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This work was partially supported by intramural funds of the University of Pisa, DKFZ, and University Hospital of Southern Jutland, Denmark, and by a grant of the French National Cancer Institute (INCA). The authors wish to thank Dr. Dominic Edelmann (Division of Biostatistics, DKFZ) for helpful advice about data analysis., There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53-4.69, p = 3.55 x 10(-15) for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34-4.33, p = 1.62 x 10(-13) for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population., University of Pisa, DKFZ, University Hospital of Southern Jutland, Denmark, Institut National du Cancer (INCA) France

From March through December 2020, 100 autopsies were performed (Semmelweis University, Budapest, Hungary), with chart review, of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection demonstrated by real-time reverse-transcription polymerase chain reaction testing (mean age, 74.73 years, range 40–102 years; 50 males, mean age 71.96 years, and 50 females, mean age 77.5 years). Classified by the date of death, 21 cases were from the pandemic’s “first wave” (March through July) and 79 from the “second wave” (August through December). Three mortality categories were defined by relevance of SARS-CoV-2 infection: (1) “strong” association (n=57), in which COVID-19 was primary responsible for death; (2) “contributive” association (n=27), in which a pre-existing condition independent of COVID-19 was primary responsible for death, albeit with substantial COVID-19 co-morbidity; (3) “weak” association (n=16), in which COVID-19 was minimally or not at all responsible for death. Distributions among categories differed between the first wave, in which the “contributive” association cases dominated (strong: 24%, contributive: 48%, weak: 28%), and the second wave, in which the “strong” association cases dominated (strong: 66%, contributive: 21%, weak: 13%). Charted co-morbidities included hypertension (85 %), cardiovascular diseases (71 %), diabetes (40 %), cerebrovascular diseases (31 %), chronic respiratory diseases (30 %), malignant tumors (20 %), renal diseases (19 %), diseases of the central nervous system (15 %), and liver diseases (6 %). Autopsy evaluation analyzed alterations on macroscopy as well as findings on microscopy of scanned and scored sections of formalin-fixed, paraffin-embedded tissue samples (50–80 blocks/case). Severity of histological abnormalities in the lung differed significantly between “strong” and “contributive” (pp

Összefoglaló. Az új típusú koronavírus-fertőzés (COVID–19) nagy terhet ró az egészségügyi ellátórendszerre és a társadalomra. A betegségnek három nagy szakasza van, melyek alapvetően meghatározzák a kezelést. Az I–IIA fázisban az antivirális, míg a IIB–III. fázisban a gyulladásgátló kezelés áll előtérben, melyhez intenzív terápiás, szupportív kezelés csatlakozik. A jelen ajánlás kizárólag a gyógyszeres kezelésre vonatkozik, és a rendelkezésre álló bizonyítékok alapján foglalja össze a terápiás lehetőségeket. Emellett egy javasolt kezelési algoritmust is tartalmaz. Orv Hetil. 2021; 162(17): 643–651. Summary. The novel coronavirus infection (COVID-19) places a heavy burden on the health care system and our society. There are three major stages in the disease that fundamentally determine treatment approaches. Phases I–IIA require primarily antiviral treatment. In phases IIB–III, anti-inflammatory treatment is needed accompanied by intensive and supportive care. This recommendation applies only to pharmacotherapy and summarizes the therapeutic options based on the available evidence. It also includes a proposed treatment algorithm. Orv Hetil. 2021; 162(17): 643–651.

Introduction It is well established that periodontal disease (PD) and diabetes mellitus (DM) can have a detrimental effect on each other’s disease course, and that cigarette smoking exacerbates both conditions. However, literature on the periodontal status of smokers with DM is scarce, and the studies conducted to date did not use healthy controls or non-smokers with DM as controls. Consequently, the individual effects of smoking and DM on PD are difficult to untangle and estimate. Methods A total of 128 participants were recruited to this study and their data analyzed. They were assigned to four groups: smoking patients with DM (SDM); non-smoking patients with DM (NSDM); smokers without DM (control group, SC) and (4) non-smokers without DM (control group, NSC). Each group consisted of 32 age-matched participants. The periodontal status of the participants was assessed by full oral examination. To express periodontal status, we used the four-stage classification introduced by Fernandes and colleagues (J Periodontol. 80(7):1062–1068, 2009). The control of DM was estimated by measuring hemoglobin A1c (HbA1c) levels in the peripheral blood. Results A significant difference in the severity of PD was found between the SC and NSC groups (p = 0.027) and between the NSC and SDM groups (p = 0.000), while the difference between the NSDM and SDM groups approached significance (p = 0.052). No person in the smoker groups could be classified as having a healthy periodontal status. The four-stage classification followed a normal distribution in the healthy, non-smoking controls (NSC). Smoking caused a shift toward medium-severe PD, while a marked shift toward the most severe stage was observed when both smoking and DM were present (SDM). There was no significant association between the type of DM and periodontal status, nor between diabetes control and the severity of PD. Persons in the SDM group had significantly fewer teeth than those in the NSC group (mean ± standard deviation: 16.0 ± 7.9 vs. 20.7 ± 5.6; p = 0.02). Conclusion Smoking damages the periodontium of even healthy individuals, but the damage is multiplied in a smoker who has DM, even though the effect of DM alone on periodontium health is relatively mild. Our results suggest a synergy between DM and smoking in terms of damage to the periodontal tissues, but the limited sample size of this study does not allow any hard conclusion to be drawn.

In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels

Introduction Type 2 diabetic patients suffering from severe hyperglycemia are often assigned a regimen involving multiple daily injections (MDI) of insulin. If the glucose toxicity resolves, the regimen can potentially be simplified, but there are no guidelines for this, and many patients are left on the MDI regimen. We aimed to prospectively examine the safety and efficacy of switching from MDI to once-daily IDegLira, a fixed-ratio combination of insulin degludec and liraglutide, in relatively well controlled (HbA1c ≤ 7.5%) subjects with type 2 diabetes on a low total daily insulin dose (TDD). Methods 62 adults with type 2 diabetes (baseline age 64.06 ± 10.24 years, HbA1c 6.42 ± 0.68%, BMI 33.53 ± 6.90 kg/m2, body weight 93.81 ± 19.26 kg, TDD 43.31 ± 10.99 IU/day, insulin requirement 0.47 ± 0.13 IU/kg, duration of diabetes 10.84 ± 7.50 years, mean ± SD) treated with MDI ± metformin were enrolled in our study. Previous insulins were stopped and once-daily IDegLira was started. IDegLira was titrated by the patients to achieve a self-measured pre-breakfast blood glucose concentration of

IntroductionThe prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care.Patients and MethodsTwenty-nine young patients with T1DM [age: 22.4 ± 2.9 years; HbA1c: 8.5 ± 2.1%, diabetes duration: 12.2 ± 5.8 years; (mean ± SD)] and 30 healthy volunteers (age: 21.5 ± 1.6 years; HbA1c: 5.3 ± 0.3%) were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometer®, Neuropad®-test, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests.ResultsT1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 vs. 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 vs. 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer®, Neuropad®-test, and Monofilament® were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test (right: 7.5 ± 1.0 vs. 7.9 ± 0.3; left: 7.5 ± 0.9 vs. 7.9 ± 0.3, p < 0.05). The Tiptherm®-test also identified a significant impairment in T1DM patients (11 sensing failures vs. 1, p < 0.001). In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls (9 vs. 0, p < 0.01).ConclusionIn this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm®-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.

