VOLUME VERSUS PRESSURE TARGETED NON-INVASIVE VENTILATION IN AMYOTROPHIC LATERAL SCLEROSIS (VOP ALS): study protocol for a randomised controlled trial (preprint)

Introduction Amyotrophic lateral sclerosis (ALS) is a rare, idiopathic, progressive, neuromuscular disease. The prevalence in England and Wales is between 4 and 5 cases per 100,000. A significant proportion of ALS cases are complicated by respiratory and sleep impairment which can reduce health related quality of life (HRQOL) and survival. Non-invasive ventilation (NIV) is the standard of care to treat respiratory and sleep symptoms. Patients who are compliant with NIV have improved survival, HRQOL and reduced symptoms. Different modes of NIV are available and broadly fall into two categories: pressure support ventilation (PSV) and volume assured pressure support (VAPS) ventilation. A clinically enhanced version of VAPS in the form of intelligent volume assured pressure support with automatic EPAP (iVAPS-AE) is now widely available and although spontaneous timed (ST) mode is the preferred choice in ALS, to date no one mode has been shown to be superior. In this single-centre randomised controlled trial we will explore the differences in NIV compliance and effect on HRQOL, between ST and iVAPS-AE NIV modes in patients diagnosed with respiratory failure due to ALS. We also want to explore the optimal NIV mode for patients diagnosed with ALS. This trial is still in the data collection phase and has the potential to guide changes in clinical respiratory practice in ALS. Methods and Analysis VOP ALS is a single blinded, single centre, RCT exploring the impact of iVAPS-AE on patient outcomes compared to ST-mode in patients diagnosed with ALS related respiratory impairment. Primary outcome is mean NIV compliance and secondary outcome is health reported quality of life, both measured over 90 days. The study aimed to recruit 40 patients, but it was revised to 15 because of the COVID-19 pandemic. The analysis will be mainly descriptive by treatment arms and summarised with 95% confidence interval. Ethics and Dissemination VOP ALS is sponsored in the UK by University Hospitals Coventry and Warwickshire NHS Trust and has been granted ethical approval by Northwest - Haydock Research Ethics Committee Ethics Committee (REC ref: 21/NW/0326). Publication of results in a peer-reviewed journal and conference presentations are expected. Trial Registration Number: NCT05328492. Registered 4th April 2022 - Retrospectively registered, https://clinicaltrials.gov/study/NCT05328492

Dual Action Potential: Bromophenol in Combatting COVID-19 and Modulating ACE2-Mediated Circulatory Hemostasis: A Molecular Modeling Study (preprint)

The possible recurrent threat of the COVID-19pandemic driven by SARS-CoV-2 underscores the critical need for innovative pharmaceutical interventions targeting Angiotensin-Converting Enzyme 2 (ACE2)  receptors. Beyond the recognized role of ACE2in viral entry, its intricate involvement in circulatory hemostasis, with potential hypotension-related complications, necessitates a comprehensive approach. This in silico study investigates the therapeutic potential of Bromophenol (BP) derived from Halophitys incurves (HIE) against both ACE2-mediated viral entry and circulatory complications, particularly hypotension. Utilizing advanced in silico techniques; we assessed the pharmacokinetic parameters of BP through SWISSADME, ADME/T, and Swisstargetprediction. The Molecular Dynamics Simulation analysis further substantiated the favorable interactions within the BP-ACE2  complex. The results elucidated a favorable performance of BP in comparison to β-D-Mannose, serving as a potent inhibitor in impeding ACE2-mediated viral entry and contributing to the regulation of circulatory hemostasis. This inquiry emphasizes BP's potential as a robust inhibitor against the multifaceted actions of ACE2, offering valuable insights into its therapeutic effectiveness against COVID-19. Additionally, it contributes to a deeper understanding of ACE2-mediated circulatory hemostasis by revealing BP's regulatory role in this physiological process. The encouraging findings warrant further exploration of BP as a novel therapeutic agent targeting ACE2 -induced dual unfavorable actions.

