Association of anxiety disorder, depression, and bipolar disorder with autoimmune thyroiditis: A bidirectional two-sample mendelian randomized study.

BACKGROUND: Anxiety disorder, depression, and bipolar disorder are common psychiatric disorders, and their association with autoimmune thyroiditis (AIT) has been of great interest. This study aimed to investigate the potential causal relationship between these psychiatric disorders and AIT. METHODS: We used publicly available summary statistics from large-scale genome-wide association studies to select, quality control and cluster genetic variant loci associated with anxiety disorder, depression, bipolar disorder and AIT as instrumental variables (IVs). The Mendelian randomization (MR) study mainly used inverse variance weighting (IVW) combined with MR-egger regression and weighted median estimation (WME) to estimate bidirectional causality between mental disorders and AIT. In addition, we conducted heterogeneity and multivariate tests to verify the validity of IVW. RESULTS: Two-sample bidirectional MR analysis revealed a positive causal link between depression and AIT. The forward MR analysis of IVW (OR 1.614, 95 % CI 1.104-2.358, P = 0.013) and WME (OR 2.314, 95 % CI 1.315-4.074, P = 0.004) demonstrated thatdepression potentially elevate the risk of AIT development, while, our investigation did not uncover a causal relationship between anxiety disorder, bipolar disorder and AIT. The results of reverse MR analysis showed that there was no significant causal relationship between AIT and anxiety disorder, depression, and bipolar disorder (P > 0.05). CONCLUSIONS: The results of the forward MR analysis suggest a positive association between depression, and AIT risk, while indicating no support for a causal link between anxiety disorder or bipolar disorder and AIT risk based on the current data. Subsequent studies will be essential for elucidating the biological mechanisms and potential confounders underlying these associations.

Effectiveness of Enriched Milk with Ashwagandha Extract and Tryptophan for Improving Subjective Sleep Quality in Adults with Sleep Problems: A Randomized Double-Blind Controlled Trial.

A randomized, double-blind and controlled study was conducted to assess the effectiveness of the intake of 250 mL of lactose-free skimmed milk enriched with ashwagandha (Withania somnifera) alone or combined with tryptophan vs. non-enriched milk (control) on the subjective quality of sleep in healthy adults with sleep problems. The duration of supplementation was 90 days. Fifty-two eligible subjects were assigned to the study arms of ashwagandha 250 mg, ashwagandha 250 mg plus tryptophan 175 mg, ashwagandha 600 mg, and control with 13 subjects in each group. It was hypothesized that ashwagandha plus tryptophan could be superior to ashwagandha alone for improving sleep-related variables. Changes in the visual analogue scale (VAS) for sleep quality were significantly higher in the three experimental groups as compared with controls (p = 0.014). Improvements in the subscales of the Pittsburg Sleep Quality Index (PSQI) were found in all groups, but between-group differences were not significant. In the index of insomnia severity, decreases were higher in the three experimental groups as compared with controls especially in the group of ashwagandha 600 mg. Daytime somnolence was also reduced in the three experimental groups. Changes in anxiety levels and Morningness-Eveningness Questionnaire were not observed. The study products did not elicit changes in body composition and were well tolerated and safe. The data did not support the hypothesis, as the combination of ashwagandha and tryptophan did not show greater benefits in improving sleep quality than ashwagandha alone. However, the results from the three experimental groups containing ashwagandha were more favorable compared to the placebo group.

Causal association of circulating immune cells and lymphoma: A Mendelian randomization study.

