Sci Rep. 2023 Sep 2;13(1):14480. doi: 10.1038/s41598-023-41271-6.

ABSTRACT

Vaccines play a crucial role in preventing infections in patients with multiple sclerosis (MS), although concerns have been raised about potential worsening of the underlying disease. To investigate this, we conducted a prospective, multicentre, non-randomized observational study assessing changes in disease activity, safety, and clinical tolerability of vaccination in 222 MS patients on disease-modifying drugs. The majority of patients were female (76.6%) and 89.6% had relapsing-remitting MS. The vaccines administered were primarily seasonal influenza (56.3%) or tetanus-based vaccines (33.8%). Disease activity, as measured by annualized relapse rate, decreased significantly from 0.64 the year prior to vaccination to 0.38 in the following year. Moreover, the extended disability status scale remained stable within six months after vaccination in comparison to pre-vaccination values. Side effects were reported in 19.2% of vaccinated subjects, most commonly local side effects (65.2%) or flu-like symptoms (34.8%). Our findings suggest that standard non-live vaccines are safe and well-tolerated in MS patients and do not negatively impact disease activity.

PMID:37660223 | PMC:PMC10475060 | DOI:10.1038/s41598-023-41271-6

Lancet. 2023 Sep 2;402(10404):809-824. doi: 10.1016/S0140-6736(23)01051-6.

ABSTRACT

Idiopathic nephrotic syndrome is the most common glomerular disease in children. Corticosteroids are the cornerstone of its treatment, and steroid response is the main prognostic factor. Most children respond to a cycle of oral steroids, and are defined as having steroid-sensitive nephrotic syndrome. Among the children who do not respond, defined as having steroid-resistant nephrotic syndrome, most respond to second-line immunosuppression, mainly with calcineurin inhibitors, and children in whom a response is not observed are described as multidrug resistant. The pathophysiology of nephrotic syndrome remains elusive. In cases of immune-mediated origin, dysregulation of immune cells and production of circulating factors that damage the glomerular filtration barrier have been described. Conversely, up to a third of cases of steroid-resistant nephrotic syndrome have a monogenic origin. Multidrug resistant nephrotic syndrome often leads to kidney failure and can cause relapse after kidney transplant. Although steroid-sensitive nephrotic syndrome does not affect renal function, most children with steroid-sensitive nephrotic syndrome have a relapsing course that requires repeated steroid cycles with significant side-effects. To minimise morbidity, some patients require steroid-sparing immunosuppressive agents, including levamisole, mycophenolate mofetil, calcineurin inhibitors, anti-CD20 monoclonal antibodies, and cyclophosphamide. Close monitoring and preventive measures are warranted at onset and during relapse to prevent acute complications (eg, hypovolaemia, acute kidney injury, infections, and thrombosis), whereas long-term management requires minimising treatment-related side-effects. A subset of patients have active disease into adulthood.

PMID:37659779 | DOI:10.1016/S0140-6736(23)01051-6

Arch Med Res. 2023 Aug 31:102884. doi: 10.1016/j.arcmed.2023.102884. Online ahead of print.

ABSTRACT

Pegvisomant, the first and currently only clinically available growth hormone receptor antagonist, is an effective therapeutic option for the medical treatment of acromegaly, a rare disorder characterized by excessive growth hormone secretion. With now over 20 years of real world experience, its safety and efficacy is well-established. However, several aspects of its clinical use are still controversially discussed. The high cost of pegvisomant has limited its use in several countries, and recent studies have reported a lower efficacy than the initial clinical trials. A reported increase in tumor volume under therapy varies between studies and has been attributed to either actual growth or re-expansion after cessation of somatostatin receptor ligand therapy. Furthermore, different combinations of pegvisomant and other therapeutic agents aiming at reduction of acromegaly disease activity have been proposed to increase or retain effectiveness while lowering side effects and cost. This review aims to assess current clinical data on the safety and efficacy of pegvisomant while also addressing controversies surrounding its use.

PMID:37659952 | DOI:10.1016/j.arcmed.2023.102884

Cochrane Database Syst Rev. 2023 Sep 1;9(9):MR000065. doi: 10.1002/14651858.MR000065.pub2.

