Rotational thromboelastometry (ROTEM) profiling of COVID-19 patients.

We evaluated coagulation abnormalities via traditional tests and rotational thromboelastometry (ROTEM) in a group of 94 patients with confirmed SARS-CoV-2 infection and different severity of pneumonia (34 moderate, 25 severe, 35 critical) with the hypothesis that ROTEM parameters differed by coronavirus disease 2019 (COVID-19) severity. Shorter than normal clotting time (CT) and higher than normal maximum clot firmness (MCF) in extrinsic rotational thromboelastometry (EXTEM) and fibrinogen rotational thromboelastometry (FIBTEM), shorter than normal EXTEM clot formation time (CFT), and higher than normal α-angle were classified as markers of hypercoagulable state. Increment in the number of patients with ≥2 hypercoagulable parameters, higher EXTEM (P = .0001), FIBTEM MCF (P = .0001) and maximum lysis decrement (P = .002) with increment in disease severity was observed (P = .0001). Significant positive correlations between IL6 and CT EXTEM (P = .003), MCF EXTEM (P = .033), MCF FIBTEM (P = .01), and negative with ML EXTEM (P = .006) were seen. Our findings based on analysis of different disease severity groups confirmed that a hypercoagulable ROTEM pattern characterized by clot formation acceleration, high clot strength, and reduced fibrinolysis was more frequent in advanced disease groups and patients with high IL6. These results supported the need for different thromboprophylaxis approaches for different severity groups.

Telomerase stability and evaluation of real-time telomeric repeat amplification protocol.

Telomerase is RNA directed polymerase which acts as reverse transcriptase based on its own RNA component. It is considered to be involved in the pathology of many diseases and is recognized as a potential biomarker. The aims were to determine the sample storage conditions and the time frame for samples analysis, then to prove reliability of enzyme activity measurement with real-time telomeric repeat amplification protocol (TRAP) and to evaluate the suitable standard samples for telomerase activity measurements. Samples used for stability and freeze-thaw study were peripheral blood leukocytes, obtained from apparently healthy persons, patients with diagnosed cancer and cell lines. Telomerase activity was measured using TRAP method, while standard evaluation was done using nuclear magnetic resonance (NMR) technique. Storage at -20 °C preserved telomerase activity in samples from cancer patients for at least 14 days (21.46 ± 0.135 versus 21.84 ± 0.357, p = .756), while samples obtained from healthy persons should be stored at -80 °C. We observed significant decrease of telomerase activity at freeze thaw cycle 5 in cancer patients' samples (21.46 ± 0.135 versus 23.09 ± 0.316, p < .05), and in healthy persons' ones already at cycle 3 (22.74 ± 0.107 versus 24.85 ± 0.151, p < .05). Telomerase activity from cell lines samples showed overall greater stability regarding the storage period and freeze-thaw cycles and it was considered for standard sample, which was confirmed by NMR analysis. Telomerase enzyme had adequate stability while efficacy, linearity, and reproducibility of TRAP method were acceptable for bio-analytical methods. All this indicated that telomerase could be a reliable biomarker.

Potentially Inappropriate Prescribing and Potential Clinically Significant Drug-Drug Interactions in Older Outpatients: Is There Any Association?

Background and Objectives: The purpose of the study was to determine the prevalence rate of potentially inappropriate prescribing (PIP), by using the Screening Tool of Older Person's potentially inappropriate Prescriptions (STOPP) criteria in older outpatients, and its association with potential clinically significant drug-drug interactions (csDDIs). Materials and Methods: A cross-sectional study included 248 outpatients ≥65 years old divided into two groups depending on the presence of csDDIs. For estimating the clinical significance of csDDIs we used Medscape's "Drug Interaction Checker". We applied the thirty PIP indicators from the STOPP criteria. Results: The presence of PIP (25.00%; all patients) was significantly higher in the group with potential csDDIs compared to the other group (43 vs. 19, respectively; Chi-square test, χ2 = 9.947; p < 0.01). The most common PIP included the inappropriate use of proton pump inhibitors, long acting benzodiazepines, usage of thiazide diuretic in patients with gout, and duplication of therapeutic class. Patients with potential csDDIs had 43 potentially inappropriate medications (PIMs) prescribed. Out of this number, 12 (27.91%) PIMs were identified to participate in potential csDDIs. There was a correlation between the number of medications prescribed and the number of PIMs (ρ = 0.297; p < 0.01) and between the number of PIPs and the number of potential csDDIs (ρ = 0.170; p < 0.01). Conclusions: Older outpatients with potential csDDIs in relation to those with no potential csDDIs had significantly more prescribed drugs in total as well as inappropriate drugs. Almost 30% of these PIMs were included in potential csDDIs.

