Clinical Immunology

Compound Heterozygous DOCK8 Mutations in a Patient with B Lymphoblastic Leukemia and EBV-Associated Diffuse Large B Cell Lymphoma Abstract Mutations in Dedicator of cytokinesis 8 (DOCK8) are a rare cause of combined immunodeficiency associated with atopy, infectious susceptibility, and risk for malignancy. We describe a 22-year-old male with a diagnosis of B cell lymphoblastic leukemia followed by Epstein-Barr virus (EBV)-associated diffuse large B cell lymphoma (DLBCL) with compound heterozygous mutations in DOCK8 and normal intracellular DOCK8 protein expression. Here, B cell lymphoblastic leukemia followed by EBV-associated DLBCL led to the discovery of DOCK8 deficiency. For instances of high clinical suspicion despite normal DOCK8 protein expression, additional functional testing is critical to make a diagnosis. Understanding the spectrum of DOCK8 mutants and their phenotypes will improve our understanding of DOCK8 deficiency.

Correction to: Life-Threatening Infections Due to Live-Attenuated Vaccines: Early Manifestations of Inborn Errors of Immunity The original version of this article unfortunately contained mistake in the following sentence in the Abstract.

Hematopoietic Stem Cell Transplantation in CARD9 Deficiency: Knight in Shining Armor?

Autoinflammation Masquerading as Autoimmunity in an Adult with Heterozygous p.E250K PSTPIP1 Mutation

Different Phenotypic Presentations of X-Linked Lymphoproliferative Disease in Siblings with Identical Mutations

Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study Abstract Purpose Selective IgA deficiency (SIgAD) is the most common humoral primary immunodeficiency. Long-term follow-up data in large cohort of pediatric patients are scarce. Methods We report on a single-center cohort of 184 pediatric patients affected with selective IgA deficiency and describe the characteristics at diagnosis and during follow-up. Results Respiratory infections were the most common clinical finding leading to the initial diagnosis (62%). Positive family history for antibody deficiencies (selective IgA deficiency, common variable immunodeficiency) led to SIgAD diagnosis in 16% of cases. During follow-up, while the incidence of respiratory infections was not particularly high, gastrointestinal symptoms were reported in 27% of patients. Allergic manifestations were found in 23% at diagnosis and an additional 16% of patients during follow-up, leading to a prevalence of atopy of 39% among SIgAD patients. Autoimmune manifestations, excluding celiac disease, were found in 9% of affected patients during follow-up. Celiac disease was found in a high prevalence (14%). Increase of serum IgA levels to partial deficiency (9%) and normal serum levels for age (4%) was observed during follow-up. A small percentage of patients (2%) progressed to common variable immunodeficiency (CVID). Conclusions In conclusion, this is the first study to describe a large single-center pediatric cohort of patients affected with SIgAD, revealing that overall most patients do well with regard to infections. Many develop CD, at a rate much higher than the general population. A few normalize their IgA levels. A few progress to CVID. Thus, careful follow-up is suggested to diagnose and treat potential complications earlier for avoiding potential morbidities.

iPLA 2 Activation Mediates Granular Exocytosis and Corrects Microbicidal Defects in ROS-Deficient and CGD Human Neutrophils Abstract Purpose The ubiquitous calcium–independent phospholipase A2 enzyme (iPLA2) is inhibited by calmodulin binding and known to be responsible for phospholipid remodeling housekeeping functions including granule exocytosis–associated membrane fusion in normal human neutrophils. We evaluate in human neutrophils the iPLA2 secretagogue effects using normal neutrophils, where reactive oxygen species (ROS) generation has been blocked by diphenyleneiodonium, as well as in neutrophils from chronic granulomatous disease (CGD) patients. Methods Neutrophils were pretreated with W7, a calmodulin inhibitor known to activate iPLA2 and exocytosis of granules, and vesicles as well as intra- and extra-microbicidal activity against Staphylococcus aureus and Aspergillus fumigatuswere evaluated. Results W7 increases exocytosis of primary, secondary, and tertiary granules and vesicles and improves neutrophil microbicidal activity against S. aureus and A. fumigatus. Conclusions In neutrophils, calmodulin-mediated iPLA2 inhibition controls granule and vesicle exocytosis in the phagosome and in the extracellular microenvironment. Relieving iPLA2 inhibition results in increased exocytosis of primary, secondary, and tertiary granules and secretory vesicles with correction of defective intracellular and extracellular microbicidal activity. In CGD patients presenting ROS defective production, this increase in the non-oxidative killing pathway partially corrects their microbicidal defects.

Efficacy and Adverse Events During Janus Kinase Inhibitor Treatment of SAVI Syndrome Abstract Objectives Mutations affecting the TMEM173 gene cause STING-associated vasculopathy with onset in infancy (SAVI). No standard immunosuppressive treatment approach is able to control disease progression in patients with SAVI. We studied the efficacy and safety of targeting type I IFN signaling with the Janus kinase inhibitor, ruxolitinib. Methods We used DNA sequencing to identify mutations in TMEM173 in patients with peripheral blood type I IFN signature. The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis. Results We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Indirect echocardiographic signs of pulmonary hypertension were present in one case. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Efficacy was persistent in one patient and only transitory in the other two patients. Clinical control of skin complications was obtained, and one patient discontinued steroid treatment. One patient, who presented with kidney involvement, showed resolution of hematuria. One patient experienced increased recurrence of severe viral respiratory infections. Monitoring of peripheral blood type I interferon signature during ruxolitinib treatment did not show a stable decrease. Conclusions We conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment.

Juvenile-Onset Immunodeficiency Secondary to Anti-Interferon-Gamma Autoantibodies Abstract Immunodeficiency secondary to anti-interferon-gamma (anti-IFN-γ) autoantibodies was first described in 2004 as an acquired defect in the IFN-γ pathway leading to susceptibility to multiple opportunistic infections, including dimorphic fungi, parasites, and bacteria, especially tuberculosis and non-tuberculous mycobacterium (NTM) species. It has so far only been described in adult patients. We present 2 cases of disseminated NTM infections in otherwise immunocompetent children. A 16-year-old girl with Sweet's syndrome–like neutrophilic dermatosis developed recurrent fever and cervical lymphadenitis secondary to Mycobacterium abscessus. A 10-year-old boy with a history of prolonged fever, aseptic meningitis, aortitis, and arteritis in multiple blood vessels developed thoracic vertebral osteomyelitis secondary to Mycobacterium avium complex. Both patients were found to have positive serum neutralizing anti-IFNγ autoantibodies. Testing for anti-IFNγ autoantibodies should be considered in otherwise healthy immunocompetent hosts with recurrent or disseminated NTM infection. This represents a phenocopy of primary immunodeficiency which has been recently described only in adults. We report the first two cases of this phenomenon to affect children.

