Varicella Zoster Virus CNS disease in hematopoietic cell transplantation: A single center experience

Background: Varciella Zoster Virus (VZV) can lead to serious complications in Hematopoietic Cell Transplant (HCT) recipients. Central nervous system (CNS) VZV can be one of the most devastating infections in transplant recipients, yet little is known about this rare disease. Objectives: To describe CNS VZV in the post-transplant period and to define potential risk factors in the HCT population. Methods: We reviewed the course of all patients who received a first HCT at the Fred Hutchinson Cancer Center (FHCRC) in Seattle, WA from 1/1996 through 12/2007. Data were collected retrospectively using the Long-Term Follow-Up database, which includes on-site examinations, outside records, laboratory tests, and yearly questionnaires. Patients were classified as CNS VZV if they had laboratory confirmation of VZV in the cerebrospinal fluid (CSF), or had zoster with associated clinical and laboratory findings consistent with CNS disease. Results: A total of six patients developed VZV CNS disease during the evaluation period (table 1). Diagnosis was confirmed in 3/6 by detection of VZV in CSF by PCR. All other patients had a clinical diagnosis based on the presence of CNS symptoms, zoster, lymphocytic pleiocytosis, and response to IV acyclovir. Patients who developed CNS disease had a mean age of 42 years (range 34-51) at time of transplant. CNS disease developed at a mean of 9 months posttransplantation (range 0.5-24 months), and severity varied, ranging from meningitis (3/6) to encephalitis/myelitis (3/6). All had active graft-versus host disease (GHVD) and all were being treated with immunosuppressive therapy at time of diagnosis. Fever and headache were the most common symptoms, but patients who developed focal CNS findings or seizures (3/6) had a more complicated clinical course. While most patients presented with classic VZV/zoster skin lesions, 2/6 patients had no dermatologic findings associated with their presentation. Four (66%) of patients who developed VZV CNS disease died, two related to VZV complications despite aggressive antiviral therapy. Conclusions: In this cohort of HCT patients, VZV CNS disease was a rare complication. Mortality due to CNS VZV is high, particularly in patients who develop focal neurologic findings or seizures. Even in the absence of skin lesions, VZV CNS disease should be considered in patients who develop fevers and neurologic symptoms.

Cricotracheal resection for laryngeal invasion by thyroid carcinoma: our experience.

Invasion of the laryngeal framework by thyroid carcinoma requires specific surgical techniques and carries a higher rate of complications that deserve to be highlighted. We reviewed our data from 1995 to 2012 and found six patients with laryngotracheal invasion by thyroid carcinoma. All underwent total thyroidectomy and single-stage cricotracheal resection, plus anterolateral neck dissection. Three had airway obstruction that necessitated prior endoscopic debulking. None of the patients needed a tracheotomy. There were four cases of papillary carcinoma, and two cases of undifferentiated carcinoma. One patient died of complications of the procedure (anastomotic dehiscence and tracheo-innominate artery fistula). Another died 2 months after the procedure from local recurrence and aspiration pneumonia. One case presented recurrence at 15 months, which was managed by re-excision and adjuvant radiotherapy; after 26 months of follow-up, he has no evidence of locoregional recurrence. The three other patients are alive without evidence of disease at 6, 18 and 41 months, respectively. Cricotracheal resection for subglottic invasion by thyroid carcinoma is an effective procedure, but carries significant risks of complications. This could be attributed to the devascularisation of the tracheal wall due to the simultaneous neck dissection, sacrifice of the strap muscles or of a patch of oesophageal muscle layer. We advocate a sternocleidomastoid flap to cover the anastomosis. Cricotracheal resection for subglottic invasion can be curative with good functional outcomes, even for the advanced stages of thyroid cancer. Endoscopic debulking of the airway prior to the procedure avoids tracheotomy.

Intra-arterial hepatic fotemustine for the treatment of liver metastases from uveal melanoma: experience in 101 patients.

BACKGROUND: Exclusive liver metastases occur in up to 40% of patients with uveal melanoma associated with a median survival of 2-7 months. Single agent response rates with commonly available chemotherapy are below 10%. We have investigated the use of fotemustine via direct intra-arterial hepatic (i.a.h.) administration in patients with uveal melanoma metastases. PATIENTS AND METHODS: A total of 101 patients from seven centers were treated with i.a.h. fotemustine, administered intra-arterially weekly for a 4-week induction period, and then as a maintenance treatment every 3 weeks until disease progression, unacceptable toxicity or patient refusal. RESULTS: A median of eight fotemustine infusions per patient were delivered (range 1-26). Catheter related complications occurred in 23% of patients; however, this required treatment discontinuation in only 10% of the patients. The overall response rate was 36% with a median overall survival of 15 months and a 2-year survival rate of 29%. LDH, time between diagnosis and treatment start and gender were significant predictors of survival. CONCLUSIONS: Locoregional treatment with fotemustine is well tolerated and seems to improve outcome of this poor prognosis patient population. Median survival rates are among the longest reported and one-third of the patients are still alive at 2 years.

