Risk Of Treatment-related Adverse Events Research Articles

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

We aim to report the latest pooled analyses to evaluate the additive efficacy and safety of probiotics in the treatment of ulcerative colitis (UC). 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. 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). 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.

Comparison of adverse effects of anti-tumor therapy for breast cancer shortly after COVID-19 diagnosis vs. the control period.

COVID-19 is an acute infectious disease caused by SARS-CoV-2. The best time to restart antitumor therapy in breast cancer patients after SARS-CoV-2 infection is unknown. This study aimed to evaluate treatment-related adverse events in breast cancer patients who received antitumor therapies within a short time after SARS-CoV-2 infection (observation) as well as before (control) and to provide safety data. We conducted a self-controlled cohort study using the data from the Breast Disease Center of Peking University First Hospital. We identified patients who received antitumor therapy within 28 days after COVID-19 infection between December 20, 2022, and January 20, 2023. The primary outcome was treatment-related adverse events. McNemar's test was used to compare the incidence rate of adverse reactions between periods. We identified 183 patients with breast cancer, of whom 109 were infected with SARS-CoV-2 within 28 days before antitumor treatment and were included. In total, 28 patients (25.7%) received neoadjuvant therapy, 60 (55.0%) received adjuvant therapy, and 21 (19.3%) received advanced rescue therapy. None of patients required hospitalization for severe or critical COVID-19, but 15 patients (13.8%) still had sequelae of COVID-19 while receiving antitumor treatment. The most common adverse events were peripheral neuropathy (n = 32 [29.4%]), pain (n = 29 [26.6%]), fatigue (n = 28 [25.7%]), nausea (n = 23 [21.1%]), and neutropenia (n = 19 [17.4%]). There was no increased risk of overall treatment-related adverse events (n = 87 [79.8%] vs. n = 91 [83.5%]; p = 0.42) or serious adverse events (n = 13 [11.9%] vs. n = 12 [11.0%]; p = 1.00) from receiving antitumor therapy shortly after the diagnosis of COVID-19. We also found no increased risk in subgroup analyses, and no patients discontinued antitumor therapy due to adverse events. Restarting antitumor therapy 2-4 weeks after having mild or moderate COVID-19 is a relatively safe strategy for breast cancer patients that does not increase the risk of treatment-related adverse events.

Efficacy and safety of botulinum toxin for treating motor dysfunction in patients with Parkinson’s disease: a systematic review and meta-analysis

ObjectiveTo evaluate the efficacy and safety of botulinum toxin (BTX) for motor dysfunction in Parkinson’s disease (PD).DesignSystematic review and meta-analysis.Data sourcesSearches of PubMed, EMBASE and the Cochrane Library, from database...

PATIENT PREFERENCES IN PHARMACEUTICAL AND DEVICE-BASED TREATMENTS FOR UNCONTROLLED HYPERTENSION

Objective: Radiofrequency renal denervation (RDN) safely reduces high blood pressure (BP) in hypertensive (HTN) patients. Patient preference regarding such a treatment over antihypertensive (AH) drugs for uncontrolled HTN is poorly understood. Design and method: A recent discrete choice experiment (DCE) study in patients with uncontrolled HTN identified the reduction in systolic BP as the most important driver of patient preference between interventional treatments (e.g. RDN) or drugs. Using a predictive model consisting of the preference weights for safety and efficacy attributes from the DCE study, we calculated patients’ treatment preferences in 3 typical clinical scenarios in HTN management. Each scenario presented a choice to either initiate/increase AH drugs, or to have interventional treatment such as RDN: (1) AH drug naïve: initiate AH drugs vs. interventional treatment (2) mild-moderate HTN, 1-3 AH drugs: increasing AH drugs vs. intervention with no drug changes, (3) severe HTN (systolic BP >150mmHg, >3 AH drugs): increasing AH drugs vs. intervention with no drug changes. In each scenario, the average predicted probability of choosing one treatment over the other was calculated based on a benefit-risk profile from the sum of preference-weighted treatment attributes (type of treatment, changes in AH drugs, office systolic BP reducing efficacy, effect duration, risk of drug side effects, interventional treatment adverse events). Values of the treatment attributes were derived from the literature, expert opinion, and published RDN studies (SPYRAL HTN OFF-MED, ON-MED, Global SYMPLICITY Registry). Results: In (1), 17% preferred interventional treatment without drugs vs 83% preferred initiation of drugs. In (2), 24% preferred interventional treatment without increasing drugs vs 76% preferred increasing drugs. In (3), 45% preferred interventional treatment without increasing drugs vs 55% preferred increasing drugs. Preference differences were driven by the magnitude of office systolic BP reductions with each treatment. Risks of treatment-related adverse events were less important to treatment choices. Conclusions: Preference for RDN ranged from one-fifth to one-half of patients depending on clinical scenario. The increase mirrored the extent of prior treatment with AH drugs and HTN severity on drugs. Patient preference was driven predominantly by efficacy and minimally by safety of treatment.

