Elective tracheostomy during COVID-19 outbreak: to whom, when, how? Early experience from Venice, Italy.

PURPOSE: The need for prolonged invasive mechanical ventilation in COVID-19 patients is placing the otorhinolaryngologist in front of an increasing request for tracheostomy. Nowadays, there is uncertainty regarding the timing of tracheostomy, the prognosis of these patients and the safety of healthcare workers. The aim of this study is to evaluate the efficacy and safety of tracheostomy placement in patients with COVID-19. METHODS: A retrospective cohort study on 23 COVID 19 patients, to analyse the timing of tracheostomy, the risk factors associated with in-hospital death and the infection of the involved health care workers. Early tracheostomy was defined as ≤ 10 days and late ones > 10 days. RESULTS: The mortality rate of COVID-19 patients admitted to ICU that underwent tracheostomy was 18%. The overall mortality of patients admitted to ICU was 53%. The univariate analysis revealed that early tracheostomy, SOFA score > 6, and D-dimer level > 4 were significantly associated with a greater risk of death. At the multivariate analysis SOFA score > 6 and D-dimer level > 4 resulted as significant factors for a higher risk of death. No health care workers associated with tracheostomy are confirmed to be infected by SARS-CoV2. CONCLUSION: We suggest to wait at least 14 days to perform tracheostomy. In patients with SOFA score > 6 and D dimer > 4, tracheostomy should not be performed or should be postponed. Optimized procedures and enhanced personal protective equipment can make the tracheostomy safe and beneficial in COVID-19 patients.

Eco-responsibility in the operating theater: An urgent need for organizational transformation.

Factors associating environmental degradation with human health have shown that air pollution is a source of morbi-mortality throughout the world. Unfortunately, hospitals are themselves "silent polluters". As healthcare professionals, we are the guarantors not only of quality of patient care, but also of proper hospital conduct. The aim of this attempt at clarification is to outline what can be done in the operating theater to reduce the environmental impact of the treatments we administer. Our recommendations will go above and beyond regulatory frameworks and draw upon daily practice concerning waste management, energy consumption, utilization of anesthetic agents and multiple forms of waste. A number of French and international pilot experimentations have been carried out and could strongly contribute to the modification of clinical practices with a societal impact, at a time when ecology has become one of the main preoccupations of our fellow citizens.

The prognostic significance of glutamic acid decarboxylase antibodies in patients with chronic pancreatitis undergoing total pancreatectomy with islet autotransplantation.

AIM: Islet autotransplantation (IAT) is considered a 'non-immune' model of islet transplant, with no risk for autoimmune-mediated beta cell loss, but we have previously observed de novo type 1 diabetes in one total pancreatectomy with islet autotransplantation (TPIAT) recipient. We aimed to investigate the clinical significance of glutamic acid decarboxylase antibodies (GADA), as a sensitive marker for autoimmune diabetes mellitus (DM), in patients with chronic pancreatitis undergoing TPIAT. METHODS: We identified 9 patients undergoing TPIAT with elevated GADA pre-TPIAT (8 non-diabetic and 1 with C-peptide positive DM), otherwise demographically similar to GADA negative TPIAT recipients (n=341). Metabolic and clinical measures related to islet cell function were recorded both before and after TPIAT. RESULTS: None of the 9 TPIAT patients achieved insulin independence after surgery, vs. 33% of GADA negative patients (n=318 with 1-yr follow-up). The two patients with the highest titters of GADA (>250 IU/mL) both experienced islet graft failure, despite normoglycaemia pre-TPIAT and high islet mass transplanted (5276 and 9378 IEQ per kg), with elevated HbA1c levels post-TPIAT (8.3%, 9.6%). The remaining 7 seven were insulin dependent with partial graft function and HbA1c levels <7%. CONCLUSION: Insulin dependence was more frequent in 9 patients with elevated GADA prior to TPIAT than in GADA negative TPIAT recipients, with graft failure in 2 cases. We speculate that beta-cell autoimmunity may occur in a small subset of TPIAT recipients and that beta cell antibody testing prior to TPIAT may be warranted to identify individuals at higher risk for insulin dependence.

Qualitative and quantitative contrast-enhanced ultrasonography for the characterisation of non-palpable testicular tumours.

