Background Our overall goal is to improve clinical care for inpatients with chronic heart failure(CHF).A retrospective assessment of CHF patients admitted to our hospital over the past decade(2005 vs.2014)indicated a ...Background Our overall goal is to improve clinical care for inpatients with chronic heart failure(CHF).A retrospective assessment of CHF patients admitted to our hospital over the past decade(2005 vs.2014)indicated a need for better strategies to evaluate clinical treatment,implement best practices and achieve optimal patient outcome.To that purpose,we developed a standardized plan to improve in-hospital treatment of acute decompensated CHF patients.Methods&Results Retrospective chart reviews were conducted to compare three cohorts of CHF patients admitted to the University Hospital of Lund at different time points over a 12-year period:2005(365 patients),2014(172 patients)and 2017-2018(57 patients).Little improvement was seen between 2005 and 2014 with respect to one-year mortality(35%vs.34%)and adequate treatment with recommended medications,e.g.,use of renin-angiotensin system blockers(45%vs.51%).A standardized treatment plan was devised to improve outcomes.A third cohort,treated under the plan(2017-2018),was compared with the 2014 cohort.One-year mortality(18%vs.34%)and 30-day readmission(5%vs.30%)were dramatically decreased,and adherence to medication guidelines was achieved.Key elements of the plan included well-defined treatment procedures,enhanced communication and teamwork,education,adequate time for treatment(5 days)and post-discharge follow-up as necessary.Natriuretic peptide(NT-proBNP)levels were useful for assessing patient status,prognosis and response to treatment.Conclusion Developmeof a standard plan for clinical management of acute decompensated CHF patients resulted in significant improvements in patient outcome,as reflected in decreased rates of 30-day readmission and one-year mortality.展开更多
Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and,thus,for public health policy and vaccine development for COVID-19.In this study,using eit...Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and,thus,for public health policy and vaccine development for COVID-19.In this study,using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein(Spike),we studied the neutralizing antibody(nAb)response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections,including patients with mild symptoms and also more severe forms,including those that required intensive care.We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels.Indeed,patients from intensive care units exhibited high nAb titers;conversely,patients with milder disease symptoms had heterogeneous nAb titers,and asymptomatic or exclusive outpatient-care patients had no or low nAbs.We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses.Moreover,we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2,indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2.Finally,we found that the D614G mutation in the spike protein,which has recently been identified as the current major variant in Europe,does not allow neutralization escape.Altogether,our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease,and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.展开更多
AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(...AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.展开更多
Dengue is an arboviruses due to single-stranded enveloped ribonucleic acid viruses, named dengue viruses(DENV), that include four serotypes and are mainly transmitted via the bite of mosquitoes of the genus Aedes(A. a...Dengue is an arboviruses due to single-stranded enveloped ribonucleic acid viruses, named dengue viruses(DENV), that include four serotypes and are mainly transmitted via the bite of mosquitoes of the genus Aedes(A. aegypti and A. albopictus). The distribution of the disease was historically limited to intertropical areas; however, during the last thirty years, the perimeter of the disease extended considerably and temperate areas are now at risk of outbreaks. The present global burden of dengue is considerable: 2.5 billion people over more than 100 countries are concerned; 50 to 100 million infections occur every year, with a number of fatal cases of approximately 20000. Although frequently asymptomatic or limited to a mild fever, dengue is responsible for severe cases mainly consecutive to the occurrence of hemorrhagic complications that can lead to shock and death, notably in children from poorresource settings. The place of DENV as a transfusiontransmitted pathogen has been recognized only in 2008. At the present time, only five cases of transfusiontransmitted dengue, including one case of dengue hemorrhagic fever, have been formerly documented. This review provides a general overview of dengue, its viruses and their vectors. It replaces the disease in the context of other viral diseases transmitted by arthropods. It discusses the threat of dengue on the supply of blood products in endemic and non endemic areas. Finally, it describes the specific and non specific measures available for improving the security of blood products with regards to this emerging risk. Interestingly, in 2009, the American Association of Blood Banks placed DENV in the highest category of emerging infectious agents for their potential impact on transfusion recipient safety for the next years in North America.展开更多
