Search

Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.

Introduction Many atopic dermatitis (AD) patients suffer from insomnia. Out of numerous factors associated with sleep disorders, melatonin seems to play a significant role. Aim To assess the relation between melatonin concentration and sleep disorders in adult patients with severe and very severe AD. Material and methods The study included 36 adult patients with severe and very severe AD and 20 healthy Caucasian volunteers. The severity of skin lesions was assessed by the EASI scale. Skin itch was evaluated by a visual-analogue scale (VAS), and sleep disorders were assessed by the Polish version of the Athens Insomnia Scale (AIS). Serum melatonin concentration of patients and controls was determined by ELISA. Results Melatonin concentration in patients with very severe AD was significantly (p < 0.001) lower than in patients with severe AD, however, melatonin concentration in the group of AD patients did not differ significantly (p = 0.33) from that observed in the control group. There was a significant negative correlation between the concentration of melatonin in the study group and the severity of itching (R = –0.54, p < 0.001). The intensity of sleep disorders was significantly higher (p < 0.001) in patients with a very severe form of AD compared to patients with severe AD. Moreover, there was a significant negative correlation between melatonin concentration and sleep disorders (R = –0.67, p < 0.001). Conclusions Our results clearly showed that sleep disturbances are more expressed in very severe AD patients compared to subjects suffering from severe disease. We also suggest that melatonin serum concentration could play a role in the pathogenesis of sleep disturbances in AD patients.

Introduction Radical cystectomy is the treatment of choice for patients with muscle invasive bladder cancer (MIBC), but it may be unsafe in older patients. Aim In this study, we investigated whether age and selected clinical characteristics were associated with outcomes of radical cystectomy. Material and methods We enrolled 434 patients with MIBC who underwent radical cystectomy between 2012 and 2016, and we classified them into three age groups: < 65, 66–74, and ≥ 75 years. Postoperative complications were classified on the Clavien-Dindo scale. Regression models were used to find predictors of major postoperative complications (Clavien-Dindo score of 3 or more), long hospital stay (> 7 days), blood loss, and operating time. The models included American Society of Anesthesiologists scores, age group, sex, body mass index, Tumor Nodes Metastasis scores, type of urine derivation (ileal conduit or orthotopic bladder vs. ureterocutaneostomy), and operation type (open vs. laparoscopic). Results In the regression models, age was not a significant predictor of major complications, long hospital stay, or blood loss (p ≥ 0.206). Older age was associated with shorter surgery times (p = 0.002). Higher preoperative American Society of Anesthesiologists scores tended to be associated with a greater risk of major complications (odds ratio, 1.47; p = 0.092). Conclusions Older age was not associated with an increased risk of major complications in patients who undergo radical cystectomy because of MIBC. Therefore, older age alone should not be a contraindication to this operation.

Introduction Mechanical circulatory support (MCS) has been established as a means of augmenting circulation in patients with critically decreased systolic function due to a variety of underlying clinical reasons. Different methods of MCS may be used, with the venous-arterial extracorporeal membrane oxygenation system (VA-ECMO) being one of the most utilized devices in everyday care. Aim To determine independent predictors influencing mortality outcomes following VA-ECMO therapy in a large, unselected, adult, critically ill patient population in cardiogenic shock (CS). Material and methods Data on 235 consecutive, real-world VA-ECMO treatments were assessed. Analysis was conducted for all subjects requiring MCS with the VA-ECMO as the first instalment, regardless of underlying cause or eventual upgrade. All potential clinical factors influencing mortality were examined and evaluated. Results Overall mortality was ~66% at median 28 days follow-up and significantly depended upon pH < 7.3 (HR = 3.56; p < 0.001), and age ≥ 65 years (HR = 1.96; p = 0.001). Acute coronary syndrome (ACS) as an indication for VA-ECMO displayed a nearly significant value (HR = 1.44; p = 0.07). Heart transplant (hTX) primary graft failure as an indication for the VA-ECMO displayed a clearly favorable outcome (HR = 0.51, p = 0.025); all data based on multivariate Cox regression analysis. Conclusions Mortality in patients requiring VA-ECMO remains high. We conclude that only decreased pH values and advanced age clearly influence mortality in this MCS scenario. ACS also bodes unfavorably, whereas hTX as an indication clearly shows better survival.

SUMMARY The aim of the study was to assess the impact of primary argon laser trabeculoplasty (ALT) on intraocular pressure (IOP) lowering and quality of life improvement in patients with pseudoexfoliative glaucoma. Sixty patients with newly diagnosed pseudoexfoliative glaucoma who underwent primary ALT (group 2) or medication therapy (group 1) were followed-up. The effect of ALT on IOP reduction, dry eye development and number of antiglaucoma drugs used was examined. Patients were examined at the beginning of the study and then after 6, 12, and 18 months. A statistically significant difference between IOP values was observed throughout the 18-month follow-up, with the highest significance recorded 6 months after ALT (p=0.009). Twelve months after the start of the study, the TBUT value was 6.0±0.8 s in group 1 and 8.4±0.7 s in group 2. In group 2, the value of Schirmer test was constantly above 10 millimeters. The number of antiglaucoma medications used in group 1 was statistically significantly higher as compared to group 2 throughout the 18-month study period. ALT was found to be better choice for temporary regulation of IOP in patients with pseudoexfoliative glaucoma.

Purpose The aim of this study was to compare survival outcomes of open radical hysterectomy and minimally invasive radical hysterectomy (MIS) in early stage cervical cancer. Methods A retrospective analysis of 148 patients with stage IB1 - IIA2 cervical cancer who underwent either minimally invasive or open radical hysterectomy. Tumor characteristics, recurrence rate, disease-free survival (DFS), and overall survival (OS) were compared according to surgical approach. Results In total, 110 and 38 patients were assigned to open surgery and MIS groups. After a medical follow-up of 42.1 months, the groups showed similar survival outcomes (recurrence rate, DFS, and OS). However, in patients with tumor size >2 cm, recurrence rate was significantly higher in MIS group (22.5% vs 0%; p=0.008). And in patients with tumor size >2 cm, MIS group showed significantly poorer DFS than open surgery group (p=0.017), although OS was similar between the two groups (p=0.252). Conclusion In patients with tumor size >2 cm, MIS was associated with higher recurrence rates and poorer DFS than open surgery. However, in patients with tumor size ≤2 cm, MIS did not seem to compromise oncologic outcomes.

Kit lot change in clinical biochemistry labs leads to variations in patient results. This study planned to identify variations during 60 reagent lot changes in our laboratory during the period from June 2018 to May 2019.A statistical analysis was performed to identify the difference between patient samples results variations and QC results. The long term drift was analyzed using a regression test.There was a significant difference between the patient and QC results in 16.7% of reagent lot changes. Moreover, the extent of variation in QC results was 3.3%. No long-term drift was seen in three analytes which were studied using regression analysis.Our results showed that, during reagent kit lot change, along with QC material, the patient samples should also be run in order to identify the variation. However, this practice is presently ignored by most of the laboratories. There was no accumulated effect in our laboratory due to reagent kit lot change.Promena setova reagenasa u biohemijskim laboratorijama na klinikama dovodi do varijacija u rezultatima pacijenata. Plan ovog istraživanja je bio da identifikuje varijacije u toku šezdeset promena setova reagenasa u našoj laboratoriji u periodu od juna 2018. godine do maja 2019. godine.Izvršena je statistička analiza kako bi se identifikovala razlika između varijacija u rezultatima pacijenata i rezultata kontrole kvaliteta (QC). Dugoročne promene su analizirane pomoću regresijskih testova.Otkrivena je značajna razlika u rezultatima pacijenata i kontrole kvaliteta u 16,7% promena setova reagenasa. Takođe, opseg varijacije u rezultatima kontrole kvaliteta bio je 3,3%. Nisu pronađene dugoročne promene u tri analita koja su analizirana regresijskim testovima.Naši rezultati ukazuju na to da bi prilikom zamene setova reagenasa, pored materijala za kontrolu kvaliteta, trebalo testirati i uzorke pacijenata kako bi se identifikovale varijacije. Međutim, većina laboratorija ovaj postupak ne primenjuje. Nije pronađen dugoročni uticaj usled nagomilavanja varijacija prilikom promene setova reagenasa u našoj laboratoriji.

