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 β‐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.
Valproate (VPA; antiepileptic/teratogen/histone deacetylase inhibitor) negatively affected embryo‐derived teratoma development in vitro and abolished its potential to recover in vivo. FTIR spectroscopy results separated all VPA‐treated and control metabolomes, while FTIR biomarkers reflected processes of apoptosis and histone acetylation assessed in teratomas by immunohistochemistry and western blotting. We propose this in vitro biological system, completed by analysis of spent media metabolomes, as a screening system for embryotoxic and antitumor agents.
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.
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.
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).
Croatian male Olympic medalists benefit from lower overall and cardiovascular mortality rates in comparison to the general Croatian male population.
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).
...Prospective observational analysis of consecutive adult acute PE patients.
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.
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%).
•The Pulmonary Embolism Severity Index (PESI) is a well-validated tool for prediction of 30-day mortality in acute pulmonary embolism (PE) patients that still needs additional improvement in early mortality risk estimation among intermediate-risk and high-risk groups•There is a need for a simple, fast, cheap and widely available marker that could be used as a reliable add-on tool to PESI in an emergency room or any clinical or organisational setting•This study showed that red cell distribution width reliably reclassified a substantial number of PESI intermediate-risk and high-risk patients into low-risk or very high-risk categories, and that its simple dichotomised use could further improve decision-making in acute pulmonary embolism in the emergency room setting with limited resources
To investigate differences in clinical presentation, anticoagulation pattern and outcomes in patients with dementia and atrial fibrillation (AF).
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.
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 CHA
2
DS
2
-VAS
C
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).
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.
Abstract 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, 7–14 cm 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.
The aim of this study was to determine the feasibility and technical aspects of a new endoluminal surgical procedure: transvaginal laparoscopically assisted endoscopic cholecystectomy.
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.
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.
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.
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.
Mechanism, degree of injury according to Abbreviated Injury Scale and Injury Severity Score, as well as surgical treatment were analyzed.
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.
Although injuries from antitank mines were ravaging, and frequently fatal, a significant number of patients survived.
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