Requiring ICU Admission Research Articles

Twelve-year review of horse-related trauma registry presentations to a regional Australian Emergency Department.

The size, strength, and unpredictability of horses, makes any interaction a potential situation for minor to severe injury. Despite this, horses continue to be popular for work and recreational activities. There have been five recent Australian publications that have examined various aspects of horse-related trauma, but none have been conducted in regional New South Wales (NSW). This study aims to report on the pattern of horse-related trauma that met the Institute of Trauma Injury Management's (ITIM) Trauma Registry criteria for people who presented to the emergency department at a regional NSW hospital, Australia. An analysis of horse-related trauma extracted from the Wagga Wagga Base Hospital's Trauma Registry from 2012 to 2023 was undertaken. Demographic and clinical variables were reported on all people (n = 85) and statistically evaluated. The cohort median age was 46 years (range 2-78). Males represented 51.8%. Fall from mounted position was the most common mechanism of injury (84.7%) followed by kick while unmounted (11.7%). The head (45.9%) and chest (32.9%) were the most common regions of injury with head (45.9%) and fractures (44.7%) the most common types of injury. 11.8% of people required ICU admission. Horse-related trauma, whether a person is mounted or unmounted, causes mild to severe injuries and can require hospitalization. Horse-related trauma has the potential to significantly impact morbidity, result in death and must not be underestimated. Establishing a protocol for horse-related trauma presentations and increasing awareness of injury patterns sustained from this mechanism has the potential to improve diagnosis and reduce morbidity.

Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-Risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A phase 3 randomized trial.

Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for mild to moderate COVID-19. This phase 2/3, double-blind, randomized (1:1) study assessed oral NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In testing the primary endpoint of COVID-19‒related hospitalization and all-cause deaths and key secondary endpoints including symptom duration and COVID-19‒related medical visits, Type I error was controlled with prespecified sequential testing and the Hochberg procedure. Among 2113 randomized patients enrolled from July 2021 through December 2021, 1966 (NMV/r, n=977; placebo, n=989) were included in the prespecified analysis population (symptom onset ≤5 days, did not receive monoclonal antibodies). NMV/r significantly reduced times to sustained alleviation (median, 13 vs 15 days; hazard ratio [HR]=1.27, p<0.0001) and resolution (16 vs 19 days; HR=1.20, p=0.0022) through Day 28 and significantly reduced the number of COVID-19‒related medical visits and the proportion of patients with such visits. Hospitalized patients treated with NMV/r had shorter stays, none required ICU admission or mechanical ventilation, and all were discharged to home/self-care. Fewer NMV/r-treated patients required additional treatment for COVID-19. No NMV/r-treated patients died through Week 24 compared with 15 placebo-treated patients. In addition to reducing COVID-19‒related hospitalization or death from any cause through Day 28, NMV/r was found to also reduce duration of COVID-19 symptoms and utilization of healthcare resources versus placebo in patients at high risk of progressing to severe disease. ClinicalTrials.gov, NCT04960202, https://clinicaltrials.gov/study/NCT04960202.

Association between serum glucose potassium ratio and mortality in critically ill patients with intracerebral hemorrhage

The effect of serum glucose-to-potassium ratio (GPR) on cerebrovascular diseases has been previously validated. However, the value of the GPR in patients with severe intracerebral hemorrhage (ICH) requiring ICU admission remains unclear. This study aimed to investigate the association between the GPR and the clinical prognosis of critically ill patients with ICH. This study identified patients with severe ICH requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database and divided them into quartiles based on GPR levels. Outcomes included 30-day, 90-day, and 1-year mortality rates. The association between the GPR and clinical outcomes in critically ill patients with ICH was elucidated using Cox proportional hazards regression analysis and restricted cubic splines. In total, 2018 patients (53.8% male), with a median age of 70 years, were enrolled in the study. The 30-day, 90-day, and 1-year mortality rates were 23.9%, 30.1%, and 38.4%, respectively. Per multivariate Cox proportional hazards analysis, an elevated GPR was significantly associated with all-cause mortality. After adjusting for age, sex, Charlson Comorbidity Index, white blood cell count, red blood cell count, platelet count, and Glasgow Coma Scale, patients with an elevated GPR had a higher 30-day mortality (hazard ratio [HR]: 1.32; 95% confidence interval [CI]: 1.22–1.42; P < 0.001), 90-day mortality (HR: 1.27; 95% CI: 1.18–1.37; P < 0.001) and 1-year mortality (HR: 1.22; 95% CI: 1.14–1.31; P < 0.001) when analyzed as a continuous variable. Furthermore, analysis using restricted cubic splines demonstrated a consistent and progressive escalation in the risk of all-cause mortality with an elevated GPR. The GPR was significantly associated with short- and long-term all-cause mortality in critically ill patients with ICH. This finding demonstrates that GPR may be useful in identifying patients with ICH at a high risk of all-cause mortality.

