Challenging Organizational Factors Associated With Admission Delay to Intensive Care Unit-A Novel Quality Indicator.

BACKGROUND: Delays in admitting patients to the intensive care unit (ICU) can defer the timely initiation of life-sustaining therapies and invasive monitoring, jeopardizing the success of the treatment. Nevertheless, the availability of research on interventions that reduce or minimize admission delays is limited. OBJECTIVES: The current study aimed to assess the factors related to delays in admission times of critically ill patients transferred to the ICU. METHODS: A software was designed to follow-up, compare and measure the defined intervals of the time to admission, implemented at the ICU for 6 months. Measurements included 5 time intervals, referral department, and work shift at admission. Data from 1004 patients admitted to the ICU between July 2017 and January 2020 were analyzed in a retrospective observational study. RESULTS: Precisely, 53.9% of total patients were referred from the hospital emergency department, and 44% were admitted during the evening shift. Significant differences were found in time intervals between shifts, showing the morning round had the longer total admission time (median: 67.8 min). Analysis showed that admission time was longer at times of full capacity compared to times of available bed (mean: 56.4 and 40.2 min, respectively; U = 68,722, p < .05). Findings demonstrated a significant shortening of time to admission after implementing a new time monitoring software by the Institutional Quality Control Commission (U = 5072, p < .001). CONCLUSIONS: Our study opens doors for potential studies on applying effective initiatives in critical care settings to improve patient care and outcomes. Additionally, it generates new insights regarding how clinicians and nursing teams can jointly develop and promote multidisciplinary interventions in intensive care work environments.

Impact in total ischemic time and ST-segment elevation myocardial infarction admissions during COVID-19.

BACKGROUND: Despite the COVID-19 pandemic, cardiovascular disease is still the main cause of death in developed countries. Of these deaths, acute coronary syndromes (ACS) account for a substantial percentage of deaths. Improvement in ACS outcomes, are achieved by reducing the time from symptom onset until reperfusion or total ischemic time (TIT). Nevertheless, due to the overwhelming reality at the beginning of the pandemic, acute coronary syndrome (ACS) care may have been compromised. OBJECTIVES: We evaluated delays in TIT based on the date and timing of admissions in patients with STEMI, by a timeline follow-up form, before and during the current COVID-19 pandemic. METHODS: Between July 2018 and June 2020, two hundred and twelve patients diagnosed with ST-segment elevation myocardial infarction (STEMI) were admitted to our medical center. Upon presentation, cases were assigned a timeline report sheet and each time interval, from onset of symptoms to the catheterization lab, was documented. The information was later evaluated to study potential excessive delays throughout ACS management. RESULTS: Our data evidenced that during the COVID-19 pandemic ACS admissions were reduced by 34.54%, in addition to several in-hospital delays in patient's ACS management including delays in door-to-ECG time (9.43 ± 18.21 vs. 18.41 ± 28.34, p = 0.029), ECG-to-balloon (58.25 ± 22.59 vs. 74.39 ± 50.30, p = 0.004) and door-to-balloon time (57.41 ± 27.52 vs. 69.31 ± 54.14, p = 0.04). CONCLUSIONS: During the pandemic a reduction in ACS admissions occurred in our hospital that accompanied with longer in-hospital TIT due to additional tests, triage, protocols to protect and prevent infection within hospital staff, and maintenance of adequate standards of care. However, door-to-balloon time was maintained under 90 min.

Prevalence of Classic and Non-Classic Antiphospholipid Antibodies in Multiple Sclerosis.

BACKGROUND: The association between antiphospholipid antibodies (aPL) and multiple sclerosis (MS) has been suggested previously, but prior studies provided contradicting findings. OBJECTIVES: To characterize the expression profile of eight classic and non-classic aPL in patients diagnosed with MS. METHODS: Using the BioPlex 2200 immunoassay, we measured the levels of serum immunoglobulin (Ig)M and IgG isotypes of three classic aPL and five non-classic aPL in 98 subjects with MS and 237 healthy controls. RESULTS: Three non-classic aPL were significantly more prevalent among MS patients in comparison to the control group. These antibodies included IgM and IgG against phosphatidylserine-ß2GPI (PS-B2), IgG prothrombin complex (PT-PT) and IgM prothrombin (PT). The positive results according to Bonferroni correction are PS-B2 IgG and PT-PT IgG. The remaining aPL profiles did not differ significantly between the two groups. CONCLUSIONS: An association between certain non-classic aPL and MS has been established. The specific role of these autoantibodies in the pathogenesis of the condition remains uncertain.

