Long gamma nail in the treatment of subtrochanteric fractures.

INTRODUCTION: The purpose of our study was to retrospectively evaluate the clinical and radiological results of subtrochanteric fractures treated with a long gamma nail (LGN). The LGN has been the implant of choice at our level-1 trauma center since 1992. MATERIALS AND METHODS: Over a period of 7 years, we have treated 90 consecutive patients with subtrochanteric fractures. In order to evaluate the clinical and radiological outcomes, we reviewed the clinical and radiographic charts of these patients followed for a mean time of 2 years (range 13-36 months). RESULTS: We found no intra- or perioperative complications nor early or late infection. Clinical and radiological union was achieved at a mean of 4.3 months in all of the patients (range 3-9 months); in 24 cases (30%) the distal locking bolts were retrieved in order to enhance callus formation and remodeling as a planned secondary surgery. Three patients (3.3%) needed unplanned secondary surgery for problems related to the nailing technique. Two mechanical failures with breakage of the nail were encountered due to proximal varus malalignment, of which one was treated with exchange nailing and grafting and the other one by removal of the broken hardware, blade-plating, and bone grafting. One fracture below a short LGN was treated by exchange nailing. CONCLUSIONS: The minimally invasive technique and simple application of the LGN lead to a low percentage of complications in these difficult fractures after a relatively short learning curve. The biomechanical properties of this implant allow early mobilization and partial weight-bearing even in patients with advanced osteoporosis.

Characteristics of eyes with secondary loss of visual acuity receiving variable dosing ranibizumab for neovascular age-related macular degeneration.

PURPOSE: The aim of this work is to investigate the characteristics of eyes failing to maintain visual acuity (VA) receiving variable dosing ranibizumab for neovascular age-related macular degeneration (nAMD) after three initial loading doses. METHODS: A consecutive series of patients with nAMD, who, after three loading doses of intravitreal ranibizumab (0.5 mg each), were re-treated for fluid seen on optical coherence tomography. After exclusion of eyes with previous treatment, follow-up less than 12 months, or missed visits, 99 patients were included in the analysis. The influence of baseline characteristics, initial VA response, and central retinal thickness (CRT) fluctuations on the VA stability from month 3 to month 24 were analyzed using subgroups and multiple regression analyses. RESULTS: Mean follow-up duration was 21.3 months (range 12-40 months, 32 patients followed-up for ≥24 months). Secondary loss of VA (loss of five letters or more) after month 3 was seen in 30 patients (mean VA improvement from baseline +5.8 letters at month 3, mean loss from baseline -5.3 letters at month 12 and -9.7 at final visit up to month 24), while 69 patients maintained vision (mean gain +8.9 letters at month 3, +10.4 letters at month 12, and +12.8 letters at final visit up to month 24). Secondary loss of VA was associated with the presence of pigment epithelial detachment (PED) at baseline (p 0.01), but not with baseline fibrosis/atrophy/hemorrhage, CRT fluctuations, or initial VA response. Chart analysis revealed additional individual explanations for the secondary loss of VA, including retinal pigment epithelial tears, progressive fibrosis, and atrophy. CONCLUSIONS: Tissue damage due to degeneration of PED, retinal pigment epithelial tears, progressive fibrosis, progressive atrophy, or massive hemorrhage, appears to be relevant in causing secondary loss of VA despite vascular endothelial growth factor suppression. PED at baseline may represent a risk factor.

