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Primary duodenal localization of Crohn's disease (CD) is rare. Medical therapy can control symptoms, but surgery is required when progressive obstructive symptoms occur. Surgical options include bypass, resection, or strictureplasty, but it is still not clear which should be the treatment of choice. Reviewing the medical records of 1253 patients undergoing surgery for CD between January 1986 and December 2011 at the Digestive Surgery Unit of the Department of Clinical Physiopathology of the University of Florence, 10 patients (6 males and 4 females) underwent operations for duodenal CD. Four patients had only a duodenal localization, 6 patients had synchronous involvement of other intestinal tracts. Strictures were distributed in all the duodenal portions: in 7 patients there were single lesions, in 3 patients there were multiple lesions. Eight patients were treated with strictureplasty: 5 with the Heineke-Mikulicz technique, 2 with Jaboulay, and 1 with a pedunculated jejunal patch. Two patients were treated with resection: one with a B2 gastro-duodenal resection, and 1 with a duodenal-jejunal resection and an end to side duodeno-jejunal anastomosis. Follow up of the patients was from 2 to 18 years. No recurrence of duodenal CD was observed in the 2 patients treated with resection, while 2 of the 8 patients treated with strictureplasty had a recurrence. In our experience, strictureplasty is indicated when less than 2 strictures are present in the 2nd or 3rd duodenal portion. In cases with multiple strictures localized in the 1st or the distal duodenal portion, resection is preferable., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Purpose: Purpose of the study was to analyze in a retrospective way the clinical and radiographic outcome of three different surgical techniques in patients who underwent anterior cervical fusion., Methods: Eighty-six patients affected by symptomatic cervical disc herniation or spondylosis underwent cervical anterior fusion. Patients were divided in three groups considering the surgical technique. Clinical outcomes were evaluated by Visual Analog Scale, Odom's criteria, Neck Disability Index. Radiographic evaluation included standard and functional X-rays., Results: At 7 years mean follow-up, a comparable improvement in clinical symptoms was observed in all groups. Radiographic findings showed a solid fusion in all patients but seven cases in group 2 showed a subsidence of the cage., Conclusions: As shown by the obtained clinical and radiographic results, the anterior interbody fusion with stand-alone peek cage containing β-tricalcium phosphate could be considered an effective and reliable procedure.

Background: Crohn's disease (CD) is an idiopathic inflammatory bowel disease (IBD) in the pathogenesis of which both Th1 and Th17 lymphocytes have been described as being involved. The NK-associated molecule CD161 has recently been described as a marker of IL-17-producing lymphocytes. In this work we assessed the presence and the functional features of CD161 T helper lymphocytes infiltrating CD-associated perianal fistulas, both before and after inoculation of anti-TNF-α mAbs along the fistula., Methods: In a group of 9 CD patients with fistulizing perianal disease, we evaluated phenotypic and functional features of T cells recovered from the fistula, comparing them with peripheral blood (PB) T lymphocytes. Moreover, the effects anti-TNF-α mAbs injections along the fistula in terms of ability to reduce the inflammatory infiltrate and to determine fistula disappearance were assessed., Results: In CD patients with fistulizing disease there is an accumulation of CD161+ T helper lymphocytes, with higher frequencies of Th1, Th17 and Th17/Th1 cells in the fistula than in PB. Local anti-TNF-α administration is associated with fistula resolution in the majority of patients with disappearance of infiltrating T lymphocytes, without any systemic effect in circulating effector T cells., Conclusions: These findings suggest that CD4+CD161+ T cells with Th17, Th17/Th1 and Th1 phenotype accumulate in CD perianal fistulas, and indicate local anti-TNF-α mAbs administration along the fistula as a promising tool for the treatment of these patients., (Copyright © 2012 S. Karger AG, Basel.)