Use of TCR α + β + /CD19 + –Depleted Haploidentical Hematopoietic Stem Cell Transplant Is a Viable Option in Patients With Primary Immune Deficiency Without Matched Sibling Donor Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many patients with primary immune deficiency (PID). Haploidentical donors have historically been associated with higher rates of graft-versus-host disease (GvHD) and graft failure. Use of T cell receptor (TCR) α+β+/CD19+–depleted grafts has resulted in improved haploidentical HSCT outcomes. We sought to evaluate outcomes of TCR α+β+/CD19+–depleted haploidentical HSCT in pediatric patients with PID at a single center in Australia. Specifically, we evaluated immune reconstitution, looking at time to T cell and B cell reconstitution, and B cell function post-HSCT. Eleven patients with a mean age of 7.92 years (range 0.33–17.17 years) were included. The median time to B cell recovery was 93 days (range 41–205 days), and the median time to cessation of immunoglobulin replacement was 281.5 days (range 41–205 days). All patients who had ceased immunoglobulin replacement had an adequate response to pneumococcal conjugate (Prevenar 13) vaccine. The median time to CD4+ recovery was 132 days (range 30–296 days), and naive T cells were present in all surviving patients by 4 months post-HSCT. Eight of 11 patients are surviving, with six patients having whole blood chimerism greater than 95%, one patient with whole blood chimerism of 82.8%, and another with 76.0%. All of these patients clinically had no evidence of underlying immunodeficiency. Likelihood of overall survival at 2 years post-HSCT was 81.8%. Cumulative incidence of acute GvHD was 27.3%. Cumulative incidence of CMV viremia was 63.6%. All patients previously exposed to CMV had reactivation post-HSCT, but were controlled with pre-emptive CMV treatment. Assuming most children with PID have a haploidentical donor available, use of this technique is likely to result in good outcomes for patients who do not have a suitable matched sibling or matched unrelated donor.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Annals of Surgical Oncology

Totally Laparoscopic Transluminal Resection Versus Combined Laparo-Endoscopic Technique for Removal of Iuxta-Cardial Gastric Stromal Tumors

ASO Author Reflections: Understanding Recurrence Patterns and Time Courses of Intrahepatic Cholangiocarcinoma After Surgery Helps in Postoperative Surveillance and Treatment

How Old is Too Old to Operate for Mesothelioma?

Sentinel Node Biopsy After Neoadjuvant Systemic Therapy for Breast Cancer: The Method Matters

ASO Author Reflections: Managing Symptoms at the End-of-Life—Some Progress, Many Unanswered Questions

Laparoscopic Complete Mesocolic Excision for Double Flexural Colon Cancers Abstract Background Laparoscopic complete mesocolic excision (CME) for hepatic or splenic flexural colon cancer is considered technically demanding. The double (hepatic and splenic) flexural colon cancers are rare, and the laparoscopic CME procedure for such disease is not standardized. Methods This video presents laparoscopic CME for double (hepatic and splenic) flexural colon cancers using a medial and cranial approach. Results The patient was a 60-year-old woman with the diagnosis of splenic flexure cancer (cT4N1M0) and hepatic flexure cancer (cT3N0M0). Laparoscopic subtotal colectomy was performed. First, the left colic artery was divided at its origin, and the inferior mesenteric vein also was divided at the same level. The descending mesocolon was widely separated from the retroperitoneal tissues using a medial approach. Then, lymph node dissection along the surgical trunk was performed using a cranial approach. Finally, the transverse mesocolon was divided at the inferior border of the pancreas, and CME was achieved. The specimen was extracted through a small incision at the umbilicus, and side-to-side ileo-sigmoid anastomosis was performed extracorporeally. Conclusions The approach presented in the video might be useful for standardization of laparoscopic CME for double flexural colon cancers.

Does a Lymph Node-Based Model Predict Clinical Value for Adjuvant Therapy in Squamous Cell Carcinoma of the Esophagus Treated With Upfront Surgery?

The Pelvis-First Approach for Robotic Proctectomy in Patients with Redundant Abdominal Colon Abstract Background Robotic surgery is increasingly performed for low rectal cancer.1 A redundant sigmoid colon makes retraction and pelvic dissection challenging. We present a 'pelvis-first' approach to robotic proctectomy where pelvic dissection occurs prior to colonic mobilization. Methods A 26-year-old woman was diagnosed with a clinical T3N1 rectal adenocarcinoma at 3 cm from the anal verge. The patient had Lynch syndrome, with a germline mutation in the PMS2 gene. A near-complete clinical response was observed after neoadjuvant chemoradiation (NCRT), and the patient wished to delay surgery and permanent colostomy. Additional FOLFOX was administered and led to a complete clinical response. After 2.5 months of watchful delay of surgery, the tumor regrew, and the patient then underwent robotic abdominoperineal resection (APR). Results Initial exploration revealed a highly redundant sigmoid colon. A pelvis-first approach was undertaken. The colon was left tethered and outside of the pelvis during the pelvic dissection. The levator ani was divided transabdominally. Vascular dissection and left colon mobilization were completed after pelvic dissection.2 The specimen was removed transanally, obviating the need for abdominal incision. An end colostomy was created laparoscopically, and the perineum was closed primarily after omental flap. The patient recovered without complications. Conclusions The 'pelvis-first' approach to proctectomy is advantageous for patients with a highly redundant sigmoid colon. Transabdominal division of the levator ani during APR ensures excellent circumferential margin. Although Lynch syndrome-associated rectal cancer can show excellent response to NCRT,3 patients undergoing watchful delay of surgery require close monitoring and prompt triggering of salvage proctectomy when tumor regrowth is observed.4,5

ASO Author Reflections: International Experience of Isolated Limb Infusion for Melanoma Shows Durable Response

ASO Author Reflections: Tending Towards a Personalized Medicine for Colorectal Carcinomatosis by Adding the RAS Mutation Status in the Workup for CRS and HIPEC

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Irish Journal of Medical Science

Supervised exercise for cardiovascular rehabilitation—the Limerick programme

Interns as medical educators: student and intern experiences from the intern-delivered teaching program at University Hospital Limerick Abstract Background The acquisition and assimilation of knowledge through history-taking and clinical skills practice are core aspects of training for medical students. Interns, who have recently graduated and have entered into clinical practice, are uniquely positioned to assume a pivotal role in student education. Aims The goal of this study was to evaluate feedback from both students as well as intern tutors on the intern-delivered teaching program at University Hospital Limerick (UHL) from 2015 to 2016. Methods Eighty-five interns participated in the program at UHL in 2015 and 2016, aiming to deliver four 1-h tutorials to 285 Year 3 or Year 4 students from UL Graduate Entry Medical (GEMS) Program. A flexible schedule focused on practical skills and knowledge translation was created with oversight from Lead Interns and Professor of Medicine, with administrative support. Feedback was assessed using anonymous survey questionnaires. Results The survey response rate was 74% in 2015 and 75% in 2016. Student feedback on the performance of intern tutors was positive. More than 50% of students deemed tutorials on history-taking and clinical examination as the most valuable. Over 76% of students indicated a desire to participate as tutors after graduation. Logistical issues in agreeing mutually suitable timeslots were identified as the major barrier for delivery of teaching. From the intern perspective, over 85% reported benefits in areas of professional development and knowledge consolidation. Conclusions Participation in intern-delivered teaching leads to clinical and educational benefits for both students and interns. However, several logistical barriers were identified and require refinement.

