CHARACTERISTICS AND OUTCOMES OF HOSPITALISED PATIENTS WITH HEART FAILURE AND SARCOIDOSIS: A PROPENISTY-MATCHED ANALYSIS OF THE NATIONWIDE READMISSIONS DATABASE 2010-2019.

BACKGROUND: Sarcoidosis is associated with a poor prognosis. There is a lack of data examining the outcomes and readmission rates of sarcoidosis patients with heart failure (SwHF) and without heart failure (SwoHF). We aimed to compare the impact of non-ischemic heart failure on outcomes and readmissions in these two groups. METHODS: The US Nationwide Readmission Database was queried from 2010-2019 for SwHF and SwoHF patients identified using the International Classification of Diseases, Ninth and Tenth Editions. Those with ischemic heart disease were excluded, and both cohorts were propensity matched for age, gender, and Charlson Comorbidity Index (CCI). Clinical characteristics, length of stay, adjusted healthcare-associated costs, 90-day readmission and mortality were analyzed. RESULTS: We identified 97,961 hospitalized patients (median age 63 years, 37.9% male) with a diagnosis of sarcoidosis (35.9% SwHF vs. 64.1% SwoHF). On index admission, heart failure patients had higher prevalences of atrioventricular block (3.3% vs. 1.4%, p<0.0001), ventricular tachycardia (6.5% vs. 1.3%, p<0.0001), ventricular fibrillation (0.4% vs. 0.1%, p<0.0001) and atrial fibrillation (22.1% vs. 7.5%, p<0.0001). SwHF patients were more likely to be readmitted (hazard ratio 1.28, p<0.0001), had higher length of hospital stay (5 vs. 4 days, p<0.0001), adjusted healthcare-associated costs ($9,667.0 vs. $9,087.1, p<0.0001) and mortality rates on readmission (5.1% vs. 3.8%, p<0.0001). Predictors of mortality included heart failure, increasing age, male sex, higher CCI and liver disease. CONCLUSION: SwHF is associated with higher rates of arrhythmia at index admission, as well as greater hospital cost, readmission and mortality rates compared to those without heart failure.

Comparing outcomes of an 'early' versus 'late' diagnosis of cardiac sarcoidosis following a baseline presentation of high-grade atrioventricular block.

BACKGROUND: There is a paucity of evidence on impact of a delay in Cardiac Sarcoidosis (CS) diagnosis after high-grade atrioventricular-block (AVB) and this study aims to fill this void. METHODS: Consecutive CS patients (n = 77) with high grade AVB referred to one specialist hospital in London between February 2007 to February 2023 were retrospectively reviewed. The median time from AVB to diagnosing CS (112 days) was used to define the Early (n = 38) and Late (n = 39) cohorts. The primary endpoint was a composite of all-cause mortality, cardiac transplantation, ventricular arrhythmic events or heart failure hospitalisation. Secondary endpoints included difference in maintenance prednisolone dose, need for cardiac device upgrade and device complications. RESULTS: The mean age of the cohort was 54.4 (±10.6) years of whom 64 % were male and 81 % Caucasian. After a mean follow up of 54.9 (±45.3) months, the primary endpoint was reached by more patients from the Late cohort (16/39 vs. 6/38, p = 0.02; multivariable HR 6.9; 95 %CI 1.5-32.2, p = 0.01). Early Group were more likely to have received an Implantable Cardioverter Defibrillator or Cardiac Resynchronisation Therapy-defibrillator as index device after AVB (19/38 vs. 6/39; p < 0.01) and had fewer device upgrades (19/38 vs. 30/39, p = 0.01) and a trend towards fewer device complications (1 vs. 5, p = 0.20). The maintenance dose of prednisolone was significantly higher in Late Group [20.7(±9.7) mg vs. 15.3(±7.9) mg, p = 0.02]. CONCLUSION: A late diagnosis of CS was associated with more adverse events, a greater probability of needing a device upgrade and required higher maintenance steroid dose.

Role of serial 18F-fludeoxyglucose positron emission tomography in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis.

