Influence of Achalasia on the Spirometry Flow-Volume Curve and Peak Expiratory Flow.

BACKGROUND: Achalasia is an esophageal motor disorder characterized by aperistalsis and the failure of the relaxation of the lower esophageal sphincter. We want to find out whether external compression or recurrent micro-aspiration of undigested food has a functional effect on the airway. METHODS: The aim of this research was to analyze the influence of achalasia on the peak expiratory flow and flow-volume curve. All of the 110 patients performed spirometry. RESULTS: The mean diameter of the esophagus was 5.4 ± 2.1 cm, and nine of the patients had mega-esophagus. Seven patients had a plateau in the inspiratory part of the flow-volume curve, which coincides with the patients who had mega-esophagus. The rest of the patients had a plateau in the expiration part of the curve. The existence of a plateau in the diameter of the esophagus of more than 5 cm was significant (p 0.003). Statistical significance between the existence of a plateau and a lowered PEF (PEF < 80) has been proven (p 0.001). Also, a statistical significance between the subtype and diameter of more than 4 cm has been proved. There was no significant improvement in the PEF values after operation. In total, 20.9% of patients had a spirometry abnormality finding. The frequency of the improvement in the spirometry values after surgery did not differ significantly by achalasia subtype. The improvement in FEV1 was statistically significant compared to the FVC values. CONCLUSIONS: Awareness of the influence of achalasia on the pulmonary parameters is important because low values of PEF with a plateau on the spirometry loop can lead to misdiagnosis. The recognition of various patterns of the spirometry loop may help in identifying airway obstruction caused by another non-pulmonary disease such as achalasia.

Deep venous thrombosis in patients with atresia of the inferior vena cava and right kidney hypoplasia (KILT syndrome): Systematic review of the literature.

Inferior vena cava (IVC) anomalies are uncommon congenital causes of deep vein thrombosis (DVT). KILT syndrome (kidney and IVC abnormalities with leg thrombosis) has only been described as case reports in the literature. Therefore, the characteristics, evaluation, and management of patients with KILT syndrome have not yet been standardized. This study aimed to systematically review and analyze the clinical and radiographic data and treatment of previously reported cases of KILT syndrome. In this systematic review, we performed a literature search of the PubMed, Scopus, and Web of Science databases in December 2023, with no restrictions on the publication date. After duplicate extractions, 4195 articles were screened. Case reports and case series reporting on KILT syndrome were included. In addition to previously published cases, we included a new case of a previously healthy 25-year-old man with KILT syndrome in the analysis. A total of 34 cases were therefore included in this study. The majority (76.5%) were male patients with a median age of 24 years. In most patients, unprovoked bilateral iliofemoral thrombosis was diagnosed, and 64.7% had left kidney abnormalities. Our study suggests that anomalies of the IVC should be suspected in all young patients, especially male patients, with proximal, recurrent, or idiopathic DVT. If an IVC anomaly is confirmed, the kidneys should be examined to monitor and preserve healthy kidneys in cases of KILT syndrome. The data collected from all patients emphasize the requirement of long-term anticoagulation and risk factor control. Surgical measures may be effective for treating symptomatic refractory cases.

King's Sarcoidosis Questionnaire (KSQ) - Validation study in Serbian speaking population of sarcoidosis patients.

