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Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory disease occurring several weeks after SARS-CoV-2 infection. The clinical similarities between MIS-C and the toxic shock syndrome, together with the preferential expansion of T cells with a T-cell receptor variable β chain (TCRVβ) skewing, suggested a superantigen theory of MIS-C. For instance, recent in silico modelling evidenced the presence of a highly conserved motif within SARS-CoV-2 spike protein similar in structure to the superantigenic fragment of staphylococcal enterotoxin B (SEB). However, experimental data on the superantigenic activity of the SARS-CoV-2 spike have not yet been provided. Here, we assessed the superantigenic activity of the SARS-CoV-2 spike by analysing inflammatory cytokine production in both Jurkat cells and the peripheral blood CD4+ T cells stimulated with the SARS-CoV-2 spike or SEB as a control. We found that, unlike SEB, the SARS-CoV-2 spike does not exhibit an intrinsic superantigen-like activity.

IL-22 is a member of the IL-10 cytokine family involved in host protection against extracellular pathogens, by promoting epithelial cell regeneration and barrier functions. Dysregulation of IL-22 production has also frequently been observed in acute respiratory distress syndrome (ARDS) and several chronic inflammatory and autoimmune diseases. We have previously described that human CD28, a crucial co-stimulatory receptor necessary for full T cell activation, is also able to act as a TCR independent signaling receptor and to induce the expression of IL-17A and inflammatory cytokines related to Th17 cells, which together with Th22 cells represent the main cellular source of IL-22. Here we characterized the role of CD28 autonomous signaling in regulating IL-22 expression in human CD4+ T cells. We show that CD28 stimulation in the absence of TCR strongly up-regulates IL-22 gene expression and secretion. As recently observed for IL-17A, we also found that CD28-mediated regulation of IL-22 transcription requires the cooperative activities of both IL-6-activated STAT3 and RelA/NF-κB transcription factors. CD28-mediated IL-22 production also promotes the barrier functions of epithelial cells by inducing mucin and metalloproteases expression. Finally, by using specific inhibitory drugs, we also identified CD28-associated class 1A phosphatidylinositol 3-kinase (PI3K) as a pivotal mediator of CD28-mediated IL-22 expression and IL-22–dependent epithelial cell barrier functions.

CD28 is an important co-stimulatory receptor for T lymphocytes that, in humans, delivers TCR-independent signal leading to the up-regulation of pro-inflammatory cytokines. We have recently reported that CD28 autonomous signaling induces the expression of IL-17A in peripheral CD4+ T lymphocytes from healthy donors, multiple sclerosis, and type 1 diabetes patients. Due to the relevance of IL-17A in the pathophysiology of several inflammatory and autoimmune diseases, we characterized the mechanisms and signaling mediators responsible for CD28-induced IL-17A expression. Here we show that CD28-mediated up-regulation of IL-17A gene expression depends on RelA/NF-κB and IL-6-associated STAT3 transcriptions factors. In particular, we found that CD28-activated RelA/NF-κB induces the expression of IL-6 that, in a positive feedback loop, mediates the activation and nuclear translocation of tyrosine phosphorylated STAT3 (pSTAT3). pSTAT3 in turn cooperates with RelA/NF-κB by binding specific sequences within the proximal promoter of human IL-17A gene, thus inducing its expression. Finally, by using specific inhibitory drugs, we also identified class 1A phosphatidylinositol 3-kinase (PI3K) as a critical upstream regulator of CD28-mediated RelA/NF-κB and STAT3 recruitments and trans-activation of IL-17A promoter. Our findings reveal a novel mechanism by which human CD28 may amplify IL-17A expression in human T lymphocytes and provide biological bases for immunotherapeutic approaches targeting CD28-associated class 1A PI3K to dampen IL-17A-mediated inflammatory response in autoimmune/inflammatory disorders.

