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Establishing the diagnosis of multiple sclerosis in Croatian patients with clinically isolated syndrome: 2010 versus 2017 McDonald criteria
Get PDFAIM: To compare the sensitivity, specificity and accuracy of the 2010 and 2017 revisions of the McDonald criteria in a Croatian cohort of patients with a clinically isolated syndrome (CIS).
----- METHODS: Prospectively collected data from 113 patients were retrospectively analyzed. Sensitivity, specificity and accuracy for both criteria were calculated regarding conversion to clinically definite multiple sclerosis (Poser CDMS) or multiple sclerosis (MS) (defined as fulfilment of clinical or MRI evidence for dissemination in space and the development of a second relapse and/or ≥1 new T2 lesions on the follow-up MRIs) during a two-year follow-up. Survival analysis was performed to estimate the cumulative risk of patients developing Poser CDMS. Binary logistic regression model was used to determine which variables are statistically significant predictors for the conversion to MS. ----- RESULTS: The 2017 revision had higher sensitivity (85 vs. 30% and 85 vs. 41%) and lower specificity (33 vs. 63% and 63 vs. 85%) compared to the 2010 revisions, for conversion to Poser CDMS and MS, respectively. Patients who did not meet the 2017 McDonald criteria had a higher chance of conversion-free survival for Poser CDMS than those who met the 2017 McDonald criteria (p = 0.037). Results of the multivariate regression analysis revealed that patients who at baseline fulfilled 2017 revisions of the McDonald criteria have the increased likelihood of conversion to MS (Exp(B) 9.68, 95%CI 3.62-25.90, p < 0.00001). ----- CONCLUSION: This study provides new information about the application of the 2017 revisions of the McDonald criteria in a Croatian cohort of patients with typical CIS
Progressive multiple sclerosis patients have a higher burden of autonomic dysfunction compared to relapsing remitting phenotype
Get PDFOBJECTIVE:
To determine autonomic dysfunction (AD) differences in patients with relapsing remitting multiple sclerosis (pwRRMS) and progressive MS (pwPMS). ----- METHODS:
Composite autonomic scoring scale (CASS) and heart rate variability (HRV) were performed in 40 pwRRMS and 30 pwPMS.
----- RESULTS:
pwPMS had a significantly higher sudomotor index and total CASS score compared to pwRRMS (p < 0.001 and p < 0.001, respectively). Disease duration positively correlated with sudomotor index and total CASS (rs = 0.409, p < 0.001 and rs = 0.472, p < 0.001, respectively), while the Expanded Disability Status Scale (EDSS) positively correlated with sudomotor index and total CASS (rs = 0.411, p < 0.001 and rs = 0.402, p = 0.001, respectively) in all patients. Type of multiple sclerosis (pwRRMS or pwPMS) corrected for age, sex and disease duration, was a statistically significant predictor of CASS value (B = 1.215, p = 0.019). Compared to pwRRMS, pwPMS had a significantly lower standard deviation of NN intervals (SDNN), low frequency (LF), and high frequency (HF), during both the supine and tilt-up phases (all p-values <0.006). pwPMS had a significantly lower LF/HF (p = 0.008) during tilt-up.
----- CONCLUSION:
There is a significant difference in autonomic function in pwRRMS and pwPMS; with pwPMS having a higher burden of AD, which is particularly evident for sweating dysfunction.
----- SIGNIFICANCE:
Further research is needed to establish whether parasympathetic and sudomotor dysfunction may serve as markers of progressive MS
Utjecaj polimorfizama gena za dopamin beta hidroksilazu i katekol-O-metil transferazu na učinkovitost liječenja inzulinom detemir u bolesnika s tipom 2 šećerne bolesti [ The influence of dopamine beta hydroxylase and catechol-O-methyltransferase gene polymorphisms on the efficacy of detemir therapy in patients with type 2 diabetes mellitus]
Get PDFBackground: Type 2 diabetes represents an important health problem designated by a progressive
course and the subsequent need of long-term insulin thearpy to achieve optimal glucose
control. It is important to stress out that a substantial number of patients with type 2 diabetes
does not achieve optimal glucose control despite intensive insulin treatment. Insulin detemir, besides
a low pharmacodynamic coefficient of variability, exihibits anorexigenic features, through
its effects on the central nervous system (CNS). It has been shown that dopaminergic system
plays an important role in modulating the regulatory metabolic pathways in CNS. Dopamine
neurotransmission underlies a reward. Several high visibility studies in humans provided proofof-
principle data suporting the hypothesis that defects in dopamine homeostasis contribute to
the pathophysiology of obesity.
The aim of the study was to investigate the possible effect of catechol-O-methyltransferase
(COMT) and dopamine beta hydroxylase (DBH) gene polimorphisms on glucoregulation, and
thus ascertain the role of dopaminergic system in achieving and maintaining optimal glycemic
control.
