A case report of biclonal immunoglobulin D lambda/lambda multiple myeloma in patient with liver echinococcosis.

Less than 2% of all symptomatic multiple myeloma (MM) has immunoglobulin D (IgD) as monoclonal protein. Biclonal gammopathy is much rarer. At the time of diagnosis, disease is often in advanced stage, including renal failure, anemia, hypercalcemia and lytic bone lesions. Due to the rarity of myeloma itself, but also due to the fact that anti-IgD antisera is not used in routine practice, there are only a few reports of IgD MM described in the literature. This case report describes a patient with IgD lambda MM with anemia and renal failure. Anemia, renal failure, and > 80 percent plasma cells in bone biopsy in our patient with IgD lambda MM meets International Myeloma Working Group criteria for diagnosis of MM. The patient clinical course was similar to other patients with IgD MM. The final result of serum protein immunofixation (s-IFE) showed IgD lambda and free lambda monoclonal bands. To prevent misdiagnosis, it is necessary to use anti-IgD and anti-IgE antisera whenever the serum protein immunofixation with IgA, IgM, IgG, kappa and lambda antiserums shows a kappa or lambda monoclonal band without monoclonal band in heavy chain.

Excretion of SARS-CoV-2 RNA in feces has no prognostic benefit in the outcome of COVID-19: A clinical and immunological study

This study explores the correlation between immunological and clinical characteristics in coronavirus disease 2019 (COVID-19) patients with detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in feces, analyzing data from 251 patients admitted to Mostar University Clinical Hospital from December 2021 to January 2022. Methods involved reverse transcription quantitative polymerase chain reaction (RT-qPCR) from nasopharyngeal swabs and feces, alongside serological tests for anti-SARS-CoV-2 spike IgGs. Demographic and clinical data were collected through questionnaires and medical records. The data analyses were performed using SPSS statistical software. Death occurred in 53 patients (21.1%, P < 0.001), mostly in the elderly (47/53, 88.7%, P = 0.001) and immunocompromised (19/53, 35.8%, P = 0.05), particularly those developing acute respiratory insufficiency (ARI) (46/53, 86.8%, P = 0.004), and severe/critical disease (46/53, 86.8%, P = 0.002). Among the patients with positive anti-SARS-CoV-2 IgG antibodies (86/251, 34.3%, P < 0.001), 41 (47.7%) were vaccinated and 45 (52.3%) unvaccinated (P = 0.666), showing no significant differences in clinical outcomes or mortality. Unvaccinated patients with a negative antibody titer had a higher incidence of ARI (96/123, 78%, P = 0.029) and intensive care unit admission (22/123, 17.9%, P = 0.026), than those with a positive antibody titer. Forty-seven (62.7%) patients, out of the 75 hospitalized who provided a feces sample, were positive for SARS-CoV-2 RNA (P = 0.028), without statistical differences between fecal SARS-CoV-2 positive and negative groups regarding vaccination status (15/47, 31.9%, P = 0.493), antibody status (18/47, 38.3%, P = 0.628) or death outcome (5/47, 10.6%, P = 0.706). In conclusion, unvaccinated hospitalized patients with a severe COVID-19 presentation and a negative anti-spike SARS-CoV-2 IgG titer had adverse outcomes more frequently. This suggests cautious consideration for the diagnostic use of fecal samples compared to nasopharyngeal swabs.

Cystatin C Concentration During the First Three Postnatal Days in Healthy Term Newborns.

OBJECTIVE: Cystatin C (Cys-C) concentration has not been examined sufficiently among healthy newborn population, particularly in terms of reference values. This study aimed to establish gender-, postnatal age- and birth weight-specific Cys-C concentration for healthy term newborns. Its objective was also to examine if there were any differences between our measured concentration and the reference interval established by the CALIPER study. METHODS: Serum samples from a total of 90 healthy term newborns were used to determine Cys-C concentration. Cys-C was measured within first three days of birth using particle-enhanced turbidimetric immunoassay (PETIA) on the Architect plus ci8200 analyzer. RESULTS: Median concentration of the Cys-C was 2.05 mg/L. There were no statistically significant differences in Cys-C concentration regarding gender (p=0.779), birth weight (p=0.505), postnatal age (p=0.512) or Apgar score (p=0.799). The value of the 2.5th and 97.5th percentile for Cys-C concentrations for girls was 0.93-3.15 mg/L and for boys it was 1.5-3.36 mg/L. CONCLUSION: Cys-C concentration in healthy term newborns does not depend on gender, birth weight, postnatal age, or Apgar score. Our measured concentration range of CyS-C in healthy newborns turned out to be slightly wider than the interval determined in the CALIPER study.

