Clinical Sequalae Research Articles

Aficamten in patients with obstructive hypertrophic cardiomyopathy: an integrated safety analysis

Abstract Background Aficamten is a next-in-class, oral, selective cardiac myosin inhibitor targeting the hypercontractility underlying hypertrophic cardiomyopathy (HCM). It relieves left ventricular outflow tract obstruction, improves exercise capacity, symptoms, quality of life, and cardiac biomarkers with a modest effect on left ventricular ejection fraction (LVEF). Purpose To present an integrated safety analysis from all aficamten trials to date. Methods Patients with obstructive HCM (oHCM) who received ≥1 dose of aficamten or placebo [PBO] in the phase 2 REDWOOD-HCM trial, phase 3 SEQUOIA-HCM trial, or the open-label extension FOREST-HCM were included. Results In the PBO-controlled pool of REDWOOD-HCM and SEQUOIA-HCM, 170 patients received aficamten and 153 PBO. In the cumulative (parent+extension) aficamten treated pool, 283 patients were analyzed from initial dose of aficamten or after enrollment in FOREST-HCM (100 PBO-to-aficamten). Overall, mean age was 59 years, 42% were female. In the PBO-controlled pool the mean cumulative follow up was 70.8 patient-years (py) on aficamten, and 66.3 py on PBO, and the total cumulative exposure period to aficamten was 205.2 py. The mean dose of aficamten in the cumulative pool was 12.6 mg/day. Treatment emergent serious adverse events (TESAE) occurred in 10 (5.9%) aficamten patients vs 14 (9.2%) PBO patients in the PBO-controlled pool, and in 24 (8.5%) aficamten patients in the cumulative pool. In the blinded phase, reported AEs were dizziness in 11 (6.5%) aficamten vs 3 (2%) PBO patients, syncope in 3 (1.8%) vs 4 (2.6%), dyspnea in 11 (6.5%) vs 8 (5.2%) and hypertension in 11 (6.5%) vs 4 (2.6%). Site-read LVEF <50%, all resulting in down-titration occurred in 9 (5.3%) aficamten patients [exposure adjusted incidence rate (EAIR) 11.2 per 100 py] and 1 (0.7%) PBO patient (EAIR: 1.3 per 100 py), and in 11 (3.9%) aficamten patients in the cumulative pool (EAIR: 5.3 per 100 py). None of the LVEF <50% events in aficamten patients were associated with heart failure symptoms; 1 PBO patient with a low LVEF had an AE of peripheral edema. During the maintenance phase of the cumulative exposure pool, 1588 echocardiograms were performed, of which 11 (0.7%) led to dose reduction due to LVEF <50%, none resulted in discontinuation or treatment interruption. In the cumulative pool, 6 (2.1%) patients terminated treatment early, none due to aficamten-related AEs. New onset atrial fibrillation occurred in 4 (2.4%) aficamten (EAIR: 4.9 per 100 py) and 5 (3.3%) PBO patients (EAIR: 6.5 per 100 py). There were no deaths during the study period. Conclusions In this integrated safety analysis, aficamten had a safety profile similar to PBO and was consistent over an extended treatment period. There was a low incidence of LVEF <50%, none of which were associated with clinical sequalae, and all were successfully managed by dose reduction. Monitoring echocardiography in the maintenance phase yielded very few actionable results.

Cardiovascular toxicities of immune therapies for cancer-a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology.

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.

Undiagnosed sagittal synostosis as cause of "idiopathic" intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a rare condition in children, but if diagnosed needs to be promptly treated to avoid clinical sequalae. The main purpose of this paper was to test our clinical experience with a cohort of normocephalic children with craniosynostosis who do not present in the routine way to craniofacial services, due to the normal head shape and age, diagnosed with IIH. We retrospectively reviewed all children who were referred to neurosurgery from 2012 to 2022 for management of IIH on our prospectively kept database. We determined what treatments were offered and if there was an associated craniosynostosis. In total, 19 children were identified with an average age at referral of 11.5years (st dev 4.0years) with 11 male and 8 female. The most common presenting symptoms and signs were papilloedema (18/19), headaches (15/19), visual deterioration (9/19), nausea and vomiting (7/19) and diplopia (4/19). Five out of 19 children (26.3%) had a sagittal suture fused that was not identified at the time of treatment and all children were normocephalic. There is a cohort of children with IIH who will have concomitant craniosynostosis and ideally would benefit from cranial vault expansion as primary surgery rather than cerebrospinal fluid (CSF) diversion. We suggest all children with IIH requiring neurosurgical intervention have cross-sectional imaging to look for occult craniosynostosis prior to intervention.

