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Primary breast lymphoma accounts for 0.04%-0.5% of all breast malignancies. Primary non-Hodgkin’s lymphomas of the breast are extremely rare and represent approximately 0.38%-0.7% of all cases. Epstein-Barr virus (EBV) has been postulated to play an important role in the pathogenesis of Hodgkin’s lymphoma. We present a case of EBV-positive primary Hodgkin’s lymphoma of the breast. Although there is no sufficient data on this challenging diagnosis, it is known that it could be misdiagnosed with inflammatory breast carcinoma. A crucial part of the proper histopathologic diagnosis is immunohistochemistry. Different modalities of treatment include operative procedure, chemotherapy and radiotherapy. Recent studies suggest chemotherapy and radiotherapy to be initial treatment for patients with primary breast lymphomas.
Drug resistance of childhood cancer neuroblastoma is a serious clinical problem. Patients with relapsed disease have a poor prognosis despite intense treatment. In the present study, we aimed to identify chemoresistance gene expression signatures in vincristine resistant neuroblastoma cells. We found that vincristine-resistant neuroblastoma cells formed larger clones and survived under reduced serum conditions as compared with non-resistant parental cells. To identify the possible mechanisms underlying vincristine resistance in neuroblastoma cells, we investigated the expression profiles of genes known to be involved in cancer drug resistance. This specific gene expression patterns could predict the behavior of a tumor in response to chemotherapy and for predicting the prognosis of high-risk neuroblastoma patients. Our signature could help chemoresistant neuroblastoma patients in avoiding useless and harmful chemotherapy cycles.
This article discusses the counterpart of interactive machine learning, i.e., human learning while being in the loop in a human-machine collaboration. For such cases we propose the use of a Contradiction Matrix to assess the overlap and the contradictions of human and machine predictions. We show in a small-scaled user study with experts in the area of pneumology (1) that machine-learning based systems can classify X-rays with respect to diseases with a meaningful accuracy, (2) humans partly use contradictions to reconsider their initial diagnosis, and (3) that this leads to a higher overlap between human and machine diagnoses at the end of the collaboration situation. We argue that disclosure of information on diagnosis uncertainty can be beneficial to make the human expert reconsider her or his initial assessment which may ultimately result in a deliberate agreement. In the light of the observations from our project, it becomes apparent that collaborative learning in such a human-in-the-loop scenario could lead to mutual benefits for both human learning and interactive machine learning. Bearing the differences in reasoning and learning processes of humans and intelligent systems in mind, we argue that interdisciplinary research teams have the best chances at tackling this undertaking and generating valuable insights.
Background: Posttraumatic stress disorder (PTSD) is one of the psychopathological consequences of sexual and/or physical abuse. The economic burden is assumed to be high, whereas health-related quality of life and education is negatively affected. This study aims to determine health care costs, health-related quality of life, and educational interruption in adolescents and young adults with PTSD after sexual and/or physical abuse in Germany.
Methods: This analysis used data of 87 participants aged 14–21 years of a randomized controlled trial. Health care utilization, health-related quality of life (EQ-5D-5L), sick leave days, productivity, and delay or failure to achieve educational aims were assessed. Health care costs from a payer perspective were calculated using unit costs for the year 2014.
Results: Mean health care costs for a six-month period were 5,243€ (SE 868€). In particular, costs of inpatient stays in psychiatric hospitals, general hospitals and rehabilitation as well as child welfare institutions were high. In addition, health-related quality of life was lower due to anxiety/depression, resulting in a mean EQ-5D index and EQ-VAS score of 0.70 and 61.0, respectively. Furthermore, participants reported on average 27 sick leave days, a productivity loss of 61%, and a delay in education attainment as well as having been unable to achieve educational aims.
Conclusion: PTSD in adolescents and young adults is associated with a high economic burden. Health-related quality of life was substantially reduced. Furthermore, delay and productivity losses in education were observed.
