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Prognostic implications of low transferrin saturation in patients with primary myelofibrosis
Get PDFOBJECTIVES:
Transferrin saturation (TSAT) 20% or less is considered to represent functional iron deficiency in the context of malignant disease, phenomenon mediated through inflammatory changes of iron homeostasis. We aimed to investigate clinical and prognostic significance of low TSAT in patients with primary (PMF) and secondary myelofibrosis (SMF), malignant diseases characterized by strong inflammatory milieu. -----
METHODS:
We retrospectively analyzed 87 patients with myelofibrosis and compared TSAT with disease specific parameters. -----
RESULTS:
One-third of patients had TSAT ≤20%. Lower TSAT was significantly associated with Janus-kinase-2 (JAK2) mutation (P = 0.007), transfusion independency (P = 0.003), higher platelets (P = 0.004), lower mean-corpuscular-volume (P < 0.001), lower ferritin (P < 0.001), higher absolute-neutrophil-count (P = 0.027), lower absolute-lymphocyte-count (P = 0.041) and lower albumin (P = 0.018). PMF patients presenting with low TSAT (≤20%) experienced significantly shorter overall-survival (OS) (HR = 2.43; P = 0.017), whereas TSAT did not affect OS of SMF patients (HR = 1.48; P = 0.623). Low TSAT remained significantly associated with inferior OS in PMF in a series of multivariate Cox regression models comparing its properties to anemia, transfusion dependency, ferritin and Dynamic-International-Prognostic-System (DIPSS). -----
CONCLUSIONS:
Low TSAT has detrimental effect on survival of PMF patients. This effect is independent of anemia and of ferritin levels that seem to be better at representing iron overload in PMF patients
Terminal ileum resection as a trigger for strongyloides stercoralis hyperinfection and ensuing serial sepsis in a 37-year-old patient with complicated Crohnʼs disease: a case report
Get PDFThe nematode Strongyloides stercoralis, outside the tropics and subtropics present in small endemic foci, can cause an infection after direct skin contact with contaminated soil containing infective filariform larvae and, rarely, after intimate interhuman contact or after transplantation of an infected solid organ. Following skin penetration, migration, and maturation through several stages, a small number of invasive filariform larvae can develop anew in the gut lumen, perpetuating new cycles of penetration, tissue migration, and reproduction, without leaving the host. In a state of immunosuppression, autoinfection can progress to life-threatening hyperinfection and/or infection disseminated through virtually any organ. In developed countries, the most frequently recognized risk for severe hyperinfection is corticosteroid therapy, but this has been also described in malnourished, alcoholic, cancer, and transplant patients. Due to the frequent need for immunosuppressive therapy, patients suffering from inflammatory bowel disease (IBD) are susceptible to develop overwhelming strongyloidiasis. Strongyloidiasis can be easily overlooked in clinical settings, and in many European regions there is poor insight into the epidemiological burden of this disease. We present a case of S. stercoralis hyperinfection that triggered 3 successive episodes of sepsis caused by pathogens of the gut flora in a young patient suffering from stenotic form of Crohn's disease. S. stercoralis hyperinfection occurred in the corticosteroid-free period, shortly after resection of the terminal ileum, which was probably the trigger for the overwhelming course. The patient was successfully treated with 10-day albendazole therapy
Mezenhimni tumor ili sindrom amnijske brazde u novorođenčeta - dijgnostička dilema [Mesenchymal tumour or amniotic band syndrome in a newborn – a diagnostic dilemma]
Get PDFA suspicion of mesenchymal tumour of the right foot dorsum was raised in a newborn with amniotic band
syndrome. A well defined spheric tumour occupied the entire foot dorsum, without edema of the rest of the foot distal
to the constriction ring. An ultrasound scan defined the tumour as firm, localized and well vascularized, while the MR
scan described the tissue as lymphedematous, although allowing other etiologies. CORE biopsy histology report did not
reveal malignant cells, but still did not rule out mesenchymal tumour. A definite hystological analysis performed after
tumour removal and Z-plasty confirmed the diagnosis of lymphedema. Correction of the constricting ring and tumour
removal resulted in an excellent functional and aesthetic result. Such atypical lymphedema presentation resulting from
amniotic constriction ring can raise suspicion of a solid mesenchymal tumor
Seroepidemiological study of Epstein-Barr virus in different population groups in Croatia
Get PDFBACKGROUND:
The Epstein-Barr virus (EBV) is one of the most common viruses found in humans, causing lifelong infection in up to 95% of the world population. ----- OBJECTIVES:
To analyze the seroprevalence of EBV infection in different population groups in Croatia.
