The activity of the aryl hydrocarbon receptor in T cells tunes the gut microenvironment to sustain autoimmunity and neuroinflammation.

Multiple sclerosis (MS) is a T cell-driven autoimmune disease that attacks the myelin of the central nervous system (CNS) and currently has no cure. MS etiology is linked to both the gut flora and external environmental factors but this connection is not well understood. One immune system regulator responsive to nonpathogenic external stimuli is the aryl hydrocarbon receptor (AHR). The AHR, which binds diverse molecules present in the environment in barrier tissues, is a therapeutic target for MS. However, AHR's precise function in T lymphocytes, the orchestrators of MS, has not been described. Here, we show that in a mouse model of MS, T cell-specific Ahr knockout leads to recovery driven by a decrease in T cell fitness. At the mechanistic level, we demonstrate that the absence of AHR changes the gut microenvironment composition to generate metabolites that impact T cell viability, such as bile salts and short chain fatty acids. Our study demonstrates a newly emerging role for AHR in mediating the interdependence between T lymphocytes and the microbiota, while simultaneously identifying new potential molecular targets for the treatment of MS and other autoimmune diseases.

Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.

Depression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in microbiome composition are associated with disease pathology. Stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes in the context of stress. Using a model of chronic stress, we show that the glycocalyx protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction of Muc13 is mediated by the Hnf4 transcription factor family. Finally, we determine that deleting Muc13 is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a novel regulator of mucin 13 expression.

Images in clin medicine: Ectopia lentis.

A 31-year-old woman with Marfan's syndrome presented with amblyopia and a history of gradual bilateral vision loss over the previous 3 to 4 months. She had also had mild sensorineural hearing loss within the previous 2 weeks.

Fistula tract curettage and the use of biological dermal plugs improve high transsphincteric fistula healing in an animal model.

PURPOSE: The treatment of high transsphincteric fistula is a complex procedure, which may be associated with the risk of recurrence and fecal incontinence. In this study, we used an animal model to compare different types of sphincter-preserving treatments for transsphincteric fistula. METHODS: Sixteen female New Zealand rabbits, weighing 2.8-4.8 kg underwent a surgical creation of high transsphincteric fistula. After 6 weeks, magnetic resonance imaging (MRI) was performed in order to confirm fistula formation and measure the fistula diameter. The rabbits were divided into three groups. Group 1 received no plug treatment (control). Autologous dermal graft and acellular dermal matrix were used as a plug in groups 2 and 3, respectively. Five weeks after treatment, fistula tract healing was determined by measuring the largest fistula diameter with MRI. All rabbits were euthanized and the anorectum excised en bloc for histopathological examination. RESULTS: According to the MRI findings, all groups showed significant healing after the treatment (p < 0.05). The healing rate of fistula diameters after treatment was 40, 66, and 29% in the control, dermal graft, and acellular dermal matrix groups, respectively. In terms of negative healing parameters such as neutrophil, eosinophil, lymphocyte, and plasmocyte accumulation, dermal graft and acellular dermal matrix groups showed significantly lower results than those in the control group (p < 0.05). CONCLUSION: According to MRI and histopathological results, fistula tract curettage and fistula orifice closure improved transsphincteric anal fistula healing. Additionally, in this study, plug treatment favoring autologous dermal graft resulted in better healing.

Clinical Application of Six Current Classification Systems for Iatrogenic Bile Duct Injuries after Cholecystectomy.

BACKGROUND/AIMS: Due to being a severe complication, iatrogenic bile duct injury is still a challenging issue for surgeons in gallbladder surgery. However, a commonly accepted classification describing the type of injury has not been available yet. This study aims to evaluate ability of six current classification systems to discriminate bile duct injury patterns. METHODOLOGY: Twelve patients, who were referred to our clinic because of iatrogenic bile duct injury after laparoscopic cholecystectomy were reviewed retrospectively. We described type of injury for each patient according to current six different classifications. RESULTS: 9 patients underwent definitive biliary reconstruction. Bismuth, Strasberg-Bismuth, Stewart-Way and Neuhaus classifications do not consider vascular involvement, Siewert system does, but only for the tangential lesions without structural loss of duct and lesion with a structural defect of hepatic or common bile duct. Siewert, Neuhaus and Stewart-Way systems do not discriminate between lesions at or above bifurcation of the hepatic duct. CONCLUSION: The Hannover classification may resolve the missing aspects of other systems by describing additional vascular involvement and location of the lesion at or above bifurcation.

Median nerve stiffness measurement by shear wave elastography: a potential sonographic method in the diagnosis of carpal tunnel syndrome.

