Current opinion: functional dyspepsia.

PURPOSE OF REVIEW: Functional dyspepsia is a common gastrointestinal disease that is under-recognized and under-diagnosed. It is a complex disorder of gut-brain interaction with no FDA-approved treatment options. The purpose of this review is to highlight updates in the proposed pathophysiology and present new data regarding potential therapies for functional dyspepsia. RECENT FINDINGS: Alterations in the intestinal microbiome and integrity of the intestinal membrane may play a crucial role in the pathogenesis of functional dyspepsia. The low FODMAP diet, in addition to modulating the microbiome with antibiotics and probiotics, are targets for large future studies. Novel methods of delivery of gut-brain therapies have shown promising results, especially virtual reality. SUMMARY: The pathophysiology and management of functional dyspepsia is complex and there is still much unknown; however, continued research is identifying new targets for treatment. New and more targeted treatment options provide clinicians a variety of tools to offer patients with functional dyspepsia.

Lidar as a potential tool for monitoring migratory insects.

The seasonal migrations of insects involve a substantial displacement of biomass with significant ecological and economic consequences for regions of departure and arrival. Remote sensors have played a pivotal role in revealing the magnitude and general direction of bioflows above 150 m. Nevertheless, the takeoff and descent activity of insects below this height is poorly understood. Our lidar observations elucidate the low-height dusk movements and detailed information of insects in southern Sweden from May to July, during the yearly northward migration period. Importantly, by filtering out moths from other insects based on optical information and wingbeat frequency, we have introduced a promising new method to monitor the flight activities of nocturnal moths near the ground, many of which participate in migration through the area. Lidar thus holds the potential to enhance the scientific understanding of insect migratory behavior and improve pest control strategies.

Development of a Risk Stratification Model for Pre-liver-Transplant Screening Colonoscopy.

BACKGROUND AND AIMS: Colonoscopies are routinely obtained before liver transplantation, although their utility is a highly debated topic in the literature. We aimed to determine the risk factors in patients with decompensated cirrhosis (DC) for post-colonoscopy complications (PCC). MATERIALS AND METHODS: We performed a single-center retrospective study of patients with DC undergoing colonoscopy as part of their pre-liver-transplant evaluation. The primary composite outcome was defined as a complication occurring within 30 days of the colonoscopy. Complications included acute renal failure, new or worsening ascites or hepatic encephalopathy, gastrointestinal bleeding, or any cardiopulmonary or infectious complication. Logistic regression analysis was utilized to derive a risk score in predicting the primary composite outcome. RESULTS: The strongest predictors of post-colonoscopy complication were MELD-Na ≥21 [aOR 4.0026 ( P =0.0050)] and history of any infection in the 30 days before colonoscopy [aOR 8.4345 ( P =0.0093)]. The area under the receiver operating characteristic curve of the final model was 0.78. The predicted risk of any complication at the lowest quartile was 16.2% to 39.4%, and the observed risk was 30.6% (95% CI: 15.5-45.6%), while the predicted risk at the highest quartile was 71.9% to 97.1%, and the observed risk was 81.3% (95% CI: 67.7-95%). CONCLUSION: In this cohort of patients with DC undergoing colonoscopy for pre-liver-transplant evaluation, a history of ascites, spontaneous bacterial peritonitis, and MELD-Na were found to be predictive of PCC. This risk score may help to predict PCC in patients with DC undergoing a pre-transplant colonoscopy. External validation is recommended.

Irritable bowel syndrome - less irritable, or better treatments?

PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a chronic, often bothersome disorder of gut-brain interaction (DGBI) characterized by abdominal pain associated with a change in stool frequency and/or caliber. Recent advancements have improved our understanding of the underlying pathophysiology, thus opening new avenues for therapeutic intervention. The purpose of this review is to summarize the current literature regarding treatment modalities for IBS. RECENT FINDINGS: Altering the gut microbiome via probiotic and antibiotic administration, avoiding dietary triggers, and modulating the gut-brain axis have all proven efficacious for the management of IBS symptoms. Several gut-specific pharmacotherapies are approved for the treatment of IBS, many of which primarily address either diarrhea or constipation, although many patients remain symptomatic despite appropriate use. Brain-gut behavioral therapies (BGBTs) are increasingly used to treat symptoms of IBS, particularly in those who do not respond to traditional therapies. Virtual reality represents an exciting new approach to treating DGBIs, like IBS, though data are limited. SUMMARY: As our understanding of IBS continues to evolve, so should our therapeutic approach. Individualizing the therapeutic approach is of utmost importance.

