Tumor Necrosis Factor‐Related Apoptosis‐Inducing Ligand (TRAIL) and Its Death Receptor (DR5) in Peyronie's Disease. A Biomolecular Study of Apoptosis Activation

IntroductionPeyronie's disease (PD) is a connective tissue disorder of tunica albuginea (TA), a thick fibrous sheath surrounding the corpora cavernosa of the penis. Relatively, little is known about the disease itself.AimTo investigate whether the apoptosis cascade in degenerated and macroscopically deformed TA from men with PD is activated through the extrinsic pathway, by assessing the immunoexpression of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and its death receptor, DR5.MethodsTA plaques from 15 men with PD and from four unaffected men were processed for TRAIL and DR5 immunohistochemistry and Western blot analysis.Main Outcome MeasuresA greater understanding of the pathophysiology of PD through a molecular approach, to gain insights that may lead to novel forms of treatment.ResultsActivation of the apoptosis mechanisms through the extrinsic pathway was demonstrated by TRAIL and DR5 overexpression in fibroblasts and myofibroblasts from affected TA.ConclusionThe finding that apoptosis activation in TA plaques occurs, at least in part, via the extrinsic pathway may help devise novel therapeutic options for these patients. Loreto C, Barbagli G, Djinovic R, Vespasiani G, Carnazza ML, Miano R, Musumeci G, Sansalone S. Tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and its death receptor (DR5) in Peyronie's disease. A biomolecular study of apoptosis activation. J Sex Med 2011;8:109–115.     

A comparison between EASI system 12-lead ECGs and standard 12-lead ECGs for improved clinical nursing practice

Aims and objectives. This study was carried out to verify the accuracy of 12‐Lead ECG, obtained through a continuous ECG monitoring system with five cables positioned in EASI mode, to identify basic ECG alterations. Background. This study concerns continuous ECG monitoring systems in Coronary Care Units. Continuous ECG monitoring is an important device for nursing surveillance and is useful in decreasing adverse events. Design and method. Thirteen patients admitted consecutively to the Coronary Care Unit for Acute Myocardial Infarction underwent daily and simultaneous recording of a12‐lead ECG using both procedures: EASI ECG and STANDARD ECG. A sample of 1164 ECG leads acquired in EASI mode was compared with a sample of as many ECG leads acquired using the standard procedure with a traditional cardiograph. Results and conclusions. In the Coronary Care Unit, Continous ECG monitoring with five cables positioned in EASI mode is a valid alternative to the standard 12‐lead ECG for cardiac rhythm abnormalities detection and for acute myocardial ischemia and old myocardial infarction assessment. Therefore, the EASI system might be advantageous for long‐term patient monitoring. Relevance to clinical practice. The EASI system represents a valid device for the nursing surveillance of patients who need continuous ECG monitoring, improves clinical nursing practice in Coronary Care Units, supports the reduction of adverse events such as cardiac arrest and reduces the hospital costs.     

Ultrasonography and stimulating perineural catheters for nerve blocks: a review of the evidence

Purpose: This narrative review summarizes the evidence derived from randomized controlled trials (RCTs) offering blinded assessment and sample size justification, in order to determine the benefits associated with adjunctive ultrasonography (US) and stimulating perineural catheters for nerve blocks. Source: The literature search for this review was conducted during the second week of December 2007 using the MEDLINE (January 1950 to November 2007) and EMBASE (January 1980 to November 2007) databases. For US-guided peripheral and neuraxial blocks, the following medical subject heading (MeSH) terms were searched: “nerve block”, “epidural anesthesia”, “epidural analgesia”, “epidural injection”, “epidural space”, “spinal anesthesia”, and “spinal injection”, the results were combined with “ultrasonography” (MeSH term) and “ultrasound” (key word). For stimulating perineural catheters, the following MeSH terms were cross referenced with the MeSH term, “nerve block”: “peripheral catheterization”, “indwelling catheterization”, “catheterization”, and keywords, “nerve catheter” and “continuous”. Subsequently, the result of this search was combined to “stimulating” (key word). Fifteen RCTs, offering blinded assessment and sample size justification, were retained for analysis. Principal findings: For axillary blocks, US guidance yields a higher success rate than a double-injection, transarterial and a triple-injection, neurostimulation-guided technique. Compared to a quadruple-stimulation technique, no major differences can be found. The addition of nerve stimulation to US guidance offers no clear benefits for axillary blocks. For femoral blocks, compared to neurostimulation, echoguidance is associated with a local anesthetic (LA) sparing effect (up to 42%). In children, US guidance yields a LA sparing effect and a longer duration of action for lower extremity nerve blocks. Compared to their blind counterparts, stimulating catheters seem to offer limited clinical benefits. Despite providing a sparing effect on LA and opioid consumption, stimulating catheters are not associated with a decrease in side effects or analgesia-related expenditures. Conclusions: Published reports of RCTs provide evidence to formulate limited recommendations regarding the use of adjunctive US and stimulating perineural catheters. Further well-designed and meticulously executed RCTs are warranted.     

