Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis.

Background The MPL(Ser505Asn) mutation has been reported to be a cause of hereditary thrombocythemia. Recently, we detected this mutation in a large proportion of children with familial thrombocythemia, suggesting that in Italy the incidence of MPL(Ser505Asn) mutation could be underestimated. DESIGN AND METHODS: We extended the search for this mutation to all patients with essential thrombocythemia who had a positive family history for thrombocytosis or essential thrombocythemia. We identified eight Italian families positive for the MPL(Ser505Asn) mutation. Clinical and hematologic data were available for members of seven families, including 21 patients with a proven mutation and 20 relatives with thrombocytosis. RESULTS: Fifteen major thrombotic episodes, nine of which were fatal, were recorded among 41 patients. The thrombotic manifestation was stroke in four cases, myocardial infarction in seven cases, fetal loss in two cases, deep vein thrombosis of the leg in one case and Budd Chiari syndrome in one case. Almost all patients over 20 years old had splenomegaly and bone marrow fibrosis, while these were rarely observed in patients under 20 years old, suggesting that these manifestations are associated with aging. Finally, the life expectancy of family members with thrombocytosis was significantly shorter than that of members without thrombocytosis (P=0.003). Conclusions Patients with familial thrombocytosis caused by a MPL(Ser505Asn) mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy

Mapping and assessment of forest ecosystems and their services - Applications and guidance for decision making in the framework of MAES

The aim of this report is to illustrate by means of a series of case studies the implementation of mapping and assessment of forest ecosystem services in different contexts and geographical levels. Methodological aspects, data issues, approaches, limitations, gaps and further steps for improvement are analysed for providing good practices and decision making guidance. The EU initiative on Mapping and Assessment of the state of Ecosystems and their Services (MAES), with the support of all Member States, contributes to improve the knowledge on ecosystem services. MAES is one of the building-block initiatives supporting the EU Biodiversity Strategy to 2020.JRC.H.3-Forest Resources and Climat

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Background Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), 416,746 individuals from 10 countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident lung cancer (n = 3731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1489 matched controls for whom serum cotinine was available. Results Haem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00-1.07), and in the highest versus lowest quintile (HR 1.16, 95% CI 1.02-1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case-control subset. Conclusions Greater haem iron intake may be modestly associated with lung cancer risk.Peer reviewe

A case of late isolated ovarian relapse of acute lymphoblastic leukemia after an allogeneic stem cell transplant.

We report the case of a 30-year-old Caucasian female who had an isolated ovarian relapse 13 years after a diagnosis of acute lymphoblastic leukemia (ALL) and 8 years after an allogeneic peripheral blood hematopoietic stem cell transplant (HSCT)

Clinical and Biological Features, Treatment and Long-Term Outcome of 65 Children with Ph- Myeloprolipherative Disorders (MPD).