Dysfunction of the nervous system is well-known in diabetes and also among patients with prediabetes, obesity and hypertension. However, there is only a limited amount of data available on the changes in neuronal function in polycystic ovary syndrome (PCOs), despite the fact that this condition is also accompanied by metabolic and vascular abnormalities. The aim of our study was to assess the cardiovascular autonomic and peripheral sensory function in patients with PCOs. The study involved 27 women with PCOs, and 24 healthy women as control subjects. Autonomic neuropathy (AN) was assessed using the four standard cardiovascular reflex tests. Peripheral sensory function was determined using the Neurometer. Electric stimulation was applied transcutaneously and the current perception threshold (CPT) values were determined on the median and peroneal nerves. No significant differences were found between the PCOs patients and the control group regarding the cardiovascular autonomic reflex tests and the AN scores. The CPT values of PCOs patients in the median and peroneal nerves were lower at all frequencies in comparison to controls. Conclusions: The cardiovascular autonomic nerve function was normal in the patients with PCOs. The current perception thresholds were consequently lower in the PCOs patients both in the upper and lower extremities at all frequencies, which serves as an early sign of neuropathy. As a novel observation, our results suggest that early neuronal damage manifests in the form of sensory hyperaesthesia in patients with PCOs.

D.C., F.C., and M.G. conceived and designed the study. A.M. and M.G. performed labwork. A.M., F.C., D.C., and M.G. drafted the manuscript. A.M., F.C., D.C., and M.G. performed data quality control and statistical analyses. All other authors provided samples and data. All authors critically read, commented, and approved the manuscript., Telomere length measured in leukocyte (LTL) has been found to be associated with the risk of developing several cancer types, including myeloproliferative neoplasms (MPNs). LTL is genetically determined by, at least, 11 SNPs previously shown to influence LTL. Their combination in a score has been used as a genetic instrument to measure LTL and evaluate the causative association between LTL and the risk of several cancer types. We tested, for the first time, the “teloscore” in 480 MPN patients and 909 healthy controls in a European multi-center case–control study. We found an increased risk to develop MPNs with longer genetically determined telomeres (OR = 1.82, 95% CI 1.24–2.68, P = 2.21 × 10−3, comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association between TERT-rs2736100-C allele and increased risk of developing MPNs and we report a novel association of the OBFC1-rs9420907-C variant with higher MPN risk (ORallelic= 1.43; 95% CI 1.15–1.77; P = 1.35 × 10−3). Consistently with the results obtained with the teloscore, both risk alleles are also associated with longer LTL. In conclusion, our results suggest that genetically determined longer telomeres could be a risk marker for MPN development

Theranostics 11(1), 292-303 (2021). doi:10.7150/thno.51872, Published by Ivyspring, Wyoming, NSW

Contains fulltext : 232394.pdf (Publisher’s version ) (Closed access) We evaluated the association between germline genetic variants located within the 3'-untranlsated region (polymorphic 3'UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case-control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3'-UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.

Abstract: Introduction: Increase of liver function is one of the most common complications after kidney transplantation due to the use of immunosuppressive therapy and hyperlipidemia in addition to hepatitis C virus (HCV) infection. Method: Following the selection criteria (n = 59), the study is based on applied immunosuppressive therapy, baseline data of patients, further correlation between HCV and liver function deterioration. Patients were subjected to fasting laboratory examination to monitor serum electrolytes, uric acid and albumin levels. We looked at the effects of immunosuppressive therapy on the lipids (TG, TC, HDL, LDL) and liver enzymes (GOT, GPT, ALP, GGT). The analysis of the relationship between lipids and liver enzymes was also included in our study. Results: The data basics were not significantly different between the tacrolimus and the cyclosporine groups. In the laboratory results, Mg levels were significantly different between the two groups (p = 0.044). The impact of HCV on the liver function was significantly different on GGT (p = 0.008). We examed the lipids and liver function level between the tacrolimus and the patients receiving cyclosporine-based immunosuppression and the total cholesterol (p = 0.005) and GOT (p = 0.05) were significantly different between the two groups. Hyperlipidemia was associated with 26% of patients taking tacrolimus-based immunosuppression, and 89% of those receiving cyclosporine; the difference was significant (p = 0.002). Regarding the effect of hyperlipidemia on liver enzymes, ALP (p = 0.006) and GGT (p = 0.0001) were significantly higher. Conclusion: Increases in hepatic enzymes, ALT and GGT indicate the damage to hepatocytes. Beside the increase of liver function, which is the main risk factor in hepatitis on HCV soil, the applied immunosuppressive therapy and hyperlipidemia lead to degradation of allograft function and long-term graft loss. Orv hetil. 2019; 160(5): 186–190.

Mastocytosis is a unique hematologic neoplasm with complex biology and pathology and a variable clinical course. The disease can essentially be divided into cutaneous mastocytosis (CM) and systemic mastocytosis (SM). In adults, SM is diagnosed in most cases and manifests as either indolent or advanced disease. Patients with advanced SM have an unfavorable prognosis with reduced survival. However, so far, little is known about the prevalence of various categories of SM and about prognostic factors. In an attempt to learn more about the behavior and evolution of various forms of CM and SM, the European Competence Network on Mastocytosis (ECNM) initiated a mastocytosis registry in 2012. In this article, the set up and start phase of this registry are described. Until 2018, more than 3000 patients from 12 countries and 25 centers have been enrolled. In a majority of all patients, robust follow-up data and relevant clinical end points are available. Using this data set, a series of registry projects have been launched, with the aim to validate previously identified diagnostic and prognostic variables and to identify new disease-related and patient-related parameters in various forms of mastocytosis. Moreover, the core data set of the registry will be useful to establish multiparametric scoring systems through which prognostication and individualized management of patients with mastocytosis should improve in the foreseeable future. (C) 2019 American Academy of Allergy, Asthma & Immunology

Abstract: Introduction: Transfer is a planned movement of patients and their medical records from one provider to another. Only a few data are available from real life in inflammatory bowel disease patients in this topic. Aim: Our aim was to retrospectively evaluate the results of the transfer of our patients without longitudinal transition. Method: Data of the transferred patients at the University of Szeged were analysed. Patients were diagnosed in paediatric care. Transfer strategy at our departments was detailed medical summary. Results: 59 patients were enrolled in this study. 28.8% of the patients had mild to moderate disease activity and 71.2% was in remission at the time of transfer. Steroid therapy was initiated in 58% of the patients within an average of 9.1 months after the transfer. Anti-tumor necrosis factor therapy was given to 24% of the patients during the paediatric care and to an additional 23% in the adult care within an average of 28 months. Almost 70% of the patients received immunosuppressive therapy during paediatric and adult care. Surgery was required in 17% of the patients within an average 10.7 months after the transfer. Conclusion: Our results revealed that one-third of the paediatric patients have been transferred to adult care in active stage of disease. Shortly after the transfer 58% of the patients required corticosteroids and 17% surgery. Every fifth patient needed biological therapy to be initiated after the transfer. Longitudinal transition may have a potential to decrease the need for therapeutic change and the relatively high rate of surgery. Orv Hetil. 2018; 159(44): 1789–1793.