AIM: To assess the diagnostic performance of conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of non-palpable intratesticular tumours. MATERIALS AND METHODS: The local ethics review board approved the protocol, and all of the patients provided written informed consent. Between December 2011 and February 2014, men with non-palpable testicular tumours and normal tumour markers who were referred for surgery were included. The tumours were analysed by conventional US, including B-mode and colour Doppler US (CDUS) as well as by CEUS. Morphological aspects and qualitative and quantitative CEUS criteria, based on visual enhancement and time-intensity curves, were assessed for each lesion. RESULTS: Forty patients were ultimately included. Based on histopathological results, the tumours were classified into three groups: benign tumours (n=16), malignant tumours (n=15), and burned-out tumours (n=9). In B-mode, the morphological aspects were significantly different between benign and malignant tumours (p-values from 0.0002 to 0.008). Qualitative and quantitative analyses of the CEUS images revealed that burned-out tumours exhibited significantly less enhancement than malignant and benign tumours: in burned-out tumours, time-intensity curves were flat, whereas in both benign and malignant tumours the curves had a bell-shaped pattern. All intensity parameters were lower for burned-out tumours compared to benign and malignant tumours (p-value from 0.0001 to 0.026). Both benign and malignant tumours enhanced strongly, however, and no significant difference between the two was noted (p-value from 0.0721 to 0.0953). CONCLUSION: Unlike conventional US, which enable benign lesions to be differentiated from malignant or burned-out tumours, CEUS failed to enabled differentiation between benign lesions and malignant vascularised testicular tumours. CEUS appears to have the potential, however, to differentiate burned-out tumours from vascularised testicular tumours.

Metastatic Pancreatic Adenocarcinoma After Total Pancreatectomy Islet Autotransplantation for Chronic Pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is being used increasingly as a definitive treatment for chronic pancreatitis. Patients with chronic pancreatitis have an elevated risk of pancreatic cancer, which can also masquerade as acute or chronic pancreatitis, making the diagnosis challenging. We describe here the first case of pancreatic ductal adenocarcinoma developing in the liver of a patient after TPIAT for presumed benign chronic pancreatitis. Retrospective analysis of the patient's preoperative serum revealed normal carbohydrate antigen 19-9 and carcinoembryonic antigen levels but elevated levels of microRNAs -10b, -30c, and -106b compared with controls. Screening guidelines are important to reduce the risk of transplantation of malignant tissue. More sensitive screening tools, including the potential use of microRNAs, are needed to detect early preclinical disease, given the highly malignant nature of pancreatic cancer.

[One day diagnosis for breast lesions: Medical and psychological assessment--EVADIASEIN study]. / Diagnostic en un jour des lésions du sein: évaluation médicale et psychologique de la prise en charge--étude EVADIASEIN.

INTRODUCTION: Breast cancer is the most frequent feminine cancer in France and its incidence increases steadily. The time of access to medical care is an indicator of the quality of the treatments recommended by the Plan Cancer 2009-2013, as it influences the diagnosis and reduces psychological morbidity during the pre-diagnosis phase. The one-day diagnosis is a recently initiated concept, which offers to get the results of the biopsy on the day it is performed and facilitates the setting-up of therapeutic care with the surgeon met during the one-day medical consultations. The aim of this study is to evaluate the satisfaction of patients who benefited from a one-day breast lesion diagnosis, as well as confirm the decrease of time of access to medical treatment. METHODS: This is an observational, non-interventional and single-centre study based on 27 patients who benefited from one-day breast lesions diagnosis over two years. The patients were only included who had a classified lesion ACR 4 or 5 and visible in the ultrasound. We analyzed the histological concordance between the biopsy and the definitive histology, the time of access to medical care, and the therapeutic treatments We analyzed the psychological impact of such an organization by sending to the patients a questionnaire including the Psychological Consequence Questionnaire (PCQ) and the Breast Cancer Anxiety Indicator (BCA) allowing to estimate the anxiety generated by the pre-diagnostic phase, the DC-Sat allowing to estimate the satisfaction of the consultation of announcement, as well as the same day diagnosis benefit. RESULTS: The patients were 59.8 years old in average [33-87]. The average time between the date of the mammography and the one-day diagnosis consultation (including the biopsy) was 15.0 days [0-60]. Fifty-seven percent of the patients considered this time as short. The average time between the biopsy date and the start of the treatment was 15.9 days [4-30]. The one-day diagnosis took an average of 1.6 days [1-5]. The results of the PCQ showed an important emotional impact during the diagnosis phase, and the average BCA score reached an average of 3.9 on a scale of 5. However, the patients were very satisfied with the diagnosis consultation with an average of 8.7 on a scale of 10, and 95% think the one-day diagnosis is beneficial to the patients. DISCUSSION: This study shows that the one-day breast-damage diagnosis enables to improve the time of access to care, and meets the current recommendations. Even though faster access to treatment does not reduce the psychological morbidity of awaiting diagnosis, the patients express their satisfaction and find the rapidity of the pre-diagnosis phase beneficial. CONCLUSION: In view of this study, the one-day breast-damage diagnosis appears to be a quality feature in the process of access to care and treatment of the patients.