Metabolic Unhealthiness is Associated With Increased Risk of Critical COVID-19 Pneumonia and Inpatient Mortality in Hospitalized Patients with Obesity or Overweight.

Background and aims Being metabolically unhealthy (MU) is defined as having either hypertension, hyperlipidemia, type 2 diabetes mellitus/pre-diabetes, or fatty liver disease. We aimed to determine if MU was associated with severe COVID-19 pneumonia (severe disease). Methods We performed a single-center retrospective study between March 2020 and August 2021 for patients with overweight or obesity hospitalized with COVID-19 pneumonia. Logistic regression analysis was utilized to derive a risk score for severe disease. The accuracy of the model was assessed using the area under the receiver operating characteristic curve (AUROCC) and bootstrap resampling. Results A total of 334 of 450 patients hospitalized with COVID-19 pneumonia (74.2%) were MU. Patients who were MU had higher in-hospital mortality (10.5% vs. 2.6%) and longer length of hospitalization (median 6 vs. 4 days). MU was not associated with severe disease, p=0.311. On multivariable analysis, older age, male sex, and Asian race were associated with severe disease. Not being vaccinated was associated with doubled odds of severe disease. The AUROCC of the final model was 0.66 (95% CI: 0.60 to 0.71). The risk score at the lowest quintile had a 33.1% to 65.5% predicted risk and a 58.7% observed risk of severe disease, whereas, at the highest quintile, there was an 85.7% to 97.7% predicted risk and an 89.7% observed risk of severe disease. Conclusion Being MU was not a predictor of severe disease, even though mortality was higher despite having higher rates of vaccination. This risk score may help to predict severe disease in hospitalized patients with obesity or overweight. External validation is recommended.

Fidaxomicin treatment for Clostridioides difficile infection in patients with inflammatory bowel disease.

BACKGROUND AND AIM: Although fidaxomicin is an effective first-line treatment for Clostridioides difficile infection, it has not been well studied in patients with inflammatory bowel disease. We aimed to assess the effectiveness of fidaxomicin for the treatment of C. difficile infection in patients with inflammatory bowel disease. METHODS: This was a multicenter retrospective study of adults with inflammatory bowel disease and C. difficile infection treated with fidaxomicin with at least 3 months of follow up. The primary outcomes were treatment response, defined as resolution of C. difficile infection-attributed diarrhea and/or negative C. difficile infection stool test, and time to C. difficile infection recurrence after fidaxomicin. RESULTS: Thirty-three patients (median age 42 years; 60.6% female) were included. Most patients had ulcerative colitis (26, 78.8%), were receiving treatment with a biologic or small molecule medication (19, 57.6%), and had a prior episode of C. difficile infection (26, 78.8%, median 2 episodes, range 0-15). Fidaxomicin led to resolution of C. difficile infection in 20 (60.6%) patients, with 6/20 (30.0%) developing a recurrence at a median of 55 days. Most patients who failed to respond to fidaxomicin underwent fecal microbiota transplantation (10/13, 76.9%) with resolution. CONCLUSIONS: In this cohort of patients with inflammatory bowel disease and C. difficile infection, 60.6% responded to treatment with fidaxomicin. Of those who did not respond, fecal microbiota transplantation was an effective therapy.

Number of bottles of esophageal biopsies in the evaluation of eosinophilic esophagitis and clinical outcomes.