Clinical Trial Registration: German Clinical Trials Register identifier: DRKS00004787; date of registration: 18th March 2013; https://www.drks.de.
Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.
Objective: To determine the impact of an exercise-based prehabilitation (EBPrehab) program on preand postoperative exercise capacity, functional capacity (FC) and quality of life (QoL) in patients awaiting elective coronary artery bypass graft surgery (CABG).
Design: A two-group randomized controlled trail.
Setting: Ambulatory prehabilitation.
Subjects: Overall 230 preoperative elective CABG-surgery patients were randomly assigned to an intervention (IG, n=88; n=27 withdrew after randomization) or control group (CG, n=115).
Intervention: IG: two-week EBPrehab including supervised aerobic exercise. CG: usual care.
Main measures: At baseline (T1), one day before surgery (T2), at the beginning (T3) and at the end of cardiac rehabilitation (T4) the following measurements were performed: cardiopulmonary exercise test, six-minute walk test (6MWT), Timed-Up-and-Go Test (TUG) and QoL (MacNew questionnaire).
Results: A total of 171 patients (IG, n=81; CG, n=90) completed the study. During EBPrehab no complications occurred. Preoperatively FC (6MWTIG: 443.0±80.1m to 493.5±75.5m, P=0.003; TUGIG: 6.9±2.0 s to 6.1±1.8 s, P=0.018) and QoL (IG: 5.1±0.9 to 5.4±0.9, P<0.001) improved significantly more in IG compared to CG. Similar effects were observed postoperatively in FC (6MWDIG: Δ-64.7m, pT1–T3=0.013; Δ+47.2m, pT1–T4<0.001; TUGIG: Δ+1.4s, pT1–T3=0.003).
Conclusions: A short-term EBPrehab is effective to improve perioperative FC and preoperative QoL in patients with stable coronary artery disease awaiting CABG-surgery.
Simple Summary
The interaction between tumors and immune cells influences tumor fate, i.e., regression, growth, or even metastases. The evaluation of tumor infiltrating lymphocytes (TILs) in human breast cancer has prognostic value. Pet rabbits develop spontaneous mammary carcinomas and have an immune system that is comparable with that of humans, so that they have the potential to provide an animal model for human breast cancer. To further substantiate this similarity, this study examined TILs in 107 pet rabbit mammary carcinomas according to criteria established for human breast cancer. For TIL evaluation routinely stained microscopic sections were examined by light microscopy. Relevant histological and immunohistochemical tumor characteristics were obtained from a data base. Results showed that increased presence of stromal TILs was statistically associated with histological tumor features indicative of a less aggressive biological behavior, i.e., reduced tumor cell proliferation and a lower histological grade. The expression by tumor cells of calponin, a presumed tumor suppressor protein, was also associated with their reduced proliferation and a higher percentage of stromal TILs. Data suggest that higher percentages of stromal TILs may have the potential to serve as favorable prognostic indicator in rabbit mammary carcinomas and support the value of pet rabbits for comparative research.