Development of Autoimmune-Mediated ß Cell Failure After Total Pancreatectomy With Autologous Islet Transplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) is performed for definitive treatment of chronic pancreatitis; patients are not diabetic before surgery, or have C-peptide positive pancreatogenous diabetes. Thus, TPIAT recipients are not traditionally considered at risk for autoimmune loss of the islet graft. We describe a 43-year-old female who underwent TPIAT with high mass islet graft of 6031 IEQ/kg, with no evidence of presurgical ß cell autoimmunity who developed type 1 diabetes within the first year after TPIAT, resulting in complete loss of beta cell function. The patient had positive GAD and insulin autoantibodies at 1 year and 18 months after TPIAT, not present prior, and undetectable C-peptide after mixed meal and intravenous glucose tolerance testing at 18 months. Glucagon secretion was preserved, suggesting the transplanted alpha cell mass was intact. HLA typing revealed a DR3/DR4 class II haplotype. This case highlights the need to consider de novo type 1 diabetes in patients with unexpected islet graft failure after TPIAT.

Imaging in upper urinary tract infections.

Most infections of the upper urinary tract are straightforward and do not require any emergency radiological investigations. A sonogram carried out within 48 hours will in most cases be sufficient to eliminate obstructed pyelonephritis requiring emergency drainage of urine. In complicated cases, or those affecting already weakened areas, an urgent CT scan is necessary, preferably after injection of iodinated contrast medium if renal function permits. CT scanning is far better at diagnosis than sonography as well as at investigating whether there are complications. Furthermore, it is essential that the radiologist is aware of unusual and rare forms of pyelonephritis, especially pseudotumoural forms, so that clinicians can be pointed towards the appropriate treatment, avoiding unnecessary and invasive interventions.

Imaging tumours of the penis.

Malignant primary epithelial tumours of the penis are rare and mainly affect uncircumcised men in their fifties to seventies. They are most frequently located in the glans and foreskin. Imaging is performed if the clinician has doubts about deep extension, after a diagnostic biopsy. High-resolution ultrasound and above all MRI are used to detect invasion of the corpora cavernosa and spongiosum. The lesion is often seen as a moderate T2 hyposignal, making it possible to distinguish it from the relative hypersignal of the corpora cavernosa. The sentinel lymph nodes are inguinal. Adenopathy is frequently present, but does not, however, necessarily reflect tumour invasion, as secondary infection of the lesion, which is often ulcerated, is common. The prognosis for T1 N0 tumours is good, at the cost of mutilating ablation. Extension to the lymph nodes is detrimental. Non-epithelial tumours and metastases are even rarer.

Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes.

We sought to determine the long-term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six recipients with hypoglycemia unawareness received one to two islet infusions. Induction therapy was with antithymocyte globulin (ATG) plus etanercept for tumor necrosis factor-alpha blockade. Recipients received cyclosporine and everolimus for maintenance immunosuppression for the first year posttransplant, with mycophenolic acid or mycophenolate mofetil subsequently substituted for everolimus. Recipients have been followed for 1173 +/- 270 days since their last infusion for islet graft function (insulin independence, hemoglobin A(1c) levels and C-peptide production) and for adverse events associated with the study protocol. Of the six recipients, five were insulin-independent at 1 year, and four continue to be insulin-independent at a mean of 3.4 +/- 0.4 years posttransplant. None of the six recipients experienced recurrence of severe hypoglycemia. Measured glomerular filtration rate decreased from 110.5 +/- 21.2 mL/min/1.73 m(2) pretransplant to 82.6 +/-19.1 mL/min/1.73 m(2) at 1 year posttransplant. In conclusion, islet transplants restored insulin independence for a mean of >3 years in four of six recipients treated with ATG and etanercept induction therapy and with cyclosporine and, initially, everolimus for maintenance. Our results suggest this immunosuppressive protocol may allow long-term graft survival.