Diagnoses of children living with HIV before and during the COVID-19 pandemic.

There is limited data on diagnoses during hospital stay among children living with HIV(CLHIV) in the antiretroviral and coronavirus disease 2019 (COVID-19) era. The aim of this study was to describe hospital diagnoses and clinical characteristics of CLHIV before and during the COVID-19 pandemic. A retrospective descriptive cross-sectional study was performed. Clinical and laboratory data were retrieved by reviewing folders and discharge summaries from January 2019 to December 2021. Period A (pre-COVID-19) was defined as the period from January 2019 to March 2020. Period B (During COVID-19) was defined as being from April 2020 to December 2021. Ninety-six children contributed 215 diagnoses over the study period. The five most common diagnoses were unspecified HIV disease (47/215, 21.9%), tuberculosis (TB) (42/215, 19.5%), pneumonia (13/215, 6.0%), encephalopathy (11/215, 5.1%) and malnutrition (11/215, 5.1%). Median CD4 count was 377 cells/mm (IQR 126, 726) and 8.0% of the children were virally suppressed. Ninety-five per cent of the children had WHO Stage 3 and 4 (95%) disease and 12.5% of children required ICU admission. No child was diagnosed with COVID-19 despite universal screening. Moreover, 81.7% of the children had a social worker referral documented. Advanced HIV disease (AHD) remains prevalent with TB being the most common diagnosis. There were no cases of COVID-19 recorded in CLHIV. The findings provide a description of the diagnoses of CLHIV in the South African setting prior to and during the COVID-19 pandemic. It highlights the need for more specific documentation of diagnoses to inform better prevention of AHD in children.

Non-COVID Admissions to the ICU After COVID Vaccination: A Multicenter Study.

The vaccination drive for COVID-19 was launched in India after the authorization of ChAdOx1 nCov-19 (Covishield), an adenoviral vector vaccine, and BBV152 COVID-19 (Covaxin), an inactivated virus vaccine. As stated by the CDC, vaccine-related adverse events can happen. In this study, we aimed to assess the timing of the COVID vaccination and admission diagnosis and their effect on ICU mortality. The time from vaccination can help identify adverse events directly related to vaccination. Methods: A retrospective cohort study was conducted across four centers in India. Patients who took the first or second dose of any vaccines and were admitted with non-COVID illness to the ICU were included in the study. Patients were categorized based on the time interval from vaccination as ≤42 days or >42 days. The primary outcome was ICU mortality. The secondary outcomes were the length of ICU stay and duration of mechanical ventilation. A total of 175 patients were included in the study. The mean age was 53.49 (15.89) years, and 61.14% were males. The ICU mortality was 24.57% (18.38% to 31.63%). Thromboembolic events such as acute coronary syndrome (ACS), cerebrovascular accident (CVA), and mesenteric ischemia were seen in 7.43%, 7.43%, and 1.14% of patients, respectively. Six patients (3.43%) developed neuromuscular illness. The mortality was higher in patients >66 years, followed by ≤35 years of age when admitted ≤42 days of vaccination (p=0.008). The mortality was higher in cerebrovascular disorders and was clinically significant (p<0.001). Patients developed thromboembolic events and neuromuscular diseases requiring ICU admission post-COVID vaccination. We observed a significantly higher mortality in the age groups >66 years and ≤35 years when admitted within 42 days of COVID vaccination. Patients admitted with cerebrovascular diseases also had higher mortality.

