The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2 , hospitalized and received supplemental O2 , admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

The Clinical, Genomic, and Transcriptomic Landscape of BRAF Mutant Cancers.

BACKGROUND: BRAF mutations are classified into four molecularly distinct groups, and Class 1 (V600) mutant tumors are treated with targeted therapies. Effective treatment has not been established for Class 2/3 or BRAF Fusions. We investigated whether BRAF mutation class differed according to clinical, genomic, and transcriptomic variables in cancer patients. METHODS: Using the AACR GENIE (v.12) cancer database, the distribution of BRAF mutation class in adult cancer patients was analyzed according to sex, age, primary race, and tumor type. Genomic alteration data and transcriptomic analysis was performed using The Cancer Genome Atlas. RESULTS: BRAF mutations were identified in 9515 (6.2%) samples among 153,834, with melanoma (31%), CRC (20.7%), and NSCLC (13.9%) being the most frequent cancer types. Class 1 harbored co-mutations outside of the MAPK pathway (TERT, RFN43) vs. Class 2/3 mutations (RAS, NF1). Across all tumor types, Class 2/3 were enriched for alterations in genes involved in UV response and WNT/ß-catenin. Pathway analysis revealed enrichment of WNT/ß-catenin and Hedgehog signaling in non-V600 mutated CRC. Males had a higher proportion of Class 3 mutations vs. females (17.4% vs. 12.3% q = 0.003). Non-V600 mutations were generally more common in older patients (aged 60+) vs. younger (38% vs. 15% p < 0.0001), except in CRC (15% vs. 30% q = 0.0001). Black race was associated with non-V600 BRAF alterations (OR: 1.58; p < 0.0001). CONCLUSIONS: Class 2/3 BRAFs are more present in Black male patients with co-mutations outside of the MAPK pathway, likely requiring additional oncogenic input for tumorigenesis. Improving access to NGS and trial enrollment will help the development of targeted therapies for non-V600 BRAF mutations.

Real-World Safety and Effectiveness of a Bevacizumab Biosimilar (ABP 215) in Metastatic Colorectal Cancer Patients in Canada.

BACKGROUND: ABP 215 is a biosimilar to the reference product, bevacizumab, and was one of the first biosimilars approved by Health Canada for the first-line treatment of metastatic colorectal cancer (mCRC). This study aimed to address gaps in real-world evidence (RWE) including patient characteristics, treatment safety (primary objective), and effectiveness (secondary objective) for first-line ABP 215 therapy in Canadian patients with mCRC. MATERIALS AND METHODS: Retrospective data were collected in 2 waves, at least 1 year (Wave 1) or 2 years (Wave 2) after commercial availability of ABP 215 at each participating site. RESULTS: A total of 75 patients from Wave 1 and 164 patients from Wave 2 treated with a minimum of 1 cycle of ABP 215 were included. At least one safety event of interest (EOI) was recorded for 34.7% of Wave 1 and 42.7% of Wave 2 patients. The median progression free survival (PFS) for Wave 1 and 2 patients were 9.47 (95% confidence interval [CI]: 6.71, 11.90) and 21.38 (95% CI: 15.82, not estimable) months, respectively. Median overall survival was not estimable for Wave 1 and was 26.45 months for Wave 2. CONCLUSION: The safety and effectiveness of ABP 215 observed in this real-world study were comparable to clinical trial findings and to other RWE with longer PFS in the current study.

Acrylamide in daily food in the metropolitan area of Hanoi, Vietnam.

Acrylamide, a colourless and odourless crystalline solid, formed via the Maillard reaction in food, has been reported with harmful properties for humans, such as toxicity and carcinogenicity. Three hundred and four processed food samples from 17 product types, collected in Hanoi, Vietnam, were analyzed by LC-MS/MS to measure the acrylamide concentration. The limit of detection (LOD) and the limit of quantification (LOQ) of acrylamide were 1 µg Kg-1 and 3 µg Kg-1, respectively. Effectively, the highest acrylamide content is usually found in processed food, which is one of the primary reasons of increased acrylamide content in food. All French fried samples contained acrylamide above 500 µg kg-1. Acrylamide concentration in non-fried noodle, vermicelli, rice noodle, pho, dried vegetable, and rice cracker is lower than in potato chips, fried potatoes, fried cake, and fried noodles. The results could be helpful to estimate exposure and risk assessment of acrylamide in Vietnam.

Serial imaging after pulmonary embolism and correlation with functional limitation at 12 months: Results of the ELOPE Study.

