Systemic sclerosis is associated with increased in-patient mortality in patients hospitalized for heart failure.

AIMS: We aimed to analyse the characteristics and in-hospital outcomes of patients hospitalized for heart failure (HF) with co-morbid systemic sclerosis (SSc) and compare them to those without SSc, using data from the National Inpatient Sample from years 2016 to 2019. METHODS AND RESULTS: International Classification of Diseases, Tenth Revision diagnosis codes were used to identify hospitalized patients with a primary diagnosis of HF and secondary diagnoses of SSc from the National Inpatient Sample database from 2016 to 2019. Patients were divided into two groups: those with and without a secondary diagnosis of SSc. Baseline characteristics including demographics and co-morbidities, outcomes of mortality, length of stay (LOS), and costs were compared between the two groups. Multivariable logistic regression analysis was performed to adjust for confounders and assess the impact of SSc on in-hospital mortality, cost, and LOS. A total of 4 709 724 hospitalizations for HF were identified, with 8150 (0.17%) having a secondary diagnosis of SSc. These patients were predominantly female (82.3% vs. 47.8%; P = 0.01), younger (mean age of 67.4 vs. 71.4; P < 0.01), and had significantly lower rates of traditional cardiovascular risk factors such as coronary artery disease (35.8% vs. 50.6%; P < 0.01), hyperlipidaemia (39.1% vs. 52.9%; P < 0.01), diabetes (22.5% vs. 49.1%; P < 0.01), obesity (13.2% vs. 25.0%; P < 0.01), and hypertension (20.2% vs. 23.8%; P < 0.01). Higher rates of co-morbid pulmonary disease in the form of interstitial lung disease (23.1% vs. 2.0%; P < 0.01) and pulmonary hypertension (36.6% vs. 12.7%; P < 0.01) were noted in the SSc cohort. Unadjusted in-hospital mortality was significantly higher in the HF with SSc group [5.1% vs. 2.6%; odds ratio: 1.99; 95% confidence interval (CI): 1.60-2.48; P < 0.001]. Unadjusted mortality was also higher among female (86.7% vs. 47.0%; P < 0.01), Black (15.7% vs. 13.0%; P < 0.01), and Hispanic (13.3% vs. 6.9%; P < 0.01) patients in the SSc cohort. After adjusting for potential confounders, SSc remained independently associated with higher in-hospital mortality (adjusted odds ratio: 1.81; 95% CI: 1.44-2.28; P < 0.001). Patients with HF and SSc also had longer LOS (6.4 vs. 5.4; adjusted mean difference [AMD]: 0.37, 95% CI: 0.05-0.68; P = 0.02) and higher hospitalization costs ($67 363 vs. $57 128; AMD: 198.9; 95% CI: -4780 to 5178; P = 0.93). CONCLUSIONS: In patients hospitalized for HF, those with SSc were noted to have higher odds of in-hospital mortality than those without SSc. Patients with HF and SSc were more likely to be younger, female, and have higher rates of co-morbid interstitial lung disease and pulmonary hypertension at baseline with fewer traditional cardiovascular risk factors.

Systemic thrombolysis with newer thrombolytics vs anticoagulation in acute intermediate risk pulmonary embolism: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) comparing systemic thrombolysis to anticoagulation in intermediate risk pulmonary embolism (PE) have yielded mixed results. A prior meta-analysis on this topic had included studies that used lower than standard dose of thrombolytics and included thrombolytic agents that are no longer available. Hence, interpreting the findings of that paper is not valid in contemporary practice. OBJECTIVES: We undertook a systematic review and meta-analysis of randomized controlled trials of systemic thrombolysis with newer thrombolytic agents vs anticoagulation in intermediate risk PE. METHODS: This systematic review and meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. RESULTS: Nine randomized controlled trials were included in the study. We did not find any difference in in-hospital mortality (RR: 0.79; 95% CI: 0.42-1.50; I2: 0) or risk of major bleeding (RR:2.08;95% CI: 0.98-4.42; I2: 23.9%) between systemic thrombolysis and anticoagulation. Systemic thrombolysis was associated with lower risks for vasopressor use (RR: 0.27; 95% CI: 0.11-0.64, I2: 0) and secondary/rescue thrombolysis (RR: 0.25; 95% CI: 0.14-0.45; I2: 0). But systemic thrombolysis was found to have an increased risk of intracranial hemorrhage (RR: 4.55; 95% CI: 1.30-15.91; I2:0). There was no difference in mechanical ventilation between the two groups (RR: 0.61; 95% CI: 0.31-1.19, I2:0). CONCLUSION: In our meta-analysis of randomized controlled trials of systemic thrombolysis vs anticoagulation in intermediate risk PE, we did not find any difference in in-hospital mortality or overall risk of major bleeding. With systemic thrombolysis, we found lower risks for vasopressor use and need for secondary/ rescue thrombolysis and an increased risk of intracranial hemorrhage.

