Total pancreatectomy with islet autotransplantation: an overview

Pain control is one of the most challenging aspects in the management of chronic pancreatitis. Total pancreatectomy can successfully relieve the intractable abdominal pain in these patients but will inevitably result in insulin-dependent diabetes. Islet autotransplantation aims to preserve, as far as possible, the insulin secretory function of the islet cell mass thereby reducing (or even removing) the requirement for exogenous insulin administration after a total pancreactomy. Despite the relatively small number of centres able to perform these procedures, there are important technical variations in the details of their approaches. The aim of this review is to provide details of the current surgical practice for total pancreatectomy combined with islet autotransplantation, and outline the potential advantages and disadvantages of the variations adopted in each centre.     

Congenital infiltrating lipomatosis of the face with lingual mucosal neuromas associated with a PIK3CA mutation

We report the case of a 5-year-old girl with congenital right-sided facial hemihypertrophy and right hemi-macroglossia with lingual mucosal neuromas. The segmental presentation of findings suggested the diagnosis of congenital infiltrating lipomatosis of the face (CILF), which belongs within the PIK3CA-related overgrowth spectrum (PROS). This was confirmed by genetic analysis showing a mosaic mutation in PIK3CA H1047R. CILF/PROS should be considered in the differential diagnosis of mucosal neuromas.     

Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice

Dominant mutations in ubiquitously expressed superoxide dismutase (SOD1) cause familial ALS by provoking premature death of adult motor neurons. To test whether mutant damage to cell types beyond motor neurons is required for the onset of motor neuron disease, we generated chimeric mice in which all motor neurons and oligodendrocytes expressed mutant SOD1 at a level sufficient to cause fatal, early-onset motor neuron disease when expressed ubiquitously, but did so in a cellular environment containing variable numbers of non-mutant, non-motor neurons. Despite high-level mutant expression within 100% of motor neurons and oligodendrocytes, in most of these chimeras, the presence of WT non-motor neurons substantially delayed onset of motor neuron degeneration, increasing disease-free life by 50%. Disease onset is therefore non-cell autonomous, and mutant SOD1 damage within cell types other than motor neurons and oligodendrocytes is a central contributor to initiation of motor neuron degeneration.     

SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

Two thirds of patients suffering from a major depressive episode (MDE) do not reach a complete response with antidepressant drugs. This lack of response is due to several factors, including genetic determinants. Since major depressive disorder is associated with inflammatory and oxidative stress abnormalities, the metabolism of superoxide anions might be involved in non‐response to antidepressant drugs. Superoxide anions are metabolized by manganese‐dependent superoxide dismutase (SOD2) in the mitochondria. A functional genetic polymorphism (SOD2, rs4880), responsible of a 40% reduction in enzyme activity, is associated with anti‐inflammatory response of rosuvastatin. We investigated the association of ala‐allele of SOD2 rs4880 and both antidepressant efficacy and inflammatory parameters in patients treated for a MDE with antidepressant drugs. The Hamilton Depression Rating Scale (HDRS) score and levels of plasma CRP and inflammatory cytokines were assessed at baseline, one month (M1), 3 months (M3) and 6 months (M6) after antidepressant treatment. They were compared according to SOD2 genetic polymorphism. Of the 484 patients studied, 361 (74.6%) carried the ala‐allele (Ala group), 123 (25.4%) of them had Val/Val genotype (Val/Val group). No significant difference was observed between the Ala and Val/Val groups neither for baseline clinical characteristics, nor for HDRS scores, response/remission rates, plasma CRP and cytokine levels throughout the study. The rs4880 SOD2 genetic polymorphism was not associated with the clinical response and cytokines levels after antidepressant treatment. These data suggest that SOD2 is not a major genetic determinant of antidepressant response. Other genes of the oxidative stress pathways should be explored in further studies.     

How to Avoid Nontherapeutic Laparotomy in Patients With Multiple Organ Failure of Unknown Origin. The Role of CT Scan Revisited

Diagnosis of intra-abdominal diseases in critically ill patients remains a clinical challenge. Physical examination is unreliable whereas exploratory laparotomy may aggravate patient''s condition and delay further evaluation. Only a few studies have investigated the place of computed tomography (CT) on this hazardous situation. We aimed to evaluate the ability of CT to prevent unnecessary laparotomy during the management of critically ill patients. Charts of all consecutive patients who had undergone an emergency nontherapeutic laparotomy from 1996 to 2013 were retrospectively studied and patient''s demographic, clinical characteristics, and surgical findings were collected. During this period 59 patients had an unnecessary laparotomy. Fifty-one patients had at least one preoperative imaging and 36 had a CT scan. CT scans were interpreted to be normal (n = 12), with minor anomalies (n = 10), or major anomalies (pneumoperitoneum, portal venous gas/pneumatosis intestinalis, thickened gallbladder wall, and small bowel obstruction signs). Surgical exploration was performed through laparotomy (n = 55) or laparoscopy. Overall mortality was 37% with a median survival after surgery of 7 days. In univariate analysis, hospitalization in ICU before surgical exploration was the only factor related to death. In our series CT scans, objectively interpreted, helped avoid unnecessary surgical exploration in 61% of our patients.Key words: Laparotomy, Critical care, Abnormalities, Digestive system, CT scansEarly diagnosis of acute nontraumatic life-threatening intra-abdominal diseases remains a clinical challenge. In critically ill patients, pathologies such as mesenteric ischemia, intestinal perforation, pancreatitis and biliary diseases carry a high mortality rate ranging from 50% to 100%.^1,2 For these patients, physical examination can be unreliable due to deep sedation and absence of acute abdomen symptoms, and use of imaging studies may therefore be necessary to identify intra-abdominal pathologies and prevent delay in diagnosis. Also, imaging studies may help avoiding unnecessary laparotomy which can be associated with a morbidity rate up to 22%.³ Ultrasonography (US) can be performed at the bedside and is a good alternative for the diagnosis of biliary tract disease; however, it is highly operator dependent, made difficult by abdominal distension,⁴ and not effective for bowel perforation or ischemia.⁵ Computed tomography (CT) scans are increasingly used for emergency patients with acute nontraumatic abdominal pain and tenderness, however, misinterpretation or overinterpretation of CT findings are not rare.^6,7 Despite the large use of imaging procedures in the evaluation of intra-abdominal pathologies, few studies have attempted to assess their impact on the management of critically ill patients.^8,9 The aim of this observational work was to evaluate the results of preoperative imaging procedures, especially CT, in a consecutive series of nontraumatic critically ill patients who underwent nontherapeutic surgical abdominal exploration in a French university tertiary care hospital.     

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.