Background: Malignant lymphoma (ML) is a group of malignant tumors originating from the lymphatic hematopoietic system. Previous studies have found a correlation between circulating immune cells and ML. Nonetheless, the precise influence of circulating immune cells on ML remains uncertain. Methods: Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and ML risk. A total of four types of immune signatures, median fluorescence intensities, relative cell, absolute cell, and morphological parameters were included. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between circulating immune cells and the risk of ML. Sensitivity analysis was conducted using Cochran's Q test, the Mendelian randomization Egger regression intercept test, and leave-one-out analysis. Results: ML had a statistically significant effect on immunophenotypes. Twenty-three immunophenotypes were identified to be significantly associated with Hodgkin lymphoma risk through the IVW approach, and the odds ratio values of CD64 on CD14- CD16+ monocyte [2.31, 95% confidence interval (CI) = 1.41-3.79, P1 = 0.001], IgD+ CD24+ B-cell %lymphocyte (2.06, 95% CI = 1.13-3.79, P1 = 0.018), B-cell %lymphocyte (1.94, 95% CI = 1.08-3.50, P1 = 0.027), CD24+ CD27+ B-cell %lymphocyte (1.68, 95% CI = 1.03-2.74, P1 = 0.039), and CD14+ CD16- monocyte %monocyte (1.60, 95% CI = 1.15-2.24, P1 = 0.006) ranked in the top five. Eleven immunophenotypes were identified to be significantly associated with non-Hodgkin lymphoma risk, CD86 on granulocyte (2.35, 95% CI = 1.18-4.69, P1 = 0.015), CD28-CD8+ T-cell absolute count (1.76, 95% CI = 1.03-2.99, P1 = 0.036), CCR2 on myeloid dendritic cell (CD24+ CD27+ B cell, 95% CI = 1.02-1.66, P1 = 0.034), CD3 on effector memory CD8+ T cell (1.29, 95% CI = 1.02-1.64, P1 = 0.012), and natural killer T %lymphocyte (1.28, 95% CI = 1.01-1.62, P1 = 0.046) were ranked in the top five. Conclusion: This study presents compelling evidence indicating the correlation between circulating immune cells and lymphoma, thus providing guidance for future clinical research.

Comparable bone penetration between antibiotic-loaded and plain bone cement in total knee arthroplasty.

INTRODUCTION: One of the main concerns around the use of antibiotic-loaded bone cement (ALBC) is the potential reduction in the mechanical properties of the cement when antibiotics are admixed. The purpose of this study was to determine whether there is a difference between plain cement and ALBC in terms of radiological intrusion into the bone in total knee arthroplasties (TKAs). METHODS: Prospective randomized study of 80 consecutive patients who underwent TKA. Depending on the cement used, patients were divided into two groups by a computer-generated randomization programme: the cement without antibiotic (Group 1) or the ALBC (Group 2). Cement intrusion was measured in postoperative radiographs in eight different regions in the tibial component and six regions in the femoral component. RESULTS: The average cement intrusion was similar in both groups (p = nonsignificance [n.s.]). Group 1 (plain cement) had an average cement intrusion in the femur of 1.4 mm (±0.4) and 2.4 mm (±0.4) in the tibia. In Group 2 (ALBC), the average cement intrusion in the femur came to 1.6 (±0.5) and 2.4 mm (±0.5) in the tibia. In 80% of the patients, the cement intrusion in the tibia averaged a minimum of 2 mm, being similar in both groups (p = n.s.). CONCLUSION: There are no differences in bone intrusion when comparing plain cement to ALBC. Therefore, the use of ALBC in primary TKA may be indicated, achieving optimal bone penetration. LEVEL OF EVIDENCE: Level I.

Has Coca-Cola treatment become the first-line therapy for gastric bezoars, both in general and specifically for western countries?

Phytobezoars is a rare disease and less common in Western countries. The stomach is the primary site for these formations, and endoscopic treatment involving fragmentation and extraction has traditionally been the most effective approach. However, medical treatments using enzymatic and chemical agents, such as cellulase and Coca-Cola, aimed at dissolving the bezoars, have also been utilized, showing varying degrees of resolution success. Notably, the oral dissolution treatment with Coca-Cola has emerged as a promising, simpler, and more cost-effective method. The study by Liu et al represents an important step in clinical research on this topic, despite some limitations that need addressing for a more comprehensive understanding of its findings. Key considerations for future research include sample size calculation, endoscopic procedure details, outpatient vs. inpatient treatment, and detailed cost calculations. The study's exclusions, such as patients with upper gastric surgery, phytobezoars older than 14 d, and cases of gastroparesis, limit its applicability to broader populations, especially in Western countries. Given the promising outcomes of the Coca-Cola treatment, it's advocated as a first-line therapy for phytobezoars. Nonetheless, further research is essential to overcome these limitations. However special situations such as perforation or small bowel obstruction will require surgical treatment.

