Pouchitis often is diagnosed based on symptoms alone. However, increased stool frequency, urgency, and abdominal pain could be due to a condition resembling irritable bowel syndrome. This study was ...designed to assess the etiology of bowel symptoms using the Pouchitis Disease Activity Index (PDAI).
Symptoms, endoscopy, and histology were assessed in 61 consecutive symptomatic patients with ulcerative colitis after ileal pouch-anal anastomosis. Pouchitis was defined as a PDAI score of > or = 7, cuffitis was defined as endoscopic and histological inflammation of the rectal cuff and no inflammation of the pouch, and irritable pouch syndrome (IPS) was defined as symptoms with a PDAI of <7 and the absence of cuffitis.
Thirty-one patients (50.8%) had pouchitis, four (6.5%) had cuffitis, and 26 (42.6%) had IPS. Demographics were similar in the three groups. Increased stool frequency, urgency, and abdominal cramps were the most common symptoms in the three groups. Rectal bleeding was seen only in cuffitis (p < 0.001). No patient in the three groups had fever. Twenty-seven patients (87.1%) with pouchitis responded to a 2-wk course of ciprofloxacin or metronidazole with a reduction in PDAI scores of > or = 3. All four patients with cuffitis responded to topical hydrocortisone or mesalamine with a reduction in the PDAI symptom component score of > or = 1. Twelve patients with IPS (46.2%) responded to antidiarrheal, anticholinergic, and/or antidepressant therapies with a reduction in the PDAI symptom component score of > or = 1, whereas the remaining patients had persistent symptoms despite therapy.
A substantial number of symptomatic patients after ileal pouch-anal anastomosis do not meet the diagnostic criteria for either pouchitis or cuffitis and have been classified as having IPS. There is an overlap of symptoms among patients with pouchitis, cuffitis, and IPS, and endoscopic evaluation can differentiate among these groups. Distinction between these three groups has therapeutic implications.
•Lp(a) level should be measured at least once in all adults.•Lp(a) levels represent a continuum of risk, not a risk threshold at a dichotomous cutpoint.•Risk classification by Lp(a) level ranges from ...low (<75 nmol/L) to high (≥125 nmol/L).•Lp(a) risk categories apply across races and ethnicities.•High Lp(a) levels warrant early and more-intensive risk factor management.
Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) Lp(a) level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75 nmol/L (30 mg/dL) are considered low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30–50 mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60 mg/dL ∼150 nmol/L) and LDL-C ≥ 100 mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (∼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention.
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: Although platelet‐rich plasma and platelet concentrates have been used to promote bone healing in orthopaedic and maxillofacial surgery, the underlying cellular‐level mechanisms remain poorly ...understood. The present in vitro study investigated the effects of human platelet lysate (PL) on selected functions of cultured bone cells. Cells from 18‐day‐old fetal rat calvaria were isolated by a collagenase digestion procedure. PL was added at different concentrations on pre‐ or post‐confluent cell stage. After 1 day, bone cellproliferation was maximal and half‐maximal in the presence of PL from 3 × 108 and 0.5 × 108 platelets/ml, respectively. During 17 h, the number of bone cells traversing the scrape border of a scrape wound model increased by 16‐fold in the presence of PL from 3 × 108 platelets/ml. The presence of PL from 3 × 108 platelets/ml in pre‐confluent bone cellcultures for 48 h resulted in a threefold decrease of alkaline phosphatase (ALP) specificactivity. In the case of confluent bone cells, the presence of PL (from 1 × 106 to 3 × 108 platelets/ml) for 11 days, the ALP specific activity and total calcium content decreased in a PL dose‐dependent manner and reached a minimum in the presence of PL from 3 × 108 platelets/ml. In summary, short‐term PL exposure (up to 24 h) promotes the proliferative and chemotactic bone cell functions while long‐term PL exposure results in adecrease of both ALP activity and mineral formation. These data show that the soluble components contained in PL may affect the bone healing process by modulating differently bone cell functions.