Comparative efficacy and safety of anti-PD-1/L1 antibody plus anti-VEGF antibody and anti-PD-1/L1 antibody plus VEGFR-targeted tyrosine kinase inhibitor as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A systematic review and network meta-analysis.

e16148 Background: Anti-PD-1/L1 antibody combined with anti-VEGF antibody and anti-PD-1/L1 antibody combined with VEGFR-targeted tyrosine kinase inhibitor are both effective first-line therapies for uHCC in clinical practice widely. However, direct comparisons across the two regimens are not available. We conducted a network meta-analysis of them in terms of overall survival (OS), progression free survival (PFS), objective response rate (ORR) and incidence of treatment-related adverse events (TRAEs). Methods: After a literature research performed in PubMed, MEDLINE, Embase, the Cochrane library and several major scientific societies from January 1 2007 to November 6 2022, 3,279 records were obtained. 6 phase III trials has been identified for the final analysis: REFLECT, IMbrave150, ORIENT-32, COSMIC-312, Qin 2022 and LEAP-002. The experiments were broadly classified into three groups: anti-PD-1/L1 antibody + anti-VEGF antibody (IMbrave150 and ORIENT-32), anti-PD-1/L1 antibody + VEGFR-targeted tyrosine kinase inhibitor (COSMIC-312, Qin 2022 and LEAP-002) and intermediate reference group (lenvatinib vs sorafenib, REFLECT). We derived hazard ratios (HR) with 95% confidence intervals (95%CI) for OS and PFS, odds ratio (OR) for ORR and relative risks (RR) for all grade and grade ≥3 TRAEs. With fixed effect models to estimate the indirect pooled HRs, ORs, RRs and 95%CI, a frequentist network meta-analysis was conducted using sorafenib as intermediate reference. Results: 4,012 patients were included in the analysis overall, among them, 1815 patients were treated with anti-PD-1/L1 antibody+VEGF-antibody (A+A), 1,099 patients were treated with anti-PD-1/L1 antibody+VEGFR-TKI (A+T), 877 patients were treated with lenvatinib (LEN) and 1,320 patients were treated with sorafenib (SOR). With a p-score of 98%, the combination of A+A provided the greatest reduction in the risk of death, was not significantly different from A+T (HR=0.84, 95%CI: 0.66-1.06). Besides, A+T were associated with the greatest effect in prolonging PFS and improving ORR with 91% for p-score, but there are no statistical differences with A+A (HR=1.06, 95%CI: 0.87-1.30, OR=0.82, 95%CI: 0.47-1.46). Considering the risk of TRAEs, A+A were significantly safer than A+T (RR=0.91, 95%CI: 0.84-0.98) in all grade of TRAEs and ≥3 grade (RR=0.91, 95%CI: 0.84-0.98). Conclusions: The combination of anti-PD-1/L1 antibody and anti-VEGF antibodies has the greatest probability of delivering the longest OS, while anti-PD-1/L1 antibody plus VEGFR-targeted tyrosine kinase inhibitor is correlated with larger PFS benefit at the cost of a lower safety rate.

