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BACKGROUND: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. METHODS: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI). RESULTS: Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function. CONCLUSIONS: CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators.
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Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Pancreatite , Humanos , Bicarbonatos/metabolismo , Cloretos , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Mutação , Pancreatite/genética , Pancreatite/metabolismo , QuinolonasRESUMO
An Italian, 46-year-old female patient carrying the complex allele p.[R74W;V201M;D1270N] in trans with CFTR dele22_24 was diagnosed at the Cystic Fibrosis (CF) Center of Verona as being affected by CF-pancreatic sufficient (CF-PS) in 2021. The variant V201M has unknown significance, while both of the other variants of this complex allele have variable clinical consequences, according to the CFTR2 database, with reported clinical benefits for treatment with ivacaftor + tezacaftor and ivacaftor + tezacaftor + elexacaftor in patients carrying the R74W-D1270N complex allele, which are currently approved (in USA, not yet in Italy). She was previously followed up by pneumologists in northern Italy because of frequent bronchitis, hemoptysis, recurrent rhinitis, Pseudomonas aeruginosa lung colonization, bronchiectasis/atelectasis, bronchial arterial embolization and moderately compromised lung function (FEV1: 62%). Following a sweat test with borderline results, she was referred to the Verona CF Center where she presented abnormal values in both optical beta-adrenergic sweat tests and intestinal current measurement (ICM). These results were consistent with a diagnosis of CF. CFTR function analyses were also performed in vitro by forskolin-induced swelling (FIS) assay and short-circuit currents (Isc) in the monolayers of the rectal organoids. Both of these assays showed significantly increased CFTR activity following treatment with the CFTR modulators. Western-blot analysis revealed increased fully glycosylated CFTR protein after treatment with correctors, in line with the functional analysis. Interestingly, tezacaftor, together with elexacaftor, rescued the total organoid area under steady-state conditions, even in the absence of the CFTR agonist forskolin. In conclusion, in ex vivo and in vitro assays, we measured a residual function that was significantly enhanced by in vitro incubation with CFTR modulators, especially by ivacaftor + tezacaftor + elexacaftor, suggesting this combination as a potentially optimal treatment for this case.
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Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Feminino , Humanos , Pessoa de Meia-Idade , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Alelos , Colforsina/uso terapêutico , Mutação , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Benzodioxóis/farmacologia , Benzodioxóis/uso terapêuticoRESUMO
BACKGROUND: The most appropriate endo-therapeutic approach to biliary anastomotic strictures is yet to be defined. AIM: To retrospectively report on the endo-therapy of duct-to-duct anastomotic strictures during 2013 in Italy. METHODS: Data were collected from 16 Endoscopy Units at the Italian Liver Transplantation Centers (BASALT study group). RESULTS: Complete endo-therapy and follow-up data are available for 181 patients: 101 treated with plastic multistenting, 26 with fully covered self-expandable metal stenting and 54 with single stenting. Radiological success was achieved for 145 patients (80%), that is, 88% of plastic multistenting, 88% of self-expandable metal stenting and 61% of single stenting (P < 0.001 vs plastic multistenting; P < 0.05 vs self-expandable metal stenting). After first-line endo-therapy failure, the patients underwent a second-line endo-therapy with plastic multistenting for 25%, fully covered self-expandable metal stenting for 53% and single stenting for 22% of cases, and radiological success was achieved for 84%, that is, 100%, 85% and 63% with plastic multistenting, self-expandable metal stenting and single stenting (P < 0.05 vs plastic multistenting or self-expandable metal stenting) respectively. Procedure-related complications occurred in 7.8% of endoscopic retrograde cholangiopancreatographies. Overall, clinical success was achieved in 87% of patients after a median follow-up of 25 months. CONCLUSION: Plastic multistenting is confirmed as the preferred first-line treatment, while fully covered self-expandable metal stenting as rescue option for biliary anastomotic strictures. Single stenting has sub-optimal results and should be abandoned.