Hepatitis C virus(HCV)is a blood-borne pathogen that has a worldwide distribution and infects millions of people.Care-associated HCV infections represented a huge part of hepatitis C burden in the past via contaminate...Hepatitis C virus(HCV)is a blood-borne pathogen that has a worldwide distribution and infects millions of people.Care-associated HCV infections represented a huge part of hepatitis C burden in the past via contaminated blood and unsafe injections and continue to be a serious problem of public health.The present review proposes a panorama of health care-associated HCV infections via the three mode of contamination that have been identified:(1)infected patient to non-infected patient;(2)infected patient to non-infected health careworker(HCW);and(3)infected HCW to non infected patient.For each condition,the circumstances of contamination are described together with the means to prevent them.As a whole,the more important risk is represented by unsafe practices regarding injections,notably with the improper use of multidose vials used for multiple patients.The questions of occupational exposures and infected HCWs are also discussed.In terms of prevention and surveillance,the main arm for combating care-associated HCV infections is the implementation of standard precautions in all the fields of cares,with training programs and audits to verify their good application.HCWs must be sensitized to the risk of blood-borne pathogens,notably by the use of safety devices for injections and good hygiene practices in the operating theatre and in all the invasive procedures.The providers performing exposed-prone procedures must monitor their HCV serology regularly in order to detect early any primary infection and to treat it without delay.With the need to stay vigilant because HCV infection is often a hidden risk,it can be hoped that the number of people infected by HCV via health care will decrease very significantly in the next years.展开更多
BACKGROUND:Large regenerative nodules (LRNs) are hyperplastic benign nodules most commonly associated with Budd-Chiari syndrome (BCS),caused by outflow obstruction of the hepatic veins or vena cava.To our knowledge,no...BACKGROUND:Large regenerative nodules (LRNs) are hyperplastic benign nodules most commonly associated with Budd-Chiari syndrome (BCS),caused by outflow obstruction of the hepatic veins or vena cava.To our knowledge,no cases of LRNs arising in BCS after transjugular intrahepatic portosystemic shunt (TIPS) positioning and detected by GdEOB-DTPA MRI have been reported in the literature.METHODS:A 58-year-old woman with BCS,on the liver transplantation (LT) list,underwent a follow-up enhanced MRI.Two years earlier,a TIPS had been placed.In 2008,recurrent hepaticoencephalopathy resistant to medical treatment fulfilled the LT criteria for BCS treated with TIPS and the patient was therefore added to the LT list.CT performed before TIPS had not detected any hepatic lesions.CT performed six months after TIPS showed its complete patency but documented two indeterminate hypervascular liver lesions.RESULTS:MRI performed with Gd-EOB-DTPA revealed additional hypervascular lesions with uptake and retention of the medium in the hepatobiliary phase,thus reflecting a benign behavior of hepatocellular composition.These MRI features were related to LRNs as confirmed by histopathologic analysis.CONCLUSIONS:Gd-EOB-DTPA-enhanced MRI is potentially superior to standard imaging using gadolinium chelates or spiral CT,especially for the differential diagnosis of hypervascular lesions.Gd-EOB-DTPA MRI may become the imaging method of choice for evaluating LT list patients with BCS after TIPS placement.展开更多
Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by ...Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.展开更多
Since it has been recognized that sarcoidosis(SA) is not an exclusive disorder of the lungs but can also affect other organs such as the liver and spleen, efforts have been made to define specific imaging criteria for...Since it has been recognized that sarcoidosis(SA) is not an exclusive disorder of the lungs but can also affect other organs such as the liver and spleen, efforts have been made to define specific imaging criteria for the diagnosis of the single organ involvement, and the concept has been reinforced that the exclusion of alternative causes is important to achieve the correct diagnosis. Ultrasound(US)is a useful tool to evaluate patients with suspected abdominal SA, such as of the liver, spleen, kidney, pancreas and other organs, showing findings such as organomegaly, focal lesions and lymphadenopathy. While the diagnosis of abdominal SA is more predictable in the case of involvement of other organs(e.g.,lungs), the problem is more complex in the case of isolated abdominal SA. The recent use of contrast-enhanced ultrasound and endoscopic ultrasound elastography has provided additional information about the enhancement patterns and tissue rigidity in abdominal SA. Here we critically review the role of US in abdominal SA, reporting typical findings and limitations of current evidence and by discussing future perspectives of study.展开更多
In the "proton pump inhibitors era",a penetrating peptic ulcer(PPU) represents an exceptional cause of abdominal pain,and was more frequently observed in the past where there was not an effective antacid tre...In the "proton pump inhibitors era",a penetrating peptic ulcer(PPU) represents an exceptional cause of abdominal pain,and was more frequently observed in the past where there was not an effective antacid treatment. Ulcer-induced pancreatitis is very rare,too,and manifests with persistent,intense pain radiating to the back. A mild to severe pancreatitis with peripancreatic fluid collection can be observed at imaging. However,only a few cases of association between PPU and emphysematous pancreatitis(EP) have been published in the literature. EP is a rare but potentially fatal form of acute necrotizing pancreatitis in which gas grows in and outside the pancreas,and typically involves the whole parenchyma in diabetic individuals.Here we report an extremely rare case of a duodenal ulcer penetrating the pancreas and complicated with EP.Unlike the classic form of EP,which involves the whole parenchyma and has a poor prognosis,we found that the emphysematous involvement of the pancreas by PPU has a benign course if a conservative therapy is promptly established. Gas is confined to the site of penetration,usual y the pancreatic head,and ulcers most often involve the duodenum.展开更多
