Publications by authors named "Jacek Czepiel"

58 Publications

Mortality Following Infection in Europe: A Retrospective Multicenter Case-Control Study.

Antibiotics (Basel) 2021 Mar 13;10(3). Epub 2021 Mar 13.

Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, 30-688 Krakow, Poland.

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were β-lactams; previous exposure to fluoroquinolones was significantly ( = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome.
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http://dx.doi.org/10.3390/antibiotics10030299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998379PMC
March 2021

Decreased Expression of the High Mobility Group Box 1 () Gene in Peripheral Blood in Patients with Mild or Moderate Infection.

Microorganisms 2020 Aug 11;8(8). Epub 2020 Aug 11.

Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, 30-688 Krakow, Poland.

Cytokines are mediators of inflammation induced in the course of infection (CDI). High Mobility Group Box 1 (HMGB1) is a cytokine playing an important role in the pathogenesis of numerous inflammatory and autoimmune diseases. The aim of the study was to assess the gene expression in the course of CDI. We have performed a prospective case-control study- including 55 adult patients, among them 27 with CDI, who were hospitalized from October 2018 to February 2020 and 28 healthy volunteers. We assessed: a complete blood count with differential leukocyte count, blood creatinine, albumin, and C-reactive protein (CRP) levels. Then, the expression of the gene was evaluated using quantitative Real-Time PCR. Patients with CDI were found to have a significant increase in white blood cells (WBC), neutrophil count, and CRP levels, they also exhibited decreased levels of albumin compared with controls. The gene expression was significantly lower among patients with CDI compared with the control group and significantly, inversely correlated with CRP level in blood. In conclusion, we have observed a decreased expression of the gene in peripheral blood of patients with mild or moderate CDI, which hypothetically could reflect their diminished capability to fight the pathogen.
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http://dx.doi.org/10.3390/microorganisms8081217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464922PMC
August 2020

Different MAF translocations confer similar prognosis in newly diagnosed multiple myeloma patients.

Leuk Lymphoma 2020 08 19;61(8):1885-1893. Epub 2020 Apr 19.

Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.

The MAF translocations, t(14;16) and t(14;20), are considered as adverse prognostic factors based on few studies with small sample sizes. We report on their prognostic impact in a large group of 254 patients - 223 (87.8%) with t(14;16) and 31 (12.2%) with t(14;20). There were no intergroup differences in survival estimates. Median progression-free survival was 16.6 months for t(14;16) and 24.9 months for t(14;20) ( = 0.28). Median overall survival (OS) was 54.0 months and 49.0 months, respectively ( = 0.62). Median OS in patients who underwent double autologous stem cell transplantation (ASCT) was 107.0 months versus 60.0 months in patients who received single ASCT ( < 0.001). ISS 3 was associated with shorter OS (HR = 1.89; 95% CI 1.24-3.19;  = 0.005) in Cox analysis. Our study suggests that t(14;20) should be considered as an adverse factor of equal prognostic implication to t(14;16).
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http://dx.doi.org/10.1080/10428194.2020.1749605DOI Listing
August 2020

A multicenter retrospective study of 223 patients with t(14;16) in multiple myeloma.

Am J Hematol 2020 05 29;95(5):503-509. Epub 2020 Feb 29.

Department of Hematology, UZ Leuven, Leuven, Belgium.

The t(14;16) translocation, found in 3%-5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real-world cohort (n = 223). A substantial fraction of patients had renal impairment (24%) and hemoglobin <10 g/dL (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor (PI) in the first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7-18.7), the median progression-free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5-2.4) and 4.1 years (95% CI 3.3-5.5), respectively. Worse OS was predicted by age > 60 years (HR = 1.65, 95% CI [1.05-2.58]), as well as revised International Scoring System (R-ISS) 3 (vs R-ISS 2; HR = 2.59, 95% CI [1.59-4.24]). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R-ISS 3 predict poor survival.
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http://dx.doi.org/10.1002/ajh.25758DOI Listing
May 2020

The level of fecal calprotectin significantly correlates with Clostridium difficile infection severity.

Folia Med Cracov 2019 ;59(3):53-65

Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Kraków, Poland.

Introduction: Fecal calprotectin (FC) rises significantly in intestinal inflammation accompanied by neutrophil activation - such as Clostridium difficile infection (CDI). The aim of the study was to evaluate the benefit of FC testing in assessing the severity of CDI.

Materials And Methods: The study group included 76 patients with CDI hospitalized in the Jagiellonian University Hospital in Krakow from July 2017 till January 2018. FC levels were measured using an EIA (Enzyme Immunoassay). Demographic, clinical information and blood tests were recorded using standardized data collection forms. The selection of patients into non-severe and severe groups was carried out in accordance with the ESCMID criteria (European Society of Clinical Microbiology and Infectious Diseases) and some modi cations to those criteria were proposed.

