Effect of prenatal PAH exposure on birth outcomes and neurocognitive development in a cohort of newborns in Poland. Study design and preliminary ambient data

Preliminary data suggest an association between infant mortality rates and several measures of ambient air pollution, including dustfall and polycyclic aromatic hydrocarbons (PAH). The effects of airborne PAH components on fetal growth and early childhood development are of primary interest since we have previously demonstrated that these pollutants were associated with significant decrements in birthweight, length and head circumference in Polish newborn babies. The undertaken research combines a state-of-the-art environmental monitoring and molecular approaches with comprehensive neurodevelopment assessments. A further innovation is the incorporation of biomarkers (lead and antioxidants in cord blood) to control for potential confounding of exposure-effect. The mean overall concentrations of specific PAH compounds in Kraków were highest for benzo(b)fluoranthene (23 ng/m3), benzo(a)anthracene (16 ng/m3), indeno(l,2,3-cd)pyrene (14 ng/m3), chyresene (13 ng/m3) and benzo(a)pyrene (12 ng/m3). In general, concentrations of the PAH compounds measured by personal monitoring were considerably higher among the residents of the higher polluted area of the city. The comparison between the Kraków and New York City monitoring ambient data demonstrates that the concentrations and proportions of specific compounds in the total PAH mixture differ widely across these cities. Thus, one may expect that the PAH-related health risks would differ between the two areas not only because exposures are different, but also because the PAH profile differs. Presumably, this different profile is a consequence, at least in part, of variations in the sources of fossil and solid fuels used in production of energy. In Poland, solid fuels such as coal is used to a much greater extent than in New York City, where fossil fuels are the universal source of energy production. Auto emissions for example, are low in benzo(a)pyrene, whereas such emissions from refuse burning are high.     

A multidisciplinary therapeutic approach for advanced previously untreated epidermoid cancer of the head and neck: preliminary report.

A pilot study was conducted using two courses of cis-diamminedichloroplatinum, vincristine (Oncovin), and bleomycin (COB) every three weeks prior to surgery(s) and/or radiotherapy in 34 patients with advanced previously untreated epidermoid cancer of the head and neck. All patients received at least one course of chemotherapy; 7 are too early for evaluation. Responses to chemotherapy were dramatic and occurred within a few days. Sixteen patients had partial remission (PR) (59.3%), 9 had minimal response (MR) (33.3%) and 2 had stable disease after one course of COB. Twenty-two patients completed a second course of chemotherapy, 6 (27.3%) had complete remission (CR), 13 (59.1%) had PR, 1 had MR and 2 had stable disease. Objective remission correlated with subjective improvement. Drug toxicity were tolerable and acceptable. Eight patients had surgical resection after chemotherapy, followed by post-operative radiation therapy, and one patient had pre-operative radiation therapy before the tumor was considered resectable. Twelve patients underwent radiotherapy, including patients with CR after chemotherapy. Presently there is no evidence of local recurrence with the longest follow-up of 15+ months. In this preliminary report, the effectiveness and feasibility of this combined modality therapy is established; further study is needed to prove its value in prolonging disease-free period and survival.     

Time from Prior Chemotherapy Enhances Prognostic Risk Grouping in the Second-line Setting of Advanced Urothelial Carcinoma: A Retrospective Analysis of Pooled,Prospective Phase 2 Trials

Background

Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM).

Objectives

The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors.

Design, setting, and participants

Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n = 570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n = 352).

Outcome measurements and statistical analysis

Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures.

Results and limitations

ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic = 0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable.

Conclusions

Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb <10 g/dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials.     

Endovascular repair of para-anastomotic aortic aneurysms

BACKGROUND: Para-anastomotic aneurysms involving the aorta and iliac arteries can occur years after aortic surgery and are at risk for rupture and erosion into surrounding structures. We report on our continued experience with patients who have been treated for these lesions with endovascular management as an alternative to traditional open repair. METHODS: Patients who underwent endovascular repair of para-anastomotic aneurysms involving the distal aortic arch, descending thoracic aorta, abdominal aorta, or iliac arteries were prospectively followed up in a database. Patient comorbidities, initial aortic pathology, initial graft configuration, aneurysm characteristics, evidence of infection, type and configuration of endograft used, and follow-up were analyzed. RESULTS: From 1997 to 2006, 53 patients with 65 para-anastomotic aneurysms were treated with endovascular stent grafts. Patients who were originally treated for aortoiliac occlusive disease presented significantly later than those treated for aneurysmal disease (15.8 vs 8.9 years, P < .01) The initial technical success rate was 98%. Endoleaks were identified in six patients (11%) < or =1 month of surgery, and three required reintervention, including open conversions. Endoleak complications were significantly associated with patients who had symptomatic para-anastomotic aneurysms (P = .01). Perioperative mortality after endovascular repair was 3.8%. Overall mortality within a mean follow-up of 18 months was 49% and was significantly associated with older age at the time of endovascular treatment (P = .03). CONCLUSION: Endovascular repair of para-anastomotic aneurysms involving the aorta and iliac arteries is technically feasible and is associated with a low perioperative morbidity and mortality. Close follow-up is required to identify endoleaks. Long-term survival is limited in older patients. We recommend endovascular stent graft repair for para-anastomotic aneurysms in anatomically suitable patients.     

