Implications of potential clinically relevant interactions between COVID-19 vaccines and concomitant medications.

COVID-19 was announced as a global pandemic in 2020. Several types of COVID-19 vaccines are available such as mRNA vaccines, adenovirus vector vaccines, and protein subunit or inactivated virus vaccines. Vaccines are often administered in patients with chronic diseases who are likely to be treated with several drugs. A growing number of clinical observations indicated the possibility of interactions between COVID-19 vaccines and drugs. A hyperinflammatory state may spark significant imbalances in drug metabolism that may result in the alteration of drug pharmacokinetics and therapeutic response. Furthermore, interactions may result in additive or antagonistic or synergistic vaccine immune response. Information about COVID-19 vaccine-drug interactions is needed by physicians and pharmacists to make rational drug-use decisions. In this review, several individual and categorical evidence-based potential COVID-19 vaccine-drug interactions of clinical importance are described. Vigilance is needed to detect previously unreported COVID-19 drug interactions and to further assess known interactions. The clinical significance of which is not fully determined. Evidence suggests that adverse events to some drugs are rare after COVID-19 vaccination and their possibility should not affect vaccination of patients at risk. Clinicians prescribing medications should be aware of the likely risk of interaction with COVID-19 vaccines and may benefit from taking into account present recommendations of the best measures to avoid consequences of such interactions to preserve vaccine efficacy and patient safety.

Additive efficacy and safety of probiotics in the treatment of ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND: We aim to report the latest pooled analyses to evaluate the additive efficacy and safety of probiotics in the treatment of ulcerative colitis (UC). METHODS: We systematically searched the relevant literature investigating the efficacy and/or safety of probiotics in patients with UC from PubMed, Embase and Web of Science up to January 2023. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included studies according to the inclusion and exclusion criteria. Any discrepancies throughout these processes were solved by consensus. All statistical analyses were performed by Review Manager version 5.4 and Stata version 15.0. RESULTS: A total of 13 articles were included in the pooled analyses, and the studies were all randomized controlled trials with a total of 930 patients. There were no significant differences between the probiotics and placebo groups concerning demographic and baseline characteristics. For patients with active UC, the probiotic group boosted the remission rate by 87% compared to the placebo group, but failed to reach a statistical difference (OR: 1.87; 95% CI 0.98, 3.57; P = 0.06, I2 = 67%); furthermore, there were no statistical differences in maintenance of clinical remission, clinical response, change in UCDAI scores, or mucosal healing outcomes in the probiotic group compared to the placebo group. For patients in clinical remission, the clinical relapse rates were significantly lower in the probiotic group than in the placebo group (OR: 0.34; 95% CI 0.14, 0.79; P = 0.01). Moreover, this study did not observe a significant difference between the two groups for general adverse events rate (OR: 1.98; 95% CI 0.69, 5.68; P = 0.20). CONCLUSION: Probiotic-assisted therapy may be effective in inhibiting UC recurrence in patients in clinical remission without increasing the risk of treatment-related adverse events; furthermore, probiotics may increase the rate of clinical remission in patients with active UC. However, caution is needed when interpreting the clinical efficacy of probiotics in improving the clinical outcome of patients with active UC.

Efficacy and safety of adalimumab in pediatric patients with Crohn's disease: A systematic review and meta-analysis.

PURPOSE: There is currently no curative treatment for childhood Crohn's disease (CD). This meta-analysis aimed to validate the efficacy and safety of adalimumab (ADA) in pediatric patients with CD. MATERIALS AND METHODS: We searched all relevant studies in the PubMed, Web of Science, Embase, and Cochrane Library databases. The primary outcomes were induction (≤ 12 weeks) and maintenance (up to 48 weeks) of remission and response. Secondary outcomes were severe adverse events and opportunistic infections to ADA. The Cochrane bias assessment tool was used to assess the risk of bias in randomized controlled trials. The methodological quality of the single-arm studies was assessed using the methodological index for non-randomized studies tool. RESULTS: Ten clinical trials involving a total of 885 patients were included. Results indicated that 59% (95% confidence interval [CI] 39-80%) of the subjects treated with ADA achieved induction of remission, and 60% (95% CI 35-86%) of the subjects treated with ADA achieved induction of response, 57% (95% CI 44-70%) achieved maintenance of remission, and 63% (95% CI 26-69%) achieved maintenance of response. CONCLUSION: Current evidence indicates that ADA is effective in children and adolescents with CD and that adverse events vary but are usually not severe. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/ , identifier CRD42023402199.

