Survival impact of microsatellite instability in stage II gastric cancer patients who received S-1 adjuvant monotherapy after curative resection.

Adjuvant S-1 monotherapy is the standard of care for stage II gastric cancer (GC) after curative resection in Japan, but its efficacy for microsatellite instability-high (MSI-H) tumors has remained unknown. Among a multi-institutional cohort of patients with stage II GC who underwent R0 resection followed by S-1 adjuvant chemotherapy between February 2008 and December 2018, we assessed MSI status with an MSI-IVD Kit (Falco). MSI status was assessable for 184 (88.5%) of the 208 enrolled patients, with MSI-H being identified in 24 (13.0%) individuals. Although neither relapse-free survival (RFS) (hazard ratio [HR] = 1.00, p = 0.997) nor overall survival (OS) (HR = 0.66, p = 0.488) differed between MSI-H versus microsatellite-stable (MSS) patients, MSI-H patients showed a nonsignificant but better RFS (HR = 0.34, p = 0.064) and OS (HR = 0.22, p = 0.057) than did MSS patients after adjustment for background characteristics by propensity score (PS) analysis. Gene expression analysis in the PS-matched cohort suggested that recurrence was associated with the immunosuppressive microenvironment in MSI-H tumors but with expression of cancer/testis antigen genes in MSS tumors. Our data reveal a better adjusted survival for MSI-H versus MSS stage II GC treated with S-1 adjuvant therapy, and they suggest that mechanisms of recurrence differ between MSI-H and MSS tumors.

Adjuvant use of melatonin for pain management in endometriosis-associated pelvic pain-A randomized double-blinded, placebo-controlled trial.

Considering the pharmacological treatment options for endometriosis-associated pain are confined to hormonal therapy and analgesics, we studied the analgesic effect of 20 mg melatonin as an adjuvant therapy in women with endometriosis-associated pain. This randomized double-blinded, placebo-controlled trial was conducted at the Research Center for Womens' Health at Södersjukhuset, a university hospital in Stockholm, Sweden. Forty women from 18 to 50 years of age with endometriosis and severe dysmenorrhea with or without chronic pelvic pain were given 20 mg Melatonin or placebo orally daily for two consecutive menstrual cycles or months. The level of pain was recorded daily on the 11-point numeric rating scale, a difference of 1.3 units was considered clinically significant. Clincaltrials.gov nr NCT03782740. Sixteen participants completed the study in the placebo group and 18 in the melatonin group. The difference in endometriosis-associated pain between the groups showed to be non-significant statistically as well as clinically, 2.9 (SD 1.9) in the melatonin group and 3.3 (SD 2.0) in the placebo group, p = 0.45. This randomized, double-blinded, placebo-controlled trial could not show that 20 mg of melatonin given orally at bedtime had better analgesic effect on endometriosis-associated pain compared with placebo. No adverse effects were observed.

A placebo-controlled randomized clinical trial of antibiotics versus probiotics as an adjuvant to nonsurgical periodontal treatment among smokers with Stage III, Grade C generalized periodontitis.

BACKGROUND: Probiotics are viable microorganisms, which if delivered in appropriate dose can provide health benefits. Lactobacillus reuteri (DM17938+ATCC PTA 5289) has been recommended as a safe choice for probiotics. The objective of this study is to compare the improvement in the periodontal parameters amongst smokers with generalized periodontitis with Stage III, Grade C treated with nonsurgical periodontal treatment (NSPT) to which either an antibiotics or probiotics were given as an adjuvant. METHODS: Sixty smokers with Stage III, Grade C generalized periodontitis were randomized in two groups after taking informed consent. Periodontal parameters including bleeding on probing (BOP), probing depth (PD), attachment loss (AL), gingival index (GI), and plaque index (PI) were recorded. Group 1 received (after NSPT and oral hygiene instructions) amoxicillin and metronidazole for 7 days and a placebo for probiotics for 30 days. Group 2 was provided (after NSPT and oral hygiene instructions) with one tablet of Lactobacillus reuteri probiotics (2 × 108 CFU) twice daily for 30 days and placebo antibiotics for 7 days. The periodontal parameters were recorded again at 1- and 3-month follow-ups as outcome variables. Mean, standard deviation, and confidence interval were reported using SPSS 20.0. RESULTS: A statistically significant clinical improvement in the PD, BOP, PI, and GI were observed in both the groups at 3-month follow-up. However, the AL remained unchanged in both the groups. CONCLUSIONS: Administration of probiotics and antibiotics along with NSPT yield statistically significant differences in PD and BOP from baseline to 3-month follow-up. However, between the group differences were not statistically significant for the periodontal parameters (AL, PD, and BOP).