INTRODUCTION: Sarcoidosis is a multiorgan, multisystem chronic disease of unknown etiology and unpredictable course. Health status is reduced in sarcoidosis and assessing it is a difficult multitask effort due to many faces this disease might have. Recently, a new questionnaire for assessing health status in sarcoidosis was developed by a group of authors from England-King's Sarcoidosis Questionnaire (KSQ). The benefit of KSQ is the ability to develop the best care plan for the patient, as well as to differentiate the efficacy of the administered treatment. OBJECTIVE: The aim of this study was to validate the KSQ in Serbian speaking population of sarcoidosis patients. The test itself is a modular, multi-organ health status measure for patients with sarcoidosis for use in clinic and the evaluation of therapies. The correlation of KSQ with different clinical course of sarcoidosis (acute vs chronic disease) and with the clinical outcome status (COS) in sarcoidosis was also investigated. METHODS: A total of 159 biopsy positive sarcoidosis patients participated in this study. The average age of the participants was 49.67, majority was female (67.3%) and majority had only pulmonary form of sarcoidosis (71.7%). KSQ - new disease-specific health status instrument, was compared with 5 other already existing instruments already used and validated in sarcoidosis (Saint George Respiratory Questionnaire- SGRQ, Daily Activity List -DAL, Fatigue Assessment Scale- FAS, Medical Research Council dyspnea scale-MRC, Borg Dyspnea Scale and 15D as general questionnaire. RESULTS: KSQ has significant correlation with other quality of life questionnaires already used in sarcoidosis. Translated version of KSQ shows significant internal reliability, similar to the original KSQ. Serbian version of KSQ has significant correlation with different clinical course of sarcoidosis and with COS as well. The translated version of KSQ is reliable sarcoidosis specific instrument for assessing health status in these patients.

Association between affective temperaments and psychosomatic symptoms in women with Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease of thyroid gland with a shared immunological mechanism with mood disorders. Affective temperament (AT) is a biologically determined personality trait that has been linked to mood disorders. The aim of this study was to examine the association between dominant AT and levels of psychosomatic symptoms in women newly diagnosed with HT in comparison to clinically healthy subjects. METHODS: The observational cross-sectional study with nested case control study was involving 146 consecutive participants, who were divided into three groups. The two study groups consisted of women with HT (73), including 49 with hypothyroid HT and 24 with euthyroid HT, and the third group was a control group of healthy participants (73). The Serbian version of the TEMPS-A was utilized to assess AT, while the 4DSQ was used to measure psychosomatic symptoms. RESULTS: The results showed that hyperthymic AT was dominant in all examined groups. The groups with HT differed from the control group in terms of depressive and cyclothymic AT. Furthermore, the study found higher levels of psychosomatic symptoms in the group with HT compared to the control group, with significant differences in distress (p = 0.005) and somatization (p = 0.023) levels. All AT was associated with levels of psychosomatic symptoms in subjects with hypothyroid HT. In contrast, in subjects with euthyroid HT, the association was only found between depressive and cyclothymic AT with distress and depression levels, as well as between somatization and cyclothymic AT. No association was found between AT and anxiety levels in subjects with euthyroid HT. CONCLUSION: The research found differences between study groups in the association between AT and levels of psychosomatic symptoms. Further research with a larger sample size is necessary to more clearly define the associations between affective temperaments and psychosomatic symptoms in women with euthyroid and hypothyroid HT.

Achalasia Subtype Differences Based on Respiratory Symptoms and Radiographic Findings.

Three subtypes of achalasia have been defined using esophageal manometry. Several studies have reported that symptoms are experienced differently among men and women, regardless of subtype. All subtypes could have some impact on the appearance of respiratory symptoms and lung complications due to compression of the trachea or aspiration of undigested food. The aim of this research was to analyze the differences in respiratory symptoms and radiographic presentation of lung pathology depending on the diameter and achalasia types. One or more respiratory symptoms were reported in 48% of 114 patients, and all of them had two or more gastrointestinal symptoms. The symptom score (SS) is statistically significant for the prediction of subtype 1 (area under the curve = 0.318; p < 0.001, cut-off score of 6.5 had 95.2% sensitivity) and subtype 2 (area under the curve = 0.626; p = 0.020, cut-off score of 7.5 had 93.1% sensitivity). The most common type was subtype 2 (50.8%), and although only 14 patients had subtype 3, they had the largest esophageal diameter (mean 5.8 cm). The difference in esophageal diameter was significant between subtype 1 and 3 (p = 0.011), subtype 2 and subtype 3 (p = 0.011). Nine patients (6%) had mega-esophagus (four patients in type 1, three in type 2 and two in type 3). More than half of all patients (51.7%) had at least one parenchymal lung change on CT scan. Recurrent micro-aspirations led to changes in the structure of the airways and lung parenchyma such as ground glass (GGO) and nodular changes (12%) and fibrosis (14.5%), and they had higher esophageal diameters (p < 0.001). Patients with chronic lung CT changes had significantly higher esophageal diameter than with acute changes (p < 0.001). Awareness of the association of achalasia and lung disorders is important in early diagnosis and treatment. More than half (57.5%) of patients with achalasia had some clinical and/or structural pulmonary abnormalities. All three subtypes had similar respiratory symptoms, meaning they cannot be used to predict the subtype of achalasia; on the contrary, SS can predict the first two subtypes. A higher diameter of the esophagus is associated with chronic structural lung changes. Although unexpected, the pathological radiological findings and diameter were significantly different in subtype 3 patients, but those parameters cannot lead us to a specified subtype.