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Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Constrição Patológica/cirurgia , Transplante de Fígado/efeitos adversos , Stents Metálicos Autoexpansíveis , Stents/classificação , Adulto , Idoso , Doenças Biliares/etiologia , Doenças Biliares/cirurgia , Colestase/etiologia , Constrição Patológica/etiologia , Feminino , Humanos , Itália , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Plásticos , Estudos Retrospectivos , Inquéritos e Questionários , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: The use of gastroprotective agents has allowed significant progress in the prevention of upper gastrointestinal bleeding (UGIB) associated with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents. Nevertheless, some concerns remain regarding the gastroprotective dosage and treatment duration. Our aim was to study the effect of gastroprotective agents in UGIB induced by NSAIDs and single- or dual-antiplatelet therapy. METHODS: A multicenter case-control study was conducted including 577 cases diagnosed with UGIB and 1343 sex-, age-, and hospital-matched controls. To estimate exposure to NSAIDs and gastroprotective agents, consumption was calculated for the 4 weeks prior to hospital admission in terms of defined daily doses (DDDs). Risk groups for UGIB induced by NSAIDs and single- or dual-antiplatelet therapy were defined as a function of each drug dose, use of gastrointestine-damaging drugs, and risk factors for UGIB. Odds ratios (ORs) with 95% confidence intervals (CIs) were adjusted for single- (model 1) and dual- (model 2) antiplatelet therapy. RESULTS: Full adherence (> 0.80DDD) to proton pump inhibitors (PPIs) was the only gastroprotective therapy that significantly reduced the risk of UGIB, considering NSAID risk (OR: 0.53; 95% CI: 0.30-0.95) and dose (OR: 0.48; 95% CI: 0.27-0.87) with ORs adjusted for single-antiplatelet therapy (model 1) and NSAID risk (OR: 0.55; 95% CI: 0.31-0.98) and dose (OR: 0.49; 95% CI: 0.28-0.89) with ORs adjusted for dual-antiplatelet therapy (model 2). CONCLUSIONS: These results reinforce the recommendation of adding a PPI at effective doses (full adherence) to prevent UGIB induced by NSAIDs, or single- or dual-antiplatelet therapy.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Hemorragia Gastrointestinal/prevenção & controle , Adesão à Medicação , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to assess whether the CYP2C9*2 and/or *3 variants might modify the risk for NSAID-related upper gastrointestinal bleeding (UGIB) in NSAID users. PATIENTS AND METHODS: We conducted a multicenter, case-control study in which cases were patients aged more than 18 years with a diagnosis of UGIB, and controls were matched (1 : 3) by sex, age, date of admission, and hospital. Exposure was defined as the mean number of defined daily doses (DDDs) of NSAIDs metabolized by CYP2C9 in the week preceding the index date. Three DDD categories were defined (0, ≤ 0.5, and > 0.5). Exposure was constructed taking both NSAID use and CYP2C9 polymorphisms into account. Patients of non-European origin were excluded from the analysis. RESULTS: A total of 577 cases and 1343 controls were finally included in the analysis: 103 cases and 89 controls consumed NSAIDs metabolized by CYP2C9, and 88 cases and 177 controls were CYP2C9*3 carriers. The adjusted odds ratios (aORs) of UGIB associated with the CYP2C9*2 and wild-type alleles proved to be similar [OR=8.79 (4.50-17.17) and 10.15 (2.92-35.35), respectively] and lower than those of the CYP2C9*3 allele [aOR=18.07 (6.34-51.53)] for consumers taking more than 0.5 DDDs of NSAIDs metabolized by CYP2C9. Grouping genotypes into carriers and noncarriers of the CYP2C9*3 variant resulted in aORs of 16.92 (4.96-57.59) for carriers and 9.72 (4.55-20.76) for noncarriers, where DDDs were greater than 0.5. CONCLUSION: The presence of the CYP2C9*3 variant increases the risk for UGIB associated with NSAID for DDDs greater than 0.5. The presence of the CYP2C9*2 allele shows no such effect.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Citocromo P-450 CYP2C9/genética , Hemorragia Gastrointestinal/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Hemorragia Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Infective endocarditis (IE) is today a public health problem, as the recent ESC Guidelines have also recalled. Abscesses can be complications of IE and their presence means that the infection is not controlled. We describe the complex case of a 57-year-old patient, presented in ED for fever and oleocranical bursitis, increase of cardiac enymes at blood samples. He was admitted to our Cardiology Unit because TTE showed a floating peduncolated formation in the left ventricle. The susequent TEE documented also the presence of a myocardial abscess, confirmed at cardiac MRI. Blood cultures were positive for MSSA and the man received specific antibiotic therapy. Anticoagulation treatment was started with UFH and then switched to Warfarin, surgical approach of the lesion would have been too dangerous according to Cardiac Surgeons. Serious and sudden neurological complications then followed, leading the patient to brain death in ICU.
