Multisystem Organ Dysfunction Research Articles

Diagnostic accuracy of pancreatic stone protein in patients with sepsis: a systematic review and meta-analysis

BackgroundSepsis is a common syndrome of multiorgan system dysfunction secondary to the dysregulated inflammatory response to infection. The role of pancreatic stone protein (PSP) in diagnosing sepsis has been investigated in previous studies. The meta-analysis aimed to comprehensively investigate the diagnostic value of PSP in identifying sepsis.MethodsPubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), were systematically searched. Studies investigating the diagnostic performance of PSP were included. Pooled sensitivity, specificity, positive Likelihood Ratio (+ LR) and negative Likelihood Ratio (-LR), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic (SROC) were calculated.ResultsThe sensitivity of PSP was 0.88 (95% CI: 0.77–0.94), and the pooled specificity was 0.78 (95% CI: 0.65–0.87). Pooled + LR, -LR, and DOR were 4.1 (2.3, 7.3), 0.16 (0.07, 0.34), and 26 (7, 98). The AUC value for the SROC of PSP was 0.90 (0.87, 0.92). The pooled sensitivity, specificity, + LR and - LR, and DOR for PSP among neonates were 0.91 (95% CI: 0.84, 0.96), 0.66 (95% CI: 0.58, 0.74), 3.97 (95% CI: 0.53, 29.58), 0.13 (95% CI: 0.02, 1.00), and 31.27 (95% CI: 0.97, 1004.60).ConclusionsThis study indicates that PSP demonstrated favorable diagnostic accuracy in detecting sepsis. Well-designed studies are warranted to ascertain the value of PSP measurement to guide early empirical antibiotic treatment, particularly in neonates.

Effect of IL-6R blockade on plasma lipids and clinical outcomes among hospitalized patients with COVID-19 infection

Plasma lipid levels are modulated by systemic infection and inflammation, but it is unknown whether these changes reflect inflammatory responses or caused directly by pathogen presence. We explored the hypothesis that anti-inflammatory intervention via interleukin 6 receptor (IL-6R) blockade would influence plasma lipid levels during severe infection, and evaluated the association of plasma lipid changes with clinical outcomes. Sarilumab (monoclonal antibody blocking IL-6R) efficacy was previously assessed in patients with COVID-19 (NCT04315298). This post hoc analysis determined whether strong inflammatory reduction by sarilumab in patients with COVID-19 pneumonia of increasing severity (severe, critical, multisystem organ dysfunction) affected plasma lipid changes between day 1 (baseline) and day 7 of study therapy. Baseline lipid levels reflected the presence of acute systemic infection, characterized by very-low HDL-C, low LDL-C, and moderately elevated triglycerides (TG). Disease severity was associated with progressively more abnormal lipid levels. At day 7, median lipid levels increased more in the sarilumab versus placebo group (HDL-C +10.3%, LDL-C +54.7%, TG +32% vs. HDL-C +1.7%, LDL-C +15.4%, TG +8.8%, respectively). No significant association between lipid changes and clinical outcomes was observed. In conclusion, severe-to-critical COVID-19 pneumonia causes profound HDL-C depression that is only modestly responsive to strong anti-IL-6R inflammatory intervention. In contrast, LDL-C depression is strongly responsive to IL-6R blockade, with LDL-C levels likely returning to the pre-disease set point. These results advance our understanding of the complex relationship between serum lipids and infection/inflammation and suggest that HDL-C depression during acute contagious disease is driven by infection and not IL-6-mediated inflammation.

Diagnosis and Management of Pulmonary Manifestations of Telomere Biology Disorders.