Thyroid disease and hyperparathyroidism are the most common endocrine disorders. The incidence of thyroid disease in patients with hyperparathyroidism ranges in the different series from 17 to 84%, and thyroid cancer occurs with an incidence ranging from 2 to 15%. The aim of our study was to analyze the management of elderly patients with concomitant thyroid and parathyroid disease in order to define the best surgical therapeutic strategy and avoid reoperations associated with a higher risk of complications. All consecutive patients (64 patients, age range 60–75 years), undergoing surgery for hyperparathyroidism, from January 2011 to June 2014, were retrospectively evaluated. Enrolled patients were divided into two study groups of patients affected by hyperparathyroidism with or without a concomitant thyroid disease. Out of 64 patients enrolled in our study (24 men, age range 60–75 years), affected by hyperparathyroidism, 34 had an associated thyroid disease and were treated with total thyroidectomy and parathyroidectomy. The group, who underwent parathyroidectomy associated with thyroidectomy, had no greater complications than the group receiving only parathyroidectomy. Thyroid disease must be excluded in patients affected by hyperparathyroidism. It is difficult to determine whether hyperparathyroidism can be considered a risk factor for thyroid disease, but an accurate preoperative study is essential for a surgery able to treat both thyroid and parathyroid disease. In this way, we avoid the elderly patient, with associated morbidity and increased surgical risk, to undergo a reoperation for thyroid disease, burdened with major complications.

Epithelial thyroid cancers (TC) comprise two differentiated histotypes (DTC), the papillary (PTC) and the follicular (FTC) thyroid carcinomas which, following dedifferentiation, are assumed to give rise to the poorly differentiated thyroid carcinomas and the rare, but highly aggressive and invariably fatal, anaplastic thyroid carcinomas. Although thyroid cancer mortality has not been changed, its annual incidence has increased over the last two decades, mainly because of the improved ability to diagnose malignant transformation in small non-palpable thyroid nodules. Despite DTC patients have a favorable prognosis, aggressive disease is more frequently observed in the elderly showing a higher disease-specific mortality. Of relevance is the high prevalence of nodular thyroid disease in aged patients being higher than 90%, in women older than 60 year, and 60% in men older than 80 year. This implies a careful evaluation of thyroid nodules in this group of patients in order to exclude malignancy. In fact, despite the tremendous progress in the comprehension of the underlying molecular mechanisms deregulated in DTC progression, several aspects of their clinical management remain to be solved and novel diagnostic strategies are sorely needed. Here, we will attempt to review new molecular approaches, which are currently being exploited in order to ameliorate the diagnosis of thyroid nodules.

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies.

OBJECTIVES: Oesophageal leiomyoma is the most common benign tumour of the oesophagus. The incidence of leiomyomas larger than 10 cm, defined as giant oesophageal leiomyomas (GELs), has been reported in 17% of all cases. Although computed tomographic scan and endoscopy are usually useful for diagnosis, big and symptomatic masses located in the lower mediastinum remain both a diagnostic and therapeutic challenge. METHODS: We describe our experience in the management of 7 patients (4 males and 3 females, with a mean age of 41 years) with GEL treated in our department. Radical resection was performed in all cases with partial oesophagectomy in order to relieve symptoms and to obtain a definitive diagnosis. RESULTS: There was no perioperative mortality. The minimum diameter of the tumours was 15 cm and the maximum was 30 cm. Definitive histological examination confirmed the diagnosis of leiomyoma in all cases without any sign of malignancy. No major postoperative complications developed. Minor complications included partial abdominal wound dehiscence in 1 case, and retention of secretions requiring bronchoscopy in 2. The mean length of hospital stay was 12 days (ranging between 9 and 14 days). After a mean follow-up of 5.4 years (ranging between 12 and 2 years), no sign of recurrence was observed. CONCLUSIONS: Whereas removal of small oesophageal leiomyomas can be performed by simple enucleation by conventional thoracotomy or video-assisted thoracoscopy, partial oesophagectomy is often necessary for giant lesions. Since it is not possible preoperatively to distinguish GEL from leiomyosarcoma when metastases are absent, partial oesophageal resection is not to be considered an overtreatment and radical resection should always be planned. A gastric tube, in our experience employed as an oesophageal substitute, is effective and could reduce the risk of significant postoperative gastro-oesophageal reflux.

