Background: Highly effective and well-tolerated direct-acting antiviral (DAA) therapies have revolutionised the management of hepatitis C virus (HCV); however, niche populations face treatment barriers. DAAs co-prescribed with several first-generation anti-epileptic drugs (AEDs) are contraindicated due to drug-drug interactions. A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir, glecaprevir and pibrentasvir due to potent cytochrome P450 (CYP) 3A4 induction. Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir's area under curve to infinite time. Sofosbuvir-velpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently, virological treatment failure. This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible, impractical or unacceptable. However, the properties of current generation DAA therapies, including high-potency non-structural protein 5A inhibitory effect, may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction.
Case summary: We present a case series of three patients with non-cirrhotic, treatment-naïve, genotype 1a, 1b, and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir, while co-prescribed carbamazepine for seizure disorders. Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants. DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration, and taken with meals to improve absorption. Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes.
Conclusion: DAA therapies, including glecaprevir-pibrentasvir, warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine, particularly if AED substitution is not feasible.
Fluid therapy/resuscitation is mandatory in acute pancreatitis due to the pathophysiology of fluid loss as a consequence of the inflammatory process. For many years, without clear evidence, early and aggressive fluid resuscitation with crystalloid solutions (normal saline solution or Ringer lactate solution) was recommended. Recently, many randomized control trials and meta-analyses on fluid therapy have revealed that high fluid rate infusion is associated with increased mortality and severe adverse events compared to those resulting from moderate fluid rates, and this has triggered a paradigm shift in fluid management strategies. Meanwhile, there is evidence to show that Ringer lactate solution is superior to normal saline solutions in this context. The purpose of this review is to provide an update on the strategies for intravenous fluid treatment in acute pancreatitis, including the type, optimal amount, rate of infusion, and monitoring guides. Recommendations from recent guidelines are critically evaluated for this review in order to reach the authors' recommendations based on the available evidence.
Background: Slow transit constipation (STC) is a disorder with delayed colonic transit. Cinnamic acid (CA) is an organic acid in natural plants, such as Radix Scrophulariae (Xuan Shen), with low toxicity and biological activities to modulate the intestinal microbiome.
Aim: To explore the potential effects of CA on the intestinal microbiome and the primary endogenous metabolites-short-chain fatty acids (SCFAs) and evaluate the therapeutic effects of CA in STC.
Methods: Loperamide was applied to induce STC in mice. The treatment effects of CA on STC mice were assessed from the 24 h defecations, fecal moisture and intestinal transit rate. The enteric neurotransmitters: 5-hydroxytryptamine (5-HT) and vasoactive intestinal peptide (VIP) were determined by the enzyme-linked immunosorbent assay. Hematoxylin-eosin and Alcian blue and Periodic acid Schiff staining were used to evaluate intestinal mucosa's histopathological performance and secretory function. 16S rDNA was employed to analyze the composition and abundance of the intestinal microbiome. The SCFAs in stool samples were quantitatively detected by gas chromatography-mass spectrometry.
Results: CA ameliorated the symptoms of STC and treated STC effectively. CA ameliorated the infiltration of neutrophils and lymphocytes, increased the number of goblet cells and acidic mucus secretion of the mucosa. In addition, CA significantly increased the concentration of 5-HT and reduced VIP. CA significantly improved the diversity and abundance of the beneficial microbiome. Furthermore, the production of SCFAs [including acetic acid (AA), butyric acid (BA), propionic acid (PA) and valeric acid (VA)] was significantly promoted by CA. The changed abundance of Firmicutes, Akkermansia, Lachnoclostridium, Monoglobus, UCG.005, Paenalcaligenes, Psychrobacter and Acinetobacter were involved in the production of AA, BA, PA and VA.
Conclusion: CA could treat STC effectively by ameliorating the composition and abundance of the intestinal microbiome to regulate the production of SCFAs.
