Aufklärung der molekularen Mechanismen in Autoimmun-Folgeerkrankungen ausgelöst durch das M-Protein von Streptokokken

Streptococcus pyogenes infects more than 600 million humans every year. Moreover, this bacterium causes acute rheumatic fever (ARF), an autoimmune sequela that frequently develops into rheumatic heart disease (RHD),a leading health problem in several low-resource regions in the world. Streptococcal M protein has been implicated in the pathogenesis of ARF. This protein triggers autoimmunity by molecular mimicry of host proteins with coiled-coil structure such as myosin or laminin. In addition, a collagen-binding A/T/E)xYLxx(L/F)N motif that occurs in the N-terminal part of some M proteins evoked collagen IV autoimmunity in vivo. This collagen IV autoimmunity is observed in ARF patients, but is not caused by molecular mimicry. Because patient and experimental data suggested a link between the collagen binding motif and the autoimmune responses in ARF, the motif was named “peptide associated with rheumatic fever” (PARF). However, the role of collagen-binding by M proteins in triggering anti-collagen IV and other autoimmune responses remained elusive. Therefore, different M proteins were tested in this work for their ability to bind collagens I or IV and to evoke autoimmune responses against these collagens and the coiled-coil proteins myosin and laminin in a mouse model. The work proved for the first time that induction of collagen IV autoimmunity is PARF-specific, thus not caused by other parts or properties of the M protein. Further evidence for the role of PARF as a trigger of autoimmunity came from experiments with a recombinant protein (PARF tandem) that contained all known naturally occuring PARF motifs. PARF tandem induced autoimmunity against collagen IV and myosin in mice. Notably, PARF tandem induced in rabbit the production of opsonizing antibodies that reacted with PARF-positive M proteins. As immunization with PARF tandem caused autoimmunity, a vaccine strategy that targets PARF would require further development. The discovery of Spa as a novel collagen binding protein that triggers autoimmunity against collagen, broadens the spectrum of potential rheumatogenic factors in S. pyogenes. For the first time, a trigger of autoimmunity was identified in an emm-type (emm18) that is clearly associated with outbreaks of ARF. The presented work clearly points towards a role of interactions between host and microbial proteins in triggering autoimmunity and may have uncovered a new facet in the pathogenesis of autoimmune diseases in general.Streptococcus pyogenes infiziert mehr als 600 Millionen Menschen im Jahr. Außer einer Vielfalt von akuten Infektionen, verursacht das Bakterium akutes rheumatisches Fieber (ARF), eine Autoimmunerkrankung, die häufig zur rheumatischen Herzerkrankung führt (RHD). RHD ist ein führendes Gesundheitsproblem in einigen Schwellen- und Entwicklungsländern. M Protein von Streptokokken ist ein Auslöser von ARF. Es verursacht Autoimmunität durch molekulare Mimikry von Coiled-Coil-Proteinen des Wirts wie Myosin und Laminin. Außerdem tragen einige M proteine, die eine Autoimmunität gegen Kollagen IV auslösen, das kollagenbindende A/T/E)xYLxx(L/F)N-Motiv. Diese Immunantwort wird auch in Patienten mit ARF beobachtet, ist aber keine Folge molekularer Mimikry. Aufgrund dieser Beobachtungen wird das Motiv “peptide associated with rheumatic fever” (PARF) genannt. Die Rolle der Kollagenbindung als Auslöser der Autoimmunität gegen Kollagen IV und anderen Wirtsproteinen war bisher nicht ausreichend untersucht. Deshalb wurden in dieser Arbeit verschiedene M proteine auf Bindung von Kollagen I oder IV und Auslösen von Autoimmunantworten gegen diese Kollagene und die Coiled-coil Proteine Myosin oder Laminin getestet. Dies wies zum ersten Mal nach, dass die Induktion der Kollagen-IV-Autoimmunität PARF-spezifisch ist und folglich nicht durch andere Teile oder Eigenschaften des M Proteins verursacht wird. Weitere Beweise für die Rolle von PARF als Auslöser für Autoimmunität kamen von Experimenten mit einem rekombinanten Protein (PARF tandem), das alle bisher bekannten natürlich vorkommenden PARF-Motive enthielt. In Mäusen induzierte PARF tandem Autoimmunität gegen Kollagen und Myosin. PARF tandem löste im Kanninchen die Produktion opsonisierender Antikörper aus, die gegen PARF-positive M proteine reagierten. Da die Immunisierung mit PARF tandem aber auch Autoimmunität verursachte, müsste eine PARF-basierte Impfstrategie weiterentwickelt werden. Die Entdeckung von Spa als neues kollagenbindendes Protein, das Autoimmunität gegen Kollagen auslöst, erweitert das Spektrum potentieller rheumatogener Faktoren in S. pyogenes. Zum ersten Mal wurde ein Auslöser von Autoimmunität in einem emm-Typ (emm18) entdeckt, der zu Ausbrüchen von ARF geführt hat. Die vorliegende Arbeit weist klar auf eine Rolle von Interaktionen zwischen Wirts- und Mikrobiellen Proteinen in der Entstehung von Autoimmunität hin und könnte eine neue Facette in der Pathogenese von Autoimmunerkrankungen aufgedeckt haben