Abstract: The authors summarize the medical history of a patient with impaired healing of a wound in the sole of foot. The 63-year-old male patient had a second-degree burn in the sole of the left foot as he stepped on the hot concrete after taking off his slipper. On admission to our department, local wound management had already been started, his wound showed no healing tendency. Bilateral X-ray was performed of his left leg, osteomyelitis was not confirmed, soft tissue drainage was applied, and bacterial culture from the wound confirmed methicillin-resistant Staphylococcus aureus infection. After soaking the leg in water, phlegmon developed on the dorsal part of the foot and the patient had septic fever. X-ray was repeated, and osteomyelitis was confirmed. Enucleation of the hallux of the left foot and metatarsal resection were performed. Wound dressing was exchanged and wound toilette was applied daily, insulin therapy was modified after consultation with a diabetologist. 7 months after the surgery, the wound was completely healed, carbohydrate metabolism of the patient was controlled. Our case draws attention to the importance of informing the patients of potential complications – in this case of the diabetic foot and its proper care. Treatment of ulcer of the lower leg requires multidisciplinary care, which means that the diabetologist and the surgeon has to cooperate in the care of these patients, carbohydrate metabolism should be balanced and regular wound care is necessary. Orv Hetil. 2018; 159(42): 1727–1730.

Essentials New VWF activity assays are increasingly used but information on their comparability is limited. This is an ISTH SSC-organized study (expert labs, 5 countries) to compare all available assays. VWF activity by six assays correlated well with each other. The new assays show improved characteristics - minor differences are noted. Summary Background Several new assays have become available to measure von Willebrand factor (VWF) activity. The new assays appear to have improved performance characteristics compared with the old reference standard, ristocetin cofactor activity (VWF:RCo), but information is limited about how they compare with VWF:RCo and each other. Methods The von Willebrand factor Subcommittee of the International Society for Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee (SSC) designed a collaborative study involving expert laboratories from several countries to compare available tests with each other and with VWF:RCo. Eight laboratories from five countries were provided with blinded samples from normal healthy individuals and well-characterized clinical cases. Laboratories measured VWF activity using all tests available to them; data from six laboratories, not affected by thawing during transportation, are included in this study. Results All tests correlated well with VWF:RCo activity (r-values ranged from 0.963 to 0.989). Slightly steeper regression lines for VWF:Ab and VWF:GPIbM were clinically insignificant. The new assays showed improved performance characteristics. Of the commercially available assays, the VWF:GPIbR using the AcuStar system was the most sensitive and could reliably detect VWF activity below 1 IU dL-1 . The lower limit of the measuring interval for the VWF:GPIbM and the VWF:GPIbR assays was in the 3-4 and 3-6 IU dL-1 range, respectively. Inter-laboratory variation was also improved for most new assays. Conclusion All VWF activity assays correlated well with each other and the VWF:RCo assay. The slight differences in characteristics found in the COMPASS-VWF study will assist the VWF community in interpreting and comparing activity results.

Background Philadelphia negative myeloproliferative neoplasms (MPNs) are characterized by frequent mutations of driver genes including JAK2, CALR and MPL. While the influence of JAK2 V617F mutant allele burden on the clinical phenotype of MPN patients is well-described, the impact of CALR mutant allele burden on clinical features needs further investigation. Patients and methods Quantitative assessment of JAK2 and CALR mutations was performed on diagnostic DNA samples from 425 essential thrombocythemia (ET) and 227 primary myelofibrosis patients using real-time quantitative PCR and fragment length analysis. Characterization of CALR mutations and detection of MPL mutations were performed by Sanger sequencing. Results Twelve novel CALR mutations have been identified. ET patients with CALRmut load exceeding the median value exhibited lower hemoglobin values (12.0 vs. 13.6 g/dL), higher LDH levels (510 vs. 351 IU/L) and higher rate of myelofibrotic transformation (19% vs. 5%). The CALRmut load was higher among ET patients presenting with splenomegaly compared to those without splenomegaly (50.0% vs. 43.5%). Conclusion Our study confirms the clinical significance of driver mutational status and JAK2mut load in MPNs; in addition, unravels a novel clinical association between high CALRmut load and a more proliferative phenotype in ET.

Abstract: Authors report on a case of a male patient of systemic mastocytosis that was associated with extensive cutaneous lesions. Chronic diarrhoea worsening his quality of life was well managed by the administration of antihistamines. The pleural fluid recurrence soon after drainage has been controlled by the administration of alpha interferon. 40 years after the onset of the first skin signs progression has been manifested in the development of “B” (bone marrow infiltration rate >30%, dysmyelopoiesis, serum tryptase >20 μg/L, hepato- and splenomegaly) and “C” symptoms (liver function test abnormalities, cytopenia, malabsorption, osteoporosis). The patient died at age of 87. The authors’ aim was to attract attention on this rare disease and emphasize that symptomatic therapy with antihistamines and drugs available based on customised rights by the National Health Insurance Fund might provide good quality of life. Orv Hetil. 2018; 159(5): 192–196.

Absztrakt A gastrointestinális vérzés oka lehet a gyomor antralis régiójának és néha a cardiatájéknak a kóros értágulata. Első leírója a múlt század 50-es éveinek elején a GAVE (Gastric Antral Vascular Ectasia) névvel illette, miután ekkor még a hasonló jelenséget a cardiatájon nem regisztrálták. Negyed századdal később – néhány eset közlése kapcsán – egy szellemes belgyógyász ragasztotta rá a görögdinnye (watermelon) elnevezést, minthogy a makroszkópos kép az említett gyümölcs „héjára hajaz”. A raritásnak számító kórkép súlyos társ betegségekkel terhelt betegünknél jelentkezett.