BACKGROUND: Myocardial inflammation and perfusion defects detected by 18F-fludeoxyglucose (FDG) and Rubidium-82 positron emission tomography (PET) may be associated with ventricular arrhythmias (VAs) in cardiac sarcoidosis (CS). The role of serial quantitative PET in determining the effect of treatment on myocardial inflammation and clinical outcomes is yet to be defined. METHODS: Newly diagnosed CS patients with active myocardial inflammation (maximum standardised uptake value (SUVmax) ≥ 2.5) were treated with immunosuppression, then underwent repeat FDG-PET, Rubidium-82, and echocardiographic imaging 6-12 months later. Serial changes in SUVmax, SUVmean, inflammatory extent, perfusion defect (PD) extent, metabolism/perfusion mismatch extent, global cardiac metabolic activity, and left ventricular ejection fraction (LVEF) were assessed. The primary endpoint was a composite of all-cause mortality, serious VA and heart-failure (HF) hospitalisation. Event data were recorded from the date of the second FDG-PET. RESULTS: The study population consisted of 113 patients (66% male, age: 55 ± 11 years, LVEF: 54 ± 13%). SUVmax reduced from 4.5 (interquartile range: 3.3-7.1) to 2.7 (2.2-3.6). Overall, 94 (83%) patients saw serial reduction in SUVmax, with 42 (37%) demonstrating complete response (SUVmax <2.5). Following a median of 46 (25-57) months, 28 (25%) patients reached the endpoint (8 deaths, 17 VAs, and 3 HF hospitalisations). PD extent (Hazard ratio 1.03, 95% confidence interval: 1.01-1.05; p = 0.035) was a significant predictor of outcome following treatment, even after accounting for LVEF and change in SUVmean. The risk of adverse events was the greatest in those with a pre-treatment or post-treatment PD extent of >10%. CONCLUSION: In our cohort with active CS, following a treatment-induced reduction in myocardial inflammation, PD extent was the main predictor of adverse events.

The role of ICDs in patients with sarcoidosis-A comprehensive review.

BACKGROUND: Implantable cardioverter defibrillator (ICD) use in cardiac sarcoidosis (CS) to prevent sudden cardiac death (SCD) is a potentially life-saving intervention. However, the factors that determine outcome in this cohort remains largely unknown. This review analyses CS patients with an ICD and highlights determinants of poor outcome. OUTCOMES: Analysis of studies which used the 2014 HRS Consensus, 2017 AHA/ACC/HRS Guideline and 2022 ESC Guidelines showed that those with class I recommendations have higher incidences of ventricular arrhythmia (VA) than those with class II recommendations. Additionally, even those with normal left ventricular ejection fraction (LVEF) and CS are at high risk of VA and SCD. SUMMARY: Compounding research emphasises the importance of cardiac imaging in those with sarcoidosis, with evidence to suggest a possible need for revision of the guidelines. Other variables such as demographics and ventricular characteristics may prove useful in predicting those to benefit most from ICD insertion.

Racial disparities among patients with cardiac sarcoidosis and arrhythmias in the United States: A propensity matched-analysis from the national inpatient sample database 2016-2020.

BACKGROUND: Cardiac sarcoidosis (CS) is frequently associated with conduction abnormalities and arrhythmias. In this study, we aim to evaluate racial disparities in the frequency of arrhythmias, and associated co-morbidities, among patients with CS. METHODS: White and African American (AA) patients diagnosed with CS were identified and compared from the 2016-2020 National Inpatient Sample (NIS) database whilst adjusting for confounders via logistic regression models. RESULTS: A total of 7,935 patients with CS were included in the study. The propensity-matched sample comprised of 5,570 patients, of whom 2,785 were White and 2,785 were AA. AA patients had a longer mean length of hospital stay (LOS) (7.84 vs. 6.94, p<0.01), a higher mean Charlson Comorbidity Index (CCI) score (3.10 vs. 2.84, p<0.01), and significantly higher incidences of cardiogenic shock [(9.2% vs 6.3%, p<0.01), aOR 1.45 (95% CI 1.17-1.78), p<0.01] and acute kidney injury (AKI) [(34.3% vs. 26.9%, p<0.01), aOR 1.41 (95% CI 1.24-1.61), p<0.01]. From an arrhythmia perspective, AA CS patients were shown to have a lower frequency of: (1) ventricular tachycardia (32.5% vs. 37.9%, p<0.01), (2) ventricular fibrillation (5.4% vs.7.2%, p<0.01), (3) first-degree AV block (1.8% vs. 4.1%, p<0.01), (4) complete AV block (6.3% vs. 14.2%, p<0.01), and (5) atrial fibrillation (31.8% vs. 34.8%, p=0.016) when compared to Whites with CS. Mortality remained higher for AAs (3.8% vs. 2.7%, p=0.024). CONCLUSION: Our study demonstrates a higher incidence of cardiac arrhythmias among White patients but a higher incidence of cardiogenic shock, AKI, mean LOS, and mortality among AA patients with cardiac sarcoidosis.

