Högskolan i Skövde

Nonalcoholic fatty liver disease (NAFLD) is increasingly being linked to obesity. Although laparoscopic sleeve gastrectomy (LSG) is effective for weight loss that can ultimately resolve NAFLD, an initial transient deterioration of liver functions could be observed during the first few months post-operatively, after which a subsequent improvement of the liver functions might occur. Rapid weight loss, nutritional deficiencies, and protein malnutrition can all contribute to hepatic dysfunction and can affect the metabolism of medications such as acetaminophen leading to more insult to a compromised liver. We report acute liver failure after LSG associated with protein calorie malnutrition, multiple nutritional deficiencies in addition to concomitant use of therapeutic doses of acetaminophen. Treatment with N-acetylcysteine, and replacement of deficient multivitamins and trace elements resulted in significant improvement in liver functions. 

Introduction: Giant/large gallstones have high risk of complications, and technical difficulties during surgery. This case series is the largest ever reported. Presentation of cases: Case 1: Female (44 years), with one year intermittent right upper quadrant colicky pain. Ultrasound: large gallstone (normal gallbladder). Elective laparoscopic cholecystectomy (LC): 6 × 4 × 3.3 cm gallstone. Case 2: Female (41 years), presented to emergency room with 3 days right upper quadrant pain/tenderness, vomiting, and positive murphy's sign. Ultrasound: large gallstone, calculus cholecystitis. Emergency LC: 4.5 × 3.1 × 3.5 cm gallstone. Case 3: Male (38 years), with history of gallstones and acute cholecystitis presented with intermittent right upper quadrant pain (2 months) and vomiting. Normal abdominal examination. Ultrasound: large gallstone. Elective LC: 4.1 × 4 × 3.6 cm gallstone. Conclusions: Gallstones >5 cm are very rare, with higher risk of complications. Gallbladder should be removed even if asymptomatic. Gallstones >3 cm have increased risk for gallbladder cancer, biliary enteric fistula and ileus. LC has challenges that include grasping the gallbladder wall, exposure of Calot's triangle, and retrieval of gallbladder out of the abdomen. LC appears to be procedure of choice and should be performed by an experienced surgeon, considering the possibility of conversion to open cholecystectomy in case of inability to expose the anatomy or intraoperative difficulties. © 2020 The Author(s)

Background: Giant parathyroid adenoma is a rare type of parathyroid adenoma defined as weighing > 3.5 g. They present as primary hyperparathyroidism but with more elevated laboratory findings and more severe clinical presentations due to the larger tissue mass. This is the first reported case of giant parathyroid adenoma from the Middle East.

Case presentation: A 52-year-old Indian woman presented with a palpable right-sided neck mass and generalized fatigue. Investigations revealed hypercalcemia with elevated parathyroid hormone and an asymptomatic kidney stone. Ultrasound showed a complex nodule with solid and cystic components, and Sestamibi nuclear scan confirmed a giant parathyroid adenoma. Focused surgical neck exploration was done and a giant parathyroid adenoma weighing 7.7 gm was excised.

Conclusions: Giant parathyroid adenoma is a rare cause of primary hyperparathyroidism and usually presents symptomatically with high calcium and parathyroid hormone levels. Giant parathyroid adenoma is diagnosed by imaging and laboratory studies. Management is typically surgical, aiming at complete resection. Patients usually recover with no long-term complications or recurrence.

OBJECTIVES: Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms.

METHODS: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed.

RESULTS: Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-γ tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified.

CONCLUSIONS: Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.

OBJECTIVE: Anti-TNF-α treatment constitutes a mainstay in the treatment of Crohn's disease (CD), but its mechanisms of action are not fully understood. We aimed to investigate the effects of adalimumab, a human monoclonal TNF-α antibody, on macrophage (MQ) and dendritic cell (DC) subsets in mucosal biopsies and peripheral blood.

MATERIAL AND METHODS: Intestinal biopsies and blood samples were obtained from 12 different CD patients both before and 4 weeks after the initiation of the induction of adalimumab treatment. Endoscopic disease activity was estimated by the Simple Endoscopic Score for Crohn's Disease. Biopsies were obtained from inflamed and non-inflamed areas. The numbers of lamina propria CD14 (+) DR(int) and CD14 (+) DR(hi) MQs, CD141(+), CD141(-) and CD103(+ )DCs subsets, and circulating monocytes and DCs were analyzed using flow cytometry.