Tamoxifen or aromatase inhibitors: which one is the culprit of urinary incontinence in premenopausal breast cancer patients receiving adjuvant hormone therapy?

AIM: The primary aim of this study was to compare tamoxifen versus aromatase inhibitors (AI) in terms of urinary incontinence (UI) in premenopausal female patients receiving adjuvant hormone therapy for breast cancer. A secondary aim was to investigate the prevalence and the affecting factors of UI. METHODS: This study was designed as a multicenter, cross-sectional that included consecutive premenopausal breast cancer patients ≤50 years of age receiving tamoxifen (with/without LHRHa) or AI (with LHRHa) for at least 6 months, between June 2021 and September 2022. Patients with urinary incontinence before hormone treatments and metastatic patients were excluded from the study. Turkish validation of The International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form (ICIQ UI-SF) was used to determine the UI. Using logistic regression methods, we analyzed potential predictive factors for UI. RESULTS: A total of 206 breast cancer patients were included in this study. A total of 120 (58.2%) patients were receiving tamoxifen plus LHRHa, 40 (19.4%) patients were receiving aromatase inhibitor plus LHRHa, and 46 (22.3%) patients were receiving tamoxifen only. In this study, the prevalence of urinary incontinence was found to be 35.9% (n:74). 41% of the patients receiving tamoxifen and 15.0% of those receiving aromatase inhibitors had complaints of urinary incontinence. There was a statistically significant difference between patients receiving tamoxifen or aromatase inhibitor in terms of urinary incontinence (p=0.001). In the univariate analysis established to predict UI, parity (≥2 vs <2) (OR = 3.23, 95% CI: 1.62-6.46, p= 0.001), tamoxifen (vs AI) (OR = 3.97, 95% CI: 1.58-9.98, p= 0.003), age ( ≥40 vs. <40) (OR = 2.80, 95% CI: 1.37-5.71, p= 0.005), vaginal deliveries (≥2 vs. <2) (OR = 3.28, 95% CI: 1.44-7.46, p= 0.005), hypertension (OR = 3.59, 95% CI: 1.43-9.02, p= 0.007), diuretic use (OR = 2.55, 95% CI: 1.09-5.95, p= 0.031) ), and body mass index (≥25 vs <25) (OR = 1.94, 95% CI: 1.05-3.63), p= 0.034) was found to be predictive. Tamoxifen (OR = 4.71, 95% CI: 1.77-12.56, p= 0.002), hypertension (OR = 3.48, 95% CI: 1.27-9.52, p= 0.015), and age (OR = 2.35, 95% CI: 1.10-5.02, p= 0.027) remained independent predictors for incontinence in multivariate analyses. CONCLUSION: We found that tamoxifen had increased the risk of urinary incontinence compared to aromatase inhibitors in patients receiving hormone therapy for breast cancer. In addition, we showed that age and hypertension were also independent predictors for UI. In the context of quality of life, we recommend close follow-up of these patients, as drug adherence may be affected in the event of urinary incontinence.

Novel antimicrobial strategies to treat multi-drug resistant Staphylococcus aureus infections.

Antimicrobial resistance is a major obstacle for the treatment of infectious diseases and currently represents one of the most significant threats to global health. Staphylococcus aureus remains a formidable human pathogen with high mortality rates associated with severe systemic infections. S. aureus has become notorious as a multidrug resistant bacterium, which when combined with its extensive arsenal of virulence factors that exacerbate disease, culminates in an incredibly challenging pathogen to treat clinically. Compounding this major health issue is the lack of antibiotic discovery and development, with only two new classes of antibiotics approved for clinical use in the last 20 years. Combined efforts from the scientific community have reacted to the threat of dwindling treatment options to combat S. aureus disease in several innovative and exciting developments. This review describes current and future antimicrobial strategies aimed at treating staphylococcal colonization and/or disease, examining therapies that show significant promise at the preclinical development stage to approaches that are currently being investigated in clinical trials.