N-acetyl-L-cysteine protects dental tissue stem cells against oxidative stress in vitro.

OBJECTIVES: The aim of our study was to investigate whether N-acetyl-L-cysteine (NAC) could protect stem cells from exfoliated deciduous teeth (SHED) against oxidative damage, during in vitro cultivation, to preserve regenerative potential of these cells. Accordingly, we examined the potential of cell culture supplementation with NAC in prevention of lipid peroxidation, unfavorable changes of total lipids fatty acid composition, and the effects on the activity of antioxidant enzymes. MATERIAL AND METHODS: We analyzed the extent of oxidative damage in SHED after 48 h treatment with different NAC concentrations. Cellular lipid peroxidation was determined upon reaction with thiobarbituric acid. All enzyme activities were measured spectrophotometrically, based on published methods. Fatty acid methyl esters were analyzed by gas-liquid chromatography. RESULTS: Concentration of 0.1 mM NAC showed the most profound effects on SHED, significantly decreasing levels of lipid peroxidation in comparison to control. This dose also diminished the activities of antioxidant enzymes. Furthermore, NAC treatment significantly changed fatty acid composition of cells, reducing levels of oleic acid and monounsaturated fatty acids and increasing linoleic acid, n-6, and total polyunsaturated fatty acid (PUFA) proportions. CONCLUSION: Low dose of NAC significantly decreased lipid peroxidation and altered fatty acid composition towards increasing PUFA. The reduced oxidative damage of cellular lipids could be strongly related to improved SHED survival in vitro. CLINICAL RELEVANCE: Low doses of antioxidants, applied during stem cells culturing and maintenance, could improve cellular characteristics in vitro. This is prerequisite for successful use of stem cells in various clinical applications.

Simvastatin and amlodipine induced thrombocytopenia in the same patient: double trouble and a literature review.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced thrombocytopenia (DITP) may be a fatal adverse reaction to many drugs. It is often misdiagnosed as primary immune thrombocytopenia (ITP), and thus diagnosis can be delayed and patients can be treated inappropriately. Amlodipine a calcium-channel blocker, and simvastatin, a statin, have very rarely been implicated in DITP. We report on an investigation of the causal relationship of amlodipine and simvastatin with thrombocytopenia occurring in the same patient, and review the literature. CASE SUMMARY: We present the case of a 78-year-old female hypertensive diabetic patient with three successive DITPs. The first attack of acute severe thrombocytopenia occurred after a 2-week course of amlodipine, and was initially misdiagnosed as ITP. Her platelet count normalized after the amlodipine was discontinued. The second attack followed her restarting simvastatin 3 weeks later. She had stopped it 2 months earlier having previously taken it for over 5 years. Again, she recovered once the simvastatin was discontinued. The third DITP attack occurred when she accidently took a single dose of amlodipine 9 months later. WHAT IS NEW AND CONCLUSION: We provide clear evidence of a causal association of amlodipine with thrombocytopenia, and probable evidence of a causal association of simvastatin with thrombocytopenia. This is the first reported case of DITPs occurring with two of the most widely prescribed drugs in the same patient. Many hypertensive patients need to take multiple drugs in order to achieve their treatment goals and this increases their risk of drug-induced adverse reactions and makes identification of the causal drug (or drugs) extremely difficult.

Disturbed Plasma Lipidomic Profiles in Females with Diffuse Large B-Cell Lymphoma: A Pilot Study.

Lipidome dysregulation is a hallmark of cancer and inflammation. The global plasma lipidome and sub-lipidome of inflammatory pathways have not been reported in diffuse large B-cell lymphoma (DLBCL). In a pilot study of plasma lipid variation in female DLBCL patients and BMI-matched disease-free controls, we performed targeted lipidomics using LC-MRM to quantify lipid mediators of inflammation and immunity, and those known or hypothesised to be involved in cancer progression: sphingolipids, resolvin D1, arachidonic acid (AA)-derived oxylipins, such as hydroxyeicosatetraenoic acids (HETEs) and dihydroxyeicosatrienoic acids, along with their membrane structural precursors. We report on the role of the eicosanoids in the separation of DLBCL from controls, along with lysophosphatidylinositol LPI 20:4, implying notable changes in lipid metabolic and/or signalling pathways, particularly pertaining to AA lipoxygenase pathway and glycerophospholipid remodelling in the cell membrane. We suggest here the set of S1P, SM 36:1, SM 34:1 and PI 34:1 as DLBCL lipid signatures which could serve as a basis for the prospective validation in larger DLBCL cohorts. Additionally, untargeted lipidomics indicates a substantial change in the overall lipid metabolism in DLBCL. The plasma lipid profiling of DLBCL patients helps to better understand the specific lipid dysregulations and pathways in this cancer.

