Cladribine (CLD) treats multiple sclerosis (MS) by selectively and transiently depleting B and T cells with a secondary long-term reconstruction of the immune system. This study provides evidence of ...CLD’s immunomodulatory role in peripheral blood mononuclear cells (PBMCs) harvested from 40 patients with untreated relapsing-remitting MS (RRMS) exposed to CLD. We quantified cytokine secretion from PBMCs isolated by density gradient centrifugation with Ficoll−Paque using xMAP technology on a FlexMap 3D analyzer with a highly sensitive multiplex immunoassay kit. The PBMC secretory profile was evaluated with and without CLD exposure. PBMCs isolated from patients with RRMS for ≤12 months had significantly higher IL-4 but significantly lower IFN-γ and TNF-α secretion after CLD exposure. PBMCs isolated from patients with RRMS for >12 months had altered inflammatory ratios toward an anti-inflammatory profile and increased IL-4 but decreased TNF-α secretion after CLD exposure. CLD induced nonsignificant changes in IL-17 secretion in both RRMS groups. Our findings reaffirm CLD’s immunomodulatory effect that induces an anti-inflammatory phenotype.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Computers have become to play an important role in people's lives throughout the world thus increasing the number of patients with ocular complaints. Also known as computer vision syndrome, ...accommodative asthenopia might be considered as a neglected occupational condition, but there is no consensus regarding diagnostic criteria, which leads to under-recognition and under-reporting. The aim of the study was to investigate the prevalence, early symptoms and specific preventive measures of accommodative asthenopia among computer-using medical students (n = 420), in a cross-sectional study. The most common early symptoms were: tired eyes/eye strain (86.1%), burning eyes (46.8%), migraines/headaches (46.8%), red-swollen eyes (43%), photophobia (41.8%), temporary blurred vision (35.4%), and eyelid spasms (32.9%). Our study identifies the most frequent early symptoms of accommodative asthenopia as a possible occupational disease, which might serve as a fundament for a future consensus strategy.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide ...polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome.
We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset.
TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34-0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21-0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock.
TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiac autonomic neuropathy (CAN) in diabetes is among the strongest risk markers for future global and cardiovascular mortality. The aim of this study was to analyse CAN prevalence and to compare ...the associations between CAN, the glycaemic control, cardiovascular risk factors, peripheral neuropathy, retinopathy and macroangiopathy in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM).
One hundred ninety-five diabetic patients were included in this study. All patients were evaluated for detection of CAN (with standardised cardiovascular reflex tests), diabetes-related microvascular complications (polyneuropathy, retinopathy), common carotid artery intima-media thickness (IMT) and ankle-brachial index (ABI).
The prevalence of CAN was 39.1% in T2DM and 61.8% in T1DM patients. Multivariate logistic regression analysis demonstrated that in T2DM, the odds OR (95% confidence intervals) of CAN increased with diabetes duration 1.67(1.42-1.92), HbA1c 1.74(1.34-2.27), cholesterol 1.01(1.00-1.01), triglycerides 1.01(0.99-1.00), smoking 2.35(1.23-4.49), systolic blood pressure 1.01(1.00-1.03), BMI 1.16(1.08-1.24), glomerular filtration rate 0.91(0.88-0.93), peripheral neuropathy 25.94(11.04-44.25), retinopathy 13.13(3.03-84.73) and IMT 10.12 (7.21-15.32). In T1DM, the odds of CAN increased with diabetes duration 1.62(1.13-2.31), HbA1c 4.49(1.27-15.9), age of patients 1.14(1.03-1.27), glomerular filtration rate 0.94(0.89-0.99), peripheral neuropathy 31.6(4.5-45.8) and IMT 5.5(2.3-8.3).