Hepatocellular carcinoma (HCC), a common type of primary liver cancer, is one of the most aggressive malignant tumors worldwide. Although overall survival (OS) rates for HCC has significantly improved in recent years, however, the exact predictive value of microRNA (miRNA) for the prognosis of HCC has not yet been recognized. Here, we aimed to identify potential prognostic miRNAs involved in HCC by bioinformatics analysis and validated expression levels through quantitative polymerase chain reaction (qPCR) and GEO database. The RNA expression profiles and corresponding clinical information of HCC were available from The Cancer Genome Atlas (TCGA) datasets. Differentially expression and standardization analysis of miRNAs, Kaplan-Meier curve and time dependent ROC curve were performed by using R tools. Differentially expressed miRNAs (DEmiRNAs) and clinical parameters involved in the OS of HCC were confirmed by Cox regression models. And functional enrichment analysis was used to establish functions of the targeted genes of DEmiRNAs. A total of 300 DEmiRNAs were significantly related with HCC, of which 40 were down-regulated and 260 were up-regulated. A total of 344 patients with DEmiRNAs, status, overall survival (OS) time were randomized into training group (172) and test group (172). Multivariate Cox regression analyses revealed that 3 miRNA (hsa-miR-139-3p, hsa-miR-760, hsa-miR-7-5p) had independent prognostic significance for the OS of HCC in both training and test group. Moreover, according to Kaplan Meier analysis, the OS of HCC patients with high-risk score was shorter in validation and entire series. The time dependent ROC curve demonstrated high accuracy of the signature for OS. Besides, target genes of three miRNAs were analyzed by functional enrichment analysis and 20 genes associated with OS were verified by using Kaplan-Meier method. Compared with normal and benign group, the relative expression level of hsa-miR-139-3p was significantly decreased, while hsa-miR-7-5p and hsa-miR-760 were distinctly increased in the plasma of HCC patients. The same results were observed in the independent cohort. Collectively, our research suggested that three-miRNA signature could serve as an independent prognostic indicator for HCC patients.

Background: To evaluate locoregional failure and its impact on survival by comparing involved field irradiation (IFI) with elective lymph node irradiation (ENI) for patients with esophageal squamous cell cancer who underwent post-operative radiotherapy. Methods and Materials: The enrolled patients were randomized allocated to IFI or ENI group. CTV of IFI was generated according to pre-operative primary tumor location and post-operative pathological characters and positive LNs regions. CTV of ENI was generated according to pre-operative tumor position to administer selective lymph node irradiation. Radiotherapy planning was delivered using either 3D-CRT or IMRT. Results: A total of 57 patients were enrolled, 28 patients in ENI group and 29 patients in IFI group. There were not statistical differences between two groups in baseline (p>0.05). The initial locoregional failure rate was 17.9 % in ENI arm and 20.7% in IFI arm respectively (p=0.085). The 1-, 3-, and 5-year Progression-free Survival (PFS) were 63.2, 43.5, and 21.8 % in ENI arm versus 78.2, 60.1, and 55.1% in IFI arm (p =0.038). The 1-, 3-, and 5-year overall survival (OS) were 78.6, 46.9, and 23.5 % in ENI arm versus 72.9, 59.7, and 54.3 % in IFI arm (p=0.06). Acute radiation pneumonitis (p=0.005) and hematological toxicities (p =0.029) also showed statistical differences between groups, ENI arm was more than IFI arm. Conclusions: The results indicated that IFI tended to improve survival and reduce toxicities for patients with operative ESCC and did not increase locoregional failure compared to ENI. It is thus suggested that IFI for ESCC PORT is worthy of clinical recommendation and further study.

Background: Diabetes mellitus (DM) is the world’s most common cause of chronic kidney diseases (CKD), with approximately 1 in 4 adults with DM having CKD and 1 out of 10 to 20% of DM patients die from CKD. Objective: The current study aims to investigate the correlation between Notch-2 and Jag-1expressions and specific inflammation biomarkers IL-1β and IL-6 with different stages of diabetic nephropathy. Methods: From August 2018 to January 2019, three hundred subjects were recruited for this study. One hundred and fifty subjects were healthy and age-matched to the diabetic group and selected as a control group. Another 150 patients with an established diagnosis of type 2 diabetes (T2DM) according to the criteria of the American Diabetes Association (ADA) were also recruited. Blood specimens were eventually used to identify the expressions Notch-2 and Jagged-1 and the levels of inflammatory biomarkers IL-1β and IL-6. Result: The current study shows a significant increase in gene expression and inflammatory biomarkers in patients with moderate and severe diabetic nephropathy compared to the control group. However, there was no significant difference between healthy control and mild diabetic nephropathy patients. This study shows a close association between the increase in the levels of inflammatory biomarkers IL-1β and IL-6 as well as the gene expressions levels of both Notch-2 and Jag-1 with human diabetic nephropathy. Conclusion: According to our findings, we emphasize the use of Notch-2 and Jag-1 expressions and IL-1β and IL-6 levels as potential biomarkers for different stages of diabetic nephropathy.

Introduction Anti-RNA polymerase III (a-RNA Pol III) antibodies are marker antibodies in patients with systemic sclerosis (SSc). Aim To assess the prevalence of a-RNA Pol III in patients with SSc and to identify the differences in the disease picture in SSc patients with and without a-RNA Pol III antibodies. Material and methods The study was performed in 126 SSc patients. The subtype of SSc, incidence of internal organ involvement, malignancy, death and serological profiles were determined in the entire group. The study groups were studied according to the presence of antibodies by applying the commercial test - EUROLINE SSc Profile. Due to the presence of a-RNA Pol III, patients were divided into two groups: the a-RNA Pol III (+) SSc group of 19 patients and the a-RNA Pol III (-) SSc group of 107 patients. Results A-RNA Pol III were present in 19/126 patients with SSc (15%), 13/19 (68.4%) patients had no other SSc marker antibodies. A-RNA Pol III were more common in patients with diffuse cutaneous SSc (p = 0.049). We showed a significant positive association between a-RNA Pol III and occurrence of malignancy (p = 0.007), scleroderma renal crisis (p = 0.001) and decreased DLCO (p = 0.007). Conclusions Anti-a-RNA Pol III antibodies are common in patients with SSc, particularly with a diffuse subtype. In more than 50% of patients with a-RNA Pol III antibodies, they may be present as the sole marker of antibodies. In SSc, a-RNA Pol III antibodies are frequently associated with malignancy occurrence, kidney and lung involvement.

Introduction: Brachytherapy (BT) and external beam radiation therapy (EBRT) are effective treatments for high-risk prostate cancer (PCa). However, the impact of these treatments on health-related quality of life (HRQL) remains unclear. In this study, we compared EBRT alone with EBRT plus a boost with high-dose rate (HDR)-BT to determine the impact on HRQL in patients with high-risk PCa. Material and methods: Prospective, multicenter study comparing patients with high-risk PCa treated with EBRT alone or EBRT + HDR-BT from 2004 to 2006. HRQL was assessed at baseline (pre-treatment) and periodically over the 5-year follow-up, using the SF-36 (v.2), EPIC, and FACT-G and FACT-P questionnaires. Results: A total of 129 patients were included in the study, of these, 41 received EBRT alone and 88 EBRT + HDR-BT. All patients received hormonotherapy. Baseline clinical characteristics were similar, except for a slightly higher mean number of comorbidities in the EBRT group. During follow-up, the only significant between-group difference was a greater worsening on EPIC hormonal domain in the EBRT alone group (p = 0.028). There were no significant differences in time and interaction of treatment in SF-36, and FACT-G and FACT-P questionnaires or EPIC urinary incontinence, urinary irritative-obstructive, and bowel and sexual domains over the 5-year follow-up. Oncological outcomes were similar in both groups. Conclusions: After five years of follow-up, EBRT alone or combined with HDR-BT boost had a similar impact on HRQL in patients with high-risk localized PCa. However, patients in the EBRT alone group experienced greater worsening of hormonal domain according to EPIC questionnaire.

