Existential decision-making in a fatal progressive disease: how much do legal and medical frameworks matter?

Background

Healthcare legislation in European countries is similar in many respects. Most importantly, the framework of informed consent determines that physicians have the duty to provide detailed information about available therapeutic options and that patients have the right to refuse measures that contradict their personal values. However, when it comes to end-of-life decision-making a number of differences exist in the more specific regulations of individual countries. These differences and how they might nevertheless impact patient’s choices will be addressed in the current debate.

Main text

In this article we show how the legal and medical frameworks of Germany, Poland and Sweden differ with regard to end-of-life decisions for patients with a fatal progressive disease. Taking Amyotrophic Lateral Sclerosis (ALS) as an example, we systematically compare clinical guidelines and healthcare law, pointing out the country-specific differences most relevant for existential decision-making. A fictional case report discusses the implications of these differences for a patient with ALS living in either of the three countries. Patients with ALS in Germany, Poland and Sweden are confronted with a similar spectrum of treatment options. However, the analysis of the normative frameworks shows that the conditions for making existential decisions differ considerably in Germany, Poland and Sweden. Specifically, these differences concern (1) the legal status of advance directives, (2) the conditions under which life-sustaining therapies are started or withheld, and (3) the legal regulations on assisted dying.

Conclusion

According to the presented data, regulations of terminating life-sustaining treatments and the framework of “informed consent” are quite differently understood and implemented in the legal setting of the three countries. It is possible, and even likely, that these differences in the legal and medical frameworks have a considerable influence on existential decisions of patients with ALS.

     

KIR,LILRB and their Ligands’ Genes as Potential Biomarkers in Recurrent Implantation Failure

Archivum Immunologiae et Therapiae Experimentalis - Reproductive failure in humans is a very important social and economic problem, because nowadays women decide to conceive later in life and delay...     

Evidence‐based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH‐HCC Guidelines)

The 3rd version of Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence‐based medicine, which was published in October 2013 in Japanese. Here, we briefly describe new or changed recommendations with a special reference to the two algorithms for surveillance, diagnosis, and treatment.     

Clinical effect of double coaxial self-expandable metallic stent in management of malignant colon obstruction

PURPOSE

We aimed to evaluate the clinical effectiveness and safety of double coaxial self-expandable metallic stent (DCSEMS) in management of malignant colonic obstruction as a bridge to surgery or palliation for inoperable patients.

METHODS

Between April 2006 and December 2012, 49 patients (27 males and 22 females; median age, 68 years; age range, 38–91 years) were selected to receive decompressive therapy for malignant colonic obstruction by implanting a DCSEMS. Application of DCSEMS was attempted in 49 patients under fluoroscopic guidance. The obstruction was located in the transverse colon (n=2), descending colon (n=7), sigmoid colon (n=24), rectosigmoid junction (n=6), and the rectum (n=10). The intended use of DCSEMS was as a bridge to elective surgery in 23 patients and palliation in 26 patients.

RESULTS

Clinical success, defined as >50% dilatation of the stent with subsequent symptomatic improvement, was achieved in 48 of 49 patients (98%). The stent was properly inserted in all patients. No immediate major procedure-related complications occurred. One patient in the bridge-to-surgery group had colon perforation three days after DCSEMS application. Four patients had late migrations of the double stent.

CONCLUSION

Application of DCSEMS is safe and effective in management of malignant colonic obstruction; it prevents stent migration and tumor ingrowth and lowers perforation rate during the stent application.Fluoroscopic or endoscopic placement of either bare or covered expandable metallic stents was shown to be a safe, easy, and effective technique as a bridge to surgery and palliative treatment of colorectal cancer (1, 2). However, tumor ingrowth and stent migration have been reported as weaknesses in conventional single bare and covered stents, respectively (2–4). The use of bare stents has been hindered by progressive tumor ingrowth through the wire filaments of the bare stents and food residue or hard fecal impaction proximal to or at the level of the stent insertion site (5, 6). In contrast, the use of covered expandable metallic stents has been associated with stent migration (5, 7). To overcome the limitations associated with conventional bare and covered stents, a double coaxial self-expandable metallic stent (DCSEMS) has been developed to combine the strengths of bare and covered stents (7, 8).The purpose of the present study was to report our experiences with fluoroscopic-guided placement of double stents in management of malignant colorectal obstruction as a bridge to surgery or palliative treatment.     

Ca2+ is a Regulator of the WNK/OSR1/NKCC Pathway in a Human Salivary Gland Cell Line