The Role of the Spleen and the Place of Splenectomy in Autoimmune Hemolytic Anemia-A Review of Current Knowledge.

Autoimmune hemolytic anemia (AIHA) is a rare, very heterogeneous, and sometimes life-threatening acquired hematologic disease characterized by increased red blood cell (RBC) destruction by autoantibodies (autoAbs), either with or without complement involvement. Recent studies have shown that the involvement of T- and B-cell dysregulation and an imbalance of T-helper 2 (Th2) and Th17 phenotypes play major roles in the pathogenesis of AIHA. AIHA can be primary (idiopathic) but is more often secondary, triggered by infections or drug use or as a part of other diseases. As the location of origin of autoAbs and the location of autoAb-mediated RBC clearance, as well as the location of extramedullary hematopoiesis, the spleen is crucially involved in all the steps of AIHA pathobiology. Splenectomy, which was the established second-line therapeutic option in corticosteroid-resistant AIHA patients for decades, has become less common due to increasing knowledge of immunopathogenesis and the introduction of targeted therapy. This article provides a comprehensive overview of current knowledge regarding the place of the spleen in the immunological background of AIHA and the rapidly growing spectrum of novel therapeutic approaches. Furthermore, this review emphasizes the still-existing expediency of laparoscopic splenectomy with appropriate perioperative thromboprophylaxis and the prevention of infection as a safe and reliable therapeutic option in the context of the limited availability of rituximab and other novel therapies.

Memorable Food: Fighting Age-Related Neurodegeneration by Precision Nutrition.

Healthcare systems worldwide are seriously challenged by a rising prevalence of neurodegenerative diseases (NDDs), which mostly, but not exclusively, affect the ever-growing population of the elderly. The most known neurodegenerative diseases are Alzheimer's (AD) and Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, but some viral infections of the brain and traumatic brain injury may also cause NDD. Typical for NDD are the malfunctioning of neurons and their irreversible loss, which often progress irreversibly to dementia and ultimately to death. Numerous factors are involved in the pathogenesis of NDD: genetic variability, epigenetic changes, extent of oxidative/nitrosative stress, mitochondrial dysfunction, and DNA damage. The complex interplay of all the above-mentioned factors may be a fingerprint of neurodegeneration, with different diseases being affected to different extents by particular factors. There is a voluminous body of evidence showing the benefits of regular exercise to brain health and cognitive functions. Moreover, the importance of a healthy diet, balanced in macro- and micro-nutrients, in preventing neurodegeneration and slowing down a progression to full-blown disease is evident. Individuals affected by NDD almost inevitably have low-grade inflammation and anomalies in lipid metabolism. Metabolic and lipid profiles in NDD can be improved by the Mediterranean diet. Many studies have associated the Mediterranean diet with a decreased risk of dementia and AD, but a cause-and-effect relationship has not been deduced. Studies with caloric restriction showed neuroprotective effects in animal models, but the results in humans are inconsistent. The pathologies of NDD are complex and there is a great inter-individual (epi)genetic variance within any population. Furthermore, the gut microbiome, being deeply involved in nutrient uptake and lipid metabolism, also represents a pillar of the gut microbiome-brain axis and is linked with the pathogenesis of NDD. Numerous studies on the role of different micronutrients (omega-3 fatty acids, bioactive polyphenols from fruit and medicinal plants) in the prevention, prediction, and treatment of NDD have been conducted, but we are still far away from a personalized diet plan for individual NDD patients. For this to be realized, large-scale cohorts that would include the precise monitoring of food intake, mapping of genetic variants, epigenetic data, microbiome studies, and metabolome, lipidome, and transcriptome data are needed.

Abnormal fatty acid distribution of the serum phospholipids of patients with non-Hodgkin lymphoma.