9202 Characterizing The Physiological Side-Effects Of Over-The-Counter Arthritis Supplements

Abstract Disclosure: K.S. Wei: None. M.O. De La Torre: None. A. Flores: None. C.E. Chiu: None. T.E. Angell: None. Introduction: Over the counter (OTC) health supplements are commonly used by patients for a variety of ailments but may contain active ingredients that are not stated, such as glucocorticoids. Here, we present a case series of 12 patients seen by the Endocrinology Consult service at an urban safety net hospital during 2022-2023 and determined to have iatrogenic adrenal insufficiency (AI) from specific OTC supplements that surreptitiously contained glucocorticoids. Clinical Cases:12 patients using OTC arthritis supplements [Artri King (n=8), Ardosons (n=3), and Ajo Rey (n=1)] were identified. Median age was 52 years and 33.3% were female. All started using the supplements because of joint pain. Median length of use prior to cessation was 6 months. The most common presenting symptoms were nausea/vomiting (42%), fatigue (42%), abdominal pain (33%), and dizziness (17%). The most common physical exam findings of steroid excess included moon facies (66%), central adiposity (66%), abdominal striae (50%), dorsocervical fat pad (33%), and bruising (33%). 3/12 patients required ICU admission. Cortisol assessment was performed in 11/12 patients, which showed normal cortisol level in 1 patient (cortisol ≥16 mcg/dL), AI in 3 patients (cortisol ≤3 mcg/dL), and an equivocal level (cortisol 3-16 mcg/dL) in 7 patients. Cosyntropin stimulation testing in 6/7 patients with equivocal cortisol levels suggested AI in 4 (cortisol level &amp;lt;16 mcg/dL at 60 minutes after ACTH stimulation), whereas 2 showed lower but normal response (cortisol levels 18.2 mcg/dL and 18.4 mcg/dL). In total, 10/12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis. The most common regimens were hydrocortisone 20mg qAM/10mg qPM (33%) and hydrocortisone 5mg qAM/5mg qPM (17%). To date, 2/10 patients have successfully discontinued steroid replacement. Conclusion: These cases demonstrate possible Cushing’s syndrome and/or adrenal insufficiency after unintentional exposure to glucocorticoids in these OTC arthritis supplements, which has only previously been reported in a small number of case reports (1). This series collected over a 2-year period offers important clinical insights: Because patients may not identify or recall a supplement, possible use of OTC medications for arthritis or other anti-inflammatory purposes should be specifically assessed in patients presenting with adrenal insufficiency (especially with concomitant findings suggesting Cushing’s syndrome). For patients on such supplements, immediate discontinuation may not be possible without cortisol replacement and should be done with caution. 1)Boncompagni A.C. et al. A case of iatrogenic Cushing syndrome and subsequent adrenal insufficiency from a hidden ingredient in the supplement Artri Ajo King. J Am Coll Emerg Physicians Open. 2023;4(4):e13007. Presentation: 6/1/2024

Management of non-vascular injuries in patients admitted in trauma ICU secondary to polytrauma with major vascular injury – Institutional experience

BackgroundVascular injuries are associated with high morbidity and mortality. The management is exceedingly demanding and requires involvement of senior clinician. There are known complications associated with vascular injury ranging from limb loss, stroke, and death. There are limited studies examining other injuries that are associated with vascular trauma. This study aimed to review the pattern, management and outcomes of the other injuries associated with vascular injuries. MethodA retrospective cross-sectional study chart review of patients with vascular trauma requiring ICU admission between January 2013 and December 2021. Additional data was prospectively collected from January 2022 to December 2022. All patients admitted to trauma ICU with polytrauma including a vascular injury were reviewed, except patients who died prior the confirmation of vascular injury. The injury was either confirmed by imaging or via exploration. The non-vascular injuries were identified. The pattern, management and outcomes were documented. A pre-designed data proforma was used identifying injury type, management strategy, and outcomes. ResultsOut of 2805 patients that were admitted in trauma ICU from 2013 to 2022, 153 (5 %) patients had vascular injuries. There were 154 documented vascular injuries and 212 associated injuries. This study found that fractures are the most common injuries to be associated with vascular injury ConclusionThe nature of vascular injury and delay to intervention determines outcome of patients, however associated injuries also play an important role in affecting outcomes. The presence of associated injury encourages the multi-disciplinary approach to optimise outcomes.

Routine ICU Surveillance after Brain Tumor Surgery: Patient Selection Using Machine Learning.

