[INFORMED CONSENT FOR SURGERY: WHAT'S REALLY GOING ON THERE?]

INTRODUCTION: The process of "informed consent" is currently being evaluated by the Ministry of Health, with the intent to recommend steps to improve patients' and doctors' satisfaction. Following the committee meetings, we decided to initiate an evaluation of the patient's perceptions regarding technical and logistic aspects of the process. AIMS: To learn about patients' perceptions on the informed consent process, by evaluating different aspects and variables. METHODS: One hundred patients who underwent an "informed consent" process, followed by general surgery, were interviewed using a formulated call-script. All the patients had surgery at Ramat Hayal Hospital during January 2020. RESULTS: All the interviewed patients reported that their surgeon was the one who participated in the informed consent process. The majority of the patients (70%) reported that the meeting lasted between 10-20 minutes. Only 35% of the patients reported that the surgeon used auxiliary materials during the meeting. Almost all patients (96-99%) noted that the explanations delineated by the surgeon during their meeting were clear, satisfactory, and congruent with their real experiences of their surgery. CONCLUSIONS: Based on the results of this study, we confirm that the informed consent process for patients having surgery at the Ramat Hayal Hospital, is adequate and follows the recommendations of the law. Analyzing our data by the funding agent did not disclose meaningful differences except regarding the use of auxiliary materials. This issue will be examined in a future study. DISCUSSION: These study results show a high compliance with the informed consent process in accordance with the law and MOH regulations.

Addressing the important error of missing surgical items in an operated patient.

BACKGROUND: We aim to analyze the characteristics of incidences of missing surgical items (MSIs) and to examine the changes in MSI events following the implementation of an MSI prevention program. METHODS: All surgical cases registered in our medical center from January 2014 to December 2019 were retrospectively analyzed. RESULTS: Among 559,910 operations, 154 MSI cases were reported. Mean patient age was 48.67 years (standard deviation, 20.88), and 56.6% were female. The rate of MSIs was 0.259/1000 cases. Seventy-seven MSI cases (53.10%) had no consequences, 47 (32.41%) had mild consequences, and 21 (14.48%) had severe consequences. These last 21 cases represented a rate of 0.037/1000 cases. MSI events were more frequent in cardiac surgery (1.82/1000 operations). Textile elements were the most commonly retained materials (28.97% of cases). In total, 15.86% of the cases were not properly reported. The risk factors associated with MSIs included body mass index (BMI) above 35 kg/m2 and prolonged operative time. After the implementation of the institutional prevention system in January 2017, there was a gradual decrease in the occurrence of severe events despite an increase in the number of MSIs. CONCLUSION: Despite the increase in the rate of MSIs, an implemented transparency and reporting system helped reduce the cases with serious consequences. To further prevent the occurrence of losing surgical elements in a surgery, we recommend educating OR staff members about responsibility and obligation to report all incidents that are caused during an operation, to develop an event reporting system as well as "rituals" within the OR setting to increase the team's awareness to MSIs. Trial registration Clinicaltrials.gov (NCT04293536). Date of registration: 08.01.2021. https://clinicaltrials.gov/ct2/show/NCT04293536 .

Ferritin and prolactin levels in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a common demyelnating disorder of the central nervous system (CNS) and ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity. OBJECTIVES: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease. METHODS: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls. RESULTS: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P < 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary-progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing-progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05) CONCLUSIONS: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.

[The dilemma regarding treatment of pulmonary embolism among elderly patients].

Pulmonary embolism is a medical condition associated with significant morbidity and mortality. However, there are serious side effects to the anticoagulation therapy. We report on a 97-year-old woman who was admitted to the internal medicine department due to dyspnea and pleuritic chest pain. In the differential diagnosis we considered pulmonary embolism. In this article we present the diagnostic and therapeutic steps according to the guidelines, and compare them to a hypothetical situation of a younger woman who is presented with the same clinical findings. We discuss the risks that are attributed to pulmonary embolism on the one hand, and to the anticoagulation therapy on the other hand, with respect to elderly patients more than 80 and 90 years old versus younger patients.

A comprehensive evaluation of serum autoantibodies in primary biliary cirrhosis.

In primary biliary cirrhosis (PBC) serum markers other than anti-mitochondrial antibodies (AMA) are promising in terms of disease severity and comorbidities, as well represented by anti-nuclear antibodies (ANA). The aim of the present study was thus to evaluate the prevalence and clinical significance of a large profile of serum autoantibodies in PBC sera. We utilized 69 sera from European patients with PBC (including 20 AMA-negative) and 297 sera from geographically and sex-matched healthy controls. All sera were tested for the presence of ANA and autoantibodies associated with thrombophilia, vasculitis, and gastrointestinal disease. Autoantibodies other than AMA were detected in 53/69 (76%) PBC sera vs. 105/297 (35%) among controls. The prevalence of ANA (targeting dsDNA, Sm, chromatin, ribosomal-P, RNP, SmRNP, SSA, SSB, and centromere) and thrombophilia-associated autoantibodies (i.e. anti-beta2GPI, phosphatydilserine, prothrombin) was common among patients with PBC. When clinical features were compared, the presence of anti-prothrombin IgM was associated with a worse prognosis as represented by a higher Mayo score. We demonstrate an increased prevalence of ANA and thrombophilia-associated autoantibodies in PBC sera and an association between the latter autoantibodies and PBC stage. The role of thrombophilia-associated antibodies will warrant further studies, based in particular on the incidence of portal hypertension at early stages of PBC.