Up to the half of twentieth century, Chievitz organ was considered an embryonal organ, disappearing with growth. But Zenker, in 1953, demonstrated the existence of this organ in adult life, too4.In this article we review the embryology, the macroscopic and microscopic anatomy, the ultrastructure, the functional significance and the pathology of the Chievitz'Juxtaparotid Organ (CJO). The CJO is not a macroscopic apparent organ, but it looks like a nerve. The CJO takes connections with buccinator muscle, at the level of the parotid duct, and the medial pterygoid muscle. The cell parenchyma is enveloped by the connective tissue, that is divided into three layers15, 16: the inner layer -"stratum fibrosum internum"-, composed of collagenous and elastic microfibrils; the middle layer - "stratum nervosum" - containing a lamellar inner core and Ruffini SNF5; the external layer - "stratum fibrosum externum", that is a collagen capsule. The parenchymal cells show a rich enzyme activity. The parenchymal cells may play the same role as glomus cells of the 1st type and Merkel cells20, 21. When a surgical resection is performed for an oral carcinoma, the CJO may be present in the specimen25. The CJO may be wrongly diagnosed as perineural invasion by carcinoma26, 27, 28.We report that Chievitz' organ is the only organ in which the cancer does not occur.Chievitz' organ, Juxtaoral organ, Parotid gland.Fino alla metà del XX secolo, l’organo di Chievitz è stato considerato un organo embrionale, che scompare con la crescita. Zenker, invece, nel 1953, ha dimostrato l’esistenza di questo organo anche nella vita adulta.In questo articolo descriviamo l’embriologia, l’anatomia macroscopica e microscopica, l’ultrastruttura, il significato funzionale e la patologia dell’organo iuxtaparotideo di Chievitz’(CJO). Il CJO non è un organo macroscopicamente evidente, ma ha l’aspetto simile ad un nervo. Il CJO prende collegamenti con il muscolo buccinatore, a livello del condotto parotideo e con il muscolo pterigoideo mediale. Il parenchima cellulare è avvolto da tessuto connettivo, che è diviso in tre strati: lo strato interno - “strato fibrosum internum” -, composto da microfibrille di collagene; lo strato intermedio - “stratum nervosum” - contenente un nucleo interno lamellare e strutture nervose di Ruffini; lo strato esterno - “stratum fibrosum externum”, che è una capsula di collagene. Le cellule parenchimali contengono enzimi, quali la fosfatasi alcalina e l’anidrasi carbonica, con una ricca attività enzimatica, simile a quella delle cellule duttali delle ghiandole salivari. Il CJO presenta, inoltre, un’importante funzione meccanosensore di questa regione. Quando viene eseguita una resezione chirurgica per un carcinoma orale, il CJO può essere presente nel pezzo operatorio. Il CJO può essere erroneamente diagnosticato come invasione perineurale da carcinoma.Sulla base della revisione della Letteratura, tuttavia, si può definire che l’organo di Chievitz è l’unico organo in cui il cancro non si verifica.

About 5% of occult gastrointestinal bleeding derives from small intestinal lesions. The intraoperative enteroscopy (IOE), although the development of double-balloon enteroscopy and capsule endoscopy reduced the indications, is still valid to locate the bleeding site in some selected cases. An 88-year-old woman presenting to the emergency department with a severe anemia underwent the laparotomic exploration and IOE. A 15-mm laparoscopy trocar with a sterile camera drape was adopted to introduce a standard colonoscope through an enterotomy. The operation was safe and effective, without intraoperative morbidity and early complications related to surgery or endoscopy. We propose a technical solution during the IOE to minimize contamination of the surgical field. Although this technique is safe and feasible, further studies are needed to evaluate the method effectiveness.

Haemorrhoidal disease is one of the most common anorectal disorders. The aim of this study is to compare the results, over the last 10 years, of stapled haemorrhoidopexy (SH) with those of standard Milligan–Morgan haemorrhoidectomy (M&M). Furthermore, we discuss the proper indications for each technique in terms of the lowest rate of complications and long-term results. Three hundred forty-three patients with different degrees of symptomatic haemorrhoids underwent SH or M&M from January 2005 to December 2007. Patients were divided into two groups, age and sex matched. The administration of painkillers drugs, antibiotics and laxatives, complication symptoms and hospital stay in all the patients were recorded after surgical treatment. The mean operative time was shorter in the stapled group compared to that in the open group (31 min versus 40 min). Postoperative pain, hospital stay and return to full activity were shorter in the stapled group. There was a significant difference in the wound healing time between the two groups. We noticed a higher rate of recurrence in patients treated with stapled haemorrhoidectomy for fourth-degree haemorrhoids. According to our experience, the Longo technique is indicated for the treatment of haemorrhoids of second- and third degree. In the latter grades of prolapse, the Milligan–Morgan haemorrhoidectomy can also be applied with good outcomes. We believe that, in case of irreducible prolapse, the M&M is to be preferred. However, operative management varies according to surgeon's interest and is tailored to meet the individual patient's need.

We report the case of a young woman who underwent total thyroidectomy for a suspect nodular thyreopathy and occasionally happened to be affected simultaneously by vagus nerve schwannoma. Symptomatology is discussed and we propose a review of the literature about this non frequent pathology and discuss the latest diagnostic procedures and surgical indications and treatment.