RESULTS: At baseline, we observed higher numbers of DR(int) MQs and lower numbers of CD103(+ )DCs in inflamed versus non-inflamed mucosa [843 vs. 391/10(5) lamina propria mononuclear cells (LPMCs) (p < 0.05) and 9 vs. 19 × 10(5) LPMCs (p = 0.01), respectively]. After four weeks of adalimumab treatment, the numbers of DR(int) MQs decreased [843 to 379/10(5) LPMCs (p = 0.03)], whereas the numbers of CD103(+ )DCs increased [9-20 × 10(5) LPMCs (p = 0.003)] compared with baseline. In peripheral blood, no alterations were observed in monocyte or DC numbers between baseline and week 4.

CONCLUSIONS: In CD, mucosal inflammation is associated with high numbers of DR(int) MQs and low numbers of CD103(+ )DCs. This composition of intestinal myeloid subsets is reversed by anti-TNF-α treatment. These results suggest that DR(int) MQs play a pivotal role in CD inflammation.

Background: Globally, only two studies appraised the long-term nutritional status of adolescents after laparoscopic sleeve gastrectomy (LSG). Methods: Retrospective chart review of all adolescents aged ≤ 18 years who underwent LSG with ≥ 5 years follow-up and had no subsequent revisional surgery (N = 146). We assessed 15 nutritional parameters preoperatively and at 1, 3, 5, 7, and 9 years post surgery. Results: Mean age was 16.51 ± 1.29 years, 51% were males. We identified three patterns:1) Significant worsening of preoperative deficiencies: 4.7% and 0.8% of the sample exhibited zinc and vitamin B12 deficiencies, worsening to 20.8% and 12.8% at 1 year, respectively. Likewise, 0.7% of the sample had low total protein, worsening to 8.3% at year 3. A total of 32.4% of females had preoperative low hemoglobin worsening to 57.9% at year 5.2) Significant improvement: the percentage of males with preoperative low hemoglobin (5.6%) was reduced to 4.1% and 5.1% at years 1 and 3, respectively.3) Persistent deficiency: all (100%) of adolescents had preoperative vitamin D deficiency that persisted through years 3 and 9 at 90.5% and 100%, respectively. The most common complications were food intolerance (51%), vomiting (47.5%), gastritis/ esophagitis (35.7%), and gastroesophageal reflux disease (20.3%). We observed one case of Wernicke’s encephalopathy. Across the 9 years, 15.4% of the adolescents underwent intra-abdominal surgeries where 12.6% had cholecystectomy and one patient had appendectomy. Conclusion: Adolescents had several preoperative nutritional deficiencies, most of which worsened or persisted on the long term. This is the first study among adolescents to assess such deficiencies beyond 5 years. Graphical Abstract: [Figure not available: see fulltext.]. 

Background and study aims: Hepatocellular carcinoma (HCC) with extrahepatic metastasis has been studied, however, data from the Middle East remain scarce. In this study, we assess epidemiology of HCC in Qatar, and identify predictors of the metastatic behaviour. Patients and methods: All newly-diagnosed HCC patients on top of liver cirrhosis between 2011 and 2015 were included in the study. Results: A total of 180 patients met our inclusion criteria. The mean age was 58.8 ± 10.5 years with a mean follow-up of 1.0 ± 1.1 years. There were 150 male patients and HCV was the most common cause of liver cirrhosis 108 (60%), and 22 (12.2%) patients were classified as Child-Pugh class C. The overall survival of 51.1%, and 47 (26%) had at least one extrahepatic metastasis at the time of diagnosis. Single site metastasis was diagnosed in 10 patients, whereas 37 patients had multiple sites metastases. We compared patients who had metastases with patients who did not have metastasis at the time of diagnosis of HCC regarding several variables, and analysis revealed that tumour diameter larger than 5 cm (OR = 6.10, 95% CI = 1.85–20.12) (p = 0.003), and bilobar liver involvement (OR = 5.49, 95% CI = 1.10–27.30) (p = 0.037) were independent predictors of metastatic behaviour of HCC. Conclusion: The incidence of HCC is rising in our population, extrahepatic metastasis is no longer rare and tumours larger than 5 cm and bilobar involvement are determinants of the extrahepatic metastasis. © 2019 Pan-Arab Association of Gastroenterology