Autoimmune pathology accounts for common manifestations in a wide range of neuro-psychiatric disorders: the olfactory and immune system interrelationship.

Smell has traditionally been considered a less important sense when compared to sight or hearing, but recent research has unraveled important features inherent to the sense of smell. Once considered just a chemical sensor for sampling the environment, data from animal models and human studies currently imply numerous and complex effects of smell on behavior, mood, and on the immune response. In this review we discuss a possible inter-relationship between olfactory impairment, autoimmunity and neurological/psychiatric symptoms in several diseases affecting the central nervous system (CNS) such as Parkinson, Alzheimer's disease, autism, schizophrenia, multiple sclerosis and neuropsychiatric lupus erythematosus. We suggest that common manifestations are not mere coincidences. Current data from animal models show that neuropsychiatric manifestations are intimately associated with smell impairment, and autoimmune dysregulation, via autoantibodies (anti-NMDAR, anti-ribosomal P) or other mechanisms. From clues of pathological manifestations, we propose a novel approach to the understanding of the interactions between the CNS, the smell and the immune system.

Coexistence of the antiphospholipid syndrome and abdominal aortic aneurysm.

The antiphospholipid syndrome is characterized by recurrent fetal loss, venous and/or arterial thrombosis, and thrombocytopenia associated with elevated titers of lupus anticoagulant and anticardiolipin antibodies. Although thrombosis is the characteristic vascular involvement in APS, the development of vascular aneurysms in patients with APS has been reported. We describe four patients with established APS who developed abdominal aortic aneurysm, and review the literature on previous published cases of arterial aneurysms developing in patients with APS. In addition, we discuss the possible pathophysiological association between APS and the development of this vascular abnormality.

Autoantibodies against protective molecules--C1q, C-reactive protein, serum amyloid P, mannose-binding lectin, and apolipoprotein A1: prevalence in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of several autoantibodies. Among the multiple factors involved in SLE development, apoptotic defects and impaired clearance of cellular debris have gained considerable interest, as they contribute to autoantigen overload. Several molecules of the innate immunity, also participate in the removal of damaged and apoptotic cells. Among them are C1q, C-reactive protein (CRP), serum amyloid P protein (SAP), mannose-binding lectin (MBL), and apolipoprotein A1 (APO A1). To evaluate the prevalence of autoantibodies against CRP, SAP, MBL, APO A1, and C1q among SLE patients, and their relationship with disease activity, a total of 150 SLE patients were screened for the presence of elevated antibody titers against C1q, CRP, SAP, MBL, and APO A1, utilizing the enzyme-linked immunosorbent assay (ELISA) method. Disease activity was assessed using the ECLAM or SLEDAI scores. The study population comprised two groups of patients: 100 patients with quiescent disease (median ECLAM score 2) comprised the first group, and 50 patients with active disease (median SLEDAI score 16) comprised group 2. Elevated titers of anti-CRP antibodies were significantly elevated only in group 1 (10% versus 4% of controls). Antibodies against SAP were evaluated only among patients in group 1, and were found at a significant high prevalence (20%). Elevated titers of anti-MBL antibodies were significantly elevated only in group 1 (15% versus 3.6%); and antibodies directed against APO A1 were significantly elevated in 21% of group 1, and 50% of group 2 patients. Elevated titers of anti-C1q were evaluated only in group 2, and were found at a significant prevalence of 66%. Significant correlation with disease activity was found only for anti-APO A1 antibodies, and only in group 1. Several patients harbored more than one of the autoantibodies tested. In patients with SLE, autoantibodies directed against protective molecules, that is, acute-phase proteins involved in the disposal of cellular and nuclear debris, can be detected. These autoantibodies may play a pathogenic role in the development or perpetuation of autoimmunity in SLE.

Colchicine-induced rhabdomyolysis.

A case of colchicine-induced rhabdomyolysis is reported. A 79-year-old man with ischemic heart disease, chronic atrial fibrillation, chronic renal failure, hypothyroidism, and gout arthritis was hospitalized because of fatigue, myalgia, and leg weakness, shortly after starting treatment with colchicine. Investigation confirmed the diagnosis of rhabdomyolysis, and discontinuation of colchicine resulted in resolution of clinical and biochemical features of rhabdomylysis. Colchicine-induced rhabdomyolysis is a rare complication, and the postulated mechanisms and risk factors for this severe complication are discussed.

