Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma

Objective: To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed. Materials and methods: The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines. The level required for statistical significance was defined as p < 0.05. Results: The data showed a predominance of M2 phenotype (high percentage of IL-10+TGF-β+) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-β was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGFβ and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months). Conclusion: A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-β production, and consequently greater lymph node involvement and reduced patient survival time. © 2012 Elsevier Ltd. All rights reserved.

The value of intraocular pressure asymmetry in diagnosing glaucoma

PURPOSE

Intensified peginterferon α-2a dosing increases sustained virologic response rates in heavy, high viral load hepatitis c genotype 1 patients with high low-density lipoprotein

BACKGROUND AND GOAL: Patients infected with hepatitis C virus (HCV) with elevated low-density lipoprotein (LDL) levels achieve higher sustained virologic response (SVR) rates after peginterferon (PegIFN)/ribavirin treatment versus patients with lower LDL. Our aim was to determine whether SVR rates in patients with low/elevated LDL can be improved by dose intensification. STUDY: In PROGRESS, genotype 1 patients with baseline HCV RNA≥400,000 IU/mL and body weight ≥85 kg were randomized to 48 weeks of 180 μg/wk PegIFN α-2a (40 kDa) plus ribavirin (A: 1200 mg/d; B: 1400/1600 mg/d) or 12 weeks of 360 μg/wk PegIFN α-2a followed by 36 weeks of 180 μg/wk, plus ribavirin (C: 1200 mg/d; D: 1400/1600 mg/d). This retrospective analysis assessed SVR rates among patients with low (<100 mg/dL) or elevated (≥100 mg/dL) LDL. Patients with high LDL (n=256) had higher baseline HCV RNA (5.86×10 IU/mL) versus patients with low LDL (n=262; 4.02×10 IU/mL; P=0.0003). RESULTS: Multiple logistic regression analysis identified a significant interaction between PegIFN α-2a dose and LDL levels on SVR (P=0.0193). The only treatment-related SVR predictor in the nested multiple logistic regression was PegIFN α-2a dose among patients with elevated LDL (P=0.0074); therefore, data from the standard (A+B) and induction (C+D) dose arms were pooled. Among patients with low LDL, SVR rates were 40% and 35% in the standard and induction-dose groups, respectively; SVR rates in patients with high LDL were 44% and 60% (P=0.014), respectively. CONCLUSIONS: Intensified dosing of PegIFN α-2a increases SVR rates in patients with elevated LDL even with the difficult-to-cure characteristics of genotype 1, high baseline viral load, and high body weight. Copyright © 2013 by Lippincott Williams & Wilkins.

Fraturas de rádio e ulna em cães no período de janeiro de 2001 a dezembro de 2011

Pós-graduação em Cirurgia Veterinária - FCAV

Avaliação da reação em cadeia pela polimerase (PCR) para a detecção do vírus rábico em amostras animais armazenadas por diferentes períodos e submetidas à decomposição

Pós-graduação em Medicina Veterinária - FMVZ

Maxillo-mandibular counter-clockwise rotation and mandibular advancement with TMJ Concepts (R) total joint prostheses Part I - Skeletal and dental stability

The purpose of this study was to evaluate skeletal and dental stability in patients who had temporomandibular joint (TMJ) reconstruction and mandibular counterclockwise advancement using TMJ Concepts total join, prostheses (TMJ Concepts Inc. Ventura, CA) with maxillary osteotomies being performed at the same operation. All patients were operated at Baylor University Medical Center, Dallas TX, USA, by one surgeon (Wolford). Forty-seven females were studied; the average post-surgical follow-up was 40.6 months. Lateral cephalograms were analyzed to estimate surgical and post-surgical changes. During surgery, the occlusal plane angle decreased 14.9 +/- 8.0 degrees. The maxilla moved forward and upward. The posterior nasal spine moved downward and forward. The mandible advanced 7.9 +/- 3.5 mm at the lower incisor tips, 12.4 +/- 5.4 mm at Point B, 17.3 +/- 7.0 mm at menton, 18.4 +/- 8.5 mm at pogonion, and 11.0 +/- 5.3 mm at gonion. Vertically, the lower incisors moved upward -2.9 +/- 4.0 mm. At the longest follow-up post surgery, the maxilla showed minor horizontal changes while all mandibular measurements remained stable. TMJ reconstruction and mandibular advancement with TMJ Concepts total joint prosthesis in conjunction with maxillary osteotomies for counter-clockwise rotation of the rnaxillo-mandibular complex was a stable procedure for these patients at the longest follow-up.