Introduction: MPD rarely occur in children and published data of pediatric patients (pts) are limited. In adults, current diagnostic criteria are those of the WHO2008 and the therapeutic options are supported by controlled studies. From our experience, we suggested that the biological markers show a clinical relevance in Ph- MPD children and may influence their management. Patients and methods: We retrospectively analyzed 65 pts aged 20 years (yrs) at diagnosis (dx) with Ph-negative MPD, observed between December 1981 and March 2009. Dx was performed according to the PVSG or WHO criteria. Since 2002, 52/65 pts were studied for JAK2 mutations, polycytemia rubra vera-1 (PRV-1) RNA expression, thrombopoietin (TPO) and its receptor (c-MPL) mutations, erythropoietin receptor (EPO-r) gene mutations, spontaneous endogenous erythroid colony (EECs) growth, clonality on female pts. Results: Thirty-nine females and 26 males with a median age at dx of 14 yrs were classified as follow: 34 (52%) essential thrombocythemia (ET), 16 (24.5%) familial thrombocythemia (FT), 11 (17%) polycythemia vera (PV), 3 (4.5%) familial polycythemia (FP) and 1 idiopathic myelofibrosis (IM). Clinical and biological data, treatment and outcome are reported. Pts with familial disease were younger than those with the sporadic form (p<.05). Hematocrit (Hct) values were higher in ET than in FT pts (p .0047). Fifty pts underwent a bone marrow aspirate and biopsy (15 FT and FP children were excluded). No chromosome abnormalities were found. Overt fibrosis was present in 1 pt. Symptoms at dx were recorded in 21/64 pts (33%) and splenomegaly was present in 13/64 (20%), more frequently in sporadic disease pts. The JAK2V617F mutation was found in 47.5% of ET and 27% of PV. Clonal myelopoiesis was present in 7/11 (63.5%) ET and 2/3 PV females. None of the FT and FP pts showed JAK2V617F mutations or clonality. EECs grew in 58% of ET, in 42% of FT and in 40% of PV. PRV-1 RNA overexpression was found in 29/44 pts (66%). No EECs growth or EPO-r gene mutation was found in FP pts. The median EPO level was 5 mU/ml (1.1–16.4) in polycythemic pts. MPLS505A mutations were detected in15/16 FT pts and a novel HIF2A mutation in 1 FP pt. Treatment was modified during follow-up (f-up): 15 children did not undergo any treatment and 16 pts received more than one cytoreductive drugs. Phlebothomies were carried out in 9 polycythemic pts. Overall, 26 pts were treated with different cytoreductive drugs (hydroxyurea, interferone-alpha, anagrelide and pipobroman). Because of the persistently higher platelet (PLT) count, ET children needed more cytoreductive drugs than FT pts (p .0006). Anti-platelet agents were used in 40 pts and stopped in 30. No hemorrhagic events were recorded; 3 pts (5%) developed thromboses. Eight pts had 11 pregnancies (4 abortions: 2 spontaneous). Five pts showed progressive splenomegaly, 2 (1 PV and 1 ET, untreated) of them developed IM. Two pts developed a cancer. All pts are alive after a median f-up of 10 yrs. Conclusions: This represents the largest reported series of pediatric MPD. A broad familial work-up combined to molecular analyses allowed us to characterize the MPD disorders in our pediatric population, to plan suitable treatments and to better manage their disease. ET (34 pts) FT (16 pts) PV (11 pts) FP (3 pts) IM (1 pt) -------------------------------------------------------------------------------- M/F 10/24 7/9 8/3 1/2 F Age at Dx (yrs) 15.53 (5.24–19.75) 11.91 (0.22–17.45) 16.47 (3.68–18.8) 11.18 (11.18–14.16) 19 WBC x 109/L 9,88 (5,62–22,22) 8,43 (5,17–16,06) 6,73 (4,86–28,67) 6,76 (5,4–6,77) 13,35 Hct % 41.65 (29–53) 36.15 (32.3–42) 53.9 (50–72.5) 53.20 (42.4–54.5) 31 PLT x 109/L 1109 (633–2800) 990,5 (611–2950) 217 (166–945) 207 (202–271) 995 Symptoms 12/33 (36%) 4/16 (25%) 5/11 (45%) 0/3 no Splenomegaly 8/34 (23.5%) 2/15 (13%) 3/11 (27%) 0/3 no Anti-platelet agents 27/34 (79.4%) 9/16 (56%) 4/11 (36%) 0/3 no Cytoreductive drugs 23/34 (68%) 2/16 (12.5%) 1/11 (9%) 0/3 no EECs pos 11/19 (58%) 5/12 (42%) 4/10 (40%) 0/3 no PRV-1 RNA overexpr 14/19 (74%) 6/12 (50%) 6/10 (60%) 3/3 (100%) yes JAK2 V617F mut 10/21 (47.5%) 0/13 3/11 (27%) 0/3 no Monoclonality 7/11 (63.5%) 0/7 2/3 (66%) 0/2 yes MPLS505A mut 0/15 15/16 (94%) – – – Thromboses 1/34 (3%) 2/16 (12.5%) 0/11 0/3 no Pregnancies 9 2 – – – F-up (yrs) 10.02 (0.37–27.28) 11.02 (0.86–26.96) 9 (0.25–17.14) 2 (2–9) 1