Impact of sleep apnoea on 30 day hospital readmission rate and cost in heart failure with reduced ejection fraction.

AIMS: In this study, we estimated the 30 day all-cause and heart failure-specific readmission rates, predictors, mortality, and hospitalization costs in patients with obstructive sleep apnoea admitted with acute decompensated heart failure with reduced ejection fraction. METHODS AND RESULTS: This is a retrospective cohort study using the Agency of Healthcare Research and Quality's National Readmission Database for the year 2019. The primary outcome was the 30 day all-cause hospital readmission rate. The secondary outcomes were (i) in-hospital mortality rate for index admissions; (ii) 30 day mortality rate for index hospitalizations; (iii) the five most common principal diagnosis for readmission; (iv) readmission in-hospital mortality rate; (v) length of hospital stay; (vi) independent risk factors for readmission; and (vii) hospitalization costs. We identified 6908 hospitalizations that met our study definition. The mean patient age was 62.8 years, and women comprised only 27.6% of patients. The 30 day all-cause readmission rate was 23.4%. 48.9% of readmissions were due to decompensated heart failure. The in-hospital mortality rate during readmissions was significantly higher than that of the index admission (5.6% vs. 2.4%; P < 0.05). The mean length of stay for patients during index admissions was 6.5 days (6.06-7.02), while during readmissions, it was 8.5 days (7.4-9.6; P < 0.05). The mean total hospitalization charges at index admissions were $78 438 (68 053-88 824), while during readmissions, they were higher at $124 282 (90 906-157 659; P < 0.05). The mean total cost of hospitalization during index admissions was $20 535 (18 311-22 758), while at readmissions, it was higher at $29 954 (24 041-35 867; P < 0.05). The total hospital charges for all 30 day readmissions were $195 million, and total hospital costs was $46.9 million. The variables found to be associated with increased rate of readmissions were patients with Medicaid insurance, higher Charlson co-morbidity Index, and longer length of stay. The variables associated with lower rate of readmissions were prior percutaneous coronary intervention and patients with private insurance. CONCLUSIONS: In patients with obstructive sleep apnoea admitted with heart failure with reduced ejection fraction, we found a substantial all-cause readmission rate of 23.4% with heart failure readmission constituting about 48.9% of readmissions. Readmissions were associated with higher mortality and resource use.

Mortality and bleeding associated with the management of sub-massive pulmonary embolism: a systematic review and Bayesian network meta-analysis.

Current guidelines recommend anticoagulation (AC) for low and intermediate-risk pulmonary embolism (PE) and systemic thrombolysis (tPA) for high risk (massive) PE. How these treatment options compare with other modalities of treatment such as catheter directed thrombolysis (CDT), ultrasound assisted catheter thrombolysis (USAT), and administering lower dose of thrombolytics (LDT) is unclear. There is no study that has compared all these treatment options. We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials in patients with submassive (intermediate risk) PE. Fourteen randomized controlled trials were included, comprising 2132 patients. On Bayesian network meta-analysis, a significant decrease in mortality was noted in tPA versus AC. There was no significant difference between USAT versus CDT. For risk of major bleeding, there was no significant difference in relative risk of major bleeding between tPA versus AC and USAT versus CDT. tPA was found to have a significantly higher risk of minor bleeding and a lower risk of recurrent PE compared to AC. Systemic thrombolysis is associated with a significant reduction in mortality and recurrent PE compared to anticoagulation but an increased risk of minor bleeding. There was no difference in risk of major bleeding. Our study also shows that while the newer modalities of treatment for pulmonary embolism are promising, there is lack of data to comment on the purported advantages.

