An insidious internal hernia 30 years after jejunoileal bypass: a case report.

Jejunoileal bypass (JIB) was an early bariatric procedure that involved bypassing most of the small bowel resulting in malabsorption and weight loss. Due to serious complications associated with the procedure, JIB was largely discontinued by the mid-1980s. We report the case of a 77-year-old woman with a history of JIB 31 years earlier. In 2022, she was hospitalized for acute abdominal pain. A computed tomography (CT) scan revealed a suspicion of internal hernia (IH) with a typical swirl sign. Due to the quick relief of symptoms an emergency surgery was not considered at the time. Nevertheless, a subsequent operation revealed a large mesenteric defect, adhesions and 100 cm of effective small bowel left. Although the procedure is no longer performed, some patients with JIB are still alive and develop late complications. To our knowledge, this is the first case report describing an IH in a patient who has undergone JIB.

Long-term outcome after implementation of endovascular-first strategy to treat acute mesenteric ischemia.

OBJECTIVE: To evaluate the rationale of an aggressive endovascular-first strategy to treat elderly patients with acute mesenteric ischemia (AMI) by studying long-term survival, readmissions, and patients' discharge to home vs nursing facility a decade after an episode of AMI. METHODS: The retrospective study cohort included 66 consecutive patients (all-comers) treated for arterial occlusive AMI between 2009 and 2013. Endovascular revascularization (EVR) was attempted in 50 patients (EVR+), whereas 16 patients were treated without attempted revascularization (EVR-). All patients were followed until death or September 2022. Studied outcomes included discharge status, long-term survival and cause of death and readmissions related to AMI. RESULTS: The mean age of all 66 patients was 78 ± 10 years: 79 ± 9 years in the EVR+ group and 76 ± 12 years in the EVR- group. EVR was technically successful in 44 patients (88%); three patients underwent subsequent open revascularization after EVR failure. One-third required bowel resection after EVR. The 30-day mortality for all patients was 44%; 32% in the EVR+ group and 81% in the EVR- group. Only two survivors were permanently institutionalized, whereas all others were discharged to the same place they lived prior to the AMI episode. There were four AMI-related readmissions during the follow-up; all were in the EVR+ group. Two patients underwent reinterventions for recurrent AMI. One-year survival was 52% for EVR+ and 19% for EVR- patients. Five-year survival rates were 18% and 13%, respectively. The causes of deaths were mesenteric ischemia in 22, other cardiovascular event in 21, and non-cardiovascular cause in 19 patients. Four patients were alive at the end of the follow-up. CONCLUSIONS: In this unselected elderly population with AMI, the aggressive strategy to attempt EVR resulted in a high revascularization rate and favorable outcomes. The high proportion of patients returning to their prior living status and low readmission rate after survival from AMI encourages active treatment of high-functioning elderly patients.

Small Intestinal Length Associates with Serum Triglycerides Before and After LRYGB.

BACKGROUND AND AIMS: Different bariatric procedures have been associated with variable weight loss and decrease in serum levels of lipids and lipoproteins. This variation could be partly related to the length of the small intestinal bypass. We evaluated the association of the small intestinal length with the non-alcoholic fatty liver disease (NAFLD) at baseline and with lipid metabolism before and after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Seventy consecutive morbidly obese patients were recruited to this prospective study. A standard 60-cm biliopancreatic limb (BPL) and 120-cm alimentary limb (AL) was performed, and thereafter, the common channel (CC) length was measured during elective LRYGB. Histological analysis of liver biopsy to diagnose NAFLD was performed. The mRNA expression of genes participating in the cholesterol and fatty acid metabolism in the liver was analyzed. RESULTS: Female sex (p = 0.006), serum triglycerides (TG, p = 0.016), serum alanine aminotransferase (ALT, p = 0.007), and liver steatosis (p = 0.001) associated with the small intestinal length (BPL + AL + CC) at baseline. Association remained significant between levels of serum TG and CC length (p = 0.048) at 1-year follow-up. Liver mRNA expression of genes regulating cholesterol synthesis and bile metabolism did not associate with the baseline small intestinal length. CONCLUSIONS: Our findings support the suggestions that small intestinal length regulates TG metabolism before and after LRYGB. Therefore, modification of the length of bypassed small intestine based on measured total small intestinal length could optimize the outcomes of the elective LRYGB.

