Establishing Reference Values for a New Computerized Cognitive Function Test Program for Children.

OBJECTIVE: To establish reference values for the computerized cognitive test and evaluate cognitive function improvements across different age groups, we introduce the computerized Cognitive Function Test program (eCFT), specifically designed for children. We aimed to establish eCFT reference values and assess cognitive function improvements across different age groups. METHODS: We included children aged 3-6 years with confirmed normal cognition based on the Korean Developmental Screening Test for Infants and Children and Kaufman Assessment Battery for Children-II. The eCFT consists of 8 subtests for visual perception, attention, memory, and executive function. RESULTS: A total of 66 participants (36 males and 30 females) with an average age of 4.4 years participated. The age 6 group consistently outperformed both age group 3 and 4 in terms of correct responses. With regard to the completed stage, the "selective auditory stimulus" test findings were 2.0 and 3.9 for the age 3 and age 6 groups, respectively (p<0.05). The "trail-making" test findings were 1.7, 2.1, 2.6, and 2.8, respectively (between ages 3 and 6, p<0.01; between ages 4 and 6, p<0.05); moreover, the age 5 group surpassed the age 3 group (2.6 and 1.7, respectively, p<0.05). CONCLUSION: The eCFT is an easily accessible tool to evaluate cognitive function in young children. We introduce reference values with a cutoff range for preschool-aged children, enabling early intervention for those with cognitive impairment. Given its accessibility and relatively short evaluation time, the eCFT has potential for clinical use.

Clinical Significance and Prognostic Implications of Discontinuous Growth Pattern in Esophageal Adenocarcinoma: A Multi-Institutional Study.

The significance of discontinuous growth (DG) of the tumor to include tumor deposits and intramural metastasis in esophageal adenocarcinoma (EAC) is unclear. Esophagectomy specimens from 151 treatment-naïve and 121 treated patients with EAC were reviewed. DG was defined as discrete (≥2 mm away) tumor foci identified at the periphery of the main tumor in the submucosa, muscularis propria, and/or periadventitial tissue. Patients' demographics, clinicopathologic parameters, and oncologic outcomes were compared between tumors with DG versus without DG. DGs were identified in 16% of treatment-naïve and 29% of treated cases ( P =0.01). Age, gender, and tumor location were comparable in DG+ and DG- groups. For the treatment-naïve group, DG+ tumors were larger with higher tumor grade and stage and more frequent extranodal extension, lymphovascular/perineural invasion, and positive margin. Patients with treated tumors presented at higher disease stages with higher rates of recurrence and metastasis compared with treatment-naïve patients. In this group, DG was also associated with TNM stage and more frequent lymphovascular/perineural spread and positive margin, but not with tumor size, grade, or extranodal extension. In multivariate analysis, in all patients adjusted for tumor size, lymphovascular involvement, margin, T and N stage, metastasis, neoadjuvant therapy status, treatment year, and DG, DG was found to be an independent adverse predictor of survival outcomes in EAC. DG in EAC is associated with adverse clinicopathologic features and worse patient outcomes. DG should be considered throughout the entire clinicopathologic evaluation of treatment-naïve and treated tumors as well as in future staging systems.

CALFAN (Low γ-Glutamyl Transpeptidase (GGT) Cholestasis, Acute Liver Failure, and Neurodegeneration) Syndrome: A Case Report with 3-Year Follow-Up after Liver Transplantation in Early Adulthood.

CALFAN syndrome is an extremely rare disease consisting of recurrent pediatric acute liver failure (PALF), neurodegenerative diseases, and skeletal abnormalities associated with SCYL1 gene mutation. To date, three of 18 patients reported underwent liver transplantation in infancy and early childhood (7-23 months). Here, we report a case of CALFAN syndrome with infantile onset, recurrent jaundice/PALF requiring liver transplantation in early adulthood. At the most recent follow-up, 3 years after transplantation, the patient is doing well.

Trends in the Incidence and Etiology of Non-Traumatic Spinal Cord Injury in Korea: A Nationwide Population-Based Study From 2007 to 2020.