Abstract WP123: Machine Learning To Predict High Risk Adverse Events In Treatment Trials For Intracerebral Hemorrhage

Background: ICH clinical trials have shown that aggressive blood pressure (BP) lowering can lead to adverse events (AEs) such as renal failure (RF) or new stroke. These studies focused on whether the study intervention causes AEs on average. By combining trials, we estimate each individual’s risk of developing AEs with BP lowering. Methods: We augmented data from ATACH2 by adding patients from the observational ERICH study and performed propensity score matching with a radius (radius=0.4, ratio=1). We estimated the individualized counterfactual outcome of renal AEs using augmented ATACH2. ERICH had 127 patients (out of 1,706) with new onset of RF during hospital stay. ATACH2 had 68 patients (out of 1000) with renal AEs (recorded by MedDRA) within 7d. We built the counterfactual prediction model using a neural network model (FlexTENet). We extracted feature importance score using Shap Deep Explainer. Results: We borrowed 1,706 patients to augment ATACH2. The augmented cohort had 2706 patients in total. FlexTENet captured the heterogeneity fairly. For factual outcome prediction accuracy, the FlexTENet achieved the best area under precision-recall curve (0.203) and the area under receiver operating curve (0.703). High diastolic BP at admission and low platelets increased the counterfactual effect of BP reduction on occurrence of renal AEs. In addition, high systolic BP and high glucose decreased the counterfactual effect on the occurrence of renal AEs. Conclusions: Identifying treatment-related AEs at an individual level has rarely been studied. Our counterfactual machine learning shows potential to predict individual patient’s risk of treatment-related adverse events.

The Effectiveness of Catheter Ablation in the Management of Ventricular Tachycardia in Comparison With Antiarrhythmic Drugs in Patients With Structural Heart Disease: A Meta-Analysis.

The aim of this meta-analysis is to compare the safety and efficacy of catheter ablation versus antiarrhythmic drugs (AADs) in the management of ventricular tachycardia (VT) in patients with structural heart diseases. Two independent investigators searched electronic databases including PubMed, Cochrane, and Excerpta Medica database (EMBASE) using keywordcombinations (Medical Subject Headings (MeSH) terms and free terms)such as "catheter ablation," "ventricular tachycardia," "escalation," and "antiarrhythmic drugs" from inception to November 30, 2022. The primary efficacy outcomes included recurrence of VT at follow-up, all-cause mortality, and cardiovascular mortality. The secondary efficacy outcomes assessed in the current meta-analysis included implantable cardioverter-defibrillator (ICD) shock and hospitalization due to cardiac reasons. Safety outcomes included treatment-related adverse events and serious adverse events. A total of three studies were included in this meta-analysis. Therewas no significant difference in the risk of recurrence of VT (RR: 0.94, 95% CI: 0.72-1.24, p-value: 0.67), all-cause mortality (RR: 0.99, 95% CI: 0.67, 1.46, p-value: 0.98), cardiovascular mortality (risk ratio (RR): 0.90, 95% confidence interval (CI): 0.56-1.45, p-value: 0.67),incidence of ICD shocks (RR: 0.99, 95% CI: 0.76-1.29, p-value: 0.93, I-square: 0%), and hospitalization due to cardiac reasons in follow-up (RR: 0.77, 95% CI: 0.55-1.07, p-value: 0.12) between the catheter ablation group and the antiarrhythmic druggroup. However, the risk of treatment-related adverse events was lower in the ablation group compared to the antiarrhythmic medicine (AAM) group (RR: 0.44, 95% CI: 0.29-0.67, p-value: 0.0001). In this meta-analysis of three randomized controlled trials (RCTs) among patients with structural heart disease who had ventricular tachycardia, the incidence of the recurrence of VT, all-cause mortality, cardiovascular mortality, and ICD shock was not significantly different between patients who received catheter ablation and antiarrhythmic drugs. However, regarding safety, catheter ablation is a safe procedure with a low risk of treatment-related events compared to antiarrhythmic drugs.

