-B-type naturietic peptide (proBNP), and electrocardiogram (ECG) abnormalities. We report the clinical course of three children with MIS-C while focusing on the unique atrioventricular (AV) conduction abnormalities. Case #1:19-year-old previously healthy Hispanic male presented with abdominal pain, fever, and non-bloody diarrhea for three days. He was febrile and hypotensive (80/47 mmHg) requiring fluid resuscitation. Symptoms, lab findings, and a positive COVID-19 antibody test were consistent with MIS-C. Methylprednisolone, intravenous immunoglobulin (IVIG), and enoxaparin were started. He required epinephrine for shock and high flow nasal cannula for respiratory distress. Initial echocardiogram demonstrated a left ventricular ejection fraction (LVEF) of 40% with normal appearing coronaries. Troponin and proBNP were 0.41 ng/mL and proBNP 15,301 pg/mL respectively. ECG showed an incomplete right bundle branch block. He eventually became bradycardic to the 30s-50s and cardiac tracing revealed a complete AV block (figure 1a). Isoproterenol, a B1 receptor agonist, supported the severe bradycardia until the patient progressed to a type 2 second degree AV block (figure 1b). A second dose of IVIG was administered improving the rhythm to a type 1 second degree AV block. An IL-6 inhibitor, tocilizumab was given as the rhythm would not improve, and the patient soon converted to a first-degree AV block. Cardiac magnetic resonance imaging showed septal predominant left ventricular hypertrophy and subepicardial enhancement along the basal inferior/anteroseptal walls typical for myocarditis. Case #2: 9-year-old previously healthy Hispanic male presented after three days of daily fevers, headaches, myalgias, diffuse abdominal pain, and ageusia. He was febrile, tachycardic, and hypotensive (68/39 mmHg). Hypotension of 50s/20s mmHg required 3 normal saline boluses of 20 ml/kg and initiation of an epinephrine drip. Severe hypoxia required endotracheal intubation. After the MIS-C diagnosis was made, he was treated with IVIG, mehtylprednisolone, enoxaparin, aspirin, and ceftriaxone. Due to elevated inflammatory markers by day 4 and patient's illness severity, a 7-day course of anakinra was initiated. Initial echocardiogram showed mild tricuspid and mitral regurgitation with a LVEF of 35-40%. Despite anti-inflammatory therapy, troponin and proBNP were 0.33 ng/mL and BNP of 25,335 pg/mL. A second echocardiogram confirmed poor function so milrinone was started. Only, after two doses of anakinra, LVEF soon normalized. Despite that, he progressively became bradycardic to the 50's. QTc was prolonged to 545 ms and worsened to a max of 592 ms. The aforementioned therapies were continued, and the bradycardia and QTc improved to 405 ms. Patient #3: 9-year-old African American male presented with four days of right sided abdominal pain, constipation, and non-bilious non-bloody emesis. He had a negative COVID test and unremarkable ultrasound of the appendix days prior. His history, elevated inflammatory markers, and positive COVID- 19 antibody were indicative of MIS-C. He was started on the appropriate medication regimen. Initial ECG showed sinus rhythm with normal intervals and echocardiogram was unremarkable. Repeat imaging by day three showed a decreased LVEF of 50%. ECG had since changed to a right bundle branch block. Anakinra as started and steroid dosing was increased. By day 5, he became bradycardic to the 50s and progressed to a junctional cardiac rhythm. Cardiac function normalized by day 7, and anakinra was subsequently stopped. Thereafter, heart rates ranged from 38-48 bpm requiring transfer to the pediatric cardiac intensive care unit for better monitoring and potential isoproterenol infusion. He remained well perfused, with continued medical management, heart rates improved. Methods used Retrospective Chart Review. Summary of results Non-specific T-wave, ST segment changes, and premature atrial or ventricular beats are the most often noted ECG anomalies. All patients initially had normal ECGs but developed bradycardia followed by either PR prolongation or QTc elongation. Two had mild LVEF dysfunction prior to developing third degree heart block and/or a junctional escape rhythm;one had moderate LVEF dysfunction that normalized before developing a prolonged QTc. Inflammatory and cardiac markers along with coagulation factors were the highest early in disease course, peak BNP occurred at approximately hospital day 3-4, and patient's typically had their lowest LVEF at day 5-6. Initial ECGs were benign with PR intervals below 200 milliseconds (ms). Collectively the length of time from initial symptom presentation till when ECG abnormalities began tended to be at day 8-9. Patients similarly developed increased QTc intervals later in the hospitalization. When comparing with the CRP and BNP trends, it appeared that the ECG changes (including PR and QTc elongation) occurred after the initial hyperinflammatory response. Conclusions Although the mechanism for COVID-19 induced heart block continues to be studied, it is suspected to be secondary to inflammation and edema of the conduction tissue. Insufficiency of the coronary arterial supply to the AV node and rest of the conduction system also seems to play a role. Although our patients had normal ECG findings, two developed bundle branch blocks prior to more complex rhythms near the peak of inflammatory marker values. Based on the premise that MIS-C is a hyperinflammatory response likely affecting conduction tissue, our group was treated with different regimens of IVIG, steroids, anakinra, and/or tocilizumab. Anakinra, being an IL-1 inhibitor, has been reported to dampen inflammation in viral myocarditis and tocilizumab has improved LVEF in rheumatoid arthritis patients. Based on our small case series, patient's with MISC can have AV nodal conduction abnormalities. The usual cocktail of IVIG and steroids helps;however, when there are more serious cases of cardiac inflammation, adjuvant immunosuppresants like anakinra and toculizumab can be beneficial. (Figure Presented).
