Assessment of platelet function after discontinuation of ticagrelor.

BACKGROUND: Patients presenting with acute coronary syndromes (ACS) are often treated by percutaneous coronary intervention (PCI) with insertion of coronary artery stents and a majority receive dual antiplatelet therapy (DAPT), usually a combination of a COX-1 inhibitor (aspirin) and a P2Y12 inhibitor (eg ticagrelor). Not seldom the question arises as to when DAPT should be discontinued prior to interventional surgery. This study was done with the primary aim of investigating thrombocyte function immediately prior to and after discontinuation of ticagrelor. MATERIALS AND METHODS: In this prospective, longitudinal, observational study including 24 patients, venous blood was obtained from patients on day 0, before stopping maintenance dose of 90 mg ticagrelor twice daily, and then on days 1, 3, 5, and 8, after discontinuation. Samples were analyzed using Multiplate® and VerifyNow® . RESULTS: Prior to urgent surgery platelet aggregation >30 aggregation units (Multiplate® ) and >208 P2Y12 reaction units (VerifyNow® ) have been shown to correlate with reduced risk of peri- and postoperative bleeding risk. On day 3 after ticagrelor discontinuation, 100% (P = .016) and 67% (P=<.001) of patients had reached these levels on Multiplate® and VerifyNow® , respectively. On day 5, the corresponding figures were 100% (P = .016) and 78% (P=<.001). CONCLUSION: Discontinuation of ticagrelor for 3 days resulted in return of adequate platelet function in all patients on Multiplate® and in a majority of patients on VerifyNow® , indicating a lower bleeding risk. A bedside test for platelet function may be considered if time to anticipated surgery is less than 5 days after ticagrelor discontinuation.

Massive air embolism as a complication of upper gastrointestinal endoscopy: A case report illustrating a stroke mimic, literature review, and suggested management.

Cerebral air embolism should be considered in case of stroke symptoms during any invasive procedure. Transport to a hospital with neurosurgical/hyperbaric oxygen treatment (HBOT) facility could improve the outcome for the patient. Absence of air on computed tomography (CT) scan should not disqualify a patient from HBOT if air embolism is suspected.

Sociodemographic Characteristics and Health Profile of the Elderly Seeking Health Care in Kampala, Uganda.

Aging entails health challenges globally, but pertinent data from low-income countries like Uganda remains scarce. A cross-sectional study was carried out at Mulago National Referral Hospital in Kampala, among 134 patients (38% men and 62% women) aged ≥60 years. Data was collected on sociodemographic characteristics, medical disorders, cognitive function, hearing handicap, and functional status, that is, Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL). The participants had high independency in BADL (89%) and IADL (75%). The most common medical conditions were bone/joint pain (35%), hypertension (24%), and visual problems (20%). More women (54%) than men (37%) reported bone and joint pain. The majority (80%) of the participants did not report any hearing handicap, and half (54%) did not have any cognitive impairment. Dependency in IADL was associated with advanced age, being female, and being financially dependent, and the risk of having a hearing handicap was higher among those above the median age (68 years). In adjusted models, the effects remained similar although statistical significance was only achieved for advanced age versus dependency in IADL (RR: 2.38, 95% CI: 1.12-5.08) and hearing handicap (RR: 2.67, 95% CI: 1.17-6.12). Thus, socioeconomic status and gender are relevant aspects when attempting to understand the health profile of the elderly in Kampala, Uganda.

High experienced continuity in breast cancer care is associated with high health related quality of life.

BACKGROUND: High experienced continuity is known to be associated with lower needs for supportive care and most likely higher quality of life. On this background, the aim of this study was to investigate if patient-experienced continuity of care was associated with health-related quality of life (HRQoL) in breast cancer patients treated at two different-sized breast cancer units. METHODS: In 2016, two questionnaires, "Statements on experienced continuity of care" and "The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)", were sent out to patients diagnosed between 2011 and 2014 at two different-sized breast cancer units in Sweden. Lead times and other data reflecting medical quality were collected from the patients' medical records and from the National Swedish Breast Cancer Quality Register. RESULTS: Of 356 eligible patients, 231 (65%) answered the questionnaires, of whom 218 patients were included in the analyses. A statistically significant association was found between high experienced continuity and high global HRQoL (p = 0.03). Continuity was higher at the smaller unit, while no major differences between the units were found regarding medical quality or lead times. CONCLUSION: The study found that high experienced continuity and HRQoL was strongly associated. A statistically significant higher continuity of care was found at the smaller unit, in line with what was expected. The absence of clinically relevant differences in lead times and medical quality may indicate that continuity could be achieved without loss of quality.

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer.

PURPOSE: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. EXPERIMENTAL DESIGN: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. RESULTS: Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. CONCLUSIONS: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer.