The usefulness of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for diagnosis and assessment of COPD severity.

BACKGROUND: Inflammation, oxidative stress and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and to assess their relationship with lung function, symptom severity scores and recent acute exacerbations. METHODS: In this observational cohort study, serum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 ratio in the peripheral blood of COPD patients with stable disease and healthy controls were determined, and their association with lung function (postbronchodilator spirometry, body plethysmography, single breath diffusion capacity for carbon monoxide), symptom severity scores (mMRC and CAT) and exacerbation history were assessed. RESULTS: COPD patients (n = 98) had significantly higher levels of serum MMP-9 and TIMP-1 and a higher MMP-9/TIMP-1 ratio than healthy controls (n = 47) (p ≤ 0.001). The areas under the receiver operating characteristic curve for MMP-9, TIMP-1 and the MMP-9/TIMP-1 ratio for COPD diagnosis were 0.974, 0.961 and 0.910, respectively (all p < 0.05). MMP-9 and the MMP-9/TIMP-1 ratio were both negatively correlated with FVC, FEV1, FEV1/FVC, VC, and IC (all p < 0.05). For MMP-9, a positive correlation was found with RV/TLC% (p = 0.005), and a positive correlation was found for the MMP-9/TIMP-1 ratio with RV% and RV/TLC% (p = 0.013 and 0.002, respectively). Patients with COPD GOLD 3 and 4 presented greater MMP-9 levels and a greater MMP-9/TIMP-1 ratio compared to GOLD 1 and 2 patients (p ≤ 0.001). No correlation between diffusion capacity for carbon monoxide and number of acute exacerbations in the previous year was found. CONCLUSIONS: COPD patients have elevated serum levels of MMP-9 and TIMP-1 and MMP-9/TIMP-1 ratio. COPD patients have an imbalance between MMP-9 and TIMP-1 in favor of a pro-proteolytic environment, which overall indicates the importance of the MMP-9/TIMP-1 ratio as a potential biomarker for COPD diagnosis and severity.

The Clinical Impact of the Extension of Acute Type A Aortic Surgery on Long-Term Outcomes: Should We Tend to Be Conservative?

Background and Objectives: Despite advances in surgical techniques, industry adjuncts, and cerebral perfusion techniques, the in-hospital mortality rate of type A acute dissection (TAAD) remains at 15-30%. This study aimed to investigate the influence of different extents of aortic resection on survival and quality of life (QoL) after long-term follow-up. Materials and Methods: A retrospective observational trial was performed, including 165 patients operated upon for TAAD. Patients were divided into two groups according to the extent of their aortic repair: the first group comprised patients who had ascending aorta replacement and the second included patients who had hemiarch or total arch replacement. The groups were compared with regard to their baseline characteristics, operative characteristics, survival, complications, and QoL during nine years of follow-up. Results: The mean follow-up time was 75.6 months (1-108 months). The mean survival in the ascending aorta repair group was 89.651 (81.242-98.061) months and was 54.801 (40.053-69.548) months in the hemiarch and arch group; the difference between the groups was significant (log-rank p < 0.001). The rate of new postoperative neurological deficits was statistically higher in the hemiarch and arch group (17.5% vs. 8.4%, p = 0.045), the most common being stroke, and was also more frequent in the hemiarch and arch group than in the ascending aorta group (with statistical significance (15.7% vs. 6.5%)). The mean SF-12 physical score from the QoL questionnaire was higher in the ascending aorta replacement group than in the hemiarch and arch group (50.1 ± 7.3 vs. 44.0 ± 11.9, p = 0.017). Additionally, the mean SF-12 mental score was higher in the ascending aorta replacement group (52.3 ± 7.3 vs. 47.1 ± 12.8, p = 0.032). Conclusions: A more aggressive approach involving aortic arch repair means a lower survival rate and lesser quality of life after long-term follow-up in comparison with the replacement of the ascending aorta. If clinically applicable, a more defensive strategy may be considered.

