Citations

Introduction: Global collaboration in cardio-oncology (CO) is needed to understand the prevalence of cancer treatment related cardiovascular disease (CTRCD) in different risk groups, practice settings and geographic locations. Furthermore, socio-economic and ethnic disparities may impact access to care. Methods: We assembled cardiologists (CA) and oncologists from academic and community settings to collaborate in the first global cardio-oncology registry (G-COR). US and international CO physicians participated in the first global virtual meeting to assess feasibility and structure for G-COR. Subsequently, a survey for sites resources, demographics and intention to participate was conducted. Results: Responses with sites demographics from 104/140 sites invited: 43 US sites from 23 states and 61 international sites from 5 continents indicated decision to participate in G-COR. Sites were more commonly led by CA (74/99) than CA and oncologists (25/99) and were more often University/teaching (68/101) than community based (33/101). Significant minorities/disadvantaged CO patient population were reported by 32/43 US sites versus 16/60 international sites. Average number CO patients treated per month was 83, range (5-1,000). Breast cancer was the first or second G-COR priority for 84 centers, hematological malignancies (HEM) for 66 centers, and immune check point inhibitors (ICI) for 36 centers. Echocardiography with strain imaging is available in 92/95 participating sites and cardiac MRI in 80/86 sites. Biomarkers are used only in suspected or confirmed CTRCD in 56/96 sites and for risk stratification in high risk patients in 40/96 sites. Subsequently, scientific committee and topic committees for breast cancer, HEM, ICI, and disparities in CO were established. A pilot phase utilizing a RedCap Cloud platform will start enrolling patients in the last quarter of 2021 and the registry for all main pillars will launch in early 2022. Conclusions: We present a global initiative for conducting collaborative research. Information learned G-COR will help understanding risk factors impacting CTRCD in different geographic locations and therefore help reducing access gaps in CO care. Additionally, mitigating strategies can be devised for the future.

Abstract Background: Although psoriasis is considered a systemic disease, no clear association has been established between psoriasis and lung diseases. Methods: Adult psoriasis patients with no known active pulmonary disease or respiratory symptoms were screened for subclinical pulmonary manifestations and possible parenchymal changes using high-resolution computed tomography (HRCT) scan of the chest. Patients were classified according to the severity of skin manifestations. The clinical characteristics and radiographic findings of these patients were evaluated.Results: A total of 59 patients with psoriasis were included, among which 47 (79.7%) had abnormal HRCT scan features. Micronodules were the most common detected lung lesions (66.1%), followed by interlobular septal thickening (23.7%), fibrosis (11.9%), and ground-glass opacity (6.8%). Other HRCT findings included emphysematous changes and calcified granulomas. Abnormal HRCT findings correlated with older age and duration of psoriasis but not with the severity of skin manifestations.Conclusions: Micronodules and interlobular septal thickening were the most detected lung lesions in patients with psoriasis. These findings of the pilot study highlight the possible pulmonary involvement in patients with psoriasis. Larger multicenter studies are needed to further clarify these findings.

