Volume 60 (2022): Edition 3 (September 2022)

Background: Improved prognosis and delay of clinical complications in diabetes mellitus can be ensured by early screening and regular monitoring after diagnosis. This requires venipuncture at regular intervals of time causing anxiety and discomfort to the patient. Hence, development of a painless, non-invasive procedure is desirable for which saliva is a potential tool. Also, this would provide easy and cost-effective means for large scale screening and epidemiological intervention.

Aim: To measure fasting plasma glucose (FPG) and compare and correlate with salivary glucose levels in normal and diabetic individuals. Also, the correlation between glycated hemoglobin (HbA1c) and salivary glucose is studied in the diabetics and controls.

Methods: Blood and salivary glucose was estimated by GOD-POD method and glycated hemoglobin by HPLC. Statistical analysis was done on SPSS 16. Mean, Standard deviation, independent t test, ANOVA (f test), Pearson’s correlation coefficient along with regression analysis was carried out and comparison was done between the control and diabetic groups and the different subgroups within the diabetic group.

Results: A significant difference between the salivary glucose levels in subjects indicating that a deranged glycemic status is reflected in saliva. Also, salivary glucose increases in proportion to an increase in the FPG and HbA1C of the diabetics. The regression coefficient was calculated and a formula was derived for prediction of FPG and HbA1c using salivary glucose.

Conclusion: Saliva can be used as a screening tool for diabetes. Standardization of the technique and setting up a reference range will also make it useful in diagnosing diabetes mellitus.

Introduction: EGFR targeted therapies, have been proved beneficial for patients with HCC, nevertheless additional research on EGFR immunoexpresion and EGFR mutations is still needed, especially in population in which it has not been done yet. The aim of this study is to evaluate EGFR immunoexpression in HCC without EGFR exons 18–21 mutations and to evaluate its influence on survival in HCC patients in North Macedonia.

Methods: We studied 31 cases of HCC for EGFR immunohistochemical expression and EGFR exons 18–21 mutations. The following clinical parameters were analyzed: Hepatitis B and C virus infection, presence of cirrhosis, tumor size, enlarged lymph nodes, metastases, alpha fetoprotein level and overall survival. Presence of the EGFR immunosignal (membranous and cytoplasmic) and the percentage of positive tumor cells in the entire tumor tissue specimen were semi-quantitatively determined.

Results: Hepatitis B and C virus infection, tumor size, metastatic disease and EGFR immunoexpression have influence on patient’s survival. No EGFR exons 18–21 mutations were detected in this group of HCCs. EGFR expression of 61%–80% in tumor tissue significantly influenced survival of the patients (p < 0.01). Multiple Cox regression confirmed tumor size of 5–10 cm (p < 0.05), tumor size > 10 cm (p < 0.01) and EGFR expression in range of 61% to 80% (p < 0.05) as independent survival predictors in patients with HCC.

Conclusion: EGFR overexpression in range of 61% to 80% was an independent survival predictor in patients with HCC, implying that these patients could benefit from EGFR inhibition. However, the absence of EGFR mutations in exons 18–21 in any of the cases of this study suggest that single drug EGFR targeted therapy in patients with HCC may be insufficient.

Introduction: Increased urinary podocalyxin, a surrogate marker of podocyte detachment, has been shown in preeclampsia and eclampsia, but there is a paucity of data of the effect of normal pregnancy on its urinary excretion. We aimed to describe these changes in this pilot study.

Methods: Urine podocalyxin levels were measured in 115 pregnant women. Of these, 12 women were in the second trimester of gestation, 57 in the third trimester and 46 women were in labor.

Results: The median [IQR] urinary podocalyxin levels were 0.81 [0.27, 3.68], 0.92 [0.44, 5.49] and 64.7 [30.5, 106.3] ng/mg creatinine in the second trimester, third trimester, and during labor, respectively (p<0.0001). Patients with hematuria during labor had higher levels of urinary podocalyxin (128.6 [79.8, 169.6] ng/mg creatinine. There was a moderate correlation between gestational age and urinary podocalyxin levels (r=0.63, p<0.0001).

Conclusion: Urinary podocalyxin levels were low in normal pregnancies and increased significantly during labor and with hematuria.

Introduction: The microRNA-326 (miR-326) gene, by targeting ETS Proto-Oncogene 1 (ETS1), regulates the differentiation and interleukin-17A production of T helper 17 (Th17) cells. Celiac disease (CD) is an intestinal autoimmune disorder, in which the cascade of Th17 cells plays an important role in its pathogenicity. The aim of this study was to evaluate the expression changes of miR-326 and its two target genes ETS1 and IL-17A in celiac disease patients under a gluten-free diet (GFD). We expected the expression of miR-326 and IL-17A gene to decrease, and the expression of the ETS1 gene to increase, following the adherence to GFD.

Methods: Peripheral blood samples of 40 CD patients under GFD (for more than 1 year) and 40 healthy individuals were collected. RNA was extracted, cDNA was synthesized and the miR-326, ETS1 and IL-17A gene expressions were evaluated by the quantitative polymerase real-time qPCR method. P-value ˂ 0.05 was considered statistically significant.