Outcomes of Open Surgery for Retroperitoneal Hematoma in Covid-19 Patients: Experience from a Single Centre.

Background: Spontaneous retroperitoneal hematoma is a severe and potentially fatal complication that appears in the course of anticoagulation therapy. Therapeutic doses of low molecular weight heparin (LMWH) are used for the prevention of thrombosis in patients seriously ill with Covid-19. Methods: We describe 27 (0.14%) patients with retroperitoneal hematomas who required emergency surgery out of 19108 patients with Covid-19 who were hospitalized in Batajnica COVID Hospital between March 2021 and March 2022. All the patients were on therapeutic doses of LMWH. The existence of retroperitoneal hematoma was confirmed by abdominal ultrasound and computed tomography scans. Results: Open surgery was performed on 27 patients with spontaneous retroperitoneal hematomas (12 female and 15 male). The mean age of the study population was 71.6+-11.9 years. D-dimer was significantly elevated two days before the surgery in comparison with the values on the day of surgery (p=0.011). Six patients (22.23%) survived, while 21 (77.77%) patients died. Conclusion: Bleeding in Covid-19 patients treated by LMWH is associated with an increased risk of developing retroperitoneal hematoma. Open surgery for retroperitoneal hematoma in Covid-19 patients on anticoagulation therapy is a procedure associated with a high rate of mortality.

The correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction.

Background: The aim of this study was to examine the correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction. Methods: Between 2014 and 2022, we prospectively evaluated 81 consecutive spina bifida children with neurogenic bowel and bladder dysfunction (35 boys and 46 girls, mean age 9.5 ± 3.4 years). All patients underwent echosonographic measurement of transverse rectal diameter and urodynamic studies. Results: We found a strong negative correlation between transverse rectal diameter and maximum bladder capacity (r = -0.682, p < 0.001) and compliance (r = -0.690, p < 0.001). There was also a strong positive correlation between transverse rectal diameter and maximal detrusor pressure (r = 0.650, p < 0.001), leak point pressure (r = 0.793, p < 0.001), and PVR (r = 0.762, p < 0.001). In ROC analysis, transverse rectal diameter demonstrated good performance for distinguishing children with upper urinary tract deterioration, with an AUC of 0.857 (95% CI 0.761-0.953). A transverse rectal diameter ≥40 mm was 83.3% sensitive and 100% specific for the diagnosis of unfavorable urodynamic patterns. Conclusion: There is a correlation between the transverse rectal diameter and urodynamic findings in children with neurogenic bowel and bladder dysfunction. Ultrasonographically assessed transverse rectal diameter of ≥40 mm may be used as a risk factor for upper urinary tract deterioration (unfavorable urodynamic findings). We suggest the transverse rectal diameter echosonographic measurement use as an integral part of the diagnostic approach in children with neurogenic bowel and bladder dysfunction, as it can help decision-making while waiting for urodynamic testing.

Association between active pulmonary tuberculosis and miRNA-146a: A preliminary study from Serbia.