Impact of left bundle branch block on heart failure with preserved ejection fraction.

BACKGROUND: The implications of LBBB in heart failure with preserved ejection fraction (HFpEF) is unclear. Our study assesses clinical outcomes among patients with LBBB and HFpEF who were admitted with acute decompensated heart failure. METHODS: This is a cross-sectional study was conducted using the National Inpatient Sample (NIS) database from 2016-2019. RESULTS: We found 74,365 hospitalizations with HFpEF and LBBB and 3,892,354 hospitalizations with HFpEF without LBBB. Patients with LBBB were older (78.9 vs 74.2 years) and had higher rates of coronary artery disease (53.05% vs 40.8%), hypertension (74.7% vs 70.8%), atrial fibrillation (32.8% vs 29.4%), sick sinus rhythm (3.4% vs 2.02%), complete heart block (1.8% vs 0.66%), ventricular tachycardia (3.5% vs 1.7%), and ventricular fibrillation (0.24% vs 0.11%). Patients with LBBB were found to have decreased in-hospital mortality (OR: 0.85; 0.76-0.96; p-0.009) but higher rates of cardiac arrest (OR: 1.39; 1.06-1.83; p-0.02) and need for mechanical circulatory support (OR: 1.7; 1.28-2.36; p-0.001). Patients with LBBB underwent a higher rate of pacemaker (OR: 2.98; 2.75-3.23; p < 0.001) and ICD (implantable cardioverter-defibrillator) placement (OR: 3.98; 2.81-5.62; p < 0.001). Patients with LBBB were also found to have a higher mean cost of hospitalization ($81,402 vs $60,358; p < 0.001) but lower length of stay (4.8 vs 5.4 days; p < 0.001). CONCLUSION: In patients admitted with decompensated heart failure with preserved ejection fraction, left bundle branch block is associated with increased odds of cardiac arrest, mechanical circulatory support requirement, device implantation and mean cost of hospitalization but decreased odds of in-hospital mortality.

Genetic Variants of DNA Repair Genes as Predictors of Radiation-Induced Subcutaneous Fibrosis in Oropharyngeal Carcinoma.

PURPOSE: To investigate the impact of genetic variants of DNA repair and pro-fibrotic pathway genes on the severity of radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radical radiotherapy. MATERIALS AND METHODS: Patients of newly diagnosed squamous cell carcinoma of oropharynx being treated with two-dimensional radical radiotherapy were enrolled in the study. Patients who had undergone surgery or were receiving concurrent chemotherapy were excluded. Patients were followed up at 6 weeks post completion of radiotherapy and every 3 months thereafter for a median of 16 months. Subcutaneous fibrosis was graded according to the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) grading system and the maximum grade was recorded over the length of the patient's follow-up. Patients with severe fibrosis (≥G3), were compared to patients with minor (≤G2) fibrotic reactions. Eight single nucleotide polymorphisms of 7 DNA repair genes and 2 polymorphisms of a single pro-fibrotic pathway gene were analyzed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and were correlated with the severity of subcutaneous fibrosis. RESULTS: 179 patients were included in the analysis. Subcutaneous fibrosis was seen in 168 (93.9%) patients. 36 (20.1%) patients had severe (grade 3) fibrosis. On multivariate logistic regression analysis, Homozygous CC genotype of XRCC3 (722C>T, rs861539) (p=0.013*, OR 2.350, 95% CI 1.089-5.382), Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) (p=0.001**, OR 11.626, 95% CI 2.490-275.901) and Homozygous TT genotype of XRCC5 (1401G>T, rs828907) (p=0.020*, OR 2.188, 95% CI 1.652-7.334) were found to be predictive of severe subcutaneous fibrosis. On haplotype analysis, the cumulative risk of developing severe fibrosis was observed in patients carrying both haplotypes of variant Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) and Homozygous TT genotype of XRCC5 (1401 G>T, rs828907) (p=0.010*, OR 26.340, 95% CI 4.014-76.568). CONCLUSION: We demonstrated significant associations between single nucleotide polymorphisms of DNA repair genes and radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radiotherapy. We propose to incorporate these genetic markers into predictive models for identifying patients genetically predisposed to the development of radiation-induced fibrosis, thus guiding personalized treatment protocols.

