Longitudinal Assessment of Left Atrial Remodeling in Patients With Chronic Severe Aortic Regurgitation.

BACKGROUND: There are significant sex and age differences in left ventricular (LV) remodeling that may lead to disparity in outcomes when used to inform the timing of aortic regurgitation (AR) intervention. OBJECTIVES: The aim of this study was to examine whether left atrial (LA) parameters might represent better criteria than LV parameters to inform the timing of AR intervention. METHODS: Using data on patients with moderate to severe or severe AR with serial echocardiography (2010-2016), the longitudinal trends in left atrial volume index (LAVI) and left atrial reservoir strain (LAr) were evaluated by sex and age. The incremental utility of these parameters in predicting adverse events over LV parameters was also determined. RESULTS: In 525 patients (25.7% women) with 1,687 echocardiograms over a median follow-up period of 2.0 years (Q1-Q3: 1.0-3.6 years), there was significant increase in LAVI (1.0 mL/m2 per year [95% CI: 0.76-1.2 mL/m2 per year]) and decrease in LAr (-1.3% per year [95% CI: -1.6% to -0.92%]), without a significant interaction by sex or age category (P for interaction ≥ 0.17). In addition, both LAVI and LAr were significant predictors of adverse events independent of LV parameters. The optimal discriminatory thresholds were 37 mL/m2 for LAVI and 35% for LAr. These thresholds were similar across categories of sex and age. Within the relatively short-term follow-up, surgery was associated with survival benefit among patients with LAVI ≥37 mL/m2 (HR: 0.33 [95% CI: 0.15-0.72]; P = 0.006) but was not statistically significant among patients with LAVI <37 mL/m2 (HR: 0.46 [95% CI: 0.18-1.17]; P = 0.09). Similarly, surgery was associated with survival for the subgroup with LAr ≤35% but not among those with LAr >35%. CONCLUSIONS: Unlike LV remodeling, LA remodeling demonstrates a similar rate of progression between categories of sex and age among patients with AR. In addition, LA parameters provide incremental prognostic value over LV parameters.

Role of aortic valve replacement in moderate aortic stenosis: a 10-year outcomes study.

OBJECTIVE: Patients with moderate aortic stenosis (AS) exhibit high morbidity and mortality. Limited evidence exists on the role of aortic valve replacement (AVR) in this patient population. To investigate the benefit of AVR in moderate AS on survival and left ventricular function. METHODS: In a retrospective cohort study, patients with moderate AS between 2008 and 2016 were selected from the Cleveland Clinic echocardiography database and followed until 2018. Patients were classified as receiving AVR or managed medically (clinical surveillance). All-cause and cardiovascular mortality were assessed by survival analyses. Temporal haemodynamic and structural changes were assessed with longitudinal analyses using linear mixed effects models. RESULTS: We included 1421 patients (mean age, 75.3±5.4 years and 39.9% women) followed over a median duration of 6 years. Patients in the AVR group had lower risk of all-cause (adjusted HR (aHR)=0.51, 95% CI: 0.34 to 0.77; p=0.001) and cardiovascular mortality (aHR=0.50, 95% CI: 0.31 to 0.80; p=0.004) compared with those in the clinical surveillance group irrespective of sex, receipt of other open-heart surgeries and underlying malignancy. These findings were seen only in those with preserved left ventricular ejection fraction (LVEF) ≥50%. Further, patients in the AVR group had a significant trend towards an increase in LVEF and a decrease in right ventricular systolic pressure compared with those in the clinical surveillance group. CONCLUSIONS: In patients with moderate AS, AVR was associated with favourable clinical outcomes and left ventricular remodelling.

Incidence, Risk Factors, and Outcomes Associated With Permanent Pacemaker Implantation Following Tricuspid Valve Surgery.

