Necrotizing Fasciitis: A Side Effect of Rituximab Administration in Steroid-Dependent Nephrotic Syndrome.

Steroid-dependent nephrotic syndrome (SDNS) is a common type of childhood nephrotic syndrome. Remission following steroid therapy is achieved in 80-90% of the patients, while the remainder show steroid-resistant nephrotic syndrome (SRNS). Rituximab is an anti-CD20 chimeric monoclonal antibody with proven therapeutic effects in several diseases and has been used with great success in the treatment of NS since its discovery. We report a case of a 4-year-old girl diagnosed with SDNS at the age of 3. As treatment with steroids, enalapril, and mycophenolate failed to produce complete remission, rituximab was initiated, and remission was successfully achieved after administration of the first dose. Due to this response, rituximab therapy was continued; however, a day after being admitted to the nephrology ward for the second dose, she started to develop a high fever, which reached up to 40°C. In addition, she also displayed symptoms of upper respiratory tract infection and an ulcerated wound on her left cheek. The patient became drowsy with reactive pupils, cold peripheries, and weak peripheral pulses. The capillary refill time was prolonged to 3-4 seconds and it was decided to withhold the second dose of rituximab. The patient was shifted to the PICU as a case of septic shock secondary to facial cellulitis and started on inotropes (epinephrine and norepinephrine), meropenem, vancomycin, and hydrocortisone 15 mg. Thereafter, surgical debridement of the wound was carried out. The patient remained in remission with regard to nephrotic syndrome and was discharged in a healthy condition. In conclusion, rituximab used in conjunction with steroids and other immunosuppressants may increase the risk of serious infections like necrotizing fasciitis (NF). Further studies are needed to explore the relationship between rituximab and NF.

Management of Polycythemia Vera: A Survey of Canadian Physician Practice Patterns.

BACKGROUND: The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows for an earlier detection of masked PV. The literature is scarce about the clinical uptake of new diagnostic algorithms for PV. In a cohort of Canadian hematologists, we aimed to identify how the revised 2016 WHO diagnostic criteria of PV are being incorporated into hematology practice, and if the treatment of PV is comparable to the approaches outlined by the Canadian Myeloproliferative Neoplasm Group. MATERIALS AND METHODS: A cross-sectional survey of practicing Canadian hematologists/oncologists was distributed to active members of the Canadian Hematology Society using an online survey-distributing website. Univariate and multivariate analysis was performed. RESULTS: The survey was completed by 86 respondents in total. Only type of practice was associated with respondents offering aspirin to all patients with PV (P = .0009). Respondents who were aware of the Canadian Myeloproliferative Neoplasm Group guidelines were more likely to phlebotomize patients to a target hematocrit of < 45% irrespective of gender (P = .042). Younger practitioners were more likely to use age over 60 years as an indication for initiating cytoreductive therapy (P = .0006). Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism. CONCLUSION: The survey confirmed that heterogeneity of practice in diagnosis and management of PV among Canadian hematologists exists, suggesting that targeted education in specific segments of the PV treatment providers may result in wider adoption of the guidelines and diagnostic criteria.

The Haiti Medical Education Project: development and analysis of a competency based continuing medical education course in Haiti through distance learning.

BACKGROUND: Recent calls for reform in healthcare training emphasize using competency-based curricula and information technology-empowered learning. Continuing Medical Education programs are essential in maintaining physician accreditation. Haitian physicians have expressed a lack access to these activities. The Haiti Medical Education Project works in alliance with Haitian medical leadership, faculty and students to support the Country's medical education system. We present the creation, delivery and evaluation of a competency-based continuing medical education curriculum for physicians in rural Haiti. METHODS: Real time lectures from local and international institutions were teleconferenced to physicians in remote Haitian sites using VidyoConferencing™ technology. With American Academy of Family Physicians (AAFP) and College of Family Physicians Canada (CFPC) guidelines as references, a competency-derived syllabus was created for a Haitian continuing medical education program. The resulting educational goals were reviewed by a committee of Haitian and North American physician/medical education practitioners to reflect local needs. All authors reviewed lectures and then conferred to establish agreement on competencies presented for each lecture. RESULTS: Sixty-seven lectures were delivered. Human immunodeficiency virus/Acquired Immunodeficiency Syndrome, ophthalmologic, infectious diseases, renal and endocrine competencies were well-represented, with more than 50 % of the joint AAFP and CFPC recommended competencies outlined. Areas under-represented included allergy and immunology, cardiology, surgery, pain management, gastroenterology, neurology, pulmonology, men's health and rheumatology; these topics accounted for less than 25 % of AAFP/CFPC recommended competencies. Areas not covered included geriatrics, nutrition, occupational health and women's health. Within practice-based lectures, only disaster medicine, health promotion and information management were included, but only partially covered. CONCLUSIONS: We identified teaching goals covered and competencies that were missing from a CME program for rural Haitian physicians. We aim to use this analysis to provide a competency-based CME lecture series that proportionally meets local needs while following recommendations of recognized national family medicine organizations.

