Impact of Artificial Intelligence on Miss Rate of Colorectal Neoplasia.

BACKGROUND & AIMS: Artificial intelligence (AI) may detect colorectal polyps that have been missed due to perceptual pitfalls. By reducing such miss rate, AI may increase the detection of colorectal neoplasia leading to a higher degree of colorectal cancer (CRC) prevention. METHODS: Patients undergoing CRC screening or surveillance were enrolled in 8 centers (Italy, UK, US), and randomized (1:1) to undergo 2 same-day, back-to-back colonoscopies with or without AI (deep learning computer aided diagnosis endoscopy) in 2 different arms, namely AI followed by colonoscopy without AI or vice-versa. Adenoma miss rate (AMR) was calculated as the number of histologically verified lesions detected at second colonoscopy divided by the total number of lesions detected at first and second colonoscopy. Mean number of lesions detected in the second colonoscopy and proportion of false negative subjects (no lesion at first colonoscopy and at least 1 at second) were calculated. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted by endoscopist, age, sex, and indication for colonoscopy. Adverse events were also measured. RESULTS: A total of 230 subjects (116 AI first, 114 standard colonoscopy first) were included in the study analysis. AMR was 15.5% (38 of 246) and 32.4% (80 of 247) in the arm with AI and non-AI colonoscopy first, respectively (adjusted OR, 0.38; 95% CI, 0.23-0.62). In detail, AMR was lower for AI first for the ≤5 mm (15.9% vs 35.8%; OR, 0.34; 95% CI, 0.21-0.55) and nonpolypoid lesions (16.8% vs 45.8%; OR, 0.24; 95% CI, 0.13-0.43), and it was lower both in the proximal (18.3% vs 32.5%; OR, 0.46; 95% CI, 0.26-0.78) and distal colon (10.8% vs 32.1%; OR, 0.25; 95% CI, 0.11-0.57). Mean number of adenomas at second colonoscopy was lower in the AI-first group as compared with non-AI colonoscopy first (0.33 ± 0.63 vs 0.70 ± 0.97, P < .001). False negative rates were 6.8% (3 of 44 patients) and 29.6% (13 of 44) in the AI and non-AI first arms, respectively (OR, 0.17; 95% CI, 0.05-0.67). No difference in the rate of adverse events was found between the 2 groups. CONCLUSIONS: AI resulted in an approximately 2-fold reduction in miss rate of colorectal neoplasia, supporting AI-benefit in reducing perceptual errors for small and subtle lesions at standard colonoscopy. CLINICALTRIALS: gov, Number: NCT03954548.

Effect of bowel preparation volume in inpatient colonoscopy. Results of a prospective, randomized, comparative pilot study.

BACKGROUND: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy; however, the optimal bowel preparation regimen for hospitalized patients is unknown. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy. METHODS: This prospective, single blinded (endoscopist), randomized controlled trial was conducted as a pilot study at a tertiary referral medical center. Hospitalized patients undergoing inpatient colonoscopy were assigned randomly to receive a high, medium, or low-volume preparation. Data collection included colon preparation quality, based on the Boston Bowel Preparation Scale, and a questionnaire given to all subjects evaluating the ability to completely finish bowel preparation and adverse effects (unpleasant taste, nausea, and vomiting). RESULTS: Twenty-five colonoscopies were performed in 25 subjects. Patients who received low-volume preparation averaged a higher mean total BBPS (7.4, SD 1.62), in comparison to patients who received high-volume (7.0, SD 1.41) and medium-volume prep (6.9, SD 1.55), P = 0.77. When evaluating taste a higher score meant worse taste. The low-volume group scored unpleasant taste as 0.6 (0.74), while the high-volume group gave unpleasant taste a score of 2.2 (0.97) and the medium-volume group gave a score of 2.1 (1.36), P < 0.01. CONCLUSION: In this pilot study we found that low-volume colon preparation may be preferred in the inpatient setting due its better rate of tolerability and comparable bowel cleanliness when compared to larger volume preparation, although we cannot overreach any definitive conclusion. Further more robust studies are required to confirm these findings. TRIAL REGISTRATION: The Affect of Low-Volume Bowel Preparation for Hospitalized Patients Colonoscopies. TRIAL REGISTRATION: NCT01978509 (terminated). Retrospectively registered on November 07, 2013.

