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Chronic pancreatitis is a multifactorial, fibroinflammatory syndrome in which repetitive episodes of pancreatic inflammation lead to extensive fibrotic tissue replacement, resulting in chronic pain, exocrine and endocrine pancreatic insufficiency, reduced quality of life, and a shorter life expectancy. The incidence and prevalence of chronic pancreatitis is rising and no curative treatment is available. Selleckchem Bafilomycin A1 Using novel diagnostic algorithms, definitive chronic pancreatitis can be diagnosed by imaging criteria alone, whereas probable chronic pancreatitis requires clinical features and imaging criteria. Criteria for the diagnosis of early chronic pancreatitis are still under discussion and need prospective validation in clinical trials. Cross-sectional imaging should be used first; endoscopic ultrasound is needed only when CT or MRI are inconclusive or to plan therapeutic interventions. Management of chronic pancreatitis requires an interdisciplinary approach including primary care practitioners, gastroenterologists, surgeons, radiologists, pain specialists, and nutritional therapists. Patients with chronic pancreatitis should be seen at least once a year and re-evaluated for causal risk factors, symptom control, and complications such as malnutrition, pancreatic exocrine insufficiency, and diabetes; refer to a specialised centre if symptoms are poorly controlled or there is risk of deterioration. Scoring systems to monitor disease progression have been developed and validated internationally. Interventional treatments for pain or cholestasis should be done by specialists only, and early discussion of treatment approaches should include all medical disciplines involved in care. Throughout this Seminar, we address research needs such as staging of pancreatitis, aspects of malnutrition and pain, and cancer surveillance, to help improve the care of patients.

Childhood is a sensitive period with rapid brain development and physiological growth, and adverse events in childhood might interfere with these processes and have long-lasting effects on health. In this study, we aimed to describe trajectories of adverse childhood experiences and relate these to overall and cause-specific mortality in early adult life.

For this population-based cohort study, we used unselected annually updated data from Danish nationwide registers covering more than 1 million children born between 1980 and 1998. We distinguished between three different dimensions of childhood adversities poverty and material deprivation, loss or threat of loss within the family, and aspects of family dynamics such as maternal separation. We used a group-based multi-trajectory clustering model to define the different trajectories of children aged between 0 and 16 years. We assessed the associations between these trajectories and mortality rates between 16 and 34 years of age using a Cox proportional hazadditional deaths per 10 000 person-years. Accidents, suicides, and cancer were the most common causes of death in this high adversity population.

Almost half of Danish children in our study experienced some degree of adversity, and this was associated with a moderately higher risk of mortality in adulthood. Among these, a small group of children had multiple adversities across social, health, and family-related dimensions. This group had a markedly higher mortality risk in early adulthood than that of other children, which requires public health attention.

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Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19.

This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019).(2·19, 1·07-4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34-4·89), or plasma cell neoplasms (2·48, 1·31-4·69), and severe or critical COVID-19 (4·08, 2·73-6·09) were associated with worse overall survival.

This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available.

Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus.

Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus.

Although diabetes has been associated with COVID-19-related mortality, the absolute and relative risks for type 1 and type 2 diabetes are unknown. We assessed the independent effects of diabetes status, by type, on in-hospital death in England in patients with COVID-19 during the period from March 1 to May 11, 2020.

We did a whole-population study assessing risks of in-hospital death with COVID-19 between March 1 and May 11, 2020. We included all individuals registered with a general practice in England who were alive on Feb 16, 2020. We used multivariable logistic regression to examine the effect of diabetes status, by type, on in-hospital death with COVID-19, adjusting for demographic factors and cardiovascular comorbidities. Because of the absence of data on total numbers of people infected with COVID-19 during the observation period, we calculated mortality rates for the population as a whole, rather than the population who were infected.

Of the 61 414 470 individuals who were alive and registered wd to ORs of 2·86 (2·58-3·18) for type 1 diabetes and 1·80 (1·75-1·86) for type 2 diabetes when also adjusted for previous hospital admissions with coronary heart disease, cerebrovascular disease, or heart failure.

The results of this nationwide analysis in England show that type 1 and type 2 diabetes were both independently associated with a significant increased odds of in-hospital death with COVID-19.