A novel approach using 3-D printing in the Irish National Centre for pelvic and acetabular surgery Abstract Background Complex pelvic fractures present the orthopaedic surgeon with many challenges. 3-D printed models may provide assistance in pre-operative planning, may lead to improvements in intra-operative (i) decision making and (ii) efficiencies (time reduction, blood loss reduction, screening reduction) and may result in improvements in post-operative outcomes (fracture reduction & quality of life). The models also provide hands-on opportunities for orthopaedic trainees and patients. This may result in improvements in (i) education/training regarding the management of pelvic and acetabular fractures for orthopaedic trainees and (ii) improvements in patient consenting and overall patient satisfaction. Design Single-centre, two orthopaedic surgeons (pelvic and acetabular fellowship trained), prospective observational study. Twenty patients with acute displaced pelvic/acetabular fracture(s); ten 3-D–printed pelvis and ten non-printed cases for comparison. The comparison cohorts were matched for fracture classification, sex and age. Outcome measures Classification assistance, intra-operative time, estimated blood loss, screening amount, post-operative reduction and infection, EQ-5D-5L, teaching/educational assistance and pre-operative counselling. Results The models provided more information regarding fracture pattern, however, this did not result in change of CT-planned approach/procedure or patient outcomes. The models scored highly on surgeon's questionnaire. The models were found to have a positive impact on trainee education and patient consenting/counselling. With regard to objective comparisons, there was no significant improvements in time-to-surgery, intra-operative time, estimated blood loss, screening amount, fracture reduction or infection rate. There was no significant difference in quality of life questionnaire ~ 12 months post-surgery (statistical tests used; Cohen's effect size and Fisher's exact test). Conclusions Whilst the authors recognize the positive subjective findings with respect to the use of 3-D printing in pelvic and acetabular trauma in our National Centre, objective findings were lacking.

A cross-sectional survey of services for young adults with life-limiting conditions making the transition from children's to adult services in Ireland Abstract Background Increasing numbers of young adults with life-limiting conditions are living into adulthood and consequently making the transition from children's to adult services. A poorly planned transition is associated with adverse outcomes such as non-adherence to treatment and loss to follow-up, together with negative social and emotional outcomes. However, there is little descriptive data on how organisations are currently managing transition. Aim To obtain an overview of organisational approaches to transition on the island of Ireland, and to explore important organisational factors that may influence the effectiveness of the process. Methods A cross-sectional questionnaire survey. One of the four Health Services Executive areas in the Republic of Ireland and the whole of Northern Ireland. Participants were service providers in statutory and non-statutory organisations providing transition services to young adults with life-limiting conditions. Results The survey was distributed to 55 organisations. The overall response rate was 29/55 (53%). The approach to transition most commonly used focused on interagency communication and collaboration. Key factors in an effective transition were reported as: early commencement; effective communication between the young adult, their family, and services; the availability of appropriate adult services; and effective preparation through collaboration with the young adult and their family. However, implementation of these processes was inconsistent. Conclusions The findings demonstrate that caring for young adults with life-limiting conditions presents a considerable challenge to organisations and that transition from children's to adult services is an important part of this challenge.

Correction to: PERioperative Fluid Management in Elective ColecTomy (PERFECT)—a national prospective cohort study The above article originally published with Christina Fleming and Irish Surgical Research Collaborative listed in the authorship line.

Automated quantification of foveal avascular zone and vascular density in Behçet's disease Abstract Purpose To measure the vascular density (VD) and foveal avascular zone (FAZ) area in patients with Behçet's disease (BD) obtained by optical coherence tomography angiography (OCTA). Methods VD and FAZ area in the deep and superficial retinal vascular networks were measured in all eyes. Results Thirty BD and 31 control subjects were included in the study. The mean overall VD measured in the entire scan was lower in BD compared with control group in both the superficial (49.52 ± 6.54 vs 53.57 ± 2.87%, respectively; p = 0.003) and deep (53.44 ± 7.44 vs 58.41 ± 3.01%, respectively; p = 0.002) areas. The FAZ in the BD group was significantly increased at the level of the superficial (0.52 ± 0.67 vs 0.28 ± 0.1 mm2, respectively; p = 0.05) and deep (0.91 ± 1.25 vs 0.39 ± 0.14 mm2, respectively; p = 0.024) areas compared with those of the control group. The deep and the superficial FAZ areas were positively correlated with disease duration and negatively with VA. Conclusion In the patients with BD, OCTA showed decreased VD in both the superficial and deep retinal vascular networks. Besides, the VA was correlated with the VD and FAZ.

Proceedings of the Psychiatry Section of the Royal Academy of Medicine in Ireland (RAMI) and the Faculty of Academic Psychiatry of the College of Psychiatrists of Ireland, BST and HST competition. Venue: Albert Theatre, Royal College of Surgeons, 123, St. Stephen's Green, Dublin 2 on Thursday 30 th May 2019

Awareness of atrial fibrillation—effectiveness of a pilot national awareness campaign Abstract Background Although atrial fibrillation (AF) causes one-third of strokes in Ireland, studies have shown that public awareness and knowledge of AF are poor. The Irish Heart Foundation conducted a national AF awareness campaign in 2013. Aims The aim of this study was to assess the effectiveness of the campaign in promoting awareness of AF in the general Irish population, by analyzing knowledge of AF at a population level pre- and post-campaign. Methods Two thousand people were surveyed before the campaign to establish baseline knowledge, and the survey was then repeated in a sample of 1000 people in 2 months after the end of the campaign. Results Awareness of AF was low, with 28% (560/2000) of those surveyed reporting they had heard of AF prior to the campaign and 30% (297/1002) after (p 0.347). Of those that had heard of the condition, 58% (174/300) in the pre-campaign group correctly identified AF as an irregular heartbeat compared with 35% (105/297) of the post-campaign group (p < 0.01). Conclusions Our study shows that overall public knowledge of AF in Ireland is generally poor. While this pilot national awareness campaign had no positive impact on awareness levels, there are several possible reasons for this including the limited funding allocation to the campaign. A further AF awareness campaign is planned for next year.

Irish Maternal Early Warning Score Abstract Early Warning Systems (EWS) track the physiological parameters of individual patients and trigger a response when the parameter threshold has been reached. The use of early warning scores in adult hospital medicine has been shown to be beneficial in facilitating the early recognition of the deteriorating patient, thereby enabling prompt treatment. In 2012, a standardised National Early Warning Score was introduced in Ireland for all non-pregnant patients. The 2007 Confidential Enquiry into Maternal and Child Health recommended that EWS be introduced into maternity practice. However, the unique physiological changes of pregnancy even in health means that any scoring system must be specially adapted. The Obstetric Early Warning Score (OEWS) aims to promote early recognition of the pregnant patient at risk of deterioration. In 2013, a standardised Irish Maternity Early Warning System (IMEWS) was introduced nationally. However, the scoring system is only part of the package, once triggered it needs to be effectively communicated and acted upon promptly by appropriately trained clinicians. Despite undoubted shortcomings, the international evidence to date is supportive of the beneficial role of the OEWS in preventing maternal morbidity. Further research is needed to improve the sensitivity and specificity of the OEWS and how to better integrate it into every-day clinical practice.