Telomere biology disorders (TBD) are a group of genetic disorders characterized by premature shortening of telomeres, resulting in accelerated aging of somatic cells. This often leads to major multisystem organ dysfunction, and TBDs have become increasingly recognized as a significant contributor to numerous disease processes within the past 10-15years. Both research and clinical practice in this field are rapidly evolving. A subset of patients with TBD suffers from interstitial lung disease, most commonly pulmonary fibrosis. Often, the clinical presentation is indistinguishable from other forms of lung fibrosis. There are no pathognomonic radiographic or histological features, and a high level of suspicion is therefore required. Telomere evaluation is thus crucial to establishing the diagnosis. This review details the clinical presentation, objective evaluation, indicated genetic testing, and recommended management strategies for patients affected by interstitial lung disease associated with TBDs. Our goal is to empower pulmonologists and other healthcare professionals who care for these patients to provide appropriate and personalized care for this population.

Clinical Characteristics and Treatment Outcomes of Idiopathic Multicentric Castleman Disease: Data from a Pediatric Cohort

Background: Idiopathic multicentric Castleman disease (iMCD) is a rare, atypical hematologic disorder characterized by diffuse lymphadenopathy and systemic inflammation causing potentially fatal multi-organ system dysfunction. Though the etiology remains unknown, interleukin-6 (IL-6) has been implicated in disease pathogenesis and siltuximab, a monoclonal antibody that antagonizes IL-6, is the only FDA-approved iMCD treatment. Despite substantial morbidity for children with iMCD, the pediatric experience has not been well characterized. It is unclear whether insights gleaned from adults apply to children or whether siltuximab, which was never prospectively studied in a pediatric population, achieves similar response rates in children. We sought to correct this knowledge gap and better characterize pediatric iMCD. Methods: The ACCELERATE longitudinal Castleman disease (CD) natural history registry was interrogated for patients under 18 years of age at time of diagnosis. For each patient, complete medical history and lymph node biopsy slides were collected and extracted, and a panel of clinicians and pathologists performed independent adjudication of the diagnosis. Demographics - including age at diagnosis, histopathologic subtype, clinical subtype, clinical symptoms, and most severe laboratory parameters present within ± 90 days from date of pathological diagnosis were aggregated. Lastly, treatments administered to the cohort of pediatric patients were inventoried and both clinical response (defined as at least 50% reduction in abnormal clinical and laboratory criteria) and durable response (defined as a positive clinical response lasting ≥ 365 days with no other CD treating drug administered in between) were determined. Results: Nineteen pediatric patients were confirmed to have iMCD, of which 14 (74%) were male and 5 (26%) were female (Table 1A). The mean (standard deviation [SD]) age at diagnosis was 13.6 (4.3), with the youngest patient diagnosed at 2 years of age. Much of the cohort demonstrated hypervascular lymph node histology (89.5%). Clinically, 84% of the patients demonstrated the severe TAFRO (thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, organomegaly) subtype while 16% were not otherwise specified. 95% of patients presented with constitutional symptoms and all but one patient presented with fatigue and fevers. All 19 patients presented with organomegaly and fluid retention (anasarca, ascites, pleural effusions, and/or peripheral edema). No patients demonstrated CD-specific skin abnormalities (violaceous lymphocytic papules or cherry hemangiomata) or interstitial lymphocytic pneumonitis. Labs indicated significant systemic inflammation, with mean (SD) C-reactive protein, erythrocyte sedimentation rates, and albumin values of 128.3 (102.7) mg/L, 74.5 (42.5) mm/hr, and 2.7 (0.6) g/dL, respectively. Eighteen (95%) patients presented with anemia, with a mean (SD) hemoglobin value of 9.5 (2.2) g/dL. Sixteen (84%) patients demonstrated platelet abnormalities, with 13 patients presenting with thrombocytopenia and three with thrombocytosis. No patient demonstrated hypergammaglobulinemia. Nine patients received three unique siltuximab regimens: siltuximab ± CS (corticosteroids), siltuximab + sirolimus ± CS, and siltuximab + other (other being defined as all other treatments such as rituximab, eculizumab, and ravulizumab) (Table 1B). Siltuximab ± CS was administered to six patients; 83% (n=5) had a positive response, and 60% of responders achieved a durable response. Lastly, two patients with TAFRO died from their disease. Conclusions: Overall, real-world medical record data from a cohort of pediatric iMCD patients enrolled in ACCELERATE reveals high disease burden within this population. A notable degree of TAFRO, the most severe iMCD subtype, was observed within this pediatric cohort, with clinical manifestations and laboratory abnormalities commonly observed in adult iMCD. This makes this population particularly vulnerable and highlights the need for prompt and accurate treatment. We also observed a high response rate to siltuximab ± CS in this small cohort, supporting its use in pediatric iMCD. Further research examining the effectiveness of siltuximab in a larger cohort of pediatric patients as well as other treatments is needed to identify optimal treatment approaches.

