Long-term outcomes and adverse effects of teduglutide in patients with short bowel syndrome: Highlighting hyperamylasemia and hyperlipasemia.

PURPOSE: Short bowel syndrome is a malabsorptive condition that occurs due to surgical removal or a congenital absence of a significant portion of the small intestine. Patients with short bowel syndrome often rely on parenteral support for extended periods or even their entire lives. Teduglutide, a glucagon-like peptide-2 analog, has shown promising results in reducing dependency on parenteral support in these patients by promoting intestinal adaptation and enhancing nutrient absorption. However, the long-term safety of teduglutide remains a concern, particularly with respect to its potential for the development of hyperamylasemia and hyperlipasemia. METHODS: This study involved patients who received teduglutide from December 2012 to December 2022 at Boston Medical Center. We evaluated outcomes and adverse events, focusing on hyperamylasemia and hyperlipasemia, through chart review. RESULTS: Thirteen eligible patients were identified who had used teduglutide. Of these, the majority (84.6%) experienced a reduction in parenteral support. A high incidence (72.7%) of nonpathological pancreatic enzyme elevation was observed in patients treated with teduglutide. These elevations were often dose dependent and were not associated with any clinical signs of acute pancreatitis or abnormal imaging findings. CONCLUSION: This study highlights the need for further investigations into the long-term safety of teduglutide and the importance of closely monitoring amylase and lipase levels in patients undergoing treatment with teduglutide.

High-dose intravenous glucocorticoid induces hyperamylasemia: a case series.

BACKGROUND: Glucocorticoids have many side effects, and high-dose intravenous application may cause rare adverse reactions such as hyperamylasemia. The aim of this study is to explore the clinical characteristics, treatment, and prognosis of hyperamylasemia induced by high-dose intravenous glucocorticoids. CASE PRESENTATION: Four Asian female patients, aged between 26 and 71 years, were diagnosed with hyperamylasemia after intravenous administration of high-dose glucocorticoid. Amylase levels were elevated to varying degrees in all patients, but the peaks were below three times the upper limit of normal, and imaging showed no significant pancreatic abnormalities. Two patients developed abdominal pain, which was resolved by inhibition of pancreatic secretion, while the other patients were asymptomatic. Two patients were discharged after a significant decrease in amylase levels, while the other two were discharged after improvement of the primary disease. CONCLUSION: High-dose intravenous glucocorticoid can cause hyperamylasemia, which should be given enough attention by clinicians. Etiological differentiation of hyperamylasemia should be emphasized in clinical practice, especially when the diagnosis of acute pancreatitis is not clear.

Brigatinib Dose Rationale in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: Exposure-Response Analyses of Pivotal ALTA Study.

Brigatinib is a kinase inhibitor indicated for patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer who progressed on or are intolerant to crizotinib. Approval was based on results from a randomized, dose-ranging phase II study (ALK in Lung Cancer Trial of AP26113 (ALTA)). Despite an apparent dose-response relationship for efficacy in ALTA, an exposure-response relationship was not discernable using static models driven by time-averaged exposure. However, exposure-response modeling using daily time-varying area under the concentration curve as the predictor in time-to-event models predicted that increasing the dose of brigatinib (range, 30 mg once daily (q.d.) to 240 mg q.d.) would result in clinically meaningful improvements in progression-free survival (PFS), intracranial PFS, and overall survival. Grade ≥ 2 rash and amylase elevation were predicted to significantly increase with brigatinib exposure. These results provided support for a favorable benefit-risk profile with the approved dosing regimen (180 mg q.d. with 7-day lead-in at 90 mg) versus 90 mg q.d.

Hiperamilasemia y broncoaspiración asociadas a Carbonatode Lantano / No disponible

No disponible

Acute pancreatitis associated with lamivudine therapy for chronic B hepatitis.

Hyperamylasemia is a common complication during lamivudine use. We report a case of a pancreatitis following lamivudine therapy. A careful monitoring of amylase levels during treatment with lamivudine is discussed, mainly in the first weeks, considering the cost of this exam and further complication.

