Red Cell Distribution Width in Acute Pulmonary Embolism Patients Improves 30-Day Mortality Risk Stratification Based on the Pulmonary Embolism Severity Index.

PURPOSE: To validate red cell distribution width (RDW) as an improvement in 30-day mortality risk stratification based on the Pulmonary Embolism Severity Index (PESI) in acute pulmonary embolism (PE). PATIENTS AND METHODS: Prospective observational analysis of consecutive adult acute PE patients. RESULTS: Among 731 patients, 30-day mortality was 11.9%. With adjustment for the PESI score and number of covariates, higher RDW was associated with higher mortality (RDW continuous: OR 1.21, 95% CI 1.06-1.38; Bayesian OR 1.22, 1.07-1.40; RDW 'high' [>14.5% in men >16.1% in women] vs normal: OR 3.83, 1.98-7.46; Bayesian OR 3.98, 2.04-7.68]. Crude mortality was 3.6% if PESI 86-105 (intermediate risk), but 1.2% if RDW normal and 7.1% if RDW high; 11.8% if PESI 106-125 (high risk), but 3.6% if RDW normal and 18.8% if RDW high. Adjusted probabilities showed higher mortality (ORs between 3.5-5.8) if RDW was high in any PESI risk subgroup. Crude mortality rates in two random-split subsets (n=365 and n=366) again showed the same patterns. CONCLUSIONS: On-admission RDW above the normal range improves 30-day mortality risk stratification based on PESI score in acute PE. Particularly, it corrects PESI-based intermediate-risk or high-risk allocation by reclassification into very low-risk (<3.5%) or very high-risk (>11.0%).

Mortality and causes of death among Croatian male Olympic medalists.

AIM: To compare the overall and disease-specific mortality of Croatian male athletes who won one or more Olympic medals representing Yugoslavia from 1948 to 1988 or Croatia from 1992 to 2016, and the general Croatian male population standardized by age and time period. METHODS: All 233 Croatian male Olympic medalists were included in the study. Information on life duration and cause of death for the Olympic medalists who died before January 1, 2017, was acquired from their families and acquaintances. We asked the families and acquaintances to present medical documentation for the deceased. Data about the overall and disease-specific mortality of the Croatian male population standardized by age and time period were obtained from the Croatian Bureau of Statistics (CBS). Overall and disease-specific standard mortality ratios (SMR) with 95% confidence intervals (CI) were calculated to compare the mortality rates of athletes and general population. RESULTS: Among 233 Olympic medalists, 57 died before the study endpoint. The main causes of death were cardiovascular diseases (33.3%), neoplasms (26.3%), and external causes (17.6%). The overall mortality of the Olympic medalists was significantly lower than that of general population (SMR 0.73, 95% CI 0.56-0.94, P=0.013). Regarding specific causes of death, athletes' mortality from cardiovascular diseases was significantly reduced (SMR 0.61, 95% CI 0.38-0.93, P=0.021). CONCLUSIONS: Croatian male Olympic medalists benefit from lower overall and cardiovascular mortality rates in comparison to the general Croatian male population.

First Croatian transvaginal laparoscopically assisted cholecystectomies.

BACKGROUND/AIMS: The aim of this study was to determine the feasibility and technical aspects of a new endoluminal surgical procedure: transvaginal laparoscopically assisted endoscopic cholecystectomy. METHODOLOGY: Three female patients underwent transvaginal laparoscopically assisted endoscopic cholecystectomy (aged 40, 61 and 33 years). Pneumoperitoneum was created through a 5mm supraumbilical incision. Through the posterior fornix of the vagina the second 10mm trocar, laparoscope and 5mm laparoscopic grasper were introduced. The gallbladder was dissected using standard 5mm laparoscopic grasper, hook, electrocoagulation and harmonic shears introduced supraumbilically. The dissected gallbladder was removed in a specimen retrieval bag. RESULTS: Transvaginal laparoscopically assisted endoscopic cholecystectomy was feasible in all patients. No intraoperative or postoperative complications were observed and there was no need for extra-umbilical skin incisions. Total operative time ranged between 60 and 75 minutes. Median length of hospital stay was 1 day. CONCLUSIONS: This was the first clinical application of transvaginal laparoscopically assisted cholecystectomy in Croatia. The initial clinical application of this technique in 3 female patients was feasible, effective and safe when performed by experienced laparoscopic surgeons using standard laparoscopic instruments.

