Macrozoobenthos in the Adriatic Sea ports: Soft-bottom communities with an overview of non-indigenous species.

The present paper is a contribution to the first initiative of the Port Baseline Survey (PBS) for Non-indigenous species (NIS) in the Mediterranean Sea. It presents a report on the soft-bottom macrobenthos from the five Adriatic ports: Bari, Ancona (Italy), Koper (Slovenia), Pula, Rijeka (Croatia), with a focus on the presence and contribution of NIS to native assemblages. Out of 451 species identified, only four were common to all ports. A total of eight NIS were recorded, five in surveyed ports and three in the lagoon connected to the Port of Koper. The highest number of NIS was recorded in Bari, and the highest abundance in Ancona and Bari. Generally, the number, abundance and contribution of NIS seems too low to cause a substantial impact on native communities in surveyed ports. The suitability of methods adopted for PBS for soft-bottom NIS was discussed and suggestion for methodological improvement is provided.

Effects of the installation of offshore pipelines on macrozoobenthic communities (northern and central Adriatic Sea).

Macrozoobenthos living around several pipelines placed at different depths and sediment types in the Western Adriatic Sea was investigated for three years after structures' deployment to detect possible effects due to their installation and presence. Three environmental habitats were considered based on the grain size (silty clay, clayey silt and sand). Samplings were taken within a radius of 100 m from the pipelines and at control sites. Multivariate and univariate analysis showed peculiarities of the three habitats due to the different sediment type, without differences between pipelines and controls inside each group. Silty clay and clayey silt communities appeared quite similar, being mainly represented by opportunistic species typical of the Adriatic coastal area. Benthic populations found at the offshore relict sand were characterized by a higher percentage of sensitive species. Independently of sediment typology, pipelines' installation seems to not affect the benthic populations that appear more influenced by environmental features.

Environmental Impact of Offshore Gas Activities on the Benthic Environment: A Case Study.

Multidisciplinary monitoring of the impact of offshore gas platforms on northern and central Adriatic marine ecosystems has been conducted since 1998. Beginning in 2006, 4-5 year investigations spanning the period before, during, and after rig installation have explored the effects of its construction and presence on macrozoobenthic communities, sediment, water quality, pollutant bioaccumulation, and fish assemblages. In this study, sediment samples collected at increasing distance from an offshore gas platform before, during and after its construction were subjected to chemical analysis and assessment of benthic communities. Ecological indices were calculated to evaluate the ecological status of the area. Ecotoxicological analysis of sediment was performed to establish whether pollutants are transferred to biota. The study applied a before-after control-impact design to assess the effects of rig construction and presence and provide reference data on the possible impacts of any further expansion of the gas extraction industry in the already heavily exploited Adriatic Sea. Only some of the metals investigated (barium, chromium, cadmium, and zinc) showed a different spatial and/or temporal distribution that may be platform-related. In the early phases, the sediment concentrations of polycyclic aromatic hydrocarbons were below the detection limit at all sites; they then became detectable, but without significant spatial differences. The present findings suggest that the environmental effects of offshore gas platforms may be difficult to quantify, interpret, and generalize, because they are influenced by numerous, often local, abiotic, and biotic variables in different and unpredictable ways.

Establishment and cryptic transmission of Zika virus in Brazil and the Americas.

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

Offshore platforms: comparison of five benthic indicators for assessing the macrozoobenthic stress levels.

Within the European Water Framework Directive, many studies have been conducted to evaluate the sensitivity/robustness of a variety of indices in relation to natural or anthropogenic disturbance events. However, these indices have rarely been applied to verify the impacts of disturbances in offshore environments, though the Marine Strategy Framework Directive recommends their use for assessing benthic community conditions and functionality. The aim of this paper was to determine which biotic indicator performed the best for detecting the impacts of offshore structures on benthic populations in the Adriatic Sea. The impacts of four rigs were investigated six months after their installation, and the H', AMBI, m-AMBI, BENTIX, and BOPA indices were assessed. Although these five indices delivered some contradictory results because of the differences in their structure and discrepancies in their assignment of species sensitivity, the BENTIX, H' and BOPA indices appear to evaluate stress levels better than the AMBI and m-AMBI indices, which tend to provide results that are slightly overly optimistic.