Hypertrophic post-acne scarring is associated with a single nucleotide polymorphism (rs243865) in the matrix metalloproteinase-2 gene.

BACKGROUND AND OBJECTIVE: Aberrant tissue expression of matrix metalloproteinases has been observed in acne. Our objective was to study the relevance of MMP-2 (-1306 C/T, rs243865) and TIMP-2 (-418 G/C, rs8179090) single nucleotide polymorphisms (SNP) in acne and post-acne scarring. PATIENTS AND METHODS: 512 patients (169 having acne without scarring, 319 having atrophic acne scarring, 24 having hypertrophic acne scarring) and 161 age-matched controls were recruited from the Dermatology Outpatient Department after obtaining informed written consent. Venous blood (5 ml) was collected for genotyping by Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (RFLP) method. The severity of acne and acne-scarring were graded. RESULTS: Males had a significantly increased risk of developing severe acne (P = 0.012), extra-facial acne (P = 0.047) and extra-facial acne scarring (P = 0.0001). The presence of inflammatory acne positively correlated with severity of scarring (P = 0.001). Subjects with a homozygous CC genotype of MMP-2 (-1306 C/T) had 1.0, 7.8 and 8.2 times the odds of developing hypertrophic scarring when compared to controls (P = 0.05, 95 % CI: 0.7-1.6), subjects having acne without scarring (P = 0.047, 95 % CI: 1.0-59.9) and subjects having atrophic scarring, respectively (P = 0.041, 95 % CI: 1.1-59.9). CONCLUSIONS: A significant association was observed between hypertrophic post-acne scarring and the CC genotype of MMP-2 (-1306 C/T).

Assoziation hypertropher Post-Akne-Narben mit Einzelnukleotid-Polymorphismus (rs243865) im Matrix-Metalloproteinase-2-Gen.

HINTERGRUND UND ZIEL: Bei Akne wurde eine abweichende Gewebeexpression von Matrix-Metalloproteinasen beobachtet. Ziel unserer Studie war es, die Bedeutung von Polymorphismen einzelner Nukleotide (single nucleotide polymorphisms, SNPs) in MMP-2 (-1306 C/T, rs243865) und TIMP-2 (-418 G/C, rs8179090) bei Akne und Post-Akne-Narben zu untersuchen. PATIENTEN UND METHODEN: 512 Patienten (169 mit Akne ohne Narbenbildung, 319 mit atrophen Aknenarben, 24 mit hypertrophen Aknenarben) und 161 gleichaltrige Kontrollen wurden nach Erhalt der schriftlichen Einwilligungserklärung aus der Ambulanz der Hautklinik in die Studie aufgenommen. Zur Genotypisierung mittels Polymerasekettenreaktion-Restriktionsfragmentlängenpolymorphismus (PCR-RFLP) wurde venöses Blut (5 ml) entnommen. Der Schweregrad von Akne und Akne-bedingter Narbenbildung wurde bestimmt. ERGEBNISSE: Männer hatten ein deutlich erhöhtes Risiko schwere Akne (p = 0,012), Akne außerhalb des Gesichts (p = 0,047) und Aknenarben außerhalb des Gesichts (p = 0,0001) zu entwickeln. Entzündliche Akne korrelierte positiv mit dem Schweregrad der Narbenbildung (p = 0,001). Die Wahrscheinlichkeit für die Bildung hypertropher Narben war bei Personen mit homozygotem CC-Genotyp von MMP-2 (-1306 C/T) gegenüber Kontrollen nicht verändert (Faktor 1,0; p = 0,05; 95 %-KI: 0,7-1,6), jedoch gegenüber Personen mit Akne ohne Narbenbildung um den Faktor 7,8 (p = 0,047; 95 %-KI: 1,0-59,9) und gegenüber Personen mit atrophen Narben um den Faktor 8,2 (p = 0,041; 95 %-KI: 1,1-59,9) erhöht. SCHLUSSFOLGERUNGEN: Es wurde eine signifikante Assoziation zwischen der Bildung hypertropher Post-Akne-Narben und dem CC-Genotyp von MMP-2 (-1306 C/T) beobachtet.

