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Gestational diabetes mellitus (GDM) is a major pregnancy complication affecting approximately 14.0% of pregnancies around the world. Air pollution exposure, particularly exposure to PM 2.5 , has become a major environmental issue affecting health, especially for vulnerable pregnant women. Associations between PM 2.5 exposure and adverse birth outcomes are generally assumed to be the same throughout a large geographical area. However, the effects of air pollution on health can very spatially in subpopulations. Such spatially varying effects are likely due to a wide range of contextual neighborhood and individual factors that are spatially correlated, including SES, demographics, exposure to housing characteristics and due to different composition of particulate matter from different emission sources. This combination of elevated environmental hazards in conjunction with socioeconomic-based disparities forms what has been described as a "double jeopardy" for marginalized sub-populations. In this manuscript our analysis combines both an examination of spatially varying effects of a) unit-changes in exposure and examines effects of b) changes from current exposure levels down to a fixed compliance level, where compliance levels correspond to the Air Quality Standards (AQS) set by the U.S. Environmental Protection Agency (EPA) and World Health Organization (WHO) air quality guideline values. Results suggest that exposure reduction policies should target certain "hotspot" areas where size and effects of potential reductions will reap the greatest rewards in terms of health benefits, such as areas of southeast Los Angeles County which experiences high levels of PM 2.5 exposures and consist of individuals who may be particularly vulnerable to the effects of air pollution on the risk of GDM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Many countries, including Italy, have experienced significant social and spatial inequalities in mortality during the Covid-19 pandemic. This study applies a multiple exposures framework to investigate how joint place-based factors influence spatial inequalities of excess mortality during the first year of the Covid -19 pandemic in the Lombardy region of Italy. For the Lombardy region, we integrated municipality-level data on all-cause mortality between 2015 and 2020 with 13 spatial covariates, including 5-year average concentrations of six air pollutants, the average temperature in 2020, and multiple socio-demographic factors, and health facilities per capita. Using the clustering algorithm Bayesian profile regression, we fit spatial covariates jointly to identify clusters of municipalities with similar exposure profiles and estimated associations between clusters and excess mortality in 2020. Cluster analysis resulted in 13 clusters. Controlling for spatial autocorrelation of excess mortality and health-protective agency, two clusters had significantly elevated excess mortality than the rest of Lombardy. Municipalities in these highest-risk clusters are in Bergamo, Brescia, and Cremona provinces. The highest risk cluster (C11) had the highest long-term particulate matter air pollution levels (PM2.5 and PM10) and significantly elevated NO2 and CO air pollutants, temperature, proportion ≤18 years, and male-to-female ratio. This cluster is significantly lower for income and ≥65 years. The other high-risk cluster, Cluster 10 (C10), is elevated significantly for ozone but significantly lower for other air pollutants. Covariates with elevated levels for C10 include proportion 65 years or older and a male-to-female ratio. Cluster 10 is significantly lower for income, temperature, per capita health facilities, ≤18 years, and population density. Our results suggest that joint built, natural, and socio-demographic factors influenced spatial inequalities of excess mortality in Lombardy in 2020. Studies must apply a multiple exposures framework to guide policy decisions addressing the complex and multi-dimensional nature of spatial inequalities of Covid-19-related mortality., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Eric S Coker reports financial support was provided by Fondazione Eni Enrico Mattei (FEEM)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: This study examines whether the "Emission Reduction Plan for Ports and Goods Movement" in California reduced air pollution exposures and emergency room visits among California Medicaid enrollees with asthma and/or chronic obstructive pulmonary disease., Method: We created a retrospective cohort of 5608 Medicaid enrollees from ten counties in California with data from 2004 to 2010. We grouped the patients into two groups: those living within 500 m of goods movement corridors (ports and truck-permitted freeways), and control areas (away from the busy truck or car permitted highways). We created annual air pollution surfaces for nitrogen dioxide and assigned them to enrollees' home addresses. We used a quasi-experimental design with a difference-in-differences method to examine changes before and after the policy for cohort beneficiaries in the two groups., Results: The reductions in nitrogen dioxide exposures and emergency room visits were greater for enrollees in goods movement corridors than those in control areas in post-policy years. We found that the goods movement actions were associated with 14.8% (95% CI, -24.0% to -4.4%; P = 0.006) and 11.8% (95% CI, -21.2% to -1.2%; P = 0.030) greater reduction in emergency room visits for the beneficiaries with asthma and chronic obstructive pulmonary disease, respectively, in the third year after California's emission reduction plan., Conclusion: These findings indicate remarkable health benefits via reduced emergency room visits from the significantly improved air quality due to public policy interventions for disadvantaged and susceptible populations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Air pollution epidemiological studies suggest that elevated exposure to fine particulate matter (PM2.5) is associated with higher prevalence of term low birth weight (TLBW). Previous studies have generally assumed the exposure-response of PM2.5 on TLBW to be the same throughout a large geographical area. Health effects related to PM2.5 exposures, however, may not be uniformly distributed spatially, creating a need for studies that explicitly investigate the spatial distribution of the exposure-response relationship between individual-level exposure to PM2.5 and TLBW. Here, we examine the overall and spatially varying exposure-response relationship between PM2.5 and TLBW throughout urban Los Angeles (LA) County, California. We estimated PM2.5 from a combination of land use regression (LUR), aerosol optical depth from remote sensing, and atmospheric modeling techniques. Exposures were assigned to LA County individual pregnancies identified from electronic birth certificates between the years 1995-2006 (N=1,359,284) provided by the California Department of Public Health. We used a single pollutant multivariate logistic regression model, with multilevel spatially structured and unstructured random effects set in a Bayesian framework to estimate global and spatially varying pollutant effects on TLBW at the census tract level. Overall, increased PM2.5 level was associated with higher prevalence of TLBW county-wide. The spatial random effects model, however, demonstrated that the exposure-response for PM2.5 and TLBW was not uniform across urban LA County. Rather, the magnitude and certainty of the exposure-response estimates for PM2.5 on log odds of TLBW were greatest in the urban core of Central and Southern LA County census tracts. These results suggest that the effects may be spatially patterned, and that simply estimating global pollutant effects obscures disparities suggested by spatial patterns of effects. Studies that incorporate spatial multilevel modeling with random coefficients allow us to identify areas where air pollutant effects on adverse birth outcomes may be most severe and policies to further reduce air pollution might be most effective., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Macrophage activation syndrome MAS describes the clinical, biological and histological symptoms related to a probably T lymphocytes/NK cell driven stimulation of macrophages with the consequence of a hemophagocytosis involving numerous organs, preferentially bone marrow, explaining the other term of "hemophagocytic syndrome". Clinical symptoms include cytopenia, multiple organ dysfunction, fever unresponsive to antibiotics, fatigue and rash. Infections (bacteria, virus or parasites), lymphoproliferative disorders, cancers, systemic diseases are the most prevalent triggers or etiologies of M.A.S. Evidence of haemaphagocytosis is obtained in the majority of cases with bone marrow specimens. In some cases haemophagocytosis can spare the bone marrow with involvement confined to other tissues such as liver and spleen. Very high levels of ferritine seem to correlate well with the presence of haemophagocytosis and is a possible marker for an early diagnosis. Early treatment initiation is mandatory. Corticosteroids, cytostatic drugs such as etoposide, cyclosporine A, plasmapherese, intravenous immunoglobulins and anti TNFalpha are proposed but no randomized trials were published.

