The Role of Platelet Function Analyzer Testing in Cardiac Surgery Transfusion Management.

BACKGROUND: Identifying high-risk patients for transfusion after cardiac operations would alter postoperative management. The aim of this study was to investigate closure time (CT) measured by platelet function analyzer (PFA) for prediction of bleeding and transfusions. METHODS: 66 patients were scheduled for coronary artery bypass graft (CABG) surgery and 30 patients for valve repair and replacement (non-CABG). Measurements of PFA-100® CT for collagen and adenosine diphosphate (cADP) and collagen and epinephrine (cEPI) were performed 15 min after protamine administration. Blood loss was measured, and the amount of transfusion products was recorded postoperatively. RESULTS: The study demonstrated significant differences between CABG patients with cADP-CT ≥ 118 s and those with cADP-CT < 118 s with regard to blood loss for 24 h (p = 0.001) and blood loss for 25-48 h (p = 0.003) as well as fresh frozen plasma (p = 0.015), platelet (p > 0.001) and red blood cell (p = 0.002) units given in 48 postoperative h. There were no differences cardiopulmonary bypass when was applied. In non-CABG patients, there were no differences in blood loss and transfusion requirements with respect to cADP-CT and cEPI-CT. CONCLUSION: Postoperative platelet dysfunction measured by a prolonged cADP-CT was significant predictor of blood loss and transfusion in CABG patients.

Extremely rare coincidence of non-radiographic axial spondyloarthropathy HLA-B27 positive and Stiff Person Syndrome--rheumatologist point of view.

Stiff Person Syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive stiffness and rigidity of truncal muscles accompanied with co-contraction of agonist-antagonist muscles. Our 51-year-old female patient was presented for the first time to physiatrists in 2006 and diagnosed with axial-spondyloarthropathy (SpA) HLA-B27 positive. SPS was diagnosed 7 years after initial symptoms. SPS should be taken into consideration in HLA-B27 positive patients if stiffness of paravertebral and abdominal muscles progresses during SpA therapy.

[Sex hormones, immune disorders, and inflammatory rheumatic diseases]. / Spolni hormoni, imunoloski poremecaji i upalne reumatske bolesti.

It is a well-documented fact that sex hormones are implicated in the immune response and that androgens and estrogens modulate susceptibility and progression of autoimmune rheumatic diseases. Estrogens are considered to stimulate cell proliferation and humoral immune responses while androgens exert suppressive effects on both humoral and cellular immune responses. Autoimmune diseases are common in females, especially during the generative period, the most representative of estrogen-related autoimmune diseases being systemic lupus erythematosus. Estrogens and androgens are involved in the pathogenesis of the disease; both exogenous and endogenous estrogens are strong stimulators of cytokine production and disease activity. Some physiological conditions, as well as some drugs and chronic stress, can modulate hormone levels. Low levels of gonadal androgens have been detected in body fluids of both male and female rheumatoid arthritis patients, supporting the possibility of the pathogenic role for decreased androgen levels. Views on hormone replacement therapy or hormonal contraception in rheumatic diseases have been modified and in most rheumatic diseases, including rheumatoid arthritis, hormones are not prohibited. There are still controversies regarding systemic lupus; the new standpoint being that hormonal contraception is not contraindicated in women with inactive or stable active SLE, except for those with positive antiphospholipid antibodies.

The Odds of One-Year Mortality in Bedridden Geriatric Patients Discharged from Acute Rehabilitation Ward Are Increased Eightfold If the Patients Have Three or More Complications.