Background/Objectives: Routine postoperative ICU admission following brain tumor surgery may not benefit selected patients. The objective of this study was to develop a risk prediction instrument for early (within 24 h) postoperative adverse events using machine learning techniques. Methods: Retrospective cohort of 1000 consecutive adult patients undergoing elective brain tumor resection. Nine events/interventions (CPR, reintubation, return to OR, mechanical ventilation, vasopressors, impaired consciousness, intracranial hypertension, swallowing disorders, and death) were chosen as target variables. Potential prognostic features (n = 27) from five categories were chosen and a gradient boosting algorithm (XGBoost) was trained and cross-validated in a 5 × 5 fashion. Prognostic performance, potential clinical impact, and relative feature importance were analyzed. Results: Adverse events requiring ICU intervention occurred in 9.2% of cases. Other events not requiring ICU treatment were more frequent (35% of cases). The boosted decision trees yielded a cross-validated ROC-AUC of 0.81 ± 0.02 (mean ± CI95) when using pre- and post-op data. Using only pre-op data (scheduling decisions), ROC-AUC was 0.76 ± 0.02. PR-AUC was 0.38 ± 0.04 and 0.27 ± 0.03 for pre- and post-op data, respectively, compared to a baseline value (random classifier) of 0.092. Targeting a NPV of at least 95% would require ICU admission in just 15% (pre- and post-op data) or 30% (only pre-op data) of cases when using the prediction algorithm. Conclusions: Adoption of a risk prediction instrument based on boosted trees can support decision-makers to optimize ICU resource utilization while maintaining adequate patient safety. This may lead to a relevant reduction in ICU admissions for surveillance purposes.

Pediatric Respiratory Hospitalizations in the Pre-COVID-19 Era: The Contribution of Viral Pathogens and Comorbidities to Clinical Outcomes, Valencia, Spain.

Viral respiratory diseases place a heavy burden on the healthcare system, with children making up a significant portion of related hospitalizations. While comorbidities increase the risk of complications and poor outcomes, many hospitalized children lack clear risk factors. As new vaccines for respiratory viral diseases emerge, this study examined pediatric respiratory hospitalizations, focusing on viral etiology, complication rates, and the impact of comorbidities to guide future policy. Data were analyzed from eight pre-COVID influenza seasons (2011/2012-2018/2019) involving patients under 18 years hospitalized with respiratory complaints across 4-10 hospitals in Valencia, Spain. Respiratory specimens were tested for eight viral targets using multiplex real-time reverse-transcription polymerase chain reaction. Demographics, clinical outcomes, discharge diagnoses, and laboratory results were examined. Among the hospitalized children, 26% had at least one comorbidity. These children had higher rates of pneumonia, asthma exacerbation, and pneumothorax, and were twice as likely to require ICU admission, though mechanical ventilation and length of stay were similar to those without comorbidities. Respiratory syncytial virus (RSV) was the most common virus detected (23.1%), followed by rhinovirus/enterovirus (9.5%) and influenza (7.2%). Viral codetection decreased with age, occurring in 4.6% of cases. Comorbidities increase the risk of complications in pediatric respiratory illnesses, however, healthcare utilization is driven largely by otherwise healthy children. Pediatric viral vaccines could reduce this burden and should be further evaluated.

Real-World Effectiveness of Nirsevimab Against Respiratory Syncytial Virus: A Test-Negative Case-Control Study.

Nirsevimab, a long-acting monoclonal antibody, has demonstrated efficacy against RSV-related lower respiratory tract infections (LRTIs) in clinical trials. Post-licensure monitoring is essential to confirm these benefits in real-world settings. To evaluate the real-world effectiveness of nirsevimab against medically attended RSV infections in infants and to assess how effectiveness varies by disease severity, dosage, and time since immunization. This test-negative case-control study used inpatient, outpatient, and emergency room data from the Yale New Haven Health System. Nirsevimab-eligible infants who were tested for RSV using polymerase chain reaction between October 1, 2023 and May 9, 2024 were included. Cases were infants with confirmed RSV infections; controls were those who tested negative. Nirsevimab immunization, verified through state immunization registries. Effectiveness was estimated using multivariable logistic regression, adjusting for age, calendar month, and individual risk factors. Separate models examined effectiveness by clinical setting, disease severity, dose, and time since immunization. Broader outcomes, including all-cause LRTI and LRTI-related hospitalization, were also analyzed, with stratification by early and late respiratory seasons. The analytic sample included 3,090 infants (median age 6.7 months, IQR 3.6-9.7), with 680 (22.0%) RSV-positive and 2,410 (78.0%) RSV-negative. 21 (3.1%) RSV-positive and 309 (12.8%) RSV-negative infants received nirsevimab. Effectiveness against RSV infection was 68.4% (95% CI, 50.3%-80.8%). Effectiveness was 61.6% (95% CI, 35.6%-78.6%) for outpatient visits and 80.5% (95% CI, 52.0%-93.5%) for hospitalizations. The highest effectiveness, 84.6% (95% CI, 58.7%-95.6%), was observed against severe RSV outcomes requiring ICU admission or high-flow oxygen. Although effectiveness against RSV infections declined over time, it remained significant at 55% (95% credible interval, 16%-75%) at 14 weeks post-immunization. Protective effectiveness was also observed against all-cause LRTI and LRTI-related hospitalizations during peak RSV season (49.4% [95% CI, 10.7%-72.9%] and 79.1% [95% CI, 27.6%-94.9%], respectively). However, from February to May, when RSV positivity was low, effectiveness against these broader outcomes was negligible. Nirsevimab provided substantial protection against RSV-related outcomes for at least three months. These findings support the continued use of nirsevimab and provide evidence that may help build public confidence in the immunization program. Question: What is the effectiveness of nirsevimab against medically attended respiratory syncytial virus (RSV) infections in infants?Findings: 680 RSV test-positive cases and 2,410 RSV test-negative controls were included in this test-negative case-control study. Nirsevimab's effectiveness was 69% against RSV infections, 81% against RSV-associated hospitalization, and 85% against severe RSV disease. Effectiveness against RSV infection declined from 79% at 2 weeks post-immunization to 55% at 14 weeks post-immunization.Meaning: Nirsevimab provides strong protection against a wide range of RSV outcomes, but its effectiveness diminishes over time. These data can be utilized to optimize nirsevimab's implementation and sustain its uptake.