Comparison of mirabegron and vibegron for clinical efficacy and safety in female patients with overactive bladder: a multicenter prospective randomized crossover trial.

PURPOSE: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients. METHODS: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable. RESULTS: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron. CONCLUSION: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence.

Marizomib for patients with newly diagnosed glioblastoma: A randomized phase 3 trial.

BACKGROUND: Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood-brain barrier. METHODS: European Organisation for Research and Treatment of Cancer 1709/Canadian Cancer Trials Group CE.8 was a multicenter, randomized, controlled, open-label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age > 18 years and Karnofsky performance status > 70. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ/RT→TMZ with patients receiving the only standard treatment in the whole population and in the subgroup of patients with MGMT promoter-unmethylated tumors. RESULTS: The trial was opened at 82 institutions in Europe, Canada, and the U.S. A total of 749 patients (99.9% of the planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs. 16.5 months; HR = 1.04; P = .64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR = 0.97; P = .67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs. 15.1 months, HR = 1.13; P = .27). More CTCAE grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm. CONCLUSIONS: Adding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.

Radiotherapy is superior to transarterial chemoembolization as adjuvant therapy after narrow-margin hepatectomy in patients with hepatocellular carcinoma: A single-center prospective randomized study.

BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.

A Tutorial on Net Benefit Regression for Real-World Cost-Effectiveness Analysis Using Censored Data from Randomized or Observational Studies.

HIGHLIGHTS: We illustrate the steps involved in carrying out cost-effectiveness analysis using net benefit regressions with possibly censored demo data by providing step-by-step guidance and code applied to a data set.We demonstrate the importance of these new methods by illustrating how naïve methods for handling censoring can lead to biased cost-effectiveness results.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Causal links between sedentary behavior, physical activity, and psychiatric disorders: a Mendelian randomization study.

BACKGROUND: Studies suggest a correlation between excessive sedentary behavior, insufficient physical activity, and an elevated likelihood of experiencing psychiatric disorder. Nonetheless, the precise influence of sedentary behavior and physical activity on psychiatric disorder remains uncertain. Hence, the objective of this research was to investigate the possible causal relationship between sedentary behavior, physical activity, and the susceptibility to psychiatric disorder (depression, schizophrenia and bipolar disorder), utilizing a two-sample Mendelian randomization (MR) approach. METHODS: Potential genetic instruments related to sedentary leisure behaviors were identified from the UK Biobank database, specifically a summary-level genome-wide association study (GWAS) involving 422,218 individuals of European descent. The UK Biobank database also provided the GWAS data for physical activity. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between sedentary behavior, physical activity, and the risk of psychiatric disorder (depression, schizophrenia and bipolar disorder). Sensitivity analysis was conducted using Cochran's Q test, the MR-Egger intercept test, the MR-pleiotropy RESidual sum and outlier test, leave-one-out analysis, and funnel plot analysis. RESULTS: According to the IVW analysis, there was a significant association between genetically predicted leisure television watching and an increased risk of depression (odds ratio [OR] = 1.027, 95% confidence interval [CI]: 1.001-1.053; P = 0.04). The IVW analysis also indicated that there was a decreased risk of depression associated with fraction accelerations of > 425 milligravities, as measured by accelerometers (OR = 0.951, 95%CI: 0.914-0.989; P = 0.013). The other MR methods obtained consistent but non-significant results in the same direction. However, there was no evidence of a causal association between genetic liability for moderate-to-vigorous physical activity, accelerometer-assessed physical activity, computer use, or driving and the risk of depression. Furthermore, IVW analysis has also found that driving has a slight effect in reducing the risk of schizophrenia (OR = 0.092, 95%CI: 0.010-0.827; P = 0.033), while leisure television viewing has a significant protective effect against the onset of bipolar disorder (OR = 0.719, 95%CI: 0.567-0.912; P = 0.006). CONCLUSION: The study provides compelling evidence of a link between depression, bipolar disorder, and excessive TV watching. Furthermore, it suggests that higher accelerometer-assessed fraction accelerations of > 425 milligravities can serve as a genetic protective factor against depression. To mitigate the risk of developing depression, it is advisable to reduce sedentary activities, particularly television watching, and prioritize engaging in vigorous physical exercise.