ABSTRACT

BACKGROUND: The World Health Organization declared the COVID-19 pandemic on 11 March 2020. Vaccine development and deployment were swiftly prioritised as a method to manage and control disease spread. The development of an effective vaccine relies on people's participation in randomised trials. Recruitment to vaccine trials is particularly challenging as it involves healthy volunteers who may have concerns around the potential risks and benefits associated with rapidly developed vaccines.

OBJECTIVES: To explore the factors that influence a person's decision to participate in a vaccine trial in the context of a pandemic or epidemic.

SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was June 2021.

SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored the perspectives of adults aged 18 years or older who were invited to take part in vaccine trials in the context of a pandemic or epidemic.

DATA COLLECTION AND ANALYSIS: We assessed the title, abstracts and full texts identified by the search. We used a sampling frame to identify data-rich studies that represented a range of diseases and geographical spread. We used QSR NVivo to manage extracted data. We assessed methodological limitations using an adapted version of the Critical Skills Appraisal Programme (CASP) tool for qualitative studies. We used the 'best-fit framework approach' to analyse and synthesise the evidence from our included studies. We then used the Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) assessment to assess our confidence in each finding and develop implications for practice.

MAIN RESULTS: We included 34 studies in our review. Most studies related to HIV vaccine trials. The other studies related to Ebola virus, tuberculosis, Zika virus and COVID-19. We developed 20 key findings, under three broad themes (with seven subthemes), that described the factors that people consider when deciding whether to take part in a vaccine trial for a pandemic or epidemic disease. Our GRADE-CERQual confidence was high in nine of the key findings, moderate in 10 key findings and low in one key finding. The main reason for downgrading review findings were concerns regarding the relevance and adequacy of the underlying data. As a result of the over-representation of HIV studies, our GRADE-CERQual assessment of some findings was downgraded in terms of relevance because the views described may not reflect those of people regarding vaccine trials for other pandemic or epidemic diseases. Adequacy relates to the degree of richness and quantity of data supporting a review finding. Moderate concerns about adequacy resulted in a downgrading of some review findings. Some factors were considered to be under the control of the trial team. These included how trial information was communicated and the inclusion of people in the community to help with trial information dissemination. Aspects of trial design were also considered under control of the trial team and included convenience of participation, provision of financial incentives and access to additional support services for those taking part in the trial. Other factors influencing people's decision to take part could be personal, from family, friends or wider society. From a personal perceptive, people had concerns about vaccine side effects, vaccine efficacy and possible impact on their daily lives (carer responsibilities, work, etc.). People were also influenced by their families, and the impact participation may have on relationships. The fear of stigma from society influenced the decision to take part. Also, from a societal perspective, the level of trust in governments' involvement in research and trial may influence a person's decision. Finally, the perceived rewards, both personal and societal, were influencing factors on the decision to participate. Personal rewards included access to a vaccine, improved health and improved disease knowledge, and a return to normality in the context of a pandemic or epidemic. Potential societal rewards included helping the community and contributing to science, often motivated by the memories of family and friends who had died from the disease.

AUTHORS' CONCLUSIONS: This review identifies many of the factors that influence a person's decision to take part in a vaccine trial, and these reflect findings from reviews that examine trials more broadly. However, we also recognise some factors that become more important in connection with a vaccine trial in the context of a pandemic or epidemic. These factors include the potential stigma of taking part, the possible adverse effects of a vaccine, the added motivation for helping society, the role of community leaders in trial dissemination, and the level of trust placed in governments and companies developing vaccines. These specific influences need to be considered by trial teams when designing, and communicating about, vaccine trials in the context of a pandemic or epidemic.

PMID:37655964 | PMC:PMC10472890 | DOI:10.1002/14651858.MR000065.pub2

J Am Heart Assoc. 2023 Sep 5;12(17):e029817. doi: 10.1161/JAHA.123.029817. Epub 2023 Sep 1.