OBJECTIVES: To measure the median nerve (MN) stiffness by quantitative shear wave elastography (SWE) at the carpal tunnel inlet and to determine whether SWE can be used in the diagnosis of carpal tunnel syndrome (CTS). METHODS: The study included 37 consecutive patients (60 wrists) with a definitive diagnosis of CTS and 18 healthy volunteers (36 wrists). The MN cross-sectional area (CSA) by ultrasound and stiffness by SWE were studied. The difference between CTS patients and controls, and the difference among subgroups based on electrodiagnostic tests were studied by the Student's t test. Interobserver variability and ROC analysis were performed. RESULTS: The MN stiffness was significantly higher in the CTS group (66.7 kPa) when compared to controls (32.0 kPa) (P < 0.001), and higher in the severe or extreme severity group (101.4 kPa) than the mild or moderate severity group (55.1 kPa) (P < 0.001). A 40.4-kPa cut-off value on SWE revealed sensitivity, specificity, PPV, NPV and accuracy of 93.3%, 88.9%, 93.3%, 88.9% and 91.7%, respectively. Interobserver agreement was excellent for SWE measurements. CONCLUSIONS: Median nerve stiffness at the carpal tunnel inlet is significantly higher in patients with carpal tunnel syndrome, for whom shear wave elastography appears to be a highly reproducible diagnostic technique. KEY POINTS: • Clinical examination is important for diagnosis of carpal tunnel syndrome • Shear wave elastography (SWE) offers new clinical opportunities within diagnostic ultrasound • SWE is highly reproducible in evaluation of median nerve stiffness • Median nerve stiffness is significantly increased in carpal tunnel syndrome • Elastography could become useful in diagnosis of carpal tunnel syndrome.

Relative proportions of stromal to cellular components of pleomorphic adenomas: determination with shear wave elastography.

OBJECTIVES: The purpose of this study was to evaluate whether the relative proportions of stromal to cellular components of pleomorphic adenomas have an effect on the shear elastic modulus determined by shear wave elastography (SWE). METHODS: This study was approved by the Ethics Committee of our institution and performed between September 2011 and December 2012. Thirty-five patients who underwent surgery for a parotid mass were included in the study. The maximum shear elastic modulus of the mass was measured by SWE. Pleomorphic adenomas were histopathologically subdivided into stroma-poor, intermediate-stroma, and stroma-rich tumors based on the relative proportion of stromal to cellular components. RESULTS: The maximum shear elastic modulus values of the pleomorphic adenomas ranged from 12.6 to 291.9 kPa (mean ± SD, 120.9 ± 92.8 kPa). The Friedman test revealed a statistically significant relationship between the stromal amount and maximum shear elastic modulus (P < .001). Stroma-poor adenomas (mean, 32.3 ± 27.7 kPa; range, 12.6-81.1 kPa) were softer on SWE than stroma-rich adenomas (mean, 174.1 ± 48.4 kPa; range, 92.7-217.2 kPa; P = .009). No such significant difference was detected between stroma-poor and intermediate-stroma tumors (mean, 146.3 ± 106.1 kPa; range, 19.1-291.9 kPa; P = .062) or between intermediate-stroma and stroma-rich tumors (P = .465). CONCLUSIONS: Shear wave elastography depicts pleomorphic adenomas with a variable appearance, which is due to the relative proportions of stromal to cellular contents in the tumors.

Extended pancreaticoduodenectomy for a huge cystic-cavernous lymphangioma: a case report.

CONTEXT: Cystic-cavernous lymphangioma is a rare cystic tumor especially for adults and pancreas. CASE REPORT: We reported a case of a 33-year-old woman who presented with a visible and palpable abdominal mass found to be a huge lymphangioma of the pancreas. An abdominal magnetic resonance imaging (MRI) showed a multiloculated, lobulated T1 hypo/hyper, T2 hyperintense cystic mass extending from right subhepatic space to the pelvis measuring 155x167x100 mm. A pancreaticoduodenectomy was performed encompassing the distal stomach and a segment of the transverse colon, because of their close, inseparable relationship to the mass. The cystic mass was histopathologically diagnosed as partly cavernous and partly cystic lymphangioma. CONCLUSION: To our knowledge this is the first case of pancreatic lymphangioma requiring additional organ resection besides a standard pancreaticoduodenectomy. To reduce recurrences, we recommend a complete resection for this pathology, even though its benign nature.

MRI in differentiating malignant versus benign portal vein thrombosis in patients with hepatocellular carcinoma: Value of post contrast imaging with subtraction.