Abstract
Tumor infiltrating lymphocytes (TILs) serve as prognostic biomarker in human breast cancer. Rabbits have the potential to act as animal model for human breast cancer, and close similarities exist between the rabbit and human immune system. The aim of this study is to characterize TILs in pet rabbit mammary carcinomas and to statistically correlate results with histological and immunohistochemical tumor characteristics. Microscopic evaluation of TILs was performed in hematoxylin and eosin stained sections of 107 rabbit mammary carcinomas according to international guidelines for human breast cancer. Data on histological features of malignancy, estrogen and progesterone receptor status and calponin expression were obtained from the data base. This study revealed a statistical association between stromal TILs in the central tumor (CT) and infiltrative margin. Higher maximal percentages of stromal TILs at the CT were statistically correlated with decreased mitotic count and lower tumor grade. An increased number of calponin positive tumor cells was statistically associated with a lower mitotic count and a higher percentage of stromal TILs. Results suggest that higher percentages of stromal TILs are useful biomarkers that may point toward a favorable prognosis in rabbit mammary carcinomas and support the concept of the use of rabbits for translational research
Degeneration of neurons, such as the inner ear spiral ganglion neurons (SGN), may be decelerated or even stopped by neurotrophic factor treatment, such as brain-derived neurotrophic factor (BDNF), as well as electrical stimulation (ES). In a clinical setting, drug treatment of the SGN could start directly during implantation of a cochlear implant, whereas electrical stimulation begins days to weeks later. The present study was conducted to determine the effects of consecutive BDNF and ES treatments on SGN density and electrical responsiveness. An electrode drug delivery device was implanted in guinea pigs 3 weeks after deafening and five experimental groups were established: two groups received intracochlear infusion of artificial perilymph (AP) or BDNF; two groups were treated with AP respectively BDNF in addition to ES (AP + ES, BDNF + ES); and one group received BDNF from the day of implantation until day 34 followed by ES (BDNF ⇨ ES). Electrically evoked auditory brainstem responses were recorded. After one month of treatment, the tissue was harvested and the SGN density was assessed. The results show that consecutive treatment with BDNF and ES was as successful as the simultaneous combined treatment in terms of enhanced SGN density compared to the untreated contralateral side but not in regard to the numbers of protected cells.
The morbidity and mortality of severely injured patients are commonly affected by multiple factors. Especially, severe chest trauma has been shown to be a significant factor in considering outcome. Contemporaneously, weight-associated endocrinological, haematological, and metabolic deviations from the norm seem to have an impact on the posttraumatic course. Therefore, the aim of this study was to determine the influence of body weight on severely injured patients by emphasizing chest trauma. A total of 338 severely injured patients were included. Multivariate regression analyses were performed on patients with severe chest trauma (AIS ≥ 3) and patients with minor chest trauma (AIS < 3). The influence of body weight on in-hospital mortality was evaluated. Of all the patients, 70.4% were male, the median age was 52 years (IQR 36–68), the overall Injury Severity Score (ISS) was 24 points (IQR 17–29), and a median BMI of 25.1 points (IQR 23–28) was determined. In general, chest trauma was associated with prolonged ventilation, prolonged ICU treatment, and increased mortality. For overweight patients with severe chest trauma, an independent survival benefit was found (OR 0.158; p = 0.037). Overweight seems to have an impact on the mortality of severely injured patients with combined chest trauma. Potentially, a nutritive advantage or still-unknown immunological aspects in these patients affecting the intensive treatment course could be argued.
Importance Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.
Objective To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.
Design, Setting, and Participants In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.
Exposure Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract.
Main Outcomes and Measures Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57).
Results Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19–related myocardial pathology.
Conclusions and Relevance In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.
Aortic stenosis is the most common valvular disease worldwide. With transcatheter aortic valve replacement (TAVR) being increasingly expanded to lower-risk populations, several challenging issues remain to be solved. The present review aims at discussing modern approaches to such issues as well as the current status of TAVR. TAVR has undergone several developments in the recent years: an increased use of transfemoral access, the development of prostheses in order to adapt to challenging anatomies, improved delivery systems with repositioning features, and outer skirts aiming at reducing paravalvular leak. The indication of TAVR is increasingly being expanded to patients with lower surgical risk. The main clinical trials supporting such expansion are reviewed and the latest data on low-risk patients are discussed. A number of challenges need still to be addressed and are also reviewed in this paper: the need for updated international guidelines including the latest evidence; a reduction of main complications such as permanent pacemaker implantation, paravalvular leak, and stroke (and its potential prevention by using anti-embolic protection devices); the appropriate role of TAVR in patients with concomitant cardiac ischemic disease; and durability of bio-prosthetic implanted valves. Finally, the future perspectives for TAVR use and next device developments are discussed.