Participants and methods: This 52-week observational study included 185 patients with
inadequate glycemic control treated with premix insulin analogues, which were replaced with
three doses of insulin aspart and one dose of insulin detemir (at bedtime), and 156 healthy controls.
After DNA isolation from blood samples, genotyping of DBH-1021C/T polymorphism
(rs1611115) and COMT Val108/158Met polymorphism (rs4680) was performed.
Results: Our results confirmed that insulin detemir did not lead to weight gain, with a significant
weight sparing effect in overweight patients. The most significant finding was that A
carriers (the combined AG and AA genotype) of the COMT Val108/158Met achieved significantly
better hemoglobin A1c (HbA1c) values compared to patients carrying GG genotype. No
association between DBH-1021C/T genotypes and weight and/or glucose control was detected
in diabetes patients or in healthy control subjects.
Conclusion: This study showed that the presence of one or two A allele of the COMT
Val108/158Met was associated with improved glycemic response, and with a better response to
insulin detemir therapy in patients with type 2 diabetes, separating them as best candidates for
detemir therapy
The frequency of micronuclei in peripheral blood lymphocytes and buccal exfoliated cells in women with cervical cancer
Get PDFA biological marker is an important aspect of the diagnosis, prognosis and risk assessment of a disease. The aim of this study was the evaluation of genomic instability in patients with cervical lesions.
The genetic damages were investigated in 100 subjects: patients with low grade squamous intraepithelial lesions (LSIL; n=20), patients with high grade squamous intraepithelial lesions (HSIL; n=20) patients with invasive squamous cervical cancer (SCC; n=20) and healthy women (n=20) with cytokinesis-block micronucleus cytome (CBMN cyt) assay in peripheral blood lymphocytes (PBL), and buccal micronucleus assay in buccal exfoliated cells (BEC), in order to assess the frequency of micronucleus (MN) in PBL and frequency of MN in BEC as well as the frequency of other nuclear anomalies such as nucleoplasmic bridges (NPBs) and nuclear bunds (NBUDs) in PBL.
The frequency of MN in BEC, MN in PBL, NPB in PBL and NBUD in PBL were significantly higher (p< 0.001), in patients compared to control. Pearson’s correlation revealed a statistically significant strong positive correlation between variables in patients groups (p<0.001).
Although larger studies are needed, our data support the predictive value of MN, NPB and NBUD as biomarkers of genomic instability for evaluation of risk level of cervical cancer diseases
Cerebral bypass surgery for internal carotid artery occlusion, complex supraclinoid carotid artery aneurysm, and tumors: a report of four cases
Get PDFDespite growing popularity of endovascular techniques, certain subsets of patients with cerebrovascular compromise may benefit from bypass surgery. We present four cases in which pending ischemic lesion was prevented by (1) A3 resection and reanastomosis following falx meningioma removal, (2) rescue superficial temporal artery-middle cerebral artery (STA-MCA) bypass after pituitary adenoma surgery, (3) STA-MCA bypass for chronic internal carotid artery occlusion, and (4) external carotid artery-MCA bypass using radial artery grafting. Following the procedure, there were no further clinical or radiological deteriorations and long-term patency was confirmed in all four cases
Influence of hyperthermal regimes on experimental teratoma development in vitro
Get PDFWe screened for the impact of hyperthermal regimes varying in the cumulative
equivalent minutes at 43°C (CEM43°C) and media composition on tumour development
using an original teratoma in vitro model. Rat embryos (three germ layers)
were microsurgically isolated and cultivated at the air-liquid interface. During
a two week period, ectodermal, mesodermal and endodermal derivatives developed
within trilaminar teratomas. Controls were grown at 37°C. Overall growth
was measured, and teratoma survival and differentiation were histologically
assessed. Cell proliferation was stereologically quantified by the volume density
of Proliferating Cell Nuclear Antigen. Hyperthermia of 42°C, applied for 15 minutes
after plating (CEM43°C 3.75 minutes), diminished cell proliferation
(P ˂ .0001) and enhanced differentiation of both myotubes (P ˂ .01) and cylindrical
epithelium (P ˂ .05). Hyperthermia of 43°C applied each day for 30 minutes
during the first week (CEM43°C 210 minutes) impaired overall growth
(P ˂ .01) and diminished cell proliferation (P ˂ .0001). Long-term hyperthermia
of 40.5°C applied for two weeks (CEM43°C 630 minutes) significantly impaired
survival (P ˂ .005). Long-term hyperthermia of 40.5°C applied from the second
day when differentiation of tissues begins (CEM43°C 585 minutes) impaired survival
(P ˂ .0001), overall growth (P ˂ .01) and cartilage differentiation
(P ˂ .05). No teratomas survived extreme regimes: 43°C for 24 hours (CEM43°C
1440 minutes), hyperthermia in the scant serum-free medium (CEM43°C
630 minutes) or treatment with an anti-HSP70 antibody before long-term hyperthermia
40.5°C from the second day (CEM43°C 585 minutes). This in vitro
research provided novel insights into the impact of hyperthermia on the development
of experimental teratomas from their undifferentiated sources and are thus
of potential interest for future therapeutic strategies in corresponding in vivo
models
Emergency care of patients receiving non-vitamin K antagonist oral anticoagulants
Get PDFNon-vitamin K antagonist oral anticoagulants (NOACs), which inhibit thrombin (dabigatran) and factor Xa (rivaroxaban,
apixaban, edoxaban) have been introduced in several clinical indications. Although NOACs have a favourable benefit-risk
profile and can be used without routine laboratory monitoring, they are associatedeas any anticoagulantewith a risk of
bleeding. In addition, treatment may need to be interrupted in patients who need surgery or other procedures. The
objective of this article, developed by a multidisciplinary panel of experts in thrombosis and haemostasis, is to provide an update on the management of NOAC-treated patients who experience a bleeding episode or require an urgent procedure.