Low muscle strength, functional score at discharge, and complications during a ten-day rehabilitation hospital stay can affect mortality rates in bedridden geriatric patients. This was a prospective observational study in a cohort of 105 bedridden geriatric patients admitted to the Rehabilitation ward after a major illness or surgery. All participants had a severe dependency on another person (Barthel's Index < 60). The one-year mortality rate in this cohort was 15.2%, with further subdivision according to the number of complications: 61.5% in patients with ≥3 complications during hospitalization, 17.6% in patients with two complications, 9.5% with one complication, and 3% in patients with no complications. The Barthel Index at discharge (OR = 0.95; p = 0.003) and ≥3 medical complications (OR = 8.33; p = 0.005) during rehabilitation ward stay were significant predictors for one-year mortality. The odds of one-year mortality after discharge increased eightfold in patients with ≥3 medical complications. Sarcopenia, age, and sex were not significant predictors of mortality in this cohort. The 10-day acute rehabilitation was too short to achieve progress from severe to moderate independence in 60% of patients. The Barthel Index at discharge and a number of complications affect the mortality rate. These findings provide valuable insights into the complex dynamics of mortality and functional outcomes in bedridden geriatric patients.

[Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitides]. / Vaskulitisi povezani s antineutrofilnim citoplazmatskim protutijelima (ANCA).

The anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are a group of uncommon diseases characterised by inflammatory cell infiltration and necrosis of blood vessel walls. ANCA there has been considerable progress towards understanding their pathogenesis. This results in endothelial activation with increased transmigration and adherence of neutrophils to vessel walls. Specific for granulomatosis with polyangiitis are nasal or oral inflammation and development of oral ulcers and purulent or bloody nasal discharge. The chest radiograph usually showed the presence of nodules or fixed infiltrates. Microscopic polyangiitis affects the smallest blood vessels and may also affect medium-sized vessels, demonstrates the tropism for the kidneys--glomerulonephritis and lungs--pulmonary capillaritis. The characteristic features of eosinophilic granulomatosis with polyangiitis are asthma, eosinophilia in peripheral blood, sinusitis and pulmonary infiltrates which may be transient, than mononeuritis multiplex. It is important to differentiate ANCA vasculitis and syndromes that may mimic them, particularly infection, malignancy and connective tissue disease.

[The existence of geographical clusters of rheumatiod arhritis according to their origin in a tertiary care based register]. / Postojanje zemljopisnih klastera reumatoidnog artritisa na osnovu podrijetla prema podacima tercijarnog centra.

The objective was to analyse epidemiological tendencies of rheumatoid arthritis (RA) in Dalmatia County in order to identify possible spatial clusters of RA. Patient-interviewers were trained to administer telephone surveys. 197 RA patients controlled at Rheumatology and immunology department of Clinical hospital of Split were mapped to place of residence by telephone survey. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. Four clusters were identified; the largest one was in the region of Sinj. The female/male ratio was 5.79:1. Majority of RA patients were among age 50 to 59 (30.45 %). The results show inter-regional variations with the marked clusters in the north of Dalmatia suggesting that clusters with higher incidence of RA have specific genetic and environmental background. Prevalence of RA in female was higher than in current literature, while the age of onset 50-59 years is similar with data from recent studies.

Neck Disability Index Detects Higher Neck-Related Disability Levels among Physiotherapists and Family Medicine Specialists than among Dentists.

BACKGROUND: Healthcare workers who are in physical contact with patients are prone to work-related musculoskeletal disorders (WMSDs). Much is known about the prevalence of neck pain, but the extent of disability associated with neck pain among physical therapists (PTs), dentists, and family medicine specialists (FMs) is unknown. METHODS: The prevalence of neck pain and Neck Disability Index (NDI) data were collected from 239 PTs, 103 FMs, 113 dentists, and 112 controls from June to August 2022. RESULTS: The highest prevalence of neck pain was found in FMs (58.3%), followed by dentists (50.4%), PTs (48.5%) and controls (34.8%). The NDI% in PTs and FMs had higher values than controls: 14.6 ± 12.4, p = 0.02 for PTs, 14.9 ± 12.4, p = 0.01 for FMs vs. 10.1 ± 10.1 controls. The dentist group did not differ from controls (11.9 ± 10.2, p = 0.13). Mild, moderate, or severe forms of disability were more common in medical professionals than in controls (44.2%, 9.5%, and 1.5% vs. 37.5%, 7%, and 0%). Dentists were the youngest group with high functionality and the lowest degree of disability, comparable to the control population. Gender or age had no effect on NDI scores in this population. FMs, who represented the oldest group, showed age dependency (eleven years older in higher disability groups). Gender had no effect on NDI. In PTs, females predominated in all disability categories and PTs became five years older with increasing disability level. CONCLUSION: By using NDI in assessing neck-related WMSDs, we can detect medical professionals prone to more serious disability and potentially plan preventive actions.