The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study.

BACKGROUND: Numerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined. METHODS: Eight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis. RESULTS: Hydrolysis of blood plasma samples prior to extraction and reporting the results as "curcumin" obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed. CONCLUSIONS: When enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products. TRIAL REGISTRATION: ClinicalTrails.gov, trial identifying number NCT04103788 , September 24, 2019. Retrospectively registered.

Peppermint Oil to Improve Visualization in Screening Colonoscopy: A Randomized Controlled Clinical Trial.

BACKGROUND: Screening colonoscopy has been associated with reduced mortality from colorectal cancer by means of early detection and timely treatment. However, visualization during colonoscopy is often impaired since the colon is naturally prone to peristalsis and spasm. There is evidence to suggest benefit of topical peppermint oil in causing smooth muscle relaxation, thereby decreasing peristalsis. The aim of our study was to determine if peppermint oil helps reduce colonic spasticity so as to allow for better visualization during screening colonoscopy. METHODS: We performed a randomized controlled, double-blinded, clinical trial where patients undergoing screening colonoscopy were assigned to receive either peppermint oil or placebo. Once cecum was reached, 50 mL of either solution was directly injected via the working channel of the colonoscope. Colonic peristalsis, spasticity and bowel visibility were documented. Bowel preparation quality, withdrawal time and adenoma detection rate (ADR) were also assessed. Continuous variables were analyzed using t-test or Wilcoxon rank-sum test while categorical variables were compared using the two-way Chi-square test. RESULTS: Forty-eight patients were included, of whom 24 patients received peppermint oil and 24 received placebo. Mean Boston bowel preparation score (BBPS) was excellent for both groups (8 points vs. 7.9 points; P = 0.98). Both mean total colonoscopy time (17.8 min vs. 21.9 min; P = 0.07) and mean cecal intubation time (7.2 min vs. 10.3 min; P = 0.04) were shorter with peppermint oil as compared to placebo. Complete absence of bowel spasticity was observed among 58.3% patients in the peppermint oil group as compared to 45.8% patients in the placebo group (P = 0.05). More than 75% of bowel was visualized in 83% of patients in both groups (P = 0.56). Mean ADR was higher in the peppermint group as compared to the placebo group (45.8% vs. 37.5%; P = 0.56). CONCLUSION: Our study suggests that topical peppermint oil reduces bowel wall spasticity, which could lead to better visualization of the bowel during screening colonoscopy. Although use of peppermint oil was associated with better ADRs, these results did not achieve statistical significance. Larger sample size and use of alternative methods of peppermint oil administration allowing for more absorption time may establish stronger results.

Beneficial effects of natural eggshell membrane versus placebo in exercise-induced joint pain, stiffness, and cartilage turnover in healthy, postmenopausal women.

PURPOSE: Despite its many health benefits, moderate exercise can induce joint discomfort when done infrequently or too intensely even in individuals with healthy joints. This study was designed to evaluate whether NEM® (natural eggshell membrane) would reduce exercise-induced cartilage turnover or alleviate joint pain or stiffness, either directly following exercise or 12 hours post exercise, versus placebo. PATIENTS AND METHODS: Sixty healthy, postmenopausal women were randomly assigned to receive either oral NEM 500 mg (n=30) or placebo (n=30) once daily for two consecutive weeks while performing an exercise regimen (50-100 steps per leg) on alternating days. The primary endpoint was any statistically significant reduction in exercise-induced cartilage turnover via the biomarker C-terminal cross-linked telopeptide of type-II collagen (CTX-II) versus placebo, evaluated at 1 and 2 weeks of treatment. Secondary endpoints were any reductions in either exercise-induced joint pain or stiffness versus placebo, evaluated daily via participant questionnaire. The clinical assessment was performed on the per protocol population. RESULTS: NEM produced a significant absolute treatment effect (TEabs) versus placebo for CTX-II after both 1 week (TEabs -17.2%, P=0.002) and 2 weeks of exercise (TEabs -9.9%, P=0.042). Immediate pain was not significantly different; however, rapid treatment responses were observed for immediate stiffness (Day 7) and recovery pain (Day 8) and recovery stiffness (Day 4). No serious adverse events occurred and the treatment was reported to be well tolerated by study participants. CONCLUSION: NEM rapidly improved recovery from exercise-induced joint pain (Day 8) and stiffness (Day 4) and reduced discomfort immediately following exercise (stiffness, Day 7). Moreover, a substantial chondroprotective effect was demonstrated via a decrease in the cartilage degradation biomarker CTX-II. Clinical Trial Registration number: NCT02751944.