Deep sedation with dexmedetomidine administered by electrophysiologists during COVID-19 pandemic compared with propofol administered by anesthesiologists for transcatheter ablation of atrial fibrillation (preprint)

Background: COVID-19 pandemic, limiting the availability of anesthesiologists, has impacted heavily on the organization of invasive cardiac procedures such as transcatheter atrial fibrillation (AF) ablation. Objective We compared the safety and efficacy of deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision, against the standard protocol performed with propofol. Methods We retrospectively included all AF ablation procedures performed in 2020: 23 patients sedated with 1% propofol (2 ml bolus followed by infusion starting at 1 mg/Kg/h), 26 patients with dexmedetomidine (infusion starting at 0.7 mcg/Kg/h). Both groups additionally received 1 mcg/Kg of midazolam as a single bolus and 0.05 mg single boluses of fentanyl prior to ablation on each pair of pulmonary veins (PV). Primary outcomes were oxygen desaturation (<90%) or need for assisted ventilation/intubation, bradycardia (heart rate <45 bpm) and persistent hypotension (systolic blood pressure <90 mmHg). Results Baseline characteristics and hemodynamic variables did not differ between the two groups (all p>0.05). In 8/23 (35%) patients propofol infusion velocity reduction was necessary to maintain the hemodynamic values, compared to 7/26 (27%) with dexmedetomidine. Inter-group comparison of hemodynamic variables during the procedure showed no statistically significant difference, despite a trend in favor of dexmedetomidine (3 respiratory depressions and 3 persistent hypotension episodes with propofol vs. 0 with dexmedetomidine; p = 0.057). Conclusion Deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision is safe and effective for AF transcatheter ablation. A trend towards a lower incidence of hypotension and respiratory depression was noted when compared to propofol.

Manifestations and outcomes of intracerebral hemorrhage during COVID‐19 pandemic in China: a multicenter, longitudinal cohort study (preprint)

Background: We just right were carrying out a multicenter cohort study about ICH when COVID-19 broke out in Wuhan，and we wondered whether COVID-19 pandemic was associated with the manifestations and outcomes of intracerebral hemorrhage (ICH). Methods: : Acute ICH patients before (1/12/2018-30/11/2019) and during COVID-19(1/12/2019-30/11/2020) pandemic at 31 centers in China, were entered into the analysis. Demographic information, clinical manifestations and outcomes were collected and compared between the two groups. Results: : From December 1, 2018 to November 30, 2020, a total of 3460 patients with ICH were enrolled and eventually analyzed. Results showed that patients with ICH were more likely to be older, have higher systolic blood pressure (BP) (P<0.001), diastolic-BP (P=0.002), higher admission NIHSS score (P=0.039) and higher fasting blood glucose (P=0.003) during COVID-19 pandemic compared with before. After adjusting age, gender, COVID-19 pandemic was associated with 3-month poor outcome (OR = 1.206, 95%CI: 1.043-1.395) and 3-month mortality (OR = 1.711, 95%CI: 1.428-2.050) after ICH onset. Conclusions: : COVID-19 pandemic deteriorated the manifestations and outcomes of ICH.

Losartan in hospitalized patients with COVID-19 in North America: An individual participant data meta-analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) have been hypothesized to benefit patients with COVID-19 via the inhibition of viral entry and other mechanisms. We conducted an individual participant data (IPD) meta-analysis assessing the effect of starting the ARB losartan in recently hospitalized COVID-19 patients. METHODS: We searched ClinicalTrials.gov in January 2021 for U.S./Canada-based trials where an angiotensin-converting enzyme inhibitors/ARB was a treatment arm, targeted outcomes could be extrapolated, and data sharing was allowed. Our primary outcome was a 7-point COVID-19 ordinal score measured 13 to 16 days post-enrollment. We analyzed data by fitting multilevel Bayesian ordinal regression models and standardizing the resulting predictions. RESULTS: 325 participants (156 losartan vs 169 control) from 4 studies contributed IPD. Three were randomized trials; one used non-randomized concurrent and historical controls. Baseline covariates were reasonably balanced for the randomized trials. All studies evaluated losartan. We found equivocal evidence of a difference in ordinal scores 13-16 days post-enrollment (model-standardized odds ratio [OR] 1.10, 95% credible interval [CrI] 0.76-1.71; adjusted OR 1.15, 95% CrI 0.15-3.59) and no compelling evidence of treatment effect heterogeneity among prespecified subgroups. Losartan had worse effects for those taking corticosteroids at baseline after adjusting for covariates (ratio of adjusted ORs 0.29, 95% CrI 0.08-0.99). Hypotension serious adverse event rates were numerically higher with losartan. CONCLUSIONS: In this IPD meta-analysis of hospitalized COVID-19 patients, we found no convincing evidence for the benefit of losartan versus control treatment, but a higher rate of hypotension adverse events with losartan.

