Anti-PD-1/PD-L1 inhibitor therapy for melanoma brain metastases: a systematic review and meta-analysis.

Melanoma brain metastases present a major challenge in cancer treatment and reduce overall survival despite advances in managing primary melanoma. Immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 pathways have shown promise in treating advanced melanoma, but their efficacy for melanoma brain metastases is debated. This systematic review and meta-analysis summarize evidence on anti-PD-1/PD-L1 inhibitors for melanoma brain metastases. This systematic review and meta-analysis followed PRISMA guidelines. PICO criteria targeted melanoma brain metastasis patients treated with PD-1/PD-L1 inhibitors, assessing overall survival, progression-free survival, and complications. Inclusion criteria were English studies on humans using PD-1/PD-L1 inhibitors for melanoma brain metastases with > 10 patients. A total of 22 trials involving 1523 melanoma brain metastase patients treated with anti-PD-1/PD-L1 inhibitors were thoroughly analyzed. Our findings show the 6-month OS rate of 0.75 [95%CI:0.67-0.84], the 6-months PFS rate of 0.42 [95%CI:0.31-0.52], the 1-year OS rate of 0.63 [95%CI:0.52-0.74], the 1-year PFS rate was 0.45 [95%CI:0.32-0.58], the 18-months OS rate of 0.52 [95%CI:0.37-0.67], the 2-year OS rate of 50% [95% CI: (34%-65%)], the 2 year PFS rate of 0.36 (95%CI:0.23-0.50), the 3-year OS rate of 0.42 (95%CI:0.17-0.67), the 4-year PFS rate of 0.35 [95%CI:0.08-0.61], the 4-year OS rate of 0.29 [95%CI:0.01-0.56], the 5-year OS rate of 0.29 (95%CI:0.09-0.50), and the 5-year PFS rate of 0.11 (95%CI:0.03-0.19). The combined disease stability rate was 0.13 [95%CI:0.05-0.20], the progressive disease rate was 0.49 [95%CI:0.37-0.62], the partial response rate was 0.14 [95%CI:0.07-0.20], the object response rate was 0.35 [95%CI:0.24-0.46], and the complete response rate was 0.22 [95%CI:0.12-0.32]. In conclusion, our meta-analysis provides compelling evidence supporting the efficacy of PD-1/PD-L1 inhibitors in patients with melanoma brain tumors, as evidenced by favorable survival outcomes and disease control rates.

Immunopathogenesis of viral infections in neurological autoimmune disease.

Autoimmune diseases develop due to self-tolerance failure in recognizing self and non-self-antigens. Several factors play a role in inducing autoimmunity, including genetic and environmental elements. Several studies demonstrated the causative role of viruses; however, some studies showed the preventive effect of viruses in the development of autoimmunity. Neurological autoimmune diseases are classified based on the targets of autoantibodies, which target intracellular or extracellular antigens rather than neurons. Several theories have been hypothesized to explain the role of viruses in the pathogenesis of neuroinflammation and autoimmune diseases. This study reviewed the current data on the immunopathogenesis of viruses in autoimmunity of the nervous system.

Uncommon cause of respiratory failure due to a bezoar in the hypopharynx: a case report.

BACKGROUND: Trichotillomania and trichophagia cause trichobezoars, which are masses made of hair. The main presentation of this condition is abdominal pain. However, other complications include gastric outlet obstruction, nausea, vomiting, weight loss, malnutrition, hematemesis, diarrhea, and constipation. CASE PRESENTATION: A 57-year-old woman with trichotillomania was admitted to the Emergency Department with the chief complaints of dyspnea on exertion, shortness of breath, dysphagia, generalized weakness, and hoarseness. Spiral chest computed tomography (CT) scan did not reveal any parenchymal lesions Pulmonary CT angiography did not reveal pulmonary embolism. The patient was admitted to the Surgery Department for hand fasciotomy due to contrast leakage, and during laryngoscopy, a trichobezoar was detected that was removed with Magill forceps. CONCLUSIONS: Rare cases of trichobezoars can be observed in humans with gastrointestinal and respiratory symptoms. Precise and timely diagnosis are key for the prevention of more invasive diagnostic procedures.

Efficacy of Common Bile Duct Stenting on the Reduction in Gallstone Migration and Symptoms Recurrence in Patients with Biliary Pancreatitis Who Were Candidates for Delayed Cholecystectomy.