Prescription Trends of Biologic DMARDs in Treating Rheumatologic Diseases: Changes of Medication Availability in COVID-19.

Biologic disease-modifying antirheumatic drugs (DMARDs) are very effective in treating rheumatic diseases with a good patient tolerance. However, high cost and individualistic approach requires dedication of the physician. Therefore, the aim of this study was to determine how the COVID-19 pandemic has affected the prescription of biologic DMARDs in rheumatology at the University Hospital of Split. The data collection was conducted through an archive search in the Outpatient Clinic for Rheumatology in the University Hospital of Split, Split, Croatia. The search included the period before and after the start of the COVID-19 pandemic in Croatia (31 March 2020). Collected data included age, sex, ICD-10 code of diagnosis, generic and brand name of the prescribed drug, date of therapy initiation, and medication administration route. In the pre-COVID-19 period, 209 patients were processed, while in the COVID-19 period, 185 patients were processed (11.5% fewer). During pre-COVID-19, 231 biologic medications were prescribed, while during COVID-19, 204. During COVID-19, IL-6 inhibitors were less prescribed (48 (21%) vs. 21 (10%) prescriptions, p = 0.003), while IL-17A inhibitors were more prescribed (39 (17%) vs. 61 (30%) prescriptions, p = 0.001). In ankylosing spondylitis (AS), adalimumab was prescribed more during pre-COVID-19 (25 vs. 15 patients, p = 0.010), while ixekizumab was prescribed less (1 vs. 10 patients, p = 0.009). In rheumatoid arthritis, tocilizumab was prescribed more in the pre-COVID-19 period (34 vs. 10 patients, p = 0.012). Overall, the prescription trends of biologic DMARDs for rheumatologic diseases did not vary significantly in the University Hospital of Split, Croatia. Tocilizumab was prescribed less during COVID-19 due to shortages, while ixekizumab was more prescribed during COVID-19 due to an increase in psoriatic arthritis patients processed and due to being approved for treating AS.

Croatian version of the neck disability index can distinguish between acute, chronic and no neck pain : Results of a validation study.

OBJECTIVE: Longitudinal study to test the validity and reliability of the Croatian version of the neck disability index (NDI-CRO) for use in patients. METHODS: Three groups were given NDI-CRO on two occasions, 48 h apart: acute whiplash neck injury group (n = 30), hospital physiotherapists-professional chronic neck pain group (n = 56) and control group (n = 65). To test validity, correlation between NDI-CRO and the pain VAS and PHQ­9 questionnaire for depression was analyzed. Reliability testing was done using the test-retest experiment and item-total score correlation. RESULTS: Test-retest showed excellent correlation in all groups: whiplash 0.86, control 0.95 and physiotherapist 0.89 (Spearman r). Item-total score in the 3 analyzed groups showed positive correlation in all 10 categories, varying from 0.43-0.85. The NDI-CRO score showed significant difference between groups (median whiplash 38%, physiotherapist 12% and control 6%, p < 0.05). Validity testing showed positive correlation between NDI and pain VAS (control r = 0.63, physiotherapist r = 0.68 and whiplash r = 0.83, p < 0.05) and PHQ­9 (control r = 0.49, physiotherapist r = 0.71 and whiplash r = 0.69, p < 0.05). No correlation was found between NDI-CRO and age, gender or radiographic findings. In the whiplash injury group 75% of patients showed moderate to severe disability. The majority of physiotherapists showed mild to moderate disability due to neck pain while 40% showed no disability. In the control group two out of three people reported no disability. CONCLUSION: The NDI-CRO is a valid index for measuring the degree of neck disability in people with acute and chronic neck pain and in control group. It is strongly correlated with pain VAS and PHQ­9 index.

Association of HLA-DRB1 alleles with rheumatoid arthritis in Split-Dalmatia County in southern Croatia.