Is the level of cleanliness using segmental Boston bowel preparation scale associated with a higher adenoma detection rate?

BACKGROUND: The impact of Boston bowel preparation scale (BBPS) scores on the adenoma detection rate (ADR) in each segment has not been adequately addressed. The aim of this study was to determine the association between segmental or overall ADR and serrated polyp detection rate (SDR) with segmental and total BBPS scores. METHODS: All outpatient screening colonoscopies with documented BBPS scores were retrospectively reviewed at a tertiary institution from January to December 2013. Chi-square tests and logistic regression were used to analyze the detection rates of adenomas and serrated polyps with bowel prep scores. Odds ratios were calculated using logistic regression that controlled for withdrawal time, age, body mass index, diabetes status and sex. RESULTS: We analyzed 1991 colonoscopies. The overall ADR was 37.5% (95% confidence interval [CI], 35.3-39.6). There was a significant difference in the overall ADR, and in SDR across all bowel category groups, with total BBPS scores of 8 and 9 having lower detection rates than scores of 5, 6 and 7. As the quality of bowel preparation increased, there was a statistical decrease in the ADR (odds ratio [OR] 0.79 [CI 0.66-0.94], P=0.04) of the right colon, while in the left colon, there was a statistical decrease in SDR (OR 0.78, [CI 0.65-0.92] P=0.019). CONCLUSION: Segmental ADR and SDR both decreased as prep scores increased, decreasing notably in patients with excellent prep scores of 8 and 9. A possible explanation for this unexpected discrepancy may be related to longer and better visualization of the mucosa when cleansing and suctioning is necessary.

Beneficial effects of natural eggshell membrane (NEM) on multiple indices of arthritis in collagen-induced arthritic rats.

OBJECTIVES: This study was performed to evaluate the potential efficacy of natural eggshell membrane (NEM) in collagen-induced arthritic rats, a well-established rodent model of inflammation and rheumatoid arthritis. METHODS: Rats with developing type II collagen-induced arthritis (CIA) were treated once daily by oral gavage on study days -14 to 17 with vehicle or NEM (52 mg/kg body weight). Rats were euthanized on study day 17. Efficacy was assessed by daily ankle caliper measurements, ankle diameter expressed as area under the curve (AUCd0-17), and histopathologic evaluation of ankles and knees. Serum biomarkers of cartilage function and inflammation [collagen type II C-telopeptide (CTXII), cartilage oligomeric matrix protein (COMP), and alpha-2-macroglobulin (A2M)] were measured by ELISA. RESULTS: Treatment with NEM resulted in significant beneficial effects on the daily ankle diameter measurements and ankle diameter AUC. Ankle and knee histopathology scores were significantly reduced (36% and 43% reduction of summed individual histopathology scores for ankle and knee, respectively; p < 0.05) toward normal for rats given NEM compared to vehicle controls. The percent reduction of serum CTXII, COMP, and A2M in NEM-treated rats ranged from 30% to 72% (p < 0.05). CONCLUSIONS: NEM significantly improved multiple aspects of inflammatory arthritis including inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation. This study provides further support for the use of CTXII, COMP, and A2M as relevant biomarkers that were responsive to NEM.

A Mysterious DRESS Case: Autoimmune Enteropathy Associated with DRESS Syndrome.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare but potentially life-threatening cutaneous hypersensitivity reaction characterized by extensive mucocutaneous eruption, fever, hematologic abnormalities, and extensive organ involvement. Here, we present a case of a young woman with DRESS syndrome following exposure to vancomycin with renal, cutaneous, and gastrointestinal involvement. To the best of our knowledge, this is the first case description in the literature of DRESS of the gastrointestinal tract with autoimmune enteropathy.

