Immunomodulatory Effects of RANK/RANKL Blockade in Patients with Cancer.

In cancer, multiple factors converge upon receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) signaling to promote the development of bone metastases; agents that inhibit RANKL signaling reduce skeletal-related events (SRE) in patients with cancer. In addition, RANKL signaling is important in augmenting the ability of dendritic cells (DC) to stimulate both naïve T-cell proliferation and the survival of RANK+ T cells. In this issue, Chang and colleagues using high-dimensional cytometry to evaluate immunomodulatory effects of denosumab in patients with advanced solid, observe early on treatment changes in multiple compartments, and greater effects in patients receiving concurrent chemotherapy or steroids. See related article by Chang et al., p. 453 (4).

Percutaneous Coronary Intervention Associated with a Higher Risk of Hypoxemia and COVID-19 Severity.

OBJECTIVE: The primary goal of the present study was to measure the implications of hypoxemia in COVID-19 patients with a history of coronary artery disease (CAD). METHODS: A systematic search of the literature published from November 1, 2019 to May 1, 2021, was conducted on PubMed/MEDLINE, Embase, and Web of Science databases. Afterwards, an observational study was designed based on the electronic health records of COVID-19 patients hospitalized in a tertiary referral hospital during the same period. A total of 179 COVID-19 cases were divided into two groups: cases with a history of CAD and percutaneous coronary intervention (CAD/PCI+, n = 89) and controls (n = 90). Clinical data were extracted from the electronic database of the hospital and statistically analyzed. RESULTS: After the application of inclusion/exclusion criteria, only three studies were deemed eligible, one of which was concerned with the impact of CAD on the all-cause mortality of COVID-19. Results from our observational study indicated that the cases were older (median age: 74 vs. 45) and more likely to develop hypoxemia (25.8% vs. 8.8%) than the controls. CAD/PCI+ was correlated with a more severe COVID-19 (11% vs. 1%). Age was a moderately significant independent predictor of increased COVID-19 severity, while hypoxemia was not. CONCLUSION: Considering the negative impact of hypoxemia on the prognosis of COVID-19 and its higher prevalence among COVID-19 patients with underlying CAD, further research is warranted to unravel the negative effects of COVID-19 on the mechanisms of gas exchange and delivery in patients with pre-existing CAD.

The Effect of Race and Area Deprivation on Symptom Profiles over the Course of Early-Stage Breast Cancer.

Purpose: This study compared common symptoms (fatigue, pain), overall physical functioning and changes over time between Black and White women receiving early-stage breast cancer (ESBC) chemotherapy. Methods: A longitudinal, repeated measures comparative design was employed. Time points of symptom measurement (PROMIS domains) at baseline, mid and end point were adjusted as per patient chemotherapy schedule. Analyses: Linear mixed models were applied. Results: There were 147 patients, 36% Black 64% White (54±12 years) recommended to receive early-stage breast cancer chemotherapy with adequate data for symptom analysis. Pain: Main effect of race was significant (F(1, 390) = 29.43, p<.001) for pain with Black patients experiencing significantly higher pain scores compared to White patients at pretherapy (Mean Difference; MD=3.7, p=.034), midpoint (MD=5.8, p=.002), and endpoint (MD=7.8, p<.001). Fatigue: Fatigue significantly increased (deteriorated) at endpoint (MDT1-T3= 8.7, p<.001) for Black patients. Among White patients, fatigue significantly increased at midpoint (MDT1-T2= 5.7) and at endpoint (MDT1-T3=10.1, p<.001; MDT2-T3=4.3, p= .017). Physical function: Black patients had significantly lower physical function scores compared to White patients at midpoint (MD=4.0, p=.027). Physical function decreased by endpoint in Black (MDT1-T3=7.8, p<.001), and White patients (MDT1-T3=7.7, p<.001). Conclusion: Symptom burden significantly increased over the course of chemotherapy for all patients. Scores for pain and physical function were higher overall for Black patients and deteriorated at a greater rate for Black vs. White women over the course of chemotherapy. This assessment holds implication for proactive assessment and mitigation strategies.