Sustained seroprevalence of SARS-CoV-2 antibodies one year after infection: one of the first COVID-19 cluster cases in Bosnia and Herzegovina.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) is a novel virus that has been identified as a causal agent of COVID-19,  an emergent infectious disease which brought about a new pandemic in the twenty-first century. The immune responses and clinical features of individuals infected with SARS-CoV-2 have not yet been fully described. Thus, in this study, we compare the seroprevalence and define the correlation between symptoms and serological results in the first COVID-19 cluster in the city of Konjic, Bosnia and Herzegovina. Of the total number, 93% of RT-PCR positive participants had positive IgG serology and 75% of them developed symptoms of COVID-19. We found that there was no significant alteration in specific IgG (p = 0.504) antibody levels during the 1-year period after COVID-19. Our results indicate that symptomatic COVID-19 patients have a higher rate of seroconversion (p < 0.01). The IgG seroconversion was correlated with high fever (p = 0.002) and headache (p = 0.007), suggesting that these symptoms could be considered as indicators of a better immune response. This study has demonstrated persistence of sustained levels of specific SARS-CoV-2 antibodies after recovering from COVID-19 infection. However, in order to gain a better insight into the immune response to SARS-CoV-2, further systematic studies should be focused on quality and longevity analyses.

Urine neutrophil gelatinase-associated lipocalin concentration in healthy newborns during the first three postnatal days.

INTRODUCTION: Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a biochemical marker significant for early prediction of acute kidney injury in adults. However, it has not been examined sufficiently among the infant population, particularly newborns in terms of reference values. The aim of our study was to determine the concentration of uNGAL in healthy term newborns and to determine if there was a difference in uNGAL concentration according to gender, postnatal age and birth weight. MATERIALS AND METHODS: Our study involved 81 healthy term newborns birth (≥ 37 weeks, Apgar score ≥ 8 in the first minute after birth, CRP < 5 mg/L). Urine NGAL was measured using chemiluminescent microparticle immunoassay (CMIA) within 72 hours after birth, on Architect plus ci8200 analyser (Abbott, Chicago, USA). Data were analysed using Statistica software. RESULTS: The median concentration of uNGAL in the whole study group of healthy term newborns was 27.1 ng/mL (16.5-56.0 ng/mL) (newborn girls, 27.1 ng/mL (15.8-47.9 ng/mL); newborn boys, 27.9 ng/mL (16.5-61.0 ng/mL), P = 0.941). Median uNGAL concentration according to postnatal age expressed in days was 28.2 ng/mL (11.7-57.2 ng/mL) 1st day, 28.9 ng/mL (16.5-64.2 ng/mL) 2nd day and 23.9 ng/mL (20.2-46.6) 3rd day, P = 0.863. Regarding birth weight for newborns < 3500 g, median concentration was 25.0 ng/mL (16.5-45.4 ng/mL) and for weight ≥ 3500 g 30.6 ng/mL (16.5-64.2 ng/mL), P = 0.455. CONCLUSIONS: There were no significant difference in uNGAL concentration in relation to gender, postnatal age and birth weight.

Levels of Nitric Oxide Metabolites and Myeloperoxidase in Subjects with Type 2 Diabetes Mellitus on Metformin Therapy .