Whipple's pancreaticoduodenectomy: Surgical technique and perioperative clinical outcomes in a single center

Introduction: Pancreatic cancer is the fourth cause of death from cancer in Western countries. The radical surgical resection is the only curative option for this pathology. The prevalence of this disease increases with age in population. The causes of pancreatic cancer are unknown, but we consider risk factors like smoke and tobacco usage, alcohol consumption coffee, history of diabetes or chronic pancreatitis. In this study we report our experience in the treatment of resectable pancreatic cancer and periampullary neoplasms with particular attention to evaluate the evolution of surgical technique and the clinical postoperative outcomes. Methods: In our Department between January 2010 and December 2014 we performed a total of 97 pancreaticoduodenectomy. We considered only resectable pancreatic cancer and periampullary neoplasms defined by absence of distant metastases, absence of local tumor extension to the celiac axis and hepatic artery as the lack of involvement of the superior mesenteric vasculature. None of these patients received neoadjuvant chemotherapy. Results: The mean age of these patients was 64.5 years. Jaundice was the commonest presenting symptom associated to anorexia and weight loss. The mean operative time was 295min (±55min). The mean blood loss was 450ml and median blood transfusion was 1 units. 12.1% of patients had an intra-abdominal complication. The commonest complication was Delayed Gastric Emptying responsable of increased length of hospital stay and readmission rate. Postoperative pancreatic fistula of grade C occurred in 4 patients. 2 patients developed a postpancreatectomy hemorrhage. Perioperative mortality was 4.1%. Conclusion: Pancreaticoduodenectomy is a complex surgical technique and the associated high morbidity and mortality resulted in initial reluctance to adopt this surgery for the management of pancreatic and periampullary tumors. Surgical outcomes of pancreatic surgery are better at high-volume experienced center reporting mortality rates below 5%. We perform an end-to-side duct-to-mucosa pancreaticojejunostomy with routinely use of internal pancreatic stent. However no one technique has been shown to definitely be the solution to the problem of postoperative pancreatic fistula. At our center we have a reasonable volume and our data are comparable to literature data

A rare case of abdominal cocoon

Abdominal cocoon is a rare cause of intestinal obstruction usually diagnosed incidentally at laparotomy. It mani- fests by forming a membrane that typically encases the small bowel loops, leading to mechanical obstruction. Preoperative diagnosis is difficult. The etiology of this condition is not well understood; however, it is a form of chronic irritation and inflammation. METHOD: A 33 years old male, from Bangladesh, presented to our emergency department complaining of abdominal pain, nausea, and vomiting. CT abdomen shows a picture of intestinal obstruction at the level of the small intestine. Intraoperative findings showed encapsulation of small bowel by a dense whitish membrane as a cocoon. Histological exam- ination showed a granulomatous peritonitis and Ascaris Lumbricoides in the bowel resected. RESULTS AND CONCLUSIONS: The preoperative diagnosis of abdominal cocoon is difficult and hence, the diagnosis is usu- ally confirmed by laparotomy. Surgery remains the cornerstone in the management of abdominal cocoon. The pathogen- esis of abdominal cocoon remains elusive and has been associated with several conditions. The initial diagnosis of our patient was bowel obstruction from cocoon syndrome (CT and intraoperative findings) probably primitive, and only his- tologically proved granulomatous peritonitis associated with the presence of the parasite

Candida spp. infections after abdominal urgent surgery: comparative analysis of histologic data for which microbiological results were positive for Candida spp.