BACKGROUND: Data regarding permanent pacemaker (PPM) implantation following tricuspid valve surgery (TVS) are limited. We sought to evaluate its incidence, risk factors, and outcomes. METHODS AND RESULTS: Medicare beneficiaries who underwent TVS from 2013 to 2020 were identified. Patients who underwent TVS for endocarditis were excluded. The primary exposure of interest was new PPM after TVS. Outcomes included all-cause mortality and readmission with endocarditis or heart failure on follow-up. Among the 13 294 patients who underwent TVS, 2518 (18.9%) required PPM placement. Risk factors included female sex (relative risk [RR], 1.26 [95% CI, 1.17-1.36], P<0.0001), prior sternotomy (RR, 1.12 [95% CI, 1.02-1.23], P=0.02), preoperative second-degree heart block (RR, 2.20 [95% CI, 1.81-2.69], P<0.0001), right bundle-branch block (RR, 1.21 [95% CI, 1.03-1.41], P=0.019), bifascicular block (RR, 1.43 [95% CI, 1.06-1.93], P=0.02), and prior malignancy (RR, 1.23 [95% CI, 1.01-1.49], P=0.04). Tricuspid valve (TV) replacement was associated with a significantly higher risk of PPM implantation when compared with TV repair (RR, 3.20 [95% CI, 2.16-4.75], P<0.0001). After a median follow-up of 3.1 years, mortality was not different in patients who received PPM compared with patients who did not (hazard ratio [HR], 1.02 [95% CI, 0.93-1.12], P=0.7). PPM placement was not associated with a higher risk of endocarditis but was associated with a higher risk of heart failure readmission (HR, 1.28 [95% CI, 1.14-1.43], P<0.001). CONCLUSIONS: PPM implantation frequently occurs after TVS, notably in female patients and patients undergoing TV replacement. Although mortality is not increased, it is associated with higher rates of heart failure rehospitalization.

Utilization and outcome disparities in allogeneic hematopoietic stem cell transplant in the United States.

Allogeneic hematopoietic stem cell transplant (allo-HSCT) is increasingly being used in the United States (US) and across the world as a curative therapeutic option for patients with certain high-risk hematologic malignancies and non-malignant diseases. However, racial and ethnic disparities in utilization of the procedure and in outcome following transplant remain major problems. Racial and ethnic minority patients are consistently under-represented in the proportion of patients who undergo allo-HSCT in the US. The transplant outcomes in these patients are also inferior. The interrelated driving forces responsible for the differences in the utilization and transplant outcome of the medical intervention are socioeconomic status, complexity of the procedure, geographical barriers, and the results of differences in the genetics and comorbidities across different races. Bridging the disparity gaps is important not only to provide equity and inclusion in the utilization of this potentially life-saving procedure but also in ensuring that minority groups are well represented for research studies about allo-HSCT. This is required to determine interventions that may be more efficacious in particular racial and ethnic groups. Various strategies at the Federal, State, and Program levels have been designed to bridge the disparity gaps with varying successes. In this review paper, we will examine the disparities and discuss the strategies currently available to address the utilization and outcome gaps between patients of different races in the US.

Immune checkpoint inhibitors in BRAF-mutated advanced colorectal cancer.

Colorectal cancer has been around for a long time, but is still a challenge nonetheless. However, the heterogeneity of the disease opens new potential therapeutic doors. BRAF-mutated advanced colorectal cancer is a demanding entity that does not respond to standard chemotherapy regimens (FOLFOX, capecitabine) and the presence of the mutation significantly weakens the prognosis, but the rise of immunotherapy could reverse the trend. Indeed, pembrolizumab and nivolumab have boasted promising outcomes and increased survival rates among this subset of patients. This article is a collection of these results which could potentially bring immunotherapy to the front line.

Case report: Primary cardiac lymphoma manifesting as superior vena cava syndrome.

A 64-year-old man presented with symptoms indicative of superior vena cava syndrome. Imaging work-up revealed an obstructing right atrial mass, which was subsequently excised and diagnosed as primary cardiac lymphoma. Post-surgery, the patient showed significant clinical improvement and was started on a chemotherapy regimen with complete remission at 1 year.

Contemporary risk models for infective endocarditis surgery: a narrative review.

Infective endocarditis is a complex heterogeneous condition involving the infection of the endocardium and heart valves, leading to severe complications, including death. Surgery is often indicated in patients with infective endocarditis but is associated with elevated risk compared with other forms of cardiac surgery. Risk models play an important role in many cardiac surgeries as they can help inform clinicians and patients regarding procedural risk, decision-making to proceed or not, and influence perioperative management; however, they remain under-utilized in the infective endocarditis settings. Another crucial role of such risk models is to assess predicted versus found mortality, thereby allowing an assessment of institutional performance in infective endocarditis surgery. Traditionally, general cardiac surgery risk models such as European System for Cardiac Operative Risk Evaluation (EuroSCORE), EuroSCORE II, and Society of Thoracic Surgeon's score have been applied to endocarditis surgery. However, there has been the development of many endocarditis surgery-specific scores over the last decade. This review aims to discuss clinical characteristics and applications of all contemporary risk scores in the setting of surgical treatment of infective endocarditis.