Understanding Patient Preferences for Chronic Lymphocytic Leukemia Treatments

Background Chemoimmunotherapy (CIT) had been the longstanding first-line treatment of chronic lymphocytic leukemia (CLL) for more than a decade. However, CIT has known toxicities, making it less tolerable for older adults, and it has proven to be ineffective for patients with high-risk biomarkers. More recently, approved targeted agents developed in the past 8 years have emerged as safe and effective therapeutic alternatives to CIT. Targeted treatments vary in their benefit-risk profiles, duration of treatment, and routes of administration. The aim of this study was to quantify respondents’ preferences for attributes associated with CLL treatments. Methods A web-based discrete-choice experiment (DCE) survey was developed and administered to respondents recruited through the CLL Society, a nonprofit organization focused on addressing the unmet needs of those with CLL and small lymphocytic leukemia. Respondents answered 12 DCE questions. Each question offered a choice between 2 hypothetical treatment profiles created by an experimental design and defined by 7 attributes with varying levels: chance of achieving progression-free survival (PFS) at 2 years, treatment results confirmed with a measurable residual disease (MRD) test or routine testing, mode and frequency of administration, duration of treatment, risk of tumor lysis syndrome (TLS), risk of atrial fibrillation, and risk of fatigue. Data were analyzed using a random-parameters logit model. The estimated preference weights were used to calculate the conditional relative importance of changing each attribute from the most preferred to the least preferred levels; they were also used to calculate the maximum risk of treatment-related adverse events the average respondent would accept to gain improvements in other attributes. Results Between April and June 2022, 229 adults in the United States with a self-reported diagnosis of CLL for at least 3 months completed the survey. The mean age was 66 years, 95.2% were White, 59.4% identified as female, 66.4% of the sample reported ever receiving treatment for CLL, and 71.1% of these respondents were currently receiving treatment. The DCE results revealed that respondents placed the most importance on increasing the chance of PFS at 2 years from 70% to 90% and confirming results with MRD testing instead of routine testing (Figure 1). The results also indicated that respondents preferred treatments by daily oral pills over intravenous infusions (IV) administered every 4 weeks, preferred treatments with a fixed duration over treat-to-progression treatments, and treatments with a lower risk of side effects. Reducing the risk of TLS from 3% to 0% was least important relative to changes in the other study attributes (Figure 2). On average, respondents were willing to accept more than a 3% risk of TLS (the largest TLS risk presented in the survey) in exchange for all the improvements in chance of PFS, duration of treatment, and mode of administration, with one exception: respondents were willing to accept a 2.7% risk of TLS (95% confidence interval [CI] 1.1-4.2) to confirm their results with MRD testing versus routine testing when the chance of PFS was 90%. Confirmation with MRD testing was more important to respondents when the chance of achieving PFS was low (70%) compared with when it was high (90%). Respondents were also willing to accept greater than a 3% risk of TLS, a 6.2% risk of atrial fibrillation (95% CI, 4.2-8.1), or a 21.2% risk of fatigue (95% CI, 12.3-30.2), to have a fixed 12-month treatment instead of a treat-to-progression therapy. For a change from IV every 4 weeks to 2 pills daily, respondents were willing to accept greater than a 3% risk of TLS, a 7.7% risk of atrial fibrillation (95% CI, 5.7-9.7), or a 27.7 risk of fatigue (95% CI, 18.5-36.9). Conclusions Improving the chance of PFS at 2 years with results confirmed by MRD testing was the most important driver of treatment preferences among adults with CLL. Respondents preferred daily oral treatments over IV treatments administered every 4 weeks and fixed duration treatments over treatments taken until progression. Respondents were also willing to accept greater than clinically relevant levels of TLS for nearly all changes in treatment attributes. Results from this study can help inform shared decision making when selecting alternative therapies for CLL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and safety of sofosbuvir/velpatasvir with or without ribavirin in hepatitis C genotype 3 compensated cirrhosis: A meta-analysis

BACKGROUNDHepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma globally. Sofosbuvir/velpatasvir (SOF/VEL) is an effective pan-genotypic direct-acting antiviral combination for treatment of chronic HCV infection. While the addition of ribavirin (RBV) to SOF/VEL improved sustained virological response (SVR12) in genotype 3 (GT3) decompensated cirrhosis patients, the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear. AIMTo evaluate the efficacy and safety of SOF/VEL, with or without RBV in GT3 compensated cirrhosis patients. METHODSWe searched four electronic databases (PubMed/Medline, Embase, Cochrane Library and Web of Science) from inception up to June 2021 using both free text and MeSH terms. There was no restriction on language, geography, publication dates and publication status (full text or abstracts). All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL, with or without RBV, were included, regardless of age, gender or prior treatment experience. The primary outcome was sustained virological response 12-wk post-treatment (SVR12). The secondary outcome was treatment-related adverse events, as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%CI and heterogeneity (I2) were estimated using Review Manager version 5.3.RESULTSFrom 1752 citations, a total of seven studies (2 randomized controlled trials, 5 cohort studies) with 1088 subjects were identified. The SVR12 was similar in GT3 compensated cirrhosis patients, regardless of the use of RBV, for both the intention-to-treat RR 1.03, 95%CI: 0.99-1.07; I2 = 0%) and the per-protocol analysis (RR: 1.03, 95%CI: 0.99-1.07; I2 = 48%). The overall pooled rate of treatment-related adverse events was 7.2%. Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL (RR: 4.20, 95%CI: 1.29-13.68; I2 = 0%). Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions. However, addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients. CONCLUSIONRibavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL. Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.

Multi-institutional analysis of central nervous system germ cell tumors in patients with Down syndrome.

Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data. A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature. Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n=13; 31.7%), followed by posterior fossa (n=7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from postsurgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas. Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered to mitigate treatment-related complications and long-term neurocognitive sequelae.

GCT-15. Multi-institutional analysis and literature review of central nervous system germ cell tumors in patients with Down syndrome

Abstract BACKGROUND: A standard-of-care has not been established for the management of patients with Down syndrome (DS) who develop primary central nervous system (CNS) germ cell tumors (GCTs) – the most common CNS neoplasm in DS – despite being more susceptible to treatment-related adverse events. METHODS: Data from large academic institutions were collected and a comprehensive review of the medical literature was conducted. RESULTS: Ten patients from six institutions (five USA, one Brazil) were reviewed. Additionally, thirty-one patients were identified in the literature from 1975-2021. Of the 41 total patients, mean age was ten years (range, birth to 35 years); males were predominant (61%). Basal ganglia were the most common tumor location (n=12; 29%), followed by posterior fossa (n=7; 17%). Sixteen patients had non-germinomatous germ cell tumors (NGGCTs) (39%), 14 had pure germinomas (34%), and eight had teratomas (20%); histology was unreported for two (5%). Nine patients (22%) experienced disease relapse, of which four died from tumor progression (one germinoma versus three teratoma). Fifteen patients (37%) experienced treatment-related complications - seven died (four germinoma versus three NGGCT). Of the germinoma patients, two died from chemotherapy-related sepsis, one from post-surgery cardiopulmonary failure, and one from Moyamoya following radiation-therapy (RT) only. Of the NGGCT patients, one died from chemotherapy-related sepsis, one from post-surgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival (OS) was 66% for all histological types - 62% germinoma, 79% for NGGCT, and 53% for teratoma. Three-year OS for patients who received RT or chemotherapy was 71% and 75% respectively. Twenty-seven patients remain alive at latest follow-up (mean follow-up from diagnosis: 46.8 months). CONCLUSIONS: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered for this patient population to mitigate treatment-related complications and long-term neurocognitive sequelae.

Risk of Toxicity with Immunotherapy–Tyrosine Kinase Inhibitors for Metastatic Renal Cell Carcinoma: A Meta-Analysis of Randomized Controlled Trials

Aim: Few data are available regarding the safety profile of immunotherapy-tyrosine kinase inhibitor (IO-TKI) combinations in metastatic renal cell carcinoma. The authors investigated all-grade and grade 3-4 (G3-4) adverse events in trials comparing IO-TKI combinations with sunitinib monotherapy. Methods: The relative risks of several all-grade and G3-4 adverse events were analyzed. Results: Relative risks were similar between patients receiving IO-TKI combinations versus sunitinib monotherapy. However, the use of IO-TKI combinations was associated with a higher risk of all-grade and G3-4 diarrhea, all-grade hypothyroidism, G3-4 decreased appetite, all-grade and G3-4 aspartate transaminase increase and all-grade and G3-4 alanine transaminase increase. Conclusion: The results of the authors' meta-analysis suggest that risks of treatment-related adverse events should be carefully considered when choosing IO-TKI combinations in metastatic renal cell carcinoma patients.