Early operative intervention is associated with better patient survival in patients with intracapsular femur fractures but not extracapsular fractures.

The purpose of this study was to determine patients' survival after undergoing an early or delayed operation. We retrospectively assessed 1849 files of patients operated for proximal femoral fracture, divided into two diagnostic groups: intracapsular (n = 640) and extracapsular (n = 1209). 1163 (63%) were treated within 48 h from hospital admission and 686 (37%) were treated >48 h afterwards. Delayed operation in patients with intracapsular fractures was associated with a 1.8-fold excess risk for 1-year mortality (HR = 1.83, P = 0.008), while no effect was observed for patients with extracapsular fractures. Males had a higher HR for mortality in both diagnostic groups. Early surgical intervention is beneficial for intra-capsular femoral fractures; male gender and a high ASA score are associated with an increased mortality hazard risk.

Assessment of Predictors for SARS-CoV-2 Antibodies Decline Rate in Health Care Workers after BNT162b2 Vaccination-Results from a Serological Survey.

Background: SARS-CoV-2 is a novel human pathogen causing Coronavirus Disease 2019 that has caused widespread global mortality and morbidity. Since health workers in Israel were among the first to be vaccinated, we had a unique opportunity to investigate the post-vaccination level of IgG anti-S levels antibodies (Abs) and their dynamics by demographic and professional factors. Methods: Prospective Serological Survey during December 2020−August 2021 at Barzilai Medical Center among 458 health care workers (HCW) followed for 6 months after the second BNT162b2 vaccine dose. Results: Antibody levels before the second dose, and 30, 90 and 180 days after were 57.1 ± 29.2, 223 ± 70.2, 172.8 ± 73.3 and 166.4 ± 100.7 AU/mL, respectively. From GEE analysis, females had higher Abs levels (ß = 26.37 AU/mL, p = 0.002). Age was negatively associated with Abs, with a 1.17 AU/mL decrease for each additional year (p < 0.001). Direct contact with patients was associated with lower Abs by 25.02 AU/mL (p = 0.009) compared to working with no such contact. The average decline rate overall for the study period was 3.0 ± 2.9 AU/mL per week without differences by demographic parameters and was faster during the first 3 months after vaccination than in the subsequent 3 months. Conclusions: All demographic groups experienced a decline in Abs over time, faster during the first 3 months. Findings of overall Abs lower in males, workers with direct contact with patients, and older workers, should be considered for policy-making about choosing priority populations for additional vaccine doses in hospital settings.

Anti-cardiolipin antibodies and endothelial function in patients with coronary artery disease.

Endothelial dysfunction is considered an important marker in atherosclerosis, having a prognostic value. Antiphospholipid antibodies are considered prothrombotic and have recently been reported to be associated also with atherosclerosis. This study was conducted to investigate a possible association of endothelial dysfunction with various antiphospholipid autoantibodies in healthy subjects and patients with cardiovascular disease. In a single-center, prospective study, 2 groups were included. The study group included patients with cardiovascular diseases (coronary disease and/or cerebrovascular disease) and healthy subjects without apparent heart disease who were referred to the endothelial function laboratory for the assessment of endothelial function. Flow-mediated dilatation, which indicates endothelial function, and nitroglycerin-mediated vasodilatation, which indicates smooth-muscle function, were measured. The 2 groups were evaluated for autoantibodies, including anticardiolipin (aCL; immunoglobulin G [IgG], immunoglobulin M [IgM], and immunoglobulin A [IgA]), antinuclear antibody, anti-beta2-glycoprotein I (IgG, IgM, and IgA), and oxidized low-density lipoprotein. One hundred seven subjects were included in the study: 45 patients (42%) and 62 healthy controls (58%). Flow-mediated dilatation was significantly lower in patients compared with healthy controls (8.0 +/- 9.5% vs 8.0 +/- 13.5%, p = 0.012). In addition, nitroglycerin-mediated vasodilatation was nonsignificantly lower in patients than in healthy controls (8.0 +/- 13.4% vs 11.0 +/- 16.7%, p = 0.084). The mean levels of anti-beta2-glycoprotein I (IgG, IgM, and IgA), aCL (IgM and IgA), antinuclear antibody, and oxidized low-density lipoprotein were not different between groups. However, the mean level of IgG aCL was significantly higher in patients than in healthy controls. In conclusion, in accordance with previous reports of an association between aCL and atherosclerosis, patients with cardiovascular disease had endothelial dysfunction and elevated levels of aCL.