In more than 20% of all patients, the Crohn's diseasepresents before the age of 18 years. The diagnosisand management of Crohn's disease in children haschanged dramatically over the last decade, mainly dueto i...In more than 20% of all patients, the Crohn's diseasepresents before the age of 18 years. The diagnosisand management of Crohn's disease in children haschanged dramatically over the last decade, mainly dueto increased awareness, availability of newer diagnosticmodalities such as magnetic resonance imaging(MRI)and newer, more powerful treatments such as biolog-ics. Imaging of the small bowel is needed for diagno-sis, management, follow-up and also evaluation of thedisease in terms of location, extent, activity and com-plications. We review all the methods(barium exami-nations, ultrasonography, computed tomography, MR,and computed tomography- positron emission tomog-raphy) commonly used for imaging the small bowel inpaediatric patients with Crohn's disease analyzing theadvantages and disadvantages of each modality, withparticular emphasis on MR imaging.展开更多
Background As a consequence of the demographic development with increasing proportion of older people,the prevalence of heart failure(HF)is expected to rise with considerable economic and societal costs.However,knowle...Background As a consequence of the demographic development with increasing proportion of older people,the prevalence of heart failure(HF)is expected to rise with considerable economic and societal costs.However,knowledge on cardiac structure and function among population-based samples of the exceptional old is lacking.Methods Population-based study of all persons(no exclusion criteria)living in the western part of Denmark and turning 100 years in the year 2015.In-home face-to-face interviews were conducted,and echocardiography and blood sampling for plasma Brain Natriuretic Peptide(BNP)were offered to those who were able to give consent.Results Out of 303 eligible,238(79%)participated,of which 125(53%)accepted echocardiography.Left ventricular(LV)dysfunction was present in 68(54%)of the participants of whom less than half had HF symptoms.Pulmonary hypertension was present in 31(42%)with no correlation to LV function.The well-known association between increased level of BNP and the prevalence of LV dysfunction could not be confirmed.Conclusions This in-home echocardiographic study shows that more than half of the participants had LV dysfunction,although mostly asymptomatic.There was no association between heart failure symptoms and LV dysfunction.Furthermore,BNP seems to have lost its biomarker potential to rule out heart failure in centenarians.Due to the latter,and the questionable symptom validity among centenarians,the current criteria to diagnose HF might be less valid in a centenarian population than in younger olds.展开更多
BACKGROUND Ampullary adenocarcinomas(AACs)are heterogeneous tumors currently classified into three important sub-classes(SC):Intestinal(INT),Pancreato-Biliary(PB)and Mixed-Type(MT).The different subgroups have similar...BACKGROUND Ampullary adenocarcinomas(AACs)are heterogeneous tumors currently classified into three important sub-classes(SC):Intestinal(INT),Pancreato-Biliary(PB)and Mixed-Type(MT).The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent.However,they respond differently to chemotherapy and have different prognostic outcomes.The SC are often difficult to identify with conventional histology alone.The clinical outcome of all three remains unclear,particularly for MT.AIM To identify two main subtypes of AACs,using an immunohistochemical(IHC)score based on CDX2,CK7 and CK20.METHODS Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2,CK7 and CK 20.An IHC score was obtained for each marker by counting the number of positive cells(0=no stained cells;1<25%;2<50%and 3>50%)and their intensity(1=weak;2=moderate and 3=strong).A global score(GS)was then obtained by summation of the IHC scores of each marker.The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype,obtaining only two AACs subtypes.The overall survival in INT and PB patients was obtained by Kaplan-Meier methods.RESULTS Histological parameters defined the AACs subtypes as follows:15%INT,45%PB and 40%MT.Using IHC expression and the GS,75%and 25%of MT samples were assigned to either the INT or the PB group.The mean value of the GS was 9.5(range 4-16).All INT samples had a GS above the average,distinct from the PB samples which had a GS score significantly below the average(P=0.0011).The INT samples were identified by high expression of CDX2 and CK20,whereas PB samples exhibited high expression of CK7 and no expression of CK20(P=0.0008).The INT group had a statistically significant higher overall survival than in the PB group(85.7 mo vs 20.3 mo,HR:8.39;95%CI:1.38 to 18.90;P=0.0152).CONCLUSION The combination of histopathological and molecular criteria enables the classification展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;">Genome-wide association studies have identified numerous genetic variants for type 2 diabetes (T2D). Most genetic lo...<div style="text-align:justify;"> <span style="font-family:Verdana;">Genome-wide association studies have identified numerous genetic variants for type 2 diabetes (T2D). Most genetic loci discovered to date were studied in Caucasians or Asian ancestry, however, there are no data regarding a quite large Italian sample. Therefore, we investigated T2D genetic susceptibility of 143 single nucleotide polymorphisms (SNPs) within 30 genes involved in glucose metabolism in a large Italian case-control study. For the study, 1875 Caucasian patients were selected from three Italian cohorts. Age, gender, BMI and fasting plasma glucose (FPG) values were collected. Population was split in cases and controls based on FPG values or T2D diagnosis. T2D subjects and whom with FPG higher that 126 mg/dL were recruited as cases whereas subjects with normal values of FPG were considered controls. In each subject 143 SNPs were genotyped. To evaluate the association between genetic variations and diabetes status, a logistic regression analysis, adjusted for age, sex and BMI, was performed. Overall, 948 (50.6%) had T2D. Twenty out of 143 variants within 11 different genes resulted significantly associated to T2D. Four of them were located into <em>TCF7L2</em> gene and presented the highest odd ratio (from 1.42 to 1.57). At least two SNPs were located within <em>KCNJ11, WFS1, ABCC8, JAZF1</em> and <em>HNF1B</em> genes and one SNP each was identified in <em>ADAMTS9, IGF2BP2, FTO, G6PC2</em> and <em>GCK</em> genes. Our findings support the role of 11 genes involved in glucose homeostasis in T2D risk development in a large Italian population. We found that such genetic information may be advantageous for predicting T2D.</span> </div>展开更多