In this commentary, we summarize some of the key points of the original paper "Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality, complications, or outcomes" and offer support for the proposed results. Specifically, we address how early percutaneous endoscopic gastrostomy (PEG) tube placement may reduce hospital length of stay and costs. We also discuss topics related to the article including PEG weaning and post-stroke nutritional formulation. However, we note that concerns purported by previous studies that early PEG placement may worsen outcomes are not fully addressed, and further research is needed.
Background: Obscure small bowel bleeding is defined as gastrointestinal bleeding (GIB) that is unidentifiable with esophagogastroduodenoscopy and a colonoscopy with video capsule endoscopy (VCE) being the next gold standard step for evaluation. Small bowel transit time (SBTT) is a metric of a VCE study that is defined as the time the capsule takes to travel through the small intestine.
Aim: To determine if SBTT within the VCE study, correlates to overall detection of obscure small bowel bleeds. Furthermore, we attempted to identify any existing correlation between SBTT and re-bleeding after a negative VCE study.
Methods: This is a single center retrospective analysis of VCE studies performed for overt and occult GIB at Einstein Medical Center, Philadelphia, between 2015 and 2019. Inclusion criteria primarily consisted of patients 18 years or older who had a VCE study done as part of the workup for a GIB. Patients with incomplete VCEs, poor preparation, or with less than 6 mo of follow up were excluded. A re-bleeding event was defined either as overt or occult within a 6-mo timeframe. Overt re-bleeding was defined as Visible melena or hematochezia with > 2 gm/dL drop in hemoglobin defined an overt re-bleeding event; whereas an unexplained > 2 gm/dL drop in hemoglobin with no visible bleeding defined an occult re-bleed.
Results: Results indicated that there was a significant and positive point biserial correlation between SBTT of 220 min and detection of a bleeding focus with a statistically significant p value of 0.008. However, the area under the curve was negligible when trying to identify a threshold time for SBTT to discriminate between risk of re-bleeding events after a negative VCE.
Conclusion: In terms of SBTT and association with accuracy of VCE finding a bleeding focus, 220 min was found to be adequate transit time to accurately find a bleeding focus, when present. It was found that no threshold SBTT could be identified to help predict re-bleeding after a negative VCE.
Background: In monotherapy studies for bleeding peptic ulcers, large volumes of epinephrine were associated with a reduction in rebleeding. However, the impact of epinephrine volume in patients treated with combination endoscopic therapy remains unclear.
Aim: To assess whether epinephrine volume was associated with bleeding outcomes in individuals who also received endoscopic thermal therapy and/or clipping.
Methods: Data from 132 patients with Forrest class Ia, Ib, and IIa peptic ulcers were reviewed. The primary outcome was further bleeding at 7 d; secondary outcomes included further bleeding at 30 d, need for additional therapeutic interventions, post-endoscopy blood transfusions, and 30-day mortality. Logistic and linear regression and Cox proportional hazards analyses were performed.
Results: There was no association between epinephrine volume and all primary and secondary outcomes in multivariable analyses. Increased odds for further bleeding at 7 d occurred in patients with elevated creatinine values (aOR 1.96, 95%CI 1.30-3.20; P < 0.01) or hypotension requiring vasopressors (aOR 6.34, 95%CI 1.87-25.52; P < 0.01). Both factors were also associated with all secondary outcomes.
Conclusion: Epinephrine maintains an important role in the management of bleeding ulcers, but large volumes up to a range of 10-20 mL are not associated with improved bleeding outcomes among individuals receiving combination endoscopic therapy. Further bleeding is primarily associated with patient factors that likely cannot be overcome by increased volumes of epinephrine. However, in carefully-selected cases where ulcer location or size pose therapeutic challenges or when additional modalities are unavailable, it is conceivable that increased volumes of epinephrine may still be beneficial.
Background: Percutaneous Endoscopic Gastrostomy (PEG) tubes are often placed for dysphagia following a stroke in order to maintain sufficient caloric intake. The 2011 ASGE guidelines recommend delaying PEG tube placement for two weeks, as half of patients with dysphagia improve within 2 wk. There are few studies comparing outcomes based on timing of PEG tube placement, and there is increasing demand for early PEG tube placement to meet requirements for timely discharge to rehab and skilled nursing facilities.