ABSTRACT

Background Thrombolysis and endovascular thrombectomy are the primary treatment for ischemic stroke. However, due to the limited time window and the occurrence of adverse effects, only a small number of patients can genuinely benefit from recanalization. Intraarterial injection of rtPA (recombinant tissue plasminogen activator) based on arterial thrombectomy could improve the prognosis of patients with acute ischemic stroke, but it could not reduce the incidence of recanalization-related adverse effects. Recently, selective brain hypothermia has been shown to offer neuroprotection against stroke. To enhance the recanalization rate of ischemic stroke and reduce the adverse effects such as tiny thrombosis, brain edema, and hemorrhage, we described for the first time a combined approach of hypothermia and thrombolysis via intraarterial hypothermic rtPA. Methods and Results We initially established the optimal regimen of hypothermic rtPA in adult rats subjected to middle cerebral artery occlusion. Subsequently, we explored the mechanism of action mediating hypothermic rtPA by probing reduction of brain tissue temperature, attenuation of blood-brain barrier damage, and sequestration of inflammation coupled with untargeted metabolomics. Hypothermic rtPA improved neurological scores and reduced infarct volume, while limiting hemorrhagic transformation in middle cerebral artery occlusion rats. These therapeutic outcomes of hypothermic rtPA were accompanied by reduced brain temperature, glucose metabolism, and blood-brain barrier damage. A unique metabolomic profile emerged in hypothermic rtPA-treated middle cerebral artery occlusion rats characterized by downregulated markers for energy metabolism and inflammation. Conclusions The innovative use of hypothermic rtPA enhances their combined, as opposed to stand-alone, neuroprotective effects, while reducing hemorrhagic transformation in ischemic stroke.

PMID:37655472 | DOI:10.1161/JAHA.123.029817

Medicine (Baltimore). 2023 Aug 25;102(34):e34735. doi: 10.1097/MD.0000000000034735.

ABSTRACT

RATIONALE: Many factors can contribute to the development of macular injury, which results in vision loss as a result of a disease. Heredity, age, underlying eye illness, internal eye surgery, or eye trauma can all cause it. A safer alternative to current therapies for macular degeneration is urgently needed since they all induce ocular irritation and postoperative recurrence as well as a host of other adverse effects.

PATIENT CONCERNS: A 12-year-old girl was the patient. A laser pen burnt her right eye. There was a spot and a shadow in the middle of her right eye's visual field.

DIAGNOSES: Macular degeneration.

INTERVENTIONS: Given the patient's age, we opted out of medicine and instead used acupuncture as a symptomatic treatment.

OUTCOMES: Two months after therapy concluded, optical coherence tomography result report indicate that the macula region of the right eye is better than it was previously. The corrected visual acuity of the right eye recovered from 0.25 to 1.0, and the clinical accompanying symptoms of the right eye disappeared.

LESSONS: No additional medication or surgical procedure was employed in this instance. We treated the macular damage with acupuncture, which relieved the patient's clinical symptoms and had no adverse effects. This demonstrates that acupuncture may be beneficial in treating ophthalmopathy in this direction.

PMID:37653781 | PMC:PMC10470758 | DOI:10.1097/MD.0000000000034735

Med Oncol. 2023 Sep 1;40(10):289. doi: 10.1007/s12032-023-02159-7.

ABSTRACT

Breast cancer is a significant health problem worldwide, and the search for effective treatments is critical. Side effects of cancer treatments such as surgery, radiotherapy, and chemotherapy reduce the patient's standard of living. Recently, natural compounds from plants have gained attention as potential anticancer agents due to their safety, low toxicity, and potential efficacy. Lycopodium Clavatum (LC) is an herb abundant in tropical regions and Europe and is known for its various medicinal properties. In this study, we investigated the cytotoxic and apoptotic effects of LC Water Extract (LC-WE) and LC Ethanol Extract (LC-EE) plant extracts on MCF-7 human breast cancer cells. Our results showed that LC treatment led to a dose and time-dependent cytotoxic effect on MCF-7 cells, indicating its potential as an anticancer agent against human breast cancer. Additionally, we observed that LC treatment activated apoptosis-related proteins, including BAX, Caspase-3, and Caspase-9. These results suggest that LC may induce apoptosis as a mechanism underlying its cytotoxic effect on MCF-7 human breast cancer cells. Previous studies have shown the anti-cancer potential of LC against different types of cancer. However, the anti-cancer effect of LC on human breast cancer cells has not been investigated to date. Therefore, our study provides novel insights into the potential of LC as an anti-cancer agent against breast cancer. Overall, our results highlight the potential of LC as a promising natural compound for breast cancer treatment.

