Combined treatment with low-dose cyclosporine and calcipotriol/betamethasone dipropionate ointment for moderate-to-severe plaque psoriasis: a randomized controlled open-label study

Combination therapy is a common approach to psoriasis, aimed at improving clinical response and minimizing the risk of side effects. The aim of this pilot randomized open-label study was to evaluate the efficacy and safety of the combination of low-dose cyclosporine (CsA) with calcipotriol-betamethasone dipropionate (CBD) ointment in the treatment of psoriasis. Sixty patients with moderate-to-severe plaque psoriasis were randomized to receive CsA, 2 mg/kg/day, combined with CBD ointment (n = 30) or CsA, at the same daily dosage, in combination with an emollient (n = 30), for 8 weeks. The primary efficacy parameter was the Psoriasis Area and Severity Index (PASI) 75 response rate at 8 weeks. Combination therapy with CsA and CBD ointment was more effective than CsA and emollient treatment, with statistically significant results, particularly less itching after 4 and 8 weeks and PASI reduction at all post-baseline visits. Significantly more patients treated with CsA + CBD achieved the PASI 75 at 8th week (87% vs 37% in the CsA-emollient group; p = 0.0001). The efficacy results were paralleled by the investigator and patient's global assessment of disease severity at the end of study. Our results suggest that the addition of CBD ointment to low-dose CsA enhances clinical response and improves the risk/benefit ratio.     

Hypotension is Uncommon in Patients Presenting to the Emergency Department with Non-traumatic Cardiac Tamponade

Background

Cardiac tamponade is a life-threatening disease in which hypotension is believed to be a common finding. Prior inpatient studies have described normotensive or hypertensive cases of tamponade; however, because the data were not collected from the Emergency Department (ED), the hemodynamic spectrum may differ from those presenting to the ED.

Objectives

We hypothesized that hypotension is uncommon in patients presenting to the ED with non-traumatic tamponade.

Methods

A retrospective chart review was conducted between January 2002 and December 2007 of patients presenting to our ED who were subsequently diagnosed with cardiac tamponade.

Results

A total of 34 patients were identified with a diagnosis of tamponade. The mean blood pressure on ED arrival was 131/79 mm Hg. Upon initial presentation to the ED, 35% (n = 12) of patients were hypertensive, 50% (n = 17) were normotensive, and 15% (n = 5) were hypotensive. Of the 5 patients who were hypotensive on ED arrival, only 2 (6% of all patients) remained hypotensive upon admission to the hospital and before a pericardiocentesis. An average of 995 mL of fluid was removed from the pericardium. The chief complaint for the majority of patients in tamponade was shortness of breath (70%); 59% were tachycardic in the ED, and 72% had cardiomegaly on chest X-ray study.

Conclusions

Hypotension is uncommon in patients presenting to the ED with non-traumatic cardiac tamponade. The majority of patients are normotensive or even hypertensive. Thus, the emergency physician should not exclude the diagnosis of tamponade even in light of normotension or hypertension.     

Ex vivo lung sonography: morphologic-ultrasound relationship

Ultrasound (US) interstitial syndrome is a sonographic lung pattern characterized by the presence of acoustic artifacts (B-lines and white lung). The purpose of this study was to demonstrate how interstitial syndrome is determined by acoustic interactions in lungs of variable density and in healthy organs deflated to a nonphysiologic level of density. Normal rabbit lungs were studied ex vivo by US at varying known degrees of inflation, and their histologic appearances were described. In this experimental setting, US interstitial syndrome recognizes a mechanism related to tissue density or porosity. Artifacts (B-lines and white lung) appear in the normal rabbit lung through air-dependent increases in density. As in pathologic conditions, US interstitial syndrome can be reproduced in histologically normal lungs that are deflated to a critical level (>0.45 g/mL) of density, which is not achievable under physiologic conditions.     

Femoral shaft fractures in the elderly--role of prior bisphosphonate therapy

Introduction

There is a recent surge in interest on bisphosphonate related femoral fractures. Most studies have examined subtrochanteric fractures in patients on long-term bisphosphonates. This study evaluates the characteristics of low-impact femoral shaft fractures in elderly patients on long-term alendronate.

Materials and methods

All patients above 60 years old admitted to the National University Hospital for femoral shaft fracture from January 2003 to January 2007 were retrospectively analysed. Of the 55 patients included, 7 had prior alendronate therapy and were examined in detail.

Results

All 7 patients on prior alendronate therapy sustained their fractures by low-impact or atraumatic mechanisms of injury. 5 of these 7 patients exhibited a characteristic fracture pattern of thickened lateral cortices at the proximal fracture fragment (p < 0.05) and all 7 patients had either transverse or short oblique fractures. Notably, none of the 7 patients had bone mineral density scans prior to their fractures. One patient was started on alendronate after a vertebral compression fracture, whilst the other 6 patients were started on alendronate without any clear clinical indication. All 7 patients reported prodromal thigh pain 3 weeks to 2 years prior to the fracture.

