Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy

Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P = 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.     

Elevated serum IGF‐1 levels synergize PTH action on the skeleton only when the tissue IGF‐1 axis is intact

There is growing evidence that insulin‐like growth factor 1 (IGF‐1) and parathyroid hormone (PTH) have synergistic actions on bone and that part of the anabolic effects of PTH is mediated by local production of IGF‐1. In this study we analyzed the skeletal response to PTH in mouse models with manipulated endocrine or autocrine/paracrine IGF‐1. We used mice carrying a hepatic IGF‐1 transgene (HIT), which results in a threefold increase in serum IGF‐1 levels and normal tissue IGF‐1 expression, and Igf1 null mice with blunted IGF‐1 expression in tissues but threefold increases in serum IGF‐1 levels (KO‐HIT). Evaluation of skeletal growth showed that elevations in serum IGF‐1 in mice with Igf1 gene ablation in all tissues except the liver (KO‐HIT) resulted in a restoration of skeletal morphology and mechanical properties by adulthood. Intermittent PTH treatment of adult HIT mice resulted in increases in serum osteocalcin levels, femoral total cross‐sectional area, cortical bone area and cortical bone thickness, as well as bone mechanical properties. We found that the skeletal response of HIT mice to PTH was significantly higher than that of control mice, suggesting synergy between IGF‐1 and PTH on bone. In sharp contrast, although PTH‐treated KO‐HIT mice demonstrated an anabolic response in cortical and trabecular bone compartments compared with vehicle‐treated KO‐HIT mice, their response was identical to that of PTH‐treated control mice. We conclude that (1) in the presence of elevated serum IGF‐1 levels, PTH can exert an anabolic response in bone even in the total absence of tissue IGF‐1, and (2) elevations in serum IGF‐1 levels synergize PTH action on bone only if the tissue IGF‐1 axis is intact. Thus enhancement of PTH anabolic actions depends on tissue IGF‐1. © 2010 American Society for Bone and Mineral Research.     

Fertility determinants after conservative surgery for mucinous borderline tumours of the ovary (excluding peritoneal pseudomyxoma)

BACKGROUND The aim of this study was to define determinants of fertility in patients treated conservatively for mucinous borderline ovarian tumours (MBOTs), and to compare outcomes after salpingo-oophorectomy or cystectomy. METHODS This was a retrospective cohort study of fertility results in a series of patients treated conservatively for MBOTs and desiring pregnancy. Conservative surgery was defined as preservation of the uterus and ovarian tissue in one or both adnexa(e). Fertility results were compared with patients who had undergone a cystectomy or a (salpingo-)oophorectomy. Only patients with a minimum of 1 year of follow-up were included. Epidemiological, surgical, histological parameters and other prognostic factors for fertility results were investigated. RESULTS A group of 31 patients who had been treated conservatively between 1997 and 2004 and who desired pregnancy were investigated. Patients were treated by unilateral salpingo-oophorectomy (USO) (n = 19) or cystectomy (n = 12). The 5-year recurrence-free survival rate was higher in the USO group compared with the cystectomy group (94.7 versus 49.1%, P = 0.041). Among the 31 women, 12 had become pregnant. The 5-year probabilities of pregnancy were comparable between the cystectomy and salpingo-oophorectomy groups (41.8 and 45.9%, respectively, P= 0.66). None of the other factors studied (epidemiological, surgical and histological parameters) were associated with fertility results. CONCLUSIONS The use of salpingo-oophorectomy rather than cystectomy should be preferred during conservative surgery for patients with MBOTs because it decreases the risk of recurrence and does not impair fertility.     