A Translational Approach to Identifying and Targeting TNF Signaling in Idiopathic Multicentric Castleman Disease

Idiopathic multicentric Castleman disease (iMCD) is a rare, immunological illness with an unknown etiology. It is characterized by multiple enlarged lymph nodes with unique histopathological features and systemic inflammation resulting from cytokine release syndrome, which can rapidly develop into multiple organ failure and death. Inhibition of the pro-inflammatory cytokine interleukin-6 (IL-6) with siltuximab, the only FDA-approved therapy for iMCD, is an effective treatment for approximately one-half of patients. Patients who do not respond to IL-6 inhibition have few treatment options beyond cytotoxic chemotherapy. A better understanding of the pathogenic mechanisms underlying iMCD is critically needed to uncover new potential treatments for patients. To characterize the immune dysregulation in iMCD, our lab previously profiled serum analytes and circulating cell types in patient blood during active disease. Serum proteomic analyses identified tumor necrosis factor (TNF) signaling as a highly enriched pathway in both siltuximab responders and non-responders. Both immunophenotypic and serum proteomic data indicated that T cells, which can produce TNF, were activated in iMCD. However, whether TNF production by activated T cells was a key mechanism promoting iMCD was unclear. To determine if T cells contribute to the characteristic cytokine storm in iMCD, we investigated the ability of T cells from iMCD patients to produce different inflammatory cytokines including TNF. Upon stimulation with phorbol myristate acetate and ionomycin (PMA/I), both naïve and non-naïve CD4 + T cells from iMCD patients (n=9) produced significantly more TNF compared to healthy controls (n=9). There was a >2-fold increase in the frequency of TNF-expressing naïve CD4 + T cells from iMCD patients versus healthy controls. We also found a significant, yet marginal, increase in the frequency of TNF + non-naïve CD4 + T cells from iMCD patients. Although TNF and IFN-γ are both well-established markers of T cell activation, we did not observe a similar rise in interferon-gamma (IFN-γ) after stimulation in either CD4 + T cell subset. Taken together, these data indicate that CD4 + T cells in iMCD patients hyper-respond to stimulation specifically by producing excess TNF. In parallel to flow cytometric, proteomic, and T cell stimulation data, we leveraged KGML-xDTD, a knowledge graph-based machine learning framework, to predict potential novel drug treatments for iMCD. Utilizing 3,659,165 nodes and 18,291,237 edges in RTX-KG2 from 70 public biomedical sources, we trained a random forest-based machine learning algorithm on true positive and true negative treatment relationships. The top three novel predicted treatments for iMCD included two TNF inhibitors, adalimumab and certolizumab pegol, and the B cell depleting agent, rituximab, the second most prescribed drug for iMCD after siltuximab. We then used the reinforcement learning module of KGML-xDTD to predict the mechanism linking adalimumab to iMCD, which included IL-4, IL-6, IL-8, IL-10, STAT3, and CD4. These data reveal a potential new treatment strategy and further implicate TNF by CD4-expressing T cells in iMCD pathogenesis. In addition to our laboratory findings and predictive modeling data that suggest that TNF production by T cells promotes iMCD, we report the successful treatment of a highly refractory iMCD patient with off-label use of a TNF blocker. When a 50-year old iMCD patient was experiencing multi-organ system dysfunction and preparing for hospice care after not responding to IL-6 inhibition, IL-1 inhibition, Bruton's tyrosine kinase (BTK) inhibition, chemotherapy, and autologous stem cell transplantation, we initiated treatment with adalimumab alongside BTK inhibition. Within 3 days of the first infusion, the patient's symptoms and organ dysfunction began to improve and the patient has been in remission for over 6 months. We utilized a translational research approach including experimental and unbiased machine learning approaches to identify TNF as a novel therapeutic target that we inhibited to treat a highly refractory iMCD patient. Together, our data suggest that over-production of TNF, in part by activated T cells, promotes iMCD pathogenesis and highlight that further research is needed into TNF inhibition as a potential treatment strategy for iMCD.