Myeloproliferative neoplasms (MPNs) are a group of diseases that cause myeloid hematopoietic cells to overproliferate. Epidemiological and familial studies suggest that genetic factors contribute to the risk of developing MPN, but the genetic susceptibility of MPN is still not well known. Indeed, only few loci are known to have a clear role in the predisposition to this disease. Some studies reported a diagnosis of MPNs and multiple myeloma (MM) in the same patients, but the biological causes are still unclear. We tested the hypothesis that the two diseases share at least partly the same genetic risk loci. In the context of a European multicenter study with 460 cases and 880 controls, we analyzed the effect of the known MM risk loci, individually and in a polygenic risk score (PRS). The most significant result was obtained among patients with chronic myeloid leukemia (CML) for PS0RS1C1-rs2285803, which showed to be associated with an increased risk (OR = 3.28, 95% CI 1.79-6.02, P = .00012, P = .00276 when taking into account multiple testing). Additionally, the PRS showed an association with MPN risk when comparing the last with the first quartile of the PRS (OR = 2.39, 95% CI 1.64-3.48, P = 5.98 × 10-6 ). In conclusion, our results suggest a potential common genetic background between MPN and MM, which needs to be further investigated.

Background: Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients. Methods: Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 μg or saline placebo, given in two vaccinations 7 days apart. The primary efficacy endpoint was all-cause mortality in patients 28 days after the first vaccination. Immunogenicity and safety were also evaluated. Findings: All-cause mortality rates at day 28 were 29.2% vs 27.7% in the IC43 and placebo groups, respectively (P =.67). Overall survival (Kaplan-Meier survival estimates, P =.46) and proportion of patients with ≥ one confirmed P. aeruginosa invasive infection or respiratory tract infection also did not differ significantly between both groups. The geometric mean fold increase in OprF/I titers was 1.5 after the first vaccination, 20 at day 28, after the second vaccination, and 2.9 at day 180. Significantly more patients in the placebo group (96.5%) had ≥ one adverse event (AE) versus the IC43 100 μg group (93.1%) (P =.04). The most frequently reported severe AEs in the IC43 and placebo groups were respiratory failure (6.9% vs 5.7%, respectively), septic shock (4.1% vs 6.5%), cardiac arrest (4.3% vs 5.7%), multiorgan failure (4.6% vs 5.5%), and sepsis (4.6% vs 4.2%). No related serious AEs were reported in the IC43 group. Interpretation: The IC43 100 μg vaccine was well tolerated in this large population of medically ill, mechanically ventilated patients. The vaccine achieved high immunogenicity but provided no clinical benefit over placebo in terms of overall mortality. Trial registration: https://clinicaltrials.gov (NCT01563263). Registration was sent to ClinicalTrials.gov on March 14, 2012, but posted by ClinicalTrials.gov on March 26, 2012. The first subject was included in the trial on March 22, 2012., SCOPUS: ar.j, info:eu-repo/semantics/published

Systemic mastocytosis (SM) is frequently associated with eosinophilia. To examine its prevalence and clinical impact in all WHO classification-based subcategories, we analyzed eosinophil counts in 2350 mastocytosis patients using the dataset of the European Competence Network on Mastocytosis. Ninety percent of patients had normal eosinophil counts, 6.8% mild eosinophilia (0.5-1.5 × 109/l), and 3.1% hypereosinophilia (HE; >1.5 × 109/l). Eosinophilia/HE were mainly present in patients with advanced SM (17%/19%), and only rarely recorded in patients with indolent and smoldering SM (5%/1%), and some patients with cutaneous mastocytosis. The eosinophil count correlated with organomegaly, dysmyelopoiesis, and the WHO classification, but not with mediator-related symptoms or allergy. Eosinophilia at diagnosis had a strong prognostic impact (p

Genetic variants in genes acting during the maturation process of immature B-cell to differentiated plasma cell could influence the risk of developing multiple myeloma (MM). During B-cell maturation, several programmed genetic rearrangements occur to increase the variation of the immunoglobulin chains. Class switch recombination (CSR) is one of the most important among these mechanisms. Germline polymorphisms altering even subtly this process could play a role in the etiology and outcome of MM. We performed an association study of 30 genetic variants in the key CSR genes, using 2632 MM patients and 2848 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the Heidelberg MM Group and the ESTHER cohort. We found an association between LIG4-rs1555902 and decreased MM risk, which approached statistical significance, as well as significant associations between AICDA-rs3794318 and better outcome. Our results add to our knowledge on the genetic component of MM risk and survival., Partially supported by intramural funds of DKFZ, by grants PI12/02688 and PI17/02276 from Fondo de Investigaciones Sanitarias (Madrid, Spain), Instituto de Salud Carlos III, co-funded by FEDER funds –a way to build Europe– grant PI14-00613 and Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723. The ESTHER study was funded by grants from the Baden-Württemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany), the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany) and the Saarland Ministry of Social Affairs, Health, Women and Family (Saarbrücken, Germany)

BACKGROUND Following kidney transplantation (KT), new-onset diabetes mellitus (NODM) is one of the most common complications. NODM usually occurs early after KT, and is diagnosed according to the general guidelines relevant for general diabetes mellitus patients. Arterial stiffness is a surrogate marker of cardiovascular risk. According to the literature, a successful KT has only limited and late beneficial effects on aortic elastic properties. The present study aimed to assess whether NODM has any additive value on the worsening of echocardiography-derived aortic elastic properties in transplanted patients. METHODS We have included 28 nondiabetic post-KT patients in the study, older than 18 years (mean age: 48.2 ± 6.9 years; 13 men, 15 women). After an oral glucose tolerance test, 8 patients were diagnosed with NODM, and their results were compared to 23 age-, sex-, and risk factor-matched controls (mean age: 54.9 ± 11.0 years; 9 men, 14 women). All post-KT patients and matched controls underwent a complete transthoracic 2-dimensional Doppler echocardiography, together with an assessment of echocardiographic aortic elastic properties. The assessments included aortic strain, aortic distensibility, and aortic stiffness index. RESULTS Aortic elastic properties showed alterations in post-KT patients compared to matched controls (aortic strain: .084 ± .039 vs .057 ± .032, P < .05; aortic distensibility: 2.36 ± 1.09 cm2/dynes 10-6 vs 1.83 ± 1.18 cm2/dynes 10-6, P = .07; aortic stiffness index: 7.15 ± 3.58 vs 11.2 ± 6.1, P