The efficacy and safety of different does of intravenous tranexamic acid on blood loss in fresh foot and ankle fractures: a prospective, randomized controlled study.

BACKGROUND: There are a few studies on the effectiveness and safety of intravenous administration of tranexamic acid(TXA) in patients who underwent foot and ankle surgery, especially for preoperative hidden blood loss in patients with freshfoot and ankle fractures. Thus, the aim of this study was to investigate whether intravenous administration of different doses of TXA can effectively reduce perioperative blood loss and blood loss before surgery and to determine its safety. METHODS: A total of 150 patients with fresh closed foot and ankle fractures from July 2021 to July 2023 were randomly divided into a control group (placebo controlled [PC]), standard-dose group (low-dose group [LD], 1 g/24 h; medium-dose group [MD], 2 g/24 h), and high-dose group (HD, 3 g/24 h; ultrahigh-dose group [UD], 4 g/24 h). After admission, all patients completed hematological examinations as soon as possible and at multiple other time points postsurgery. RESULTS: There was a significant difference in the incidence of hidden blood loss before the operation between the TXA group and the control group, and the effect was greater in the overdose groups than in the standard-dose groups. There were significant differences in surgical blood loss (intraoperative and postoperative), postoperative HGB changes, and hidden blood loss among the groups. The TXA groups showed a significant decrease in blood loss compared to that of the control group, and the overdose groups had a more significant effect than the standard-dose groups. A total of 9 patients in the control group had early wound infection or poor healing, while only 1 patient in the other groups had this complication, and the difference among the groups was significant. No patients in any group suffered from late deep wound infection, cardiovascular or cerebrovascular events or symptomatic VTE. CONCLUSION: This is the first study on whether TXA can reduce preoperative hidden blood loss in patients with freshfoot and ankle fractures. In our study, on the one hand, intravenous application of TXA after foot and ankle fractures as soon as possible can reduce preoperative blood loss and postoperative blood loss. On the other hand, TXA can also lower wound complications, and over-doses of TXA are more effective than standard doses. Moreover, overdoses of TXA do not increase the incidence of DVT.

Immune checkpoint inhibitor combined with chemotherapy versus chemotherapy alone in the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: a meta-analysis of random controlled trials.

PURPOSE: Immune checkpoint inhibitor (ICI) monotherapy and chemotherapy (CT) have been used to treat recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC), with demonstrated survival benefits and good safety. However, whether combination therapy is superior to CT alone remains unclear. We summarized the existing evidence comparing the effectiveness and toxicities of ICI combined with CT versus CT alone. METHODS: Online databases was conducted for eligible randomized controlled trials (RCTs) published up to November 1, 2023. Progression-free survival (PFS) and overall survival (OS) were the primary endpoint. Objective response rates (ORRs) and adverse events (AEs) were the secondary endpoint. RESULTS: Three randomized controlled trials (Capture-1st, JUPITER-02, and RATIONALE-309) were included. First-line ICI therapy combined with CT showed significant improvement in PFS (hazard ratio[HR], 0.53; 95% confidence interval[CI]: 0.44-0.64), OS (HR, 0.63;95%CI: 0.49-0.81) and ORRs (odds ratio[OR], 1.79;95%CI: 1.30-2.46), when compared with CT alone. AEs ≥ grade 3 during treatment and treatment-related deaths were not significantly different between the two groups. CONCLUSIONS: In patients with R/M-NPC, ICI therapy combined with CT showed improved ORRs, PFS, and OS, with similar safety as CT alone.