BACKGROUND: In patients with severe biliary pancreatitis, delayed cholecystectomy associated with a high risk of recurrence is recommended. The current study aimed to evaluate the effect of common bile duct (CBD) stenting on reducing gallstones migration and recurrence of symptoms in patients with pancreatitis and delayed cholecystectomy candidates. METHODS: To this purpose, the randomized, controlled clinical trial was performed on 40 patients with biliary pancreatitis who were candidates for delayed cholecystectomy. Patients were randomly divided into two groups of A and B that underwent CBD stenting after ERCP and received endoscopic treatment without stenting, respectively. A checklist recorded demographics and complications. Group A was followed up after four weeks to remove the stent and record the complications. Group B underwent MRCP to examine the migration of new gallstones as well as the complications. RESULTS: Of the 40 patients, 20 subjects (11 males and 9 females) were allocated to each group, matched for demographic variables. In the one-month follow-up, only one subject in group A manifested symptoms of gallstone migration and recurrence, while in group B, recurrence was observed in 6 patients (P = 0.037). There was no significant difference in the success rate of ERCP and the incidence of complications between the two groups. CONCLUSION: CBD stenting in patients with biliary pancreatitis and gallstone could reduce the risk of recurrence and remigration of gallstones in delayed cholecystectomy cases.

Clinical Manifestations of Gastrointestinal Symptoms in COVID-19 Patients: An Integrative Review.

After the outbreak of novel coronavirus disease 2019 (COVID-19) in Wuhan, China, its spread to other countries is rapidly increasing. In this integrative review, we report the prevalence of gastrointestinal symptoms in patients with COVID-19. For this purpose, available articles on gastrointestinal manifestations in patients with COVID-19, which were reported from China, were reviewed. All reviewed articles were searched from December 11, 2019, to June 20, 2020, based on specific key words. Related findings in these articles show that the main target of COVID-19 is lung tissue, as after the virus enters the body, it mainly causes respiratory symptoms in affected patients. But in addition to respiratory symptoms, it is possible that, over time, these patients present with other symptoms, the most obvious of which are gastrointestinal symptoms. It is well documented that diarrhea and vomiting are the most common gastrointestinal symptoms in COVID-19 patients. As part of this report, we also look at the incidence and frequency of gastrointestinal symptoms in COVID-19 patients in Iran. The results can be used by providers as a guideline for better management of gastrointestinal symptoms in these patients.

Adding ursodeoxycholic acid to the endoscopic treatment and common bile duct stenting for large and multiple biliary stones: Will it improve the outcomes?

BACKGROUND: The role of common bile duct (CBD) stenting in the establishment of bile stream in the elderly patients and the ones who are not good candidates for surgery due to not responding to treatments was well documented in previous studies. The current study aimed at investigating the effect of adding Ursodeoxycholic acid (UDCA) to CBD stenting alone in order to reduce the size of large and multiple CBD stones. METHODS: Clinical outcomes including success rates in CBD stones clearance, incidence of pancreatitis, perforation, bleeding, as well as, decrease in size of stones and liver enzymes after a two-month period were assessed in the UDCA + CBD stenting group. RESULTS: A total of 64 patients referring to Shahid Beheshti Hospital in Qom, Iran with multiple or large CBD stones (above three or larger than 15 mm) received standard endoscopic therapies and UDCA + CBD stenting (group B) and controls only received standard endoscopic therapies with only CBD stenting (group A). The mean reduction in the size of stones in group B was significantly higher than that of group A (3.22 ± 1.31 vs 4.09 ± 1.87 mm) (p = 0.034). There was no difference in the incidence rate of complications including pancreatitis, cholangitis, bleeding, and perforation between the two groups (P > 0.05). CONCLUSION: Adding UDCA to CBD stenting, due to decrease in the stone size and subsequently facilitation of the stones outlet, can be considered as the first-line treatment for patients with large and multiple CBD stones. Also, in the cases with large or multi stones may be effective in reducing size and subsequently stone retrieval. Trial registry The study protocol was approved by the Ethics Committee of Qom University of Medical Sciences (ethical code: IR.MUQ.REC.1397.075); the study was also registered in the Iranian Registry of Clinical Trials (No. IRCT20161205031252N8). This study adheres to CONSORT guidelines.

Radioprotective effects of montelukast, a selective leukotriene CysLT1 receptor antagonist, against nephrotoxicity induced by gamma radiation in mice.

PURPOSE: In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice. MATERIALS AND METHODS: Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99m Tc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant. RESULTS: The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR-treated group. Also, 99m Tc-DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group. CONCLUSIONS: According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy.

99mTc-HYNIC-(tricine/EDDA)-FROP peptide for MCF-7 breast tumor targeting and imaging.