Outbreak of acute gastroenteritis in young children with death due to rotavirus genotype G9 in Rio Branco, Brazilian Amazon region, 2005.

BACKGROUND: An epidemic of acute gastroenteritis occurred in Rio Branco City, Acre State, in Brazil's Amazon region in 2005. An investigation was conducted to confirm the etiology and identify possible risk factors for death. METHODS: Rio Branco municipality surveillance data for the period May to October 2005 were reviewed. In a case-control study, children who died following acute gastroenteritis were compared to age-matched controls with acute gastroenteritis who survived. Rotavirus A (RV-A) was investigated in 799 stool samples and genotyped by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The cumulative incidence of diarrhea in children aged <5 years was 21%. A fatal outcome was significantly associated with uncovered household water storage containers. RV-A was identified in 88% of samples and G9 was the prevalent genotype (71%). CONCLUSIONS: Oral rehydration solution and boiling or chlorinating drinking water likely limited mortality. This epidemic was caused by RV-A genotype G9. After the outbreak, a rotavirus vaccine was introduced into the official childhood immunization schedule in Brazil.

Alternating gemcitabine and cisplatin with gemcitabine and radiation in stage IV squamous cell carcinoma of the head and neck.

BACKGROUND: In order to improve our cisplatin-5-fluorouracil (5-FU)-based alternating chemo-radiotherapy regimen, in 1996 we started an investigational program to explore a modified alternating regimen including gemcitabine given both with radiosensitizing and cytotoxic intent. MATERIALS AND METHODS: Based on our previous feasibility trial, we conducted a second study testing the feasibility and activity of the following schedule: gemcitabine 800 mg/m(2) on day 1 and cisplatin 20 mg/m(2) on days 2-5 (weeks 1, 4, 7 and 10) alternated with three courses of radiotherapy (RT) (weeks 2-3, 5-6 and 8-9) with conventional fractionation up to 60 Gy. Gemcitabine 300 mg/m(2) was also administered on the Monday of each week of RT. RESULTS: Forty-seven patients with stage IV (41 patients) unresectable squamous cell carcinoma of the head and neck (SCC-HN) or who had relapsed after surgery (6 patients) were enrolled. None had previously received chemotherapy or radiotherapy. Eight patients (18%) did not complete the treatment. Main grade 3-4 toxicities were as follows: neutropenia (44%); neutropenia with fever (12%); thrombocytopenia (37%); anemia (30% grade 3). One patient died in therapy due to sepsis. Most patients needed hospitalization and tube-feeding or parenteral nutrition. However, 44% of patients had a weight loss >10%. Thirty-four patients had a complete response (72%). Three partial responders were rendered disease-free by surgery (final complete response rate, 79%). At a median follow-up of 38 months actuarial 3-year overall survival, progression-free survival and loco-regional control are 43%, 39% and 64%, respectively. Data of locoregional control favorably compare with those from our database of patients treated with alternating cisplatin-fluorouracil and radiation within controlled clinical trials (64% versus 40%). CONCLUSIONS: The inclusion of gemcitabine into an alternating regimen seems to improve the results achievable with the original alternating program in stage IV patients. However, due to the high acute toxicity correlated, this intensive regimen should be managed by institutions well trained in multidisciplinary treatments.

Gemcitabine, cisplatin, and radiation in advanced, unresectable squamous cell carcinoma of the head and neck: a feasibility study.