Development of a simulation-based sub-module in undergraduate medical education Abstract Background It is well documented that medical students struggle to bridge the theory-practice gap. Competently integrating classroom-taught skills into the clinical setting is a challenge. Methods A survey of final year medical students identified a lack of confidence in managing common clinical emergencies that are experienced in the Intern role. The researchers devised a new sub-module to include high-fidelity simulation in the undergraduate medical curriculum. This development was underpinned by an educational curriculum model. Students attended small group teaching using high-fidelity simulation training (Sim-Man 3G ™) and practiced managing common emergencies. Training sessions were facilitated by clinical tutors and anaesthetic lecturers. Cases were supplied by clinical staff. An evidence-based format was utilised as an integrative teaching method. Results A simulation-based sub-module based on Finks Taxonomy was planned, introduced and evaluated. Utilisation of a high-fidelity simulation-based approach to teaching had a marked effect on student's confidence in their ability to manage clinical emergencies. Students reported very positive attitudes to this new method of teaching, specifically related to the integration of previously acquired knowledge and skills. A hands-on practical approach in a safe learning environment was valued by students. Conclusions The module descriptor devised can be used as a template for further curricular reform. Simulation-based teaching is feasible in the undergraduate setting and may ease the transition to postgraduate teaching modalities.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

ACG Case Reports Journal, published by the American College of Gastroenterology and edited exclusively by GI fellows, provides an open access peer-reviewed publishing outlet for GI fellows, private practice clinicians, and other healthcare providers to share interesting case reports. ACG Case Reports Journal publishes case reports, images, videos, and letters to the editor in all topics of gastroenterology and hepatology, including: Biliary Colon Endoscopy Esophagus Functional Bowel Disorders Inflammatory Bowel Disease Liver Nutrition and Obesity Pancreas Pathology Pediatric Small Bowel Stomach

Melanoma Metastatic to the Jejunum Diagnosed by Double-Balloon Enteroscopy No abstract available

Diffuse Subcutaneous Air due to Rectal Perforation No abstract available

Detailed Observation of Fish Tapeworm Using Colonoscopy No abstract available

Syphilis, The Great Mimicker, Presents As a Rare Case of Concurrent Hepatitis and Gastroparesis Syphilis has been called "the great mimicker" given its ability to affect a wide variety of organs and subsequently present with a vast array of symptoms. The variability in clinical presentation seen in syphilis can make the diagnosis challenging. We describe a unique presentation of syphilis manifesting as hepatitis and gastroparesis. To our knowledge, this is the first case report with simultaneous hepatic and gastric involvement.

Endoscopic Sinusotomy Using Needle Knife Technique for Treatment of H-Pouch With Leak and Sinus A 62-year-old patient with a history of ulcerative colitis and total colectomy with ileal pouch-anal anastomosis was referred to our pouch center for rectal pain, loose stool, and perianal swelling. He was diagnosed with chronic fistula and anastomotic stricture for which he had excision of J-pouch and creation of H-pouch. Surveillance workup after surgery revealed pouch sinus, which was treated with needle-knife sinusotomy (NKSi). This is the first case in the literature of an H-pouch complicated with anastomotic sinus successfully treated with NKSi. We propose using NKSi as the preferred technique for pouch sinuses.

Acute Dermato-Lymphangio-Adenitis Following Administration of Infliximab for Crohn's Disease Tumor necrosis factor-α inhibitor (TNF-α) is frequently used for Crohn's disease and other autoimmune conditions. Increased risk of infection is an accepted adverse effect of TNF-α, and routine screening for potential infections are carried out before initiation of therapy. We report the case of a patient who developed a localized painful swelling near the injection site, which was diagnosed as acute dermato-lymphangio-adenitis due to filarial infection. This adds to the limited number of case reports on parasitic complications following TNF-α therapy.

Successful Curative Cryoablation of an Esophageal Gastrointestinal Stromal Tumor Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The most common location of GIST is the stomach; however, occurrences of GIST in the esophagus are also possible albeit rare. Although the current standard of care for gastric and intestinal GIST involves surgery and tyrosine kinase inhibitors, this case report focuses on the potential of treating esophageal GIST through a novel means of cryoablation therapy.

Duodenal Erosion and Obstruction Caused by a Mesocaval Prosthesis In the past, vascular prostheses have been developed for mesocaval shunt surgeries in the treatment of portal hypertension. Penetration of prosthesis into the duodenum is a rare complication. We report the case of a 65-year-old man who presented with duodenal erosion and obstruction caused by the prosthesis, 22 years after its insertion. This is the ninth reported case of such events, but it demonstrates the longest interval to date between insertion and complication.

Consideration of Maternal Anti-enterocyte IgA Transfer With Resulting Infantile Alloimmune Enteropathy Autoimmune enteropathy is a rare cause of infantile diarrhea. Cases typically involve infants with a protracted course of diarrhea found to have underlying autoimmune disease or immune dysfunction, leading to chronic intestinal inflammation. We describe a case of immune-mediated enteropathy in an infant with no identifiable autoimmune disease. The patient was exclusively breastfed by his mother who had Crohn's disease, and he was found to have circulating anti-enterocyte immunoglobulin A (IgA) antibody. There was no circulating anti-enterocyte immunoglobulin G or immunoglobulin M. The patient's disease and symptoms resolved with cessation of breastfeeding, and no immunomodulatory medications have been needed in 20 months of follow-up. The case raises suspicion for alloimmune disease, and it is hypothesized that intestinal injury was mediated by maternally transmitted anti-enterocyte IgA antibody.

Successful Treatment of Hereditary Hemorrhagic Telangiectasia With Octreotide Hereditary hemorrhagic telangiectasia (HHT) is a disorder characterized by telangiectasias and arteriovenous malformations. We present a case report of a 74-year-old man diagnosed with HHT having a favorable response to a somatostatin analogue for treatment. This patient had been suffering from chronic anemia from recurrent gastrointestinal bleeding, requiring oral/intravenous iron replacement, frequent endoscopic ablations, and blood transfusions. Due to insufficient treatment, he was started on subcutaneous octreotide, with significant improvement as evidenced by a steady increase in the hemoglobin level, decreased endoscopic interventions, and decreased blood transfusions, making this the first case of HHT successfully treated with octreotide.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Psychiatric Practice

On the Border No abstract available

State of the Art Treatment Options for Actual and Potential Sexual Offenders and New Prevention Strategies Sexual violence is a significant and devastating issue for men and women throughout the world. Its consequences are not only disastrous for victims of sexual violence but are also extremely costly (estimated cost of $41,000 per rape) for society. Successful treatment of sexual offenders is therefore an important goal for society as well as for victims and offenders themselves. Over the years, multiple treatment approaches for sex offenders have been developed. Treatment programs range from the risk-need-responsivity (RNR) model, which focuses on providing tailored treatment for high-risk and low-risk offenders, to psychodynamic models. This article presents an overview for clinicians of state-of-the-art offender treatment, describing the most common treatment approaches, in particular the RNR model, cognitive-behavioral programs (relapse prevention programs, sexual offender treatment programs), psychodynamic approaches (transference-focused psychotherapy, mentalization-based therapy), the Good Lives Model, as well as pharmacological options. In addition, it provides an evaluation of the various treatment programs. However, given the fact that most acts of sexual violence will never be reported to the police, the question arises if treating convicted perpetrators is enough. Do we need rather—in terms of preventive work—a program for potential sexual offenders and men with delinquent sexual fantasies? Given the prevalence of sexual violence and its impact on victims, society, and the medical community, it would be remiss not to try to reach potential/unconvicted perpetrators. This article offers novel ideas and a project the goal of which is to prevent sexual offenses against women by introducing the "I CAN CHANGE" program from Hannover Medical School.