Treatment-Related Adverse Events with PD-1 or PD-L1 Inhibitors: A Systematic Review and Meta-Analysis.

Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. Results: a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85–2.96), rash (RR: 1.53, 95% CI: 1.25–1.87), ALT elevation (RR 1.54, 95% CI 1.23–1.92), AST elevation (AST: RR 1.49, 95% CI 1.20–1.85), hepatitis (RR: 3.54, 95% CI: 1.96–6.38) and hypothyroid (RR: 5.29, 95% CI: 4.00–6.99) compared with that of control group. Besides that, PD-1/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21–1.48), dyspnea (RR:1.23, 95% CI: 1.12–1.35) and chest pain (RR: 1.26, 95% CI: 1.07–1.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13–2.12). The risk of arthralgia was increased with PD-1/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10–1.47). Although the risk of myalgia was similar with PD-1/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45–0.70) compared with that of chemotherapy. Conclusions: our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration.

Banded RYGB Ring Slippage Endoscopic Removal with Self-expandable Stents: a Comparative Study Between Metallic and Plastic One.

Banded Roux-en-Y gastric bypass (RYGB) was a common bariatric procedure in the 2000s, and the ring slippage is one of its late adverse events. Both plastic and metallic stents have been reported as adjunct methods to induce erosion and facilitate endoscopic removal of the ring. To compare the safety and effectiveness of self-expanding metallic stents (SEMS) and plastic stents (SEPS) to treat ring slippage. We conducted a retrospective longitudinal study analyzing consecutive patients with ring dysfunction treated with stents plus endoscopic removal. Ninety patients were enrolled (36 SEMS vs. 54 SEPS). The mean age was 48.56 ± 13.07 and 45.6 ± 12.1 in the SEMS and SEPS groups, respectively. All patients had band slippage, but 24 from SEMS group and 23 from SEPS group had further complications. There were more complications in metallic stent concerning mean absolute number of therapy-related adverse events (1.33 ± 0.48 vs. 1.72 ± 0.5, p > 0.05) and time until erosion (14.9 ± 1.6 vs. 13.8 ± 1.4days, p > 0.05). Female sex and age > 41years old correlated with longer time to band erosion and higher incidence of adverse events in SEMS patients. In SEPS group, only female sex was a risk factor for adverse events. Both procedures were efficient at inducing band erosion with similar safety profiles. Older and female patients are at a higher risk of treatment-related adverse events, especially those receiving SEMS.

CT-based assessment of body composition and skeletal muscle in melanoma: A systematic review.

Sarcopenia (low skeletal muscle index) and myosteatosis (low skeletal radiodensity) have been associated with poor outcomes in melanoma. This systematic review was performed to summarize and critically evaluate current literature surrounding body composition in melanoma. MEDLINE and Embase databases were searched for studies of melanoma patients with computed tomography (CT) based body composition analysis from 2000 to 2020. Outcomes of interest were survival, including overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS), as well as treatment-related adverse events (AEs). Nine studies of 914 patients were included in the final review. The majority of studies were of metastatic melanoma patients treated with immunotherapy. Studies demonstrated a variety of CT analysis techniques and cut-offs to define sarcopenia and myosteatosis. Associations of sarcopenia or myosteatosis with survival (OS, PFS, DFS) or risk of treatment-related AEs were conflicting. Multiple studies had low quality of evidence due to small sample sizes, use of non-validated CT measures, and lack of multivariable analyses. Due to methodologic heterogeneity and low quality of evidence, impacts of CT-derived body composition parameters on outcomes in melanoma are unclear. Further research should be conducted to elucidate impacts of body composition in melanoma.

