Sublingual sufentanil tablet system (SSTS) versus a single shot peri-nervous injection of ropivacaine for the management of postoperative pain after total knee arthroplasty: a single-center randomized trial.

INTRODUCTION: For several years, ropivacaine has been the standard-of-care for establishing postoperative femoral nerve block in total knee arthroplasty (TKA) setting and is still widely in use but new approaches such as the patient-controlled administration of sublingual sufentanil tablets system (SSTS) seem to offer good clinical results. Our aim is to compare the SSTS to single shot peri-nervous injection of ropivacaine (single shot) after TKA in terms of effectiveness in pain management and of time to recovery. MATERIALS AND METHODS: A total of 165 patients undergoing TKA were enrolled. Eighty-four patients were randomly allocated in the SSTS group and 81 patients in the single shot group. The primary objective of the study was to evaluate performance of Timed Up and Go test. Secondary objectives were to measure the length of stay, NRS pain scale, the adherence to the prescribed plan, the joint mobility, the frequency of rescue analgesic use, side effects and patients' satisfaction. RESULTS: Of all patients of the single shot group, 64 were withdrawn from the study as they unable to achieve pain control; only one patient was withdrawn from the SSTS group. Times for the "Timed Up and Go" test on the 3rd postoperative day were 8.4 ± 1.6 and 11.8 ± 3.6 in the SSTS group (n = 83) and single shot group (n = 17), respectively (p < .001). CONCLUSIONS: SSTS provides better pain management when compared to peri-nervous ropivacaine single shot injection after TKA.

Use of chloroprocaine in orthopedic day surgery: a brief report in a cohort of patients undergoing knee arthroscopy.

OBJECTIVE: Spinal anesthesia with local anesthetics is a viable alternative to general anesthesia in orthopedic surgery, and it is currently considered the standard of care for knee arthroscopy. The use of chloroprocaine may offer several potential advantages over other local anesthetics, including, above all, its rapid onset and short duration of action. The aim of the present retrospective study is to evaluate the post-surgical outcomes of patients who underwent knee arthroscopy using spinal anesthesia with chloroprocaine in an outpatient orthopedic setting. PATIENTS AND METHODS: Data from patients who underwent elective knee arthroscopy between January 2022 and December 2022 were collected for the present study. Spinal anesthesia with chloroprocaine 10 mg/mL was administered in the designated subarachnoid space (L3-L4 in the majority of patients). A dosage of 40 mg was used to obtain a satisfactory sensory and motor block. RESULTS: A total number of 302 patients met the inclusion criteria. No complications were reported during surgery in the present series of patients. None of the patients required bladder catheterization. In 84% of cases, the PADSS (Post-Anesthetic Discharge Scoring System) score at discharge was 10, whereas in 16% of cases, the PADSS score was 9. The mean time from anesthesia induction to first urination was 75±9.4 minutes, while the mean time from the anesthesia induction to the discharge from the hospital was 152±18.5 minutes. CONCLUSIONS: Spinal chloroprocaine for knee arthroscopy demonstrated a short motor block duration, resulting in a fast time to discharge. These limited data show that chloroprocaine may be safely and effectively applied in outpatient knee arthroscopy procedures. However, more studies, possibly with a randomized design, are required to confirm these findings.

Ankle sprain and podoscopic footprint pattern in female volleyball players.

Ankle sprain (AS) is the most common sports injury that can be complicated by chronic joint instability. The aim of this study was to examine the relationship between foot types and the ankle sprain events suffered during the sport career in female volleyball players. In this retrospective study, we randomly selected 98 female volleyball players competing in several divisions. Data were obtained from self-administered questionnaires in which the athlete noted data about volleyball practice, whether they had had ankle sprains and the number of these events. Plantar footprint was photographed by a plantoscope classifying each foot as normal, flat or cavus (196 feet). Of the 196 feet, 145 (74.0%) were normal, 8 (4.1%) were flat 43 and (21.9%) were cavus. Thirthy-five athletes reported at least one AS during volleyball practice. In total 65 sprain injuries were reported (35 to the right side and 30 to the left side). In 22 ankles (14 right, 8 left) sprain reinjure (AS >1) have been reported. A higher AS reinjury rate is correlated to the cavus footprint pattern (p = 0,005). Cavus foot associates to a higher risk of reinjury for ankle sprains in female volleyball players. Knowing the athletes which are more likely to sustain a reinjure may be helpful for the orthopedic surgeon to plan preventive strategies.