Effectiveness of NEM® brand eggshell membrane in the treatment of suboptimal joint function in dogs: a multicenter, randomized, double-blind, placebo-controlled study.

INTRODUCTION: Sub-optimal joint function is extremely prevalent in dogs. Therefore, a 6-week, prospective, randomized, double-blind, placebo-controlled study was conducted at eight different veterinary clinics to evaluate the efficacy, safety, and tolerability of NEM® brand eggshell membrane (EM), a novel dietary supplement shown in other species to help maintain healthy joints and connective tissues. SUBJECTS AND METHODS: Fifty-one dogs received oral EM ~13.5 mg/kg (6 mg/lb) or placebo (excipients) once daily for 6 weeks. The primary outcome measure of this study was to evaluate the change in mean joint function following 1 week and 6 weeks of supplementation as determined via the Canine Brief Pain Inventory (CBPI) questionnaire (Q#5-10) in the treatment group versus the placebo group. Secondary outcome measures were for changes in mean CBPI pain and CBPI quality of life, and mean joint pain, mobility and lameness via Veterinary Canine Scoring Assessments (VCSA). A final secondary outcome measure was for a change in serum levels of the cartilage degradation biomarker, c-terminal cross-linked telopeptide of type-II collagen (CTX-II). RESULTS: Supplementation with EM produced a significant treatment response versus placebo at 1 week (20.5% improvement, P=0.028), but fell shy of significance at 6 weeks post-treatment (22.5% improvement) for the primary outcome measure (CBPI Function), despite a sizeable treatment effect. Similarly, there was also a significant treatment response versus placebo at 1 week for CBPI Pain (19.4% improvement, P=0.010), but fell just shy of significance at 6 weeks (22.5% improvement), again despite a sizeable treatment effect. Results were not significant versus placebo at 1 week for CBPI quality of life (14.0% improvement), but produced a significant treatment response by the end of the 6-week study (26.8% improvement, P=0.033). Additionally, EM produced a significant treatment response versus placebo at 6 weeks for VCSA pain (23.6% improvement, P=0.012), but fell shy of significance for VCSA mobility and VCSA lameness (walking & trotting). Serum CTX-II levels in EM-supplemented dogs was significantly improved versus placebo at 6 weeks (47.9% improvement, P=0.018). There were no serious adverse events reported during the study and subject dog owners reported that EM was well tolerated by their pets. CONCLUSION: Supplementation with EM, ~13.5 mg/kg (6 mg/lb) taken once daily, significantly reduced joint pain and improved joint function rapidly (CBPI 1 week) and demonstrated a lasting improvement in joint pain (VCSA 6 weeks) leading to an improved quality of life (CBPI 6 weeks). Moreover, a profound chondroprotective effect was demonstrated following 6 weeks of supplementation with EM (CTX-II).

Kinematic analysis of wrist motion during simulated colonoscopy in first-year gastroenterology fellows.

BACKGROUND AND STUDY AIMS: Gastroenterology trainees acquire skill and proficiency in performing colonoscopies at different rates. The cause for heterogeneous competency among the trainees is unclear. Kinematic analysis of the wrist joint while performing colonoscopy can objectively assess the variation in wrist motion. Our objective was to test the hypothesis that the time spent by the trainees in extreme ranges of wrist motion will decrease as the trainees advance through the fellowship year. SUBJECTS AND METHODS: Five first-year gastroenterology fellows were prospectively studied at four intervals while performing simulated colonoscopies. The setting was an endoscopy simulation laboratory at a tertiary care center. Kinematic assessment of wrist motion was done using a magnetic position/orientation tracker held in place by a custom-made arm sleeve and hand glove. The main outcome measure was time spent performing each of four ranges of wrist motion (mid, center, extreme, and out) for each wrist degree of freedom (pronation/supination, flexion/extension, and adduction/abduction). RESULTS: There were no statistically significant differences in the time spent for wrist movements across the three degrees of freedom throughout the study period. However, fellows spent significantly less time in extreme range (1.47 ±â€Š0.34 min vs. 2.44 ±â€Š0.34 min, P = 0.004) and center range (1.02 ±â€Š0.34 min vs 1.9 ±â€Š0.34 min, P = 0.01) at the end of the study compared to the baseline evaluation. The study was limited by the small number of subjects and performance of colonoscopies on a simulator rather than live patients. CONCLUSIONS: Gastroenterology trainees alter the time spent at the extreme range of wrist motion as they advance through training. Endoscopy training during the first 10 months of fellowship may have beneficial effects on learning ergonomically correct motion patterns.