Characterisation and management of expected and unexpected urgent findings from positron emission tomography with 18F-fluorodeoxyglucose integrated with computed tomography in cardiovascular disease.

BACKGROUND: Cardiac 18F-fluorodeoxyglucose (FDG)-PET-CT plays an important role in the assessment of cardiovascular diseases. Effective management of urgent scan findings facilitates optimal patient care. METHODS: We characterised the management of urgent, expected and unexpected findings in patients referred for cardiac [18F]fluorodeoxyglucose integrated with computed tomography (FDG-PET-CT) at the Royal Brompton Hospital (United Kingdom). Urgent findings are escalated by the reporting physicians/radiologists raising RadAlert notifications to the referring clinician. We characterised the indications and time to management (TTM) between the RadAlert and the resulting management. As controls, we characterised the TTM of 33 urgent findings identified before the RadAlert system was implemented. RESULTS: Of the 1497 consecutive FDG-PET-CT scans screened (April 2021 to February 2023), 93 RadAlerts were suitable for analysis (TTM 7 days [interquartile range: 2-14]). Expected urgent findings included active cardiac sarcoidosis (56%; TTM 8 days [5-18]), heart transplant rejection (12%; 6 ± 4 days), infective endocarditis (9%; 2 days [1-12]), cardiac device infections (5%; 1 day [0-2]), acute myocarditis (2%; 5 and 14 days) and epicardial mass (1%; 1 day). TTM did not differ significantly between indications (P = 0.06). RadAlert cases had significantly shorter TTM than controls without RadAlert, P = 0.001. After the RadAlerts, 81% of patients had clinical reviews, and 55% had escalation of medical/surgical therapies. Unexpected findings (total N = 45; median TTM 6 days [1-10]) included malignancies (N = 3), infections (N = 2), pneumothorax (N = 1), benign diagnosis (N = 30), unclear diagnosis (N = 5) and 4 findings disappeared on repeat imaging. CONCLUSIONS: Cardiac FDG-PET-CT identifies expected and unexpected findings in a range of cardiovascular diseases. Serious, unexpected findings are rare and can be effectively escalated by the RadAlert system.

Multiple intussusceptions secondary to Peutz-Jegher's syndrome in an adult male: a case report from Pakistan.

Intussusception is a medical condition characterized by invagination of the intestinal segment, causing obstruction and leading to potential complications such as ischemia, necrosis and perforation. While paediatric intussusception is well documented with a peak in ages between 4 and 36 months, adult intussusception is a rare condition usually involving a lead point. In this article, we present an uncommon case of an adult male with worsening of his long-standing lower abdominal pain for the last 2 months. Radiological test reports revealed target-like lesions demonstrating two intestinal intussusceptions, for which he underwent a small bowel anastomosis, exploratory laprotomy and resection. On receiving the histopathology report, hamartomatous polyps with features favouring Peutz-Jegher's syndrome were identified as a possible lead point.

Bilateral Rasmussen Encephalitis: Good Outcome Following Hemispherotomy.