Conclusions

Low-impact femoral shaft fractures in elderly patients on long-term alendronate therapy represent a new entity of insufficiency fractures, with characteristic low-impact modes of injury and fracture patterns on radiograph. Prodromal thigh pain is a warning sign for impending fracture in this group of patients and should be evaluated closely. Teriparatide is a possible alternative to alendronate following such a fracture though more long-term clinical studies are required.     

Does Perception of Usefulness of Arthroscopic Simulators Differ with Levels of Experience?

Background  

Some commercial simulators are available for training basic arthroscopic skills. However, it is unclear if these simulators allow training for their intended purposes and whether the perception of usefulness relates to level of experience.     

Survivin and laryngeal carcinoma prognosis: nuclear localization and expression of splice variants

Marioni G, Agostini M, Bedin C, Blandamura S, Stellini E, Favero G, Lionello M, Giacomelli L, Burti S, D’Angelo E, Nitti D, Staffieri A & De Filippis C
(2012) Histopathology  61, 247–256 Survivin and laryngeal carcinoma prognosis: nuclear localization and expression of splice variants Aims: Aberrant survivin expression in cancer cells has been associated with tumour progression, radiation/drug resistance and shorter patient survival. The aim of the present study was to investigate survivin expression in laryngeal carcinoma (LSCC) tissue and – for the first time at this site – the expression of survivin splice variants. P53 was also studied. Methods and results: Survivin and p53 expression was determined immunohistochemically in 86 consecutive patients operated for LSCC. Survivin mRNA expression was assessed by quantitative real‐time polymerase chain reaction (PCR). Hot‐spot mutations in exons 5, 6, 7 and 8 of the TP53 gene were studied by sequencing analysis. A nuclear localization for survivin predominated. There was a significant association between a higher nuclear survivin expression and LSCC recurrence (P = 0.046). Disease‐free survival (DFS) for LSCC patients with a nuclear survivin expression >7.0% was shorter than in cases whose expression was ≤7.0% (P = 0.05). Wild‐type survivin correlated significantly with nuclear survivin expression (P = 0.02). p53 expression was associated with the co‐expression of wild‐type survivin and survivin‐2B (P = 0.01). Conclusions: Nuclear expression of survivin appears to influence LSCC aggressiveness, a higher nuclear survivin expression correlating with a higher recurrence rate and a shorter DFS. Wild‐type survivin was the most frequently detected splice variant in LSCC tissues.     

Evaluation of dose-volume metrics for microbeam radiation therapy dose distributions in head phantoms of various sizes using Monte Carlo simulations

This work evaluates four dose-volume metrics applied to microbeam radiation therapy (MRT) using simulated dosimetric data as input. We seek to improve upon the most frequently used MRT metric, the peak-to-valley dose ratio (PVDR), by analyzing MRT dose distributions from a more volumetric perspective. Monte Carlo simulations were used to calculate dose distributions in three cubic head phantoms: a 2 cm mouse head, an 8 cm cat head and a 16 cm dog head. The dose distribution was calculated for a 4 × 4 mm2 microbeam array in each phantom, as well as a 16 × 16 mm2 array in the 8 cm cat head, and a 32 × 32 mm2 array in the 16 cm dog head. Microbeam widths of 25, 50 and 75 μm and center-to-center spacings of 100, 200 and 400 μm were considered. The metrics calculated for each simulation were the conventional PVDR, the peak-to-mean valley dose ratio (PMVDR), the mean dose and the percentage volume below a threshold dose. The PVDR ranged between 3 and 230 for the 2 cm mouse phantom, and between 2 and 186 for the 16 cm dog phantom depending on geometry. The corresponding ranges for the PMVDR were much smaller, being 2-49 (mouse) and 2-46 (dog), and showed a slightly weaker dependence on phantom size and array size. The ratio of the PMVDR to the PVDR varied from 0.21 to 0.79 for the different collimation configurations, indicating a difference between the geometric dependence on outcome that would be predicted by these two metrics. For unidirectional irradiation, the mean lesion dose was 102%, 79% and 42% of the mean skin dose for the 2 cm mouse, 8 cm cat and 16 cm dog head phantoms, respectively. However, the mean lesion dose recovered to 83% of the mean skin dose in the 16 cm dog phantom in intersecting cross-firing regions. The percentage volume below a 10% dose threshold was highly dependent on geometry, with ranges for the different collimation configurations of 2-87% and 33-96% for the 2 cm mouse and 16 cm dog heads, respectively. The results of this study illustrate that different dose-volume metrics exhibit different functional dependences on MRT geometry parameters, and suggest that reliance on the PVDR as a predictor of therapeutic outcome may be insufficient.     

A case of recurrent basilar artery occlusion successfully treated with repeated intravascular procedures

Basilar artery occlusion has a poor prognosis, but intra-arterial revascularization therapy has been shown to improve outcome. We report the case of a 32-year-old patient who suffered recurrent basilar artery occlusion and was successfully treated first with mechanical and pharmacological thrombolysis, then with stenting, in 2 separate angiographic sessions. An etiology of vascular dissection may account for the early postprocedural recurrence.