Advanced basal cell carcinoma treated with vismodegib: impact on the lives of patients and their families.

Locally advanced basal cell carcinoma (laBCC) represented an uncommon, difficult-to-treat form of skin cancer until the recent approval of the Hedgehog inhibitor vismodegib. Approximately 80% of laBCCs occur in the head and neck region, causing disfiguring skin changes that have an impact on patient quality of life (QoL). Because the lives of patients with advanced BCCs are severely disrupted, it would be expected that the QoL family members involved in caregiving would also be affected. The aim of our study was to quantify the QoL of both patients and family members during vismodegib treatment using the Dermatology Life Quality Index and the Family Dermatology Life Quality Index, respectively.

Isolation of Neofusicoccum parvum from withered grapes: strain characterization, pathogenicity and its detrimental effects on passito wine aroma.

AIMS: There is scarce information on the occurrence of several fungi that infect withered grapes to produce passito wine. Isolation and characterization of Neofusicoccum parvum strains and evaluation of their effects on withered grape and wine were carried out. METHODS AND RESULTS: Nine isolates were phenotypically characterized by colony morphology and genetically discriminated by molecular methods. Two representative strains were identified as N. parvum according to the phylogenetic analysis of internal transcribed spacer (ITS), and a part of translation elongation factor 1-alfa (TEF) and ß-tubulin DNA sequences. The pathogenicity of both strains on grape berries varied according to the inoculation and incubation conditions. Under withering conditions, infected berries showed browning and shrivelling and some berries showed pycnidial development on the surface. The infection affected laccase, esterase, ß-glucosidase and tannase on grape juice as well as the content of several aroma molecules on resulting wines. Strain-specific effects on wine composition were also observed. CONCLUSIONS: Neofusicoccum parvum occurred in withered grapes and was able to infect grapes under withering condition changing the aroma wine. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports for the first time the N. parvum isolation in fruit-drying rooms and indicates its important role on postharvest grape infection.

[Recurrent episodes of brushite nephrolithiasis revealing primary hyperparathyroidism]. / Néphrolithiases récurrentes de brushite révélant une hyperparathyroïdie primaire.

INTRODUCTION: Nephrolithiasis is a frequent disease observed in 1 to 20 % of the general population. This disease predominates in male patients (2:1) and is characterized by a high rate of recurrences (about 50 %). CASE REPORT: We report the case of a 45-year old male patient who experienced during about ten years recurrent bilateral renal colic episodes due to brushite lithiasis. These stones were treated with multiple extracorporeal shock wave lithotripsy sessions. A pyeloureteral junction syndrome predisposing to bulky stones formation has been put in evidence and required a pyeloplasty. After more than ten years of disease activity, a biochemical screening diagnosed primary hyperparathyroidism (PHPT). Radiological assessment identified a parathyroid gland adenoma. Successful surgical removal of this lesion was followed by resolution of the symptomatic kidney stones formation. DISCUSSION: PHPT is associated with kidney stones in about 20 % of the patients. Hypercalciuria is the main risk factor of stones formation but other predisposing factors are also probably involved. Patients carrying a polymorphism located in the coding sequence of the calcium-sensing receptor gene or in the regulatory region of this gene seem to experience an increased occurrence of urinary lithiasis. CONCLUSION: The present case stresses the importance of a metabolic assessment in all patients with recurrent nephrolithiasis, especially in case of bilateral episodes.

Golimumab improves health-related quality of life of patients with moderate-to-severe ulcerative colitis: Results of the go-care study.

BACKGROUND: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. METHODS: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). RESULTS: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48. CONCLUSIONS: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.

A 1-year follow-up study on checkpoint inhibitor-induced colitis: results from a European consortium.

BACKGROUND: Data regarding the clinical outcome of patients with immune checkpoint inhibitor (ICI)-induced colitis are scant. We aimed to describe the 12-month clinical outcome of patients with ICI-induced colitis. MATERIALS AND METHODS: This was a retrospective, European, multicentre study. Endoscopy/histology-proven ICI-induced colitis patients were enrolled. The 12-month clinical remission rate, defined as a Common Terminology Criteria for Adverse Events diarrhoea grade of 0-1, and the correlates of 12-month remission were assessed. RESULTS: Ninety-six patients [male:female ratio 1.5:1; median age 65 years, interquartile range (IQR) 55.5-71.5 years] were included. Lung cancer (41, 42.7%) and melanoma (30, 31.2%) were the most common cancers. ICI-related gastrointestinal symptoms occurred at a median time of 4 months (IQR 2-7 months). An inflammatory bowel disease (IBD)-like pattern was present in 74 patients (77.1%) [35 (47.3%) ulcerative colitis (UC)-like, 11 (14.9%) Crohn's disease (CD)-like, 28 (37.8%) IBD-like unclassified], while microscopic colitis was present in 19 patients (19.8%). As a first line, systemic steroids were the most prescribed drugs (65, 67.7%). The 12-month clinical remission rate was 47.7 per 100 person-years [95% confidence interval (CI) 33.5-67.8). ICI was discontinued due to colitis in 66 patients (79.5%). A CD-like pattern was associated with remission failure (hazard ratio 3.84, 95% CI 1.16-12.69). Having histopathological signs of microscopic colitis (P = 0.049) and microscopic versus UC-/CD-like colitis (P = 0.014) were associated with a better outcome. Discontinuing the ICI was not related to the 12-month remission (P = 0.483). Four patients (3.1%) died from ICI-induced colitis. CONCLUSIONS: Patients with IBD-like colitis may need an early and more aggressive treatment. Future studies should focus on how to improve long-term clinical outcomes.