INTRODUCTION: Tuberculosis (TB) continues to be a significant public health problem. The role of small non-coding RNAs, such as microRNAs (miRNAs), was investigated extensively in Mycobacterium tuberculosis (MTB) infection as well as in a variety of other pathophysiological processes in recent years. It was found that miRNAs act as regulators of both early reaction to MTB infection and in process of adaptation of the host immune cells during latent course of the disease. Molecule miRNA-146a is expressed exclusively in immune cells and it has the most prominent role in modulation of innate immunity. METHODOLOGY: We investigated the level of expression of miRNA-146a using an RT-qPCR technique in peripheral blood mononuclear cells of 44 patients with active pulmonary TB and 17 healthy individuals. We also analyzed the significance of miRNA-146a rs2910164 SNV for expression profile of miRNA-146a, in order to investigate potential usage of miRNA-146a as a biomarker for TB. RESULTS: There was statistically significant decrease of expression of miRNA-146a in TB group compared to control group. When gender cohorts were analyzed, the expression levels in TB male and TB female subgroup were significantly lower than the expression levels in the same gender control subgroups. CONCLUSIONS: Our results indicate that miRNA-146a plays a significant role in the pathogenesis of TB, suggesting that miRNA-146a could be used as a biomarker for active pulmonary TB.

Gastrointestinal Biopsy Obtained During Cancer Screening, a Biological Marker for α-Synucleinopathy?

The hallmark alteration in α-synucleinopathies, α-synuclein, is observed not only in the brain but also in the peripheral tissues, particularly in the intestine. This suggests that endoscopic biopsies performed for colon cancer screening could facilitate the assessment of α-synuclein in the gastrointestinal (GI) tract. Using immunohistochemistry for α-synuclein, we assessed whether GI biopsies could be used to confirm an ongoing α-synucleinopathy. Seventy-four subjects with cerebral α-synucleinopathy in various Braak stages with concomitant GI biopsies were available for study. In 81% of the subjects, α-synuclein was seen in the mucosal/submucosal GI biopsies. Two subjects with severe cerebral α-synucleinopathy and a long delay between biopsy and death displayed no α-synuclein pathology in the gut, and 11 subjects with sparse cerebral α-synucleinopathy displayed GI α-synuclein up to 36 years prior to death. The finding that there was no GI α-synuclein in 19% of the subjects with cerebral α-synucleinopathy, and α-synuclein was observed in the gut of 11 subjects (15%) with sparse cerebral α-synucleinopathy even many years prior to death is unexpected and jeopardizes the use of assessment of α-synuclein in the peripheral tissue for confirmation of an ongoing cerebral α-synucleinopathy.

Meta-Analysis of Circulating Cell-Free DNA's Role in the Prognosis of Pancreatic Cancer.

INTRODUCTION: The analysis of cell-free DNA (cfDNA) for genetic abnormalities is a promising new approach for the diagnosis and prognosis of pancreatic cancer patients. Insights into the molecular characteristics of pancreatic cancer may provide valuable information, leading to its earlier detection and the development of targeted therapies. MATERIAL AND METHODS: We conducted a systematic review and a meta-analysis of studies that reported cfDNA in pancreatic ductal adenocarcinoma (PDAC). The studies were considered eligible if they included patients with PDAC, if they had blood tests for cfDNA/ctDNA, and if they analyzed the prognostic value of cfDNA/ctDNA for patients' survival. The studies published before 22 October 2020 were identified through the PubMED, EMBASE, Web of Science and Cochrane Library databases. The assessed outcomes were the overall (OS) and progression-free survival (PFS), expressed as the log hazard ratio (HR) and standard error (SE). The summary of the HR effect size was estimated by pooling the individual trial results using the Review Manager, version 5.3, Cochrane Collaboration. The heterogeneity was assessed using the Cochran Q test and I2 statistic. RESULTS: In total, 48 studies were included in the qualitative review, while 44 were assessed in the quantitative synthesis, with the total number of patients included being 3524. Overall negative impacts of cfDNA and KRAS mutations on OS and PFS in PDAC (HR = 2.42, 95% CI: 1.95-2.99 and HR = 2.46, 95% CI: 2.01-3.00, respectively) were found. The subgroup analysis of the locally advanced and metastatic disease presented similar results (HR = 2.51, 95% CI: 1.90-3.31). In the studies assessing the pre-treatment presence of KRAS, there was a moderate to high degree of heterogeneity (I2 = 87% and I2 = 48%, for OS and PFS, respectively), which was remarkably decreased in the analysis of the studies measuring post-treatment KRAS (I2 = 24% and I2 = 0%, for OS and PFS, respectively). The patients who were KRAS positive before but KRAS negative after treatment had a better prognosis than the persistently KRAS-positive patients (HR = 5.30, 95% CI: 1.02-27.63). CONCLUSION: The assessment of KRAS mutation by liquid biopsy can be considered as an additional tool for the estimation of the disease course and outcome in PDAC patients.