COVID-19 Coinfection with Malaria and Its Presentation with Bilateral Pleural Effusion: A Case Report and Literature Review (preprint)

Background There could be misdiagnosis of COVID 19 for malaria and vice versa because of their similar presentation, particularly when clinician relies mainly on symptoms. Coinfection with COVID-19 and malaria is associated with increased all-cause in-hospital mortality compared to isolated infection with SARS-CoV-2. Presentation with pleural effusion adds another challenge in the diagnosis of COVID-19.Case summary: This is a 57-year-old woman who presented with symptoms of acute febrile illness associated with shortness of breath and cough. Physical examination was remarkable for fever, hypotension, tachycardia, tachypnea, desaturation, decreased air entry and dullness over bilateral lower 1/3rd of the chest. Upon investigations, she was found to have ring-form trophozoites of plasmodium falciparum and bilateral ground glass opacities, bilateral consolidations and bilateral pleural effusions. She was managed with supportive treatments, antimalarial agents and antibiotics. COVID-19 was diagnosed late due to the initial high diagnostic inertia.Conclusion Clinicians should be aware of the possibility of COVID-19 in any patient who presents with acute febrile illness or respiratory complaints like shortness of breath and cough. In patients with symptoms such as fever, fatigue, and headache, both malaria and COVID-19 tests should always be performed. Though pleural effusion is rarely reported in COVID-19 patients, viral etiologies like COVID-19 should be considered if alternative diagnoses are lacking.

Evaluation of pre-induction dynamic arterial elastance as an adjustable predictor of post-induction hypotension: A prospective observational study.

STUDY OBJECTIVE: Dynamic arterial elastance (Eadyn) has been suggested as a functional measure of arterial load. We aimed to evaluate whether pre-induction Eadyn can predict post-induction hypotension. DESIGN: Prospective observational study. PATIENTS: Adult patients undergoing general anesthesia with invasive and non-invasive arterial pressure monitoring systems. MEASUREMENTS: We collected invasive and non-invasive Eadyns (n = 38 in each), respectively. In both invasive and non-invasive Eadyns, pre-induction Eadyns were obtained during one-minute tidal and deep breathing in each patient before anesthetic induction. Post-induction hypotension was defined as a decrease of >30% in mean blood pressure from the baseline value or any absolute mean blood pressure value of <65 mmHg for 10 min after anesthetic induction. The predictabilities of Eadyns for the development of post-induction hypotension were tested using receiver-operating characteristic curve analysis. MAIN RESULTS: Invasive Eadyn during deep breathing showed significant predictability with an area under the curve (AUC) of 0.78 (95% Confidence interval [CI], 0.61-0.90, P = 0.001). But non-invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.49-0.81, P = 0.096) and deep breathing (AUC = 0.53, 95% CI, 0.36-0.70, P = 0.75), and invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.41-0.74, P = 0.095) failed to predict post-induction hypotension. CONCLUSION: In our study, invasive pre-induction Eadyn during deep breathing -could predict post-induction hypotension. Despite its invasiveness, future studies will be needed to evaluate the usefulness of Eadyn as a predictor of post-induction hypotension because it is an adjustable parameter.

Life-threatening hypotension in the immediate postoperative period of cataract surgery under topical anesthesia: a report of two cases.

BACKGROUND: Cataract surgery is one of the most frequent surgeries in the world. It is a very safe procedure mostly performed under topical anesthesia in outpatients centers. Due to the growing lack of anesthesiologists, cataract surgeries are more frequently performed without an anesthesiologist present in the operating room. Although extremely rare, life-threatening complications may occur. CASES PRESENTATION: We report two cases of cataract surgery complicated by severe hypotension that required emergency resuscitation in the immediate postoperative period and hospitalization in intensive care unit. Anaphylactic shock was confirmed in the first case and suspected in the second. CONCLUSIONS AND IMPORTANCE: Even though cataract surgery is a very safe procedure, it is essential to ensure the presence of an anesthesiologist to manage potential, though extremely rare, life-threatening complications such as anaphylactic reactions.