Transplantation in children is the best option to treat renal failure. Over the last 25 years the improvements in therapy have dramatically reduced the risk of early acute rejection and graft loss, however the long te...Transplantation in children is the best option to treat renal failure. Over the last 25 years the improvements in therapy have dramatically reduced the risk of early acute rejection and graft loss, however the long term results in terms of graft survival and morbidity still require search for new immunosuppressive regimens. Tolerance of the graft and minimization of side effects are the challenges for improving the outcome of children with a grafted kidney. Notwithstanding the difficulties in settling in children large multicenter trials to derive statistically useful data, many important contributions in the last years brought important modifications in the immunosuppressive therapy, including minimization protocols of steroids and calcineurin inhibitors and new induction drugs. New methods for diagnosis of anti HLA antibodies and some new protocols to improve both chance and outcome of transplantation in immunized subjects represent area of ongoing research of extreme interest for children.展开更多
Objective： Prognosis of colorectal cancer strongly depends on stage at diagnosis, which can be cured in most cases at an early stage. The results were supported by different screening programmes. Few data concerning ...Objective： Prognosis of colorectal cancer strongly depends on stage at diagnosis, which can be cured in most cases at an early stage. The results were supported by different screening programmes. Few data concerning analysis of different phases of Colorectal Cancer Program were reported in literature. The aim of this study is to analyze ＂step by step＂, from a longitudinal type, the Colorectal Cancer Program, active at our Institution, verifying compliance with standards of care.Methods： We compared two different populations during the same period： patients referring to our Clinical Oncology Unit coming from Regional Colorectal Cancer Screening Program and the other population that was not in any Colorectal Cancer Program.Results： Considering patients from the Regional Colorectal Cancer Screening Program（19 patients, corresponding to 24.0% of the general case study）, 3（15.8%） were deceased and 16（84.2%） were alive without evidence of the disease（NED）. Concerning patients that are not coming from Regional Colorectal Cancer Screening Program（61 patients, corresponding to 76.0% of the general case study）, 9（14.8%） were deceased, 43（70.5%） were NED, 8（13.1%） were alive with metastases and 1（1.6%） was lost during follow-up（PFU）. Conclusions： On the basis of this experience, we concluded for high-quality care for both populations. Any critical point should be carefully analyzed in order to implement quality of care.展开更多
Crohn’s disease affects more than 500000 individuals in the United States, and about 25% of cases are diagnosed during the pediatric period. Imaging of the bowel has undergone dramatic changes in the past ...Crohn’s disease affects more than 500000 individuals in the United States, and about 25% of cases are diagnosed during the pediatric period. Imaging of the bowel has undergone dramatic changes in the past two decades. The endoscopy with biopsy is generally considered the diagnostic reference standard, this combination can evaluates only the mucosa, not inflammation or fibrosis in the mucosa. Actually, the only modalities that can visualize submucosal tissues throughout the small bowel are the computed tomography (CT) enterography (CTE) with the magnetic resonance enterography (MRE). CT generally is highly utilized, but there is growing concern over ionizing radiation and cancer risk; it is a very important aspect to keep in consideration in pediatric patients. In contrast to CTE, MRE does not subject patients to ionizing radiation and can be used to detect detailed morphologic information and functional data of bowel disease, to monitor the effects of medical therapy more accurately, to detect residual active disease even in patients showing apparent clinical resolution and to guide treatment more accurately.展开更多
Comamonas testosteroni(C. testosteroni) has been rarely observed as an infectious agent in clinical practice. Few reports described its potential pathogenicity in bloodstream and abdominal infections. Here, we report ...Comamonas testosteroni(C. testosteroni) has been rarely observed as an infectious agent in clinical practice. Few reports described its potential pathogenicity in bloodstream and abdominal infections. Here, we report our experience in the treatment of a C. testosteroni-associated peritonitis in a four-year-old girl receiving chronic peritoneal dialysis(PD). The organism was shown to be highly susceptible to appropriate antibiotic therapy. Infection responded promptly and the patient was managed conservatively without withdrawal from PD.展开更多
AIM To investigate one-year outcomes after percutaneous mitral valve repair with Mitra Clip~? in patients with severe mitral regurgitation(MR). METHODS Our study investigated consecutive patients with symptomatic seve...AIM To investigate one-year outcomes after percutaneous mitral valve repair with Mitra Clip~? in patients with severe mitral regurgitation(MR). METHODS Our study investigated consecutive patients with symptomatic severe MR who underwent Mitra Clip~?implantation at the University Hospital Bergmannsheil from 2012 to 2014. The primary study end-point was all-cause mortality. Secondary end-points were degree of MR and functional status after percutaneous mitral valve repair.RESULTS The study population consisted of 46 consecutive patients(mean logistic Euro SCORE 32% ± 21%). The degree of MR decreased significantly(severe MR before Mitra Clip~? 100% vs after Mitra Clip~? 13%; P < 0.001),and the NYHA functional classes improved(NYHA III/IV before Mitra Clip~? 98% vs after Mitra Clip~? 35%; P < 0.001). The mortality rates 30 d and one year after percutaneous mitral valve repair were 4.3% and 19.5%,respectively. During the follow-up of 473 ± 274 d,11 patients died(90% due to cardiovascular death). A preprocedural plasma B-type natriuretic peptide level > 817 pg/m L was associated with all-cause mortality(hazard ratio,6.074; 95%CI: 1.257-29.239; P = 0.012).CONCLUSION Percutaneous mitral valve repair with Mitra Clip~? has positive effects on hemodynamics and symptoms. Despite the study patients' multiple comorbidities and extremely high operative risk,one-year outcomes after Mitra Clip~? are favorable. Elevated B-type natriuretic peptide levels indicate poorer mid-term survival.展开更多