The non-nucleoside reverse transcriptase inhibitor VM1500A is approved for the treatment of HIV/AIDS in its N-acyl sulphonamide prodrug form elsulfavirine (Elpida®). Biochemical profiling against twelve human carbonic anhydrase (CA, EC 4.2.1.1) isoforms showed that while elsulfavirine was a weak inhibitor of all isoforms, VM1500A potently and selectively inhibited human (h) hCA VII isoform, a proven target for the therapy of neuropathic pain. The latter is a common neurologic complication of HIV infection and we hypothesise that by using Elpida® in patients may help alleviate this debilitating symptom., Graphical Abstract

Introduction It has been claimed that patients with systemic sclerosis (SSc) have an increased risk of developing cardiac arrhythmias and atrioventricular conduction disorders, but it is unknown whether SSc may be a cause of sinoatrial conduction abnormalities. Aim To establish the incidence of sinoatrial conduction abnormalities in patients with SSc and verify the relationship of these disorders with various clinical descriptors of SSc. Material and methods Forty women with systemic sclerosis of varying duration and severity underwent 24-hour ambulatory ECG monitoring. The occurrence of type I second-degree sinoatrial block (SA-block) and calculation of sinoatrial conduction time (SACT) were evaluated to establish the incidence of sinoatrial conduction abnormalities. The measurements of SACT were obtained using spontaneous atrial premature beats. The effect of various clinical descriptors on sinoatrial conduction abnormalities was assessed. Results The mean ± SD SACT for the 40 patients was 150 ±15 ms. Prolonged (> 150 ms) SACT was found in 20 patients. In 14 (35%) patients SA-block occurred during ambulatory ECG monitoring. The discriminant analysis identified the severity of SSc cutaneous manifestation as an independent marker for developing SA-block (p < 0.005) and SACT prolongation (p < 0.0002). Conclusions Patients with SSc are at an increased risk of developing type I second-degree sinoatrial block and prolonged sinoatrial conduction time. The occurrence of these abnormalities is related to the severity of skin involvement. Therefore, cardiological diagnosis using 24-hour ambulatory ECG in this group of patients should be focused also on this type of disorders. Prospective, controlled studies are needed to assess their prognostic role.

Introduction Epidermolysis bullosa (EB) is a rare genetic skin disorder inherited either in autosomal recessive (AR) or autosomal dominant (AD) manner and characterized by blistering of the skin and mucous membranes. According to a subtype of EB, the oral manifestations and dental involvement vary in frequency and in severity. The most severe dental problems occur in patients with junctional epidermolysis bullosa (JEB) and severe generalized dystrophic epidermolysis bullosa (RDEB) and involve enamel erosion and development of blisters followed by painful oral wounds. Oral mucosa lesions decrease patients’ quality of life and may contribute to difficulties in nutrition leading to cachexia. Aim Assessment of efficacy of gentamicin 0.3% solution in the healing and preventing of oral erosions in patients with RDEB and evaluating its impact on the expression of type VII collagen. Material and methods The study included four female patients with RDEB, aged 16–42 who show different mutations in the COL7A1 gene and were administered the mouth rinse two times daily with a solution of 0.3% gentamycin for 4 consecutive weeks. Prior to and at the end of the study, the samples from oral mucosa were collected to estimate the expression of type VII collagen by immunofluorescence test. Results The clinical improvement of oral wounds healing and reduced number of new blisters and mucous membrane soreness as well as partial re-expression of type VII collagen was observed in all studied patients. Conclusions Topical gentamicin therapy of oral cavity in RDEB patients resulted in clinical improvement of mucosal lesions and re-expression of collagen type VII.

Emotional functioning is one of the factors affecting medication adherence in patients with multiple sclerosis (MS). Adherence to treatment is a very important element in the therapy of patients with MS and requires from them cooperation, positive emotional status and acceptance of illness. This study evaluated the role of depression, anxiety, and the acceptance of illness on adherence to disease-modifying therapies (DMT) in MS. A group of 226 MS patients was included. The Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale-Modified Version (HADS-M), the Acceptance of Illness Scale (AIS) and the Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ) were used. It was shown that 41% of patients reported the symptoms of anxiety, 28% reported the symptoms of depression, and 63% were irritated and aggressive (HADS-M). Over 80% of patients accept their disease to varying degrees. There was a correlation between the results of HADS-M, BDI, and AIS and the domains of MS-TAQ. Analysis of the multiple-regression model showed that only being very satisfied with treatment positively affects adherence to DMT in MS patients. It has to be concluded that anxiety and depression have a significant negative impact on medication adherence in MS patients. However, MS patients with an increased acceptance of their illness have a higher rate of adherence to DMT. The emotional state of a patient is an important factor that can both positively and negatively affect their adherence and their resulting prognosis.

Highlights • We found impaired selective attention in patients with PMNE. • The impaired selective attention was more evidence in patients with severe PMNE. • Measures to improve selective attention might help in treatment of severe PMNE., Objectives Primary monosymptomatic nocturnal enuresis (PMNE) is a very common problem in school age children. It is thought that PMNE represents a maturational lag in the central nervous system of those children. We did this case control study to assess the selective attention and resource allocation in those children using the P300 wave of the Event-Related Potentials (ERPs) and its relation to disease severity. Methods Forty four patients with PMNE and twenty three healthy controls were included in this study. Patients were diagnosed according to the criteria of international children’s continence society and were classified into two groups; patients with frequent wetting (≥4 episodes/week), and patients with infrequent wetting (

Pancreatic cancer is associated with poor prognosis due to limited therapeutic options. Excision repair cross-complementing 3 (ERCC3) is an important member of nucleotide excision repair (NER) that is overexpressed in some cancers and may be regarded as a poor prognostic factor. Yet, its role in pancreatic cancer remains unclear. This study aimed to investigate the expression and functions of ERCC3 in pancreatic cancer patients and its relation with clinicopathological features. Our data suggested that the protein expression level of ERCC3 was higher in tumor tissues than in adjacent tissues. In addition, the expression of ERCC3 has shown to be associated with the tumor extent (p=0.035). Besides, analysis of the dataset in The Cancer Genome Atlas (TCGA) revealed that high expression of ERCC3 was associated with poor overall survival in pancreatic cancer patients (p=0.0136). In Cox regression analysis, ERCC3 was an independent prognostic factor for overall survival in pancreatic cancer (p

Acute coronary syndrome (ACS) is a critical illness in cardiovascular disease. The purpose of this study was to investigate the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and D-dimer in predicting the occurrence of no reflow in emergency percutaneous coronary intervention (PCI) in patients with ACS. One hundred and sixty-eight ACS patients were recruited, including 88 patients with normal reflow and 80 patients with no reflow after emergency PCI. The levels of serum NT-proBNP and D-dimer in the patients were detected before PCI, immediately after PCI, 2 hours, and 6 months after PCI. The ROC curve was used to evaluate the predictive value of NT-proBNP and D-dimer in no-reflow phenomenon. Logistic regression model was used to analyze the independent influencing factors of no reflow phenomenon. Logistic regression analysis confirmed that NT-proBNP and D-dimer were independent predictors of the occurrence of no reflow in the total population. The ROC curve showed that the AUC value was 0.909 when NT-proBNP combined with D-dimer. The detection of NT-proBNP combined with D-dimer was helpful to predict the occurrence of no-reflow phenomenon after emergency PCI in ACS patients.

Primary Sjögren's syndrome (pSS) is a disease associated with the overexpression of proinflammatory cytokines, and oxidative stress is one of the factors responsible for its etiopathogenesis. This study aimed to investigate the thiol/disulphide homeostasis in pSS patients.The study included 68 pSS patients and 69 healthy controls. Thiol/disulphide homeostasis (total thiol, native thiol, and disulphide levels) was measured using the automatic spectrophotometric method developed by Erel and Neselioglu, and the results of the 2 groups were compared.The gender and age distributions of the pSS and control groups were similar (It was concluded that the thiol/disulphide balance shifted towards disulphide in patients with pSS.Primarni Sjögrenov sindrom (pSS) je bolest povezana sa prekomernom ekspresijom proinflamatornih citokina, dok je oksidativni stres jedan od faktora odgovornih za njegovu etiopatogenezu. Cilj ove studije je bio da ispita tioldisulfidnu homeostazu kod pacijenata sa pSS-om.Studija je obuhvatila 68 pacijenata sa pSS-om i 69 zdravih kontrolnih pojedinaca. Homeostaza tiol-disulfida (nivoi ukupnog tiola, nativnog tiola i disulfida) je izmerena pomoću automatske spektrofotometrijske metode koju su razvili Erel i Neselioglu. Rezultati dve grupe su upoređeni.Raspodela po polu i starosti pacijenata sa pSSom i pojedinaca u kontrolnoj grupi je bila slična (Zaključeno je da se ravnoteža tiol/disulfid pomera prema disulfidu kod pacijenata sa pSS-om.