Results: the studied population included 76 patients (39 men and 37 women) with CDI aged from 24 to 98 years (mean: 72). Median calprotectin level was 739 (Q25-Q75: 612-799 μg/g), characteristic of patients with colitis. A statistically significant difference in FC concentration in patients with severe vs non-severe CDI was observed (severe - 770 vs non-severe - 659 μg/g, p = 0.009). FC directly correlated with platelets level; however, no correlation between FC level and the blood parameters prognostic for CDI (leukocyte, neutrophil count, albumin, creatinine levels) was found.

Conclusion: FC level is an indication of ongoing intestinal inflammation in CDI patients. FC level significantly correlated with CDI severity, which demonstrates that FC could serve as a predictive marker for assessing CDI severity.
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May 2020

Clostridium difficile caused changes in fatty acids profile and resolvin D1 content in plasma of infected patients.

Eur J Gastroenterol Hepatol 2020 03;32(3):318-324

Department of Infectious and Tropical Diseases.

Objectives: Clostridium difficile infection (CDI) is an acute gastrointestinal infection caused by anaerobic, toxin-producing bacteria. During the course of CDI, there is a general inflammatory state. In order to gain a deeper understanding of the role of fatty acids (FAs) in the pathogenesis of acute infection we analyzed their plasma content in both patients with CDI and controls.

Methods: The study groups included 40 patients with CDI and 40 healthy volunteers. Plasma FA content was analyzed by gas chromatography, resolvin D1 (RvD1) level using ELISA assay, and we assessed the white blood cell (WBC) count, neutrophil count and C-reactive protein (CRP) level.

Results: Patients with CDI were characterized by significantly higher values of WBC, neutrophils, platelets and CRP compared with the control group. The saturated FA index was statistically higher and total n-3 FA was significantly decreased in the plasma of CDI patients as compared with the control group. RvD1 content was significantly higher in the control group as compared with patients with CDI.

Conclusion: In patients with good outcomes, we probably observed the effective resolution of inflammation, as reflected in n-3 FA metabolism and their significant decrease in plasma. This may indicate the therapeutic role of n-3 FA in CDI infection.
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http://dx.doi.org/10.1097/MEG.0000000000001600DOI Listing
March 2020

Prevalence of Function-Dependent Temporomandibular Joint and Masticatory Muscle Pain, and Predictors of Temporomandibular Disorders among Patients with Lyme Disease.

J Clin Med 2019 Jun 28;8(7). Epub 2019 Jun 28.

Department of Orofacial Pain and Dysfunction, Academic Centre forDentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, 1081 LA Amsterdam, The Netherlands.

The aim was to determine the occurrence of temporomandibular disorders (TMDs) in patients with Lyme disease (LD), and to estimate the contribution of factors that may identify TMD among LD patients. In seventy-six ( = 76) adult patients with LD (mean age 57.6 ± 14.6 years) and 54 healthy non-Lyme volunteers with a mean age of 56.4 ± 13.5 years, possible function (i.e., non-pain) diagnoses were established using the Research Diagnostic Criteria of Temporomandibular Disorders (RDC/TMD). Pain diagnoses were established by means of the function-dependent dynamic and static tests. The two groups did not significantly differ in the frequency of disc displacements diagnoses and function-dependent pain diagnoses. LD showed a significantly higher frequency ( < 0.001) of osteoarthrosis than the control group. For the prediction of pain diagnoses in LD patients, the single regression analyses pointed out an association with age, sleep bruxism (SB), and awake bruxism (AB). Two predictors (i.e., SB ( = 0.002) and AB ( = 0.017)) were statistically significant in the final multiple variable model. The frequency of TMD in patients with LD based on function-dependent tests was not significantly different from that in the control group. This investigation suggests that the contribution of bruxism to the differentiation between patients with Lyme and TMD is high.
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http://dx.doi.org/10.3390/jcm8070929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679175PMC
June 2019

Analysis of cases of Lyme arthritis in patients hospitalized in Infectious Diseases Department, University Hospital in Cracow.

Folia Med Cracov 2019 ;59(1):5-14

Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Kraków, Poland.

Lyme disease is an emerging problem in Poland. Analysis has been undertaken of the medical documentation of 86 patients hospitalized in the Infectious Diseases Department, University Hospital in Cracow in 2013-2016, suspected of Lyme arthritis. It has especially considered medical history including potential exposure to the infection, detailed characteristics of the symptoms, diagnostic challenges and results of the treatment. Only some patients had a history of erythema migrans and not all of them recalled tick-bite. The majority of the patients had affected large joints, especially knee joints, and polyarthritis was rarely observed. Symptoms were resolved completely or partially after antibiotic treatment in most patients. The diagnosis of Lyme arthritis in areas endemic for Lyme disease is still a diagnostic challenge in patients with other rheumatic diseases, including osteoarthritis.
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December 2019

Diarrhea caused by in patients with primary HIV infection.