BACKGROUND: The number of bottles of esophageal biopsies needed for the evaluation of eosinophilic esophagitis (EoE) is unclear, despite cost differences. AIMS: Assess the clinical outcomes between patients with one and two bottles of esophageal biopsies for the assessment of EoE. METHODS: Retrospective study of adults who underwent esophagogastroduodenoscopy (EGD) for esophageal symptoms between January 2015 and June 2021 and findings of ≥15 eosinophils per high power field (eos/hpf). Patients with one bottle (1 bottle-EoE) had biopsies from the entire or proximal esophagus. Patients with two bottles had biopsies separated from the distal and proximal esophagus and were separated into those with ≥ 15 eos/hpf in both bottles (2 bottle Dif-EoE), or the distal bottle alone (2 bottle Lim-EoE). The primary outcomes were endoscopic findings at follow-up EGD as assessed by the Eosinophilic Esophagitis Endoscopic Reference Score (EREFS) and the presence of ≥15 eos/hpf. RESULTS: Of 85 patients with esophageal eosinophilia who met inclusion criteria, 49 had 2 bottle Dif-EoE, 18 had 2 bottle Lim-EoE, and 18 had 1 bottle-EoE. At median follow-up of 3.3-5.6 months, more patients with 1 bottle EoE had dysphagia (p = 0.029), however there were no differences in the EREFS (p = 0.14) or presence of ≥15 eos/hpf (p = 0.39). More patients with 2 bottle Dif-EoE were treated with topical steroids (16.3% vs. 0% vs. 0%, p = 0.039) and diet (20.4% vs. 0% vs. 5.6%, p = 0.05). CONCLUSION: Endoscopic and histologic outcomes were similar in patients who had one and two bottles for esophageal biopsies in the evaluation of EoE.

Burn Pits: A Possible Trigger for Achalasia.

A 45-year-old female veteran of the United States Air Force (USAF), who was exposed to burn pits on multiple occasions while deployed in the Middle East, presented for a second opinion regarding ongoing chest pain and regurgitation after a Heller myotomy for achalasia. An esophageal X-ray showed no meaningful peristalsis, a slight diverticulum in the distal esophagus, and easy passage of liquids through the lower esophageal sphincter (LES). Esophageal manometry findings were consistent with type 3 achalasia. Based on these and endoscopic evaluation, the prior surgical intervention appeared to be successful for lower esophageal sphincter disruption, so symptoms were managed medically with a proton pump inhibitor, trazodone, and a long-acting nitrate resulting in 70% improvement. We present this case because the patient developed achalasia with a notable history of exposure to open-air burn pits during her military service. While we acknowledge that causality cannot be proven, our case is the first we are aware of that shows a temporal association between burn pit exposure and achalasia. In August of 2022, the United States Congress passed the Promise to Address Comprehensive Toxics (PACT) Act, which expanded the healthcare benefits of veterans exposed to burn pits, making identification of associated conditions a relevant and important endeavor.

An Unusual Cause of GI Blood Loss.

Chronic gastrointestinal bleeding is the leading cause of iron deficiency anemia in developed countries, and most occult bleeds are attributed to upper gastrointestinal tract lesions, which are broadly categorized into mass lesions, vascular, infectious, and inflammatory abnormalities. Gastric polyps account for an exceedingly small portion of these lesions but are of clinical importance because of the risk for progression to malignancy. We describe a patient found to have a gastric foveolar-type adenoma as a rare cause of iron deficiency anemia, with an incidentally found gastric neuroendocrine tumor.

Association Between Coronavirus Disease 2019 and Acute Complicated Diverticulitis.

Background Gastrointestinal manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized. Through potentially overlapping pathophysiology, co-occurrence of COVID-19 and first-time acute diverticulitis has been reported. Our study aims to further characterize this association in COVID-19-positive patients within a large tertiary care academic center. Methodology Patients diagnosed with COVID-19 who subsequently developed acute diverticulitis within 30 days were identified between 2020 and 2022. COVID-19 and acute diverticulitis were diagnosed by polymerase chain reaction and computed tomography, respectively. Patients with prior history of acute diverticulitis were excluded. Patient characteristics and comorbid conditions were collected. Characterization of the COVID-19 course (treatment setting, medical/ventilatory therapy) and acute diverticulitis (treatment setting, medical/surgical therapy, complications) was performed retrospectively. Subanalysis was performed by COVID-19 vaccination status, the severity of COVID-19, and the timing of acute diverticulitis diagnosis. Results A total of 81 patients were identified, with a median duration between COVID-19 diagnosis and acute diverticulitis of 13 days (interquartile range = 2.5-21.0), with 44.4% of patients requiring hospitalization for COVID-19. The all-cause complication rate of acute diverticulitis was noted to be 59.3%, most commonly intestinal perforation (39.5%), abscess formation (37.0%), and peritonitis (14.8%). Although a trend toward increased all-cause complications (65.9%), intestinal perforation (43.9%), and peritonitis (19.5%) was noted in unvaccinated patients, this did not reach significance. Although all-cause complication rate did not differ in patients diagnosed with acute diverticulitis at the time of COVID-19 presentation, a significantly elevated incidence of intestinal perforation (55.9% vs. 27.7%, p = 0.01), peritonitis (29.4% vs. 4.3%, p < 0.01), and the need for emergent surgical intervention (38.2% vs. 10.6%, p < 0.01) was noted. Conclusions Our study indicates that patients diagnosed with first-time acute diverticulitis within 30 days of COVID-19 infection have a high complication rate, most commonly intestinal perforation. Additionally, patients diagnosed with acute diverticulitis at the same time as COVID-19 detection had a significantly elevated rate of complications and emergent surgical needs. Given the high complication rate, patients who develop diverticulitis within a short timeframe of COVID-19 infection may benefit from increased clinician vigilance and monitoring.

