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Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
International Journal of Molecular... Jun 2024A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory... (Review)
Review
A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). The study analysed articles published in JCR journals from 2019 to 2024. The search strategy comprised the MESH, free terms of "Neuroinflammation", and selective searches for the following single biomarkers that had previously been selected from the relevant literature: "High mobility group box 1/HMGB1", "Toll-Like-Receptor 4/TLR-4", "Interleukin-1/IL-1", "Interleukin-6/IL-6", "Transforming growth factor beta/TGF-β", and "Tumour necrosis factor-alpha/TNF-α". These queries were all combined with the MESH terms "Epileptogenesis" and "Epilepsy". We found 243 articles related to epileptogenesis and neuroinflammation, with 356 articles from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 55 evaluated by the authors. A total of 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. As conclusion, this systematic review provides acceptable support for five biomarkers, including TNF-α and some of its soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 and IL-33. Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control of epileptic seizures. Their value will be better defined by future studies.
Topics: Humans; Biomarkers; Neuroinflammatory Diseases; HMGB1 Protein; Epilepsy; Cytokines; Toll-Like Receptor 4; Drug Resistant Epilepsy
PubMed: 38928193
DOI: 10.3390/ijms25126488 -
Cureus May 2024Sodium-glucose co-transporter 2 (SGLT2) inhibitors, initially developed for glycemic control in type 2 diabetes, have demonstrated benefits in reducing heart failure... (Review)
Review
Sodium-glucose co-transporter 2 (SGLT2) inhibitors, initially developed for glycemic control in type 2 diabetes, have demonstrated benefits in reducing heart failure hospitalizations, slowing chronic kidney disease, and decreasing major cardiovascular events. Recent studies have shown that SGLT2 inhibitors can elevate serum magnesium levels in patients with type 2 diabetes, suggesting potential benefits in managing refractory hypomagnesemia. This systematic review analyzed relevant case reports, observational studies, and randomized controlled trials (RCTs) to investigate the association between SGLT2 inhibitors and hypomagnesemia. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and study quality was assessed using the CAse REport (CARE) guidelines. It encompassed four case reports, one retrospective observational study, one post-hoc analysis of 10 RCTs, and one meta-analysis of 18 RCTs, with a total study population of 19,767 patients. The meta-analysis revealed that SGLT2 inhibitors significantly increased serum magnesium levels in patients with type 2 diabetes, with a linear dose-dependent increase noted particularly for canagliflozin. Additionally, the case reports and other studies suggested that SGLT2 inhibitors could exert extraglycemic effects, potentially enhancing magnesium balance beyond their impact on urinary magnesium excretion. This systematic review underscores the effectiveness of SGLT2 inhibitors in addressing refractory hypomagnesemia linked with urinary magnesium wasting. It also suggests promising avenues for the application of these drugs in diverse patient populations.
PubMed: 38910615
DOI: 10.7759/cureus.60919 -
International Journal of Retina and... Jun 2024Macular holes (MHs), including atraumatic idiopathic and refractory MHs, affect central vision acuity due to full-thickness defects in the retinal tissue. The existing... (Review)
Review
Macular holes (MHs), including atraumatic idiopathic and refractory MHs, affect central vision acuity due to full-thickness defects in the retinal tissue. The existing controversy regarding the pathophysiology and management of MHs has significantly improved with the implementation of internal limiting membrane (ILM) surgical techniques and improved MH closure rates. Thus, to determine the effect of ILM techniques on large idiopathic and refractory MH management, the present study systematically reviewed 5910 original research articles extracted from online literature databases, including PubMed, Cochrane, Google Scholar, and Embase, following the PRISMA guidelines. The primary outcome measures were MH closure rate and postoperative visual acuity. A total of 23 randomized controlled trials (RCTs) with adequate patient information and information on the effect of ILM peeling, inverted ILM flaps, autologous retinal transplantation (ART), and ILM insertion techniques on large idiopathic and refractory MH patients were retrieved and analyzed using RevMan software (version 5.3) provided by the Cochrane Collaboration. Statistical risk of bias analysis was also conducted on the selected sources using RoB2, which showed a low risk of bias in the included studies. A meta-analysis indicated that the inverted ILM flap technique had a significantly greater MH closure rate for primary MH than the other treatment methods (OR = 3. 22, 95% CI 1.34-7.43; p = 0.01). Furthermore, the findings showed that the inverted ILM flap group had significantly better postoperative visual acuity than did the other treatment options for patients with idiopathic MH (WMD = - 0.13; 95% CI = 0.22-0.09; p = 0.0002). The ILM peeling technique had the second highest statistical significance for MH closure rates in patients with idiopathic MH (OR = 2. 72, 95% CI: 1.26-6.32; p = 0.016). In refractory MHs, autologous retinal transplant (ART) and multilayer ILM plug (MIP) techniques improve the closure rate and visual function; human amniotic membrane grafting (hAMG) provides a high degree of anatomical outcomes but disappointing visual results. This study demonstrated the reliability and effectiveness of ILM techniques in improving the functional and anatomical outcomes of large idiopathic and refractory MH surgery. These findings will help clinicians choose the appropriate treatment technique for patients with idiopathic and refractory MH.