Serum, liver and bile sitosterol and sitostanol in obese patients with and without NAFLD.

Background and aims: Non-alcoholic fatty liver disease (NAFLD) associates with low levels of serum plant sterols in cross-sectional studies. In addition, it has been suggested that the hepatic sterol transport mechanisms are altered in NAFLD. Therefore, we investigated the association between serum, liver and bile plant sterols and sitostanol with NAFLD.Methods: Out of the 138 individuals (age: 46.3 ± 8.9, body mass index: 43.3 ± 6.9 kg/m², 28% men and 72% women), 44 could be histologically categorized to have normal liver, and 94 to have NAFLD. Within the NAFLD group, 28 had simple steatosis and 27 had non-alcoholic steatohepatitis. Plant sterols and sitostanol were measured from serum (n=138), liver (n=38), and bile (n=41). The mRNA expression of genes regulating liver sterol metabolism and inflammation was measured (n=102).Results: Liver and bile sitostanol ratios to cholesterol were higher in those with NAFLD compared to those with histologically normal liver (all P<0.022). Furthermore, liver sitostanol to cholesterol ratio correlated positively with histological steatosis and lobular inflammation (rs > 0.407, P<0.01 for both). In contrast, liver sitosterol to cholesterol ratio correlated negatively with steatosis (rs = -0.392, P=0.015) and lobular inflammation (rs = -0.395, P=0.014). Transcriptomics analysis revealed suggestive correlations between serum plant sterol levels and mRNA expression.Conclusion: Our study showed that liver and bile sitostanol ratios to cholesterol associated positively and liver sitosterol ratio to cholesterol associated negatively with liver steatosis and inflammation in obese individuals with NAFLD..

Evaluation of the Effect of Bariatric Surgery-Induced Weight Loss on Knee Gait and Cartilage Degeneration.

The objective of the study was to investigate the effects of bariatric surgery-induced weight loss on knee gait and cartilage degeneration in osteoarthritis (OA) by combining magnetic resonance imaging (MRI), gait analysis, finite element (FE) modeling, and cartilage degeneration algorithm. Gait analyses were performed for obese subjects before and one-year after the bariatric surgery. FE models were created before and after weight loss for those subjects who did not have severe tibio-femoral knee cartilage loss. Knee cartilage degenerations were predicted using an adaptive cartilage degeneration algorithm which is based on cumulative overloading of cartilage, leading to iteratively altered cartilage properties during OA. The average weight loss was 25.7±11.0 kg corresponding to a 9.2±3.9 kg/m2 decrease in body mass index (BMI). External knee rotation moment increased, and minimum knee flexion angle decreased significantly (p < 0.05) after weight loss. Moreover, weight loss decreased maximum cartilage degeneration by 5±23% and 13±11% on the medial and lateral tibial cartilage surfaces, respectively. Average degenerated volumes in the medial and lateral tibial cartilage decreased by 3±31% and 7±32%, respectively, after weight loss. However, increased degeneration levels could also be observed due to altered knee kinetics. The present results suggest that moderate weight loss changes knee kinetics and kinematics and can slow-down cartilage degeneration for certain patients. Simulation results also suggest that prediction of cartilage degeneration is subject-specific and highly depend on the altered gait loading, not just the patient's weight.

Regulation of alternative splicing in human obesity loci.

OBJECTIVE: Multiple obesity susceptibility loci have been identified by genome-wide association studies, yet the mechanisms by which these loci influence obesity remain unclear. Alternative splicing could contribute to obesity by regulating the transcriptomic and proteomic diversity of genes in these loci. METHODS: Based on a database search, 72 of the 136 genes at the 13 obesity loci encoded multiple protein isoforms. Thus, alternative splicing of these genes in adipose tissue samples was analyzed from the Metabolic Syndrome in Men population-based study and from two weight loss intervention studies (surgical and very low calorie diet). RESULTS: Alternative splicing was confirmed in 11 genes with PCR capillary electrophoresis in human subcutaneous adipose tissue. Interestingly, differential splicing of TRA2B, BAG6, and MSH5 was observed between lean individuals with normoglycemia and overweight individuals with type 2 diabetes. Of these genes, we detected fat depot-dependent splicing of TRA2B and BAG6 and weight loss-induced regulation of MSH5 splicing in the intervention studies. Finally, body mass index was a major determinant of TRA2B, BAG6, and MSH5 splicing in the combined data. CONCLUSIONS: This study provides evidence for alternative splicing in obesity loci, suggesting that alternative splicing at least in part mediates the obesity-associated risk in these loci.