Patients with dementia and atrial fibrillation less frequently receive direct oral anticoagulants (DOACs) and experience higher thrombotic and mortality risk.

OBJECTIVE: To investigate differences in clinical presentation, anticoagulation pattern and outcomes in patients with dementia and atrial fibrillation (AF). METHODS: A total of 1217 hospitalized patients with non-valvular AF from two institutions were retrospectively evaluated. Diagnosis of dementia was established by a psychiatrist or a neurologist prior to or during hospitalization. Adequacy of warfarin anticoagulation was assessed during follow-up using at least 10 standardized international ratio values. In addition to unmatched comparison, nested case-control study was performed to further evaluate differences in clinical outcomes between patients with and without dementia. RESULTS: A total of 162/1217 (13.3%) patients were diagnosed with dementia. Among other associations, patients with dementia were significantly older with higher number of comorbidities, had lower estimated glomerular filtration rate (eGFR) and lower left ventricular ejection fraction (LVEF), (P < 0.05 for all analyses). Patients with dementia were significantly less likely to receive direct oral anticoagulants (DOACs; 27.2% vs 40.3%; P = 0.001) and were significantly more likely to be inadequately anticoagulated with warfarin (38.9% vs 28.6%; P = 0.008) than patients without dementia. After matching based on age, eGFR, LVEF, and CHA2DS2-VASC patients with dementia were significantly more likely to experience inferior overall survival (HR = 1.8; P = 0.001) and shorter time to thrombosis (HR = 2.3; P = 0.019). CONCLUSION: Our findings speak in support of increased thrombotic and mortality risks in patients with dementia, possibly due to inadequate anticoagulation and higher number of comorbidities.

Changes of recommended anticoagulation therapy in patients with atrial fibrillation and high thrombotic risk: long-term follow-up data from two hospital centers.

Aim : To investigate changes of anticoagulation therapy in patients with atrial fibrillation (AF) and high thrombotic risk.Methods : We retrospectively analyzed 1061 patients with non-valvular AF and indication for anticoagulation therapy referred in a period from 2013 to 2018 and followed-up for a median time of 38 months.Results : Therapy change occurred in 206 (19.5%) patients (195 switches and 11 permanent discontinuations). Only 37% of patients on warfarin had optimal dosing and their duration of therapy was significantly shorter compared to direct oral anticoagulants (DOACs; (adjusted HR 1.21, 95% CI 1.09-1.37). Therapy change occurred in only 33% of patients with poorly controlled warfarin, and in only 24% of patients that experienced a thrombotic event while taking warfarin. Optimal dosing was an independent factor for any therapy change during follow-up, irrespective of type of anticoagulant drug at baseline. DOAC swapping occurred in 39% of all DOAC to DOAC switches, with one bleeding event and no thrombotic events documented after a DOAC swap.Conclusion : High risk patients with AF rarely discontinue anticoagulation therapy. The need for therapy change should be emphasized in patients with non-optimal dosing, and in patients that experience thrombotic events while taking warfarin.

The Risk of Falling and Consequences of Falling in Patients with Atrial Fibrillation Receiving Different Types of Anticoagulant.