PMID:37658180 | DOI:10.1007/s12032-023-02159-7

J Med Syst. 2023 Sep 1;47(1):96. doi: 10.1007/s10916-023-01988-3.

ABSTRACT

Medical students in the Netherlands have a relatively low exposure to cardiothoracic surgery and cardiology. This results in discrepancies between starting levels of medical residents and expected standards in clinical practice. Another side effect is the international decline in interest in a career in these cardiovascular fields. To compensate for this, extracurricular education programs focused on cardiothoracic surgery and cardiology have been set up. This study aims to evaluate the impact and benefits of an extracurricular education program on students' knowledge of cardiothoracic surgery and cardiology and to explore possible factors involved in (academic) career decision making. 66 participants were enrolled in the extracurricular education program VECTOR and were included in a cross-sectional cohort study. All participants scored their familiarity with different aspects of cardiothoracic surgery and cardiology prior to and after the course. Data was analyzed using Linear regression and Wilcoxon Signed Rank testing. Participants demonstrated a significant trend towards improved familiarity with cardiothoracic surgery and cardiology after the program (p = < .001). Significant increased knowledge scores were reported for all specified subdomains after the course with an increase in academic interest in cardiology (p = < .001) and cardiothoracic surgery (p = < .001). Students revealed that clinical responsibilities and a healthy work-life balance were considered most important when deciding upon their future career. This study highlights the benefit of an extracurricular education program in cardiothoracic surgery and cardiology for undergraduates and could possibly aid students in preparing for clinical practice.

PMID:37656317 | PMC:PMC10473978 | DOI:10.1007/s10916-023-01988-3

F1000Res. 2022 Aug 8;10:1305. doi: 10.12688/f1000research.74506.2. eCollection 2021.

ABSTRACT

A clear understanding of the origin and role of the different subtypes of the B cell lineage involved in the activity or remission of multiple sclerosis (MS) is important for the treatment and follow-up of patients living with this disease. B cells, however, are dynamic and can play an anti-inflammatory or pro-inflammatory role, depending on their milieu. Depletion of B cells has been effective in controlling the progression of MS, but it can have adverse side effects. A better understanding of the role of the B cell subtypes, through the use of surface biomarkers of cellular activity with special attention to the function of memory and regulatory B cells (Bregs), will be necessary in order to offer specific treatments without inducing undesirable effects.

PMID:37655229 | PMC:PMC10467621 | DOI:10.12688/f1000research.74506.2

Medicine (Baltimore). 2023 Aug 25;102(34):e34643. doi: 10.1097/MD.0000000000034643.

ABSTRACT

Interventional therapies including chemotherapies and radiotherapies are the most preferred treatment for liver cancer. However, these therapies have adverse effects. Therefore, careful care is required to relieve these adverse effects. The objectives of this study were to evaluate the quality of life, pain, anxiety, depression, adverse effects, and satisfaction of patients with liver cancer who received pre- and post-operative comprehensive nursing care against those of patients who received conventional nursing care. Patients with liver cancer who underwent surgeries and interventional therapies for liver cancer received pre- and post-operative comprehensive nursing care (CMN cohort, n = 105) or conventional nursing care (CNN cohort, n = 135), or did not receive any kind of nursing care (NNC cohort, n = 175). Before the non-treatment intervention(s) (BL), none of the patients had absent post-operative pain, all patients had mild or moderate anxiety and depression, and patients had ≤70 overall quality of life score. In the NNC cohort, a few of the patients reported being completely dissatisfied with overall personal satisfaction, and anxiety, depression, and overall the quality of life of patients were clinically worse during the follow-up period generally after completion of all doses of chemo radiotherapies (EL) as compared to BL. Hospital stays due to surgery, visual analog scale (VAS) score, Zung Self-rating Anxiety Scale score, the Self-rating Depression Scale score, and rehospitalization due to any reason(s) in follow-up were fewer and overall quality of life score and overall personal satisfaction score were higher for patients of the CMN cohort than those of patients at BL and those of patients of the CNN and the NNC cohorts at EL (P < .05 for all). Fever, bleeding, urinary retention, gastrointestinal disturbance, and hepatic and renal impairments reported in patients of the NNC cohort. Fever, bleeding, and urinary retention reported in patients of the CNN cohort (P < .05 for all). Nursing non-treatment intervention(s) is necessary for liver cancer patients after surgery, in the follow-up, and between 2 doses of chemoradiotherapies. Pre- and post-operative comprehensive nursing care relieves postoperative pain, psychological burden and improves quality of life in the follow-up period in patients who underwent surgeries and interventional therapies for liver cancer (Level of Evidence: IV; Technical Efficacy: Stage 5).