Abstract Background: Endocrine therapy (ET) reduces breast cancer (BC) recurrence risk and improves BC outcomes. However, patients (pts) may refuse ET, potentially impacting their outcomes. However, the exact incidence and factors associated with ET refusal are largely unknown. Methods: We conducted a retrospective study of BC pts in the National Cancer Data Base between 2003 and 2017. Demographic, socioeconomic, co-morbidity index and tumor-specific data were compared between BC pts who refused ET versus those who agreed to ET using bivariate and multivariate models. Female pts 18 to 89 years of age with stage I, II, and III were included. Logistic regression was used to determine associations with ET refusal. Results: Among 463,228 pts, the incidence of ET refusal was 5.26% (24, 401). Of these pts, 85% were non-Hispanic White, 7.9% were Non-Hispanic Black, 3.1% non-Hispanic Asian/pacific islander, and 3.6% were Hispanic. A majority (56.9%) had government insurance, and 87.2% were from a metro residential area. Infiltrating ductal carcinoma BC subtype comprised 78% of pts. Most pts were 51-89 years of age (80%), and 20% were 18-50 years of age. On multivariable analysis (Table 1), non-Hispanic black (OR 0.82), non-Hispanic Asian (OR 0.72), and Hispanic (OR 0.84) pts had a reduced odds of refusing ET than non-Hispanic white pts. Pts with government insurance (OR 1.6, p<0.001) and noninsured pts (OR 1.3, p<0.001) had increased odds of refusing ET compared to privately insured pts. Estrogen receptor (ER) -/Progesterone (PR) +, and ER +/PR - had increased odds of refusing therapy (OR 2.9, and 1.1 respectively, p<0.001) than ER +/PR + pts. Patients with positive lymph nodes had reduced odds of refusing ET than those with negative lymph nodes (p<0.001). Additionally, pts with a 2.1-5 cm (OR 0.92) or >5 cm (OR 0.87) tumor size had a reduced odd of refusing ET than those with tumors less than 2 cm (p<0.001). Finally, patients with well-differentiated BC (grade I) had increased odds of refusing ET (OR 1.2, p<0.001) than moderately differentiated (grade II) BC. Conclusions: The incidence of ET therapy refusal is relatively low; however, survival outcomes may be negatively impacted. This is the first study to evaluate specific demographic and disease-specific factors associated with ET refusal, which can inform strategies to improve ET acceptance rate. Table 1.Multivariable Logistic Regression – ET Therapy Acceptance (Referent) vs. Refusal.VariableOR95% CIp-valueAge51 - 89 years18 - 50 years0.940.900.970.001Race/EthnicityWhite Non-HispanicBlack Non-Hispanic0.820.760.88<0.001Pacific Islander Non-Hispanic0.720.660.76<0.001Hispanic0.840.790.87<0.001InsurancePrivateGovernment1.61.521.61<0.001Not insured1.31.181.47<0.001ResidenceMetroUrban0.900.870.87<0.001Rural0.870.780.970.014HistologyInfiltrating ductal carcinomaLobular carcinoma0.840.800.87<0.001Infiltrating duct and lobular carcinoma0.900.850.95<0.001Others1.171.101.24<0.001Positive Nodes01 - 30.620.600.65<0.0014 - 90.610.570.66<0.00110 +0.610.550.68<0.001VariableOR95% CIp-valueER/PR ExpressionER +/PR +ER -/PR +2.92.563.18<0.001ER +/PR -1.11.061.14<0.001Tumor size≤ 2 cm2.1 - 5 cm0.920.880.94<0.001> 5 cm0.870.800.93<0.001GradeIII1.211.181.25<0.001III0.980.951.020.518Charlson-Deyo Score010.940.910.980.00421.070.991.150.071≥31.120.981.280.079 Citation Format: Pooja P Advani, Ricardo Torres Guzman, Francisco Avila Verduzco, Karla Maita, John Garcia, Abdullah Eldaly, Antonio Forte, Aaron Spaulding. Factors associated with endocrine therapy refusal in hormone receptor-positive breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-14-16.

Abstract In dengue‐endemic regions, the co‐infection with SARS‐CoV‐2 and dengue is a significant health concern. Therefore, we performed a literature search for relevant papers in seven databases on 26 Spetember 2021. Out of 24 articles, the mortality rate and intensive care unit (ICU) admission were 19.1% and 7.8%, respectively. The mean hospital stay was 11.4 days. In addition, we identified two pregnancies with dengue and COVID‐19 co‐infection; one ended with premature rupture of membrane and intrauterine growth restriction fetus, while the other one ended with maternal mortality and intrauterine fetal death. COVID‐19 and dengue co‐infection had worse outcomes regarding mortality rates, ICU admission, and prolonged hospital stay. Thus, wise‐decision management approaches should be adequately offered to these patients to enhance their outcomes. Establishing an early diagnosis might be the answer to reducing the estimated significant burden of these conditions.

An 85-year-old male presented to the podiatry clinic following a 1st to 5th left toe amputation as a complication of severe peripheral arterial disease and nonhealing wound despite endovascular intervention with an angiogram. At the visit, cellulitis with gangrene of the surgical site was noted. The patient was admitted to the brick and mortar (BAM) hospital and taken to surgery for a transmetatarsal amputation of the left limb. In the immediate postoperative period, the incisional margins appeared dusky creating concern for flap viability. The medical team recommended a vascular bypass versus a below-knee amputation. However, given the age, comorbidities, and nutritional status, the family refused further surgical intervention. As such, Mayo Clinic’s home hospital program, Advanced Care at Home (ACH), was consulted for continued nonsurgical acute management at home. The patient was transferred to ACH and transported home three days after BAM admission to continue IV antibiotic therapy and wound care. Discharge from ACH occurred 11 days after admission to the BAM hospital. This case highlights the importance of developing health care alternatives to traditional hospitalization and demonstrates that ACH can manage highly complex, elder postoperative patients from the comfort of their homes.