Non-Conventional Prognostic Markers in Life-Threatening COVID-19 Cases-When Less Is More.

Background/Objectives: In this study, we aimed to compare the predictive power of non-conventional (neutrophil/lymphocyte ratio-NLR; platelet/lymphocyte ratio-PLR) and conventional markers (C-reactive protein-CRP; procalcitonin-PCT; interleukin-6-IL-6) in terms of disease progression and mortality in severe SARS-CoV-2 patients. Methods: In this prospective observatory study, blood samples were collected daily, focusing on the established inflammatory markers. Critically ill COVID-19 patients who required ICU admission were included. Patient treatment followed established COVID-19 protocols, and the data analysis was performed using SPSS with non-normal distribution methods. The study cohort primarily included patients infected with the delta variant. Results: A mortality rate of 76.6% was observed among 167 patients during the study period. Significant differences in conventional and non-conventional markers between survivor and non-survivor groups were observed. The PCT levels were significantly elevated (p < 0.005) in the deceased group. Among the non-conventional markers, the NLR was consistently higher in non-survivors and emerged as a significant predictor of mortality, whereas the PLR was not elevated among the non-survivors. ROC analyses indicated that PCT and the NLR were the markers with the highest predictive power for mortality. The multivariate logistic regression analysis identified NLR, PCT, CRP, and IL-6 as significant predictors of mortality across different days. The NLR showed a consistent, though not always statistically significant, association with increased mortality risk, particularly on Days 2 and 5. Conclusions: The NLR's accessibility and simplicity of determination make it a valuable and practical tool for monitoring inflammatory processes in viral infections. Our findings suggest that incorporating NLR analysis into routine clinical practice could enhance the early identification of high-risk patients, thereby improving patient management and outcomes.

Association between the stress hyperglycemia ratio and mortality in patients with acute ischemic stroke

The stress hyperglycemia ratio (SHR) is established as a reliable marker for assessing the severity of stress-induced hyperglycemia. While its effectiveness in managing patients with Acute Ischemic Stroke (AIS) remains to be fully understood. We aim to explore the relationship between SHR and clinical prognosis in AIS patients and to assess how diabetes status influences this relationship. In this study, we analyzed data from the Medical Information Mart for Intensive Care (MIMIC-IV) database, selecting patients with AIS who required ICU admission. These patients were categorized into tertiles based on their SHR levels. We applied Cox hazard regression models and used restricted cubic spline (RCS) curves to investigate relationships between outcomes and SHR. The study enrolled a total of 2029 patients. Cox regression demonstrated that a strong correlation was found between increasing SHR levels and higher all-cause mortality. Patients in the higher two tertiles of SHR experienced significantly elevated 30-day and 90-day mortality rates compared to those in the lowest tertile. This pattern remained consistent regardless of diabetes status. Further, RCS analysis confirmed a progressively increasing risk of all-cause mortality with higher SHR levels. The findings indicate that SHR is association with increased 30-day and 90-day mortality among AIS patients, underscoring its potential value in risk stratification. Although the presence of diabetes may weaken this association, significant correlations persist in diabetic patients.

Anesthesia's Influence on Postoperative In-Hospital Morbidity-Mortality in Proximal Femoral Fractures in the Elderly.