Incidence and distribution of lower extremity deep vein thrombosis in rehabilitation patients: implications for screening

Patients admitted to in-patient rehabilitation programs have an increased risk for developing deep venous thrombosis (DVT). However, the utility of screening for lower extremity DVT using duplex ultrasound in this high-risk population is not well characterized. The purpose of this study is to identify whether or not screening lower-extremity duplex exams are indicated in this high-risk population. Screening lower extremity duplex exams were performed on all patients admitted to the rehabilitation center at Mt. Sinai Hospital over a 3-year period. Charts were reviewed for patient age, gender, diagnosis, date of screening and follow-up duplex exams, presence and location of venous thrombosis at each duplex exam, history of anticoagulation, and medical DVT prophylaxis. The presence of DVT at screening, the location of DVT along the lower extremity, and the outcome of calf DVT were analyzed in terms of gender, underlying diagnosis, and history of DVT prophylaxis. Lower extremity DVT was detected in 34% of patients. Twenty-three percent of patients had isolated calf vein thrombosis. Men were more likely than women to have DVT. Calf DVTs progressed in 3% of patients over an average follow-up of 2 weeks. The presence of DVT, its location along the lower extremity, and the outcome of calf vein DVT had no significant relationship to underlying diagnosis or history of prophylaxis. Screening duplex exams to detect lower extremity DVT in rehabilitation patients is useful. Screening altered management in 26% of patients, prompting either anticoagulation or repeat duplex exam.     

Nutrition intervention for migraine: a randomized crossover trial

Background

Limited evidence suggests that dietary interventions may offer a promising approach for migraine. The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency.

Methods

Forty-two adult migraine sufferers were recruited from the general community in Washington, DC, and divided randomly into two groups. This 36-week crossover study included two treatments: dietary instruction and placebo supplement. Each treatment period was 16 weeks, with a 4-week washout between. During the diet period, a low-fat vegan diet was prescribed for 4 weeks, after which an elimination diet was used. Participants were assessed at the beginning, midpoint, and end of each period. Significance was determined using student’s t-tests.

Results

Worst headache pain in last 2 weeks, as measured by visual analog scale, was initially 6.4/10 cm (SD 2.1 cm), and declined 2.1 cm during the diet period and 0.7 cm during the supplement period (p=0.03). Average headache intensity (0–10 scale) was initially 4.2 (SD 1.4) per week, and this declined by 1.0 during the diet period and by 0.5 during the supplement period (p=0.20). Average headache frequency was initially 2.3 (SD 1.8) per week, and this declined by 0.3 during the diet period and by 0.4 during the supplement period (p=0.61). The Patient’s Global Impression of Change showed greater improvement in pain during the diet period (p<0.001).

Conclusions

These results suggest that a nutritional approach may be a useful part of migraine treatment, but that methodologic issues necessitate further research.

Trial registration

Clinicaltrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01699009","term_id":"NCT01699009"}}NCT01699009 and {"type":"clinical-trial","attrs":{"text":"NCT01547494","term_id":"NCT01547494"}}NCT01547494.     

First-, second-, third-line therapy for mRCC: benchmarks for trial design from the IMDC

Background:

Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counselling and clinical trial design.

Methods:

Outcomes of mRCC patients from the International mRCC Database Consortium database treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) were calculated using different population inclusion criteria.

Results:

In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P<0.0001). On multivariable analysis, 2 lines and 3+ lines of therapy were each associated with better OS (HR=0.738 and 0.626, P<0.0001). Survival outcomes for the subgroups were as follows: for all patients, OS 20.9 months and PFS 7.2 months; for those similar to eligible patients in the first-line ADAPT trial, OS 14.7 months and PFS 5.6 months; for those similar to patients in first-line TIVO-1 trial, OS 24.8 months and PFS 8.2 months; for those similar to patients in second-line INTORSECT trial, OS 13.0 months and PFS 3.9 months; and for those similar to patients in the third-line GOLD trial, OS 18.0 months and PFS 4.4 months.

Conclusions:

Patients who are able to receive more lines of TT live longer. Survival benchmarks provide context and perspective when interpreting and designing clinical trials.