Hemodynamic changes in patients with SARS-CoV-2 infection presenting for cesarean delivery under spinal anesthesia: a retrospective case-control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with adverse maternal and neonatal outcomes. Early studies suggested that COVID-19 was associated with a higher incidence of hypotension following neuraxial anesthesia in parturients. We explored the hemodynamic response to spinal anesthesia for cesarean delivery in pregnant severe respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) positive patients, using a retrospective case-control design. METHODS: We searched our electronic medical records for patients who received spinal anesthesia for cesarean delivery, and were SARS-CoV-2 positive or recovered at delivery, and used historical and SARS-CoV-2 negative controls from two tertiary care hospitals. We compared the demographic, clinical, and hemodynamic variables between patients who were SARS-CoV-2 positive at delivery, those who were positive during pregnancy and recovered before delivery, and controls. Analyses were stratified by normotensive versus hypertensive status of the patients at delivery. RESULTS: We identified 22 SARS-CoV-2 positive, 73 SARS-CoV-2 recovered, and 1517 controls. The SARS-CoV-2 positive, and recovered pregnant patients, had on average 5.6 and 2.2 mmHg, respectively, higher post-spinal mean arterial pressures (MAPs) than control patients, adjusting for covariates. Additionally, the lowest post-spinal MAP was negatively correlated with the number of daysbetween the onset of COVID-19 symptoms and delivery in patients with hypertension (correlation -0.55, 95% CI -0.81 to -0.09). CONCLUSIONS: Patients with SARS-CoV-2 infection during pregnancy exhibit less spinal hypotension than non-infected patients. While the clinical significance of this finding is unknown, it points to important cardiovascular effects of the virus.

Investigating Autonomic Nervous System Dysfunction among Patients with Post- Covid Condition and Prolonged Cardiovascular Symptoms (preprint)

The variability of heart rate (HR) and arterial pressure (AP), and their responses to head-up tilt test (HUTT) was investigated in post-Covid-19 syndrome (PCS) patients, reporting tachycardia and/or postural hypotension. PCS patients were tachycardic and showed attenuation of the following parameters: RMSSD; power of RR spectra at HF; occurrence of 2UV pattern of RR (symbolic analysis); and sample entropy. Basal AP and LF power of systolic AP were similar between PCS patients and control subjects; while 0V patterns of AP were exacerbated in PCS patients. Despite tachycardia and decrease in RMSSD, no parameter changed during HUTT in PCS patients. PCS patients reassessed after 6 months showed higher HF power of RR spectra and higher percentage of 2UV pattern of RR. Moreover, the reassessed PCS patients showed a lower occurrence of 0V patterns of AP, while the HUTT elicited HR and AP responses identical to control subjects. The HR and AP variability suggest an autonomic dysfunction with sympathetic predominance in PCS patients; while the lack of responses of HR and BP variability indices during HUTT indicates a marked impairment of autonomic control. However, the reassessment of PCS patients showed that the noxious effect of the PCS tended to fade over time.

Capillary Leak Syndrome after SARS-CoV-2 Infection and COVID-19 Vaccines: A Comparative Review (preprint)

Systemic capillary leak syndrome (SCLS) is an uncommon, potentially life-threatening disorder defined as recurrent attacks of pseudo-shock. This syndrome occurs due to the disruption of endothelial cells, which leads to increased vascular permeability, causing intravascular fluid to leak into the extravascular space and albumin to be retained in the interstitial space. SCLS can lead to hypovolemia, peripheral hypoperfusion, and acute renal insufficiency. The syndrome is presented with fever, generalized edema, pleural effusions, dyspnea, hypovolemia, hemoconcentration, prerenal azotemia, shock, and syncope. After ruling out other causes of hypovolemic shock, the diagnosis of SCLS can be considered on the presence of the classical triad of hypotension, hemoconcentration, and hypoalbuminemia. Eliminating the precipitating factors is the cornerstone of SCLS management. It is advisable to be very cautious and weigh the risks and benefits of vaccination of people with a history of this condition. This review will discuss and compare different aspects of SLCS after SARS-CoV-2 infection and COVID-19 vaccination.