Localized malignant lymphohistiocytoid pleural mesothelioma.

We report a case of a 42-year-old man with a right pleural mesothelioma. This neoplasm has 3 rare features. Firstly, it was a localized form: suspected by imaging, visualized by video-assisted thoracoscopy, at the time of the curative-thoracotomy and confirmed by the pathological analysis. The second characteristic is its histological type: "malignant lymphohistiocytoid mesothelioma". This rare subtype has been reported in only 4 papers. Third, after pleuro-pneumonectomy, our patient is alive after 6 years and 5 months postoperatively without any sign of recurrence. Only one case with a long follow-up has been reported but with recurrence at 5 years postoperatively.

[Pulmonary granulomatous necrotizing vasculitis: an extra-intestinal manifestation of ulcerative colitis or Wegener's granulomatosis?]. / Vasculite granulomateuse nécrosante pulmonaire : une manifestation extra-intestinale de la rectocolite ulcéro-hémorragique ou une maladie de Wegener isolé ?

Respiratory symptoms are rare manifestations of ulcerative colitis as well as intestinal manifestations in Wegener granulomatosis. We report the case of a 17-year old man previously diagnosed as having ulcerative colitis who presented with diffuse thoracic pain. Hypermetabolic pulmonary nodules were discovered at the positron emission tomographic scan. Necrotizing granulomatous vasculitis was demonstrated at lung biopsy. In this paper, we describe the association between pulmonary nodules and ulcerative colitis and we discuss the possibility of an overlap syndrome between ulcerative colitis and Wegener granulomatosis.

CD4 T cells mediate mucosal and systemic immune responses to experimental hookworm infection.

Hookworm infection is associated with anaemia and malnutrition in many resource-limited countries. Ancylostoma hookworms have previously been shown to modulate host cellular immune responses through multiple mechanisms, including reduced mitogen-mediated lymphocyte proliferation, impaired antigen presentation/processing, and relative reductions in CD4(+) T cells in the spleen and mesenteric lymph nodes. Syrian hamsters were depleted of CD4(+) for up to 9 days following intraperitoneal injection (200 microg) of a murine anti-mouse CD4 monoclonal IgG (clone GK1.5). CD4(+) T-cell-depleted hamsters infected with the hookworm Ancylostoma ceylanicum exhibited a threefold higher mean intestinal worm burden and more severe anaemia than animals that received isotype control IgG. In addition, depletion of CD4(+) T cells was associated with impaired cellular and humoral (serum and mucosal) immune responses to hookworm antigens. These data demonstrate an effector role for CD4(+) T cells in hookworm immunity and disease pathogenesis. Ultimately, these studies may yield important insights into the relationship between intestinal nematode infections and diseases that are associated with CD4(+) T-cell depletion, including HIV.

Case report: Caustic foreign body insertion into the male urethra.

Self-insertion of foreign bodies into the male urethra is a rare presentation. We report a unique case of urethral insertion involving three AAA batteries and the resulting battery acid leakage and urinary obstruction. This report discusses the approach to management, extraction techniques and effects of battery acid within the male urethra.

Azathioprine for prevention of clinical recurrence in Crohn's disease patients with severe endoscopic recurrence: an IG-IBD randomized double-blind trial.

OBJECTIVE: The recurrence of Crohn's Disease after ileo-colonic resection is a crucial issue. Severe endoscopic lesions increase the risk of developing early symptoms. Prevention and treatment of post-operative Endoscopic Recurrence (ER) have been studied with conflicting results. We compare effi cacy of azathioprine (AZA) vs. high-dose 5-aminosalicylic acid (5-ASA) in preventing clinical recurrence and treating severe post-operative ER. PATIENTS AND METHODS: We performed a 1-year multicenter randomized double-blind double-dummy trial. Primary end-points were endoscopic improvement and therapeutic failure (clinical recurrence or drug discontinuation due to lack of efficacy or adverse events) 12 months after randomization. We also performed a post-trial analysis on symptomatic and endoscopic outcomes 10 years after the beginning of the trial, with a median follow-up of 60 months. RESULTS: Therapeutic failure occurred in 8 patients (17.4%) within 12 months from randomization, with no significant difference between patients treated with 5-ASA (20.8%, 5 patients) and those with AZA (13.6%, 3 patients). Therapeutic failure was due to clinical recurrence in the 5-ASA group and to adverse events in the AZA group. Endoscopic improvement at 12 months was observed in 8 patients, 2 (11.8%) in the 5-ASA group and 6 (30%) in the AZA group. No serious adverse event was recorded. At the post-trial analysis (median follow-up 60 months), 47.8% (22/46) of patients experienced clinical recurrence: 54.2% (13/24) in the 5-ASA group and 40.9% (9/22) in the AZA group, p=0.546. Patients treated with AZA had lower risk of drug escalation. Clinical recurrence was associated with smoking (p=0.031) and previous surgery (p=0.003). CONCLUSIONS: Our trial indicates that there was no difference in terms of treatment failure between 5-ASA and AZA in patients with severe ER. The main limit of AZA is its less favorable safety profile.

