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Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis.

Several studies have found that antifibrosis treatment for nonalcoholic fatty liver disease (NAFLD) can cause a variety of side effects. No network meta-analysis (NMA) analyzes the adverse events of antifibrotic drugs for NAFLD. This NMA aimed to systematically compare the drug-related side effects when using different pharmacological agents for the treatment of liver fibrosis in NAFLD. PubMed, EMBASE, Web of Science and Cochrane Library were systematically searched to select related studies published in English from the database inception until 30 June 2022. We conducted Bayesian fixed-effects NMA using data from randomized controlled trials (RCTs) to derive relative risks (RRs). The surface under the cumulative ranking (SUCRA) probabilities was used to assess ranking. A total of 26 RCTs with 19 interventions met the inclusion criteria. SUCRA analysis suggested that the lanifibranor group had the highest risk of diarrhea (SUCRA, 94), whereas the liraglutide group had the highest risk of constipation (SUCRA, 92.9). The semaglutide group showed the highest incidence of nausea (SUCRA, 81.2) and abdominal pain (SUCRA, 90.5), respectively. The cenicriviroc group showed the highest risk in the incidence of fatigue (SUCRA, 82.4). The MSDC-0602K group had the highest risk of headache (SUCRA, 76.4), whereas the obeticholic acid group had the highest risk of pruritus (SUCRA, 80.1). The risk of side effects significantly varied among different pharmacologic regimens, and evidence showed that lanifibranor, liraglutide, semaglutide, cenicriviroc, MSDC-0602K and obeticholic acid were the pharmacological interventions with the highest risk in patients with NAFLD. This study may guide clinicians and support further research.

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Randomised controlled trial: standard lightweight mesh vs self-gripping mesh in Lichtenstein procedure.

<b> Introduction:</b> Lichtenstein hernioplasty has been a gold standard of hernioplasty for 30 years now. However, the procedure may be followed by an unacceptably high rate of chronic pain, numbness and discomfort. </br></br> <b>Aim:</b> To compare outcomes of Lichtenstein repair using a Parietene ProGrip self-fixing mesh versus the standard lightweight macroporous mesh. </br></br> <b>Material and methods:</b> As many as 141 patients with unilateral primary inguinal hernia participated in this single-centre, randomised, prospective, single-blind (patient-blinded) study. Randomisation yielded two treatment groups: control group of 88 patients treated with Lichtenstein method using lightweight standard mesh (LS) and study group of 53 patients receiving treatment with self-fixing mesh (PG). Patients were followed up for 6 months. Primary outcome was the presence and severity of postoperative pain at discharge, at 30 days and 6 months post-procedure. Other study parameters were: duration of the procedure, duration of hospitalisation, presence of early and late complications, time needed to return to full activity and patient satisfaction. </br></br> <b>Results:</b> No statistically significant differences in pain severity were demonstrated at discharge or at long-term follow-up. In the first 30 days post-procedure the patients in the PG group complained of pain of greater severity on the NRS (2.0 vs 1.4) (P = 0.0466). The duration of the procedure in the PG group was 9.4 minutes shorter than in the LS group (P = 0.0027). No statistically significant differences between the groups were found in other studied parameters. </br></br><b>Conclusions:</b> Self-fixing mesh can be safely used in inguinal canal repair procedures. It significantly shortened the duration of the procedure but at the same time did not reduce the severity of pain, including the rate of chronic postoperative inguinal pain.

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Comparison of the results of using a self-adhesive mesh and a polypropylene mesh in open inguinal hernia repair: a prospective randomized controlled study.

<b> Introduction:</b> Inguinal hernia repair is the most common operation worldwide. The essential factors in hernia repair have been the postoperative quality of life, early return to work, low recurrence rate, and chronic pain prevention. </br></br> <b>Aim:</b> The aim of this study was to compare the short- and long-term results of the self-adhesive mesh and the conventional polypropylene mesh in Lichtenstein repair. </br></br> <b> Material and methods:</b> A total of 100 male patients were randomized and operated on, 50 with the self-adhesive mesh (S group), 50 with the conventional polypropylene mesh (P group). Prospectively, the patients were followed for an average of 36 months. The two groups were compared for the duration of surgery, duration of hospital stay, duration of daily activity/resumption of work, postoperative pain, chronic pain, recurrence, wound infection, hematoma/seroma formation, and postoperative analgesic consumption. </br></br> <b>Results:</b> The study involved 39 patients in the P group and 37 patients in the S group who underwent inguinal hernia surgery. The P group had a longer mean operation time than the S group, and the difference between the two groups was statistically significant (45.1 ± 6.6 min vs. 28.8 ± 3.0 min, P = 0.0001). In recurrence, postoperative discomfort, chronic pain, length of hospital stay, daily activity/return to work, wound infection, hematoma/seroma, and postoperative analgesic use, there was no statistically significant difference between the two groups. </br></br> <b>Conclusion:</b> It was found that the self-adhesive mesh did not produce statistically significant advantages over the conventional polypropylene mesh, except for operative time, in the Lichtenstein repair.