Female patients affected by non-valvular atrial fibrillation (NVAF) have a higher risk of stroke compared with male patients. Left atrial appendage (LAA) closure has been demonstrated as a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF. However, the impact of sex-related differences on outcomes in patients undergoing LAA closure (LAAC) remains unclear. Our study investigated the differences in LAAC efficacy and safety endpoints between sexes. 387 consecutive patients undergoing WATCHMAN device implantation were enrolled and stratified by sex. Baseline clinical characteristics, procedural data, severe peri-procedural complications and long-term outcomes were compared between men and women. Measurements of LAA width and depth, device implantation success rate, and the frequency of severe peri-procedural complications were comparable between the two groups. After an average follow-up length of two years post LAAC, no significant differences were observed in the risks for composite thromboembolic events (P = 0.096), major bleeding (P = 0.129), and combined primary (co-primary) efficacy events (P = 0.231) between sexes, but the risk of all-cause death decreased significantly in women compared with men (P = 0.045). After performing propensity matching adjustment for residual confounders, the sex-related differences in the cumulative ratio of freedom from all-cause death did not reach statistical significance (P = 0.062), as was also observed with the cumulative ratio of freedom from composite thromboembolic events (P = 0.104), major bleeding (P = 0.134), and co-primary efficacy events (P = 0.241). The observed annual rate of thromboembolic events was significantly decreased by 67.1% (P < 0.01) and 52.5% (P < 0.05) and the observed annual rate of bleeding was reduced by 33.6% (P < 0.05) and 43.5% (P < 0.05) in men and women when compared with the predicted risk based on CHA2DS2VASc score and HAS-BLED score, respectively. LAAC can be considered as an effective and safe strategy in preventing thromboembolic events and decreasing bleeding risks in NVAF patients, regardless of sex. LAAC appears to normalize the sex-specific differences in NVAF patients both in terms of safety and efficacy.

Background: Several randomized controlled trials have examined the benefits of multidisciplinary CKD care on estimated glomerular filtration rate (eGFR). But, the results are inconclusive. Purpose: This study aimed to evaluate whether or not multidisciplinary CKD care was beneficial in terms of CKD progression. Methods: This is a randomized controlled trial and conducted at community hospital, Thailand. The inclusion criteria were patients with age of 18 years or older and diagnosed with up to stage 3b CKD based on the KDIGO guidelines. Eligible patients divided into two groups: intervention and control group. The intervention group received a type of multidisciplinary treatment, while patients in the control group received the standard treatment administered at the outpatient clinic. The primary outcome was eGFR outcomes at three months after enrollment. Results: During the study period, there were 334 patients who met the study criteria. Eligible patients were divided into two groups: intervention (166 patients; 49.70%) and control (168 patients; 50.30%). There were three outcomes that differed significantly between the two groups at 3 months: mean difference of eGFR from baseline, proportion of patients with eGFR decline greater than 4 mL/min/1.73 m2, and difference in CKD stage from baseline. A significantly higher percentage of patients in the intervention group experienced CKD improvement by one stage (24.10% vs 5.95%), and a significantly lower percentage experienced decline by one stage (8.43% vs 35.12%) than in the control group. Conclusion: Slower renal progression in patients with up to stage 3b CKD was shown in patients who were treated by a multidisciplinary approach.

Hepatoblastoma (HB) is the most prevalent primary hepatic cancer in children aged 6 months to 3 years. LIN28A is recurrently mutated in various diseases, and critically involved in tumorigenesis. However, a limited number of studies have examined the involvement of LIN28A polymorphisms in HB risk. We used the TaqMan assay to genotype four LIN28A polymorphisms (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) in 275 Chinese children with HB and 1018 cancer-free controls from five medical centers in China. Their association with HB risk was evaluated on the basis of odds ratio (OR) and corresponding 95% confidence interval (CI). Overall, no significant associations were found in single locus and combine analysis. Interestingly, in the stratified analysis, we found that subjects with 1-3 risk genotypes were more likely to develop HB in patients ≥17 months of age (adjusted OR=1.76, 95% CI=1.04-2.98, P=0.034). The rs3811464 GA/AA genotypes were associated with decrease HB risk in patients with clinical stage III+IV disease (adjusted OR=0.50, 95% CI=0.26-0.96, P=0.038). Our results suggest that the LIN28A polymorphisms have a weak association with HB susceptibility in the Chinese children. LIN28A rs3811464 G>A may decrease HB risk in stage III+IV patients which need further validations with larger samples and different ethnicities.

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC). Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis. Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the “LVSI index” as “TD×%MMI×tumor grade×cervical stromal involvement.” The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200. Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.

Background: [¹⁷⁷Lu]-PSMA-617 (Lu-PSMA) therapy is a promising therapeutic option for end-stage prostate cancer patients. Early treatment response at the first restaging after two therapy cycles might correlate with high treatment efficacy and long overall survival (OS). Therefore, the aim of this study was to evaluate whether early reduction in tumor volume is a positive prognosticator for OS. To this end, PSMA PET prior to therapy (baseline) and at first restaging after two therapy cycles (interim; i.e., 12 weeks) were compared. Methods: Patients with metastatic castration-resistant prostate cancer who received Lu-PSMA therapy were reviewed for this analysis. All patients with available baseline and interim [68Ga]-PSMA-11 PET/CT were included in this analysis (n = 33). All PSMA avid metastases in baseline and interim PETs were semi-automatically segmented. The average PSMA expression (mean SUVmax of all metastases), total tumor volume (PSMA-TV) and TLQ (quotients of tumor volume and SUVmean summed over all metastases) were quantified at baseline and interim timepoints. Response in PSMA-TV was assumed when a decline > 30% was present. OS and biochemical response were available for all patients. Results: Baseline PSMA-TV was a statistically significant prognosticator of OS (HR = 1.618 95%CI: 1.117 - 2.343, p = 0.011). Reduction in PSMA-TV was not a statistically significant positive prognosticator of OS in the total cohort (HR = 0.829 95%CI: 0.559 - 1.230, p = 0.352). Likewise, there was no statistical difference in survival time comparing patients with PSMA-TV response to those without (13.2 vs. 15.6 months, p = 0.1). In the subgroup of patients with PSMA-TV response, mean SUVmax was a statistically significant prognosticator of OS (binarized by median; HR = 0.15; 95%CI: 0.03 - 0.83; p < 0.05). If patients with low PSMA expression at baseline were excluded from the analysis, reduction in PSMA-TV became a positive prognosticator of OS in uni- and multivariable Cox regression (HR = 0.290; 95%CI: 0.108 - 0.782; p = 0.015). Conclusion: PSMA-TV reduction was a positive prognosticator of OS only if patients with low PSMA expression were excluded. This might indicate that the PSMA-PETs of patients with low PSMA expression may not be suited for assessing PSMA-TV reduction. Future studies investigating the interplay of PSMA-TV and low PSMA expression response are warranted. CA Extern

Aim of the study The study aimed to investigate serum and ascitic fluid D-dimer level in patients with liver cirrhosis with and without ascites and to evaluate the impact of spontaneous bacterial peritonitis (SBP) on circulating serum and ascitic fluid D-dimer levels. Material and methods This study was conducted on 60 subjects who were further subdivided into group I comprising 15 patients with liver cirrhosis and no ascites, group II comprising 15 cirrhotic patients with ascites, group III comprising 15 cirrhotic patients with ascites and SBP, and group IV comprising 15 healthy controls. All patients were subjected to full history taking, physical examination, laboratory investigations, and measurement of serum D-dimer in all groups and ascitic fluid D-dimer in groups II and III. The diagnostic performance of serum D-dimer was tested to detect SBP. Results Serum D-dimer differed significantly between groups III and IV, whilst no significant differences were detected between the other groups and group IV. Moreover, group III showed a significantly higher level of serum D-dimer. Ascitic fluid D-dimer mean levels showed no statistically significant differences. A statistically significant positive correlation was found between serum D-dimer level and ascitic fluid D-dimer in group III, r = 0.682. Using a sensitivity and specificity level of 80%, a cut-off value (COV) of > 323.2 ng/ml could differentiate between patients with SBP and patients with ascites only. Conclusions Serum D-dimer significantly correlated with ascitic fluid D-dimer in patients with SBP, whereas no significant correlation was found in patients with cirrhotic ascites without bacterial infection. D-dimer showed good diagnostic performance for SBP among patients with liver cirrhosis.