Abstract 12495: Modes of In-Hospital Death in Patients With Cardiogenic Shock (CS): An Analysis From the Critical Care Cardiology Trials Network (CCCTN)

Introduction: Mortality from cardiogenic shock (CS), a syndrome of multi-organ system dysfunction, remains high. However, data regarding how patients with CS expire are limited and may have implications for designing clinical trials, identifying therapeutic strategies, and improving outcomes. Aim: We sought to describe primary modes of in-hospital death among patients admitted with CS to cardiac intensive care units (CICUs). Methods: CCCTN is a multi-national research network of advanced CICUs coordinated by the TIMI Study Group (Boston, MA). Using standardized definitions, site investigators classified the direct mode of in-hospital death for patients with CS. Categories included 8 possible modes of cardiovascular (CV) and non-CV death ( Fig ). Subgroups defined by cardiac arrest prior to CICU admission and use of mechanical circulatory support (MCS) were explored. Results: Among 1098 CS cases captured from 10/2021-09/2022, 358 (32.6%) died during the index hospitalization with a median time to death of 4.3 (Q1-Q3, 1.1-10.9) days from CICU admission. Among the deaths, 50%, 41%, and 9% occurred in the context of HF-CS, AMI-CS, and secondary CS, respectively. Overall, mode of death was CV in 82% of cases ( Fig A ). Refractory CS was the dominant mode of death (66%), followed by arrhythmia (13%), anoxic brain injury (6%), and respiratory failure (5%; Fig A ). Compared to patients without preceding cardiac arrest, those with cardiac arrest prior to CICU admission were more likely to die from anoxic brain injury (10% vs. 1%; p<0.01; Fig B ). Compared to patients managed without MCS, those with MCS were more likely to die from refractory shock (p<0.01), either cardiogenic (74% vs. 61%) or non-cardiogenic (6% vs. 3%; Fig C ). Conclusions: Most in-hospital deaths in patients with CS are related to direct CV causes, particularly refractory CS. However, there is potentially important heterogeneity in mode of death across subgroups defined by preceding cardiac arrest and use of MCS.

Acute heart failure with incidentally found cystic adrenal mass.

Pheochromocytomas are rare adrenal tumors characterized by excessive catecholamine secretion. Symptoms and signs associated with pheochromocytomas are usually intermittent and chronic but can rarely develop into life-threatening crises. We describe a case of acute severe congestive heart failure in a previously healthy female, who recovered rapidly (4 days after admission) with acute medical therapy. The etiology on evaluation was a spontaneous bleed in a previously undiagnosed pheochromocytoma, resulting in a pheochromocytoma crisis and transient stress cardiomyopathy, followed by quick recovery of cardiac function. Our aim is to describe pheochromocytoma as a rare cause of stress cardiomyopathy. We discuss the evaluation of pheochromocytoma during critical illness and triggers/treatment strategies for pheochromocytoma crises. Hemorrhage in a pheochromocytoma can result in a pheochromocytoma crisis, with sudden release of excess catecholamines resulting in multisystem organ dysfunction and high mortality. Acute decompensated heart failure can be a rare presentation of pheochromocytoma, in a patient with no cardiac risk factors. Measurement of metanephrines in acutely stressful clinical situations can have considerable overlap with the biochemical picture of pheochromocytoma. Early imaging studies may help with the differential diagnosis. Pheochromocytoma should be ruled out before performing an adrenal biopsy. Emergent adrenalectomy in pheochromocytoma crisis results in high mortality. Medical management of the acute crisis followed by elective adrenalectomy after alpha-blockade results in better outcomes.