Int J STD AIDS 2019 07 2;30(8):814-816. Epub 2019 May 2.

1 Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Krakow, Poland.

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http://dx.doi.org/10.1177/0956462418813060DOI Listing
July 2019

Differences between palpation and static/dynamic tests to diagnose painful temporomandibular disorders in patients with Lyme disease.

Clin Oral Investig 2019 Dec 13;23(12):4411-4416. Epub 2019 Apr 13.

Department of Orofacial Pain and Dysfunction, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Objectives: The aim was to determine the frequency of Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD)-based pain diagnoses and dynamic/static tests-based pain diagnoses, and to assess the agreement of palpation tests with static/dynamic tests.

Materials And Methods: Eighty-six (N = 86) adult patients with Lyme disease (mean age 57.0 ± 14.3 years; male/female ratio was 42/44) were examined according to techniques described in the RDC/TMD. Additionally, dynamic/static tests were performed. For RDC/TMD-based pain diagnoses and dynamic/static tests-based pain diagnoses, descriptive frequencies were calculated. Differences between the frequency of palpation-based diagnoses and of dynamic/static-based diagnoses as well as the agreement between pain diagnoses established with the two diagnostic approaches were assessed.

Results: RDC/TMD-based pain diagnoses were made in 61 patients for myofascial pain and in 11 patients for arthralgia and/or osteoarthritis. Based on dynamic/static tests, mainly myogenous pain was diagnosed in 6 patients, and a mainly arthrogenous pain in 5. The agreement of palpation tests with static/dynamic tests in Lyme disease population was poor.

Conclusion: A high prevalence of TMD symptoms was found in patients with Lyme disease. The results suggest that using palpation tests alone could overestimate primary TMDs when comorbid conditions are present.

Clinical Relevance: Dynamic/static tests should be used as part of the routine TMD assessment. In case of Lyme disease as the actual cause of the facial pain, while the dentist might be suspecting TMD when dynamic/static TMD tests are negative, referral to an appropriate specialist for the diagnosis and treatment of Lyme disease needs to be made.
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http://dx.doi.org/10.1007/s00784-019-02890-4DOI Listing
December 2019

Clostridium difficile infection: review.

Eur J Clin Microbiol Infect Dis 2019 Jul 3;38(7):1211-1221. Epub 2019 Apr 3.

Department of Infectious and Tropical Diseases, Jagiellonian University, Medical College, Śniadeckich 5, 31-501, Krakow, Poland.

Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and in the environment. In the last decade, the frequency and severity of C. difficile infection has been increasing worldwide to become one of the most common hospital-acquired infections. Transmission of this pathogen occurs by the fecal-oral route and the most important risk factors include antibiotic therapy, old age, and hospital or nursing home stay. The clinical picture is diverse and ranges from asymptomatic carrier status, through various degrees of diarrhea, to the most severe, life threatening colitis resulting with death. Diagnosis is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay, but no single test is suitable as a stand-alone test confirming CDI. Antibiotics of choice are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered as inferior. The goal of this review is to update physicians on current scientific knowledge of C. difficile infection, focusing also on fecal microbiota transplantation which is a promising therapy.
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http://dx.doi.org/10.1007/s10096-019-03539-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570665PMC
July 2019

2019 update of the WSES guidelines for management of () infection in surgical patients.

World J Emerg Surg 2019;14. Epub 2019 Feb 28.

Vital Care, Inc, Meridian, MS USA.

In the last three decades, infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.
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http://dx.doi.org/10.1186/s13017-019-0228-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394026PMC
June 2019

Analysis of risk factors and outcomes of Clostridium difficile infection.

Folia Med Cracov 2018;58(4):105-116

Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Kraków; University Hospital in Kraków, Poland.

Introduction: Clostridium difficile (C. difficile) is a Gram-positive, anaerobic rod-shaped bacteria, widely spread in the human environment. In the last decade, the frequency and severity of Clostridium difficile infection (CDI) have been increasing, making this particular disease one of the most significant nosocomial infections. The aim of our study was an analysis of CDI risk factors, its course and consequences.

Materials And Methods: Medical documentation of the patients treated for CDI in the University Hospital in Cracow and St Anne's Hospital in Miechów has been analysed. The analysis focused on epidemiological data, blood parameters, comorbidities, recurrence rate, and complication rate (deaths included). As part of risk factors analysis, antibiotic use or hospitalisation in a period of 3 months before the episode of infection was considered relevant. Blood tests have been performed using routinely employed, standard methods.

Results: We evaluated data of 168 people infected with C. difficile, out of which there were 102 women (61%) and 66 men (39%). The median age of the patients was 74 years for the entire population with 76 years for women and 71 years for male patients. One hundred thirteen people (67%) had been previously hospitalised, and 5 person was a pensioner of a nursing home. 99 people (59%) were treated with antibiotics within 3 months before the first episode of infection. An average length of the hospital stay because of CDI was 11 days. One hundred thirty persons (77%) experienced only 1 episode whereas 38 people (23%) had more than 1 episode of infection. The person with the largest number of recurrences had 9 of them.