PURPOSE: To evaluate MR imaging parameters including quantitative multiphasic post-contrast enhancement with subtraction and qualitative diffusion weighted imaging (DWI) in differentiating benign versus malignant portal venous thrombosis (PVT) in patients with hepatocellular carcinoma (HCC). METHOD: Radiology reports over a 6-year period ending February 2016 were searched for key words indicating presence of both HCC and PVT on abdominal MRI. 39 patients were identified with PVT characterized as benign or malignant based on pathologic data or serial imaging growth criteria. Image review was performed by two subspecialized radiologists blinded to the diagnosis and medical chart. Signal intensity for regions of interest were recorded within the portal vein thrombus as well as the portal vein on pre-contrast and dynamic post-contrast phases without and with subtraction. Qualitative parameters for DWI and presence of PV expansion were also evaluated. RESULTS: Percent enhancement generated high area under the curve (AUC) for both readers on all non-subtraction phases: arterial (0.95/0.98), portal venous (0.97/0.97) and delayed phase (0.96/0.99) and subtraction phases: arterial (0.91/0.96), portal venous (0.94/0.99) and delayed phases (0.96/0.97). Statistically significant differences were observed between benign and malignant PVT for both readers for PV expansion (p= <0.001/0.006). No qualitative DWI parameter reached statistical significance for both readers. CONCLUSIONS: Post-contrast and subtraction MRI can reliably distinguish malignant from benign PVT in patients with HCC using subtracted or non-subtracted images and at arterial, portal venous, or delayed phase timing.

Clinical Significance of Pulmonary Nodules in the Pretransplant Evaluation of Liver Transplant Recipients With Hepatocellular Carcinoma.

OBJECTIVES: Pulmonary nodules are common in patients with hepatocellular carcinoma who are being evaluated for a possible liver transplant. MATERIALS AND METHODS: In this retrospective study, we analyzed the records of liver transplant recipients at our institution with a primary diagnosis of hepatocellular carcinoma who received transplants between 2000 and 2015. All patients had magnetic resonance imaging-confirmed disease within Milan criteria and a concurrent staging chest computed tomography. Patient survival was estimated using Kaplan-Meier methods and compared between pulmonary nodule characteristic groups. A Cox proportional hazards model was constructed for adjusted analysis. RESULTS: Of the 197 liver transplant recipients who met our study inclusion criteria (median follow-up, 40 mo), 115 (58.4%) had a total of 231 pulmonary nodules, with 57 (49.6%) having multiple nodules and 108 (93.9%) having nodules ≤ 1 cm. The presence of pulmonary nodules did not negatively affect patient survival, per our univariate and multivariate analysis, nor did their presence affect their number, location, laterality, shape, edge, density, or the presence of calcifications (P ≥.05). However, pulmonary nodules ≥ 1 cm were associated with decreased overall survival. CONCLUSIONS: In our pretransplant evaluation of patients with hepatocellular carcinoma, pulmonary nodules ≤ 1 cm did not portend worse patient or graft survival posttransplant.

Anterior and Posterior Vertebral Column Resection Versus Posterior-only Technique: A Comparison of Clinical Outcomes and Complications in Congenital Kyphoscoliosis.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of this study is to compare the anterior-posterior surgery to posterior-only vertebra resection for congenital kyphoscoliosis in pediatric patients. SUMMARY OF BACKGROUND DATA: Vertebral column resection is a very powerful correction technique mainly used in the treatment of severe and rigid spinal deformities. The technique can be applied with combined anterior and posterior vertebral column resection (APVCR) or posterior-only vertebral column resection (PVCR) approaches. PVCR has gained popularity recently due to several apparent advantages, but APVCR is still believed by some to be a viable alternative, despite the use of an anterior exposure. MATERIALS AND METHODS: A retrospective chart and radiographic review was performed including the patients with congenital kyphoscoliosis up to 16 years of age who were operated on by a single senior surgeon in our department after 2005. The data included surgical time, estimated blood loss, duration of hospital and postoperative intensive care unit stay, intraoperative and postoperative complications. Preoperative, postoperative, and follow-up radiographs were evaluated for scoliosis, kyphosis, and spinal balance. RESULTS: Twenty-six patients (20 girls, 6 boys) met the inclusion criteria. APVCR was performed on 17 (median age, 13.2 y) and PVCR on 9 (median age, 10.7 y). Scoliosis correction at the time of last follow-up was 54.3% and 52.6% for APVCR and PVCR, respectively, whereas the average kyphosis correction was 25.4 degrees in APVCR and 30.1 degrees in PVCR group. Surgical time, hospital stay, and estimated blood loss were all significantly higher in the APVCR group, whereas the complication rates were similar. No neurological or vascular complications were encountered. CONCLUSIONS: This study showed that although the operative time and surgical blood loss were higher with APVCR, there were no major complications and the radiologic outcomes were similar between APVCR and PVCR. APVCR should be considered as an acceptable technique especially in deformities where PVCR would be technically difficult or at the beginning of the spine surgeon's learning curve. LEVEL OF EVIDENCE: Level III.

