Prognostic value of respiratory compliance course on mortality in COVID-19 patients with vv-ECMO.

BACKGROUND: COVID-19-associated acute respiratory distress syndrome (ARDS) supported by veno-venous extra-corporal membrane oxygenation (vv-ECMO) results in a high in-hospital mortality rate of more than 35%. However, after cannulation, no prognostic factor has been described to guide the management of these patients. The objective was to assess the association between static respiratory compliance over the first 10 days post-vv-ECMO implantation on 180-day mortality. RESULTS: In this multicentric retrospective study in three ECMO referral centers, all patients with COVID-19-associated ARDS supported by vv-ECMO were included from 03/01/2020 to 12/31/2021. Patients were ventilated with ultra-protective settings targeting a driving pressure lower than 15 cmH2O. 122 patients were included. Median age was 59 IQR (52-64), 83 (68%) were male, with a median body mass index of 33 (28-37) kg/m2. Delay between first symptoms to vv-ECMO implantation was 16 (10-21) days. Six-month death was 48%. Over the first ten days, compliance increased in 180 day survivors [from 18 (12-25) to 20 (15-27) mL/cmH2O] compared to non-survivors [from 12 (9-20) to 10 (8-14) mL/cmH2O, p interaction < 0.0001]. A time varying multivariable Cox model found age, history of chronic lung disease, compliance from day one to day ten and sweep gas flow from day one to day ten as independent factors associated with 180-day mortality. CONCLUSIONS: In COVID-19-associated ARDS, static respiratory compliance course over the first ten days post-vv-ECMO implantation is associated with 180-day mortality. This new information may provide crucial information on the patient's prognosis for intensivists.

[Auer rod-like inclusions in non blast cells]. / Inclusions « corps d'Auer like ¼ au sein de cellules non blastiques.

We report a 69-year-old adult case with a monoclonal gammopathy incidentally discovered, associated with a moderate thrombocytopenia of 90 G/L. Study of blood smear revealed the presence of tumor cells presenting Auer rod-like inclusions, although there were not blast cells. Blood cytology as well as immunophenotyping allowed us to make the diagnosis of malignant hemopathy.

[Immunoglobulin G4-related lung disease: Case report and literature review]. / Maladie à immunoglobuline G4 pulmonaire : rapport de cas et revue de littérature.

We report the case of a 61-year-old man with a pulmonary nodule discovered while staging the metastasis of a squamous cell carcinoma. No primary cancer was found. Histological examination of the resected specimen (lingula) was in favor of IgG4-related inflammatory pseudotumor. Histological criteria were described in 2012, combining a dense lymphoplasmacitic infiltrate rich in IgG4-positive plasma cell, storiform fibrosis and obliterative phlebitis. IgG4/IgG plama cell ratio>40 % is mandatory for histological diagnosis of IgG4-related disease. This is a rare and often underdiagnosed disease. Diagnostic criteria are now defined and consensual, combining clinical signs, biology and histology.

p16 INK4a overexpression and p16/Ki-67 dual labeling versus conventional urinary cytology in the evaluation of urothelial carcinoma.

BACKGROUND: Taking into consideration the known overexpression of p16(INK4a) in histologically demonstrated high-grade urothelial malignancies, the objective of the current study was to examine the value of p16(INK4a) overexpression and of p16/Ki-67 dual labeling versus urinary cytology in the detection of urothelial lesions. METHODS: Immunolabeling was performed on demounted and destained Papanicolaou slides after liquid-based ThinPrep processing. Actual diagnoses were ascertained by cystoscopy controls and histopathology. Negative cases, papillary urothelial neoplasia of low malignant potential/low-grade tumor, and high-grade lesions were considered separately. RESULTS: A total of 216 urine samples were collected from new patients with symptoms who were referred for cystoscopy (92 cases) or patients who were being followed after conservative treatment for lesions involving the bladder (117 cases) or the upper urinary tract (7 cases). p16(INK4a) positivity was assessed in 171 of the 216 cases (79.2%) and in 93 of 99 high-grade cases with positive cytology (93.9%). Coexpression of p16/Ki-67 in the same cells was observed in 119 of 216 cases (55.1%) and was noted in 18 of 51 cases of negative or papillary urothelial neoplasia of low malignant potential/low-grade tumor (35.3%) and in 80 of 101 high-grade tumors (79.2%) (P < .0001). Thirteen of 14 high-grade intraurothelial lesions (92.8%) were dual labeled. When high-grade tumors, disease progression (increased grade, muscle infiltration, and extension into the upper urinary tract), and cancer-related death were grouped together as an endpoint, dual labeling demonstrated a sensitivity that was slightly higher than that of urinary cytology (82.5% vs 80.8%; P = .8), with 94.9% overall specificity. CONCLUSIONS: When applied to the search for high-grade and aggressive disease, p16/Ki-67 dual labeling and urinary cytology appear to demonstrate comparable performance.

BAGE hypomethylation, a new epigenetic biomarker for colon cancer detection.