Erythema nodosum after azacitidine in a patient with acute myeloid leukemia.

INTRODUCTION: Nodular skin lesions in patients with acute myeloid leukemia (AML) raise clinical suspicion for leukemia cutis versus fungal infections. Here, we report a rare case of treatment-related erythema nodosum (EN) in a patient with AML. CASE REPORT: Approximately 5 weeks after the initiation of sorafenib and one week after azacitidine initiation, a 32-year-old man with primary refractory AML presented with several painful red nodules on the lower extremities. Histological examination established a diagnosis of EN. MANAGEMENT AND OUTCOME: Treatment with topical and oral steroids led to complete resolution of the nodules. However, once the dose of steroids was reduced, the lesions rapidly recurred. Higher dose steroids were reinitiated, again with a resolution of the nodules, confirming steroid responsiveness of the underlying process. DISCUSSION: Given the onset of lesions one week after the initiation of azacitidine and 5 weeks after the initiation of sorafenib, azacitidine was considered the more likely culprit. Only 2 cases of EN-like eruption after azacitidine and 1 case after sorafenib have been reported. Although fungal infections and leukemia cutis are the top differentials considered for skin nodules in a patient with AML, EN should be considered as an alternative diagnosis. Correct diagnosis is critical because it will guide treatment.

Turmeric for Treatment of Irritable Bowel Syndrome: A Systematic Review of Population-Based Evidence.

Background: Irritable bowel syndrome (IBS) is a highly prevalent disorder of the gut interaction characterized by abdominal discomfort and pain associated with altered bowel habits in the absence of structural abnormalities. In spite of IBS' high prevalence and disease burden across the globe, no explanations have been given as to its underlying pathophysiology. As for the treatment of IBS, there is no specific medication, and the most beneficial treatment is usually supportive therapy. Recent animal and human studies have demonstrated the therapeutic potential of curcumin or turmeric in the treatment of IBS. Methods: We systematically reviewed all available evidence supporting curcumin and turmeric's therapeutic potential in relieving IBS symptoms in the present study. For this purpose, a database search was performed using curcumin, turmeric, and IBS and all their equivalents as of the search terms in Web of Science, Pub-Med, Scopus, Ovid, Embase, and Google Scholar from1990 up to Feb 2021. The investigation was then limited to clinical trials, and then nine articles were collected for data analysis. Results: The findings of the included literature showed that curcumin and turmeric alone or in combination with other medications could improve the severity of IBS as well as the quality of life among people who suffer from IBS symptoms. Conclusion: Overall, medications containing curcumin and turmeric extract due to these compounds' anti-inflammatory effects may improve IBS symptoms, particularly abdominal pain and life quality.

Ventricular versus atrial side ablation for treatment of atrioventricular accessory pathways: a randomized controlled clinical trial.

BACKGROUND: The earliest atrial (A)/ventricular (V) activation potentials, or fused A/V potentials, are commonly used as ablation targets for atrioventricular (AV) accessory pathways (APs). However, these targets can be achieved in a relatively wide area of the heart around AV rings at both atrial and ventricular sides. The aim of this study is to analyze the height of intracardiac A and V waves and their correlation to find the most appropriate side for successful delivery of radiofrequency energy, atrial or ventricular edge. METHODS: Ninety patients diagnosed with orthodromic AV re-entrant tachycardia (AVRT) or Wolff-Parkinson-White syndrome were enrolled. Local atrial/ventricular (A/V) amplitude potentials with the earliest activation or fused AV potentials were measured. Patients were randomly assigned into two groups with a 2:1 ratio. In group 1, ablation was done at the site where A was greater than V. In group 2, V was greater than A. Primary endpoint was success at first attempt, achieving antegrade AP conduction block, AV block during right ventricle pacing, or AVRT termination with no AP conduction. RESULTS: Fifty-one patients (56.7%) were male. Thirty patients had an ablation at an atrial site (A > V) and 60 at a ventricular site (V > A). Ablation was more successful at the ventricular site (87% vs 100%, P = 0.011). All 30 patients in the atrial arm and 71% of the ventricular group underwent ablation via the antegrade method. CONCLUSIONS: Success of catheter ablation of APs is higher where V > A (ventricular site of AP), indicating the priority of the ventricular edge of the mitral ring for a better outcome.