Que faire d'un stagiaire dans votre consultation [Tips for hosting a medical student in a PC consultation].

Hosting a medical student in one's primary care consultation challenges the practitioner to be a clinical teacher as well as providing high-quality patient care. A few tips can make this double task easier. Before the consultation it is possible to define the student's learning objectives and to plan the consultation. During the consultation itself some teaching models exist (One minute preceptor, SNAPP) that facilitate the teaching by maximising the teaching moments for each student-patient encounter. And finally after the consultation a time of reflection where both student and clinical teacher can think about what went well and what could be done better.

Influence d'une hospitalisation prénatale sur les facteurs de stress parentaux lors d'une naissance prématurée [Influence of prenatal hospitalization on parental stressful experience in the case of a premature birth].

OBJECTIVES: To investigate the influence of prenatal hospitalization before a premature birth, on the parental stressful experience, parental symptoms of post-traumatic stress and quality of parent-infant interaction during the hospitalization in neonatology. POPULATION AND METHODS: Population: 51 preterm infants born and 25 full term infants control. Four groups: controls, premature without prenatal hospitalization, premature with a short (<8 days) prenatal hospitalization and premature with a long (≥8 days) prenatal hospitalization. Instruments: the Parental Stressor Scale: Neonatal Intensive Care Unit (PSS: NICU, Miles et al., 1993 [14]) and the Perinatal PTSD Questionnaire (PPQ, Quinnell and Hynan, 1999 [16]). RESULTS: When prenatal hospitalization of the mother occurred, parents acknowledged increased stress induced by the environmental factors during the infant's hospitalization. Furthermore, mothers from the group with a short prenatal hospitalization presented significantly more symptoms of post-traumatic stress. Parents presenting more symptoms of post-traumatic stress describe a significantly more difficult interaction with their infant in neonatology. CONCLUSION: This study highlights the necessity to deliver special care to women hospitalized shortly (<8 days) prior to the delivery of their premature baby. This group is at high risk of presenting post-traumatic stress symptoms, which could have a negative impact on the quality of parent-infant interactions.

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study.

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400 copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90-125 days). The median number of past regimens was 6 (IQR, 3-8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.

The GraftConnector experience. Long-term patency and histological work up in an animal model.

BACKGROUND: A device to perform sutureless end-to-side coronary artery anastomosis has been developed by means of stent technology (GraftConnector). The present study assesses the long-term quality of the GraftConnector anastomosis in a sheep model. METHODS: In 8 adult sheep, 40-55 kg in weight, through left anterior thoracotomy, the right internal mammary artery (RIMA) was prepared and connected to the left anterior descending artery (LAD) by means of GraftConnector, on beating heart, without using any stabilizer. Ticlopidine 250 mg/day for anticoagulation for 4 weeks and Aspirin 100 mg/day for 6 months were given. The animals were sacrificed after 6 months and histological examination of anastomoses was carried out after slicing with the connector in situ for morphological analysis. RESULTS: All animals survived at 6 months. All anastomoses were patent and mean luminal width at histology was 1.8 +/- 0.2 mm; mean myotomia hyperplasia thickness was 0.21 +/- 0.1 mm. CONCLUSIONS: Long-term results demonstrate that OPCABGs performed with GraftConnector had 100% patency rate. The mean anastomotic luminal width corresponds to mean LAD's adult sheep diameter. We may speculate that myotomia hyperplasia occurred as a result of local device oversizing.

Fathers of girls, fathers of boys: influence of child's gender on fathers' experience of, engagement in, and representations of paternity.

The aim of this study was to examine the influence of child's gender on several dimensions-of paternity: the fathers' personal experience of paternity, their involvement in child rearing, and their representations. A total of 147 Swiss fathers of 18-month-old children (65 girls and 82 boys) relationship to the child or relationship with the child's completed questionnaires. The child's gender had little influence on paternal experience, mother. Globally, the fathers took on few responsibilities which were largely devolved to mothers. Fathers of boys were more involved in child care than fathers of girls. Finally, a discrepancy was found between the fathers representations of paternal roles in rearing girls and boys and the actual level of responsibility that fathers adopted in their relationship with their child.