Is the internal connection more efficient than external connection in mechanical, biological, and esthetical point of views? A systematic review

This systematic review aimed to evaluate if the internal connection is more efficient than the external connection and its associated influencing factors. A specific question was formulated according to the Population, Intervention, Control, and Outcome (PICO): Is internal connection more efficient than external connection in mechanical, biological, and esthetical point of views? An electronic search of the MEDLINE and the Web of Knowledge databases was performed for relevant studies published in English up to November 2013 by two independent reviewers. The keywords used in the search included a combination of dental implant and internal connection or Morse connection or external connection. Selected studies were randomized clinical trials, prospective or retrospective studies, and in vitro studies with a clear aim of investigating the internal and/or external implant connection use. From an initial screening yield of 674 articles, 64 potentially relevant articles were selected after an evaluation of their titles and abstracts. Full texts of these articles were obtained with 29 articles fulfilling the inclusion criteria. Morse taper connection has the best sealing ability. Concerning crestal bone loss, internal connections presented better results than external connections. The limitation of the present study was the absence of randomized clinical trials that investigated if the internal connection was more efficient than the external connection. The external and internal connections have different mechanical, biological, and esthetical characteristics. Besides all systems that show proper success rates and effectiveness, crestal bone level maintenance is more important around internal connections than external connections. The Morse taper connection seems to be more efficient concerning biological aspects, allowing lower bacterial leakage and bone loss in single implants, including aesthetic regions. Additionally, this connection type can be successfully indicated for fixed partial prostheses and overdenture planning, since it exhibits high mechanical stability.

Estudo retrospectivo de implantes osseointegrados instalados imediatamente após exodontias

Objectives: to evaluate implant survival immediately placed after tooth extraction considering different sites, prosthodontic modalities, and the need for biomaterials. Material and methods: dental records of 500 patients treated with dental implants between 2004 and 2011 were screened. Results: only 200 records (20%) corresponded to immediate implants. Reasons for tooth extraction included extensive caries, bone loss, and root fractures. From the 197 immediate dental implants, 86 were placed in the maxilla with a survival rate of 93.9% and 111 in the mandible (survival rate of 99.1%). The overall survival rate was 97.46%. Prosthodontic modalities identified were: Brånemark classic complete denture screwed prostheses (36%), overdentures (5.6%), fixed partial denture (31%), and single-tooth prostheses (27.4%). Also, it was observed that in 33% of cases there was a need for the use of grafts and/or biomaterials. Conclusion: it can be concluded that, when correctly indicated, immediate implants are an excellent choice. The anterior mandibular region, screwed and overdenture-type prostheses presented higher success rates when associated to immediate implant placement. The need for bone graft/biomaterial does not affect the clinical results.

Índice de resistência múltipla aos antimicrobianos, concentração inibitória e beta-lactamases de espectro estendido em linhagens de Proteus mirabilis e Proteus vulgaris isoladas de diferentes afecções em animais domésticos

Pós-graduação em Medicina Veterinária - FMVZ

Effects of ocean acidification on the brown alga "Padina pavonica": decalcification due to acute and chronic events