Hypersensitivity pneumonitis secondary to lovebirds: a new cause of bird fancier's disease.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease due to the repetitive inhalation of antigens. Most new cases arise from residential exposures, notably to birds, and are thus more difficult to recognise. The present authors report a 59-yr-old male who complained of dyspnoea and cough while being treated with amiodarone. Pulmonary function tests revealed restriction and obstruction with low diffusing lung capacity for carbon monoxide and partial pressure of oxygen. A high-resolution computed tomography chest scan and bronchoalveolar lavage showed diffuse bilateral ground-glass attenuation and lymphocytic alveolitis, respectively. Initial diagnosis was amiodarone pulmonary toxicity, but because of a rapidly favourable evolution, this diagnosis was questioned. A careful environmental history revealed a close contact with lovebirds shortly before the onset of symptoms. Precipitins were strongly positive against lovebird droppings, but were negative against other avian antigens. The patient was diagnosed with hypersensitivity pneumonitis to lovebirds. Avoidance of lovebirds and steroid treatment led to rapid improvement. The present observation identifies a new causative agent for hypersensitivity pneumonitis and highlights the importance of a thorough environmental history and of searching for precipitins against antigens directly extracted from the patient's environment. These two procedures should allow a more precise classification of some cases of pneumonitis, and thus might avoid progression of active undiagnosed hypersensitivity pneumonitis to irreversible fibrosis or emphysema.

Malignant glioma after ependymoma: an unusual secondary malignancy

Purpose : Secondary malignancies (SM) are a known long-­‐term problem in children surviving brain tumors. We report on two unusual cases of SM observed after treatment of ependymoma. Case reports : 1. The first case is a female survivor of a low-­‐grade ependymoma (Grade II). She had been treated at the age of 3 months with surgery and chemotherapy. A relapse of the primary tumor happened two years later, which was completely removed and treated with local radiotherapy to the posterior fossa. Fifteen years after the first cancer, she developed a pontine glioma near the location of the previous radiotherapy. 2. The second case is a femal survivor of an ependymoma (Grade III) which was removed and irradiated when she was 4 years old. The child developed a pontine glioma near the location of the previous radiotherapy ten years after the diagnosis of the first cancer. Further extension of the disease showed after biopsy PNET-­‐ like features. Both patients passed away. Discussion and Conclusion : Second malignant neoplasia is a rare phenomenon and this risk should not overshadow the great success in treating cancer of childhood. Among the studied risk factors, young age and radiotherapy are well established. The reported patients were followed annually to ensure their remission and both developed symptoms and an unusual unreported secondary cancer a few months after the annual monitoring that was considered as normal. This issue highlights the complexity of monitoring cancer survivors and raises the question of the best way for their long-­‐term follow-­‐up.

Treatment of hepatitis C in HCV mono-infected and in HIV-HCV co-infected patients: an open-labelled comparison study.

BACKGROUND/AIMS: Treatment of chronic HCV infection has become a priority in HIV+ patients, given the faster progression to end-stage liver disease. The primary endpoint of this study was to evaluate and compare antiviral efficacy of Peginterferon alpha 2a plus ribavirin in HIV-HCV co-infected and HCV mono-infected patients, and to examine whether 6 months of therapy would have the same efficacy in HIV patients with favourable genotypes 2 and 3 as in mono-infected patients, to minimise HCV-therapy-related toxicities. Secondary endpoints were to evaluate predictors of sustained virological response (SVR) and frequency of side-effects. METHODS: Patients with genotypes 1 and 4 were treated for 48 weeks with Pegasys 180 microg/week plus Copegus 1000-1200 mg/day according to body weight; patients with genotypes 2 and 3 for 24 weeks with Pegasys 180 microg/week plus Copegus 800 mg/day. RESULTS: 132 patients were enrolled in the study: 85 HCV mono-infected (38: genotypes 1 and 4; 47: genotypes 2 and 3), 47 HIV-HCV co-infected patients (23: genotypes 1 and 4; 24: genotypes 2 and 3). In an intention-to-treat analysis, SVR for genotypes 1 and 4 was observed in 58% of HCV mono-infected and in 13% of HIV-HCV co-infected patients (P = 0.001). For genotypes 2 and 3, SVR was observed in 70% of HCV mono-infected and in 67% of HIV-HCV co-infected patients (P = 0.973). Undetectable HCV-RNA at week 4 had a positive predictive value for SVR for mono-infected patients with genotypes 1 and 4 of 0.78 (95% CI: 0.54-0.93) and of 0.81 (95% CI: 0.64-0.92) for genotypes 2 and 3. For co-infected patients with genotypes 2 and 3, the positive predictive value of SVR of undetectable HCV-RNA at week 4 was 0.76 (95%CI, 0.50-0.93). Study not completed by 22 patients (36%): genotypes 1 and 4 and by 12 patients (17%): genotypes 2 and 3. CONCLUSION: Genotypes 2 or 3 predict the likelihood of SVR in HCV mono-infected and in HIV-HCV co-infected patients. A 6-month treatment with Peginterferon alpha 2a plus ribavirin has the same efficacy in HIV-HCV co-infected patients with genotypes 2 and 3 as in mono-infected patients. HCV-RNA negativity at 4 weeks has a positive predictive value for SVR. Aggressive treatment of adverse effects to avoid dose reduction, consent withdrawal or drop-out is crucial to increase the rate of SVR, especially when duration of treatment is 48 weeks. Sixty-one percent of HIV-HCV co-infected patients with genotypes 1 and 4 did not complete the study against 4% with genotypes 2 and 3.