Introduction: Crohn's involvement of duodenum is a rare event and may be associated to proteiform symptoms and uncommon pathological aspects which make diagnosis and treatment complex., Presentation of Case: The peculiar aspect of this case was a suspected duodeno-biliary fistula. The patient (female, 22 years old) was affected by duodenal Crohn's disease. Magnetic resonance imaging showed a dilated common bile duct, whose final part linked to a formation containing fluid, and characterized by filling of the contrast medium in the excretory phase. Abdominal ultrasound showed intra-hepatic and intra-gallbladder aerobilia. At surgery, the duodenum was mobilized showing an inflammatory stricture and a slight dilatation of the common bile duct, with no signs of fistulas. The opened duodenum was anastomized side to side to a transmesocolic loop of the jejunum. After surgery, the general condition of the patient improved., Discussion: Only two cases of fistula between a narrow duodenal bulb and the common bile duct have been described in literature and the Authors were not be able to verify the occurrence of a duodenal biliary fistula at surgery. The association between duodenal Crohn's disease and Sphincter of Oddi incontinence is a very rare finding with different etiology: chronic intestinal pseudo-obstruction, common bile duct stones, progressive systemic sclerosis., Conclusion: The treatment to resolve Sphincter of Oddi incontinence for primary duodenal Crohn's disease is not clear. Strictureplasty could be the treatment of choice, because, resolving the stricture, the duodenal pressure is likely to decrease and the reflux through the incontinent sphincter can be avoided., (Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: Desmoid tumors are rare benign tumors that originates in the fibrous sheath or musculo-aponeurotic structure. Histologically benign, they tends to invade locally and to be recurrent., Presentation of Case: We report a rare case of an intra-abdominal desmoid tumor in a patient affected by familial adenomatous polyposis, which degenerated into abscess. Male, 38 years, was hospitalized for abdominal pain, bowel obstruction and fever. The computed tomography showed a big dishomogeneous mass occupying the whole mesentery with internal massive liquefaction. The mass extended from the epigastrium for 13cm up to L3. On the right mesogastric side a solid, thick mass of about 2cm, with a length of 4.5cm, was identified; it was not cleavable from the wall and from some of the loops. We decided to perform a computed tomography-guided percutaneous drainage. Two hundred ml of purulent necrotic material was aspirated, and washing with antibiotic solution was carried out. Cytological examination of fluid drainage showed histiocytes and neutrophils. At follow-up, the patient's clinical condition had improved. An abdominal ultrasound showed a substantial reduction in the diameter of the mass., Discussion: Diagnosis and treatment of desmoids tumor in patients with familial adenomatous polyposis may be difficult, especially when desmoids are located intra-abdominally and in the mesentery. Seldom will desmoid tumors be complicated by abscess formation., Conclusion: The management of desmoids tumors is not easy and the choice of the best treatment may be difficult due to the different possible anatomical presentations., (Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: The Median Arcuate Ligament Syndrome is a rare condition characterized by postprandial abdominal pain, bowel function disorder and weight loss. We report the first case to our knowledge of Crohn's disease and Median Arcuate Ligament Syndrome., Presentation of Case: The patient was a 33 year-old female with a previous diagnosis of Crohn's disease. Acute postprandial abdominal pain affected the patient every day; she was, therefore, referred to US-Doppler and magnetic resonance angiography of the abdominal vessels and received a diagnosis of Median Arcuate Ligament Syndrome. Consequently, the patient was surgically treated, releasing the vascular compression. After the operation, she reported a complete relief from postprandial pain which was one of her major concerns. Subocclusive symptoms occurred after six months due to the inflammatory reactivation of the terminal ileitis., Discussion: The diagnosis of Median Arcuate Ligament Syndrome is mainly based on the exclusion of other intestinal disorders but it should be always confirmed using noninvasive tests such as US-Doppler, angio-CT or magnetic resonance angiography., Conclusion: This case demonstrates that the Median Arcuate Ligament Syndrome could be the major cause of symptoms, even in presence of other abdominal disorders., (Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Aim: To investigate the status of the lymphatic vessels in the small bowel affected by Crohn's disease (CD) at the moment of surgery., Methods: During the period January 2011-June 2011, 25 consecutive patients affected by CD were operated on in our Institution. During surgery, Patent Blue V was injected subserosally and the way it spread along the subserosa of the intestinal wall, through the mesenterial layers towards the main lymphatic collectors and eventually to the lymph nodes was observed and recorded. Since some patients had been undergone strictureplasty at previous surgery, we also examined the status of intestinal lymph vessels after previous strictureplasties. The same procedure was performed in a control group of 5 patients affected by colorectal cancer. Length of lesions, caliber, maximal thickness of the diseased intestinal wall, thickness of the wall at injection site and thickness of the mesentery were evaluated at surgery., Results: We observed three features after the injection of Patent Blue V in the intestinal loops: (1) Macroscopically healthy terminal ileum of patients with CD or colon cancer showed thin lymphatic vessels linearly directed toward the mesentery; (2) In mild lesions in which the intestinal wall did not reach 8 mm of thickness, we observed short, wide and tortuous lymphatic vessels directed longitudinally along the intestinal axis toward disease-free areas and then transversally toward the mesentery; and (3) Injection in the severely affected lesions, that had a thickness of the intestinal wall over 10 mm, did not show any feature of lymphatic vessels at least on the subserosal surface. There was a correlation between the thickness of the parietal wall and the severity of the lymphatic alterations. Normal lymphatic vessels were observed at previous strictureplasties in the presence of complete regression of the inflammation., Conclusion: Injection of Patent Blue V in the intestinal wall could help distinguish healthy tracts of the small bowel from those macroscopically borderline.