Purpose: Median survival in advanced colorectal cancer patients treated with 5-fluoro-uracil (5FU) and leucovorin (LV) is between 12 and 18 months. The aim of this study was to evaluate long term survival in this disease., Methods: We report here, retrospectively, the survival of 445 patients who entered in first-line prospective studies with LV-5FU-based regimen chemotherapy, between 1985 and 1995., Results: Median survival was 18 months. The 3, 5 and 10 year survival were respectively 17.9%, 4.5% and 2.4%. Seventy-five patients survived more than 3 years, among them, 10 achieved a complete and 34 a partial response, 12 had curative liver or lung surgery. Fifteen patients lived more than 5 years, 2 achieved a complete and 7 a partial response. Seven had curative surgery. Eleven patients were still alive in 2002, among them 7 in complete remission at 5 years, including 3 who did not have surgery., Conclusion: This study shows that some patients with metastatic colorectal cancer can achieve long survival, especially when secondary curative surgery can be performed. However, 1% of the patients can be cured with LV-5FU chemotherapy alone. These results will be probably improve with the use of the new drugs: oxaliplatin and irinotecan.

Background: Studies of bimonthly 48-hour regimens of high-dose leucovorin (LV) (FOLinic acid), 5-fluorouracil (5-FU) by continuous infusion combined with OXaliplatin (FOLFOX) in pretreated patients with metastatic colorectal cancer suggest that oxaliplatin dose intensity is an important prognostic factor for response rate and progression-free survival (PFS). To help define the optimal dose schedule for oxaliplatin in pretreated metastatic colorectal cancer, we retrospectively analyzed data from three phase II studies using different FOLFOX regimens (FOLFOX2, 3 and 6)., Patients and Methods: Data on 126/161 patients were analyzed. FOLFOX2 included oxaliplatin 100 mg/m2; FOLFOX3, 85 mg/m2; and FOLFOX6, 100 mg/m2 (added to a simplified LV-5-FU regimen), all as two-hour infusions. A total of 47 patients received low dose intensity oxaliplatin (LDI: < or = 85 mg/m2/2 weeks) and 79 patients high dose intensity oxaliplatin (HDI: > 85 mg/m2/2 weeks)., Results: Objective responses occurred in 31 (39%) HDI patients and 9 (19%) LDI patients (P = 0.03). Median PFS was 28 weeks, with 52% of HDI patients progression free at 6 months, and 26 weeks with 36% of LDI patients progression free at six months (P = 0.02). Increased oxaliplatin dose intensity was not associated with increased neurotoxicity or other toxicities. FOLFOX are among the most effective regimens for treating LV-5-FU-resistant metastatic colorectal cancer., Conclusions: This study shows that oxaliplatin dose intensification significantly improves response rate and PFS in pretreated metastatic disease without increasing severe toxicity.