Surgical treatment of lumbar spinal stenosis. Five-year follow-up.

We carried out a retrospective review of 155 patients with lumbar spinal stenosis who had been treated surgically and followed up regularly: 77 were evaluated at a mean of 6.5 years (5 to 8) after surgery by two independent observers. The outcome was assessed using the scoring system of Roland and Morris, and the rating system of Prolo, Oklund and Butcher. Instability was determined according to the criteria described by White and Panjabi. A significant decrease in low back pain and disability was seen. An excellent or good outcome was noted in 79% of patients; 9% showed secondary radiological instability. Surgical decompression is a safe and efficient procedure. In the absence of preoperative radiological evidence of instability, fusion is not required.

A comparison of dequalinium chloride vaginal tablets (Fluomizin®) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-blind, randomized clinical trial of efficacy and safety.

AIMS: To investigate if vaginal application of dequalinium chloride (DQC, Fluomizin®) is as effective as vaginal clindamycin (CLM) in the treatment of bacterial vaginosis (BV). METHODS: This was a multinational, multicenter, single-blind, randomized trial in 15 centers, including 321 women. They were randomized to either vaginal DQC tablets or vaginal CLM cream. Follow-up visits were 1 week and 1 month after treatment. Clinical cure based on Amsel's criteria was the primary outcome. Secondary outcomes were rate of treatment failures and recurrences, incidence of post-treatment vulvovaginal candidosis (VVC), lactobacillary grade (LBG), total symptom score (TSC), and safety. RESULTS: Cure rates with DQC (C1: 81.5%, C2: 79.5%) were as high as with CLM (C1: 78.4%, C2: 77.6%). Thus, the treatment with DQC had equal efficacy as CLM cream. A trend to less common post-treatment VVC in the DQC-treated women was observed (DQC: 2.5%, CLM: 7.7%; p = 0.06). Both treatments were well tolerated with no serious adverse events occurring. CONCLUSION: Vaginal DQC has been shown to be equally effective as CLM cream, to be well tolerated with no systemic safety concerns, and is therefore a valid alternative therapy for women with BV [ClinicalTrials.gov, Med380104, NCT01125410].

Anti-Nogo-A Antibody Treatment Promotes Recovery of Manual Dexterity after Unilateral Cervical Lesion in Adult Primates--re-examination and Extension of Behavioral Data.