Aim: To assess the safety of early (≤ 7 d post stroke) vs late (> 7 d post stroke) PEG tube placement and evaluate whether pre-procedural risk factors could predict mortality or complications.
Methods: We performed a retrospective study of patients undergoing PEG tube placement for dysphagia following a stroke at two hospitals in Saint Louis, MO between January 2011 and December 2017. Patients were identified by keyword search of endoscopy reports. Mortality, peri-procedural complication rates, and post-procedural complication rates were compared in both groups. Predictors of morbidity and mortality such as protein-calorie malnutrition, presence of an independent cardiovascular risk equivalent, and presence of Systemic inflammatory response syndrome (SIRS) criteria or documented infection were evaluated by multivariate logistic regression.
Results: 154 patients had a PEG tube placed for dysphagia following a stroke, 92 in the late group and 62 in the early group. There were 32 observed deaths, with 8 occurring within 30 d of the procedure. There was an increase in peri-procedural and post-procedural complications with delayed PEG placement which was not statistically significant. Hospital length of stay was significantly less in patients with early PEG tube placement (12.9 vs 22.34 d, P < 0.001). Protein calorie malnutrition, presence of SIRS criteria and/or documented infection prior to procedure or having a cardiovascular disease risk equivalent did not significantly predict mortality or complications.
Conclusion: Early PEG tube placement following a stroke did not result in a higher rate of mortality or complications and significantly decreased hospital length of stay. Given similar safety outcomes in both groups, early PEG tube placement should be considered in the appropriate patient to potentially reduce length of hospital stay and incurred costs.
Background: Acute pancreatitis (AP) presenting as an initial manifestation of primary hyperparathyroidism (PHPT) is uncommon, and its timely diagnosis is crucial in preventing recurrent attacks of pancreatitis.
Aim: To determine the clinical, biochemical, and radiological profile of PHPT patients presenting as AP.
Methods: This is a retrospective observational study, 51 consecutive patients admitted with the diagnosis of PHPT during January 2010 and October 2021 at a tertiary care hospital in Puducherry, India was included. The diagnosis of AP was established in the presence of at least two of the three following features: abdominal pain, levels of serum amylase or lipase greater than three times the normal, and characteristic features at abdominal imaging.
Results: Out of the 51 consecutive patients with PHPT, twelve (23.52%) had pancreatitis [5 (9.80%) AP, seven (13.72%) chronic pancreatitis (CP)]. PHPT with AP (PHPT-AP) was more common among males with the presentation at a younger age (35.20 ± 16.11 vs 49.23 ± 14.80 years, P = 0.05) and lower plasma intact parathyroid hormone (iPTH) levels [125 (80.55-178.65) vs 519.80 (149-1649.55, P = 0.01)] compared to PHPT without pancreatitis (PHPT-NP). The mean serum calcium levels were similar in both PHPT-AP and PHPT-NP groups [(11.66 ± 1.15 mg/dL) vs (12.46 ± 1.71 mg/dL), P = 0.32]. PHPT-AP also presented with more gastrointestinal symptoms like abdominal pain, nausea, and vomiting with lesser skeletal and renal manifestations as compared to patients with PHPT-NP.
Conclusion: AP can be the only presenting feature of PHPT. Normal or higher serum calcium levels during AP should always draw attention towards endocrine causes like PHPT.
Biliary atresia (BA) and choledochal cysts are diseases of the intrahepatic and extrahepatic biliary tree. While their exact etiopathogeneses are not known, they should be treated promptly due to the potential for irreversible parenchymal liver disease. A diagnosis of BA may be easy or complicated, but should not be delayed. BA is always treated surgically, and performing the surgery before the age of 2 mo greatly increases its effectiveness and extends the time until the need for liver transplantation arises. While the more common types of choledochal cysts require surgical treatment, some can be treated with endoscopic retrograde cholangiopancreatography. Choledochal cysts may cause recurrent cholangitis and the potential for malignancy should not be ignored.
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