Human pluripotent stem cell-derived hepatocytes (hPSC-HEP) display many properties of mature hepatocytes, including expression of important genes of the drug metabolizing machinery, glycogen storage, and production of multiple serum proteins. To this date, hPSC-HEP do not, however, fully recapitulate the complete functionality of in vivo mature hepatocytes. In this study, we applied versatile bioinformatic algorithms, including functional annotation and pathway enrichment analyses, transcription factor binding-site enrichment, and similarity and correlation analyses, to datasets collected from different stages during hPSC-HEP differentiation and compared these to developmental stages and tissues from fetal and adult human liver. Our results demonstrate a high level of similarity between the in vitro differentiation of hPSC-HEP and in vivo hepatogenesis. Importantly, the transcriptional correlation of hPSC-HEP with adult liver (AL) tissues was higher than with fetal liver (FL) tissues (0.83 and 0.70, respectively). Functional data revealed mature features of hPSC-HEP including cytochrome P450 enzymes activities and albumin secretion. Moreover, hPSC-HEP showed expression of many genes involved in drug absorption, distribution, metabolism, and excretion. Despite the high similarities observed, we identified differences of specific pathways and regulatory players by analyzing the gene expression between hPSC-HEP and AL. These findings will aid future intervention and improvement of in vitro hepatocyte differentiation protocol in order to generate hepatocytes displaying the complete functionality of mature hepatocytes. Finally, on the transcriptional level, our results show stronger correlation and higher similarity of hPSC-HEP to AL than to FL. In addition, potential targets for further functional improvement of hPSC-HEP were also identified. 

BACKGROUND: The autonomic nervous system (ANS) modulates intestinal inflammation in animal models. Human evidence confirming such modulating influence is limited. We aimed to investigate whether ANS function is associated with inflammatory parameters at disease onset, and whether it predicts the evolution of inflammation in patients with ulcerative colitis (UC).

METHODS: We prospectively monitored 51 patients from onset of UC for 3 years. Upon remission of the onset flare, ANS activity was assessed by heart rate variability analysis and compared with healthy controls. Inflammatory parameters in blood, stool, and colonic biopsies obtained at onset and during follow-up visits were analyzed. Generalized linear models were used to test cross-sectional associations between ANS activity and inflammatory parameters at onset; linear mixed models were used to test whether ANS function at onset predicted the evolution of inflammation over the following 3 years.

KEY RESULTS: Sympathovagal balance was different in UC patients compared to healthy controls, and cross-sectional associated with higher levels of systemic (erythrocyte sedimentation rate [ESR], CRP, TNF-α, IFN-γ) and mucosal inflammation (interleukin-8, IFN-γ) at onset. Conversely, a negative cross-sectional association with parasympathetic activity was found for ESR & TNF-α. Longitudinally, parasympathetic activity at onset predicted systemic (ESR, WBC), but not mucosal inflammation during follow-up.

CONCLUSIONS & INFERENCES: This study further strengthens the association between the ANS system and intestinal inflammation previously found in animal models and recently in patients with inflammatory bowel disease. These results may have important implications for the pathogenesis and treatment of UC.

Inflammatory bowel disease is characterized by a number of immunological alterations, not the least in the T-cell compartment. Numerous animal models of colitis have revealed aberrant thymocyte dynamics associated with skewed thymocyte development. The recent advancements in quantitative methods have proposed critical kinetic alterations in the thymocyte development during the progression of colitis. This review focuses on the aberrant thymocyte dynamics in G alpha i2-deficient mice as this mouse model provides most quantitative data of the thymocyte development associated with colitis. Herein, we discuss several dynamic changes during the progression of colitis and propose a hypothesis for the underlying causes for the skewed proportions of the thymocyte populations seen in the G alpha i2-deficient mice and in other mouse models of colitis.

BACKGROUND: Gastrointestinal symptoms (GI) compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in remission. The causes of these symptoms remain to be clarified. Our aim was to investigate prevalence and factors associated with IBS-like symptoms in patients with UC in deep remission.