L-Methylfolate Calcium Supplementation in Adolescents and Children: A Retrospective Analysis Previous studies have shown l-methylfolate to be a safe and beneficial therapy for neuropsychiatric conditions, including major depressive disorder and schizophrenia in adults. The purpose of this study was to assess safety and describe patient experience using l-methylfolate calcium in a real-world pediatric and adolescent population. A retrospective chart review of patients (7 to 20 y of age, mean age 16 y) prescribed l-methylfolate calcium at a psychiatry clinic in Amherst, NY, between January 1, 2010 and November 10, 2015 was conducted. Patients to whom l-methylfolate calcium 15 mg/d (n=139) or 7.5 mg/d (n=7) was administered were identified; 44 patients who were prescribed but to whom l-methylfolate calcium was not administered were included as a comparator population. Common neuropsychiatric diagnoses included anxiety disorders (68% in the treatment population vs. 50% in the comparator population) and mood disorders (57% in the treatment population vs. 52% in the comparator population). Antidepressants (69% vs. 55%) and mood stabilizers or antiepileptic drugs (63% vs. 57%) were frequently prescribed in combination with l-methylfolate calcium. Adverse events occurred less frequently in the treated population, possibly due to the addition of l-methylfolate calcium (10% vs. 25%, P=0.02). The most common adverse events in the treated population were impaired sleep (5 patients) and increased anxiety (3 patients). Rates of laboratory abnormalities did not differ significantly between the treated and comparator populations (P=0.13). Positive subjective treatment experiences were reported by 22.5% of treated patients and negative subjective treatment experiences were reported by 5.4% of treated patients. L-methylfolate calcium was well-tolerated in a pediatric/adolescent population and may provide benefits for patients with a range of neuropsychiatric conditions.

Evaluating the Use of a Computerized CBT Program for Outpatients on a Waitlist in a University CBT Unit Objectives and Design: The goal of this pilot randomized controlled trial was to determine whether a computerized cognitive-behavioral therapy (cCBT) program for depression and anxiety could reduce symptoms in outpatients on a waitlist for face-to-face CBT for a variety of mental health complaints. Methods: Sixty-seven outpatients referred for CBT for disparate problems (eg, anxiety, depression, obsessions or compulsions) were randomized to 1 of 2 conditions: (1) the cCBT program "Good Days Ahead," which included weekly guidance and support, or (2) a control condition where patients were referred to a freely available online CBT workbook. Measures of psychological distress were administered at the start of study and at the end of the waiting period, when participants were formally diagnosed and assessed for face-to-face therapy. Results: For the most part, mixed-design analyses of variances revealed no statistically significant changes in symptom measures over time. Nonsignificant interactions and modest effect sizes between groups across time suggest that the cCBT group did not do better than the control group. The majority of cCBT participants reported that the program was "very" or "extremely useful," while only a portion of the control group felt the same about the workbook. There were notable differences in the completion rates of the 2 groups in favor of the cCBT program. Conclusions: Offering a general cCBT program to waiting list patients may not confer an advantage over referring them to an online workbook, at least in terms of symptom reduction. Results could be partly explained by difficulties translating knowledge into practice, especially if participants' main problem was not directly addressed by the intervention.

Borderline Personality Features in Inpatients with Bipolar Disorder: Impact on Course and Machine Learning Model Use to Predict Rapid Readmission Background: Earlier research indicated that nearly 20% of patients diagnosed with either bipolar disorder (BD) or borderline personality disorder (BPD) also met criteria for the other diagnosis. Yet limited data are available concerning the potential impact of co-occurring BPD and/or BPD features on the course or outcome in patients with BD. Therefore, this study examined this comorbidity utilizing the standardized Borderline Personality Questionnaire (BPQ). Methods: This study involved 714 adult patients with a primary diagnosis of BD per DSM-IV criteria who were admitted to the psychiatric unit at an academic hospital in Houston, TX between July 2013 and July 2018. All patients completed the BPQ within 72 hours of admission. Statistical analysis was used to detect correlations between severity of BD, length of stay (LOS), and scores on the BPQ. A machine learning model was constructed to predict the parameters affecting patients' readmission rates within 30 days. Results: Analysis revealed that the severity of certain BPD traits at baseline was associated with mood state and outcome measured by LOS. Inpatients with BD who were admitted during acute depressive episodes had significantly higher mean scores on 7 of the 9 BPQ subscales (P<0.05) compared with those admitted during acute manic episodes. Inpatients with BD with greater BPQ scores on 4 of the 9 BPQ subscales had significantly shorter LOS than those with lower BPQ scores (P<0.05). The machine learning model identified 6 variables as predictors for likelihood of 30-day readmission with a high sensitivity (83%), specificity (77%), and area under the receiver operating characteristic curve of 86%. Conclusions: Although preliminary, these results suggest that inpatients with BD who have higher levels of BPD features were more likely to have depressive rather than manic symptoms, fewer psychotic symptoms, and a shorter LOS. Moreover, machine learning models may be particularly valuable in identifying patients with BD who are at the highest risk for adverse consequences including rapid readmission.

Drug-Drug Interactions (DDIs) in Psychiatric Practice, Part 6: Pharmacodynamic Considerations This column is the sixth in a series exploring drug-drug interactions (DDIs) with a special emphasis on psychiatric medications. The first 3 columns in this DDI series discussed why patients being treated with psychiatric medications are at increased risk for taking multiple medications and thus experiencing DDIs, how to recognize such DDIs, strategies for avoiding and/or minimizing adverse outcomes from such DDIs, and pharmacokinetic considerations concerning DDIs in psychiatric practice. The fourth and fifth columns in this series presented a pair of parallel tables, one of which outlined the primary, known mechanism(s) of action of all commonly used psychiatric medications and one of which summarized major types of pharmacodynamic DDIs based on mechanism of action. Clinicians can use these 2 tables together to predict pharmacodynamically mediated DDIs. This sixth column in the series discusses some key issues related to pharmacodynamic interactions involving commonly used psychiatric medications. The column first discusses 3 types of pharmacological agents that deserve special mention because of the widespread types of pharmacodynamic DDIs they can have with psychiatric and other medications: ethanol, opioids, and monoamine oxidase inhibitors, with a special focus on hypertensive crises and serotonin syndrome with monoamine oxidase inhibitors. The column also discusses DDIs in terms of effects on the cardiovascular system, including QTc prolongation, blood pressure and heart rate regulation, increased risk of bleeding and abnormal bleeding, and valvular heart disease, and on the central nervous system, including increased sedation, respiratory depression, body temperature regulation, and tardive dyskinesia. The overall goal of this series of columns is to present a simple way of conceptualizing neuropsychiatric medications in terms of their pharmacodynamics and pharmacokinetics to allow prescribers to take these facts into consideration when they need to use more than 1 drug in combination to optimally treat a patient.

One Hundred Years of Austen Riggs This column reviews the history of the Austen Riggs Center on the occasion of its centennial. Riggs has come to stand for high quality, state of the art, biopsychosocial, psychodynamic treatment in contemporary psychiatry and psychoanalysis. This column reviews elements of the positioning of Riggs in the field, and contributions that have emerged from Riggs that continue to have an impact on psychiatry, psychoanalysis, and their intersection—psychodynamic psychiatry.