A rapid recovery protocol for hip and knee replacement surgery: a report of the outcomes in a referral center.

OBJECTIVE: The number of joint replacements is expected to dramatically increase, and the optimization of the available resources is fundamental to maintain high clinical standards while providing an efficient treatment to an increasing number of patients. The present study describes the outcomes of the application of a rapid recovery (RR) protocol in a referral center for hip and knee replacement surgery. PATIENTS AND METHODS: The medical records of every patient undergoing primary hip or knee replacement in 2019 were identified and all the relevant data were retrospectively extracted and compared to those of year 2016 (the last year before the onset of the rapid recovery protocol). The following outcomes were considered: 1) length of stay (LOS); 2) total number of TKR and THR; 3) pre- and post-operative subjective questionnaires; 4) NRS for pain at day 1 following surgery; 5) mean hemoglobin value at discharge; 6) number of blood transfusion performed; 7) complications following surgery. RESULTS: The mean LOS was significantly lower for patients managed through the rapid recovery protocol: 5.1 ± 1.4 days vs. 10.4 ± 2.3 days (p < 0.0001). The earlier discharge of patients promoted an overall increase in the total number of joint replacement procedures performed (2,806 in year 2019 vs. 2,236 in year 2016; p < 0.0001). Higher hemoglobin values at discharge were found in the RR group (10.6 ± 1.4 g/dl vs. 9.6 ± 1.2 g/dl, p = 0.049). No difference was observed in terms of clinical scores and overall complication rate. CONCLUSIONS: The application of a multimodal RR protocol for THR and TKR patients was able to reduce the length of stay and optimize the use of blood products, without increasing the risk of complications or jeopardizing the functional recovery.

SARS-CoV-2 Igg seroprevalence in IBD patients treated with biologics: first vs. second pandemic wave in a prospective study.

OBJECTIVE: In a prospective study, SARS-CoV-2 IgG seroprevalence was assessed during the second pandemic wave (W2) in a cohort of Inflammatory Bowel Disease (IBD) patients using biologics. The secondary aim was to compare, in the same cohort, the frequency of seropositivity and of COVID-19 during the second vs. the first (W1) wave. PATIENTS AND METHODS: From November 2020 to March 2021, SARS-CoV-2 IgG seropositivity and the prevalence of COVID-19 were assessed in a cohort of IBD patients using biologics already studied at W1. INCLUSION CRITERIA: age ≥ 18 years; diagnosis of IBD; follow-up; written consent. EXCLUSION CRITERIA: SARS-CoV-2 vaccination. Risk factors for infection, compatible symptoms, history of infection or COVID-19, nasopharyngeal swab test were recorded. Data were expressed as median [range]. The χ2 test, Student's t-test, logistic regression analysis was used. RESULTS: IBD cohort at W1 and W2 included 85 patients: 45 CD (52.9%), 40 UC (47.1%). When comparing the same 85 patients at W2 vs. W1, a higher SARS-CoV-2 seroprevalence at W2 was at the limit of the statistical significance (9.4% vs. 2.3%; p=0.05). The prevalence of COVID-19 at W2 vs. W1 was 3.5% (3/85) vs. 0% (0/85) (p=0.08). Contacts with COVID-19 patients and symptoms compatible with COVID-19 were more frequent at W2 vs. W1 (18.8 % vs. 0%; p=0.0001; 34.1% vs. 15.3%; p=0.004). At W2, history of contacts and new onset diarrhea were more frequent in seropositive patients [4/8 (50%) vs. 12/77 (15.6%); p=0.01 and 4/8 (50%) vs. 2/77 (2.6%); p=0.0001]. At W2, the risk factors for seropositivity included cough, fever, new onset diarrhea, rhinitis, arthromyalgia, dysgeusia/anosmia at univariate (p<0.05), but not at multivariate analysis. History of contacts was the only risk factor for seropositivity at univariate (p=0.03), but not at multivariate analysis (p=0.1). CONCLUSIONS: During W2, characterized by a high viral spread, IBD and biologics appeared not to increase the prevalence of SARS-CoV-2 infection or COVID-19 disease. New onset diarrhea mimicking IBD relapse may be observed in patients with SARS-CoV-2 infection.

Clinical efficacy of implementing a Patient Blood Management (PBM) Protocol in joint replacement surgery: a retrospective cohort study in a national referral center.

