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The significance of prostate specific antigen persistence in prostate cancer risk groups on long-term oncological outcomes
No full textObjective: To assess the significance of prostate-specific antigen (PSA) persistence at the first measurement after radical prostatectomy (RP) on long-term outcomes in different prostate cancer risk groups. Methods: Persistent PSA was defined as ≥0.1 ng/mL at 4–8 weeks after RP. Patients were stratified into low-, intermediate- and high-risk groups, according to the preoperative PSA, pathological stage, grade group and lymph nodes status. The ten-year cumulative incidence of biochemical recurrence (BCR), metastases, cancer-specific mortality (CSM) and overall mortality (OM) were calculated in patients with undetectable and persistent PSA in different PCa-risk groups. Multivariate regression analyses depicted the significance of PSA persistence on each study endpoint. Results: Of all 1225 men, in 246 (20.1%), PSA persistence was detected. These men had an increased risk of BCR (hazard ratio (HR) 4.2, p < 0.0001), metastases (HR: 2.7, p = 0.002), CRM (HR: 5.5, p = 0.002) and OM (HR: 1.8, p = 0.01) compared to the men with undetectable PSA. The same significance of PSA persistence on each study endpoint was found in the high-risk group (HR: 2.5 to 6.2, p = 0.02 to p < 0.0001). In the intermediate-risk group, PSA persistence was found as a predictor of BCR (HR: 3.9, p < 0.0001), while, in the low-risk group, PSA persistence was not detected as a significant predictor of outcomes after RP. Conclusions: Persistent PSA could be used as an independent predictor of worse long-term outcomes in high-risk PCa patients, while, in intermediate-risk patients, this parameter significantly predicts only biochemical recurrence and has no impact on the outcomes in low-risk PCa patients
The effect of temperature increases on brain tissue oxygen tension in patients with traumatic brain injury: a Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury substudy
No full textFever may aggravate secondary brain injury after traumatic brain injury (TBI). The aim of this study was to identify episodes of temperature increases through visual plot analysis and algorithm supported detection, and to describe associated patterns of changes in on brain tissue oxygen tension (PbtO2). Data derive from the high-resolution cohort of the multicenter prospective Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Temperature increases (≥0.5°C) were visually identified in 33 patients within the first 11 days of monitoring. Generalized estimating equations were used to detect significant changes of systemic and neuromonitoring parameters from baseline to the highest temperature. Patients were median 50 (interquartile range [IQR], 35-62) years old, and presented with a Glasgow Coma Scale (GCS) of 8 (IQR, 4-10). In 202 episodes of temperature increases, mean temperature rose by 1.0°C ± 0.5°C within 4 hours. Overall, PbtO2 slightly increased (ΔPbtO2 = 0.9 ± 6.1 mmHg, p = 0.022) during temperature increases. PbtO2 increased in 35% (p < 0.001), was stable in 49% (p = 0.852), and decreased in 16% (p < 0.001) of episodes. During episodes of temperature increases and simultaneous drops in PbtO2, cerebral perfusion pressure (CPP) decreased (ΔCPP -6.3 ± 11.5 mmHg; p < 0.001). Brain tissue hypoxia (PbtO2 <20 mmHg) developed during 27/164 (17%) episodes of effervescences, in the remaining 38/202 episodes baseline PbtO2 was already <20 mmHg. Comparable results were found when using algorithm-supported detection of temperature increases. In conclusion, during effervescences, PbtO2 was mostly stable or slightly increased. A decrease of PbtO2 was observed in every sixth episode, where it was associated with a decrease in CPP. Our data highlight the need for special attention to CPP monitoring and maintenance during episodes of fever
A placebo-controlled randomised trial of budesonide for primary biliary cholangitis following an insufficient response to UDCA