PMID:37653829 | DOI:10.1097/MD.0000000000034643

Medicine (Baltimore). 2023 Aug 25;102(34):e34756. doi: 10.1097/MD.0000000000034756.

ABSTRACT

To analyze the factors associated with infection after flap transfer for hand trauma and use them to develop nursing strategies and observe the effects of their application. Eighty-two patients admitted to our hospital for flap transfer for hand trauma from January 2020 to May 2020 were selected for the retrospective analysis. Logistic regression analysis was performed to analyze the factors associated with postoperative infections to develop care strategies. Another 88 patients admitted for flap transfer for hand trauma from September 2020 to June 2021 were retrospectively analyzed and divided into the observation (n = 44) and control groups (n = 44) according nursing strategies that they received. The operative time, intraoperative bleeding, incision healing time, first postoperative time to get out of bed on their own and hospital stay were compared between the 2 groups. The patients postoperative adverse effects and flap survival rates were also counted. visual analogue score, total active motion, manual muscle test, Barthel index, self-rating anxiety scale, self-rating depression scale scores were used to assess patients pain, hand function recovery and psychology before and after treatment. Logistic regression analysis manifested that postoperative bed rest time, affected limb immobilization, and pain were independent factors affecting postoperative infection after flap transfer (P < .05). After using targeted care strategies, the observation group had dramatically shorter operative time, intraoperative bleeding, incision healing time, time to first postoperative bed release on their own, and hospital stay, less postoperative pain and adverse effects, and higher flap survival rate than the control group (P < .05). Total active motion, manual muscle test, and Barthel index were higher in the observation group than in the control group after treatment, while self-rating anxiety scale and self-rating depression scale scores were lower than in the control group (P < .05). Finally, total satisfaction was higher in the observation group than in the control group (P < .05). Postoperative bedtime, fixation of the affected limb, and pain are independent factors affecting postoperative infection after flap transfer for hand trauma. Implementing infection prevention care strategies based on these factors can effectively improve the safety of flap transfer, reduce the possibility of infection, and shorten the recovery period of patients, which has high clinical application value.

PMID:37653820 | DOI:10.1097/MD.0000000000034756

Medicine (Baltimore). 2023 Aug 25;102(34):e34895. doi: 10.1097/MD.0000000000034895.

ABSTRACT

BACKGROUND: Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total joint arthroplasty (TJA). However, there is still no consensus on its effectiveness and safety. We conducted the meta-analysis to investigate the analgesic effect and safety of duloxetine for the treatment of patients received total knee or hip arthroplasty.

METHODS: Pubmed, Cochrane Central Registry for Clinical Trials, Embase, OVID, Web of Science, and Google Scholar were searched using a predetermined search strategy from inception to September 21, 2022. Only randomized controlled trials of duloxetine in treatment of patients after total knee or hip arthroplasty were included. Data collection and extraction, quality assessment, and data analyses were performed according to the Cochrane standards.

RESULTS: A total of 8 randomized controlled trials with 739 patients were included in the literature review of postoperative pain and adverse effects. The result of meta-analysis showed statistically significant lower opioid requirement with duloxetine (P < .05) for the different postoperative period. Duloxetine group had significant reductions in visual analog score for the 24-hour (walking: WMD = -0.98; 95% confidence interval [CI] = -1.69 to -0.26, P = .007; resting: WMD = -1.06; 95%CI = -1.85 to -0.27, P = .008) and 1-week (walking: WMD = -0.96; 95%CI = -1.42 to -0.50, P < .001; resting: WMD = -0.69; 95%CI = -1.22 to -0.16, P = .01); knee injury and osteoarthritis outcome score over 3-month (WMD = 2.94; 95%CI = -0.30 to 6.18, P = .008) and complication (odds ratio = 4.74; 95%CI = 0.23 to 96.56, P = .01) postoperative period compared with the control group. However, no difference on numeric rating scale (P > .05) for the different postoperative period; visual analog score (P > .05) for the 6-week or 3-month and knee injury and osteoarthritis outcome score (P > .05) for the 6-week postoperative period. Furthermore, it did not increase the incidence of adverse effects (odds ratio = 0.87; 95%CI = 0.72 to 1.05, P = .15).