EV0515 ePoster Viewing Diagnostic/laboratory methods other than molecular Candida spp. infections after abdominal urgent surgery: comparative analysis of histologic data for which microbiological results were positive for Candida spp. V. Rodolico1, G. Gulotta1, L. Montana1, G. Salamone1, D.C. Paola1 1Department of Sciences for Health Promotion and Mother Child Care, Palermo, Italy Objectives: Microbiological identification is justified when the yeast is isolated from a sterile site, the potential clinical impact of identified isolates from non sterile sites such as intra- abdominal organs don’t help the clinicians to determine whether the strain isolate represents contamination, colonization, or true infection. To investigate the contribute of hystopathological investigations in surgical patients who survive the initial postoperative period we compare histological and microbiological results positive for Candida spp. Methods: A retrospective study of abdominal intraoperative tissue or biopsy specimens obtained from patients admitted for acute abdomen with post-operative microbiological samples positive for Candida spp was performed for the years January 2008 to December 2012. Specimens obtained from autopsy cases were excluded. For each case, demographic data, mortality, comorbidity conditions, antimicrobial therapy, specimen type, the use of special histologic stains, any reported suggestion to correlate with or defer to microbiology, and the individual surgical pathologist were recorded. Results: we evaluated 66 positive candida spp culture reports of which 56 had a concurrent surgical pathology specimen; of the 56 cases 5 were excluded because of a known history of fungal infection, among the remaining we selected 23 (15%) histological results because in these patients clinical, microbiological and enventual other histopathological follow-up data were available. Table 1 showed microbiological and hystopathological data. When other than blood culture specimens such as drainage were positive for candida infection the result was suitable with histological picture. On the other hand, when the blood culture was positive the hystopathological results (proliferative and granulomatous inflammation accompanied by numerous macrophages, lymphocytes, plasma cells and neutrophils) were compatible with the patients’ complications to confirm that Candida spp. is a frequent opportunistic pathogen especially in cancer disease. In table we showed comparative analysis of 23 histologic data for which microbiological results were positive for Candida spp. Microbiological Specimen Positive for Candida spp (n) Concorde Histological features Candida specie Comorbidity Outcome (Died) Blood 6 1 C. albicans=3C. nonalbicans= 3 Cancer=5; Cholecistitis=1 3 (c. albican=2) Bile 4 / C. albicans=1C. non albicans=3 Cancer=2Chronic gastritis plus cholecystitis =2 Drainage 6 6 C. albicans=4C. non albicans=2 Cancer= 4Fistula=2 3 ( c. albicans) Biopsy 4 4 C. albicans=4C. non albicans= Cancer=2Fistula=2 1 (c. non albicans) Urine 1 1 C. albicans Bile plus blood 2 2 C. albicans Conclusions: Post- operative Candida spp infection is an important cause of morbidity and is frequently associated with poor prognosis, particularly in higher risk patients. Complicated intra-abdominal infections diagnosis is mainly a clinical diagnosis, therefore, low expansive supplemental procedures for diagnosis, such as histopathology examination provide insight into the diagnostic significance of Candida spp isolated from surgical specimens other than blood samples

Muscle degeneration in inguinal hernia specimens.

There are few articles in the literature reporting the histological changes of groin structures affected by inguinal hernia. A deeper knowledge of this matter could represent an important step forward in the identification of the causes of hernia protrusion. This study aimed to recognise the pathological modifications of muscular structures in autopsy specimens excised from tissues surrounding the hernia orifice. METHODS: Inguinal hernia was identified in 30 autopsied cadavers, which presented different varieties of hernia, including indirect, direct and mixed. Tissue specimens were resected for histological study from structures of the inguinal area surrounding the hernia opening, following a standardised procedure. The histological examination was focussed on the detection of structural changes in the muscle tissues. The results were compared with biopsy specimens resected from corresponding sites of the inguinal region in a control group of 15 fresh cadavers without hernia. RESULTS: Significant modification of the muscular arrangement of the inguinal area was recognized. Pathological alterations such as atrophy, hyaline and fibrotic degeneration, as well as fatty dystrophy of the myocytes were detected. These findings were observed consistently in the context of multistructural damage also involving vessels and nerves. In cadavers with hernia these alterations were always present independent of hernia type. No comparable damage was found in control cadavers without hernia. CONCLUSIONS: The high degree of degenerative changes in the muscle fibres in the inguinal area involved in hernia protrusion described in this report seems to be consistent with chronic compressive damage. These alterations could embody one important factor among the multifactorial sources of hernia genesis. Conjectures concerning its impact on the physiology and biodynamics of the inguinal region are made. The relationship between the depicted degenerative injuries and the genesis of inguinal hernia is also a focus of discussion in this article

Role and outcomes of laparoscopic cholecystectomy in the elderly.