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Background: Treatment of iron deficiency anaemia (IDA) involves replenishing body iron stores either intravenously (IV) or orally. Previous studies of IV iron in pregnancy have been unblinded, which creates potential for bias measuring primary outcomes. We aimed to determine the feasibility of blinding pregnant women with IDA to IV iron (brown solution) compared to oral iron. Method(s): Two-arm, placebo-controlled randomised trial, with blinding of patients, clinicians and outcome assessors, at 2 Sydney maternity hospitals, 2021.2022. Pregnant women, .18 years of age, 26.32 + 6 weeks' gestation, with mildmoderate IDA (Haemoglobin 80.104 g/L and Ferritin <30 mug/ L), planning to give birth at one of the study hospitals were included. Women were randomised to either (1) a single IV ferric carboxymaltose 1000 mg infusion plus daily placebo oral capsules, or (2) oral capsules 80 mg elemental iron daily and a single placebo intravenous saline infusion, from treatment allocation to birth. Result(s): The study closed after recruiting 16/50 (32%) planned women, at a median gestation of 30 weeks. The baseline median haemoglobin was 101.5 g/L [interquartile range (IQR) 99.0-103.75 g/L] and baseline median ferritin was 11.5 mug/L [IQR 8.0-17.5 mug/L]. Two thirds of women (69%) correctly determined their treatment allocation on the infusion day, increasing to 87% at 4 weeks post infusion (100% of women IV iron). Median,[IQR] haemoglobin increased to 116 g/L, [113-120] and 110 g/L, [104-114] at 4 weeks in IV and oral iron groups respectively. Compliance, acceptability and side effects were measured. Conclusion(s): Blinding of women to IV iron was not successful at 4 weeks post-infusion. Trial recruitment was delayed and interrupted by COVID.
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Case report Background: P olyethylene g lycol ( PEG) a llergy i s g enerally c onsidered a contraindication to COVID-19 mRNA vaccines as they are formulated in lipid nanoparticles that contain a PEGylated lipid. However, there is an uncertain risk of allergy to mRNA vaccines in PEG-allergic patients and sensitivity of skin testing in the diagnosis of PEG allergy is poor. Our patient presented to Allergy and Immunology Clinic with a history of systemic reaction to PEG (in bowel prep), now requiring a mRNA booster. The patient had tolerated two doses of the AstraZeneca vaccine prior but this vaccine was no longer available in our health region due to safety concerns. Method(s): The chart was reviewed, skin prick testing to polyethylene glycol (PEG) 3350 (Restoralax diluted in water) was negative. Intradermal testing to the Pfizer-BioNTech vaccine at a dilution of 1:100 was positive at 11mm. Histamine and saline controls were appropriate. Result(s): Graded administration of the Pfizer-BioNTech vaccine was offered and consent was obtained. The patient tolerated administration of the vaccine in four divided doses (0.03cc, 0.06cc, 0.09cc, and 0.12cc). The patient was observed for 20 minutes between doses and an hour after the last dose with no reaction. Conclusion(s): We found that skin test reactivity to the Pfizer-BioNTech COVID-19 vaccine, at a nonirritating concentration (1:100), does not reliably predict reactivity on vaccine inoculation. This case highlights that it is possible to safely administer COVID-19 mRNA vaccines to patients with positive intradermal testing to the vaccine and a high suspicion for PEG allergy.