The Pathophysiology of Inherited Renal Cystic Diseases.

Renal cystic diseases (RCDs) can arise from utero to early adulthood and present with a variety of symptoms including renal, hepatic, and cardiovascular manifestations. It is well known that common RCDs such as autosomal polycystic kidney disease and autosomal recessive kidney disease are linked to genes such as PKD1 and PKHD1, respectively. However, it is important to investigate the genetic pathophysiology of how these gene mutations lead to clinical symptoms and include some of the less-studied RCDs, such as autosomal dominant tubulointerstitial kidney disease, multicystic dysplastic kidney, Zellweger syndrome, calyceal diverticula, and more. We plan to take a thorough look into the genetic involvement and clinical sequalae of a number of RCDs with the goal of helping to guide diagnosis, counseling, and treatment.

The Clinical Relevance of Diabetes Distress versus Major Depression in Type 2 Diabetes: A Latent Class Analysis from the Fremantle Diabetes Study Phase II.

The nosological position and clinical relevance of the concept of diabetes distress (DD) are uncertain. The aim of this study was to use latent class analysis (LCA) to categorise classes of people with type 2 diabetes and to compare their characteristics. Data from 662 participants in the longitudinal observational Fremantle Diabetes Study Phase II were analysed. LCA identified latent subgroups based on individual responses to the Patient Health Questionnaire-9, the Generalised Anxiety Disorder Scale, and the 5-item Problem Areas in Diabetes Scale. Four classes were identified: Class 1 (65.7%, no symptoms), Class 2 (14.0%, DD), Class 3 (12.6%, subsyndromal depression (SSD)), and Class 4 (7.6%, major depression (MD)). Multinomial regression analysis with Class 1 as reference showed significant associations between the DD class and Southern European and Asian ethnic background, HbA1c, and BMI. The SSD class was significantly associated with HbA1c, cerebrovascular disease, and coronary heart disease (CHD). The MD class had significant associations with age (inversely), Southern European ethnic background, HbA1c, BMI, and CHD. In conclusion, LCA identified a pure DD group comprising 14.0% of participants. The only variable uniquely associated with the DD class was Asian ethnic background. Although identification of DD may have some utility in assessing the psychological wellbeing of individuals with type 2 diabetes, it adds little to the assessment of depressive disorder and its significant clinical sequalae.

Clinical Sequalae of Initial Insurance Denials in a Large Academic Radiation Oncology Center

The objective of this study is to investigate the clinical sequalae of initial radiation oncology insurance denials. The hypothesis is that while the majority of initial insurance case denials are ultimately overturned, there are potential clinical implications to these initial denials. Data were extracted from an institutional registry of patient cases initially denied authorization by their insurers from January 2022 to December 2022. Chi-Square tests using statistical software were employed. Two hundred six cases from November 2021 to December 2022 were identified. The majority (n = 199 [96.6%]) of insurers were commercial payers, while 7 (3.4%) were Medicare/Medicare Advantage. 161 (78.1%) patients were <65 years of age, and 45 (21.8%) 65 or older. One hundred forty-one (68.4%) cases were metastatic, 60 (29.1%) definitive, and 5 (2.4%) were recurrent. Of the 206 cases, 127 (61.6%) cases were ultimately successful in authorization of the ordered treatment without any change to the requested treatment technique or prescription dose after P2P (Peer to Peer review), second-level appeal, comparison plan submission, employer request, insurance carrier change, and/or external appeal, and 56 (27.2%) cases were authorized though with insurer-requested modification to radiation treatment technique and/or prescription dose. Of 21 cases with a requested change in prescription dose, the median decrease in biologically effective dose (BED) was 24 Gy (range: 2.3-51). Of 58 cases with requested change in RT technique, 20 (34.5%) changed from IMRT to 3D-CRT, 16 (27.6%) SBRT to 3D, 15 (25.9%) SBRT to IMRT, 6 (10.3%) SBRT to 2D, and 1 (1.7%) 3D-CRT to 2D. 19 (9.2%) cases remained unauthorized by the insurer but proceeded with treatment via departmental administrative clearance. Of 196 cases which went on to treatment, 72 (36.7%) cases were delayed for a mean of 7.8 days and median of 5 days (range: 1-49). P2P was performed by the treating radiation oncologist in 169 (82.0%) cases, of which 78 (46.1%) were successful in authorization of the ordered treatment. Of the 91 unsuccessful cases, 62 (68.1%) second-level appeals were performed, of which 39 (62.9%) were successful in overturning denied authorization. Of the 23 cases not authorized either through P2P or second-level appeal, 3 (13.0%) cases were successful in authorization of the requested treatment via employer request, external appeal through an independent review organization, or insurance carrier change. Our institutional analysis suggests that while the majority of initial insurance case denials are ultimately overturned without any change to the requested treatment technique or prescription dose through a number of requests made by the insurer to the radiation oncologist, there are clinical implications with a significant percentage of case denials leading to treatment delays, decrease in prescription BED, and less conformal treatment technique.