In rodents and nonhuman primates subjected to spinal cord lesion, neutralizing the neurite growth inhibitor Nogo-A has been shown to promote regenerative axonal sprouting and functional recovery. The goal of the present report was to re-examine the data on the recovery of the primate manual dexterity using refined behavioral analyses and further statistical assessments, representing secondary outcome measures from the same manual dexterity test. Thirteen adult monkeys were studied; seven received an anti-Nogo-A antibody whereas a control antibody was infused into the other monkeys. Monkeys were trained to perform the modified Brinkman board task requiring opposition of index finger and thumb to grasp food pellets placed in vertically and horizontally oriented slots. Two parameters were quantified before and following spinal cord injury: (i) the standard 'score' as defined by the number of pellets retrieved within 30 s from the two types of slots; (ii) the newly introduced 'contact time' as defined by the duration of digit contact with the food pellet before successful retrieval. After lesion the hand was severely impaired in all monkeys; this was followed by progressive functional recovery. Remarkably, anti-Nogo-A antibody-treated monkeys recovered faster and significantly better than control antibody-treated monkeys, considering both the score for vertical and horizontal slots (Mann-Whitney test: P = 0.05 and 0.035, respectively) and the contact time (P = 0.008 and 0.005, respectively). Detailed analysis of the lesions excluded the possibility that this conclusion may have been caused by differences in lesion properties between the two groups of monkeys.

Early investigational drugs that target epidermal growth factor receptors for the treatment of head and neck cancer.

INTRODUCTION: Squamous-cell carcinoma of the head and neck (SCCHN) remains a challenging clinical problem, due to the persistent high rate of local and distant failures and the occurrence of secondary primaries. For locally advanced SCCHN, a combination of chemotherapy (CT), radiation or surgery is often used, but there are limitations, which may reduce compliance. Molecular targeted therapies, namely anti-EGFR treatments, are in development with the aim of improving clinical outcomes and mitigating treatment-related toxicities. AREAS COVERED: This review provides an overview of early investigational drugs that target EGFR for the treatment of SCCHN and discusses the ongoing trials in this domain. EXPERT OPINION: Targeted therapies are increasingly used in oncology, especially in SCCHN. Cetuximab has demonstrated a significant improvement in the treatment outcome, both as a curative treatment in combination with radiation therapy and as a palliative treatment in combination with CT; however, it failed to show any benefit in combination with concomitant chemoradiotherapy. Presently, there are many new agents, including monoclonal antibodies and small-molecule tyrosine kinase inhibitors, which are either currently under investigation for or which warrant further investigation for treating SCCHN. The discovery of predictive factors that help to identify patients most likely to respond to EGFR inhibitors as well as patient-customized therapies would help to improve patient outcomes in the future.

Extra-articular knee resection for a secondary chondrosarcoma evolving from an isolated enchondroma of the distal femur: A case report.

Introduction: Enchondromas are among the most current benign bone tumours. Malignant degeneration is extremely rare (<1%) and generally presents as a low grade chondrosarcoma. For localized grade 1 lesions, the treatment of choice is curettage. Wide excision and reconstruction is generally not necessary, unless locally advanced or more aggressive behaviour is suspected at presentation. Case report: A healthy 72 yo male presented with pain and recurrent knee joint effusion. X-rays show a classical central distal metaphyseal enchondroma of the femur associated with subtle osteolysis of the lateral condyle. MRI confirms the presence of a locally aggressive chondromatous lesion based in a classical enchondroma. Core needle biopsy revealed a grade 1 chondrosarcoma, which was in contrast to the radiological aggressiveness of the lesion. Total body CT-scan did not reveal metastatic disease. A wide resection was planned, as a high-grade lesion and joint contamination was suspected. We performed an extra-articular knee resection and reconstruction with a hinged modular total knee megaprosthesis. The definitive histology was grade 1 chondrosarcoma, the surgical margins were wide. The evolution was favourable and the patient was able to perform all his activities of daily living independently without pain at 6 weeks postop. Knee flexion reached 90°. The oncologic screening at 18 months did not show local or distant recurrence. Conclusion: Joints near a benign tumour that suddenly become symptomatic or present an effusion might indicate a malignant transformation. Wide resection and prosthetic reconstruction remains an effective treatment option even in low grade cartilaginous lesions if (1) the adjacent joint is contaminated, or (2) joint-sparing surgery would result in a severe functional impairment of the limb.

Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency.