INTRODUCTION: Risk factors for exercise limitation after acute pulmonary embolism (PE) are unknown. As a planned sub-study of the prospective, multicenter ELOPE (Evaluation of Long-term Outcomes after PE) Study, we aimed to describe the results of serial imaging by computed tomography pulmonary angiography (CTPA) and perfusion scan during 1 year after a first episode of acute pulmonary embolism, and to assess the association between imaging parameters and exercise limitation at 1 year. METHODS: In a prospective cohort study, 100 patients were recruited between June 2010 and February 2013 at five Canadian university-affiliated hospitals. CT pulmonary angiography was performed at baseline and 12 months, perfusion scan at 6 and 12 months, and cardio-pulmonary exercise testing at 1 and 12 months. Imaging parameters included: on CT pulmonary angiography, CT obstruction index (CTO) (% clot burden in the pulmonary vasculature), and on perfusion scan, pulmonary vascular obstruction (PVO) (% perfusion defect). Abnormal cardio-pulmonary exercise test (primary outcome) was defined as percent of predicted peak oxygen uptake (VO2) <80%. RESULTS: Mean (median; SD) CT obstruction index was 28.1% (27.5%; 18.3%) at baseline, 1.2% (0%; 4.3%) at 12 months. Mean (median; SD) pulmonary vascular obstruction was 6.0% (0%; 9.6%) at 6 months, 5.6% (0%; 9.8%) at 12 months. Eighty-six patients had exercise testing at 12 months, and 46.5% had VO2 < 80% predicted. Mean (median; SD) CT obstruction index at 1 year was similar in patients with percent-predicted VO2 peak <80% vs >80% on 1-year cardio-pulmonary exercise testing (1.4% [0%; 5.7%] vs 1.0% [0%; 2.4%]; P = .70). Mean (SD) pulmonary vascular obstruction at 6 and at 12 months was similar in patients with percent-predicted VO2 peak <80% vs >80% (6 months: 5.9% [0%; 10.4%] vs 6.2% [4.5%; 9.0%]; P = .91; 12 months: 5.1% [0%; 10.2%] vs 6.0% [0%; 9.7%]; P = .71). CONCLUSIONS: Imaging findings after pulmonary embolism did not predict exercise limitation. Residual thrombus does not appear to explain long-term functional limitation after pulmonary embolism.

A multicenter prospective study of risk factors and treatment of unusual site thrombosis.

Unusual site deep vein thrombosis (USDVT) is an uncommon form of venous thromboembolism (VTE) with heterogeneity in pathophysiology and clinical features. While the need for anticoagulation treatment is generally accepted, there is little data on optimal USDVT treatment. The TRUST study aimed to characterize the epidemiology, treatment and outcomes of USDVT. From 2008 to 2012, 152 patients were prospectively enrolled at 4 Canadian centers. After baseline, patients were followed at 6, 12 and 24months. There were 97 (64%) cases of splanchnic, 33 (22%) cerebral, 14 (9%) jugular, 6 (4%) ovarian and 2 (1%) renal vein thrombosis. Mean age was 52.9years and 113 (74%) cases were symptomatic. Of 72 (47%) patients tested as part of clinical care, 22 (31%) were diagnosed with new thrombophilia. Of 138 patients evaluated in follow-up, 66 (48%) completed at least 6months of anticoagulation. Estrogen exposure or inflammatory conditions preceding USDVT were commonly associated with treatment discontinuation before 6months, while previous VTE was associated with continuing anticoagulation beyond 6months. During follow-up, there were 22 (16%) deaths (20 from cancer), 4 (3%) cases of recurrent VTE and no fatal bleeding events. Despite half of USDVT patients receiving <6months of anticoagulation, the rate of VTE recurrence was low and anticoagulant treatment appears safe. Thrombophilia testing was common and thrombophilia prevalence was high. Further research is needed to determine the optimal investigation and management of USDVT.

Refractory IgG Warm Autoimmune Hemolytic Anemia Treated with Eculizumab: A Novel Application of Anticomplement Therapy.

Warm autoimmune hemolytic anemia (wAIHA) is the most common form of AIHA, with corticosteroids in first-line treatment resulting in a 60-80% response rate. Atypical wAIHA and IgG plus complement mediated disease have a higher treatment failure rate and higher recurrence rate. We report a case of severe wAIHA secondary to Waldenström macroglobulinemia with life threatening intravascular hemolysis refractory to prednisone, rituximab, splenectomy, and plasmapheresis. A four-week treatment of eculizumab in this heavily pretreated patient resulted in a sustained increase in hemoglobin and transfusion independence, suggesting a role for complement inhibition in refractory wAIHA.