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Abscesso , Antibacterianos , Ecocardiografia Transesofagiana , Endocardite Bacteriana , Trombose , Humanos , Pessoa de Meia-Idade , Masculino , Abscesso/microbiologia , Abscesso/diagnóstico por imagem , Abscesso/tratamento farmacológico , Antibacterianos/uso terapêutico , Resultado do Tratamento , Evolução Fatal , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/complicações , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/diagnóstico por imagem , Trombose/diagnóstico por imagem , Trombose/microbiologia , Trombose/etiologia , Trombose/tratamento farmacológico , Trombose/cirurgia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico , Anticoagulantes/uso terapêutico , Imageamento por Ressonância MagnéticaRESUMO
The endothelium is a continuous layer of cells that coats the interior walls of arteries, capillaries, and veins. It has an essential regulatory role in hemostatic function, vascular tone, inflammation, and platelet activity. Endothelial dysfunction is characterized by a shift to a proinflammatory and prothrombic state, and it could have a bidirectional relationship with heart failure (HF). Due to neurohormonal activation and shear stress, HFrEF may promote endothelial dysfunction, increase ROS synthesis, and reduce nitric oxide production. Different studies have also shown that endothelium function is damaged in HFpEF because of a systemic inflammatory state. Some clinical trials suggest that drugs that have an effect on endothelial dysfunction in patients with HF or cardiovascular disease may be a therapeutic option. The aim of this review is to highlight the pathogenetic correlation between endothelial dysfunction and heart failure and the related potential therapeutic options.
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BACKGROUND: A submucosal tumor (SMT) of the stomach, which is an occasional finding during routine upper gastrointestinal endoscopy, may pose diagnostic and therapeutic challenges. METHODS: To assess whether endoscopic submucosal dissection (ESD) is a feasible approach to definitively cure SMTs, the authors performed a retrospective cohort study with two endoscopic italian centers. RESULTS: The study consisted of 20 patients with SMTs who underwent ESD. The patients underwent ESD and were followed up by endoscopy. We analyzed complete resection rate, frequency of complications, and survival. The overall rate of R0 resection was 90 % (18/20), with two endoscopic failures, one for a submucosal tumor and one for a neoplasm deeply infiltrating the proper muscle layer. The median procedure time was 119.1 min (range 40-240 min). The median size of the resected specimens was 29 mm (range 15-60 mm). Perforation occurred in 3 patients; all were treated conservatively. There were no cases of severe bleeding. Based on histopathological findings, 6 cases of ectopic pancreas, 1 of ectopic spleen, 3 of leiomyoma, and 10 of gastrointestinal stromal tumor (GIST) were diagnosed. Complete resection was obtained in all GIST cases. Among the 10 GIST cases treated by ESD, no death occurred: the 5-year disease-specific survival rate was 100 %. CONCLUSIONS: The high success rate of 90 % and the low incidence of complications should indicate ESD is the correct diagnostic and definitive treatment in selected patients.
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Endoscopia , Gastrectomia , Mucosa Gástrica/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Leiomioma/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Seguimentos , Mucosa Gástrica/patologia , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Leiomioma/mortalidade , Leiomioma/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
We present a rare case of a 77-year-old Italian woman, admitted to the neurology unit with the diagnosis of West Nile virus encephalitis. Twenty days after the onset of the neurological symptoms, new negative T-waves appeared on the ECG in association with serum elevation of myocardial necrosis enzymes and regional cardiac wall motion abnormalities on echocardiography, so that a coronary angiography was performed. The exam showed significant stenosis on the left circumflex artery, treated with percutaneous coronary intervention. In addition, a cardiovascular magnetic resonance was performed for further investigation: the T2-weighted images revealed edema in the anterior wall and mid-wall late gadolinium enhancement, significant findings of acute myocardial inflammation. Because of the recent diagnosis of West Nile virus encephalitis and the high serum level of specific IgM antibody, the clinical presentation was suggestive of West Nile myocarditis.