Conclusions: The development of CDI is an increasing problem in a group of hospitalised persons, particularly of an old age. The general use of beta-lactam antibiotics is the cause of a larger number of infections with C. difficile. Vast majority of patients have had at least one typical risk factor of CDI.
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September 2019

Fatty acids and selected endocannabinoids content in cerebrospinal fluids from patients with neuroinfections.

Metab Brain Dis 2019 02 5;34(1):331-339. Epub 2018 Dec 5.

Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Krakow, Poland.

Neuroinfections are a significant medical problem and can have serious health consequences for patients. Their outcome, if not fatal, can be associated with permanent residual deficits. Cerebrospinal fluid (CSF) examination is commonly used for meningitis confirmation. Fatty acids (FA) are precursors of lipid mediators with pharmacological activity. They actively modulate inflammation as well as contribute to its resolution. Therefore the aim of this study was to determine the FA and selected endocannabinoids (ECB) content in the CSF obtained from patients with bacterial (BM) and viral meningitis (VM) using chromatographic techniques. A significantly lower level of saturated FA was found in patients with BM and VM as compared to controls. There was a significantly higher concentration of long-chain monounsaturated FA and polyunsaturated n-6 FA in the CSF obtained from patients with neuroinfection. Moreover, a significant reduction of n-3 FA in CSF obtained from patients with BM and VM was demonstrated. The highest amount of ECB was detected in the CSF of patients with VM: eicosapentaenoyl ethanolamide (1.65 pg/mL), docosahexaenoyl ethanolamide (655.5 pg/mL) and nervonoyl ethanolamide (3.09 ng/mL). Results indicate the participation of long-chain monounsaturated and polyunsaturated FA and their derivatives in the inflammatory process and likely in the process of resolution of inflammation during neuroinfection. It seems that the determination of the FA and ECB profile in CSF may be a valuable biomarker of health and may allow the development of new pharmacological strategies, therapeutic goals and fatty acids supplementation necessary in the fight against inflammation of the central nervous system.
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http://dx.doi.org/10.1007/s11011-018-0347-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351517PMC
February 2019

Clostridium difficile infection in young people - 2 case reports.

Pol Merkur Lekarski 2018 Jun;44(264):284-286

Infectious Diseases Ward, University Hospital, Krakow, Poland; Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Krakow, Poland.

Clostridium difficile infection (CDI) remains one of the most important healthcare-associated infections of the last two decades. The pathogen is a Gram-positive, toxin-producing, anaerobic, rod-shaped and sporeforming bacterium; it is ubiquitous in the human environment. Transmission occurs by the fecal-oral route. The consequence of the action of bacterial toxins is initially a local inflammatory reaction, which then goes into systemic inflammation. Clinical presentation is varied; some patients are asymptomatic, in symptomatic form the main symptom is diarrhea of varying severity, which is sometimes accompanied by acute abdominal pain, nausea, vomiting and high fever. Risk factors of CDI include prior antibiotic use, increasing age and recent hospitalisation. Extremely rarely does CDI occur in immunocompetent patients under 30 years of age, even if previously treated with an antibiotic. Here presented are two untypical cases of CDI development in the lower age group, in the presence of additional risk factors of comorbid gastrointestinal tract infections. Both developed infections are following recent infection - Salmonella enterididis in the first case and Salmonella typhi in the second case. Therefore, the article also contains basic principles for the diagnosis and treatment of Salmonella spp.
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June 2018

Secondary plasma cell leukemia: a multicenter retrospective study of 101 patients.

Leuk Lymphoma 2019 01 2;60(1):118-123. Epub 2018 Jul 2.

b Dana-Farber Cancer Institute , Harvard Medical School , Boston , MA , USA.

This multicenter retrospective study included 101 patients (median age 62 years) with secondary plasma cell leukemia (sPCL). The median time from initial multiple myeloma diagnosis to sPCL was 31 months. Fifty-five out of 72 patients (75%) who received any therapy were treated with immunomodulators (IMiDs) and/or proteasome inhibitors (PIs), and 14/72 (19%) underwent salvage autologous stem cell transplantation (ASCT). The overall response rate in patients who received ASCT or PI (either alone or in combination) was higher than in those who did not (93% vs. 36% and 60% vs. 30%, respectively). The median overall survival (OS) in patients who received therapy was 4.2 months (95% CI: 1.3; 8.0) with a 1-year OS of 19%. Platelet count ≤100 × 10/L at sPCL diagnosis was the only independent predictor of a poorer OS in treated patients (HR = 3.98, p = .0001). These findings suggest that patients with sPCL may benefit from salvage ASCT- and PI-based regimens.
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http://dx.doi.org/10.1080/10428194.2018.1473574DOI Listing
January 2019

Meningoencephalitis caused by Lactobacillus plantarum - case report.

