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Acta Stomatol Croat ; 58(1): 76-84, 2024 Mar.
Article En | MEDLINE | ID: mdl-38562219

Background: Epstein-Barr virus (EBV) is a widely disseminated herpesvirus for which antibodies have been demonstrated in over 90% of adults worldwide. After subclinical primary EBV infections, as well as after infectious mononucleosis, the virus can be shed in saliva for a prolonged period of time. Aim: Diseases and disorders that can induce EBV salivary shedding include mental disorders and sex, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, malaria and HIV infection. Since the occurrence of EBV in saliva during acute infectious diseases has not yet been systematically researched, we aimed to investigate the possible relationship between acute infectious diseases and salivary shedding of EBV. Material and methods: This pilot cross-sectional study included consenting adults hospitalized for acute infectious conditions and their peers free of acute infectious diseases. A total of 40 patients with acute infectious diseases were enrolled, along with 41 adults free of acute infections. Peripheral venous blood samples for serodiagnosis and saliva samples for EBV PCR testing were collected from both groups. We fitted logit and general linear models to proportions and to ln (viral copy counts) to generate adjusted proportions and geometric mean values in the two groups of subjects. We used SAS for Windows 9.4. Results: The most common acute infectious disease was COVID-19 pneumonia, followed by hemorrhagic fever with renal syndrome. Crude proportions of people with positive serological test results and those with saliva viral shedding were similar in the two groups. Conclusions: The presented preliminary data do not indicate acute infectious conditions as a marked "contributor" in increasing salivary EBV shedding.

Croat Med J ; 64(5): 344-353, 2023 Oct 31.
Article En | MEDLINE | ID: mdl-37927189

AIM: To evaluate the association between carotid intima-media thickness (CIMT) at hospital admission and unfavorable outcomes in adults without advanced vascular diseases presenting with non-severe COVID-19 pneumonia to assess the feasibility of evaluating CIMT as a risk stratification aid in this setting. METHODS: This proof-of-concept nested case-control study enrolled consecutive non-vaccinated adults free of advanced vascular diseases presenting with verified non-severe COVID-19 pneumonia between December 2020 and June 2021. CIMT was measured at admission, and patients were managed in line with the national Ministry of Health guidelines. Those who died or required mechanical ventilation (MV) during the index hospital stay were considered cases and were matched (entropy balancing, exact matching) on a set of covariates to survivors not requiring MV (controls). Frequentist and Bayesian logistic models were fitted to the case status. RESULTS: The study enrolled 207 patients: 27 (13%) cases and 180 controls. All were retained in the analysis after entropy balancing, while 27 cases were exactly matched to 99 controls. Higher CIMT at the proximal internal carotid artery (both left and right) was consistently associated with higher odds of being a case: all odds ratio point-estimates were ≥1.50 with lower limits of the 99% confidence intervals/credibility intervals ≥1.00 with two-sided probabilities of OR>1.00 greater than 99.5%. The susceptibility of the estimates to unmeasured confounding was low. CONCLUSION: This study supports the feasibility of CIMT as a risk stratification aid in adults free of advanced vascular disease presenting with non-severe COVID-19 pneumonia.

COVID-19 , Vascular Diseases , Humans , Adult , Carotid Intima-Media Thickness , Risk Factors , Case-Control Studies , Bayes Theorem
Article En | MEDLINE | ID: mdl-37793994