GEMSP: A New Therapeutic Approach to Multiple Sclerosis

A new therapeutic approach called Endotherapia (GEMSP) for the treatment of Multiple Sclerosis (MS) is suggested. Endotherapia is the result of an immunopathological strategy addressing chronic incurable diseases with a multifactorial etiology. This approach combines a biomedical evaluation of circulating immunoglobulins directed against specific self-antigens and self-antigens modified by free radicals. GEMSP is a "tailor-made" combination of small molecules (fatty acids, antioxidants, radical scavengers, amino acids) linked to a non-immunogenic linear chain of poly-L.lysine (PLL). Each individual linkage or PLL derivative offers great advantages, such as an increase in the half-life of the active small molecules. GEMSP inhibits brain leukocyte infiltration and abolishes episodes of experimental autoimmune encephalomyelitis. In a clinical trial with 102 MS patients treated with GEMSP Endotherapia, 28% of them showed a worsening of their state; 20% showed a decrease in the progression of the disease; 17% showed disease stabilization; and 35% showed a reversal of the evolution of disease; i.e., an improvement in their disease state. In 72% of the cases, a positive evolution of the state of the MS patients treated with Endotherapia was observed (a decrease or stabilization of disease evolution or an improvement). Endotherapia is very safe and no side-effects were reported for GEMSP. Moreover, GEMSP showed no toxicity either in experimental animals or in humans. It seems that Endotherapia is a promising therapy for MS, with no side-effects, which should be considered in the management of long-term pathologies.     

Treatment of chronic disruption of the patellar tendon in Osteogenesis Imperfecta with allograft reconstruction

We present a case of chronic disruption of the patellar tendon in a patient with Osteogenesis Imperfecta. This patient was treated with a customized extensor mechanism allograft. Results were excellent at 5 years follow up. To our knowledge this treatment has not previously been published in this situation. We present this as a reliable treatment option.     

Lymphocoele: a rare and little known complication of anterior lumbar surgery

Lymphocoele is a rare and little known complication with only a handful of reports available. We report two cases of lymphocoele after anterior lumbar surgery that have occurred in two different centres and discuss diagnosis and management options. The first case is that of a 53-year-old male patient undergoing two level anterior lumbar interbody fusion (ALIF) for disabling back pain due to disc degeneration in the context of an old spondylodiscitis. He developed a large fluid mass postoperatively. Fluid levels of creatinin were low and intravenous urography ruled out a urinoma suggesting the diagnosis of a lymphocoele. Following two unsuccessful drainage attempts he underwent a laparoscopic marsupialization. The second case was that of a 32-year-old female patient developing a large fluid mass following a L5 corpectomy for a burst fracture. She was treated successfully with insertion of a vacuum drain during 7 days. Lymphocoele is a rare complication but should be suspected if fluid collects postoperatively following anterior lumbar spine procedures. Chemical analysis of the fluid can help in diagnosis. Modern treatment consists of laparoscopic marsupialization. Lymph vessel anatomy should be borne in mind while exposing the anterior lumbar spine.     

Pure ‘natural orifice transluminal endoscopic surgery’ for transvaginal nephrectomy in the porcine model

OBJECTIVES

To determine the technical feasibility and reproducibility of pure natural orifice transluminal endoscopic surgery (NOTES) transvaginal nephrectomy using NOTES‐specific instrumentation, with no transabdominal assistance.

MATERIALS AND METHODS

Five female farm pigs (mean weight 45 kg) had a right NOTES nephrectomy, using a single‐channel gastroscope in the first three pigs and a dual‐channel gastroscope in the remaining two. The peritoneal cavity was accessed through the posterior fornix of the vagina. Dissection was started at the lower pole of the kidney, and the ureter was retracted laterally and followed towards the hilum. An XL articulated 60 cm endo‐GIA stapler (US Surgical, Norwalk, CO, USA), inserted transvaginally via a separate vaginal incision, was used for tissue retraction and renal hilar transection. The kidney was freed, entrapped in an impermeable sac, and extracted intact transvaginally.

RESULTS

All five procedures were successful with no addition of a transabdominal laparoscopic port or open conversion. The total operative duration decreased from 200 min in the first pig to 60 min in the last (mean 113 min); the mean blood loss was <50 mL, the mean kidney length was 13.9 cm and the weight was 142 g. There were no intraoperative complications; at autopsy, there was no pelvic or bowel injury.

CONCLUSIONS

Pure NOTES transvaginal nephrectomy is feasible in the porcine model. It has the potential of a less morbid approach, providing truly scar‐less surgery. Further development of instrumentation is necessary.