A case report of patient with cerebellar variant of stiff person syndrome

Stiff person syndrome (SPS) is a rare autoimmune neurological disorder with antibodies against antigens involved in neurotransmission of gamma-aminobutyric acid (GABA). About 10% of patients with SPS may develop ataxia. This cerebellar variant is a distinct subset of SPS with more severe and complex clinical phenotype. We report the clinical, neuropsychological and neuroradiological findings in a 39-year-old female with cerebellar variant of SPS

A case report of patient with cerebellar variant of stiff person syndrome

Stiff person syndrome (SPS) is a rare autoimmune neurological disorder with antibodies against antigens involved in neurotransmission of gamma-aminobutyric acid (GABA). About 10% of patients with SPS may develop ataxia. This cerebellar variant is a distinct subset of SPS with more severe and complex clinical phenotype. We report the clinical, neuropsychological and neuroradiological findings in a 39-year-old female with cerebellar variant of SPS

Plasma centrifugation does not influence thrombin-antithrombin and plasmin-antiplasmin levels but determines platelet microparticles count

Introduction: Centrifugation is an essential step for plasma preparation to remove residual elements in plasma, especially platelets and platelet-derived microparticles (PMPs). Our working hypothesis was that centrifugation as a preanalytical step may influence some coagulation parameters. Materials and methods: Healthy young men were recruited (N = 17). For centrifugation, two protocols were applied: (A) the first centrifugation at 2500 x g for 15 min and (B) at 2500 x g for 20 min at room temperature with a light brake. In protocol (A), the second centrifugation was carried out at 2500 x g for 15 min, whereas in protocol (B), the second centrifugation involved a 10 min spin at 13,000 x g. Thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes concentrations were determined by enzyme-linked immunosorbent assays. PMPs were stained with CD41 antibody and annexin V, and analyzed by flow cytometry method. Procoagulant activity was assayed by the Calibrated Automated Thrombogram method as a slope of thrombin formation (CAT velocity). Results: Median TAT and PAP concentrations did not differ between the centrifugation protocols. The high speed centrifugation reduced the median (IQR) PMP count in plasma from 1291 (841-1975) to 573 (391-1010) PMP/µL (P = 0.001), and CAT velocity from 2.01 (1.31-2.88) to 0.97 (0.82-1.73) nM/min (P = 0.049). Spearman’s rank correlation analysis showed correlation between TAT and PMPs in the protocol A plasma which was (rho = 0.52, P < 0.050) and between PMPs and CAT for protocol A (rho = 0.74, P < 0.050) and protocol B (rho = 0.78, P < 0.050). Conclusion: Centrifugation protocols do not influence the markers of plasminogen (PAP) and thrombin (TAT) generation but they do affect the PMP count and procoagulant activit

Utility assessment of 99mTc labelled human polyclonal immunoglobulin G scintigraphy for the diagnosis of limb lymphoedema

Wstęp. Metodą referencyjną w diagnostyce obrzęków limfatycznych jest limfoscyntygrafia. Oceny czynnościowej układu chłonnego dokonuje się na podstawie sprawności odpływu znacznika z miejsca podania, czasu pojawienia się radiofarmaceutyku w węzłach chłonnych, stopnia jego wychwytu w regionalnych węzłach chłonnych oraz obecności patologicznych dróg odpływu (wsteczny odpływ skórny). W piśmiennictwie podaje się, że istnieje możliwość wykorzystania w limfoscyntygrafii poliklonalnej immunoglobuliny G (IgG) znakowanej izotopem technetu (99mTc). Materiał i metody. Badaniem objęto 17 pacjentów z podejrzeniem obrzęku pochodzenia limfatycznego (11 kończyn górnych i 6 kończyn dolnych). Każdemu pacjentowi podawano podskórnie 0,1 ml kompleksu 99mTc-IgG (o aktywności ok. 50 MBq) w drugą przestrzeń międzypalcową obu rąk lub stóp. Akwizycję dynamiczną z użyciem gamma kamery Nucline AP rozpoczynano w momencie podania znacznika do obu kończyn. Aby przyspieszyć odpływ znacznika z miejsca podania, pacjenci w trakcie badania wykonywali delikatne ruchy palcami. Obrazowanie statyczne całego ciała wykonywano po 1, 3 i 4 godzinie od podania radiofarmaceutyku. Wyniki. U wszystkich badanych zaobserwowano odpływ znacznika z miejsca podania w fazie dynamicznej. Tempo przepływu radiofarmaceutyku było zróżnicowane i nie wykazywało związku z podłożem obrzęku limfatycznego. W 4 przypadkach (23,5%) stwierdzono wsteczny odpływ skórny i retencję znacznika w tkankach miękkich w późnym obrazowaniu. Zaobserwowano długotrwałą retencję znacznika w naczyniach limfatycznych. U żadnego z pacjentów nie odnotowano miejscowych lub ogólnoustrojowych objawów niepożądanych. Wnioski. Scyntygrafia z użyciem kompleksu 99mTc-IgG jest przydatną metodą w diagnostyce obrzęków limfatycznych kończyn.Background. Lymphoscintigraphy is the "gold standard" examination in lymphoedema diagnosis. The assessment of lymphatic system function is done on the base of outflow efficiency of the radiotracer, time of its appearance in lymph nodes, degree of its uptake in regional lymph nodes and presence of pathological backflow ways (dermal backflow). Some authors suggest the possibility of application of 99mTc labelled immmunoglobulin G (IgG) in lymphoscintigraphy. Material and methods. 17 patients suspected of lymphoedema have been examined (11 upper limbs, 6 lower limbs). Each patient received subcutaneous 99mTc-IgG complex in a volume 0.1 mL with activity 50 MBq. The site of injection was the second web space of the affected extremity and the contralateral normal limb. Dynamic data acquisition with the use of Nucline AP gamma camera has been started immediately post injection (p.i.) to both extremities. The patients made small movement of fingers during examination in order to speed up the tracer outflow. The static visualization of whole body has been performed after 1, 3 and 4 hours p.i. Results. The radiotracer outflow from the site of injection has been noticed in all cases of dynamic phase of examination. Flow rate of the radiopharmaceutics was differentiated and did not to show any correlation with the reason of lymphoedema. Dermal backflow has been observed in four cases (23.5%) connected with the tracer retention in soft tissues during delayed visualization. Additionally, long-time retention of the tracer in lymphatic vessels has been observed. There was no case of any local or general undesirable symptoms. Conclusions. Scintigraphy 99mTc-IgG is a useful method in limb lymphoedema diagnosis