Impact of the first tumor response at eight weeks on overall survival in metastatic breast cancer patients treated with first-line combination chemotherapy.

The aim of this was to determine whether the change of size observed at the first response evaluation after initiation of first-line combination chemotherapy correlates with overall survival (OS) in patients with metastatic breast cancer (MBC). The change in size of tumors derived from measurements according to Response Evaluation Criteria In Solid Tumors (RECIST) at the first evaluation on computed tomography (CT) was obtained from a multicenter, randomized phase III trial ("TEX trial," n = 287) comparing treatment with a combination of epirubicin and paclitaxel alone or with capecitabine (TEX). Cox regression and Kaplan-Meier analyses were performed to evaluate the correlations between the first change in tumor size, response according to RECIST and OS. Data from CT evaluations of 233 patients were available. Appearance of new lesions or progression of non-target lesions (new/non-target) indicated short OS by univariable regression analysis (HR 3.76, 95 % CI 1.90-7.42, p < 0.001). A decrease by >30 % at this early time point was prognostic favorable (HR 0.69, 95 % CI 0.49-0.98, p = 0.04) and not significantly less than the best overall response according to RECIST. After adjustment for previous adjuvant treatment and the treatment given within the frame of the randomized trial, OS was still significantly shorter in patients with new/non-target lesions after a median 8 weeks of treatment (HR 4.41, 95 % CI 2.74-7.11, p < 0.001). Disease progression at the first evaluation correlates with OS in patients with MBC treated with first-line combination chemotherapy. The main reason for early disease progression was the appearance of new lesions or progression of non-target lesions. These patients had poor OS even though more lines of treatment were available. Thus, these factors should be focused on in the response evaluations besides tumor size changes.

A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer.

The aim of the study was to evaluate the feasibility of tailored and dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant breast cancer therapy. Material and methods. Patients with node-positive breast cancer received either four cycles of biweekly and tailored EC (epirubicin 38-60-75-90-105-120 mg/m(2), cyclophosphamide 450-600-900-1200 mg/m(2)) followed by four cycles of docetaxel (60-75-85-100 mg/m(2)) (arm A) or the same regimen with fixed doses (E(90)C(600) + 4 → T(75) + 4) (arm B) or docetaxel, doxorubicin and cyclophosphamide (T(75)A(50)C(500)) every three weeks for six cycles (arm C). All patients received G-CSF support and prophylactic ciprofloxacin. Results. One-hundred and twenty-four patients were randomised in the study. In the A, B and C arm, 17% 19% and 3% of the patients had one or more cycles delayed due to side-effects whereas 24%, 5% and 15% experienced a grade 3 infection or febrile neutropenia. After the introduction of an extra week between the EC and T parts in the A and B arms, grade 3 hand-foot-skin reactions were reduced from 5 to 0.2%. Twenty-nine percent (A and B) and 20% (C) of the patients were hospitalised due to side-effects. Discussion. Dose-dense and tailored EC/T can be given with manageable toxicity and is after adjustment presently studied in the phase III Panther trial.

TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer.

The purpose of this study was to evaluate amplification of topoisomerase IIalpha (TOP2A) and HER2 genes as predictors of response to chemotherapy in advanced breast cancer. Gene copy number of TOP2A and HER2 were analysed with chromogenic in situ hybridization (CISH) on paraffin-embedded tissue sections from the primary tumour of 85 patients treated with anthracycline containing chemotherapy. TOP2A gene amplification was present in 14 (16%) and HER2 gene amplification in 38 (45%) of the primary tumours. Two of the 14 cases with TOP2A amplification were amplified without concurrent HER2 amplification. Neither TOP2A nor HER2 gene amplification were significantly associated with response to chemotherapy (p = 0.35 and p = 0.49, respectively).

A population-based study on the first forty-eight breast cancer patients receiving trastuzumab (Herceptin) on a named patient basis in Sweden.

Several studies have presented data on the efficacy and tolerability of trastuzumab within clinical trials. As a minority of patients is included in these trials, we undertook this retrospective study to describe trastuzumab therapy in clinical routine and its tolerability. We reviewed the medical records of the first 48 patients in Sweden who received treatment with trastuzumab on a named patient basis with (n = 29) and without (n = 19) chemotherapy. Forty-six patients had metastatic disease and had failed to respond to several prior regimens before starting antibody treatment. Two patients had locally advanced breast cancer failing on given neoadjuvant therapy. Patients with breast cancers with strong (3+) c-erbB-2 overexpression tended to have an improved survival from start of trastuzumab treatment versus those with a moderate (2+) overexpression (p = 0.09). Adverse events were registered in 22 patients (46%). The most common and acute side effects were fever and chills (7 patients, 15%). The toxicity seemed reasonable but two patients (4%) suffered serious cardiac events, both of them having received previous treatment with antracyclines.