This study indicated that CAN is a more frequent complication in T1DM. Apart from glycaemic control, the existence of CAN is associated with potentially modifiable cardiovascular risk only in T2DM patients. The presence of other micro- and macrovascular complications increases the probability of having CAN in both types of DM (but more pronounced in T2DM).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Programmed death ligand-1 (PD-L1) immunohistochemical (IHC) status is used to predict which patients with metastatic urothelial carcinoma (UC) will respond to immunotherapy. We aimed to compare ...QR1(Quartett), 22C3 (Dako), and SP263 (Ventana) detection of PD-L1 expression in muscle-invasive UCs and determine the best scoring algorithm for assessment of PD-L1 expression when using the QR1 clone. Our study included 69 UCs. For SP263 and 22C3, PD-L1-positive tumor cell (TC) and/or immune cell (IC) percentages (TC%/IC%) and the Combined Positive Score (CPS) were assessed, respectively (positivity cut-offs of ≥ 25% and ≥ 10). For QR1, both interpretation systems were evaluated. The concordances between assays were calculated. PD-L1 IHC staining characteristics were comparable between QR1, 22C3, and SP263 in both conventional and variant histology UCs. We demonstrated strong or very strong correlations between clones; the strongest correlation for TCs was between QR1 and SP263 (r = 0.92;
p
= 0.001) and for ICs was between QR1 and 22C3 (r = 0.85;
p
= 0.001). Our comparative analysis of the scoring algorithms revealed very good concordances among the three assays (range 0.791–0.878); the highest concordance was between QR1 and SP263 when CPS was used as the scoring algorithm for QR1 (0.878;
p
< 0.001). Our study is the first to demonstrate that the QR1 clone can be used to evaluate PD-L1 status in UCs, with a very good agreement rate with the reference clones. QR1 appeared to be more similar to the SP263 clone. With regard to the scoring algorithm, when evaluating PD-L1 expression using QR1 clone, CPS performed better compared with the TC%/IC% score.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
The COVID-19 outbreak has placed substantial pressure on the medical systems worldwide. This study aimed to investigate the influence of the prepandemic vs. pandemic period on the activity of the ...Vascular Surgery Unit of a large emergency hospital in Eastern Europe. We performed a retrospective review of the vascular surgery cases admitted, comparing the statistics from the two time periods. We examined data of a total of 1,693 patients over the two periods. We report a 34.51% decrease in the surgical procedures performed during the pandemic period, with a disproportionate 80.6% decrease in the number of cases admitted with a diagnosis of venous insufficiency diagnosis and an increase of 67.21% in the number of patients admitted with acute arterial ischemia. Furthermore, individuals not classed as emergencies were delayed or denied surgical care. The number of nonurgent procedures conducted by our Vascular Surgery Unit decreased significantly, whereas the number of emergency surgeries increased. COVID-19′s effect is projected to have a long-term impact on how surgical treatments are provided in Romania.
Background: Abdominal aortic aneurysm (AAA) is a complex vascular disease characterized by progressive and irreversible local dilatation of the aortic wall. Currently, the indication for repair is ...linked to the transverse diameter of the abdominal aorta, using computed tomography angiography imagery, which is one of the most used markers for aneurysmal growth. This study aims to verify the predictive role of imaging markers and underlying risk factors in AAA rupture. Methods: The present study was designed as an observational, analytical, retrospective cohort study and included 220 patients over 18 years of age with a diagnosis of AAA, confirmed by computed tomography angiography (CTA), admitted to Vascular Surgery Clinic of Mures County Emergency Hospital in Targu Mures, Romania, between January 2018 and September 2022. Results: Patients with a ruptured AAA had higher incidences of AH (p = 0.006), IHD (p = 0.001), AF (p < 0.0001), and MI (p < 0.0001), and higher incidences of all risk factors (tobacco (p = 0.001), obesity (p = 0.02), and dyslipidemia (p < 0.0001)). Multivariate analysis showed that a high baseline value of all imaging ratios markers was a strong independent predictor of AAA rupture (for all p < 0.0001). Moreover, a higher baseline value of DAmax (OR:3.91; p = 0.001), SAmax (OR:7.21; p < 0.001), and SLumenmax (OR:34.61; p < 0.001), as well as lower baseline values of DArenal (OR:7.09; p < 0.001), DACT (OR:12.71; p < 0.001), DAfemoral (OR:2.56; p = 0.005), SArenal (OR:4.56; p < 0.001), SACT (OR:3.81; p < 0.001), and SThrombusmax (OR:5.27; p < 0.001) were independent predictors of AAA rupture. In addition, AH (OR:3.33; p = 0.02), MI (OR:3.06; p = 0.002), and PAD (OR:2.71; p = 0.004) were all independent predictors of AAA rupture. In contrast, higher baseline values of SAmax/Lumenmax (OR:0.13; p < 0.001) and ezetimibe (OR:0.45; p = 0.03) were protective factors against AAA rupture. Conclusions: According to our findings, a higher baseline value of all imaging markers ratios at CTA strongly predicts AAA rupture and AH, MI, and PAD highly predicted the risk of rupture in AAA patients. Furthermore, the diameter of the abdominal aorta at different levels has better accuracy and a higher predictive role of rupture than the maximal diameter of AAA.