[EN] Since the industrial revolution, anthropogenic CO2 emissions have caused ocean acidification, which particularly affects calcified organisms. Given the fan-like calcified fronds of the brown alga Padina pavonica, we evaluated the acute (shortterm) effects of a sudden pH drop due to a submarine volcanic eruption (October 2011–early March 2012) affecting offshore waters around El Hierro Island (Canary Islands, Spain). We further studied the chronic (long-term) effects of the continuous decrease in pH in the last decades around the Canarian waters. In both the observational and retrospective studies (using herbarium collections of P. pavonica thalli from the overall Canarian Archipelago), the percent of surface calcium carbonate coverage of P. pavonica thalli were contrasted with oceanographic data collected either in situ (volcanic eruption event) or from the ESTOC marine observatory data series (herbarium study). Results showed that this calcified alga is sensitive to acute and chronic environmental pH changes. In both cases, pH changes predicted surface thallus calcification, including a progressive decalcification over the last three decades. This result concurs with previous studies where calcareous organisms decalcify under more acidic conditions. Hence, Padina pavonica can be implemented as a bio-indicator of ocean acidification (at short and long time scales) for monitoring purposes over wide geographic ranges, as this macroalga is affected and thrives (unlike strict calcifiers) under more acidic conditions

Development of musculoskeletal models for the design and the pre-clinical validation of hip resurfacing prosthesis

Background. The surgical treatment of dysfunctional hips is a severe condition for the patient and a costly therapy for the public health. Hip resurfacing techniques seem to hold the promise of various advantages over traditional THR, with particular attention to young and active patients. Although the lesson provided in the past by many branches of engineering is that success in designing competitive products can be achieved only by predicting the possible scenario of failure, to date the understanding of the implant quality is poorly pre-clinically addressed. Thus revision is the only delayed and reliable end point for assessment. The aim of the present work was to model the musculoskeletal system so as to develop a protocol for predicting failure of hip resurfacing prosthesis. Methods. Preliminary studies validated the technique for the generation of subject specific finite element (FE) models of long bones from Computed Thomography data. The proposed protocol consisted in the numerical analysis of the prosthesis biomechanics by deterministic and statistic studies so as to assess the risk of biomechanical failure on the different operative conditions the implant might face in a population of interest during various activities of daily living. Physiological conditions were defined including the variability of the anatomy, bone densitometry, surgery uncertainties and published boundary conditions at the hip. The protocol was tested by analysing a successful design on the market and a new prototype of a resurfacing prosthesis. Results. The intrinsic accuracy of models on bone stress predictions (RMSE < 10%) was aligned to the current state of the art in this field. The accuracy of prediction on the bone-prosthesis contact mechanics was also excellent (< 0.001 mm). The sensitivity of models prediction to uncertainties on modelling parameter was found below 8.4%. The analysis of the successful design resulted in a very good agreement with published retrospective studies. The geometry optimisation of the new prototype lead to a final design with a low risk of failure. The statistical analysis confirmed the minimal risk of the optimised design over the entire population of interest. The performances of the optimised design showed a significant improvement with respect to the first prototype (+35%). Limitations. On the authors opinion the major limitation of this study is on boundary conditions. The muscular forces and the hip joint reaction were derived from the few data available in the literature, which can be considered significant but hardly representative of the entire variability of boundary conditions the implant might face over the patients population. This moved the focus of the research on modelling the musculoskeletal system; the ongoing activity is to develop subject-specific musculoskeletal models of the lower limb from medical images. Conclusions. The developed protocol was able to accurately predict known clinical outcomes when applied to a well-established device and, to support the design optimisation phase providing important information on critical characteristics of the patients when applied to a new prosthesis. The presented approach does have a relevant generality that would allow the extension of the protocol to a large set of orthopaedic scenarios with minor changes. Hence, a failure mode analysis criterion can be considered a suitable tool in developing new orthopaedic devices.