Initial treatment strategy for classical Hodgkin lymphoma in adults

Four cycles of ABVD followed by 30 Gy IFRT (ISRT) is a standard regimen, as an initial treatment, for patients with early-stage classical Hodgkin lymphoma (cHL), whereas 2 cycles of ABVD followed by 20 Gy IFRT (ISRT) is an alternative regimen for those with favorable early-stage cHL. For patients with unfavorable early-stage cHL including bulky disease, local radiotherapy can be safely omitted if negative findings on interim PET are obtained after 2 cycles of escalated BEACOPP plus 2 cycles of ABVD. ABVD (6/8 cycles) or brentuximab vedotin (BV) with concurrent AVD (6 cycles) is a standard regimen for patients with advanced-stage cHL. For elderly cHL patients (60 years of age or older) and multiple comorbidities, the risk of treatment-related adverse events is higher, which can potentially lead to poor outcomes. BV with sequential AVD therapy, which is a unique combination strategy, has been developed for elderly cHL patients. The combination of anti-PD-1 antibodies with AVD therapies is currently being evaluated in some clinical trials. This review includes current evidence that primarily focuses on randomized clinical trials for newly diagnosed adult cHL patients and management points in clinical practice for those patients.

Hypertension Management in Patients with Chronic Kidney Disease in the Post-SPRINT Era.

The management of high blood pressure (BP) is crucial for improving outcomes in patients with chronic kidney disease (CKD). The updated Kidney Disease: Improving Global Outcomes 2021 BP guideline proposes treating adults with CKD to a target systolic BP (SBP) of <120 mmHg based on the standardized office BP measurement. This suggestion is largely based on the finding of SPRINT (Systolic Blood Pressure Intervention Trial) that targeting an SBP of <120 mmHg versus <140 mmHg is beneficial for cardiovascular and mortality outcomes, regardless of the patient’s kidney disease status. However, extended follow-up studies of CKD trials showed that intensive versus usual BP control was associated with a lower risk of kidney failure in patients with, but not in those without, proteinuria. Similarly, a recent population-based study in Korea demonstrated that the optimal on-treatment BP for composite cardiorenal and mortality outcomes was left-shifted in adults with CKD, particularly in those with albuminuria, relative to that in patients without CKD. Moreover, in meta-analyses of randomized trials, more intensive versus standard BP control was associated with a lower risk of all-cause mortality in patients with CKD and albuminuria but not in those without CKD. Meanwhile, a 2020 Cochrane review reported that lower BP targets (≤135/85 mmHg), compared with standard targets (≤140/90 mmHg), resulted in a small reduction in cardiovascular events, an increase in other serious adverse events, and no reduction in total serious adverse events. Lowering SBP to <120 mmHg can potentially increase the risk of treatment-related adverse events beyond the cardioprotective benefits, and standardized BP measurement increases the burden on patients and resources. Thus, targeting a BP of <130/80 mmHg with appropriate office BP measurement can be an option in patients with CKD. The presence of albuminuria would need to be additionally considered to determine individualized BP targets.

Comparative Efficacy and Safety of PD-1/PD-L1 Inhibitors for Patients with Solid Tumors: A Systematic Review and Bayesian Network Meta-analysis.

Purpose: The clinical use of immunotherapies targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) is rapid expanding, but the equivalency of these inhibitors remains unclear. We aimed to comprehensively compare the efficacy and safety of PD-1/PD-L1 inhibitors with a systematic review and Bayesian network meta-analysisMethods: We searched PubMed, Web of Knowledge, related reviews and abstracts for randomized controlled trials of five PD-1/PD-L1 inhibitors for patients with solid tumors before November 30th, 2018. We estimated summary hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for grade 3-5 treatment-related adverse events (TrAEs) using pairwise and network meta-analysis with random-effects. This study was registered with PROSPERO (#CRD42018116624).Results: Totally, 43 reports of 35 trials comprising 21261 patients were eligible for the analysis. Nivolumab, pembrolizumab, atezolizumab and durvalumab were more effective than control treatment, and no significant differences were identified in OS and PFS between any two inhibitors. Avelumab was associated with significantly inferior OS to nivolumab (HR 1.37, 95%CrI 1.05-1.78) and pembrolizumab (HR 1.33, 95%CrI 1.02-1.73), and with inferior PFS to nivolumab (HR 1.60, 95%CrI 1.03-2.51). Compared with placebo, nivolumab had increased risk of grade 3-5 TrAEs (OR 2.35, 95%CrI 1.35-4.17). Compared with standard-of-care, nivolumab (OR 0.39, 95%CrI 0.28-0.54), pembrolizumab (OR 0.43, 95%CrI 0.30-0.60), atezolizumab (OR 0.37, 95%CrI 0.21-0.64) and avelumab (OR 0.24, 95%CrI 0.12-0.48) significantly reduced grade 3-5 TrAEs. There were not significant differences in grade 3-5 TrAEs between any two inhibitors.Conclusion: This Bayesian network meta-analysis revealed that nivolumab, pembrolizumab, atezolizumab and durvalumab yielded equivalent survival, while avelumab was associated with unfavorable survival. PD-1/PD-L1 inhibitors were comparable in the risk of TrAEs, and safer than conventional therapies.