BACKGROUND: Although patients with non-traumatic spinal cord injury (NTSCI) have distinct epidemiological characteristics compared to those with traumatic spinal cord injury, no previous study has reported the incidence of NTSCI on a national scale in Korea. In this study, we examined the trend in incidence of NTSCI in Korea and described the epidemiological characteristics of patients with NTSCI using nationwide insurance data. METHODS: National Health Insurance Service data were reviewed for the period from 2007 to 2020. The International Classification of Diseases, 10th revision, was used to identify patients with NTSCI. Inpatients with newly diagnosed NTSCI on their first admission during the study period were included. Crude incidence was calculated using the annual number of NTSCI cases divided by the mid-year population estimates. Age-specific incidence was calculated by dividing the number of cases in 10-year age groups by the total number of individuals in that age group. Age-adjusted incidence was calculated using direct standardization. Annual percentage changes were calculated using Joinpoint regression analysis. The Cochrane-Armitage trend test was conducted to examine the trends of NTSCI incidence according to the types or etiologies of NTSCI. RESULTS: The age-adjusted incidence of NTSCI increased continuously from 24.11 per million in 2007 to 39.83 per million in 2020, with a significant annual percentage change (4.93%, P < 0.05). The age-specific incidence for those in their 70s and 80s or older was the highest and rapidly increased from 2007 to 2020. According to the types of paralysis in NTSCI, the proportion of tetraplegia decreased, whereas those of paraplegia and cauda equina increased significantly from 2007 to 2020. The proportion of degenerative diseases was the largest among all etiologies and increased significantly during the study period. CONCLUSION: The annual incidence of NTSCI in Korea is increasing significantly, particularly among older adults. As Korea is one of the countries with most rapidly aging population in the world, these results have significant implications, indicating that preventive strategies and sufficient rehabilitation medical services are warranted for the population of older adults.

Immunophenotypic profiles and prognosis for colorectal mucinous adenocarcinomas are dependent on anatomic location.

BACKGROUND: The prognostic value of mucinous adenocarcinomas (MCAs, exhibiting >50% extracellular mucin) of the colorectum, in relation to their anatomic location is not well studied. MATERIALS AND METHODS: We compared MCAs (n = 175) with non-MCAs (NMCAs, n = 1015) and the cancer-specific survival rates were evaluated, based on their anatomic site, by univariate Kaplan-Meier and multivariate Cox methods. Subsets of these tumors were immunostained for MUC1, MUC2, Bcl-2, and p53. RESULTS: MCAs were more commonly found in the right colon, were of high-grade, and were more prevalent in younger patients (<40 years). They exhibited strong expression of MUC2 and Bcl-2 and showed less p53 nuclear staining. In contrast, most NMCAs were low-grade with high expression of MUC1. MCAs of the rectum were associated with poorer outcomes relative to NMCAs (HR 1.85, CI 95% 1.15-2.97), even though the distributions of advanced-stage tumors were similar. CONCLUSION: Late-stage disease and age were poor independent prognostic indicators of cancer-specific deaths across all tumor locations. In summary, rectal MCAs have a poor prognosis.

Levetiracetam Liver Injury: A Benign Antiepileptic Agent?

Levetiracetam is a commonly prescribed antiepileptic agent and has rarely been linked to hepatotoxicity. This case describes a patient with drug-induced autoimmune hepatitis secondary to levetiracetam.

Molecular characterization of visible low-grade dysplastic lesions in patients with inflammatory bowel disease.

We studied pathogenic gene mutations and tumor mutation burden (TMB) in visible low-grade dysplastic lesions in patients with inflammatory bowel disease (IBD). The dysplastic lesions with histologically normal mucosa in the background (group 1) were compared with dysplastic lesions occurring either in a background of chronic active colitis (group 2) or associated with synchronous carcinomas regardless of the status of the background mucosa (group 3). The TMB in group 3 was consistently higher in comparison to the group 1 and group 2 lesions, although the difference was not statistically significant. There also seem to be different mutation profiles between the groups, indicating different pathways of tumor pathogenesis. More frequent APC mutations were seen in group 1 as compared to other groups and TP53 mutations were seen in groups 2 and 3, but none in group 1. Molecular characterization could potentially be used as an ancillary prognostic marker in challenging cases to guide the further management of IBD patients with visible dysplastic lesions.