Background: Aortic stenosis (AS) is the most prevalent primary heart valve disease and the third most prevalent cardiovascular disease in the world, having a severe and slowly progressive evolution. The implementation of Transcatheter Aortic Valve Implantation (TAVI) is necessary because the population is constantly ageing, and most elderly people have various comorbidities, which places them among patients with high surgical risk. The aim was to report immediate and 9 months follow-up results of first TAVI implantations in the Republic of Moldova.
Material and methods: Three patients with severe symptomatic AS and high surgical risk underwent TAVI implantation using Portico valves.
Results: The mean age was 76.7 ± 1.2 years, 2 women and 1 man. The mean Logistic EuroSCORE II was 5.68 ± 0.67%. Procedural success was achieved in all (100%) patients. After the intervention, it was shown that the GP mean decreased by an average of 20.27±1.61 mmHg, the Vmax of the jet through AoV decreased on average by 2.05±0.19 m/s, and they were maintained all over the nine months follow-up period. Quality of life, using the TASQ (Toronto Aortic Stenosis Quality of Life) questionnaire, was improved by 62.3 ± 2.2 points.
Conclusions: TAVI, as a new minimally invasive method of treatment for aortic valve stenosis appears to be safe, with a low rate of early and late complications in elderly patients at high surgical risk, with good clinical outcomes at 9 months. Its implementation in the Republic of Moldova is welcome in the conditions of continuously ageing population and the prevalence of associated comorbidities.
Relapsing fever (RF) is claimed a neglected arthropod-borne disease caused by a number of diverse human pathogenic Borrelia (B.) species. These RF borreliae are separated into the groups of tick-transmitted species including B. duttonii, B. hermsii, B. parkeri, B. turicatae, B. hispanica, B. persica, B. caucasica, and B. myiamotoi, and the louse-borne Borrelia species B. recurrentis. As typical blood-borne pathogens achieving high cell concentrations in human blood, RF borreliae (RFB) must outwit innate immunity, in particular complement as the first line of defense. One prominent strategy developed by RFB to evade innate immunity involves inactivation of complement by recruiting distinct complement regulatory proteins, e.g., C1 esterase inhibitor (C1-INH), C4b-binding protein (C4BP), factor H (FH), FH-like protein-1 (FHL-1), and factor H-related proteins FHR-1 and FHR-2, or binding of individual complement components and plasminogen, respectively. A number of multi-functional, complement and plasminogen-binding molecules from distinct Borrelia species have previously been identified and characterized, exhibiting considerable heterogeneity in their sequences, structures, gene localization, and their capacity to bind host-derived proteins. In addition, RFB possess a unique system of antigenic variation, allowing them to change the composition of surface-exposed variable major proteins, thus evading the acquired immune response of the human host. This review focuses on the current knowledge of the immune evasion strategies by RFB and highlights the role of complement-interfering and infection-associated molecules for the pathogenesis of RFB.
Drug resistance is an obstacle in the therapy of acute lymphoblastic leukemia (ALL). Whether the physical properties such as the motility of the cells contribute to the survival of ALL cells after drug treatment has recently been of increasing interest, as they could potentially allow the metastasis of solid tumor cells and the migration of leukemia cells. We hypothesized that chemotherapeutic treatment may alter these physical cellular properties. To investigate the motility of chemotherapeutics-treated B-cell ALL (B-ALL) cells, patient-derived B-ALL cells were treated with chemotherapy for 7 days and left for 12 h without chemotherapeutic treatment. Two parameters of motility were studied, velocity and migration distance, using a time-lapse imaging system. The study revealed that compared to non-chemotherapeutically treated B-ALL cells, B-ALL cells that survived chemotherapy treatment after 7 days showed reduced motility. We had previously shown that Tysabri and P5G10, antibodies against the adhesion molecules integrins α4 and α6, respectively, may overcome drug resistance mediated through leukemia cell adhesion to bone marrow stromal cells. Therefore, we tested the effect of integrin α4 or α6 blockade on the motility of chemotherapeutics-treated ALL cells. Only integrin α4 blockade decreased the motility and velocity of two chemotherapeutics-treated ALL cell lines. Interestingly, integrin α6 blockade did not affect the velocity of chemoresistant ALL cells. This study explores the physical properties of the movements of chemoresistant B-ALL cells and highlights a potential link to integrins. Further studies to investigate the underlying mechanism are warranted.