文摘Background Our overall goal is to improve clinical care for inpatients with chronic heart failure(CHF).A retrospective assessment of CHF patients admitted to our hospital over the past decade(2005 vs.2014)indicated a need for better strategies to evaluate clinical treatment,implement best practices and achieve optimal patient outcome.To that purpose,we developed a standardized plan to improve in-hospital treatment of acute decompensated CHF patients.Methods&Results Retrospective chart reviews were conducted to compare three cohorts of CHF patients admitted to the University Hospital of Lund at different time points over a 12-year period:2005(365 patients),2014(172 patients)and 2017-2018(57 patients).Little improvement was seen between 2005 and 2014 with respect to one-year mortality(35%vs.34%)and adequate treatment with recommended medications,e.g.,use of renin-angiotensin system blockers(45%vs.51%).A standardized treatment plan was devised to improve outcomes.A third cohort,treated under the plan(2017-2018),was compared with the 2014 cohort.One-year mortality(18%vs.34%)and 30-day readmission(5%vs.30%)were dramatically decreased,and adherence to medication guidelines was achieved.Key elements of the plan included well-defined treatment procedures,enhanced communication and teamwork,education,adequate time for treatment(5 days)and post-discharge follow-up as necessary.Natriuretic peptide(NT-proBNP)levels were useful for assessing patient status,prognosis and response to treatment.Conclusion Developmeof a standard plan for clinical management of acute decompensated CHF patients resulted in significant improvements in patient outcome,as reflected in decreased rates of 30-day readmission and one-year mortality.
基金The laboratory of FLC received financial support from the LabEx Ecofect(ANR-11-LABX-0048)the“Universitéde Lyon,”within the program“Investissements d’Avenir”(ANR-11-IDEX-0007)+1 种基金operated by the French National Research Agency(ANR),the ANR(grant from RA-Covid-19)the Fondation pour la Recherche Médicale(FRM),and Inserm Transfert.We thank D.Lavillette for providing the SARS-CoV-2 spike expression vector and B.La Scola for providing a clone of Vero-E6 cells.We acknowledge the contribution of SFR Biosciences(UMS3444/CNRS,US8/Inserm,ENS de Lyon,UCBL)ANIRA-Cytometry facility for excellent technical assistance and support.
文摘Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and,thus,for public health policy and vaccine development for COVID-19.In this study,using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein(Spike),we studied the neutralizing antibody(nAb)response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections,including patients with mild symptoms and also more severe forms,including those that required intensive care.We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels.Indeed,patients from intensive care units exhibited high nAb titers;conversely,patients with milder disease symptoms had heterogeneous nAb titers,and asymptomatic or exclusive outpatient-care patients had no or low nAbs.We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses.Moreover,we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2,indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2.Finally,we found that the D614G mutation in the spike protein,which has recently been identified as the current major variant in Europe,does not allow neutralization escape.Altogether,our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease,and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.
文摘AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.
文摘Dengue is an arboviruses due to single-stranded enveloped ribonucleic acid viruses, named dengue viruses(DENV), that include four serotypes and are mainly transmitted via the bite of mosquitoes of the genus Aedes(A. aegypti and A. albopictus). The distribution of the disease was historically limited to intertropical areas; however, during the last thirty years, the perimeter of the disease extended considerably and temperate areas are now at risk of outbreaks. The present global burden of dengue is considerable: 2.5 billion people over more than 100 countries are concerned; 50 to 100 million infections occur every year, with a number of fatal cases of approximately 20000. Although frequently asymptomatic or limited to a mild fever, dengue is responsible for severe cases mainly consecutive to the occurrence of hemorrhagic complications that can lead to shock and death, notably in children from poorresource settings. The place of DENV as a transfusiontransmitted pathogen has been recognized only in 2008. At the present time, only five cases of transfusiontransmitted dengue, including one case of dengue hemorrhagic fever, have been formerly documented. This review provides a general overview of dengue, its viruses and their vectors. It replaces the disease in the context of other viral diseases transmitted by arthropods. It discusses the threat of dengue on the supply of blood products in endemic and non endemic areas. Finally, it describes the specific and non specific measures available for improving the security of blood products with regards to this emerging risk. Interestingly, in 2009, the American Association of Blood Banks placed DENV in the highest category of emerging infectious agents for their potential impact on transfusion recipient safety for the next years in North America.