Acute Limb Ischemia (ALI) of the lower limb is defined as a sudden drop in arterial limb perfusion, which is a medical emergency requiring prompt intervention with high amputation and mortality rates ...in the absence of revascularization. This observational, analytical, and retrospective cohort study with longitudinal follow-up aimed to confirm the relevance of the preoperative inflammatory biomarkers neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting the 30-day poor prognosis of patients with Rutherford classification (RC) grades II and III ALI. The ROC analysis found a strong association of an NLR > 4.33 with all studied outcomes, while a PLR > 143.34 was associated with all studied outcomes, except the composite endpoint in all RC stages. Depending on the optimal cut-off value, the ROC analysis found a higher incidence of all adverse outcomes in all high NLR (>4.33) and high PLR (>143.34) groups. A multivariate analysis showed that a high baseline value for NLR and PLR was an independent predictor of amputation (OR:11.09; 95% CI: 5.48−22.42; p < 0.0001; and OR:8.97; 95% CI: 4.44−18.16; p < 0.0001), mortality (OR:22.24; 95% CI: 9.61−51.47; p < 0.0001; and OR:8.32; 95% CI: 3.90−17.73; p < 0.0001), and composite endpoint (OR:21.93; 95% CI: 7.91−60.79; p < 0.0001; and OR:9.98; 95% CI: 3.89−25.55; p < 0.0001), respectively. Furthermore, for all hospitalized patients, the RC grade III (OR:7.33; 95% CI: 3.73−14.26; p < 0.0001) was an independent predictor of amputation (OR:7.33; 95% CI: 3.73−14.26; p < 0.0001), mortality (OR:8.40; 95% CI: 4.08−17.31; p < 0.0001), and composite endpoint (OR: 10.70; 95% CI: 4.48−25.56; p < 0.0001), respectively. The NLR and PLR are excellent predictors of risks associated with ALI for primary and secondary prevention. Our study showed that increased pre-operative values for NLR and PLR are indicators of a poor outcome in patients with RC grades II and III ALI.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background and Objectives: Shoulder disorders are associated with pain, restricted range of motion and muscular strength, moderate disability and diminished proprioception. This study aimed to ...compare the effectiveness of an innovative technology-supported and a classical therapist-based proprioceptive training program in addition to conventional physiotherapy, on joint position sense (JPS), pain and function, in individuals with different musculoskeletal shoulder disorders, such as rotator cuff tear, subacromial impingement syndrome and superior labrum anterior and posterior tear. The innovative element of the proprioceptive training programme consists of the use of the Kinesimeter, a device created for both training and assessing shoulder JPS. Materials and Methods: The shoulder JPS test and the DASH outcome questionnaire were applied to fifty-five individuals (28 females, 27 males, mean age 56.31 ± 6.75), divided into three groups: 17 in the conventional physiotherapy group (control group); 19 in the conventional physiotherapy + classical proprioceptive training program group (CPT group); and 19 in the conventional physiotherapy + innovative proprioceptive training program group (KPT group). Assessments were performed before and after a four-week rehabilitation program, with five physiotherapy sessions per week. Results: When baseline and post-intervention results were compared, the value of the shoulder JPS and DASH outcome questionnaire improved significantly for the KPT and CPT groups (all p < 0.001). Both KPT and CPT groups showed statistically significant improvements in JPS, pain and function, compared to the control group which received no proprioceptive training (all p < 0.05). However, the KPT group showed no significant benefits compared to the CPT group. Conclusions: Our findings indicate that using the Kinesimeter device as a novel, innovative proprioceptive training tool has similar effects as the classical proprioceptive training programs among individuals with different non-operated musculoskeletal shoulder disorders such as: rotator cuff tear, subacromial impingement syndrome, and superior labrum anterior and posterior tear.
•Dermal exposure to VOCs is becoming increasingly important in industrial settings.•Exposure to toluene, acetone and styrene occurred in the studied work environment.•Skin penetration to VOCs was ...assessed using ACC patches and predictive tools.•A good correlation between air/dermal exposure and urinary levels was found.•Workers exposure evaluation should comprise an integrated approach.
The assessment of dermal exposure to volatile organic compounds (VOCs) is becoming increasingly important in industrial settings. The study aimed to evaluate the overall exposure (inhalation and dermal) of workers to VOCs, and to assess the suitability of activated charcoal cloth (ACC) patches for the evaluation of the contribution of dermal exposure (vs. inhalation exposure) to the whole body burden, as reflected by human biomonitoring.
Inhalation exposure to toluene, acetone and styrene (passive 3 M organic vapour monitors, OVMs) and dermal exposure (ACC patches on the index finger, thumb and neck) were measured simultaneously in 37 subjects performing different tasks in a factory of thermoplastic panels. Systemic exposure was assessed in urine by quantification of mandelic acid (MA) and phenyl glyoxylic acid (PGA), as biomarkers for styrene, as well as acetone and hippuric acid (HA) as biomarkers for acetone and toluene, respectively.
High styrene (range 30.66–302 mg/m3) and acetone (range 11–644 mg/m3) concentrations were found in the air of the workplace, while toluene was less abundantly present (range 0.05–2.6 mg/m3). On the ACC patches, considerable amounts of these VOCs were found. For employees manually handling styrene, dermal exposure on the index finger and thumb were substantially higher compared to the neck ACC patch. A good correlation between air and urinary levels of acetone exposure was found. MA and PGA levels in urine, markers for styrene exposure, were correlated with both air and dermal exposure.
These data suggest that there is a substantial benefit from assessing dermal exposure in the work place in addition to the more conventional air monitoring and urinary biomonitoring.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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