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Diabetes has been associated with increased COVID-19-related mortality, but the association between modifiable risk factors, including hyperglycaemia and obesity, and COVID-19-related mortality among people with diabetes is unclear. We assessed associations between risk factors and COVID-19-related mortality in people with type 1 and type 2 diabetes.

We did a population-based cohort study of people with diagnosed diabetes who were registered with a general practice in England. National population data on people with type 1 and type 2 diabetes collated by the National Diabetes Audit were linked to mortality records collated by the Office for National Statistics from Jan 2, 2017, to May 11, 2020. We identified the weekly number of deaths in people with type 1 and type 2 diabetes during the first 19 weeks of 2020 and calculated the percentage change from the mean number of deaths for the corresponding weeks in 2017, 2018, and 2019. The associations between risk factors (including sex, age, ethnicity, socioecity was U-shaped in type 1 diabetes, compared with a BMI of 25·0-29·9 kg/m

, a BMI of less than 20·0 kg/m

had an HR of 2·45 (95% CI 1·60-3·75, p<0·0001) and a BMI of 40·0 kg/m

or higher had an HR of 2·33 (1·53-3·56, p<0·0001); the corresponding HRs for type 2 diabetes were 2·33 (2·11-2·56, p<0·0001) and 1·60 (1·47-1·75, p<0·0001).

Deaths in people with type 1 and type 2 diabetes rose sharply during the initial COVID-19 pandemic in England. Increased COVID-19-related mortality was associated not only with cardiovascular and renal complications of diabetes but, independently, also with glycaemic control and BMI.

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Patients with COVID-19 who develop severe acute respiratory distress syndrome (ARDS) can have symptoms that rapidly evolve to profound hypoxaemia and death. The efficacy of extracorporeal membrane oxygenation (ECMO) for patients with severe ARDS in the context of COVID-19 is unclear. We aimed to establish the clinical characteristics and outcomes of patients with respiratory failure and COVID-19 treated with ECMO.

This retrospective cohort study was done in the Paris-Sorbonne University Hospital Network, comprising five intensive care units (ICUs) and included patients who received ECMO for COVID-19 associated ARDS. Patient demographics and daily pre-ECMO and on-ECMO data and outcomes were collected. Possible outcomes over time were categorised into four different states (states 1-4) on ECMO, in the ICU and weaned off ECMO, alive and out of ICU, or death. Daily probabilities of occupation in each state and of transitions between these states until day 90 post-ECMO onset were estimated with use of a multi-atory failure despite optimised care.

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None.Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In this study, we have assessed the pro-apoptotic effect of fluorizoline in 3 different multiple myeloma cell lines and 12 primary samples obtained from treatment-naïve multiple myeloma patients. Fluorizoline induced apoptosis in both multiple myeloma cell lines and primary samples at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline. Moreover, fluorizoline increased the mRNA and protein levels of the pro-apoptotic BCL-2 family member NOXA both in cell lines and primary samples analyzed. Finally, NOXA-depletion by CRISPR/Cas9 in cells that do not express BIM conferred resistance to fluorizoline-induced apoptosis in multiple myeloma cells. These results suggest that targeting prohibitins could be a new therapeutic strategy for myeloma multiple.To investigate the role of P2X7 receptor to preserve retinal ganglion cells (RGCs) structure and function in a genetic mouse model (DBA/2J mouse) of age-related glaucomatous neurodegeneration. Chronic treatment with P2X7 receptor antagonist eye drops was carried out in order to assess RGCs function and density by pattern electroretinogram (PERG) and RBPMS immunostaining, respectively. Further, microglia activation was assessed in flat-mounted retina by using Iba-1 immunostaining. Untreated glaucomatous eyes displayed significant microglia activation, alteration of PERG signal, and RGCs loss. In the P2X7 receptor antagonist-treated eyes, the PERG signal was significantly (p less then 0.05) improved compared to controls, along with a significant (p less then 0.05) reduction in terms of retinal microglial activation, and remarkable preservation of RGCs density. Altogether, these findings demonstrated that topical treatment with a P2X7 receptor antagonist has a neuroprotective effect on RGCs in glaucomatous mice, suggesting an appealing pharmacological approach to prevent retinal degenerative damage in optic neuropathy.