BACKGROUND: Breast cancer is the most common malignancy among women in the world. Development of novel tumor-specific radiopharmaceuticals for early breast tumor diagnosis is highly desirable. In this study we developed 99mTc-HYNIC-(tricine/EDDA)-Lys-FROP peptide with the ability of specific binding to MCF-7 breast tumor. METHODS: The FROP-1 peptide was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC) and labeled with 99mTc using tricine/EDDA co-ligand. The cellular specific binding of 99mTc-HYNIC-FROP was evaluated on different cell lines as well as with blocking experiment on MCF-7 (human breast adenocarcinoma). The tumor targeting and imaging of this labeled peptide were performed on MCF-7 tumor bearing mice. RESULTS: Radiochemical purity for 99mTc-HYNIC-(tricine/EDDA)-FROP was 99% which was determined with ITLC method. This radiolabeled peptide showed high stability in normal saline and serum about 98% which was monitored with HPLC method. In saturation binding experiments, the binding constant (Kd) to MCF-7 cells was determined to be 158 nM. Biodistribution results revealed that the 99mTc-HYNIC-FROP was mainly exerted from urinary route. The maximum tumor uptake was found after 30 min post injection (p.i.); however maximum tumor/muscle ratio was seen at 15 min p.i. The tumor uptake of this labeled peptide was specific and blocked by co-injection of excess FROP. According to the planar gamma imaging result, tumor was clearly visible due to the tumor uptake of 99mTc-HYNIC-(tricine/EDDA)-FROP in mouse after 15 min p.i. CONCLUSIONS: The 99mTc-HYNIC-(tricine/EDDA)-FROP is considered a promising probe with high specific binding to MCF-7 breast cancer cells.

The effects of tumor-derived supernatants (TDS) on cancer cell progression: A review and update on carcinogenesis and immunotherapy.

Tumors can produce bioactive substances called tumor-derived supernatants (TDS) that modify the immune response in the host body. This can result in immunosuppressive effects that promote the growth and spread of cancer. During tumorigenesis, the exudation of these substances can disrupt the function of immune sentinels in the host and reinforce the support for cancer cell growth. Tumor cells produce cytokines, growth factors, and proteins, which contribute to the progression of the tumor and the formation of premetastatic niches. By understanding how cancer cells influence the host immune system through the secretion of these factors, we can gain new insights into cancer diagnosis and therapy.

WITHDRAWN: Comparison of the Efficacy of Oral Magnesium with Oral Ketorolac for Postoperative Pain Management in Anorectal Surgery: A Double-blinded Randomized Clinical Trial

The article has been withdrawn at the request of the editor of the journal Reviews on Recent Clinical Trials.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Comparison of the Effects of Govarcin Herbal Capsule and Metoclopramide for Alleviating Gastrointestinal Symptoms in Patients with Functional Dyspepsia: A Randomized Double-blind Clinical Trial.

BACKGROUND: Functional dyspepsia (FD) is felt as a discomfort or pain on the center line or upper abdomen. In this study, we aimed to compare the effects of Govarcin herbal capsule and Metoclopramide for alleviating gastrointestinal symptoms in patients with FD. METHODS: Totally, 106 patients enrolled in a double-blind, clinical trial study. The participants had FD and were divided into two groups receiving Govarcin and Metoclopramide by block randomization. The patients were treated for four weeks, taking one Govarcin capsule or Metoclopramide tablet after each meal. The rate of improvement in patients was assessed by mitigation of clinical symptoms, including epigastric pain, fullness, discomfort, nausea, vomiting and heartburn. Also, before and after intervention, we used Nepin questionnaire and ROME III. SPSS statistics 25 software was used for data analyzing. RESULTS: Clinical symptom score changes between Govarcin and Metoclopramide patients' groups showed that there was no significant difference in any of the clinical symptom scores (except for heartburn, p-value=0.012) between the study groups. Nepean score in Govarcin group before and after treatment were 19.3±4.8 and 8.9±2.8, respectively (p-value<0.001). For Metoclopramide group, these values were 19.8±3.5 and 9.4±2.1 respectively (p-value<0.001). No significant difference was found in terms of Nepean score between the Govarcin and Metoclopramide groups (p-value=0.995). CONCLUSION: Govarcin herbal capsule can be used to remedy symptoms in patients with FD. It seems that Govarcin is as effective as Metoclopramide in fighting symptoms of FD as no significant difference in efficacy has been demonstrated between them.

A Single-group, Clinical Interventional Study on the Effect of Iron Deficiency Anemia on Blood Glucose and Insulin Resistance in Women with Type II Diabetes.