METHODS: We included 298 patients with UC and used Mayo score, sigmoidoscopy, and fecal calprotectin to define deep remission versus active disease. Presence of IBS-like symptoms according to the Rome III criteria, severity of GI, extraintestinal and psychological symptoms, stress levels, and quality of life were measured with validated questionnaires. Serum cytokines and high-sensitive C-reactive peptide were determined.

RESULTS: The criteria for deep remission was fulfilled by 132 patients (44%) and 24 of these fulfilled the Rome III criteria for IBS (18%). Patients with UC in deep remission with IBS-like symptoms had comparable levels of GI symptoms, non-GI somatic symptoms, and quality of life as patients with active UC. The patients with UC in deep remission with IBS-like symptoms had similar levels of fecal calprotectin as patients in deep remission without IBS-like symptoms (18 versus 31 μg/g, P = 0.11), but higher levels of serum cytokines (interleukin [IL]-1β, IL-6, IL-13, IL-10 and IL-8, P < 0.05) and higher levels of anxiety (P < 0.001), depression (P = 0.02) and perceived stress (P = 0.03).

CONCLUSIONS: IBS-like symptoms in patients with UC in deep remission are common, but not as prevalent as previously reported. Poor psychological well-being and increased serum cytokine levels, but not colonic low-grade inflammation, were associated with IBS-like symptoms.

Purpose

Loss of expression of DLG2 has been identified in a number of cancers to contribute to the disease by resulting in increased tumor cell proliferation and poor survival. In light of the previous evidence that DLG2 alters the cell cycle and affects proliferation, combined with indications that DLG2 is involved in NLRP3 inflammasome axis we speculated that DLG2 has an immune function. So far, there is no data that clearly elucidates this role, and this study was designed to investigate DLG2 in inflammatory colon disease and in colon cancer as well as its impact on inflammasome induction.

Methods

The DLG2 expression levels were established in publicly available inflammation, colon cancer and mouse model datasets. The overexpression and silencing of DLG2 in colon cancer cells were used to determine the effect of DLG2 expression on the activation of the inflammasome and subsequent cytokine release.

Results

The expression of DLG2 is repressed in inflammatory colon diseases IBD and Ulcerative colitis as well as colorectal cancer tissue compared to healthy individuals. We subsequently show that induction with inflammatory agents in cell and animal models results in a biphasic alteration of DLG2 with an initial increase followed by an ensuing decrease. DLG2 overexpression leads to a significant increase in expression of IL1B, IκBζ and BAX, components that result in inflammasome formation. DLG2 silencing in THP1 cells resulted in increased release of IL-6 into the microenvironment which once used to treat bystander COLO205 cells resulted in an increase in STAT3 phosphorylation and an increase proliferating cells and more cells in the G2/M phase. Restoration of DLG2 to the colon resulted in reduced AKT and S6 signaling.

Conclusion

DLG2 expression is altered in response to inflammation in the gut as well as colon cancer, resulting in altered ability to form inflammasomes.

Trial registration

NCT03072641.

BACKGROUND & AIMS: Patients with irritable bowel syndrome (IBS) can be assigned to groups with different gastrointestinal (GI) symptoms based on results from a combined nutrient and lactulose challenge. We aimed to identify factors that predict outcomes to this challenge and to determine whether this can be used in noninvasive assessment of visceral sensitivity in patients with IBS.

METHODS: We performed a prospective study of 100 patients with IBS diagnosed according to Rome III criteria (all subtypes) and seen at a secondary or tertiary care center. After an overnight fast, subjects were given a liquid breakfast (400 mL; Nutridrink) that contained 25 g lactulose. Before the challenge, we assessed visceral sensitivity (via rectal barostat), oro-anal transit time, and fecal microbiota composition (via 16S ribosomal RNA pyrosequencing); we determined IBS severity using questionnaires. The intensity of 8 GI symptoms, the level of digestive comfort, and the amount of exhaled H2 and CH4 in breath were measured before and during a 4-hour period after the liquid breakfast.

RESULTS: Based on the intensity of 8 GI symptoms and level of digestive comfort during the challenge, patients were assigned to groups with high-intensity GI symptoms (HGS; n = 39) or low-intensity GI symptoms (LGS; n = 61); patients with HGS had more severe IBS (P < .0001), higher somatization (P < .01), and lower quality of life (P < .05-.01) than patients with LGS. Patients with HGS also had significantly higher rectal sensitivity to random phasic distensions (P < .05-.001, compared with patients with LGS). There were no significant differences between groups in fecal microbiota composition, exhaled gas in breath, or oro-anal transit time.