Ketone body production is differentially altered in steatosis and non-alcoholic steatohepatitis in obese humans.

BACKGROUND & AIMS: Levels of ketone bodies have been reported to be both increased and decreased in individuals with non-alcoholic fatty liver disease. We investigated whether the metabolism of ketone bodies is different in simple steatosis and in non-alcoholic steatohepatitis (NASH). METHODS: Serum low molecular weight molecules including ketone bodies were measured using high-throughput proton (1H) nuclear magnetic resonance in 116 (76 categorized unequivocally to those with normal liver, simple steatosis or NASH) morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, body mass index 45.1 ± 6.1 kg/m(2) , 39 men and 77 women] with histological assessment of NASH and analysis of gene expression in the liver. Finally, we correlated ß-hydroxybutyrate (ß-OHB) levels with NASH predicting score in Metabolic Syndrome in Men Study (METSIM) population study (n = 8749 non-diabetic men). RESULTS: Levels of ketone bodies were lower in individuals with NASH compared to individuals with simple steatosis (P = 0.004 and P = 0.018 for ß-OHB and acetoacetate respectively). Lower levels of ß-OHB were associated with the NASH predicting score in the METSIM study (P = 0.001). Liver inflammation correlated with mRNA expression of genes regulating ketolysis in the liver (Spearman correlation 0.379-0.388, P < 0.0006 for ACAT1, ACSS2 and BDH1). CONCLUSION: Lower levels of ketone bodies in individuals with NASH compared to individuals with simple steatosis suggest a decrease in ketone body metabolism in NASH.

Lipoprotein subclass metabolism in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is associated with increased synthesis of triglycerides and cholesterol coupled with increased VLDL synthesis in the liver. In addition, increased cholesterol content in the liver associates with NASH. Here we study the association of lipoprotein subclass metabolism with NASH. To this aim, liver biopsies from 116 morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, BMI 45.1 ± 6.1 kg/m², 39 men and 77 women] were used for histological assessment. Proton NMR spectroscopy was used to measure lipid concentrations of 14 lipoprotein subclasses in native serum samples at baseline and after obesity surgery. We observed that total lipid concentration of VLDL and LDL subclasses, but not HDL subclasses, associated with NASH [false discovery rate (FDR) < 0.1]. More specifically, total lipid and cholesterol concentration of VLDL and LDL subclasses associated with inflammation, fibrosis, and cell injury (FDR < 0.1), independent of steatosis. Cholesterol concentration of all VLDL subclasses also correlated with total and free cholesterol content in the liver. All NASH-related changes in lipoprotein subclasses were reversed by obesity surgery. High total lipid and cholesterol concentration of serum VLDL and LDL subclasses are linked to cholesterol accumulation in the liver and to liver cell injury in NASH.

A population-based study on the prevalence of NASH using scores validated against liver histology.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease in Western countries. Diagnosis of NASH requires a liver biopsy. We estimated the prevalence of NASH non-invasively in a population-based study using scores validated against liver histology. METHODS: Clinical characteristics, PNPLA3 genotype at rs738409, and serum cytokeratin 18 fragments were measured in 296 consecutive bariatric surgery patients who underwent a liver biopsy to discover and validate a NASH score ('NASH score'). We also defined the cut-off for NASH for a previously validated NAFLD liver fat score to diagnose NASH in the same cohort ('NASH liver fat score'). Both scores were validated in an Italian cohort comprising of 380, mainly non-bariatric surgery patients, who had undergone a liver biopsy for NASH. The cut-offs were utilized in the Finnish population-based D2D-study involving 2849 subjects (age 45-74 years) to estimate the population prevalence of NASH. RESULTS: The final 'NASH Score' model included PNPLA3 genotype, AST and fasting insulin. It predicted NASH with an AUROC 0.774 (0.709, 0.839) in Finns and 0.759 (0.711, 0.807) in Italians (NS). The AUROCs for 'NASH liver fat score' were 0.734 (0.664, 0.805) and 0.737 (0.687, 0.787), respectively. Using 'NASH liver fat score' and 'NASH Score', the prevalences of NASH in the D2D study were 4.2% (95% CI: 3.4, 5.0) and 6.0% (5.0, 6.9%). Sensitivity analysis was performed by taking into account stochastic false-positivity and false-negativity rates in a Bayesian model. This analysis yielded population prevalences of NASH of 3.1% (95% stimulation limits 0.2-6.8%) using 'NASH liver fat score' and 3.6% (0.2-7.7%) using 'NASH Score'. CONCLUSIONS: The population prevalence of NASH in 45-74 year old Finnish subjects is ∼ 5%.