CONCLUSION: Duloxetine could decrease the opioids consumption and relieve early postoperative pain without increasing the risk of adverse medication effects in patients undergoing total knee or hip arthroplasty. Considering the ongoing opioid epidemic, duloxetine could act as a good supplement in multimodal pain management protocol for patients undergoing total joint arthroplasty.

PMID:37653762 | DOI:10.1097/MD.0000000000034895

IEEE/ACM Trans Comput Biol Bioinform. 2023 Sep 1;PP. doi: 10.1109/TCBB.2023.3311015. Online ahead of print.

ABSTRACT

Predicting drug side effects before they occur is a critical task for keeping the number of drug-related hospitalizations low and for improving drug discovery processes. Automatic predictors of side-effects generally are not able to process the structure of the drug, resulting in a loss of information. Graph neural networks have seen great success in recent years, thanks to their ability of exploiting the information conveyed by the graph structure and labels. These models have been used in a wide variety of biological applications, among which the prediction of drug side-effects on a large knowledge graph. Exploiting the molecular graph encoding the structure of the drug represents a novel approach, in which the problem is formulated as a multi-class multi-label graph-focused classification. We developed a methodology to carry out this task, using recurrent Graph Neural Networks, and building a dataset from freely accessible and well established data sources. The results show that our method has an improved classification capability, under many parameters and metrics, with respect to previously available predictors. The method is not ready for clinical tests yet, as the specificity is still below the preliminary 25 % threshold. Future efforts will aim at improving this aspect.

PMID:37656647 | DOI:10.1109/TCBB.2023.3311015

Pharmacoepidemiol Drug Saf. 2023 Sep 1. doi: 10.1002/pds.5677. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to evaluate the efficacy and safety of moxifloxacin monotherapy for the treatment of uncomplicated pelvic inflammatory disease (uPID).

METHODS: The literatures from PubMed, ScienceDirect, Google Scholar, Cochrane library and the http://clinicaltrials.gov/ were retrieved until February 2023. Only randomized controlled trials (RCTs) comparing the efficacy and safety of moxifloxacin with other antibiotics for treating uPID were included. The primary outcomes were clinical cure rate (CCR), bacteriological success rates (BSR) and risk of drug-related adverse events (AEs). We used random-effects modelled meta-analysis, trial sequential analysis, and the Grading of Recommendations Assessment, Development, and Evaluation. This study was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42023428751).

RESULTS: A total of four RCTs that enrolled 3201 women patients with uPID were included. In the per-protocol populations, no significant difference was observed between patients given moxifloxacin and those given other antibiotics with regard to CCR at test-of-cure (TOC) (2485 patients, odds ratio [OR] = 0.84, 95% confidence interval [CI] 0.68-1.04, p = 0.12). Similarly, there was no statistically significant difference between patients given moxifloxacin and those given other antibiotics in terms of BSR at TOC (471 patients, OR = 1.17, 95% CI 0.70-1.96, p = 0.56) in the microbiologically valid population. However, drug-related AEs occurred less frequently with moxifloxacin than with other antibiotics (2973 patients, OR = 0.74, 95% CI 0.64-0.86, p < 0.0001), especially gastrointestinal AEs (2973 patients, OR = 0.59, 95% CI 0.47-0.74, p < 0.00001).

CONCLUSIONS: In the treatment of uPID, moxifloxacin monotherapy can achieve similar efficacy as other combination therapy regimens. Moreover, moxifloxacin had a better safety profile than that of comparators. Based on its additional advantages (i.e., better safety profile, no dosage adjustment and better compliance), moxifloxacin may be a more fascinating option compared with the currently used regimens.

PMID:37655831 | DOI:10.1002/pds.5677

Therap Adv Gastroenterol. 2023 Aug 23;16:17562848231191664. doi: 10.1177/17562848231191664. eCollection 2023.