Documentation of shared decision making around primary prevention defibrillator implantations.

INTRODUCTION: Patients eligible for primary prevention implantable cardioverter-defibrillator (ICD) therapy are faced with a complex decision that needs a clear understanding of the risks and benefits of such an intervention. In this study, our goal was to explore the documentation of primary prevention ICD discussions in the electronic medical records (EMRs) of eligible patients. METHODS: In 1523 patients who met criteria for primary prevention ICD therapy between 2013 and 2015, we reviewed patient charts for ICD-related documentation: "mention" by physicians or "discussion" with patient/family. The attitude of the physician and the patient/family toward ICD therapy during discussions was categorized into negative, neutral, or positive preference. Patients were followed to the end-point of ICD implantation. RESULTS: Over a median follow-up of 442 days, 486 patients (32%) received an ICD. ICD was mentioned in the charts of 1105 (73%) patients, and a discussion with the patient/family about the risks and benefits of ICD was documented in 706 (46%) charts. On multivariable analyses, positive cardiologist (hazard ratio [HR]: 7.9, 95% confidence of intervals [CI]: 1.0-59.7, P < .05), electrophysiologist (HR: 7.7, 95% CI: 1.9-31.7, P < .001), and patient/family (HR: 9.9, 95% CI: 6.2-15.7, P < .001) preferences toward ICD therapy during the first documented ICD discussion were independently associated with ICD implantation. CONCLUSIONS: In a large cohort of patients eligible for primary prevention ICD therapy, a discussion with the patient/family about the risks and benefits of ICD implantation was documented in less than 50% of the charts. More consistent documentation of the shared decision making around ICD therapy is needed.

A Celiac Disease Phenotype After Checkpoint Inhibitor Exposure: An Example of Immune Dysregulation After Immunotherapy.

Celiac disease is characterized by duodenal inflammation after exposure to gluten. Checkpoint inhibitors are antibodies that inhibit the inhibitory signals of the cytotoxic T lymphocytes to enhance antitumor responses. A 79-year-old man with an unknown history of celiac disease underwent treatment with pembrolizumab for recurrent left maxillary melanoma. He subsequently developed diarrhea and weight loss. Serology was positive for anti-tissue transglutaminase immunoglobulin A. Upper endoscopy revealed duodenal villous atrophy, which was confirmed on biopsy. A gluten-free diet was not tolerated, and symptoms resolved with withdrawal of pembrolizumab and steroid administration for another medical reason.

Cardiac myxoma causing acute ischemic stroke in a pediatric patient and a review of literature.

BACKGROUND: Ischemic stroke in the pediatric population is a rare occurrence, and its possible causes span a wide differential that includes atrial myxomas. Myxomas are friable cardiac tumors that produce "showers" of emboli resulting in transient neurological deficits, cutaneous eruptions, and ophthalmologic deficits. PATIENT: We present an 11-year-old boy with a months-long history of an intermittent spotted "rash" who presented with acute ischemic stroke caused by a left atrial myxoma. We also review clinical features in all 16 other cases of cardiac myxoma causing pediatric stroke reported in the literature. RESULTS: Our case, along with the review of the literature, highlights the fact that myxomas often initially present as stroke with acute hemiplegia and transient cutaneous eruptions due to fragmentation of the tumor. CONCLUSIONS: Cardiac myxoma should be considered in any child presenting with ischemic stroke, and transient skin findings may provide an important diagnostic clue prior to onset of neurological symptoms.