BACKGROUND: Valproate inhibits clearance of lamotrigine and greatly increases its concentrations. We assessed whether this effect was moderated by a polymorphism (ABCG2 c.421C>A) of the breast cancer resistance protein. METHODS: In two consecutive independent studies in adults with epilepsy on lamotrigine monotherapy or cotreated with valproate: (i) Exposure to valproate was considered treatment, (ii) dose-adjusted lamotrigine troughs at steady state were the outcome, and (iii) ABCG2 c.421C>A genotype (wild-type [wt] homozygosity or variant carriage) was the tested moderator. We used entropy balancing (primary analysis) and exact/optimal full matching (secondary analysis) to control for confounding, including polymorphisms (and linked polymorphisms) suggested to affect exposure to lamotrigine (UGT1A4*3 c.142T>G, rs2011425; UGT2B7-161C>T, rs7668258; ABCB1 1236C>T, rs1128503) to generate frequentist and Bayesian estimates of valproate effects (geometric means ratios [GMR]). RESULTS: The two studies yielded consistent results (replicated); hence, we analyzed combined data (total N = 471, 140 treated, 331 controls, 378 ABCG2 c.421C>A wt subjects, 93 variant carriers). Primary analysis: in variant carriers, valproate effect (GMR) on lamotrigine (treated, n = 21 vs. controls, n = 72) was around 60% higher than in wt subjects (treated, n = 119 vs. controls, n = 259)-ratio of GMRs 1.61 (95%CI 1.23-2.11) (frequentist) and 1.63 (95%CrI 1.26-2.10) (Bayes). Similar differences in valproate effects between variant carriers and wt subjects were found in the secondary analysis (valproate troughs up to 364 µmol/L vs. no valproate; or valproate ≥364 µmol/L vs. no valproate). Susceptibility of the estimates to unmeasured confounding was low. CONCLUSION: Data suggest that polymorphism rs2231142 moderates the effect of valproate on exposure to lamotrigine.

J Clin Med ; 12(14)2023 Jul 22.
Article En | MEDLINE | ID: mdl-37510956

BACKGROUND: The impact of concomitant coronary artery bypass grafting (CABG) on aortic valve replacement (AVR) in octogenarians is still debated. We analyzed the characteristics and long-term survival of octogenarians undergoing isolated AVR and AVR + CABG. METHODS: All octogenarians who consecutively underwent AVR with or without concomitant CABG at our tertiary cardiac center between 2000 and 2022 were included. Patients with redo, emergent, or any other concomitant procedures were excluded. The primary endpoints were 30-day and long-term survival. The secondary endpoints were early postoperative outcomes and determinants of long-term survival. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of 30-day mortality, and Cox regression analysis was performed for predictors of adverse long-term survival. RESULTS: A total of 1011 patients who underwent AVR (83.0 [81.0-85.0] years, 42.0% males) and 1055 with AVR + CABG (83.0 [81.2-85.4] years, 66.1% males) were included in our study. Survival at 30 days and at 1, 3, and 5 years in the AVR group was 97.9%, 91.5%, 80.5%, and 66.2%, respectively, while in the AVR + CABG group it was 96.2%, 89.6%, 77.7%, and 64.7%, respectively. There was no significant difference in median postoperative survival between the AVR and AVR + CABG groups (7.1 years [IQR: 6.7-7.5] vs. 6.6 years [IQR: 6.3-7.2], respectively, p = 0.21). Significant predictors of adverse long-term survival in the AVR group included age (hazard ratio (HR): 1.09; 95% CI: 1.06-1.12, p < 0.001), previous MI (HR: 2.08; 95% CI: 1.32-3.28, p = 0.002), and chronic kidney disease (HR 2.07; 95% CI: 1.33-3.23, p = 0.001), while in the AVR + CABG group they included age (HR: 1.06; 95% CI: 1.04-1.10, p < 0.001) and diabetes mellitus (HR: 1.48; 95% CI: 1.15-1.89, p = 0.002). Concomitant CABG was not an independent risk factor for adverse long-term survival (HR: 0.89; 95% CI: 0.77-1.02, p = 0.09). CONCLUSIONS: The long-term survival of octogenarians who underwent AVR or AVR + CABG was similar and was not affected by adding concomitant CABG. However, octogenarians who underwent concomitant CABG with AVR had significantly higher in-hospital mortality. Each decision should be discussed within the heart team.

Life (Basel) ; 13(7)2023 Jun 23.
Article En | MEDLINE | ID: mdl-37511807

This Special Issue of Life features compelling original research and reviews related to current trends in lung transplantation (LTx) [...].

