Photoplethysmographic waveform characteristics of newborns with coarctation of the aorta.

OBJECTIVE: Fetal echocardiography, physical examination and pulse oximetry detect only half of coarctation of aorta (CoA) cases. We aimed to quantify delayed arrival and diminished amplitude of lower extremity photoplethysmographic (PPG) pulses relative to the right hand in affected patients. STUDY DESIGN: We studied 8 CoA infants and 32 healthy controls. The pulse arrival time difference between foot and hand (f-hTD) and pulse amplitude ratio (F/H) were measured on PPG signal waveforms by digitally-determining maxima and minima of systolic decrease of light transmission. Mann-Whitney test was used for group comparisons. RESULTS: In comparison to healthy newborns, CoA infants' PPG waveforms demonstrated prolonged f-hTD (mean±s.d. of 73.2±26.6 versus 35.2±8.3 ms, P<0.001) and lower F/H (0.57±0.26 versus 0.99±0.58, P=0.014). CONCLUSIONS: F-hTD and F/H are quantifiable from hand- and foot-derived PPG waveforms and are significantly different in CoA versus healthy newborns. Larger studies are needed to validate PPG for improved critical congenital heart disease screening.

Tumor MGMT promoter hypermethylation changes over time limit temozolomide efficacy in a phase II trial for metastatic colorectal cancer.

BACKGROUND: Objective response to dacarbazine, the intravenous form of temozolomide (TMZ), in metastatic colorectal cancer (mCRC) is confined to tumors harboring O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter hypermethylation. We conducted a phase II study of TMZ enriched by MGMT hypermethylation in archival tumor (AT), exploring dynamic of this biomarker in baseline tumor (BT) biopsy and plasma (liquid biopsy). PATIENTS AND METHODS: We screened 150 mCRC patients for MGMT hypermethylation with methylation-specific PCR on AT from FFPE specimens. Eligible patients (n = 29) underwent BT biopsy and then received TMZ 200 mg/m(2) days 1-5 q28 until progression. A Fleming single-stage design was used to determine whether progression-free survival (PFS) rate at 12 weeks would be ≥35% [H0 ≤ 15%, type I error = 0.059 (one-sided), power = 0.849]. Exploratory analyses included comparison between MGMT hypermethylation in AT and BT, and MGMT methylation testing by MethylBEAMing in solid (AT, BT) and LB with regard to tumor response. RESULTS: The PFS rate at 12 weeks was 10.3% [90% confidence interval (CI) 2.9-24.6]. Objective response rate was 3.4% (90% CI 0.2-15.3), disease control rate 48.3% (90% CI 32.0-64.8), median OS 6.2 months (95% CI 3.8-7.6), and median PFS 2.6 months (95% CI 1.4-2.7). We observed the absence of MGMT hypermethylation in BT in 62.7% of tumors. CONCLUSION: Treatment of mCRC with TMZ driven by MGMT promoter hypermethylation in AT samples did not provide meaningful PFS rate at 12 weeks. This biomarker changed from AT to BT, indicating that testing BT biopsy or plasma is needed for refined target selection.

Volar fixation of distal radial fracture using compression plate: clinical and radiographic evaluation of 20 patients.

Distal radius fractures can be treated with different methods, depending on the type of fracture and, on our experience, according to the Fernandez algorithm. The report presents our experience treating distal radius fractures using a volar plate. We reviewed retrospectively 20 patients treated, during a period of 3 years (May 2008-May 2011) at our center, for unstable distal radius fractures using a volar plate. All patients were reviewed by thorough clinical examination and standard radiographs of the operated wrist. For the clinical evaluation, we used Mayo Wrist Score and DASH Score. At review, the injured wrist had recovered an average range of motion in flexion-extension of 120°, and the grip strength was an average of 50% compared to contralateral side. Overall, results at Mayo Wrist Score were good to excellent in 30%, satisfactory in 55%, and poor in 15%; results at DASH Score were good to excellent in 90%, satisfactory in 10% with no poor case. The majority of patients were fully satisfied with the results (65%), 20% of patients were partially satisfied, 5% were poorly satisfied, and 10% were not satisfied. At review, 4 patients reported the presence of transient paresthesia localized to the first three rays of the hand. At radiographic evaluation, the majority of patients had a radial tilt between 20 and 23, ulnar variance between 0 and 3, and dorsal tilt between 9 and 14. The treatment of unstable distal radius fractures with a volar plate provided stable internal fixation and allowed early function and was associated with a low complication rate.