The data about the fatty acid (FA) status of non-Hodgkin lymphoma (NHL) patients are poor. Therefore, the aim of this study was to investigate the FA profile of serum phospholipids in NHL patients related to the aggressiveness and clinical stage of NHL. We analyzed the FA profile of serum phospholipids in 47 newly diagnosed, untreated NHL patients and in 29 healthy subjects. Significantly higher (p < 0.001) levels of palmitic (16:0), oleic (18:1 n-9) and arachidonic acids (20:4 n-6), saturated and monounsaturated FA were found in NHL patients, while linoleic acid (18:2 n-6) and the levels of total polyunsaturated FA (PUFA), n-3 PUFA, eicosapentaenoic (20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) were significantly reduced (p < 0.01). The level of oleic acid in patients with indolent NHL was significantly lower (p < 0.05) than in more aggressive types of disease. Contents of palmitoleic acid, docosatetraenoic (22:4 n-6), and PUFA was lower in very aggressive NHL. According to clinical stage (CS), patients with CS I had significantly higher SFA and lower n-6 FA than other three groups, and group with CS IV showed significantly decreased DHA and n-3 PUFA. Our results showed an abnormal FA profile in serum phospholipids in NHL patients.

Lipid Peroxidation and Antioxidant Supplementation in Neurodegenerative Diseases: A Review of Human Studies.

Being characterized by progressive and severe damage in neuronal cells, neurodegenerative diseases (NDDs) are the major cause of disability and morbidity in the elderly, imposing a significant economic and social burden. As major components of the central nervous system, lipids play important roles in neural health and pathology. Disturbed lipid metabolism, particularly lipid peroxidation (LPO), is associated with the development of many NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), all of which show elevated levels of LPO products and LPO-modified proteins. Thus, the inhibition of neuronal oxidation might slow the progression and reduce the severity of NDD; natural antioxidants, such as polyphenols and antioxidant vitamins, seem to be the most promising agents. Here, we summarize current literature data that were derived from human studies on the effect of natural polyphenols and vitamins A, C, and E supplementation in patients with AD, PD, and ALS. Although these compounds may reduce the severity and slow the progression of NDD, research gaps remain in antioxidants supplementation in AD, PD, and ALS patients, which indicates that further human studies applying antioxidant supplementation in different forms of NDDs are urgently needed.

Plasma phospholipid changes are associated with response to chemotherapy in non-Hodgkin lymphoma patients.

Limited studies have been performed to associate abnormal phospholipid (PL) profile and disease activity in hematological malignancies, including non-Hodgkin lymphoma (NHL). The aim of his study was to evaluate the levels of plasma PL fractions in NHL patients, in response to chemotherapy. Forty non-treated patients with NHL and 25 healthy individuals were recruited. Blood samples from patients were taken before chemotherapy, after 3 cycles and after the end of the treatment, and PL fractions were resolved by one-dimensional thin-layer chromatography. To assess potential relationship between plasma PL profile and response to therapy, patients were divided according to clinical outcome in 3 groups: complete remission (CR), stable disease (SD) and progression (PG). Despite significant differences between NHL patients and healthy controls, no differences were found at baseline among patients divided according to clinical outcome. During and after chemotherapy important alterations in PL profile were observed. Levels of total PLs and all PL fractions decreased in patients with PG while in patients who responded to therapy (CR, SD) PLs significantly increased. Results of our study suggest that changes of total PLs and PL fractions during the therapy are associated with the effects of therapy and clinical outcome in patients with NHL.

Primary hyperfibrinolysis as the presenting sign of prostate cancer: A case report.

Introduction: A bleeding syndrome in the setting of primary hyperfibrinolysis in a prostate cancer patient is only 0.40­ 1.65% of cases. The laboratory diagnosis of primary hyperfibrinolysis is based on the increase of biomarkers like D-dimer, fibrinogen split products, plasminogen, and euglobulin lysis test. These tests are not specific for primary hyperfibrinolysis. We reported a rare case of hemorrhagic syndrome caused by primary hyperfibrinolysis as the first clinical symptom of metastatic prostate cancer. Case report: A 64-year-old male was admitted to our hospital with large hematomas in the right pectoral and axillary areas (20 x 7 cm), right hemiabdomen (30 x 30 cm) and the left lumbal area, (25 x 5 cm). The patient had no subjective symptoms nor used any medication. Initial coagulation testing, prothrombin time (PT), and activated partial thromboplastin time (APTT) were within the normal range, while fibrinogen level was extremely low (1.068 g/L) (normal range 2.0­5.0) and the D-dimer assay result was high 1.122 mg/L (normal range < 0.23). The results obtained by rotation thrombelastometry pointed to primary fibrinolysis. Further clinical and laboratory examination indicated progressive malignant prostate disease. First line treatment for the patient was a combined administration of tranexamic acid (3 x 500 mg iv) and transfusion of ten units of cryoprecipitate (400 mL). Next day, fibrinolytic function measurements by rotation thrombelastometry were within the normal ranges. Fibrinogen level was normalized within two days (2.4 g/L). There were no newly developed hematomas. Conclusion: This case report shows primary hyperfibrinolysis with bleeding symptoms, which is an uncommon paraneoplastic phenomenon within expanded prostate malignancy. Rotation thrombelastometry in this severe complication helped to achieve the prompt and proper diagnosis and treatment.