Minerva Anestesiol ; 89(10): 895-905, 2023 10.
Article En | MEDLINE | ID: mdl-37307031

BACKGROUND: Sepsis diagnostic and prognostic scoring systems have changed over time. It remains uncertain which scoring system is the best predictor of unfavorable outcomes. We aimed to evaluate prediction of community-acquired bacteremia (CAB) outcomes using on-admission systemic inflammatory response syndrome (SIRS), sequential organ failure assessment (SOFA) and quick sequential organ failure assessment (qSOFA). METHODS: We present a retrospective observational cohort study of consecutive adult patients hospitalized with CAB over ten years. SIRS, qSOFA and SOFA scores calculated on admission were dichotomized as ≥2 or 0-1. Raw and adjusted incidence of a composite unfavorable outcome (death, septic shock, invasive mechanical ventilation, extra-corporeal membrane oxygenation, renal replacement therapy) over 35 days were compared. RESULTS: Among 1930 patients, 1221 (63.3%) had SIRS, 196 (10.2%) had qSOFA, and 1117 (57.9%) had SOFA≥2. Respective raw and adjusted probabilities of the outcome were similar. Incidence for qSOFA≥2 was high (41.3%) and still considerable for qSOFA 0-1 (5.4%). SOFA≥2 indicated higher risk than SIRS≥2 (14.7% vs. 12.4%), while SOFA 0-1 indicated lower risk than SIRS 0-1 (1.2% vs. 3.1%). This relationship between SOFA and SIRS was also observed in patients with qSOFA 0-1. CONCLUSIONS: qSOFA≥2 was associated with highest probability of unfavorable outcome, but dichotomized SOFA was more precise at high vs. low-risk distinction. Consecutive use of dichotomized qSOFA and SOFA on admission of adults with CAB enables fast and reliable identification of patients at high (qSOFA≥2, risk ~≥35%), moderate (qSOFA 0-1, SOFA≥2, risk ~10%), and low risk (qSOFA 0-1, SOFA 0-1, risk 1-2%) of subsequent unfavorable events.

Bacteremia , Sepsis , Adult , Humans , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Organ Dysfunction Scores , Retrospective Studies , Hospital Mortality , Prognosis , Intensive Care Units , Sepsis/diagnosis , Sepsis/epidemiology , Bacteremia/diagnosis , Bacteremia/epidemiology , ROC Curve
Eur J Clin Pharmacol ; 79(8): 1117-1129, 2023 Aug.
Article En | MEDLINE | ID: mdl-37340142

PURPOSE: To estimate whether epilepsy patients with variant UGT2B7 -161C > T (rs7668258) or UGT1A4*3 c.142 T > G (rs2011425) alleles differ from their wild-type (wt) peers in exposure to lamotrigine. METHODS: Consecutive adults on lamotrigine monotherapy or lamotrigine + valproate co-treatment undergoing routine therapeutic drug monitoring, otherwise generally healthy and free of interacting drugs, were genotyped for UGT2B7 -161C > T and UGT1A4*3 c.142 T > G. Heterozygous, variant homozygous, or combined heterozygous/variant homozygous subjects were compared to their wt controls for dose-adjusted lamotrigine troughs with adjustment for age, sex, body weight, rs7668258/rs2011425, polymorphisms of efflux transporter proteins ABCG2 c.421C > A (rs2231142) and ABCB1 1236C > T (rs1128503), and level of exposure to valproate using covariate entropy balancing. RESULTS: Of the 471 included patients, 328 (69.6%) were on monotherapy and 143 were co-treated with valproate. Dose-adjusted lamotrigine troughs in UGT2B7 -161C > T heterozygous (CT, n = 237) or variant homozygous (TT, n = 115) subjects were closely similar to those in their wt controls (CC, n = 119): geometric means ratios (GMRs) (frequentist and Bayes) 1.00 (95%CI 0.86-1.16) and 1.00 (95%CrI 0.83-1.22) for CT vs. CC; and 0.97 (0.81-1.17) and 0.97 (0.80-1.20) for TT vs. CC subjects. Lamotrigine troughs were also closely similar in UGT1A4*3 c.142 T > G variant carriers (n = 106: 102 TG + 4 GG subjects) and wt controls (TT, n = 365): GMR = 0.95 (0.81-1.12) frequentist, 0.96 (0.80-1.16) Bayes. GMRs for variant carriers vs. wt controls were around unity also at different levels of exposure to valproate. CONCLUSION: Dose-adjusted lamotrigine troughs in epilepsy patients with variant UGT2B7 -161C > T or UGT1A4*3 c.142 T > G alleles are equivalent to those in their respective wt peers.