Temporal progression of sepsis on critical care COVID-19 patients: a retrospective cohort study.

OBJECTIVE: This study aimed to describe sepsis progression in critical COVID-19 patients using the SOFA score and investigate its relationship with mortality. METHODS: Three researchers collected and analyzed retrospective clinical and laboratory data found in electronic health records from all patients admitted to a severe COVID-19 exclusive intensive care unit from March 2020 to October 2020. Mixed-effect logistic regression was used to evaluate SOFA (Sepsis-3) score variables as mortality prediction markers, while Kaplan-Meier survival curves were used to compare mortality between groups of patients. Cox proportional hazard models were used to further stratify mortality association between variants. RESULTS: A total of 73 patients were included. Temporal COVID-19-related sepsis progression analysis indicates difference in degrees and timing between different organ dysfunction over time. Sepsis-3 Cardiovascular Dysfunction characterized by severe hypotension added to the use of any vasopressor drugs was the only parameter associated with in-hospital death during the first 5 days of hospital admission (OR 2.19; 95%CI 1.14-4.20; p=0.01). CONCLUSION: Increased Sepsis-3 Cardiovascular Dysfunction score, characterized as hypotension associated with the use of vasopressor drugs in the first days of intensive care unit stay, is related to higher mortality in COVID-19 patients and may be a useful prognostic prediction tool.

Hemodynamic changes associated with neuraxial anesthesia in pregnant women with covid 19 disease: a retrospective case-control study.

BACKGROUND: Neuraxial blocks is the recommended mode of analgesia and anesthesia in parturients with Coronavirus 19 (COVID-19). There is limited data on the hemodynamic responses to neuraxial blocks in COVID-19 patients. We aim to compare the hemodynamic responses to neuraxial blocks in COVID-19 positive and propensity-matched COVID-19 negative parturients. METHODS: We conducted retrospective, cross-sectional case-control study of hemodynamic changes associated with neuraxial blocks in COVID-19 positive parturients in a Tertiary care academic medical center. Fifty-one COVID-19 positive women confirmed by nasopharyngeal reverse transcription-polymerase chain reaction (RT-PCR), were compared with propensity-matched COVID negative controls (n = 51). Hemodynamic changes after neuraxial block were recorded by electronic medical recording system and analyzed using paired and unpaired T- test and Wilcoxon-Mann-Whitney Rank Sum tests. The primary outcome was ≥ 20% change in MAP and HR after neuraxial block placement. RESULTS: In the epidural group, 7% COVID-19 positive parturients had > 20% decrease in mean arterial pressure (MAP) from baseline compared to 15% COVID-19 negative parturients (P = 0.66). In the spinal group, 83% of COVID-19 positive parturients had a decrease in MAP more than 20% from baseline compared to 71% in control (P = 0.49). MAP drop of more than 40% occurred in 29% COVID positive parturients in the spinal group versus 17% in COVID-19 negative parturients (P = 0.5465). In COVID-19 positive spinal group, 54% required vasopressors whereas 38% in COVID-19 negative spinal group required vasopressors (P = 0.387). We found a significant correlation between body mass index (BMI) > 30 and hypotension in COVID ( +) parturient with odds ratio (8.63; 95% CI-1.93 - 37.21) (P = 0.007). CONCLUSION: Incidence and severity of hypotension after neuraxial blocks were similar between COVID-19 positive and COVID-19 negative parturients. BMI > 30 was a significant risk factor for hypotension as described in preexisting literature, this correlation was seen in COVID-19 positive parturients. The likely reason for parturients with BMI > 30 in COVID negative patients not showing similar correlation, is that the sample size was small.