OBJECTIVE: The aging of population has dramatically broadened the total number of Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA) performed worldwide. To optimize the number of blood transfusions performed, a multimodal and multidisciplinary approach was introduced, called Patient Blood Management (PBM). The aim of the present retrospective study is to evaluate the feasibility and clinical outcomes of a PBM protocol applied in a national referral center for joint replacement surgery. PATIENTS AND METHODS: Clinical reports of 9,635 patients undergoing primary THA or TKA, from 2014 to 2019, were screened. The trends of hemoglobin value at admission and at day 4 after surgery were analyzed. Furthermore, the trend of blood bags' requests and blood transfusions was longitudinally evaluated to assess the efficacy of our PBM protocol and its potential impact in reducing the length of stay in the hospital. RESULTS: In 2014, mean hemoglobin (Hb) levels at postoperative day 4 were 10.3 g/dl and 10.2 g/dl for TKA (unilateral and bilateral, respectively), and in 2019 were 11.3 g/dl and 11.6 g/dl (unilateral and bilateral, respectively, p=0.001). Total requested red blood cell (RBC) transfusions by each surgery over time have decreased for THA (277 in 2014 vs. 120 in 2019, p=0.001).  A correlation matrix analysis between Hb level, body mass index (BMI), age, days spent in orthopedic (OR) ward and number of requested transfusions showed that RBC bags transfusions were related to the length of the hospital stay. CONCLUSIONS: A timely application of a PBM protocol in the perioperative period of TKA and THA was significantly associated to the reduction of blood transfusions and total length of hospital stay, with clear benefits for both the patients and the hospital.

The role of congenital malformations of the thoracic outlet in the development of the syndrome.

BACKGROUND: Thoracic outlet syndrome (TOS) represents a clinical condition caused by compression of the neurovascular structures that cross the thoracic outlet. TOS can be classified in: 1) neurogenic TOS (NTOS), 2) venous TOS (VTOS), 3) arterial TOS (ATOS). Many different causes can determine the syndrome: congenital malformations, traumas, and functional impairments. MATERIALS AND METHODS: This manuscript reviews how the congenital malformations play an important role in adult age; however, TOS also affects patients of all ages. RESULTS: Radiological imaging like X-ray (radiography), magnetic resonance and computed tomography can provide useful information to assess TOS causes and decide a potential surgery. 79% of the patients included in the first two stages of nerve, artery, vein (NAV) staging experienced excellent results with kinesiotherapy; whereas patients included in the third and fourth stage of NAV staging were subject to surgery. CONCLUSIONS: The treatment of acute forms of TOS involves thrombolysis and anticoagulant therapy; surgery is appropriate for true NTOS, vascular TOS and in some cases when conservative treatment fails.

Multiple hepatic and brain abscesses caused by Parvimonas micra: A case report and literature review.

Gram-positive anaerobic cocci (GPAC) are responsible for 30% of anaerobic infections. Parvimonas micra is an emergent pathogen that is part of the oral and gastrointestinal commensal flora, and its role in several infection processes has recently emerged thanks to the improvement of diagnostic techniques. P. micra bacteraemia is reported in immunocompromised patients and is often complicated by abscesses. Here, we present a case study of multiple hepatic and brain abscesses caused by P. micra bacteraemia in a patient with complicated diverticulitis.

Low prevalence of SARS-CoV-2 infection in inflammatory bowel disease.

OBJECTIVE: Treatments used in Inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections and viral reactivation, however, it remains unclear whether IBD patients have increased risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The aim of the study was to examine the prevalence of SARS-CoV-2 IgG positivity in IBD patients followed at our referral center. The role of treatments for IBD and risk factors for infection were also evaluated. PATIENTS AND METHODS: In a prospective study, all IBD patients followed at our referral centre between May 27th and July 21st, 2020 and fulfilling the inclusion criteria were tested for SARS-CoV-2 IgG. Specific IgG antibodies were evaluated by a commercial ELISA kit and SARS-CoV-2 nasopharyngeal swab was performed in seropositive patients. RESULTS: Two-hundred and eighteen patients, 128 Crohn's disease (CD) and 90 Ulcerative colitis (UC) [age 44, (19-77) years; ongoing biologics in 115 (52.7%)] were enrolled. No patient had major SARS-CoV-2-related symptoms. SARS-CoV-2 IgG were detected in 3 out of 218 (1.37%) patients with IBD (2 CD and 1 UC), all on biologics (2.6%). In all of the 3 seropositive patients, the nasopharyngeal swab was negative. There was no relationship between SARS-CoV-2 seroprevalence and the demographic/clinical characteristics of IBD patients. In contrast, history of recent travel was more frequent in the SARS-CoV-2 seropositive patients (2/3; 66.6%) than in SARS-CoV-2 seronegative patients [7/215 (3.25%); p<0.0001]. CONCLUSIONS: The prevalence of SARS-CoV-2 IgG seropositivity in IBD patients appears to be comparable to the non-IBD population and not influenced by ongoing treatments. Risk factors for infection common to the general non-IBD population should be considered when managing patients with IBD.