Background: Various blockers of tumor necrosis factor-α are available for treatment of Crohn's disease. Randomized controlled trials have demonstrated the effects of systemic therapy with adalimumab, a fully humanized monoclonal antibody against tumor necrosis factor-α., Objective: The aim of this study was to investigate the effectiveness and safety of local injection of adalimumab along the fistula in the treatment of perianal Crohn's disease., Design and Setting: This was a prospective, uncontrolled, open-label observational study performed at a university tertiary care center., Patients: A total of 12 outpatients (9 women, 3 men) treated for fistulizing perianal Crohn's disease between 2009 and 2010 were enrolled. The mean age was 43.5 (range, 27-59) years. The fistula was classified as anovaginal in 3 patients, transsphincteric in 7 patients (low in 2, high in 5), and complex (multiple tracts) in 2 patients. Pikarsky's Perianal Crohn's Disease Activity Index was used to evaluate severity of the perianal disease., Intervention: Adalimumab was injected locally along the fistula tract and around the internal orifice every 2 weeks., Main Outcome Measures: The primary end point of the study was the proportion of patients in whom complete or improved healing of fistulas was observed at follow-up, with improvement based on the number of daily changes of sanitary pads., Results: The median number of injections per patient was 7 (range, 4-16). The mean length of follow-up was 17.5 (range, 5-30) months; 75% of patients (9 of 12) reached complete cessation of fistula drainage, and 3 patients (25%), all with transsphincteric fistula, showed improvement. Comparison of overall follow-up scores on the Perianal Crohn's Disease Activity Index with baseline showed significant improvement (p = 0.002). No adverse side effects were noted., Limitations: The study was limited by its small sample size and by the absence of a control group., Conclusions: This pilot study suggests that a high local concentration of adalimumab favors prompt and definitive healing of the fistulous tract in patients with perianal Crohn's disease. Future randomized trials with well-defined selection criteria are needed to determine the relative risks and benefits of available anti-TNF-α blockers (chimeric vs fully humanized) and the optimal mode of administration (systemic use vs local injection) in the treatment of fistulizing perianal Crohn's disease.

We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present.

Objective: This study aimed to evaluate the accuracy of preoperative and intraoperative diagnostic tools and the surgical strategy to obtain cure in multiple endocrine neoplasia type 1 (MEN-1) patients affected with insulinoma., Methods: Eight MEN-1 patients (1992-2009) were operated on for hypoglycemic crisis. Preoperative tumor localization was carried out. Ultrasound and modification of the insulin/glucose (I/G) ratio were applied intraoperatively. Pancreatic lesions larger than 0.5 cm were removed by resection of the most affected pancreatic region and by enucleation of nodules in least affected regions., Results: Two pancreatoduodenectomies and 6 distal pancreatectomies were performed; enucleation of nodules was necessary in 6 patients. There was no postoperative mortality. At the histopathologic analysis, a mean of 6 macrotumors and of 15.5 microlesions were found. Intraoperative ultrasound proved a sensitivity of 87.5% for detecting pancreatic insulinoma. Decrease in the I/G ratio after resection predicted postoperative outcome in all patients. At a mean follow-up of 81.5 months, all patients were normoglycemic with no evidence of disease recurrence., Conclusions: Multiple endocrine neoplasia type 1 insulinomas should be considered surgically curable. Pancreatic resection seems preferable to a less radical surgical approach in ensuring higher cure rates. Intraoperative ultrasound and I/G ratio are of value in the assessment of surgical decision and in the evaluation of the surgical cure.