Association of Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Expression with Breast Cancer Metastasis in Iran.

BACKGROUND: Metastasis is an important factor in the survival estimate of patients with breast cancer. The present study aimed to examine the frequency of epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression in relation to the metastatic site, pattern, and tumor size in patients with metastatic breast cancer (MBC). METHODS: In this retrospective study, the medical records of patients diagnosed with MBC at Motahari Clinic (Shiraz, Iran) during 2017-2019 were examined. Metastasis was confirmed using computed tomography, and a total of 276 patients were included in the study. Based on the expression of receptors, the patients were categorized into luminal A, luminal B, HER2, and TNBC groups. The frequency and percentage of receptors in relation to the metastatic site, size, and pattern were compared using the Chi square test. P<0.05 was considered statistically significant. RESULTS: The frequency of receptor positivity in the 276 selected medical records were of the subtype HER2-enriched (n=48), luminal A (n=43), luminal B (n=146), and TNBC (n=39). The most common metastatic sites were the bones (47.1%), lungs (34.4%), liver (27.9%), brain (20.3%), and other organs (12.7%). The first site of metastasis occurred in the bones (36.6%), lungs (17.4%), liver (15.6%), brain (10.5%), and other organs (7.6%). The frequency of receptor expression was different in relation to the first metastatic site (P=0.024). There was a statistically significant difference between the frequency of receptor expression in patients with bone (P=0.036), brain (P=0.031), and lung (P=0.020) metastases. The frequency of receptor expression was also significantly different in relation to the size of liver metastasis (P=0.009). Luminal A and B subtypes showed higher rates of bone metastasis as the first metastatic site. CONCLUSION: The difference in the frequency of receptor expression in relation to the metastatic site and tumor size can be used as predictive and prognostic factors in patients with breast cancer.

Comparison of ultrasound-accelerated versus conventional catheter-directed thrombolysis for deep vein thrombosis: A systematic review and meta-analysis.

BACKGROUND: Recent in vitro and clinical studies have shown that ultrasound-accelerated catheter-directed thrombolysis (USACDT) can accelerate thrombolysis. Therefore, in this meta-analysis, we aimed to compare the efficacy and safety of USACDT with conventional catheter-directed thrombolysis in patients with deep vein thrombosis. METHODS: A systematic search of the following electronic databases was performed from their dates of inception to 20 June 2020: MEDLINE, Scopus, Google Scholar, CINAHL, Cochrane Library, and EMBASE. All randomized controlled trials that directly compared the complications and efficacy of USACDT and conventional catheter-directed thrombolysis in patients with deep vein thrombosis were identified. The statistical analysis was performed using comprehensive meta-analysis software. RESULTS: Finally, 18 studies with a total of 597 participants were included in our meta-analysis according to the eligibility criteria. Pooled proportion of USACDT success in patients with deep vein thrombosis was 87.8% (18 studies; 95% CI: 83.1-91.3). Success rate was significantly higher in USACDT treatment than in conventional catheter-directed thrombolysis treatment (seven studies; OR: 2.96; 95% CI: 1.69-5.16; P < 0.01)). Although the mean infusion time was higher in catheter-directed thrombolysis treatment compared to USACDT treatment, this difference was not statistically significant (three studies; MD: -1.46; 95% CI: -3.25-0.32; P = 0.10). Moreover, pooled rate of complications was lower in USACDT than catheter-directed thrombolysis which was not statistically significant (seven studies; OR: 0.49; 95% CI: 0.13-1.76; P = 0.27). CONCLUSION: This meta-analysis revealed that USACDT significantly increased the success rate of thrombolysis compared to conventional catheter-directed thrombolysis. Furthermore, USACDT was associated with lower rate of complication and infusion time. Taken together, these findings confirm the superiority of this novel intervention over conventional catheter-directed thrombolysis in treatment of patients with deep vein thrombosis.