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Encefalite , Miocardite , Vírus do Nilo Ocidental , Feminino , Humanos , Idoso , Miocardite/diagnóstico , Meios de Contraste , GadolínioRESUMO
The aorta and aortic wall have a complex biological system of structural, biochemical, biomolecular, and hemodynamic elements. Arterial stiffness could be considered a manifestation of wall structural and functional variations, and it has been revealed to have a strong connection with aortopathies and be a predictor of cardiovascular risk, especially in patients affected by hypertension, diabetes mellitus, and nephropathy. Stiffness affects the function of different organs, especially the brain, kidneys, and heart, promoting remodeling of small arteries and endothelial dysfunction. This parameter could be easily evaluated using different methods, but pulse-wave velocity (PWV), the speed of transmission of arterial pressure waves, is considered the gold standard for a good and precise assessment. An increased PWV value indicates an elevated level of aortic stiffness because of the decline in elastin synthesis and activation of proteolysis and the increase in fibrosis that contributes to parietal rigidity. Higher values of PWV could also be found in some genetic diseases, such as Marfan syndrome (MFS) or Loeys-Dietz syndrome (LDS). Aortic stiffness has emerged as a major new cardiovascular disease (CVD) risk factor, and its evaluation using PWV could be very useful to identify patients with a high cardiovascular risk, giving some important prognostic information but also being used to value the benefits of therapeutic strategies.
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Marijuana consumption is growing up becoming very common especially between young people. 9-THC, the main psychoactive compound in cannabis, acts on the endocannabinoid system having different cardiovascular effects, including arrhythmias, acute coronary syndrome, and sudden cardiac death. We present the case of a young man from Gambia with no cardiovascular risk factors, marijuana consumer, presenting to the emergency department with ST-elevation myocardial infarction. At coronary angiography, thrombotic left anterior descending coronary artery subocclusion was documented. We also describe the association between acute coronary syndrome and cannabis abuse.
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Síndrome Coronariana Aguda , Cannabis , Trombose Coronária , Abuso de Maconha , Infarto do Miocárdio com Supradesnível do Segmento ST , Masculino , Humanos , Adolescente , Abuso de Maconha/complicações , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/etiologia , Síndrome Coronariana Aguda/complicações , Cannabis/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Angiografia Coronária , Vasos CoronáriosRESUMO
Mutation targeted therapy in cystic fibrosis (CF) is still not eligible for all CF subjects, especially for cases carrying rare variants such as the CFTR genotype W57G/A234D (c.169T>G/c.701C>A). We performed in silico analysis of the effects of these variants on protein stability, which we functionally characterized using colonoids and reprogrammed nasal epithelial cells. The effect of mutations on cystic fibrosis transmembrane conductance regulator (CFTR) protein was analyzed by western blotting, forskolin-induced swelling (FIS), and Ussing chamber analysis. We detected a residual CFTR function that increases following treatment with the CFTR modulators VX661±VX445±VX770, correlates among models, and is associated with increased CFTR protein levels following treatment with CFTR correctors. In vivo treatment with VX770 reduced sweat chloride concentration to non-CF levels, increased the number of CFTR-dependent sweat droplets, and induced a 6% absolute increase in predicted FEV1% after 27 weeks of treatment indicating the relevance of theratyping with patient-derived cells in CF.
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Ductos Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/estatística & dados numéricos , Colestase/cirurgia , Constrição Patológica/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/patologia , Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colestase/diagnóstico por imagem , Colestase/etiologia , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/etiologia , Seguimentos , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Humanos , Itália , Angiografia por Ressonância Magnética , Seleção de Pacientes , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Stents , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Caseous calcification of the mitral annulus is an uncommon variant of mitral annular calcification. It appears as a round echodense mass containing central areas of echolucencies resembling liquefaction and with no flow in the central zone on color Doppler. In most cases it involves the posterior mitral annulus region, particularly in female subjects. The pathogenesis remains unclear: hypercholesterolemia and the dissolution of lipid-rich macrophages may be implicated in liquefaction necrosis. Transthoracic and transesophageal echocardiography represents the most reliable technique for diagnosis, whereas cardiac magnetic resonance imaging is the choice in doubtful cases. We report the case of an 82-year-old female patient describing different aspects of this particular clinical condition.
