Evaluating Clinical Use of a Ceramide-dominant, Physiologic Lipid-based Topical Emulsion for Atopic Dermatitis

Objectives: The objective of this study was to evaluate the efficacy of a ceramide-dominant, physiologic lipid-based topical emulsion, inclusive of ceramides, cholesterol, and fatty acids in a 3:1:1 ratio, in the clinical practice setting in subjects with mild-to-moderate atopic dermatitis. The included subjects presented with a wide range of demographic characteristics thus building upon the results reported with this agent from an earlier clinical trial in atopic dermatitis subjects. In addition, the utility of this important treatment approach of starting with a product directed at epidermal barrier repair was explored. Methods: In a 50-center, open-label, interventional study, the ceramide-dominant, physiologic lipid barrier repair emulsion was evaluated for three weeks in 207 patients either as monotherapy or in combination with another atopic dermatitis treatment. Outcome measures included investigator global assessment, investigator and subject satisfaction, subject-perceived improvement in atopic dermatitis, pruritus severity, and two quality-of-life questions. Results: Overall, approximately half of the subjects achieved success with investigator global assessment (clear or almost clear investigator global assessment scores) after three weeks of treatment with the ceramide-dominant, physiologic lipid barrier repair emulsion as monotherapy or in combination with another treatment. A large proportion of subjects (75% of subjects) and investigators (for 77% of subjects) reported satisfaction after three weeks of treatment. Pruritus and quality of life improved during the study. Conclusion: The ceramide-dominant, physiologic lipid-based product was shown to be an effective agent, with or without additional topical therapy, to provide good clinical efficacy and high levels of investigator and patient satisfaction for many patients with mild-to-moderate atopic dermatitis. The results of this study are consistent with results noted in a previous study of atopic dermatitis patients using this same barrier repair agent. The treatment approach of using a skin barrier repair cream as an integral and standard component of initial atopic dermatitis therapy, either as monotherapy or as a part of combination topical therapy, is supported by the outcomes observed in this study. This specific ceramide-dominant, physiologic lipid-based product may be used when initiating topical therapy for atopic dermatitis based on results from this and other studies.     

Satisfaction and regret after open retropubic or robot-assisted laparoscopic radical prostatectomy

BACKGROUND: To counsel patients adequately, it is important to understand the variables influencing satisfaction and regret following prostatectomy. OBJECTIVE: To identify independent predictors for satisfaction and regret after radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Patients who had undergone retropubic radical prostatectomy (RRP) or robot-assisted laparoscopic radical prostatectomy (RALP) between 2000 and 2007 were mailed cross-sectional surveys composed of sociodemographic information, the Expanded Prostate Cancer Index Composite (EPIC), and questions regarding satisfaction and regret. MEASUREMENTS: Sociodemographic variables, perioperative complications, type of procedure, length of follow-up, and EPIC scores were evaluated as independent predictors of satisfaction and regret in multivariate logistic regression analysis. RESULTS AND LIMITATIONS: A total of 400 patients responded (response rate 61%) of whom 84% were satisfied and 19% regretted their treatment choice. In multivariate analysis, lower income (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.03-0.23), shorter follow-up (OR, 0.63; 95% CI, 0.41-0.98), having undergone RRP versus RALP (OR, 4.45; 95% CI, 1.90-10.4)], urinary domain scores (OR, 2.70; 95% CI, 1.60-4.54), and hormonal domain scores (OR, 2.01; 95% CI, 1.30-3.12) were independently associated with satisfaction (p相似文献   

Contemporary outcomes after superficial femoral artery angioplasty and stenting: the influence of TASC classification and runoff score

OBJECTIVE: A recent randomized trial suggested nitinol self-expanding stents (SES) were associated with reduced restenosis rates compared with simple percutaneous transluminal angioplasty (PTA). We evaluated our results with superficial femoral artery (SFA) SES to determine whether TransAtlantic InterSociety Consensus (TASC) classification, indication for intervention, patient risk factors, or Society of Vascular Surgery (SVS) runoff score correlated with patency and clinical outcome, and to evaluate if bare nitinol stents or expanded polytetrafluoroethylene (ePTFE) covered stent placement adversely impacts the tibial artery runoff. METHODS: A total of 109 consecutive SFA stenting procedures (95 patients) at two university-affiliated hospitals from 2003 to 2006 were identified. Medical records, angiographic, and noninvasive studies were reviewed in detail. Patient demographics and risk factors were recorded. Procedural angiograms were classified according to TASC Criteria (I-2000 and II-2007 versions) and SVS runoff scores were determined in every patient; primary, primary-assisted, secondary patency, and limb salvage rates were calculated. Cox proportional hazard model was used to determine if indication, TASC classification, runoff score, and comorbidities affected outcome. RESULTS: Seventy-one patients (65%) underwent SES for claudication and 38 patients (35%) for critical limb ischemia (CLI). Average treatment length was 15.7 cm, average runoff score was 4.6. Overall 36-month primary, primary-assisted, and secondary rates were 52%, 64%, and 59%, respectively. Limb salvage was 75% in CLI patients. No limbs were lost following interventions in claudicants (mean follow-up 16 months). In 24 patients with stent occlusion, 15 underwent endovascular revision, only five (33%) ultimately remained patent (15.8 months after reintervention). In contrast, all nine reinterventions for in-stent stenosis remained patent (17.8 months). Of 24 patients who underwent 37 endovascular revisions for either occlusion or stenosis, eight (35%) had worsening of their runoff score (4.1 to 6.4). By Cox proportional hazards analysis, hypertension (hazard ratio [HR] 0.35), TASC D lesions (HR 5.5), and runoff score > 5 (HR 2.6) significantly affected primary patency. CONCLUSIONS: Self-expanding stents produce acceptable outcomes for treatment of SFA disease. Poorer patency rates are associated with TASC D lesions and poor initial runoff score; HTN was associated with improved patency rates. Stent occlusion and in-stent stenosis were not entirely benign; one-third of patients had deterioration of their tibial artery runoff. Future studies of SFA interventions need to stratify TASC classification and runoff score. Further evaluation of the long-term effects of SFA stenting on tibial runoff is needed.     