Recent advances in the development of targeted reversal agents are expected to help streamline the management of
NOAC-treated patients in whom rapid reversal of anticoagulation is required
Serum concentrations of asymmetric and symmetric dimethylarginine are associated with mortality in acute heart failure patients
Get PDFBACKGROUND:
Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine are established predictors of total and cardiovascular mortality. However, the predictive capacity of ADMA and SDMA for hospital and 3-months mortality of patients with acute heart failure (AHF) is unknown. ----- METHODS & RESULTS:
Out of 152 included AHF patients, 79 (52%) were female, and the mean patient age was 75.2 ± 10.3 years. Hospital and three-month mortality rates were 14.5% and 27.4%, respectively. Serum ADMA and SDMA levels at admission, determined by reversed phase high performance liquid chromatography, were higher in patients having at least one of the three signs implying venous volume overload (enlarged liver, ascites, peripheral edema), a consequence of right-sided heart failure, compared to patients without those signs. Univariable logistic regression analyses revealed a significant positive association of ADMA and SDMA concentrations with hospital mortality [odds ratio (OR) and 95% confidence interval (CI) per standard deviation (SD) increase: 2.22 (1.37-3.79), p = 0.002, and 2.04 (1.34-3.18), p = 0.001, respectively], and 3-months mortality [2.06 (1.36-3.26), p = 0.001, and 2.52 (1.67-4.04), p < 0.001, respectively]. These associations remained significant after adjusting for age, sex, mean arterial pressure, low-density lipoprotein cholesterol, glomerular filtration rate, and N-terminal pro-brain natriuretic peptide. ----- CONCLUSIONS:
We conclude that ADMA and SDMA concentrations are associated with hospital and 3-month mortality and are increased by venous volume overload in AHF patients
Attention deficit/hyperactivity disorder as an associated feature in OCTN2 deficiency with novel deletion (p.T440-Y449)
Get PDFThis boy presented with ADHD at 3 years and at 8 years was hyperactive with no documented hypoglycemia and had myopathy, cardiomyopathy, and very low serum carnitine. L-carnitine improved his exercise intolerance, cardiomyopathy, and behavior. Analysis of SLC22A5 revealed a premature stop codon (p.R282*) and a novel in-frame deletion (p.T440-Y449)
Molecular mechanisms of Chlamydia trachomatis resistance to antimicrobial drugs
Get PDFChlamydia trachomatis (C. trachomatis) is a leading cause of bacterial sexually transmitted infections in developed and undeveloped countries, and therefore a global public health issue. In an era of increasing bacterial resistance to antibiotics, resistance has been an exceedingly rare phenomenon in C. trachomatis; however, clinical treatment failures attributed to multidrug-resistant C. trachomatis strains have been described on several occasions. Cell culture systems using McCoy cells and subsequent immunofluorescent staining are still the most common methodology used for antimicrobial susceptibility testing, but the presence of resistance markers should be appraised by further genetic analysis. Azithromycin resistance of C. trachomatis is often a result of the mutations in the peptidyl transferase region of 23S rRNA genes, tetracycline resistance is usually linked to the presence of foreign genomic islands integrated in chlamydial chromosome, whereas a predominant mechanism of fluoroquinolone resistance is a point mutation in the gyrA quinolone-resistance-determining region. A nucleotide substitution in rpoB gene is responsible for rifampin resistance, and different mechanisms have been involved in the development of resistance to aminoglycosides, lincomycin and sulphonamide/trimethoprim combinations