Epilepsy , Valproic Acid , Humans , Adult , Lamotrigine/therapeutic use , Valproic Acid/therapeutic use , Alleles , Bayes Theorem , Polymorphism, Single Nucleotide , Epilepsy/drug therapy , Epilepsy/genetics , Anticonvulsants/therapeutic use , Glucuronosyltransferase/genetics , Glucuronosyltransferase/metabolism , Genotype , UDP-Glucuronosyltransferase 1A9
Croat Med J ; 64(2): 67-74, 2023 Apr 30.
Article En | MEDLINE | ID: mdl-37131308

AIM: To evaluate the relationship between serological indicators of Herpesviridae infection and evolution of symptoms in children with chronic spontaneous urticaria (CSU). METHODS: In this observational study, consecutive children with CSU underwent, at presentation, clinical and laboratory work-up, autologous serum skin test (ASST) to identify autoimmune urticaria (CAU), disease severity assessment (urticaria activity score 7, UAS7), serological diagnostics for Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus-6 (HHV-6), and parvovirus B19, as well as for Mycoplasma pneumoniae and Chlamydia pneumoniae. Children were re-assessed at 1, 6, and 12 months after the commencement of antihistamine/antileukotriene treatment. RESULTS: None of the 56 included children had an acute CMV/EBV or HHV-6 infection, but 17 (30.3%) had IgG antibodies against CMV, EBV, or HHV-6 (five were also seropositive for parvovirus B19); 24 (42.8%) suffered from CAU; and 9 (16.1%) were seropositive for Mycoplasma/Chlamydia pneumoniae. The initial symptom severity was moderate-to-severe (UAS7 quartiles 18-32) and comparable between Herpesviridae-seropositive and Herpesviridae-seronegative patients. At 1, 6, and 12 months, UAS7 was consistently higher in seropositive children. In a multivariable analysis (adjusted for age, baseline UAS7, ASST, mean platelet volume, and other serology), Herpesviridae seropositivity was associated with higher UAS scores: mean difference 4.2 score points (95% confidence interval 0.5-7.9; Bayes estimate 4.2, 95% credible interval 1.2-7.3) in a mixed model for repeated measures. This estimate was comparable between children with positive (CAU) and negative (CSU) ASST. CONCLUSION: A history of CMV/EBV/HHV-6 infection might contribute to a slower-resolving CSU in children.

Chronic Urticaria , Cytomegalovirus Infections , Epstein-Barr Virus Infections , Herpesviridae , Humans , Child , Bayes Theorem , Herpesvirus 4, Human , Chronic Disease
Pediatr Infect Dis J ; 42(7): e229-e231, 2023 Jul 01.
Article En | MEDLINE | ID: mdl-37054396

This prospective nationwide study in Croatia (March 1, 2020-December 31, 2021) embraced 121 children with multisystem inflammatory syndrome. Incidence rates, disease course and outcomes were similar to those reported from other European countries. The severe acute respiratory syndrome coronavirus 2 virus Alpha strain appeared associated with a higher propensity to result in multisystem inflammatory syndrome in children than the Delta strain but did not appear related to disease severity.

COVID-19 , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/complications , Incidence , Croatia/epidemiology , Pandemics , Prospective Studies , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/complications
Eur J Cardiothorac Surg ; 63(5)2023 05 02.
Article En | MEDLINE | ID: mdl-36946284