How Three Self-Secreted Biofilm Exopolysaccharides of Pseudomonas aeruginosa, Psl, Pel, and Alginate, Can Each Be Exploited for Antibiotic Adjuvant Effects in Cystic Fibrosis Lung Infection.

In cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a cause of increased morbidity and mortality, especially in patients for whom infection becomes chronic and there is reliance on long-term suppressive therapies. Current antimicrobials, though varied mechanistically and by mode of delivery, are inadequate not only due to their failure to eradicate infection but also because they do not halt the progression of lung function decline over time. One of the reasons for this failure is thought to be the biofilm mode of growth of P. aeruginosa, wherein self-secreted exopolysaccharides (EPSs) provide physical protection against antibiotics and an array of niches with resulting metabolic and phenotypic heterogeneity. The three biofilm-associated EPSs secreted by P. aeruginosa (alginate, Psl, and Pel) are each under investigation and are being exploited in ways that potentiate antibiotics. In this review, we describe the development and structure of P. aeruginosa biofilms before examining each EPS as a potential therapeutic target for combating pulmonary infection with P. aeruginosa in CF, with a particular focus on the current evidence for these emerging therapies and barriers to bringing these therapies into clinic.

Adherence to adjuvant tamoxifen and associated factors in breast cancer survivors.

PURPOSE: Adjuvant endocrine therapy reduces the recurrence and mortality of early hormone receptor-positive breast cancer in both pre- and postmenopausal women. The aim of this study was to investigate adjuvant tamoxifen adherence and associated factors in breast cancer survivors. METHODS: This descriptive, prospective study was conducted in 2019-2020 with the participation of 531 women who survived breast cancer and were under follow-up at the Senology Institute of a hospital in Istanbul. Inclusion criteria were having completed treatment for early hormone receptor-positive breast cancer, being prescribed tamoxifen, and being 18 years or older. Data were collected using a patient information form and the Morisky Medication Adherence Scale-8 (MMAS-8). RESULTS: The mean age of the participants was 44.9 ± 6.5 years, and the mean duration of tamoxifen use was 834.4 ± 685.7 days. The women's mean MMAS-8 score was 6.86 ± 1.39. Medication adherence was significantly positively correlated with current age (p = 0.006) and age at diagnosis (p = 0.002). There was a statistically significant difference between tamoxifen adherence according to participants' employment status (p = 0.028), chronic disease status (p = 0.018), loss of libido (p = 0.012), treatment-related changes in mood changes (p = 0.004), and having negative effects affecting daily life (p < 0.001). CONCLUSION: Overall, breast cancer survivors in this study reported moderate adherence to tamoxifen. The women's individual characteristics and the adverse effects of treatment influenced medication adherence. Healthcare professionals can help increase adherence to this treatment, which reduces the risk of mortality, by explaining the importance of the medication, identifying and eliminating barriers to adherence, and informing women about evidence-based interventions to increase medication compliance.

The prediction of lymphocyte count and neutrophil count on the efficacy of Xuebijing adjuvant treatment for severe community-acquired pneumonia: A post hoc analysis of a randomized controlled trial.