----- METHODS:
During a 2 year period (2015-2016), a total of 2022 consecutive serum samples collected from Croatian residents were tested for the presence of EBV-specific viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies using an enzyme-linked immunoassay. IgM/IgG-positive samples were further tested for IgG avidity.
----- RESULTS:
The overall prevalence of EBV IgG antibodies was 91.4%. Females had significantly higher IgG seroprevalence than males (93.1% vs. 89.9%, P = 0.008). According to age, IgG seropositivity increased progressively from 59.6% in children age 40. All IgM positive participants > 40 years showed high IgG avidity. Logistic regression showed that age is associated with EBV IgG seropositivity.
----- CONCLUSIONS:
EBV is widespread in the Croatian population. Older age appears to be the main risk factor for EBV seropositivity
Coexistence of genital lichen sclerosus and genital warts
Get PDFLichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of the genital and extragenital skin. Anogenital warts are benign proliferative lesions caused by human papillomavirus (HPV), which is found in > 95% of lesions. We present two cases of the coexistence of LS and genital warts: one patient with and one without a previous history of genital warts. According to our knowledge and a literature search, only a few cases of the coexistence of LS and genital warts have been reported
Evaluation of nutritional status and physical performance in patients with chronic obstructive pulmonary disease [Procjena nutritivnog statusa i fizičke sposobnosti bolesnika s kroničnom opstrukcijskom bolešću pluća]
Get PDFPhysical inactivity and skeletal muscle mass wasting are frequent findings in patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to compare nutritional status and body composition in COPD patients with poor and normal physical performance, which was assessed in three different ways – exercise capacity evaluated by the 6-minute walk test, gait speed measured by the 4-metre gait speed test and physical activity expressed as average daily step count. In the population of 111 patients with moderate to very severe COPD, those with poor physical performance were older, had worse lung function, higher symptom burden, more frequent exacerbations, worse health-related quality of life, and deficient nutritional status, which manifested dominantly with lower parameters of muscle/bone tissue and serum protein levels. There were no significant differences in the body-mass index and parameters related to fat tissue. In the multivariate analysis the variables that were independently and significantly associated with poor exercise capacity were older age, previous exacerbations, lung hyperinflation, reduced lung diffusion capacity and higher dyspnoea level. Likewise, older age, reduced lung diffusion capacity and dyspnoea level were independently associated with poor physical activity. However, none of the nutritional parameters were independently related to poor physical performance
Ekspresija plakofilina 3 u difuznom malignom pleuralnom mezoteliomu [Expression of plakophilin 3 in diffuse malignant pleural mesothelioma]
Get PDFDiffuse malignant pleural mesothelioma (DMPM) is the most common primary malignant pleural neoplasm which implies diagnostic, prognostic and therapeutic challenges. Plakophilin 3 is a protein incorporated in desmosomes of stratified and simple epithelia of healthy tissues, but also malignant cells of various tumors where it contributes to process of tumorigenesis. This study aimed to investigate expression of plakophilin 3 in DMPM, its prognostic significance and connection to histological parameters of tumor spread. Used were 100 archival samples of DMPM tissue and classified into three histological types of DMPM (epithelioid, sarcomatoid, biphasic). Additional subclassification of epithelioid mesotheliomas based on the prevalent histological component of the tumor was performed. After immunohistochemical staining, cytoplasmic and membranous tumor cells immunopositivity was assesed by scoring the intensity of staining from 0 ( no staining) to 4 (very strong staining). Prognostic value and expression of plakophilin 3 with consideration to histologically estimated tumor spread were statistically analyzed using non- parametric tests. The results demonstrated higher level of plakophilin 3 expression in tumor samples with histologically estimated spread to fatty tissue and/ or skeletal muscle. Prognostic value was not statistically significant. This research suggests plakophilin 3 to be involved in tumor spread of DMPM
Upalne stanice u stijenci aneurizme trbušne aorte aterosklerotskoga podrijetla [Inflammatory cells in the atherosclerotic abdominal aortic aneurysm]
Get PDFThe inflammatory reaction is defined as the key regulatory atherosclerotic process.