A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma

BACKGROUND: Surgical resection of malignant pleural mesothelioma is reported to have up to an 80% rate of local recurrence. We performed a phase II trial of high-dose hemithoracic radiation after complete resection to determine feasibility and to estimate rates of local recurrence and survival. METHODS: Patients were eligible if they had a resectable tumor, as determined by computed tomographic scanning, and adequate cardiopulmonary function for extrapleural pneumonectomy or pleurectomy/decortication. After complete resection, patients received hemithoracic radiation (54 Gy) and then were followed up with serial computed tomographic scanning. RESULTS: From 1995 to 1998, 88 patients (73 men and 15 women; median age, 62.5 years) were entered into the study. The operations performed included 62 extrapleural pneumonectomies (70%) and 5 pleurectomies/decortications; procedures for exploration only were performed in 21 patients. Seven (7.9%) patients died postoperatively. Adjuvant radiation administered to 57 patients (54 undergoing extrapleural pneumonectomy and 3 undergoing pleurectomy/decortication) at a median dose of 54 Gy was well tolerated (grade 0-2 fatigue, esophagitis), except for one late esophageal fistula. The median survival was 33.8 months for stage I and II tumors but only 10 months for stage III and IV tumors (P =.04). For the patients undergoing extrapleural pneumonectomy, the sites of recurrence were locoregional in 2, locoregional and distant in 5, and distant only in 30. CONCLUSION: Hemithoracic radiation after complete surgical resection at a dose not previously reported is feasible. This approach dramatically reduces local recurrence and is associated with prolonged survival for early-stage tumors. Stage III disease has a high risk of early distant relapse and should be considered for trials of systemic therapy added to this regimen of resection and radiation.     

Protease inhibitor monotherapy is associated with a higher level of monocyte activation,bacterial translocation and inflammation

Introduction

Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation.

Methods

We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed.

Results

CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16−CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16−CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01).

Conclusions

Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.     

A case of a bleeding benign gastrocolic fistula in 2014

INTRODUCTION

In the era of proton pump inhibitors in the treatment of peptic ulcer disease, the incidence of a gastrocolic fistula arising from unoperated gastric ulcers is extremely low.

PRESENTATION OF CASE

We present the case of a 68-year old farmer who presented with melaena and was found to have a benign gastrocolic fistula in the setting of untreated peptic ulcer disease, chronic NSAID ingestion and heavy alcohol intake. The diagnosis was made by gastroscopy. En bloc surgery was undertaken due to the size of the fistula and concomitant significant bleeding of the ulcer which would not have made it amenable to medical management.

DISCUSSION

The symptoms of a gastrocolic fistula are undifferentiated and the diagnosis can easily be missed in the setting of other complications such as bleeding or perforation of a hollow viscus. Barium enamas are the most accurate for the diagnosis but gastroscopy with biopsy is usually performed to rule out malignancy. The mainstay of treatment is usually surgical, though patients can be medically managed if he/she is not a surgical candidate.

CONCLUSION

Benign gastrocolic fistulas are rare and its diagnosis is easily missed.     

Collagen type III alpha 1 polymorphism (rs1800255, COL3A1 2209 G>A) assessed with high-resolution melting analysis is not associated with pelvic organ prolapse in the Dutch population

Introduction and hypothesis

The rs1800255, COL3A1 2209 G>A polymorphism in the alpha 1 chain of collagen type III has been associated with an increased risk of pelvic organ prolapse (POP). In one of our previous studies however, polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) misdiagnosed rs1800255, COL3A1 2209 G>A in 6 % of cases. The high-resolution melting (HRM) analysis on the contrary obtained a 100 % accordance for this specific polymorphism and was used in the present study to validate this risk factor for POP.

Methods

In this case–control study, women with and without symptoms of POP were included and compared. DNA was extracted from blood samples. HRM analysis was used to assess for the presence of the homozygous rs1800255. Groups were compared using the Pearson chi-square, Mann–Whitney, and t tests. The discrepancy between HRM and PCR-RFLP results was investigated using PCR-RFLP results available from our previous study.