ABSTRACT

BACKGROUND: Methotrexate monotherapy is recommended as a maintenance therapy for Crohn's disease (CD). However, long-term follow-up data are scarce.

OBJECTIVES: We aimed to examine the effectiveness and tolerability of methotrexate monotherapy in 94 CD patients from three inflammatory bowel disease Clinics in Korea.

DESIGN: This was a multicenter retrospective observational study.

METHODS: Patients with active CD treated with methotrexate monotherapy were included. Clinical characteristics, laboratory indicators, endoscopy indices were evaluated at baseline, 6, 12, and 24 months. Independent factors associated with long-term clinical and endoscopic outcomes were determined.

RESULTS: Methotrexate was administered orally (70.2%) or parenterally (29.8%). The mean methotrexate induction dose was 15.3 ± 0.4 mg/week, and the mean duration of therapy was 26.2 months. Of 76 patients who were treated for >6 months, the clinical remission rates were 76.3%, 74.6%, and 80.0% at 6, 12, and 24 months, respectively, by per-protocol analysis. The mean CRP levels were 7.5 ± 1.3, 5.3 ± 1.2, 3.8 ± 0.7, and 2.6 ± 0.5 mg/L at 0, 6, 12, and 24 months, respectively. Of 31 patients who underwent follow-up endoscopy after 27.5 months, the endoscopic remission rate was 38.7%. Baseline hemoglobin level <10 g/dL was a significant independent factor negatively associated with clinical remission at 6 [odds ratio (OR): 0.023, 95% confidence interval (CI): 0.003-0.206, p = 0.001] and 12 (OR: 0.079, 95% CI: 0.009-0.699, p = 0.023) months. Parenteral administration was a significant independent factor positively associated with clinical remission (OR: 11.231, 95% CI: 1.027-122.811, p = 0.047) and endoscopic remission (hazard ratio: 4.711, 95% CI: 1.398-15.874, p = 0.012) at 12 months.

CONCLUSIONS: Methotrexate monotherapy was effective and tolerable as a maintenance therapy in CD patients.

PMID:37655055 | PMC:PMC10467270 | DOI:10.1177/17562848231191664

Cureus. 2023 Jul 31;15(7):e42743. doi: 10.7759/cureus.42743. eCollection 2023 Jul.

ABSTRACT

Diagnosing acute pancreatitis induced by any drug is often overlooked and warrants careful evaluation. Drug-induced acute pancreatitis is relatively rare, and diagnosis of exclusion after ruling out alcohol, gallstones, hypertriglyceridemia, and intervention. Levofloxacin, a class of fluoroquinolones, is generally recommended against various bacterial infections. While levofloxacin is mainly known for its potential side effects, such as photosensitivity and liver toxicity, it can also rarely induce acute pancreatitis. We report a case of acute pancreatitis in a female patient precipitated by levofloxacin. The patient exhibited typical manifestations of acute pancreatitis and had been taking levofloxacin for a urinary tract infection over the past three days. After ruling out other possible causes, her clinical presentation, laboratory results, and imaging findings confirmed levofloxacin-induced acute pancreatitis.

PMID:37654929 | PMC:PMC10467605 | DOI:10.7759/cureus.42743

Open Forum Infect Dis. 2023 Aug 7;10(8):ofad422. doi: 10.1093/ofid/ofad422. eCollection 2023 Aug.

ABSTRACT

BACKGROUND: Drug-induced liver injury (DILI) may lead to the discontinuation of antituberculosis (anti-TB) treatment (ATT). Some studies have suggested that metabolic disorders increase the risk of DILI during ATT. This study aimed to identify risk factors for DILI, particularly metabolic disorders, during ATT.

METHODS: A multicenter prospective observational cohort study to evaluate adverse events during ATT was conducted in Korea from 2019 to 2021. Drug-susceptible patients with TB who had been treated with standard ATT for 6 months were included. The patients were divided into 2 groups depending on the presence of 1 or more metabolic conditions, such as insulin resistance, hypertension, obesity, and dyslipidemia. We monitored ATT-related adverse events, including DILI, and treatment outcomes. The incidence of DILI was compared between individuals with and without metabolic disorders, and related factors were evaluated.