Confirmed COVID-19 in a Patient with Pre-Existing Pulmonary Tuberculosis: A Case Report (preprint)

Co-infection with COVID-19 and TB frequently results in fever, coughing, hypotension, a changed blood cell count, raised liver enzymes, and decreased hemoglobin. On May 19, 2022, a retired black African woman in her 59s arrived at the emergency room with a tuberculosis diagnosis. She had no recent travel history and was COVID-19-infected. Five days prior to her admission, her sons, who worked in the medical field, were found to be infected with the COVID-19 infection. The patient arrived at the emergency room with weak muscles, a fever, a productive cough, a sore throat, a lack of appetite, a headache, night sweats, and shortness of breath that had lasted for a day. On chest auscultation, there were reduced breath sounds in the right middle and upper lungs. A Mycobacterium tuberculosis infection without rifampicin resistance was detected in a sputum sample using the GeneXpert Mycobacterium tuberculosis and rifampicin tests. After 36 hours, a throat swab polymerase chain reaction test produced positive findings, confirming the presence of the COVID-19 infection. The patient required continuous oxygen at a rate of four liters per minute via a nasal cannula for the first five days while in the hospital, and she is still taking her anti-tubercular medications. In order to combat hospital-acquired infections, she was given therapy with broad-spectrum antibiotics consisting of 500 mg of azithromycin given once a day for five days and 1 g of intravenous ceftriaxone administered daily for five days.

Venovenous Extracorporeal Membrane Oxygenation After Cardiac Arrest for Acute Respiratory Distress Syndrome Caused by Legionella: A Case Report (preprint)

Background: Legionella remains underdiagnosed in the intensive care unit and can progress to acute respiratory distress syndrome (ARDS), multiorgan failure and death. In severe cases, venovenous extracorporeal membrane oxygenation (VV-ECMO) allows time for resolution of disease with Legionella-targeted therapy. VV-ECMO outcomes for Legionella are favorable with reported survival greater than 70%. Rapid molecular polymerase chain reaction (PCR) testing of the lower respiratory tract aids in diagnosing Legionella with high sensitivity and specificity. We present a unique case of a patient with a positive COVID-19 test and ARDS who suffered a cardiac arrest. The patient was subsequently cannulated for VV-ECMO, and after lower respiratory tract PCR testing, Legionella was determined to be the cause. She was successfully treated and decannulated from VV-ECMO after 8 days.Case Presentation: A 53-year-old female presented with 1 week of dyspnea and a positive COVID-19 test. She was hypoxemic, hypotensive and had bilateral infiltrates on imaging. She received supplemental oxygen, intravenous fluids, vasopressors, broad spectrum antibiotics, and was transferred to a tertiary care center. She developed progressive hypoxemia and suffered a cardiac arrest, requiring 10 minutes of CPR and endotracheal intubation to achieve return of spontaneous circulation (ROSC). Despite mechanical ventilation and paralysis, she developed refractory hypoxemia and was cannulated for VV-ECMO. Dexamethasone and remdesivir were given for presumed COVID-19. Bronchoscopy with bronchoalveolar lavage (BAL) performed with PCR testing was positive for Legionella pneumophila and negative for COVID-19. Steroids and remdesivir were discontinued and she was treated with azithromycin. Her lung compliance improved, and she was decannulated after 8 days on VV-ECMO. She was discharged home on hospital day 16 breathing room air and neurologically intact.Conclusions: This case illustrates the utility of rapid PCR testing to diagnose Legionella in patients with respiratory failure and the early use of VV-ECMO in this patient population. Moreover, many patients encountered in the ICU may have prior COVID-19 immunity, and though a positive COVID-19 test may be present, further investigation with lower respiratory tract PCR testing may provide alternative diagnoses. Patients with ARDS should undergo Legionella-specific testing, and if positive, early VV-ECMO should be considered in patients with refractory hypoxemia.

Evaluation of a camera-based monitoring solution against regulated medical devices to measure: Heart Rate, Respiratory Rate, Oxygen Saturation, and Blood Pressure (preprint)

ABSTRACT Regular monitoring of common physiological signs, including heart rate, blood pressure, and oxygen saturation, can be an effective way to either prevent or detect several potential conditions. In particular, cardiovascular diseases (CVDs) are a worldwide concern. According to the World Health Organization, 31% of all deaths worldwide are from CVDs. Recently, the COVID-19 pandemic has increased the interest in remote monitoring. At present, contact devices are required to extract most of an individual’ s physiological information, which can be inconvenient for users and may cause discomfort. However, remote photoplethysmography (rPPG) technology offers a solution for this issue, which enables contactless monitoring of the blood volume pulse signal using a regular camera, and ultimately can provide the same physiological information as a contact device. In this paper we propose an evaluation of rPPG technology against medical devices in a clinical environment, with a variety of subjects in a wide range of age, height, weight, and baseline vital signs. Results have shown that rPPG technology was able to meet the initial hypothesis of mean error of +/-3 units for Heart rate, Respiration Rate, and SpO2 estimation, as well as +/-10 mmHg for Systolic and Diastolic Blood Pressure.