Physical examination and ECG screening in relation to echocardiography findings in young healthy adults.

BACKGROUND AND AIMS: Cardiovascular screening in young adults is an important tool in many occupational settings. Our aim was to test whether screening physical examination and ECG influence the rate of abnormal echocardiogarphic findings in young healthy subjects. METHODS: Consecutive echocardiography results of 18- to 20-year-old flight candidates were analyzed retrospectively. Echocardiographies were performed as part of a screening protocol, which includes ECG, physical examination and referral for echocardiography for any positive finding. A second stage includes universal echocardiography for all candidates. RESULTS: 1,066 subjects were evaluated; 489 subjects underwent echocardiography following referral because of abnormal auscultatory or ECG findings. Findings (mostly mild valvular insufficiencies) were demonstrated in 12.7%, with only 0.6% of subjects disqualified. In subjects who underwent universal echocardiography (n = 577), findings (mostly mild valvular insufficiencies) were detected in 18%, with only 0.5% of subjects disqualified. CONCLUSIONS: The rate of significant echocardiography findings is extremely low in this young and healthy population. The presence of abnormal findings on either physical examination or ECG screening was not demonstrated to alter the rate of abnormal echocardiographic findings. We suggest that the low yield of screening should be weighed against the cost of an unidentified congenital cardiac lesion in the specific setting.

Low dose intravenous immunoglobulin in systemic lupus erythematosus: analysis of 62 cases.

BACKGROUND: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations that cannot always be regulated by steroids and immunosuppressive therapy. Intravenous immunoglobulin is an optional immunomodulatory agent for the treatment of SLE, but the appropriate indications for its use, duration of therapy and recommended dosage are yet to be established. In SLE patients, most publications report the utilization of a high dose (2 g/kg body weight) protocol. OBJECTIVES: To investigate whether lower doses of IVIg are beneficial for SLE patients. METHODS: We retrospectively analyzed the medical records of 62 patients who received low dose IVIg (approximately 0.5 g/kg body weight). RESULTS: The treatment was associated with clinical improvement in many specific disease manifestations, along with a continuous decrease in SLEDAI scores (SLE Disease Activity Index). However, thrombocytopenia, alopecia and vasculitis did not improve following IVIg therapy. CONCLUSIONS: Low dose IVIg is a possible therapeutic option in SLE and is associated with lower cost than the high dose regimen and possibly fewer adverse effects.

A latitudinal gradient study of common anti-infectious agent antibody prevalence in Italy and Colombia.

BACKGROUND: Infectious agents are important in the pathogenesis of autoimmune disease since they are a major part of the environmental trigger of autoimmunity. A negative relationship between latitude and infectious disease species richness has been suggested. OBJECTIVES: To examine whether their prevalence differs in two latitudinally different populations. METHODS: The prevalence of infections with Toxoplasma gondii, rubella virus, cytomegalovirus, Epstein-Barr virus and Treponema pallidum was compared between subjects from Italy and Colombia. RESULTS: We found high titers of antibodies against four of five microorganisms tested, Toxoplasma gondii (50.8%), rubella virus (German measles) (75%), cytomegalovirus (86.3%), Epstein-Barr virus (83.3%) and Treponema pallidum (6.3%) in completely healthy individuals from a tropical country (Colombia) and a European country (Italy). Differences between two groups of volunteers were noted regarding two infectious agents. The prevalence of immunoglobulin G anti-rubella antibodies was significantly higher among Italian subjects (85% vs. 67.9%, P = 0.002), whereas antibodies against CMV were less prevalent among Italian as compared to Colombian subjects (77% vs. 92.9%, P < 0.001). CONCLUSIONS: These differences might also result in a different tendency towards development of autoimmune diseases associated with these infectious agents in different populations.