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Calcinose , Doenças das Valvas Cardíacas , Feminino , Humanos , Idoso de 80 Anos ou mais , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Calcinose/diagnóstico por imagem , Doenças das Valvas Cardíacas/diagnóstico por imagem , Ecocardiografia Transesofagiana , LipídeosRESUMO
To explore the putative role of the Merkel cell polyomavirus in human colon cancer, a prospective molecular case-control study was undertaken in patients and their relatives enrolled during a screening program. Fresh tissue samples from 64 cases of colon cancer (mean age 69.9 ± 11.0 years; 40 males) and fresh biopsies from 80 relatives (mean age 53.7 ± 8.6 years; 43 male; 55 son/daughter, 23 brother/sister, 2 parents) were analyzed by PCR and sequencing. Pre-cancerous lesions, namely adenomas and polyps, were detected in 15 (18.8%) and 9 (11.2%) of the controls, respectively. In addition, 144 blood samples were examined. Merkel cell polyomavirus DNA was detected in 6.3% of cases and 8.8% of controls. This difference was not statistically significant in the logistic regression analysis, after adjustment for age. Whereas blood samples from both cases and controls tested negative, the DNA Merkel cell polyomavirus was identified in 12.5% of adenoma/polyp tissues. No statistically significant difference was found when prevalence rates of Merkel cell polyomavirus in normal, pre-cancerous and cancer tissues were compared. Sequence analysis of the viral LT3 and VP1 regions showed high homology (>99%) with those of strains circulating worldwide, especially with genotypes detected in France. The findings of this survey are consistent with the hypothesis that the Merkel cell polyomavirus, in addition to other human polyomaviruses, can be recovered frequently from the gastrointestinal tract, because it is transmitted throughout the fecal-oral route. Moreover, the study does not indicate a role for Merkel cell polyomavirus in the genesis of colon cancer.
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Neoplasias do Colo/virologia , Células de Merkel/virologia , Infecções por Polyomavirus/epidemiologia , Polyomavirus/isolamento & purificação , Infecções Tumorais por Vírus/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Análise por Conglomerados , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Genótipo , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/virologia , Prevalência , Análise de Sequência de DNA , Infecções Tumorais por Vírus/virologiaRESUMO
To explore the involvement of the simian polyomavirus SV40 in human colon cancer, a molecular case-control study was undertaken in patients and in their relatives living in an area where the spread of SV40 has already been documented. From 2006 to 2008, 94 colon cancer patients (age: 37-90 years) and 91 subjects (age: 32-70 years) relatives of each index case were enrolled. A blood sample and a specimen of cancer tissue or biopsy were collected, from each patient or control, respectively. Samples were analyzed twice for Polyomavirus (i.e., SV40, JCV, and BKV) by PCR and by quantitative real-time PCR (RT-qPCR) with reproducible results. No BKV/JCV was detected either in normal or pathological tissues. SV40 was not present in control subjects, either normal tissue or in biopsies from adenomas or polyps. All blood samples were negative. Conversely, six adenocarcinoma specimens were positive for SV40 sequences (overall prevalence 6.4%, P = 0.03 in comparison with controls). Nevertheless, the SV40-associated colon cancer risk proved statistically not significant (OR = 3.91; P = 0.115) when adjusted for age. Quantitation of SV40 DNA performed by RT-qPCR showed a low viral load ranging from 6.2 x 10(1) to 9 x 10(3) copies per reaction. This molecular case-control survey showed, for the first time in fresh samples and by RT-qPCR, that SV40 can be detected in colon cancer tissue. However, the finding was not statistically significant when compared with a well-structured community control group. Thus, the role of SV40 and other polyomavirus in colon cancer genesis deserves further investigation.
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Adenocarcinoma/virologia , Neoplasias do Colo/virologia , Infecções por Polyomavirus/diagnóstico , Vírus 40 dos Símios/isolamento & purificação , Infecções Tumorais por Vírus/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Vírus BK/genética , Vírus BK/isolamento & purificação , Estudos de Casos e Controles , DNA Viral/genética , Feminino , Humanos , Itália , Vírus JC/genética , Vírus JC/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/virologia , Vírus 40 dos Símios/genética , Infecções Tumorais por Vírus/virologiaRESUMO
BACKGROUND: Endoscopic submucosal dissection (ESD) has been developed as treatment for early gastric cancer (EGC) by Japanese authors. However, there are no reports about its possible implementation in the Western setting. The aim of the present work is to determine the safety and efficacy of the endoscopic treatments for EGC in an Italian cohort. METHODS: Forty-five patients for a total of 48 gastric lesions were enrolled in the study. Thirty-six EMR procedures were performed with the strip biopsy technique using a double-channel endoscope. En bloc resection refers to resection in one piece, while piecemeal refers to resections in which the lesion was removed in multiple fragments. A total of 12 ESD were performed and completed with IT knife. We define as curative treatment lateral and vertical margins of the resected specimens free of cancer and repeat endoscopic finding of no recurrent disease. RESULTS: Out of 36 EMR procedures, 10 were piecemeal resections (28%), while 26 were en bloc (72%). ESD led to en bloc resection in 11/12 cases (92%). Histological assessment of curability in the EMR group was achieved in 56% of the cases, and in 92% of the ESD group. Mean follow-up period was 31 months (range: 12-71 months). There was no local recurrence or distant metastasis in the curative group patients. CONCLUSIONS: These results seem to confirm the safety and the clinical efficacy of the ESD procedure in the Western world too.