Background and Objectives: The incidence of proximal femoral fractures (PFFs) is rising, causing significant morbidity and mortality. Regional anesthesia (RA)'s benefits include the avoidance of intubation and mechanical ventilation, decreased blood loss, and improved analgesia. General anesthesia (GA) offers improved hemodynamic stability. This study examines the in-hospital post-surgical morbidity and mortality seen in PFFs in a cohort of the elderly undergoing GA or RA. Materials and Methods: This is a retrospective cohort study of 319 PFF patients older than 65 years over a single year. Results: In total, 73.7% of patients underwent GA. The patient characteristics were identical between groups, except for smoking. Hypertension was the most frequent comorbidity, followed by hyperlipidemia, NIDDM, and IHD. The overall patient complication rate was 11.4%. Pneumonia was the most common complication (5.1% in GA, 8.4% in RA). A total of 0.9% of patients required ICU admission. Overall, the in-hospital mortality rate was 2.3%, with no statistically significant difference between GA and RA. The GA and RA cohorts were similar in terms of their patient demographics, medical history, and preoperative parameters. In total, 73% of surgeries were under GA. No statistically significant differences were found in total anesthesia time or complication rates. Conclusions: We did not find a difference between general and spinal anesthesia regarding complication rates, anesthesia time, or morbidity. General anesthesia remains best suited for patients receiving anticoagulation treatment and undergoing semi-urgent surgery, but, other than that, the mode of anesthesia administered remains up to the anesthesiologist's preference.

Hematological features and alternate diagnoses in critically ill thrombotic antiphospholipid syndrome patients.

Severe thrombotic antiphospholipid syndrome (APS) frequently affects the kidney, heart, and central nervous system. The precise frequency, clinical picture, differential diagnoses, and outcome of APS-related hematological involvement are lacking, especially in patients requiring ICU admission. This study aimed to describe the hematological manifestations associated with critically ill thrombotic APS patients and catastrophic antiphospholipid syndrome. This French, national, multicenter, retrospective study, conducted, from January 2000 to September 2018, included all APS patients admitted to 24 participating centers' ICUs with any new thrombotic manifestation. The prevalence of hematological manifestations and their associated outcomes were studied. One hundred and thirty-four patients, female 72%, median [IQR] age 45 [34-56] years, with 152 episodes were included. Anemia was present in 95% of episodes and thrombocytopenia in 93%. The lowest values for hemoglobin and platelets were 7.1 [6.3-8.8] g/dL and 38 [21-60] g/L, respectively. The lowest platelet count below 20g/L was significantly associated with a higher in-ICU mortality rate (50%, p < 0.0001). A thrombotic microangiopathy syndrome (TMA) syndrome was seen in 16 patients (12%) and was associated with higher in-hospital mortality (p = 0.05). Median ADAMTS-13 levels were 44% [27-74]. Anti-ADAMTS13 antibodies were tested in 11 patients and found negative in all. A suspicion of heparin-induced thrombocytopenia (HIT) was raised in 66 patients but only four patients were classified as definite HIT. Disseminated intravascular coagulation (DIC) was seen in 51% of patients. Thrombocytopenia is very frequent in severe APS patients and may be related to TMA, HIT, or DIC. Deciphering the mechanisms of thrombocytopenia is decisive in CAPS patients. Key Points • Thrombocytopenia is the hallmark laboratory finding in CAPS. • A complete thrombotic microangiopathy pattern is infrequent in CAPS patients. • Alternate diagnoses of CAPS, especially heparin-induced thrombocytopenia, need to be adequately investigated.

Damage sensing through TLR9 Regulates Inflammatory and Antiviral Responses During Influenza Infection.

Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA, which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), which binds to unmethylated CpG DNA sequences such as those present in bacterial and mitochondrial DNA. To avoid direct pathogen sensing by TLR9, we utilized the influenza virus, which lacks ligands for TLR9, to determine how damage sensing by TLR9 contributes to anti-influenza immunity. Our data show that TLR9-mediated sensing of tissue damage promotes an inflammatory response during early infection, driven by the epithelial and myeloid cells. Along with the diminished inflammatory response, the absence of TLR9 led to impaired viral clearance manifested as a higher and prolonged influenza components in myeloid cells including monocytes and macrophages rendering them highly inflammatory. The persistent inflammation driven by infected myeloid cells led to persistent lung injury and impaired recovery in influenza-infected TLR9-/- mice. Further, we show elevated TLR9 activation in the plasma samples of patients with influenza and its association with the disease severity in hospitalized patients, demonstrating its clinical relevance. Overall, we demonstrate an essential role of damage sensing through TLR9 in promoting anti-influenza immunity and inflammatory response.