AIMS: Iron deficiency anemia (IDA) is one of the disorders recently associated with an increase in insulin resistance (IR) and, consequently, diabetes mellitus (DM) affection by causing oxidative stress. In this study, we look at how IDA may contribute to developing type II diabetes mellitus (T2DM), controlling diabetes, and reducing IR in women with T2DM. METHODS: In this single group, clinical interventional study, we enrolled 40 women with T2DM and IDA. Before and after intervention with ferrous sulfate tablets, their blood glucose (BG) levels and IR levels were evaluated. This study was approved by the Ethics Committee of Qom University of Medical Sciences (ethics code: IR.MUQ.REC.1397.031) and registered at the Iranian Center for Clinical Trials (No. IRCT20170215032587N3). A significant level was considered p <0.05. RESULT: The mean age of patients was 48.18 ± 4.6 years, with 5.3-5.8 years duration of T2DM. After the intervention, the mean fasting blood glucose (FBG) level reached 198.53 ± 48.11 to 170.93 ± 37.41, which was significant (p <0.0001). Also, hemoglobin A1C level reached from 8.49 ± 0.9 to 7.96 ± 0.58, which was significant (p <0.0001). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) demonstrating a significant reduction of IR levels after intervention with ferrous sulfate tablets (p <0.018). CONCLUSIONS: IDA treatment in patients with T2DM can significantly reduce the BG and IR levels. To better control BG, checking iron status and its correction may provide better clinical outcomes in these patients. CLINICAL TRIAL REGISTRATION NUMBER: IRCT20170215032587N3.

Role of T follicular helper cells in autoimmune rheumatic Diseases: A systematic review on immunopathogenesis and response to treatment.

BACKGROUND: T follicular helper (Tfh) cells are a subdivision of T helper cells involved in antigen-specific B cell immunity. Tfh cells play an essential role in the interaction of T cells/B cells in the germinal centers (GC), and dysregulation of Tfh actions can offer pathogenic autoantibody formation and lead to the development of autoimmune diseases. This study seeks to evaluate changes in Tfh frequency and its related cytokines in autoimmune disease, its association with disease phase, severity, prognosis, and the effect of immunosuppressive treatment on the Tfh population. METHOD: The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. Electronic databases, including PubMed, Scopus, Web of Science, and Embase, were systematically searched for potentially eligible studies up to January 1, 2024. RESULTS: We identified 4998 articles in the initial search, from which 1686 similar titles were removed. A total of 3312 articles were initially screened, and 3051 articles were excluded by title/abstract screening. A total of 261 studies were considered for full-text assessment, and 205 articles were excluded by reason. Finally, a total of 56 studies were included in our review. CONCLUSION: The population of Tfh cells is generally higher in autoimmune diseases versus Health control. Moreover, the number of Tfh cells is associated with the disease severity and can be considered for determining the prognosis of studies. Also, peripheral blood circulating Tfh (cTfh) cells are an available sample that can be used as an indicator for diagnosing diseases.

Choosing the Right Protocol to Establish MCF-7 Tumor Xenograft in Nude Mice.

BACKGROUND: Xenografts of various human cancers in nude mice provide a helpful model in cancer research. This study aimed to develop a xenograft mouse model of MCF-7 breast cancer using injectable estradiol valerate. METHODS: Thirty healthy female C57 nu/nu mice were engrafted with three protocols to establish an MCF-7 tumor. Injectable estradiol valerate (10 mg/ml) was used as a substitute for estradiol pellets. The development of tumors was recorded daily, and data were statistically analyzed. Histology of bladder, kidney, and tumors was used to estimate tumor establishment and probable urinary adverse effects. RESULTS: According to the findings, the duration of MCF-7 tumor growth was the lowest for protocol B (tumor tissue). Also, this protocol had the highest xenograft yield within the shortest time duration (37 days for protocol B vs. 73 days for protocol A) without causing urinary adverse effects. CONCLUSION: Our findings revealed that estradiol valerate, which is way less expensive than estradiol pellets, can be used as a tumor proliferator to establish MCF-7 tumors with the highest yield when MCF-7 tumors have been used for xenograft.

Effects of Pregabalin as a Neural Pathway Inhibitor for the Treatment of Resistant Subacute and Chronic Cough: A Pilot Clinical Trials Study.

BACKGROUND: Cough hypersensitivity syndrome is one of the causes of chronic cough. Small clinical trials have suggested the effects of pregabalin as a neural pathway inhibitor in treating subacute and chronic cough resistance. METHODS: This study is an 8-week, pilot study randomized, double-blind clinical trial on 30 patients' resistant to treatment of the underlying cause who were referred to an ultra-specialized lung clinic, Shahid Beheshti Hospital, between 2021-2022. The samples were randomly divided into control (dextromethorphan and placebo) and intervention (dextromethorphan and pregabalin). Patients were evaluated at the beginning, during, and after eight weeks of treatment, using the modified standard Leicester Cough Questionnaire (LCQ) regarding the changes and the rate of recovery compared to before Participation in the study. FINDINGS: The quality of life score of patients eight weeks after treatment had a significant difference and was higher in the intervention group (In the pregabalin group) than in the control group (p =0.006). The recovery rate of cough in 26% of patients was equal to 70%, but others were reported up to 50%. CONCLUSION: Pregabalin increases the quality of life in patients with subacute and chronic cough resistant to standard treatment and increases the rate of recovery in these patients.