Background For patients with type 2 diabetes (T2D), cardiovascular disease (CVD) is the single most common cause of mortality. In 2008 and 2012, the Federal Drug Administration (FDA) and the European Medicines Agency (EMA) respectively mandated cardiovascular outcomes trials (CVOTs) on all new anti-diabetic agents, as prospective trials statistically powered to rule out excess cardiovascular risk in patients with T2D. Unexpectedly, some of these CVOTs have demonstrated not only cardiovascular safety, but also cardioprotective effects, as was first shown for the SGLT2 inhibitor empagliflozin in EMPA-REG OUTCOME. Expert opinion To debate newly available CVOT data and to put them into context, we convened as a group of medical experts from the Central and Eastern European Region. Here we describe our discussions, focusing on the conclusions we can draw from EMPA-REG OUTCOME and other SGLT2 inhibitor CVOTs, including when considered alongside real-world evidence. Conclusion CVOTs investigating SGLT2 inhibitors have suggested benefits beyond glucose lowering that have been confirmed in real-world evidence studies.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm. Virtually all PV patients are iron deficient at presentation and/or during the course of their disease. The co-existence of iron deficiency and polycythemia presents a physiological disconnect. Hepcidin, the master regulator of iron metabolism, is regulated by circulating iron levels, erythroblast secretion of erythroferrone, and inflammation. Both decreased circulating iron and increased erythroferrone levels, which occur as a consequence of erythroid hyperplasia in PV, are anticipated to suppress hepcidin and enable recovery from iron deficiency. Inflammation which accompanies PV is likely to counteract hepcidin suppression, but the relatively low serum ferritin levels observed suggest that inflammation is not a major contributor to the dysregulated iron metabolism. Furthermore, potential defects in iron absorption, aberrant hypoxia sensing and signaling, and frequency of bleeding to account for iron deficiency in PV patients have not been fully elucidated. Insufficiently suppressed hepcidin given the degree of iron deficiency in PV patients strongly suggests that disordered iron metabolism is an important component of the pathobiology of PV. Normalization of hematocrit levels using therapeutic phlebotomy is the most common approach for reducing the incidence of thrombotic complications, a therapy which exacerbates iron deficiency, contributing to a variety of non-hematological symptoms. The use of cytoreductive therapy in high-risk PV patients frequently works more effectively to reverse PV-associated symptoms in iron-deficient relative to iron-replete patients. Lastly, differences in iron-related parameters between PV patients and mice with JAK2 V617F and JAK2 exon 12 mutations suggest that specific regions in JAK2 may influence iron metabolism by nuanced changes of erythropoietin receptor signaling. In this review, we comprehensively discuss the clinical consequences of iron deficiency in PV, provide a framework for understanding the potential dysregulation of iron metabolism, and present a rationale for additional therapeutic options for iron-deficient PV patients.

A relationship is suspected between autonomic neuropathy (AN) and glucose variability (GV) as variability is associated with oxidative stress responsible for neuronal damage while the impaired autonomic function has a detrimental effect on metabolism. The oxidative stress associated with glucose variability might be responsible for neuronal damage while autonomic neuropathy has a detrimental effect on metabolism. The aim of the study was to find relationship between AN and GV in type 1 diabetic patients and to identify further factors that affect GV. The aim of the study was to find relationship between AN and GV in type 1 diabetic patients and to determine further factors in the pathogenesis of GV. Patients and methods: 20 type 1 diabetic patients were involved (age: 39.5±3.4 years, duration of diabetes: 17.5±2.5 years; HbA1c: 8.1±0.2%, mean±SE). AN was assessed by the cardiovascular reflex tests (CRT). The interstitial glucose levels were determined following insertion of a subcutaneous electrode during the continuous glucose monitoring (CGM) method on 6 consecutive days. GV was characterized by calculation of 4 parameters. Results: Standard deviation of interstitial glucose values (SD) correlated positively with the overall AN score and the degree of the orthostatic reduction of systolic blood pressure (AN-score-SD ρ=0.47, p

Objective: To assess the utility of visual electrophysiological methods, visual evoked potentials (VEPs) and pattern electroretinograms (PERGs) were recorded for the detection of subclinical optic nerve and retinal involvement in patients with diabetes mellitus. Subjects and Methods: The data of 63 patients (126 eyes) with no vascular retinopathy or optic neuropathy were retrospectively analyzed. The patients were divided into polyneuropathic/nonpolyneuropathic groups to differentiate between early and late subclinical stages. The recorded parameters were compared with local reference values. Results: 116 eyes (92%) had VEP and 76 (60%) had PERG abnormalities. The most frequent alteration was latency delay, but waveform and amplitude irregularities were also observed. The simultaneous use of the two methods allowed us to differentiate abnormal VEPs of purely optic nerve origin from those reflecting retinal involvement. Conclusions: We suggest that regular electrophysiological screening should receive more attention in the ophthalmological care of diabetic patients.

Objective: Changes in left atrial (LA) function can be observed in type 1 diabetes mellitus (T1DM). Three-dimensional (3-D) speckle tracking echocardiography (STE) seems to be a promising tool for volumetric and functional evaluation of LA. The objective of the present study was to compare 3DSTE-derived LA volumetric and strain parameters between T1DM patients and matched healthy controls. Methods: This prospective study consists of 17 subcutaneous insulin pump-treated non-obese patients with T1DM (mean age: 33.5±8.2 years, 8 males). To exclude possible cardiovascular disease, patients with complaints of chest pain, dyspnea, or signs of cerebrovascular disease or peripheral artery disease were not included. Their results were compared with 20 age-matched and gender-matched healthy controls (mean age: 36.9±11.0 years, 9 males). Independent sample Student t-test and Fisher’s exact test were used for comparisons. Bland–Altman method was used for evaluating intraobserver and interobserver correlations. Results: Anemia and impaired renal function were not confirmed in T1DM patients. Calculated LA maximum and minimum volumes and LA volume before atrial contraction were significantly increased in T1DM patients. Total atrial stroke volume was increased (23.6±6.9 mL vs. 19.6±4.6 mL, p=0.04), whereas mean segmental circumferential peak strain was decreased (28.9%±11.4% vs. 37.3%±12.5%, p=0.04). Segmental basal longitudinal and area strains were increased, whereas segmental superior circumferential and area strains and midatrial 3-D strain were decreased in T1DM. Conclusion: Both 3DSTE-derived volumetric and strain analysis confirmed alterations in LA function, suggesting early LA remodeling in patients with T1DM. (Anatol J Cardiol 2016; 16: 587-93)

Paroxysmal nocturnal hemoglobinuria is a rare hematological disease. It is associated with increased maternal and fetal complications to such an extent that pregnancy has been considered relatively contraindicated in woman with paroxysmal nocturnal haemoglobinuria. Recently, eculizumab, a monoclonal antibody, has been shown to decrease complications during pregnancies. The highest risk is thromboembolic complication and, therefore, anticoagulant is a standard therapy during pregnancy. In the presented case, a 29-year-old woman with a 5-year history of paroxysmal nocturnal haemoglobinuria had a pregnancy. It was her first pregnancy and was complicated by a sinus thrombosis at the 11th gestational week. After the introduction of eculizumab treatment, the remaining period of pregnancy and delivery were uncomplicated. There are only a few cases in the literature about pregnancy in woman with paroxysmal nocturnal hemoglobinuria who are treated with eculizumab. This monoclonal antibody seems to be safe and it likely prevents many of the complications otherwise observed. Orv. Hetil., 2016, 157(23), 916–918.