Endoscopic findings of primary follicular lymphoma.

A 79-year-old female with benign past medical history presented to the gastroenterology clinic complaining of long-standing symptoms of dyspepsia. Esophagogastroduodenoscopy showed nodular smooth mucosa in the second part of the duodenum. The morphologic and immunophenotypic findings were consistent with low-grade follicular lymphoma. The purpose of this manuscript is to educate the reader on this unusual finding that is pathognomonic for gastrointestinal lymphoma.

Endoscopic findings of primary follicular lymphoma / Hallazgo endoscópico de linfoma folicular primario

A 79-year-old female with benign past medical history presented to the gastroenterology clinic complaining of long-standing symptoms of dyspepsia. Esophagogastroduodenoscopy showed nodular smooth mucosa in the second part of the duodenum. The morphologic and immunophenotypic findings were consistent with low-grade follicular lymphoma. The purpose of this manuscript is to educate the reader on this unusual finding that is pathognomonic for gastrointestinal lymphoma.

Una mujer de 79 años, sin antecedentes patológicos de importancia, consultó al servicio de gastro enterología por síntomas de dispepsia de larga data. Se practicó una esofagogastroduodenoscopia en la que se observó mucosa nodular en la segunda porción del duodeno. Esta morfología y los hallazgos inmunofenotípicos eran indicativos de linfoma folicular de bajo grado. El propósito de este manuscrito es ilustrar al lector sobre esta inusual condición en el duodeno, la cual es patognomónica de linfoma.

Eggshell membrane hydrolyzates activate NF-κB in vitro: possible implications for in vivo efficacy.

PURPOSE: Eggshell membrane (ESM) has been shown to contain naturally occurring bioactive components, and biological activities such as reducing proinflammatory cytokines, liver fibrosis, and joint pain in osteoarthritis sufferers have also been reported for ESM matrix as a whole. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) is a signaling protein found in the cytoplasm of nearly all human and animal cell types and is a primary regulator of immune function. The studies reported herein were designed to investigate the possible role that NF-κB activity might play in the reported biological activities of ESM. METHODS: Three ESM hydrolyzates produced via fermentation, enzymatic, or chemical hydrolysis were evaluated in vitro in either human peripheral blood mononuclear cell or THP-1 (human leukemic monocyte) cell cultures for NF-κB activity following 4-hour exposure. The hydrolyzates were compared with untreated control cells or cells incubated with lipopolysaccharide or ascorbic acid. The source of ESM activity was also evaluated. RESULTS: NF-κB levels were increased above levels found in untreated cells at all three dilutions (1:100, 1:1,000, and 1:10,000) for the fermentation hydrolyzate of ESM (ESM-FH) (P=0.021, P=0.020, P=0.009, respectively) in peripheral blood mononuclear cells. The enzymatic hydrolyzate of ESM (ESM-EH) also produced statistically significant levels of activated NF-κB at the 1:100 and 1:1,000 dilutions (P=0.004, P=0.006, respectively) but fell just shy of significance at the 1:10,000 dilution (P=0.073). Similarly, ESM-FH (P=0.021, P=0.002) and ESM-EH (P=0.007, P=0.007) activated NF-κB in THP-1 cells at 1:1,000 and 1:10,000 dilutions, respectively. The chemical hydrolyzate of ESM (ESM-CH) showed statistically significant levels of activation at the 1:1,000 dilution (P=0.005) but failed to differ from untreated cells at the 1:10,000 dilution (P=0.193) in THP-1 cells. CONCLUSION: Results from our studies provide evidence that ESM hydrolyzates significantly activate NF-κB, and the source of this activity was investigated to confirm that it is inherent to ESM and not derived from bacterial contamination. Based on our findings, we propose a plausible hypothesis as to how increased NF-κB activity might translate into the in vivo efficacy that has been observed with ESM via an "oral tolerance" mechanism.