Retrospective Comparison of Influenza and COVID-19-Associated Acute Respiratory Distress Syndrome (ARDS): An Experience From a Tertiary Care Hospital.

Background The COVID-19 pandemic has had a profound impact on global healthcare systems, often compared to seasonal influenza due to similarities in clinical presentation. This study aims to compare the clinical characteristics, comorbidities, and outcomes of critically ill patients with COVID-19 and those with influenza admitted to a tertiary care hospital in Islamabad, Pakistan. Methods This retrospective cohort study included 120 patients, 60 with confirmed COVID-19 and 60 with confirmed influenza, all of whom required ICU admission and mechanical ventilation between January 1, 2021, and January 1, 2024. Data were collected from electronic medical records, including demographic information, comorbidities, and clinical outcomes. Descriptive statistics were used to compare the two groups. Results The median age of COVID-19 patients was 55 years (range 30-78), while that of influenza patients was 58 years (range 31-80). Both groups had a slight male predominance (COVID-19: 66.7%, Influenza: 63.3%). Comorbidities were common in both groups, with 75.0% of COVID-19 patients and 83.3% of influenza patients having at least one comorbidity. The most common comorbidities included hypertension (COVID-19: 30.0%, Influenza: 33.3%) and diabetes (COVID-19: 20.0%, Influenza: 25.0%). Clinical outcomes revealed a higher mortality rate among influenza patients (43.3%) compared to COVID-19 patients (28.3%). ICU admission rates were identical for both groups at 66.7%, and mechanical ventilation was required for 66.7% of ICU-admitted patients in both groups. The presence of cardiovascular comorbidities significantly impacted patient outcomes, with higher mortality observed in influenza patients with such comorbidities (44.7%) compared to COVID-19 patients (28.9%). Conclusion This study highlights the significant burden of both COVID-19 and influenza on critically ill patients, particularly those with cardiovascular comorbidities. While influenza patients in this cohort exhibited higher mortality rates, both groups demonstrated substantial ICU admission rates and a need for mechanical ventilation.

The Role of Early Hemoadsorption in Severe COVID-19 Treatment: A Pilot Randomized Controlled Trial

Introduction: Hemoadsorption, an extracorporeal apheresis technique, is reportedly used in severe COVID-19 patients. However, limited evidence from randomized clinical trials supports this practice. Methods: In this single-center study, severe COVID-19 patients requiring ICU admission were randomly assigned (1:1) to receive HA-330 hemoadsorption in combination with standard treatment or standard therapy alone. Both groups received tocilizumab intravenously if their clinical conditions worsened within 24–48 h. The primary outcome was mortality from any cause within 28 days after randomization. Secondary outcomes included mechanical ventilator-free days, daily C-reactive protein levels, oxygenation (defined by PaO2/FiO2 ratio), daily sequential organ failure assessment score, and severity score of lung infiltration on chest X-rays (CXR RALE score). Results: A total of 28 patients underwent randomization, with 14 (50%) receiving HA-330 hemoadsorption. Only 9 out of 14 patients (64.3%) in the control group experienced clinical worsening and were subsequently administered intravenous tocilizumab. At 28 days, the mortality rate was significantly lower in the intervention group (28.57% vs. 78.57%, p = 0.021), with a hazard ratio of death of 0.26 (95% CI = 0.08–0.81; p = 0.021). All of secondary outcomes were comparable in both groups. Conclusion: Based on our pilot randomized trial, the early application of HA-330 hemoadsorption in patients with severe COVID-19 may establish a favorable outcome in term of mortality. These data provide the initial proof of concept for conducting a large-scale study in the future.

Impact of SARS-CoV-2 vaccination in patients with vascular liver diseases: Observations from a VALDIG multicenter study