Hyperammonemic disorders in pediatric patients lead to poorly understood irreversible effects on the developing brain that may be life-threatening. We showed previously that some of these NH4+-induced irreversible effects might be due to impairment of axonal growth that can be protected under ammonium exposure by creatine co-treatment. The aim of the present work was thus to analyse how the genes of arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), allowing creatine synthesis, as well as of the creatine transporter SLC6A8, allowing creatine uptake into cells, are regulated in rat brain cells under NH4+ exposure. Reaggregated brain cell three-dimensional cultures exposed to NH4Cl were used as an experimental model of hyperammonemia in the developing central nervous system (CNS). We show here that NH4+ exposure differentially alters AGAT, GAMT and SLC6A8 regulation, in terms of both gene expression and protein activity, in a cell type-specific manner. In particular, we demonstrate that NH4+ exposure decreases both creatine and its synthesis intermediate, guanidinoacetate, in brain cells, probably through the inhibition of AGAT enzymatic activity. Our work also suggests that oligodendrocytes are major actors in the brain in terms of creatine synthesis, trafficking and uptake, which might be affected by hyperammonemia. Finally, we show that NH4+ exposure induces SLC6A8 in astrocytes. This suggests that hyperammonemia increases blood-brain barrier permeability for creatine. This is normally limited due to the absence of SLC6A8 from the astrocyte feet lining microcapillary endothelial cells, and thus creatine supplementation may protect the developing CNS of hyperammonemic patients.

A new approach in the treatment of high flow native AV fistula: the open-pore external scaffolding prosthesis

Objective: The vascular access steal syndrome is a complication occurring in 1-6% after native arterio-venous (AV) fistulas, often due to huge diameter of the vein. This results in very high flow, which could also be responsible for cardiac overload. The aim of this study is to evaluate the efficiency of a new approach in the treatment of this pathology using open-pore external scaffolding prosthesis.Methods: This a retrospective review of all patients presenting symptomatic high flow after native AV fistula between January 2007 and December 2009 in 3 vascular centers. Pre-operative duplex exam confirmed the diagnosis of high flow. The operation consisted in preparation of the whole fistula, measurement of the flow and section on the venous side. The vein was wrapped with this 6 to 8 mm open-pore external scaffolding prosthesis (ProVena, BBraun, Germany) according to its diameter and to the flow and then sutured. Measurement of the flow was repeated. Patients were followed by duplex exam at 1 week and at 1, 3, 6 and 12 months. Procedural success was defined as complete implantation of the prosthesis and reduction of the flow. Primary outcomes were reduction of the flow and recovery of the symptoms and secondary endpoint was patency of the fistula.Results: During the study period, 14 patients, with a mean age of 65・8 years old, have been operated with this technique.There were 2 native forearmfistulas and 12 on the armwith a mean pre-operative flow of 2600 ml/min (1800-3800). The mode of presentation was pain in 6 patients, neurological disorders in 10 and necrosis in 4. Moreover, 3 patients had cardiac insufficiency due to high flow in the fistula. The procedure was technically successful in 100% of cases. Re-intervention was necessary in 2 patients due to hematoma. Recovery of the initial symptoms occurred in 13 patients (93%). The mean flow reduction was 1200 ml/min (600-2000). In 1 patient, a persistent steal syndrome despite flow reduction to 1400 ml/min resulted in fistula closure 2 months later. At a mean follow-up of 22 months (4-35), all remaining patients (13/14) presented a patent fistula without recurrence.Conclusion: This new approach seems to be safe and effective in the treatment of symptomatic high flow native AV fistulas by significantly reducing the flow and avoiding closure of the vascular access. Longer follow-up with more patients are necessary to evaluate the risk of recurrence.

Once-daily dolutegravir is superior to once-daily darunavir/ritonavir in treatment-naïve HIV-1-positive individuals: 96 week results from FLAMINGO.