OBJECTIVE: Our objective was to investigate the predictors of falls requiring a visit to the emergency department in patients with nonvalvular atrial fibrillation (AF) receiving different types of anticoagulants and to investigate the clinical consequences of falling in the same population. METHODS: A total of 1217 patients with nonvalvular AF from two institutions were retrospectively evaluated. Each patient underwent a physical examination, and clinical histories and medication profiles were taken from each patient at baseline. RESULTS: The median age of our cohort was 71 years; 52.3% were males, and 86.1% of patients were receiving anticoagulation at study baseline. The 5-year freedom-from-falling rate was 81.6%. The use and type of anticoagulation was not significantly associated with the risk of falling (P = 0.222), whereas higher Morse Fall Scale (MFS), CHA2DS2-VASC (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category), and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly [> 65 years], drugs/alcohol concomitantly) scores were significantly associated with a higher hazard of the first fall in univariate analyses. In the multivariate Cox regression model, MFS, older age, osteoporosis, higher levels of high-density lipoprotein cholesterol, higher diastolic blood pressure, and use of amiodarone, diuretics, or short- and medium-acting benzodiazepines were mutually independent predictors of the first fall. Of 163 patients, 93 (57%) had a bone fracture during the fall. Type of anticoagulation significantly affected survival after the first fall (P < 0.001): patients inadequately anticoagulated with warfarin had worse survival rates, and patients receiving apixaban and dabigatran had the best survival rates after the first fall. CONCLUSION: Older patients who had comorbidities and were taking amiodarone, diuretics, or short- or medium-acting benzodiazepines had the highest risk of falls. The type and quality of anticoagulation did not seem to affect the risk of falling but did significantly affect survival after the first fall.

Embryo-derived teratoma in vitro biological system reveals antitumor and embryotoxic activity of valproate.

Antiepileptic/teratogen valproate (VPA) is a histone deacetylase inhibitor/epigenetic drug proposed for the antitumor therapy where it is generally crucial to target poorly or undifferentiated cells to prevent a recurrence. Transplanted rodent gastrulating embryos-proper (primitive streak and three germ layers) are the source of teratoma/teratocarcinoma tumors. Human primitive-streak remnants develop sacrococcygeal teratomas that may recur even when benign (well differentiated). To screen for unknown VPA impact on teratoma-type tumors, we used original 2-week embryo-derived teratoma in vitro biological system completed by a spent media metabolome analysis. Gastrulating 9.5-day-old rat embryos-proper were cultivated in Eagle's minimal essential medium (MEM) with 50% rat serum (controls) or with the addition of 2 mmVPA. Spent media metabolomes were analyzed by FTIR. Compared to controls, VPA acetylated histones; significantly diminished overall teratoma growth, impaired survival, increased the apoptotic index, and decreased proliferation index and incidence of differentiated tissues (e.g., neural tissue). Control teratomas continued to grow and differentiate for 14 days in isotransplants in vivo, but in vitro VPA-treated teratomas resorbed. Principal component analysis of FTIR results showed that spent media metabolomes formed well-separated clusters reflecting the treatment and day of cultivation. In metabolomes of VPA-treated teratomas, we found elevation of previously described histone acetylation biomarkers [amide I α-helix and A(CH3 )/A(CH2 )]) with apoptotic biomarkers within the amide I region for ß-sheets, and unordered and CH2 vibrations of lipids. VPA may be proposed for therapy of the undifferentiated component of teratoma tumors and this biological system completed by metabolome analysis, for a faster dual screening of antitumor/embryotoxic agents.

Periprocedural myocardial and renal injury in patients undergoing elective percutaneous coronary interventions - is there an association?