OBJECTIVE: The aim of this study was to investigate the distribution of HLA-DRB1 alleles in patients with rheumatoid arthritis (RA) in the Sinj Region (SR) and the rest of the Split-Dalmatia County (SDC) in Croatia and to determine their relationship with disease severity. METHODS: A total of 74 RA patients and 80 healthy controls from the SR, and 74 RA patients and 80 healthy controls from the rest of the SDC were genotyped using sequence-specific oligonucleotide primed PCR. High-resolution typing of HLA-DRB1*04 alleles was performed using the single specific primed polymerase chain reaction (PCR-SSP) method. Serum anti-CCP, rheumatoid factor, C­reactive protein, and erythrocyte sedimentation rate were measured in all RA patients, whereas disease activity was assessed by DAS-28 and functional status by the Health Assessment Questionnaire Disability Index. RESULTS: The HLA-DRB1*04 allele was more frequent in patients with RA from the SR than that in patients from the rest of the SDC (18.2% vs. 9.5%; P = 0.014), whereas the HLA-DRB1*15 allele was more frequent in patients with RA from the rest of the SDC than in patients from the SR (16.2% vs. 7.4%; P = 0.010). Shared epitope (SE) positive patients from the SR had significantly higher serum anti-CCP and RF antibody levels (P = 0.014 and P = 0.004, respectively), higher disease activity (P = 0.043), and worse functional status (P < 0.001), than SE-positive patients from the rest of the SDC. CONCLUSION: The observed higher incidence of more severe forms of RA in the SR in comparison to the rest of the SDC might be associated with the higher incidence of HLA-DRB1*04 allele in the SR.

Ultrasound-Verified Peripheral Arthritis in Patients with HLA-B*35 Positive Spondyloarthritis.

BACKGROUND: We aimed to investigate possible association between the HLA-B*35 allele and peripheral arthritis, tenosynovitis and enthesitis. METHODS: Ultrasound of peripheral joints and tendons was performed in 72 HLA-B*35 positive patients with preliminary diagnosis of undifferentiated axial form of spondyloarthitis and joint and tendon pain. Patients with other known types of axial and peripheral spondyloarthritis were excluded as well as patients with other known types of arthritis. RESULTS: Pathological changes were found in the joints of 33 (46%) patients and on the tendons in 13 (18%) patients. The most common ultrasound findings were joint effusion and synovial proliferation with positive power Doppler signal grade 1. The most common ultrasound finding in patients with painful tendons was tenosynovitis. A higher disease activity and an increased incidence of elevated CRP (≥5 mg/L) were more often observed in the group with positive ultrasound findings. CONCLUSION: In this study, we showed that the HLA-B*35 allele could be a potential risk factor for developing peripheral arthritis, but not for tenosynovits and enthesitis in patients with the undifferentiated axial form of spondyloarthritis. This result may influence the follow up of these patients, especially since it gives us an opportunity to consider the use of different types of DMARDs in the treatment of these patients.

The occurrence of sacroiliitis in HLA-B*35-positive patients with undifferentiated spondyloarthritis. A cross sectional MRI study.