Development of Epigallocatechin 3-gallate-Loaded Hydrogel Nanocomposites for Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a chronic progressive disease associated with increased collagen deposition and TGF-ß1 release. The current therapy and management have been a limited success due to low efficacy and adverse drug reactions. This study aimed to evaluate epigallocatechin 3-gallate (EGCG) encapsulated nanoparticles loaded mucoadhesive hydrogel nanocomposite (HNC) for OSF. Developed HNC formulations were evaluated for their permeation behaviour using in vitro as well as ex vivo studies, followed by evaluation of efficacy and safety by in vivo studies using areca nut extract-induced OSF in rats. The disease condition in OSF-induced rats was assessed by mouth-opening and biochemical markers. The optimized polymeric nanoparticles exhibited the required particle size (162.93 ± 13.81 nm), positive zeta potential (22.50 ± 2.94 mV) with better mucoadhesive strength (0.40 ± 0.002 N), and faster permeation due to interactions of the positively charged surface with the negatively charged buccal mucosal membrane. HNC significantly improved disease conditions by reducing TGF-ß1 and collagen concentration without showing toxicity and reverting the fibroid buccal mucosa to normal. Hence, the optimized formulation can be further tested to develop a clinically alternate therapeutic strategy for OSF.

Efficacy and safety of MAS825 (anti-IL-1ß/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function.

MAS825, a bispecific IL-1ß/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated patients with COVID-19 pneumonia (n = 138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on the day of discharge (whichever was earlier) with worst-case imputation for death. Other study endpoints included safety, C-reactive protein (CRP), SARS-CoV-2 presence, and inflammatory markers. On Day 15, the APACHE II score was 14.5 ± 1.87 and 13.5 ± 1.8 in the MAS825 and placebo groups, respectively (P = 0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days), and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels, and 16% lower interferon-γ levels, indicative of IL-1ß and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID-19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related.

Patient-derived organoids for precision oncology: a platform to facilitate clinical decision making.

BACKGROUND: Despite recent advances in research, there are still critical lacunae in our basic understanding of the cause, pathogenesis, and natural history of many cancers, especially heterogeneity in patient response to drugs and mediators in the transition from malignant to invasive phenotypes. The explication of the pathogenesis of cancer has been constrained by limited access to patient samples, tumor heterogeneity and lack of reliable biological models. Amelioration in cancer treatment depends on further understanding of the etiologic, genetic, biological, and clinical heterogeneity of tumor microenvironment. Patient-derived organoids recapitulate the basic features of primary tumors, including histological complexity and genetic heterogeneity, which is instrumental in predicting patient response to drugs. METHODS: Human iPSCs from healthy donors, breast and ovarian cancer patients were successfully differentiated towards isogenic hepatic, cardiac, neural and endothelial lineages. Multicellular organoids were established using Primary cells isolated from tumor tissues, histologically normal tissues adjacent to the tumors (NATs) and adipose tissues (source of Mesenchymal Stem Cells) from ovarian and breast cancer patients. Further these organoids were propagated and used for drug resistance/sensitivity studies. RESULTS: Ovarian and breast cancer patients' organoids showed heterogeneity in drug resistance and sensitivity. iPSCs-derived cardiomyocytes, hepatocytes and neurons showed donor-to-donor variability of chemotherapeutic drug sensitivity in ovarian cancer patients, breast cancer patients and healthy donors. CONCLUSION: We report development of a novel integrated platform to facilitate clinical decision-making using the patient's primary cells, iPSCs and derivatives, to clinically relevant models for oncology research.

Efficacy and safety of nilotinib as frontline treatment in elderly (> 65 years) chronic myeloid leukemia patients outside clinical trials.