Apparent Diffusion Coefficient Measurement in Mediastinal Lymphadenopathies: Differentiation between Benign and Malignant Lesions.

OBJECTIVES: We aimed to prospectively assess the diagnostic value of apparent diffusion coefficient (ADC) measurement in the differentiation of benign and malignant mediastinal lymphadenopathies. MATERIALS AND METHODS: The study included 63 consecutive patients (28 women, 35 men; mean age 59.3 years) with 125 mediastinal lymphadenopathies. Echoplanar diffusion-weighted magnetic resonance imaging of the mediastinum was performed with b-factors of 0 and 600 mm2/s before mediastinoscopy and mediastinotomy, and ADC values were measured. The ADC values were compared with the histological results, and statistical analysis was done. P < 0.05 was considered statistically significant. RESULTS: The mean ADC value of malignant mediastinal lymphadenopathy (1.030 ± 0.245 × 10-3 mm2/s) was significantly lower (P < 0.05) when compared to benign lymphadenopathies (1.571 ± 0.559 × 10-3 mm2/s). For differentiating malignant from benign mediastinal lymphadenopathy, the best result was obtained when an ADC value of 1.334 × 10-3 mm2/s was used as a threshold value; area under the curve 0.848, accuracy 78.4%, sensitivity 66%, specificity of 86%, positive predictive value 76.7%, and negative predictive value of 79.2%. Interobserver agreement was excellent for ADC measurements. CONCLUSIONS: ADC measurements could be considered an important supportive method in differentiating benign from malignant mediastinal lymphadenopathies.

Long-Term Progression of Coronary Artery Calcification Is Independent of Classical Risk Factors, C-Reactive Protein, and Parathyroid Hormone in Renal Transplant Patients.

AIMS: Compared to the general population, mortality is significantly increased in renal transplant recipients. In the general population, coronary artery calcification (CAC) and its evolution over time are associated with cardiovascular and all-cause mortality, and the study of this biomarker could provide useful information for describing the long-term progression of coronary heart disease in renal transplant recipients. METHODS: We followed up a cohort of 113 renal transplant patients by performing three multi-detector computed tomography studies over 83.6 ± 6.8 months. Data analysis was performed by logistic regression analysis and by mixed linear modelling. RESULTS: Progression was observed in 34.5% of patients. Baseline CAC and time-to-transplantation were the sole variables that predicted CAC evolution over time. Neither classical nor nontraditional risk factors, biomarkers of renal function (GFR) and kidney damage (albuminuria) or biomarkers of bone mineral disorder (BMD), such as serum phosphorus, calcium, and PTH, were associated with the long-term progression of coronary calcification. Serum triglycerides predicted CAC progression only in logistic regression analysis, while in addition to baseline CAC, time to transplantation was the sole variable predicting CAC progression when the data were analyzed by mixed linear modelling. These data suggested that, in addition to the background calcification burden, other unmeasured factors play major roles in promoting the evolution of coronary calcification in the transplant population. CONCLUSION: CAC progression continued over the long-term follow-up of renal transplant patients. This phenomenon was unaccounted for by classical and nontraditional risk factors, as well as by biomarkers of renal dysfunction and renal damage.

Evaluation of anterior mediastinal solid tumors by CT perfusion: a preliminary study.

PURPOSE: We aimed to assess the role of computed tomography (CT) perfusion in differentiation of thymoma from thymic hyperplasia, lymphoma, thymic carcinoma, and lung cancer invading anterior mediastinum. METHODS: In this study, 25 patients with an anterior mediastinal lesion underwent CT perfusion imaging from January 2015 to February 2016. Diagnoses included thymoma (n=7), thymic hyperplasia (n=8), lymphoma (n=4), thymic carcinoma (n=3), and invasive lung cancer (n=3). Lymphoma, thymic carcinoma, and lung cancer were grouped as malignant tumors for statistical analysis. Values for blood flow, blood volume, and permeability surface were measured in CT perfusion. RESULTS: Blood flow and blood volume values were higher in thymoma in comparison to thymic hyperplasia; however, the difference was not statistically significant. Blood volume values were significantly higher in thymoma (mean, 11.4 mL/100 mL; range, 5.2-20.2 mL/100 mL) compared with lymphoma (mean, 5.3 mL/100 mL; range, 2.5-7.2 mL/100 mL) (P = 0.023). Blood flow and blood volume values were significantly higher in thymoma compared with non-thymoma malignant tumors (P = 0.025). CONCLUSION: CT perfusion is helpful in differentiating thymoma from non-thymoma malignancies including lymphoma, thymic carcinoma, and invasive lung cancer involving the anterior mediastinum.

