Skoura – a genetic island for congenital insensitivity to pain and anhidrosis among Moroccan Jews, as determined by a novel mutation in the NTRK1 gene

Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV is a rare, autosomal recessive neurologic disorder, characterized by absence of reaction to painful stimuli, mental retardation, self- mutilating behavior, anhidrosis, and recurrent episodes of hyperthermia. Mutations in the neurotrophic tyrosine kinase receptor 1, a receptor phosphorylated by nerve growth factor, have been documented in diverse ethnic groups. We identified the same novel nonsense mutation in two unrelated families of Moroccan Jewish descent, each with two affected siblings. This possible founder mutation may trace to the rural Jewish village in southern Morocco from where both these families originated. Genetic screening for the causative mutation among 300 unrelated Moroccan Jews did not reveal carriers for the causative mutation, thus excluding high risk for CIPA in this ethnic subpopulation.     

Delivering affordable cancer care in high-income countries

The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.     

The demographics of significant firearm injury in Canadian trauma centres and the associated predictors of inhospital mortality

Objective

Our primary objective was to evaluate demographic and causal factors of inhospital mortality for significant firearm-related injuries (i.e., those with an Injury Severity Score [ISS] > 12) in Canadian trauma centres.

Methods

We analyzed data submitted to the Canadian Institute for Health Information (CIHI) in the National Trauma Registry for all firearm-injured patients for fiscal years 1999–2003. Univariate and bivariate adjusting for ISS and multivariate logistic regression were performed.

Results

Men accounted for 94% of the 784 injured. In all patients, the percentages of self-inflicted, intentional, unintentional and unknown injuries were 27.8%, 60.3%, 6.1% and 5.7%, respectively. The inhospital fatality rate was 39.8%, with 83% of fatalities occurring on the first day. Two-thirds of patients were discharged home. Univariate and adjusted analysis found that ISS, first systolic blood pressure (BP), first systolic BP under 100, first Glasgow Coma Scale (GCS) score, age over 45 years, self-inflicted injury, intentional injury and injury at home significantly worsened the odds ratio of death in hospital and that police shooting was relatively beneficial. BP under 100, age over 45 years and a low GCS score had an adjusted odds ratio of death of 4.12, 1.99 and 0.64 per point increase, respectively. The multivariate model showed that ISS, BP under 100, first GCS score, sex and self-inflicted injury were significant in predicting inhospital death.

Conclusion

A predominance of young men are injured intentionally with handguns in Canada, whereas older patients suffer self-inflicted injuries with long guns. The significant number of firearm deaths, largely in the first day, highlights the importance of preventative strategies and the need for rapid transport of patients to trauma centres for urgent care.     

Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases

One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma.     

Autoimmune haemolytic anaemia after ABO-match, ABDR full match kidney transplantation

We report a case of autoimmune haemolysis after an ABO- andABDR-identical kidney transplantation which leads to the discussionof the role of cyclosporin A (CsA). A 46-year-old woman with end-stage renal disease and no historyof auto-immune disease received an ABO- and ABDR-identical firstrenal allograft from a cadaver donor. On day 16, while on aheavy sequential immunosuppressive regimen including anti-thymoglobulins,azathioprine (Aza), prednisolone (Pred) and CsA, she developedan autoimmune haemolysiswith positive Coombs test, IgM+C type.Elution of antierythrocyte antibodies did not enable us to identifyany specificity. Haemolysis lasted 45 days before haemoglobinslowly increased after CsA had been greatly reduced. Directantiglobulin tests remained positive 5 months after transplantationand became negative the following month. Eight months afterthe transplantation the patient had a normal haemoglobin leveland normal renal function. Although the typing of autoantibodies was not possible, ourdata suggest that this patient's haemolysis may be related tothe clonal development of donor B lymphocytes in the recipient,favoured by an HLA A-B-DR identity and post-transplant CsA therapy,as exceptionally reported in the literature.     

Neoadjuvant chemotherapy of breast cancer

About 80% of patients with breast cancer ultimately die of metastatic disease at 20 years. Distant metastases are more important as a cause of death than local or regional relapses. It is for this reason that adjuvant chemotherapy is necessary, especially in young patients and those with extensive disease. Initial chemotherapy preceding any local or regional treatment is justified on the grounds that both surgery and anaesthesia lead to immunodepression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials by Nissen-Meyer, Bonadonna and Cooper (1-3). In the present study 145 patients, including 67 with inflammatory breast cancer (IBC), were treated with 4-6 weeks of Velbe, thiotepa, methotrexate, fluorouracil and prednisone, with Adriblastin added for patients with IBC, T greater than 7 cm, or N2, N3. Because of tumour regression of greater than 50% observed in 80% of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium), resulting in complete remission in all these cases. Maintenance treatment with the same drugs was prescribed for 6-18 months depending on the initial stage. Tumour regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest being 42 months. Overall survival at 2 years for IBC is 90%, with a disease-free survival of 80%. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.     

DASS21: A Useful Tool in the Psychological Profile Evaluation of Dialysis Patients

Background

The effect of dialysis treatment is complex, with both clinical and socio-psychological effects. In this study, we aimed to assess the psychological status of this growing population of end-stage renal disease.

Atypical Presentation of Hepatocellular Carcinoma Mimicking a Gastric Hepatoid Adenocarcinoma: A Case Report

The diagnosis of hepatocellular carcinoma (HCC) relies on imaging tools and biopsy. It usually does not present to be a challenge.Here we report the case of a 69-year-old patient with HCC, initially mistaken for a gastric hepatoid adenocarcinoma (HAC), with a favorable outcome after neoadjuvant chemotherapy.The initial presentation (clinical signs, morphological features, and histological findings) led to the diagnosis of a gastric hepatoid adenocarcinoma. Neoadjuvant chemotherapy by epirubicin, oxaliplatin, and capecitabine protocol was administered. Biological (alpha-fetoprotein [AFP] decreased by a factor of 10), radiological (−35% RECIST), and histological (20% of necrosis) responses were observed. Complete surgical resection was then performed. The final pathological diagnosis was a well-differentiated HCC, staged pT4 N0 (0/24) R0.There are no guidelines as to how such tumors should be managed. Nonetheless, neoadjuvant chemotherapy yielded a good outcome. This observation stresses the importance of the final pathological findings and addresses the issue of neoadjuvant therapy in some cases of HCC.