Here, we report real-world evidence on the safety and efficacy of nilotinib as a first-line treatment in elderly patients with chronic phase CML, treated in 18 Italian centers. Sixty patients aged > 65 years (median age 72 years (65-84)) were reported: 13 patients were older than 75 years. Comorbidities were recorded at baseline in 56/60 patients. At 3 months of treatment, all patients obtained complete hematological response (CHR), 43 (71.6%) an early molecular response (EMR), while 47 (78%) reached a complete cytogenetic response (CCyR). At last follow-up, 63.4% of patients still had a deep molecular response (MR4 or better), 21.6% reached MR3 as best response and 11.6% persisted without MR. Most patients (85%) started the treatment at the standard dose (300 mg BID), maintained at 3 months in 80% of patients and at 6 months in 89% of them. At the last median follow-up of 46.3 months, 15 patients discontinued definitively the treatment (8 due to side effects, 4 died for unrelated CML causes, 1 for failure, 2 were lost to follow-up). One patient entered in treatment-free remission. As to safety, 6 patients (10%) experienced cardiovascular events after a median time of 20.9 months from the start. Our data showed that nilotinib could be, as first-line treatment, effective and relatively safe even in elderly CML patients. In this setting, more data in the long term are needed about possible dose reduction to improve the tolerability, while maintaining the optimal molecular response.

Efficacy and safety of ruxolitinib in patients with newly-diagnosed polycythemia vera: futility analysis of the RuxoBEAT clinical trial of the GSG-MPN study group.

Patients (pts) with polycythemia vera (PV) suffer from pruritus, night sweats, and other symptoms, as well as from thromboembolic complications and progression to post-PV myelofibrosis. Ruxolitinib (RUX) is approved for second-line therapy in high-risk PV pts with hydroxyurea intolerance or resistance. The RuxoBEAT trial (NCT02577926, registered on October 1, 2015, at clinicaltrials.gov) is a multicenter, open-label, two-arm phase-IIb trial with a target population of 380 pts with PV or ET, randomized to receive RUX or best available therapy. This pre-specified futility analysis assesses the early clinical benefit and tolerability of RUX in previously untreated PV pts (6-week cytoreduction was allowed). Twenty-eight patients were randomly assigned to receive RUX. Compared to baseline, after 6 months of treatment, there was a significant reduction of median hematocrit (46 to 41%), the median number of phlebotomies per year (4.0 to 0), and median patient-reported pruritus scores (2 to 1), and a trend for reduced night sweat scores (1.5 to 0). JAK2V617F allele burden, as part of the scientific research program, also significantly decreased. One hundred nine adverse events (AEs) occurred in 24/28 patients (all grade 1 to 3), and no pt permanently discontinued treatment because of AEs. Thus, treatment with ruxolitinib in untreated PV pts is feasible, well-tolerated, and efficient regarding the above-mentioned endpoints.

Efficacy and safety of Gutong Patch compared with NSAIDs for knee osteoarthritis: A real-world multicenter, prospective cohort study in China.

The Gutong Patch (GTP) is common in clinical practice for bone diseases. This study compared the efficacy and safety of GTP and nonsteroidal anti-inflammatory drugs (NSAIDs) for KOA patients from 35 medical centers assigned to GTP, selective COX-2 inhibitor (SCI), GTP + SCI, non-selective COX-2 inhibitor (NSCI), and GTP + NSCI groups. The visual analog scale (VAS) pain score, EuroQol-VAS, EuroQol 5D-3 L, time to articular pain relief / disappearance, and joint motion recovery were the efficacy assessments. Safety assessments included contact dermatitis, gastrointestinal disorders, etc. The p-value < 0.05 was considered statistically significant. After statistical analysis, the SCI and GTP + SCI groups showed better improvement of VAS than the GTP group; the time to articular pain relief in the NSCI group was shorter than that in GTP and SCI group; the time to joint motion recovery in the GTP + NSCI group was longer than that in the SCI group. Additionally, the improvement of the quality of life in all groups was significant after treatments. While the incidence of gastrointestinal adverse events in the NSAIDs group was higher than that in the GTP and GTP + NSAIDs groups. GTP and NSAIDs are effective for KOA patients, and GTP is more suitable for KOA patients with cardiovascular and gastrointestinal comorbidities. This study was approved by the Ethics Committee at Peking Union Medical College Hospital (HS-1766) and registered in the Chinese Clinical Trial Registry (ChiCTR2100046391).