Calculation of left ventricular volumes and systolic indices in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism.

BACKGROUND/AIM: Subclinical hypothyroidism (SCH) is defined as high thyroid-stimulating hormone (TSH) and normal thyroxine (T4) levels. Data on the effects of early substitution with levothyroxine on psychophysical health in SCH are not consistent enough to support its general administration. The aim of this study was to examine the effect of 3-months levothyroxine (LT4) treatment on cardiovascular function in symptomatic SCH with TSH <10 mIU/L. METHODS: Anthropometric, biochemical, electro- and echocardiographic indices were measured in 35 patients with persistent symptomatic SCH (4 mIU/L < TSH <10 mIU/L; mean ± SD: 7.0 ± 2.1 mIU/L) and 40 healthy controls at baseline and three months after the euthyroid state had been achieved on LT4 for SCH group, or 3 months of follow-up for controls. RESULTS: The analyses showed a significant reduction in body weight (P = .030), systolic and diastolic blood pressure (P = .024, P = .019), TSH (P < .001) and thyroid peroxidase antibodies (TPO Ab) (P < .001) on LT4 in the SCH group. There was a statistically significant decrease in end-systolic (ESV) and end-diastolic volumes (EDV) (P < .001, P < .001, respectively) after LT4 treatment. LT4 therapy significantly increased values of ejection fraction (EF), global longitudinal, circumferential and radial strains (P < .001, P < .001, P < .001, respectively). CONCLUSIONS: Our study confirmed an echocardiographic improvement of cardiac structure and function in treated individuals. Findings suggest the role of electrocardiographic and echocardiographic examination in objective monitoring for LT4 therapeutic effects.

Decreased ERß expression and high cyclin D1 expression may predict early CRC recurrence in high-risk Duke's B and Duke's C stage.

PURPOSE: Despite many known risk factors for the colorectal cancer (CRC) recurrence, significant differences in disease-free survival (DFS) impose the need to look for new explanations. This study aimed to determine the degree of expression of ERα, ERß, PR, Cyclin D1, and Bcl-2 and their association with early CRC relapse. METHODS: This retrospective study included 101 radically operated CRC patients in high-risk Duke's B and Duke's C stage. Tissue samples were retrieved from paraffin blocks and clinical and diagnostic data from medical records obtained during further clinical treatment and follow up. Patients were divided into DFS≤24 months group and DFS≥48 months group. Immunostaining of ERα, ERß, PR, Cyclin D1, and Bcl-2 was performed and analyzed. RESULTS: ERα was not expressed in all patients. ERß moderate expression was present in 25% of all patients, more often in the DFS≥48 group (p=0.001). PR and Bcl-2 showed only moderate expression in 1/5 and 1/3 of the patients, respectively, without significant difference between groups (p=0.145;p=0.566). Cyclin D1 was expressed in the whole sample of patients with strong expression statistically more often in DFS≤24 group (p=0.011) and had 5.2 higher odds of having DFS˂24 months. Moderate expression of ERß was joined with 79.2% smaller odds for shorter DFS. Advanced T stage had 11.3 times higher odds of having DFS˂24 months. CONCLUSION: Early recurrence of CRC in high-risk Duke's B and Duke's C stage relates with reduced ERß expression and the high cyclin D1 expression, so they could be considered independent prognostic factors, especially in patients in advanced T stage.