INTRODUCTION: Endothelial dysfunction is involved in the pathogenesis of insulin resistance, diabetes mellitus type 2, diabetic complications and preceded clinical manifestation of cardiovascular complications. Increased myeloperoxidase activity has been linked to a number of pathologies with compelling evidence in initiation and progression of inflammatory events. The aim of this study was to compare concentrations of metabolite nitric oxide and myeloperoxidase in the plasma of diabetes mellitus type 2 patients on metformin therapy, without clinical signs of cardiovascular disease and healthy subjects, as well as evaluation of concentrations of analytes in association with glycemic control. MATERIALS AND METHODS: Forty four study subjects with diabetes mellitus type 2 and thirty healthy subjects were included in this study. The concentration of myeloperoxidase was determined by enzyme-linked immunosorbent assay, the concentration of nitrate and nitrite with high performance liquid chromatography method. Student's t test, Mann-Whitney U test, Chi-square test and Fisher's exact test were used for statistical analysis. RESULTS: The mean concentration of myeloperoxidase was significantly higher in the diabetic group compared to the control group (16.2±4.9 vs. 3.7±1.8; P<0.001).The nitrite concentration was comparable in both groups while the concentration of nitrate was significantly higher in the diabetic group (41.2 [42.9] vs 31.9 [23]; P=0.017). In this study, plasma myeloperoxidase (Spearman's rho=0.421; P=0.004) and nitrate concentration was significantly positively associated with the HbA1c levels while nitrate concentration (Spearman's rho=- 0.308; P=0.047) were was significantly positively negatively associated with the HbA1c levels. CONCLUSION: Concertation of MPO and nitric oxide were significantly increased in a T2DM subject even when on metformin therapy. However, increased concentration of NO strongly correlates with lower levels of HbA1c showing a postive effect of a gylcemic control on endothelial dysfuction. Increased concentrations of NO3- in T2DM subject compared to control, indicates the variety of NO pathways that should be taken into consideration win relation to endothelial function.

A relation of serum homocysteine, uric acid and C-reactive protein level in patients with acute myocardial infarction.

Aim To determine the relationship of homocysteine (HCY), uric acid (UA) and C-reactive protein (CRP) in serum of patients with acute myocardial infarction (AMI) prior to application of percutaneous coronary intervention (PCI) and their level of correlation in serum of patients with normal and elevated CRP (predictor of worse cardiovascular outcomes). Methods The study involved 85 patients with diagnosed AMI. Before the PCI, venous blood samples were taken into the vacuum test tubes. The analysis of HCY, UA, inflammatory markers CRP and neutrophil to lymphocyte ratio (NLR) as well as lipoprotein status were performed on a different type of analysers and according to accepted protocols of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Results Elevated level of both HCY and UA in AMI patients as well as a positive correlation between HCY and UA level was observed. Classification of patients on the basis of mean UA concentration showed significant difference at the level of HCY concentration (p=0.022). Conclusion Since HCY and UA participate in the atherosclerotic process and their metabolism, as well as the effects on the cardiovascular system show significant overlaps, their serum level should be analysed synchronously with the level of CRP and NLR (indicators of significant inflammatory process in vessels). Considering a potential link between all parameters observed, further research involving a greater number of patients and including the post treatment effects should be conducted.

Predictive Value of High Sensitive Troponin I Assay in Acute Coronary Syndrome Compared to Classic Biochemical Markers.

The aims of this study were to compare predictive values of hsTroponin I assay with contemporary assays and its usefulness in diagnosis of acute coronary syndrome (ACS). We also aimed to determine reference values of the assay and the possibility of fast ACS diagnosis using hsTnI. The study included 26 patients with ongoing chest pains and suspected ACS. ACS diagnosis was determined using electrocardiographic changes and international guidelines. Biochemical parameters were measured using standard tests which included Troponin I, hsTroponin I, CK, CK-MB and CRP. 10 (38.5 %) patients out of 26 were diagnosed with ACS. Median age was 63.92 years. Comparison of predictive values showed that hsTnI and TnI had an advantage before CK, CK-MB and CRP. hsTnI showed no significant improvements over TnI. With an perfect negative predictive value at admission, hsTnI is recommended for use as a rule-out method for ACS in patients with chest pain and suspected ACS on admission. hsTnI was superior to contemporary TnI assays only as a rule-out method for suspected ACS patients at admission.

Immunohystochemical Expression of Vitamin D Receptor in Development Stages of Colorectal Carcinoma.