OBJECTIVES: Studies concerning factors associated with long-term outcomes in adult congenital heart disease (ACHD) patients after infective endocarditis (IE) are scarce, while IE-related mortality in these patients remains a burden. We evaluated the factors associated with long-term survival in ACHD patients admitted for IE. METHODS: We performed a retrospective single-centre study of all ACHD patients admitted for IE to a tertiary cardiothoracic centre between 1999 and 2015. Underlying ACHD, detailed echocardiographic and clinical data, surgical treatment and long-term follow-up were analysed. RESULTS: We identified 151 ACHD patients admitted due to 176 episodes IE with 30-day, 6-month and 1-, 5- and 10-year survival of 95.4%, 92.7%, 92.7%, 84.7% and 75.6%, respectively. In a multivariable analysis, adjusted estimated probability of death was consistently higher after an IE episode among patients with complex as compared to simple/moderate ACHD: 10.6% vs 2.4% at 30 days, 15.0% vs 3.4% at 6 months and 1 year, 30.4% vs 7.8% at 5 years and 44.9% vs 13.1% at 10 years. Risk of death was higher among patients with prosthetic valve in comparison with those without (risk ratios 1.73-1.92). Surgical treatment was required in 76 (43.2%) episodes with 30-day mortality of 3.9%. Risk of death appeared to be lower than in the conservatively treated subgroup (risk ratios 0.71-0.78). CONCLUSIONS: We demonstrated satisfactory long-term survival in ACHD patients who were treated for IE in a tertiary cardiothoracic centre. Early mortality tended to be lower in the surgically treated subgroup. Factors negatively associated with long-term survival were complex ACHD and presence of prosthetic valve.

Endocarditis, Bacterial , Endocarditis , Heart Defects, Congenital , Humans , Adult , Retrospective Studies , Heart Defects, Congenital/complications , Heart Defects, Congenital/surgery , Endocarditis, Bacterial/complications , Endocarditis/complications , Endocarditis/surgery
Eur J Clin Pharmacol ; 79(5): 643-655, 2023 May.
Article En | MEDLINE | ID: mdl-36961578

PURPOSE: To assess the effect of exposure to fluvoxamine around the COVID-19 diagnosis on subsequent hospitalizations and mortality in COVID-19 outpatients in a real-life setting. METHODS: Using nationwide administrative data, we identified adult COVID-19 outpatients diagnosed up to August 15, 2021 and conducted two cohort studies. Study 1 included subjects prescribed fluvoxamine around the index COVID-19 diagnosis (Cohort A), their peers suffering similar psychiatric difficulties but not prescribed fluvoxamine (Cohort B) and those free of psychiatric difficulties/treatments (Cohort C). Study 2 included subjects prescribed fluvoxamine (Cohort Fluvoxamine) and their peers prescribed paroxetine (Cohort Paroxetine). Cohorts were mutually exactly matched and incidence of COVID-19-related hospitalization, 30-day all-cause hospitalization and of COVID-19-related mortality was estimated. RESULTS: Of the 416,030 first-episode outpatients, Study 1 included 1016 Cohort A, 95,984 Cohort B and 275,804 Cohort C patients. Matched Cohort A (n = 749) vs. Cohort B (n = 31,336) relative risks (95%CI/CrI), frequentist and Bayes with skeptical, otpimistic and pesimistic priors, were COVID-related hospitalization 1.37 (0.56-3.33), 1.15 (0.55-2.11), 1.03 ( and 1.43 (0.63-2.94), respectively; 30-day all-cause hospitalization 1.88 (0.76-4.67), 1.76 (1.39-2.25), 1.76 (1.39-2.24) and 1.86 (1.43-2.38), respectively; COVID-19-related mortality 0.73 (0.35-1.55), 0.93 (0.53-1.76), 0.79 (0.40-1.54) and 0.88 (0.37-2.11), respectively. Matched Cohort A vs. C (866 vs. 222,792) comparison yielded similar estimates, as did the matched Cohort Fluvoxamine vs. Paroxetine comparison in Study 2 (344 of 994 matched to 535 of 1796 patients). CONSLUSION: Outpatients prescribed fluvoxamine around the time of COVID-19 diagnosis were not at a reduced risk of hospitalizations and mortality compared to their non-prescribed peers.

COVID-19 , Fluvoxamine , Adult , Humans , Fluvoxamine/therapeutic use , Paroxetine , Cohort Studies , Outpatients , Bayes Theorem , COVID-19 Testing , COVID-19 Drug Treatment , COVID-19/diagnosis , COVID-19/epidemiology , Hospitalization
Br J Clin Pharmacol ; 89(2): 787-831, 2023 02.
Article En | MEDLINE | ID: mdl-36094656