Introduction: Posterior dynamic stabilisation (PDS) aims at relieving lumbar discogenic pain and preserving adjacent levels from accelerated degeneration., Purpose: To evaluate the results of a novel PDS system in 32 adult patients affected by chronic low back pain (CLBP) due to degenerative lumbar spine instability (DLSI)., Method: A progressive follow-up for 12 months of 32 patients, with collection of complete clinical (ODI and VAS back + leg) and radiological data (resting + functional radiographs and MRI)., Results: Mean ODI scores improved from 49 to 6%, VAS back from 5 to 1 and VAS leg from 7 to 2. Twenty-two patients underwent fusion of a lower lumbar segment and stabilisation of an upper segment (hybrid fusion) whereas ten underwent dynamic stabilisation. In 16/32 patients, decompression was added to treat radicular pain. Motion in non-fused instrumented levels was unrestricted on functional X-rays and MRIs did not show significant morphologic changes. Four patients (12.5%) had unchanged functional and pain scores while two (6.3%) suffered worsening low back pain necessitating implant removal and spinal fusion. No infection, no new neurologic deficit or implant failure was recorded., Conclusions: The 1 year follow-up shows that the tested PDS system is able to provide a significant improvement in pain and disability scores when applied to patients affected by DLSI. The system does not provide better clinical results when compared to similar trials on posterior fusion. Further follow-up is ongoing to investigate the potential preservation of adjacent levels from accelerated degeneration.

Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1) correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2) avoid persistent hypoparathyroidism; and 3) facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1) subtotal parathyroidectomy with removal of at least 3-3 K glands; and 2) total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1) the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2) the surgeon's experience; 3) the timing of surgery; 4) the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay) of the curative potential of the surgical procedure; and, 5) the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence.

Aortic stiffness is a major cause of age-related increase in arterial pulse pressure (PP) and associated increase in work load for the heart. A method to treat this condition is proposed: wrapping the ascending aortic wall with a highly compliant elastic material such that reducing the vessel diameter will shift the pulsatile load from the aortic wall to the wrap, thus increasing the functional compliance of the ascending aorta and decreasing the cardiac load. A multibranched mathematical model of the arterial system, in which every segment of the arterial tree is represented as a uniform elastic circular tube, has been used to simulate the effect of the wrapping procedure on PP and impedance changes, by varying the radius (R) and the stiffness (E) of the ascending aortic segment. The results of the simulation show that PP decreases with an increase in R and a decrease in E. A similar trend, but with a different sensitivity, is observed for the characteristic impedance (Z(c)) changes. The model shows that PP in the ascending aorta can be lowered by 8.8% by reducing R of 20% and decreasing the functional E by 80%, in good agreement with preliminary results obtained from an in vitro pilot study of elastic wrap in aortas. In conclusion, the modelling study demonstrates that the proposed aortic wrapping procedure is able to compensate for the increase in PP associated with R reduction by a decrease in PP determined by a reduction in functional E. Therefore, it supports the use of the aortic wrap as a potential non-pharmacological treatment of age-related increase in PP.

Objective: To analyze the surgical approach to multiple endocrine neoplasia type 1 (MEN 1)-related pancreatic endocrine tumors (PETs)., Methods: We reviewed selected publications and our personal experience with MEN 1-associated PETs to delineate their general characteristics, current practice and controversies, preoperative imaging and intraoperative assessment, and appropriate therapeutic strategies including radical surgical procedures., Results: The penetrance of PETs in the setting of MEN 1 is similar to that of parathyroid tumors, even though hyperparathyroidism is usually the first manifestation of MEN 1 syndrome. In contrast with the sporadic counterparts, MEN 1-related PETs are characterized by an early onset, multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histologic type and the size of these tumors correlate with malignant potential., Conclusion: The rationale for surgical considerations for these tumors is to curtail the malignant progression of the disease and to cure or aid in management of the associated biochemical syndromes. A surgical procedure is often the treatment of choice for PETs in patients with MEN 1. Monitoring of pancreatic peptides and use of diagnostic imaging allow an early pancreatic resection, in conjunction with prevention of metastatic PETs and improvement of long-term survival. Hepatic metastatic lesions can be successfully treated by surgical resection.