PubMed: 38907361
DOI: 10.1186/s40942-024-00564-2 -
Critical Care Explorations Jul 2024Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.
DATA SOURCES
We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.
STUDY SELECTION
We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration.
DATA EXTRACTION
Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.
DATA SYNTHESIS
We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events.
CONCLUSIONS
Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed.
REGISTRATION
Center for Open Science (https://osf.io/hpy4j).
Topics: Methylene Blue; Humans; Shock, Septic; Randomized Controlled Trials as Topic; Length of Stay; Critical Illness
PubMed: 38904978
DOI: 10.1097/CCE.0000000000001110 -
JGH Open : An Open Access Journal of... Jun 2024Hepatic sarcoidosis is an uncommon clinical condition in which clear recommendations are lacking in its treatment. We aimed to review systematically the literature on... (Review)
Review
BACKGROUND
Hepatic sarcoidosis is an uncommon clinical condition in which clear recommendations are lacking in its treatment. We aimed to review systematically the literature on hepatic sarcoidosis treatment to guide clinicians.
METHODS
Using MEDLINE, PubMed, CINAHL, Cochrane Library, and Google Scholar databases, we searched original articles on clinical studies reporting the outcome of adult hepatic sarcoidosis patients following treatment with various pharmacological agents. The primary end point was focused on assessing symptomatic relief and biochemical improvement posttreatment.
RESULTS
Out of 614 retrieved references, 34 published studies were eligible, providing data for a total of 268 patients with hepatic sarcoidosis. First-line therapy with corticosteroids alone was reported in 187 patients, whilst ursodeoxycholic acid (UDCA) was used in 40 patients. Symptomatic and biochemical responses were reported among 113(60.4%) and 80(42.8%) cases of corticosteroids respectively, whereas UDCA showed a complete response in 23(57.5%) patients. Second-line therapy was used in steroid-refractory cases, with most cases being reported for azathioprine ( = 32) and methotrexate ( = 28). Notably, 15(46.9%) and 11(39.2%) patients showed both clinical and biochemical responses respectively. Biological therapy including anti-tumor necrosis factor (anti-TNF) was used as third line therapy in twelve cases with a 72.7% symptomatic and biochemical response rate each.
CONCLUSION
The quality of evidence for the treatment of hepatic sarcoidosis was poor. Nevertheless, it appears that corticosteroid or UDCA may be utilized as first-line therapy. For cases that are refractory to corticosteroids, steroid-sparing immunosuppressive agents and anti-TNF have shown some promising results, but further high-quality studies are required.
PubMed: 38903487
DOI: 10.1002/jgh3.13076 -
Journal of Pharmacy & Bioallied Sciences Apr 2024May-Thurner syndrome (MTS) is an anatomical condition of external luminal compression of common iliac vein due to a partial obstruction of the common iliac vein between... (Review)
Review
May-Thurner syndrome (MTS) is an anatomical condition of external luminal compression of common iliac vein due to a partial obstruction of the common iliac vein between common iliac artery and lumbar vertebra causes deep-vein thrombosis, venous hypertension, and chronic venous insufficiencies. In this article, we review present evidence of the clinical diagnosis and management of MTS. Here, we conducted a literature review of studies on MTS. We also reviewed different clinical features, presentation, diagnostic methods, and therapeutic procedure for this condition. Most studies mentioned the diagnosis of this condition is performed by color Doppler, computed tomographic angiography, venography, and problem-solving cases by intravascular ultrasound technique. Nonsurgical methods of management are first line, and vascular surgery is reserved for refractory cases. Multiple modalities are required to reach the diagnosis of MTS, and noninvasive intervention radiology methods are the first line of management. This review highlights the presentations of MTS and outlines diagnostic procedure and management.