Bilateral sacroiliac joint fusion in long constructs using self-harvesting porous S2-alar iliac screws with an integrated tulip: technical considerations and early clinical and radiographic experience.

The incidence of sacroiliac joint (SIJ) dysfunction after lumbosacral fusion is high. Upfront bilateral SIJ fusion using novel fenestrated self-harvesting porous S2-alar iliac (S2AI) screws could reduce the incidence of SIJ dysfunction and need for subsequent SIJ fusion. In this study, the authors report their early clinical and radiographic results of SIJ fusion using this novel screw. The authors began using self-harvesting porous screws in July 2022. This is a retrospective review of consecutive patients at a single institution who underwent long thoracolumbar surgery with extension to the pelvis using this porous screw. Radiographic parameters of regional and global alignment were collected preoperatively and at the time of last follow-up. The incidence of intraoperative complications and need for revision were collected. The incidences of mechanical complications, including screw breakage, implant loosening/pullout, and screw cap dislocation at the time of last follow-up were also collected. Ten patients with a mean age of 67 years were included, 6 of whom were male. Seven patients had a thoracolumbar construct with extension to the pelvis. Three patients had upper instrumented vertebrae at the proximal lumbar spine. Intraoperative breach was not encountered in any of the patients (0%). Postoperatively, 1 patient (10%) had screw breakage at the neck of the tulip of the modified iliac screw discovered at routine follow-up without clinical sequalae. Use of self-harvesting porous S2AI screws incorporated into long thoracolumbar constructs was safe and feasible, demanding unique technical considerations. Long-term clinical and radiographic follow-up with a large patient cohort is necessary to determine their durability and efficacy to achieve SIJ arthrodesis and prevent SIJ dysfunction.

Clinical Impact and Safety of Non-Target Punctures (NTP) during Portal Vein Access in TIPS Procedure.

Although non-target puncture (NPT)-related complications are well known to clinicians performing TIPS, there is no NTP-focused study to assess the true clinical sequalae of NTP-related complications. In this study, the aim was to evaluate the incidence, safety, clinical outcomes and complications related to NTPs during the portal access of TIPS procedures. A retrospective review of 369 TIPS procedures from October 2007 to September 2019 was performed. We identified inadvertent NTPs, including biliary, hepatic artery, lymphatic and capsular punctures. Next, the medical records and images were reviewed and analyzed to assess the safety and clinical outcomes of these cohorts. A total of 71 NTPs were identified in 56 patients (15.18% of 369 patients). Of 369 TIPS patients, there were (1) 28 biliary punctures (7.6%), (2) 16 extracapsular punctures (4.3%), (3) 15 lymphatic punctures (4.1%) and (4) 12 hepatic artery punctures (3.3%). The overall complication rate was 2.2% (8/369). Based on the Clavien-Dindo classification, three patients (0.8%) had a minor complication. In addition, five patients (1.4%) experienced grade II-V major complications, such as symptomatic hemoperitoneum, arterio-biliary fistula or hemorrhagic shock leading to death. Mortality (0.5%) was only caused by extracapsular puncture combined with other NTP. NTPs during the portal access of TIPS procedures are associated with low complication risk. However, when extracapsular punctures are combined with other NTPs, a more severe complication, including mortality, can occur. Nevertheless, all patients with NTP should be closely monitored at a higher level of care after TIPS placement.

