Coarctation Angioplasty in Young Children: Does IMPACT Registry Data Accurately Reflect Clinical Outcomes?

Balloon angioplasty for recoarctation of the aorta is routinely performed in young children and is considered successful when the systolic gradient is reduced to < 10 mmHg. IMPACT defines acute procedural success solely based on a final gradient of < 10 mmHg and stratifies participating institutions based on these acute outcomes. Between February 2012 and December 2020, IMPACT data was analyzed for 110 coarctation interventions. Electronic medical records were reviewed, and primary endpoints were one of the following: (1) final analysis end date (June 2021), (2) patient death, or (3) most recent transcatheter or surgical reintervention. 64 (58.2%) interventions had a post-procedure CA gradient < 10 mmHg. Comparison of clinical patient outcome for acute success demonstrated no significant relationship using IMPACT (p = 0.70) criteria. There was no statistically significant difference between clinical success and failure for: pre- and post-treatment systolic gradients; absolute or percent change in systolic gradient; and pre-treatment aorta diameter. Clinical outcome and patient age did show a significant difference (p = 0.0093) with better clinical outcomes in older patients. Our analysis did not reveal a statistically significant difference between IMPACT criteria for successful treatment of CA and clinical outcome. These findings underscore a need to identify other clinical metrics that better predict outcome following CA balloon angioplasty treatment.

Incidence and severity of radiological lateral osteoarthritis 15 years following medial unicompartmental knee arthroplasty.

To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics. Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSWL) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%. The mean age was 80.6 years (SD 8.3), with 84 females and 79 males. The mean JSWL was 5.6 mm (SD 1.4), and was not significantly related to age, sex, or intraoperative findings. Those with BMI > 40 kg/m2 had a smaller JSWL than those with a 'normal' BMI (p = 0.039). The incidence of severe and moderate lateral OA were both 4.9%. Overall, 2/142 (1.4%) of those with nil/mild lateral OA, 1/8 (13%) with moderate, and 2/8 (25%) with severe subsequently had a revision. Those with severe (mean OKS 35.6 (SD 9.3)) and moderate OA (mean OKS 35.8 (SD 10.5)) tended to have worse outcome scores than those with nil/mild (mean OKS 39.5 (SD 9.2)) but the difference was only significant for OKS-Function (p = 0.044). This study showed that the rate of having severe or moderate radiological lateral OA at 15 years after medial UKA was low (both 4.9%). Although patients with severe or moderate lateral OA had a lower OKS than those with nil/mild OA, their mean scores (OKS 36) would be classified as good.

Relationship between pre-existing allergies and anaphylactic reactions post mRNA COVID-19 vaccine administration.

Two mRNA vaccines for COVID-19, Pfizer-BioNTech and Moderna, are approved for emergency use in the United States. After their approval and dosing in millions of recipients, reports of anaphylaxis began to appear in the Vaccine Adverse Reporting System (VAERS). Here we provide an analysis of the relationship between prior history of allergy and/or anaphylaxis and anaphylaxis rates following the administration of mRNA COVID-19 vaccines. Overall reported incidence of anaphylaxis was estimated to be rare at 4.2 cases per million doses. It appeared that the relative incidence of anaphylaxis following administration of these COVID-19 vaccines was two and seven times higher for recipients with a prior history of allergies and/or anaphylaxis, respectively. This report provides valuable metrics to make evidence-based decisions for subjects with pre-existing allergic conditions receiving a COVID-19 mRNA vaccine.

The MEK-Inhibitor Selumetinib Attenuates Tumor Growth and Reduces IL-6 Expression but Does Not Protect against Muscle Wasting in Lewis Lung Cancer Cachexia.

Cachexia, or wasting of skeletal muscle and fat, afflicts many patients with chronic diseases including cancer, organ failure, and AIDS. Muscle wasting reduces quality of life and decreases response to therapy. Cachexia is caused partly by elevated inflammatory cytokines, including interleukin-6 (IL-6). Others and we have shown that IL-6 alone is sufficient to induce cachexia both in vitro and in vivo. The mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor Selumetinib has been tested in clinical trials for various cancers. Moreover, Selumetinib has also been shown to inhibit the production of IL-6. In a retrospective analysis of a phase II clinical trial in advanced cholangiocarcinoma, patients treated with Selumetinib experienced significant gains in skeletal muscle vs. patients receiving standard therapy. However, the use of Selumetinib as a treatment for cachexia has yet to be investigated mechanistically. We sought to determine whether MEK inhibition could protect against cancer-induced cachexia in mice. In vitro, Selumetinib induced C2C12 myotube hypertrophy and nuclear accretion. Next we tested Selumetinib in the Lewis lung carcinoma (LLC) model of cancer cachexia. Treatment with Selumetinib reduced tumor mass and reduced circulating and tumor IL-6; however MEK inhibition did not preserve muscle mass. Similar wasting was seen in limb muscles of Selumetinib and vehicle-treated LLC mice, while greater fat and carcass weight loss was observed with Selumetinib treatment. As well, Selumetinib did not block wasting in C2C12 myotubes treated with LLC serum. Taken together, out results suggest that this MEK inhibitor is not protective in LLC cancer cachexia despite lowering IL-6 levels, and further that it might exacerbate tumor-induced weight loss. Differences from other studies might be disease, species or model-specific.