BACKGROUND: Bilateral Rasmussen encephalitis is a rare variant of a debilitating, typically unihemispheric disease with limited treatment options. Few cases with bilateral histopathology have been reported, all with poor seizure control following surgery. Here we report a favorable outcome following hemispherotomy in a four-year-old male with biopsy-confirmed bilateral disease. CASE: The patient presented with right hemispheric focal seizures with behavioral arrest and over a year progressed to left lower extremity clonic seizures, epilepsia partialis continua, and loss of ambulation, with transient response to steroids and tacrolimus. Histopathology confirmed bilateral disease. The patient developed super-refractory status epilepticus and underwent right functional hemispherotomy 4.5 years after initial presentation. In a 2.5-year follow-up period, an Engel 1D outcome classification was observed with substantially improved quality of life. CONCLUSION: Previous reports of bilateral Rasmussen encephalitis describe universally poor outcomes, and hemispherotomy is often considered contraindicated. However, hemispherotomy in a patient with bilateral Rasmussen encephalitis may have a good outcome if seizures are unihemispheric.

Predictors of outcome in a contemporary cardiac sarcoidosis population: Role of brain natriuretic peptide, left ventricular function and myocardial inflammation.

AIMS: Cardiac sarcoidosis (CS) is a potentially fatal condition that varies in its clinical presentation. Here, we describe baseline characteristics at presentation along with prognosis and predictors of outcome in a sizable and deeply phenotyped contemporary cohort of CS patients. METHODS AND RESULTS: Consecutive CS patients seen at one institution were retrospectively enrolled after undergoing laboratory testing, electrocardiogram, echocardiography, cardiac magnetic resonance (CMR) imaging and 18 F-flourodeoxyglucose positron emission tomography (FDG-PET) at baseline. The composite endpoint consisted of all-cause mortality, aborted sudden cardiac death, major ventricular arrhythmic events, heart failure hospitalization and heart transplantation. A total of 319 CS patients were studied (67% male, 55.4 ± 12 years). During a median follow-up of 2.2 years (range: 1 month-11 years), 8% of patients died, while 33% reached the composite endpoint. The annualized mortality rate was 2.7% and the 5- and 10-year mortality rates were 6.2% and 7.5%, respectively. Multivariate analysis showed serum brain natriuretic peptide (BNP) levels (hazard ratio [HR] 2.41, 95% confidence interval [CI] 1.34-4.31, p = 0.003), CMR left ventricular ejection fraction (LVEF) (HR 0.96, 95% CI 0.94-0.98, p < 0.0001) and maximum standardized uptake value of FDG-PET (HR 1.11, 95% CI 1.04-1.19, p = 0.001) to be independent predictors of outcome. These findings remained robust for different patient subgroups. CONCLUSION: Cardiac sarcoidosis is associated with significant morbidity and mortality, particularly in those with cardiac involvement as the first manifestation. Higher BNP levels, lower LVEF and more active myocardial inflammation were independent predictors of outcomes.

Machine learning models for predicting seizure outcome after MR-guided laser interstitial thermal therapy in children.

OBJECTIVE: MR-guided laser interstitial thermal therapy (MRgLITT) is associated with lower seizure-free outcome but better safety profile compared to open surgery. However, the predictors of seizure freedom following MRgLITT remain uncertain. This study aimed to use machine learning to predict seizure-free outcome following MRgLITT and to identify important predictors of seizure freedom in children with drug-resistant epilepsy. METHODS: This multicenter study included children treated with MRgLITT for drug-resistant epilepsy at 13 epilepsy centers. The authors used clinical data, diagnostic investigations, and ablation features to predict seizure-free outcome at 1 year post-MRgLITT. Patients from 12 centers formed the training cohort, and patients in the remaining center formed the testing cohort. Five machine learning algorithms were developed on the training data by using 10-fold cross-validation, and model performance was measured on the testing cohort. The models were developed and tested on the complete feature set. Subsequently, 3 feature selection methods were used to identify important predictors. The authors then assessed performance of the parsimonious models based on these important variables. RESULTS: This study included 268 patients who underwent MRgLITT, of whom 44.4% had achieved seizure freedom at 1 year post-MRgLITT. A gradient-boosting machine algorithm using the complete feature set yielded the highest area under the curve (AUC) on the testing set (AUC 0.67 [95% CI 0.50-0.82], sensitivity 0.71 [95% CI 0.47-0.88], and specificity 0.66 [95% CI 0.50-0.81]). Logistic regression, random forest, support vector machine, and neural network yielded lower AUCs (0.58-0.63) compared to the gradient-boosting machine but the findings were not statistically significant (all p > 0.05). The 3 feature selection methods identified video-EEG concordance, lesion size, preoperative seizure frequency, and number of antiseizure medications as good prognostic features for predicting seizure freedom. The parsimonious models based on important features identified by univariate feature selection slightly improved model performance compared to the complete feature set. CONCLUSIONS: Understanding the predictors of seizure freedom after MRgLITT will assist with prognostication.