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An open comparative study was conducted to assess the efficacy and safety of cytoflavin in the treatment of 50 patients who underwent SARS-CoV-2 infection, with subsequently developed mild cognitive impairment after leaving an infectious disease hospital. The survey was carried out using the Montreal Cognitive Assessment Scale (MoCA test) for the study of cognitive status, as well as the SF-36 questionnaire to determine parameters of the quality of life of patients and to assess the level of asthenia, anxiety and depression during follow-up (at the beginning of study and after 10 days of fluid therapy). Patients of the main group received intravenous infusion of cytoflavin for 10 days at a dose of 10 mL per 100 mL of 0.9% sodium chloride solution, while the comparison group received "active placebo" (100.0 mL of 0.9 sodium chloride solution) also for 10 days. During observation, the main test group patients showed significant discrepancies in the amount of complaints such as dizziness, headache, and decreased cognitive performance versus placebo group. According to the MoCA test results, patients of the main group showed higher total score on the background of improved cognitive functions: attention improved by 13.2%, p < 0.05 (subtest "repetition" of the number series in forward and reverse order and the "cotton" subtest with letter "A");regulatory skills improved by 9.8%, p < 0.05 (speaking "fluency" subtest);visual-constructive skills improved by 11.4%, p < 0.05 ("clock drawing" subtest);phrase repetition improved by 11.3%, p < 0.05, and literature associations improved by 11.3%, p < 0,05. Based on the results of the SF-36 questionnaire, the life quality was also significantly improved, by 19.5%, p < 0.05 on the average (including physical functioning and condition, pain intensity, general condition, vitality and mental health indicators). The tolerance of cytoflavin in all patients was good and there were no side effects related to the drug. Thus, the use of cytoflavin in the complex treatment of SARS-CoV-2 patients, who suffered from the infection with encephalopathy/mild cognitive impairment developed as part of the postvoid syndrome, reduces neurological deficit and helps to restore neurocognitive functions.Copyright © 2021 Eieeaeoea aaoiia
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Introduction: Following second wave of COVID 19 infection in India there has been unprecedented spike in mucormycosis cases. Liposomal amphotericin(LAmB) is the drug of choice in most of these cases. Though nephrotoxicity of conventional amphotericin has been well described in literature, there is sparse data on nephrotoxicity following of LAmB use.Herein we describe spectrum of kidney disease and electrolyte abnormalities that arised following LAmB use in patients afflicted with mucormycosis. Method(s): It is a single centre retrospective observational study. Hospitalised patients with mucormycosis who were started on LamB and if they develop Acute Kidney Injury (AKI)criteria as per KDIGO2012 guidelines during hospital stay were included in the study after excluding patients with pre existing Chronic Kidney Diseases( CKD),concomitant use of other Nephrotoxic medications,use of nonLAmB formulations for mucormycosis treatment,AKI at the time of admission and critical illness requiring ICU stay.Their demographic characteristics,co morbidities,salient clinical examination findings and laboratory parameters were entered in excel sheet.Descriptive statistics were used to analyse data. Result(s): Mean Age of study population was 51.03 years. Male to female ratio was 25:6.Among comorbidities, Diabetes was seen in 74.19% cases, Hypertension was seen in 35.4% and Ischemic Heart disease was seen 9.6% cases. When risk factors for mucormycosis were analysed 100% of study population had recent COVID19 infection, 93.5% of study population had prior steroid use and 9.6% of the patients had received Tocilizumab. Out of 102 patients who received LAmB 31(30.3%) developed AKI. Among these cases, Stage1 AKI was seen in 8 (25.8 %) cases,Stage 2 AKI was seen in 17 (54.8%) cases and Stage3 AKI was seen in 6 (19.3%) cases. None of these patients had oliguria or requirement of dialysis during hospital stay. 54.8% of patients had persistent AKI at the time of discharge.Hypokalemia was seen in 77.4% cases and 41.9% had severe hypokalemia requiring IV potassium treatment.Hyponatremia was seen in 51.6% cases, most of these cases were mild and only one patient had severe hyponatremia requiring hypertonic saline infusion.Hypomagnesemia was seen in 29 % cases. Conclusion(s): LAmB was associated with significant nephrotoxicity resulting in development of AKI in 30% of cases.Most of these cases had stage 2 AKI and none of them required dialysis support.Almost half of the study population had persistent AKI at the time of discharge.Among the electrolyte disorders,Hypokalemia was particularly severe. No conflict of interestCopyright © 2023