Int J Neurosci 2019 Jul 26;129(7):715-718. Epub 2019 Feb 26.

a Department of Infectious and Tropical Diseases , Jagiellonian University Medical College , Krakow , Poland.

Specific strains of Lactobacillus spp. are widely used as probiotic agents but it has been repeatedly reported that may have a pathogenic potential. We present the report on a case of meningoencephalitis caused by Lactobacillus plantarum in a 63-year-old man with newly diagnosed metastatic planoepitheliale lung cancer. The patient was hospitalised due to newly diagnosed cancer and during the course of hospitalisation developed symptoms of neuroinfection. On the basis of the symptoms and results of the conducted tests the patient was diagnosed with bacterial meningoencephalitis. In microbiological tests of the blood and cerebrospinal fluid L. plantarum was cultured. During the course of antibiotic therapy the patient's condition improved. Lactobacilli are now recognised as a causative agent of infection, most notably bacteraemia. To our knowledge, this is the fourth documented case of Lactobacillus-associated neuroinfection, and only the second in an adult. Lactobacilli cause mostly opportunistic infections in immunocompromised individuals.
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http://dx.doi.org/10.1080/00207454.2018.1482293DOI Listing
July 2019

Blocking MET receptor signaling in multiple myeloma cells in vitro and in vivo.

Adv Clin Exp Med 2018 Feb;27(2):153-158

Department of Transplantology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland.

Background: Numerous studies have shown a role of the hepatocyte growth factor (HGF) as a ligand for the MET receptor in promoting aggressiveness in myeloma cells.

Objectives: The aim of this study was to confirm the presence of the MET receptor in myeloma cell lines, to establish a stable lentiviral construct directed against MET receptor mRNA and then to evaluate the effect of blocking MET receptor expression both in vitro and in vivo.

Material And Methods: The U266 and INA6 cells were transduced using a lentiviral vector carrying siRNA to achieve the reduction of MET receptor expression. The ocular sinus of NOD/SCID mice was injected with wt-U266, shMET-U266 and shLacZ-U266 cells.

Results: MET receptor expression was demonstrated in all tested myeloma cell lines. Blocking the HGF/MET axis did not affect the growth of transduced U266 and INA6 cell lines. The inoculation of NOD/SCID mice with myeloma cells with reduced expression of MET led to increased survival of the animals.

Conclusions: MET receptor expression was constituently expressed in all tested myeloma cell lines. A lentiviral construct can effectively reduce the expression of the MET receptor in myeloma cells. Further studies are necessary to evaluate the effect of the reduction of MET receptor expression in multiple myeloma, focusing on animal models with a larger test group size.
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http://dx.doi.org/10.17219/acem/68271DOI Listing
February 2018

The presence of IL-8 +781 T/C polymorphism is associated with the parameters of severe Clostridium difficile infection.

Microb Pathog 2018 Jan 2;114:281-285. Epub 2017 Dec 2.

Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Krakow, Poland.

Purpose: There is large variation in the clinical manifestations of Clostridium difficile infection (CDI). We also still can not predict which patients are more susceptible to reinfection with CDI. The aim of our study was to evaluate the effect of gene single nucleotide polymorphisms (SNP) of proinflammatory cytokines, specifically IL-1β, IL-8 on the development, clinical course and recurrence of CDI.

Methods: We performed a prospective study of adults (130 people ≥ 18 years) including 65 patients with CDI treated in tertiary hospital and 65 healthy persons. The following 3 variants were analyzed for the occurrence of gene polymorphisms in patients with CDI versus the control group: IL-1β +3953 A/G (rs1143634), IL-1β -31 A/G (rs1143627), and IL-8 +781 T/C (rs2227306). Then, we assessed the correlation between these genetic polymorphisms and biochemical parameters important in CDI course, CDI severity as well as CDI recurrence.

Results And Conclusions: The presence of genetic polymorphisms of IL-1β +3953 A/G, -31 A/G and IL-8 +781 T/C did not have an effect on the development or recurrence of CDI. The presence of IL-8 +781 T/C polymorphism is associated with the severe CDI.
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http://dx.doi.org/10.1016/j.micpath.2017.11.066DOI Listing
January 2018

Similar survival outcomes in patients with biclonal versus monoclonal myeloma: a multi-institutional matched case-control study.

Ann Hematol 2017 Oct 1;96(10):1693-1698. Epub 2017 Aug 1.