Nonmyeloablative conditioning does not prevent telomere shortening after allogeneic stem cell transplantation.

BACKGROUND: Stem cell transplantation (SCT) may be associated with premature aging of the hematopoietic stem cells. Telomere length reflects the proliferative history of a cell. In most studies published so far on telomere dynamics after myeloablative allogeneic SCT, recipients had shorter telomeres than their respective donors, thus reflecting "accelerated aging" of hematopoietic cells. We evaluated telomere dynamics in patients who underwent transplantation with nonmyeloablative protocols, assuming that the decreased intensity of chemotherapy might prevent telomere attrition. METHODS: Telomere length was measured using FISH-FACS method. Telomeres of recipients were compared to their respective donors. Twenty-three consecutive patients after nonmyeloablative SCT were evaluated. A control group consisted of 10 donor-recipient pairs after conventional myeloablative transplantation. RESULTS: There was significant telomere shortening in both recipients of nonmyeloablative and myeloablative conditioning (0.487+/-0.65 kb, P=0.003; 0.361+/-0.50 kb, P=0.047 respectively). The extent of telomere shortening in the two groups was not different (P=0.64). There was no correlation between the degree of shortening and parameters such as time interval from transplant, age of donor or recipient, and the number of infused cells. CONCLUSIONS: This is the first study on telomere dynamics after nonmyeloablative conditioning SCT. The study demonstrates significant shortening of telomeres in recipients in spite of decreased intensity conditioning. Results of this study suggest that the main mechanism following transplantation is the proliferative stress imposed upon the stem cells and not direct damage by cytotoxic drugs. The different kinetics of restoration of hematopoiesis and the probable ongoing process of graft-versus-leukemia in the bone marrow do not prevent the attrition of telomeric ends of chromosomes.

Coexistence of thyroid autoimmunity with other autoimmune diseases: friend or foe? Additional aspects on the mosaic of autoimmunity.

Autoimmunity encompasses a wide spectrum of diseases from organ-specific diseases like Hashimoto thyroiditis, to systemic diseases such as systemic lupus erythematosus. These diseases are characterized by inflammation and the production of a wide range of autoantibodies directed against multiple autoantigens. Although their etiology is still poorly understood, genetic, immunological, hormonal, and environmental factors are major predisposing and triggering factors. These multiple factors, like pieces in a mosaic, may interplay in different forms, leading to the expression of various autoimmune manifestations and diseases. This phenomenon, which has been referred by us as the "mosaic of autoimmunity", illuminates the diversity of autoimmune manifestations among susceptible individuals. From this theoretical framework we conducted a wide search of the literature, on the prevalence of thyroid autoimmunity, the commonest of the autoimmune conditions, among other autoimmune diseases, and discuss the possible clinical significance of this association.

The neuroendocrine-immune interactions in systemic lupus erythematosus: a basis for understanding disease pathogenesis and complexity.

Much progress has been made in the understanding of the impact of the neuroendocrine immune interactions and the pathogenic role in systemic lupus erythematosus, clinically and at the molecular level. This article focuses on the intertwining networks that involve the hypothalamic-pituitary-adrenal axis, cytokines within the central nervous system, and the sympathetic system. Hormones (estrogen, prolactin, gonadotropin-releasing hormone, and leptin) play an important role as immunomodulatory agents.

Systemic thromboembolism in inflammatory bowel disease: mechanisms and clinical applications.

Systemic thromboembolism is an extraintestinal manifestation of inflammatory bowel disease (IBD), and an important cause of patient morbidity and mortality. The underlying basis for the hypercoagulable state in IBD is complex, and involves altered activity of all three components that govern hemostasis: platelets, fibrinolysis, and the coagulation cascade. Currently, there are no distinct guidelines for treating or preventing thromboembolic (TE) events in IBD patients compared with the general population. However, the prothrombotic state in IBD stems, at least in part, from several modifiable factors, such as hyperhomocysteinemia and an active inflammatory state. In this review we summarize the mechanisms that favor thrombosis in IBD, and the principles that need to be applied for the primary and secondary prevention of TE in this selected group of patients.

The effect of chemotherapy on telomere dynamics: clinical results and possible mechanisms.

Telomeres are the chromosomal end components, and their length in hematopoietic stem cells correlates with the bone marrow proliferative reserve. There are few data regarding telomere dynamics in hematopoietic stem cells after exposure to chemotherapy. We show that the attrition of telomeres after cytotoxic treatment correlates with the intensity of chemotherapy. Using cytotoxic drugs with differential effects on hematopoietic stem cells, our data imply that chemotherapy-induced telomere shortening results from direct damage to hematopoietic stem cells and/or the induction of proliferative stress on bone marrow while sparing repopulating stem cells. These results gain importance considering the current long survival of patients with cancer.