HIGHLIGHTS • D-dimer levels can discriminate between COVID 19 patients with and without worse clinical outcomes (all-cause mortality, ICU admission or ARDS) • Elevated D-dimer levels are associated with increased risk of adverse clinical outcomes in patients hospitalized with COVID 19 infection • Patients who died had higher D-dimer levels than patients who survived • A substantial elevation in D-dimers may be an indicator of progressive disease, Aim To determine if D-dimers are elevated in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who have adverse clinical outcomes including all-cause mortality, intensive care unit (ICU) admission or acute respiratory distress syndrome (ARDS). Methods We conducted a systematic review and meta-analysis of the published literature in PubMed, Embase and Cochrane databases through April 9, 2020 for studies evaluating D-dimer levels in SARS-COV-2 infected patients with and without a composite clinical endpoint, defined as the presence of all-cause of mortality, Intensive care unit (ICU) admission or acute respiratory distress syndrome (ARDS). A total of six studies were included in the meta-analysis. Results D-dimers were significantly increased in patients with the composite clinical end point than in those without (SMD, 1.67 ug/ml (95% CI, 0.72-2.62 ug/ml). The SMD of the studies (Tang et al, Zhou et al, Chen et al), which used only mortality as an outcome measure was 2.5 ug/mL (95% CI, 0.62-4.41 ug/ml). Conclusion We conclude that SARS-CoV-2 infected patients with elevated D-dimers have worse clinical outcomes (all-cause mortality, ICU admission or ARDS) and thus measurement of D-dimers can guide in clinical decision making.

Purpose Brachytherapy with iodine-125 (125I) has been extensively used as a conservative treatment for uveal melanoma (UM). Surgical technique for correct placement of episcleral radioactive plaques (ERP) in UM cases with posterior choroidal location and/or small size can be difficult and inaccurate. In this study, the correct positioning of plaques was assessed by intra-operative ultrasound control. Material and methods This was a longitudinal, retrospective study of consecutive 20 patients with UM (small-medium size and/or posterior location) who received 125I brachytherapy. Location of plaques was adjusted by intra-operative ocular ultrasonography control. To perform ocular intra-operative ultrasonography, a 10 MHz probe was used to longitudinal and transverse bases in corresponding dummy plaques. Results The study included 8 males and 12 females, with a mean age of 66.3 years (SD = 14.53), 5 right eyes (RE) and 15 left eyes (LE). In ultrasound examination, 4 UMs were of mushroom morphology and the rest nodular. Means of the size of UM by ultrasound were (mm): Lb: 10.60 (SD = 2.24) × Tb: 9.88 (SD = 1.54) × H: 4.02 (SD = 1.44) (3 cases corresponding to small size of collaborative ocular melanoma study (COMS), and 17 cases to medium). The plaques used were between 14 and 20 mm in diameter, with an average distance between the edge of greater base of the tumor and the edge of plate of 2.44 mm (SD = 0.34). It was necessary to surgically reposition the plaque in 4 cases (20%). Conclusions Intra-operative ultrasound control improves the accuracy of radioactive plaque placement for the treatment of medium-small UMs in posterior location. Probably, this technique should be applied in all cases of brachytherapy, regardless of the isotope chosen and the location of tumor mass, in order to perfectly adjust therapeutic position.

Construction of a diverting stoma can significantly reduce the onset of severe anastomotic leakage in patients with rectal cancer. High-output stoma is one of the most important potential surgical complications after anal function-preserving surgery with ileostomy. Culture-independent techniques have revealed the interaction of the complex intestinal bacterial ecology with various diseases. Our objective was to evaluate the differences in patient characteristics and gut microbiota distribution features in patients with high-output stomas. The cases of 24 consecutive patients who underwent curative resection for rectal cancer at our hospital between November 2016 and June 2018 were reviewed, and the patients were categorized into high-output and low-output groups. Their microbiota were analyzed using next-generation sequencing of ileostomy stool samples collected on postoperative day 7. There was a significant difference in the percentage of Bacteroidetes between the high-output and low-output groups (14.8% vs 0.5%; p=0.01). The percentage of Clostridium butyricum was increased in the low-output group (p=0.01). After the exclusion of those treated with the probiotic Miya-BM, whose principal component is C. butyricum, analyses revealed no significant differences between the high-output and low-output groups. This pilot study provides the first evidence correlating gut microbiota with the pathogenesis of high- output stoma compared with low-output stoma.

Acute myeloid leukemia (AML) is a deadly heterogeneous hematologic malignancy. Despite the well-characterized genetic characteristics and new promising targeted therapies for AML, the clinical outcome remains suboptimal. Galectin-9 (Gal-9) is a good potential target due to its immunosuppressive capacity in inflammatory processes. In our study, we firstly performed a wide range of integrated bioinformatical approach to assess the importance of Gal-9 by analyzing the expression, potential function and prognostic impact in AML. The results indicated that Gal-9 is overexpressed in AML cells, especially when relapse after hematopoietic stem cell transplantation (HSCT) and predicts poor prognosis. Co-expression analysis showed Gal-9 has a strong positive correlation with proteasome subunit beta type-8 (PSMB8), which was also highly expressed in AML with poor prognosis, implying a synergy in cell survival, cell signaling and the development of AML. In summary, we have confirmed the overexpression of Gal-9 and its partner PSMB8 in AML and validated their importance as prognostic factors. We propose that Gal-9 and PSMB8 could be a promising molecular target for treatment of AML and may provide more combined treatment options, especially in patients with relapse after HSCT.

Background: Immune checkpoint inhibitors (ICIs) show clinical benefit in patients with refractory advanced gastric cancer (GC). The ICIs in routine clinical practice have been used in various treatment lines. Therefore, we investigated the timing for application of ICI in patients with refractory advanced GC. Methods: We analyzed 187 patients with refractory advanced or recurrent GC who received ICIS as a 3rd- or 4th-line treatment between September 2015 and October 2020. Clinical outcomes of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were evaluated. Results: Among 187 patients, 105 received ICIs as a 3rd-line treatment and 82 as a 4th line. The ORR for ICIs was 10.5% (11/105) in 3rd line and 8.5% (7/82) in 4th line. The DCR for ICIs was 36.2% (38/105) in 3rd-line treatment and 31.7% (26/82) in 4th line. There was no significant difference for ORR (P = 0.819) or DCR (P = 0.870). The median PFS and OS to ICIs was 1.4 months (95% CI, 1.1 to 1.8 months) and 4.4 months (95% CI, 1.6 to 7.2 months) in 3rd line and 1.8 months (95% CI, 1.4 to 2.3 months) and 2.8 months (95% CI, 2.2 to 3.4 months) in 4th line. The median PFS and OS to ICIs was not different between 3rd line and 4th line (P = 0.495 and P=0.208, respectively). There were also no significant difference for PFS and OS between PD-L1-positive tumors (CPS≥1) and PD-L1-negative tumors (P = 0.910 and P=0.931, respectively). Conclusions: ICIs showed similar clinical benefits in the 3rd-line and 4th-line settings. ICIs might be a reasonable approach for patients with refractory GC in the setting of 3rd-line or 4th-line treatment options.