Surgical Management of Sirenomelia: A Case Study.

Sirenomelia is a rare congenital condition characterized by fusion of the lower limbs. Patients with sirenomelia generally do not survive long after birth because the condition is associated with multisystem organ dysfunction due to developmental anomalies. Considering the low incidence and few cases surviving the neonatal period, there is minimal understanding regarding the surgical management of sirenomelia. We present a unique case of an infant born with type 1 sirenomelia, absence of external genitalia, presence of a cloaca, absence of the bladder, and presence of an imperforate and vestigial anus, who not only survived the birth process, but, at the age of 11 months, was determined to be a candidate for surgical separation of the lower extremities. This case was approached much like a dorsal rectangular flap syndactyly release. Large Z-plasty flaps were designed and raised, and the soft tissue within the skin bridge was meticulously dissected to preserve anatomy and to provide adequate skin flaps without perineal skin grafting. A quadrangular flap was designed to reconstruct the perineum and produce a neo-vulva using de-epithelialization. Successful lower extremity separation was achieved. There were no major postoperative complications. The patient progressed with lower extremity function, and eventually achieved independent ambulation. Management of sirenomelia is incredibly challenging, and data to guide surgical management are limited. This report details our approach to a successful lower extremity separation, repair, and neo-vulvar reconstruction in a case of type I sirenomelia.

E43 Multisystem inflammatory syndrome in children: an experience from Batna –Algeria

Abstract Introduction Multisystem Inflammatory Syndrome in Children (MIS-C) is a new phenomenon reported worldwide with temporal association with Covid-19. MIS-C is defined as a clinically serious condition requiring hospitalization with fever, multi-system organ dysfunction, inflammatory biomarkers increase. Objectives The aim of this study was to describe the demographic, clinical features, therapeutic aspects, complications, and outcomes of patients with Multisystem Inflammatory Syndrome in Children (MIS-C) in our region. Methods A retrospective descriptive study was conducted in the COVID-19 area of the Department of Pediatrics of the university hospital center (CHU Benflis Touhami Batna) over a three-year period from March 2019 to March 2022. Demographic and clinical data were collected. Results As at April 01, 2022, a total of 24 patients were hospitalized for MIS-C in our COVID-19 area of the Department of Pediatrics. The mean age was 5 years [3 months to 15 years]; 58% were male. The most common presenting symptoms were fever (88%), rash (60%), conjunctival injection (56%). 45% had gastrointestinal symptoms and 33% had respiratory symptoms. Elevated levels of C-reactive protein, d-dimer, and procalcitonin were found in 80%, 63%, and 50% of the patients, respectively. For treatment, intravenous immunoglobulin was used in 11 (46%), corticosteroids in 18 (75%). All patients were discharged home. Conclusion the incidence of MIS-C among children infected with SARS-CoV-2 is unclear as children often present with mild symptoms of Covid-19. This serious disease condition requires more surveillance and study. Disclosure statement: None declared.

Evaluation and Medical Management of Chronic Pelvic Pain.

Chronic pelvic pain (CPP) is a challenging condition affecting an estimated 15% of females in the United States. Multiorgan system dysfunction results in the complex clinical pain presentation. Similar to other chronic pain syndromes, CPP is influenced by biopsychosocial factors and requires a multimodal approach for optimal pain management. This review summarizes the clinical evaluation and medical management of CPP with a comprehensive approach.

Management of Acutely Decompensated Pulmonary Hypertension.