Head and neck cancer patients want us to support them psychologically in the posttreatment period: Survey results.

OBJECTIVES: No study systematically has investigated the supportive care needs of general head and neck cancer patients using validated measures. These needs include physical and daily living needs, health system and information needs, patient care and support needs, psychological needs, and sexuality needs. Identifying the unmet needs of head and neck cancer patients is a necessary first step to improving the care we provide to patients seen in our head and neck oncology clinics. It is recommended as the first step in intervention development in the Pan-Canadian Clinical Practice Guideline of the Canadian Partnership Against Cancer (see Howell, 2009). This study aimed to identify: (1) met and unmet supportive care needs of head and neck cancer patients, and (2) variability in needs according to demographics, disease variables, level of distress, and quality-of-life domains. METHODS: Participants were recruited from the otolaryngology-head and neck surgery clinics of two university teaching hospitals. Self-administered questionnaires included sociodemographic and medical questions, as well as validated measures such as the Supportive Care Needs Survey-Short Form (SCNS-SF34), the Hospital Anxiety and Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) and Head and Neck Module (FACT-H&N) (quality of life measures). RESULTS: One hundred and twenty-seven patients participated in the survey. 68% of them experienced unmet needs, and 25% revealed a clinically significant distress level on the HADS. The highest unmet needs were psychological (7 of top 10 needs). A multiple linear regression indicated a higher level of overall unmet needs when patients were divorced, had a high level of anxiety (HADS subscale), were in poor physical condition, or had a diminished emotional quality of life (FACT-G subscales). SIGNIFICANCE OF RESULTS: The results of this study highlight the overwhelming presence of unmet psychological needs in head and neck cancer patients and underline the importance of implementing interventions to address these areas perceived by patients as important. In line with hospital resource allocation and cost-effectiveness, one may also contemplate screening patients for high levels of anxiety, as well as target patients who are divorced and present low levels of physical well-being, as these patients may have more overall needs to be met.

Functional redundancy of exon 12 of BRCA2 revealed by a comprehensive analysis of the c.6853A>G (p.I2285V) variant.

Variants of unknown significance (VUS) in BRCA1 and BRCA2 are common, and present significant challenges for genetic counseling. We observed that BRCA2: c.6853A>G (p.I2285V) (Breast Cancer Information Core [BIC] name: 7081A>G; http://research.nhgri.nih.gov/bic/) co-occurs in trans with the founder mutation c.5946delT (p.S1982RfsX22) (BIC name: 6174delT), supporting the published classification of p.I2285V as a neutral variant. However, we also noted that when compared with wild-type BRCA2, p.I2285V resulted in increased exclusion of exon 12. Functional assay using allelic complementation in Brca2-null mouse embryonic stem cells revealed that p.I2285V, an allele with exon 12 deleted and wild-type BRCA2 were all phenotypically indistinguishable, as measured by sensitivity to DNA-damaging agents, effect on irradiation-induced Rad51 foci formation, homologous recombination, and overall genomic integrity. An allele frequency study showed the p.I2285V variant was identified in 15 out of 722 (2.1%) Ashkenazi Jewish cases and 10 out of 475 (2.1%) ethnically-matched controls (odds ratio, 0.99; 95% confidence interval: 0.44-2.21; P=0.97). Thus the p.I2285V variant is not associated with an increased risk for breast cancer. Taken together, our clinical and functional studies strongly suggest that exon 12 is functionally redundant and therefore missense variants in this exon are likely to be neutral. Such comprehensive functional studies will be important adjuncts to genetic studies of variants.