Background and AimsPatients with vascular liver diseases(VLD) are at higher risk for both severe courses of COVID-19 disease and thromboembolic events. The impact of the SARS-CoV-2 vaccination in VLD patients has not been described and represent the aim of our study. MethodsInternational multicenter prospective observational study in patients with VLD analyzing the incidence of COVID-19 infection after vaccination, severity of side effects, occurrence of thromboembolic events and hepatic decompensation. In a subgroup of patients, the humoral and cellular responses to vaccination were also analyzed. Results898 patients from 14 European centers part of the VALDIG network were included, 872(97.1%) patients received two vaccine doses (fully vaccinated), and 674(75.1%) three doses.Of the total cohort, 151/898 had a COVID-19 infection prior to vaccination, of which 9/151(5.9%) were re-infected. Of the previously 747/898 patients who were not previously infected, 11.2%(84/747) were diagnosed with a COVID-19 infection during the study period.Two infected patients required ICU admission and infection was fatal in two fully vaccinated patients. Main adverse effects were reported in around 40% of patients, being local side effects the most frequent.During the study period, 31(3.5%) patients had thromboembolic events and 21(2.3%) hepatic decompensations. No vaccine-induced-thrombocytopenia (VITT) case was reported.Vaccine immunogenicity was assessed in 36 patients; seroconversion reached 100% and IFNy-T cell responses significant increased post two mRNA-1273 vaccine doses. ConclusionPatients with VLD seems to have a preserved immune response to SARS-CoV-2 vaccination, which appears to be safe and effective in preventing severe COVID-19 infection. Our study cannot definitively establish a direct link between vaccination and thrombotic events, however the contribution of vaccination as a cofactor in VLD remains to be elucidated.

Association between glucose levels at admission and outcomes of pneumonia: a systematic review and meta-analysis

BackgroundElevated blood glucose at hospital admission is frequently observed and has been associated with adverse outcomes in various patient populations. This meta-analysis sought to consolidate existing evidence to assess the association between elevated blood glucose at admission and clinical outcomes amongst pneumonia patients.MethodsWe searched PubMed, Medline, Cochrane library, Web of Science (WoS), and Scopus databases for studies, published up to 31 August 2023, and reporting on the clinical outcomes and the blood glucose levels at admission. Data were extracted by two independent reviewers. Random-effects meta-analyses were used to pool odds ratios (ORs) with 95% confidence intervals (CI) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes.ResultsA total of 23 studies with 34,000 participants were included. Elevated blood glucose at admission was significantly associated with increased short-term (pooled OR: 2.67; 95%CI: 1.73–4.12) and long-term mortality (pooled OR: 1.70; 95%CI: 1.20–2.42). Patients with raised glucose levels were more likely to require ICU admission (pooled OR: 1.86; 95%CI: 1.31–2.64). Trends also suggested increased risks for hospital readmission and mechanical ventilation, though these were not statistically significant. Elevated blood glucose was linked with approximately 0.72 days longer duration of hospital stay.ConclusionElevated blood glucose level at the time of hospital admission is associated with several adverse clinical outcomes, especially mortality, in patients with pneumonia. These findings underscore the importance of recognizing hyperglycemia as significant prognostic marker in pneumonia patients. Further research is needed to determine whether targeted interventions to control glucose levels can improve these outcomes.

Clinical characteristics of COVID-19 in children: a large multicenter study from Iran.

During the COVID-19 pandemic, pediatric cases typically exhibit milder symptoms and lower mortality rates. However, the delay in pediatric vaccination poses major risks for children. This multicenter study aimed to comprehensively analyze demographic characteristics, clinical features, disease severity, and risk factors for ICU admission in Iran. This observational study enrolled children aged 0-21 years with confirmed or probable COVID-19 diagnoses, referred from selected hospitals across 17 counties in Mazandaran province, Iran, between February 19 and August 14, 2021. Patients were categorized into mild, moderate, severe, or critical cases based on clinical and radiographic criteria. Data were extracted from medical records and analyzed using statistical methods. Logistic regression analysis was performed to identify factors associated with ICU admission and disease severity. Among the 1,031 children included in the study, 61 were diagnosed with MIS-C. The distribution of patients by severity was 156 mild, 671 moderate, and 204 severe/critical cases. Age distribution significantly differed across severity groups (P < 0.001), with 55.19% aged over 5 years and 54% being male. 11.44% had underlying diseases. Fever (71.97%) was the most common symptom, followed by cough (34.43%) and dyspnea (24.83%). Within the inpatient group, 19.77% required ICU admission, with 0.91% mortality, including 3 MIS-C cases. Children with underlying diseases, gastrointestinal symptoms, and obesity had 4.16, 3.10-, and 2.17-times higher likelihood of ICU admission, respectively. Our study emphasized the importance of recognizing pediatric COVID-19 severity and symptoms. While fever, cough, and dyspnea prevailed, mortality rates were relatively low. However, comorbidities, obesity, and gastrointestinal symptoms linked to ICU admission, stressing early intervention. BMI also impacted disease severity and admission rate. Vaccination and targeted interventions are essential for protecting vulnerable children and easing healthcare strain.