Graves’ orbitopathy (GO) is a serious, progressive eye condition seen in patients with autoimmune thyroid disease. GO is characterized by inflammation and swelling of soft orbital tissues. Adipose tissue produces cytokine mediators called adipokines. The present study focuses on the relationship between serum levels of selected adipokines in patients with GO, comparing them with the control group, and uniquely describes the effect of high-dose systemic corticosteroids (HDSC) on their levels. For the purposes of this study, we collected blood samples before and after the treatment with HDSC from 60 GO patients and 34 control subjects and measured serum levels of adiponectin, AIF-1, A-FABP and FGF-21. Levels of adiponectin significantly differed among the three study groups (ANOVA p = 0.03). AIF-1 levels were also significantly different among the study groups (ANOVA p

Objective: Compare the oncologic outcomes of patients with advanced stage endometrial cancer who were staged by minimally invasive surgery with the outcomes of patients who underwent open surgery. Methods: Data from 138 patients with advanced stage endometrial cancer who were treated between January 2009 and January 2019 were reviewed. The patients' data were retrieved from five institutions. The patients were divided into two groups: those who underwent open surgery and those who underwent minimally invasive surgery. Tumor characteristics, recurrence rate, disease-free survival, and overall survival were compared according to surgical approach. Results: Among the 138 patients included in this study, 72 underwent open surgery (52.2%) and 66 underwent MIS (47.8%). In patients with advanced-stage endometrial cancer, the recurrence rate was significantly higher among those who underwent open surgery (43.1% vs. 25.8%, p = 0.033). Patients with advanced-stage endometrial cancer who underwent open surgery had a significantly lower disease-free survival (p = 0.029) than those who underwent minimally invasive surgery, however, the overall survival (p = 0.051) was similar between the two groups. Conclusion: Minimally invasive surgery showed better survival outcomes when compared to open surgery in advanced-stage EC patients irrespective of the histologic type.

Purpose: To establish a preoperative nomogram incorporating morphological and dynamic contrast-enhanced (DCE) features to individually predict the risk of malignancy in patients with breast tumor. Methods A total of 447 consecutive female patients who were divided into the primary cohort (n=326) and the validation cohort (n=121) were enrolled between March 2015 to January 2018. Univariate and multivariate logistic regression analyses were used to identify the potential independent indicators of malignancy. An MRI-based nomogram integrating morphological features and kinetic curves was developed to achieve individualized risk prediction of malignancy in patients with breast masses. The discrimination, calibration ability and clinical utility of the MRI-based model were assessed using C-index, calibration curve and decision curve analysis. Results: Age, tumor size, margin, internal enhancement characteristics, and kinetic curve were confirmed as the independent predictors of malignancy. The AUC of MRI-based nomogram was 0.940 (95% CI: 0.911-0.970) and 0.894 (95% CI: 0.816-0.974) in the primary cohort and validation cohort, respectively. 447 patients were subdivided into the low-risk group (n=107) and high-risk group (n=340) based on the optimal cut-off value of 21.704. The high-risk patients had a higher likelihood of harboring malignancy. Conclusion: The MRI-based nomogram can be used to achieve an accurate individualized risk prediction of malignancy and reduce unnecessary breast biopsy.

Introduction Pulmonary artery hypertension and its consequences still constitutes an underestimated clinical problem in asthma patients and its non-invasive early detection may influence proper treatment. Aim To non-invasively examine the pulmonary artery flow parameters and right ventricular function in patients with asthma of various severity. Material and methods The analysis of parameters of echocardiography and first-pass and gated radionuclide angiography, and baseline examination in 31 patients with bronchial asthma and 16 healthy controls. Results Patients with severe asthma had higher mean pulmonary artery pressure (MPAP) compared to the healthy controls. The subgroup analysis of patients who suffered from asthma in their childhood showed that individuals with severe asthma were characterized by significantly higher MPAP than those with the mild/moderate condition (19.16 ±7.51 mm Hg vs. 5.0 ±1.15 mm Hg, p = 0.025). Gated, but not first-pass, radionuclide angiography revealed that individuals with severe asthma were characterized by a lower right ventricular ejection fraction (RVEF). Further analysis of the subgroup of patients in whom the initial manifestation of dyspnoea occurred no earlier than 6 years prior to the study showed that the RVEF of individuals with severe asthma was significantly lower compared to those with mild/moderate asthma (39.8 ±4.79% vs. 51.4 ±8.65%, p = 0.019). Conclusions The pulmonary artery pressure in patients with severe asthma is significantly higher than in healthy individuals; in contrast, these two groups did not differ significantly in terms of the right ventricular echocardiographic characteristics. Gated radionuclide angiography, but not the first-pass technique, allowed for the detection of subtle right ventricular ejection fraction changes in asthma patients.

The purposes of this study were as follows: to compare premorbid IQ with present IQ in patients with more severe anorexia nervosa restricting type (AN-R) and to investigate the relationship between decreasing IQ and symptoms in patients with severe AN-R. Twenty-two participants were recruited (12 were AN-R patients; 10 were healthy controls). The average BMI in AN-R patients and healthy controls was 12.65 and 19.82, respectively. We assessed the outcomes using the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Japanese Adult Reading Test, The Eating Disorders Inventory-2 (EDI-2), Beck Depression Scale-2 (BDI-2) and State-Trait Anxiety Index. In two-way ANOVA, there were significant interactions for the FIQ and PIQ. Only in the AN-R group, a significant single main effect of time was evidenced for the FIQ and PIQ. In the AN-R group, a significantly high positive correlation was found between changes in the PIQ and the body dissatisfaction subscale of the EDI-2. These findings raise the possibility that in patients with severe AN-R, an excessive decrease in body weight induces decreased PIQ; as a result, they have worse dissatisfaction with their body shape.

Background: Sarcopenia is a muscle disease with significant morbidity and mortality. Vitiligo is a common autoimmune inflammatory disease which results from absence, deficiency, or dysfunction of melanocytes. Links between sarcopenia and autoimmune inflammatory processes were reported. However, no previous reports on association between sarcopenia and vitiligo were identified. Objective: To assess presarcopenia in patients with vitiligo and to evaluate the effect of sociodemographic and clinical characteristics of vitiligo patients of sarcopenia if present. Subject and methods: This case control study included 63 patients with Vitiligo and 63 apparently healthy control group matched in age and gender. Sarcopenia was diagnosed by measuring the Appendicular Lean Mass Index. Cut off point required for sarcopenia is

Introduction Nasal polyps are a multifactorial inflammatory condition of the upper airways. Nasal polyps typically affect middle-aged and elderly patients, average age at diagnosis is 40 to 60, and men are affected more commonly than women. Aim To analyse the reported prevalence of nasal polyps in the Polish population, including demographics and co-morbidities, and to estimate the costs of outpatient and hospital (inpatient) services financed by the National Health Fund. Material and methods Statistical analysis of data extracted from the National Health Fund (NHF) registers for 2008-2018. Results In 2018, the recorded prevalence of nasal polyps in Poland was 52.0/10,000 population (0.52%), amounting to 64.6/10,000 (0.65%) in men and 40.2/10,000 (0.40) in women. Nasal polyps were much more frequent in patients aged 55-59 (98.1/10000) and 75-79 years (98.7/10,000). Among men, the highest prevalence was found in the 75-79 age group (164.3/10,000 population), and among women in the 55-59 age group (75.1/10,000). In 2018, the Polish NHF spent PLN 17.2 million (equivalent to EUR 4.0 million/USD 4.7 million) on health services related to the diagnosis of nasal polyps. Hospital services accounted for 77.4% of the total cost. Conclusions Nasal polyps are more than one and a half times as prevalent in men than in women. The recorded prevalence of nasal polyps increases with age, with the rates peaking in those between 75 and 79 years old, and is more often in urban than rural areas.

