-
Journal of Clinical Medicine Aug 2023Patients with Crohn's disease can present with a variety of clinical manifestations; treatment strategies should focus on long-term remission and improvement of quality... (Review)
Review
Patients with Crohn's disease can present with a variety of clinical manifestations; treatment strategies should focus on long-term remission and improvement of quality of life. There is no standardized process of diagnosing, predicting prognosis, and treating the disease. This narrative review was based on a literature search using PubMed, Embase, and Science Direct. Data on unmet challenges in patients with Crohn's disease were extracted from identified manuscripts. The aim was to discuss present research on standardized processes in the management of patients with Crohn's disease and to identify the unmet needs in clinical evaluation and treatment approaches. There is no consensus on standardized diagnostic, treatment, and surveillance algorithms, particularly in assessing complications of Crohn's, such as stricturing disease, intestinal cancer risk, and cutaneous manifestations. Complications and treatment failure rates of conventional, interventional, and surgical therapy place emphasis on the need for standardized treatment algorithms, particularly in the case of acute complications of the disease. Research on standardized clinical approaches, reliable biomarkers for disease diagnosis and therapy monitoring, and new treatment agents is necessary to improve therapy and reduce complications in patients with Crohn's disease.
PubMed: 37685662
DOI: 10.3390/jcm12175595 -
International Journal of Pharmaceutics:... Dec 2023Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular...
Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular structure, its delivery through the oral route is challenging, limiting its administration to only via the parenteral route. The rectal route offers an alternative way for administering infliximab, allowing it to be localised at the disease site and circumventing its passage across the alimentary canal and thus, maintaining its integrity and bioactivity. Three-dimensional (3D) printing is an advanced production technology that permits the creation of dose-flexible drug products from digital designs. The current study assessed the feasibility of utilising semi-solid extrusion 3D printing for the fabrication of infliximab-loaded suppositories for the local treatment of IBD. Various printing inks composed of Gelucire® (48/16 or 44/14) mixed with coconut oil and/or purified water were investigated. It was shown that following reconstitution in water, the infliximab solution can be directly incorporated into the printing ink of Gelucire® 48/16 and can withstand the extrusion process, resulting in well-defined suppositories. Since water content and temperature are critical for safeguarding infliximab's potency, the effect of changing the composition of the printing inks and printing parameters on infliximab's biologic efficiency was evaluated by measuring its binding capacity (i.e., the amount of infliximab that actively binds to its antigen to exert an effect). Despite drug loading assays showing that infliximab remains intact following printing, it was found that the incorporation of water in isolation results in only ∼65% binding capacity. However, when oil is added to the mixture, infliximab's binding capacity increases up to ∼85%. These promising results demonstrate that 3D printing has the potential to be exploited as a novel platform for fabricating dosage forms containing biopharmaceuticals, avoiding patients' compliance issues observed with injectables and addressing their unmet needs.
PubMed: 37396625
DOI: 10.1016/j.ijpx.2023.100176 -
Revista Espanola de Enfermedades... Feb 2024Ogilvie syndrome is a functional disorder of colonic motility that causes acute and progressive dilation, which can lead to necrosis and perforation. Early diagnosis and...
Ogilvie syndrome is a functional disorder of colonic motility that causes acute and progressive dilation, which can lead to necrosis and perforation. Early diagnosis and management are essential to avoid serious complications. The case of a patient with Ogilvie syndrome refractory to medical and endoscopic treatment that required surgery is presented. This is a 68-year-old man with decreased level of consciousness and abdominal distension for 3 days. Last bowel movement 4 days ago. The data and tests appear in table 1. We are faced with a patient with neurological alteration and hemodynamically unstable secondary to complicated Ogilvie syndrome. After admission to the ICU, where a 2.5 mg bolus of neostigmine was administered, he was transferred to the ward. Despite 250 mg of intravenous erythromycin every 6 hours together with metoclopramide every 8 hours, high doses of polyethylene glycol and daily cleansing enemas and rectal catheterization, only a brief and mild improvement is achieved. Given the failure of conservative measures, colectomy was performed, achieving complete resolution. Ogilvie syndrome is a functional disorder1 that usually associates predisposing factors that impact intestinal motility 2 ; In our case: bedridden, the use of anticholinergics, hydroelectric alteration both due to the use of antidepressants and the creation of a third space secondary to colonic dilation and severe intestinal ischemia². In one third it is resolved by early correction of the triggering factors, adding neostigmine if necessary with high rates of effectiveness¹. In our case, a second bolus of neostigmine could have been administered or even as an infusion since greater efficacy has been demonstrated in this way given its short half-life². Electrolyte imbalance is a predictor of poor response to neostigmine, a factor that was associated with our patient 3. Colonic decompression and finally surgery are reserved as a last measure, being necessary in a very small percentage as in this case 1. As a preventive measure, the administration of 29.5 g of oral polyethylene glycol per day has been effective 4. Therefore, we should suspect Ogilvie syndrome in patients with predisposing factors who present acute dilation of the colon without mechanical obstruction, and although it usually resolves with medical and endoscopic treatment, we should not delay surgery to avoid complications.