AIMS: To assess whether exposure to proton-pump inhibitors (PPIs) shortly preceding COVID-19 diagnosis affected the risk of subsequent hospitalizations and mortality. METHODS: This population-based study embraced first COVID-19 episodes in adults diagnosed up to 15 August 2021 in Croatia. Patients were classified based on exposure to PPIs and burden of PPI-requiring morbidities as nonusers (no issued prescriptions, no recorded treatment-requiring conditions between 1 January 2019 and COVID-19 diagnosis), possible users (no issued prescriptions, but morbidities present; self-medication possible) and users (≥1 prescription within 3 months prior to the COVID-19 diagnosis; morbidities present). Subsets were mutually exactly matched for pre-COVID-19 characteristics. The contrast between users and possible users informed about the effect of PPIs that is separate of the effect of PPI-requiring conditions. RESULTS: Among 433 609 patients, users and possible users were matched 41 195 (of 55 098) to 17 334 (of 18 170) in the primary and 33 272 to 16 434 in the sensitivity analysis. There was no relevant difference between them regarding mortality (primary: relative risk [RR] = 0.93 [95% confidence interval 0.85-1.02; absolute risk difference [RD] = -0.34% [-0.73, 0.03]; sensitivity: RR = 0.88 [0.78-0.98]; RD = -0.45% [-0.80, -0.11]) or hospitalizations (primary: RR = 1.04 [0.97-1.13]; RD = 0.29% [-0.16, 0.73]; sensitivity: RR = 1.05 [0.97-1.15]; RD = 0.32% [-0.12, 0.75]). The risks of both were slightly higher in possible users or users than in nonusers (absolutely by ~0.4-1.6%) indicating the effect of PPI-requiring morbidities. CONCLUSION: Premorbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID-19 patients, but PPI-requiring morbidities seemingly slightly increase the risk of both.

COVID-19 , Proton Pump Inhibitors , Adult , Humans , Proton Pump Inhibitors/adverse effects , Cohort Studies , COVID-19 Testing , Hospitalization
Adv Ther ; 40(2): 601-618, 2023 02.
Article En | MEDLINE | ID: mdl-36434147

INTRODUCTION: Polymorphism ABCG2 c.421C>A (rs2231142) results in reduced activity of the important drug efflux transporter breast cancer-resistance protein (BCRP/ABCG2). One study has suggested that it may affect enterohepatic recirculation of mycophenolic acid (MPA). We evaluated the effect of rs2231142 on steady-state exposure to MPA in renal transplant recipients. METHODS: Consecutive, stable adult (age ≥ 16 years) renal transplant recipients on standard MPA-based immunosuppressant protocols (N = 68; 43 co-treated with cyclosporine, 25 with tacrolimus) underwent routine therapeutic drug monitoring after a week of initial treatment, and were genotyped for ABCG2 c.421C>A and 11 polymorphisms in genes encoding enzymes and transporters implicated in MPA pharmacokinetics. ABCG2 c.421C>A variant versus wild-type (wt) patients were matched with respect to demographic, biopharmaceutic, and genetic variables (full optimal combined with exact matching) and compared for dose-adjusted steady-state MPA pharmacokinetics [frequentist and Bayes (skeptical neutral prior) estimates of geometric means ratios, GMR]. RESULTS: Raw data (12 variant versus 56 wt patients) indicated around 40% higher total exposure (frequentist GMR = 1.45, 95% CI 1.10-1.91; Bayes = 1.38, 95% CrI 1.07-1.81) and around 30% lower total body clearance (frequentist GMR = 0.66, 0.58-0.90; Bayes = 0.71, 0.53-0.95) in variant carriers than in wt controls. The estimates were similar in matched data (11 variant versus 43 wt patients): exposure GMR = 1.41 (1.11-1.79) frequentist, 1.39 (1.15-1.81) Bayes, with 90.7% and 85.5% probability of GMR > 1.20, respectively; clearance GMR = 0.73 (0.58-0.93) frequentist, 0.71 (0.54-0.95) Bayes. Sensitivity analysis indicated low susceptibility of the estimates to unmeasured confounding. CONCLUSIONS: Loss-off-function polymorphism ABCG2 c.421C>A increases steady-state exposure to MPA in stable renal transplant patients.