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Multiple myeloma is a plasma cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow and associated organ damage. Usually, patients with myeloma present with a single monoclonal protein in serum and/or urine constituted by one heavy chain and one light chain. In less than 5% of the patients, more than one monoclonal protein can be identified. The aim of our retrospective multicenter matched case-control study was to describe the characteristics of cases with biclonal myeloma and compare them against a control group of monoclonal myeloma patients matched by age, sex, and year of diagnosis. A total of 50 previously untreated cases with biclonal myeloma and 50 matched controls with monoclonal myeloma were included in this study. The controls were matched (1:1) for age, sex, year of diagnosis, and participating center. There were no differences in the rates of anemia (52 vs. 59%; p = 0.52), renal dysfunction (36 vs. 34%; p = 0.83), hypercalcemia (9 vs. 16%; p = 0.28), or presence of lytic lesions (23 vs. 16%; p = 0.38) between groups. Similarly, there was no difference in the rates of overall response to therapy (85 vs. 90%; p = 0.88) or survival rates of cases with biclonal myeloma and controls with monoclonal myeloma (4-year survival 72 vs. 76%; p = 0.23). Results of our study suggest that patients with biclonal myeloma have similar response and survival rates than patients with monoclonal myeloma.
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http://dx.doi.org/10.1007/s00277-017-3084-9DOI Listing
October 2017

IgM myeloma: A multicenter retrospective study of 134 patients.

Am J Hematol 2017 Aug 26;92(8):746-751. Epub 2017 May 26.

The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL with 19% of patients presenting with levels >6,000 mg dL . International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes.
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http://dx.doi.org/10.1002/ajh.24753DOI Listing
August 2017

[Diagnostic difficulties in amebic liver abscess].

Med Dosw Mikrobiol 2017 ;69(1):35-41

Amebiasis is a widespread parasitic infection caused by the human-specific protozoan Entamoeba histolytica (E.- histolytica). Tropical and subtropical regions with poor socioeconomic and sanitary conditions belong to endemic areas. The highest rates of E. histolytica infection are observed in India, Mexico, Africa, some parts ofCentral and South America. Up to 90% of infections remain asymptomatic, about 10% of patients develop amebic colitis. About 10% of symptomatic individuals may present with an extraintestinal manifestation, mostly amebic liver abscess (ALA). Clinical symptoms of ALA appear within 5 months after an exposition to E. histolytica cysts. Anamnesis revealing a travel to endemic area plays a crucial role in a diagnostic process, which is further supported by an physical examination, radiological findings, serology and parasitology test. The following article presents the difficulties which may occur when the ALA is suspected in a patient traveling from endemic areas.
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November 2018

Resolvin D1 down-regulates CYP1A1 and PTGS2 gene in the HUVEC cells treated with benzo(a)pyrene.

Pharmacol Rep 2016 Oct 27;68(5):939-44. Epub 2016 Jun 27.

Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA.

Background: Polycyclic aromatic hydrocarbons (PAHs) can interact with lipids and their derivatives and have been known to induce atherosclerosis. The aim of this study was to evaluate the impact of Resolvin D1 (RvD1) on inflammatory-state realted proteins and genes in the human primary umbilical vein endothelial HUVEC cells exposed to benzo(a)pyrene (BaP).

Methods: We analyzed the influence of RvD1 and/or BaP on cyclooxygenase-2 (COX-2), cytosolic prostaglandine E2 synthase (cPGES), glutathione S transferase (GSTM1) and aryl hydrocarbon receptor (AhR) protein expression by Western blot. Additionaly, phospholipase A2 (cPLA2) and cytochrome P450 (CYP1A1) activity, as well as AhR, CYP1A1, phospholipase A2 (PLA2G4A) and prostaglandin synthase 2 (PTGS2) gene expression by qRT-PCR was studied.

Results: RvD1 down-regulates cytochrome P450 (CYP1A1) and prostaglandin synthase 2 (PTGS2) gene expression in HUVEC cells exposed to BaP. Repressesion of COX-2, cPGES and overexpressesion of GSTM1 protein was noted after co-treatment with RvD1 and BaP. After incubation with RvD1 an increase of cPLA2 and a decrease of CYP1A1 activity was observed when compared to BaP treated alone endothelial cells.

Conclusions: Our data suggests that RvD1 can significantly contributes on vascular function and alleviates the harmful effects caused by BaP, which might potentially aid in the repair of the injured endothelium.
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http://dx.doi.org/10.1016/j.pharep.2016.05.005DOI Listing
October 2016

n-3 and n-6 Fatty Acid Changes in the Erythrocyte Membranes of Patients with 658240251 Clostridium difficile Infection.