EPH83 Characteristics, Comorbid Gi Conditions, and Treatment Patterns Among Individuals Diagnosed with Rett Syndrome

rett syndrome (rtt) is a rare, neurodevelopmental disorder primarily affecting females1 often resulting in early loss of acquired skills including hand use, walking, and verbal communication. disorders of gastrointestinal (gi) motility such as gastroesophageal reflux disease (gerd) and constipation are common for individuals diagnosed with rtt. few studies have examined the characteristics, clinical sequalae, medication and healthcare service utilization in response to gi comorbidities associated with rtt.

A Systematic Review of Intracranial Complications in Adults with Pott Puffy Tumor over Four Decades

The purpose of this study is to investigate the risk factors of intracranial complications in adult patients with Pott Puffy Tumor (PPT). A systematic review was conducted of clinical studies from January 1983 to December 2022 that reported on PPT adult patients. The full-text articles were reviewed for the patients' ages, sex, cultured organisms, surgical procedures, clinical sequalae, and underlying diseases that may affect the onset of intracranial complications in PPT adult patients. A total of 106 studies were included. Medical data were reviewed for 125 patients (94 males, 31 females). The median age was 45 years. A total of 52% had comorbidities, mostly head trauma (24.5%), sinus/neurosurgical operations (22.4%), immunosuppression conditions (13.3%), diabetes mellitus (9.1%), cocaine use (7.1%), or dental infections (6.1%). A total of 28 cultures revealed Streptococcus (22.4%), 24 contained staphylococci (19.2%), and 22 cultures contained other pathogens (17.6%). An amount of 30.4% developed intracranial complications, with the most common being epidural abscesses or empyemas (55.3%), as well as subdural (15.7%) and extradural lesions (13.2%). Age, DM, and immunosuppression conditions are significantly associated with intracranial complications (p < 0.001, p = 0.018 and p = 0.022, respectively). Streptococcus infection is associated with intracranial complications (p = 0.001), although Staphylococcus and other microorganisms are not. Surgical intervention, mainly ESS, and broad-spectrum antibiotics remain the cornerstones of treatment.

Abstract Number: LBA4 Platelet Function Testing and Acute Thrombotic Events in Intracranial Aneurysm Patients Undergoing Flow Diversion

Introduction Introduction The role of platelet function testing in patients with intracranial aneurysms undergoing flow diversion remains controversial with limited evidence of its influence on thrombotic outcomes. We report an observational cohort analysis evaluating the association of P2Y12 assay testing with thrombotic events in patients undergoing flow diversion. Methods We performed a retrospective review of our prospectively maintained procedural database to identify patients who underwent flow diversion between January 2020 and July 2022. One physician within our practice never performs P2Y12 assay testing. All other physicians utilize P2Y12 assay testing as part of routine practice. These two different patient cohorts were compared. Acute thrombotic events were our primary outcome. Secondary outcomes included delayed intracerebral hemorrhage, intimal hyperplasia without clinical sequalae, and transient neurologic deficits. Results We identified 150 patients who underwent flow diversion at our institution between January 2020 and July 2022. Median age was 59 years old (Interquartile range (IQR) 49–67), with 113 females (82.5%) and 24 males (17.5%). Out of 150 patients, 93 (62.0%) patients were treated by physicians who performed routine pre and postoperative testing of aspirin and Plavix assays, with subsequent adjustment of antithrombotic dosing accordingly, while 57 patients (38.0%) were treated by the single physician who prescribes aspirin and clopidogrel pre‐operatively without testing. In all, seven out of 150 patients (4.7%) had an acute thrombotic event requiring intraarterial anti‐thrombotic infusion or urgent thrombectomy, or both. Of these, six where from the 93 patient testing cohort (6.5%), and one in 57 patients non‐testing cohort (1.8%) (p = 0.2). Patients who had a thrombotic event were more likely to have underlying atrial fibrillation (28.6% vs 4.9%, p = 0.01) but otherwise had similar demographics, vascular risk factors, maximal aneurysmal diameter, and parent vessel diameter (Table 1). In a multivariable analysis adjusting for age, maximal aneurysm diameter, ruptured aneurysms, and atrial fibrillation, P2Y12 sensitivity assay testing was not significantly associated with acute thrombotic events in aneurysm patients undergoing flow diversion (Odds Ratio (OR) = 0.15, 95% Confidence Interval (CI) = 0.01‐2.67), p = 0.2). Secondary outcomes were also comparable between both groups; transient neurologic deficits were noted in 4/93 in the testing group (4.3%), and 6/57 in the non‐testing group (10%) (p = 0.14), intracranial hemorrhage occurred in only 2 patients, both in the testing group (p = 0.3), and mild intimal hyperplasia was observed in 18.3% in the testing group versus 12.3% in the non‐testing group (p = 0.33). Conclusions Platelet function testing showed no significant correlation with thrombotic events or outcomes in our cohort. The role of platelet function testing remains controversial, albeit widely used in patients undergoing flow diversion of intracranial aneurysms.