The impact of Twitter/X promotion on visibility of research articles: Results of the #TweetTheJournal study.

Aim: Social media (SoMe) are emerging as important tools for research dissemination. Twitter/X promotion has been shown to increase citation rates in well-established journals. We aimed to test the effect of a SoMe promotion strategy on the Mendeley reader counts, the Altmetric Attention Score and the number of citations in an upcoming open-access journal. Methods: The #TweetTheJournal study is a randomized, controlled study. Articles published in seven subsequent issues of the International Journal of Cardiology Heart & Vasculature (April 2021-April 2022) were randomized to a Twitter/X promotion arm (articles were posted four times) and to a control arm (without active posting). Articles with accompanied editorials were excluded. Primary endpoint of the study was Mendeley reader count, secondary endpoints were Altmetric Attention Score and number of citations. Follow-up was one year. Results: SoMe promotion of articles showed no statistically significant difference in Mendeley reader counts or number of citations at one year follow up. SoMe promotion resulted in a statistically significant higher Altmetric Attention Score in the intervention compared to the control group (RR 1.604, 95 % CI 1.024-2.511, p = 0.039). In the overall group, Altmetric Attention Score showed a correlation with Mendeley reader counts (Spearman's ρ = 0.202, p = 0.010) and Mendeley reader counts correlated significantly with number of citations (Spearman's ρ = 0.372, p < 0.001). Conclusion: A dedicated SoMe promotion strategy did not result in statistically significant differences in early impact indicators as the Mendeley reader count in a upcoming journal, but increased the Altmetric Attention Score.

Comparison of efficacy between levonorgestrel intrauterine system and dienogest in adenomyosis: a randomized clinical trial.

Background: Medical management of adenomyosis is an emerging perspective in modern gynecology. Though levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG) effectively relieve symptoms in adenomyosis, neither has been approved for the same indication. Our study aims to compare the efficacy and safety of these progestins in treating adenomyosis. Objective: To study the efficacy and safety of LNG-IUS versus DNG in patients with symptomatic adenomyosis. Design: Open-labeled, parallel, single-centered, randomized clinical trial. Methods: Patients with adenomyosis-associated pain with or without abnormal uterine bleeding were randomly allocated to either LNG-IUS group or DNG group. The primary outcome was a reduction in painful symptoms after 12 weeks of treatment measured by visual analog scale (VAS) score. Changes in menstrual blood loss (MBL), improvement in quality of life (QoL), and adverse drug reactions were also analyzed. Results: The VAS score significantly decreased from baseline in both groups. The baseline and post-treatment VAS scores in the LNG-IUS group were 6.41 ± 1.07 and 3.41 ± 1.04 (p = <0.001) and in the DNG group, were 6.41 ± 0.95 and 3.12 ± 1.40 (p = <0.001), respectively. A significantly greater proportion of patients in the LNG-IUS group experienced lighter MBL as compared to the DNG group [27/30 (90%) in the LNG-IUS group versus 17/22 (77.2%) in the DNG group (p = 0.006)]. Both the groups had improvement in QOL scores calculated by the World Heath Organisation QOL scale (WHOQOL BREF) questionnaire; however, it was more pronounced in the DNG group [(28.76 ± 30.47 in the LNG-IUS group versus 48.26 ± 44.91 in the DNG group (p = 0.04)]. Both the agents were safe as there were no reported major adverse drug reactions. Conclusion: DNG can be an effective and safe alternative to LNG-IUS for the medical management of adenomyosis. Trial registration: The trial was prospectively registered at the clinical trial registry - India (CTRI) vide CTRI number CTRI/2020/05/025186.