Résumé
Bien que les concentrés en plaquettes et le plasma riche en plaquettes ont été utilisés pour promouvoir la guérison osseuse dans la chirurgie maxillo‐faciale et orthopédique, les mécanismes aux niveaux cellulaires sous‐jacents restent peu connus. L'étude in vitro présente a étudié les effets du lysate de plaquettes humaines (PL) sur des fonctions sélectives de cellules osseuses en culture. Des cellules du crâne d'un foetus de rat âgé de18 jours ont été isolées par un processus de digestion par collagénase. PL a été ajoutéà différentes concentrations sur les étapes cellulaires pré‐ et post‐confluentes. Après une journée, la prolifération cellulaire osseuse était respectivement maximale et demi‐maximale en présence de PL de 3 × 108 et 0,5 × 108 plaquettes/ml. Durant 17h le nombre de cellules osseuses traversant la bordure rugueuse d'un modèle de guérison non‐lisse augmentait de 16x en présence de PL de 3 × 108 plaquettes/ml. La présence de PL de 3 × 108 plaquettes/ml dans les cultures cellulaires osseuses préconfluentes pendant 48h résultait en triplicata d'activité spécifique de la phosphatase alcaline (ALP). Dans le cas de cellules osseuses confluentes, la présence de PL (de 1 × 106à 3 × 108 plaquettes/ml) pour 11 jours, l'activité spécifique ALP et la teneur totale en calcium diminuaient d'une manière dépendant de la dose de PL et atteignaient un minimum en présence de PL de 3 × 108 plaquettes/ml. L'exposition à court terme de PL (jusqu'à 24h) améliore la prolifération et le chémotactisme des cellules osseuses tandis qu'à long terme il s'ensuit une diminution tant de l'activité ALP que de la formation minérale. Ces données montrent que les composants solubles contenus dans PL peuvent affecter le processus de guérison en modulant différemment les fonctions cellulaires osseuses.
Zusammenfassung
Obwohl plättchenreiches Plasma und Thrombozytenkonzentrate angewendet wurden, um die Knochenheilung in der orthopädischen und maxillofazialen Chirurgie zu fördern, werden die grundlegenden Mechanismen auf Zellularniveau immer noch schlecht verstanden. Die vorliegende in vitro Studie untersuchte die Effekte von menschlichem Thrombozyten‐Lysat (PL) auf ausgewählte Funktionen von gezüchteten Knochenzellen. Zellen von der Kalvaria von 18 Tage alten fötalen Ratten wurden durch ein Kollagenaseverdauungsverfahren isoliert. PL in verschiedenen Konzentrationen wurden dem prä‐ und postkonfluentem Zellstadium zugeführt. Nach einem Tag war die Knochenzellproliferation maximal bei PL von 3 × 108 und halbmaximal bei 0.5 × 108 Thrombozyten/ml. Während 17 Stunden nahm die Anzahl der Knochenzellen, welche die Grenze des Kratzwundenmodells überschritten, bei einer PL von 3 × 108 Thrombozyten/ml um das 16‐fache zu. Die Präsenz von PL in der Konzentration von 3 × 108 Thrombozyten/ml bei prä‐konfluenten Knochenzellkulturen für 48 Stunden bewirkte eine 3‐fache Abnahme der spezifischen Aktivität der alkalischen Phosphatase (ALP). Im Falle von konfluenten Knochenzellen bewirkte PL (von 1 × 106 bis 3 × 108 Thrombozyten/ml) während 11 Tagen, dass die spezifische Aktivität der ALP und der totale Kalziumgehalt in einer PL‐konzentrationsabhängigen Art abnahmen und bei einer Konzentration derPL von 3 × 108 Thrombozyten/ml das Minimum erreichten. Zusammenfassend kann festgehalten werden, dass die kurzzeitige Anwendung (bis 24 Stunden) von PL die proliferativen und chemotaktischen Knochenzellfunktionen fördert, während die langfristige Anwendung von PL zu einer Abnahme von sowohl der ALP Aktivität als auch der Mineralbildung führt. Diese Daten zeigen, dass die löslichen Komponenten, welche in PL enthalten sind, die Prozesse der Knochenheilung durch die Modulation von verschiedenen Knochenzellfunktionen beeinflussen können.