No full textBackground & Aims: In patients with primary biliary cholangitis (PBC) the utility of budesonide, a synthetic corticosteroid displaying high first-pass metabolism, is unresolved. In a placebo-controlled, double-blind trial, we evaluated the added-value of budesonide in those with PBC and ongoing risk of progressive disease despite ursodeoxycholic acid (UDCA). Methods: We evaluated 62 patients with PBC who had histologically confirmed hepatic inflammatory activity, according to the Ishak-score, and an alkaline phosphatase (ALP) >1.5x upper limit of normal (ULN), after at least 6 months of UDCA therapy. Participants were randomly assigned 2:1 to receive budesonide (9 mg/day) or placebo once daily, for 36 months, with UDCA treatment (12-16 mg/kg body weight/day) maintained. Primary efficacy was defined as improvement of liver histology with respect to inflammation and no progression of fibrosis. Secondary outcomes included changes in biochemical markers of liver injury. Results: Recruitment challenges resulted in a study underpowered compared to original intent. The primary histologic endpoint, comparing patients with paired biopsies only (n= 43), was not met (p>0.05). The proportion of patients with ALP <1.67xULN, ≥15% decrease and normal bilirubin, was higher in the budesonide group than in the placebo group at 12, 24, and 36 months (p<0.05, each). In contrast to placebo, budesonide reduced mean ALP, and 35% of budesonide-treated patients had normalisation of ALP (Placebo: 9%; p=0.023). Serious adverse events occurred in 10 patients receiving budesonide and 7 patients receiving placebo. Conclusion: Budesonide add-on therapy in patients with PBC, and insufficient response to UDCA, did not associate with improvement in liver histology; improvements in biochemical markers of disease activity were demonstrated in secondary analyses
Age-related morphological peculiarities of human testes
No full textThis study aimed the comparison of the isolated testes size, volume, weight and density changes with age and establishing the suitability of three formulas of testicular volume calculation for 18-50 and 51-70-year-old men groups. 206 testes of 103 men (59 of 18-50-year-old and 44 of 51-70-year-old men) were weighed and their size was measured by the sliding calliper. The accurate volume was determined by water displacement and compared with volume calculated using three formulas, and the density of testicular tissues was calculated. The mean length and height of both testes and length and height of right and left testes decreased significantly with age. The mean width of both testes and width of right and left testes decreased with age insignificantly. The mean of water displacement volume and weight and volume and weight of right and left testes decreased with age significantly. The mean density of testicular tissues and the density of the right and left testes increased significantly with age. In the same age group, the size, water displacement volume and weight of right testes was insignificantly major than the left, and the density of testicular tissues was similar in the right and left testes. The prolate spheroid formula was most suitable for calculation of testes volume for 18-50-year-old men and prolate ellipsoid formula was most suitable for calculation of 51-70-year-old men testes volume
Pulp vitality testing with a developed universal pulse oximeter probe holder
No full textBackground and Objectives: An accurate determination of the pulp status is relevant for a proper endodontic diagnosis. Objectives: The aim was to develop a universal pulse oximeter probe holder for measuring the oxygen saturation and to evaluate the use of pulse oximetry as a test for pulp vitality, by comparing the levels of oxygen saturation in the index finger and in the healthy dental pulp. Materials and Methods: The universal holder was designed with software and printed with a 3D printer. The study was carried out on 128 healthy teeth. They were divided into eight groups according to tooth type. Ten root canal treated teeth served as a negative control group. For each patient, a pulse oximeter was first applied on the tooth followed by the index finger. The significance level (α) was set at 0.05. Results: The developed and manufactured universal pulse oximeter probe holder was suitable to measure the pulp vitality of all types of teeth. The handle allowed for holding the pulse oximeter on the tooth in parallel, firmly and securely. Significantly higher oxygen saturation was observed in the index finger (97.22%) compared to the dental pulp (93.17%) (p<0.001). No correlation was observed between the maxillary teeth and index finger oxygen saturation values (r=0.05, p=0.72), whereas, between the mandibular teeth and index finger, a positive correlation was detected (r=0.29, p=0.02). There were no significant differences in the pulp oxygen saturation values between different teeth groups. Conclusion: The newly developed universal pulse oximeter probe holder is an effective device for pulp vitality testing
