Citations

AbstractBackgroundGastrointestinal bleeding (GIB) in patients with continuous flow left ventricular assist devices (CF‐LVADs) is often related to GI angiodysplasia (GIAD). We previously reported data on VEGF inhibition with IV bevacizumab in the treatment of LVAD‐associated GIAD bleeding, and now present follow‐up data on patients treated with IV bevacizumab and/or low‐dose oral pazopanib.MethodsAll consecutive adult patients with LVAD‐associated GIB from GIAD treated with bevacizumab or pazopanib, from July 20, 2017 to June 22, 2022, were included in the analysis. Data on hospitalizations, GI endoscopic procedures, and blood transfusions were obtained from first admission for GIB up to a median of 35.7 months following treatment initiation (range 1.3–59.8 months).ResultsEleven patients (91% male, mean 69.5 ± 8.9 years) were included. Eight patients (73%) received IV bevacizumab, two patients (18%) received oral pazopanib, and one patient (9%) received bevacizumab followed by pazopanib therapy. We observed a significantly decreased number of annualized hospitalizations for GIB (median difference − 2.87, p = 0.002), blood transfusions (median difference − 20.9, p = 0.01), and endoscopies (median difference − 6.95, p = 0.007) in patients pre‐ and post‐anti‐angiogenic therapy (bevacizumab and/or pazopanib). Similarly, a significant improvement in these clinical outcomes was noted in the bevacizumab group with decreased annualized hospitalizations (median difference − 2.75, p = 0.014), blood transfusions (median difference − 24.5, p = 0.047), and number of endoscopies (median differences −6.88, p = 0.006).ConclusionAnti‐angiogenic therapy with IV bevacizumab and/or low‐dose oral pazopanib appears to provide benefits in patients with LVAD‐associated GIB with reduced hospitalizations, blood transfusions, and need for GI endoscopic procedures.

Introduction: The performance of automated left ventricular ejection fraction (LVEF) assessment in patients with altered cardiac chamber geometry, such as those with obstructive hypertrophic cardiomyopathy (HCM), is not well described. Aims: Accurate assessment of LVEF is required for dose titration and continuation of myosin inhibitors in obstructive HCM. From the VALOR-HCM trial (NCT04349072), the agreement of two commercially available software packages was compared with blinded core lab assessment of LVEF. Methods: From baseline and week 16, among 112 patients randomized to either mavacamten or placebo, 178 echocardiograms were analyzed. Representative clips were manually selected, and automated LVEFs were calculated. Comparisons of LVEFs were made using Pearson’s correlation coefficients and Bland-Altman analysis. Results: With core lab assessment, the overall median LVEF was 68% (Q1 66%, Q3 70%). The correlation with vendor 1 was moderate (r = 0.47, 95% CI 0.35-0.58, p <0.001) and weak with vendor 2 (r =0.21, 95% CI 0.07-0.35, p =0.004). Correlation was also weak between vendor 1 and 2 (r = 0.14, 95% CI 0.00-0.28, p = 0.06). Vendors 1 and 2 had an underestimation bias of LVEF of 8% (95% CI 6-9%) and 8% (95% CI 7-9%), respectively, compared to core lab LVEF (Figure 1). Conclusions: In VALOR-HCM, the concordance of LVEF between different commercially available software packages with each other and with a core lab assessment was limited. Further study is needed to evaluate and improve the performance of automated LVEF tools in obstructive HCM patients who have altered cardiac chamber geometry.