Physical activity counseling in primary health care is regarded as a useful complementary preventive and therapeutic measure and is advocated by leading public health institutions. This integrative review summarizes the available data on physical activity counseling in primary care in Germany. A systematic literature search in various databases (peer reviewed and grey literature) was carried out for quantitative and qualitative studies on physical activity counseling and use of “Exercise on Prescription”. The 25 studies included show a very high methodological diversity and, in some cases, considerable risks of bias, with limited comparability across studies. Counseling was provided in all studies by physicians. They report frequent physical activity counseling, which is partly confirmed and partly refuted by patient data. The use of “Exercise on Prescription” is at a very low level. Information on the frequency of physical activity counseling in Germany varies depending on data source and is sometimes contradictory. Our review provides a synthesis of various perspectives on routine physical activity counseling in primary care in Germany. Future studies using standardized and validated instruments in representative samples are needed to further knowledge on counseling and to be able to establish trends in prevalence. Strengthening the topics of physical activity and health and physical activity counseling in medical curriculum is strongly recommended.
To understand the development of public health in Croatia, there are newer insights into the life and work of John the Baptist Lalangue. John the Baptist Lalangue is most valued for implementation of the imperial law on public health and promotion of midwifery in Croatia during the second half of the 18th century. Lalangue is the author of the first printed medical textbook in Croatian, published in 1776, entitled Medicina ruralis iliti Vrachtva ladanyszka, za potrebochu musev, y sziromakov Horvatczkoga orszaga y okolu nyega, blisnesseh mest, Trattnern, Varaždin. In the same period, Lalangue published the first Croatian midwifery textbook entitled Brevis institute de reobstetritia iliti kratek navuk od mestrie pupkorezne za potrebochu muskeh y sziromaskeh ladanovskaya horvatskoga orszaga y okolo nyega blisnesseh sztrankih, Trattnern, Zagreb. In 1779, Lalangue published his balneological debut in Croatian, the book Tractatus de aquis medicati Regnorum Croatiae et Slavoniae Iliti Izpiszavanye vrachtvenih vod Horvatzkoga y Slavonskoga orszaga y od nachina nye vsivati za potrebochu lyudih, Trattnern, Zagreb. Lalangue’s works were used in systematic training and education of midwives and they, as well as Lalangue, have an inevitable place in the history of Croatian midwifery. During his life and work, John the Baptist Lalangue made immeasurable contribution to the development of Croatian public health.
The 14-3-3 protein family are molecular chaperones involved in several biological functions and neurological diseases. We previously pinpointed YWHAZ (encoding 14-3-3ζ) as a candidate gene for autism spectrum disorder (ASD) through a whole-exome sequencing study, which identified a frameshift variant within the gene (c.659-660insT, p.L220Ffs*18). Here, we explored the contribution of the seven human 14-3-3 family members in ASD and other psychiatric disorders by investigating the: (i) functional impact of the 14-3-3ζ mutation p.L220Ffs*18 by assessing solubility, target binding and dimerization; (ii) contribution of common risk variants in 14-3-3 genes to ASD and additional psychiatric disorders; (iii) burden of rare variants in ASD and schizophrenia; and iv) 14-3-3 gene expression using ASD and schizophrenia transcriptomic data. We found that the mutant 14-3-3ζ protein had decreased solubility and lost its ability to form heterodimers and bind to its target tyrosine hydroxylase. Gene-based analyses using publicly available datasets revealed that common variants in YWHAE contribute to schizophrenia (p = 6.6 × 10−7), whereas ultra-rare variants were found enriched in ASD across the 14-3-3 genes (p = 0.017) and in schizophrenia for YWHAZ (meta-p = 0.017). Furthermore, expression of 14-3-3 genes was altered in post-mortem brains of ASD and schizophrenia patients. Our study supports a role for the 14-3-3 family in ASD and schizophrenia.