Age-specific seasonal influenza vaccine effectiveness against different influenza subtypes in the hospitalized population in Lithuania during the 2015–2019 influenza seasons
No full textBackground: Continuous monitoring of seasonal influenza vaccine effectiveness (SIVE) is needed due to the changing nature of influenza viruses and it supports the decision on the annual update of vaccine composition. Age-specific SIVE was evaluated against different influenza sub-types in the hospitalized population in Lithuania during four influenza seasons. Methods: A test-negative case-control study design was used. SIVE and its 95% confidence intervals (95% CI) were calculated as (1 – odds ratio (OR)) × 100%. Results: Adjusted SIVE in 18–64-year-old individuals against influenza A, A(H1N1)pdm09 and B/Yamagata were 78.0% (95% CI: 1.7; 95.1%), 88.6% (95% CI: −47.4; 99.1%), and 76.8% (95% CI: −109.9; 97.4%), respectively. Adjusted SIVE in individuals aged 65 years and older against influenza A, influenza B, and B/Yamagata were 22.6% (95% CI: −36.5; 56.1%), 75.3% (95% CI: 12.2; 93.1%) and 73.1% (95% CI: 3.2; 92.5%), respectively. Unadjusted SIVE against influenza A(H3N2) among 18–64-year-old patients was 44.8% (95% CI: −171.0; 88.8%) and among those aged 65 years and older was 5.0% (95% CI: −74.5; 48.3%). Conclusions: Point estimates suggest high SIVE against influenza A in 18–64-year-old participants, and against influenza B and B/Yamagata in those 65 years old and older
Global characterisation of coagulopathy in isolated traumatic brain injury (iTBI): a CENTER-TBI analysis
No full textBACKGROUND: Trauma-induced coagulopathy in patients with traumatic brain injury (TBI) is associated with high rates of complications, unfavourable outcomes and mortality. The mechanism of the development of TBI-associated coagulopathy is poorly understood. METHODS: This analysis, embedded in the prospective, multi-centred, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, aimed to characterise the coagulopathy of TBI. Emphasis was placed on the acute phase following TBI, primary on subgroups of patients with abnormal coagulation profile within 4 h of admission, and the impact of pre-injury anticoagulant and/or antiplatelet therapy. In order to minimise confounding factors, patients with isolated TBI (iTBI) (n = 598) were selected for this analysis. RESULTS: Haemostatic disorders were observed in approximately 20% of iTBI patients. In a subgroup analysis, patients with pre-injury anticoagulant and/or antiplatelet therapy had a twice exacerbated coagulation profile as likely as those without premedication. This was in turn associated with increased rates of mortality and unfavourable outcome post-injury. A multivariate analysis of iTBI patients without pre-injury anticoagulant therapy identified several independent risk factors for coagulopathy which were present at hospital admission. Glasgow Coma Scale (GCS) less than or equal to 8, base excess (BE) less than or equal to - 6, hypothermia and hypotension increased risk significantly. CONCLUSION: Consideration of these factors enables early prediction and risk stratification of acute coagulopathy after TBI, thus guiding clinical management
Detection of ischemic episodes based on two consecutive declines in the JT/ST algebraic relationship
No full textThe main objective of this paper is to explore if the JT/ST algebraic relationship could be helpful for the identification of ischemic changes in the human cardiovascular system. The suggested visualization technique highlights the specifics of complex dynamical processes in the self-organization of the heart system during the load and recovery processes. It is demonstrated that the nonlinear algebraic relationship between the duration of the JT interval and the ST amplitude can be beneficial for a deeper interpretation of dynamical processes in the human cardiovascular system. The JT/ST relationship is used for the identification of the ischemic changes and for the characterization of individual performance of the person during the load and recovery processes