Direct repair of spondylolisthesis can save a functional segment in young patients with slight slipping. Since 1968 many surgeons have proposed different technical solutions to obtain the isthmic repair. Their results changed according to the technique used, the extent of listhesis and the age of the patient. The aim of our study was to perform a retrospective review on the long-term results of the direct repair of spondylolisthesis, according to the different techniques used. We operated 62 patients for isthmic repair, with three different techniques, from 1994 to 2007. We analysed the clinical and radiographic results of 52 cases, with an average follow-up of 9 ± 3 years (range 2-15). Ten patients were lost to the follow-up. The results were different depending on the technique used. Good or excellent clinical outcome by Odom's criteria were observed in the 83.3% of patients operated with the modified Scott technique. These results are better than those obtained in the group of patients operated with the Scott (62.5%) and the Buck technique (28.5%). Patients with clinical and radiological failure, who then underwent spinal fusion, were 57% with the Buck technique, 12.5% with the Scott technique and 2.7% with the Scott modified technique. The reasons for a new operation were symptomatic pseudarthrosis and progression of slipping. In conclusion, the pars defect repair is a helpful technique in lumbar spondylolisthesis, especially in young patient with slight slipping and painful symptoms resistant to conservative treatment. In our experience, the modified Scott technique seems to provide a better outcome than the Scott and Buck techniques.

Existing studies on micro-endoscopic lumbar discectomy report similar outcomes to those of open and microdiscectomy and conflicting results on complications. We designed a randomised controlled trial to investigate the hypothesis of different outcomes and complications obtainable with the three techniques. 240 patients aged 18-65 years affected by posterior lumbar disc herniation and symptoms lasting over 6 weeks of conservative management were randomised to micro-endoscopic (group 1), micro (group 2) or open (group 3) discectomy. Exclusion criteria were less than 6 weeks of pain duration, cauda equina compromise, foraminal or extra-foraminal herniations, spinal stenosis, malignancy, previous spinal surgery, spinal deformity, concurrent infection and rheumatic disease. Surgery and follow-up were made at a single Institution. A biomedical researcher independently collected and reviewed the data. ODI, back and leg VAS and SF-36 were the outcome measures used preoperatively, postoperatively and at 6-, 12- and 24-month follow-up. 212/240 (91%) patients completed the 24-month follow-up period. VAS back and leg, ODI and SF36 scores showed clinically and statistically significant improvements within groups without significant difference among groups throughout follow-up. Dural tears, root injuries and recurrent herniations were significantly more common in group 1. Wound infections were similar in group 2 and 3, but did not affect patients in group 1. Overall costs were significantly higher in group 1 and lower in group 3. In conclusion, outcome measures are equivalent 2 years following lumbar discectomy with micro-endoscopy, microscopy or open technique, but severe complications are more likely and costs higher with micro-endoscopy.

Grob et al. (Eur Spine J 5:281-285, 1996) illustrated a new fixation technique in inveterate cases of grade 2-3 spondylolisthesis (degenerative or spondylolytic): a fusion without reduction of the spondylolisthesis. Fixation of the segment was achieved by two cancellous bone screws inserted bilaterally through the pedicles of the lower vertebra into the body of the upper slipped vertebra. Since 1998 we have been using this technique according to the authors' indications: symptomatic spondylolisthesis with at least 25% anterior slippage and advanced disc degeneration. Afterwards this technique was used also in spondylolisthesis with low reduction of the disc height and slippage less than 25%. In every case we performed postero-lateral fusion and fixation with two AO 6.5 Ø thread 16 mm cancellous screws. From 1998 to 2002 we performed 62 fusions for spondylolisthesis with this technique: 28 males (45.16%) and 34 females (54.84%), mean age 45 years (14-72 years). The slipped vertebra was L5 in 57 cases (92%), L4 in 2 cases (3.2%), L3 in 1 case (1.6%), combined L4 and L5 in 2 cases (3.2%). In all cases there was an ontogenetic spondylolisthesis with lysis. Lumbar pain was present in 22 patients and lumbar-radicular pain was present in 40 patients. The mean preoperative VAS was 6.2 (range 5-8) for lumbar pain, and 5.5 (range 4-7) for leg pain. The fusion area was L5-S1 in 53 cases (85.5%), L3-L4 in 1 case (1.6%), L4-S1 in 8 cases (12.9%). A decompression of the spinal canal by laminectomy was performed in 33 procedures (53%). When possible a bone graft was done from the removed neural arc, and from the posterior iliac crest in the other cases. The mean blood loss was about 254 ml (100-1,000). The mean operative time was 75 min (range 60-90). The results obtained by computerized analysis at follow-up at least 5 years after surgery showed a significant improvement in preoperative symptoms. The patients were asymptomatic in 52 cases (83.9%); strained-back pain was present in 8 cases (12.9%), and there was persistent lumbar-radicular pain in 2 cases (3.2%). The mean ODI score was 2.6%, the mean VAS back pain was 1.3, the mean VAS leg pain 0.7. Some complications were observed: a nerve root compression by a screw invasion of intervertebral foramen, resolved by screw removal; an iliac artery compression by a lateral exit screw from pediculo, resolved by screw removal; a deep iliac vein phlebitis with thrombosis caused by external compression due to a wrong intraoperative position, treated by medicine. Two cases of synthesis mobilization and two cases of broken screws was detected. No cases of pseudoarthrosis and immediate or late superficial or deep infection were observed. The analysis of the long-term results of the spondylolisthesis surgical treatment with direct pediculo-body screw fixation and postero-lateral fusion gave a very satisfactory response. The technique is reliable in allowing an optimal primary stability, creating the best biomechanical conditions to obtain a solid fusion.