文摘Hepatitis C virus(HCV)is a blood-borne pathogen that has a worldwide distribution and infects millions of people.Care-associated HCV infections represented a huge part of hepatitis C burden in the past via contaminated blood and unsafe injections and continue to be a serious problem of public health.The present review proposes a panorama of health care-associated HCV infections via the three mode of contamination that have been identified:(1)infected patient to non-infected patient;(2)infected patient to non-infected health careworker(HCW);and(3)infected HCW to non infected patient.For each condition,the circumstances of contamination are described together with the means to prevent them.As a whole,the more important risk is represented by unsafe practices regarding injections,notably with the improper use of multidose vials used for multiple patients.The questions of occupational exposures and infected HCWs are also discussed.In terms of prevention and surveillance,the main arm for combating care-associated HCV infections is the implementation of standard precautions in all the fields of cares,with training programs and audits to verify their good application.HCWs must be sensitized to the risk of blood-borne pathogens,notably by the use of safety devices for injections and good hygiene practices in the operating theatre and in all the invasive procedures.The providers performing exposed-prone procedures must monitor their HCV serology regularly in order to detect early any primary infection and to treat it without delay.With the need to stay vigilant because HCV infection is often a hidden risk,it can be hoped that the number of people infected by HCV via health care will decrease very significantly in the next years.
文摘BACKGROUND:Large regenerative nodules (LRNs) are hyperplastic benign nodules most commonly associated with Budd-Chiari syndrome (BCS),caused by outflow obstruction of the hepatic veins or vena cava.To our knowledge,no cases of LRNs arising in BCS after transjugular intrahepatic portosystemic shunt (TIPS) positioning and detected by GdEOB-DTPA MRI have been reported in the literature.METHODS:A 58-year-old woman with BCS,on the liver transplantation (LT) list,underwent a follow-up enhanced MRI.Two years earlier,a TIPS had been placed.In 2008,recurrent hepaticoencephalopathy resistant to medical treatment fulfilled the LT criteria for BCS treated with TIPS and the patient was therefore added to the LT list.CT performed before TIPS had not detected any hepatic lesions.CT performed six months after TIPS showed its complete patency but documented two indeterminate hypervascular liver lesions.RESULTS:MRI performed with Gd-EOB-DTPA revealed additional hypervascular lesions with uptake and retention of the medium in the hepatobiliary phase,thus reflecting a benign behavior of hepatocellular composition.These MRI features were related to LRNs as confirmed by histopathologic analysis.CONCLUSIONS:Gd-EOB-DTPA-enhanced MRI is potentially superior to standard imaging using gadolinium chelates or spiral CT,especially for the differential diagnosis of hypervascular lesions.Gd-EOB-DTPA MRI may become the imaging method of choice for evaluating LT list patients with BCS after TIPS placement.
文摘Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.
文摘Since it has been recognized that sarcoidosis(SA) is not an exclusive disorder of the lungs but can also affect other organs such as the liver and spleen, efforts have been made to define specific imaging criteria for the diagnosis of the single organ involvement, and the concept has been reinforced that the exclusion of alternative causes is important to achieve the correct diagnosis. Ultrasound(US)is a useful tool to evaluate patients with suspected abdominal SA, such as of the liver, spleen, kidney, pancreas and other organs, showing findings such as organomegaly, focal lesions and lymphadenopathy. While the diagnosis of abdominal SA is more predictable in the case of involvement of other organs(e.g.,lungs), the problem is more complex in the case of isolated abdominal SA. The recent use of contrast-enhanced ultrasound and endoscopic ultrasound elastography has provided additional information about the enhancement patterns and tissue rigidity in abdominal SA. Here we critically review the role of US in abdominal SA, reporting typical findings and limitations of current evidence and by discussing future perspectives of study.
文摘In the "proton pump inhibitors era",a penetrating peptic ulcer(PPU) represents an exceptional cause of abdominal pain,and was more frequently observed in the past where there was not an effective antacid treatment. Ulcer-induced pancreatitis is very rare,too,and manifests with persistent,intense pain radiating to the back. A mild to severe pancreatitis with peripancreatic fluid collection can be observed at imaging. However,only a few cases of association between PPU and emphysematous pancreatitis(EP) have been published in the literature. EP is a rare but potentially fatal form of acute necrotizing pancreatitis in which gas grows in and outside the pancreas,and typically involves the whole parenchyma in diabetic individuals.Here we report an extremely rare case of a duodenal ulcer penetrating the pancreas and complicated with EP.Unlike the classic form of EP,which involves the whole parenchyma and has a poor prognosis,we found that the emphysematous involvement of the pancreas by PPU has a benign course if a conservative therapy is promptly established. Gas is confined to the site of penetration,usual y the pancreatic head,and ulcers most often involve the duodenum.