Introduction: Laparoscopic cholecystectomy is the standard of treatment for gallstones disease and acute colecystitis. The prevalence of this disease increases with age and the population is aging in industrialized countries. So, in this study we report our experience in the treatment of gallstone disease in elderly patients, particularly analyzing the outcomes of laparoscopic approach. Methods: Between January 2010 and May 2014 we performed a total of 1227 cholecystectomies. In this retrospective study age group was the primary independent variable: 351 patients were 65-79 years of age and 65 were 80 years of age or older. Results: Only 65 patients (5.3%) of all population had primary open cholecystectomy, but the rate in young group was 3.7% respect the highest frequency (9.2%) in the elderly group. The conversion rate was higher (1.2%) in the older group but there was no significant difference with younger group. LC in emergency setting was performed in 10.3% of young patients and in 13.8% of elderly group. Conclusion: Laparoscopic cholecystectomy is a feasible and safe procedure in elderly patients and might be performed during the same hospitalization like definitive treatment of gallstone disease. The old age and subsequent comorbidity are the fundamental predictor of surgical outcomes. Elective treatment should be recommended when repeated gallstone symptoms have occurred in the elderly patient before the development of acute cholecystitis and related complications

Appendiceal mucinous neoplasms: An uncertain nosological entity. Report of a case

Introduction: Appendiceal mucocele is a relatively rare condition characterized by progressive dilation of the appendix caused by intraluminal accumulation of mucoid substance. Its incidence is 0.07 - 0,63% of all appendectomies performed. Case report: We report the case of a 70-year-old man who came to our observation with gravative pain in right lower abdominal region. A computed tomography abdominal scan revealed a cystic/tubular structure like an appendicular mass with wall enhancement but without calcifications suggestive of a mucocele. Into peritoneal cavity we found profuse mucinous material with a 1,5 cm size parietal nodule. We also identified a free perforation of the cecum with consensual spillage of gelatinous material mimicking a pseudomyxoma peritonei. We decided to perform a right hemicolectomy with excision of peritoneal lesion. Discussion: The controversy in the pathologic terminology can give rise to a clinical dilemma in terms of the management and follow-up plans. For mucosal hyperplasia and cystadenoma simple appendectomy is curative. Only in case of large base of implantation it may be necessary the resection of the ileum and caecum or right hemicolectomy. In case of mucinous cystoadenocarcinoma authors perform a right hemicolectomy. Conclusion: Appendiceal mucinous neoplasms are different pathological entities. The correct surgical management depends on size and location of lesion. A preoperative diagnosis is obviously needed in order to perform the correct treatment. CT abdominal scan is the better diagnostic tool, but different authors show their inability to reach a preoperative diagnosis in the larger majority of cases

Histological findings in direct inguinal hernia : Investigating the histological changes of the herniated groin looking forward to ascertain the pathogenesis of hernia disease.

Abstract BACKGROUND: The study is focused on recognizing the histological changes of the structures close to and around the hernia opening in patients having direct inguinal hernia. METHODS: In 15 patients with primary bilateral direct inguinal hernia who underwent a Stoppa open posterior inguinal hernia repair, tissue specimens from the abdominal wall surrounding a direct hernia border were excised for histological examination. These findings in patients with direct inguinal hernia were compared with tissue specimens excised from the fossa inguinalis media of cadavers without hernia. RESULTS: Significant degenerative modifications such as fibrohyaline degeneration and fatty substitution of the muscle fibers were seen in the biopsy samples. Inflammatory infiltration with lympho-histiocitary elements, artery sub-occlusion and vascular congestion were also constantly identified. Noteworthy injuries of the nervous structures such as edema, degenerative fibrosis and atrophy were also detected. No comparable tissue damage was witnessed in the control samples. CONCLUSION: Presence of inflammatory infiltration, vascular damage and regressive nerve lesions, as well as fibrohyaline degeneration and fatty dystrophy of the muscle fibers are the features seen within the examined structures surrounding the direct hernia opening. These findings could represent a reason for a structural and functional weakening of the inguinal region. Consequently, the described results lead the authors to depict these changes as a plausible cause of direct inguinal hernia protrusion