T helper (Th) 17 cells represent a novel subset of CD4+ T cells that are protective against extracellular microbes, but are responsible for autoimmune disorders in mice. However, their properties in humans are only partially known. We demonstrate the presence of Th17 cells, some of which produce both interleukin (IL)-17 and interferon (IFN)-gamma (Th17/Th1), in the gut of patients with Crohn's disease. Both Th17 and Th17/Th1 clones showed selective expression of IL-23R, CCR6, and the transcription factor ROR gamma t, and they exhibited similar functional features, such as the ability to help B cells, low cytotoxicity, and poor susceptibility to regulation by autologous regulatory T cells. Interestingly, these subsets also expressed the Th1-transcription factor T-bet, and stimulation of these cells in the presence of IL-12 down-regulated the expression of ROR gamma t and the production of IL-17, but induced IFN-gamma. These effects were partially inhibited in presence of IL-23. Similar receptor expression and functional capabilities were observed in freshly derived IL-17-producing peripheral blood and tonsillar CD4+ T cells. The demonstration of selective markers for human Th17 cells may help us to understand their pathogenic role. Moreover, the identification of a subset of cells sharing features of both Th1 and Th17, which can arise from the modulation of Th17 cells by IL-12, may raise new issues concerning developmental and/or functional relationships between Th17 and Th1.

The isosteric CH----N substitution in the class of 2-arylpenems results in improved antibacterial activity, with retention of the favorable characteristic of stability towards renal dehydropeptidase. High therapeutic efficacy was demonstrated in experimental mice septicemias with the 2-(3-pyridyl) derivative 2b and its orally absorbed acetoxymethyl ester prodrug 4n.

Introduction of a hydroxyl group into the thiazole ring nitrogen of cephalosporins belonging to the cefotiam and cefotaxime families gave rise to products, better described by the tautomeric N-oxide form, which proved particularly active against Gram-negative bacteria. Cephems bearing a (Z)-alkoxyimino functionality are of special interest for broadness of spectrum; among them, 7 beta-[(Z)-2-(2-amino-4-thiazolyl-N-oxide)-2 -methoxyiminoacetamido]-3-(tetrazolo-[1,5-b] pyridazin-6-yl)thiomethyl-3-cephem-4-carboxylic acid (5c-7, FCE 20635), in other ways similar to cefotaxime, showed useful levels of activity against cephalosporinase-producing strains resistant to the reference drug. Preliminary in vivo studies demonstrated the therapeutic efficacy of the new compound in the treatment of experimental systemic, subcutaneous and urinary tract infections in mice.

The synthesis and in vitro activity of 7 alpha-methoxy-7 beta-vinylenethioacetamido cephalosporins with various substituents at the 3-position are described. These cephalosporins showed good activity against beta-lactamase producing Gram-negative bacteria. 7 alpha-Methoxy-7-[(Z)-beta-cyano-vinylenethioacetamido]-3-[(1-methyl-1H-tetrazol -5-yl)thiomethyl]-3-cephem-4-carboxylic acid (3) was several times more active in vitro than cefoxitin and comparable to cefmetazole.