Brunner's gland adenoma is a rare benign tumour of the duodenum. His most common location is the posterior wall of the duodenum near the junction of its first and second portion. It is usually small and asymptomatic often discovered incidentally with upper gastrointestinal endoscopy, but sometimes may become large causing symptoms (haemorrhage or intestinal obstruction). We report a rare case of a very large Brunner's gland adenoma in a 38-year-old female presenting with severe anaemia but without obstructive symptoms and detected by ultrasonography. The tumour was managed by surgical removal and during a six month follow-up the patient remained symptom-free without any recurrence. The literature on Brunner's gland adenoma is reviewed.

Morgagni's hernia is a rare and congenital type of diaphragmatic hernia. The majority of these are asymptomatic and diagnosed incidentally during evaluation or treatment for other conditions. When diagnosis is made surgery is mandatory. The Authors report the laparoscopic repair of small Morgagni hernia, followed by review of the literature.A case of 55-year-old woman complaining a sensation of tightness in her chest, but especially an oppressive epigastric pain with episodes of fainting fit and breathless is described. The definitive diagnosis was confirmed by laparoscopy. The hernia was repaired laparoscopically using a mesh fixed by hernia stapler after excision of the sac.In the postoperative patients has presented an episode of heart condition due to pericarditis treated pharmacologically. The patient was discharged on the seventh postoperative day symptom-free.Laparoscopic technique must be considered as a first line approach for the treatment of Morgagni hernia, easy and safe by carry out. We recommend do not excise hernia sac, even if small, and particular cure in the use of the mesh fixed by metal staples.

The aim of our study was to compare the efficacy of the circular compression stapler and the circular mechanical stapler in transanal colorectal anastomosis after left colectomy or anterior rectal resection.We performed a retrospective analysis of 10 patients with disease of the, sigmoid colon or rectum (carcinoma or diverticular disease) who underwent left colectomy or anterior rectal resection with end-to-side transanal colorectal anastomosis. A follow-up was planned for all patients at 1, 3 and 6 months after surgery and the anastomosis was evaluated by colonoscopy at 1 year.In all patients an end-to-side transanal colorectal anastomosis was performed using a circular compression stapler (CCS group) or circular mechanical staplers with titanium staples (CMS group). The mean distance of the anastomosis from the anal margin was 6.4 ± 1.5 cm in the CCS group and 18.2 ± 11.2 cm in the CMS group. All patients in the CCS group expelled the ring after a mean time of 8.2 postoperative days. At 12 months colonoscopy revealed that all CCS patients had a satisfactory anastomosis with mean size of the colic lumen at the level of anastomotic line of 26.3 mm.In our experience the circular compression stapler a valuable alternative to the circular mechanical stapler for the creation of transanal colorectal anastomosis, in line with the relevant literature.Anastomotic leakage, Anastomotic stenosis, Circular compression stapler, Circular mechanical stapler, Transanal colorectal anastomosis.Lo scopo del nostro studio è confrontare l’efficacia della suturatrice circolare a compressione rispetto alla suturatrice circolare meccanica negli interventi di emicolectomia sinistra e resezione anteriore del retto.È stata effettuata un’analisi retrospettiva di 10 pazienti affetti da patologie del colon discendente, sigma o retto (carcinoma o malattia diverticolare) sottoposti a emicolectomia sinistra o resezione anteriore del retto con anastomosi colorettale transanale termino-laterale. Il follow-up è stato effettuato in tutti i pazienti a 1, 3 e 6 mesi dopo l’intervento chirurgico e l’anastomosi è stata valutata mediante endoscopia a 1 anno.In tutti i pazienti è stata effettuata un’anastomosi colorettale transanale termino-laterale utilizzando la suturatrice circolare a compressione (gruppo CCS) o la suturatrice meccanica circolare con clip di titanio (gruppo CMS). La distanza media dell’anastomosi dal margine anale è di 6.4 ± 1.5 centimetri nel gruppo CCS e di 18.2 ± 11.2 centimetri nel gruppo CMS. Tutti i pazienti del gruppo CCS hanno espulso l’anello dopo un tempo medio di 8.2 giorni postoperatori. Un’anastomosi soddisfacente è stata rilevata nei pazienti del gruppo CCS valutati endoscopicamente a 12 mesi con calibro medio del lume colico a livello della linea anastomotica di 26.3 mm.Nella nostra esperienza il dispositivo a compressione si è rivelato valido quanto la suturatrice circolare meccanica tradizionale per il confezionamento di anastomosi colorettale transanale, in linea con gli studi presenti in letteratura.