Efficacy and safety of pyronaridine-artesunate versus artemether-lumefantrine in the treatment of acute uncomplicated malaria in children in South-West Nigeria: an open-labelled randomized controlled trial.

BACKGROUND: In Nigeria, declining responsiveness to artemether-lumefantrine (AL), the artemisinin-based combination therapy (ACT) of choice since 2005, has been reported. Pyronaridine-artesunate (PA) is a newer fixed-dose ACT recently prequalified by the WHO for the treatment of uncomplicated falciparum malaria. However, PA data from the Nigerian pediatric population is scarce. Therefore, the efficacy and safety of PA and AL using the WHO 28-day anti-malarial therapeutic efficacy study protocol in Ibadan, southwest Nigeria, were compared. METHODS: In an open-labelled, randomized, controlled clinical trial, 172 children aged 3-144 months with a history of fever and microscopically confirmed uncomplicated Plasmodium falciparum malaria were enrolled in southwest Nigeria. Enrollees were randomly assigned to receive PA or AL at standard dosages according to body weight for 3 days. Venous blood was obtained for hematology, blood chemistry, and liver function tests on days 0, 3, 7, and 28 as part of the safety evaluation. RESULTS: 165 (95.9%) of the enrolled individuals completed the study. About half (52.3%; 90/172) of enrollees were male. Eighty-seven (50.6%) received AL, while 85 (49.4%) received PA. Day 28, adequate clinical and parasitological response for PA was 92.7% [(76/82) 95% CI 83.1, 95.9] and 71.1% [(59/83) 95% CI 60.4, 79.9] for AL (0.001). Fever and parasite clearance were similar in both groups. Two of six and eight of 24 parasite recurrences were observed among PA- and AL-treated children, respectively. PCR-corrected Day-28 cure rates for PA were 97.4% (76/78) and 88.1% (59/67) for AL (= 0.04) in the per-protocol population after new infections were censored. Hematological recovery at day 28 was significantly better among PA-treated patients (34.9% 2.8) compared to those treated with AL (33.1% 3.0) (0.002). Adverse events in both treatment arms were mild and similar to the symptoms of malaria infection. Blood chemistry and liver function tests were mostly within normal limits, with an occasional marginal rise. CONCLUSION: PA and AL were well-tolerated. PA was significantly more efficacious than AL in both the PCR-uncorrected and PCR-corrected per-protocol populations during this study. The results of this study support the inclusion of PA in the anti-malarial treatment guidelines in Nigeria. RETROSPECTIVE TRIAL REGISTRATION: Clinicaltrials.gov: NCT05192265.

Short-term efficacy and safety of personalized antiplatelet therapy for patients with acute ischaemic stroke or transient ischaemic attack: A randomized clinical trial.

AIMS: The aim of this study was to determine whether the testing strategy for clopidogrel and/or aspirin resistance using CYP2C19 genotyping or urinary 11-dhTxB2 testing has an impact on clinical outcomes. METHODS: A multicentre, randomized, controlled trial was conducted at 14 centres in China from 2019 to 2021. For the intervention group, a specific antiplatelet strategy was assigned based on the CYP2C19 genotype and 11-dhTxB2, a urinary metabolite of aspirin, and the control group received nonguided (ie, standard of care) treatment. 11-dhTXB2 is a thromboxane A2 metabolite that can help quantify the effects of resistance to aspirin in individuals after ingestion. The primary efficacy outcome was new stroke, the secondary efficacy outcome was a poor functional prognosis (a modified Rankin scale score ≥3), and the primary safety outcome was bleeding, all within the 90-day follow-up period. RESULTS: A total of 2815 patients were screened and 2663 patients were enrolled in the trial, with 1344 subjects assigned to the intervention group and 1319 subjects assigned to the control group. A total of 60.1% were carriers of the CYP2C19 loss-of-function allele (*2, *3) and 8.71% tested positive for urinary 11-dhTxB2- indicating aspirin resistance in the intervention group. The primary outcome was not different between the intervention and control groups (P = .842). A total of 200 patients (14.88%) in the intervention group and 240 patients (18.20%) in the control group had a poor functional prognosis (hazard ratio 0.77, 95% confidence interval [CI] 0.63 to 0.95, P = .012). Bleeding events occurred in 49 patients (3.65%) in the intervention group and 72 patients (5.46%) in the control group (hazard ratio 0.66, 95% CI 0.45 to 0.95, P = .025). CONCLUSIONS: Personalized antiplatelet therapy based on the CYP2C19 genotype and 11-dhTxB2 levels was associated with favourable neurological function and reduced bleeding risk in acute ischaemic stroke and transient ischaemic attack patients. The results may help support the role of CYP2C19 genotyping and urinary 11-dhTxB2 testing in the provision of precise clinical treatment.

