To document the real-world experience with the use of pneumatic pulsatile mechanical circulatory support (MCS) with the PulseCath iVAC2L during high-risk percutaneous coronary interventions (HR-PCIs). Background: The use of MCS in HR-PCIs may reduce the rate of major adverse cardiovascular events (MACEs) at 90 days. The PulseCath iVAC2L is a short-term pulsatile transaortic left ventricular (LV) assist device that has been in use since 2014. The iVAC2L Registry tracks its safety and efficacy in a variety of hospitals worldwide. Methods: The iVAC2L Registry is a multicenter, observational registry that aggregates clinical data from patients treated with the iVAC2L worldwide. A total of 293 consecutive cases were retrospectively collected and analyzed. Estimated rates of in-hospital clinical endpoints were described. All-cause mortality was used as the primary endpoint and other outcomes of interest were used as secondary endpoints. The rates obtained were reported and contextualized. Results: The in-hospital rate of all-cause mortality was 1.0%, MACE was 3.1%. Severe hypotension occurred in 8.9% of patients. Major bleeding and major vascular complications occurred in 1.0% and 2.1%, respectively. Acute myocardial infarction occurred in 0.7% of patients. Cerebrovascular events occurred in 1.4% of patients. Cardiac arrest occurred in 1.7% of patients. A statistically significant improvement in blood pressure was observed with iVAC2L activation. Conclusions: The results of the present study suggest that the iVAC2L is capable of improving hemodynamics with a low rate of adverse events. However, confirmatory studies are needed to validate these findings.
- Publication type
- Journal Article MeSH
Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.
- Publication type
- Journal Article MeSH
Alpelisib is an α-selective phosphatidylinositol 3-kinase inhibitor used for treating hormone receptor-positive (HR+), human epidermal growth receptor 2-negative (HER2-), PIK3CA-mutated locally advanced or metastatic breast cancer following disease progression on or after endocrine therapy. Hyperglycemia is an on-target effect of alpelisib affecting approximately 60% of treated patients, and sometimes necessitating dose reductions, treatment interruptions, or discontinuation of alpelisib. Early detection of hyperglycemia and timely intervention have a key role in achieving optimal glycemic control and maintaining alpelisib dose intensity to optimize the benefit of this drug. A glycemic support program implemented by an endocrinology-oncology collaborative team may be very useful in this regard. Lifestyle modifications, mainly comprising a reduced-carbohydrate diet, and a designated stepwise, personalized antihyperglycemic regimen, based on metformin, sodium-glucose co-transporter 2 inhibitors, and pioglitazone, are the main tools required to address the insulin-resistant hyperglycemia induced by alpelisib. In this report, based on the consensus of 14 oncologists and seven endocrinologists, we provide guidance for hyperglycemia management strategies before, during, and after alpelisib therapy for HR+, HER2-, PIK3CA-mutated breast cancer, with a focus on a proactive, multidisciplinary approach.
- Publication type
- Journal Article MeSH
- Review MeSH
Programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) is accepted as a predictive biomarker for the selection of immune checkpoint inhibitors. We evaluated the staining quality and estimation of the tumor proportion score (TPS) in non-small-cell lung cancer during two external quality assessment (EQA) schemes by the European Society of Pathology. Participants received two tissue micro-arrays with three (2017) and four (2018) cases for PD-L1 IHC and a positive tonsil control, for staining by their routine protocol. After the participants returned stained slides to the EQA coordination center, three pathologists assessed each slide and awarded an expert staining score from 1 to 5 points based on the staining concordance. Expert scores significantly (p < 0.01) improved between EQA schemes from 3.8 (n = 67) to 4.3 (n = 74) on 5 points. Participants used 32 different protocols: the majority applied the 22C3 (56.7%) (Dako), SP263 (19.1%) (Ventana), and E1L3N (Cell Signaling) (7.1%) clones. Staining artifacts consisted mainly of very weak or weak antigen demonstration (63.0%) or excessive background staining (19.8%). Participants using CE-IVD kits reached a higher score compared with those using laboratory-developed tests (LDTs) (p < 0.05), mainly attributed to a better concordance of SP263. The TPS was under- and over-estimated in 20/423 (4.7%) and 24/423 (5.7%) cases, respectively, correlating to a lower expert score. Additional research is needed on the concordance of less common protocols, and on reasons for lower LDT concordance. Laboratories should carefully validate all test methods and regularly verify their performance. EQA participation should focus on both staining concordance and interpretation of PD-L1 IHC.
- MeSH
- B7-H1 Antigen analysis antagonists & inhibitors MeSH
- Artifacts MeSH
- Tissue Array Analysis MeSH
- Immunohistochemistry * MeSH
- Immune Checkpoint Inhibitors therapeutic use MeSH
- Clinical Decision-Making MeSH
- Humans MeSH
- Biomarkers, Tumor analysis antagonists & inhibitors MeSH
- Lung Neoplasms drug therapy immunology pathology MeSH
- Carcinoma, Non-Small-Cell Lung drug therapy immunology pathology MeSH
- Observer Variation MeSH
- Predictive Value of Tests MeSH
- Reproducibility of Results MeSH
- Laboratory Proficiency Testing MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
PURPOSE: In the integrated analysis of phase III head-to-head trials in patients with advanced solid tumors, denosumab demonstrated superiority over zoledronic acid in preventing skeletal-related events (SREs). Regular and continued drug use (persistence) is a precondition of clinical efficacy; persistence in real-life is yet undetermined for denosumab. METHODS: This was a single-arm, prospective, observational, non-interventional study in 598 patients with bone metastases from breast, prostate, lung, or other solid tumors treated with denosumab every four weeks in real-world clinical practice in Austria, Czech Republic, Hungary, Slovakia, and Bulgaria. Persistence was defined as denosumab administration at ≤ 35-day intervals over 24 or 48 weeks, respectively. RESULTS: Previous SREs were found in 10.9% of patients. 62.6% were persistent over 24 weeks and 40.1% over 48 weeks. The Kaplan-Meier median (95% CI) time to non-persistence was 274.0 days (232.0, 316.0). The most frequent reason for non-persistence was delayed administration. There was a trend towards weaker analgesics over time, with approximately 60% of patients not requiring any analgesics. Serum calcium remained within the normal range throughout the study. Adjudicated osteonecrosis of the jaw was documented in three patients with an incidence per patient-year (95% CI) of 0.012 (0.004, 0.029). CONCLUSIONS: Most patients received denosumab regularly once every four weeks over 24 weeks of treatment. Non-persistence was mainly due to delayed administration. The incidence of adverse drug reactions, especially of osteonecrosis of the jaw, was in line with expectations from previous studies.