PURPOSE Targeting the BCL-XL pathway has demonstrated the ability to overcome Janus kinase inhibitor resistance in preclinical models. This phase II trial investigated the efficacy and safety of adding BCL-XL/BCL-2 inhibitor navitoclax to ruxolitinib therapy in patients with myelofibrosis with progression or suboptimal response to ruxolitinib monotherapy (ClinicalTrials.gov identifier: NCT03222609 ). METHODS Thirty-four adult patients with intermediate-/high-risk myelofibrosis who had progression or suboptimal response on stable ruxolitinib dose (≥ 10 mg twice daily) were administered navitoclax at 50 mg once daily starting dose, followed by escalation to a maximum of 300 mg once daily in once in weekly increments (if platelets were ≥ 75 × 109/L). The primary end point was ≥ 35% spleen volume reduction (SVR35) from baseline at week 24. Secondary end points included ≥ 50% reduction in total symptom score (TSS50) from baseline at week 24, hemoglobin improvement, change in bone marrow fibrosis (BMF) grade, and safety. RESULTS High molecular risk mutations were identified in 58% of patients, and 52% harbored ≥ 3 mutations. SVR35 was achieved by 26.5% of patients at week 24, and by 41%, at any time on study, with an estimated median duration of SVR35 of 13.8 months. TSS50 was achieved by 30% (6 of 20) of patients at week 24, and BMF improved by 1-2 grades in 33% (11 of 33) of evaluable patients. Anemia response was achieved by 64% (7 of 11), including one patient with baseline transfusion dependence. Median overall survival was not reached with a median follow-up of 21.6 months. The most common adverse event was reversible thrombocytopenia without clinically significant bleeding (88%). CONCLUSION The addition of navitoclax to ruxolitinib in patients with persistent or progressive myelofibrosis resulted in durable SVR35, improved TSS, hemoglobin response, and BMF. Further investigation is underway to qualify the potential for disease modification.

Multisystem Inflammatory Syndrome in Children (MIS-C), representing a new entity in the spectrum of manifestations of COVID-19, bears symptomatic resemblance with Kawasaki Disease (KD). This review explores the possible associations between KD and the human coronaviruses and discusses the pathophysiological similarities between KD and MIS-C and proposes implications for the pathogenesis of MIS-C in COVID-19. Since 2005, when a case-control study demonstrated the association of a strain of human coronavirus with KD, several studies have provided evidence regarding the association of different strains of the human coronaviruses with KD. Thus, the emergence of the KD-like disease MIS-C in COVID-19 may not be an unprecedented phenomenon. KD and MIS-C share a range of similarities in pathophysiology and possibly even genetics. Both share features of a cytokine storm, leading to a systemic inflammatory response and oxidative stress that may cause vasculitis and precipitate multi-organ failure. Moreover, antibody-dependent enhancement, a phenomenon demonstrated in previous coronaviruses, and the possible superantigenic behavior of SARS-CoV-2, possibly may also contribute toward the pathogenesis of MIS-C. Lastly, there is some evidence of complement-mediated microvascular injury in COVID-19, as well as of endotheliitis. Genetics may also represent a possible link between MIS-C and KD, with variations in FcγRII and IL-6 genes potentially increasing susceptibility to both conditions. Early detection and treatment are essential for the management of MIS-C in COVID-19. By highlighting the potential pathophysiological mechanisms that contribute to MIS-C, our review holds important implications for diagnostics, management, and further research of this rare manifestation of COVID-19.

AbstractLeishmaniasis is considered a tropical neglected disease, which is caused by an intramacrophagic parasite, Leishmania. It is endemic in 89 different countries. Autophagy‐related protein 8 (Ldatg8) is responsible for the transformation of parasites from promastigote to amastigote differentiation. Ldatg8 is one of the key drug targets of Leishmania donovani (L. donovani) responsible for the defense of parasites during stress conditions. Virtual screening of natural ligand library had been performed against Ldatg8 to identify novel and potent inhibitors. Molecular docking and molecular dynamics simulation studies showed that urolithin A stably blocked Ldatg8. Urolithins are combinations of coumarin and isocoumarin. Further, we evaluated the antileishmanial effects of urolithin A by antileishmanial assays. Urolithin A inhibited the growth and proliferation of L. donovani promastigotes with an IC50 value of 90.3 ± 6.014 μM. It also inhibited the intramacrophagic parasite significantly with an IC50 value of 78.67 ± 4.62 μM. It showed limited cytotoxicity to the human THP‐1 differentiated macrophages with a CC50 value of 190.80 ± 16.89 μM. Further, we assayed reactive oxygen species (ROS) generation and annexin V/PI staining upon urolithin A treatment of parasites to have an insight into the mechanism of its action. It induced ROS significantly in a dose‐dependent manner, which caused apoptosis partially in parasites. The potential inhibitors for Ldatg8, identified in this study, would provide the platform for the development of an effective and affordable antileishmanial drug.