By comparing the type and volume of inflammatory cells in the abdominal aortic
aneurysm (AAA) walls and the only atherosclerotic abdominal aorta abnormalities,
the influence of inflammation on the formation of atherosclerotic plaque and the
development of ATA was investigated.
Comparison of the type and volume of inflammatory cells - macrophage, mast cell,
lymphocyte B, plasma cells, auxiliary CD4 + lymphocytes T, cytotoxic CD8 +
lymphocytes, in the AAA strain (40 patients treated with open surgical aneurysm
repair) and rocks only atherosclerotic altered abdominal aorta (20 patients) T and
regulatory CD4 + Foxp3 + lymphocytes T. Inflammatory cells are characterized by
the representation of specific cellular markers by immunohistochemical method on
paraffinic tissue cuts. The morphological characteristics of AAA (diameter,
morphological type - fusiform / saccular, isolated abdominal aorta aneurysm or
extended with one and / or two iliac arteries , presence of intraluminal thrombus),
laboratory parameters (CRP, D-dimer, total cholesterol (age, gender, body weight,
body weight, body mass index (ITM), smoking, blood pressure - systolic/diastolic,
diabetes mellitus, presence of peripheral atherosclerosis, other peripheral
aneurysms), and clinical risk factors of atherosclerosis, taking medicines - statins).
In the AAA strains, a significantly higher number of cytotoxic CD8 + lymphocytes T,
regulatory CD4 + Foxp3 + lymphocytes T and plasma cells were found in
comparison to the only atherosclerotic abdominal aortic ventricular wall. Significantly
larger number of auxiliary CD4 + lymphocytes T and macrophages were found in the
abdominal aorta of the control group. In the largest number of patients, the diameter
of AAA was 45-75 mm, aneurysms were more often sacrilege (32/40), isolated
without the involvement of one and/or two iliac arteries with branches (36/40) and
with intraluminal thrombosis (28/40). By comparison of the type and volume of the examined inflammatory cells in the AAA strain and the morphological characteristics
of the AAA, a statistically significant higher incidence of lymphocyte B was found in
the fusiform type of AAA. The type and frequency of the examined inflammatory cells
are not related to other analyzed morphological characteristics of AAA. By
comparing the type and volume of the investigated inflammatory cells with the
investigated laboratory indicators and clinical factors of atherosclerosis risk,
statistically significant results of plasma cell-related correlation with LDL and total
cholesterol, cytotoxic CD8 + lymphocyte T and plasma cells were found with diastolic
pressure values and regulatory CD4 + Foxp3 + lymphocytes with ITM and body
weight of patients have no specific clinical relevance. By comparing the
morphological characteristics of AAA with the investigated laboratory indicators and
the clinical factors of atherosclerosis risk, the AAA diameter was significantly
associated with elevated CRP values. The extended AAA type with the involvement
of one and/or two lipid arteries with the ribs was statistically significantly more
frequent in elderly patients.
The higher incidence of cytotoxic CD8 + lymphocytes T in AAA is responsible for
damage to smooth muscle cells and the destruction of the aortic wall. The
inflammatory reaction in atherosclerotic alteration of the abdominal aorta was
characterized by a higher incidence of auxiliary CD4 + lymphocytes T and
macrophages important in the initial stage and stimulation of inflammation. An
increased number of regulatory CD4 + Foxp3 + T lymphocytes and AAA plasma
cells suggests overcoming the inhibitory inflammatory response in AAA. Different
characteristics of the inflammatory response in the parts only atherosclerotic aortic
and aorta scars indicate changes in the characteristics of the inflammatory reaction
with atherosclerosis and the emergence of aneurysmatic complications. The fusiform
type of AAA is characterized by an increased inhibitory inflammatory response of
lymphocytes B. The type and frequency of the examined inflammatory cells are not
related to other morphological characteristics of the AAA diameter, isolated or
extended aneurysm with the involvement of one and / or two iliac arteries with the
branches and the presence of intraluminal thrombus. The AAA diameter is
statistically significantly associated with elevated CRP values, indicating the
importance of inflammation in atherosclerosis progression and the development of
aneurysmatic complications. The extended AAA type with the involvement of one and/or two iliac arteries with the bra nches is significantly more frequent in elderly
patients, pointing to the aetiology of AAA in elderly patients
Brzina cerebralnoga protoka u bolesnika s prvom psihotičnom epizodom [Velocity of Cerebral Blood Flow in Patients with First Psychotic Episode]
Get PDFChanges in cerebral hemodynamics have been reported in schizophrenia and proposed
as underlying the cognitive deficits seen in patients. The objective of our study was to
compare changes of the cerebral blood flow velocity during neurocognitive tasks
between the patients with the first episode of psychosis and healthy controls.