Resumen
Aunque el plasma rico en plaquetas y los concentrados de plaquetas han sido utilizados para promover la cicatrización ósea en cirugía ortopédica y maxilofacial, los mecanismos subyacentes a nivel celular permanecen pobremente comprendidos. El presente estudio in vitro investigó los efectos del lisato plaquetario humano (PL) en funciones seleccionadas de cultivos de células óseas. Se aislaron células de la calvaria fetal de una rata de 18 días por medio de un procedimiento de digestión de colagenasa. Se añadió PL a diferentes concentraciones en fase de pre o post confluencia celular. Tras un día, la proliferación de células óseas fue máxima y medio‐máxima en presencia de PL de 3 × 108 y 0.5 × 108 plaquetas/ml, respectivamente. Durante 17 horas, el número de células óseas que atravesaron el borde arañado de una herida de arañazo aumentó 16 veces en presencia de PL de 3 × 108 plaquetas/ml. La presencia de PL de 3 × 108 plaquetas/ml en cultivos de células óseas preconfluentes durante 48 horas resultó en un descenso de 3 veces de la actividad específica de la fosfatasa alcalina (ALP). En el caso de células óseas confluentes, la presencia de PL (de 1 × 106 a 3 × 108 plaquetas/ml) durante 11 días, la actividad específica de ALP y el contenido total de calcio descendieron en una manera PL dosis dependiente y alcanzó un mínimo en presencia de PL de 3 × 108 plaquetas/ml. En resumen, la exposición de PL a corto plazo (hasta 24 horas) promueve las funciones proliferativas y quimiotácticas de las células óseas mientras que la exposición a largo plazo resulta en un descenso de tanto la actividad de ALP como de la formación mineral. Estos datos muestran que los componentes solubles contenidos en PL pueden afectar al proceso de cicatrización óseo modulando diferentes funciones de las células óseas.
This study investigated the effects of rabbit autologous platelet lysates (APL) on the performance of fillers consisting of calcium carbonate ceramic particles (CP) pertinent to new bone formation ...and repair. Critical-size defects in rabbit femurs and calvaria were filled with CP alone, CP plus APL, and CP plus APL with or without thrombin (THR). After 6 weeks, resorption of CP occurred under all conditions tested in the present study. Compared with respective CP alone controls, addition of APL resulted in significantly higher ceramic resorption, as evidenced by decreased ceramic particle diameter (p < 0.01) and number (p < 0.01) at both defect sites. The presence of THR prevented reduction of both CP diameter and number in the femoral defect sites. Addition of APL to the CP resulted in a significant (p < 0.03) decrease in new bone area at the calvarial sites, but not at the femoral sites; moreover, when THR was added to the CP plus APL fillers, bone formation in the femoral defects was significantly (p < 0.05) reduced. In addition to differences in the respective anatomical and cellular milieu, the biochemical events induced by mechanical loading at the femurs may explain the reduced ceramic particle resorption as well as the enhanced new bone formation when compared with the results obtained at the calvarial defect sites.
There is a direct relationship between the duration and level of exposure to low density lipoprotein cholesterol (LDL-C) levels over one's lifespan and cardiovascular events. Early treatment to lower ...elevated LDL-C is crucial for better outcomes with multiple therapies currently available to reduce atherogenic lipoproteins. Statins remain the foundation of LDL-C lowering therapy as one of the most cost-effective drugs to reduce atherosclerotic events (ASCVD) and mortality. Nonetheless, LDL-driven goal attainment remains suboptimal globally, highlighting a considerable need for non-statin therapies to address residual risk related to statin intolerance, non-adherence, and inherited lipoprotein disorders. LDL-C lowering interventions beyond statins include ezetimibe, PCSK9 monoclonal antibodies, inclisiran and bempedoic acid with specific guideline recommendations as to when to consider each. For patients with homozygous familial hypercholesterolemia requiring more advanced therapy, lomitapide and evinacumab are available, providing mechanisms that are not LDL receptor dependent. Lipoprotein apheresis remains an effective option for clinical familial hypercholesterolemia as well as elevated lipoprotein (a). There are investigational therapies being explored to add to our current armamentarium including CETP inhibitors, a third-generation PCSK9 inhibitor (small recombinant fusion protein oral PCSK9 inhibitor) and gene editing which aims to directly restore or disrupt genes of interest at the DNA level. This article is a brief review of the pharmacotherapy options beyond statins for lowering LDL-C and their impact on ASCVD risk reduction. Our primary aim is to guide physicians on the role these therapies play in achieving appropriate LDL-C goals, with an algorithm of when to consider each based on efficacy, safety and outcomes.