Safety of intravenous immunoglobulin (IVIG) therapy.

Intravenous immunoglobulin (IVIg) is administered both for the treatment of immunodeficiencies and for an expanding list of autoimmune diseases. Most adverse effects are mild and transient including headaches, flushing, fever, chills, fatigue, nausea, diarrhea, blood pressure changes and tachycardia. IgA deficiency-related anaphylactic reactions are largely preventable. Late adverse events are rare and include acute renal failure and thromboembolic events. Acute renal failure, usually oliguric and transient, occurs generally in insufficiently hydrated patients and with sucrose-stabilized products due to osmotic injury. Thromboembolic complications occur due to hyperviscosity especially in patients having risk factors including advanced age, previous thromboembolic events, immobilization, diabetes mellitus, hypertension, dyslipidemia or those receiving high-dose IVIg in a rapid infusion rate or excessive dose. Slow infusion rate and good hydration may prevent renal failure, thromboembolic events and aseptic meningitis. In our experience in more than 200 patients receiving IVIg for different autoimmune diseases and near 10000 infusions for relapsing-remitting multiple sclerosis patients, the occurrence of adverse effects was 24-36% after high dose IVIg, most were headaches and all were mild adverse events. We conclude that IVIg is a safe therapy when given in a slow infusion rate in well-hydrated patients, better avoiding patients with known risk factors.

The fine-tuning of anti-oxidized low-density lipoprotein antibodies in cardiovascular disease and thrombosis.

Anti-oxidised low-density lipoprotein (anti-oxLDL) antibodies are a heterogeneous group of autoantibodies including both pathogenic and protective subsets. Whereas in most studies the levels of anti-oxLDL antibodies were associated with enhanced atherosclerosis as evaluated by different methods, immunization with oxLDL leads to elevated levels of anti-oxLDL and protection against atherosclerosis. Anti-oxLDL can also be used for immunomodulation of atherosclerosis (i.e. possible therapeutic use of intravenous immunoglobulin, oral tolerance). More specific autoantibodies out of total anti-oxLDL should be selected, for instance, anti-oxLDL/beta-2-glycoprotein I complex, hence defining the fine-tuning of anti-oxLDL antibodies might detect which autoantibodies are pathogenic and which can be used therapeutically.

Precocious atherosclerosis in rheumatoid arthritis: role of traditional and disease-related cardiovascular risk factors.

The risk of cardiovascular (CV) disease increases in patients with rheumatoid arthritis (RA). This is due to a number of different triggers including traditional and disease-related factors. Among established risk factors for CV disease, smoking may exert a more dangerous effect on arterial wall in RA than in the general population by a synergic effect with inflammatory processes of the disease. Although persistent inflammation and immune dysregulation of RA may contribute to favor other well-known CV risk factors, such as dyslipidemia, it is now clear that the disease itself represents an independent risk factor for CV disease by the action of RA chronic inflammatory process as well as humoral and cell-mediated immune mechanisms. There is evidence that CV risk is associated with severity and extension of the disease and it is of interest the fact that the presence of circulating anticyclic citrullinated peptide antibodies appears to be associated with stronger evidence of subclinical atherosclerosis in RA.

Early atherosclerosis and autoantibodies to heat-shock proteins and oxidized LDL in systemic sclerosis.

