Post-menopausal vaginal bleeding caused by carcinoma of the appendix: a case report

<p>Abstract</p> <p>Introduction</p> <p>Post-menopausal blood loss is a common complaint of patients seen in gynecological practice. The most frequent malignancy found in cases of post-menopausal bleeding is endometrial cancer. Other causes can be malignancies of the rest of a woman's genital tract or metastases from other tumors. To the best of our knowledge, it appears that this is the first published case of a post-menopausal primary appendiceal carcinoma presenting with vaginal blood loss.</p> <p>Case presentation</p> <p>A 75-year-old Caucasian woman with a history of vaginal hysterectomy presented with a 10-month history of post-menopausal blood loss. After extensive examination and discussion, ovarian carcinoma was suggested. Microscopic examination of the tissue removed at laparotomy revealed an adenocarcinoma of the appendix. She was treated with adjuvant radiotherapy and with palliative chemotherapy after 14 months because of intra-abdominal metastatic disease.</p> <p>Conclusion</p> <p>Post-menopausal blood loss in a patient with a history of hysterectomy is uncommon and always needs further investigation.</p

Engaging community-dwelling older adults in fall prevention programs: a qualitative study on strategies promoting participation in fall prevention programs among community-dwelling older adults

IntroductionFall rates and fall-related injuries among community-dwelling older adults (≥65 years) are expected to increase rapidly, due to the aging population worldwide. Fall prevention programs (FPPs), consisting of strength and balance exercises, have been proven effective in reducing fall rates among older adults. However, these FPPs have not reached their full potential as most programs are under-enrolled. Therefore, this study aims to identify promising strategies that promote participation in FPPs among community-dwelling older adults.MethodsThis is an exploratory qualitative study. Previously, barriers and facilitators for participation in FPPs by older adults had been identified. Next, six strategies had been designed using the Intervention Mapping approach: (1) reframing; (2) informing about benefits; (3) raising awareness of risks; (4) involving social environment; (5) offering tailored intervention; (6) arranging practicalities. Strategies were validated during semi-structured interviews with community-dwelling older adults (n = 12) at risk of falling. Interviews were audio-recorded, transcribed, and analyzed following a qualitative thematic methodology, with a hybrid approach.ResultsAll strategies were considered important by at least some of the respondents. However, two strategies stood out: (1) reframing ‘aging’ and ‘fall prevention’: respondents preferred to be approached differently, taking a ‘life course’ perspective about falls, and avoiding confronting words; and (2) ‘informing about benefits’ (e.g., ‘living independently for longer’); which was mentioned to improve the understanding of the relevance of participating in FPPs. Other strategies were considered important to take into account too, but opinions varied more strongly.DiscussionThis study provides insight into potential strategies to stimulate older adults to participate in FPPs. Results suggest that reframing ‘aging’ and ‘fall prevention’ may facilitate the dialogue about fall prevention, by communicating differently about the topic, for example ‘staying fit and healthy’, while focusing on the benefits of participating in FPPs. Gaining insight into the strategies’ effectiveness and working mechanisms is an area for future research. This could lead to practical recommendations and help professionals to enhance older adults’ participation in FPPs. Currently, the strategies are further developed to be applied and evaluated for effectiveness in multiple field labs in a central Dutch region (Utrecht)

Tracking of structural and functional cardiac measures from infancy into school-age

Objective Cardiac structure and function are important predictors for cardiovascular disease in adults. Not much is known about tracking of cardiac measures, other than left ventricular mass, from early life onwards. We examined whether and to what extent cardiac measures track from infancy into school-age. Methods We performed a population-based prospective cohort study among 1072 children. Aortic root diameter, left atrial diameter, left ventricular mass, relative wall thickness and fractional shortening were measured repeatedly by echocardiography. We explored tracking between infancy (1.5, six and 24 months) and school-age (six and 10 years). Results Of all cardiac measures, aortic root diameter, left atrial diameter and left ventricular mass were significantly correlated between infancy and school-age (r = 0.10-0.42, all p-values < 0.01), with the strongest correlations between 24 months and 10 years. Of the different structures, aortic root diameter showed the strongest correlations. Approximately 30% of children who were in the lowest or highest quartile of a measure at the age of 1.5 months remained in that quartile at the age of 10 years. When analysing the effects of the infant cardiac measures on the same outcomes at 10 years in conditional regression models, we observed ef

Categorical Dimensions of Human Odor Descriptor Space Revealed by Non-Negative Matrix Factorization

In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain unclear. Here, we use non-negative matrix factorization (NMF) – a dimensionality reduction technique – to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor dimensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner. We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures

A guide to immunotherapy for COVID-19

Immune dysregulation is an important component of the pathophysiology of COVID-19. A large body of literature has reported the effect of immune-based therapies in patients with COVID-19, with some remarkable successes such as the use of steroids or anti-cytokine therapies. However, challenges in clinical decision-making arise from the complexity of the disease phenotypes and patient heterogeneity, as well as the variable quality of evidence from immunotherapy studies. This Review aims to support clinical decision-making by providing an overview of the evidence generated by major clinical trials of host-directed therapy. We discuss patient stratification and propose an algorithm to guide the use of immunotherapy strategies in the clinic. This will not only help guide treatment decisions, but may also help to design future trials that investigate immunotherapy in other severe infections

Cardiac allograft vasculopathy and donor age affecting permanent pacemaker implantation after heart transplantation

AIMS: The need for permanent pacemakers (PMs) after heart transplantation (HT) is increasing. The aim was to determine the influence of cardiac allograft vasculopathy (CAV), donor age, and other risk factors on PM implantations early and late after HT and its effect on survival. METHODS AND RESULTS: A retrospective, single‐centre study was performed including HTs from 1984 to July 2018. Early PM was defined as PM implantation ≤90 days and late PM as PM > 90 days. Risk factors for PM and survival after PM were determined with (time‐dependent) multivariable Cox regression. Out of 720 HTs performed, 62 were excluded (55 mortalities ≤30 days and 7 retransplantations). Of the remaining 658 patients, 95 (14%) needed a PM: 38 (6%) early and 57 (9%) late during follow‐up (median 9.3 years). Early PM risk factors were donor age [hazard ratio (HR) 1.06, P < 0.001], ischaemic time (HR 1.01, P < 0.001), and in adults amiodarone use before HT (HR 2.02, P = 0.045). Late PM risk factors were donor age (HR 1.03, P = 0.024) and CAV (HR 3.59, P < 0.001). Late PM compromised survival (HR 2.05, P < 0.001), while early PM did not (HR 0.77, P = 0.41). CONCLUSIONS: Risk factors for early PM implantation were donor age, ischaemic time, and in adults amiodarone use before HT. Late PM implantation risk factors were donor age and CAV. Late PM diminished survival, which is probably a surrogate marker for underlying progressive cardiac disease

Dysregulated innate and adaptive immune responses discriminate disease severity in COVID-19

The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive pro-inflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis reveals no specific inflammatory endotypes in COVID-19 patients. Functional assays reveal abrogated adaptive cytokine production (interferon-gamma, interleukin-17 and interleukin-22) and prominent T cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlight potential biomarkers of disease severity

Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants

Introduction: Biallelic damaging variants in ALPK3, encoding alpha-protein kinase 3, cause pediatric-onset cardiomyopathy with manifestations that are incompletely defined. Methods and Results: We analyzed clinical manifestations of damaging biallelic ALPK3 variants in 19 pediatric patients, including nine previously published cases. Among these, 11 loss-of-function (LoF) variants, seven compound LoF and deleterious missense variants, and one homozygous deleterious missense variant were identified. Among 18 live-born patients, 8 exhibited neonatal dilated cardiomyopathy (44.4%; 95% CI: 21.5%-69.2%) that subsequently transitioned into ventricular hypertrophy. The majority of patients had extracardiac phenotypes, including contractures, scoliosis, cleft palate, and facial dysmorphisms. We observed no association between variant type or location, disease severity, and/or extracardiac manifestations. Myocardial histopathology showed focal cardiomyocyte hypertrophy, subendocardial fibroelastosis in patients under 4 years of age, and myofibrillar disarray in adults. Rare heterozygous ALPK3 variants were also assessed in adult-onset cardiomyopathy patients. Among 1548 Dutch patients referred for initial genetic analyses, we identified 39 individuals with rare heterozygous ALPK3 variants (2.5%; 95% CI: 1.8%-3.4%), including 26 missense and 10 LoF variants. Among 149 U.S. patients without pathogenic variants in 83 cardiomyopathy-related genes, we identified six missense and nine LoF ALPK3 variants (10.1%; 95% CI: 5.7%-16.1%). LoF ALPK3 variants were increased in comparison to matched controls (Dutch cohort, P = 1.6×10−5; U.S. cohort, P = 2.2×10−13). Conclusion: Biallelic damaging ALPK3 variants cause pediatric cardiomyopathy manifested by DCM transitioning to hypertrophy, often with poor contractile function. Additional extracardiac features occur in most patients, including musculoskeletal abnormalities and cleft palate. Heterozygous LoF ALPK3 variants are enriched in adults with cardiomyopathy and may contribute to their cardiomyopathy. Adults with ALPK3 LoF variants therefore warrant evaluations for cardiomyopathy