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Overview of oxidative stress and the role of micronutrients in critical illness.

Inflammation and oxidative stress represent physiological response mechanisms to different types of stimuli and injury during critical illness. Its proper regulation is fundamental to cellular and organismal survival and are paramount to outcomes and recovery from critical illness. A proper maintenance of the delicate balance between inflammation, oxidative stress, and immune response is crucial for resolution from critical illness with important implications for patient outcome. The extent of inflammation and oxidative stress under normal conditions is limited by the antioxidant defense system of the human body, whereas the antioxidant capacity is commonly significantly compromised, and serum levels of micronutrients and vitamins significantly depleted in patients who are critically ill. Hence, the provision of antioxidants and anti-inflammatory nutrients may help to reduce the extent of oxidative stress and therefore improve clinical outcomes in patients who are critically ill. As existing evidence of the beneficial effects of antioxidant supplementation in patients who are critically ill is still unclear, actual findings about the most promising anti-inflammatory and antioxidative candidates selenium, vitamin C, zinc, and vitamin D will be discussed in this narrative review. The existing evidence provided so far demonstrates that several factors need to be considered to determine the efficacy of an antioxidant supplementation strategy in patients who are critically ill and indicates the need for adequately designed multicenter prospective randomized control trials to evaluate the clinical significance of different types and doses of micronutrients and vitamins in selected groups of patients with different types of critical illness.

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Integration of Cannabis Extract Tetrahydrocannabinol:Cannabidiol in an Interdisciplinary Therapy Setting: A Case of Chronic Multilocular Pain Disorder.

Multilocular pain syndromes with advanced chronification lead to a significant reduction in the quality of life of patients. The administration of cannabis is currently being discussed in the context of therapy-resistant pain and increasing opiate abuse. In this case study, possible side effects from the administration of a cannabis extract tetrahydrocannabinol:cannabidiol are examined. Furthermore, the effect on pain intensity and sleep quality is recorded. Due to numerous comorbidities in the patient, interactions with other medications are documented.

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Alterations in Functional Connectivity of Thalamus and Primary Somatosensory Cortex in Painful and Painless Diabetic Peripheral Neuropathy.

In this study we aimed to investigate the functional connectivity of brain regions involved in sensory processing in diabetes with and without painful and painless diabetic peripheral neuropathy (DPN) and the association with peripheral nerve function and pain intensity.

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Red Light-Mediated Photoredox Catalysis Triggers Nitric Oxide Release for Treatment of Induced Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) has been known as a highly prevalent and disabling disease, which is one of the main causes of low back pain and disability. Unfortunately, there is no effective cure to treat this formidable disease, and surgical interventions are typically applied. Herein, we report that the local administration of nitric oxide (NO)-releasing micellar nanoparticles can efficiently treat IVDD associated with Modic changes in a rat model established by infection with (). By covalent incorporation of palladium(II) meso-tetraphenyltetrabenzoporphyrin photocatalyst and coumarin-based NO donors into the core of micellar nanoparticles, we demonstrate that the activation of the UV-absorbing coumarin-based NO donors can be achieved under red light irradiation via photoredox catalysis, although it remains a great challenge to implement photoredox catalysis reactions in biological conditions due to the complex microenvironments. Notably, the local delivery of NO can not only efficiently eradicate pathogens but also inhibit the inflammatory response and osteoclast differentiation in the intervertebral disc tissues, exerting antibacterial, anti-inflammatory, and antiosteoclastogenesis effects. This work provides a feasible means to efficiently treat IVDD by the local administration of NO signaling molecules without resorting to a surgical approach.

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Cannabis in Cancer Survivors Who Report High Impact Chronic Pain: Findings from a 1500+ Patient Survey.

Chronic pain in cancer survivors negatively impacts quality of life. This study sought to investigate the relationship between high-impact chronic pain (HICP) — defined as chronic pain that limits life or work activities on most days or every day in the past 3 months — and cannabis in cancer survivors.

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Are CGRP and PACAP involved in the pathophysiology of peripheral neuropathic pain?

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COVID-19 vaccine short-term adverse events in the real-life family practice in Krakow, Poland.

In manufacturers' trials, vaccination against COVID-19 proved to be safe and effective. The officially reported frequency of vaccine adverse events (VAEs) in Poland is lower than that declared by the manufacturers. The anti-vaccination activists questioned the trustworthiness of official data.

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