- MeSH
- Denosumab administration & dosage adverse effects MeSH
- Adult MeSH
- Bone Density Conservation Agents administration & dosage adverse effects MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Bone Neoplasms drug therapy secondary MeSH
- Neoplasms drug therapy pathology MeSH
- Osteonecrosis chemically induced MeSH
- Prospective Studies MeSH
- Drug Administration Schedule MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
BACKGROUND: Correct identification of the EGFR c.2369C>T p.(Thr790Met) variant is key to decide on a targeted therapeutic strategy for patients with acquired EGFR TKI resistance in non-small cell lung cancer. The aim of this study was to evaluate the correct detection of this variant in 12 tumor tissue specimens tested by 324 laboratories participating in External Quality Assessment (EQA) schemes. METHODS: Data from EQA schemes were evaluated between 2013 and 2018 from cell lines (6) and resections (6) containing the EGFR c.2369C>T p.(Thr790Met) mutation. Adequate performance was defined as the percentage of tests for which an outcome was available and correct. Additional data on the used test method were collected from the participants. Chi-squared tests on contingency tables and a biserial rank correlation were applied by IBM SPSS Statistics version 25 (IBM, Armonk, NY, USA). RESULTS: In 26 of the 1190 tests (2.2%) a technical failure occurred. For the remaining 1164 results, 1008 (86.6%) were correct, 151 (12.9%) were false-negative and 5 (0.4%) included incorrect mutations. Correct p.(Thr790Met) detection improved over time and for repeated scheme participations. In-house non-next-generation sequencing (NGS) techniques performed worse (81.1%, n = 293) compared to non-NGS commercial kits (85.2%, n = 656) and NGS (97.0%, n = 239). Over time there was an increase in the users of NGS. Resection specimens performed worse (82.6%, n = 610 tests) compared to cell line material (90.9%, n = 578 tests), except for NGS (96.3%, n = 344 for resections and 98.6%, n = 312 for cell lines). Samples with multiple mutations were more difficult compared to samples with the single p.(Thr790Met) variant. A change of the test method was shown beneficial to reduce errors but introduced additional analysis failures. CONCLUSIONS: A significant number of laboratories that offer p.(Thr790Met) testing did not detect this relevant mutation compared to the other EQA participants. However, correct identification of this variant is improving over time and was higher for NGS users. Revising the methodology might be useful to resolve errors, especially for resection specimens with low frequency or multiple variants. EQA providers should include challenging resections in the scheme.
- MeSH
- ErbB Receptors genetics MeSH
- Genetic Testing methods standards MeSH
- Polymorphism, Single Nucleotide MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Mutation * MeSH
- Tumor Cells, Cultured MeSH
- Lung Neoplasms diagnosis enzymology genetics MeSH
- Follow-Up Studies MeSH
- Carcinoma, Non-Small-Cell Lung diagnosis enzymology genetics MeSH
- Quality Control MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Statin intolerance (SI) occurs in patients with dyslipidemia treated with statins. Statin-associated symptoms have been reported, but the overall patient experience is poorly understood. No instruments are available to collect this patient experience. Our aim is to develop a patient survey to define SI from the patient's perspective, inform clinical practice, and identify potential patient characteristics and barriers associated with discontinuing treatment when statin-related difficulties are encountered. METHODS: We conducted qualitative concept elicitation interviews with 65 patients across 12 European study sites. A semi-structured qualitative interview guide was developed based on literature review and clinician interviews. Concept elicitation interviews with patients were used to describe the patient experience and develop the conceptual framework for the survey. RESULTS: Symptoms experienced by patients included muscle and non-muscle-related pain and discomfort; other muscle-related symptoms; gastrointestinal, cardiovascular, cold-like, fatigue-related, and sensory and systems symptoms; mood changes; and cognitive and memory problems. Impacts included limitations on general physical functioning; physical activities; social functioning; emotional impacts; sleep disturbances; decreased productivity; and increased healthcare use. Conceptual framework elements to support survey goals include demographic and clinical characteristics, health information and beliefs, statin side-effect history, symptom severity, and impact severity. CONCLUSIONS: Symptoms and impacts described by patients showed a wider range of symptoms and impacts than usually discussed clinically. The patient survey is designed to capture information from patients who experience difficulties with statin therapy and may be useful in identifying patients who are at higher risk for giving up or discontinuing their treatment. FUNDING: Amgen Inc.
- MeSH
- Anticholesteremic Agents adverse effects therapeutic use MeSH
- Pain chemically induced MeSH
- Adult MeSH
- Dyslipidemias drug therapy epidemiology MeSH
- Qualitative Research MeSH
- Middle Aged MeSH
- Humans MeSH
- Surveys and Questionnaires MeSH
- Aged MeSH
- Patient Satisfaction statistics & numerical data MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects therapeutic use MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe MeSH