We recruited 46 patients with the first episode of psychosis and 41 control subjects.
Transcranial Doppler ultrasonography monitoring of BFV in both middle cerebral
arteries was recorded during 25-minute long neurocognitive assessment with
Phonemic Verbal Fluency test, Trial Making Test B and Stroop test. Between every
consecutive test resting periods were recorded.
Patients with first episode of psychosis
had significantly lower blood flow velocity in left anterior cerebral artery during
neurocognitive tetsing. Decreased blood flow velocity during the execution of
neurocognitive tasks in patients with first episode of psychosis, compared to control
subjects might indicate impaired hemodynamic function in the prefrontal brain areas,
and possibly provide an explanation of some of the observed neurocognitive deficits
in patients with the first episode of psychosis
Polimorfizam gena tiopurinmetiltransferaze u bolesnika s upalnom bolešću crijeva [Polymorphism of thiopurinementhyltranserase gene in patients with the inflammatory bowel disease]
Get PDFThiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. 37 variant TPMT-encoding alleles have been discovered so far.
These variants produce enzyme with reduced enzymatic activity. Wild-type enzyme is denoted TPMT*1/*1, while variants were given numbers successively as they were discovered. The latest variant, TPMT*37, was discovered in 2014. The most common variant alleles of TPMT gene are: TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C. Patients who are heterozygous for the enzyme, should have a thiopurine drug dose reduction, while homozygous patients should either stay free of this drug, or should have up to 10x drug dose reduction. Furthermore, blood parameters should be checked regularly.
According to early studies of this enzyme, variant homozygosity is present in 1/300 persons; however – further population studies have revealed different ratios in Caucasian, Asiatic and African population.
The first aim of this study was to investigate frequencies of the most common variant alleles in Croatian inflammatory bowel disease (IBD) patients and in healthy individuals. 685 participants are included, out of whom 459 are IBD patients (338 Crohn’s disease patients and 221 ulcerative colitis patients) and 226 are healthy volunteers. 94.55% IBD of patients and 94.25% of healthy volunteers have homozygous wild-type enzyme (TPMT*1/*1).
TPMT*1/*2 and TPMT*1/*3C are present in 0.87% and 1.53% IBD patients, respectively; these variants are not present in healthy volunteers. TPMT*1/*3A is present in 3.05% IBD patients and 5.75% healthy volunteers. TPMT*3B allele is not found in any group.
Variant genotypes are statistically significantly more common in Crohn's disease than in ulcerative colitis subgroup (p=0.032).
We also compared frequencies of variant TPMT alleles in our population to selected countries which had had results published earlier. We found the overall frequency of variant alleles in our population statistically nonsignificantly lower when compared with other populations of Caucasian origin.
Azathioprine is a thiopurine drug registered in IBD treatment in Croatia. Patients who have variant TPMT genotype, i.e. reduced enzyme activity, possibly develop severe adverse effects. The most common azathioprine adverse effect is myelotoxicity. Additionaly, concomitant therapy possibly influences adverse effects occurrence.
Regarding aforementioned, the other aim of the study was to investigate a relationship between the most common TPMT polymorphisms, AZA adverse effects and concomitant therapy that is regularly applied in IBD. Out of 263 patients treated with AZA, 64 have developed adverse effects (24%). The most common adverse effects is myelotoxicity, with thrombocytopenia slightly more prevalent than leukopenia. The most common toxic hepatic manifestation is diffuse liver lesion, while pancreatic toxicity usually presents with acute pancreatitis.
The majority of adverse effects occurs in patients with wild-type genotype.
Statistical analysis shows that only TPMT genotype influences adverse effects occurrence (p=0.0038), notably TPMT*3A variant (p=0.0036). There is no influence of concomitant therapy – either aminosalicylate, corticosteroid or anti-TNF – on AZA-related toxicity