Effect of intravenous ferric carboxymaltose supplementation in non-anaemic iron deficient patients undergoing hip and knee arthroplasty.

Preoperative anaemia and non-anaemic iron deficiency are independent risk factors for perioperative blood transfusion, morbidity, and mortality. Although the efficacy to treat anaemia with iron infusion before elective surgery has been widely studied, the literature offers few data about the efficacy of treating iron deficient, non-anaemic patients before elective surgery. This retrospective study assessed the effect of preoperative ferric carboxymaltose (FC) administration on the concentration of Haemoglobin (Hb) in iron deficient, non-anaemic individuals following total knee or hip arthroplasty. A treatment group of 83 non-anaemic iron deficient individuals scheduled for arthroplasty were administered a 1000mg FC infusion over 15 minutes 4 weeks prior to surgery. In the control group (n=62) FC was not administered preoperatively. No individual from either group was given any iron supplement following the pre-operative visit. Blood tests were performed and analysed 4-weeks before surgery, on admission, and then 2-days, 4-days and 4-weeks postoperatively. Number of blood transfusions performed and adverse events were recorded. Hb concentration did not change substantially after iron supplementation prior to surgery. No difference in the number of blood transfusions was observed. In the treatment, group postoperative Hb concentration recovered significantly more quickly compared to control (p=0.0047). No adverse event was reported. The administration of FC in non-anaemic iron deficient individuals quickens the restoration of Hb concentration following THA or TKA procedures.

Hepatic follicular lymphoma in an old patient with Crohn's disease: a rare case and review of the literature.

OBJECTIVE: Crohn's Disease (CD) has been associated with non-Hodgkin lymphoma. Follicular Lymphoma (FL) limited to the liver is extremely rare, accounting for 1% to 4.4% of all Primary Hepatic Lymphoma (PHL). CASE PRESENTATION: In 2018, an 85-years old male patient with post-operative recurrence of ileal CD referred rare episodes of fever and mild diffuse abdominal pain. Since cholecystectomy in 2001, clinical history was characterized by recurrent episodes of cholangitis and common bile duct stones. In 2018, ultrasonography and MRI showed a solid focal hepatic lesion (FHL)(4.5 cm x 2.5 cm) in the IV hepatic segment. The radiographic aspect of the lesion was unusual. Initially, focal nodular hyperplasia was suspected. Clinical history of cholangitis and radiological findings subsequently suggested a diagnosis of Hepatic Abscess (HA). A progressive enlargement of the FHL (7.3 cm x 5.8 cm) despite antibiotic treatments, led to perform a liver biopsy. Histological and immunophenotypical analysis of the FHL (7.5 cm x 5.4 cm) enabled a final diagnosis of FL. The "in situ" hybridization for Epstein-Barr virus (EBER) was negative. No additional lesions related to FL were initially detected, thus suggesting a very rare case of PHL in an old patient with CD never treated with thiopurines. CONCLUSIONS: This case report highlights the need to consider a rare diagnosis of FL of the liver in patients showing a challenging focal hepatic lesion of unknown origin.

mTOR sustains inflammatory response in celiac disease.