First Carpometacarpal Joint Motion and Proximal Migration of the First Metacarpal After Tensioning of a Suture Device Suspensionplasty Compared With Trapeziectomy: A Biomechanical Cadaver Study.

PURPOSE: The purpose of this cadaveric biomechanical experiment was to evaluate the effects of suture button suspensionplasty of the first carpometacarpal joint on thumb biomechanics and thumb position compared with an intact, arthritic specimen. METHODS: Six tendons in 8 cadaver hands were loaded to simulate 6 activities of daily living and passively moved through a circumduction motion. Proximal migration of the base of the first metacarpal was measured using optical motion sensors in the intact hand, after trapeziectomy, and following insertion of a suture button suspensionplasty with nominal tightening (approximately 4.5 N) and with firm tightening (approximately 44.5 N). RESULTS: Removal of the trapezium caused a significant increase in the proximal migration of the first metacarpal during a simulated jar grasp, opposition, flexion, extension, and abduction (average, 9.5 mm) compared with its location with the thumb in the intact, neutral position (average, 3.8 mm). Firm tightening of the tightrope caused a near elimination of the proximal migration of the first metacarpal (average, 0.7 mm). In all 6 static loading cases with the trapezium removed, firm tightening caused a significantly smaller migration than in the absence of tightening. CONCLUSIONS: This biomechanical cadaver study supports the hypothesis that trapeziectomy results in proximal migration of the first metacarpal. Suture suspensionplasty mitigates against this migration while maintaining normal motion of the first metacarpal compared with the intact state. Firm tightening of the suture does not adversely affect the first metacarpal's mobility and further decreases proximal migration. However, firm tightening may cause impingement between the first and second metacarpals. CLINICAL RELEVANCE: Suture button suspensionplasty can be used in addition to trapeziectomy in the treatment of basal joint arthritis, and may diminish the need for ligament reconstruction or temporary K-wire insertion.

HLA-G and CD152 Expression Levels Encourage the Use of Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells as an Alternative for Immunosuppressive Therapy.

Mesenchymal stromal cells (MSCs) have been used in immunosuppressive therapy due to their therapeutic effects, with the HLA-G molecule seeming to play a fundamental role. This work evaluated alternative MSC sources to bone marrow (BM), namely, umbilical cord tissue (UC), adipose tissue (AD) and dental pulp tissue (DP), and the influence of interferon-γ (IFN-γ) and hypoxia on the cultivation of these cells for use in immunosuppression therapies. Expression of costimulatory markers CD40, CD80 and CD86 and immunosuppressive molecules CD152 and HLA-G was analyzed. Lymphocyte inhibition assays were also performed. Sequencing of the HLA-G gene from exons 1 to 5 was performed using next-generation sequencing to determine the presence of alleles. UC-derived MSCs (UCMSCs) expressed higher CD152 and HLA-G1 under standard cultivation. UCMSCs and DP-derived MSCs (DPSCs) secreted similar levels of HLA-G5. All MSC sources inhibited the proliferation of peripheral blood mononuclear cells (PBMCs); growth under regular versus hypoxic conditions resulted in similar levels of inhibition. When IFN-γ was added, PBMC growth was inhibited to a lesser extent by UCMSCs. The HLA-G*01:04:01:01 allele appears to generate a more efficient MSC response in inhibiting lymphocyte proliferation. However, the strength of this conclusion was limited by the small sample size. UCMSCs are an excellent alternative to BM in immunosuppressive therapy: they express high concentrations of inhibitory molecules and can be cultivated without stimuli, which minimizes cost.

