Near complete remission of an inoperable pancreatic acinar cell carcinoma after BRAF-/MEK-inhibitor treatment-A case report and review of the literature.

INTRODUCTION: Pancreatic acinar cell carcinomas are rare malignant neoplasms. High-quality evidence about the best treatment strategy is lacking. We present the case of a 52-year-old male with a BRAFV600E -mutated PACC who experienced a complete remission after chemotherapy with BRAF-/MEK-inhibitors. CASE: The patient presented with upper abdomen pain, night sweat, and weight loss. CT scan showed a pancreatic tumor extending from the pancreas head to body. Histological workup identified an acinar cell carcinoma. As the tumor was inoperable, chemotherapy with FOFIRNIOX was initiated and initially showed a slight regression of disease. The regimen had to be discontinued due to severe side effects. Molecular analysis identified a BRAFV600E mutation, so the patient was started on BRAF- and MEK-inhibitors (dabrafenib/trametinib). After 16 months, CT scans showed a near complete remission with a markedly improved overall health. DISCUSSION: Studies suggest that up to one-fourth of PACCs carry a BRAF mutation and might therefore be susceptible to a BRAF-/MEK-inhibitor therapy. This offers a new therapeutic pathway to treat this rare but malignant neoplasm.

Patient-relevant outcomes following elective, aseptic revision knee arthroplasty: a systematic review.

BACKGROUND: The aim of this systematic review was to summarise the evidence for the clinical effectiveness of revision knee arthroplasty (rKA) compared to non-operative treatment for the management of patients with elective, aseptic causes for a failed knee arthroplasty. METHODS: MEDLINE, Embase, AMED and PsychINFO were searched from inception to 1st December 2020 for studies on patients considering elective, aseptic rKA. Patient-relevant outcomes (PROs) were defined as implant survivorship, joint function, quality of life (QoL), complications and hospital admission impact. RESULTS: No studies compared elective, aseptic rKA to non-operative management. Forty uncontrolled studies reported on PROs following elective, aseptic rKA (434434 rKA). Pooled estimates for implant survivorship were: 95.5% (95% CI 93.2-97.7%) at 1 year [seven studies (5524 rKA)], 90.8% (95% CI 87.6-94.0%) at 5 years [13 studies (5754 rKA)], 87.4% (95% CI 81.7-93.1%) at 10 years [nine studies (2188 rKA)], and 83.2% (95% CI 76.7-89.7%) at 15 years [two studies (452 rKA)]. Twelve studies (2382 rKA) reported joint function and/or QoL: all found large improvements from baseline to follow-up. Mortality rates were low (0.16% to 2% within 1 year) [four studies (353064 rKA)]. Post-operative complications were common (9.1 to 37.2% at 90 days). CONCLUSION: Higher-quality evidence is needed to support patients with decision-making in elective, aseptic rKA. This should include studies comparing operative and non-operative management. Implant survivorship following elective, aseptic rKA was ~ 96% at 1 year, ~ 91% at 5 years and ~ 87% at 10 years. Early complications were common after elective, aseptic rKA and the rates summarised here can be shared with patients during informed consent. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020196922.

Development and Validation of a Machine Learning Wrist-worn Step Detection Algorithm with Deployment in the UK Biobank.

Background: Step count is an intuitive measure of physical activity frequently quantified in a range of health-related studies; however, accurate quantification of step count can be difficult in the free-living environment, with step counting error routinely above 20% in both consumer and research-grade wrist-worn devices. This study aims to describe the development and validation of step count derived from a wrist-worn accelerometer and to assess its association with cardiovascular and all-cause mortality in a large prospective cohort study. Methods: We developed and externally validated a hybrid step detection model that involves self-supervised machine learning, trained on a new ground truth annotated, free-living step count dataset (OxWalk, n=39, aged 19-81) and tested against other open-source step counting algorithms. This model was applied to ascertain daily step counts from raw wrist-worn accelerometer data of 75,493 UK Biobank participants without a prior history of cardiovascular disease (CVD) or cancer. Cox regression was used to obtain hazard ratios and 95% confidence intervals for the association of daily step count with fatal CVD and all-cause mortality after adjustment for potential confounders. Findings: The novel step algorithm demonstrated a mean absolute percent error of 12.5% in free-living validation, detecting 98.7% of true steps and substantially outperforming other recent wrist-worn, open-source algorithms. Our data are indicative of an inverse dose-response association, where, for example, taking 6,596 to 8,474 steps per day was associated with a 39% [24-52%] and 27% [16-36%] lower risk of fatal CVD and all-cause mortality, respectively, compared to those taking fewer steps each day. Interpretation: An accurate measure of step count was ascertained using a machine learning pipeline that demonstrates state-of-the-art accuracy in internal and external validation. The expected associations with CVD and all-cause mortality indicate excellent face validity. This algorithm can be used widely for other studies that have utilised wrist-worn accelerometers and an open-source pipeline is provided to facilitate implementation.

Re-revision Knee Arthroplasty in a Tertiary Center: Infection and Multiple Previous Surgeries Were Associated With Poor Early Clinical and Functional Outcomes.