Acute pancreatitis associated with lamivudine therapy for chronic B hepatitis

Hyperamylasemia is a common complication during lamivudine use. We report a case of a pancreatitis following lamivudine therapy. A careful monitoring of amylase levels during treatment with lamivudine is discussed, mainly in the first weeks, considering the cost of this exam and further complication.

Toxicogenética del tratamiento antirretroviral (y II): neurotoxicidad, hepatotoxicidad, acidosis láctica, daño renal y otros efectos adversos del tratamiento antirretroviral / Toxicogenetics of antiretroviral treatment (II): Neurotoxicity, hepatotoxicity, lactic acidosis, kidney damage, and other adverse effects of antiretroviral drugs

Diversos estudios farmacogenéticos han analizado la influencia de determinados polimorfismos genéticos en la toxicidad del tratamiento antirretroviral. En esta revisión se describen algunos de los efectos adversos de los fármacos antirretrovirales en los que se ha documentado que puede existir una predisposición genética: la toxicidad neurológica en pacientes en tratamiento con efavirenz, por lo general asociada al polimorfismo 516G>T de la isoenzima hepática 2B6 del sistema del citocromo P450 (CYP2B6); las reacciones de hipersensibilidad a nevirapina asociadas con alelos específicos del complejo mayor de histocompatibilidad (HLA), principalmente el alelo HLADRB1* 0101 que, en combinación con un recuento elevado de linfocitos CD4, se ha asociado a reacciones sistémicas y hepatitis en pacientes de raza caucásica, y el alelo HLACw8 asociado con las reacciones de hipersensibilidad en personas de la isla italiana de Cerdeña y de Japón; la hepatotoxidad con nevirapina (NVP) asociada al polimorfismo C>T en la posición 3435T del gen ABCB1 (MDR-1) que codifica la glucoproteína P (gp- P) (protector); la hiperbilirrubinemia en pacientes expuestos a atazanavir o indinavir portadores del polimorfismo UGT1A1*28; la neuropatía periférica con análogos de nucleósidos asociada al haplogrupo T del genoma mitocondrial (mayor riesgo) y al genotipo HFE C282Y del gen de la hemocromatosis (protector); la mutación en el codón 964 (R964C) del gen POLG que codifica la ADN polimerasa mitocondrial gamma descrita en un paciente tailandés con acidosis láctica; los haplotipos ABCC2 asociados con la tubulopatía proximal inducida por tenofovir, y el riesgo de pancreatitis en las personas con mutaciones en los genes CFTR y SPINK-1(AU)

Several pharmacogenetics studies have analyzed the influence of specific genetic polymorphisms on the toxicity of antiretroviral treatment. The present review describes some of the adverse effects of antiretroviral drugs in which a genetic predisposition may be involved: efavirenz-induced neurological toxicity, generally associated with the 516G>T polymorphism of liver enzyme cytochrome P450 2B6 (CYP2B6); hypersensitivity reactions to nevirapine, associated with specific alleles of major histocompatibility complex, mainly the HLADRB1* 0101 allele, which, in combination with a high CD4 lymphocyte count, has been associated with systemic reactions and hepatitis in Caucasians, and the HLA-Cw8 allele, which is associated with hypersensitivity reactions in persons from the Italian island of Sardinia and from Japan; nevirapine-induced hepatotoxicity associated with the C>T polymorphism in position 3435T of the ABCB1 (MDR-1) gene codifying for glycoprotein P (lower risk); hyperbilirubinemia in patients exposed to atazanavir or indinavir carrying the UGT1A1*28 polymorphism; peripheral neuropathy with nucleoside analogues associated with haplogroup T of the mitochondrial genome (higher risk) and with the HFE C282Y genotype of the hemochromatosis gene (lower risk); the mutation in codon 964 (R964C) of the POLG gene that codifies the mitochondrial polymerase DNA gamma described in a Thai patient with lactic acidosis; the ABCC2 gene haplotypes associated with tenofovir-induced proximal tubulopathy, and the risk of pancreatitis in persons with mutations in the CFTR and SPINK-1 genes(AU)

Propofol-induced hyperamylasaemia in a general intensive care unit.

