A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer.

Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline. Eighteen evaluable patients were accrued (11 ER-positive; seven TNBC). Only three patients had a response (ORR = 17%), thus the study did not proceed to the second stage. Responses were only observed in patients with TNBC (ORR = 43%). Responders versus non-responders had upregulation of CD8, granzyme A, and perforin 1 gene expression, and higher mutational and neoantigen burden. Patients with TNBC had an oligoclonal shift of the most abundant TCR-beta clonotypes compared to those with ER-positive disease, p = 0.004. We conclude responses are low in unselected metastatic breast cancer, however, higher rates of clinical benefit were observed in TNBC. Immunogenomic dynamics may help identify phenotypes most likely to respond to immunotherapy.

Non-arthroplasty treatment of osteoarthritis of the knee.

The American Academy of Orthopaedic Surgeons has developed an Appropriate Use Criteria (AUC) on the Non-Arthroplasty Treatment of Osteoarthritis of the Knee (OAK). Evidence-based information, in conjunction with clinical expertise of physicians, was used to develop the criteria to improve patient care and obtain best outcomes while considering the subtleties and distinctions necessary in making clinical decisions. The OAK AUC clinical scenarios were derived from patient indications that generally accompany OAK as well as from the current evidence-based clinical practice guidelines and its supporting literature. The 576 patient scenarios and 10 treatments were developed by the Writing Panel, a group of clinicians who are specialists in this AUC topic. Next, the Review Panel, a separate group of volunteer physicians, independently reviewed these materials to ensure that they were representative of patient scenarios clinicians are likely to encounter in daily practice. Finally, the multidisciplinary Voting Panel (made up of specialists and nonspecialists) rated the appropriateness of treatment of each patient scenario using a 9-point scale to designate a treatment as Appropriate (median rating, 7 to 9), May Be Appropriate (median rating, 4 to 6), or Rarely Appropriate (median rating, 1 to 3). The final appropriateness ratings assigned by the voting panel can be accessed online via the AAOS OAK AUC web-based mobile application at: www.aaos.org/aucapp.

Optimizing the management of full-thickness rotator cuff tears.

The American Academy of Orthopaedic Surgeons has developed Appropriate Use Criteria (AUC) on Optimizing the Management of Full-Thickness Rotator Cuff Tears (RC). Evidence-based information, in conjunction with clinical expertise of physicians, was used to develop the criteria to improve patient care and obtain best outcomes while considering the subtleties and distinctions necessary in making clinical decisions. The RC AUC Writing Panel began the development of the clinical scenarios by identifying clinical indications typical of patients commonly presenting with full-thickness rotator cuff tears in clinical practice, as well as from the current evidence-based clinical practice guidelines and its supporting literature. The 432 patient scenarios and 5 treatments were developed by the Writing Panel, a group of clinicians who are specialists in this AUC topic. Next, the Review Panel, a separate group of volunteer physicians, independently reviewed these materials to ensure that they were representative of patient scenarios that clinicians are likely to encounter in daily practice. Finally, the multidisciplinary Voting Panel (made up of specialists and nonspecialists) rated the appropriateness of treatment of each patient scenario using a 9-point scale to designate a treatment as appropriate (median rating, 7 to 9), may be appropriate (median rating, 4 to 6), or rarely appropriate (median rating, 1 to 3).

Treatment of distal radius fractures.

The American Academy of Orthopaedic Surgeons has developed Appropriate Use Criteria (AUC) for treating distal radius fractures (DRF). Evidence-based information, in conjunction with the clinical expertise of physicians, was used to develop the criteria to improve patient care and obtain best outcomes while considering the subtleties and distinctions necessary in making clinical decisions. The DRF AUC clinical patient scenarios were derived from patient indications that generally accompany a DRF, as well as from current evidence-based clinical practice guidelines and supporting literature. The 216 indications and 10 treatments were developed by the Writing Panel, a group of clinicians who are specialists in this AUC topic. Next, the Review Panel, a separate group of volunteer physicians, independently reviewed these materials to ensure that they were representative of patient scenarios that clinicians are likely to encounter in daily practice. Finally, the multidisciplinary Voting Panel (made up of specialists and nonspecialists) rated the appropriateness of treatment of each patient scenario using a 9-point scale to designate a treatment as Appropriate (median rating, 7 to 9), May Be Appropriate (median rating, 4 to 6), or Rarely Appropriate (median rating, 1 to 3).

Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental Procedures.

The Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental Procedures evidence-based clinical practice guideline was codeveloped by the American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association. This guideline replaces the previous AAOS Information Statement, "Antibiotic Prophylaxis in Bacteremia in Patients With Joint Replacement," published in 2009. Based on the best current evidence and a systematic review of published studies, three recommendations have been created to guide clinical practice in the prevention of orthopaedic implant infections in patients undergoing dental procedures. The first recommendation is graded as Limited; this recommendation proposes that the practitioner consider changing the long-standing practice of routinely prescribing prophylactic antibiotic for patients with orthopaedic implants who undergo dental procedures. The second, graded as Inconclusive, addresses the use of oral topical antimicrobials in the prevention of periprosthetic joint infections. The third recommendation, a Consensus statement, addresses the maintenance of good oral hygiene.