Early Life Stress in Mice Leads to Impaired Colonic Corticosterone Production and Prolonged Inflammation Following Induction of Colitis.

BACKGROUND: Early life stress (ELS) is an environmental trigger believed to promote increased risk of IBD. Our goal was to identify mechanisms whereby ELS in mice affects susceptibility to and/or severity of gut inflammation. METHODS: We utilized 2 published animal models of ELS. In the first model, newborn mice were separated from the dam daily for 4 to 8 hours starting on postnatal day 2 and then weaned early on postnatal day 17. Control mice were left undisturbed with the dams until weaning on postnatal day 21. In the second model, dams were fed dexamethasone or vehicle ad libitum in drinking water on postpartum days 1 to 14. Plasma and colonic corticosterone were measured in juvenile and adult mice. Colitis was induced in 4-week-old mice via intraperitoneal injection of interleukin (IL)-10 receptor blocking antibody every 5 days for 15 days. Five or 15 days later, colitis scores and transcripts for Tnf, glucocorticoid receptors, and steroidogenic enzymes were measured. RESULTS: Mice exposed to ELS displayed reduced plasma and colonic corticosterone. Control animals showed improvements in indices of inflammation following cessation of interleukin-10 receptor blockade, whereas ELS-exposed animals maintained high levels of Tnf and histological signs of colitis. In colitic animals, prior exposure to ELS was associated with significantly lower expression of genes associated with corticosterone synthesis and responsiveness. Finally, TNF stimulation of colonic crypt cells from ELS mice led to increased inhibition of corticosterone synthesis. CONCLUSIONS: Our study identifies impaired local glucocorticoid production and responsiveness as a potential mechanism whereby ELS predisposes to chronic colitis in susceptible hosts.

Using 2 distinct animal models, this study shows that in mice, early life stress leads to reduced colonic corticosterone and that induction of colitis after stress removal results in reduced transcription of glucocorticoid synthesis genes, increased Tnf, and enhanced chronicity of intestinal inflammation.

Role of Hepatitis C Infection in Acute Liver Injury/Acute Liver Failure in North America.

BACKGROUND: While hepatitis A and B are well-known causes of acute liver failure (ALF), few well-documented cases of hepatitis C virus (HCV) infection (absent preexisting liver disease or other liver insults) have been described that result in ALF. We reviewed the Acute Liver Failure Study Group registry for evidence of HCV as a primary or contributing cause to ALF. METHODS: From January 1998 to January 2017, 2,332 patients with ALF (INR ≥ 1.5, any degree of hepatic encephalopathy) and 667 with acute liver injury (ALI; INR ≥ 2.0, no hepatic encephalopathy) were enrolled. Anti-HCV testing was done routinely, with confirmatory RT-PCR testing for HCV RNA where necessary. RESULTS: A total of 136 patients were anti-HCV-antibody positive, as follows: 56 HCV RNA negative, 65 HCV RNA positive, and 8 with no result nor sera available for testing. Only three subjects with ALI/ALF were determined to represent acute HCV infection. Case 1: 47-year-old female with morbid obesity (BMI 52.4) developed ALF and recovered, experiencing anti-HCV seroconversion. Case 2: 37-year-old female using cocaine presented with ALI and fully recovered. Case 3: 54-year-old female developed ALF requiring transplantation and was anti-HCV negative but viremic prior to transplant experiencing anti-HCV seroconversion thereafter. Among 1636 APAP overdose patients, the 52 with concomitant chronic HCV had higher 3-week mortality than the 1584 without HCV (31% vs 17%, p = 0.01). CONCLUSIONS: ALI/ALF solely related to acute hepatitis C infection is very rare. Chronic HCV infection, found in at least 65 (2.2%) of ALI/ALF patients studied, contributed to more severe outcomes in APAP ALI/ALF; ClinicalTrials.gov number, NCT000518440. Trial Registration ClinicalTrials.gov number NCT000518440.