Background Frailty is common in patients with chronic heart failure (CHF) and is associated with poor outcomes. The natural history of frail patients with CHF is unknown. Methods Frailty was assessed using the clinical frailty scale (CFS) in 467 consecutive patients with CHF (67% male, median age 76 years, median NT-proBNP 1156 ng/L) attending a routine follow-up visit. Those with CFS > 4 were classified as frail. We investigated the relation between frailty and treatments, hospitalisation and death in patients with CHF. Results 206 patients (44%) were frail. Of 291 patients with HF with reduced ejection fraction (HeFREF), those who were frail (N = 117; 40%) were less likely to receive optimal treatment, with many not receiving a renin–angiotensin–aldosterone system inhibitor (frail: 25% vs. non-frail: 4%), a beta-blocker (16% vs. 8%) or a mineralocorticoid receptor antagonist (50% vs 41%). By 1 year, there were 56 deaths and 322 hospitalisations, of which 25 (45%) and 198 (61%), respectively, were due to non-cardiovascular (non-CV) causes. Most deaths (N = 46, 82%) and hospitalisations (N = 215, 67%) occurred in frail patients. Amongst frail patients, 43% of deaths and 64% of hospitalisations were for non-CV causes; 58% of cardiovascular (CV) deaths were due to advancing HF. Among non-frail patients, 50% of deaths and 57% of hospitalisations were for non-CV causes; all CV deaths were due to advancing HF. Conclusion Frailty in patients with HeFREF is associated with sub-optimal medical treatment. Frail patients are more likely to die or be admitted to hospital, but whether frail or not, many events are non-CV. Graphical abstract

Background: Treatment outcomes of laparoscopic liver resection (LLR) and percutaneous radiofrequency ablation (p-RFA) for small single hepatocellular carcinomas (HCCs) have not yet been fully compared. The aim of this study was to compare LLR and p-RFA as first-line treatment options in patients with single nodular HCCs ≤3 cm. Methods: From January 2014 to December 2016, a total of 566 patients with single nodular HCC ≤3 cm treated by either LLR (n = 251) or p-RFA (n = 315) were included. The recurrence-free survival (RFS) and cumulative incidence of local tumor progression (LTP) were estimated using Kaplan-Meier methods and compared using the log-rank test. Treatment outcome of 2 treatment modalities was compared in the subgroup of patients according to the tumor location. Results: There were no significant differences in overall survival between LLR and p-RFA (p = 0.160); however, 3-year RFS was demonstrated to be significantly higher after LLR (74.4%) than after p-RFA (66.0%) (p = 0.013), owing to its significantly lower cumulative incidence of LTP (2.1% at 3 years after LLR vs. 10.0% after p-RFA, p < 0.001). The complication rate of p-RFA was significantly lower than that of LLR (5.1 vs. 10.0%, p = 0.026). LLR also provided significantly better local tumor control than p-RFA for subscapular tumors (3-year LTP rates: 1.9 vs. 8.8%, p = 0.012), perivascular tumors (3-year LTP rates: 0.0 vs. 17.2%, p = 0.007), and tumors located in anteroinfero-lateral liver portions (3-year LTP rates: 0.0 vs. 10.7%, p < 0.001). However, there were no significant differences in LTP rates between LLR and p-RFA for non-subcapsular and non-perivascular tumors (p = 0.482) and for tumors in postero-superior liver portions (p = 0.380). Conclusions: LLR can provide significantly better local tumor control than p-RFA for small single HCCs in subcapsular, perivascular, and anteroinferolateral liver portions and thus may be the preferred treatment option for these tumors.

Aim: The aim of the study was to clarify whether the motor disability and the fatigue-related syndrome affect the level of compliance with therapeutic recommendations. Methods: Prospective studies were conducted among 165 patients treated under the drug program - Treatment of Multiple Sclerosis (MS) at the Department of Neurology and Clinical Neuroimmunology of the Regional Specialist Hospital in Grudziadz (Poland). The research was carried out by the method of diagnostic survey, questionnaire technique with the use of standardized research tools. The Adherence in Chronic Diseases Scale (ACDS) was used to assess the level of compliance with therapeutic recommendations. The Expanded Disability Status Scale (EDSS) was used to assess the degree of disability, and the Modified Fatigue Impact Scale (MFIS) was used to assess the degree of disability. The Chi-square test, Shapiro-Wilk test and Kruskal-Wallis were used. Results: The statistical analysis showed that there is a relationship (p=0.0055) between the patient's motor disability assessed in the EDSS scale and the level of compliance with therapeutic recommendations assessed in the ACDS scale. The higher the patient's disability level (EDSS 4.5-6.5), the lower the treatment adherence rate. The conducted research shows that the average score in the MFIS scale for individual levels of compliance with therapeutic recommendations expressed in the ACDS scale is, respectively: for the low level - 38.3 MFIS points, for the medium level - 34.4 MFIS points and for the high level- 33.2 MFIS points. The obtained results were not statistically significant (p=0.6098). Conclusion: It was found that the level of adherence to therapeutic recommendations in patients with relapsing-remitting multiple sclerosis treated with immunomodulation in the study group remained high. There is a relationship between the patient's disability and the level of adherence to therapeutic recommendations.

Lung adenocarcinoma (LUAD) has been the major cause of tumor-associated mortality in recent years and has a poor prognosis. Pyroptosis is regulated via the activation of inflammasomes and participates in tumorigenesis. However, the effects of pyroptosis-related lncRNAs (PRlncRNAs) on LUAD have not yet been completely elucidated. Therefore, we attempted to systematically explore patterns of cell pyroptosis to establish a novel signature for predicting LUAD survival. Based on TCGA database, we set up a prognostic model by incorporating PRlncRNAs with differential expression using Cox regression and LASSO regression. Kaplan–Meier analysis was conducted to compare the survival of LUAD patients. We further simplified the risk model and created a nomogram to enhance the prediction of LUAD prognosis. Altogether, 84 PRlncRNAs with differential expression were discovered. Subsequently, a new risk model was constructed based on five PRlncRNAs, GSEC, FAM83A-AS1, AL606489.1, AL034397.3 and AC010980.2. The proposed signature exhibited good performance in prognostic prediction and was related to immunocyte infiltration. The nomogram exactly forecasted the overall survival of patients and had excellent clinical utility. In the present study, the five-lncRNA prognostic risk signature and nomogram are trustworthy and effective indicators for predicting the prognosis of LUAD., Graphical abstract

Objectives To investigate the relationship between the dynamic changes of serum 2019-nCoV IgM/IgG and immunity alteration for patients after 6-month hospital discharge. Methods One IgM(+) and IgG(−), 32 IgM(+) and IgG(+), 38 IgM(−) and IgG(+), and 40 IgM(−) and IgG(−) patients were included. Demographic data were collected. IgM and IgG antibodies, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and lymphocyte subsets in serum were determined at weeks 0, 2 and 4. Results The hs-CRP and IL-6 levels of all patients were within the normal ranges. The number of patients with all lymphocyte subset testing items within normal ranges was 12/110 (10.9%) at week 0, 15/110 (13.6%) at week 2 and 18/110 (16.4%) at week 4. The percentages of CD8 + cells, NK cells and B lymphocytes in the IgM(+) and IgG(+) group were quite different from those in the IgM(−) and IgG(+) group and the IgM(−) and IgG(−) group, with much higher percentages of CD8 + cells and much lower percentages of NK cells and B lymphocytes at weeks 0, 2 and 4. Twelve IgM(+) patients in the IgM(+) and IgG(+) group converted to IgM(−), and the percentages of NK cells and B lymphocytes in these patients were significantly increased at week 4. Conclusions The changes of serum IgM and IgG are closely related to immunity in patients in the recovery stage. However, immunity does not recover when the patients test negative for these antibodies.

Leukocytapheresis, a blood purification therapy, exerts anti-inflammatory effects by removing activated leukocytes from the peripheral blood through extracorporeal circulation. It is a potential option of treatment for patients with inflammatory bowel diseases (IBD), especially those with ulcerative colitis (UC), who do not respond to conventional therapy. Given that it has a favourable safety profile and seems to have steroid sparing effects, its position in the treatment of UC is likely to expand. However, there is inadequate evidence to draw any conclusions about the efficacy of leukocytapheresis in patients with Crohn's disease, and it should only be used in accordance with special arrangements for consent. Considering the current level of knowledge, it is essential to conduct large, well-designed, randomized clinical trials to evaluate the effects of leukocytapheresis in the management of IBD patients.