Alternating chemoradiotherapy was shown by our institution to be superior to standard radiation in patients with nonsurgical squamous cell carcinoma of the head and neck (SCC-HN). Gemcitabine has shown in vitro and in vivo radiosensitizing properties, synergistic activity with cisplatin, and cytotoxic activity against SCC-HN. Thus, the authors tested the feasibility and antitumoral activity of a modified alternating chemoradiotherapy program that includes gemcitabine. Fourteen patients with stage IV (nine patients) or relapsed after surgery (five patients) unresectable SCC-HN were enrolled. None had previously received chemotherapy or radiotherapy. The treatment plan consisted of cisplatin, 20 mg/m2/day, days 1 to 5, weeks 1 and 5, and gemcitabine 800 mg/m2, day 5, weeks 1, 2, 3, and 5, 6, 7. Radiation was administered during weeks 2, 3, and 4 and 6, 7, and 8 with conventional fractionation up to 60 Gy. At the end of the combined therapy, patients had to receive two additional courses of cisplatin, 20 mg/m2/day, and fluorouracil, 200 mg/m2/day, for 5 days every 21 days. All the patients are evaluable for toxicity and 11 for response. Main grade III-IV toxicities and frequencies were: neutropenia (79%), neutropenia with fever (50%), thrombocytopenia (57%), anemia (35%), mucositis (100%), and cutaneous toxicity (14%). Ten patients (71%) had a weight loss greater than 10%. All but two patients needed hospitalization and tube feeding or parenteral nutrition. The median relative dose intensity of gemcitabine actually delivered was 83%. Two patients died 1 month after the end of treatment before the final evaluation. One patient died of sepsis during the additional cisplatin and fluorouracil courses before response assessment. Ten patients reached a complete response (intention to treat: 71%), and 1 patient had a partial response (9%). At a median follow-up of 34 months, the actuarial 3-year progression-free survival and overall survival are 41% and 63%, respectively. The estimated 3-year locoregional control is 70%. Considering the expected poor prognosis of the enrolled patients, this combined regimen showed an impressive antitumoral activity, but the severity of acute local and hematologic toxicity correlated makes the exportation of this regimen unproposable. However, the activity observed warrants the exploration of different, less toxic, chemo-radiotherapy programs including gemcitabine.

Induction chemotherapy followed by alternating chemo-radiotherapy in stage IV undifferentiated nasopharyngeal carcinoma.

In locally advanced undifferentiated nasopharyngeal carcinoma (UNPC), concomitant chemo-radiotherapy is the only strategy that gave better results over radiation alone in a phase III trial. Adding effective chemotherapy to a concomitant chemo-radiotherapy programme may be a way to improve the results further. 30 patients with previously untreated T4 and/or N2-3 undifferentiated nasopharyngeal carcinoma were consecutively enrolled and initially treated with 3 courses of epidoxorubicin, 90 mg/m2, day 1 and cisplatin, 40 mg/m2, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/m2/day, days 1-4 and fluorouracil, 200 mg/m2/day, days 1-4, i.v. bolus, (weeks 1, 4, 7) alternated to 3 courses of radiation (week 2-3, 5-6, 8-9-10), with a single daily fractionation, up to 70 Gy. WHO histology was type 2 in 30% and type 3 in 70% of the patients. 57% had T4 and 77% N2-3 disease. All the patients are evaluable for toxicity and response. All but one received 3 courses of induction chemotherapy. Toxicity was mild to moderate in any case. At the end of the induction phase 10% of CRs, 83.3% of PRs and 6.7% of SD were recorded. All the patients but one had the planned number of chemotherapy courses in the alternating phase and all received the planned radiation dose. One patient out of 3 developed grade III-IV mucositis. Haematological toxicity was generally mild to moderate. At the final response evaluation 86.7% of CRs and 13.3% of PRs were observed. At a median follow-up of 31 months, 13.3% of patients had a loco-regional progression and 20% developed distant metastases. The 3-year actuarial progression-free survival and overall survival rates were 64% and 83%. Induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients' compliance optimal. This approach showed a very promising activity on locally advanced UNPC and merits to be investigated in phase III studies.