OBJECTIVE: To investigate possible association between sacroiliitis and HLA-B*35 positivity. METHOD: After excluding patients with axial spondyloarthritis and HLA-B*27 positivity, psoriasis inflammatory bowel disease, preceding infections, or juvenile type of spondyloarthritis, 110 patients were recruited with a diagnosis of undifferentiated axial spondyloarthritis. All of them had inflammatory back pain of short duration (3 months to 2 years) and 72 were HLA-B*35 positive. In order to determine if there is a possible association of sacroiliitis and HLA-B*35 positivity, all patients underwent MRI of sacroiliac joints. RESULTS: A statistically significant association between the detection of bone marrow edema at sacroiliac joints on MRI and HLA-B*35 positivity (χ2 = 6.25; p = 0.022) was found. A logistic regression analysis revealed that the presence of HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI (OR 6, 95% CI 1.3-27, p = 0.021). HLA-B*35 positivity was also associated with a 4.7 times greater chance of finding elevated CRP (OR 4.7, 95% CI 1-11.9, p = 0.047) and a 5 times greater chance of finding peripheral joint synovitis (OR 5, 95% CI 1.75-14.3, p = 0.003). HLA-B*35-positive patients had high disease activity (mean ± SD of Bath Ankylosing Spondylitis Disease Activity Index 6.1 ± 1.72 and Ankylosing Spondylitis Disease Activity Score C-reactive protein Index 3 ± 0.64) with a high degree of functional limitations (mean ± SD of Bath Ankylosing Spondylitis Functional Index 5.3 ± 2.16). CONCLUSION: The data clearly show the association between bone marrow edema on MRI at sacroiliac joints and HLA-B*35 allele in patients with undifferentiated spondyloarthritis. Further work is needed to understand how much this result may influence follow-up of these patients. Key Points • HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI in un-axSpa patients. • HLA-B*35 allele was also associated with a 4.7 times greater chance of finding elevated CRP and a 5 times greater chance of finding peripheral joint synovitis in un-axSpa patients. • HLA-B*35 allele could be a potential risk factor for developing sacroiliitis and axSpA.

Does tocilizumab contribute to elevation of rheumatoid factor and induction of paradoxical syaloadenitis in rheumatoid arthritis patients?

A 56-year-old woman, treated with tocilizumab (TCZ) for 8 months for severe rheumatoid arthritis (RA), was admitted to the hospital due to the swelling and tenderness of parotid glands. The patient was diagnosed with seropositive erosive RA in 1988, and treated with different disease modifying antirheumatic drugs (DMARDs) that were used together with a low dosage of glucocorticoides, followed by biologic therapy with infliximab and adalimumab which also proved to be inefficient. The patient had an excellent initial response on TCZ therapy. After 8 months, she was presented with an extreme enlargement of parotid glands. Bacterial, viral, and granulomatous diseases were excluded. A spectrum of autoantibodies including anti-Ro and anti-La showed normal values, expect for slightly elevated anti-cyclic citrullinated peptide (anti-CCP) and extreme elevation of the rheumatoid factor (RF) to 10,100 IU/ml. The biopsy of salivary glands was done and histological specimen showed limphoplasmocytic syaloadenitis. Tocilizumab therapy was stopped and the dosage of glucocorticoids and methotrexate (MTX) was raised. After 6 weeks, the patient was in better condition with slightly lower levels of RF (9,010 IU/ml). We hypothesise that in this patient, TCZ stimulated RF hyper production which can induce a paradoxical secondary syaloadenitis in RA.

Physical and rehabilitation medicine training center in Split, Croatia: striving to achieve excellence in education of a rehabilitation team.

PURPOSE: The aim of this manuscript is to describe recent changes in rehabilitation medicine education in Croatia, and to highlight the effort that was made at University of Split School of Medicine, as well as at University Hospital Split in order to improve training in rehabilitation medicine. METHOD: Critical collection and study of pertinent data on evolvement and present state of physical and rehabilitation medicine (PRM) education in Croatia. RESULTS: Education in physical medicine and rehabilitation in Croatia was mainly focused on rheumatology rather than rehabilitation. In order to satisfy the new standards set for quality of rehabilitation medicine national curriculum reform was made for medical students, specialist and physiotherapists and new rehabilitation medicine training centers were established throughout the country. CONCLUSIONS: Academic setting such as PRM training center Split enables education for different health professionals at the same place and time, which provides opportunities for learning about competencies of other team members and development of future collaboration. Also, a uniform approach to education in rehabilitation medicine is provided for all health professionals. All of this sets a solid foundation for education of integrated rehabilitation team and achieving excellence in contemporary Croatian PRM. Implications for Rehabilitation In order to achieve high quality rehabilitation it is necessary to make education accessible to all rehabilitation team members. Implementation of rehabilitation principles in undergraduate education sets a good foundation for the development of postgraduate and specialty training in rehabilitation medicine. Academic setting such as physical and rehabilitation medicine training center Split provides a uniform approach to education in rehabilitation medicine for all health professionals.