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Introduction: Pulmonary transit time (PTT), the time taken for contrast to travel from the left to right ventricle, can be used as a surrogate marker for cardiac output. There have been previous studies evaluating the prognostic significance of Magnetic Resonance (MR) and Computed Tomography (CT) PTT in heart failure patients. This study used dynamic CT images to determine the PTT and study its correlation with left and right ventricular ejection fraction and left and right cardiac output in COVID patients, with a known range of cardiac outputs. Method(s): 123 COVID-19 patients were retrospectively studied. A single contrast bolus timing scan was acquired with a 320-detector CT (Acquilion ONE, Canon). A single 2 mm slice was placed axially where left and right ventricle and descending aorta were visualised. Contrast administration and scan acquisition began at the same with 20 ml of Omnipaque with 40 ml saline flush at 5 ml/s. One image was acquired every second and the total scan time was 26 seconds. A circular ROI was placed in the centre left and right ventricle, the signal intensity was plotted over time for each of these regions. Matlab software was used to extract the peak contrast time between the right and left ventricles. MR cardiac images were acquired on a 3 T Prisma, which determined MR PTT, left and right ejection fraction (LVEF, RVEF) and left and right ventricle cardiac output (LVCO, RVCO). These values were already computed from a previous study where this data was taken from. Correlations were studied using the Pearson correlation method using Minitab software. Result(s): There was correlation between MR PTT and LVEF and RVEF, r = - 0.433 p<0.05 and r=-0.358 p<0.05 respectively. A correlation was also seen with CT PTT and LVEF (figure 1) and RVEF, r=-0.-345 p<0.05 and r=-0.2 p=0.029 respectively. A correlation was seen for MR PTT and LVCO and RVCO, r=-0.322 p<0.05 and r=-0.295 p<0.05 but not for CT PTT and LVCO and RVCO, r=-0.1 p=0.297 and r=-0.04 p=0.668 respectively. Conclusion(s): A correlation was seen between MR PTT and CT PTT for both LVEF and RVEF, but this was not seen for CT PTT and LVCO and RVCO. Further work is required to understand the limitations of the CT PTT and why it fails to correlate with these parameters. Limitations may include dynamic CT temporal resolution or due to poor image quality due to motion from breathing. Compared to previous studies there is agreement between the MR PTT and MR cardiac parameters. At this stage there is an indication that CT PTT could be a potential tool to estimate LVEF and RVEF. [Formula presented]Copyright © 2023
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Background: In our multi-disciplinary airways service, we assess refractory breathlessness due to suspected inducible laryngeal obstruction (ILO) and/or breathing pattern disorder (BPD). A significant proportion of patients have evidence of uncontrolled co-morbidity, including rhinitis and asthma, which aggravate airway symptoms. Aim(s): To identify the impact of rhinitis management on i) nasal symptoms ii) asthma control and iii) cough control, for individuals referred with suspected ILO +/- BPD and evidence of rhinitis. Method(s): Patient demographics/clinical data were collected between January 2021 and January 2022. Symptoms were recorded using the Total Nasal Symptom Score (TNSS), Asthma Control Questionnaire (ACQ) in those with asthma and a 10-point self-rating scale in chronic refractory cough (CRC). Result(s): Data were available for 43 patients [72% female, 18% atopic, median (IQR) age 54 (41-64) years] with symptoms of rhinitis, confirmed by nasendoscopy in 41% (not all patients had nasendoscopy due to COVID-19 pandemic). Co-morbidities included asthma 54% (39%, of whom were on biologic treatment), CRC (21%), ILO (35%) and BPD (35%). Rhinitis management comprised education (100%), nasal corticosteroids (91%), saline nasal douche (49%) and antihistamines (10%). TNSS scores improved [from 5 (4-6) to 3 (2-4), p<0.001] following intervention. In those with asthma, there was improvement in ACQ [2.98 (2.15-3.70) to 2.00 (0.95-3.05), p<0.001], and in those with chronic refractory cough in self-rating score [8 (4-9) to 2 (2-6), p=0.11]. Conclusion(s): Optimisation of medical treatment for individuals with rhinitis is important and can improve outcomes in patients with asthma, CRC, ILO and BPD.