Celiac disease (CD) is an enteropathy triggered by the ingestion of gluten proteins in genetically predisposed individuals and characterized by excessive activation of effector immune cells and enhanced production of inflammatory cytokines. However, factors/mechanisms that amplify the ongoing mucosal inflammation in CD are not fully understood. In this study, we assessed whether mammalian target of Rapamycin (mTOR), a pathway that combines intra- and extra-cellular signals and acts as a central regulator for the metabolism, growth, and function of immune and non-immune cells, sustains CD-associated immune response. Our findings indicate that expression of phosphorylated (p)/active form of mTOR is increased in protein lysates of duodenal biopsy samples taken from patients with active CD (ACD) as compared to normal controls. In ACD, activation of mTOR occurs mainly in the epithelial compartment and associates with enhanced expression of p-4EBP, a downstream target of mTOR complex (mTORC)1, while expression of p-Rictor, a component of mTORC2, is not increased. Stimulation of mucosal explants of inactive CD patients with pepsin-trypsin-digested (PT)-gliadin or IFN-γ/IL-21, two cytokines produced in CD by gluten-specific T cells, increases p-4EBP expression. Consistently, blockade of such cytokines in cultures of ACD mucosal explants reduces p-4EBP. Finally, we show that inhibition of mTORC1 with rapamycin in ACD mucosal explants reduces p-4EBP and production of IL-15, a master cytokine produced by epithelial cells in this disorder. Our data suggest that ACD inflammation is marked by activation of mTORC1 in the epithelial compartment.

Smad7 positively regulates keratinocyte proliferation in psoriasis.

BACKGROUND: Transforming growth factor (TGF)-ß1 exerts inhibitory effects on keratinocyte proliferation. OBJECTIVES: To examine whether Smad7, a known inhibitor of TGF-ß1 signalling, is involved in psoriasis-associated keratinocyte hyperproliferation. METHODS: Smad7 was evaluated in skin sections of patients with psoriasis and healthy controls and in mice with Aldara-induced skin pathology by real-time polymerase chain reaction and immunohistochemistry. To assess whether Smad7 positively regulates in vivo keratinocyte growth, mice treated with Aldara received daily cutaneous administration of Smad7 antisense oligonucleotide (AS). Keratin (K)6 and K16, cell-cycle-associated factors, cell-cycle and cell proliferation were evaluated in HaCaT cells either treated with Smad7 AS or transfected with Smad7 plasmid and in mice given Smad7 AS. RESULTS: Smad7 was highly expressed in keratinocytes of patients with psoriasis and of mice treated with Aldara. In HaCaT cells, Smad7 knockdown inhibited cell growth, reduced K6 and K16 expression and promoted accumulation of cells in the S-phase of the cell cycle. Smad7-deficient keratinocytes exhibited reduced levels of CDC25A protein, a phosphatase that facilitates progression of cells through the S-phase, and hyperphosphorylation of eukaryotic initiation factor 2 (eIF2)α, a negative regulator of CDC25 protein translation. Consistently, Smad7 overexpression in HaCaT cells was followed by induction of K6 and K16 and increased cell proliferation. Topical application of Smad7 AS to Aldara-treated mice reduced epidermal thickness. CONCLUSIONS: Our data show that Smad7 is overexpressed in human and murine psoriasis and suggest a key role of this molecule in the control of keratinocyte proliferation.

Impact of patient characteristics on the clinical efficacy of mongersen (GED-0301), an oral Smad7 antisense oligonucleotide, in active Crohn's disease.

BACKGROUND: In a phase 2 study, mongersen, an oral antisense oligonucleotide targeting Smad7, was effective in inducing clinical remission in approximately 60% of patients with active Crohn's disease (CD). AIM: In a post hoc analysis to evaluate those patient disease characteristics that may have influenced the efficacy and safety of mongersen therapy. METHODS: Patients with steroid-dependent/resistant, active CD were randomised to mongersen 10, 40 or 160 mg/day or placebo for 2 weeks; patients were followed for 10 weeks. Clinical remission [Crohn's Disease Activity Index (CDAI) score <150] and clinical response (CDAI score reduction ≥100 points) were assessed at weeks 2, 4 and 12 for these subgroups: disease duration <5/≥5 years, human serum C-reactive protein (hsCRP) <3/≥3 mg/L, and CDAI at baseline ≤260/>260. Additional patient baseline and disease characteristics were explored. RESULTS: Clinical remission and response rates were significantly higher in patients receiving mongersen 40 and 160 mg/day but not 10 mg/day vs. placebo and independent of disease duration and hsCRP. Patients with baseline CDAI ≤260 had significantly higher remission rates with 40 and 160 mg/day. In patients with baseline CDAI >260, remission rates were statistically greater with 160 mg/day and numerically better with 40 mg/day vs. placebo. Adverse event rates were similar across treatment groups. Mongersen was safe and well tolerated. CONCLUSIONS: Patients with higher CDAI scores achieved clinical remission most frequently with the highest mongersen dose. Disease duration and baseline human serum C-reactive protein did not appear to significantly impact efficacy of mongersen in this study (EudraCT Number: 2011-002640-27.).