This study examined the incidence of hyperamylasaemia, in the absence of other plausible causes of pancreatic dysfunction, in intensive care unit (ICU) patients who received propofol. One-hundred-and-seventy-two consecutive patients of a general ICU who stayed for more than 24 hours were studied. Patients with a diagnosis consistent with elevated serum amylase levels at admission were excluded from the study, as were patients who had received medications known to raise serum amylase levels. Forty-four patients 53 +/- 20 years of age and median duration of ICU stay of five days (range two to 55) were eligible. Thirty of those, aged 54 +/- 21 years and median duration of ICU stay of five days (range two to 27) received continuous infusion of propofol for sedation (maximum dose 45 microg/kg/min). Of the 30 patients who received propofol, 16 (53%) developed hyperamylasaemia (125 to 466 IU/l) after two to nine days of continuous infusion. Liver and kidney function remained normal throughout the observation period. Of the 14 patients who did not receive propofol (aged 51 +/- 18 years), only two (14%) developed hyperamylasaemia, a significantly lower incidence (P = 0.021). Propofol infusion is associated with biochemical evidence of pancreatic injury. Amylase levels monitoring of propofol-sedated patients is warranted.

Hyperamylasemia and acute pancreatitis following anticholinesterase poisoning.

A prospective study was undertaken to find the incidence of hyperamylasemia and acute pancreatitis in patients with anticholinesterase poisoning. This was done by serial estimation of total serum amylase and pancreatic imaging by ultrasonography and confirmed, if necessary, by computerized tomography. Anticholinesterase poisoning was caused by either ingestion or accidental exposure to organophosphates or carbamates; it was diagnosed when patients presented with features of cholinergic crisis, depressed serum butyrylcholinesterase activity of >50% and showed improvement following administration of atropine alone or atropine and 2-PAM. All the patients admitted with anticholinesterase poisoning between July 2001 and June 2005 were prospectively studied for elevated serum amylase. The serum amylase levels were estimated daily up to 10 days in survivors and in nonsurvivors till they survived. Ultrasonography of the abdomen was carried out in all to find swelling of the pancreas. Computerized tomography was undertaken in those who had a swollen pancreas or whose serum amylase levels were elevated significantly (> or =800 S.U). Of the 86 patients enrolled, 79 were taken up for analysis as data were incomplete in 7. Of the 79 patients, serum amylase was found to be elevated that is, >200 S.U. in 37 patients (46.95%). In three patients it was 800 S.U. One of them showed swollen pancreas on ultrasonography, which was confirmed by computerized tomography. This patient had ingested propoxyfur. In the other two patients, evidence of acute pancreatitis was not observed (on autopsy in one who died and on imaging in the other who survived). They had ingested chlorpyrifos. There was no significant correlation between the nature of the compounds (organophosphate or carbamates), inhibition of serum BUChE at admission, duration and severity of cholinergic syndrome and increase and time course of increase in serum amylase. Except for fenthion, significant persistent increase in serum amylase was not observed with individual compounds. The other associated abnormalities were polymorphonuclear leukocytosis (TLC >11,000/cumm) in all 37 patients who had elevated amylase, hyperglycemia (6/37) and, elevated transaminases (6/37). Mild elevation of serum amylase is common in patients with anticholinesterase poisoning. However, acute pancreatitis is rare.

Efecto de la administración de indometacina rectal sobre los niveles séricos de amilasa posteriores a colangiopancreatografía retrógrada endoscópica y su impacto en la aparición de episodios de pancreatitis secundaria / Effect of the rectal administration of indomethacin on amylase serum levels after endoscopic retrograde cholangiopancreatography, and its impact on the development of secondary pancreatitis episodes