BACKGROUND: Adjuvant Xuebijing therapy exhibited a protective effect on severe community-acquired pneumonia (SCAP) in previous studies. Blood inflammatory biomarkers related to the disease subtype and severity of SCAP might be associated with the effects of Xuebijing on clinical outcomes of SCAP. PURPOSE: To investigate whether neutrophils or lymphocytes are a useful biomarker of the therapeutic effect of Xuebijing on mortality and inflammation damage index. STUDY DESIGN: A post hoc analysis of a randomized, placebo-controlled and double-blinded clinical trial of Xuebijing in patients with SCAP (Clinical Trial Registration: ChiCTR-TRC-13003534). METHODS: We compared 28-day mortality (primary outcome) and four clinical scores (secondary outcome), including pneumonia severity index (PSI) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, and systemic inflammatory response syndrome (SIRS) score, according to the baseline strata of neutrophil count and lymphocyte count. RESULTS: A total of 675 patients were included in the analyses, of which 334 received Xuebijing and 341 received the placebo. Xuebijing was more effective in SCAP patients with higher lymphocyte counts and lower neutrophil counts. In the lymphocyte-dominated inflammation (LDI) subgroup, defined as neutrophil count <13 × 109 cells/l and lymphocyte count ≥0.65 × 109 cells/l, Xuebijing reduced 28-day mortality by 15% while mortality of the neutrophil-dominated inflammation (NDI) subgroup decreased by 4.7% (p = 0.050). There was also greater improvement in the PSI, SOFA, APACHE II, and SIRS scores following Xuebijing treatment in the LDI subgroup compared with the NDI subgroup. CONCLUSIONS: Xuebijing treatment shows stronger protective effects in SCAP patients with higher lymphocyte and lower neutrophil counts. Our findings may facilitate the selection of the most appropriate treatments for individual patients with SCAP, including who will receive Xuebijing injections.

Adjuvant alternative cytokine-induced killer cell combined with natural killer cell immunotherapy improves the prognosis of post-mastectomy breast cancer.

Breast cancer is one of the most common cancers in women. Triple-negative breast cancer (TNBC) has a significantly worse prognosis due to the lack of endocrine receptors including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). In this study, we investigated adjuvant cellular immunotherapy (CIT) in patients with post-mastectomy breast cancer. We enrolled 214 post-mastectomy breast cancer patients, including 107 patients in the control group (who received chemotherapy/radiotherapy/endocrine therapy) and the other 107 patients in the CIT group (who received chemotherapy/radiotherapy/endocrine therapy and subsequent immune cell infusion). Of these 214 patients, 54 had TNBC, including 26 patients in the control group and 28 patients in the CIT group. Survival analysis showed that the overall survival rate of patients treated with cellular immunotherapy was higher than that of patients who were not treated with CIT. Compared to those who received cytokine-induced killer (CIK) cells alone, the patients who received CIK combined with natural killer (NK) cell immunotherapy showed the best overall survival rate. In subgroup analyses, adjuvant CIT significantly improved the overall survival of patients in the TNBC subgroup and the patients who were aged over 50 years. Our study indicates that adjuvant CIK cell combined with NK cell treatment is an effective therapeutic strategy to prolong the survival of post-mastectomy patients, particularly for TNBC patients and those who are aged over 50 years.

Efficacy and safety of Fufang Biejia Ruangan Tablets as an adjuvant treatment for chronic hepatitis B liver fibrosis: A systematic review and meta-analysis.

BACKGROUND: Meta-analysis was used to evaluate the efficacy of Fufang Biejia Ruangan Tablets in the treatment of chronic hepatitis B (CHB) liver fibrosis. METHODS: Databases, including PubMed, China Knowledge Network (CNKI), China Biomedical Database (CBM), Wan Fang, VIP database, Embase, and Cochrane Library were searched. The time was searched up to May 2022. The participant intervention comparator outcomes of this study were as follows: P, patients with CHB liver fibrosis; I, Fufang Biejia Ruangan Tablets; C, pharmacological placebo; O, the efficacy rate, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), procollagen III protein (PIIIP), hyaluronic acid (HA), laminin (LN), collagen C type IV (IV-C), portal vein diameter, spleen thickness and HBV-DNA negative conversion rate. The Cochrane Risk of Bias tool, Begg's test and Egger's test were used to evaluate the methodological quality of eligible studies. A randomized controlled trial of Fufang Biejia Ruangan Tablets was used to treat CHB liver fibrosis. Three reviewers independently selected trials, extracted data, cross-checked, and performed methodological quality assessments. Data analysis was completed by Review Manager 5.3. RESULTS: Twenty-six studies with 2717 patients were included in the meta-analysis. The meta-analysis showed that Fufang Biejia Ruangan Tablets was effective by increasing the efficacy. Fufang Biejia Ruangan Tablets was more efficient in improving ALT, AST, TBIL, ALB, PIIIP, HA, LN, IV-C, portal vein diameter, spleen thickness, and HBV-DNA negative conversion rate with no serious adverse reactions. CONCLUSION: It was shown that Fufang Biejia Ruangan Tablets can effectively improve liver function and relieve liver fibrosis, but future research should focus on rigorously designed, multicenter, and large randomized controlled trials.

