Chagas Disease: Epidemiology, Diagnosis, and Treatment.

PURPOSE OF REVIEW: This review seeks to describe the updates in the literature - particularly with regards to the epidemiology and diagnosis of Chagas disease. Additionally, this paper describes updates to the antiparasitic treatment for Chagas disease. RECENT FINDINGS: With regards to changing epidemiology, autochthonous cases are being found within the USA in addition to Latin America. Additionally, there appears to be more intermixing of discrete typing units-meaning, they are not confined to specific geographic regions. Screening for Chagas disease is recommended in persons who lived in areas with endemic Chagas, persons wtih family member diagnosed with Chagas Disease, persons who have lived in homes of natural material in Latin America, and persons with history of kissing bug bites. Treatment for the parasitic infection remains limited to benznidazole and nifurtimox, and the role of these treatments in Chagas cardiomyopathy has not yet been definitively defined. Finally, indications for and management of heart transplant in the setting of Chagas disease are discussed. FUTURE RESEARCH: Use of antiparasitics during chronic chagas disease should be further explored. Additionally, future research identifying other markers of infection would be valuable to defining cure from infection.

Predicting Long-Term Clinical Outcomes of Patients With Recurrent Pericarditis.

BACKGROUND: Recurrent pericarditis (RP) is a complex condition associated with significant morbidity. Prior studies have evaluated which variables are associated with clinical remission. However, there is currently no established risk-stratification model for predicting outcomes in these patients. OBJECTIVES: We developed a risk stratification model that can predict long-term outcomes in patients with RP and enable identification of patients with characteristics that portend poor outcomes. METHODS: We retrospectively studied a total of 365 consecutive patients with RP from 2012 to 2019. The primary outcome was clinical remission (CR), defined as cessation of all anti-inflammatory therapy with complete resolution of symptoms. Five machine learning survival models were used to calculate the likelihood of CR within 5 years and stratify patients into high-risk, intermediate-risk, and low-risk groups. RESULTS: Among the cohort, the mean age was 46 ± 15 years, and 205 (56%) were women. CR was achieved in 118 (32%) patients. The final model included steroid dependency, total number of recurrences, pericardial late gadolinium enhancement, age, etiology, sex, ejection fraction, and heart rate as the most important parameters. The model predicted the outcome with a C-index of 0.800 on the test set and exhibited a significant ability in stratification of patients into low-risk, intermediate-risk, and high-risk groups (log-rank test; P < 0.0001). CONCLUSIONS: We developed a novel risk-stratification model for predicting CR in RP. Our model can also aid in stratifying patients, with high discriminative ability. The use of an explainable machine learning model can aid physicians in making individualized treatment decision in RP patients.

Immune checkpoint inhibitors and pericardial disease: a systematic review.

INTRODUCTION: Despite the growing use of immune checkpoint inhibitors (ICI) in cancer treatment, data regarding ICI-associated pericardial disease are primarily derived from case reports and case series. ICI related pericardial disease can be difficult to diagnose and is associated with significant morbidity. We conducted a systematic review to further characterize the epidemiology, clinical presentation, and outcomes of this patient population. METHODS: A search of four databases resulted in 31 studies meeting inclusion criteria. Patients > 18 years old who presented with ICI mediated pericardial disease were included. Intervention was medical + surgical therapy and outcomes were development of cardiac tamponade, morbidity, and mortality. RESULTS: Thirty- eight patients across 31 cases were included. Patients were majority male (72%) with a median age of 63. Common symptoms included dyspnea (59%) and chest pain (32%), with 41% presenting with cardiac tamponade. Lung cancer (81%) was the most prevalent, and nivolumab (61%) and pembrolizumab (34%) were the most used ICIs. Pericardiocentesis was performed in 68% of patients, and 92% experienced symptom improvement upon ICI cessation. Overall mortality was 16%. DISCUSSION: This study provides the most comprehensive analysis of ICI-mediated pericardial disease to date. Patients affected were most commonly male with lung cancer treated with either Nivolumab or Pembrolizumab. Diagnosis may be challenging in the setting of occult presentation with normal EKG and physical exam as well as delayed onset from therapy initiation. ICI-associated pericardial disease demonstrates high morbidity and mortality, as evidenced by a majority of patients requiring pericardiocentesis.

Concurrent BRAFV600E and BRCA Mutations in MSS Metastatic Colorectal Cancer: Prevalence and Case Series of mCRC patients with prolonged OS.

BACKGROUND: BRAF V600E+ microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients comprise up to 10% of advanced CRC. They have a poor prognosis with a median survival typically <1 year. Despite use of multi-agent 1st line chemotherapy regimens and combination targeted therapies, outcomes are still poor. In our Institutional Molecular Tumor Board (MTB) database, we identified 3 mCRC patients with MSS/BRAF V600E who also had a BRCA1 or BRCA2 co-mutation and had relatively long overall survivals. Prior studies suggested that BRCA mutations are uncommon in CRC and we queried the Foundation Medicine (FM) genomic database to evaluate the prevalence of these cases as well as those with co-mutations in other homologous recombination genes. METHODS: 36,966 CRC pts were sequenced by FMI using hybrid capture comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA) for pathogenic BRAF mutations and/or a mutation in BRCA1/2 or a co-mutation in other homologous recombination (HR) genes (BARD1, CDK12, FANCL, PALB2, ATM, RAD54L, CHEK2, BRAF, BRIP1, RAD51D, RAD51C, RAD51B, CHEK1). Selected cohort analysis of BRAF V600E co-mutated with BRCA1 and BRCA2 were separated into MSI-H and MSS cohorts. The clinicopathological features and genomic loss of heterozygosity (gLOH) of those with a BRAF V600E and a BRCA1/BRCA2 mutation were collected and analyzed. We also describe 3 consecutive cases of mCRC patients, identified through the Inova Schar Cancer Institute (ISCI) MTB registry, whom had prolonged OS. RESULTS: Of 36,966 colorectal cancer pts, 6.6% were BRAF V600E+ and 1.5% had any co-occurring HR gene mutation(s) with 0.6% of the total mCRC population having co-ocurring BRAF V600E and BRCA1/2 alterations. BRCA co-mutations were higher in MSI-High BRAF V600E, however 24.1% of co-occurrences were observed in MSS samples. BRCA1 co-mutation was more commonly associated with MSS BRAF V600E and was associated with a higher gLOH than MSI-H BRAF V600E (18.7% vs 2.8%; p <0.001). In our institutional MTB database, (3/241;1.2%) CRC patients were MSS, BRAF V600E+ with BRCA1 or BRCA2 co-mutations, all somatic in origin, with an average gLOH of 21.4% and overall survivals of 72+(alive), 17+(alive), and 30 months, respectively. CONCLUSION: Co-existence of BRAF V600E/BRCA1/2 may represent a unique subset of advanced MSS CRC that may have a better prognosis and represent an opportunity to test novel targeted therapies. The elevated gLOH in these cases may also be a valuable biomarker for these pts. Larger prospective clinical validation trials in this subset is warranted.