Ultrasonographic evaluation of the shoulder in elite Italian beach volleyball players.

AIM: Beach volleyball is an overhead sport that subjects the hitting shoulder to intense functional loads. The purpose of this study is to identify ultrasonographically the prevalence of myotendinous alterations in professional Italian beach volleyball players at the Italian championship and to look for associations between ultrasound findings and the other data collected. METHODS: Fifty-three beach volleyball players (31 women, 22 men) were recruited during the second stage of the Italian championship held in July 2012 in Rome, Italy. Clinical history was obtained from all subjects, followed by physical exam. Each athlete completed a questionnaire regarding sports activities. Bilateral ultrasonographic evaluation of the shoulders was then performed. RESULTS: Calcific tendinopathy of the rotator cuff of the hitting shoulder was identified ultrasonographically in 30% of the athletes. The mean age of the athletes with calcific tendinopathy was older than subjects with other abnormalities on ultrasonographic examination (33.1 years vs. 25.8 years, t-test; P<0.0001). Impingement was recognized ultrasonographically in the hitting shoulder in 10 of the athletes (18.8%). The Neer's test was positive in the cases of anterior impingement (χ2; P<0.002). CONCLUSION: Calcific tendinopathy of the rotator cuff of the hitting shoulder in professional beach volleyball players has a prevalence of 30% ultrasonographically, greater than that reported in the general population. In these athletes, the presence of calcific tendinopathy correlates positively with age.

Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth.

Colorectal cancers (CRCs) often show a dense infiltrate of cytokine-producing immune/inflammatory cells. The exact contribution of each immune cell subset and cytokine in the activation of the intracellular pathways sustaining CRC cell growth is not understood. Herein, we isolate tumor-infiltrating leukocytes (TILs) and lamina propria mononuclear cells (LPMCs) from the tumor area and the macroscopically unaffected, adjacent, colonic mucosa of patients who underwent resection for sporadic CRC and show that the culture supernatants of TILs, but not of LPMCs, potently enhance the growth of human CRC cell lines through the activation of the oncogenic transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-kB). Characterization of immune cell complexity of TILs and LPMCs reveals no differences in the percentages of T cells, natural killer T cells, natural killer (NK) cells, macrophages and B cells. However, T cells from TILs show a functional switch compared with those from LPMCs to produce large amounts of T helper type 17 (Th17)-related cytokines (that is, interleukin-17A (IL-17A), IL-17F, IL-21 and IL-22), tumor necrosis factor-α (TNF-α) and IL-6. Individual neutralization of IL-17A, IL-17F, IL-21, IL-22, TNF-α or IL-6 does not change TIL-derived supernatant-driven STAT3 and NF-kB activation, as well as their proproliferative effect in CRC cells. In contrast, simultaneous neutralization of both IL-17A and TNF-α, which abrogates NF-kB signaling, and IL-22 and IL-6, which abrogates STAT3 signaling, reduces the mitogenic effect of supernatants in CRC cells. IL-17A, IL-21, IL-22, TNF-α and IL-6 are also produced in excess in the early colonic lesions in a mouse model of sporadic CRC, associated with enhanced STAT3/NF-kB activation. Mice therapeutically given BP-1-102, an orally bioavailable compound targeting STAT3/NF-kB activation and cross-talk, exhibit reduced colon tumorigenesis and diminished expression of STAT3/NF-kB-activating cytokines in the neoplastic areas. These data suggest that strategies aimed at the cotargeting of STAT3/NF-kB activation and interaction between them might represent an attractive and novel approach to combat CRC.

Serum regenerating islet-derived 3-alpha is a biomarker of mucosal enteropathies.