5-Fluorouracil dose intensification and granulocyte-macrophage colony-stimulating factor in cisplatin-based chemotherapy for relapsed squamous cell carcinoma of the head and neck: a phase II study.

A previous phase I study showed that in a 5-day combination of cisplatin (CDDP) 20 mg/m2/day and 5-fluorouracil (5-FU) intravenous bolus, the maximum tolerable dose of 5-FU is 200 mg/m2/day without the use of growth factors and 300 mg/m2/day with recombinant human granulocyte-monocyte colony-stimulating factor (rhGM-CSF) support. In the present phase II study, 26 patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated with CDDP, 20 mg/m2/day, and 5-FU, 300 mg/m2/day intravenous bolus, for 5 consecutive days every 3 weeks. Granulocyte-macrophage colony-stimulating factor, 5 mg/kg/day subcutaneously, was administered from days 8 to 19. All patients had previously undergone surgery and/or radiation treatment. None had previously received chemotherapy. Mucositis (19% of the patients) and thrombocytopenia (42%) were the most frequent, but generally mild, toxicities. Relevant, GM-CSF-related side effects were detected in 12% of the patients. The median number of cycles delivered was four. Three complete and five partial responses were recorded (31% overall response rate). Further investigation of this regimen is unwarranted because of both its lack of improvement in antitumoral activity and the high costs incurred with the use of growth factors.

Primary site as predictive factor of local control in advanced head and neck tumors treated by concomitant boost accelerated radiotherapy.

AIMS AND BACKGROUND: The purpose of this phase II study was to assess the efficacy and toxicity of an accelerated radiotherapy schedule with the concomitant boost technique in the management of patients with advanced head and neck squamous cell carcinomas (HN-SCC) of various primary sites. METHODS: From May 1989 to December 1992 45 patients were scheduled to receive a total dose of 75 Gy in 40 fractions over 40 days. The boost encompassing the macroscopic disease was given as a second daily dose during the last 2 weeks of the basic treatment. RESULTS: Severe mucositis was recorded in 27 (60%) patients. Late side effect occurred in 2. As regards local control the primary tumor site was the most significant prognostic factor: at a median follow-up of 24 months (range 12-52 months) the actuarial local control rate was 79%, 48% and 15% for oronasopharyngeal, laryngohypopharyngeal and oral cavity primary sites, respectively (p = 0.004). CONCLUSIONS: This high dose concomitant boost regimen appears feasible in advanced HN-SCC. However, our results indicate the primary tumor site as a major prognostic factor even with an accelerated treatment schedule.

Alternating cisplatin-5-fluorouracil and radiotherapy in head and neck cancer.

Thirty-four patients with advanced (stage IV) or relapsing squamous cell carcinoma of the head and neck (SCC-HN) were treated alternately with chemotherapy (CT) and radiotherapy (RT). Patients' characteristics were as follows: male: female ratio, 27:7; median age, 55 (34-76), median P.S., 1 (ECOG scale) (range 0-2). Patients studied had no renal, hepatic, or cardiac impairments, a life expectancy of greater than or equal to 3 months, and no previous treatment with RT or CT. Seventeen patients were previously untreated, and 17 had a relapse after radical surgery. The CT regimen consisted of 20 mg/m2 cisplatin, with 2 h forced diuresis, from day 1 to 5, and 200 mg/m2 i.v., from day 1 to 5, every 3 weeks, administered four times. The RT was performed after the first, second, and third CT course, and consisted of three courses of 20 Gy each, 2 Gy daily, 5 days per week. Weekend intervals were planned between CT and RT treatments. The 17 previously untreated patients showed an overall response rate of 88.2% [eight complete response (CR), seven partial response (PR), one stable disease (SD), one progression disease (PD)]; the 17 patients treated at relapse after radical surgery reached an overall response rate of 64.7% (six CR, five PR, six PD). Actuarial median survival is 47 weeks: 51 weeks in untreated patients, and 42 weeks in previously treated patients. Toxicity was mild, and only 10 patients suffered from grade III (WHO scale) gastrointestinal (2 patients), hematological (5 patients), mucosal (2 patients), and neurological (1 patient) toxicity. Neither grade IV toxicity nor treatment-related deaths have been observed. In our study, cisplatin and 5-FU alternating with RT has shown an interesting antitumor activity and moderate side effects.