Introducción: hiperamilasemia y pancreatitis aguda representan las complicaciones mayores más frecuentes posteriores a colangiopancreatografía retrógrada endoscópica (CPRE), apareciendo en 1-30% de los casos. Objetivo: determinar la incidencia de hiperamilasemia y pancreatitis posterior a CPRE y evaluar la utilidad de indometacina rectal para la prevención de estos. Material y métodos: ensayo clínico controlado. Durante un periodo de 12 meses se incluyeron 150 pacientes. Estos fueron divididos en grupo de estudio (n = 75), a quienes se administró indometacina rectal 100 mg 2 horas previas al procedimiento, y control (n = 75) que recibió glicerina. Dos horas posteriores a la CPRE se determinó el nivel de amilasa sérica y se clasificaron en: 0 = 600 UI/l. Los episodios de pancreatitis clínica se cuantificaron y clasificaron de acuerdo a los criterios de Ranson. Resultados: distribución por género: 100 mujeres y 50 hombres. Edad media: 55,37 ± 18,0 para el grupo de estudio y 51,1 ± 17,0 para el control. El diagnóstico de patología benigna se presentó en 56 (74,7%) casos del grupo de estudio y 59 (78,7%) del control. Posterior al procedimiento, 13 (17,3%) pacientes del grupo experimental y 28 (37,3%) del control desarrollaron hiperamilasemia (p 600 UI/l en 3 pacientes del grupo de estudio y 10 del control (p = 0,001). Se detectó pancreatitis leve en 5,3% de los pacientes del grupo de estudio y 16% del control (p < 0,05). No hubo mortalidad ni eventos adversos. Conclusiones: indometacina rectal previo a CPRE disminuye el riesgo de hiperamilasemia y pancreatitis. La indometacina es accesible, de bajo costo con mínimos o nulos efectos secundarios

Background: hyperamylasemia and acute pancreatitis represent the most frequent major complication after endoscopic retrograde cholangiopancreatography (ERCP), developing in 1-30% of cases. Objective: to determine the incidence of hyperamylasemia and acute pancreatitis after ERCP, and to assess the utility of rectal indomethacin to prevent these events. Material and methods: a randomized clinical trial. During a 12-month period 150 patients were included. They were divided up into a study group (n = 75), where 100 mg of rectal indomethacin were administered 2 hours prior to the procedure, and a control group (n = 75), which received rectal glycerin. Two hours after ERCP serum amylase levels were measured and classified as follows: 0 = 600 IU/L. Clinical pancreatitis episodes were quantified and classified according to Ranson’s criteria. Results: gender distribution: 100 women and 50 men. Mean age: 55.37 ± 18.0 for the study group, and 51.1 ± 17.0 for the control group. A diagnosis of benign pathology was present in 56 (74.7%) cases in the study group, and 59 (78.7%) controls. After ERCP 13 (17.3%) patients in the study group and 28 (37.3%) in the control group developed hyperamylasemia (p 600 IU/L was found in 3 patients in the study group, and in 10 in the control group (p = 0.001). Mild pancreatitis was detected in 4 (5.3%) patients in the study group, and in 12 (16%) patients in the control group (p = 0.034). There were no deaths or adverse drug reactions. Conclusions: rectal indomethacin before ERCP decreases the risk of hyperamylasemia and pancreatitis. Indomethacine is a feasible, low-cost drug with minimal or nil side effects

Hyperamylasaemia and acute pancreatitis in paracetamol poisoning.

BACKGROUND: Hyperamylasaemia and even acute pancreatitis have been reported in patients with paracetamol poisoning. AIMS: To describe the incidence, clinical characteristics, and prognostic implications of hyperamylasaemia in paracetamol poisoning. PATIENTS: Six hundred and two patients transferred to a specialized unit with severe paracetamol poisoning and 212 unselected patients admitted from the local region. METHODS: Retrospective study based on hospital charts. The optimum threshold of serum amylase to discriminate non-survivors was identified. RESULTS: An elevated serum amylase (>100 U/L) occurred in 28 of the unselected patients (13%), in 218 of the transferred patients (36%), and in 118 of 148 patients (80%) with fulminant hepatic failure. Only 33 cases of paracetamol-associated acute pancreatitis were diagnosed. A threshold serum amylase of 150 U/L to discriminate non-survivors had sensitivity 76%, specificity 85%, positive predictive value 33%, and negative predictive value 97%. In a logistic regression analysis, a serum amylase > 150 U/L was associated with an excess mortality (odds ratio 5.0, 2.6-9.7). CONCLUSIONS: Hyperamylasaemia is frequent in patients with paracetamol poisoning, whereas clinical acute pancreatitis occurs rarely. The incidence of hyperamylasaemia increases with the degree of hepatic dysfunction. A serum amylase exceeding 1.5 times the upper normal limit indicates a poor prognosis.