Venous thromboembolism in hospitalized patients: an updated analysis of missed opportunities for thromboprophylaxis at a university-affiliated tertiary care center.

Thromboprophylaxis remains often underused in hospitalized patients. In 2001, a cohort study done at our institution, a tertiary care center in Montreal, Canada, showed that 67.7% of VTE cases necessitating thromboprophylaxis were potentially preventable with adequate use of American College of Chest Physicians (ACCP) guidelines. Following implementation of an institution-wide policy in 2005, we assessed the changes in the rate of potentially preventable VTE. We conducted a retrospective cohort study including all hospitalized patients with objectively diagnosed VTE in 2010 at our institution. Each case was classified as preventable (thromboprophylaxis indicated but inadequately administered), non-preventable (thromboprophylaxis indicated and correctly administered), spontaneous (thromboprophylaxis not indicated), and ineligible (contraindication to thromboprophylaxis). The results were compared to those obtained in 2001. Of the 230 cases of VTE, 55 cases were classified as potentially preventable (23.9%), 85 were non-preventable (37.0%), 74 were spontaneous (32.2%) and 16 (7.0%) were ineligible. Of the 140 cases requiring thromboprophylaxis, 39.3% were potentially preventable. The potentially preventable cases were mostly due to omission of thromboprophylaxis (50.9%), occurred during general medical admissions (74.5%), and the most common VTE risk factor was cancer (47.2%). In conclusion, we demonstrate a lower frequency of potentially preventable cases in 2010 compared to 2001 (39.3% vs 67.7%, respectively), partially due to physician education and adoption of an institution-wide policy. However, patients with medical indications for thromboprophylaxis, particularly those with cancer, are more prone to having preventable VTE, indicating an area for potential improvement.

Wilms tumor arising in a child with X-linked nephrogenic diabetes insipidus.

We report on a child with X-linked nephrogenic diabetes insipidus (NDI) who developed Wilms tumor (WT). Nephrogenic diabetes insipidus is caused by mutations of the arginine vasopressin receptor (AVPR2) or aquaporin-II (AQP2) genes. Wilms tumor is also genetically heterogeneous and is associated with mutations of WT1 (15-20%), WTX (20-30%) and other loci. The boy presented at 5 months with failure to thrive, polyuria, hypernatremia and abdominal mass. Analysis of leukocyte DNA showed a novel missense mutation (Q174H) of the AVPR2 gene, which was not present in his mother. In cells (WitS) isolated from the tumor, WTX mRNA expression and coding sequence were intact. However, we identified a 44-kb homozygous deletion of the WT1 gene spanning exons 4 to 10. The WT1 deletion was not present in leukocyte DNA from the patient or his mother. We also noted strong beta-catenin (CTNNB1) expression in the tumor cells and identified a heterozygote missense Ser45Cys mutation of exon 3 of CTNNB1. However, the mutation was absent both in the constitutional DNA of the patient and his mother. The concurrence of WT and NDI has not been previously reported and may be unrelated. Nevertheless, this case nicely illustrates the sequence of events leading to sporadic Wilms tumor.

Septic Arthritis of the Hip Caused by Brucella abortus: A Case Report / 대한정형외과학회잡지

Brucellosis is a glbally distributed zoonotic infection of the Brucella genus that can involve multiple tissue and organ. In Korea, Brucellosis is caused mainly by B. abortus. but there is no reported case of pyogenic hip joint infection due to Brucella infection in Korea. The authors report a rare case of B. abortus infection in a 40-year-old male cattle breeder male who presented with septic arthritis of the hip joint as the first clinical manifestation.

Femoral Nerve Palsy caused by Iliopsoas Bursitis Associated with Osteonecrosis of the Femoral Head : A Case Report

Iliopsoas bursitis is known to occur in relation to hip joint lesions such as osteoarthritis, rheumatoid arthritis, synovial chondromatosis, pigmented villonodular synovitis and rarely osteonecrosis of the femoral head, but femoral nerve palsy due to iliopsoas bursitis is a very rare condition. A patient visited to the emergency room because of anesthesia of the anterior thigh. A mass had developed and this enlarged to 3x5 cm in size after 2 weeks, and this was probably due to progression of osteonecrosis of the femoral head. The patient was finally diagnosed with femoral nerve palsy that was caused by a distended iliopsoas bursa, which was detected by ultrasonography and enhanced MRI. Total hip arthroplasty via the posterior approach was done and the connected iliopsoas bursa was removed. After operation, the anesthesia of the anterior thigh and the motor power were improved. We report here on a case of femoral nerve palsy due to iliopsoas bursitis that was related to osteonecrosis of the femoral head, and we review the relevant medical literature.