Comparison of effectiveness and safety of Mirena (LNG-IUS) with dienogest for treatment of adenomyosis Adenomyosis is a condition affecting women, typically aged 40­50, but its incidence is rising in younger women, impacting fertility. It causes painful symptoms like dysmenorrhea, dyspareunia, chronic pelvic pain, and heavy menstrual bleeding. Managing symptoms is crucial, and medical approaches include levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG). LNG-IUS is reversible contraception, approved for eight years, effectively treating symptoms. DNG, a newer progestin, is effective for endometriosis, but evidence for adenomyosis is limited. This single-center, open-label randomized clinical trial compared LNG-IUS and DNG in treating adenomyosis. Women over 20 with pelvic pain were diagnosed using ultrasound and met specific criteria. After informed consent, participants were assigned randomly to LNG-IUS or DNG groups. Treatment outcomes, including pelvic pain, quality of life (QoL), and adverse effects, were assessed over 12 weeks. Out of 84 assessed, 74 women were recruited, with 34 in each group analyzed. After 12 weeks, both groups showed significantly reduced pelvic pain (VAS scores), but no significant difference was found between the groups. LNG-IUS resulted in a significantly greater reduction in heavy menstrual bleeding (HMB), whereas DNG showed better improvement in overall QOL. Adverse effects were similar in both groups, with hot flushes reported in the DNG group. This study is one of the few comparing LNG-IUS and DNG for adenomyosis, finding both effective for symptom relief. Although LNG-IUS was superior in reducing HMB, DNG showed better overall improvement in QoL. Safety profiles were similar. Previous studies support the efficacy of DNG in reducing adenomyosis symptoms. To conclude, both LNG-IUS and DNG effectively alleviate adenomyosis symptoms, with LNG-IUS superior in reducing heavy menstrual bleeding and DNG showing better overall improvement in QOL. DNG is a viable and effective alternative to LNG-IUS.

Use of 5-ALA fluorescence-guided surgery versus white-light conventional microsurgery for the resection of newly diagnosed glioblastomas (RESECT study): a French multicenter randomized phase III study.

OBJECTIVE: Only one phase III prospective randomized study, published in 2006, has assessed the performance of 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) for glioblastoma resection. The aim of the RESECT study was to compare the onco-functional results associated with 5-ALA fluorescence and with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care. METHODS: This was a phase III prospective randomized single-blinded study, involving 21 French neurosurgical centers, comparing 5-ALA FGS with white-light conventional microsurgery in patients with glioblastoma managed according to the current standards of care, including neuronavigation use and postoperative radiochemotherapy. Randomization was performed in a 1:1 ratio stratified by institution. 5-ALA (20 mg/kg) or placebo (ascorbic acid) was administered orally 3-5 hours before the incision. The primary endpoint was the rate of gross-total resection (GTR) blindly assessed by an independent committee. Patients without a confirmed pathological diagnosis of glioblastoma or with unavailable postoperative MRI studies were excluded from the per-protocol analysis. RESULTS: Between March 2013 and August 2016, a total of 171 patients were assigned to the 5-ALA fluorescence group (n = 88) or to the placebo group (n = 83). Twenty-four cases were excluded because the WHO histological criteria of grade 4 glioma were not met. The proportion of GTR was significantly higher in the 5-ALA fluorescence group (53/67, 79.1%) than in the placebo group (33/69, 47.8%; p = 0.0002). After adjustment for age, preoperative Karnofsky Performance Scale score, and tumor location, GTR was still associated with 5-ALA fluorescence (OR 4.13 [95% CI 1.94-8.79]). The mean 7-day postoperative Karnofsky Performance Scale score (≥ 80% in 49/71, 69.0% [5-ALA group]; 50/71, 70.4% [placebo group], p = 0.86) and the proportion of patients with a worsened neurological status 3 months postoperatively (9/68, 13.2% [5-ALA group]; 9/70, 12.9% [placebo group], p = 0.95) were similar between groups. Adverse events related to 5-ALA intake were rare and consisted of photosensitization in 4/87 (4.6%) patients and hepatic cytolysis in 1/87 (1.1%) patients. The 6-month PFS (70.2% [95% CI 57.7%-79.6%] and 68.4% [95% CI 55.7%-78.1%]; p = 0.39) and 24-month OS (30.1% [95% CI 18.9%-42.0%] and 37.7% [95% CI 25.8%-49.5%]; p = 0.89) did not significantly differ. In multivariate analysis, GTR was an independent predictor of PFS (hazard ratio 0.56 [95% CI 0.36-0.86], p = 0.008) and OS (hazard ratio 0.65 [95% CI 0.42-1.01], p = 0.05). The use of 5-ALA FGS generates a significant extra cost of 2732.36€ (95% CI 1658.40€-3794.11€). CONCLUSIONS: The authors found that 5-ALA FGS is an easy-to-use, cost-effective, and minimally time-consuming technique that safely optimizes the extent of resection in patients harboring glioblastoma amenable to a large resection.

