Association of Multimodal Pain Control with Patient-Reported Outcomes in Children Undergoing Surgery

IntroductionOur aim was to describe practices in multimodal pain management at US children's hospitals and evaluate the association between non-opioid pain management strategies and pediatric patient-reported outcomes (PROs).MethodsData were collected as part of the 18-hospital ENhanced Recovery In CHildren Undergoing Surgery (ENRICH-US) clinical trial. Non-opioid pain management strategies included use of preoperative and postoperative non-opioid analgesics, regional anesthetic blocks, and a biobehavioral intervention. PROs included perioperative nervousness, pain-related functional disability, health-related quality of life (HRQoL). Associations were analyzed using multinomial logistic regression models.ResultsAmong 186 patients, 62 (33%) received preoperative analgesics, 186 (100%) postoperative analgesics, 81 (44%) regional anesthetic block, and 135 (73%) used a biobehavioral intervention. Patients were less likely to report worsened as compared to stable nervousness following regional anesthetic block (relative risk ratio [RRR]:0.31, 95% confidence interval [CI]:0.11–0.85), use of a biobehavioral technique (RRR:0.26, 95% CI:0.10–0.70), and both in combination (RRR:0.08, 95% CI:0.02–0.34). There were no associations of non-opioid pain control modalities with pain-related functional disability or HRQoL.ConclusionUse of postoperative non-opioid analgesics have been largely adopted, while preoperative non-opioid analgesics and regional anesthetic blocks are used less frequently. Regional anesthetic blocks and biobehavioral interventions may mitigate postoperative nervousness in children.Level of evidenceIII.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Top advances of the year: Precision oncology

The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.     

An update in pathologic diagnosis of uterine mesenchymal tumours

Recent discovery of new disease-defining molecular alterations and development of novel targeted therapies has dramatically changed the classification and management of uterine mesenchymal neoplasms. This review discusses diagnostic updates in endometrial stromal sarcoma, PEComa, uterine tumor resembling ovarian sex cord tumor (UTROSCT), inflammatory myofibroblastic tumor, NTRK fusion uterine sarcoma, COL1A1-PDGFB fusion sarcoma, and SMARC-deficient uterine sarcoma. Key clinical, morphologic, immunophenotypic, and molecular features are reviewed, with emphasis on common differential diagnoses and pitfalls, and their impact on prognosis or management. Where applicable, the role of novel targeted therapies is discussed. A stepwise approach to uterine mesenchymal neoplasms can achieve a proper diagnosis and guide appropriate clinical management in most cases. Nonetheless, given the rarity of these tumors, their overlapping pathologic features, and rapid evolution in their classification and management, we advocate a low threshold for diagnostic consultation.     

Update on adrenal cortical neoplasia

The adrenal cortex gives rise to a biologically heterogenous group of neoplasms, each with a distinct morphology, antigen expression and molecular profile. Adrenal cortical adenomas have excellent prognosis and are usually cured by surgical resection alone, while adrenal cortical carcinomas are very aggressive tumors with a poor prognosis regardless of therapy. These tumors are rare and often challenging for a pathologist to diagnose, as significant overlap exists between benign and malignant lesions in some cases. In this review, we attempt to summarize most important histologic and clinical features of adrenal cortical adenomas and carcinomas, clarify the use of different grading systems, the use of special stains and the differential diagnosis for practicing pathologists. Most relevant hereditary syndromes associated with adrenal cortical tumors are listed. Updates in molecular alterations in adrenal cortical neoplasms and hyperplastic diseases as well as their clinical significance and potential therapeutic implications are also discussed.