Preeclamptic Women Have Disrupted Placental microRNA Expression at the Time of Preeclampsia Diagnosis: Meta-Analysis.

Introduction: Preeclampsia (PE) is a pregnancy-associated, multi-organ, life-threatening disease that appears after the 20th week of gestation. The aim of this study was to perform a systematic review and meta-analysis to determine whether women with PE have disrupted miRNA expression compared to women who do not have PE. Methods: We conducted a systematic review and meta-analysis of studies that reported miRNAs expression levels in placenta or peripheral blood of pregnant women with vs. without PE. Studies published before October 29, 2021 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Standardized mean difference (SMD) was used as a measure of effect size. Results: 229 publications were included in the systematic review and 53 in the meta-analysis. The expression levels in placenta were significantly higher in women with PE compared to women without PE for miRNA-16 (SMD = 1.51,95%CI = 0.55-2.46), miRNA-20b (SMD = 0.89, 95%CI = 0.33-1.45), miRNA-23a (SMD = 2.02, 95%CI = 1.25-2.78), miRNA-29b (SMD = 1.37, 95%CI = 0.36-2.37), miRNA-155 (SMD = 2.99, 95%CI = 0.83-5.14) and miRNA-210 (SMD = 1.63, 95%CI = 0.69-2.58), and significantly lower for miRNA-376c (SMD = -4.86, 95%CI = -9.51 to -0.20). An increased level of miRNK-155 expression was found in peripheral blood of women with PE (SMD = 2.06, 95%CI = 0.35-3.76), while the expression level of miRNA-16 was significantly lower in peripheral blood of PE women (SMD = -0.47, 95%CI = -0.91 to -0.03). The functional roles of the presented miRNAs include control of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and angiogenesis. Conclusion: miRNAs play an important role in the pathophysiology of PE. The identification of differentially expressed miRNAs in maternal blood creates an opportunity to define an easily accessible biomarker of PE.

The Prospects of Secondary Moderate Mitral Regurgitation after Aortic Valve Replacement -Meta-Analysis.

Aortic valve replacement for aortic stenosis represents one of the most frequent surgical procedures on heart valves. These patients often have concomitant mitral regurgitation. To reveal whether the moderate mitral regurgitation will improve after aortic valve replacement alone, we performed a systematic review and meta-analysis. We identified 27 studies with 4452 patients that underwent aortic valve replacement for aortic stenosis and had co-existent mitral regurgitation. Primary end point was the impact of aortic valve replacement on the concomitant mitral regurgitation. Secondary end points were the analysis of the left ventricle reverse remodeling and long-term survival. Our results showed that there was significant improvement in mitral regurgitation postoperatively (RR, 1.65; 95% CI 1.36-2.00; p < 0.00001) with the average decrease of 0.46 (WMD; 95% CI 0.35-0.57; p < 0.00001). The effect is more pronounced in the elderly population. Perioperative mortality was higher (p < 0.0001) and long-term survival significantly worse (p < 0.00001) in patients that had moderate/severe mitral regurgitation preoperatively. We conclude that after aortic valve replacement alone there are fair chances but for only slight improvement in concomitant mitral regurgitation. The secondary moderate mitral regurgitation should be addressed at the time of aortic valve replacement. A more conservative approach should be followed for elderly and high-risk patients.

Therapeutic effects of desmopressin in primary monosymptomatic noctural enuresis treatment depending on Patients'Age.