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The airborne transmission of SARS-CoV-2 has been quickly suggested based on the stability of SARS-CoV-2 in aerosol for 3 hours. Nebulization, by a possible microorganisms contamination and/or by the aerosolization of contaminated particles, may expose health care workers. Thus, various guidelines on nebulization emerged during the SARS-CoV-2 pandemic to ensure a maximal protection. This study aimed to address the risk of airborne transmission in patients hospitalized with severe COVID-19. Ten severe COVID-19 patients were recruited at the admission in the hospital. They were treated by nebulization with a standard single-use jet nebulizer operating at 8 L/min with a T piece connected to a mouthpiece and a filter. Immediately after the first nebulization, the residual solution of each nebulizer was sampled. Then, the nebulizers were refilled with isotonic saline solution to complete the residual volume. The filter was replaced by a BioSampler (SKC 20-mL) loaded with 20 mL phosphatebuffered saline and 0.5% bovine serum albumin. The nebulizer was driven by a compressed air supply, and a 10minnebulization was performed again on the bench. The emitted aerosol was continuously collected during the nebulization. The nominal and emitted dose were sampled. The SARS-CoV-2 viral load was quantified in all samples by RT-PCR. No SARS-CoV-2 RNA was found in any sample for all nebulizations. The result of this study shows no SARS-CoV-2 nebulizers contamination by COVID-19 patients at hospital and does not support the role of nebulizers in terms of aerosol virus dissemination in air. Nevertheless, exhaled virus by the patient itself remains and must be considered independently to the nebulizer.
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Background and aim: The COVID-19 pandemic has led to a proliferation of intubation barriers designed to protect healthcare workers from infection. We developed the Suction-Assisted Local Aerosol Containment Chamber (SLACC) and tested it in the operating room. The primary objectives were to determine the ease and safety of airway management with SLACC, and to measure its efficacy of aerosol containment to determine if it significantly reduces exposure to health care workers. Method(s): In this randomized clinical trial, adult patients scheduled to undergo elective surgery with general endotracheal anesthesia were screened and informed consent obtained from those willing to participate. Patients were randomized to airway management either with or without the SLACC device. Patients inhaled nebulized saline before and during anesthesia induction to simulate the size and concentration of particles seen with severe symptomatic SARS-CoV-2 infection. Result(s): 79 patients were enrolled and randomized. Particle number concentration (PNC) at the patients' and healthcare workers' locations were measured and compared between the SLACC vs. control groups during airway management. Ease and success of tracheal intubation were recorded for each patient. All intubations were successful and time to intubation was similar between the two groups. Healthcare workers were exposed to significantly lower particle number concentrations (#/cm3) during airway management when SLACC was utilized vs. control. The particle count outside SLACC was reduced by 97% compared to that inside the device. Conclusion(s): The SLACC device does not interfere with airway management and significantly reduces healthcare worker exposure to aerosolized particles during airway management.Copyright © 2023 Elsevier Ltd
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Background: When facing unprecedented emergencies such as the coronavirus disease 2019 (COVID-19) pandemic, a predictive artificial intelligence (AI) model with real-time customized designs can be helpful for clinical decision-making support in constantly changing environments. We created models and compared the performance of AI in collaboration with a clinician and that of AI alone to predict the need for supplemental oxygen based on local, non-image data of patients with COVID-19. Materials and methods: We enrolled 30 patients with COVID-19 who were aged >60 years on admission and not treated with oxygen therapy between December 1, 2020 and January 4, 2021 in this 50-bed, single-center retrospective cohort study. The outcome was requirement for oxygen after admission. Results: The model performance to predict the need for oxygen by AI in collaboration with a clinician was better than that by AI alone. Sodium chloride difference >33.5 emerged as a novel indicator to predict the need for oxygen in patients with COVID-19. To prevent severe COVID-19 in older patients, dehydration compensation may be considered in pre-hospitalization care. Conclusion: In clinical practice, our approach enables the building of a better predictive model with prompt clinician feedback even in new scenarios. These can be applied not only to current and future pandemic situations but also to other diseases within the healthcare system.