CONCLUSIONS: We found, in a prospective study, that results from a lactulose challenge test could be used to determine visceral sensitivity and severity of IBS. The intensity of patient symptoms did not correlate with the composition of the fecal microbiota. The lactulose challenge test may help better characterize patients with IBS and evaluate the efficacy of new treatments. ClinicalTrial.gov no: NCT01252550.

Several Butyrophilin (BTN) and Btn-like (BTNL) molecules control T lymphocyte responses, and are genetically associated with inflammatory disorders and cancer. In this study, we present a comprehensive expression analysis of human and murine BTN and BTNL genes in conditions associated with intestinal inflammation and cancer. Using real-time PCR, expression of human BTN and BTNL genes was analyzed in samples from patients with ulcerative colitis, irritable bowel syndrome, and colon tumors. Expression of murine Btn and Btnl genes was examined in mouse models of spontaneous colitis (Muc2(-/-)) and intestinal tumorigenesis (Apc(Min/+)). Our analysis indicates a strong association of several of the human genes with ulcerative colitis and colon cancer; while especially BTN1A1, BTN2A2, BTN3A3, and BTNL8 were significantly altered in inflammation, colonic tumors exhibited significantly decreased levels of BTNL2, BTNL3, BTNL8, and BTNL9 as compared to unaffected tissue. Colonic inflammation in Muc2(-/-) mice significantly down-regulated the expression of particularly Btnl1, Btnl4, and Btnl6 mRNA, and intestinal polyps derived from Apc(Min/+) mice displayed altered levels of Btn1a1, Btn2a2, and Btnl1 transcripts. Thus, our data present an association of BTN and BTNL genes with intestinal inflammation and cancer and represent a valuable resource for further studies of this gene family.

Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14(+)DR(int) MQs characterized inflamed intestinal mucosa while total CD141(+) or CD1c(+) DCs numbers were unchanged. However, CD103(+) DCs, including CD141(+)CD103(+) and CD1c(+)CD103(+) DCs, were reduced in inflamed intestine. In MLNs, two CD14(-) DC populations were identified: CD11c(int)HLADR(hi) and CD11c(hi)HLADR(int) cells. A marked increase of CD11c(hi)HLADR(int) DC, particularly DR(int)CD1c(+) DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn's colon. In contrast, no difference in the frequency of ALDH(+) cells among blood precursors was detected between UC patients and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.

Background: The clinical disease course of ulcerative colitis (UC) varies substantially between individuals and can currently not be reliably predicted. The gut microbiota and the host's immune defense are key players for gut homeostasis and may be linked to disease outcome. The aim of this study was to determine fecal microbiota composition and mucosal antibacterial response profile in untreated patients with newly diagnosed UC and the impact of these factors on disease course. Methods: Stool samples and intestinal biopsies were obtained from therapy-naive newly diagnosed patients with UC. Patients were defined to have mild or moderate/severe disease course assessed by disease activity during the 3 years follow-up. Fecal microbiota was analyzed by the GA-map Dysbiosis test (n = 18), and gene expression in intestinal biopsies was analyzed by RT2 Profiler polymerase chain reaction array (n = 13) and real-time polymerase chain reaction (n = 44). Results: At the time of diagnosis of UC, the fecal microbiota composition discriminated between patients with mild versus moderate/severe disease course. Also, the mucosal antibacterial gene expression response profile differed between patients with mild versus moderate/severe disease course with bactericidal/permeability-increasing protein (BPI) being most important for the discrimination. Mucosal bactericidal/permeability-increasing protein gene expression at diagnosis was higher in patients with mild versus moderate/severe disease course when confirmed in a larger patient cohort (P = 0.0004, n = 44) and was a good predictor for the number of flares during the 3 years follow-up (R-2 = 0.395, P < 0.0001). Conclusions: In patients with newly diagnosed UC, fecal microbiota composition and mucosal antibacterial response profile, especially bactericidal/permeability-increasing protein, are linked to disease course.

BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome.

METHODS: Serum and biopsies were obtained from UC patients naïve to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12-14 weeks after baseline.

