Ambulatory surgery for perianal Crohn’s disease. Study of feasibility

Background. One-third of Crohn’s disease (CD) patients present perianal fistula. The gold standard in the diagnosis and treatment of symptomatic perianal disease (PAD) in CD is the exploration of the anal canal and distal rectum under anesthesia (EUA). This procedure is mainly conducted as a day case surgery. Unfortunately, it is not always possible to proceed within the ideal timing and any delay may well represent a relevant clinical issue. The aim of this study was to evaluate the feasibility of outpatient treatment of symptomatic perianal fistulas in CD patients. Methods. All CD patients under regular follow-up at our inflammatory bowel disease referral center, presenting with symptomatic perianal fistulas, were offered surgical consultation. The data of patients were prospectively collected for three years (February 2014 to February 2017) for the purpose of the study. All clinical information, including previous EUA and/or records from MRI and endoscopic ultrasound, was included. Outpatient anal canal and distal rectum exploration and treatment (OE) were undertaken during the specialist surgical consultation. Fistulas were classified according to Parks’s classification; the type of outpatient treatment and compliance of patients were recorded. Pain was assessed by VAS at the time of the procedure and during the first control. Patients were followed up in the surgical clinic in relation to the study. Results. Ninety-two CD patients with symptomatic perianal fistulas had surgical consultation during the study period. OE was offered to all but 18 patients who fulfilled the exclusion criteria or had an extremely severe disease; six patients refused the OE (8.11%). Of the 68 patients undergoing OE, eleven (16.18%) had previous surgery for perianal disease. The OE was accomplished in sixty-one patients (89.71%), while in 7 patients, it was abandoned for scarce compliance. Nine patients (14.75%) underwent drainage of perianal abscess; in 3 of them, it was possible to probe the fistula tract, find the internal orifice, and pass a loose seton. Overall, setonage was performed in 50 patients (81.97%). Rectovaginal setons were placed in 3 patients and more than one seton (up to 3) in 6 cases. Fistulotomy was performed in 4 simple subcutaneous fistulous tracts. Concordance with the preoperative findings was found in 54 out of 61 patients. EUA was scheduled at the time of OE for the 7 patients who did not complete the procedure. All sixty-one patients who had the OE were followed up for a minimum of 12 months. Conclusions. This preliminary study indicates that OE in CD patients with symptomatic perianal fistulas is safe and feasible in a high-volume referral center. It might provide several benefits, including patients’ logistics, reduce or remove patients’ symptoms and discomfort, allow for a timely start of medical therapy, and avoid further complications

Endoscopic radiofrequency facet joint treatment in patients with low back pain: technique and long-term results. A prospective cohort study

Aims: The aim of the study was to evaluate the efficacy of endoscopic rhizotomy (ER) for denervation of lumbar facet joints in patients with chronic low back pain (LBP) due to facet joint syndrome (FJS). Methods: A total of 50 consecutive patients suffering from chronic LBP due to facet joints were screened to be treated with ER. The patients participating in the study had a 2-year follow up. Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI) were assessed in the preoperative and postoperative period. To evaluate secondary endpoints, patients were divided into groups. One group included the patients previously treated with percutaneous radiofrequency (RF). The other group comprised patients at their first interventional treatment. We also compared patients dividing them by age and by number of joints treated, trying to elucidate if these parameters could be predictive of effectiveness of the procedure. Results: All patients had a reduction in NRS and an improvement in ODI. NRS was reduced significantly after 1 month and remained the same until the end of the study. ODI was significantly improved from T1 (1 month after surgery) up to T7 (end of the study). The improvements did not differ whether already treated with percutaneous rhizotomy or not. Patients less than 60 years or with 1–2 joints treated had better improvement compared with the others. Conclusion: The results obtained demonstrate that ER for denervation of the facet joint is an effective treatment in patients with chronic LBP, with consistent and stable results at 2-year follow up. The technique has a rapid learning curve and no major complications occurred. Moreover, the previous percutaneous RF treatment had no influence on the results obtained with endoscopic technique. There is evidence that best results are obtained in younger patients and/or in patients with 1–2 joints treated. Lay summary: Low-back pain has facet joints inflammation or degeneration as pain generator in 20–40% of cases. Nervous lesion of the dorsal ramus innervating the facet joints has been shown as an efficacious treatment to obtain good analgesia. Percutaneous techniques have provided short term results for several reasons. This research aimed to see whether endoscopic denervation, which guarantees a more precise approach to anatomical structure, would result in more durable results. The study conducted on 40 patients has made it clear that this approach gives significant analgesia for at least 2 years, which was the time of patient follow up