The 8 cases of primary breast angiosarcoma which were diagnosed, treated and had their follow-up at the Gustave-Roussy Institute between 1954 and 1995 are reported. The age at presentation ranged from 32 to 68 years. In 4 patients the vascular nature of their mammary lesion was conspicuous by a violaceous discolorations of the overlying skin. No patient had enlarged ipsilateral axillary lymph nodes. One patient had metastases. In 2 out of 5 patients who had a partial surgical or fine-needle biopsy before treatment, the diagnosis was missed, and adequate treatment was unduly delayed. The tumor most often presents as an ill defined area made of dense endothelium-lined papillae. A remarkable picture of "soap bubbles" has been identified in 4 cases. The "meshes" of fatty areas appear to be reinforced as they are infiltrated by tumor cells. This appearance may be specific of mammary angiosarcoma. By the French Cancer Centers' grading system for soft tissue sarcomas in general, grade is III in 3 tumors, II in 2 tumors, I in 3 tumors. Five tumors were treated by total mastectomy only. In 3 cases a total mastectomy was followed by radiation therapy to the chest wall. At diagnosis a chemotherapy was administered only to the patient who had metastases. Median disease-free survival was 9 months. Median overall survival was 13 months. From a review of the literature a simple mastectomy appears to be necessary as well as enough for local treatment. Patients with a grade III angiosarcoma of the breast should be included into a therapeutical trial of adjuvant chemotherapy for soft tissue sarcomas in general.

Preliminary studies suggest synergy between oxaliplatin and fluorouracil (5-FU). To assess this issue, we performed a study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. Regimen consisted of oxaliplatin day 1, 130 mg/m2 every two cycles (folfox 1) or 100 mg/m2/cycle (folfox 2) or 85 mg/m2/cycle (folfox 3) and leucovorin 500 mg/m2 as a 2-hour infusion, followed by 5-FU 22 h infusion 1.5-2 g/m2 for two consecutive days every 2 weeks. One hundred and thirteen patients have been treated. One complete response (CR) and 32 partial responses (PRs) were observed for an overall response rate of 29.2%. Sixty-seven patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU than the one used in the folfox regimens, among them 18 had PRs (26.9%). The best response rate was observed in patients treated with the folfox 2 regimen: 41.7%. From start of folfox, median progression-free survival was 6 months and median survival 13 months. Limiting toxicities were peripheral neuropathy and neutropenia. Fifty-four percent of the patients experienced WHO toxicity > or = grade 3 with the folfox1 regimen, 45% with the folfox2 and 40% with the folfox3. The folfox regimens achieve a high response rate in pretreated patients with CRC. Further studies are needed to determine the best oxaliplatin dose-intensity.

The rational of leucovorin modulation of 5-fluorouracil and the clinical results in colorectal cancer are reviewed with special emphasis on the monthly schedule of low dose leucovorin and 5FU bolus for 5 consecutive days (NCCTG-Mayo Clinic regimen) and the bimonthly schedule of high-dose leucovorin and 5FU bolus plus continuous infusion for two consecutive days (LV5FU2) which is now considered as a new standard.

A 70-year-old woman presented with bilateral anterior uveitis. She was on a gluten-free diet because of a celiac disease which had been diagnosed 3 months before. An anterior chamber aspirate contained a majority of large granular lymphocytes (LGL). The investigation of a chronic neutropenia led to the diagnosis of an otherwise typical T-LGL leukemia. This seems to be the first report of a CD3+ CD4- CD8+ T-LGL leukemia causing anterior uveitis through infiltration of leukemic cells, and the second report of an intriguing association of celiac disease with T-LGL leukemia.

Aim of the Study: To determine the characteristics of 51 cases of isolated local regional breast cancer recurrence., Methods: Retrospective study from 1980 to 1992, survival calculated according to Kaplan-Meier and log-rank test., Results: Twenty-five patients had had a conservative treatment of her primary tumour, 26 had been treated by modified radical mastectomy. Local regional recurrence rate was 9%: 44% of recurrences after lumpectomy and 43% of recurrences after mastectomy occurred within 2 years after the initial treatment. Site of local regional recurrence was chest wall only (16 cases), breast only (15 cases) or axillary or supraclavicular node with or without chest wall or breast involvement (20 cases). The actuarial 5-year survival rate after recurrence is 54%. It depends on the time to recurrence (40% if time to recurrence was less than 2 years, 68% if more than 2 years, p < 0.10), on initial node involvement (36% for N+, 71% for N-, p < 0.15) and on the site of recurrence (chest wall: 43%; breast: 48%; regional node: 12%, p < 0.10)., Conclusion: Like in the literature, severe recurrences are early recurrences, lymph node recurrences and recurrences following a primary tumour with involved axillary nodes.