[MRI and staging evaluation of prostate cancer]. / IRM et bilan d'extension du cancer de la prostate.

MRI can assess local and locoregional spread of a newly diagnosed prostate cancer by detecting extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node invasion. Endorectal MRI remains the only accurate means to assess local extension. Pelvic MRI with surface coils and the use of superparamagnetic particules provide the sensitivity and the specificity which have never been obtained by the sole measurement of node size of the lymphatic chains draining the prostate gland. With the endorectal coil, only direct signs of extracapsular extension have been maintained and indirect signs have been discarded, giving their too low specificity. Early SVI can only be consistently detected if result of TRUS guided biopsies show involvement of the prostate base. With the pelvic phased array coil, superparamagnetic particules show that metastatic lymph nodes have a specific MR signal which can be detected in normal size nodes. Indications of imaging relies on results of parametrers available before MR imaging. More important than PSA level and Gleason score on biopsies is the so called quantitative histology, represented by the number of sextants involved by tumor and the amount of cancer (measured in mm of tumor) present on biopsies which determine a risk of extraprostatic spread. Of the risk of extraprostatic spread depends indication of MR, which is most probably unnecessary in patients at low risk (<20%) of extraprostatic extension.

Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned myoblasts: searching for a gene expression pattern with a microarray analysis of 5000 skeletal muscle genes.

BACKGROUND AND AIMS: We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts. METHODS: Myoblasts were incubated with control or pancreatic cancer CM for 24 and 48 hours. RESULTS: Lactate significantly increased in CM compared with non-conditioned myoblasts. No variations in expression levels of the main genes involved in glycolysis were found in CM myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed, while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin alpha, troponin T1, and filamin A were underexpressed in CM myoblasts. CONCLUSIONS: Our findings demonstrate that pancreatic cancer cell conditioned media enhanced lactate production and induced proteolysis, possibly by altering expression levels of a large number of genes, not only those involved in protein biosynthesis and degradation or glucose metabolism, but also those involved in the tricarboxylic acid cycle and in vesicle traffic.

Currently used non-specific extracellular MR contrast media.

Magnetic resonance contrast agents have demonstrated their clinical usefulness in a variety of organs for improved detection of various neoplastic, inflammatory and functional abnormalities. Gadolinium chelates are the most widely used. They are extracellular, non-specific contrast agents. Their use in many clinical indications is justified because, in conjunction with improved imaging techniques, these safe and image-enhancing contrast agents add morphologic and functional information compared with unenhanced MR images. This article describes the commercially available compounds, and summarizes their approval status on the international market regarding indications and doses. Their mechanisms of action, biodistributions, toxicities and tolerance profiles in normal and high-risk patient populations are described. Additionally, this article reviews the specific recommendations by the manufacturers for patients at risk. Finally, their main clinical applications are reviewed.

Evaluation of retroperitoneal and pelvic lymph node metastases with MRI and MR lymphangiography.

Local, regional lymph node involvement is an essential prognostic factor and an important determinant of treatment choices for patients with retroperitoneal and pelvic cancer. Current cross-sectional imaging modalities, including computed tomography and magnetic resonance (MR) imaging, use the nonspecific criterion of size and are limited in their ability to differentiate benign from malignant lymph nodes. MR lymphography is a promising imaging modality in differentiating benign from metastatic lymph nodes and provides information on lymph node morphology and function. Ultrasmall superparamagnetic iron oxide (USPIO) particles with a long plasma circulation time are suitable as an MR contrast agent for intravenous MR lymphography. They are taken up by macrophages in normally functioning nodes and reduce the signal intensity of tissue in which they accumulate because of T2 and susceptibility effects of iron oxide. In metastatic nodes, macrophages are replaced by cancer cells, which lack reticuloendothelial activity and cannot take up USPIO. The main mechanisms that might explain a heterogeneous node appearance after USPIO injection are discussed. In published reports, USPIO has shown high degrees of sensitivity and specificity for characterizing lymph nodes in cancer patients. We review the development of USPIO compounds, their imaging characteristics, and our clinical experience.