Kidney Transplantation , Mycophenolic Acid , Adult , Humans , Adolescent , Mycophenolic Acid/therapeutic use , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Kidney Transplantation/methods , Cohort Studies , Bayes Theorem , Polymorphism, Single Nucleotide , Multidrug Resistance-Associated Protein 2 , Neoplasm Proteins/genetics , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/pharmacokinetics
Acta Clin Croat ; 62(1): 193-200, 2023 Apr.
Article En | MEDLINE | ID: mdl-38304375

Chronic rhinitis and rhinosinusitis (CR and CRS) can lead to impairment of the health-related quality of life (HRQL) with higher psychological perceived distress, resulting in disease worsening and poor treatment outcomes. W aimed to evaluate the potential association between disease severity and HRQL impairment with the perceived acute psychological distress in newly diagnosed CR/CRS patients. This single-center cross-sectional study included otherwise healthy consecutive adults with newly diagnosed CR/CRS (European position paper on rhinosinusitis and nasal polyp criteria and International Consensus Statement on Allergy and Rhinology - Allergic Rhinitis criteria or non-allergic rhinitis), who were evaluated for CR/CRS symptom severity and HRQL (Sino Nasal Outcome Test 22 [SNOT-22], visual analog scale [VAS]) and acute perceived distress (Perceived Stress Scale [PSS]). Principal component analysis (SNOT-22 items, VAS) identified 6 components as CR/CRS severity indicators, i.e,, poor sleep, wakes-up tired, nasopharynx, obstruction, torment and rhinorrhea, which were evaluated for association with PSS score. Of the 63 included patients (20 men, age median 38, range 19-75 years), 27 suffered from CR and 36 from CRS. Upon adjustment for age and sex, higher total SNOT-22 (geometric means ratio [GMR]=1.04, 95% CI 1.01-1.06), higher "torment" (GMR=1.13, 1.04-1.24), higher "poor sleep" (GMR=1.11, 1.02-1.21) and higher "wakes-up tired" (GMR=1.11, 1.01-1.21) scores were each associated with a higher PSS score, overall and consistently in CR and CRS patients. In conclusion, more severe CR/CRS is associated with greater perceived psychological distress already at earlier stages of the disease. Paying attention to patient level of distress and anxiety over time may enable better understanding of the connection between exacerbations, symptom severity and psychological burden of the disease.

Psychological Tests , Rhinitis, Allergic , Rhinitis , Self Report , Sinusitis , Adult , Male , Humans , Young Adult , Middle Aged , Aged , Quality of Life , Cross-Sectional Studies , Sinusitis/complications , Sinusitis/diagnosis , Rhinitis/complications , Rhinitis/diagnosis , Chronic Disease , Rhinitis, Allergic/complications
J Card Surg ; 37(11): 3801-3810, 2022 Nov.
Article En | MEDLINE | ID: mdl-36040710

BACKGROUND: Although concomitant pulmonary vein isolation (PVI) is used more frequently than the Cox-Maze procedure, which is currently the gold standard treatment for atrial fibrillation (AF), data on the comparative effectiveness of the two procedures after concomitant mitral valve (MV) surgery are still limited. OBJECTIVE: We conducted a systematic review to identify randomized controlled trials (RCTs) and observational studies comparing the mid-term mortality and recurrence of AF after concomitant Cox-Maze and PVI in patients with AF undergoing MV surgery based on 12-month follow-up. METHODS: Medline, EMBASE databases, and the Cochrane Library were searched from 1987 up to March 2022 for studies comparing concomitant Cox-Maze and PVI. Additionally, a meta-analysis of RCTs was performed to compare the mid-term clinical outcomes between these two surgical ablation techniques. RESULTS: Three RCTs and three observational studies meeting the inclusion criteria were included in this systematic review with 790 patients in total (532 concomitant Cox-Maze and 258 PVI during MV surgery). Most studies reported that the concomitant Cox-Maze procedure was associated with higher freedom from AF at 12-month follow-up than PVI. Regarding AF recurrence, estimates pooled across the three RCTs indicated large heterogeneity and high uncertainty. In the largest and highest quality RCT, 12-month AF recurrence was higher in the PVI arm (risk ratio = 1.58, 95% CI: 0.91-2.73). In two out of three higher-quality observational studies, 12-month AF recurrence was higher in PVI than in the Cox-Maze arm (estimated adjusted probabilities 11% vs. 8% and 35% vs. 17%, respectively). RCTs demonstrated comparable 12-month mortality between concomitant Cox-Maze and PVI, while observational studies demonstrated the survival benefit of Cox-Maze. CONCLUSIONS: Concomitant Cox-Maze in AF patients undergoing MV surgery is associated with better mid-term freedom from AF when compared to PVI with comparable mid-term survival. Large observational studies suggest that there might be a mid-term survival benefit among patients after concomitant Cox-Maze. Further large RCTs with longer standardized follow-up are required to clarify the benefits of concomitant Cox-Maze in AF patients during MV surgery.

Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Atrial Fibrillation/complications , Catheter Ablation/methods , Humans , Maze Procedure , Mitral Valve/surgery , Pulmonary Veins/surgery , Recurrence , Treatment Outcome
Life (Basel) ; 12(7)2022 Jun 29.
Article En | MEDLINE | ID: mdl-35888068

Rashes and skin lesions are a common reason for patient visits to emergency departments and physicians' offices. The differential diagnosis includes a variety of infectious and non-infectious diseases, some of which can be life-threatening. The aim of this retrospective study was to evaluate the quantity and type of skin lesions among outpatients and inpatients at a tertiary care university-affiliated teaching hospital for infectious diseases over a three-year period to assess disease burden and physicians' experience in diagnosing skin lesions. Diagnoses (by ICD-10 codes) were classified into three groups: infectious diseases that include skin lesions, non-infectious skin lesions and undiagnosed skin lesions. During the observed period, out of the total of 142,416 outpatients, 14.8% presented with some form of skin lesion. Among them, 68% had skin lesions inherent to infectious disease, 10.8% suffered from non-infectious skin lesions and 21.2% remained with undiagnosed skin lesions. The most common infectious diagnoses were chickenpox, herpes zoster and unspecified viral infections characterized by skin and mucous membrane lesions. The most common non-infectious diagnoses were urticaria and atopic dermatitis. Overall, the most common individual diagnosis (ICD-10 code) was "nonspecific skin eruption" (n = 4448, 21.1%), which was followed by chickenpox and herpes zoster. Among the 17,401 patients hospitalized over the observed period, 13.1% had skin lesion as the main reason for hospitalization, almost all (97.5%) of which were infectious in etiology. The most common diagnoses were cellulitis, erysipelas and herpes zoster. The presented data suggest that the burden of diseases presenting with skin lesions is significant in everyday infectious disease practice, but the overwhelming number of undiagnosed patients implies the need for further education in this area.

Comput Biol Med ; 144: 105391, 2022 05.
Article En | MEDLINE | ID: mdl-35290809

BACKGROUND: Assessment of neuromuscular function is critical for understanding pathophysiological changes related to motor system dysfunction in many rodent disease models. Among methods used for quantification of grip performance in rodents, gauge-based grip strength meters provide the most reliable results, however, such instruments are unaffordable by many laboratories. The present aim was to demonstrate how to build a rodent grip strength apparatus from scratch using a digital kitchen scale, an empty cage, and a microcontroller, with both hardware and software being completely open-source to enable maximal modularity and flexibility of the instrument in concordance with the principles of open-source bioinstrumentation. METHODS: NodeMCU ESP-32S was connected to a hacked digital kitchen scale-based platform and load cell data were acquired using custom open-source scripts. Data were analyzed in R using semi-automatic analysis algorithms implemented in the ratPASTA package. griPASTA system was tested by quantifying muscular rigidity in the rat model of Parkinson's disease (PD) induced by bilateral intrastriatal administration of 6-hydroxydopamine (6-OHDA). RESULTS: In contrast to commercial instruments, the flexibility and modularity of the proposed platform enable collecting raw data and controlling for potential confounding effects on the grip strength. Muscular rigidity is significantly increased in the rat model of PD regardless of the dose used or reboxetine pretreatment. Neither trial speed nor animal weight was recognized as an important confounder. CONCLUSIONS: griPASTA provides a cheap, easy, precise, and reliable way to measure grip strength in rodents using widely available equipment and open-source software.

Parkinson Disease , Rodentia , Animals , Hand Strength/physiology , Muscle Rigidity , Rats