The significant impact of age on the clinical outcomes of laparoscopic appendectomy : results from the Polish Laparoscopic Appendectomy multicenter large cohort study

Acute appendicitis (AA) is the most common surgical emergency and can occur at any age. Nearly all of the studies comparing outcomes of appendectomy between younger and older patients set cut-off point at 65 years. In this multicenter observational study, we aimed to compare laparoscopic appendectomy for AA in various groups of patients with particular interest in the elderly and very elderly in comparison to younger adults. Our multicenter observational study of 18 surgical units assessed the outcomes of 4618 laparoscopic appendectomies for AA. Patients were divided in 4 groups according to their age: Group 1- 8 days. Logistic regression models comparing perioperative results of each of the 3 oldest groups compared with the youngest one showed significant differences in odds ratios of symptoms lasting >48hours, presence of complicated appendicitis, perioperative morbidity, conversion rate, prolonged LOS (>8 days). The findings of this study confirm that the outcomes of laparoscopic approach to AA in different age groups are not the same regarding outcomes and the clinical picture. Older patients are at high risk both in the preoperative, intraoperative, and postoperative period. The differences are visible already at the age of 40 years old. Since delayed diagnosis and postponed surgery result in the development of complicated appendicitis, more effort should be placed in improving treatment patterns for the elderly and their clinical outcome

Risk factors for serious morbidity, prolonged length of stay and hospital readmission after laparoscopic appendectomy : results from Pol-LA (Polish Laparoscopic Appendectomy) multicenter large cohort study

Laparoscopic appendectomy (LA) for treatment of acute appendicitis has gained acceptance with its considerable benefits over open appendectomy. LA, however, can involve some adverse outcomes: morbidity, prolonged length of hospital stay (LOS) and hospital readmission. Identification of predictive factors may help to identify and tailor treatment for patients with higher risk of these adverse events. Our aim was to identify risk factors for serious morbidity, prolonged LOS and hospital readmission after LA. A database compiled information of patients admitted for acute appendicitis from eighteen Polish and German surgical centers. It included factors related to the patient characteristics, peri- and postoperative period. Univariate and multivariate logistic regression models were used to identify risk factors for serious perioperative complications, prolonged LOS, and hospital readmissions in acute appendicitis cases. 4618 laparoscopic appendectomy patients were included. First, although several risk factors for serious perioperative complications (C-D III-V) were found in the univariate analysis, in the multivariate model only the presence of intraoperative adverse events (OR 4.09, 95% CI 1.32-12.65, p = 0.014) and complicated appendicitis (OR 3.63, 95% CI 1.74-7.61, p = 0.001) was statistically significant. Second, prolonged LOS was associated with the presence of complicated appendicitis (OR 2.8, 95%CI: 1.53-5.12, p = 0.001), postoperative morbidity (OR 5.01, 95% CI: 2.33-10.75, p < 0.001), conversions (OR 6.48, 95% CI: 3.48-12.08, p < 0.001) and reinterventions after primary procedure (OR 8.79, 95% CI: 3.2-24.14, p < 0.001) in the multivariate model. Third, although several risk factors for hospital readmissions were found in univariate analysis, in the multivariate model only the presence of postoperative complications (OR 10.33, 95% CI: 4.27-25.00), reintervention after primary procedure (OR 5.62, 95% CI: 2.17-14.54), and LA performed by resident (OR 1.96, 95%CI: 1.03-3.70) remained significant. Laparoscopic appendectomy is a safe procedure associated with low rates of complications, prolonged LOS, and readmissions. Risk factors for these adverse events include complicated appendicitis, postoperative morbidity, conversion, and re-intervention after the primary procedure. Any occurrence of these factors during treatment should alert the healthcare team to identify the patients that require more customized treatment to minimize the risk for adverse outcomes