PubMed: 38305678
DOI: 10.17235/reed.2024.10287/2024 -
Trauma Case Reports Oct 2023The rectum is an anatomically protected and well vascularized structure. Injury to the rectum is usually the result of penetrating perineal mechanisms or reported...
The rectum is an anatomically protected and well vascularized structure. Injury to the rectum is usually the result of penetrating perineal mechanisms or reported scalding enemas. Here, we report a case of isolated rectal necrosis following a 72 % total body surface area burn that resulted from a motor vehicle crash. The patient's rectal injury was managed with open resection, left in discontinuity and ultimately expired. In presenting this case, we hope to share an unusual development in a patient with critical illness and guide future care.
PubMed: 37654702
DOI: 10.1016/j.tcr.2023.100886 -
Mucosal Immunology Dec 2023This study investigated the role of Alpha-tocopherylquinone (TQ) in regulating the intestinal immune system and the underlying mechanisms. In the experimental dextran...
Alpha-tocopherylquinone-mediated activation of the Aryl Hydrocarbon Receptor regulates the production of inflammation-inducing cytokines and ameliorates intestinal inflammation.
This study investigated the role of Alpha-tocopherylquinone (TQ) in regulating the intestinal immune system and the underlying mechanisms. In the experimental dextran sodium sulfate and T cell-mediated colitis models, TQ significantly reduced the mRNA levels of interleukin (IL)-6, IL-1β, IL-17A, IL-23, and tumor necrosis factor (TNF)-α and the abundance of proinflammatory macrophages, T helper (Th)17 cells, and ILC3s in the colons of wild-type mice. TQ also prevented lipopolysaccharide (LPS)-induced activation of NFκB and signal transducer and activator of transcription (Stat)-3 pathways in the human macrophage U937 cells. Pharmacological inhibition or CRISPR-Cas-9-mediated knockout of Aryl hydrocarbon Receptor (AhR) prevented the anti-inflammatory effects of TQ in the LPS-treated U937 cells. Furthermore, TQ reduced the mRNA levels of the LPS-induced pro-inflammatory cytokines in the WT but not Ahr mice splenocytes. TQ also reduced IL-6R protein levels and IL-6-induced Stat-3 activation in Jurkat cells and in vitro differentiation of Th17 cells from wild-type but not Ahr mice naive T cells. Additionally, TQ prevented the pro-inflammatory effects of LPS on macrophages and stimulation of T cells in human PBMCs and significantly reduced the abundance of tumor necrosis factor-α, IL-1β, and IL-6 inflammatory macrophages and Th17 cells in surgically resected Crohn's disease (CD) tissue. Our study shows that TQ is a naturally occurring, non-toxic, and effective immune modulator that activates AhR and suppresses the Stat-3-NFκB signaling.
Topics: Mice; Humans; Animals; Cytokines; Interleukin-6; Receptors, Aryl Hydrocarbon; Lipopolysaccharides; Inflammation; Tumor Necrosis Factor-alpha; RNA, Messenger
PubMed: 37716509
DOI: 10.1016/j.mucimm.2023.09.003 -
International Journal of Molecular... Mar 2024Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn's disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual's drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Biological Products; Biomarkers
PubMed: 38612528
DOI: 10.3390/ijms25073717 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2023To summarize and analyze the clinical characteristics of patients diagnosed with hepatic portal venous gas (HPVG). (Observational Study)
Observational Study
OBJECTIVE
To summarize and analyze the clinical characteristics of patients diagnosed with hepatic portal venous gas (HPVG).
METHODS
This was a single center retrospective observational study. All of the patients were diagnosed with HPVG. The patients were admitted to Peking University Third Hospital from January 2017 to January 2021. Demographic characteristics, clinical manifestations, laboratory tests, abdominal imaging, treatment of the primary disease, and clinical outcomes of the patients were collected via electronic medical records. The study was approved by institutional review board and the information of all the patients was kept de-identified.
RESULTS
A total of seven cases were included in the study. The median age of the patients was 67 (63, 81) years. Six of the patients were male. The seven patients all presented with sudden onset of severe abdominal pain, which was the most common symptom. Six patients developed septic shock after admission. The signs of HPVG were detected by CT scans in all the patients, showing gas embolization. It might also be found as unique "aquarium sign" in abdominal ultrosonography. Four cases were caused by intestinal lesions, including acute volvulus, intestinal obstruction, and rectal abscess. Two were caused by ischemic bowel disease and the other one was caused by severe acute pancreatitis. The gas accumulation could disappear after effective anti-shock therapy and surgery (Cases 1, 2, and 6). Two patients had good postoperative outcomes, and one patient was discharged after non-surgical treatment. However, the prognosis was poor in the patients with intestinal ischemia necrosis accompanied by shock and multiple organ dysfunction (Cases 3, 4, 5, and 7 all died).
CONCLUSION
The HPVG patients generally have acute abdominal pain and show up at Emergency Department. The prognosis depends on the potential cause of HPVG. The mechanism and clinical management for the appearance of gas in the portal vein is not well understood. Patients complicated with shock, ascites, and peritonitis may have intestinal necrosis, which indicates surgical intervention and higher mortality. CT is the preferred diagnostic method in standard clinical practice. Physicians need to have a comprehensive understanding of the proactive diagnostic strategy, and active treatment for the primary disease.