INTRODUCTION: Dolutegravir (DTG) 50 mg once daily was superior to darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily through Week 48, with 90% vs. 83% of participants achieving HIV RNA 50 c/mL (p=0.025) [1]. We present data through Week 96. MATERIAL AND METHODS: FLAMINGO is a multicentre, randomized, open-label, Phase IIIb non-inferiority study, in which HIV-1-positive ART-naïve adults with HIV-1 RNA≥1000 c/mL and no evidence of viral resistance were randomized 1:1 to receive DTG or DRV/r, with investigator-selected backbone NRTIs (TDF/FTC or ABC/3TC). Participants were stratified by screening HIV-1 RNA (≤100K c/mL) and NRTI backbone. RESULTS: A total of 484 adults were randomized and treated; 25% had baseline HIV RNA 100K c/mL. At Week 96, the proportion of participants with HIV RNA 50 c/mL was 80% in the DTG arm vs. 68% in the DRV/r arm (adjusted difference 12.4%; 95% CI 4.7, 20.2%; p=0.002). Secondary analyses supported primary results: per-protocol [(DTG 83% vs. DRV/r 70%), 95% CI 12.9 (5.3, 20.6)] and treatment-related discontinuation = failure [(98% vs. 95%), 95% CI 3.2 (-0.3, 6.7)]. Overall virologic non-response (DTG 8%; DRV/r 12%) and non-response due to other reasons (DTG 12%; DRV/r 21%) occurred less frequently on DTG. As at Week 48, the difference between arms was most pronounced in participants with high baseline viral load (82% vs. 52% response through Week 96) and in the TDF/FTC stratum (79% vs. 64%); consistent responses were seen in the ABC/3TC stratum (82% vs. 75%). Six participants (DTG 2, none post-Week 48; DRV/r 4, two post-Week 48) experienced protocol-defined virologic failure (PDVF; confirmed viral load 200 c/mL on or after Week 24); none had treatment-emergent resistance to study drugs. Most frequent drug-related adverse events (AEs) were diarrhoea, nausea and headache, with diarrhoea significantly more common on DRV/r (24%) than DTG (10%). Significantly more participants had Grade 2 fasting LDL toxicities on DRV/r (22%) vs. DTG (7%), p<0.001; mean changes in creatinine for DTG (~0.18 mg/dL) observed at Week 2 were stable through Week 96. CONCLUSIONS: Once-daily DTG was superior to once-daily DRV/r in treatment-naïve HIV-1-positive individuals, with no evidence of emergent resistance to DTG in virologic failure and relatively similar safety profiles for DTG and DRV/r through 96 Weeks.

Cost-effectiveness of low-molecular-weight heparin for treatment of pulmonary embolism.

BACKGROUND: Low-molecular-weight heparin (LMWH) appears to be safe and effective for treating pulmonary embolism (PE), but its cost-effectiveness has not been assessed. METHODS: We built a Markov state-transition model to evaluate the medical and economic outcomes of a 6-day course with fixed-dose LMWH or adjusted-dose unfractionated heparin (UFH) in a hypothetical cohort of 60-year-old patients with acute submassive PE. Probabilities for clinical outcomes were obtained from a meta-analysis of clinical trials. Cost estimates were derived from Medicare reimbursement data and other sources. The base-case analysis used an inpatient setting, whereas secondary analyses examined early discharge and outpatient treatment with LMWH. Using a societal perspective, strategies were compared based on lifetime costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio. RESULTS: Inpatient treatment costs were higher for LMWH treatment than for UFH (dollar 13,001 vs dollar 12,780), but LMWH yielded a greater number of QALYs than did UFH (7.677 QALYs vs 7.493 QALYs). The incremental costs of dollar 221 and the corresponding incremental effectiveness of 0.184 QALYs resulted in an incremental cost-effectiveness ratio of dollar 1,209/QALY. Our results were highly robust in sensitivity analyses. LMWH became cost-saving if the daily pharmacy costs for LMWH were < dollar 51, if > or = 8% of patients were eligible for early discharge, or if > or = 5% of patients could be treated entirely as outpatients. CONCLUSION: For inpatient treatment of PE, the use of LMWH is cost-effective compared to UFH. Early discharge or outpatient treatment in suitable patients with PE would lead to substantial cost savings.