Pulmonary arterial hypertension is a severe life-threatening condition associated with increased pulmonary vascular resistance and resulting right heart dysfunction. Admission to intensive care unit with acutely decompensated right heart failure is a significant negative prognostic event with a high risk of multisystem organ dysfunction and death. Presentations are heterogenous and may combine signs of both diastolic and systolic dysfunction complicating management. Renal dysfunction is often present, but other organ systems can be involved resulting in findings such as acute hepatic dysfunction or bowel wall congestion and ischemia. The goals of therapy are to rapidly reverse ventriculo-arterial decoupling and reduce right ventricular afterload to prevent progression to refractory or irreversible right heart failure. Triggering events must be investigated for and addressed urgently if identified. Volume status management is critical and both noninvasive and invasive testing can aid in prognostication and guide management, including the use of inotropes and vasopressors. In cases of refractory right heart dysfunction, consideration of urgent lung transplantation and mechanical circulatory support is necessary. These patients should be managed at expert centers in an intensive care setting with a multidisciplinary team of practitioners experienced in the management of right heart dysfunction given the high short- and long-term mortality resulting from acute decompensated right heart failure.

Predicting inpatient mortality in pediatric traumatic brain injury: insights from a national database.

The purpose of this study was to determine factors significantly associated with mortality and length of stay (LOS) in admissions to the pediatric intensive care unit (PICU) for traumatic brain injury (TBI). A cross-sectional, retrospective cohort study that identified PICU admissions with TBI from forty-nine hospitals in the USA using the Pediatric Health Information System database from 2016 to 2021. Univariable analyses comparing those who did and did not experience mortality were performed. The following regression analyses were conducted: logistic regression with mortality as dependent variable; linear regression with LOS as the dependent variable; logistic regression with mortality as the dependent variable but only included patients with cerebral edema; and linear regression with LOS as the dependent variable but only included patients who survived. From the regression analysis for mortality in all TBI patients was utilized to develop a mortality risk score. A total of 3041 admissions were included. Those with inpatient mortality (18.5%) tended to be significantly younger (54 vs. 92months, p < 0.01), have < 9 pediatric Glasgow Coma Scale on admission (100% vs. 52.9%, p < 0.01) and more likely to experience acute renal, hepatic and respiratory failure, acidosis, central diabetes insipidus, hyperkalemia, and hypocalcemia. Regression analysis identified that pediatric Glasgow Coma Scale, alkalosis and cardiac arrest significantly increased risks of mortality. The TBI mortality risk score had an area under the curve of 0.89 to identify those with mortality; a score of 6 ≤ was associated with 88% mortality. Patients admitted to the PICU with TBI have 18.5% risk of inpatient mortality with most occurring the first 48h and these are characterized with greater multisystem organ dysfunction, received medical and mechanical support. TBI mortality risk score suggested is a practical tool to identify patients with an increase likelihood to die.

Multi-Inflammatory Syndrome in Children (MIS-C) in 2023: Is It Time to Forget about It?

Multisystem inflammatory syndrome in children (MIS-C) is defined as a clinically serious condition requiring hospitalization involving fever, multi-system organ dysfunction, and an increase in inflammatory biomarkers. The syndrome was originally described as a post-infectious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which usually causes COVID-19. During the COVID-19 pandemic, not only did the virus undergo mutations but vaccines against SARS-CoV-2 were also developed. Both these conditions led to a decrease in the incidence of MIS-C. This narrative review summarizes the recent updates for MIS-C, particularly regarding the change in incidence, the link between the SARS-CoV-2 vaccine and MIS-C, and new updates of MIS-C treatments.