Pathophysiology of Crohn’s disease inflammation and recurrence

Chron's Disease is a chronic inflammatory intestinal disease, first described at the beginning of the last century. The disease is characterized by the alternation of periods of flares and remissions influenced by a complex pathogenesis in which inflammation plays a key role. Crohn's disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration in the sites of inflammation, promoting a TH1 response, through the production of cytokines such as IL-12 and TNF-α. IL-12 itself and IL-23 have been targeted for the medical treatment of CD. Giving the limited success of medical therapies, the treatment of the disease is invariably surgical. This review will highlight the role of inflammation in CD and describe the surgical approaches for the prevention of the almost inevitable recurrence

Case Report: Whole Exome Sequencing Revealed Disease-Causing Variants in Two Genes in a Patient With Autism Spectrum Disorder, Intellectual Disability, Hyperactivity, Sleep and Gastrointestinal Disturbances

Autism Spectrum Disorder (ASD) refers to a broad range of conditions characterized by difficulties in communication, social interaction and behavior, and may be accompanied by other medical or psychiatric conditions. Patients with ASD and comorbidities are often difficult to diagnose because of the tendency to consider the multiple symptoms as the presentation of a complicated syndromic form. This view influences variant filtering which might ignore causative variants for specific clinical features shown by the patient. Here we report on a male child diagnosed with ASD, showing cognitive and motor impairments, stereotypies, hyperactivity, sleep, and gastrointestinal disturbances. The analysis of whole exome sequencing (WES) data with bioinformatic tools for oligogenic diseases helped us to identify two major previously unreported pathogenetic variants: a maternally inherited missense variant (p.R4122H) in HUWE1, an ubiquitin protein ligase associated to X-linked intellectual disability and ASD; and a de novo stop variant (p.Q259X) in TPH2, encoding the tryptophan hydroxylase 2 enzyme involved in serotonin synthesis and associated with susceptibility to attention deficit-hyperactivity disorder (ADHD). TPH2, expressed in central and peripheral nervous tissues, modulates various physiological functions, including gut motility and sleep. To the best of our knowledge, this is the first case presenting with ASD, cognitive impairment, sleep, and gastrointestinal disturbances linked to both HUWE1 and TPH2 genes. Our findings could contribute to the existing knowledge on clinical and genetic diagnosis of patients with ASD presentation with comorbidities

Nazivi četvorni metar i kubni metar

The aim of this study was to determine the perioperative behavior of C-reactive protein (CRP) in Crohn's disease (CD) patients undergoing elective ileo-cecal (IC) resection and to identify association between perioperative CRP levels and endoscopic recurrence at 1 year. Study hypothesis was that perioperative CRP changes are disease specific and could detect subset of patients with more aggressive pathopysiology. Seventy-five patients undergoing IC resection for CD were prospectively enrolled. Serial CRP levels were assessed: preoperative, postoperative day 1 (POD1) and day 5 (POD5). CD patients' values were compared against same interval assessments of control groups undergoing right colectomy and appendicectomy. At POD1, the serum concentration increase was significantly higher in CD patients than in controls. Comparing with control groups, CRP levels remained remarkably high and showed a lower reduction in CD at POD5. Difference between groups was statistically significant. Optimal cutoff levels have been identified: serum CRP concentrations of >39.8 mg/l at POD1 and of >23.2 mg/l at POD5 have shown a significant association to endoscopic recurrence when using bivariate correlation. In this preliminary series, binary logistic regression could not demonstrate statistical relationship between endoscopic recurrence and any of the variables evaluated as prognostic factor. This is the only study so far that investigates and confirms a disease-specific upregulation of CRP response in the perioperative period for CD patients undergoing surgery. The postoperative CRP levels and kinetics seem to be related to the grade of mucosal inflammation and recurrence rate according to our 12 months endoscopic evaluation

MKS3/TMEM67 mutations are a major cause of COACH syndrome, a joubert syndrome related disorder with liver involvement

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/ aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the “molar tooth sign”, a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs

On the use of Laser-Induced Fluorescence for biological agent detection

The uncontrolled spread of biological agents, such as bacteria and viruses, could be hazardous for human health. Despite the interest in detecting their presence, the common methods are usually impracticable, since the diagnosis methods are time-consuming, could be invasive or require a lot of consumables which make the cost unsustainable. A good candidate to perform biological agent detection is the Laser-Induced Fluorescence (LIF) spectroscopy since the emitted spectra are characteristic of the chemical composition of the agent. For this study, some tests with this technique on some biological agents have been performed and the classification and detection performances have been evaluate