Liquid biopsies and minimal residual disease in lymphoid malignancies.

Minimal residual disease (MRD) assessment using peripheral blood instead of bone marrow aspirate/biopsy specimen or the biopsy of the cancerous infiltrated by lymphoid malignancies is an emerging technique with enormous interest of research and technological innovation at the current time. In some lymphoid malignancies (particularly ALL), Studies have shown that MRD monitoring of the peripheral blood may be an adequate alternative to frequent BM aspirations. However, additional studies investigating the biology of liquid biopsies in ALL and its potential as an MRD marker in larger patient cohorts in treatment protocols are warranted. Despite the promising data, there are still limitations in liquid biopsies in lymphoid malignancies, such as standardization of the sample collection and processing, determination of timing and duration for liquid biopsy analysis, and definition of the biological characteristics and specificity of the techniques evaluated such as flow cytometry, molecular techniques, and next generation sequencies. The use of liquid biopsy for detection of minimal residual disease in T-cell lymphoma is still experimental but it has made significant progress in multiple myeloma for example. Recent attempt to use artificial intelligence may help simplify the algorithm for testing and may help avoid inter-observer variation and operator dependency in these highly technically demanding testing process.

Intestinal barrier functions in hematologic and oncologic diseases.

The intestinal barrier is a complex structure that not only regulates the influx of luminal contents into the systemic circulation but is also involved in immune, microbial, and metabolic homeostasis. Evidence implicating disruption in intestinal barrier functions in the development of many systemic diseases, ranging from non-alcoholic steatohepatitis to autism, or systemic complications of intestinal disorders has increased rapidly in recent years, raising the possibility of the intestinal barrier as a potential target for therapeutic intervention to alter the course and mitigate the complications associated with these diseases. In addition to the disease process being associated with a breach in the intestinal barrier functions, patients with hematologic and oncologic diseases are particularly at high risks for the development of increased intestinal permeability, due to the frequent use of broad-spectrum antibiotics and chemoradiation. They also face a distinct challenge of being intermittently severely neutropenic due to treatment of the underlying conditions. In this review, we will discuss how hematologic and oncologic diseases are associated with disruption in the intestinal barrier and highlight the complications associated with an increase in the intestinal permeability. We will explore methods to modulate the complication. To provide a background for our discussion, we will first examine the structure and appraise the methods of evaluation of the intestinal barrier.

Chronic graft-versus-host disease in pediatric patients: Differences and challenges.

Despite the use of high-resolution molecular techniques for tissue typing, chronic graft-versus-host disease (cGVHD) remains a major complication following allogeneic hematopoietic stem cell transplant. cGVHD adversely affects the life-expectancy and quality of life. The latter is particularly important and functionally relevant in pediatric patients who have a longer life-expectancy than adults. Current laboratory evidence suggests that there is not any difference in the pathophysiology of cGVHD between adults and pediatric patients. However, there are some clinical features and complications of the disease that are different in pediatric patients. There are also challenges in the development of new therapeutics for this group of patients. In this review, we will discuss the epidemiology, pathophysiology, clinical features and consequences of the disease, and highlight the differences between pediatric and adult patients. We will examine the current treatment options for pediatric patients with moderate to severe cGVHD and discuss the challenges facing therapeutic development for cGVHD in the pediatric population.

Update on immunotherapy in the management of gallbladder cancer.

Gallbladder cancer (GBC) is a relatively infrequent but highly lethal cancer with a poor prognosis. Management remains challenging and controversial, and most patients are diagnosed at an advanced stage. However, with the progressive advances in the use of immunotherapies, new treatment modalities are being implemented. In September 2022, the US FDA approved durvalumab (a PD-L1 inhibitor) in combination with chemotherapy for adult patients with locally advanced or metastatic GBC. This groundbreaking news is the first FDA approval for the use of immunotherapy in biliary tract cancers. This article reviews the newest advances and trials regarding immunotherapy for GBC.