BACKGROUND: Chemo preventive and antitumor role of vitamin D is manifested through genetic and non genetic ways with a powerful antproliferatory and proapopoptic effect, which is proven by numerous epidemiologic studies. The genetic activity of vitamin D is determined through vitamin D receptors (VDR), a member of stero-thyreoidal family of nuclear receptors, which with vitamin D form a cell nucleus complex responsible for the chemo preventive and antitumor effect. VDR in tissue cells is present in the cytoplasm and the nucleus and manifests its genetic activity after transfer from the cytoplasm to the nucleus. The mechanisms for the transport and genetic control of the transport of VDR from cytoplasm to the nucleus in not yet completely understood. SUBJECTS AND METHODS: By using immunohystochemistry we are evaluating the correlation of cytoplasmic and nuclear expression of VDR during different stages of colorectal carcinoma: normal colorectal mucosa, hyperplasic polyp, low grade adenoma (LGD), high grade adenoma (HGD) and colorectal cancer. RESULTS: Our results confirm that the nuclear VDR expression is strongest in normal colorectal mucosa and in hyper plastic polyps, is gradually weakened in low and high grade adenoma while it is extremely weak or absent in colorectal carcinoma. At the same time the expression of cytoplasm VDR is weakest in normal colorectal mucosa and hyper plastic polyps while it grows during the adenoma stage and is most expressed during colorectal carcinoma. CONCLUSION: We conclude that vitamin D has a strong chemo preventive and antitumor effect in normal colorectal mucosa and hyper plastic polyps, while its antitumor and chemopreventive effect is progressively weakened and ultimately absent in colorectal carcinoma.

Body Composition and Inflammation in Hemodialysis Patients.

The volume state of dialysis patients is important in guiding the dialysis process. Volume overload in these patients is associated with inflammation. The objectives of the present study were to assess the body composition of patients on hemodialysis; to determine the concentrations of B-type natriuretic peptide (BNP) in plasma and evaluate the association of BNP concentrations with volume overload; to determine the concentrations of C-reactive protein (CRP), albumin and superoxide dismutase (SOD) activities as indicators of inflammatory or antioxidant processes. The study included 79 maintenance hemodialysis patients. Assessment of body compartments was carried out using a body composition monitor (BCM). After BCM measurements, blood samples were taken from the patients for laboratory tests. There were 40 (50.6%) volume-overloaded patients (relative overhydration >15%). These patients had a higher prevalence of arterial hypertension (P < 0.05), significantly higher concentrations of BNP (P = 0.01), lower body mass index (P < 0.05) and lower fat tissue index (P < 0.05). There was a positive correlation between plasma BNP and CRP concentrations (ρ = 0.231; P < 0.05), and a negative correlation between (log) BNP and albumin (r = -0.021; P < 0.05), as well as (log) CRP and albumin concentrations (r = -3; P < 0.01). SOD activity was positively correlated with albumin concentrations (r = 0.254; P < 0.05). The concentrations of BNP in this study were associated with volume overload and inflammatory markers. Patients with a higher albumin concentration had higher SOD activity.

Kappa Free Light Chains in Cerebrospinal Fluid of Patients with Identified Oligoclonal Immunoglobulin G.

BACKGROUND: Production of kappa free light chains (KFLC) represents a part of humoral immune response, along with the synthesis of intrathecal immunoglobulins. Increased concentrations of immunoglobulin G light chains, kappa and lambda chains, were identified through research of numerous diseases of central nervous system. The qualitative method of isoelectric focusing (IEF) followed by immunofixation currently represents the accepted standard in identifying oligoclonal bands (OCB), but establishing a sensitive immunonephelometric method for quantification of kappa free light chains (KFLC) in cerebrospinal fluid (CSF) has paved a way for new diagnostic possibilities. Andersson classified the pattern types of OCB, ranging from type 1 to type 5, wherein types 2 and 3 indicate intrathecal synthesis. Our aim was to determine KFLC in CSF of patients with clinically isolated syndrome (CIS) who had presented with type 2 and type 3 OCB, to determine if there is a difference in concentrations between those two groups and to establish a borderline value of KFLC which would enable differential diagnostics. SUBJECTS AND METHODS: 70 patients, who underwent lumbar punction for CSF analysis and had their blood sampled through the cubital vein, participated in the study. Patients were classified according to Andersson as type 2 or type 3, which besides adulthood, represented the inclusion criteria. The average age of patients classified as type 2 was 36 years, and those classified as type 3 was 39 years, where it is evident that there was not a statistically significant difference (p=0.0685). We used a qualitative electrophoretic technique of IEF with agarose gel followed by immunofixation, and a quantitative immunonephelometric method. All results were interpreted on a level of statistic significance of p<0.05. RESULTS: CSF KFLC concentrations in type 3 were statistically and significantly elevated with regard to type 2 (Mann-Whitney test, p=0.0430). The median for KFLC in type 2 was 0.9 mg/L, while the median for KFLC in type 3 was 2.71 mg/L, and the detection limit for both types was 0.18 mg/L. We used a statistical ROC curve to determine that KFLC concentration can be used for differential diagnostics, meaning it can discriminate type 2 from type 3 with clinical sensitivity of 61% and clinical specificity of 71% (AUC=0.641) (p=0.037). CONCLUSION: Despite the obtained statistically significant differences in concentrations of KFLC between types of OCBs and ROC analysis results, determination of KFLC by a nephelometric method, insufficiently strong clinical sensitivity and specificity does not justify abandonment of IEF method followed by immunofixation.