Outcomes of COVID-19 patients undergoing extracorporeal membrane oxygenation: A systematic review and meta-Analysis.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has been ongoing for over 3 years, during which numerous clinical and experimental studies have been conducted. The objective of this systematic review and meta-analysis was to assess the survival probability and complications of COVID-19 patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: We searched the databases by using Population-Intervention-Comparison-Outcome-Study Design (PICOS). We conducted a search of the PubMed, Web of Science, and EMBASE databases to retrieve studies published until December 10, 2022. A random-effects meta-analysis, subgroup analysis, and assessed the studies using the Newcastle-Ottawa Scale score. The results were presented as pooled morbidity with 95% confidence intervals. RESULTS: The study was conducted on 19 studies that enrolled a total of 1494 patients, and the results showed a pooled survival probability of 66.0%. The pooled morbidity for intracranial hemorrhage was 8.7%, intracranial thrombosis 7.0%, pneumothorax 9.0%, pulmonary embolism 11.0%, pulmonary hemorrhage 9.0%, heart failure 14.0%, liver failure 13.0%, renal injury 44.0%, gastrointestinal hemorrhage 6.0%, gastrointestinal ischemia 6.0% and venous thrombosis 31.0%. CONCLUSION: This systematic review and meta-analysis of observational studies focused on the survival probability and complications of COVID-19 patients undergoing ECMO, which are significant in evaluating the use of ECMO in COVID-19 patients and provide a basis for further research. TRIAL REGISTRATION: Our study was registered on PROSPERO with registration number CRD42022382555.

The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized study.

Background: Type 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, there's no recognized solution. There is an increasing body of evidence from numerous observational studies indicating a significant correlation between gut flora and metabolic disease progression, particularly in relation to T2DM. Despite this, the direct impact of gut microbiota on T2DM isn't fully understood yet. Methods: The summary statistical figures for intestinal microbiota were sourced from the MiBioGen consortium, while the summary statistical data for T2DM were gathered from the Genome-Wide Association Studies (GWAS) database. These datasets were used to execute a two-sample Mendelian randomization (MR) investigation. The Inverse Variance Weighted (IVW), Maximum Likelihood, MR-Egger, Weighted Median, and Weighted Models strategies were employed to assess the impact of gut microbiota on T2DM. Findings were primarily obtained using the IVW technique. Techniques like MR-Egger were employed to identify the occurrence of horizontal pleiotropy among instrumental variables. Meanwhile, Cochran's Q statistical measures were utilized to assess the variability or heterogeneity within these instrumental variables. Results: The outcomes from the IVW analysis demonstrated that the genus Alistipes (OR = 0.998, 95% confidence interval: 0.996-1.000, and P = 0.038), genus Allisonella (OR = 0.998, 95% confidence interval: 0.997-0.999, P = 0.033), genus Flavonifractor (OR = 0.995, 95% confidence interval: 0.993-0.998, P = 3.78 × 10-3), and genus Haemophilus (OR = 0.995, 95% confidence interval: 0.993-0.998, P = 8.08 × 10-3) all acted as defense elements against type 2 diabetes. Family Clostridiaceae1 (OR = 1.003, 95% confidence interval: 1.001-1.005, P = 0.012), family Coriobacteriaceae (OR = 1.0025, 95% confidence interval: 1.000-1.005, P = 0.043), genus Actinomyces (OR = 1.003,95% confidence interval: 1.001-1.005, P = 4.38 × 10-3), genus Candidatus Soleaferrea (OR = 1.001,95% confidence interval: 1.000-1.002 P = 0.012) were risk factors for type 2 diabetes. False Discovery Rate correction was performed with finding that genus.Allisonella, genus.Alistipes, family Coriobacteriaceaeand T2DM no longer displayed a significant causal association. In addition, no significant heterogeneity or horizontal pleiotropy was found for instrumental variable. Conclusion: This MR study relies on genetic variation tools to confirm the causal effect of genus Flavonifractor, genus Haemophilus, family Clostridiaceae1, genus Actinomyces and genus Candidatus Soleaferrea on T2DM in the gut microbiome, providing new directions and strategies for the treatment and early screening of T2DM, which carries significant clinical relevance. To develop new biomarkers and better understand targeted prevention strategies for T2DM, further comprehensive investigations are required into the protective and detrimental mechanisms exerted by these five genera against T2DM.