Endovascular treatment of unruptured cavernous carotid aneurysms using flow diverter devices in Vietnam: A single-center prospective study

ObjectiveThis prospective study aims to investigate the safety and effectiveness of flow diverter (FD) in the treatment of unruptured cavernous carotid aneurysms (CCAs) in Vietnam. MethodsA single-center, prospective case series of 32 patients with unruptured CCAs treated by FD at our center from January 2017 to January 2022 was performed. We analyzed the aneurysm characteristics, procedure details, aneurysm occlusion rate, evolution of clinical symptoms, complications, and functional outcomes after treatment. Angiographic study was scheduled at the 6-month and 12-month follow-up. The occlusion rate was evaluated according to the O’Kelly-Marotta (OKM) Scale. Results35 FDs were deployed to treat 32 unruptured CCAs in 32 patients (mean age, 59.25; mean aneurysm size, 12.13 mm). Stent implantation was successful in all patients. Single FD was used in 29 cases (90.6%). Adjunctive coils were placed in five patients (15.6%). Complete aneurysm occlusion was achieved in 61.3% at 6 months and 96.4% at 12 months. Favorable outcome defined as mRS 0–2 was reported in all except one patient. Complete resolution or significant improvement of clinical symptoms was noted in 29 of 30 symptomatic patients (96.7%). Periprocedural complications included vessel perforation with severe SAH leading to death in one case (3.1%), minor vasospasm in four (12.5%), acute in-stent thrombosis in two (6.3%), and puncture-related hematoma in two (6.3%). All of these patients were successfully managed without clinical sequalae after the procedure except for one case. ConclusionFD represents a safe and effective treatment modality that might be considered as a valuable alternative to standard endovascular coiling techniques or carotid sacrifice for unruptured CCAs.

Patterns of Infectious Disease Associated With Injection Drug Use in Massachusetts.

Since 2014, multiple outbreaks of human immunodeficiency virus (HIV) among people who inject drugs have occurred across the United States along with hepatitis C virus (HCV), skin and soft tissue infections (SSTIs), and infective endocarditis (IE), creating a converging public health crisis. We analyzed the temporal patterns of infectious disease and overdose using a hierarchical Bayesian distributed lag logistic regression model examining the probability that a given geographic area experienced at least 1 HIV case in a given month as a function of the counts/rates of overdose, HCV, SSTI, and IE and associated medical procedures at different lagged time periods. Current-month HIV is associated with increasing HCV cases, abscess incision and drainage, and SSTI cases, in distinct temporal patterns. For example, 1 additional HCV case occurring 5 and 7 months previously is associated with a 4% increase in the odds of observing at least 1 current-month HIV case in a given locale (odds ratios, 1.04 [90% credible interval {CrI}: 1.01-1.10] and 1.04 [90% CrI: 1.00-1.09]). No such associations were observed for echocardiograms, IE, or overdose. Lagged associations in other infections preceding rises in current-month HIV counts cannot be described as predictive of HIV outbreaks but may point toward newly discovered epidemics of injection drug use and associated clinical sequalae, prompting clinicians to screen patients more carefully for substance use disorder and associated infections.