Embolism of a pellet after shotgun injury: From liver to right ventricle.

Bullet embolism to the heart is a rare but serious complication of penetrating trauma. Distant migration of foreign bodies via the vascular system must be taken into consideration following penetrating gunshot trauma. Delays in diagnosis may result in poor management and subsequent complications that may lead to grave prognosis. Presently described was a conservatively managed case of asymptomatic intracardiac pellet embolization. Highlighted was the importance of serial scanning for intravascular migration of pellet following penetrating gunshot injury, in addition to conservative management in asymptomatic patients.

Life-threatening complication of percutaneous transthoracic fine-needle aspiration biopsy: systemic arterial air embolism.

Computed tomography-guided percutaneous transthoracic fine-needle aspiration biopsy of lung lesions is a well known diagnostic technique. Nevertheless, it has some complications; such as pneumothorax, intraparenchymal hemorrhage and hemoptysis, which are not rare. Air embolism is one of the rare but potentially fetal complications of this procedure. Herein, we report the case of a 69-year-old male, in which case of systemic air embolism developed after the performance of lung biopsy. Early diagnosis and prompt oxygen therapy is crucial for patient's survival so careful reviewing of the obtained computed tomography images during the biopsy may prevent a missing systemic air embolism and provide an adequate therapy.

Perianal Fistula With and Without Abscess: Assessment of Fistula Activity Using Diffusion-Weighted Magnetic Resonance Imaging.

BACKGROUND: Magnetic resonance imaging (MRI) is highly accurate for the depiction of both the primary tract of fistula and abscesses, in patients with perianal disease. In addition, MRI can be used to evaluate the activity of fistulas, which is a significant factor for determining the therapeutic strategy. OBJECTIVES: This study aimed to determine the usefulness of diffusion-weighted (DW) MRI for assessing activity and visibility of perianal fistula. PATIENTS AND METHODS: Fifty-three patients with 56 perianal fistulas were included in the current retrospective study. The T2-weighted imaging (T2WI) and DWMRI were performed and apparent diffusion coefficient (ADC) values of fistulas were measured. Fistulas were classified into two groups: only perianal fistulas and fistulas accompanied by abscess. Fistulas were also classified into two groups, based on clinical findings: positive inflammatory activity (PIA) and negative inflammatory activity (NIA). RESULTS: Mean ADC value (mm(2)/s) of PIA group was significantly lower than that of NIA group, regarding lesions in patients with abscess-associated fistulas (1.371 × 10(-3) ± 0.168 × 10(-3) vs. 1.586 × 10(-3) ± 0.136 × 10(-3); P = 0.036). No statistically significant difference was found in mean ADC values between PIA and NIA groups, in patients with only perianal fistulas (P = 0.507). Perianal fistula visibility was greater with combined evaluation of T2WI and DWMRI than with T2WI, for two reviewers (P = 0.046 and P = 0.014). CONCLUSION: The DWMRI is a useful technique for evaluating activity of fistulas with abscess. Perianal fistula visibility is greater with combined T2WI and DWMRI than T2WI alone.

The journey of gastric phytobezoar followed by tomography.

Phytobezoars are a rare cause of intestinal obstruction. They are usually present in patients with predisposing factors such as previous gastric surgery, diabetes, and edentulousness. In this case report, an uncommon cause of intestinal obstruction due to the migration of gastric phytobezoar in a patient with no known predisposing factor is reported.

Simultaneous thrombosis of superior mesenteric artery and superior mesenteric vein following chemotherapy: MDCT findings.

A case of acute mesenteric ischemia due to thrombosis of superior mesenteric artery and vein in a 44-year-old woman following chemotherapy for invasive laryngeal carcinoma was diagnosed on a multi-detector CT scan. Although the link between malignancy and thromboembolism is widely recognized in patients with cancer, chemotherapy further elevates the risk of thrombosis. Acute mesenteric ischemia associated or not associated with chemotherapy rarely occurs in patients with cancer. Moreover, co-occurrence of superior mesenteric artery and superior mesenteric vein thrombosis is reported for the first time.