Perioperative outcome, long-term mortality and time trends in elderly patients undergoing low-, intermediate- or major non-cardiac surgery

Background: Decision-making whether older patients benefit from surgery can be a difficult task. This report investigates characteristics and outcomes of a large cohort of inpatients, aged 80 years and over, undergoing non-cardiac surgery. Methods: This observational study was performed at a tertiary university medical centre in the Netherlands. Patients of 80 years or older undergoing elective or urgent surgery from January 2004 to June 2017 were included. Outcomes were length of stay, discharge destination, 30-day and long-term mortality. Patients were divided into low-, intermediate and high-risk surgery subgroups. Univariable and multivariable logistic regression were used to evaluate the association of risk factors and outcomes. Secondary outcomes were time trends, assessed with Mantel–Haenszel chi-square test. Results: Data of 8251 patients, undergoing 19,027 surgical interventions were collected from the patients’ medical record. 7032 primary procedures were suitable for analyses. Median LOS was 3 days in the low-risk group, compared to six in the intermediate- and ten in the high-risk group. Median LOS of the total cohort decreased from 5.8 days (IQR 1.9–14.5) in 2004–2007 to 4.6 days (IQR 1.9–9.0) in 2016–2017. Three quarters of patients were discharged to their home. Postoperative 30-day mortality in the low-risk group was 2.3%. In the overall population 30-day mortality was high and constant during the study period (6.7%, ranging from 4.2 to 8.4%). Conclusion:Patients should not be withheld surgery solely based on their age. However, even for low-risk surgery, the mortality rate of more than 2% is substantial. Deciding whether older patients benefit from surgery should be based on the understanding of individual risks, patients’ wishes and a patient-centred plan.</p

Photoplethysmography and intracardiac pressures:early insights from a pilot study

Aims: Invasive haemodynamic monitoring of heart failure (HF) is used to detect deterioration in an early phase thereby preventing hospitalizations. However, this invasive approach is costly and presently lacks widespread accessibility. Hence, there is a pressing need to identify an alternative non-invasive method that is reliable and more readily available. In this pilot study, we investigated the relation between wrist-derived photoplethysmography (PPG) signals and the invasively measured pulmonary capillary wedge pressure (PCWP). Methods and results: Fourteen patients with aortic valve stenosis who underwent transcatheter aortic valve replacement with concomitant right heart catheterization and PPG measurements were included. Six unique features of the PPG signals [heart rate, heart rate variability, systolic amplitude (SA), diastolic amplitude, crest time (CT), and large artery stiffness index (LASI)] were extracted. These features were used to estimate the continuous PCWP values and the categorized PCWP (low &lt; 12mmHg vs. high ≥ 12mmHg). All PPG features resulted in regression models that showed low correlations with the invasively measured PCWP. Classification models resulted in higher performances: the model based on the SA and the model based on the LASI both resulted in an area under the curve (AUC) of 0.86 and the model based on the CT resulted in an AUC of 0.72. Conclusion: These results demonstrate the capability to non-invasively classify patients into clinically meaningful categories of PCWP using PPG signals from a wrist-worn wearable device. To enhance and fully explore its potential, the relationship between PPG and PCWP should be further investigated in a larger cohort of HF patients.</p

Photoplethysmography and intracardiac pressures:early insights from a pilot study

Aims: Invasive haemodynamic monitoring of heart failure (HF) is used to detect deterioration in an early phase thereby preventing hospitalizations. However, this invasive approach is costly and presently lacks widespread accessibility. Hence, there is a pressing need to identify an alternative non-invasive method that is reliable and more readily available. In this pilot study, we investigated the relation between wrist-derived photoplethysmography (PPG) signals and the invasively measured pulmonary capillary wedge pressure (PCWP). Methods and results: Fourteen patients with aortic valve stenosis who underwent transcatheter aortic valve replacement with concomitant right heart catheterization and PPG measurements were included. Six unique features of the PPG signals [heart rate, heart rate variability, systolic amplitude (SA), diastolic amplitude, crest time (CT), and large artery stiffness index (LASI)] were extracted. These features were used to estimate the continuous PCWP values and the categorized PCWP (low &lt; 12mmHg vs. high ≥ 12mmHg). All PPG features resulted in regression models that showed low correlations with the invasively measured PCWP. Classification models resulted in higher performances: the model based on the SA and the model based on the LASI both resulted in an area under the curve (AUC) of 0.86 and the model based on the CT resulted in an AUC of 0.72. Conclusion: These results demonstrate the capability to non-invasively classify patients into clinically meaningful categories of PCWP using PPG signals from a wrist-worn wearable device. To enhance and fully explore its potential, the relationship between PPG and PCWP should be further investigated in a larger cohort of HF patients.</p