Psychiatric Advance Directives: Origins, Benefits, Challenges, and Future Directions Psychiatric advance directives (PADs) are legal documents that allow individuals with psychiatric illness to designate decisions, while competent, about their future psychiatric care were they to lose competency due to psychiatric illness in the future. Among other items, these documents often include preferences regarding a surrogate decision-maker, types of medications, doses and routes of medications, seclusion and restraints, electroconvulsive therapy, and instructions for care of their property while incapacitated. While the concept and legal recognition of PADs has existed in the United States for several decades, use of PADs by patients and familiarity with PADs among mental health providers remain limited. This column reviews the origin of PADs, discusses several commonly considered arguments for and against the use of these documents, and concludes with a discussion of how PADs are currently used in the United States and their potential future role in mental health treatment.

A Call for Caution in Prescribing Gabapentin to Individuals With Concurrent Polysubstance Abuse: A Case Report Gabapentin is an anticonvulsant medication with an indication from the US Food and Drug Administration for use in partial onset seizures and postherpetic neuralgia in the United States. Currently, gabapentin is only classified as a controlled substance subject to stricter prescribing and distributing regulations in certain states, as opposed to pregabalin, an anticonvulsant with a similar mechanism of action which is a considered a Schedule V medication under federal law. Gabapentin shares a structural similarity to pregabalin, and several case reports have suggested that gabapentin has a similar propensity for abuse. The mechanisms of the gabapentin reward pathway, addiction, and withdrawal, however, are not well known. This case report describes a patient with long-term polysubstance abuse and new onset gabapentin dependence and demonstrates the need for increased surveillance of gabapentin prescribing.

Commentary on "A Call for Caution in Prescribing Gabapentin to Individuals with Concurrent Polysubstance Abuse: A Case Report" Gabapentin is an anticonvulsant medication with an indication from the US Food and Drug Administration for use in partial onset seizures and postherpetic neuralgia in the United States. Currently, gabapentin is only classified as a controlled substance subject to stricter prescribing and distributing regulations in certain states, as opposed to pregabalin, an anticonvulsant with a similar mechanism of action which is a considered a Schedule V medication under federal law. Gabapentin shares a structural similarity to pregabalin, and several case reports have suggested that gabapentin has a similar propensity for abuse. The mechanisms of the gabapentin reward pathway, addiction, and withdrawal, however, are not well known. This case report describes a patient with long-term polysubstance abuse and new onset gabapentin dependence and demonstrates the need for increased surveillance of gabapentin prescribing.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Sports Medicine

Featuring Lauren M. Simon, MD, MPH, FACSM, FAAP No abstract available

Fatal Exertional Heat Stroke in Football: The Coaches Are the Culprits No abstract available

Web Alert No abstract available

Pelvic Floor Dysfunction in Female Athletes: Is Relative Energy Deficiency in Sport a Risk Factor? Due to the unique demands of sport participation on the body, female athletes are at increased risk for pelvic floor dysfunction (PFD) and relative energy deficiency in sport (RED-S). A high number of female athletes suffer from PFD, especially urinary incontinence. Several biomechanical and physiological risk factors may play a role in the development of PFD in female athletes. RED-S has been shown to be associated with PFD. The goal of this commentary is to discuss RED-S as a risk factor for PFD and propose a mechanism for this relationship.

Strategies to Counter Weight Loss-Induced Reductions in Metabolic Rate A significant percentage of the population is classified as obese, and there is a growing need to develop novel therapy to reduce body weight. It has long been appreciated that caloric restriction and exercise are the cornerstones of any weight loss method. This review outlines the challenges faced when attempting to achieve weight loss and the metabolic adaptations that ensue upon reductions in body weight which make sustaining weight loss extremely difficult. We discuss the need for novel approaches to weight loss that would increase basal metabolic rate and counter the biological adaptations that provide barriers for maintaining weight reduction. We introduce two metabolic processes, hypobaric hypoxia and cold exposure, which, when activated, cause increased metabolic rate even in the presence of reduced caloric intake. While we do not suggest that these are long-term viable options for methods to achieve weight loss, we are introducing these as pathways that may be targeted to eventually develop novel therapies to achieve sustainable weight loss.

Intermittent Fasting and Its Effects on Athletic Performance: A Review Intermittent fasting (IFast) has been around for most of human history, and its proposed health benefits have been mentioned in ancient civilizations. However, recently, there has been a renewed public interest in IFast. Given the importance of nutrition in optimizing athletic performance, there is a concern about the effects of IFast on athletics. Most of the studies looking at performance and fasting are regarding athletes who observe Ramadan. Looking at high-intensity, endurance, and resistance exercises, studies have been varied but are uniform in showing that there is no benefit to athletic performance while fasting. More long-term studies need to be done to evaluate specific fasting protocols during sport.

Nutrition Considerations for Athletes with Physical Disabilities Nutrition, which is an important factor that improves physical performance, has a major place in the lives of both disabled and nondisabled athletes. The main purpose of nutritional assessment of disabled athletes is to assess the individual's consumption to determine the insufficiencies and to suggest the necessary changes to design the most appropriate nutrition plan. Nutrition strategies play a key role in confirming the performance of disabled athletes. Considering the nature of the disability and the specific sports branch, it is important to determine the necessary nutrition solutions to ensure the best protection for the athletes concerned. The literature on the specific nutritional needs for the best sports performance of disabled athletes is insufficient and should be considered in light of current information on specific disability physiology.

Dogs as Support and Motivation for Physical Activity Physical activity behavior change theorists are actively shifting the field to better align with the science of motivation and decision making. With this shift has come increasing interest in the role of affective judgments, habit, and identity in long-term physical activity maintenance, as well as the importance of framing physical activity in ways that protect autonomy and support personal values. This special communication makes the case for dog walking as a physical activity modality that fits well with the field's new focus. The authors provide an overview of dog walking research performed to date and discuss unanswered research questions. Given the large percentage of U.S. households that own a dog and the mainstream animal welfare movement to rehome adoptable shelter pets, there are innumerable opportunities to leverage the human-dog bond to increase physical activity levels. Dog walking interventions may be a highly practical approach to population-level physical activity promotion.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Clinical Gastroenterology

World Gastroenterology Organisation (WGO) News and Events No abstract available

Quantitative Elastography Versus Fine-needle Aspiration by Endoscopic Ultrasound for the Assessment of Pancreatic Solid Masses Background and Aims: Pancreatic solid masses (PSM) are difficult to assess; endoscopic ultrasound with fine-needle aspiration (FNA) enables tissue acquisition, but has high false-negative rates. Quantitative elastography (QE) predicts diagnosis on the basis of the strain ratio (SR). We aimed to compare both methods to evaluate PSM. Materials and Methods: This prospective study, carried out between January and December 2016, included suspected PSM cases; those with advanced disease and cystic components were excluded. Both procedures were performed; histologic information was obtained for the final diagnoses. Diagnostic tests and receiver-operating characteristic curve were calculated. P<0.05 was considered statistically significant. Results: We included 134 patients (53% women; mean, 53±16.2 y). The median tumor size was 30 (10 to 78) mm, with 69.4% and 30.6% malignant and benign tumors (median SR: 19.5 vs. 7.5; P=0.000), respectively, and 87% were pancreatic adenocarcinoma. QE with SR cutoff ≥10 showed similar parameters to FNA in both PSM types: sensitivity, 94% in both; specificity, 85% versus 87%; positive predictive value, 93% versus 94%; negative predictive value, 87% in both; and accuracy, 92% for malignant and sensitivity, 85% versus 87%; specificity, 94% in both; positive predictive value, 87% in both; negative predictive value, 93% versus 94%; and accuracy, 92% for benign. The area under the curve was 0.96 (P<0.000; 95% confidence interval, 0.940-0.995). New classifications on the basis of positive likelihood ratio were grouped as follows: A ≤8.7 (benign tumor); B >8.7 to <15.5 (indeterminate); and C ≥15.5 (malignant). Conclusions: QE has similar capacity to FNA in PSM evaluation. However, the former can be used potentially as a substitute of the latter in certain cases on the basis of these new SR cutoff-based classifications.