BACKGROUND: The incidence of re-revision knee arthroplasty (re-revision KA) is increasing and associated with high complication and failure rates. The aim of this study was to investigate re-revision rates, complications, and patient-reported outcomes following re-revision KA and factors associated with poor outcome. METHODS: This was a retrospective cohort study of 206 patients (250 knees) undergoing re-revision KA at a major revision center from 2015 to 2018. The mean follow-up was 26 months (range, 0 to 61) and mean age at re-revision KA was 69 years (range, 31 to 91 years). The main indications for surgery were prosthetic joint infection (PJI) (n = 171/250, 68.4%) and aseptic loosening (n = 25/250, 10.0%). We compared re-revision rates, joint function, and complications for aseptic and infective indications. Logistic regressions were performed to identify risk factors for further reoperation. RESULTS: The estimated re-revision rates at 2 years were 28.7% (95% confidence interval [CI]: 22.7-35.9) and at 4 years were 42.0% (95% CI: 32.8-52.6). Mean Oxford Knee Score was 26 points (range, 1 to 48). Mean EuroQoL-5D-5L utility was 0.539 (range, -0.511 to 1.000). Multivariable analyses demonstrated that PJI (Odds Ratio [OR] 2.39, 95% CI 1.06-5.40, P = .036), greater number of previous surgeries (OR 1.18, 95% CI 1.04-1.33, P = .008), and higher Elixhauser score (OR 1.06, 95% CI 1.01-1.13, P = .045) were independently associated to further surgery. CONCLUSION: Re-revision KA carried a high risk of early failure. Multiple revised joints and patients with more comorbidities had worse function. Patients undergoing re-revision KA for PJI should be counseled to expect higher failure rates and complications than patients who have aseptic indications.

Implant survivorship, functional outcomes and complications with the use of rotating hinge knee implants: a systematic review.

BACKGROUND: With more complex primary and revision total knee arthroplasty procedures there is often the need to use more constrained prostheses. This study aims to investigate patient-relevant outcomes following primary and revision rotating-hinged total knee arthroplasty. METHODS: Electronic searches were performed using four databases from their date of inception to January 2021. Relevant studies were identified, with data extracted and analysed using PRIMSA guidelines. RESULTS: Nineteen studies were included, producing a cohort of 568 primary and 413 revision rotating hinge total knee arthroplasties (TKAs). Survival was assessed at 1-, 5-, and 10-year post-implantation. Sensitivity analyses based on person-time incidence ratios (PTIRs) were prespecified for studies not reporting survival at these timepoints. From the primary hinge TKA cohort, the median survival at 1 year was 93.4% and at 10 years it was 87%. The PTIR at long-term follow-up of this primary cohort was 1.07 (95% CI 0.4-1.7) per 100 person-years. From the revision hinge TKA cohort, the median survival at 1 year was 79.6%, and at 10 years it was 65.1%. The PTIR at long term-follow-up of this revision cohort was 1.55 (95% CI 0.9-2.3) per 100 person-years. Post-operative flexion range of motion (ROM) was 110° for primary hinge TKA and 103° for revision hinge TKA. Compared with baseline, the Knee Society Score (KSS) and Knee Society Function Score (KSFS) improved for both groups post-operatively (primary: KSS 17 to 86, KSFS 28 to 58; revision: KSS 37 to 82, KSFS 34 to 61). CONCLUSION: The quality of the evidence for patient-relevant outcomes following hinged knee arthroplasty was limited. While there is the potential for high early revision rates, where successful, large functional benefits may be achieved.

Management of aseptic failure of the mobile-bearing Oxford unicompartmental knee arthroplasty.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) accounts for 9.1% of primary knee arthroplasties (KAs) in the UK. However, wider uptake is limited by higher revision rates compared with total knee arthroplasties (TKA) and concerns over subsequent poor function. The aim of this study was to understand the revision strategies and clinical outcomes for aseptic, failed UKAs at a high-volume centre. METHODS: This was a retrospective, single-centre cohort study of 48 patients (31 female, 17 male) with 52 revision UKAs from 2006 to 2018. Median time to revision was 67 (range 4-180) months. Indications for revision were progression of osteoarthritis (n = 31 knees, 59.6%), unexplained pain (n = 10 knees, 19.2%), aseptic loosening (n = 6 knees, 11.5%), medial collateral ligament incompetence (n = 3 knees, 5.8%) and recurrent bearing dislocation (n = 2 knees, 3.8%). Technical details of surgery, complications and functional outcome were recorded. RESULTS: Failed UKAs were revised to primary TKAs (n = 29 knees, 55.8%), revision TKAs (n = 9 knees, 17.3%), bicompartmental KAs (n = 11 knees, 21.2%), or unicompartmental-to-unicompartmental KAs (n = 3 knees, 5.8%). Median follow up was 81 (range 24-164) months. Four patients (7.7%) died from unrelated causes. No re-revisions were identified. Surgical complications required re-operation in five knees (9.6%). Median Oxford Knee Score at latest follow up was 38 (range 9-48) points and median EQ5D3L index 0.707 (range -0.247 to 1.000). CONCLUSIONS: Aseptic, revision UKA at a high-volume centre had good clinical outcomes. Bicompartmental KA demonstrated excellent function and should be considered an alternative to TKA for progression of osteoarthritis for appropriately trained surgeons.