Correlation between water hardness and cardiovascular diseases in Mostar city, Bosnia and Herzegovina.

The aim of this study was to determine the association of cardiovascular disease (CVD) of selected human subjects with the hardness of water they consume. Laboratory testing of physical and chemical parameters of water were made using standardized methods: Standard Methods 19th edn, 1995 (APHA, AWWA & WEF, Washington, DC), and ISO 7888:1985, ISO 10523:1998. Pearson's chi-squared test was used for the statistical analysis of data, with the significance level of 0.05. The obtained data were analysed using the statistical program SPSS 16.0. The study sample consisted of 1,021 individuals divided into two groups: soft water consumers, 603 individuals, and, hard water consumers, 618 individuals. Results indicate that a statistically significant (χ(2) = 5.315; df = 1; p = 0.021) number of individuals with CVD drink soft water. The prevalence of CVD in the age group 45-60 years in the study area where soft water is consumed was 21.3% and in the study area where hard water is consumed the prevalence of CVD was 13.7%. The summary results indicate significant correlation between the prevalence of CVD in the population group who drink soft water. The value of the relative risk is 1.127.

Endothelin-1, big endothelin-1, and nitric oxide in patients with chronic renal disease and hypertension.

The complex pathogenesis of chronic renal disease (CRD) depends on endothelin (ET) axis (ETs and ET receptors) and nitric oxide (NO) because of their vasoactive effects and their role in general modulation of vascular homeostasis. Various renal cells synthesize ETs and NO that play a significant role in renal hemodynamics as well as in water and salt excretion via urine. ET-1 is a strong vasoconstrictor. Besides its vasoactive effects, ET-1 modulates mitosis and apoptosis in a cell type-dependent manner, and may play an important role in CRD pathogenesis. The aims of this study were to emphasize the role and interactions of ET-1, Big ET-1, and NO in CRD. Concentrations of these vasoactive molecules were measured in plasma/serum and/or urine of 57 patients with diabetic nephropathy (subgroup 1), arterial hypertension (subgroup 2) or CRD with chronic renal insufficiency (subgroup 3), and in healthy control subjects (n=18). In comparison with control group, urine concentration of Big ET-1 was significantly increased (13.13 pmol/L vs. 11.34 pmol/L; P<0.001) in CRD patients, whereas plasma and urine concentrations of ET-1 did not differ significantly. NO concentrations were also significantly increased in CRD patients (serum, 72.55 micromol/L; P<0.001, and urine 141.74 micromol/L; P<0.05) as compared to control group. Study results indicated that Big ET-1 and NO could be useful diagnostic parameters in CRD for their diagnostic sensitivity and diagnostic specificity (Big ET-1 in urine: 56.1 and 88.9%, and NO in serum: 66.7 and 83.3%, respectively). In addition, Big ET-1 may prove useful in the differential diagnosis of diabetic nephropathy (78.6% diagnostic sensitivity and 88.9% diagnostic specificity).

The role of endothelin-1 and nitric oxide in the pathogenesis of hypertension in diabetic patients.

The pathogenesis of renal hypertension has not yet been fully clarified. As the potential role of endothelin-1 (ET-1) and nitric oxide (NO) has been postulated, their concentrations were determined in plasma and urine of diabetic patients. The study included 30 diabetic patients (both IDDM and NIDDM) with initial or advanced diabetic nephropathy (decreased endogenous creatinine clearance, proteinuria) and 20 healthy control subjects. The correlation with blood pressure and other renal function parameters was monitored and compared with the control group. Also, the effect of ACE inhibitors (ACEI) on ET-1 and NO patterns was monitored in correlation with arterial hypertension. In diabetic patients that did not receive ACEI therapy, the increase in plasma ET-1 was associated with both systolic and diastolic blood pressure elevation, whereas in those administered ACEI the increase in plasma ET-1 was associated with a systolic blood pressure decline. In addition, the increase in plasma NO was accompanied by a statistically significant decline of both systolic and diastolic blood pressure in diabetic patients receiving ACEI.