Tumor Lysis Syndrome in a Low-Risk Pancreatic Cancer Patient.

Tumor lysis syndrome (TLS) is the most common hematologic emergency encountered during the treatment of high-grade malignancies. While it can lead to death, the prognosis is typically excellent if caught early on in the course. Risk stratification prior to treatment initiation is paramount in deciding the utility of prophylaxis and ultimately in reducing morbidity and mortality. The following case describes the development of TLS in a patient categorized as low risk and highlights the need for further elucidation of a unified risk stratification system.

Carpal Motion in Chronic Geissler IV Scapholunate Interosseous Ligament Wrists.

PURPOSE: This study evaluated the biomechanics of Geissler IV (G4) wrists in cadavers and compared them with intact specimens after multiple ligament sectioning to create scapholunate instability. It also evaluated carpal motion changes after sectioning of the lunotriquetral interosseous ligament (LTIL). METHODS: Eight cadaver wrists determined to be G4 arthroscopically were tested using a wrist joint motion simulator. The LTIL was then sectioned, and carpal motion was recorded again. Carpal motions were compared with 37 normal wrists after sectioning of the scapholunate interosseous ligament and other ligaments to create a G4 wrist. RESULTS: Carpal motion of the 37 normal wrists after ligamentous sectioning was similar to motion of the 8 specimens noted to be G4. These wrists did not demonstrate subluxation of the scaphoid that may occur after ligament sectioning. After sectioning of the LTIL, there were significant changes in lunate and triquetral motion. CONCLUSIONS: These findings support the hypothesis that sectioning multiple ligaments in normal wrists to create scapholunate instability causes average motion comparable to that seen in G4 wrists. Ligamentous sectioning can cause a range of scaphoid instability. Lunotriquetral interosseous ligament sectioning in native G4 wrists caused greater changes in triquetral than scaphoid range of motion. CLINICAL RELEVANCE: Patients with arthroscopically determined G4 lesions have an incompetent SLIL and scapholunate instability but do not necessarily have scapholunate dissociation and subluxation. Cadaver studies that evaluate instability by sectioning specific intact wrist ligaments are similar to the G4 specimens and thus are a good approximation of naturally occurring wrist instability. The functionality of secondary stabilizers not seen arthroscopically may explain the differences in motion. Geissler IV wrists and ligament-sectioned wrists are points on the spectrum of carpal instability, which is determined by the extent of damage to multiple ligamentous structures.

The Expression Profile of Dental Pulp-Derived Stromal Cells Supports Their Limited Capacity to Differentiate into Adipogenic Cells.

Mesenchymal stromal cells (MSCs) can self-renew, differentiate into specialised cells and have different embryonic origins-ectodermal for dental pulp-derived MSCs (DPSCs) and mesodermal for adipose tissue-derived MSCs (ADSCs). Data on DPSCs adipogenic differentiation potential and timing vary, and the lack of molecular and genetic information prompted us to gain a better understanding of DPSCs adipogenic differentiation potential and gene expression profile. While DPSCs differentiated readily along osteogenic and chondrogenic pathways, after 21 days in two different types of adipogenic induction media, DPSCs cultures did not contain lipid vacuoles and had low expression levels of the adipogenic genes proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and CCAAT/enhancer-binding protein alpha (CEBPA). To better understand this limitation in adipogenesis, transcriptome analysis in undifferentiated DPSCs was carried out, with the ADSC transcriptome used as a positive control. In total, 14,871 transcripts were common to DPSCs and ADSCs, some were unique (DPSCs: 471, ADSCs: 1032), and 510 were differentially expressed genes. Detailed analyses of overrepresented transcripts showed that DPSCs express genes that inhibit adipogenic differentiation, revealing the possible mechanism for their limited adipogenesis.