The impact of incomplete registration on survival rate of children with very rare tumors
No full textPediatric very rare tumors (VRTs) represent a heterogeneous subset of childhood cancers, with reliable survival estimates depending dramatically on each (un)registered case. The current study aimed to evaluate the number of VRTs among Lithuanian children, to assess the impact of the registration status on survival rates and to track changes in treatment outcomes over the 16-year study period. We performed a population-based retrospective study across children below 18 years old diagnosed with VRTs in Lithuania between the years 2000 and 2015. The identified cases were cross-checked with the Lithuanian Cancer Registry-a population-based epidemiology cancer registry-for the fact of registration and survival status. The overall survival was calculated in relation to the registration status and treatment period. Thirty-seven children with VRTs were identified within the defined time frame. Six of them (16.2%) were not reported to the Lithuanian Cancer Registry at diagnosis. The probability of overall survival at 5 years (OS5y) differed significantly between the registered (n = 31) and unregistered (n = 6) cohorts: 51.6% versus 100%, respectively (p = 0.049). A 5-year survival estimate for children diagnosed with a VRT at the age of 0-14 years differed by 10 percentage points according to the registration completeness: 52.1% calculated for the entire cohort versus 42.1% for registered patients only. The OS5y has not improved over the analyzed period: 61.1% in 2000-2007 versus 57.9% in 2008-2015 (p = 0.805). The survival continued to decline beyond 5 years post-diagnosis due to late cancer-related adverse events: 59.5% of patients were alive at 5 years as compared to 44.3% at 10 years. The OS5y of children affected by VRT was lower than in more common childhood cancers. The survival rate of the unregistered patients may lead to misinterpretation of treatment outcomes. Meticulous registration of VRTs is crucial for correct evaluation of treatment outcomes, especially across small countries with few cases
Anatomical evidence of non-parasympathetic cardiac nitrergic nerve fibres in rat
No full textNeuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) plays a major role in the neural control of circulation and in many cardiovascular diseases. However, the exact mechanism of how NO regulates these processes is still not fully understood. This study was designed to determine the possible sources of nitrergic nerve fibres supplying the heart attempting to imply their role in the cardiac neural control. Sections of medulla oblongata, vagal nerve, its rootlets and nodose ganglia, vagal cardiac branches, Th1 -Th5 spinal cord segments, dorsal root ganglia of C8 -Th5 spinal nerves, and stellate ganglia from 28 Wistar rats were examined applying double immunohistochemical staining for nNOS combined with choline acetyltransferase (ChAT), peripherin, substance P, calcitonin gene-related peptide, tyrosine hydroxylase or myelin basic protein. Our findings show that the most abundant population of purely nNOS-immunoreactive (IR) neuronal somata (NS) was observed in the nodose ganglia (37.4 ± 1.3%). A high number of nitrergic NFs spread along the vagal nerve and entered its cardiac branches. All nitrergic neuronal somata (NS) in the nucleus ambiguus were simultaneously immunoreactive (IR) to ChAT and composed only a small subset of neurons (6%). In the dorsal nucleus of vagal nerve, biphenotypic nNOS-IR/ChAT-IR neurons composed 7.0 ± 1.0%, while small purely nNOS-IR neurons were scarce. Nitrergic NS were plentifully distributed within the nuclei of solitary tract. In the examined dorsal root and stellate ganglia, a few nitrergic NS were sporadically present. The majority of sympathetic NS in the intermediolateral nucleus were simultaneously immunoreactive for nNOS and ChAT. In conclusion, an abundant population of nitrergic NS in the nodose ganglion implies that neuronal NO is involved in afferent cardiac innervation. Nevertheless, nNOS-IR neurons identified within vagal nuclei may play a role in the transmission of preganglionic parasympathetic [...]