PubMed: 38882842
DOI: 10.4103/jpbs.jpbs_1135_23 -
Plastic and Reconstructive Surgery.... Jun 2024Raynaud disease of the hands is a complex disorder resulting in inappropriate constriction and/or insufficient dilation in microcirculation. There is an emerging role...
BACKGROUND
Raynaud disease of the hands is a complex disorder resulting in inappropriate constriction and/or insufficient dilation in microcirculation. There is an emerging role for botulinum toxin type A (BTX-A) in the treatment armamentarium for refractory Raynaud disease. The aim of this systematic review was to critically evaluate the management of primary and secondary Raynaud disease treated with BTX-A intervention.
METHODS
We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of clinical studies assessing treatment of primary or secondary Raynaud disease with BTX-A by searching Ovid MEDLINE and Embase databases from inception to first August 2023. The review protocol was prospectively registered on the PROSPERO database (CRD42022312253).
RESULTS
Our search strategy identified 288 research articles, of which 18 studies [four randomized controlled trials (RCTs), two non-RCTs, five case series, and seven retrospective cohort studies] were eligible for analysis. Meta-analysis demonstrated that the probability of pain visual analog scale score improvement with BTX-A intervention was 81.95% [95% confidence interval (74.12-87.81) = 0.19, heterogeneity = 26%] and probability of digital ulcer healing was 79.37% [95% confidence interval (62.45-89.9) = 0.02, heterogeneity = 56%].
CONCLUSIONS
Delivery of BTX-A to digital vessels in the hand may be an effective management strategy for primary and secondary Raynaud disease. A definitive, appropriately-powered RCT with objective functional and patient-reported outcome measures is required to accurately assess and quantify the efficacy of BTX-A in Raynaud disease of the hands.
PubMed: 38881966
DOI: 10.1097/GOX.0000000000005885 -
Journal of Psychiatric Research Jun 2024Patients with severe or treatment-refractory obsessive-compulsive disorder (OCD) often need an extensive treatment which cannot be provided by outpatient care.... (Review)
Review
Effects of inpatient, residential, and day-patient treatment on obsessive-compulsive symptoms in persons with obsessive-compulsive disorder: A systematic review and meta-analysis.
INTRODUCTION
Patients with severe or treatment-refractory obsessive-compulsive disorder (OCD) often need an extensive treatment which cannot be provided by outpatient care. Therefore, we aimed to estimate the effects and their moderators of inpatient, residential, or day-patient treatment on obsessive-compulsive symptoms in patients with OCD.
METHODS
PubMed, PsycINFO, and Web of Science were systematically screened according to the PRISMA guidelines. Studies were selected if they were conducted in an inpatient, residential, or day-patient treatment setting, were using a number of pre-defined instruments for assessing OCD symptom severity, and had a sample size of at least 20 patients.
RESULTS
We identified 43 eligible studies in which inpatient, residential, or day-patient treatment was administered. The means and standard deviations at admission, discharge, and-if available-at follow-up were extracted. All treatment programs included cognitive-behavioral treatment with exposure and response prevention. Only one study reported to not have used psychopharmacological medication. Obsessive-compulsive symptoms decreased from admission to discharge with large effect sizes (g = -1.59, 95%CI [-1.76; -1.41]) and did not change from discharge to follow-up (g = 0.06, 95%CI [-0.09; 0.21]). Length of stay, age, sex, and region did not explain heterogeneity across the studies but instrument used did: effects were larger for clinician-rated interviews than for self-report measures.
CONCLUSIONS
Persons with OCD can achieve considerable symptom reductions when undertaking inpatient, residential, or day-patient treatment and effects are-on average-maintained after discharge.
PubMed: 38875774
DOI: 10.1016/j.jpsychires.2024.06.007 -
Clinical Gastroenterology and... Jun 2024Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and... (Review)
Review
BACKGROUND AND AIMS
Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.
METHODS
We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach.
RESULTS
Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on six structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with longstanding (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus(SCCA) and anorectal carcinoma. Risk factors for SCCA, notably human papilloma virus (HPV), should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an exam under anesthesia (EUA) with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers.
CONCLUSION
Inflammatory bowel disease (IBD) clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.
PubMed: 38871152
DOI: 10.1016/j.cgh.2024.05.029