MiR-214-3p targets Ras-related protein 14 (RAB14) to inhibit cellular migration and invasion in esophageal Cancer cells.

BACKGROUND: MicroRNA (miR)-214-3p is emerging as an important tumor suppressor in esophageal cancer. In this study, we examined the interaction between miR-214-3p and RAB14, a membrane trafficking protein shown to exert oncogenic functions in other malignancies, in esophageal cancer cells. METHODS: Studies were performed in a human esophageal epithelial cell line and a panel of esophageal cancer cell lines, as well in human specimens. MiR-214-3p expression was measured by digital PCR. Biotinylated RNA pull-down and luciferase reporter assays assessed binding. The xCELLigence RTCA system measured cell migration and invasion in real time. A lentiviral expression vector was used to create an esophageal cancer cell line stably expressing miR-214-3p. RESULTS: MiR-214-3p expression was decreased in esophageal cancer cell lines and human specimens compared to non-malignant controls. RAB14 mRNA stability and protein expression were decreased following miR-214-3p overexpression. Binding between miR-214-3p and RAB14 mRNA was observed. Either forced expression of miR-214-3p or RAB14 silencing led to a marked decrease in cellular migration and invasion. Esophageal cancer cells stably expressing miR-214-3p demonstrated decreased growth in a subcutaneous murine model. CONCLUSIONS: These results further support the tumor-suppressive role of miR-214-3p in esophageal cancer cells by demonstrating its ability to regulate RAB14 expression.

Hedgehog blockade remodels the gut microbiota and the intestinal effector CD8+ T cells in a mouse model of mammary carcinoma.

Given the gut microbiome's rise as a potential frontier in cancer pathogenesis and therapy, leveraging microbial analyses in the study of breast tumor progression and treatment could unveil novel interactions between commensal bacteria and disease outcomes. In breast cancer, the Hedgehog (Hh) signaling pathway is a potential target for treatment due to its aberrant activation leading to poorer prognoses and drug resistance. There are limited studies that have investigated the influences of orally administered cancer therapeutics, such as Vismodegib (a pharmacological, clinically used Hh inhibitor) on the gut microbiota. Using a 4T1 mammary carcinoma mouse model and 16 S rRNA sequencing, we longitudinally mapped alterations in immunomodulating gut microbes during mammary tumor development. Next, we identified changes in the abundance of commensal microbiota in response to Vismodegib treatment of 4T1 mammary tumor-bearing mice. In addition to remodeling gut microbiota, Vismodegib treatment elicited an increase in proliferative CD8+ T cells in the colonic immune network, without any remarkable gastrointestinal-associated side effects. To our knowledge, this is the first study to assess longitudinal changes in the gut microbiome during mammary tumor development and progression. Our study also pioneers an investigation of the dynamic effects of an orally delivered Hh inhibitor on the gut microbiome and the gut-associated immune-regulatory adaptive effector CD8+ T cells. These findings inform future comprehensive studies on the consortium of altered microbes that can impact potential systemic immunomodulatory roles of Vismodegib.

Reference Standards for Nerve Conduction Studies of Individual Nerves of Lower Extremity With Expanded Uncertainty in Healthy Korean Adults.

OBJECTIVE: To develop a set of reference standards for tibial motor, common peroneal motor, sural sensory, and superficial peroneal sensory nerve conduction studies (NCSs) with expanded uncertainty in a healthy Korean population. METHODS: Standardized procedures were conducted for individual lower extremity NCSs of 199 healthy participants in their 20s (n=100) and 50s (n=99). Mean values and expanded uncertainties for parameters were analyzed with thorough consideration of multiple uncertainty factors under the International Guide to the Expression of Uncertainty in Measurement. In addition, side-to-side differences in onset latency, amplitude, and nerve conduction velocity (NCV) were analyzed. RESULTS: Mean (reference range) for distal onset latency, baseline to negative peak amplitude, NCV of tibial motor nerve in males in their 20s were 4.3 ms (3.1-5.4 ms), 7.1 mV (3.4-10.9 mV), and 50.7 m/s (42.2-59.3 m/s), respectively; sural sensory nerve baseline to negative peak amplitude in males in their 20s was 21.7 µV (8.3-35.2 µV). Including the aforementioned data, we present a vast dataset of normative mean values and expanded uncertainties for NCSs of the leg in a healthy Korean population. Furthermore, upper limits for normal side-to-side differences for onset latency, amplitude, and NCV of each nerve are suggested. CONCLUSION: To our knowledge, this is the first study to present the reference standards of leg NCSs with consideration for multifactorial uncertainties in an Asian population. We expect these results to help practitioners make reliable and reproducible clinical decisions.