Soft tissue profile changes after bilateral sagittal split osteotomy for mandibular setback: a systematic review

PURPOSE: To evaluate the ratio of soft tissue to hard tissue in bilateral sagittal split setback osteotomy with rigid internal fixation or wire fixation. MATERIALS AND METHODS: A literature search was performed using PubMed, Medline, CINAHL, Web of Science, the Cochrane Library, and Google Scholar Beta. From the original 766 articles identified, 8 articles were included. Two articles were prospective and 6 retrospective. The follow-up period ranged from 1 year to 12.7 years for rigid internal fixation. Two articles on wire fixation were found to be appropriate for inclusion. RESULTS: The differences between short- and long-term ratios of the lower lip to lower incisors for bilateral sagittal split setback osteotomy with rigid internal fixation or wire fixation were quite small. The ratio was 1:1 in the long term and by trend slightly lower in the short term. No distinction was seen between the short- and long-term ratios for mentolabial fold. The ratio was found to be 1:1 for the mentolabial fold to point B. In the short term, the ratio of the soft tissue pogonion to the pogonion showed a 1:1 ratio, with a trend to be lower in the long term. The upper lip showed mainly protrusion, but the amount was highly variable. CONCLUSIONS: This systematic review shows that evidence-based conclusions on soft tissue changes are difficult to draw. This is mostly because of inherent problems of retrospective studies, inferior study designs, and the lack of standardized outcome measurements. Well-designed prospective studies with sufficient samples and excluding additional surgery, ie, genioplasty or maxillary surgery, are needed.

Soft tissue profile changes after bilateral sagittal split osteotomy for mandibular advancement: a systematic review

PURPOSE: The purpose of the present systematic review was to evaluate the soft tissue/hard tissue ratio in bilateral sagittal split advancement osteotomy (BSSO) with rigid internal fixation (RIF) or wire fixation (WF). MATERIALS AND METHODS: The databases PubMed, Medline, CINAHL, Web of Science, Cochrane Library, and Google Scholar Beta were searched. From the original 711 articles identified, 12 were finally included. Only 3 studies were prospective and 9 were retrospective. The postoperative follow-up ranged from 3 months to 12.7 years for RIF and 6 months to 5 years for WF. RESULTS: The short- and long-term ratios for the lower lip to lower incisor for BSSO with RIF or WF were 50%. No difference between the short- and long-term ratios for the mentolabial-fold to point B and soft tissue pogonion to pogonion could be observed. It was a 1:1 ratio. One exception was seen for the long-term results of the soft tissue pogonion to pogonion in BSSO with RIF; they tended to be greater than a 1:1 ratio. The upper lip mainly showed retrusion but with high variability. CONCLUSIONS: Despite a large number of studies on the short- and long-term effects of mandibular advancement by BSSO, the results of the present systematic review have shown that evidence-based conclusions on soft tissue changes are still unknown. This is mostly because of the inherent problems of retrospective studies, inferior study designs, and the lack of standardized outcome measures. Well-designed prospective studies with sufficient sample sizes that have excluded patients undergoing additional surgery (ie, genioplasty or maxillary surgery) are needed.

Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study

There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage.

Postoperative radiotherapy after radical prostatectomy: indications and open questions

Biochemical relapse after radical prostatectomy occurs in approximately 15-40% of patients within 5 years. Postoperative radiotherapy is the only curative treatment for these patients. After radical prostatectomy, two different strategies can be offered, adjuvant or salvage radiotherapy. Adjuvant radiotherapy is defined as treatment given directly after surgery in the presence of risk factors (R1 resection, pT3) before biochemical relapse occurs. It consists of 60-64 Gy and was shown to increase biochemical relapse-free survival in three randomized controlled trials and to increase overall survival after a median followup of 12.7 years in one of these trials. Salvage radiotherapy, on the other hand, is given upon biochemical relapse and is the preferred option, by many centers as it does not include patients who might be cured by surgery alone. As described in only retrospective studies the dose for salvage radiotherapy ranges from 64 to 72 Gy and is usually dependent on the absence or presence of macroscopic recurrence. Randomized trials are currently investigating the role of adjuvant and salvage radiotherapy. Patients with biochemical relapse after prostatectomy should at the earliest sign of relapse be referred to salvage radiotherapy and should preferably be treated within a clinical trial.