Recurrent Hepatitis C After Liver Transplantation Experience of the First 21 Patients Treated in Lausanne

BACKGROUND AND AIM: Recurrent hepatitis C is a major cause of morbidity and mortality after liver transplantation (LT), and optimal treatment algorithms have yet to be defined. Here, we present our experience of the first 21 patients with recurrent hepatitis C treated in Lausanne. PATIENTS AND METHODS: Twenty-one patients with histologyproven recurrent hepatitis C after LT were treated since 2003. Treatment was initiated with pegylated interferon-α2a 135 μg per week and ribavirin 400 mg per day in the majority of patients, and subsequent doses were adapted individually based on on-treatment virological responses and clinical and/or biochemical side effects. RESULTS: On an intention-to-treat basis, sustained virological response (SVR) was achieved in 12/21 (57%) patients (5/11 [45%], 2/3 [67%], 4/5 [80%] and 1/2 [50%] of patients infected with genotypes 1, 2, 3 and 4, respectively). Two patients experienced relapse and 6 did not respond to treatment (NR). Treatment duration ranged from 24 to 90 weeks. It was stopped prematurely due to adverse events in 5/21 (24%) patients (with SVR achieved in 2 patients, NR in 2 patients, and death of one patient awaiting re-transplantation). Of note, SVR was achieved in a patient with combined liver and kidney transplantation. Importantly, SVR was achieved in some patients despite the lack of an early virological response or HCV RNA negativity at week 24. Darbepoetin α and filgrastim were used in 33% and 14%, respectively. CONCLUSION: Individually adapted treatment of recurrent hepatitis C can achieve SVR in a substantial proportion of LT patients. Conventional stopping rules do not apply in this setting so that prolonged therapy may be useful in selected patients.

Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

BACKGROUND: Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined. METHODS: To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated. RESULTS: Thirty-nine patients with uveal melanoma were identified, including 34 patients who received 3 mg/kg ipilimumab and 5 who received 10 mg/kg ipilimumab. Immune-related response criteria and modified World Health Organization criteria were used to assess the response rate (RR) and the combined response plus stable disease (SD) rate after 12 weeks, after 23 weeks, and overall (median follow-up, 50.4 weeks [12.6 months]). At week 12, the RR was 2.6%, and the response plus SD rate was 46.%; at week 23, the RR was 2.6%, and the response plus SD rate was 28.2%. There was 1 complete response and 1 late partial response (at 100 weeks after initial SD) for an immune-related RR of 5.1%. Immune-related adverse events were observed in 28 patients (71.8%) and included 7 (17.9%) grade 3 and 4 events. Immune-related adverse events were more frequent in patients who received 10 mg/kg ipilimumab than in those who received 3 mg/kg ipilimumab. The median overall survival from the first dose of ipilimumab was 9.6 months (95% confidence interval, 6.3-13.4 months; range, 1.6-41.6 months). Performance status, lactate dehydrogenase level, and an absolute lymphocyte count ≥ 1000 cells/μL at week 7 were associated significantly with survival. CONCLUSIONS: In this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed.

Partial cricotracheal resection for severe pediatric subglottic stenosis: update of the Lausanne experience.

Until recently, severe pediatric subglottic stenosis (SGS) has been treated almost exclusively by laryngotracheoplasty procedures. Even in the most experienced centers, the results of single-stage operations for Cotton's grade III and IV stenoses have been disappointing. This paper reports our experience on 31 partial cricotracheal resections for severe SGS in infants and children. The stenosis was congenital in 6 cases and acquired after prolonged intubation in 25 cases. Twenty-seven patients were tracheotomy-dependent at the time of surgery. Twenty-two cases were classified as grade III and 9 cases as grade IV stenoses according to Cotton. The decannulation rate was 97% (30 of 31 cases) after an open procedure. There were no fatalities and no lesions to the recurrent laryngeal nerves, but there was 1 complete restenosis. Twenty-seven patients show no exertional dyspnea, 3 have a slight stridor with some dyspnea while exercising, and 1 patient is not decannulated. The voice is normal in 21 cases, a dysphonia is present in 9 cases, and the patient with complete restenosis acquired an esophageal voice. Postoperative follow-up is longer than 10 years in 8 cases and longer than 5 years in an additional 6 cases. All patients who reached adulthood show normal growth of the larynx and trachea. Considering the excellent results obtained in this consecutive series of 31 cases, partial cricoid resection with primary thyrotracheal anastomosis should be considered an important treatment option for severe SGS in infants and children.