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1. L’OBSERVATION : Une femme, âgée de 64 ans, était hospitalisée à la fin du mois d’avril pour dyspnée évoluant depuis un mois. Dans ses antécédents, on notait un reflux gastro-œsophagien, une hypothyroïdie substituée, des migraines, une hypertension artérielle, une hypercholestérolémie et une arthrodèse lombaire. Elle était fonctionnaire, ne fumait pas et consommait de l’alcool de manière occasionnelle. Elle appréciait les balades en forêt. Son traitement comportait : propanolol 40 mg/j, oméprazole 20 mg/j, L-thyroxine 25 μg/j, acide folique 4 mg/j. Fin mars, après une chute de la 11e marche d’un escalier, elle présentait une fracture et une plaie du poignet, nécessitant une attelle plâtrée puis une chirurgie de l’extenseur de l’index droit. C’est en revoyant l’orthopédiste à la consultation de contrôle post-opératoire qu’elle mentionnait pour la première fois une dyspnée de grade 3, associée à des douleurs thoraciques d’effort. Elle était donc hospitalisée en cardiologie où un bilan était réalisé : ECG montrant des ondes T négatives de V1 à V3, échographie cardiaque retrouvant une discrète hypertension artérielle pulmonaire (HTAP), angioscanner pulmonaire négatif, coronarographie normale. Une anémie macrocytaire (hémoglobine : 7,2 g/L) était découverte. Le bilan biologique montrait également une carence en folate substituée. Une gastroscopie mettait en évidence une petite ulcération antrale traitée par oméprazole. Il existait un syndrome inflammatoire (CRP : 200 mg/L), pour lequel les prélèvements bactériologiques (hémocultures, culture urinaire) restaient stériles. [...] Titre en anglais : Dyspnea in a 64 year-old woman

The Aristolochic Acid (AA)-specific mutational pattern was recently characterized in urothelial carcinoma (UC) from Belgian AA Nephropathy (AAN) patients (n=5). Besides the A>T transversion hallmark, a specific AA-mutational pattern was found in the TP53 hotspot region in p53-positive immunohistochemistry (IHC) areas and consisted of poly- or multiclonal TP53 alterations and an unusual high prevalence of G>T transversion. In the current study, these data were complemented using the same validated methodology for assessing the complete coding sequence of the TP53 gene in tumor areas stratified according to the percentage of p53-stained cells (i.e., [+], ≥60%; [+/-], 1-59%, [-], no staining). Results were compared to existing data (i.e., other series of AA-associated UC and IARC TP53 database). Aside of the TP53 hotspot region (exons 5-8), multiple mutations were also found in exons 4 and 10. A unique TP53 mutational pattern was characterized by a large spectrum of mutations among which A>T and C>T have the highest prevalence. Most A>T mutations were characterized by the 5'Py-A-Pu sequence. Interestingly, the majority of p53-negative areas were dysplastic (low grade intra-urothelial neoplasia) and disclosed TP53 mutations among which a majority of A>T transversions. Beside nonsense p53-negative mutations, several missense mutations are also known to affect p53 DNA- or zinc-binding domains, hence probably impairing the antigen binding site and/or masking the antigenic epitope. These uncommon histologic, immunopathologic and genetic features in Belgian AAN patients probably result from the unique pattern of duration and extent of AA exposure which led to a cumulative toxic dose ingested over a short period of time. Consequenlty, current results bring additional and valuable evidence unravelling the molecular pathogenesis of AA-induced carcinogenesis and the origin of related high-grade UCs.