BACKGROUND: The clinical presentation of organic and functional intestinal disorders can overlap and clinicians often rely on invasive and time-consuming procedures to make a final diagnosis. Regenerating islet-derived 3-alpha (Reg3α) is detectable in the circulation of patients with intestinal graft-versus host disease and patients with inflammatory bowel disease (IBD). AIM: To determine whether serum Reg3α testing is useful for discriminating mucosal enteropathies from functional intestinal disorders. METHODS: We prospectively included 47 patients with active coeliac disease (ACD), 13 patients with refractory coeliac disease (RCD), seven patients with common variable immunodeficiency (CVID), 72 patients with active Crohn's disease, 22 patients with active ulcerative colitis (UC) and 28 patients with irritable bowel syndrome (IBS)-related diarrhoea. Sera were also taken from 10 CD patients before and after 6-12 months of a gluten-free diet (GFD) and from 14 patients with IBD before and after induction therapy with Infliximab (IFX). Sera of 119 healthy volunteers were used to determine the cut-off value. Reg3α levels were measured by a commercial ELISA kit. RESULTS: Levels of Reg3α exceeded the cut-off value of the assay in 43/47(91%) ACD patients, 13/13(100%) RCD patients, 7/7(100%) CVID patients, 65/72(90%) Crohn's disease patients, 17/22(77%) UC patients and one patient with IBS(4%). Reg3α levels distinguished mucosal enteropathies from IBS with a sensitivity of 90% and a specificity of 96%. Reg3α levels significantly decreased in CD patients following a GFD and in IBD patients after treatment with IFX. CONCLUSION: Reg3α is a serum biomarker of intestinal damage that, combined with clinical data, identifies patients who should undergo invasive tests for diagnosing enteropathies.

You are in sync with me: neural correlates of interpersonal synchrony with a partner.

Interpersonal synchrony is characterized by a temporary alignment of periodic behaviors with another person. This process requires that at least one of the two individuals monitors and adjusts his/her movements to maintain alignment with the other individual (the referent). Interestingly, recent research on interpersonal synchrony has found that people who are motivated to befriend an unfamiliar social referent tend to automatically synchronize with their social referents, raising the possibility that synchrony may be employed as an affiliation tool. It is unknown, however, whether the opposite is true; that is, whether the person serving as the referent of interpersonal synchrony perceives synchrony with his/her partner or experiences affiliative feelings toward the partner. To address this question, we performed a series of studies on interpersonal synchrony with a total of 100 participants. In all studies, participants served as the referent with no requirement to monitor or align their behavior with their partners. Unbeknown to the participants, the timings of their "partner's" movements were actually determined by a computer program based on the participant's (i.e., referent's) behavior. Overall, our behavioral results showed that the referent of a synchrony task expressed greater perceived synchrony and greater social affiliation toward a synchronous partner (i.e., one displaying low mean asynchrony and/or a narrow asynchrony range) than with an asynchronous partner (i.e., one displaying high mean asynchrony and/or high asynchrony range). Our neuroimaging study extended these results by demonstrating involvement of brain areas implicated in social cognition, embodied cognition, self-other expansion, and action observation as correlates of interpersonal synchrony (vs. asynchrony). These findings have practical implications for social interaction and theoretical implications for understanding interpersonal synchrony and social coordination.

Defective expression of SIRT1 contributes to sustain inflammatory pathways in the gut.

In inflammatory bowel disease (IBD), tissue damage is driven by an excessive immune response, poorly controlled by counter-regulatory mechanisms. SIRT1, a class III NAD+-dependent deacetylase, regulates negatively the expression of various proteins involved in the control of immune-inflammatory pathways, such as Stat3, Smad7, and NF-κB. Here we examined the expression, regulation, and function of SIRT1 in IBD. SIRT1 RNA and protein expression was less pronounced in whole biopsies and lamina propria mononuclear cells (LPMCs) of IBD patients in comparison with normal controls. SIRT1 expression was downregulated in control LPMC by tumor necrosis factor (TNF)-α and interleukin (IL)-21, and upregulated in IBD LPMC by neutralizing TNF-α and IL-21antibodies. Consistently, SIRT1 expression was increased in mucosal samples taken from IBD patients successfully treated with Infliximab. Treatment of IBD LPMC with Cay10591, a specific SIRT1 activator, reduced NF-κB activation and inhibited inflammatory cytokine synthesis, whereas Ex527, an inhibitor of SIRT1, increased interferon (IFN)-γ in control LPMC. SIRT1 was also reduced in mice with colitis induced by 2,4,6-trinitrobenzenesulphonic acid or oxazolone. Cay10591 prevented and cured experimental colitis whereas Ex527 exacerbated disease by modulating T cell-derived cytokine response. Data indicate that SIRT1 is downregulated in IBD patients and colitic mice and suggest that SIRT1 activation can help attenuate inflammatory signals in the gut.