Assessment of Patency of Internal Jugular Vein in Carcinoma Oral Cavity Patients Undergoing Neck Dissection: A Prospective Observational Study

ABSTRACT Background: Neck dissections in carcinoma oral cavity are associated with various postoperative comorbidities. Internal jugular vein (IJV) occlusion and stenosis is a rare serious complication, which leads to serious clinical sequalae. Existing medical literature reports an incidence of this complication varying from 0% to 30%. Lacunae exist regarding any correlation between clinicopathological parameters and treatment options, of such patients, with the incidence of this complication, which might aid in adapting a preventive approach accordingly. Aims and Objectives: a. Primary objective: To study the patency of IJV postoperatively with preoperative status b. Secondary objective: Correlation of postoperative IJV patency with clinicopathological parameters (age, subsite, and pathological nodal status) and treatment options offered (neck dissection, radiotherapy, and reconstruction). Subject and Methods: Patency of IJV was analyzed preoperatively and postoperatively and correlated with various parameters, after neck dissection in 50 carcinoma oral cavity patients. Settings and Design: Prospective observational study at a tertiary care hospital done over 2 years. Statistical Analysis Used: Data were recorded in Excel data sheet and statistically analyzed by using the SPSS Ver 22.0. Results: IJV occlusion was demonstrated in 2 (4%) patients and IJV stenosis in 7 (14%) patients. Postradiotherapy patients had higher incidence of occlusion compared to patients who did not undergo radiotherapy (11.7% vs. 0%; P &lt; 0.05). The incidence of stenosis and occlusion was significantly higher in left side neck dissection (20.6%; P &lt; 0.05). Conclusion: Radiotherapy and left sided neck dissection are statistically significant risk factors for postoperative IJV occlusion in carcinoma oral cavity patients.

Post-acute sequelae of COVID-19 among hospitalized patients in Estonia: Nationwide matched cohort study.

Post-acute COVID-19 sequelae refers to a variety of health complications involving different organ systems that have been described among individuals after acute phase of illness. Data from unselected population groups with long-time follow up is needed to comprehensively describe the full spectrum of post-acute COVID-19 complications. In this retrospective nationwide cohort study, we used data obtained from electronic health record database. Our primary cohort were adults hospitalized with confirmed COVID-19 and matched (age, sex, Charlson Comorbidity Index) unaffected controls from general population. Individuals included from February 2020 until March 2021 were followed up for 12 months. We estimated risks of all-cause mortality, readmission and incidence of 16 clinical sequelae after acute COVID-19 phase. Using a frailty Cox model, we compared incidences of outcomes in two cohorts. The cohort comprised 3949 patients older than 18 years who were alive 30 days after COVID-19 hospital admission and 15511 controls. Among cases 40.3% developed at least one incident clinical sequelae after the acute phase of SARS-CoV-2 infection, which was two times higher than in general population group. We report substantially higher risk of all-cause mortality (adjusted hazard ratio (aHR) = 2.57 (95%CI 2.23-2.96) and hospital readmission aHR = 1.73 (95%CI 1.58-1.90) among hospitalized COVID-19 patients. We found that the risks for new clinical sequalae were significantly higher in COVID-19 patients than their controls, especially for dementia aHR = 4.50 (95% CI 2.35-8.64), chronic lower respiratory disease aHR = 4.39 (95% CI 3.09-6.22), liver disease aHR 4.20 (95% CI 2.01-8.77) and other (than ischemic) forms of heart diseases aHR = 3.39 (95%CI 2.58-4.44). Our results provide evidence that the post-acute COVID-19 morbidity within the first year after COVID-19 hospitalization is substantial. Risks of all-cause mortality, hospitalisation and majority of clinical sequelae were significantly higher in hospitalized COVID-19 patients than in general population controls and warrant targeted prevention efforts.