Efficacy and safety of lamotrigine in pediatric mood disorders: A systematic review.

AIM: To appraise the current evidence on the efficacy and safety of lamotrigine (LAM) in the treatment of pediatric mood disorders (PMD) (i.e., Major Depressive disorder [MDD], bipolar disorder [BD]). METHODS: Major databases were searched for randomized controlled trials (RCTs), open-label trials, and observational studies reporting on pediatric (age < 18 years) patients treated with LAM for mood disorders. RESULTS: A total of 3061 abstracts were screened and seven articles were selected for inclusion. Seven studies (319 BD and 43 MDD patients), including one RCT (n = 173), three prospective (n = 105), and three retrospective (n = 84) studies, met the study criteria with a study duration range from 8 to 60.9 weeks. The mean age of this pooled data is 14.6 ± 2.0 years. LAM daily dosage varied from 12.5 to 391.3 mg/day among the studies. In an important finding, the RCT reported favorable outcomes with LAM (HR = 0.46; p = 0.02) in 13- to 17-year-old age group as compared with 10- to 12-year-old age group (HR = 0.93; p = 0.88). In addition, time to occurrence of a bipolar event trended toward favoring LAM over placebo. All the studies identified LAM as an effective and safe drug in PMDs especially, BDs. Overall, LAM was well tolerated with no major significant side effects and no cases of Stevens-Johnson syndrome. CONCLUSIONS: Most studies suggested that LAM was safe and effective in pediatric patients with mood disorders. However, the data regarding the therapeutic range for LAM are lacking. Based on the data, there is inconsistent evidence to make conclusive recommendations on therapeutic LAM dosage for mood improvement in the pediatric population. Further studies including larger sample sizes are required to address this relevant clinical question.

Efficacy and safety of esophageal submucosal tumors treated with internal traction method-assisted submucosal tunneling endoscopic resection: a single-center, single-blind, randomized controlled study.

BACKGROUND AND OBJECTIVES: Submucosal tunnel endoscopic resection (STER) is an effective technique for treating esophageal submucosal tumors, but the efficacy and safety of treating esophageal submucosal tumors with internal traction method-assisted STER have not been determined. The objectives of this study were to assess the feasibility, safety, and efficacy of internal traction method-assisted STER for the removal of esophageal submucosal tumors. PATIENTS AND METHODS: Eighty patients who underwent STER for esophageal submucosal tumors were included in the study. They were randomized and assigned to the two groups. The dual-knife method was used for STER. Forty patients underwent conventional STER (control group) and 40 underwent internal traction method-assisted STER in which self-made rubber band traction with clips was used (study group). In the study group, one end of the self-made rubber band was fixed on the surface of esophageal submucosal tumors with a clip, and the other end of the self-made rubber band was set on the anal side of the contralateral esophageal wall with a clip. RESULTS: STER was successful in all cases. Lesion features and demographics were similar between the two groups. In addition, broad exposure of the submucosal tissue was obtained by applying tension to the self-made rubber band traction with clips. The en bloc resection rate and complete resection rate were both 100% in the study group. However, the en bloc resection rate and complete resection rate were 85.0% and 100%, respectively, in the control group. Complications, such as perforation and pneumomediastinum, were significantly reduced in the study group, and there was a significant difference in the number of occurrences of bleeding, operation duration, fasting time, and patient length of stay between the study group and control group (P < 0.05). During the mean 13.7 month follow-up, there were no patients with esophageal fistula, recurrence, or distant metastasis in either group. CONCLUSIONS: This original study showed that esophageal submucosal tumors could be effectively and safely treated with internal traction method-assisted STER, and this technique might be superior to conventional STER due to its fewer complications, shorter operation duration, and shorter inpatient length of stay.

