Postoperative digestive fistulas. Etiopathogenic considerations

The digestive fistula is one of the most serious complications that might appear following different types of resectional digestive surgery. This condition still carries a considerable morbidity and mortality rate and therefore all surgical and ICU staff pay a great deal of attention and intensify their care to avoid the fatalities. The postoperative digestive fistulas, through their physiopathological and clinical complexity induce the disturbance of the biological equilibrium with vital consequences. The trend of the last decades is the increasing of digestive fistulas incidence with a variable mortality rate after different authors. A therapeutic algorithm is needed. The mortality rate due to digestive fistulas, two decades ago was, around 60%; at the present there is a decrease of the mortality rate, which is around 10%. The explanation is the introduction of the new methods of treatment such as lactic acid lavage aspiration for alkaline fistulas or total parenteral nutrition, continuous enteral nutrition and antiexocrine chemotherapy. A fistula is a communication between two epithelial or endothelial surfaces, lined by granulation tissue. It can be a life-threatening condition.     

Cerebral aspergillosis caused by Aspergillus ustus following orthotopic heart transplantation: case report and review of the literature

Abstract:  This report describes the first case of cerebral aspergillosis in a heart transplantation patient caused by Aspergillus ustus and reviews 15 previously reported cases of invasive aspergillosis in immunocompromised hosts caused by this mold. The utility of molecular analysis for the identification of unusual fungal pathogens is also described. The refractory nature of A. ustus to treatment is similar to other Aspergillus species and treatment options are reviewed.     

TLR4 and MyD88 control protection and pulmonary granulocytic recruitment in a murine intranasal RSV immunization and challenge model

An intranasal vaccine composed of Toll-like receptor 2 (TLR2) ligand Neisseria meningitidis outer membrane proteins and Toll-like receptor 4 (TLR4) ligand Shigella flexneri lipopolysaccharide (LPS) (Protollin) and enriched respiratory syncytial virus (RSV) proteins (eRSV) has been demonstrated to promote balanced Th1/Th2 responses without eosinophil recruitment and to protect against challenge in mouse models. We used TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) knock-out (-/-) mice to investigate the roles of these signalling pathways on immunogenicity, protection and pulmonary infiltrates following RSV immunization and challenge. Antigen-specific systemic and mucosal antibody production was significantly impaired only in TLR4-/- mice following Protollin–eRSV immunization. In contrast, an intact MyD88 pathway was crucial to elicit a balanced type 1:type 2 immune response, characterized by increased splenocyte production of antigen-induced IFNγ and IL-10 with concomitant reduction of IL5, IgG2a isotype switching and abrogation of pulmonary eosinophil recruitment following challenge. MyD88-dependent signalling also contributed to neutrophil recruitment to the lungs following immunization with eRSV antigen, in the presence or absence of Protollin, compared to a mock antigen or vaccine. Both TLR4 and MyD88-signalling were required for optimal protection against challenge. The upregulation of early signalling molecules IFN-β, TNFα, CD40 and CD86 were studied in splenocytes isolated from naïve TLR2, TLR4 and MyD88-/- mice following stimulation with vaccine components. Splenocytes from TLR4-/- mice displayed reduced IFN-β while those of MyD88-/- mice elicited less TNFα and lower expression of CD40 and CD86 on CD11c+ cells. Together, our results suggest that optimal immunogenicity and protection against RSV without risk of enhanced pulmonary inflammation requires intact TLR4/MyD88-dependent signalling.     

Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens

Multiple sclerosis affects more women than men. The reasons for this are unknown. Previously, we have shown significant differences in women versus men in inflammatory cytokine responses to the major protein component of myelin, proteolipid protein (PLP), which is thought to be a target in MS patients. Here, using the ELISPOT assay, we examined sex differences in single-cell secretion of Th1 and Th2 cytokines from freshly isolated PBMC between relapsing remitting (RR) MS patients and healthy individuals. Cells were stimulated with MS-associated antigens including proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and non-disease related antigens. Our data show a sex bias in the cytokine responses to multiple MS-relevant myelin antigens: Women with MS show IFNgamma-skewed responses and men with MS show IL-5-skewed responses. These data extend our previous findings [Pelfrey, C.M., Cotleur, A.C., Lee, J.C., Rudick, R.A. 2002. Sex differences in cytokine responses to myelin peptides in multiple sclerosis. J. Neuroimmunol. 130, 211-223.]: (1) by demonstrating gender skewing in cytokine responses to an expanded myelin antigen repertoire, which includes MBP, MOG and PLP; (2) by showing TNFalpha and IL-10 do not display comparable gender skewing compared to IFNgamma and IL5; (3) by defining the patient population as early, untreated RRMS patients to avoid confounding factors, such as different disease stages/disability and immunomodulatory therapy; and (4) by showing HLA type does not appear to underlie the gender differences. These findings may explain increased susceptibility to MS in women and could contribute to the differences in disease severity between men and women.     

Acute interstitial nephritis of fluindione: about three cases

Acute interstitial nephritis is a frequent cause of acute renal failure, representing about 10% of all biopsied cases. Early recognition of drug-induced acute immunoallergic interstitial nephritis prevents the development of severe chronic renal injury. The list of imputable drugs includes phenindione, a vitamin K antagonist. Fluindione which is also an indanedione derivative is another vitamin K antagonist. We report three biopsy-proved cases of fluindione related acute interstitial nephritis with recovery of renal function after drug withdrawal and prednisone therapy.     

Cardiac failure in the newborn. Diagnostic pitfalls

Echocardiography commonly represents the diagnostic clue in neonatal heart failure (HF). Congenital heart diseases are the most frequent causes of HF in this age group. Arterio-venous malformations are the most common noncardiac causes of HF. Normal cardiac structural findings on echocardiography require further investigations in order to exclude other causes of HF. We present three male patients admitted in the interval 2003-2007 with neonatal HF, systolic murmur, cardiomegaly, normal cardiac structure on echocardiography and intracranial bruit. All three cases were diagnosed with vein of Galen aneurysmal malformation (VGAM) by head ultrasound. According to age and malformation type, different presentation patterns were noticed: early neonatal intractable HF mimicking aortic coarctation, postnatal HF stabilized by drug treatment, and chronic HF in a VGAM with tendency to spontaneous regression. Both head ultrasound and cranial auscultation are mandatory in newborns or infants with no cardiac primary cause of HF.     

Correction: Compressive strength evaluation of thin occlusal veneers from different CAD/CAM materials,before and after acidic saliva exposure

In the present study are depicted valuable observations for practitioners, obtained from an in vitro study which aims to evaluate the compressive strength of occlusal veneers fabricated from 3 type of restorative materials, before and after 1 month of acidic artificial saliva exposure (pH = 2.939). In this context, 90 extracted human molars were prepared to receive computer-aided design/computer-aided manufacturing (CAD/CAM) occlusal veneers. The restorative materials considered in this study were: Cerasmart; Straumann Nice and Tetric CAD. The occlusal veneers were designed, milled and cemented with an adhesive dual-cure resin cement. From all the extracted human molars, only sixty specimens were immersed in acidic artificial saliva, for 1 month, at 37 °C ± 1 °C and part of this specimens were also thermo-cycled, between 5 and 55 °C ± 2 °C, before compressive strength test. The results showed a lower compressive strength for both the samples exposed to acidic artificial saliva as well as for the samples exposed to acidic artificial saliva and thermo-cycled. Scanning electron microscopy (SEM) showed that after compressive strength, all the specimens non-exposed to acidic artificial saliva, present extensive cracks formation at the surface of the restorations, and after exposure to acidic artificial saliva for 1 month, the surface damage was characterized by longitudinal and profound fractures of the restoration, as well as the fracture of the tooth structure. Between CAD/CAM materials tested, nanoceramic resin shows more favorable fracture patterns, both before and after acidic artificial saliva exposure.