EORTC 1409 GITCG/ESSO 01 - A prospective colorectal liver metastasis database for borderline or initially unresectable diseases (CLIMB): Lessons learnt from real life. From paradigm to unmet need.

AIM: Multidisciplinary management of metastatic colorectal liver metastases (CRLM) is still challenging. To assess postoperative complications in initially unresectable or borderline resectable CRLM, the prospective EORTC-1409 ESSO 01-CLIMB trial capturing 'real-life data' of European centres specialized in liver surgery was initiated. MATERIAL AND METHODS: A total of 219 patients were registered between May 2015 and January 2019 from 15 centres in nine countries. Eligible patients had borderline or initially unresectable CRLM assessed by pre-operative multidisciplinary team discussion (MDT). Primary endpoints were postoperative complications, 30-day and 90-days mortality post-surgery, and quality indicators. We report the final results of the 151 eligible patients that underwent at least one liver surgery. RESULTS: Perioperative chemotherapy with or without targeted treatment were administered in 100 patients (69.4%). One stage resection (OSR) was performed in 119 patients (78.8%). Two stage resections (TSR, incl. Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS)) were completed in 24 out of 32 patients (75%). Postoperative complications were reported in 55.5% (95% CI: 46.1-64.6%), 64.0% (95% CI: 42.5-82%), and 100% (95% CI: 59-100%) of the patients in OSR, TSR and ALPPS, respectively. Post-hepatectomy liver failure occurred in 6.7%, 20.0%, and 28.6% in OSR, TSR, and ALPPS, respectively. In total, four patients (2.6%) died after surgery. CONCLUSION: Across nine countries, OSR was more often performed than TSR and tended to result in less postoperative complications. Despite many efforts to register patients across Europe, it is still challenging to set up a prospective CRLM database.

Acute toxicities of intravenous, intraperitoneal, or intratumoral injection of natural killer cells in human pancreatic adenocarcinoma-bearing mice: Randomized study.

AIMS: To investigate the possible acute toxicities and pathological changes associated with intravenous, intraperitoneal, or intratumoral injection of natural killer (NK) cells in mice subcutaneously bearing human pancreatic adenocarcinoma (PaC). METHODS: 100 NPG tumor-bearing mice (50/sex) were engrafted subcutaneously with human PaC BXPC-3 cells 9 days before administration. They were randomly divided into 10 groups with 5 males and 5 females in each group. Mice in Group 1 were given sodium chloride intravenously as vehicle control, and mice in Groups 2-4 human peripheral blood-derived NK cells intravenously at doses of 2 × 107, 1 × 108, and 5 × 108 cells/kg, respectively; mice in Groups 5-7 were injected with NK cells intraperitoneally at doses of 2 × 107, 1 × 108, and 5 × 108 cells/kg, respectively, and mice in Groups 8-10 with NK cells intratumorally at doses of 4 × 103, 2 × 104, and 1 × 105 cells/mm3, respectively. Each group was given a single dose; the mice were observed clinically, and body weight, food intake, blood biochemistry, and tumor volume were measured. On Day 15, the mice were euthanized for gross anatomy and histopathology. RESULTS: On planned euthanasia, in Groups 2-4 no gross or microscopic pathological changes related to cells injection were found; in Groups 5-7 mice of both sexes showed a decrease in extramedullary hematopoiesis of spleen, and at the dose of 5 × 108 cells/kg, mice of both sexes showed an increase in the composition of spleen white pulp cells. In Groups 8-10, mice of both sexes at doses of 4 × 103 and 1 × 105 cells/mm3 and female mice at the dose of 2 × 104 cells/mm3 showed a decrease in extramedullary hematopoiesis of spleen, and female mice at a dose of 4 × 103 cells/mm3 and mice of both sexes at doses of ≥ 2 × 104 cells/mm3 showed an increase in the composition of spleen white pulp cells; perivascular/peribronchiolar inflammatory cell infiltration in lung and bronchus was observed in mice of both sexes at doses of ≥ 2 × 104 cells/mm3, and inflammatory cell infiltration in liver was observed in mice of both sexes at a dose of 1 × 105 cells/mm3. No other abnormal changes with toxicological significance in clinical observation, body weight, food intake, or blood biochemistry were observed in each group. CONCLUSIONS: In our study intravenous injection appears the safest way to give NK cells to human PaC-bearing mice. Using intraperitoneal or intratumoral administration, spleen, liver, and lung were the most often affected organs, albeit with mostly mild pathological changes.

