Correction of traumatic tricuspid regurgitation using the double orifice technique

We present a case of acute traumatic tricuspid regurgitation in a 39-year-old man who was involved in a motor vehicle accident. A large ecchymotic region over the anterior chest wall prompted evaluation by both transthoracic and transesophageal echocardiography which confirmed the valvular injury. At surgery, valvular incompetence was found to be the result of a flail anterior leaflet due to papillary muscle rupture. The valve was successfully repaired using a single stitch double orifice technique in combination with a ring annuloplasty. The valve remains competent 18 months after surgery.     

Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation

Ebola virus (EBOV) and Marburg virus (MARV) cause rapidly progressive hemorrhagic fever with high mortality and may possess specialized mechanisms to evade immune destruction. We postulated that immune evasion could be due to the ability of EBOV and MARV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. We demonstrate that EBOV and MARV infected and replicated in primary human DCs without inducing cytokine secretion. Infected DC cultures supported exponential viral growth without releasing interferon (IFN)-alpha and were impaired in IFN-alpha production if treated with double-stranded RNA. Moreover, EBOV and MARV impaired the ability of DCs to support T cell proliferation, and infected, immature DCs underwent an anomalous maturation. These findings may explain the profound virulence of EBOV and MARV--DCs are disabled, and an effective early host response is delayed by the necessary reliance on less-efficient secondary mechanisms.     

SecA2-dependent secretion of autolytic enzymes promotes Listeria monocytogenes pathogenesis

Pathogenic bacteria secrete proteins that promote invasion of host tissues and resistance to immune responses. However, secretion mechanisms that contribute to the enormous morbidity and mortality of Gram-positive bacteria are largely undefined. An auxiliary protein secretion system (SecA2) has recently emerged in Listeria monocytogenes and eight other Gram-positive pathogens. Here, a proteomics approach identified seventeen SecA2-dependent secreted and surface proteins of L. monocytogenes, the two most abundant of which [the p60 and N-acetylmuramidase (NamA) autolysins] hydrolyze bacterial peptidoglycan (PGN) and contribute to host colonization. SecA2-deficient (DeltaSecA2) bacteria were rapidly cleared after systemic infection of murine hosts, and in cultured cells showed reduced cell-cell spread. p60 or NamA deficiencies (Deltap60 and DeltaNamA) caused intermediate reductions in bacterial virulence in vivo, yet showed no defect for infection of cultured cells. Restoration of virulence in Deltap60 bacteria required full-length p60 with an intact catalytic domain, suggesting that PGN hydrolysis by p60 is crucial for L. monocytogenes virulence. Coordinated PGN hydrolysis by p60 and NamA activities is predicted to generate a muramyl glycopeptide, glucosaminylmuramyl dipeptide (GMDP), which is known to modify host inflammatory responses. Thus, SecA2-dependent secretion may promote release of muramyl peptides that subvert host pattern recognition.     

A descriptive study of persistent oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer

Background

Prolonged neurotoxicity after systemic chemotherapy has the potential to impact on quality of life. We explored the frequency of persistent peripheral neuropathy in patients who received oxaliplatin for colorectal cancer at two local centres.

Patients and methods

Questionnaires were sent to patients who completed treatment with oxaliplatin for colorectal cancer at least 20 months prior to entering the study. Neuropathy questions were adapted from the FACT/GOG-Ntx (V.4) questionnaire.

Results

Of the 56 eligible patients, 27 returned the questionnaire. Twenty-five patients (93 %) experienced neuropathic symptoms during their treatment; 11 had grade-2, and two had grade-3 symptoms. At the time of completing the questionnaire, 17 patients (63.0 %; 95%CI 43.9–79.4 %) were still symptomatic with 12 patients (44.4 %; 95%CI 26.8–63.3) having grade-2 or grade-3 symptoms and three patients (11.1 %; 95%CI 2.9–27.3) having grade-3 neuropathic symptoms. Participants who received more than 900 mg/m² oxaliplatin had a significantly higher risk of persistent grade-2 or grade-3 neuropathy (p?=?0.031, RR?=?8.3 95%CI?=?1.2–57.4). There was a trend toward increased risk of persistent neuropathy of any grade among participants with a history of regular alcohol use (p?=?0.051; RR?=?1.7 95%CI 1.0–2.8).

Conclusion

Persistent oxaliplatin-induced neuropathy is not as uncommon as previously suggested, and the rate of grade-2 and grade-3 symptoms could be considerably higher than previous reports.