Adipose tissue INSR splicing in humans associates with fasting insulin level and is regulated by weight loss.

AIMS/HYPOTHESIS: The insulin receptor (INSR) has two protein isoforms based on alternative splicing of exon 11. INSR-A promotes cell growth whereas INSR-B predominantly regulates glucose homeostasis. In this study we investigated whether weight loss regulates INSR alternative splicing and the expression of splicing factors in adipose tissue. METHODS: To determine the relative ratio of the INSR splice variants, we implemented the PCR-capillary electrophoresis method with adipose tissue samples from two weight-loss-intervention studies, the Kuopio Obesity Surgery study (KOBS, n = 108) and a very low calorie diet (VLCD) intervention (n = 32), and from the population-based Metabolic Syndrome in Men study (METSIM, n = 49). RESULTS: Expression of INSR-B mRNA variant increased in response to weight loss induced by both bariatric surgery (p = 1 × 10(-5)) and the VLCD (p = 1 × 10(-4)). The adipose tissue expression of INSR-B correlated negatively with fasting insulin levels in the pooled data of the three studies (p = 3 × 10(-22)). Finally, expression of several splicing factors correlated negatively with the expression of the INSR-B variant. The strongest correlation was with HNRNPA1 (p = 1 × 10(-5)), a known regulator of INSR exon 11 splicing. CONCLUSIONS/INTERPRETATION: INSR splicing is regulated by weight loss and associates with insulin levels. The effect of weight loss on INSR splicing could be mediated by changes in the expression of splicing factors.

A Pancreaticobronchial Fistula Associated With Previous Trauma and Pancreas Pseudocysts: A Case Report.

We describe a rare case of a pancreaticobronchial fistula caused by pancreatic pseudocysts due to previous trauma. A 54-year-old man with a history of traumatic hemothorax was referred to central hospital for investigations due to cough, dyspnea, vertigo and fever. An ultrasound scan and abdominal computed tomography scan showed huge pancreatic pseudocysts around the pancreas extending to the right side of the mediastinum with gas. The etiology for the pseudocysts was unconfirmed. First, the patient recovered with antibiotics and external pseudocyst drainage. After five months the patient started to suffer from respiratory symptoms again, such as coughing with sputum, dyspnea and mild fever. The computer tomography scan confirmed the pancreaticobronchial fistula as a diagnosis and the patient was referred to the university hospital for further treatment.

Imaging and Treatment Features of Idiopathic Pancreatitis and Pancreas Divisum in a Young Man: A Case Report.

Some patients with pancreas divisum (PD) develop symptoms of recurrent pancreatitis. This is probably caused by insufficient drainage of the pancreatic duct. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive test reported to be highly accurate in diagnosing PD. Endoscopic minor papilla sphincterotomy is most effective in the treatment of patients with PD and pancreatic stones. We report a case of 17-year-old boy who has suffered from several abdominal pain attacks throughout his childhood without a specific diagnosis. Radiological findings after the first episode of pancreatitis were typical for PD and led to specific treatment and cure.

[Gastric bypass as weight loss operation: 10-year experience of one center and challenges of follow-up]. / Mahalaukun ohitus lihavuusleikkauksena: yhden keskuksen kymmenen vuoden kokemukset ja seurannan haasteet.