Periprocedural myocardial injury (PMI) and contrast-induced nephropathy (CIN) are frequent complications of percutaneous coronary intervention (PCI) associated with early and late major adverse cardiovascular events. Both conditions are associated with similar risk factors, which could imply their possible association. The aim of our study was to assess the correlation of PMI and early postprocedural creatinine shift (ECS) as a marker of renal injury.A total of 209 hospitalized patients with stable coronary artery disease (CAD) were enrolled, who underwent an elective PCI in a period of 12 months. All patients had their serum high-sensitivity troponin I (hsTnI) measured at baseline and 16 hours after the PCI. PMI was defined according to the elevation of postprocedural hsTnI using criteria provided by both the most recent consensus documents as well as evidence-based data. Renal injury was evaluated using the ECS concept. Serum creatinine (SCr) was also measured at baseline and at 16 hours. ECS was defined as SCr >5% at 16 hours compared to baseline.Although incidence of both PMI (77.5%) and ECS (44.5%) were high, no association of these 2 conditions could be found. Further analyses of our data showed that diabetes is associated with a higher incidence of ECS, while patients on beta-blocker therapy had a lower incidence of ECS.In our study, no association between PMI and ECS was found. Additional studies with a larger number of patients and longer patient observation are needed to assess the correlation between PMI and CIN as well as to validate the attractive, but controversial, concept of ECS as an early marker of CIN.

[Amusia and aphasia of Bolero's creator--influence of the right hemisphere on music]. / Amuzija i afazija tvorca Boléra--utjecaj desne hemisfere na glazbu.

OBJECTIVES: The experience with cortical localization (BA 44, 45, 22) of language (Broca, Wernicke and others) in the left hemisphere has been repeatedly tested over the last 150 years and is now generally accepted. A single case report with autopsy findings (Leborgne, Tan tan), has enabled to localize the seat of spoken language in the left third frontal convolution. As music and language have a lot in common and even share the same hearing system, it is logical to try to localize the cognitive centers for music too. METHODS: The disabling neurological disease illness of Maurice Ravel (1875-1937), a French impressionist composer, is not the right example to localize music center as that of Broca's language center, but it demonstrates the role of the right hemisphere in music production. In the last five years of his life, Ravel suffered from an unknown disease that affected the left hemisphere causing aphasia, apraxia, alexia, agraphia and amusia. It was the reason why Ravel could not compose during the last years of his life. In contrast to Ravel, Shebalin and Britten continued writing music works of their own although aphasic after having sustained two strokes to the left hemisphere. While lacking clinical cases with selective ablative brain lesions, research into the music localization can be done using modern imaging technologies such as fMRI and PET. RESULTS: Exercising music (professionally) develops analytical process in the left hemisphere whereas other individuals process music in their right hemisphere. There is right ear (left hemisphere) predominance in musicians and vice versa in musical amateurs. Music lateralization towards the right hemisphere is seen in women and in inattentive listeners. It can be subject to cultural influence, so the Japanese process their traditional popular music in the left hemisphere, whereas Westerners process the same music in the right hemisphere. Music and language are processed separately; they are localized in homologous regions of the opposite hemispheres. In 1937, Ravel underwent neurosurgical procedure performed by Vincent; autopsy was not done. It is believed that the cause of hi disease was primary progressive aphasia associated with Pick's disease. CONCLUSION: Boléro and Concerto for the Left Hand were the last Ravel's works (the onset of his disease), so it is possible that the projected the influence of the healthy right hemisphere onto his music (and on the creative process) because Ravel's left hemispher was damaged. Indeed, in these last music works one can feel the predominance of changes in pitch (timbre), i. e. right hemisphere, in comparison to only few changes of melody (left hemisphere).

Mine clearance injuries in South Croatia.

OBJECTIVE: The purpose of this retrospective study was to describe and analyze casualties in mine-clearance operations in South Croatia from 1991 to 1995. During the war in Croatia, the laying of mines by both sides was largely unplanned, without mapping or documentation, making demining, an already expensive, complicated task, even more dangerous. METHODS: The study comprised all those injured in mine-clearance operations treated at Clinical Hospital Split. The type of mines used, the mechanism of the incident, and the location and severity of injury according to the Abbreviated Injury Scale and the Injury Severity Score were analyzed. RESULTS: In a 5-year period, 160 pyrotechnicians of the Croatian Army performed demining in Southern Croatia. In 29 incidents, 53 deminers were injured. The degree of injury according to the Abbreviated Injury Scale was 2.85 +/- 0.6 and Injury Severity Score grade was 19.68 +/- 8.57. Two of the injured died. CONCLUSION: To find and remove approximately 2 million mines laid in Croatia will take at least 10 years and 2,000 to 3,000 specialized personnel. Unfortunately, the results of the study demonstrate that a significant number of deminers will suffer grave injuries or die in the process.