Eosinophilic granulomatosis with polyangiitis and diffuse gastrointestinal involvement.

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg-Strauss syndrome, is a rare systemic small- and medium-sized-vessel vasculitis, characterized by the presence of severe asthma as well as blood and tissue eosinophilia. Gastrointestinal (GI) symptoms, like diarrhea and abdominal pain, are common; however, there are few reports of histologic evidence of GI involvement. We report the case of a patient on treatment for EGPA who presented with recurrent small bowel obstruction and choledocholithiasis. Biopsies of the esophagus, small bowel and common bile duct showed diffuse eosinophilia, with clear EGPA in the GI tract. Improved awareness of GI EGPA may allow for timely management of this disorder.

Characterization of right wrist posture during simulated colonoscopy: an application of kinematic analysis to the study of endoscopic maneuvers.

BACKGROUND: Endoscopic maneuvers are associated with a high incidence of musculoskeletal injuries. OBJECTIVE: To quantify wrist motion patterns during simulated endoscopic procedures to identify potential causes of endoscopy-related overuse injury. DESIGN: Twelve endoscopists with different levels of experience were tested on 2 simulated endoscopic procedures that differed in their level of difficulty. SETTING: Right wrist movement patterns were recorded during simulated colonoscopies by using a magnetic motion-tracking device. Analysis focused on 3 wrist degrees of freedom: abduction/adduction, flexion/extension, and pronation/supination. INTERVENTIONS: Subjects were tested on 2 GI lower endoscopies (colonoscopies) on a simulator. MAIN OUTCOME MEASUREMENTS: Time spent within ranges of the entire wrist range of motion for 3 wrist degrees of freedom. RESULTS: Endoscopists spent up to 30% of the duration of the procedures at the extremes of the wrist joint range of motion. Endoscopic experience did not affect the time spent at the extremes of the wrist joint of motion. The time spent within each range of motion differed depending on the wrist degrees of freedom and difficulty of procedure. LIMITATIONS: This study examined only 1 upper limb joint in a limited number of subjects and did not measure interaction forces with endoscopic tools. CONCLUSIONS: We identified wrist movement patterns that can potentially contribute to the occurrence of musculoskeletal injury in endoscopists. This study lays the foundation for future work on establishing links between upper limb movement patterns and the occurrence of overuse injury caused by repetitive performance of endoscopic procedures.

Cronkhite-Canada syndrome diagnosis in the absence of gastrointestinal polyps: a case report.

A 66-year-old male patient presented with nausea, abdominal pain, occasional rectal bleeding, progressive dysgeusia, onicodystrophy, and alopecia. Endoscopic exam and biopsies revealed severe atrophy and diffuse marked edema of mucosa of stomach and duodenum. No evidence of polyps was found in any portion of the gastrointestinal tract. The diagnosis of Cronkhite-Canada syndrome (CCS) was rendered. The patient symptoms resolved completely after initiation of steroid treatment. This additional case of CCS illustrates how the diagnosis of CCS does not require the presence of polyps but is defined by the appreciation of the diffuse marked edema and atrophy of the gastrointestinal mucosa.

Safety evaluation of a natural eggshell membrane-derived product.

Natural Eggshell Membrane (NEM®) is a novel dietary ingredient that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. NEM® was evaluated for safety via in vitro and in vivo toxicological studies. This included testing for cytotoxicity, genotoxicity, acute oral toxicity, and 90-day repeated-dose oral toxicity. NEM® did not exhibit any cytotoxic effects at a dose of 100 µg in an in vitro human cell viability assay after incubation for up to 20 h. NEM® did not exhibit any genotoxic effects in an in vitro assay of four strains of histidine-dependent Salmonella typhimurium and one strain of tryptophan-dependent Escherichia coli at a dose of up to 5000 µg/plate. NEM® did not exhibit any signs of acute toxicity in rats at a single oral dose of up to 2000 mg/kg body weight, nor signs of toxicity (via urinalysis, hematology, clinical chemistry, or histopathological evaluation) in rats at a repeated oral dose of up to 2000 mg/kg body weight per day for 90 days. The results of these studies suggest that NEM® may be safe for human consumption.