文摘In more than 20% of all patients, the Crohn's diseasepresents before the age of 18 years. The diagnosisand management of Crohn's disease in children haschanged dramatically over the last decade, mainly dueto increased awareness, availability of newer diagnosticmodalities such as magnetic resonance imaging(MRI)and newer, more powerful treatments such as biolog-ics. Imaging of the small bowel is needed for diagno-sis, management, follow-up and also evaluation of thedisease in terms of location, extent, activity and com-plications. We review all the methods(barium exami-nations, ultrasonography, computed tomography, MR,and computed tomography- positron emission tomog-raphy) commonly used for imaging the small bowel inpaediatric patients with Crohn's disease analyzing theadvantages and disadvantages of each modality, withparticular emphasis on MR imaging.
基金support from the Novo Nordisk Foundationthe Faculty of Health Sciences, University of Southern Denmark+2 种基金the Health Foundation (Helsefonden) (Grant No.16B-0271)the Lundbeck Foundation (Grant No. R260-2017722)supported by a grant from the Velux Foundation
文摘Background As a consequence of the demographic development with increasing proportion of older people,the prevalence of heart failure(HF)is expected to rise with considerable economic and societal costs.However,knowledge on cardiac structure and function among population-based samples of the exceptional old is lacking.Methods Population-based study of all persons(no exclusion criteria)living in the western part of Denmark and turning 100 years in the year 2015.In-home face-to-face interviews were conducted,and echocardiography and blood sampling for plasma Brain Natriuretic Peptide(BNP)were offered to those who were able to give consent.Results Out of 303 eligible,238(79%)participated,of which 125(53%)accepted echocardiography.Left ventricular(LV)dysfunction was present in 68(54%)of the participants of whom less than half had HF symptoms.Pulmonary hypertension was present in 31(42%)with no correlation to LV function.The well-known association between increased level of BNP and the prevalence of LV dysfunction could not be confirmed.Conclusions This in-home echocardiographic study shows that more than half of the participants had LV dysfunction,although mostly asymptomatic.There was no association between heart failure symptoms and LV dysfunction.Furthermore,BNP seems to have lost its biomarker potential to rule out heart failure in centenarians.Due to the latter,and the questionable symptom validity among centenarians,the current criteria to diagnose HF might be less valid in a centenarian population than in younger olds.
基金Supported by ARPA Foundation(www.fondazionearpa.it).
文摘BACKGROUND Ampullary adenocarcinomas(AACs)are heterogeneous tumors currently classified into three important sub-classes(SC):Intestinal(INT),Pancreato-Biliary(PB)and Mixed-Type(MT).The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent.However,they respond differently to chemotherapy and have different prognostic outcomes.The SC are often difficult to identify with conventional histology alone.The clinical outcome of all three remains unclear,particularly for MT.AIM To identify two main subtypes of AACs,using an immunohistochemical(IHC)score based on CDX2,CK7 and CK20.METHODS Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2,CK7 and CK 20.An IHC score was obtained for each marker by counting the number of positive cells(0=no stained cells;1<25%;2<50%and 3>50%)and their intensity(1=weak;2=moderate and 3=strong).A global score(GS)was then obtained by summation of the IHC scores of each marker.The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype,obtaining only two AACs subtypes.The overall survival in INT and PB patients was obtained by Kaplan-Meier methods.RESULTS Histological parameters defined the AACs subtypes as follows:15%INT,45%PB and 40%MT.Using IHC expression and the GS,75%and 25%of MT samples were assigned to either the INT or the PB group.The mean value of the GS was 9.5(range 4-16).All INT samples had a GS above the average,distinct from the PB samples which had a GS score significantly below the average(P=0.0011).The INT samples were identified by high expression of CDX2 and CK20,whereas PB samples exhibited high expression of CK7 and no expression of CK20(P=0.0008).The INT group had a statistically significant higher overall survival than in the PB group(85.7 mo vs 20.3 mo,HR:8.39;95%CI:1.38 to 18.90;P=0.0152).CONCLUSION The combination of histopathological and molecular criteria enables the classification
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">Genome-wide association studies have identified numerous genetic variants for type 2 diabetes (T2D). Most genetic loci discovered to date were studied in Caucasians or Asian ancestry, however, there are no data regarding a quite large Italian sample. Therefore, we investigated T2D genetic susceptibility of 143 single nucleotide polymorphisms (SNPs) within 30 genes involved in glucose metabolism in a large Italian case-control study. For the study, 1875 Caucasian patients were selected from three Italian cohorts. Age, gender, BMI and fasting plasma glucose (FPG) values were collected. Population was split in cases and controls based on FPG values or T2D diagnosis. T2D subjects and whom with FPG higher that 126 mg/dL were recruited as cases whereas subjects with normal values of FPG were considered controls. In each subject 143 SNPs were genotyped. To evaluate the association between genetic variations and diabetes status, a logistic regression analysis, adjusted for age, sex and BMI, was performed. Overall, 948 (50.6%) had T2D. Twenty out of 143 variants within 11 different genes resulted significantly associated to T2D. Four of them were located into <em>TCF7L2</em> gene and presented the highest odd ratio (from 1.42 to 1.57). At least two SNPs were located within <em>KCNJ11, WFS1, ABCC8, JAZF1</em> and <em>HNF1B</em> genes and one SNP each was identified in <em>ADAMTS9, IGF2BP2, FTO, G6PC2</em> and <em>GCK</em> genes. Our findings support the role of 11 genes involved in glucose homeostasis in T2D risk development in a large Italian population. We found that such genetic information may be advantageous for predicting T2D.</span> </div>
文摘Transplantation in children is the best option to treat renal failure. Over the last 25 years the improvements in therapy have dramatically reduced the risk of early acute rejection and graft loss, however the long term results in terms of graft survival and morbidity still require search for new immunosuppressive regimens. Tolerance of the graft and minimization of side effects are the challenges for improving the outcome of children with a grafted kidney. Notwithstanding the difficulties in settling in children large multicenter trials to derive statistically useful data, many important contributions in the last years brought important modifications in the immunosuppressive therapy, including minimization protocols of steroids and calcineurin inhibitors and new induction drugs. New methods for diagnosis of anti HLA antibodies and some new protocols to improve both chance and outcome of transplantation in immunized subjects represent area of ongoing research of extreme interest for children.