Purpose: Sarcopenia, defined as a loss of muscle mass and quality, has been associated with impaired oncological outcome and treatment toxicities in several malignancies. However, its role in anal squamous cell carcinoma (ASCC) remains less well explored.
Methods/Materials: Planning CT scans were used to measure cross-sectional skeletal muscle area (SMA) to calculate the skeletal muscle index (SMI). The association of sarcopenia with clinical and treatment-related parameters, and toxicity was assessed in 114 patients with ASCC that underwent standard 5-Fluorouracil/Mitomycin C chemoradiotherapy (CRT). The prognostic impact of sarcopenia on local relapse-free survival (LRFS), disease-free survival (DFS), and overall survival was examined using a Cox regression analysis.
Results: 29 (25.4%) patients had sarcopenia. Patients with sarcopenia had lower baseline hemoglobin levels (p = 0.002), worse Karnofsky Performance Status (p = 0.001) lower BMI (p < 0.001), and a significantly lower body surface area (p = 0.03), and lower incidence of involved lymph nodes (p = 0.03). Regarding acute toxicity, sarcopenia was associated with a significantly higher incidence of ≥grade 3leukopenia (OR: 3.5; 95% CI: 1.6–7.5, p = 0.007) and ≥grade 3 thrombopenia (OR: 5.1; 95% CI: 1.3–21, p = 0.018) after CRT. Despite higher hematologic toxicity in sarcopenic patients, total treatment time was similar between patients with and without sarcopenia (median 44 vs 45 days, p = 0.95). There was no significant prognostic impact of sarcopenia on either LRFS, DFS, or OS.
Conclusion: This is the largest study to assess the impact of sarcopenia on toxicity and oncological outcome in patients with ASCC. Increased clinician awareness of higher hematological toxicity risk is needed for sarcopenic patients with ASCC undergoing CRT to facilitate closer monitoring of side effects and earlier introduction of supportive measures. Further prospective studies are needed to elucidate the prognostic role and impact of sarcopenia on CRT-related toxicity in ASCC.
Introduction End-of-life care is an essential task performed by most healthcare providers and often involves decision-making about how and where patients want to receive care. To provide decision support to healthcare professionals and patients in this difficult situation, we will systematically review a knowledge cluster of the end-of-life care preferences of older patients with multimorbidity that we previously identified using an evidence map.
Methods and analysis We will systematically search for studies reporting end-of-life care preferences of older patients (mean age ≥60) with multimorbidity (≥2 chronic conditions) in MEDLINE, CINAHL, PsycINFO, Social Sciences Citation Index, Social Sciences Citation Index Expanded, PSYNDEX and The Cochrane Library from inception to September 2019. We will include all primary studies that use quantitative, qualitative and mixed methodologies, irrespective of publication date and language.
Two independent reviewers will assess eligibility, extract data and describe evidence in terms of study/population characteristics, preference assessment method and end-of-life care elements that matter to patients (eg, life-sustaining treatments). Risk of bias/applicability of results will be independently assessed by two reviewers using the Mixed-Methods Appraisal Tool. Using a convergent integrated approach on qualitative/quantitative studies, we will synthesise information narratively and, wherever possible, quantitatively.
Ethics and dissemination Due to the nature of the proposed systematic review, ethics approval is not required. Results from our research will be disseminated at relevant (inter-)national conferences and via publication in peer-reviewed journals. Synthesising evidence on end-of-life care preferences of older patients with multimorbidity will improve shared decision-making and satisfaction in this final period of life.
Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C).
Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE).
Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina.
Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081).
Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).