Folia Biol (Krakow) 2016 ;64(1):3-10

The implications of circulating essential fatty acids (FA) on the inflammatory risk profile and clinical outcome are still unclear. In order to gain a deeper understanding of the role of polyunsaturated fatty acids (PUFA) in the pathogenesis of acute infection, we analyzed the FA content in red blood cell (RBC) membranes of patients with Clostridium difficile infection (CDI) and controls. We prospectively studied 60 patients including 30 patients with CDI and 30 controls to assess lipid concentrations in erythrocyte membranes using gas chromatography. We observed a higher level of saturated fatty acids (SFA) in RBC membranes from patients with CDI. In patients with CDI, we also noticed a higher level of 20:4 n-6 FA and only a small amounts of C20:2n-6, C20:3n-6 FAs, arachidonic acid (AA) precursors, which suggest an intense inflammatory reaction in the organism during infection. We also noticed low levels of n-3 FA in the RBC membranes of patients infected with CDI. There is a deficit of n-3 FA in patients with CDI. n-3 FA are probably used during CDI as precursors of pro-resolving mediators that may indicate a therapeutic role of n-3 PUFAs in CDI. The changes in fatty acids in erythrocyte membranes during CDI alter their functions which may have an impact on the clinical outcome.
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http://dx.doi.org/10.3409/fb64_1.3DOI Listing
June 2016

Central nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice.

Am J Hematol 2016 06 24;91(6):575-80. Epub 2016 Apr 24.

National and Kapodistrian University of Athens, Athens, Greece.

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575-580, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ajh.24351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502095PMC
June 2016

n-3 Fatty acids regulate the inflammatory-state related genes in the lung epithelial cells exposed to polycyclic aromatic hydrocarbons.

Pharmacol Rep 2016 Apr 15;68(2):319-28. Epub 2015 Sep 15.

Laboratory of Forensic Chemistry, Faculty of Chemistry, Jagiellonian University in Kraków, Kraków, Poland.

Background: Chronic airway inflammation is coordinated by a complex of inflammatory mediators, including eicosanoids. The aim of this study was to evaluate the impact of polycyclic aromatic hydrocarbons (PAHs) on the human lung epithelial carcinoma A549 cells supplemented with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids.

Methods: We analyzed the influence of DHA, EPA and/or benzo(a)pyrene (BaP), chrysene (Chr), fluoranthene (Flu) and benzo(a)anthracene (Baa) treatment on the fatty acids (FAs) profile and the formation of isoprostanes. We studied the cyclooxygenase-2, FP-receptor, peroxisome proliferator-activated receptors PPARδ and PPARγ, transcription factor NF-кB p50 and p65 expression by Western blot, phospholipase A2 (cPLA2) activity, as well as aryl hydrocarbon receptor (AHR), cytochrome P450 (CYP1A1), phospholipase A2 (PLA2G4A) and prostaglandin synthase 2 (PTGS2) gene expression by qRT-PCR.

Results: DHA or EPA supplementation and BaP or Baa treatment resulted in a higher level of PGF3α. COX-2 expression was decreased while PPARδ expression and cPLA2 activity was increased after fatty acid supplementation and PAHs treatment. DHA and EPA up-regulated AHR and PLA2G4A genes.

Conclusions: Supplementation with n-3 FAs resulted in changes of inflammatory-state related genes in the lung epithelial cells exposed to PAHs. The altered profile of lipid mediators from n-3 FA as well as repression of the COX-2 protein by n-3 PUFAs in A549 cells incubated with PAHs suggests anti-inflammatory and pro-resolving properties of DHA and EPA. It remains to be shown whether these pleiotropic and protective actions of n-3 FAs contribute to fish oil's therapeutic effect in asthma.
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http://dx.doi.org/10.1016/j.pharep.2015.09.001DOI Listing
April 2016

The ring-stage of Plasmodium falciparum observed in RBCs of hospitalized malaria patients.

Analyst 2015 Dec 2;140(23):8007-16. Epub 2015 Nov 2.

Faculty of Chemistry, Jagiellonian University, Kraków, Poland.

Raman spectra of the blood samples obtained directly from hospitalized malaria patients with Plasmodium falciparum (P. falciparum) in the ring-stage were analyzed. Changes observed in the Raman band intensities of the infected patients compared to healthy volunteers are the result of parasite activity inside red blood cells. The obtained spectra were discussed by analyzing differences in particular spectral regions by evaluating changes in the band intensity ratios as well as using PCA analysis. The alterations of erythrocyte membranes caused by parasite penetration are visible by a reduced I1130/I1075 intensity ratio expressing the lowering of the amount of domains arranged in trans conformation. The I2930/I2850 ratio, which is a measure of modifications in structures of membrane proteins and lipids, in infected red blood cells increases, which is caused by malaria protein export to the erythrocyte membrane and expresses the membrane disarrangement. In the pyrrole ring vibration region, the ν4 band marker of the oxygenated-Hb shows at 1371 cm(-1) whereas the ν4 band at 1353 cm(-1) related to the deoxygenated-Hb is observed for malaria patients and is characterized by a higher intensity in infected erythrocytes. The amide I analysis shows the modifications in the secondary structure composition in the infected RBCs. We found that the P. falciparum infection leads to a decrease in the α-helical content and a concurrent increase in undefined (random-coil) structures. It was observed that the Raman spectra changes are also the result of the hemozoin formation process. In the pyrrole ring stretching vibration region, the increase of 1220 cm(-1) (deoxyHb) as against 1248 cm(-1) (oxyHb) may be considered as a signal of hemozoin formation in the RBCs. Relatively intense band patterns at 1560 cm(-1) and also at 1570 cm(-1) and 1552 cm(-1) may be due to the hemozoin that is formed according to parasite activity. The results of medical diagnostic tests had not presented changes in patient RBC parameters. A significant reduction in WBC count was noticed along with a decrease in neutrophil and platelet count when compared with the control group. Although no change is observed in the overall picture of the erythrocytes, pathological changes are evident in the Raman spectrum.
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http://dx.doi.org/10.1039/c5an01598gDOI Listing
December 2015