Antipersonnel mine injuries in Southern Croatia.

OBJECTIVES: In this retrospective study, antipersonnel mine casualties in Southern Croatia from 1991 to 1995 are analyzed and treatment options are discussed. METHODS: Mechanism, degree of injury according to Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS), as well as surgical treatment were analyzed. RESULTS: Of a 2,693 war trauma population, 422 (15.67%) patients sustained antipersonnel mine injuries, 241 (57.11%) from pressure mines and 181 (42.89%) from fragmentation mines. Military personnel were injured in 329 cases, civilians in 60 cases, and children in 33 cases. AIS was 3.01 +/- 0.56 and ISS was 17.92 +/- 6.59. Of 39 fatalities (9.24%) with a mean age of 27.98 +/- 1.70 years, 34 were soldiers, 4 were civilians, and 1 was a child. AIS was 5.35 +/- 0.39 and ISS was 54.94 +/- 2.36. CONCLUSION: Fatalities and morbidity arising from antipersonnel mines can be reduced by the provision of appropriate surgical and evacuation facilities at the actual battlefield.

Injuries from Antitank mines in Southern Croatia.

OBJECTIVE: Antitank mines inflict devastating injuries that are usually fatal. The objective of this retrospective study was to analyze antitank mine casualties in South Croatia during the period from 1991 to 1995. METHODS: Mechanism, degree of injury according to Abbreviated Injury Scale and Injury Severity Score, as well as surgical treatment were analyzed. FINDINGS: Of 464 mine victims, 42 (9.0%) patients sustained antitank mine injuries, and 12 of these were fatal (29%). Abbreviated Injury Scale of the antitank mine injuries was 5.3 +/- 10.6. Military personnel were injured in 29 cases, and civilians were injured in 13 cases. CONCLUSION: Although injuries from antitank mines were ravaging, and frequently fatal, a significant number of patients survived.

Outcome of emergency endovascular treatment of large internal iliac artery aneurysms with guidewires.

PURPOSE: Guidewires have been reported as a useful occlusion material for large aneurysms of different locations with good short-term results. In this study we retrospectively evaluate long-term results of emergency embolization technique with guidewires in symptomatic internal iliac artery aneurysm (IIAA) impending rupture. PATIENTS AND METHODS: In four patients presented with acute abdominal pain, multidetector computed tomography revealed unstable, 7-14cm large, IIAAs. Two patients were treated with coil embolization of distal branches followed by occlusion of aneurysmal sac with guidewires. In two patients embolization of aneurysmal sac alone was performed. RESULTS: In three patients complete or near complete occlusion of the aneurysmal sac was achieved and abdominal pain ceased within hours. Two patients treated with embolization of distal iliac artery branches and aneurysmal sac developed claudication that lasted up to 1 year. Their aneurysms remained thrombosed and they were without symptoms until they died 31 and 56 months later of causes unrelated to IIAA. Two patients treated with embolization of the aneurysm alone were free of ischemic symptoms. Because of incomplete embolization of the sac in one patient open surgery treatment in a non-emergency setting was performed. Complete filling of aneurysmal sac was achieved in other patient but 2 years later his aneurysm re-opened and required open surgery treatment. CONCLUSION: Embolization of aneurysmal sac of large IIAA with guidewires may be effective for immediate treatment of impending rupture. Long-term results were better when embolization of the aneurysmal sac was combined with embolization of distal IIA branches.