Reversible posterior leukoencephalopathy in a venomous snake (Bothrops asper) bite victim

An 18-year-old man developed posterior reversible leukoencephalopaty after being bitten by a venomous snake (Bothrops asper). It is possible that this previously unrecognized neurological complication of snake bite envenoming occurred as the result of endothelial dysfunction induced by the venom of the offending snake. This pathogenetic mechanism has also been implicated as the cause of cerebral infarctions in snake bite victims. Alternatively, the leukoencephalopathy might have been a complication of antivenom therapy.     

High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma

The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated.     

Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth

Membrane-anchored ephrinB2 and its receptor EphB4 are involved in the formation of blood and lymphatic vessels in normal and pathologic conditions. Eph/ephrin activation requires cell-cell interactions and leads to bidirectional signaling pathways in both ligand- and receptor-expressing cells. To investigate the functional consequences of blocking ephrinB2 activity, 2 highly specific human single-chain Fv (scFv) Ab fragments against ephrinB2 were generated and characterized. Both Ab fragments suppressed endothelial cell migration and tube formation in vitro in response to VEGF and provoked abnormal cell motility and actin cytoskeleton alterations in isolated endothelial cells. As only one of them (B11) competed for binding of ephrinB2 to EphB4, these data suggest an EphB-receptor-independent blocking mechanism. Anti-ephrinB2 therapy reduced VEGF-induced neovascularization in a mouse Matrigel plug assay. Moreover, systemic administration of ephrinB2-blocking Abs caused a drastic reduction in the number of blood and lymphatic vessels in xenografted mice and a concomitant reduction in tumor growth. Our results show for the first time that specific Ab-based ephrinB2 targeting may represent an effective therapeutic strategy to be used as an alternative or in combination with existing antiangiogenic drugs for treating patients with cancer and other angiogenesis-related diseases.     

Morbidity related to defunctioning loop ileostomy in low anterior resection

Aim

A defunctioning loop ileostomy in low anterior resection reduces the incidence and morbidity of an anastomotic leakage, but complications related to the stoma may occur. We explored stoma-associated complications during the stoma period and after stoma reversal.

Methods

A retrospective analysis of rectal cancer patients operated with low anterior resection and a defunctioning loop ileostomy at Helsingborg Hospital and Malm? University Hospital from January 2007 to June 2009 was undertaken.

Results

Ninety-two patients were included, of whom 82 (89?%) underwent stoma reversal. The median stoma period was 6.2?±?3.2?months. Sixty-six percent of the patients suffered from minor or major stoma-associated morbidity. The complication rate was significantly related to the stoma time (p?<?0.01). Twenty-nine percent (27/92) had at least one episode of dehydration, leading to readmittance in half of the cases. Elderly patients were more prone to develop dehydration. Dehydration most commonly occurred early in the postoperative period (mean, 5.8?weeks). The mean hospital stay for stoma reversal was 6.5?±?4.0?days. Forty percent (33/82) had some complication associated with the reversal.

Conclusion

This study indicates high morbidity associated with defunctioning loop ileostomy. Our data suggest that the stoma time should be limited to reduce complications. Monitoring and early stoma reversal should be considered in elderly patients. Furthermore, stoma reversal is not uneventful, and more studies are needed to address how to minimize complications.     

Metastatic Crohn's disease. Response to adalimumab dose intensification

Inflammatory bowel disease is accompanied by extraintestinal manifestations in a high percentage of patients. Cutaneous lesions are the second most prevalent of these manifestations, and within these, metastatic Crohn's disease is one of the least common, being the least frequent specific cutaneous manifestation of Crohn's disease. This entity includes cutaneous and subcutaneous lesions with a non-caseating granulomatous appearance on histological analysis identical to that of Crohn's disease. These lesions are not found adjacent to the digestive tract. Due to the low prevalence of these manifestations, conclusive trials on the treatment of choice have not been performed and there is no well-defined therapeutic strategy. Distinct therapies with varying results have been reported. We report the case of a female patient with longstanding and complex Crohn's disease who developed metastatic cutaneous manifestations while receiving adalimumab. The cutaneous manifestations responded well to dose intensification of this drug. A review of the literature is provided.