Gallbladder cancer (GBC) is a malignant tumor that affects the cells of the gallbladder. Management of this condition is challenging and continuously evolving. Surgery, radiotherapy and chemotherapy are the current standards of care. However, recently, immunotherapy, a treatment that stimulates the host's immune system to target cancerous cells, has proven to be effective as a line of treatment. Promising results are continuously published. This article reviews the major advances in immunotherapy regarding the management of GBC.

Imaging and haemodynamic parameters associated with clinical outcomes following isolated tricuspid valve surgery.

INTRODUCTION: Isolated tricuspid valve surgery (TVS) may be associated with high morbidity and mortality. The aim of this study was to investigate the association of preoperative imaging and haemodynamic data derived from echocardiography (ECHO), cardiac magnetic resonance (CMR) and right heart catheterisation (RHC) with postoperative outcomes following TVS. METHODS: In a retrospective cohort study, patients who underwent isolated TVS at our institution between 2012 and 2020 were screened and followed up to 1 year. We only included those who had all three tests before surgery: ECHO, CMR and RHC. Patients with congenital heart disease, infective endocarditis and those who underwent concomitant valve or pericardial surgery were excluded. The primary outcome was a composite of mortality and congestive heart failure at 1 year. Time-to-event analyses at 1 year and Cox proportional hazards regression analyses were performed. RESULTS: A total of 60 patients were included (mean age of 60±14 years, 63% women), of whom 67% underwent TV repair. The primary outcome occurred in 16 patients (27%) with a 1-year mortality of 7%. It was associated with ECHO-derived right ventricular (RV) free wall strain and RHC-derived RV systolic and diastolic as well as mean pulmonary pressures. On multivariable Cox regression analysis, only RV systolic and diastolic pressures were significantly associated with the primary outcome at 1 year (HRs=5.9 and 3.4, respectively, p<0.05). CONCLUSION: Baseline invasive haemodynamic assessment could have a strong association with clinical outcomes and help risk-stratify patients undergoing isolated TVS.

The Lung Microbiota and Lung Cancer: A Growing Relationship.

The lung is home to a dynamic microbial population crucial to modulating immune balance. Interest in the role of the lung microbiota in disease pathogenesis and treatment has exponentially increased. In lung cancer, early studies suggested an important role of dysbiosis in tumor initiation and progression. These results have helped accelerate research into the lung microbiota as a potential diagnostic marker and therapeutic target. Microbiota signatures could represent diagnostic biomarkers of early-stage disease. Lung microbiota research is in its infancy with a limited number of studies and only single-center studies with a significant methodological variation. Large, multicenter longitudinal studies are needed to establish the clinical potential of this exciting field.

Adhesion molecules in multiple myeloma oncogenesis and targeted therapy.

Every day we march closer to finding the cure for multiple myeloma. The myeloma cells inflict their damage through specialized cellular meshwork and cytokines system. Implicit in these interactions are cellular adhesion molecules and their regulators which include but are not limited to integrins and syndecan-1/CD138, immunoglobulin superfamily cell adhesion molecules, such as CD44, cadherins such as N-cadherin, and selectins, such as E-selectin. Several adhesion molecules are respectively involved in myelomagenesis such as in the transition from the precursor disorder monoclonal gammopathy of undetermined significance to indolent asymptomatic multiple myeloma (smoldering myeloma) then to active multiple myeloma or primary plasma cell leukemia, and in the pathological manifestations of multiple myeloma.

Tsunami of immunotherapies in the management of esophageal cancer.

Esophageal cancer (EC) is relatively frequent and highly lethal cancer, being the sixth most common cause of cancer death worldwide. The progressive approvals of immunotherapy as first-line and second-line treatment options have paved the way for an evolving new approach to the treatment of this disease. Management of esophageal cancer is challenging and requires a multimodality approach. Treatment options include surgery, chemoradiotherapy and, recently, immunotherapy. The newest guidelines and FDA approvals regarding immunotherapy for esophageal cancer are reviewed here.

Esophageal cancer is a malignant tumor that affects the cells in the esophagus. To treat this condition, doctors may use surgery, radiation therapy, chemotherapy and immunotherapy. Depending on the characteristics of the tumor and the medical history of the patient, these treatments may be used alone or in combination to optimize their effects. Immunotherapy is a treatment that aims to stimulate the immune defenses of the body against cancerous cells. Recently, it has proven to be very effective in the management of esophageal cancer, with very favorable results. It is now becoming the standard of care in the management of this disease.