The management of a pulmonary artery aneurysm.

A 51-year-old woman with a giant pulmonary artery aneurysm was referred to our department for surgical opinion. Imaging study confirmed a large aneurysmal dilatation of the left pulmonary artery starting in the pulmonary trunk. There was no underlying pathology except for a pulmonary commissurotomy 20 years previously for a significant valvular pulmonary stenosis. The role of surgery in this entity is not well defined. We report the management of one case.

Mucosal antibody responses in experimental hookworm infection.

Hookworms are bloodfeeding nematodes that reside in the intestinal mucosa. These parasites secrete proteins that induce robust systemic immune responses in humans and experimental animals. By contrast, mucosal immune responses in and around the site of attachment are not described as well. This paper presents data from studies aimed at examining hookworm-specific mucosal antibody responses in a hamster model of Ancylostoma ceylanicum infection. Intestinal flush prepared from infected hamsters was analysed by ELISA and shown to be enriched in IgA-specific for A. ceylanicum excretory-secretory (ES) products. Evaluation of mucosal IgA responses by immunoblot demonstrated that infected hamsters recognized a broad range of ES proteins. Hamsters repeatedly exposed to drug-terminated infections were shown to have enhanced serum IgG and mucosal IgA responses, as well as a high level of protection from challenge infection. Parasite-specific IgA was also detected in the faeces of hamsters undergoing a primary infection, and increasing faecal IgA responses were coincident with significant reductions in intestinal worm burdens and faecal ES output over time. Together these results suggest that secretory IgA may act in concert with other components of the mucosal and systemic immune response to promote protective immunity against hookworm infection and/or disease.

Genotyping by Amplified Fragment Length Polymorphism and malate metabolism performances of indigenous Oenococcus oeni strains isolated from Primitivo wine.

The Amplified Fragment Length Polymorphism (AFLP) technique was applied for the first time to investigate the genotyping of Oenococcus oeni, the most important species involved in malolactic fermentation (MLF) in wine. A total of 87 out of 220 lactic acid bacteria, isolates from "Primitivo" wine (Apulia, Italy) undergoing MLF, identified as O. oeni by species-specific PCR and 16S rRNA sequence analysis, were studied by AFLP analysis. Four main clusters were distinguished and three of them showed intraspecific homology higher than 60%. A total of 28 strains, representative of AFLP clusters, were tested for malate metabolism in order to gain information on their malolactic performances. Significant differences were observed among strains for malic acid consumed, biomass produced and specific malic acid consumption rate. These findings indicated that AFLP technique is reliable for typing O. oeni strains and that, together with metabolism studies it may be used to individuate possible candidates as industrial malolactic starters.

Infliximab in severe ulcerative colitis: short-term results of different infusion regimens and long-term follow-up.

BACKGROUND: Severe ulcerative colitis is a life-threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy. AIM: To evaluate short- and long-term effectiveness and safety of infliximab in severe refractory ulcerative colitis. METHODS: Eighty-three patients with severe ulcerative colitis (i.v. glucocorticoids treatment-refractory) were treated with infliximab in 10 Italian Gastroenterology Units. Patients underwent one or more infusions according to the choice of treating physicians. Short-term outcome was colectomy/death 2 months after the first infusion. Long-term outcome was survival free from colectomy. Safety data were recorded. RESULTS: Twelve patients (15%) underwent colectomy within 2 months. One died of Legionella pneumophila infection 12 days after infliximab. Early colectomy rates were higher in patients receiving one infusion (9/26), compared with those receiving two/more infusions (3/57, P = 0.001, OR = 9.53). Seventy patients who survived colectomy and did not experience any fatal complications were followed-up for a median time of 23 months; 58 patients avoided colectomy during the follow-up. Forty-two patients were maintained on immunosuppressive drugs. No clinical features were associated with outcomes. CONCLUSIONS: Infliximab is an effective and relatively safe therapy to avoid colectomy and maintain long-term remission for patients with severe refractory ulcerative colitis. In the short term, two or more infusions seem to be more effective than one single infusion.