PURPOSE: To test the therapeutic effects of Desmopressin (dDAVP) in primary monosymptomatic nocturnal enuresis (PMNE) treatment depending on patients'age. MATERIAL AND METHODS: The prospective research was carried out in the 2014-2018 period, during which 89 patients were observed who were treated with dDAVP due to the previously diagnosed PMNE. The patients were divided into two age groups. The first group (Group 1) consisted of 43 patients age 5 to 6, with the average age of 5.6 ± 0.5, out of whom 35 (81.4%) were boys, and 8 (18.6%) girls. The second group (Group 2) consisted of 46 patients age over 7 to 12, with the average age of 9.7 ± 1.6, out of whom 30 (65.2%) were boys, and 16 (34.8%) were girls. There was no statistically relevant difference according to sex (p = 0.086). After the 3-month treatment, all the patients in both groups were tested for the effects of dDAVP in PMNE treatment. RESULTS: The average enuresis frequency in the first group (Group 1) before therapy was 26.0 ± 6.2 per month, whereas the average enuresis frequency after therapy was 11.0 ± 8.0 per month (p = 0.040). The average enuresis frequency in the second group (Group 2) before therapy was 23.1 ± 6.2 per month, whereas the average enuresis frequency after therapy was 3.8 ± 3.6 per month (p = 0.036). ANOVA data analysis of repeated measurements has indicated that there is a statistically relevant interaction between the groups (p = 0.006), i.e. enuresis frequency decreases considerably more in the second group (Group 2). CONCLUSION: PMNE with dDAVP is noticeably more effective with patients over 7 years of age.

Introducing Clinical Informatics Course in Medical School Curricula: Lessons Learned from Medical Faculty University of Belgrade.

The healthcare environment in Serbia has changed dramatically over a last two decades, pointing out the necessity of clinical informatics (CI) education for future MDs. Total of 77 students were enrolled and 72 (93.5%) have successfully finished this course during 4 academic years. Mean total score for all students was 83.4 Âs 9.0 points, without difference between genders. We presented blended learning module as an effective way of gaining competences in CI and recommend this course to be required for future MDs.

Genes and metabolic pathway of sarcoidosis: identification of key players and risk modifiers.

INTRODUCTION: Sarcoidosis is a rare multisystem granulomatous disease with unknown etiology. The interplay of vitamin D deficiency and genetic polymorphisms in genes coding for the proteins relevant for metabolism of vitamin D is an important, but unexplored area. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in CYP2R1 (rs10741657), CYP27B1 (rs10877012), DBP (rs7041; rs4588), and VDR (rs2228570) genes and sarcoidosis, as well as the association between these SNPs and 25(OH)D levels in sarcoidosis patients. MATERIAL AND METHODS: For that purpose we genotyped 86 sarcoidosis patients and 50 healthy controls using the PCR-RFLP method. RESULTS: Subjects carrying the CC genotype of CYP27B1 rs10877012 have 10 times lower odds of suffering from sarcoidosis. Moreover, DBP rs4588 AA genotype was shown to be a susceptibility factor, where carriers of this genotype had eight times higher odds for developing sarcoidosis. In addition, the A allele of the DBP gene (rs4588) was associated with lower levels of 25(OH)D in sarcoidosis patients. CONCLUSIONS: These results suggest that patients with vitamin D deficiency should be regularly tested for genetic modifiers that are related to sarcoidosis in order to prevent development of serious forms of sarcoidosis.

Reveal, Don't Conceal: Transforming Data Visualization to Improve Transparency.

Reports highlighting the problems with the standard practice of using bar graphs to show continuous data have prompted many journals to adopt new visualization policies. These policies encourage authors to avoid bar graphs and use graphics that show the data distribution; however, they provide little guidance on how to effectively display data. We conducted a systematic review of studies published in top peripheral vascular disease journals to determine what types of figures are used, and to assess the prevalence of suboptimal data visualization practices. Among papers with data figures, 47.7% of papers used bar graphs to present continuous data. This primer provides a detailed overview of strategies for addressing this issue by (1) outlining strategies for selecting the correct type of figure depending on the study design, sample size, and the type of variable; (2) examining techniques for making effective dot plots, box plots, and violin plots; and (3) illustrating how to avoid sending mixed messages by aligning the figure structure with the study design and statistical analysis. We also present solutions to other common problems identified in the systematic review. Resources include a list of free tools and templates that authors can use to create more informative figures and an online simulator that illustrates why summary statistics are meaningful only when there are enough data to summarize. Last, we consider steps that investigators can take to improve figures in the scientific literature.