Screening Performance Characteristics of Ultrasonography in Confirmation of Endotracheal Intubation; a Systematic Review and Meta-analysis.

INTRODUCTION: Recent studies have suggested that point-of-care ultrasonography can be used for confirming the placement of endotracheal tube. This systematic review and meta-analysis aimed to investigate the sensitivity and specificity of ultrasonography for confirming endotracheal tube placement. METHODS: In this meta-analysis, systematic search of the previous published papers investigating the diagnostic accuracy of ultrasonography for confirmation of endotracheal tube placement was performed. Seven electronic databases, including PubMed, Scopus, Google Scholar, EBSCO, EMBASE, Web of Science, and Cochrane Database were searched up to July 2021, for all relevant articles published in English on this topic. Meta-DiSc version 1.4 software was used for statistical analysis. RESULTS: The estimated pooled sensitivity and specificity of ultrasonography for confirmation of endotracheal tube location were 0.98 (95% CI: 0.98-0.99) and 0.94 (95% CI 0.91-0.96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 5.94 (95% CI 4.41-7.98) and 0.03 (95% CI: 0.02-0.04), respectively. The diagnostic odds ratio of ultrasonography was 281.47 and the area under hierarchical summary receiver operating characteristic (HSROC) revealed an appropriate accuracy of 0.98. CONCLUSION: Ultrasonography has high diagnostic accuracy and can be used as a promising tool for confirmation of endotracheal tube placement, especially in critically ill patients or when capnography is not available, or its result is equivocal.

Myocardial contractile dispersion: A new marker for the severity of cirrhosis?

Introduction: Cirrhotic cardiomyopathy (CCM) develops in about half of all cirrhotic patients, affecting the long-term morbidity and mortality. Although some studies have shown an increased QT-interval in cirrhotic patients, no evidences of myocardial contractile and QT dispersion (QTd) changes are available. This study aimed to compare myocardial contractile dispersion (MCd), using tissue Doppler imaging (TDI), as well as QTd between cirrhotic patients and healthy individuals, investigating their associations with cirrhosis severity. Methods: This prospective cross-sectional study was conducted on patients with confirmed liver cirrhosis and healthy individuals. Participants with structural heart disease, heart ventricular pacing, electrolyte abnormalities, using drugs affecting QT interval were excluded. All individuals underwent 2D echocardiography, and TDI by vivid E9 echo machine. MCd and QTd were considered as main outcomes. Chi-square, independent-sample t test, and Pearson correlation test, were used for statistical analyses by SPPS version 17.0. P value <0:05 was considered statistically significant. Results: Sixty participants (40 male/20 female) with a mean age of 40.1 ± 7.1 years in two groups of cirrhotic patients (n=30) and healthy individuals (n=30) were studied. Both groups were statistically similar in terms of age (P = 0.31) and gender (P = 0.39). MCd and QTd of cirrhotic patients were significantly higher than healthy individuals (MCd: 41.0 ± 26.8 versus 27.6±18.1; P = 0.028; and QTd: 37.0 ± 22.1 versus 25.3 ± 8.9; P = 0.010). Cirrhotic patients with MELD score <15 had a lower MCd in comparison to score ≥15 (29.2 ± 13.8 versus 50.0 ± 31.1, P = 0.034). Conclusion: Cirrhosis was associated with increased MCd, assessed by TDI. Also, MCd and QTd were associated with a higher MELD score. According to the results, it seems that MCd and QTd might be useful predictor of ventricular arrhythmia and negative prognostic factor in cirrhotic patients.