A high frequency of celiac disease is reported in patients with collagenous colitis. Limited information is available on the frequency of celiac disease in lymphocytic colitis. The aim of our study ...was to determine the prevalence of celiac disease in microscopic colitis (collagenous and lymphocytic colitis). Patients were identified from a pathology registry of microscopic colitis from 1987 to 1999. Pathology reports and medical records were reviewed for previous small bowel biopsies and/or celiac serology. We identified 113 patients with microscopic colitis, and 46 patients underwent a small bowel biopsy and/or celiac serology. Of these, 27 patients had lymphocytic colitis (63% female; age, 58.6 +/- 16.2 years) and 19 patients had collagenous colitis (79% female; age, 61.8 +/- 13.6 years). Small bowel biopsy alone was performed in 28 of 46 patients, celiac serology alone was performed in 10, and both small bowel biopsy and celiac serology were performed in 8. Celiac disease was identified in 4 patients by small bowel histology; all had lymphocytic colitis (4 of 27 patients, 15%). This frequency of celiac disease is significantly higher than the highest reported U.S. prevalence of celiac disease (4/1,000 individuals; p < 0.01). There is a high frequency of celiac disease in patients with lymphocytic colitis. Given the importance of the early detection of celiac disease, it should be excluded in all patients with lymphocytic colitis, particularly if diarrhea does not respond to conventional treatment.
Background & Aims: Parenteral control of gastric acid hypersecretion in conditions such as Zollinger–Ellison syndrome (ZES) or idiopathic gastric acid hypersecretion is necessary perioperatively or ...when oral medications cannot be taken for other reasons (e.g., during chemotherapy, acute upper gastrointestinal bleeding, or in intensive care unit settings).
Methods: We evaluated the efficacy and safety of 15-minute infusions of the proton pump inhibitor pantoprazole (80–120 mg every 8–12 hours) in controlling acid output for up to 7 days. Effective control was defined as acid output >10 milliequivalents per hour (mEq/h) (<5 mEq/h in patients with prior acid-reducing surgery) for 24 hours.
Results: The 21 patients enrolled had a mean age of 51.9 years (range, 29–75) and a mean disease duration of 8.1 years (range, <0.5–21); 13 were male, 7 had multiple endocrine neoplasia syndrome type I, 4 had undergone acid-reducing surgery, 2 had received chemotherapy, and 13 had undergone gastrinoma resections without cure. Basal acid output (mean ± SD) was 40.2 ± 27.9 mEq/h (range, 11.2–117.9). In all patients, acid output was controlled within the first hour (mean onset of effective control, 41 minutes) after an initial 80-mg intravenous pantoprazole dose. Pantoprazole, 80 mg every 12 hours, was effective in 17 of 21 patients (81%) for up to 7 days. Four patients required upward dose titration, 2 required 120 mg pantoprazole every 12 hours, and 2 required 80 mg every 8 hours. At study end, acid output remained controlled for 6 hours beyond the next expected dose in 71% of patients (n = 15); mean acid output increased to 4.0 mEq/h (range, 0–9.7). No serious or unexpected adverse events were observed.
Conclusions: Intravenous pantoprazole, 160–240 mg/day administered in divided doses by 15-minute infusion, rapidly and effectively controlled acid output within 1 hour and maintained control for up to 7 days in all ZES patients.
GASTROENTEROLOGY 2000;118:696-704
Gastric volvulus is a life threatening condition characterized by an abnormal rotation of the stomach around an axis. Although the first line treatment of this disorder is surgical, we report here a ...case of gastric volvulus that was endoscopically managed using a novel strategy. An 83-year-old female with a history of pancreatic cancer status postpylorus-preserving Whipple procedure presented with a cecal volvulus requiring right hemicolectomy. Postoperative imaging included a CT scan and upper GI series that showed a gastric volvulus with the antrum located above the diaphragm. An upper endoscopy was advanced through the pylorus into the duodenum and left in this position to keep the stomach under the diaphragm. A second pediatric endoscope was advanced alongside and used to complete percutaneous endoscopic gastrostomy (PEG) placement for anterior gastropexy. The patient’s volvulus resolved and there were no complications. From our review of the literature, the dual endoscopic technique employed here has not been previously described. Patients who are poor surgical candidates or those who do not require emergent surgery can possibly benefit the most from similar minimally invasive endoscopic procedures as described here.
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