Abstract 9395: Natural History of Myocardial Injury Following Covid-19 Vaccine Associated Myocarditis

Introduction: Acute myocarditis is a rare complication of mRNA-based COVID-19 vaccination. The natural history and clinical sequalae of this complication are of critical importance to estimate the impact on population health. Objective: To study the impact of COVID-19 vaccine associated myocarditis on convalescent myocardial health, symptoms, and clinical outcomes. Methods: This study was performed at two tertiary care hospitals. Baseline and convalescent (≥3 month) CMR imaging was performed for 20 consecutive patients meeting Updated Lake Louise Criteria for acute myocarditis within 10 days of mRNA-based vaccination and with no evidence of active viral infection. Global and segmental CMR-based markers of myocardial injury were studied at baseline and convalescence, inclusive of chamber volumetry, LV ejection fraction (LVEF), LV mass, T1 and T2 mapping, late gadolinium enhancement (LGE) imaging, and extracellular volume (ECV) fraction. Major clinical outcomes were captured. Results: The median age was 23.1 years (range 18-39 years) with 17 (85%) being male. Convalescent CMR evaluations were performed at a median (IQR) of 3.7 (3.3-6.2) months. Five patients (25%) had a baseline LVEF &lt;50%. All patients showed abnormal LGE inclusive of a sub-epicardial pattern with a mean LGE burden of 8.6+/-5.3% LV mass using a &gt;5SD of reference threshold. At follow-up, a mean 3% absolute improvement in LVEF was observed, accompanied by a 7% reduction in LVEDV and 5% reduction in LV mass (all p&lt;0.015). Global LGE volume reduced by 66% (p&lt;0.001). Absolute reductions in global T2, native T1, and ECV of 2.1msec, 58msec, and 2.9%, respectively were documented (all p≤0.001). All patients with LVEF &lt;50% at baseline recovered above this threshold. However, 18 (90%) patients showed persistence of LGE at follow-up with 15% having a burden &gt;5% of the LV mass. No patient experienced major clinical outcomes. Conclusion: COVID-19 mRNA vaccine associated myocarditis shows rapid improvement in CMR-based markers of tissue edema, contractile function, and LGE, and was not associated with adverse events at intermediate range follow-up. However, convalescent fibrosis was commonly observed, justifying ongoing need for clinical surveillance in this population.

Current approaches to the management of pneumatosis intestinalis: an American Pediatric Surgical Association membership survey.

Pneumatosis intestinalis (PI) remains difficult to treat as it can lead to a broad range of clinical sequalae and there are little published data available to guide management. Our aim was to evaluate how pediatric surgeons currently manage children with PI, how treatment varies based on etiology, and to identify opportunities to optimize current PI management strategies. We administered a web-based survey of practicing pediatric surgeons in the United States and Canada. The survey was distributed to all members of the American Pediatric Surgical Association. Of 1508 distributed surveys, 333 responses were received (22% response rate); 174 were complete and included in analysis (12% analyzed). For all scenarios, respondents recommended treatment for PI include a median 7days of bowel rest and 7days antibiotics. Only 41% reported their approach to PI management was optimal. Ways to optimize care include treatment based on etiology (83%), decreased number of repeat images (64%), shorter NPO course (49%), and shorter antibiotic course (47%). Pediatric surgeons manage PI similarly regardless of etiology but most report this is suboptimal. Future work is needed to prospectively evaluate management protocols that consider etiology.

Methods to Evaluate the Potential Clinical Significance of Antibodies to Red Blood Cells.

Immune-mediated red blood cell (RBC) destruction due to antibodies is an ongoing problem in transfusion medicine for the selection of the safest blood. Serological testing often revealed incompatibility with donors' RBCs. When this incompatible blood was transfused, destruction was due mostly to extravascular-mediated phagocytosis of the antibody-opsonized RBCs; however, intravascular hemolysis was sometimes observed without explanation. Based on serology, antibodies with potential for clinical sequalae could not be ascertained; thus, antigen-negative blood was usually selected for transfusion to avoid problems. Antibodies to antigens having very high frequency in the general population (>95%), however, made selection of antigen-negative blood difficult and sometimes impossible. Some patients, who were sensitized by previous transfusions or by pregnancy, developed multiple antibodies, again creating a problem for finding compatible blood for transfusion, without the ability to discern which of the antibodies may be clinically irrelevant and ignored. Transfusion medicine scientists began searching for an in vitro means to determine the in vivo outcome of transfusion of blood that was serologically incompatible. Methods such as chemiluminescence, monocyte-macrophage phagocytosis, and antibody-dependent cellular cytotoxicity (ADCC) were described. Over the years, the monocyte monolayer assay (MMA) has emerged as the most reliable in vitro assay for the prediction of the clinical relevance of a given antibody. ADCC has not been fully studied but has the potential to be useful for predicting which antibodies may result in intravascular hemolysis. This article captures the protocols for the implementation and readout of the MMA and ADCC assays for use in predicting the clinical significance of antibodies in a transfusion setting. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Monocyte monolayer assay (MMA) Basic Protocol 2: Antibody-dependent cellular cytotoxicity assay (ADCC).