Renal diseases are frequently associated with monoclonal gammopathies. Heavy chain deposition disease (HCDD) is an extremely rare condition, one of the 3 entities of monoclonal immunoglobulin deposition disease (MIDD). It is characterized by the presence of nodular glomerulosclerosis and glomerular and tubular deposition of monoclonal HC without associated light chains (LC). Here, we reported a case of HCDD associated with other manifestations, e.a. pulmonary fibrosis and cutis laxa. A 38-year-old Polish woman was referred to the emergency room for a 2-month history of fatigue, 10 kg weight gain and NYHA II dyspnea. She has been treated in 2014 by corticosteroids for a nephrotic syndrome responsible to acute renal failure, attributed to a minimal change glomerulonephritis, evolving with time to a progressive decrease of her renal function. In addition, she presented a 3-year history of skin changing appearance with premature ageing of the face, neck, chest, arms and feet. On physical examination, she looked much older than her age, with a sagging of the skin and a lack of elasticity that predominates in the neck, axillary regions, back and abdomen. She had peripheral edema and a blood pressure at 160/90 mmHg. Initial lab tests revealed a terminal stage chronic renal failure (creatinine, 10.24 mg/dL) with microcytic anemia (hemoglobin, 7.2 g/dL), hypogammaglobulinemia (IgG, 5 g/L) with a discreet IgG Lambda M-protein and low C3 levels. Both kappa and lambda light chains were elevated with a normal kappa/lambda ratio, and associated to a significant proteinuria (4.78 g/L) with excess lambda LC and micro-hematuria. Kidney biopsy confirmed the presence of nodular glomerulosclerosis with peritubular anti-IgG staining and 'powdery punctate' deposits along the inner aspect of the tubular basement membranes, confirming the diagnosis of HCDD. IgG and C3 deposits were also reported on skin biopsies, in addition to elastic fibers degenerative changes responsible for cutis laxa. Functional pulmonary evaluation revealed a marked restrictive syndrome with a decreased diffusion capacity suggesting an interstitial lung disease, probably related to the elastolysis seen in cutis laxa. Bortezomib-based chemotherapy was started, with the prospect to collect stem cells later on, and in case of complete hematological response, proceed to kidney transplantation. Monoclonal gammapathies are rarely found in patients under the age of 40, and can be associated with numerous clinical manifestations such as MGRS. HCDD is an extremely rare condition, in which patients presented with nephrotic syndrome, hematuria and hypertension, develop progressive renal failure, but can be successfully treated with chemotherapy.

The spectrum of kidney damage associated with monoclonal gammopathy is wide, and notably encompasses diseases secondary to the abnormal precipitation or deposition of monoclonal immunoglobulins. Crystal(cryo)globulin-induced kidney disease is a rare but dramatic complication of monoclonal gammopathy, characterized by spontaneous crystallization of monoclonal immunoglobulins in the renal and systemic vasculature.

WOS: 000354124400016 PubMed ID: 25959163 Background: Hepatitis C virus (HCV) status cannot be reliably predicted in anti-HCV positive/HCV-RNA negative individuals who may either have recovered spontaneously or have a false-positive test due to antibody cross-reaction. Investigating T lymphocyte responses in individuals with different HCV status may help understand the cellular immune mechanisms underlying spontaneous recovery, treatment response, and chronicity. Objective: We aimed to determine whether anti-HCV positive, HCV-RNA negative individuals are truly spontaneous recoverers from acute HCV infection. Study design: We used enzyme-linked immunosorbent spot (ELISPOT) assay to compare HCV-specific lymphocyte response among anti-HCV positive/HCV-RNA negative individuals, patients with sustained virological response to interferon-gamma/ribavirin treatment, and patients with chronic HCV infection. Results: We found that 83% of anti-HCV positive/HCV-RNA negative individuals without a past medical history of acute icteric hepatitis had an HCV-specific T lymphocyte response in peripheral blood. Lymphocyte responses in these individuals were similar in magnitude to treatment responders unlike patients with chronic HCV whose virus-directed immunity was significantly suppressed. Conclusions: Detection of HCV-specific T lymphocyte responses using ELISPOT is a feasible method to ascertain past asymptomatic acute HCV infection. Office of Scientific Research Projects, Istanbul University [BYPS-1-26/31012007] This study is funded in part by the Office of Scientific Research Projects, Istanbul University (no: BYPS-1-26/31012007).

Background: Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes. Methods: The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case–control study of surviving and non-surviving patients was conducted. Results: Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2–52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p = 0.015) and prolonged neutropenia (p = 0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p = 0.001 and p = 0.001, adjusted r2 = 0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p

BACKGROUND: To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer. PATIENTS AND METHODS: Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level). RESULTS: Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response. CONCLUSIONS: Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.

This report describes the distribution of different contaminants (fungi, free-living amoebae, bacteria including Legionella) in the water of in-use oxygen humidifier reservoirs. We investigated reasons of contamination and also gave recommendations that may decrease the incidence of pneumonia related to use of contaminated humidifiers. The water of humidifiers is the major environmentassociated reservoir for nosocomial pneumonia pathogenes such as Pseudomonas aeruginosa, Legionella, and Aspergillus. 1 Inhalation of contaminated aerosols leads todirectinoculation of these pathogenes tothe airway, 2 and some free-living amoebae (FLA) serve as natural hosts for legionellae in the environments. 3 At particular risk for acquiring fungal infections are individuals who are immunocompromised. 4 Although many studies have been published on the contamination of humidifier’s water with bacteria, few highlighted fungal and amoebal contamination.