Purpose: The study aimed to compare the diagnostic performance of the Liver Imaging Reporting and Data System (LI-RADS), which incorporates fixed criteria, and the Likert scale (LS), which mainly depends on an overall impression in liver lesion diagnosis. Material and methods: Diagnostic data of 110 hepatic nodules in 103 high-risk patients for hepatocellular carcinoma (HCC) were included. Data including diameter, arterial hyperenhancement, washout, and capsule were reviewed by 2 readers using LI-RADS and LS (range, score 1-5). Inter-reader agreement (IRA), intraclass agreement (ICA), and diagnostic performance were determined by Fleiss, Cohen's k, and logistic regression, respectively. Results: There were 53 triphasic enhanced computed tomography (CT) and 50 dynamic magnetic resonance (MR) examinations. Overall, IRA was excellent (k = 0.898). IRA was good for arterial hyperenhancement (k = 0.705), washout (k = 0.763), and capsule (k = 0.771) and excellent for diameter (k = 0.981) and tumour embolus (k = 0.927). Overall, ICA between LI-RADS and LS was fair 0.32; ICA was good for scores of 1 (k = 0.682), fair for scores of 2 (k = 0.36), moderate for scores of 5 (k = 0.52), but no agreement was found for scores of 3 (k = –0.059) and 4 (k = –0.022). LIRADS produced relatively high accuracy (87.3% vs. 80%), relatively low sensitivity (84.3% vs. 98%), and significantly higher specificity (89.83% vs. 64.4%) and positive likelihood ratio (+LR: 8.29 vs. 2.75) compared to LS approach. Conclusions: LI-RADS revealed higher diagnostic accuracy as compared to LS with statistical proof higher specificity and +LR showing its ability to foretell malignancy in high-risk patients. We recommend the practical application of the LI-RADS system in the detection and treatment response monitoring of patients with HCC.

Highlights • Heart rates increased with neck myoclonus events. • The rate of increase was higher for neck myoclonus with cortical arousal than for those without. • Neck myoclonus may be associated with excessive daytime sleepiness or abnormal behaviors during REM sleep., Objective This study was conducted to evaluate heart rate (HR) change and clinical characteristics in patients with neck myoclonus (NM), a physiological motor phenomenon occurring during sleep. Methods For 18 consecutive patients in whom NM was confirmed from video-polysomnography, we analyzed 576 NMs. Change rate of HR at each 1 sec point towards the averaged HR in prior 5 sec period was calculated before and after all NM events. Results Findings show NM events as more prevalent during REM sleep than during NREM sleep (83.9% vs. 16.1%). For NM without cortical arousal in REM and NREM sleep, the respective HR increased 20 s before NM (p

Objective: Several P-wave parameters reflect atrial conduction characteristics and have been used to predict atrial fibrillation (AF). The aim of this study was to determine the relationship between maximum P-wave duration (PMax) and new P-wave parameters, with atrial conduction times (CT), and to assess their predictive value of AF during electrophysiological studies (AF-EPS). Subjects and Methods: This was a cross-sectional study in 153 randomly selected patients aged 18–70 years, undergoing EPS. The patients were divided into 2 groups designated as no AF-EPS and AF-EPS, depending on whether AF occurred during EPS or not. Different P-wave parameters and atrial CT were compared for both study groups. Subsequently, the predictive value of the P-wave parameters and the atrial CT for AF-EPS was evaluated. Results: The values of CT, PMax, and maximum Ppeak-Pend interval (Pp-eMax) were significantly higher in patients with AF-EPS. Almost all P-wave parameters were correlated with the left CT. PMax, Pp-eMax, and CT were univariate and multivariate predictors of AF-EPS. The largest ROC area was presented by interatrial CT (0.852; p < 0.001; cutoff value: ≥82.5 ms; sensitivity: 91.1%; specificity: 81.1%). Pp-eMax showed greater sensitivity (79.5%) to discriminate AF-EPS than PMax (72.7%), but the latter had better specificity (60.4% vs. 41.5%). Conclusions: Left atrial CT were directly and significantly correlated with PMax and almost all the parameters of the second half of the P-wave. CT, PMax, and Pp-eMax (new parameter) were good predictors of AF-EPS, although CT did more robustly.

Introduction Numerous cases of pneumonia caused by coronavirus disease 2019 (COVID-19) were reported in Wuhan, China. Chest computed tomography (CT) scan is highly important in the diagnosis and follow-up of lung disease treatment. The present meta-analysis was performed to evaluate chest CT scan findings in COVID-19 patients. Material and methods All research steps were taken according to the Meta-Analysis of Observational Studies In Epidemiology (MOOSE) protocol and the final report was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We registered this review at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42019127858). Results Forty eligible studies including 4598 patients with COVID-19 were used for meta-analysis. The rate of positive chest CT scan in patients with COVID-19 was 94.5% (95% CI: 91.7-96.3). Bilateral lung involvement, pure ground-glass opacity (GGO), mixed (GGO pulse consolidation or reticular), consolidation, reticular, and presence of nodule findings in chest CT scan of COVID-19 pneumonia patients were respectively estimated to be 79.1% (95% CI: 70.8-85.5), 64.9% (95% CI: 54.1-74.4), 49.2% (95% CI: 35.7-62.8), 30.3% (95% CI: 19.6-43.6), 17.0% (95% CI: 3.9-50.9) and 16.6% (95% CI: 13.6-20.2). The distribution of lung lesions in patients with COVID-19 pneumonia was peripheral (70.0% [95% CI: 57.8-79.9]), central (3.9% [95% CI: 1.4-10.6]), and peripheral and central (31.1% [95% CI: 19.5-45.8]). The pulmonary lobes most commonly involved were the right lower lobe (86.5% [95% CI:57.7-96.8]) and left lower lobe (81.0% [95% CI: 50.5-94.7]). Conclusions The most important outcomes in chest CT scan of patients with COVID-19 pneumonia were bilateral lung involvement, GGO or mixed (GGO pulse consolidation or reticular) patterns, thickened interlobular septa, vascular enlargement, air bronchogram sign, peripheral distribution, and left and right lower lobes involvement. Our study showed that chest CT scan has high sensitivity in the diagnosis of COVID-19, and may therefore serve as a standard method for diagnosis of COVID-19.

Background: Gastric cancer (GC) is a heterogeneous disease, and alternative splicing (AS) is a powerful universal transcriptional regulatory mechanism that contributes to the occurrence and development of cancer. However, the systematic analysis of AS events in GC is lacking; therefore, further studies are needed. Methods: Genome-wide analysis of AS events was performed using RNA-Seq data to evaluate the difference between GC and adjacent tissues at the AS level. Prognostic signatures based on differentially expressed alternative splicing (DEAS) events and a correlation network between DEAS and genes were built. Results: We identified 48,141 AS events, of which 2325 showed differential expression patterns. The parental genes before DEAS events play an essential role in regulating GC-related processes such as ribosome (FDR < 0.0001) and thermogenesis (FDR = 0.0002). There were 76 survival-associated DEAS cases. Stratifying patients according to the percent spliced in index value of six types of splicing patterns formed significant Kaplan-Meier curves in the overall survival analysis. A prognostic feature based on DEAS performed well for stratification in patients with GC. Conclusion: The present study will enrich our understanding regarding the distinction of GC and provide a generous amount of biomarkers and potential targets for the treatment of GC.

Introduction Systemic sclerosis (SSc) is a multisystemic disease with an extensive microvasculopathy. The gold standard for its investigation is nailfold videocapillaroscopy (NVC). Aim To assess the value of thermography (IRT) for the assessment of microvasculopathy in patients with SSc. Material and methods Nineteen patients with limited cutaneous SSc were enrolled in the study. They underwent IRT imaging and NVC. An average temperature (Tavg) at the nailfold and a gradient of temperatures (ΔTavg) between the central metacarpus of the hand and the nailfold was determined for all fingers. NVC pictures were classified to capillaroscopic patterns according to Cutolo et al. system and they were analysed quantitatively to measure the density of capillaries and to calculate capillaroscopic skin ulcers risk index (CSURI) for each finger separately. Results There was only a moderate correlation (0.4 < r < 0.6) between thermographic parameters and density of capillaries in fingers II–V (r = 0.5; p < 0.001 for Tavg and r = –0.45; p < 0.001 for ΔTavg), but none in thumbs (r = 0.29; p = 0.089 for Tavg and r = –0.19; p = 0.275 for ΔTavg). Early pattern was associated with a significantly greater surface temperature (Tavg) of nailfolds and essentially milder ΔTavg in fingers II–V when compared to all other capillaroscopic patterns in fingers II–V. Surface temperature (Tavg) was significantly lower and ΔTavg was markedly more pronounced in fingers II–V with a greater risk of development of digital ulcers (DU) calculated by CSURI. Conclusions Although IRT measurements correlate only moderately with density of capillaries, this technique seems to be substantial to determine the capillaroscopic pattern and to identify patients at greater risk of DU development.