RESULTS: At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders.

CONCLUSIONS: Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.

BACKGROUND & AIMS: We have limited knowledge about the association between the composition of the intestinal microbiota and clinical features of irritable bowel syndrome (IBS). We collected information on the fecal and mucosa-associated microbiota of patients with IBS and evaluated whether these were associated with symptoms.

METHODS: We collected fecal and mucosal samples from adult patients who met the Rome III criteria for IBS at secondary or tertiary care outpatient clinics in Sweden, as well as from healthy subjects. The exploratory set comprised 149 subjects (110 with IBS and 39 healthy subjects); 232 fecal samples and 59 mucosal biopsy samples were collected and analyzed by 16S ribosomal RNA targeted pyrosequencing. The validation set comprised 46 subjects (29 with IBS and 17 healthy subjects); 46 fecal samples, but no mucosal samples, were collected and analyzed. For each subject, we measured exhaled H2 and CH4, oro-anal transit time, and the severity of psychological and gastrointestinal symptoms. Fecal methanogens were measured by quantitative polymerase chain reaction. Numeric ecology analyses and a machine learning procedure were used to analyze the data.

RESULTS: Fecal microbiota showed covariation with mucosal adherent microbiota. By using classic approaches, we found no differences in fecal microbiota abundance or composition between patients with vs without IBS. A computational statistical technique-like machine learning procedure allowed us to reduce the 16S ribosomal RNA data complexity into a microbial signature for severe IBS, consisting of 90 bacterial operational taxonomic units. We confirmed the robustness of the intestinal microbial signature for severe IBS in the validation set. The signature was able to discriminate between patients with severe symptoms, patients with mild/moderate symptoms, and healthy subjects. By using this intestinal microbiota signature, we found IBS symptom severity to be associated negatively with microbial richness, exhaled CH4, presence of methanogens, and enterotypes enriched with Clostridiales or Prevotella species. This microbiota signature could not be explained by differences in diet or use of medications.

CONCLUSIONS: In analyzing fecal and mucosal microbiota from patients with IBS and healthy individuals, we identified an intestinal microbiota profile that is associated with the severity of IBS symptoms.

TRIAL REGISTRATION NUMBER: NCT01252550.

Introduction: Amyand's hernia (AH) is rare, schistosomiasis of the appendix is very uncommon, and both conditions coexisting together is an extremely rare event. Pre-operative diagnosis of each of the two conditions is usually difficult. To the best of our knowledge, the current paper is first to report both these two conditions in coexistence. Presentation of case: A 31-year old man who had no comorbidities was admitted electively as a day case of non-complicated right indirect inguinal hernia. Further history and physical examination were unremarkable. Intraoperatively the patient was found to have right sliding AH with appendicular schistosomiasis (AS). The patient underwent Lichtenstein repair of the hernia with appendectomy. On follow up he was referred to infectious disease clinic, and the post-operative course was uneventful. Conclusions: Intraoperative identification of non-typical hernia sac before its opening should alert the surgeon to the possibility of sliding hernia and the presence of an organ as a part of the sac. Rare causes of appendicular masses like schistosomiasis granuloma should be considered in endemic areas or immigrants from these areas, despite the difficulty of preoperative diagnosis. Management should follow general guidelines of appendectomy, hernia repair and dealing with the associated pathology if present. 

Background: Varicella zoster virus presents clinically as primary (chickenpox) or secondary (herpes zoster) infection. Cutaneous and extracutaneous dissemination may occur, usually in immunocompromised patients. VZV hepatitis that progresses to fulminant hepatic failure is very rare and fatal. To the best of our knowledge, 9 cases have been reported to date, of which 7 were in immunocompromised adults, and only one patient was on short duration steroid therapy. Presentation of case: We present a 26-year old man who was admitted initially with acute abdomen as query persistent biliary colic. Later, he showed clinical and laboratory findings of VZV hepatitis that progressed rapidly despite maximal medical ICU support and he expired on day 3 of admission. Conclusions: Acute VZV infection may present as fulminant hepatitis. The presentation may initially be challenging for the diagnosis and should be considered if the patient has been in contact with a sick case. Low dose corticosteroid could carry a risk for fatal VZV fulminant hepatitis and should be used very cautiously especially with VZV patients’ contacts. Further causative relationships remain to be established.