0800 Pediatric PSG Flagging Etiologies and Impact on Clinical Timeline

Abstract Introduction There is a paucity of literature regarding “flagged PSGs”, a term used to triage emergent PSGs for expedited scoring and reporting. Given the morbidity and multi organ-system dysfunction of untreated OSAS in children, it is extremely important to identify and treat expediently. The aim of this study was to review flagged PSGs at a tertiary level pediatric sleep center, including management and intervention timelines. Methods This is an IRB-approved retrospective chart review of flagged PSGs (N=266) over a three-year period (2019-2022) at a pediatric sleep center. PSGs were flagged based on laboratory protocols and provider discretion. Demographic, clinical, and PSG data were obtained from EMR. Results Patients with flagged studies were white (49.2%), non-Hispanic (87.2%), males (66.9%) with (mean ± SD) age (6.9 ± 6.0) years and BMI of (23.3 ± 11.6) kg/m2, respectively. Reasons for flagging studies were repetitive brief oxygen desaturations &amp;lt; 80% (46.6%), sustained desaturations &amp;lt; 85% (32.3%), sustained EtC02 &amp;gt;60mmHg (5.6%), or other concerning events (15.5%). Most common comorbidity was pulmonary (41.4%), followed by genetic (30.5%), cardiac (23.3%), and neuromuscular (11.7%). 23.3% children were obese. 30.1% had prior airway surgeries; most commonly being adenotonsillectomy (70.0%). Mean Apnea-hypopnea index was 47.2 ± 36.1 events/hr. 35% children had hypoxemia and 36.8 % had hypoventilation. Time duration from flagging study to finalized report, surgical, or medical intervention was 4.3 ± 6.0, 78.2 ± 105 and 26.6 ± 93.0 days, respectively. Medical (40.6%) and surgical (37.9%) intervention were similar in frequency; however, children &amp;lt; 8 were more likely to undergo surgery (p&amp;lt; 0.001). Most frequent surgical intervention was adenotonsillectomy (82.1%). Patients with AHI&amp;gt;30 had less time between PSG and surgical intervention (65.3 ± 96.7 days vs 112 ± 119 days, p=0.04). Conclusion Most frequent reason for flagging PSG was repetitive brief desaturations. Time to surgical intervention was longer than medical intervention; however, they occurred in similar frequency. Pandemic staffing shortages and PAP machine recalls impacted both interventions. Patients with higher disease severity experienced quicker scoring, report finalization, and surgical intervention. Future directions include establishing protocols between sleep laboratory and surgical teams, assess the impact of this and further streamline care. Support (if any)

Characterization of a robust mouse model of heart failure with preserved ejection fraction.

Heart failure (HF) is a leading cause of morbidity and mortality particularly in older adults and patients with multiple metabolic comorbidities. Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome with multisystem organ dysfunction in which patients develop symptoms of HF as a result of high left ventricular (LV) diastolic pressure in the context of normal or near normal LV ejection fraction (LVEF; ≥50%). Challenges to create and reproduce a robust rodent phenotype that recapitulates the multiple comorbidities that exist in this syndrome explain the presence of various animal models that fail to satisfy all the criteria of HFpEF. Using a continuous infusion of angiotensin II and phenylephrine (ANG II/PE), we demonstrate a strong HFpEF phenotype satisfying major clinically relevant manifestations and criteria of this pathology, including exercise intolerance, pulmonary edema, concentric myocardial hypertrophy, diastolic dysfunction, histological signs of microvascular impairment, and fibrosis. Conventional echocardiographic analysis of diastolic dysfunction identified early stages of HFpEF development and speckle tracking echocardiography analysis including the left atrium (LA) identified strain abnormalities indicative of contraction-relaxation cycle impairment. Diastolic dysfunction was validated by retrograde cardiac catheterization and analysis of LV end-diastolic pressure (LVEDP). Among mice that developed HFpEF, two major subgroups were identified with predominantly perivascular fibrosis and interstitial myocardial fibrosis. In addition to major phenotypic criteria of HFpEF that were evident at early stages of this model (3 and 10 days), accompanying RNAseq data demonstrate activation of pathways associated with myocardial metabolic changes, inflammation, activation of extracellular matrix (ECM) deposition, microvascular rarefaction, and pressure- and volume-related myocardial stress.NEW & NOTEWORTHY Heart failure with preserved ejection fraction (HFpEF) is an emerging epidemic affecting up to half of patients with heart failure. Here we used a chronic angiotensin II/phenylephrine (ANG II/PE) infusion model and instituted an updated algorithm for HFpEF assessment. Given the simplicity in generating this model, it may become a useful tool for investigating pathogenic mechanisms, identification of diagnostic markers, and for drug discovery aimed at both prevention and treatment of HFpEF.