[Sequential or alternate chemo-radiotherapy in the treatment of advanced head and neck tumors. Results of a randomized study]. / Chemio-radioterapia sequenziale o alternata nella cura dei tumori avanzati della testa e del collo. Risultati di uno studio randomizzato.

Between 1983 and 1986, a multicenter randomized study was conducted to compare a sequential program of induction chemotherapy (CT) followed by radiotherapy (RT), Arm A, with an alternation of 4 cycles of CT with 3 courses of RT (20 Gy/10 fractions up to a total dose of 60 Gy), Arm B, in advanced head and neck cancer patients. The same CT (VBM: Vinblastine, Bleomycin, Methotrexate) was used on both arms; one hundred and sixteen patients (pts) entered the study, 55 in Arm A, 61 in Arm B. Fourty-five pts had stage III and 71 stage IV cancers. The two arms are fully comparable. Up to October 1987, 116 pts are evaluable for survival, while 112 are evaluable for toxicity and 105 for response. In 21 patients (10 in Arm A, 11 in B) the association CT-RT was followed by surgery. Response analysis shows 14 complete responses in Arm A and 30 in Arm B (p less than or equal to 0.03). The median disease-free survival and median overall survival are also statistically different, with an advantage for Arm B (33 vs 22 weeks, p less than or equal to 0.0007, and 59 vs 38 weeks, p less than 0.03 respectively). The actuarial overall survival of complete responders at 50 months is 43% (B) and 21% (A). Toxicity (mainly stage III-IV mucositis) is superior in Arm B (30% vs 4%). Our experience demonstrates the advantages of alternate over sequential CT-RT. A comparison of this cyclic association with RT alone is in progress.

Simultaneous cisplatin and 5-fluorouracil as second-line treatment of head and neck cancer.

Between November 1983 and January 1986, 70 patients with recurrent squamous cell carcinoma of the head and neck were treated with simultaneous cisplatin (20 mg/m2 for 5 consecutive days) and 5-fluorouracil (400-200 mg/m2 by iv push for 5 consecutive days) every 3 weeks. Sixty-seven patients were fully evaluable. The major toxic effect was myelosuppression, and two patients died from septic or hemorrhagic complications. Other toxic effects were moderate and quite rare, including nausea and vomiting. All of the patients were treated in the outpatient clinic. The overall response rate was 52.2% (14 complete responses +21 partial responses). The worst prognostic factor in the present series was the persistence of disease after front-line therapy. This treatment has shown an acceptable toxicity and its antitumoral activity seems to be in the range of the higher activity reported by literature in these kind of patients.

Non-functioning parathyroid carcinoma: a case report.

Non-functioning parathyroid carcinoma is a very rare disease. Only 12 cases have been reported in the literature. The clinical behavior is characterized by the appearance and growth of a neck mass or nodule, which often has been present for many years, and is not accompanied by clinical or laboratory evidence of hypercalcemia or elevated levels of parathyroid hormone (PTH) in peripheral blood. Pathologic findings are similar to those of functioning tumors, and the proof of malignancy is established on the basis of an increased mitotic index only. Data on survival from cases reported in the literature are not conclusive; however, the non-functioning type of parathyroid carcinoma seems to be a more aggressive disease. Radiotherapy seems to be effective in the local control of the disease, but most patients become metastatic. Even if no data are available on response to chemotherapy, the course of the disease is relatively indolent.