文摘Objective： Prognosis of colorectal cancer strongly depends on stage at diagnosis, which can be cured in most cases at an early stage. The results were supported by different screening programmes. Few data concerning analysis of different phases of Colorectal Cancer Program were reported in literature. The aim of this study is to analyze ＂step by step＂, from a longitudinal type, the Colorectal Cancer Program, active at our Institution, verifying compliance with standards of care.Methods： We compared two different populations during the same period： patients referring to our Clinical Oncology Unit coming from Regional Colorectal Cancer Screening Program and the other population that was not in any Colorectal Cancer Program.Results： Considering patients from the Regional Colorectal Cancer Screening Program（19 patients, corresponding to 24.0% of the general case study）, 3（15.8%） were deceased and 16（84.2%） were alive without evidence of the disease（NED）. Concerning patients that are not coming from Regional Colorectal Cancer Screening Program（61 patients, corresponding to 76.0% of the general case study）, 9（14.8%） were deceased, 43（70.5%） were NED, 8（13.1%） were alive with metastases and 1（1.6%） was lost during follow-up（PFU）. Conclusions： On the basis of this experience, we concluded for high-quality care for both populations. Any critical point should be carefully analyzed in order to implement quality of care.
文摘Crohn’s disease affects more than 500000 individuals in the United States, and about 25% of cases are diagnosed during the pediatric period. Imaging of the bowel has undergone dramatic changes in the past two decades. The endoscopy with biopsy is generally considered the diagnostic reference standard, this combination can evaluates only the mucosa, not inflammation or fibrosis in the mucosa. Actually, the only modalities that can visualize submucosal tissues throughout the small bowel are the computed tomography (CT) enterography (CTE) with the magnetic resonance enterography (MRE). CT generally is highly utilized, but there is growing concern over ionizing radiation and cancer risk; it is a very important aspect to keep in consideration in pediatric patients. In contrast to CTE, MRE does not subject patients to ionizing radiation and can be used to detect detailed morphologic information and functional data of bowel disease, to monitor the effects of medical therapy more accurately, to detect residual active disease even in patients showing apparent clinical resolution and to guide treatment more accurately.
文摘Comamonas testosteroni(C. testosteroni) has been rarely observed as an infectious agent in clinical practice. Few reports described its potential pathogenicity in bloodstream and abdominal infections. Here, we report our experience in the treatment of a C. testosteroni-associated peritonitis in a four-year-old girl receiving chronic peritoneal dialysis(PD). The organism was shown to be highly susceptible to appropriate antibiotic therapy. Infection responded promptly and the patient was managed conservatively without withdrawal from PD.
文摘AIM To investigate one-year outcomes after percutaneous mitral valve repair with Mitra Clip~? in patients with severe mitral regurgitation(MR). METHODS Our study investigated consecutive patients with symptomatic severe MR who underwent Mitra Clip~?implantation at the University Hospital Bergmannsheil from 2012 to 2014. The primary study end-point was all-cause mortality. Secondary end-points were degree of MR and functional status after percutaneous mitral valve repair.RESULTS The study population consisted of 46 consecutive patients(mean logistic Euro SCORE 32% ± 21%). The degree of MR decreased significantly(severe MR before Mitra Clip~? 100% vs after Mitra Clip~? 13%; P < 0.001),and the NYHA functional classes improved(NYHA III/IV before Mitra Clip~? 98% vs after Mitra Clip~? 35%; P < 0.001). The mortality rates 30 d and one year after percutaneous mitral valve repair were 4.3% and 19.5%,respectively. During the follow-up of 473 ± 274 d,11 patients died(90% due to cardiovascular death). A preprocedural plasma B-type natriuretic peptide level > 817 pg/m L was associated with all-cause mortality(hazard ratio,6.074; 95%CI: 1.257-29.239; P = 0.012).CONCLUSION Percutaneous mitral valve repair with Mitra Clip~? has positive effects on hemodynamics and symptoms. Despite the study patients' multiple comorbidities and extremely high operative risk,one-year outcomes after Mitra Clip~? are favorable. Elevated B-type natriuretic peptide levels indicate poorer mid-term survival.