Results

The study included 354 women: 272 patients with POP and 82 controls; 18 (7 %) cases versus 3 (4 %) controls had a homozygous rs1800255, COL3A1 2209 G>A polymorphism (odds ratio 1.9, 95 % confidence interval 0.5–6.9, compared to the wild type), and thus no association between POP and the homozygous polymorphism could be demonstrated. A discrepancy between HRM and PCR-RFLP results was found in 8 % of the samples.

Conclusions

The previously found statistically significant association between the rs1800255, COL3A1 2209 G>A polymorphism as measured with PCR-RFLP and POP could no longer be demonstrated. This raises concerns regarding the results of other association studies using PCR-RFLP.     

Outcomes following Microvascular Free Tissue Transfer in Reconstructing Skull Base Defects

Objective Successful resection of complex tumors involving the skull base (SB) depends on the ability to reconstruct the resulting defects. The objective of this study was to assess the outcomes of patients undergoing reconstruction after resection of SB tumors with free flaps.Methods From 1995 to 2010 a retrospective review of cases was undertaken. Demographics, histology, surgical management, complications, locoregional control, and survival were analyzed.Results We performed 62 flaps in 57 patients. There was a preponderance of sinonasal malignancies (45%), and most lesions involved the anterior SB (81%). A total of 94% of patients underwent radiotherapy. Reconstruction was undertaken mainly with anterolateral thigh (37%) or radial forearm (34%) flaps. Complications occurred in 17% of patients, and the flap''s success rate was 94%.Conclusion Free flaps are versatile and highly reliable for reconstructing defects resulting from resections of the SB. They should be considered for SB reconstruction of large three-dimensional defects as well as defects involving an irradiated field. Successful reconstruction of the SB can be performed using a small number of highly dependable flaps.     

Respiratory function changes after chemotherapy: an additional risk for postoperative respiratory complications?

BACKGROUND: Patients receiving chemotherapy for lung cancer usually modify their lung function during treatment with increases in forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) and decreases in lung diffusion for carbon monoxide (DLCO). This prospective study was designed to evaluate functional changes in forced expiratory volume in 1 second, forced vital capacity, and DLCO after three courses of induction chemotherapy with cisplatinum and gemcitabine in stage IIIa lung cancer patients and to assess their impact on respiratory complications after lung resection. METHODS: From March 1998 to January 2001, 30 consecutive patients with N2 nonsmall cell lung cancer had surgical resection after neoadjuvant treatment. Pre-chemotherapy and postchemotherapy results of standard respiratory function tests and DLCO were compared in patients with and without postoperative respiratory complications. RESULTS: All 30 patients completed the chemotherapy protocol without respiratory complications. Significant improvements (p < 0.05) were recorded after chemotherapy in transition dyspnea score, PaO(2) (mean value from 79.8 to 86.4 mm Hg), forced expiratory volume in 1 second % (from 78.1% to 87.5%) and forced vital capacity % (from 88.1% to 103.3%). Lung diffusion for carbon monoxide was significantly impaired after chemotherapy (from 74.1% to 65.7%; p = 0.0006), as well as DLCO adjusted for alveolar volume (from 92.8% to 77.4%; p < 0.0001). One patient died after surgery and 4 patients (13.3%) experienced postoperative respiratory complications. Compared with patients without complications, these 4 patients had higher mean increase in FEV(1) after chemotherapy (+26.8% vs + 6.7%; p = 0.025), but greater mean decrease in DLCO/Va (-27.8% vs -13.6%; p = 0.03). Impact of change in DLCO on postoperative respiratory complications was not confirmed by multiple logistic regression analysis (p = 0.16). CONCLUSIONS: In lung cancer patients, forced expiratory volume in 1 second and forced vital capacity assessed after neoadjuvant chemotherapy are not reliable indicators of the likelihood of respiratory complications after surgery. The risk of respiratory complication may be directly linked to loss of DLCO/Va. Lung diffusion for carbon monoxide assessed after neoadjuvant chemotherapy is probably the most sensitive risk indicator of respiratory complications after surgery. We recommend that DLCO studies be performed before and after chemotherapy in lung cancer patients undergoing induction therapy.     

Imported furuncular myiasis in Germany

Furuncular myiasis is a parasitic infestation of human and other vertebrate tissues by fly larvae of primarily two species: Dermatobia hominis (human botfly, t6rsalo, or berne) in Mexico and South and Central America and Cordylobia anthropophaga (tumbu fly or mango fly) in Africa. Cuterebra species (rabbit and rodent botflies) are also rarely reported to cause furuncular myiasis only within the United States. Although these species inhabit different geographic regions and have different life cycles, their clinical presentations can be similar. We describe a case of "imported" human botfly (D. hominis) furuncular myiasis in a U.S. Army soldier stationed in Germany. We review the life cycles of human botflies and key aspects of their clinical presentation, differential diagnosis, and various therapeutic modalities. Most physicians may never encounter myiasis and attribute a patient's complaints to an insect bite or skin infection that will heal without treatment. However, the diagnosis of furuncular myiasis should be considered by remembering the basic elements of this condition: recent travel history to the tropics and a sterile, persistent furuncle with sensations of movement and pain.