Oral and Otorhinolaryngological Findings in Adults Who Were Diagnosed With Pediatric Onset Crohn's Disease: A Controlled Study Background: Up to 50% of pediatric patients with Crohn's disease (CD) report oral manifestations, but less is known about their oral health when they become adults. Goals: Our aim was to provide detailed descriptions of the presence of oral and otorhinolaryngological manifestations in patients with pediatric onset CD once they reached adulthood, to look for predisposing factors and to compare the findings to matched controls. Study: Adult patients diagnosed with CD in childhood at the Children's Hospital, University of Helsinki, Finland, after 2000 were invited for a follow-up appointment in 2016 and 24 were examined by a dentist and otorhinolaryngologist. They were compared with 22 matched controls from the Population Register Centre. The participants completed questionnaires about their general health, any special diets, and their health-related quality of life. Their nutrition was evaluated from food records. Results: Patients with CD had minor oral manifestations at a median of 9 years after their childhood diagnosis and the most common was angular cheilitis, which affected 6 patients and 1 control, but was not statistically significant (P=0.0984). CD with perianal abscessing disease correlated to orofacial findings (P=0.0312). Most of the patients had normal otorhinolaryngological findings. Subjects with oral lesions had lower mean health-related quality of life scores than subjects without oral findings and the differences were clinically but not statistically significant. Oral manifestations were not associated with differences in energy intake. Conclusions: Oral manifestations in adult patients with pediatric onset CD were mild and were not associated with otorhinolaryngological pathology.

Evaluation of the Severity of Hyperlipidemia Pancreatitis Using CT-measured Visceral Adipose Tissue Background: Computed tomography–measured visceral adipose tissue (VAT) and the distribution of VAT are highly correlated with the severity and prognosis of acute pancreatitis (AP). To date, all available data are from the overall AP patient population; no subgroup analysis has been conducted to evaluate patients with moderately severe AP or patients with hyperlipidemia acute pancreatitis (HLAP) as independent populations. Currently, studies on the relationship between VAT and HLAP are lacking. Materials and Methods: A total of 235 patients with moderately severe AP or severe acute pancreatitis were divided into 2 groups according to whether hyperlipidemia was present: the HLAP group and the non-HLAP group. The general inpatient information was collected, and computed tomography was used to measure VAT, subcutaneous adipose tissue (SAT), total adipose tissue, and VAT/SAT (V/S). The data were subjected to t test, χ2 test, matrix scatter plot, logistic regression, and receiver operating characteristic analyses to evaluate the relationship between VAT and HLAP severity. Results: Significant differences were observed in VAT, SAT, total adipose tissue, and triglycerides (TGs) between the HLAP group and the non-HLAP group (P<0.001). Significant correlations were observed between VAT and body mass index (r=0.425, P=0.017) and between VAT and TG (r=0.367, P=0.042). In the HLAP group, VAT, V/S, TG, and local complications may have significant effects on disease severity. The receiver operating characteristic curves showed that VAT and V/S were more reliable than TGs in evaluating disease severity [area under the curve (AUC) of VAT: 0.819, P<0.001; AUC of V/S: 0.855, P<0.001; AUC of TG: 0.671, P=0.04]. Disease severity was reliably evaluated at 139 cm2, the cut-off value of VAT. The cut-off value of V/S was 1.145; high V/S was associated with extended intensive care unit stay. VAT and its distribution had no significant effects on mortality. Conclusions: For patients with moderately severe to severe HLAP, VAT was correlated with body mass index and TG. VAT and V/S were valuable factors for evaluating disease severity and prognosis. However, VAT had no effect on mortality, and VAT could not be used to evaluate patients with moderately severe to severe non-HLAP.

Abdominal Obesity is More Predictive of Advanced Colorectal Neoplasia Risk Than Overall Obesity in Men: A Cross-sectional Study Goals: We aimed to ascertain whether waist circumference (WC) is associated with risk of colorectal neoplasia (CRN), independent of body mass index (BMI). Background: Although several studies have reported the association between abdominal obesity, measured by WC, and CRN, it remains unclear whether their association is biased by BMI. Study: A cross-sectional study was performed on 154,552 asymptomatic examinees who underwent colonoscopy for a health check-up. Results: The mean age was 42.6 years, and the proportion of males was 65.2%. The prevalence rate of CRN in subjects in WC quartiles 1, 2, 3, and 4 was 15.6%, 18.1%, 20.4%, and 22.0% among men and 7.8%, 9.4%, 12.2%, and 15.8% among women, respectively. WC and BMI were independent risk factors for overall CRN and nonadvanced CRN in both men and women. In men, the association of BMI with advanced CRN was attenuated to null after adjusting for WC [Q2, Q3, and Q4 vs. Q1; odds ratios (95% confidence intervals), 0.93 (0.79-1.10), 0.85 (0.71-1.03), and 0.99 (0.80-1.22), respectively; Ptrend=0.822], whereas the association of WC with advanced CRN significantly persisted even after adjusting for BMI [Q2, Q3, and Q4 vs. Q1; 1.20 (1.02-1.42), 1.45 (1.20-1.75), and 1.64 (1.32-2.04), respectively; Ptrend<0.001]. In women, neither WC nor BMI was associated with the risk of advanced CRN. Conclusions: Abdominal obesity is associated with an increased risk of advanced CRN, independent of overall obesity (BMI) in men. Our findings suggest that abdominal obesity is more strongly predictive of advanced CRN than overall obesity in men.