Gastrointestinal Manifestations of COVID-19 Infection: Clinicopathologic Findings in Intestinal Resections Performed at Single Institution.

It is now known that COVID-19 not only involves the lungs, but other organs as well including the gastrointestinal tract. Although clinic-pathological features are well-described in lungs, the histopathologic features of gastrointestinal involvement in resection specimens are not well characterized. Herein, we describe in detail the clinicopathologic features of intestinal resection specimens in four patients with COVID-19 infection. COVID-19 viral particles by in situ hybridization and immunofluorescence studies are also demonstrated. All four patients were males, aged 28-46 years, with comorbidities. They initially presented with a severe form of pulmonary COVID-19 and showed gastrointestinal symptoms, requiring surgical intervention. Histopathologic examination of resected GI specimens, mostly right colectomies, revealed a spectrum of disease, from superficial mucosal ischemic colitis to frank transmural ischemic colitis and associated changes consistent with pneumatosis cystoides intestinalis. Three patients were African American (75%), and one was Caucasian (25%); three patients died due to complications of their COVID-19 infection (75%), while one ultimately recovered from their GI complications (25%), but experienced prolonged sequela of COVID-19 infection including erectile dysfunction. In conclusion, COVID-19 infection, directly or indirectly, can cause ischemic gastrointestinal complications, with predilection for the right colon.

Vedolizumab Therapy in Refractory Enteropathy Associated With CVID.

Common variable immunodeficiency (CVID) is a disorder of typically adult-onset hypogammaglobulinemia in the absence of other known causes. Noninfectious gastrointestinal tract manifestations are common, and a subset of patients with CVID present with a severe enteropathy manifesting as severe malabsorption, weight loss, and diarrhea. A 63-year-old man presented with CVID and severe enteropathy who failed to improve with cytomegalovirus therapy, multiple empiric therapies, and corticosteroids. Vedolizumab infusions were initiated with a dramatic, rapid, and durable complete clinical response.

Pharmacokinetics and Safety Studies in Rodent Models Support Development of EPICERTIN as a Novel Topical Wound-Healing Biologic for Ulcerative Colitis.

The novel wound-healing biologic EPICERTIN, a recombinant analog of cholera toxin B subunit, is in early development for the management of ulcerative colitis. This study established for the first time the pharmacokinetics (PK), bioavailability (BA), and acute safety of EPICERTIN in healthy and dextran sodium sulfate-induced colitic mice and healthy rats. For PK and BA assessments, single administrations of various concentrations of EPICERTIN were given intravenously or intrarectally to healthy and colitic C57BL/6 mice and to healthy Sprague-Dawley rats. After intravenous administration to healthy animals, the drug's plasma half-life (t 1/2) for males and females was 0.26 and 0.3 hours in mice and 19.4 and 14.5 hours in rats, respectively. After intrarectal administration, drug was detected at very low levels in only four samples of mouse plasma, with no correlation to colon epithelial integrity. No drug was detected in rat plasma. A single intrarectal dose of 0.1 µM (0.6 µg/mouse) EPICERTIN significantly facilitated the healing of damaged colonic epithelium as determined by disease activity index and histopathological scoring, whereas 10-fold higher or lower concentrations showed no effect. For acute toxicity evaluation, healthy rats were given a single intrarectal administration of various doses of EPICERTIN with sacrifice on Day 8, recording body weight, morbidity, mortality, clinical pathology, and gross necropsy observations. There were no drug-related effects of toxicological significance. The no observed adverse effect level (intrarectal) in rats was determined to be 5 µM (307 µg/animal, or 5.2 µg drug/cm2 of colorectal surface area), which is 14 times the anticipated intrarectally delivered clinical dose. SIGNIFICANCE STATEMENT: EPICERTIN is a candidate wound-healing biologic for the management of ulcerative colitis. This study determined for the first time the intravenous and intrarectal pharmacokinetics and bioavailability of the drug in healthy and colitic mice and healthy rats, and its acute safety in a dose-escalation study in rats. An initial therapeutic dose in colitic mice was also established. EPICERTIN delivered intrarectally was minimally absorbed systemically, was well tolerated, and induced epithelial wound healing topically at a low dose.