Lack of evidence for a causal role of CALR3 in monogenic cardiomyopathy

The pathogenicity of previously published disease-associated genes and variants is sometimes questionable. Large-scale, population-based sequencing studies have uncovered numerous false assignments of pathogenicity. Misinterpretation of sequence variants may have serious implications for the patients and families involved, as genetic test results are increasingly being used in medical decision making. In this study, we assessed the role of the calreticulin-3 gene (CALR3) in cardiomyopathy. CALR3 has been included in several cardiomyopathy gene panels worldwide. Its inclusion is based on a single publication describing two missense variants in patients with hypertrophic cardiomyopathy. In our national cardiomyopathy cohort (n = 6154), we identified 17 unique, rare heterozygous CALR3 variants in 48 probands. Overall, our patient cohort contained a significantly higher number of rare CALR3 variants compared to the ExAC population (p = 0.0036). However, after removing a potential Dutch founder variant, no statistically significant difference was found (p = 0.89). In nine probands, the CALR3 variant was accompanied by a disease-causing variant in another, well-known cardiomyopathy gene. In three families, the CALR3 variant did not segregate with the disease. Furthermore, we could not demonstrate calreticulin-3 protein expression in myocardial tissues at various ages. On the basis of these findings, it seems highly questionable that variants in CALR3 are a monogenic cause of cardiomyopathy

A mutation update for the FLNC gene in myopathies and cardiomyopathies

Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrim

A mutation update for the FLNC gene in myopathies and cardiomyopathies

Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype–phenotype correlations based on available evidence

Correlation between Discharged Worms and Fecal Egg Counts in Human Clonorchiasis

Clonorchiasis is a major neglected disease in East Asia. Worm data in infected humans are very limited, and only egg counts roughly estimate infection burden of the worms. In endemic areas, we recruited infected cases and tried to collect the adult worms from them. They were treated with 3 doses of praziquantel, and purged next day under fasting. Adult worms of C. sinensis were recovered from their diarrheal feces. The worms discharged from humans after treatment are minimum confirmed numbers. The worm recovery rate noticeably increased in subjects with higher egg counts. The number of collected worms was well-correlated with the egg counts. Worm collection by praziquantel medication and purgation is a safe non-invasive method to get worm information from human. The present study confirms that at least 110 worms are infected in a human body with egg counts per gram of feces around 3,000, and egg productivity of a worm per day is around 4,000

Acute Muscular Sarcocystosis: An International Investigation Among Ill Travelers Returning From Tioman Island, Malaysia, 2011-2012

A large outbreak of acute muscular sarcocystosis (AMS) among international tourists who visited Tioman Island, Malaysia, is described. Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS in their differential diagnosi

In Vitro and In Vivo Efficacy of Monepantel (AAD 1566) against Laboratory Models of Human Intestinal Nematode Infections

Soil-transmitted helminthiases affect more than one billion people among the most vulnerable populations in developing countries. Currently, control of these infections primarily relies on chemotherapy. Only five drugs are available, all of which have been in use for decades. None of the drugs are efficacious using single doses against all soil-transmitted helminths (STH) species and show low efficacy observed against Trichuris trichiura. In addition, the limited availability of current drug treatments poses a precarious situation should drug resistance occur. Therefore, there is great interest to develop novel drugs against infections with STH. Monepantel, which belongs to a new class of veterinary anthelmintics, the amino-acetonitrile derivatives, might be a potential drug candidate in humans. It has been extensively tested against livestock nematodes, and was found highly efficacious and safe for animals. Here we describe the in vitro and in vivo effect of monepantel, on Ancylostoma ceylanicum, Necator americanus, Trichuris muris, Strongyloides ratti, and Ascaris suum, five parasite-rodent models of relevance to human STH. Since we observed that monepantel showed only high activity on one of the hookworm species and lacked activity on the other parasites tested we cannot recommend the drug as a development candidate for human soil-transmitted helminthiases

Existential Loneliness and end-of-life care: A Systematic Review

Contains fulltext : 88662.pdf (publisher's version ) (Closed access)Patients with a life-threatening illness can be confronted with various types of loneliness, one of which is existential loneliness (EL). Since the experience of EL is extremely disruptive, the issue of EL is relevant for the practice of end-of-life care. Still, the literature on EL has generated little discussion and empirical substantiation and has never been systematically reviewed. In order to systematically review the literature, we (1) identified the existential loneliness literature; (2) established an organising framework for the review; (3) conducted a conceptual analysis of existential loneliness; and (4) discussed its relevance for end-of-life care. We found that the EL concept is profoundly unclear. Distinguishing between three dimensions of EL-as a condition, as an experience, and as a process of inner growth-leads to some conceptual clarification. Analysis of these dimensions on the basis of their respective key notions-everpresent, feeling, defence; death, awareness, difficult communication; and inner growth, giving meaning, authenticity-further clarifies the concept. Although none of the key notions are unambiguous, they may function as a starting point for the development of care strategies on EL at the end of life.1 april 201