PD-1/PD-L1 inhibitor plus chemotherapy versus standard of care in the first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor plus chemotherapy vs standard of care (SoC) treatment in the first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M-SCCHN). METHODS: Randomized controlled trials (RCTs) that investigated PD-1/PD-L1 inhibitor plus chemotherapy vs SoC as first-line treatment for R/M-SCCHN were searched from electronic databases (PubMed, Embase and Cochrane Library). The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). RESULTS: In total, three phase 3 RCTs (KEYNOTE-048, CAPTAIN-1st, and JUPITER-02; n = 1120) with three PD-1 inhibitors (pembrolizumab, camrelizumab and toripalimab) were included in the analysis. Compared with SoC, PD-1 inhibitor plus chemotherapy significantly prolonged PFS (hazard ratio [HR] 0.66, 95% CI 0.40-0.93, p < 0.001) and OS (HR 0.73, 95% CI 0.60-0.86, p < 0.001) of patients. There was no statistical differences in ORR (odds ratio [OR] 1.26; 95% CI 0.97-1.64, p = 0.086), grade 3 or higher AEs (OR 0.77, 95% CI 0.50-1.17, p = 0.221), and treatment-related deaths (OR 1.34, 95% CI 0.60-2.98, p = 0.470) between the two groups. CONCLUSION: PD-1 inhibitor plus chemotherapy showed more survival benefit than SoC in the first-line treatment for R/M-SCCHN, with a similar safety profile.

Efficacy and safety of ultrasound-guided foam sclerotherapy combined with endoluminal radiofrequency closure in patients with varicose veins of lower extremities.

We aimed to explore the efficacy and safety of ultrasound-guided foam sclerotherapy combined with endoluminal radiofrequency closure in patients with varicose veins of lower extremities (VVLEs); furthermore, we aimed to provide a theoretical basis for the effective management of VVLE patients in clinical work. From January 1, 2020, to March 1, 2021, 88 patients with VVLE admitted to Third Hospital of Shandong Province were included in this retrospective study. Depending on the type of treatment, the patients were divided into study groups and control groups. The study group consisted of 44 patients who were given ultrasound-guided foam sclerotherapy combined with endoluminal radiofrequency closure. The control group consisted of 44 patients who were given high ligation and stripping of the great saphenous vein. Efficacy indicators included postoperative venous clinical severity score (VCSS) of affected limb and postoperative visual analogue scale (VAS) score. Safety indicators included length of operation, intraoperative blood loss, length of postoperative rest in bed, length of hospital stay, postoperative heart rate, preoperative blood saturation (SpO2 ), preoperative mean arterial pressure (MAP), and complications. The VCSS score 6 months after operation in the study group was significantly lower than that in the control group (P < .05). The pain VAS score in the study group was significantly lower than that in the control group at 1 and 3 days after operation (both P < .05). Compared with the control group, the study group was significantly lower in length of operation, intraoperative blood loss, postoperative in-bed time, and hospital stays (all P < .05). Heart rate and SpO2 were significantly higher, and MAP was significantly lower in the study group compared with that in the control group 12 hours after surgery (all P < .05). The overall postoperative complication rate in the study group was significantly lower than that in the control group (P < .05). In conclusion, compared with surgical treatment of high ligation and stripping of the great saphenous vein, ultrasound-guided foam sclerotherapy combined with endoluminal radiofrequency ablation for the treatment of VVLE disease has better efficacy and safety, which is worthy of clinical promotion.

Comparison of the efficacy and safety of different immunization routes induced by human respiratory syncytial virus F protein with CpG adjuvant in mice.