Autoimmune diseases are characterized by enhanced atherosclerosis. Humoral immune responses to mycobacterial HSP-65, human HSP-60, and to oxLDL have been established in a number of human autoimmune diseases and are considered to be associated with atherosclerosis. The aim of this study was to evaluate carotid artery intima-media thickness (IMT) in patients having systemic sclerosis (SSc) and to find out whether early atherosclerosis is associated with these autoantibodies. Forty-four patients having SSc underwent clinical evaluation and carotid artery IMT measurement. Several autoantibodies were tested among patients and a control group. The antibodies against human HSP-60 were measured by antihuman (IgG/IgM) HSP-60 ELISA kit. IgGs and IgMs antimycobacterial HSP-65 were determined using an ELISA with mycobacterial recombinant HSP-65 antigens. Similarly, anti-oxLDL antibodies were measured by an ELISA kit. Abnormal IMT levels were significantly more common in SSc patients compared with control subjects. Age was found as the sole most significant clinical parameter associated with carotid artery IMT in SSc. Disease duration, type of SSc, lung function tests, and cardiovascular risk factors were not associated with IMT in these patients. Levels of HSP-60, HSP-65, and oxLDL autoantibodies were similar among patients compared with controls, and in patients having "positive" IgM anti-HSP-65, higher IMT values were found. Abnormal carotid IMT is more prevalent in SSc than in normal subjects. Age rather than other clinical parameters is associated with early atherosclerotic changes in SSc. Autoantibodies to oxLDL, HSP-60, and HSP-65 are not elevated in SSc and there is only a borderline association with carotid artery IMT.

Heat-shock protein 65 autoantibodies are differently associated with early atherosclerosis in rheumatoid arthritis and in healthy subjects.

The aim of this study was to examine whether heat-shock protein (HSP)-65 autoantibodies are associated with early atherosclerosis in rheumatoid arthritis (RA). Intima-media thickness (IMT) was measured in the carotid arteries of 100 RA patients and 69 control subjects. The IMT was evaluated on both carotid arteries in the common carotid, bifurcation, and internal arteries. Every patient underwent anti-HSP-65 antibody evaluation. Anti-HSP-65 antibodies were not more prevalent among patients compared with controls. Among controls, patients having "positive" anti-HSP-65 tended to have increased carotid artery IMT compared with "negative" patients, whereas among RA patients the opposite association was noted, and positive patients had significantly decreased carotid bifurcation IMT than negative patients without elevated levels of anti-HSP-65. As opposed to the association with cardiovascular diseases and atherosclerosis of anti-HSPs in the general population, among RA patients anti-HSP-65 cannot be regarded as associated with early atherosclerosis.

Antiphospholipid syndrome (APS): where does it come from?

The antiphospholipid syndrome (APS) is the most common acquired thrombophilia. It is characterized by venous and arterial thrombosis, recurrent pregnancy loss, and various other clinical manifestations in the presence of antiphospholipid antibodies (aPL). Like other autoimmune diseases, the etiology of APS derives from a combination of genetic and environmental factors. The most significant environmental factors in APS are infectious agents, followed by trauma and drugs. Infections can induce aPL and, in the catastrophic variant of APS, about one-third of cases are associated with a clear recent infection. On their formation, aPL have been clearly shown to be pathogenic, because they influence all arms of the coagulation system and because passive transfer and active immunization protocols have demonstrated. Therefore, in a genetically susceptible individual, exposure to one or more infectious agent can cause a molecular mimicry and result in the production of pathogenic aPL that can induce thrombosis and pregnancy loss. Identification of the epitopes within the beta-2-glycoprotein-I molecule that serves as the target for autoantibodies makes them the target for immunomodulation of the syndrome.

Outcome of patients having dermatomyositis admitted to the intensive care unit.

Patients having systemic rheumatic diseases constitute a small percentage of admissions to the medical intensive care units (ICUs). Dermatomyositis (DM) is one of the rheumatic diseases that have secondary complications that may lead to a critical illness requiring hospitalization in the ICU. Herein, we present the features, clinical course, and outcome of critically ill patients having DM who were admitted to the ICU. The medical records of six DM patients admitted to the ICU in a large tertiary hospital in a 12-year period were reviewed. The mean age of patients at time of admission to the ICU was 38 (range 16-37). Mean disease duration from diagnosis to admission to the ICU was 1.6 years (range 1 month-8 years), while the main reason for admission to the ICU was acute respiratory failure. Two of six patients died during the hospitalization. The main causes of death were respiratory complications and sepsis. The outcome of DM patients admitted to the ICU was generally not different from the outcome of other patients hospitalized in the ICU. The main reason for hospitalization was acute respiratory failure. As there are many reasons for respiratory failure in DM, an early diagnosis and aggressive appropriate treatment may help to further reduce the mortality in these patients.

The association of endothelial dysfunction and cardiovascular events in healthy subjects and patients with cardiovascular disease.