Predictors of morbidity and in-hospital mortality following procedure-related cardiac tamponade.

Background: Cardiac tamponade (CT) can be a complication following invasive cardiac procedures. We assessed CT following common cardiac electrophysiology (EP) procedures to facilitate risk prediction of associated morbidity and in-hospital mortality. Methods: Patients who underwent various EP procedures in the cardiac catheterization lab (ablations and device implantations) were identified using the International Classification of Diseases, Ninth and Tenth Edition, Clinical Modification (ICD-9-CM and ICD-10-CM, respectively) from the Nationwide Inpatient Sample (NIS) database. Patient demographics, presence of comorbidities, CT-related events, and in-hospital death were also abstracted from the NIS database. Results: The frequency of CT-related events in patients with EP intervention from 2010 to 2017 ranged from 3.4% to 7.0%. In-hospital mortality related to CT-related events was found to be 2.2%. Increasing age was the only predictor of higher mortality in atrial fibrillation (AF) ablation and cardiac resynchronization therapy (CRT) groups (OR [95% CI]: AF ablation = 11.15 [1.70-73.34], p = .01; CRT = 1.41 [1.05-1.90], p = .02). Conclusions: In the real-world setting, CT-related events in EP procedures were found to be 3.4%-7.0% with in-hospital mortality of 2.2%. Older patients undergoing AF ablation were found to have higher mortality.

Synthesis, density functional theory and kinetic studies of aminopyridine based α-glucosidase inhibitors.

Aims: The current study aimed to develop new thiourea derivatives as potential α-glucosidase inhibitors for the management of hyperglycemia in patients of Type 2 diabetes, with a focus on identifying safer and more effective antidiabetic agents. Materials & methods: New thiourea derivatives (1-16) were synthesized through single-step chemical transformation and evaluated for in vitro α-glucosidase inhibition. Kinetic studies identified the mode of inhibition, free energy and type of interactions were analyzed through density functional theory and molecular docking. Results & conclusion: Compound 5 was identified as the most potent, noncompetitive and noncytotoxic inhibitor of α-glucosidase enzyme with a half-maximal inhibitory concentration of 24.62 ± 0.94 µM. Computational studies reinforce experimental results, demonstrating significant enzyme interactions via hydrophobic and π-π stacking forces.

Opportunities and Advances in Radiomics and Radiogenomics for Pediatric Medulloblastoma Tumors.

Recent advances in artificial intelligence have greatly impacted the field of medical imaging and vastly improved the development of computational algorithms for data analysis. In the field of pediatric neuro-oncology, radiomics, the process of obtaining high-dimensional data from radiographic images, has been recently utilized in applications including survival prognostication, molecular classification, and tumor type classification. Similarly, radiogenomics, or the integration of radiomic and genomic data, has allowed for building comprehensive computational models to better understand disease etiology. While there exist excellent review articles on radiomics and radiogenomic pipelines and their applications in adult solid tumors, in this review article, we specifically review these computational approaches in the context of pediatric medulloblastoma tumors. Based on our systematic literature research via PubMed and Google Scholar, we provide a detailed summary of a total of 15 articles that have utilized radiomic and radiogenomic analysis for survival prognostication, tumor segmentation, and molecular subgroup classification in the context of pediatric medulloblastoma. Lastly, we shed light on the current challenges with the existing approaches as well as future directions and opportunities with using these computational radiomic and radiogenomic approaches for pediatric medulloblastoma tumors.

Management of Severe Hemophilia A: Low-Dose Prophylaxis vs. On-Demand Treatment.