FRAIL Questionnaire Screening Tool and Short-Term Outcomes in Geriatric Fracture Patients

Objectives

There are limited screening tools to predict adverse postoperative outcomes for the geriatric surgical fracture population. Frailty is increasingly recognized as a risk assessment to capture complexity. The goal of this study was to use a short screening tool, the FRAIL scale, to categorize the level of frailty of older adults admitted with a fracture to determine the association of each frailty category with postoperative and 30-day outcomes.

Locally advanced breast cancer: comparison of mammography,sonography and MR imaging in evaluation of residual disease in women receiving neoadjuvant chemotherapy

The accuracy of mammography, sonography and magnetic resonance imaging (MRI) in identifying residual disease after neoadjuvant chemotherapy is evaluated and imaging findings are correlated with pathologic findings. Fifteen patients enrolled in an experimental protocol of preoperative neoadjuvant chemotherapy underwent clinical examination, mammography, sonography and dynamic MRI, performed in this order, before and respectively after 2 and 4 cycles of neoadjuvant chemotherapy. Four radiologists, two for mammography, one for sonography and one for MR, examined the images, blinded to the results of the other examinations. All patients underwent radical or conservative surgery, and imaging findings were compared with pathologic findings. MRI identified 2/15 (13.3.%) clinically complete response (CR), 9/15 (60%) partial response (PR), 3/15 (20%) stable disease (SD) and 1/15 (6.7%) progressive disease. Mammography identified 1/15 (6.7%) clinically CR, 8/15 (53.3%) PR and 4/15 (27%) SD, and was not able to evaluate the disease in 2/15 (13%) cases. Sonography presented the same results as MRI. Therefore, MRI and sonography compared to mammography correctly identified residual disease in 100 vs. 86%. MRI resulted in two false-negative results because of the presence of microfoci of in situ ductal carcinoma (DCIS) and invasive lobular carcinoma (LCI). MRI was superior to mammography in cases of multifocal or multicentric disease (83 vs. 33%). Sonography performed after MRI improves the accuracy in evaluation of uncertain foci of multifocal disease seen on MR images with an increase of diagnostic accuracy from 73 to 84.5%. MRI assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination and mammography.     