RESULTS: Of 684 patients, 52 (7.6%) experienced DILI, and 92.9% of them had metabolic disorders. In the multivariable analyses, underlying metabolic disorders (adjusted hazard ratio [aHR], 2.85; 95% CI, 1.01-8.07) and serum albumin <3.5 g/dL (aHR, 2.26; 95% CI, 1.29-3.96) were risk factors for DILI during ATT. In the 1-month landmark analyses, metabolic disorders were linked to an elevated risk of DILI, especially significant alanine aminotransferase elevation. The treatment outcome was not affected by the presence of metabolic disorders.

CONCLUSIONS: Patients with metabolic disorders have an increased risk of ATT-induced liver injury compared with controls. The presence of metabolic disorders and hypoalbuminemia adversely affects the liver in patients with ATT.

PMID:37654787 | PMC:PMC10468151 | DOI:10.1093/ofid/ofad422

Recent Adv Food Nutr Agric. 2023 Aug 31. doi: 10.2174/2772574X14666230831100901. Online ahead of print.

ABSTRACT

BACKGROUND: Hydroxychloroquine (HCQ) is a common antimalarial drug that has been used effectively in the treatment of various rheumatic and auto-immunity diseases. The major side effects and drawbacks associated with HCQ are cardiotoxicity, retinopathy, gastrointestinal upset, and neuromyopathy however, cardiotoxicity is an increasing concern and it is critical to avoid heart dysfunction induced by HCQ. The present work is focused on receptor and signaling molecules associated with pathways attributing to drug-induced cardiotoxicity. We analyzed the therapeutic efficacy of selected natural products in HCQ-induced cardiotoxicity through insilico. We selected Syzygium cumini polyphenols, quercetin, and p-coumaric acid. The motivation behind selecting quercetin, and p-coumaric acid is their wide applicability as an antioxidative, anti-inflammatory, antiapoptotic, and cardioprotective.

METHOD: For predicting quercetin, p-coumaric acid, and HCQ toxicity and physicochemical properties, in silico studies were performed using ProTox II and Swiss ADME. We further performed molecular docking using Autodock Vina and Discovery Studio visualizer to find the affinity of selected polyphenols against signaling molecules and receptors. Then we performed network pharmacological studies of selected signaling molecules.

RESULTS: We analyzed that the computational method indicated quercetin (Δ G -9.3 kcal/mol) has greater binding affinity than p-Coumaric acid for prevention and restoration of the disease while hydroxychloroquine was taken as a control.

CONCLUSION: It can be concluded that Syzygium cumini, polyphenols may aid in the future therapeutic potential against HCQ-induced cardiotoxicity.

PMID:37653628 | DOI:10.2174/2772574X14666230831100901

Sci Rep. 2023 Aug 31;13(1):14326. doi: 10.1038/s41598-023-41213-2.

ABSTRACT

Environmental exposures produce heritable traits that can linger in the population for one or two generations. Millions of individuals consume substances such as artificial sweeteners daily that are declared safe by regulatory agencies without evaluation of their potential heritable effects. We show that consumption of aspartame, an FDA-approved artificial sweetener, daily for up to 16-weeks at doses equivalent to only 7-15% of the FDA recommended maximum daily intake value (equivalent to 2-4 small, 8 oz diet soda drinks per day) produces significant spatial learning and memory deficits in mice. Moreover, the cognitive deficits are transmitted to male and female descendants along the paternal lineage suggesting that aspartame's adverse cognitive effects are heritable, and that they are more pervasive than current estimates, which consider effects in the directly exposed individuals only. Traditionally, deleterious environmental exposures of pregnant and nursing women are viewed as risk factors for the health of future generations. Environmental exposures of men are not considered to pose similar risks. Our findings suggest that environmental exposures of men can produce adverse impact on cognitive function in future generations and demonstrate the need for considering heritable effects via the paternal lineage as part of the regulatory evaluations of artificial sweeteners.

PMID:37652922 | PMC:PMC10471780 | DOI:10.1038/s41598-023-41213-2

Br J Gen Pract. 2023 Aug 31;73(734):396. doi: 10.3399/bjgp23X734769. Print 2023 Sep.

NO ABSTRACT

PMID:37652734 | DOI:10.3399/bjgp23X734769