Results: Although miR-326 mRNA expression was significantly lower in CD patients (P = 0.001), no significant difference was observed in ETS1 mRNA level between the two groups (P = 0.54), but IL-17A was significantly overexpressed in CD patients (P=0.002). No significant correlation was observed between the expression of the studied genes and the patientsʼ symptoms and Marsh classification.

Conclusion:Adherence to the GFD for one to two years did not have the expected effect on the expression of genes in this panel. The most important finding that contradicted our hypothesis was the observation of high IL-17A levels in CD patients despite dieting, which may be related to the protective effect of this cytokine on intestinal tight junctions, which needs to be confirmed in further studies.

Introduction: Patients with chronic inflammatory rheumatic diseases (CIRD) who receive intravenous therapy requiring hospitalization are likely to be more affected than those with receiving oral therapy during COVID-19 pandemic. We aimed to investigate the effect of the COVID-19 pandemic on adherence to treatment in patients with CIRD receiving intravenous treatments.

Methods: We evaluated patients with CIRD who were treated with intravenous immunosuppressive therapy such as rituximab (RTX), cyclophosphamide (CTX), infliximab (IFX), tocilizumab (TCZ) and abatacept (ABA) in our inpatient rheumatology clinic. The patientsʼ medical treatment compliance and clinical follow-up were evaluated. Treatment discontinuation was decided according to postponement of at least one dose and discontinuation of CIRD treatments. Demographics and clinical characteristics were compared between treatment-incompliant (TI) and treatment-compliant (TC) groups.

Results: A total of 181 CIRD patients were enrolled. Rheumatoid arthritis was the most common disease requiring intravenous immunosuppressive treatment followed by axial spondyloarthritis and Behçet’s disease. Joint involvement was the most common followed by lung and kidney involvements. Rituximab was the most widely used intravenous immunosuppressive treatment for the CIRD. 34% patients have postponed at least one dose of their intravenous CIRD treatment and 25% discontinued. Fear of COVID-19 and SARS-CoV-2 positivity were the most common reasons. The TI group had a longer disease duration and a higher frequency of inflammatory arthritis than the TC group (p=0.013 and p=0.044, respectively).

Conclusions: Fear of COVID-19 and SARS-CoV-2 positivity seemed to be the major reasons for discontinuing/postponing intravenous treatments in CIRD patients. Patients with long disease duration and less systemic involvement may be more prone to discontinuing their treatments.

Background: Atrial fibrillation (AF) is an emerging epidemic worldwide, responsible for a twofold increase in mortality, independent of other risk factors. Stroke prevention is the cornerstone of AF management. However, oral anticoagulation imposes an increased risk of bleeding. Several risk scores have been developed for estimating both the thromboembolic and the bleeding risks. The aim of the study was to determine the usefulness of different stroke risk scores as predictors of mortality and hemorrhagic events in AF patients.

Methods: We retrospectively enrolled 211 AF patients hospitalized in the Cardiology Ward of our tertiary hospital. The primary endpoints were mortality and non-minor bleeding events. The mean follow-up period was 378 days for bleeding events and 5 years and 1 month for mortality. For each patient, we evaluated the following stroke risk scores: CHADS2, CHA2DS2-VASc, R2CHADS2, ABC, ATRIA, GARFIELD.

Results: The mean age in our cohort is 66, with a slight predominance of women (52.2%). For a CHA2DS2-VASc ≥ 4 as well as for a score of 2-3, 5-year survival was worse than for patients with a score of 0–1(chi-squared=8.13; p=0.01). Similarly, all subgroups of patients with an ABC <2%, had a worse 5-year survival when compared with an ABC score of ≥2% (chi-squared=12.85; p=0.005). C-statistics show a modest predictive value for mortality, for all stroke scores except Garfield, with similar AUCs, the highest being for CHA2DS2-VASc (AUC 0.656; p=0.0001). CHA2DS2-VASc also correlates with bleeding events, having a good predictive ability (AUC 0.723; 95%CI 0.658–0.782, p=0.001), mildly superior to HAS-BLED (AUC 0.674; 95% CI 0.523–0.825; p = 0.04) and very close to Garfield-bleeding (0.765; 95%CI 0.702–0.80; p=0.0001).

Conclusions: CHA2DS2-VASc is comparable to HAS-BLED and Garfield-bleeding in predicting bleeding events in AF patients. CHA2DS2-VASc and ABC correlate directly and consistently with mortality rate. For CHA2DS2-VASc, the AUCs for our endpoints are similar to the ones for stroke prediction, highlighting the potential of extending its applicability to various outcomes.

A 59-year-old man who had smoked for 23 pack-years was admitted to our hospital because of two-month history of back pain. The chest computed tomography scan demonstrated combined pulmonary fibrosis and emphysema (CPFE) and an irregular shaped nodule in the left lower lobe of the lung. A biopsy obtained from samples from subcarinal lymph nodes revealed non-small cell lung cancer. Anti-aminoacyl-tRNA synthetase (ARS) antibody was elevated up to 166 U/mL, although he had no symptoms suggestive connective tissue diseases. It is well known that most of CPFE patients are current or former heavy smokers, and some researchers described the relationship between CPFE and connective tissue diseases. To our best knowledge, this was the first report of lung cancer in patient with anti-ARS antibody-positive CPFE. In some anti-ARS antibody-positive patients, smoking might have a relationship with development of CPFE and lung cancer.