Clinical Subphenotypes of Multisystem Inflammatory Syndrome in Children: An EHR-based cohort study from the RECOVER program (preprint)

Background: Multi-system inflammatory syndrome in children (MIS-C) represents one of the most severe post-acute sequelae of SARS-CoV-2 infection in children, and there is a critical need to characterize its disease patterns for improved recognition and management. Our objective was to characterize subphenotypes of MIS-C based on presentation, demographics and laboratory parameters. Methods: We conducted a retrospective cohort study of children with MIS-C from March 1, 2020 - April 30, 2022 and cared for in 8 pediatric medical centers that participate in PEDSnet. We included demographics, symptoms, conditions, laboratory values, medications and outcomes (ICU admission, death), and grouped variables into eight categories according to organ system involvement. We used a heterogeneity-adaptive latent class analysis model to identify three clinically-relevant subphenotypes. We further characterized the sociodemographic and clinical characteristics of each subphenotype, and evaluated their temporal patterns. Findings: We identified 1186 children hospitalized with MIS-C. The highest proportion of children (44.4%) were aged between 5-11 years, with a male predominance (61.0%), and non-Hispanic white ethnicity (40.2%). Most (67.8%) children did not have a chronic condition. Class 1 represented children with a severe clinical phenotype, with 72.5% admitted to the ICU, higher inflammatory markers, hypotension/shock/dehydration, cardiac involvement, acute kidney injury and respiratory involvement. Class 2 represented a moderate presentation, with 4-6 organ systems involved, and some overlapping features with acute COVID-19. Class 3 represented a mild presentation, with fewer organ systems involved, lower CRP, troponin values and less cardiac involvement. Class 1 initially represented 51.1% of children early in the pandemic, which decreased to 33.9% from the pre-delta period to the omicron period. Interpretation: MIS-C has a spectrum of clinical severity, with degree of laboratory abnormalities rather than the number of organ systems involved providing more useful indicators of severity. The proportion of severe/critical MIS-C decreased over time.

A retrospective comparative analysis of factors affecting the decision and outcome of initial intravenous immunoglobulin alone or intravenous immunoglobulin plus methylprednisolone use in children with the multisystem inflammatory syndrome.

BACKGROUND: For children with the multisystem inflammatory syndrome(MIS-C), intravenous immunoglobulins (IVIG) with or without methylprednisolone are the most effective treatment. In this study, IVIG combined with methylprednisolone was compared to IVIG used alone in children with MIS-C. METHODS: This retrospective cohort study was carried out between April 1, 2020, and November 1, 2021. This study covered all children with MIS-C. According to whether they received IVIG alone or IVIG with methylprednisolone as an initial treatment for MIS-C, the patients were split into two groups. The IVIG dosage for the patients in group I was 2 gr/kg, whereas the IVIG dosage for the patients in group II was 2 gr/kg + 2 mg/kg/day of methylprednisolone. These two groups were contrasted in terms of the frequency of fever, length of hospital stay, and admission to the pediatric intensive care unit. RESULTS: The study comprised 91 patients who were diagnosed with MIS-C and were under the age of 18. 42 (46.2%) of these patients were in the IVIG alone group (group I), and 49 (53.8%) were in the IVIG + methylprednisolone group (group II). Patients in group II had a severe MIS-C ratio of 36.7%, which was substantially greater than the rate of severe MIS-C patients in group I (9.5%) (p 0.01). When compared to group I (9.5%), the rate of hypotension was considerably higher in group II (30.6%) (p = 0.014). Additionally, patients in group II had considerably higher mean serum levels of C-reactive protein. The incidence of fever recurrence was 26.5% in group II and 33.3% in group I, however the difference was not statistically significant (p > 0.05). CONCLUSIONS: The choice of treatment for patients with MIS-C should be based on an individual evaluation. In MIS-C children with hypotension and/or with an indication for a pediatric intensive care unit, a combination of IVIG and methylprednisolone may be administered. For the treatment modalities of children with MIS-C, however, randomized double-blind studies are necessary.