Long-term changes in community composition and life-history traits in a highly exploited basin (northern Adriatic Sea): the role of environment and anthropogenic pressures.

The changes in a marine community in the northern Adriatic Sea were explored over a period of 65 years using landings data from a commercial fishing fleet, and the role of fishing pressure and environmental variations in driving these changes was investigated. A total of 40 taxonomic categories, including one or several species, were analysed, representing 93·7% of the total landings. From 1945 to 2010 a significant decrease in the evenness index was observed, indicating a trend towards landings dominated by fewer taxa. The composition of the landings showed a temporal shift during the 1980s; from 1945 to the 1980s a continuous, clear change in composition took place, probably driven by an increase in fishing pressure as well as riverine nutrient inputs. Since the 1980s, a different trend of changing composition emerged. Among the analysed predictors, fishing capacity, summer seawater temperature, inflow from the Po River (the major river of the northern Adriatic Sea) and nutrients were related to the changes in landings. In relation to life-history traits of the landed species, the community shifted from large, late-maturing species to more fecund, smaller and earlier-maturing species. A high fishing pressure is probably the major cause of these changes, possibly acting synergistically with environmental variations.

Beneficial effects on water management of simple hydraulic structures in wetland systems: the Vallevecchia case study, Italy.

Conflicting water uses in coastal zones demand integrated approaches to achieve sustainable water resources management, protecting water quality while allowing those human activities which rely upon aquatic ecosystem services to thrive. This case study shows that the creation and simple management of hydraulic structures within constructed wetlands can markedly reduce the non-point pollution from agriculture and, simultaneously, benefit agricultural activities, particularly during hot and dry periods. The Vallevecchia wetland system is based on a reclaimed 900 ha-large drainage basin in Northern Italy, where droughts recently impacted agriculture causing water scarcity and saltwater intrusion. Rainwater and drained water are recirculated inside the system to limit saltwater intrusion, provide irrigation water during dry periods and reduce the agricultural nutrient loads discharged into the bordering, eutrophic Adriatic Sea. Monitoring (2003-2009) of water quality and flows highlights that the construction (ended in 2005) of a gated spillway to control the outflow, and of a 200,000 m3 basin for water storage, dramatically increased the removal of nutrients within the system. Strikingly, this improvement was achieved with a minimal management effort, e.g., each year the storage basin was filled once: a simple management of the hydraulic structures would greatly enhance the system efficiency, and store more water to irrigate and limit saltwater intrusion.

Adjuvant chemotherapy of bladder cancer.

BACKGROUND: Bladder cancer is one of the most common genitourinary cancer. 1/3 of patients presents with invasive disease. Radical cystectomy is the standard treatment for patients with muscle invasive disease: although local treatment can be curative, about 50% of patients will develop distant metastases. Optimal treatment for high risk patients includes local and perioperative systemic therapy (adjuvant or neoadjuvant chemotherapy). PATIENTS AND METHODS: We performed a review of clinical trials and metanalysis of adjuvant treatment for muscle-invasive bladder cancer. RESULTS: Data from single published trials of adjuvant chemotherapy (CT) are not univocal, and several methodological problems were found. A recent meta-analysis of individual patient data (IPD) from all eligible published and unpublished trials, found that adjuvant chemotherapy administration provides a significant survival and disease free survival advantage. Two large, multi-center, randomized trials are on-going to clarify the role of post-operative CT. CONCLUSIONS: A trend in favour of adjuvant chemotherapy comes out from some of the trials reviewed by us and by the metanalysis performed by the ABC collaborative group. However it is not clear yet which patients might derive the maximum benefit from such an approach and which ones might be safety candidate to deferred treatment, on relapse. The incoming results of the EORTC trial and of the Italian trial which are currently comparing the value of early vs. deferred treatment of patients at higher risk of relapse will probably provide an adequate answer to this question. Outside clinical trials, the potential benefit of adjuvant chemotherapy should be appropriately weighted versus the putative hazards and decision making appropriately tailored in the individual patients according to the aggressiveness of his/her disease and the presence of comorbidities.

Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression.

Weekly docetaxel and gemcitabine as first-line treatment for metastatic breast cancer: results of a multicenter phase II study.

OBJECTIVES: We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. METHODS: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m2 and gemcitabine 800 mg/m2 i.v. on days 1, 8, 15 every 28 days. RESULTS: All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53-28.67) and median time to tumor progression was 13.6 months (95% CI: 10.71-16.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3-4 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. CONCLUSION: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule, in agreement with other published studies, need to be further confirmed within a phase III study.