Understanding Hematopoietic Stem Cell Development through Functional Correlation of Their Proliferative Status with the Intra-aortic Cluster Architecture.

During development, hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region through a process of multi-step maturation and expansion. While proliferation of adult HSCs is implicated in the balance between self-renewal and differentiation, very little is known about the proliferation status of nascent HSCs in the AGM region. Using Fucci reporter mice that enable in vivo visualization of cell-cycle status, we detect increased proliferation during pre-HSC expansion followed by a slowing down of cycling once cells start to acquire a definitive HSC state, similar to fetal liver HSCs. We observe time-specific changes in intra-aortic hematopoietic clusters corresponding to HSC maturation stages. The proliferative architecture of the clusters is maintained in an orderly anatomical manner with slowly cycling cells at the base and more actively proliferating cells at the more apical part of the cluster, which correlates with c-KIT expression levels, thus providing an anatomical basis for the role of SCF in HSC maturation.

Stabilizing hepatocellular phenotype using optimized synthetic surfaces.

Currently, one of the major limitations in cell biology is maintaining differentiated cell phenotype. Biological matrices are commonly used for culturing and maintaining primary and pluripotent stem cell derived hepatocytes. While biological matrices are useful, they permit short term culture of hepatocytes, limiting their widespread application. We have attempted to overcome the limitations using a synthetic polymer coating. Polymers represent one of the broadest classes of biomaterials and possess a wide range of mechanical, physical and chemical properties, which can be fine-tuned for purpose. Importantly, such materials can be scaled to quality assured standards and display batch-to-batch consistency. This is essential if cells are to be expanded for high through-put screening in the pharmaceutical testing industry or for cellular based therapy. Polyurethanes (PUs) are one group of materials that have shown promise in cell culture. Our recent progress in optimizing a polyurethane coated surface, for long-term culture of human hepatocytes displaying stable phenotype, is presented and discussed.

Reduced thymic output in elite athletes.

Athletes undergoing intensive training schedules have chronic exposure to stress-induced hormones such as cortisol that can depress immune function. We compared the circulating levels of T cell receptor excision circles (TREC), a marker of recent thymic emigrants, as well as the levels of naïve and memory subsets in a group of elite endurance athletes and in controls. The athletes showed a reduction in absolute numbers of naïve T cells, particularly in CD4 T cells. In contrast, memory cells were increased. TREC levels in the athletes were significantly reduced compared to age-matched controls. Such changes resemble premature ageing of the T cell component of the immune system. Since thymic production of T cells naturally decline with age, these results raise the concern that prolonging high intensity exercise into the 4th decade of life may have deleterious consequences for athletes' health.

Directed osteogenic differentiation of human mesenchymal stem/precursor cells on silicate substituted calcium phosphate.

Insufficient, underactive, or inappropriate osteoblast function results in serious clinical conditions such as osteoporosis, osteogenesis imperfecta and fracture nonunion and therefore the control of osteogenesis is a medical priority. In vitro mesenchymal stem cells (MSCs) can be directed to form osteoblasts through the addition of soluble factors such as ß-glycerophosphate, ascorbic acid, and dexamethasone; however this is unlikely to be practical in the clinical setting. An alternative approach would be to use a scaffold or matrix engineered to provide cues for differentiation without the need for soluble factors. Here we describe studies using Silicate-substituted calcium phosphate (Si-CaP) and unmodified hydroxyapatite (HA) to test whether these materials are capable of promoting osteogenic differentiation of MSCs in the absence of soluble factors. Si-CaP supported attachment and proliferation of MSCs and induced osteogenesis to a greater extent than HA, as evidenced through upregulation of the osteoblast-related genes: Runx2 (1.2 fold), Col1a1 (2 fold), Pth1r (1.5 fold), and Bglap (1.7 fold) Dmp1 (1.1 fold), respectively. Osteogenic-associated proteins, alkaline phosphatase (1.4 fold), RUNX2, COL1A1, and BGLAP, were also upregulated and there was an increased production of mineralized bone matrix (1.75 fold), as detected by the Von Kossa Assay. These data indicate that inorganic substrates are capable of directing the differentiation programme of stem cells in the absence of known chemical drivers and therefore may provide the basis for bone repair in the clinical setting.