Effects of natural eggshell membrane (NEM) on cytokine production in cultures of peripheral blood mononuclear cells: increased suppression of tumor necrosis factor-α levels after in vitro digestion.

Tumor necrosis factor-α (TNF-α) plays an important role in inflammatory processes. This study examined the effects of natural eggshell membrane (NEM(®)) (ESM Technologies, LLC, Carthage, MO, USA) on interleukin (IL)-2, IL-4, IL-6, IL-10, interferon-γ (IFN-γ), and TNF-α cytokine production by 4-day peripheral blood mononuclear cell (PBMC) cultures exposed to serial dilutions of either an aqueous extract of natural eggshell membrane (NEM-AQ) or NEM subjected to in vitro digestion (NEM-IVD). The effects on cytokine production were also assessed in the presence of phytohemagglutinin (PHA) and pokeweed mitogen (PWM) where exposure to NEM-AQ resulted in reduced levels of proliferation and statistically significant effects on IL-6, IL-10, IFN-γ, and TNF-α cytokine production. NEM-AQ reduced levels of IL-6, IL-10, IFN-γ, and TNF-α in cultures exposed to PHA. In cultures containing PWM, NEM-AQ reduced production of IL-10 and at the highest dose tested increased IL-6 and decreased TNF-α cytokine levels. NEM-IVD, at the two lowest concentrations of product, significantly reduced TNF-α production by PBMC cultures exposed to PWM compared with the in vitro digest control or native NEM. Taken together, these results suggest that NEM-AQ can influence signaling events in response to the T cell-specific mitogen PHA as well as to the mitogen PWM that require cellular cross-talk and that these effects may be partially mediated through a reduction in level of the pro-inflammatory cytokine TNF-α. The suppression of TNF-α production in the presence of NEM-IVD is promising for the use of NEM as a consumable anti-inflammatory product.

Eggshell membrane: a possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies.

BACKGROUND: Natural Eggshell Membrane (NEM) is a novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. Two single center, open-label human clinical studies were conducted to evaluate the efficacy and safety of NEM as a treatment for pain and inflexibility associated with joint and connective tissue disorders. METHODS: Eleven (single-arm trial) and 28 (double-arm trial) patients received oral NEM 500 mg once daily for four weeks. The primary outcome measure was to evaluate the change in general pain associated with the treatment joints/areas (both studies). In the single-arm trial, range of motion (ROM) and related ROM-associated pain was also evaluated. The primary treatment response endpoints were at seven and 30 days. Both clinical assessments were performed on the intent-to-treat (ITT) population within each study. RESULTS: Single-arm trial: Supplementation with NEM produced a significant treatment response at seven days for flexibility (27.8% increase; P = 0.038) and at 30 days for general pain (72.5% reduction; P = 0.007), flexibility (43.7% increase; P = 0.006), and ROM-associated pain (75.9% reduction; P = 0.021). Double-arm trial: Supplementation with NEM produced a significant treatment response for pain at seven days for both treatment arms (X: 18.4% reduction; P = 0.021. Y: 31.3% reduction; P = 0.014). There was no clinically meaningful difference between treatment arms at seven days, so the Y arm crossed over to the X formulation for the remainder of the study. The significant treatment response continued through 30 days for pain (30.2% reduction; P = 0.0001). There were no adverse events reported during either study and the treatment was reported to be well tolerated by study participants. CONCLUSIONS: Natural Eggshell Membrane (NEM) is a possible new effective and safe therapeutic option for the treatment of pain and inflexibility associated with joint and connective tissue (JCT) disorders. Supplementation with NEM, 500 mg taken once daily, significantly reduced pain, both rapidly (seven days) and continuously (30 days). It also showed clinically meaningful results from a brief responder analysis, demonstrating that significant proportions of treated patients may be helped considerably from NEM supplementation. The Clinical Trial Registration numbers for these trials are: NCT00750230 and NCT00750854.