Food allergy oral immunotherapy

Food allergy oral immunotherapy (OIT) has demonstrated efficacy in promoting clinically relevant immunomodulation that leads to desensitization (reduced reactivity while on OIT) in the majority of treated individuals; however, sustained unresponsiveness after OIT cessation for a specified interval has only been observed in a subset. The potential therapeutic benefits of OIT must be balanced with the risk for adverse events. These adverse events may range from self-limited or easily treated oropharyngeal, respiratory, or gastrointestinal symptoms to persistent abdominal symptoms that lead to cessation of therapy and to anaphylaxis. To date, the majority of studies have evaluated single-allergen OIT approaches; however, multi-allergen OIT has demonstrated favorable safety and efficacy outcomes, and is the subject of ongoing investigation. Recent U.S. Food and Drug Administration approval of the first licensed OIT product for peanut allergy challenges the long-standing paradigm of dietary food avoidance as the sole option for individuals with food allergy. Yet, the limitations of this “first-generation” treatment support the need for continued research and development of next-generation therapies to improve efficacy, minimize risk, and allow for broad applicability to both individuals with single-food allergy and those with multifood allergies. Optimizing future therapies will require developing novel approaches that maximize both efficacy and safety and/or tolerability outcomes, potentially through the combination with biologic therapies or adjuvants. Shared decision-making among patients, physicians, and parents and/or caregivers is critical to select optimal candidates for treatment with OIT by balancing the potential therapeutic benefit and possible risk reduction with a realistic consideration of OIT treatment burden and the risk of treatment-related adverse events.

Caring for older adults with multiple myeloma during the COVID-19 Pandemic: Perspective from the International Forum for Optimizing Care of Older Adults with Myeloma

The novel coronavirus (SARS-CoV-2, COVID-19) was first identified in the province of Wuhan, China in December 2019 [1], following the emergence of new cases of pneumonia of unknown etiology. Since then, the manifestations of COVID-19 infections have ranged from asymptomatic to severe respiratory infections, with increased morbidity in older adults including those with co-morbidities and cancer [2,3]. Presently, global mortality is reported at 4.7%, but this varies widely by location, from 0.7% in Germany to 10.8% in Italy [4]. As of April 13, 2020, the number of infections continues to rise well beyond the 1.9 million cases, and approximately 120,000 COVID-19-related deaths that have already occurred globally [5]. Multiple myeloma (MM) is a malignant plasma cell dyscrasia which predominantly affects older and often frail adults. Although tremendous gains have been made for older adults with MM, infections, including respiratory infections, significantly impact the rate of early mortality in these patients [6,7]. Furthermore, older adults with MM have age-associated vulnerabilities leading to heterogeneity in outcomes [8]. The complexity of caring for older patients have increased substantially during this pandemic, due to concern about their risk of severe morbidity of COVID19 infection. Optimal strategies for these patients will involve staging the malignancy/aging, while simultaneously considering the local prevalence of COVID-19 infection. Herein, we discuss strategies for the risk reduction of COVID-19 transmission, treatment stratification of anti-myeloma therapy and discussion regarding goals of care for older adults with MM during the COVID-19 pandemic.