Wnk kinase maintains cell volume, regulating various transporters such as sodium-chloride cotransporter, potassium-chloride cotransporter, and sodium-potassium-chloride cotransporter 1 (NKCC1) through the phosphorylation of oxidative stress responsive kinase 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). However, the activating mechanism of Wnk kinase in specific tissues and specific conditions is broadly unclear. In the present study, we used a human salivary gland (HSG) cell line as a model and showed that Ca²⁺ may have a role in regulating Wnk kinase in the HSG cell line. Through this study, we found that the HSG cell line expressed molecules participating in the WNK-OSR1-NKCC pathway, such as Wnk1, Wnk4, OSR1, SPAK, and NKCC1. The HSG cell line showed an intracellular Ca²⁺ concentration ([Ca²⁺]_i) increase in response to hypotonic stimulation, and the response was synchronized with the phosphorylation of OSR1. Interestingly, when we inhibited the hypotonically induced [Ca²⁺]_i increase with nonspecific Ca²⁺ channel blockers such as 2-aminoethoxydiphenyl borate, gadolinium, and lanthanum, the phosphorylated OSR1 level was also diminished. Moreover, a cyclopiazonic acid-induced passive [Ca²⁺]_i elevation was evoked by the phosphorylation of OSR1, and the amount of phosphorylated OSR1 decreased when the cells were treated with BAPTA, a Ca²⁺ chelator. Finally, through that process, NKCC1 activity also decreased to maintain the cell volume in the HSG cell line. These results indicate that Ca²⁺ may regulate the WNK-OSR1 pathway and NKCC1 activity in the HSG cell line. This is the first demonstration that indicates upstream Ca²⁺ regulation of the WNK-OSR1 pathway in intact cells.     

Negative pressure pulmonary edema in a patient undergoing open rhinoplasty: A case report

Rationale:Negative pressure pulmonary edema (NPPE) is associated with serious postoperative complications. Compact nasal packing is always done after an open rhinoplasty procedure which makes it difficult to achieve positive pressure ventilation via a mask if NPPE arises.Patient concerns:A 21-year-old healthy man got an open rhinoplasty, septal perforation repair, and revisional septal reconstruction. After surgery, he became so agitated that it was difficult to calm him. We decided to remove the endotracheal tube. On arrival at the post-anesthesia care unit, he was cyanotic and his SpO₂ had decreased to about 2%. We attempted positive pressure ventilation using mask bagging; however, it was ineffective due to the nasal packing.Diagnoses:Negative pressure pulmonary edemaInterventions:Emergent reintubation was immediately done and Ambu bagging was commenced. A considerable pinkish secretion came out of the tube. A T-piece was applied to him using 15 L/min of oxygen supply. The patient was eventually transferred to the intensive care unit of our hospital.Outcomes:On postoperative day (POD) 1, a decision was made to extubate, and the oxygen supply was shifted to 3L/min using a venturi-mask. On POD 2, a chest posteroanterior radiograph was taken and indicated no active lung lesion. The patient was subsequently discharged without any complications. He had no symptoms on POD 6, 11, and 18 at follow-up visits to our outpatient clinic.Lessons:Anesthesiologists should be alert to the possibility of NPPE and its treatment because of its rapid onset but positive clinical outcome if there is a proper intervention. In nasal surgery cases in particular, early re-intubation should be conducted and extubation should be done to fully awaken the patients.     

Deoxycholic acid-modified polyethylenimine based nanocarriers for RAGE siRNA therapy in acute myocardial infarction

The activation of receptor for advanced glycation end products (RAGE) signaling is mainly associated with myocardial ischemia/reperfusion injury. Thus the blockade of RAGE-ligands axis can be considered as a potential therapeutic strategy to protect myocardial infarction after ischemia/reperfusion injury. Herein, we strengthened the cardioprotective effect with combinatorial treatment of soluble RAGE (sRAGE) and RAGE siRNA (siRAGE) causing more effective suppression of RAGE-mediated signaling transduction. For pharmacological blockade of RAGE, sRAGE, the extracellular ligand binding domain of RAGE, acts as a pharmacological ligand decoy and inhibits the interaction between RAGE and its ligands. For genetic deletion of RAGE, siRAGE suppresses the expression of RAGE by participating in RNA interference mechanism. Therefore, we combined these two RAGE blockade/deletion strategies and investigated the therapeutic effects on rat ischemic and reperfused myocardium. According to our results, based on RAGE expression level analysis and infarct size/fibrosis measurement, co-treatment of sRAGE and siRAGE exhibited synergic cardioprotective effects; thus the newly designed regimen can be considered as a promising candidate for the treatment of myocardial infarction.     

Allogeneic Dentin Graft: A Review on Its Osteoinductivity and Antigenicity

Studies on allogeneic demineralized dentin matrix (Allo-DDM) implantation in the 1960s and 1970s provided the most reliable preclinical evidence of bone formation and antigenicity in an extraosseous site. Recently, applications of Allo-DDM at skeletal sites were studied, and have provided reliable evidence of bone-forming capacity and negligible antigenicity. However, the osteoinductivity and antigenicity properties of Allo-DDM in extraskeletal sites have not yet been investigated due to the lack of follow-up studies after the initial research. The clinical applications of autogenous DDM (Auto-DDM) have been standardized in some countries. Long-term clinical studies have reported the development of several shapes of Auto-DDM, such as powders, blocks, moldable forms, and composites, with recombinant human bone morphogenetic protein-2. For the development of Allo-DDM as a reliable bone graft substitute next to Auto-DDM, we reviewed preclinical studies on the bone induction capacity of allogeneic dentin at extraskeletal as well as skeletal sites. Electronic databases were screened for this review in January 2020 and searched from 1960 to 2019. This review aims to provide a foundation on the preclinical studies of Allo-DDM, which could enable future researches on its osteogenic capability and antigenicity. In conclusion, Allo-DDM showed great potential for osteoinductivity in extraskeletal sites with low antigenicity, which neither adversely affected osteogenic capability nor provoked immunologic reactions. However, the risk of viral disease transmission should be researched before the clinical application of Allo-DDM.