Extended Adjuvant Endocrine Treatment in Luminal Breast Cancers in the Era of Genomic Tests.

In patients with early-stage endocrine receptor-positive (ER+) breast cancer (BC), adjuvant endocrine therapy (ET) for 5 years is the standard of care. However, for some patients, the risk of recurrence remain high for up to 15 years after diagnosis and extended ET beyond 5 years may be a reasonable option. Nevertheless, this strategy significantly increases the occurrence of side effects. Here we summarize the available evidence from randomized clinical trials on the efficacy and safety profile of extended ET and discuss available clinical and genomic tools helpful to select eligible patients in daily clinical practice.

Probiotic therapy, a novel and efficient adjuvant approach to improve glycemic status: An umbrella meta-analysis.

BACKGROUND: Probiotics exert several promoting effects on the glycemic status, however, the results of meta-analyses are inconsistent. we conducted an umbrella meta-analysis, across existing systematic reviews and meta-analyses of clinical trials to determine the definite effects of supplementation with probiotics on glycemic indices. METHODS: A comprehensive systematic search of PubMed/Medline, Scopus, EMBASE, and Web of Science was carried out till August 2021. The random-effects model was employed to conduct meta-analysis. Meta-analysis studies of randomized clinical trials examining the impacts of probiotics supplementation on glycemic indices were qualified in the current umbrella meta-analysis. RESULTS: 48 articles out of 693 in the literature search qualified for inclusion in the umbrella meta-analysis. Pooled effects of probiotics on fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), and insulin levels were reported in articles 45, 21, 35, and 33, respectively. The analysis indicated a significant decrease of FPG (ES= -0.51 mg/dL; 95% CI: -0.63, -0.38, p < 0.001), HbA1c (ES = -0.32 mg/dL; 95% CI: -0.44, -0.20, p < 0.001), HOMA-IR (ES= -0.56; 95% CI: -0.66, -0.47, p < 0.001), and insulin levels (ES= -1.09 IU/mL; 95% CI: -1.37, -0.81, p = 0.006) by probiotics supplementation. CONCLUSION: Probiotics have amending effects on FPG, HbA1c, HOMA-IR, and insulin levels. A < 8-week period of probiotic supplementation in the moderate dosages (108 or 109 CFU) is an efficacious approach in improving glycemic parameters. Overall, probiotics could be recommended as an adjuvant anti-hyperglycemic agent.

Low-intensity ultrasound: A novel technique for adjuvant treatment of gliomas.

Glioma is the most common primary malignant tumor of the central nervous system. Although surgical treatment combined with radiotherapy, chemotherapy, and immunotherapy are commonly used for glioma treatment, the prognosis of glioma is still unsatisfactory. The poor effect of glioma treatment could be due to the blocking effect of blood-brain barrier (BBB) on most drugs and the multidrug resistance in tumor cells. In recent years, preclinical trials have shown that low-intensity ultrasound (LIUS) can reversibly open the BBB, inhibit the proliferation of tumor cells, and improve the delivery of drugs to brain tissue. This technology has also recently been used in clinical trials, and achieved encouraging preliminary results. In this review, the existing research results, the effect of LIUS on the adjuvant therapy of glioma under safe conditions, and the physical and biological mechanisms have been discussed. This review aims to show the potential and prospect of LIUS technique in the clinical treatment of glioma.

Comparison of Different Doses of Dexmedetomidine as Adjuvant for Infraumbilical Surgery in Patients Receiving Bupivacaine Spinal Anesthesia: A Randomized Controlled Trial.