Background: Robust models exist to predict risk-adjusted mortality following congenital heart surgery. It is known that underlying diagnosis modifies predicted risk of operations, and institution-level outcomes vary based on their unique case mix. We therefore evaluated risk-adjusted outcomes for a subset of diagnosis-procedure (D-P) combinations within the Society of Thoracic Surgeons' (STS) congenital heart surgery database (CHSD). Methods: A clinician panel identified the most frequently encountered D-P combinations in CHSD between 07/2017 and 06/2021. Candidate modeling techniques were compared in a random 80% development cohort. Model performance was assessed using internal and cross-validation calibration, discrimination plots and optimism adjusted C-statistics. The final selected model was evaluated in the 20% validation sample. Results: The chosen subset of D-P combinations represented 45,384 of 87,589 (52%) unique episodes of surgical care in CHSD during this time-period. The development cohort (36,350 episodes) had 1.8% mortality (667 deaths). All candidate models had excellent discrimination with C-statistics ranging from 0.862 to 0.876. The model with the best combination of discrimination, calibration, and clinical face validity was a modified version of the current STS mortality risk model. This version included all current risk model variables with the addition of indicator variables for D-P combinations. In the 20% validation sample (9,034 episodes), this model was well calibrated (Figure) and had excellent discrimination (C = 0.879). Conclusion: We describe a cohort of D-P combinations widely encountered in the STS CHSD. Further, we refined the existing STS CHSD risk model for application to these D-P dyads to derive empirical risk-adjusted benchmark outcomes. This approach will benefit quality improvement efforts at an institutional level and may have implications for publicly reporting congenital heart surgery outcomes.

Background: Thoracic aortic aneurysms (TAAs) can be found in 1-2/1000 individuals in the general population and are commonly associated with genetic disorders of connective tissue and bicuspid aortic valve (BAV). Larger size, distal aneurysms, high DBP and presence of BAV are some factors that can accelerate aneurysm growth. Case: A 37-year-old male without a history of recent trauma or stimulant use presented to the emergency room with 2 days of chest tightness. He had acute worsening overnight and awoke with chest pain, discomfort in the suprasternal notch and between the shoulder blades. He had no other medical history, however, was treated with a 10-day course of Ciprofloxacin for epididymitis 3 weeks prior. On presentation, the patient had active pleuritic chest pain, tachycardia and tachypnea with no abnormalities on cardiac auscultation. EKG showed sinus tachycardia, PVCs, and nonspecific ST elevations in leads II, III and aVF with normal troponins and chest X-ray. CT chest angiogram revealed a 60 mm ascending aortic aneurysm ( Fig. 1a ). Doming of the right cusp of the aortic valve in the parasternal view ( Fig. 1b ) raised suspicion for BAV which was confirmed with the classic fish mouth appearance on the TEE ( Fig. 1c ). The patient underwent successful aortic repair with graft placement. First degree relatives were offered screening for BAV. Ciprofloxacin was replaced with Sulfamethoxazole-Trimethoprim for treating his residual epididymal infection. Discussion: TAA rupture is associated with a >90% mortality rate. It is important to be aware of echocardiographic features of BAV as this can predispose to accelerated aneurysm growth. Additionally, fluoroquinolones (FQs) are a commonly prescribed class of antibiotics that may affect the structural integrity of the aorta, associated with aneurysm enlargement and rupture. This case offers an important example to highlight why the FDA recommends against the use of FQs in patients with known TAA or risk factors for it.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

Background: Radiographic surveillance of colorectal cancer (CRC) after curative-intent therapy is costly and unreliable. Methylated DNA markers (MDMs) detected primary CRC and metastatic recurrence with high sensitivity and specificity in cross-sectional studies. This study evaluated using serial MDMs to detect recurrence and monitor the treatment response to anti-cancer therapies. Methods: A nested case-control study was drawn from a prospective cohort of patients with CRC who completed curative-intent therapy for CRC of all stages. Plasma MDMs were assayed vis target enrichment long-probe quantitative-amplified signal assays, normalized to B3GALT6, and analyzed in combination with serum carcinoembryonic antigen to yield an MDM score. Clinical information, including treatment and radiographic measurements of the tumor burden, were longitudinally collected. Results: Of the 35 patients, 18 had recurrence and 17 had no evidence of disease during the study period. The MDM score was positive in 16 out of 18 patients who recurred and only 2 of the 17 patients without recurrence. The MDM score detected recurrence in 12 patients preceding clinical or radiographic detection of recurrent CRC by a median of 106 days (range 90–232 days). Conclusions: Plasma MDMs can detect recurrent CRC prior to radiographic detection; this tumor-agnostic liquid biopsy approach may assist cancer surveillance and monitoring.