Lymphoproliferative neoplasms and renal cell carcinoma of clear cell type--Where is the link?

INTRODUCTION: The etiology of higher than expected occurrence of lymphoproliferative neoplasms (LPN) and renal cell carcinoma (RCC) in the same patient has not yet been clarified. Several explanations for this co-occurrence have been postulated: prior cytotoxic treatment, viral infections, immunomodulatory effects of tumor itself and shared genetic and/or environmental factors. CASE REPORT: Medical records of 680 consecutive patients with LPN and 570 consecutive patients with RCC diagnosed between January 1997 and December 2011 in two centers were retrospectively analyzed. Co-occurrence of both diseases was registered in five of the patients (3 males, 2 females) and their demographic, clinical and pathological characteristics were presented. CONCLUSION: Synchronous occurrence of LPN neoplasms and RCC or a short latent period between the diagnoses of these two malignancies in the same patient, as well as the lack of cytotoxic treatment for firstly occurring neoplasm implies a possible common pathobiology of both diseases.

Distribution of plasma fatty acids is associated with response to chemotherapy in non-Hodgkin's lymphoma patients.

Our recent data have linked plasma phospholipid fatty acid (FA) profile in patients with non-Hodgkin's lymphoma (NHL) with the clinical stage and aggressiveness of the disease. Thus, we proposed that plasma FA status in these patients may influence the effect of chemotherapy. The aim of this work was to assess FA status in NHL patients undergoing chemotherapy in relation to their response to therapy. We analyzed plasma FA profile in 47 newly diagnosed NHL patients before chemotherapy, after 3 cycles and after the end of the planned chemotherapy. Patients were treated according to the hospital protocol: 28 patients with cyclophosphamide, doxorubicin, vincristine and prednisone, 7 with other anthracycline-containing regimens, 4 patients with cyclophosphamide, vincristine and prednisone and 8 with fludarabine-based regimens. Rituximab was added in 22 patients. Ten patients who did not receive all planned chemotherapy due to death or toxicity (non-completers) had significantly lower (p < 0.05) baseline proportion of palmitoleic, linoleic, eicosapentaenoic and docosahexaenoic acid, as well as n-3 and n-6 FA, than the patients who completed chemotherapy (completers). Furthermore, the completers were divided according to the response to chemotherapy to complete remission (CR), stable disease and progressive disease (PD). Proportion of palmitic acid after the end of chemotherapy was the highest in the PD group, while stearic acid showed the opposite trend. Palmitoleic acid and all n-3 FA (18:3, 20:5, 22:5 and 22:6) were the highest in the patients in remission and the lowest in PD (p < 0.001). Linoleic acid decreased and arachidonic acid increased from the CR to the PD group (p < 0.001). These results suggest that aberrations in plasma FA may influence response to chemotherapy in patients with NHL.

Prognostic factors for therapy-related acute myeloid leukaemia (t-AML)--a single centre experience.