Under-Representation of Racial Groups in Genomics Studies of Gastroenteropancreatic Neuroendocrine Neoplasms.

Not all populations are poised to benefit from advancing genomics in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), as genomics have focused on White patients. This study aimed to evaluate racial populations represented in genomic studies of GEP-NENs and to provide evidence of differential genomic findings between racial groups in GEP-NENs. Manuscripts analyzing DNA, RNA, or DNA methylation in GEP-NENs were queried using PUBMED and EMBASE. NIH race/ethnicity term frequency was then determined by Natural Language Processing, followed by manual evaluation of tumor types and subjects by racial group. IHC of institutional tissue micro-arrays and analysis of AACR GENIE data analyzed was performed to determine mutational differences between Black and White pancreatic NEN (pNEN) patients. 313 manuscripts conducted the requisite genomic analyses, 16 of which included subject race data. Race data were included in 13/184 DNA, 4/107 RNA, and 1/54 DNA Methylation analyses. These studies included 89% White subjects (n = 2032), 5.8% Asian subjects (n = 132), 4.0% "Other" subjects (n = 93), and 1.2% Black subjects (n = 27). No Native American/Alaska Native, Native Hawaiian/Pacific Islander, or ethnically Hispanic/Latinx subjects were represented. There were significant differences in MEN1 mutations among Black and White patients in immunohistochemical (13:40) and GENIE data (24:268 patients per group, respectively), with 9 additional genes differentially mutated in the GENIE dataset. Genomic sequencing data for GEP-NENs is almost racially homogenous. Differences in pNEN genomics may exist between racial groups, highlighting a need for diversity in future genomic analyses of GEP-NENs to understand the putative influence of interracial genomic variation on GEP-NEN prevention, diagnosis, and therapy. Significance: There is little diversity in genomic studies of GEP-NENs, which may exhibit clinically impactful variation in their tumor biology among racial groups. Improved diversity in such studies is imperative for understanding this variation and its potential impacts on disease prevention, diagnosis, therapeutic targeting, and clinical outcomes.

Security Management Suitable for Lifecycle of Personal Information in Multi-User IoT Environment.

In recent years, as all actions of Internet users become information, the importance of personal information is emphasized, but in reality, the management of personal information is still insufficient. With the advent of the concept of sharing systems such as the sharing economy, the numbers of IoT application services (for example, a healthcare service using sharing IoT devices, or a vehicle sharing system with IoT devices) using users' personal information are increasing, but the risk of using personal information is not managed. To solve this issue, the European GDPR stipulates the content of personal information protection. In this paper, we present a method to securely manage personal information in IoT devices in IoT application environments in accordance with the GDPR. We first describe the lifecycle stages of personal information occurring in IoT application services and propose a method to securely manage personal information at each stage of the lifecycle according to the flow of personal information in IoT devices. We also evaluated the usefulness and applicability of the proposed scheme through two service scenarios. Since the proposed method satisfies the requirements for personal information management in IoT application environments, it is expected to contribute to the development of the IoT business field that handles personal information.

Clinical Practice Guideline for Postoperative Rehabilitation in Older Patients With Hip Fractures.