De-escalation therapy in ventilator-associated pneumonia

OBJECTIVE: To evaluate de-escalation of antibiotic therapy in patients with ventilator-associated pneumonia. DESIGN: Prospective observational study during a 43-month period. SETTING: Medical-surgical intensive care unit. PATIENTS: One hundred and fifteen patients admitted to the intensive care unit with clinical diagnosis of ventilator-associated pneumonia. All the episodes of ventilator-associated pneumonia received initial broad-spectrum coverage followed by reevaluation according to clinical response and microbiology. Quantitative cultures obtained by bronchoscopic examination or tracheal aspirates were used to modify therapy. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty-one episodes of ventilator-associated pneumonia were diagnosed. Change of therapy was documented in 56.2%, including de-escalation (the most frequent cause) in 31.4% (increasing to 38% if isolates were sensitive). Overall intensive care unit mortality rate was 32.2%. Inappropriate antibiotic therapy was identified in 9% of cases and was associated with 14.4% excess intensive care unit mortality. Quantitative tracheal aspirates and bronchoscopic samples (58 protected specimen brush and three bronchoalveolar lavage) were associated with 32.7% and 29.5% intensive care unit mortality and 29.3% and 34.4% de-escalation rate. De-escalation was lower (p < .05) in the presence of nonfermenting Gram-negative bacillus (2.7% vs. 49.3%) and in the presence of late-onset pneumonia (12.5% vs. 40.7%). When the pathogen remained unknown, half of the patients died and de-escalation was not performed. CONCLUSION: De-escalation was the most important cause of antibiotic modification, being more feasible in early-onset pneumonia and less frequent in the presence of nonfermenting Gram-negative bacillus. The impact of quantitative tracheal aspirates or bronchoscopic techniques was comparable in terms of mortality.     

Immunolocalization and expression of lubricin in the bilaminar zone of the human temporomandibular joint disc

Lubricin, which is a boundary joint lubricant, was investigated immunohistochemically in the bilaminar zone (BZ) of the human temporomandibular joint (TMJ), without any degenerative changes. Immunohistochemistry for lubricin detection was carried out on 33 TMJ discs obtained from 17 cadavers. Sections were incubated with diluted rabbit polyclonal anti-lubricin antibody and scored according to the percentage of lubricin immunopositive cells. Three different TMJ disc tissue compartments were analyzed, namely: the upper lamina, the inferior lamina and the loose connective tissue in the space between the laminae. The Mann-Whitney U test was used to compare protein expression (lubricin) among disc specimens’ regions. Staining was noted within the TMJ disc cell populations in every disc tissue sample, with almost every cell immunolabeled by the lubricin antibody. The number of disc cells immunolabeled was almost the same in the 3 bilaminar zone regions. Positive extracellular matrix staining was also seen. The results of the present study suggest that lubricin is expressed in the TMJ disc bilaminar zone. Lubricin may have a role in normal disc posterior attachment physiology through the prevention of cellular adhesion as well as providing lubrication during normal bilaminar zone function.     

Immunohistochemical overexpression of platelet-derived growth factor receptor-beta (PDGFR-β) is associated with PDGFRB gene copy number gain in sarcomatoid non-small-cell lung cancer

Introduction

Sarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We hypothesized that the PDGF-B/PDGF-Rβ pathway may be dysregulated in sarcomatoid lung cancer.

Methods

We conducted immunohistochemical (IHC) and gene copy number gain studies of PDGF-B/PDGFR-β on archived surgically resected specimens, 43 sarcomatoid NSCLCs and 42 control NSCLCs that were age, gender and stage-matched. Biomarkers were correlated to patient demographics, tumor characteristics, and survival.

Results

Sarcomatoid tumors had higher PDGFR-β IHC expression than control NSCLC (median score 2.69 vs. 1.93; P < 0.0001). No difference was seen between the two groups of PDGF-B IHC expression; and neither PDGF-B nor PDGFR-β IHC levels correlated with gender, age, clinical or pathologic TNM status, or overall survival. PDGFRB gene copy number was evaluated by FISH using three ways: presence of amplification, gene copy number gain, and gene copy ratio between tumor and normal tissue. PDGFRB gene copy number gain was associated with sarcomatoid histology (P = 0.006), lower clinical and pathologic T-stage (P = 0.07, P = 0.048), and higher pathologic N-stage (P = 0.013). Sarcomatoid NSCLC patients (P = 0.006) and female patients (P = 0.03) had higher gene copy ratios above 1.83. Higher PDGFR-β IHC expression in tumor cells was associated with gene copy number gain (P = 0.021) and higher gene copy ratio status (P = 0.005).

Conclusion

This is the first study to demonstrate high PDGFR-β IHC expression and gene copy number gain in sarcomatoid NSCLC tumors and suggests that further studies are warranted to determine whether PDGFR-β is a feasible therapeutic target in this population.     