BACKGROUND: Infraumbilical surgery today is done preferentially under subarachnoid block. The relatively short duration of analgesia is a limiting factor which is overcome by adding an adjuvant to intrathecal bupivacaine. We aimed to determine optimum dose of intrathecal dexmedetomidine as adjuvant to 0.5% hyperbaric bupivacaine in infraumbilical surgery. METHODS: A parallel group, double blind, randomized controlled trial was done with 105 adult patients posted for infraumbilical surgery under subarachnoid block. All subjects received 3.0 mL (15.0 mg) of 0.5% hyperbaric bupivacaine. Groups D5.0, D7.5, and D10.0 (n = 35 each) received additionally 5.0, 7.5, and 10.0 mcg intrathecal dexmedetomidine as adjuvant. The onset time of sensory block, its peak level and time to this level, maximum motor block and time to it, total duration of analgesia (time to first rescue), and vital parameters were recorded at intervals. Postoperative analgesia was assessed by visual analog scale score at 15 and 30 minutes, then every 30 minutes until 2 hours and then every hour until 6 hours. Treatment emergent adverse events (bradycardia, hypotension, and sedation) were documented. RESULTS: Maximum sensory level achieved was higher in Group D10.0 than in the other two groups. There was significant and dose-dependent shortening of the mean time to peak sensory block (3.9, 3.3, and 2.9 min; P ＜ 0.001) and peak motor block (5.6, 5.3, and 4.8 min; P ＜ 0.001), and prolongation of postoperative analgesia duration (206.9, 220.8, and 244.0 min; P ＜ 0.001) with escalating doses (5.0, 7.5, and 10.0 mcg, respectively) of dexmedetomidine. Hemodynamic effects and adverse events were comparable in the three groups. CONCLUSIONS: Intrathecal dexmedetomidine (10.0 mcg), as adjuvant to 0.5% hyperbaric bupivacaine (15.0 mg), facilitates rapid onset sensory and motor block and prolongs duration of postoperative analgesia in spinal anesthesia without significant adverse effects. Although absolute differences are modest, the results are better compared to 5.0 and 7.5 mcg doses.

Analysis of thromboembolic events in patients with non-small cell lung cancer who received adjuvant chemotherapy: single-center real-world data.

Thromboembolic events (TEEs) are common in cancer patients, with increased risk of TEE by chemotherapy in patients with lung cancer. However, TEEs in patients with non-small cell lung cancer (NSCLC) who received adjuvant chemotherapy have rarely been reported. This study retrospectively analyzed real-world data of 275 patients with NSCLC treated with adjuvant chemotherapy after surgery from October, 2005 to June, 2020, in a single institution. The incidence of TEEs during or within one year of completion of adjuvant chemotherapy was investigated, and factors related to TEEs were analyzed. TEEs were confirmed in nine patients (3.3%), without fatal event related to TEEs. None of the factors, including Khorana score, was significantly associated with the occurrence of TEEs. All patients with TEEs had pathologic stage IIB or higher and a history of smoking, except for one patient. In conclusion, TEEs occurred in a smaller proportion of patients with NSCLC treated with adjuvant chemotherapy in the real world compared with those treated with palliative chemotherapy in previous reports. Furthermore, prophylactic anticoagulation in patients with NSCLC receiving adjuvant chemotherapy may not be needed except for high-risk patients, although those patients should be informed about the possible risk of TEEs.

Efficacy of Cinnamon as an Adjuvant in Reducing the Glycemic Biomarkers of Type 2 Diabetes Mellitus: A Three-Month, Randomized, Triple-Blind, Placebo-Controlled Clinical Trial.

The major aim of this randomized, placebo-controlled, triple-blind clinical trial was to evaluate the efficacy of cinnamon as an adjuvant treatment in reducing glycemic levels in people with type 2 diabetes, compared to a placebo. The study was conducted between August and December 2019, with 160 people with type 2 diabetes, in five Primary Health Units, in Parnaíba, Brazil. Inclusion criteria were: persons of both genders using oral antidiabetic agents, with glycated hemoglobin ≥ 6.0%, and between 18 and 80 years of age. The primary outcome was change in glycated hemoglobin levels after 90 days of intervention. Other biomarkers evaluated were fasting blood glucose, insulin level, and HOMA-IR index. Participants were divided equally into two groups of 80 individuals each, and were given 3 g capsules of either cinnamon or placebo to be taken in combination with their usual oral antidiabetic agents. After 90 days, participants in the cinnamon group had statistically significant reductions of 0.2% of glycated hemoglobin and 0.55 mmol/L of fasting venous glucose, when compared with the placebo group. Cinnamon reduced the glycemic measures of persons with type 2 diabetes, albeit with modest reductions. TRIAL: RBR-2KKB6D.