The authors review current advances in the therapy of diabetic neuropathy. The role of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are discussed. As further options of pathogenetically oriented treatment, recent knowledge on benfotiamine and alpha-lipoic acid is comprehensively reviewed. Alpha-lipoic acid is a powerful antioxidant and clinical trials have proven its efficacy in ameliorating neuropathic signs and symptoms. Benfotiamine acts via the activation of transketolase and thereby inhibits alternative pathways triggered by uncontrolled glucose influx in the cells comprising polyol, hexosamine, protein-kinase-C pathways and formation of advanced glycation end products. Beyond additional forms of causal treatment, choices of symptomatic treatment will be summarized. The latter is mostly represented by the anticonvulsive agents pregabalin and gabapentin as well as duloxetine widely acknowledged as antidepressant. Finally, non-pharmacological therapeutic alternatives are summarized. The authors conclude that combination therapy should be more often suggested to our patients; especially the combination of pathogenetic and symptomatic agents.

Grant sponsor: Polish Ministry of Science and Higher Education; Grant number: NN402178334; Grant sponsors: Research Fund at Region Sjaelland, DK; Baden-Wurttemberg State Ministry of Science, Research and Arts; CRIS Foundation

Background New-onset diabetes after transplantation (NODAT) is one of the most common complications after kidney transplantation. Methods Patients were randomly assigned to receive cyclosporine A–based or tacrolimus-based immunosuppression. Fasting and oral glucose tolerance tests were performed, and the patients were assigned to one of the following 3 groups, on the basis of the results: normal, impaired fasting glucose/impaired glucose tolerance, or NODAT. NODAT developed in 14% of patients receiving cyclosporine A–based immunosuppression and in 26% of patients taking tacrolimus ( P = .0002). Results Albumin levels were similar, but uric acid level ( P = .002) and the age of the recipient ( P = .003) were significantly different between the diabetic and the normal groups. Evaluation of tissue samples revealed that acute cellular rejection and interstitial fibrosis/tubular atrophy were significantly different in the NODAT group. Changes in the Banff score provided significant difference regarding tubulitis and interstitial inflammation ( P = .05). Conclusions The pathological effect of new-onset diabetes after kidney transplantation can be detected in the morphology of the renal allograft earlier, before the development of any sign of functional impairment.

Mastocytosis is a clonal mast cell proliferative disease, divided into cutaneous and systemic forms. The characteristic symptoms are caused by neoplastic mast cell infiltrations in different organs and/or the release of mediators.The aim of the authors was to summarize their clinical observations in patients with mastocytosis.22 adult patients diagnosed consecutively with mastocytosis were enrolled in the study. Skin and bone marrow biopsies were taken to establish the diagnosis and perform c-KIT mutation (D816V) analysis.One of the 22 patients had teleangiectasia macularis eruptiva perstans, while 20/22 patients had urticaria pigmentosa. All patients had cutaneous lesions. In 12 patients iliac crest biopsy was performed and 9 of them had bone marrow involvement, classified as indolent systemic mastocytosis. The c-kit mutation D816V was found in one subject both in skin and bone marrow samples. The patients were treated with antihistamine, PUVA, interferon-α or imatinib.The authors draw attention to this rare disease in order to help recognition of relevant signs and symptoms and establish an early diagnosis.Bevezetés: A mastocytosis a hízósejtek (mastocyták) felszaporodásával járó ritka megbetegedés, amely a WHO-besorolás szerint cutan és szisztémás formákra osztható. A klinikai tünetekhez a hízósejtek szöveti infiltrációja és/vagy a mediátorfelszabadulás vezet. Célkitűzés: A szerzők a Semmelweis Egyetem Mastocytosis Hálózat részeként a jellegzetes bőrtüneteket mutató betegek kivizsgálásával szerzett tapasztalatainak összefoglalását tűzték ki célul. Módszer: Összesen 22 mastocytosisos felnőtt beteget vizsgáltak. A diagnózis felállítása bőrszövettani vizsgálat, csontvelővizsgálat, D816V szomatikus c-KIT-mutációanalízis alapján történt. Eredmények: Húsz beteg esetében urticaria pigmentosát, egy esetben teleangiectasia macularis eruptiva perstanst észleltek. A bőr szövettani vizsgálata minden esetben igazolta a klinikai diagnózist. Cristabiopsziával 9/12 esetben a csontvelői részvétel alapján indolens szisztémás mastocytosis diagnózisa volt felállítható. c-KIT-mutációt (D816V) egy betegben igazoltak mind a csontvelőben, mind a bőrben. A betegek a klinikum függvényében antihisztamin, PUVA, a c-kit-szekvenálás eredménye alapján alfa-interferon vagy tirozinkináz-gátló terápiában részesültek. Következtetések: A mastocytosis diagnózisának felállításában a bőrgyógyász szerepe kiemelten fontos, de a betegség kiterjedtségének tisztázására a csontvelő vizsgálatát minden esetben tanácsos elvégezni. Orv. Hetil., 2013, 154, 1469–1475.

Preeclampsia is characterized by maternal systemic anti-angiogenic and pro-inflammatory states. Syndecan-1 is a cell surface proteoglycan expressed by the syncytiotrophoblast, which plays an important role in angiogenesis and resolution of inflammation. Our aim was to examine placental syndecan-1 expression in preeclampsia with or without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Placentas were obtained from women in the following groups: (1) late-onset preeclampsia (n = 8); (2) early-onset preeclampsia without (n = 7) and (3) with HELLP syndrome (n = 8); (4) preterm controls (n = 5); and (5) term controls (n = 9). Tissue microarrays (TMAs) were constructed from paraffin-embedded placentas. TMA slides were immunostained for syndecan-1 and evaluated using microscopy, virtual microscopy, and semi-automated image analysis. Maternal sera from patients with preeclampsia (n = 49) and controls (n = 32) were immunoassayed for syndecan-1. BeWo cells were treated with Forskolin or Latrunculin B or kept in ischemic conditions. SDC1 expression and syndecan-1 production were investigated with qRT-PCR, confocal microscopy, and immunoassays. Syndecan-1 was localized to the syncytiotrophoblast apical membrane in normal placentas. Syndecan-1 immunoscores were higher in late-onset preeclampsia (p = 0.0001) and early-onset preeclampsia with or without HELLP syndrome (p = 0.02 for both) than in controls. Maternal serum syndecan-1 concentration was lower in preeclampsia (median, 673 ng/ml; interquartile range, 459-1,161 ng/ml) than in controls (1,158 ng/ml; 622-1,480 ng/ml). SDC1 expression and syndecan-1 immunostainings in BeWo cells and syndecan-1 concentrations in supernatants increased during cell differentiation. Disruption of the actin cytoskeleton with Latrunculin B decreased syndecan-1 release, while ischemic conditions increased it. Syncytiotrophoblastic syndecan-1 expression depends on the differentiation of villous trophoblasts, and trophoblastic syndecan-1 release is decreased in preeclampsia and HELLP syndrome. This phenomenon may be related to the disturbed syncytiotrophoblastic cortical actin cytoskeleton and associated with maternal anti-angiogenic and pro-inflammatory states in these syndromes.