Smoking is associated with increased risk of cardiovascular events, disease severity, and mortality among patients hospitalized for SARS-CoV-2 infections.

The clinical sequalae of SARS-CoV-2 infection are in part dependent upon age and pre-existing health conditions. Although the use of tobacco products decreases cardiorespiratory fitness while increasing susceptibility to microbial infections, limited information is available on how smoking affects COVID-19 severity. Therefore, we examined whether smokers hospitalized for COVID-19 are at a greater risk for developing severe complications than non-smokers. Data were from all hospitalized adults with SARS-CoV-2 infection from the American Heart Association's Get-With-The-Guidelines COVID-19 Registry, from January 2020 to March 2021, which is a hospital-based voluntary national registry initiated in 2019 with 122 participating hospitals across the United States. Patients who reported smoking at the time of admission were classified as smokers. Severe outcome was defined as either death or the use of mechanical ventilation. Of the 31,545 patients in the cohort, 6,717 patients were 1:2 propensity matched (for age, sex, race, medical history, medications, and time-frame of hospital admission) and classified as current smokers or non-smokers according to admission data. In multivariable analyses, after adjusting for sociodemographic characteristics, medical history, medication use, and the time of hospital admission, patients self-identified as current smokers had higher adjusted odds of death (adjusted odds ratio [aOR], 1.41; 95% CI, 1.21-1.64), the use of mechanical ventilation (aOR 1.15; 95% CI 1.01-1.32), and increased risk of major adverse cardiovascular events (aOR, 1.27; 95% CI 1.05-1.52). Independent of sociodemographic characteristics and medical history, smoking was associated with a higher risk of severe COVID-19, including death.

Reduced cerebral vascular fractal dimension among asymptomatic individuals as a potential biomarker for cerebral small vessel disease

Cerebral small vessel disease is a neurological disease frequently found in the elderly and detected on neuroimaging, often as an incidental finding. White matter hyperintensity is one of the most commonly reported neuroimaging markers of CSVD and is linked with an increased risk of future stroke and vascular dementia. Recent attention has focused on the search of CSVD biomarkers. The objective of this study is to explore the potential of fractal dimension as a vascular neuroimaging marker in asymptomatic CSVD with low WMH burden. Df is an index that measures the complexity of a self-similar and irregular structure such as circle of Willis and its tributaries. This exploratory cross-sectional study involved 22 neurologically asymptomatic adult subjects (42 ± 12 years old; 68% female) with low to moderate 10-year cardiovascular disease risk prediction score (QRISK2 score) who underwent magnetic resonance imaging/angiography (MRI/MRA) brain scan. Based on the MRI findings, subjects were divided into two groups: subjects with low WMH burden and no WMH burden, (WMH+; n = 8) and (WMH−; n = 14) respectively. Maximum intensity projection image was constructed from the 3D time-of-flight (TOF) MRA. The complexity of the CoW and its tributaries observed in the MIP image was characterised using Df. The Df of the CoW and its tributaries, i.e., Df (w) was significantly lower in the WMH+ group (1.5172 ± 0.0248) as compared to WMH− (1.5653 ± 0.0304, p = 0.001). There was a significant inverse relationship between the QRISK2 risk score and Df (w), (rs = − .656, p = 0.001). Df (w) is a promising, non-invasive vascular neuroimaging marker for asymptomatic CSVD with WMH. Further study with multi-centre and long-term follow-up is warranted to explore its potential as a biomarker in CSVD and correlation with clinical sequalae of CSVD.