WSES guidelines for management of Clostridium difficile infection in surgical patients.

World J Emerg Surg 2015 20;10:38. Epub 2015 Aug 20.

Faculty of Medicine, Transilvania University, Infectious Diseases Hospital, Brasov, Romania.

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.
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http://dx.doi.org/10.1186/s13017-015-0033-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545872PMC
August 2015

Docosahexaenoic acid regulates gene expression in HUVEC cells treated with polycyclic aromatic hydrocarbons.

Toxicol Lett 2015 Jul 5;236(2):75-81. Epub 2015 May 5.

Department of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland; Center for Medical Genomics-OMICRON, Jagiellonian University Medical College, Kraków, Poland.

The molecular mechanism of inflammation and carcinogenesis induced by exposure of polycyclic aromatic hydrocarbons (PAHs) is not clearly understood. Our study was undertaken due to the strong pro-carcinogenic potential and reactivity of PAH-metabolites, as well as the susceptibility of polyunsaturated fatty acids to oxidation. The aim of this study was to evaluate the pro- or anti-inflammatory impact of n-3 docosahexaenoic acid on human primary umbilical vein endothelial cells (HUVEC) exposed to polycyclic aromatic hydrocarbons. We analysed the influence of docosahexaenoic acid (DHA) and/or PAHs supplementation on the fatty acid profile of cell membranes, on cyclooxygenase-2 (COX-2), aryl hydrocarbon receptor (AHR), and glutathione S transferase Mu1 (GSTM1) protein expression as well as on the prostaglandin synthase 2 (PTGS2), AHR, GSTM1, PLA2G4A, and cytochrome P450 CYP1A1 gene expression. We observed that COX-2 and AHR protein expression was increased while GSTM1 expression was decreased in cells exposed to DHA and PAHs. Docosahexaenoic acid down-regulated CYP1A1 and up-regulated the AHR and PTGS2 genes. Our findings suggested that DHA contributes significantly to alleviate the harmful effects caused by PAHs in endothelial cells. Moreover, these results suggest that a diet rich in n-3 fatty acids is helpful to reduce the harmful effects of PAHs exposure on human living in heavily polluted areas.
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http://dx.doi.org/10.1016/j.toxlet.2015.05.002DOI Listing
July 2015

n-3 Fatty acids as resolvents of inflammation in the A549 cells.

Pharmacol Rep 2015 Jun 15;67(3):610-5. Epub 2015 Jan 15.

Department of Radioligands, Jagiellonian University Medical College, Faculty of Pharmacy, Kraków, Poland.

Background: Fatty acids and their derivatives are one of the most crucial inflammation mediators. The aim of our study was to evaluate the impact of polyunsaturated fatty acids as eicosanoids precursors on the A549 cell line.

Methods: Cells were incubated with 40 μM of arachidonic, eicosapentaenoic or docosahexaenoic acid for 24h, then activated with LPS. Fatty acids content in the cell membranes were determined using gas chromatography. COX-2, cPGES and FP-receptor quantities were determined by Western blot. 8-Isoprostane F2α concentrations were determined by EIA. Maresin and protectin D1 contents were analyzed by UHPLC/MS-TOF method.

Results: Significant differences in membrane fatty acids and levels of 8-isoPGF2α in the activated cells were detected. Elevated expression of COX-2 and FP-receptor was observed in cells treated with AA and activated with LPS. Moreover, compared to AA and AA+LPS groups, cells incubated with EPA, DHA, EPA+LPS and DHA+LPS showed decreased expression of COX-2, cPGES and FP-receptor. In cells incubated with EPA or DHA and activated with LPS maresin and protectin D1 were detected.

Conclusions: The results of the study have revealed the pro-inflammatory properties of AA, while the EPA and DHA had the opposite, resolving effect. Interestingly, FP-receptor inhibition by EPA and DHA demonstrated the unique role of the FP-receptor as a potential target for antagonists, in the diseases of inflammatory character. This study provides new information about n-3 fatty acids and their pro-resolving mediators, which can be used in the process of developing new anti-inflammatory drugs.
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http://dx.doi.org/10.1016/j.pharep.2015.01.001DOI Listing
June 2015