Myelodysplastic syndromes (MDS) often transform into acute leukemia (AL-MDS), although its prognostic details have not been examined thoroughly. We retrospectively analyzed the prognosis of 189 AL-MDS patients. Ninety-four patients received best supportive care (BSC), and 94 patients received disease-modifying therapies (DMT) that included chemotherapy (CHT) for 65 patients, allogeneic stem-cell transplantation (allo-SCT) for 21 patients, and other therapies for 8 patients. The median survival time was 142 days. In patients treated with BSC, platelet count alone was an independent prognostic factor. In younger patients treated with DMT (

Hematological neoplasms associated with systemic mast cell disease are most frequently of myeloid origin. There are a few reports, however, of systemic mastocytosis (SM) cases associated with lymphoid or plasma cell neoplasms as well. In this report, the authors present a case of SM (with D816V mutation in the c-KIT gene) associated with JAK2 V617F mutation negative essential thrombocythemia. The leading symptom of the 78-year-old female was recurring hydrothorax that responded only to interferon alpha therapy. During the first year of therapy, the patient developed insulin-dependent diabetes and hypothyroidism. The hematological workup also revealed IgG kappa monoclonal gammopathy that was non-progressive in the following next three years. Low levels of complements without known clinical significance accompanied the entire picture.

Correspondence.-- et al.

The aim of this study was to evaluate the effectivity and safety of insulin therapy in patients with DM secondary to underlying chronic pancreatitis with initially inappropriate glycemic control.Pancreatic DM patients treated with oral antidiabetics (OAD) or pre-mixed insulin (PMI) with HbA1c ≥7.0% were recruited. Intensive conservative insulin treatment (ICT) (Group A, n = 16) or PMI (Group B, n = 8) was introduced instead of OAD, or the initial PMI therapy was switched to ICT (Group C, n = 10). The changes in HbA1c, fasting plasma glucose, body weight and hypoglycemic events from baseline to 2 years were followed.The patients in Group A and B had been treated with oral antidiabetics for 55 ± 68 months before switching to insulin therapy. The level of HbA1c had worsened from 8.3 ± 1.5% to 9.8 ± 1.7% during this period. The ICT had reduced HbA1c significantly from 9.7 ± 1.8% to 7.6 ± 1.4% after 12 weeks, in Group A, and five patients had HbA1c7.0%. The introduction of PMI in Group B reduced HbA1c from 10.0 ± 1.4% to 9.0 ± 0.6% by 12 weeks. None of the patients had HbA1c7.0%. By 12 weeks, the introduction of ICT in Group C had reduced the level of HbA1c from 8.8 ± 1.7% to 7.7 ± 1.2%. Two patients reached HbA1c7.0%. There were two severe hypoglycemic episodes during the 2 years, one-one case in Group A and B.Oral medication becomes insufficient early in pancreatic DM. Long-term improvement of glycemic control can be achieved through intensified insulin therapy and in selected cases through PMI with a low risk of hypoglycemia.

Multiple myeloma (MM) is a heterogeneous disease group regarding prognosis, clinical course, and response to therapeutic interventions. Numerous prognostic factors have been identified however there was no consensus about the best prognostic indicators or the proper staging systems. In a previous study the A/M ratio containing albumin (A) and monoclonal component (M) emerged as reliable predictor of survival duration in patients treated with conventional chemotherapy. In the current retrospective study authors evaluated the prognostic role of this fraction in the era of novel agents. They assessed the A/M ratio prior treatment in 56 newly diagnosed MM patients from the aspect of the survival time. According to the results the A/M being

P. Kempler, G. Amarenco, R. Freeman, S. Frontoni, M. Horowitz, M. Stevens, P. Low, R. Pop-Busui, A. A. Tahrani, S. Tesfaye, T. Varkonyi, D. Ziegler, P. Valensi, on behalf of The Toronto Consensus Panel on Diabetic Neuropathy

Auriel E, Bornstein NM, Berenyi E, Varkonyi I, Gabor M, Majtenyi K, Szepesi R, Goldberg I, Lampe R, Csiba L. Clinical, radiological and pathological correlates of leukoaraiosis. Acta Neurol Scand: 2011: 123: 41–47. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Introduction - Leukoaraiosis is characterized by an abnormal appearance of the brain white matter on imaging. Its pathogenesis is still a matter of investigation. The purpose of this study was to investigate the radiological, clinical and pathological correlates of leukoaraiosis. Methods - The study population consisted of 93 deceased patients. The pre-mortem T2W magnetic resonance images were evaluated for the presence and grading of leukoaraiosis. The clinical and pathological characteristics based on the clinical charts and autopsy reports were evaluated. Tissue specimens of the blocks of 19 brains that demonstrated severe leukoaraiosis and those of five control brains were excised and stained. Results - The variables found to be significantly associated with leukoaraiosis were age and a clinical history of Parkinson’s disease. Other risk factors and pathological markers of atherosclerosis were not significantly correlated with leukoaraiosis. No significant difference was found between the scoring of the myelin integrity, glial fibrillary acidic protein, cluster of differentiation 68 and smooth muscle actin. There was a significant difference with respect to thickening of vessels walls. Conclusions - Our pathological results indicate that structural vascular abnormalities characterized by vessel wall thickening are associated with leukoaraiosis, supporting the assertion that vascular changes and ischemia generate leukoaraiosis. The relations between parkinsonism and leukoaraiosis may be explicable through vascular effects on the circuitry of the basal ganglia.

The diagnosis, classification, and prognostication of patients with myelodysplastic syndromes (MDS) are usually based on clinical parameters, analysis of peripheral blood and bone marrow smears, and cytogenetic determinants. However, a thorough histologic and immunohistochemical examination of the bone marrow is often required for a final diagnosis and exact classification in these patients. Notably, histology and immunohistology may reveal dysplasia in megakaryocytes or other bone marrow lineages and/or the presence of clusters of CD34-positive precursor cells. In other cases, histology may reveal an unrelated or co-existing hematopoietic neoplasm, or may support the conclusion the patient is suffering from acute myeloid leukemia rather than MDS. Moreover, histologic investigations and immunohistology may reveal an increase in tryptase-positive cells, a coexisting systemic mastocytosis, or bone marrow fibrosis, which is of prognostic significance. To discuss diagnostic algorithms, terminologies, parameters, and specific issues in the hematopathologic evaluation of MDS, a Working Conference involving a consortium of US and EU experts, was organized in June 2010. The outcomes of the conference and resulting recommendations provided by the faculty, are reported in this article. These guidelines should assist in the diagnosis, classification, and prognostication in MDS in daily practice as well as in clinical trials.