Acute Biliary Pancreatitis is Associated With Adverse Outcomes in the Elderly: A Propensity Score–Matched Analysis Goals and Background: In the elderly (age, 65 y or older), acute pancreatitis is most frequently because of gallstones; however, there is a paucity of national estimates evaluating outcomes of acute biliary pancreatitis (ABP). Hence, we utilized a representative population database to evaluate the outcomes of ABP among the elderly. Study: The National Readmission Database provides longitudinal follow-up of inpatients for 1 calendar-year. All adult inpatients (18 y or older) with an index primary admission for ABP between 2011 and 2014 were evaluated for clinical outcomes of mortality, severe acute pancreatitis (SAP), and 30-day readmission. Outcomes between age groups (≥65 vs. <65 y) were compared using multivariate and one-to-one propensity score–matched analyses. Results: Among 184,763 ABP admissions, 41% were elderly. Index mortality and SAP rates in the elderly were 1.96% and 21.5%, respectively. Elderly patients underwent more ERCPs (27.5% vs. 23.6%; P<0.001) and less frequent cholecystectomies (44.4% vs. 58.7%; P<0.001). Elderly patients had increased odds of mortality and SAP along with an age-dependent increase in the odds of adverse outcomes; patients aged 85 years or older demonstrated the highest odds of SAP [odds ratio (OR), 1.3; 95% confidence interval (CI): 1.2, 1.4] and mortality (OR, 2.2; 95% CI: 1.7, 2.9) within in the elderly cohort. Propensity score–matched analysis substantiated that mortality (OR, 2.8; 95% CI: 2.2, 3.5) and SAP (OR, 1.2; 95% CI: 1.1, 1.3) were increased in the elderly. Conclusions: Current national survey reveals adverse clinical outcomes among elderly patients hospitalized with ABP. Consequently, there is a need for effective management strategies for this demographic as the aging population is increasing nationally.

Intestinal Hyperpermeability in Gulf War Veterans With Chronic Gastrointestinal Symptoms Background: Well over 700,000 United States military personnel participated in the Persian Gulf War in which they developed chronic health disorders of undetermined etiology. Up to 25% of Veterans had persistent and chronic gastrointestinal (GI) symptoms, which they suspected were related to their military service in the Gulf. Aim: The overall aim of the current study was to evaluate intestinal permeability in previously deployed Gulf War Veterans who developed chronic GI symptoms during their tour in the Persian Gulf. Methods: To accomplish this, we evaluated intestinal permeability (IP) using the urinary lactulose/mannitol test. Measurements of intestinal permeability were then correlated with mean ratings of daily abdominal pain, frequency of bowel movements, and consistency of bowel movements on the Bristol Stool Scale in all Veterans. Results: A total of 73 veterans had documented chronic GI symptoms (diarrhea, abdominal pain) and were included in the study. A total of 29/73 (39%) of veterans has increased IP and had a higher average daily stool frequency (P<0.05); increased liquid stools as indicated by a higher Bristol Stool Scale (P<0.01); and a higher mean M-VAS abdominal pain rating (P<0.01). Pearson correlation coefficients revealed that there was a positive correlation between increased IP and stool frequency, Bristol Stool Scale, and M-VAS abdominal pain rating. Conclusions: Our study demonstrates that deployed Gulf War Veterans with persistent GI symptoms commonly have increased intestinal permeability that potentiates the severity of abdominal pain, diarrhea, and stool consistency. These new findings in our study are important as they may lead to novel diagnostic biomarkers for returning Gulf War Veterans who suffer from chronic functional gastrointestinal disorders. These advances are also important for an increasing number of veterans who are now serving in the Persian Gulf and are at a high risk of developing these chronic pain disorders.

Clinical Predictors for Poor Quality of Life in Patients With Covert Hepatic Encephalopathy Background: Current EASL/AASLD guidelines recommend treatment of covert hepatic encephalopathy (HE) only in symptomatic patients, for example, in those with impaired quality of life or with affected driving abilities. Goals: Because testing for impaired quality of life is time consuming, the aim of the present study was to identify simple clinical predictors for poor quality of life in patients with covert HE (CHE). Study: In total, 139 cirrhotic in- and outpatients without a history of overt hepatic encephalopathy were enrolled. Diagnosis of HE grade 1 (HE1) was diagnosed clinically according to the West-Haven Criteria. Critical flicker frequency and the Psychometric Hepatic Encephalopathy Score were used to detect minimal HE (MHE). Chronic Liver Disease Questionnaire was used to assess health-related quality of life (HrQoL). Results: CHE was detected in 51 (36.7%) patients. Multivariate analysis identified a history of falls in the previous year (P=0.003) and female gender (P=0.030) as independent predictors of reduced HRQoL in patients with CHE. Comparison of patients with and without a history of falls revealed relevant differences in the subdomains—abdominal symptoms, fatigue, systemic symptoms, emotional functions and worries. Conclusions: A history of falls and female gender are associated with impaired HRQoL in patients with CHE. These data indicate that a history of falls should be considered as a treatment indication in patients with CHE to improve HRQoL and ultimately prognosis.

Recent Advances in Cognitive Behavioral Therapy For Digestive Disorders and the Role of Applied Positive Psychology Across the Spectrum of GI Care Background: Although cognitive behavior therapies (CBTs) have shown great promise in the reduction of symptom burden from as well as anxiety around various gastrointestinal (GI) disorders, there are substantial issues involving the scalable delivery of such interventions within the clinical setting of a gastroenterology practice, leaving most patients without access to psychological care. Goals: This paper discusses the application of positive psychology principles and techniques for adoption by various GI providers to initiate early, effective psychological care for patients with GI disorders, saving CBTs for more complex cases. Study/Results: Authors provide a comprehensive framework of patient well-being known as REVAMP, which is consistent with CBT principles, and elaborate on research and interventions that can be adopted within the gastroenterology practice setting. Building positive resources can bolster patients with GI disorders against comorbid psychological and psychiatric distress. Conclusions: Positive psychology interventions can be implemented within gastroenterology practice. Research is necessary to evaluate the efficacy and acceptability of positive psychology interventions among patients with different digestive disorders and baseline psychological characteristics, as well as the feasibility of administration by different clinicians in the gastroenterology practice setting.

Supplementary Sorafenib Therapies for Hepatocellular Carcinoma—A Systematic Review and Meta-Analysis: Supplementary Sorafenib for Liver Cancer Background: Hepatocellular carcinoma (HCC) is the third deadliest cancer worldwide. Sorafenib is considered a supplementary treatment to surgical or locoregional therapies for improving outcomes. We evaluated the efficacy of sorafenib as a supplementary therapy for HCC. Methods: We conducted a meta-analysis including 11 randomized controlled trials. Patients with HCC and studies in which sorafenib was administered alone and compared with placebo or those in which sorafenib was administered in combination with another treatment and compared with that treatment alone were included. The overall effects (OEs) on overall survival and time to progression were pooled as hazard ratios. Results: The OEs of sorafenib as a first-line therapy versus placebo for unresectable HCC were 0.62 [95% confidence interval (CI): 0.50-0.77] and 0.58 (95% CI: 0.47-0.70), respectively. The OEs of sorafenib as a second-line therapy versus placebo for progressive HCC were 0.73 (95% CI: 0.47-1.13) and 0.54 (95% CI: 0.30-0.97), respectively. The OEs of sorafenib as an adjuvant therapy versus placebo for early HCC were 1.00 (95% CI: 0.76-1.30) and 0.89 (95% CI: 0.74-1.08), respectively. The OEs of sorafenib combined with transarterial chemoemboliztion (TACE) versus placebo combined with TACE were 0.80 (95% CI: 0.54-1.21) and 0.85 (95% CI: 0.70-1.04), respectively. The OEs of sorafenib as an adjuvant to TACE versus placebo as an adjuvant to TACE for intermediate HCC were 1.06 (95% CI: 0.69-1.64) and 0.65 (95% CI: 0.31-1.36), respectively. Conclusions: Sorafenib was effective as a first-line therapy for unresectable HCC, but it was ineffective as a second-line or adjuvant therapy. Sorafenib did not increase the efficacy of TACE.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com