BACKGROUND: Endothelial dysfunction is recognized as a major factor in the development of atherosclerosis and it has a prognostic value. OBJECTIVES: To detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects and patients with cardiovascular disease. METHODS: We prospectively assessed brachial artery flow-mediated dilatation in 110 consecutive subjects (46 CVD patients and 64 healthy controls), mean age 57 +/- 11 years; 68 were men. After an overnight fast and discontinuation of all medications for > or = 12 hours, percent improvement in FMD and nitroglycerin-mediated vasodilatation were assessed using high resolution ultrasound. RESULTS: %FMD but not %NTG was significantly lower in CVD patients (9.5 +/- 8.0% vs. 13.5 +/- 8.0%, P = 0.012) compared to healthy controls (13.4 +/- 8.0% vs. 16.7 +/- 11.0%, P = 0.084; respectively). In addition, an inverse correlation between %FMD and the number of traditional CVD risk factors was found among all study participants (r = -0.23, P = 0.015) and healthy controls (r = -0.23, P = 0.036). In a mean follow-up of 15 +/- 2 months, the composite CVD endpoints (all-cause mortality, myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions) were significantly more common in subjects with FMD < 6% compared to subjects with FMD > 6% (33.3% vs. 12.1%, P < 0.03, respectively). CONCLUSIONS: Thus, brachial artery %FMD provides important prognostic information in addition to that derived from traditional risk factor assessment.

Tobacco smoking and autoimmune rheumatic diseases.

Autoimmune rheumatic diseases are considered to be influenced by both genetic and environmental factors. Tobacco smoking has been linked to the development of rheumatic diseases, namely systemic lupus erythematosus and rheumatoid arthritis, and has been shown to interact with genetic factors to create a significant combined risk of disease. Smoking also affects both the course and the outcome of rheumatic diseases. Smoking increases the risk of dermatologic features and nephritis in systemic lupus erythematosus, rheumatoid nodules and multiple joint involvement in rheumatoid arthritis and digital ischemia in systemic sclerosis, as well as further increasing the risk of accelerated atherosclerosis in these diseases. Smoking is known to modulate the immune system through many mechanisms, including the induction of the inflammatory response, immune suppression, alteration of cytokine balance, induction of apoptosis, and DNA damage that results in the formation of anti-DNA antibodies. No sole mechanism, however, has been linked to any of the autoimmune illnesses, which therefore complicates full comprehension of the 'smoking effect'. Further studies, perhaps using animal models, are needed to analyze the exact effect of smoking on each disease separately.

Intravenous immunoglobulin for immunomodulation of systemic lupus erythematosus.

Intravenous immunoglobulin (IVIg) is used for replacement therapy in immunodeficiency states and for immunomodulation of various autoimmune diseases. Several case reports and series support a beneficial role of IVIg in systemic lupus erythematosus (SLE), both as salvage immunotherapy and in control of disease activity in general and amelioration of classical disease manifestations. Further, lupus nephritis can also be treated usually successfully with IVIg. A few questions remain unanswered as to the appropriate therapeutic dosage and the clinical manifestations that can be best treated with IVIg.

The infectious etiology of the antiphospholipid syndrome: links between infection and autoimmunity.

Like many other autoimmune diseases, the antiphospholipid syndrome (APS) is considered as of a multifactorial etiology, mainly genetic susceptibility coinciding with environmental triggers, of which infectious agents are considered most prominent. Different clinical and experimental studies of the beta2 glycoprotein I (beta 2 GPI) molecule, one of the target autoantigens in APS, have linked infection to the development of APS. Using a peptide phage library, it has been shown that target epitopes of beta 2 GPI share similarities with common infectious pathogens. Also, circulating anti-beta 2 GPI antibodies have been identified in the sera of patients with different infectious conditions, and have been associated with various clinical APS manifestations. Molecular mimicry as a key mechanism linking infection and APS has been demonstrated in experimental models. In these studies, APS was induced by immunization of mice to various microbial pathogens. Anti-beta 2 GPI titers were found to be especially high following immunization with Haemophilus influenzae, Neisseria gonorrheae or tetanus toxoid. These findings contribute greatly to the understanding of APS pathogenesis, as well as create new directions for therapy modalities, namely specific peptide toleragens and antimicrobial treatment.