In the STD Centre of Hungary at our department, we have been providing care for patients with syphilis, gonorrhoea and other STD infections since 2004. Our STD centre includes a screening station where we perform anonymous screening for HIV and syphilis. Between the 1st of January 2005 and the 31st of December 2008, there were a total of 42,114 patient-doctor encounters. We performed 25,362 screening examinations for HIV and syphilis, in association with a medical visit (HIV: 12,337; syphilis: 13,025). Voluntary screening examinations were performed in 18,883 cases (HIV: 16,614; syphilis: 2,269). During the 4 years, we diagnosed 600 and 339 new cases of syphilis and gonorrhoea, respectively. The obligatory HIV screening of STI patients resulted in a total of 47 new HIV infections, and we diagnosed 63 new infections of syphilis or gonorrhoea among the known HIV-seropositive patients under care. By including the network of care providers in the whole country, we performed successful contact tracing...

Klinikánk STD Centrumában 2004 óta végezzük a syphilis, gonorrhoea és egyéb STD-fertőzésben szenvedők ellátását. STD Centrumunkon szűrőállomás működik, ahol anonim HIV- és syphilisszűrést végzünk. 2005. január 1-jétől 2008. december 31-ig összesen 42 114 orvos–beteg találkozás történt. 25 362 HIV- és syphilisszűrő vizsgálatot végeztünk el, orvosi vizittel egybekötve (HIV: 12 337, syphilis: 13 025). Önkéntes szűrővizsgálat 18 883 esetben történt (HIV: 16 614, syphilis: 2269). Négy év alatt 600 új syphilis- és 339 új gonorrhoeafertőzést diagnosztizáltunk. A kötelezően ajánlott HIV-szűrés során a 4 év alatt összesen 47 új HIV-fertőzést találtunk, illetve ismert és gondozott HIV-szeropozitív betegek közül 63 esetben állapítottunk meg új syphilis- vagy gonorrhoeafertőzést. Országosan, a gondozói hálózat bevonásával sikeres kontaktuskutatást syphilisnél évente 400, gonorrhoeánál évi 150–200 alkalommal végeztünk. Cikkünk célja, hogy felhívjuk a figyelmet a klasszikus nemi betegségek közé számító syphilis- és gonorrhoeafertőzések, valamint a többszörös STD-betegségek jelentőségére.

The prevalence of adult-type hypolactasia varies ethnically and geographically among populations. A C/T(-13910) single nucleotide polymorphism (SNP), upstream of the lactase gene, is known to be associated with lactase non-persistence. The aim of this study was to determine the prevalence of lactase-persistent and non-persistent genotypes in the Hungarian population, the age at onset and the applicability of the lactose H2 breath test in comparison with genetic screening. The prevalence of the C/C(-13910) genotype among adults was 37%. Hypolactasia starts to appear at around 5 years of age. Over the age of 12 years, almost all of those with a C/C(-13910) genotype have lactase non-persistence. The C/C(-13910) genotype was closely associated with a positive lactose H2 breath test in symptomatic children, whereas the lactase-persistent genotypes correlated better with a negative H2 test in a control group. In conclusion, supplementary non-invasive breath and genotyping tests furnish a perfect clinical diagnosis.

Udgivelsesdato: 2008-Nov BACKGROUND AND AIMS: Somatosensory hyperalgesia in the referred pain area (RPA) in patients with acute or chronic abdominal pain syndromes may result from the convergence of nerve fibers from visceral and somatic tissues at the spinal and supraspinal levels. Chronic biliary pain in patients with the postcholecystectomy syndrome (i.e., biliary hypersensitivity) may be explained by persistent hyperexcitability of neurons in the central nervous system (CNS). The aim of this study was to evaluate the cutaneous neural sensory perception in the RPA in patients with chronic postcholecystectomy biliary pain and a sphincter of Oddi (SO) dysfunction (SOD). METHODS: Forty-two patients with persistent biliary pain and suspected SOD, 27 age-matched healthy volunteers, and 18 age-matched asymptomatic cholecystectomized controls were prospectively investigated by quantitative sensory testing (Neurometer CPT). The biliary symptoms and the severity of pain were classified on a visual analog pain severity scale system via a previously validated and standardized questionnaire. The patients helped the doctors locate the RPA in the right upper quadrant. The sensory detection threshold was determined noninvasively (Neurometer CPT) with transcutaneous electrical stimulation at 5, 250, and 2,000 Hz, and different current intensities (range from 0.01 to 9.99 mA) applied in a single (patient) blinded method. These three frequencies selectively excite small unmyelinated (C fibers), small myelinated (A-delta), and large myelinated (A-beta) fibers, which transmit dull pain, sharp pain, and touch, respectively. The contralateral region of the abdomen left upper quadrant served as the control area. The sensory current perception threshold ratio (SCPTR) of the data measured in the contralateral area and the RPA was calculated. RESULTS: The SCPTRs in the definite SOD patients with biliary pain, healthy volunteers, the asymptomatic cholecystectomized controls, and the symptomatic cholecystectomized patients but without SOD were 2.32 +/- 1.4 versus 1.06 +/- 0.24 versus 0.97 +/- 0.16 versus 0.83 +/- 0.35 at 2,000 Hz; 2.19 +/- 1.0 versus 1.01 +/- 0.26 versus 1.02 +/- 0.25 versus 0.88 +/- 0.35 at 250 Hz; and 2.19 +/- 1.1 versus 1.12 +/- 0.26 versus 0.99 +/- 0.37 versus 0.84 +/- 0.32 at 5 Hz, respectively. Significant hypersensitivity was detected in the RPA at different stimulation frequencies in the SOD patients with biliary pain versus the cholecystectomized controls: at 5 Hz: P = 0.00001; at 250 Hz: P = 0.00001; and at 2,000 Hz: P = 0.0001, respectively. CONCLUSION: Continuous visceral pain (biliary pain) caused by local inflammatory/sensitizing processes or a CNS malfunction could lead to significant hypersensitivity of the peripheral nociceptive nerve fibers in SOD patients. Postcholecystectomy pain may be explained by persistent hyperexcitability of the nociceptive neurons in the CNS with or without objective motility disorders of the SO.

Allelic distribution of −308 G > A (TNF 1/2) polymorphism of the TNF-alpha, and the +252 A > G promoter polymorphism of the LT-alpha gene, the 1267 A > G polymorphism of the HSP70-2 gene as well as the −429 T > C promoter polymorphism of the RAGE gene were tested in 94 MM cases and 141 controls. Significantly less MM patients than controls carried the TNF2 allele (p = 0.018) and the TNF2-LTA 252G haplotype (p = 0.025). The difference was, however, restricted to the females, as well as the relatively young (