Human respiratory syncytial virus (HRSV) is a leading cause worldwide of severe respiratory illness in infants and the elderly. The ideal HRSV vaccine should induce a systemic immune response, especially mucosal immunity. In this study, mice were immunized twice with F protein combined with CpG adjuvant to compare the safety and efficacy of 4 immunization routes, including intranasal primed/intramuscular boosted immunization (CpG + F/in+im), intramuscular primed/intranasal boosted immunization (CpG + F/im+in), intramuscular primed/intramuscular boosted immunization (CpG + F/im + im) and intranasal primed/intranasal boosted immunization (CpG + F/in+in). Compared with the control group (CpG/in+im, CpG/im+in, CpG/im + im and CpG/in+in), all 4 immunization routes induced a high titer of neutralizing antibodies and a strong cellular immune response. Mice in the CpG + F/in+in group induced the highest antibody neutralization titer, and IgA antibody in bronchoalveolar lavage fluid (BALF) was the highest. The copy of HRSVs in the lung decreased by approximately 3 log10. As seen from the IgG1/IgG2a and IFN-γ/IL-4-secreting lymphocyte ratios, compared with the mice in the CpG + F/im + im group, mice in the CpG + F/in+in group induced Th1-baised humoral and cellular immune responses and significantly reduced lung pathological injury. In conclusion, among the 4 immunization routes, the safety and efficacy induced by the mice in the CpG + F/in+in group were the best. We can conclude that intranasal immunization is superior to intramuscular immunization using F protein with CpG adjuvant as vaccine candidates.

An omics perspective on drug target discovery platforms.

The drug discovery process starts with identification of a disease-modifying target. This critical step traditionally begins with manual investigation of scientific literature and biomedical databases to gather evidence linking molecular target to disease, and to evaluate the efficacy, safety and commercial potential of the target. The high-throughput and affordability of current omics technologies, allowing quantitative measurements of many putative targets (e.g. DNA, RNA, protein, metabolite), has exponentially increased the volume of scientific data available for this arduous task. Therefore, computational platforms identifying and ranking disease-relevant targets from existing biomedical data sources, including omics databases, are needed. To date, more than 30 drug target discovery (DTD) platforms exist. They provide information-rich databases and graphical user interfaces to help scientists identify putative targets and pre-evaluate their therapeutic efficacy and potential side effects. Here we survey and compare a set of popular DTD platforms that utilize multiple data sources and omics-driven knowledge bases (either directly or indirectly) for identifying drug targets. We also provide a description of omics technologies and related data repositories which are important for DTD tasks.

The efficacy and safety of immune checkpoint inhibitor plus chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of immune checkpoint inhibitor (ICI) and chemotherapy (CT) versus CT alone in advanced non-small-cell lung cancer (NSCLC). METHODS: Databases (PubMed, Embase and Cochrane Library) were searched for relevant randomized controlled trials (RCTs). Clinical outcome measures including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade 3-5 treatment-related adverse events (AEs) were analyzed by Stata 15.0 software; significance level was 0.05. RESULTS: Eight RCTs involving 4227 patients were included. The results showed ICI + CT significantly improved OS (hazard ratio [HR] = 0.74, 95% CI: 0.62-0.85, p < 0.001), PFS (HR = 0.66, 95% CI: 0.57 - 0.75, p < 0.001) and ORR (odds ratio [OR] = 1.89; 95% CI, 1.43-2.49, p < 0.001) compared with CT alone. Subgroup analysis indicated that significantly longer OS was also observed in subgroups including combination regimens (pembrolizumab + CT, atezolizumab + CT, ipilimumab + CT, and nivolumab + ipilimumab + CT) and PD-L1 status [negative (< 1%), positive (≥ 1%), low (1-49%) and high (≥ 50%)]. However, ICI + CT showed signifcantly higher grade 3-5 treatment-related AEs than CT (OR = 1.46, 95% CI: 1.19 - 1.79, p < 0.001). CONCLUSIONS: ICI + CT showed better clinical efficacy than CT alone in patients with advanced NSCLC, with increased treatment-related AEs.