OBJECTIVE: The incidence of hip fractures is increasing worldwide with the aging population, causing a challenge to healthcare systems due to the associated morbidities and high risk of mortality. After hip fractures in frail geriatric patients, existing comorbidities worsen and new complications are prone to occur. Comprehensive rehabilitation is essential for promoting physical function recovery and minimizing complications, which can be achieved through a multidisciplinary approach. Recommendations are required to assist healthcare providers in making decisions on rehabilitation post-surgery. Clinical practice guidelines regarding rehabilitation (physical and occupational therapies) and management of comorbidities/complications in the postoperative phase of hip fractures have not been developed. This guideline aimed to provide evidence-based recommendations for various treatment items required for proper recovery after hip fracture surgeries. METHODS: Reflecting the complex perspectives associated with rehabilitation post-hip surgeries, 15 key questions (KQs) reflecting the complex perspectives associated with post-hip surgery rehabilitation were categorized into four areas: multidisciplinary, rehabilitation, community-care, and comorbidities/complications. Relevant literature from four databases (PubMed, EMBASE, Cochrane Library, and KoreaMed) was searched for articles published up to February 2020. The evidence level and recommended grade were determined according to the grade of recommendation assessment, development, and evaluation method. RESULTS: A multidisciplinary approach, progressive resistance exercises, and balance training are strongly recommended. Early ambulation, weigh-bearing exercises, activities of daily living training, community-level rehabilitation, management of comorbidities/complication prevention, and nutritional support were also suggested. This multidisciplinary approach reduced the total healthcare cost. CONCLUSION: This guideline presents comprehensive recommendations for the rehabilitation of adult patients after hip fracture surgery.

ICOS ligand and IL-10 synergize to promote host-microbiota mutualism.

Genome-wide association studies have identified ICOSLG, which encodes the inducible costimulator ligand (ICOSLG or ICOSL) as a susceptibility locus for inflammatory bowel disease. ICOSL has been implicated in the enhancement of pattern recognition receptor signaling in dendritic cells, induction of IL-10 production by CD4 T cells, and the generation of high-affinity antibodies to specific antigens-all of which can potentially explain its involvement in gastrointestinal inflammation. Here, we show that murine ICOSL deficiency results in significant enrichment of IL-10-producing CD4 T cells particularly in the proximal large intestine. Transient depletion of IL-10-producing cells from adult ICOSL-deficient mice induced severe colonic inflammation that was prevented when mice were first treated with metronidazole. ICOSL-deficient mice displayed reduced IgA and IgG antibodies in the colon mucus and impaired serum antibody recognition of microbial antigens, including flagellins derived from mucus-associated bacteria of the Lachnospiraceae family. Confirming the synergy between ICOSL and IL-10, ICOSL deficiency coupled with CD4-specific deletion of the Il10 gene resulted in juvenile onset colitis that was impeded when pups were fostered by ICOSL-sufficient dams. In this setting, we found that both maternally acquired and host-derived antibodies contribute to the life anti-commensal antibody repertoire that mediates this protection in early life. Collectively, our findings reveal a partnership between ICOSL-dependent anti-commensal antibodies and IL-10 in adaptive immune regulation of the microbiota in the large intestine. Furthermore, we identify ICOSL deficiency as an effective platform for exploring the functions of anti-commensal antibodies in host-microbiota mutualism.

Monomorphic Epitheliotropic Intestinal T-cell Lymphoma: A Study of Four Cases and Review of Literature.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary and highly aggressive intestinal T-cell lymphoma derived from intraepithelial lymphocytes. MEITL is previously designated as type II enteropathy-associated T cell lymphoma (EATL). Unlike to classic form of EATL, MEITL is not associated with celiac disease. The diagnosis of MEITL is very challenging and the clinical outcome of patients with MEITL is very poor. Herein we describe a series of four patients diagnosed with MEITL identified upon a 10-year institutional retrospective review. Histopathologic examination of these cases revealed monotonous population of medium sized cells infiltrating intestinal mucosa, positive for CD3, CD8 and CD56 in all four cases. Two patients had the combination chemotherapy; however, the average survival time was only 7.5 months for these two patients after diagnosis. The aim of the present case series is to highlight the pathology, diagnosis and clinical course of the patients with MEITL based on the current literature.