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Adenocarcinoma/cirurgia , Gastroscopia/métodos , Neoplasias Gástricas/cirurgia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Coortes , Corantes , Dissecação , Diagnóstico Precoce , Desenho de Equipamento , Feminino , Mucosa Gástrica/cirurgia , Gastroscópios , Humanos , Índigo Carmim , Itália , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Acute recurrent pancreatitis (ARP) is characterized by episodes of acute pancreatitis in an otherwise normal gland. When no cause of ARP is identifiable, the diagnosis of "idiopathic" ARP is given. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene increase the risk of ARP by 3- to 4-times compared to the general population, while cystic fibrosis (CF) patients present with a 40- to 80-times higher risk of developing pancreatitis. CASE SUMMARY: In non-classical CF or CFTR-related disorders, CFTR functional tests can help to ensure a proper diagnosis. We applied an individualized combination of standardized and new CFTR functional bioassays for a patient referred to the Verona CF Center for evaluation after several episodes of acute pancreatitis. The CFTR genotype was G542X+/- with IVS8Tn:T7/9 polymorphism. The sweat (Cl-) values were borderline. Intestinal current measurements were performed according to the European Cystic Fibrosis Society Standardized Operating Procedure. Recent nasal surgery for deviated septum did not allow for nasal potential difference measurements. Lung function and sputum cultures were normal; azoospermia was excluded. Pancreas divisum was excluded by imaging but hypoplasia of the left hepatic lobe was detected. Innovative tests applied in this case include sweat rate measurement by image analysis, CFTR function in monocytes evaluated using a membrane potential-sensitive fluorescent probe, and the intestinal organoids forskolin-induced swelling assay. CONCLUSION: Combination of innovative CFTR functional assays might support a controversial diagnosis when CFTR-related disorders and/or non-classical CF are suspected.
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Acute esophageal necrosis, also known as "black esophagus syndrome", is a rare acute esophageal disease that is often associated with vomiting and upper gastrointestinal haemorrhage. At present, little is known regarding the pathogenesis of this disease. We present the case of a 50-year-old white male patient with diabetic ketoacidosis suffering from acute esophageal necrosis with nausea and vomiting but without any clinical signs of upper gastrointestinal bleeding.
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OBJECTIVE: To determine the feasibility and efficacy of the laparoscopic intraoperative rendezvous technique for common bile duct stones (CBDS). DESIGN: Case series. SETTING: Verona University Hospital, Verona, Italy. PATIENTS: A total of 110 patients were enrolled in the study; 47 had biliary colic; 39, acute cholecystitis; 19, acute biliary pancreatitis; and 5, acute biliary pancreatitis with associated acute cholecystitis. INTERVENTIONS: In all patients, CBDS diagnosis was reached by intraoperative cholangiography. Intraoperative endoscopy with rendezvous performed during laparascopic cholecystectomy for confirmed CBDS; for such a procedure, a transcystic guide wire was positioned into the duodenum. Intraoperative endoscopy with rendezvous was performed for retrieved CBDS during a laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Laparoscopic rendezvous feasibility, morbidity, postprocedure pancreatitis, and mortality. RESULTS: The laparoscopic rendezvous proved to be feasible in 95.5% (105 of 110 patients). The rendezvous failed in 3 cases of successfully performed laparoscopic cholecystectomy, and a conversion of the laparoscopy was needed in 2 cases of successful rendezvous. Two major complications and 2 cases of bleeding were registered after sphincterotomy was successfully performed with rendezvous, and severe acute pancreatitis complicated a traditional sphincterotomy performed after a failed rendezvous. CONCLUSIONS: Rendezvous is a feasible option for treatment of CBDS; it allows one to perform only 1 stage of treatment, even in acute cases such as cholecystitis and pancreatitis. Positioning of the guide wire may allow reduced complications secondary to papilla cannulation but not those of the endoscopic sphincterotomy.