     

The role of gender in non-small cell lung cancer: a narrative review

The role of gender in the development, treatment and prognosis of thoracic malignancies has been underappreciated and understudied. While most research has been grounded in tobacco-related malignancies, the incidence of non-smoking related lung cancer is on the rise and disproportionately affecting women. Recent research studies have unveiled critical differences between men and women with regard to risk factors, timeliness of diagnosis, incongruent screening practices, molecular and genetic mechanisms, as well as response to treatment and survival. These studies also highlight the increasingly recognized need for targeted therapies that account for variations in the response and complications as a function of gender. Similarly, screening recommendations continue to evolve as the role of gender is starting to be ellucidated. As women have been underrepresented in clinical trials until recently, the data regarding optimal care and outcomes is still lagging behind. Understanding the underlying similarities and differences between men and women is paramount to providing adequate care and prognostication to patients of either gender. This review provides an overview of the critical role that gender plays in the care of patients with non-small cell lung cancer and other thoracic malignancies, with an emphasis on the need for increased awareness and further research to continue elucidating these disparities.     

ERM proteins regulate growth cone responses to Sema3A

Axonal growth cones initiate and sustain directed growth in response to cues in their environment. A variety of events such as receptor internalization, kinase activation, and actin rearrangement can be stimulated by guidance cues and are essential for mediating targeted growth cone behavior. Surprisingly little is known about how such disparate actions are coordinated. Our data suggest that ezrin, radixin, and moesin (ERMs), a family of highly homologous, multifunctional proteins may be able to coordinate growth cone responses to the guidance cue Semaphorin 3A (Sema3A). We show that active ERMs concentrate asymmetrically in neocortical growth cones, are rapidly and transiently inactivated by Sema3A, and are required for Sema3A-mediated growth cone collapse and guidance. The FERM domain of active ERMs regulates internalization of the Sema3A receptor, Npn1, and its coreceptor, L1CAM, while the ERM C-terminal domain binds and caps F-actin. Our data support a model in which ERMs can coordinate membrane and actin dynamics in response to Sema3A.     

In Situ Intestinal Ischemia-Reperfusion Injury in the Pig: A Model Using the First Jejunal Artery for Flushing

Background We describe a new surgical technique of in situ intestinal ischemia–reperfusion injury in the pig, which includes transection of the small bowel, extrinsic autonomic denervation, lymphatic disruption, and finally in-situ cold ischemia of the graft by flushing through the first jejunal artery. Material and methods Ten female pigs were used for the study. All neural and lymphatic connections to the jejunoileum were transected. The stripped superior mesenteric vessels remained as the only connections. The skeletonized mesenteric vessels were clamped and the superior mesenteric artery was cannulated through the first jejunal artery. The isolated jejunoileum was flushed with cold IGL-1 solution. A small incision on the superior mesenteric vein was made to allow outflow of the effluent. After the flushing process was complete, the small incision in the superior mesenteric vein was closed and the vascular clamps were removed. The proximal 70% of the graft was resected. Results The mean preoperative weight of the animals was 25.8 ±7.6 kg. The mean duration of the operation was 242.0 ± 28.6 min. The mean cold ischemia time was 47.6 ± 3.9 min. All animals survived the procedure and were sacrificed at day 8. At sacrifice, there were no adhesions. The small bowel appeared normal. On intestinal histology, there were no significant changes between specimens obtained from the animal immediately at the end of cold flushing (T0), 2 h after reperfusion (T1), and at sacrifice (T2). Conclusions This novel technique for intestinal ischemia–reperfusion injury in the pig provides an extremely useful model for experimental studies of immunological and cold ischemia–reperfusion injury of transplanted small bowels.