A population based assessment of the use of orthopedic surgery in patients with rheumatoid arthritis

OBJECTIVE: To describe the use of orthopedic surgery, including joint replacement surgery, in a well defined population based cohort of patients with rheumatoid arthritis (RA) and to identify characteristics that predict such use. METHODS: A retrospective medical record review was performed of cases of RA incident in Rochester, MN, during the years 1955-85. Patients were followed until 1998. All joint surgeries were recorded, including joint reconstructive surgeries, total joint arthroplasty (TJA), and other joint reconstructive procedures (JRP) such as tendon transfers and resections, joint fusions, and surgeries for fractures and infections involving joints. RESULTS: Of the total 424 RA incident cases, 148 (34.9%) patients underwent one or more (maximum of 20/patient) surgical procedures involving joints during their followup (median 14.8 yrs, range 0.2-42.8 yrs). Overall, this RA cohort had 9.7 surgeries per 100 person-yrs of followup. The estimated cumulative incidence of surgical procedures for RA at 30 yrs was 52.7% +/- SE 4.2. Surgeries for arthritis related joint disease of RA included: primary TJA 76 patients (31.3 +/- 4.1); JRP joint fusion 78 patients (29.4 +/- 3.5); JRP soft tissue 92 patients (29.8 +/- 3.3); and cervical spine fusion one patient. Non-RA (trauma and other) joint surgeries included TJA 26 patients (13.5 +/- 3.4) and arthrotomy for septic arthritis 8 patients (2.4 +/- 0.9). Based on Cox proportional hazards regression, the risk of having a disease related joint surgery for RA is increased in patients who are younger (p < 0.001), have positive rheumatoid factor (p = 0.01), and those with rheumatoid nodules (p < 0.001). There was a borderline significant increase in the risk of first joint surgery in women (p = 0.09). Women also had significantly more joint surgeries (11.5/100 person-yrs) than men (4.9/100 person-yrs; p < 0.001). Survival of patients who had surgery for RA related joint disease was similar to those who did not. CONCLUSION: This is the first population based assessment of joint surgeries performed in patients with RA. Reconstructive surgeries were common, and women had significantly more surgeries than men. Survivorship among patients with RA undergoing surgeries was similar to that of the RA patient population at large.     

Human mammary gland and breast carcinoma contain immunoreactive inhibin/activin subunits: evidence for a secretion into cystic fluid.

OBJECTIVE: Inhibins and activins are members of the transforming growth factor beta superfamily and are known to modulate the growth and differentiation of several cell types. The present study investigated the localization of inhibin and activin subunits in human normal and pathological breast tissues. DESIGN: A cross-sectional study comparing the expression of inhibin/activin subunits alpha, betaA and betaB in surgical specimens from women undergoing reductive mammoplasty (classified, according to the phase of the menstrual cycle, as follicular, luteal, or postmenopausal), and patients submitted to lumpectomy for fibrocystic disease, benign (intraductal papilloma, adenomyoepithelioma, and hamartoma) or malignant breast neoplams (intraductal, intralobular, and invasive carcinoma). METHODS: Immunohistochemistry was used to localize inhibin alpha and activin betaA and betaB subunits in the cytoplasm of epithelial cells of mammary glands. Dimeric activin A, inhibin A and inhibin B were measured by specific two-site enzyme immunoassay in the cystic fluid collected from patients with fibrocystic disease. RESULTS: An intense staining for the alpha inhibin subunit and a mild staining for betaA and betaB subunits were present in samples obtained from normal breast tissue regardless of menstrual cycle phase, and in fibrocystic disease and benign neoplasms. Carcinoma cells stained weakly to moderately for alpha subunit and were negative for betaA and betaB subunits. Fibrocystic disease was associated with absence of betaA subunit expression in normal epithelial cells and intense staining for all subunits in the apocrine cells. Immunoreactive inhibin A, inhibin B, and activin A were also present in cystic fluid, suggesting a local secretion of these proteins. CONCLUSION: These data suggest a local expression and secretion of inhibin and activin in human normal, fibrocystic disease and neoplastic breast tissues. The low expression of these proteins may facilitate abnormal cell proliferation in breast carcinoma.