Topics: Humans; Male; Female; Acute Disease; Pancreatitis; Portal Vein; Vascular Diseases; Necrosis; Abdominal Pain
PubMed: 37534661
DOI: 10.19723/j.issn.1671-167X.2023.04.028 -
Journal of Dairy Science Apr 2024This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant...
Rectal microbiomes and serum metabolomics reveal the improved effect of Artemisia ordosica crude polysaccharides on the lactation performance, antioxidant and immune responses of lactating donkeys.
This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant status, and immune status of lactating donkeys and analyzing rectal microbiomes and serum metabolomes. Fourteen lactating Dezhou donkeys with similar age (6.16 ± 0.67 years of BW ± SD), weight (250.06 ± 25.18 kg), days in milk (39.11 ± 7.42 d), and averaged parity of 3 were randomly allocated into 2 treatments: a control group (CON, basal diet) and an AOCP group (AOCP, basal diet with 1.0 g/kg DM AOCP). Ten weeks were allotted for the experiment, 2 weeks for adaptation, and 8 weeks for collecting data and samples. The results showed that supplementation of donkey diets with AOCP increased lactation performance, including dry matter intake, milking yield, estimated milk yield, solids-corrected milk, energy-corrected milk, milk fat yield, milk protein yield, milk lactose yield, milk total solids yield, and milk solid not fat yield. The digestibility of dry matter, crude protein, acid detergent fiber, and neutral detergent fiber was increased in the AOCP group compared with the CON group. The AOCP group increased the concentrations of immunoglobulin A, immunoglobulin G, and immunoglobulin M, the activities of the superoxide dismutase, catalase and total antioxidant capacity in the serum. AOCP decreased the concentrations of tumor necrosis factor-α, nitric oxide, reactive oxygen species, and malondialdehyde in the serum. Compared with the CON group, AOCP increased propionate, butyrate, isovalerate, and total VFA concentrations in rectal feces (P < 0.05). The addition of AOCP to increased diversity (Shannon index) and altered structure of the rectal microflora. As a result of AOCP supplementation, there has been a significant improvement in the colonization of beneficial bacteria, including Lactobacillus, Unclassified_f_Prevotellacea, Ruminococcus, and Fibrobacter genera. In contrast, a decrease in the colonization of the Clostridium_sensu_stricto_1 bacterial genus and other pathogenic bacteria was observed. Meanwhile, metabolomics analysis found that AOCP supplementation upregulated metabolites L-tyrosine content while downregulating 9(S)-HODE, choline, sucrose, LysoPC (18:0), LysoPC (18:1(9Z), and LysoPC (20:2(11Z,14Z)) concentrations. These altered metabolites were involved in the PPAR signaling pathway, prolactin signaling pathway, glycerophospholipid metabolism, carbohydrate digestion and absorption, and tyrosine metabolism pathways, which were mainly related to antioxidant capacity, immune responses, and protein metabolism in the lactating donkeys. As a consequence of feeding AOCP diets, beneficial bacteria were abundant, and antioxidant and protein metabolism-related pathways were enriched, which may enhance lactation performance in donkeys. Therefore, supplementing AOCP diets is a desirable dietary strategy to improve donkey health and lactation performance.
PubMed: 38608958
DOI: 10.3168/jds.2023-24570 -
Tidsskrift For Den Norske Laegeforening... Dec 2023Fluoropyrimidines have been linked to cardiovascular toxicity.
BACKGROUND
Fluoropyrimidines have been linked to cardiovascular toxicity.
CASE PRESENTATION
A woman in her forties with locally advanced rectal cancer received curative-intent treatment according to the RAPIDO protocol. Shortly after starting the first 5-fluorouracil infusion she developed chest/epigastric pain, nausea and vomiting. Electrocardiogram showed mild ST elevation in multiple contiguous leads. Troponin I was elevated. Transthoracic echocardiogram (TTE) displayed signs suggestive of myocardial infarction. Coronary angiogram indicated no obstructive coronary artery disease. Ventriculography demonstrated apical hypokinesia and basal hyperkinesia. MRI revealed no signs of myocardial infarction or myocarditis. The patient was diagnosed with Takotsubo syndrome, possibly induced by 5-fluorouracil. Follow-up TTE three weeks later was normal. Subsequently, she received treatment with tegafur/gimeracil/oteracil (Teysuno®) in place of 5-fluorouracil, combined with oxaliplatin. No further cardiotoxicity was observed during three cycles.
INTERPRETATION
The patient was diagnosed with Takotsubo syndrome following 5-fluorouracil infusion, likely to represent 5-fluorouracil-induced cardiotoxicity. Following replacement of 5-fluorouracil with Teysuno®, she experienced no signs of cardiotoxicity.
Topics: Female; Humans; Cardiotoxicity; Electrocardiography; Fluorouracil; Myocardial Infarction; Takotsubo Cardiomyopathy; Adult; Middle Aged
PubMed: 38088292
DOI: 10.4045/tidsskr.23.0338