Progression/Recurrence-Free Survival 2 in Adjuvant Melanoma.

The long-term outcome of patients with stage III melanoma - that is, melanoma that has spread to nearby lymph nodes, lymphatics, or skin - who have received treatment with immune checkpoint inhibitors is of substantial interest. The article by Eggermont et al.1 published in this issue of NEJM Evidence reports 5-year outcomes from the stage III melanoma trial, KEYNOTE-054, which compared pembrolizumab (anti-programmed cell death protein 1 [PD-1]) with placebo. The data show durable recurrence-free survival (RFS) and distant metastasis-free survival (DMFS).

Five-Year Analysis of Adjuvant Pembrolizumab or Placebo in Stage III Melanoma.

Pembrolizumab or Placebo in Stage III MelanomaPatients with stage III melanoma randomly received adjuvant pembrolizumab or placebo. Five-year recurrence-free survival was 55.4% (95% CI, 50.8 to 59.8) versus 38.3% (33.9 to 42.7) and 5-year metastasis-free survival was 60.6% (56.0 to 64.9) versus 44.5% (39.9 to 48.9) for adjuvant pembrolizumab and placebo, respectively. No new safety signals were associated with adjuvant pembrolizumab.

Treatment of disseminated nocardiosis: a host-pathogen approach with adjuvant interferon gamma.

Disseminated nocardiosis is a rare, life-threatening disease. Particularly at risk are immunocompromised patients, highlighting the crucial role of host factors. Conventional intensive antibiotic treatment has improved survival rates, but the overall prognosis of patients with disseminated nocardiosis remains unsatisfactory. In this Grand Round, we present a case of severe nocardiosis that did not respond to standard therapy. The patient's condition deteriorated when antibiotic therapy was given alone and improved substantially only after coadministration of interferon gamma. We review the literature relevant to adjuvant interferon gamma therapy of nocardiosis and discuss its potential harms and benefits. Overall, we consider such treatment as beneficial and low risk if the patient is followed-up closely. We conclude that clinicians should consider this regimen in refractory cases of severe Nocardia infection.

Efficacy of probiotic adjuvant therapy for irritable bowel syndrome in children: A systematic review and meta-analysis.

OBJECTIVE: Irritable bowel syndrome (IBS) affects children's quality of life and learning. The purpose of this research was to systematically evaluate the efficacy of probiotic adjuvant therapy for IBS in children. METHODS: The Web of Science, PubMed, Cochrane Library, EMBASE and Clinical Trials databases were electronically searched for randomized controlled trials (RCTs) published prior to January 2021 exploring the use of probiotic adjuvant therapy for IBS in children. Strict screening and quality evaluations of the eligible articles were performed independently by 2 researchers. Outcome indexes were extracted, and a meta-analysis of the data was performed using RevMan 5.4.1 and STATA 16 software. Finally, the risk of bias in the included studies was assessed with the RCT bias risk assessment tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (5.1.0). RESULTS: A total of nine RCTs were included. In children, probiotics significantly reduced the abdominal pain score (I2 = 95%, SMD = -1.15, 95% (-2.05, -0.24), P = 0.01) and Subject's Global Assessment of Relief (SGARC) score (I2 = 95%, MD = -3.84, 95% (-6.49, -1.20), P = 0.004), increased the rate of abdominal pain treatment success (I2 = 0%, RR = 3.44, 95% (1.73, 6.87), P = 0.0005) and abdominal pain relief (I2 = 40%, RR = 1.48, 95% (0.96, 2.28), P = 0.08), and reduced the frequency of abdominal pain (I2 = 2%, MD = -0.82, 95% (-1.57, -0.07), P = 0.03). However, we found that it might not be possible to relieve abdominal pain by increasing the daily intake of probiotics. CONCLUSIONS: Probiotics are effective at treating abdominal pain caused by IBS in children, however, there was no significant correlation between abdominal pain and the amount of probiotics ingested. More attention should be given to IBS in children, and a standardized evaluation should be adopted.