An open-label, non-randomized study investigating the safety and efficacy of smallpox vaccine, LC16, as post-exposure prophylaxis for mpox.

Mpox is an acute exanthematous disease caused by the monkeypox virus. Since May 2022, it has spread as a community-acquired infection, mainly in Europe and the United States, and urgent measures to prevent this infection were also required in Japan. In this study, we investigated the post-exposure prophylaxis of mpox and safety after inoculating the smallpox vaccine. Participants in close contact with patients with mpox were inoculated with "Freeze-dried cell culture Smallpox Vaccine LC16," within 14 days after close contact. Six cases were registered, and all the participants were inoculated. No mpox symptoms or related complications were observed in the participants for 21 days after the close contact. Adverse events due to inoculation, such as rash, fever, lymphadenopathy, and local reaction at the inoculation site (comprising erythema, swelling, induration, and pain) were observed in the participants; however, all inoculation-related events were non-severe and non-serious, and the participants recovered during the 28-day observation period. The findings of this study suggest that inoculation with LC16 is an effective post-exposure prophylaxis in individuals who had close contact with patients with mpox. Further large-scale studies are warranted to validate these findings.

Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review.

Coronavirus disease-2019 (COVID-19) is an extremely contagious illness caused by the SARS-CoV-2 virus and has been declared a pandemic by the World Health Organization (WHO). There are currently no particular treatments, however, nebulized heparin has been offered as a viable therapy. The purpose of this systematic review is to assess the efficacy of nebulized heparin in COVID-19 patients with respiratory symptoms. Methods: Relevant studies were identified through a systematic search of the PubMed, Medline, Embase, Cochrane Library and Web of Science, and Scopus databases. The search terms included "nebulized heparin," "COVID-19," and "SARS-CoV-2." Studies that evaluated the use of nebulized heparin in COVID-19 patients with respiratory symptoms were included. The rest of the studies along with those that were not published in English were excluded. The systematic review was registered under PROSPERO-CRD42023413927. Observations: Five studies have been included in this systematic review. Case reports, case series, observational studies, and randomized controlled trial (RCT) comprised the studies. The patient sample sizes ranged from 2 to 98. The studies assessed the efficacy of nebulized heparin in COVID-19 patients with variable disease severity. The evaluated outcomes included mortality, hospital stay duration, oxygen requirements, and laboratory parameters. Conclusion: Based on the clinical studies included in this systematic review, nebulized heparin may be useful in the management of COVID-19. Oxygen saturation was greater, inflammatory indicators were lower, and hospital stays were shorter in these patients. However, the studies had limitations, including inconsistent sample sizes, varying dosages of nebulized heparin, and no control groups. Nebulized heparin in patients with COVID-19 needs to be studied further to determine its safety and effectiveness. How to cite this article: Gupta B, Ahluwalia P, Gupta N, Gupta A. Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review. Indian J Crit Care Med 2023;27(8):572-579.