Early detection of colorectal cancer is a decisive step in the successful and complete cure of the disease. Epigenetic markers, in particular, those based on aberrant DNA methylation, can be used to diagnose cancer. B melanoma antigens (BAGE) are a family of genes and truncated genes located in the heterochromatic regions of several human chromosomes. Our previous work showed that BAGE loci (i.e., genes and truncated genes) were hypermethylated in normal tissues and hypomethylated in 98% of human cancers. In the present study, we analyzed DNA methylation of the BAGE loci in 54 colon cancers and in neighboring histopathologic normal tissue samples. Using a combined bisulfite restriction assay, we showed that BAGE loci were hypomethylated in 81% of carcinoma samples. Colon cancer could be diagnosed with 94% specificity, 83% sensitivity, and 89% accuracy. No correlation was found between DNA methylation of BAGE loci and age, gender of patients, nor with the tumor stage or site. Based on the hypothesis that during neoplastic transformation, hypomethylation occurs in juxtacentromeric CpG islands, we suggest that other genes located in the heterochromatic compartment should be tested. These new markers enrich the list of currently studied epigenetic alterations in colon cancer and could be associated with hypermethylation markers to develop reliable diagnostic tests.

Comparative histological analysis of anterior vaginal wall in women with pelvic organ prolapse or control subjects. A pilot study.

The purpose of this study was to compare smooth muscle content of anterior vaginal wall in women with pelvic organ prolapse (POP) and control subjects. Specimens were taken in the midline from the apex of anterior vaginal cuff from eleven women with POP and eight control subjects operated for hysterectomy without prolapse. Masson's trichrome stain was used to determine the distribution of collagen in the extracellular matrix of the vaginal muscularis and to quantify the collagen in area of interest. Slides of alpha smooth muscle actin were detected using antibodies. Morphometric analysis was used to compare and to quantify the smooth muscle content of the vaginal muscularis. Fractional area of nonvascular vaginal smooth muscle of women with POP was significantly decreased in comparison to control subjects (41.9 vs 61.9%, p = 0.005). Fractional area of connective tissue was significantly increased (56.8 vs 35%, p = 0.004). Fractional area of blood vessels was similar (2.2 vs 3.4%, p = 0.20).

[Mohs Micrographic Surgery for the management of basal cell carcinoma: experience at the Nîmes Univeristy Hospital]. / La chirurgie micrographique de Mohs dans la prise en charge des carcinomes basocellulaires. Application au CHU de Nîmes.

AIMS: The goal of this work was to assess the validity of Mohs Micrographic Surgery (MMS) for basal cell carcinoma (BCC) in a routine clinical setting. MATERIAL AND METHODS: Our adaptation of the technique described by Mohs and coll allows intraoperative histological examination of all surgical edges of the resection. Sixteen men and 4 women were selected. RESULTS: Average operative time was 2 hours 30 minutes. No false results were noted. The cosmetetic and functional outcomes were good. CONCLUSION: MMS is a safe and reproducible surgical technique made possible by solid team work. It is adapted for the treatment of BCC with a high risk of recurrence. The cosmetetic and functional results are quite satisfactory. The recurrence rate at 5 years is 10 times less than with other methods of treatment. The additional time required for this surgery be put in balance with the number of tumors for which a second intervention would have been necessary if conventional surgery had been used. All procedures were performed under local anesthesia, and none or the patients required a second intervention.

[Gastrointestinal adenocarcinomas with a choriocarcinomatous component: 2 cases and a review of 120 cases in the literature]. / Adénocarcinome gastro-intestinal à composante choriocarcinomateuse: à propos de 2 cas et revue des 120 cas de la littérature.

Gastrointestinal adenocarcinoma with a choriocarcinomatous component (GACC) is an extremely rare and highly malignant human chorionic gonadotrophin-producing neoplasm. The development of this tumour from dedifferentiation or trans-differentiation of adenocarcinomatous cells is the most likely mechanism. 102 of the 120 cases reviewed in the literature presented enough clinicopathological information to be analysed. This tumour can be purely choriocarcinomatous or associated with an adenocarcinoma as in half of the observations. It is usually found in the stomach although it may be found throughout the digestive tract. The diagnosis of GACC should only be retained after having clearly eliminated a metastasis from a choriocarcinoma in particular in the gonads. The prognosis is very poor in particular in the gastric forms of this disease, with death observed within 12 months following diagnosis in 2/3 of the patients. There is no treatment consensus, and it is decided on a case-by-case basis.

[Primary angiosarcoma of the male breast]. / Angiosarcome primitif du sein chez l'homme.

We report an exceptional case of primary breast angiosarcoma in a 58-year-old man. This is a very rare breast tumor (0.04% of breast tumors) which may be difficult to diagnose. Treatment is now standardized: radical mastectomy associated with adjuvant chemotherapy for grade III or poorly differentiated tumors. Prognosis is variable, depending on tumor size and histological grade. Diagnosis should be established as early as possible because the 10-year overall survival rate is 80% for low grade tumors and only 20% for high grade tumors.

Three-dimensional polarization sensitizes hepatocytes to Fas/CD95 apoptotic signalling.

Maintenance of epithelial cell shape and polarity determines many vital cell functions, including the appropriate response to external stimuli. Murine hepatocytes cultured in a three-dimensional Matrigel matrix formed highly polarized organoids characterized by specific localization of an ERM (ezrin/radixin/moesin) protein, radixin, at microvillus-lined membrane domains. These apical domains surrounded a lumen and were bordered by tight junctions. The hepatocyte organoids were functional as judged by the high level of albumin secretion and accumulation of bilirubin. Stimulation of the Fas/CD95 death receptor, which is highly hepatotoxic in vivo, was a strong inducer of apoptosis in the polarized organoids. This was in sharp contrast to the monolayer hepatocyte cultures, which were protected from death by exacerbated NF-kappaB signalling following engagement of the death receptors. Thus, hepatocytes in polarized, functional organoids modulate an intracellular signal transduction pathway, allowing the recapitulation of their physiological response to an apoptotic stimulus.