INTRODUCTION: Data about the implementation of long-term follow-up of weight loss operation patients and their nutritional status has been lacking in Finland. PATIENTS AND METHODS: We examined the postoperative complications and long-term outcome in respect of weight control, symptoms, nutritional status and medication of 173 patients having undergone gastric bypass. The data were collected from patient records and by questionnaires. RESULTS: Postoperative complications and weight loss were at the international level. The number of those using antidiabetic and antihypertensive drugs decreased. CONCLUSIONS: The results are in agreement with the international level, but follow-up treatment requires attention in Finland.

Desmosterol in human nonalcoholic steatohepatitis.

UNLABELLED: Dysregulation of the cholesterol synthesis pathway and accumulation of cholesterol in the liver are linked to the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, we investigated the association of serum and liver levels of cholesterol precursors with NASH. Liver histology was assessed in 110 obese patients (Kuopio Obesity Surgery Study [KOBS] study, age 43.7 ± 8.1 years [mean ± standard deviation, SD], body mass index [BMI] 45.0 ± 6.1 kg/m(2) ). Serum and liver levels of cholesterol precursors were measured with gas-liquid chromatography. The association between cholesterol precursors and serum alanine aminotransferase (ALT), as a marker of liver disease, was also investigated in a population cohort of 717 men (Metabolic Syndrome in Men Study [METSIM] study, age 57.6 ± 5.8 years, BMI 27.1 ± 4.0 kg/m(2) ). Serum desmosterol levels and the desmosterol-to-cholesterol ratio were higher in individuals with NASH, but not in individuals with simple steatosis, compared to obese subjects with normal liver histology (P = 0.002 and P = 0.003, respectively). Levels of serum and liver desmosterol correlated strongly (r = 0.667, P = 1 × 10(-9) ), suggesting a shared regulation. Both serum and liver desmosterol levels correlated positively with steatosis and inflammation in the liver (P < 0.05). Serum desmosterol had a higher correlation with the accumulation of cholesterol in the liver than serum cholesterol. Serum desmosterol levels (P = 2 × 10(-6) ) and the serum desmosterol-to-cholesterol ratio (P = 5 × 10(-5) ) were associated with serum ALT in the population study. CONCLUSION: Levels of desmosterol in serum and the liver were associated with NASH. These results suggest that serum desmosterol is a marker of disturbed cholesterol metabolism in the liver. Whether desmosterol has a more specific role in the pathophysiology of NASH compared to other cholesterol precursors needs to be investigated.

Adipose tissue TCF7L2 splicing is regulated by weight loss and associates with glucose and fatty acid metabolism.

We investigated the effects of obesity surgery-induced weight loss on transcription factor 7-like 2 gene (TCF7L2) alternative splicing in adipose tissue and liver. Furthermore, we determined the association of TCF7L2 splicing with the levels of plasma glucose and serum free fatty acids (FFAs) in three independent studies (n = 216). Expression of the short mRNA variant, lacking exons 12, 13, and 13a, decreased after weight loss in subcutaneous fat (n = 46) and liver (n = 11) and was more common in subcutaneous fat of subjects with type 2 diabetes than in subjects with normal glucose tolerance in obese individuals (n = 54) and a population-based sample (n = 49). Additionally, there was a positive correlation between this variant and the level of fasting glucose in nondiabetic individuals (n = 113). This association between TCF7L2 splicing and plasma glucose was independent of the TCF7L2 genotype. Finally, this variant was associated with high levels of serum FFAs during hyperinsulinemia, suggesting impaired insulin action in adipose tissue, whereas no association with insulin secretion or insulin-stimulated whole-body glucose uptake was observed. Our study shows that the short TCF7L2 mRNA variant in subcutaneous fat is regulated by weight loss and is associated with hyperglycemia and impaired insulin action in adipose tissue.

Response to Brosch et al.

We would like to respond to Brosch et al. regarding our manuscript "Expression of the Splicing Factor Gene SFRS10 Is Reduced in Human Obesity and Contributes to Enhanced Lipogenesis" (Pihlajamäki et al., 2011b). Brosch performed RT-PCR in liver samples from 13 lean and 34 obese individuals, finding no differences in SFRS10 or LPIN1 expression. We wish to address points raised by Brosch, including experimental strategy and analysis of human SFRS10 expression.