Prognostic parameters for treatment outcome in 42 consecutive patients with t-AML diagnosed and treated in a single centre between 2000-2010 (mean age: 56.07 years, range: 23-84; 30 females) were evaluated retrospectively/prospectively. Antecedent malignancy occurred in 37 patients (88.15%): 28 solid cancers (breast, n=14), nine haematological. History of previous chemotherapy (CT), radiotherapy (RT) alone and combined CT/RT was present in 42.9%, 6.19% and 30.1% patients, respectively. Primary disease was active in 11 patients (six relapsed or metastatic cancers; five autoimmune diseases). Myelodysplastic syndrome preceded t-AML in 29% of patients. Median latency period from prior CT/RT was 54.62 months (range: 6-243). Median WBC count was 27.23 × 109/L, platelet count 62.29 × 109/L, haemoglobin level 87.83 g/L, peripheral blood and bone marrow blast percentage 30.7% and 66.7% respectively, serum LDH 1216 U/L. Aberrant expression of B or T lymphoid markers was registered in seven out of 39 and six out of 39 patients, respectively. Aberrant karyotype was detected in 24 out of 33 (72.7%) of eligible patients: favourable: 15.2%, intermediate: 42.4% and unfavourable: 42.4%. Eastern Cooperative Oncology Group (ECOG) performance status greater or equal to 2 and Haematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) greater or equal to 3 exhibited 83.3% and 76.2% patients, respectively. Intensive induction CT for t-AML was administered in 24 patients. The median follow-up and the median overall survival (OS) for the whole cohort were 2 months and 5.94 months (range: 0.5-34), respectively. In 10 patients (23.8%) achieving complete remission (CR), median disease free survival (DFS) was 11.8 months (range: 4-32). Only CD19 expression, pretreatment karyotype, ECOG PS, HCT-CI and activity of primary disease had impact on OS (P<0.05).

Concomitant administration of simvastatin and danazol associated with fatal rhabdomyolysis.

BACKGROUND: Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, is indicated for the treatment of hypercholesterolemia and plays an important role in both the primary and secondary prevention of cardiovascular disease. Danazol is a steroid analogue approved for the treatment of endometriosis, fibrocystic breast disease, and hereditary angioedema. Despite not being licensed, danazol has been used for other off-label indications, such as idiopathic thrombocytopenic purpura (ITP), paroxysmal nocturnal hemoglobinuria, and aplastic anemia. OBJECTIVE: We report a case of fatal rhabdomyolysis that occurred after concomitant administration of simvastatin and danazol in a patient with ITP. CASE SUMMARY: An 80-year-old white male (height, 182 cm; weight, 90 kg) presented to the emergency department of the Clinical Hospital Centre Zemun, Belgrade, Serbia, with head injuries after an accidental fall caused by generalized weakness. He denied other complaints, except fatigue, mild pretibial edema, and progressive bilateral leg pain and cramping that began 7 days before. At the time of presentation, he was receiving aspirin 100 mg/d, clopidogrel 75 mg/d, ramipril 2.5 mg/d, pantoprazole 40 mg/d, danazol 600 mg/d, prednisone 60 mg/d, simvastatin 40 mg/d, and long-acting insulin 24 IU/d. After the injuries were treated, he was diagnosed with collapse and nasal contusion, and discharged without any changes in his therapy. Two days after initial presentation, the patient was readmitted to the hospital due to nausea, dark urine, and oliguria. All clinical signs (oliguria, dark urine, muscle pain, and tenderness) and laboratory markers (creatine kinase levels approximately 100 times the upper limit of normal, along with hyperkalemia, hyperphosphatemia, and hypoalbuminemia) were consistent with severe rhabdomyolysis. Despite intravenous hydration, forced diuresis, and hemodialysis, oliguria persisted and the patient died 6 days after admission. A score of 5 on the Naranjo adverse drug reaction probability scale was consistent with a probable association of rhabdomyolysis and concomitant treatment with simvastatin and danazol in this patient. CONCLUSIONS: Statin-induced rhabdomyolysis must be considered whenever muscle or motor symptoms occur, especially when concomitant treatment with known inhibitors of statin metabolism is administered. Patients must be strictly monitored and the statin should be promptly discontinued with the onset of first signs and symptoms of myopathy. Clinicians should be aware of the potentially fatal consequences of both approved and unapproved treatments and be alert for the early detection of toxicity.

[Agranulocytosis induced by metamizole and its management with granulocyte growth factor]. / Agranulocitoza izazvana metamizolom i terapija granulocitnim faktorom rasta.

Drug-induced agranulocytosis was defined as a severe selective neutropenia caused by an unexpected drug reaction. Metamizole was the most common nonopioid analgesic drug associated with agranulocytosis. It was also associated with combined blood dyscrasias and other severe immunologic disorders. The risk of agranulocytosis by metamizole seemed to be considerably higher than estimated formerly. Modern management with broad-spectrum antibiotics and haematopoietic growth factors reduced the mortality in those patients. Two cases of agranulocytosis caused by metamizole were reported.