ATYPICAL HEMOLYTIC UREMIC SYNDROME – A RARE CASE REPORT

Atypical hemolytic uremic syndrome (aHUS), a rare variant of thrombotic microangiopathy, is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The condition is associated with poor clinical outcomes with high morbidity and mortality. Atypical HUS predominantly affects the kidneys but has the potential to cause multi-organ system dysfunction. This uncommon disorder is caused by a genetic abnormality in the complement alternative pathway resulting in over-activation of the complement system and formation of microvascular thrombi. Abnormalities of the complement pathway may be in the form of mutations in key complement genes or autoantibodies against specic complement factors. We discuss , clinical manifestations, diagnosis, complications, and management of aHUS.

A tale of 2 conversions: Dichotomous decision in the spectrum of Shone syndrome is still a dilemma

A tale of 2 conversions: Dichotomous decision in the spectrum of Shone syndrome is still a dilemma

Review article: Practical considerations for fluid resuscitation in cirrhosis.

Standard clinical methods of assessing volume and providing resuscitation are not always applicable to patients with advanced or decompensated cirrhosis. Despite this being well known from a clinical perspective, there remains relatively little evidence to guide clinicians though fluid management in patients with cirrhosis and, often, multi-organ system dysfunction. This review summarises the current understanding of the circulatory dysfunction in cirrhosis, modalities for assessing volume status, and considerations for fluid selection. It additionally provides a practical approach to fluid resuscitation. We review current literature on cirrhosis pathophysiology in steady-state and shock, clinical implications of fluid resuscitation, and strategies to assess intravascular volume. Literature reviewed here was identified by the authors through PubMed search and review of selected papers' references. Clinical management of resuscitation in advanced cirrhosis remains relatively stagnant. Although several trials have attempted to establish the superior resuscitative fluid, the lack of improvement in hard clinical outcomes leaves clinicians without clear guidance. The absence of consistent evidence for fluid resuscitation in patients with cirrhosis limits our ability to produce a clearly evidence-based protocol for fluid resuscitation in cirrhosis. However, we propose a preliminary practical guide to managing fluid resuscitation in patients with decompensated cirrhosis. Further studies are needed to develop and validate volume assessment tools in the specific context of cirrhosis, while randomised clinical trials of protocolized resuscitation may improve care of this patient population.

A pilot study to evaluate clinical factors associated with iron and ferritin elevations during pediatric extracorporeal membrane oxygenation.

Introduction: Elevations in serum ferritin and serum iron occur during pediatric extracorporeal membrane oxygenation (ECMO). Previous reports attribute the elevation to frequent red blood cell transfusions and/or hemolysis. Chronic transfusion can cause iron deposition in tissues leading to multisystem organ dysfunction. This study aims identify clinical factors associated with elevated ferritin and iron in pediatric ECMO patients, along with post-decannulation magnetic resonance imaging (MRI) assessment of iron deposition in liver and brain.Methods: Prospective, pilot study, using descriptive statistics to investigate potential associations between patient characteristics, serum ferritin and iron levels, and post-decannulation hepatic and basal ganglia iron deposition.Results: In this study, nine patients (100%) had elevated serum ferritin levels during ECMO. High ferritin levels were more common with veno-arterial than with veno-venous cannulation (p = 0.026) and were also associated with high plasma free hemoglobin levels (p < 0.001). Five patients presented with elevated serum iron levels. High serum iron levels were associated with higher daily (p = 0.016) and cumulative transfusion volumes (p = 0.013) as well ECMO duration beyond 7days. MRI scans were performed on three patients with no evidence of abnormal iron deposition detected in the liver or brain.Conclusions: This pilot study shows that during pediatric ECMO, elevations in serum ferritin and serum iron occur and those elevations may be related to the cannulation modality, ECMO duration, amount of hemolysis, and volume of red blood cell transfusions. Further investigation is warranted to fully understand the implications of elevated serum iron and ferritin in pediatric ECMO.

Editor's Choice Articles for February.

Editor's Choice Articles for February.