INTRODUCTION: Prophylactic clotting factor infusion regimens to prevent bleeding and joint deformity has become the standard of care in severe hemophilia A patients. AIM: To assess low-dose factor prophylaxis in our population as an alternative approach to managing severe hemophilia A. METHODS: A prospective cohort study that included 68 hemophilia A patients divided into two groups, i.e., Prophylaxis and on-demand. The two groups were compared for annualized bleeding rate (ABR), hospitalization, units of factor VIII (FVIII) infused, or plasma products transfused, i.e., fresh frozen plasma (FFP) and cryoprecipitate (CP), and development of FVIII inhibitors. RESULTS: Of the 68 patients recruited in this study, 25 (36.7%) were in the prophylaxis group, and 43(63.3%) were in the on-demand group. The on-demand group presented a higher median-IQR ABR [8(20-3) vs. 5(10-1.5), p-value 0.024], several hospitalizations (39.7% vs. 0, p-value 0.001), and inhibitor development (9.3% vs. 0, p-value 0.289) compared to the prophylaxis group. The prophylaxis approach demonstrated a significant negative correlation of ABR with FVIII prophylaxis (r=-0484, p=value=0.014). Moreover, no hospitalizations or inhibitor development was observed in the prophylaxis group. The estimated annual consumption of FVIII was 328 IU/kg/year in the on-demand group and 1662.6 IU/kg/year in the prophylaxis group. However, a highly significant difference in plasma product utilization was observed between the two groups, i.e., p-value <0.001 and 0.038 for FFP and CP, respectively. CONCLUSION: Low-dose factor prophylaxis resulted in improved outcomes compared to on-demand treatment in terms of ABR, joint bleeding, hospitalization, and the development of inhibitors. This treatment approach should be adopted as an economically feasible alternative to high-dose Prophylaxis in resource-constrained countries.

Early experience of intravascular lithotripsy in unprotected calcified left main coronary artery disease.

BACKGROUND: Treatment of unprotected severely calcified left main coronary artery (LMCA) disease is a complex interventional procedure. Intravascular lithotripsy (IVL) and rotational atherectomy (RA) are safe and effective methods of treating coronary calcification in the non-LMCA setting. This retrospective analysis assessed the feasibility of IVL versus RA in unprotected LMCA disease. METHODS: We analyzed IVL and RA procedures performed at a large tertiary hospital in the Northeast of England from January 1, 2019 to April 31, 2022. Major safety and efficacy endpoints were procedural and angiographic success, defined by stent delivery with <50 % residual stenosis and without clinical or angiographic complications, respectively. Another important clinical endpoint was the composite of major adverse cardiac events (MACE) at 1 year. RESULTS: From 242 patients, 44 had LMCA IVL, 81 had LMCA RA and 117 had non-LMCA IVL. Patients with LMCA disease were older and more likely to have aortic stenosis. IVL was a second-line or bailout technique in 86.4 % LMCA and 92.2 % non-LMCA cases. Procedural and angiographic success rates were ≥ 84 % across all groups (p > 0.05). In 3 LMCA IVL and 3 LMCA RA cases arrhythmias and cardiac tamponade complicated the procedures respectively. At 1 year, MACE occurred in 10/44 (22.7 %) LMCA IVL, 16/81 (19.8 %) LMCA RA and 25/117 (21.4 %) cases (p > 0.05). CONCLUSION: In our single center retrospective analysis, IVL is feasible in unprotected calcified LMCA as a second-line and third-line adjuvant calcium modification technique. Its use in unprotected calcified LMCA disease should be formalized with the undertaking of large randomized controlled trials.

A rare case of extensive biventricular cardiac sarcoidosis with reversible torrential tricuspid regurgitation.

Reversal of torrential tricuspid regurgitation is rarely seen. We describe a case in which effective immunosuppression alongside conventional heart failure therapies lead to reversibility of torrential tricuspid regurgitation in a patient with cardiac sarcoidosis. We also discuss the diagnostic challenge in distinguishing cardiac sarcoidosis from other myocardial diseases in a patient presenting with biventricular failure.