Identification of miRSNPs associated with the risk of multiple myeloma

Accepted articleMultiple myeloma (MM) is a malignancy of plasma cells usually infiltrating the bone marrow, associated with the production of a monoclonal immunoglobulin (M protein) which can be detected in the blood and/or urine. Multiple lines of evidence suggest that genetic factors are involved in MM pathogenesis, and several studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to the disease. SNPs within miRNA-binding sites in target genes (miRSNPs) may alter the strength of miRNA-mRNA interactions, thus deregulating protein expression. MiRSNPs are known to be associated with risk of various types of cancer, but they have never been investigated in MM. We performed an in silico genome-wide search for miRSNPs predicted to alter binding of miRNAs to their target sequences. We selected 12 miRSNPs and tested their association with MM risk. Our study population consisted of 1,832 controls and 2,894 MM cases recruited from seven European countries and Israel in the context of the IMMEnSE (International Multiple Myeloma rESEarch) consortium. In this population two SNPs showed an association with p<0.05: rs286595 (located in gene MRLP22) and rs14191881 (located in gene TCF19). Results from IMMEnSE were meta-analyzed with data from a previously published genome-wide association study (GWAS). The SNPs rs13409 (located in the 3UTR of the POU5F1 gene), rs1419881 (TCF19), rs1049633, rs1049623 (both in DDR1) showed significant associations with MM risk. In conclusion, we sought to identify genetic polymorphisms associated with MM risk starting from genome-wide prediction of miRSNPs. For some mirSNPs, we have shown promising associations with MM risk. What's new? Even though deregulation of miRNA expression has been associated with human cancers little information is available regarding their relation with MM susceptibility. We performed an in silico genome-wide search for miRSNPs and selected the most promising ones for an association study. The SNPs with the strongest associations with MM risk are localized in genes which have never been related with MM.This work was partially funded by: intramural funds of German Cancer Research Center (DKFZ), Grant ref. HUS412A1271 from the “Gerencia Regional de Salud de la Junta de Castilla y Léon”. This work was supported by grants from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688). Catalan Government DURSI grant 2014SGR647 and Instituto de Salud Carlos III, co7funded by FEDER funds –a way to build Europe– grants PI11701439 and PIE13/00022info:eu-repo/semantics/publishedVersio

Genetically determined telomere length and multiple myeloma risk and outcome

This work was partially supported by intramural funds of Univerity of Pisa and DKFZ; by Fondo de Investigaciones Sanitarias (Madrid, Spain) [PI12/02688 to J. S., PI17/02276 to J.S.]; by Instituto de Salud Carlos III, co-funded by FEDER funds —a way to build Europe—[PI14-00613 to V.M.] and by Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Barcelona, Spain) [2017SGR723 to V.M.]. Open Access funding enabled and organized by Projekt DEAL.Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the "teloscore" in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36-2.11; P = 2.97 x 10(-6) for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86-0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.Univerity of PisaHelmholtz AssociationInstituto de Salud Carlos III PI12/02688 PI17/02276Instituto de Salud Carlos IIIEuropean CommissionFEDER funds-a way to build Europe PI14-00613Agency for Management of University and Research Grants (AGAUR) of the Catalan Government (Barcelona, Spain) 2017SGR723Projekt DEA

Mechanical thrombectomy in acute stroke – Five years of experience in Poland

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines

Cyclodepsipeptide Biosynthesis in Hypocreales Fungi and Sequence Divergence of The Non-Ribosomal Peptide Synthase Genes

Fungi from the Hypocreales order synthesize a range of toxic non-ribosomal cyclic peptides with antimicrobial, insecticidal and cytotoxic activities. Entomopathogenic Beauveria, Isaria and Cordyceps as well as phytopathogenic Fusarium spp. are known producers of beauvericins (BEAs), beauvenniatins (BEAEs) or enniatins (ENNs). The compounds are synthesized by beauvericin/enniatin synthase (BEAS/ESYN1), which shows significant sequence divergence among Hypocreales members. We investigated ENN, BEA and BEAE production among entomopathogenic (Beauveria, Cordyceps, Isaria) and phytopathogenic (Fusarium) fungi; BEA and ENNs were quantified using an LC-MS/MS method. Phylogenetic analysis of partial sequences of putative BEAS/ESYN1 amplicons was also made. Nineteen fungal strains were identified based on sequence analysis of amplified ITS and tef-1&alpha; regions. BEA was produced by all investigated fungi, with F. proliferatum and F. concentricum being the most efficient producers. ENNs were synthesized mostly by F. acuminatum, F. avenaceum and C. confragosa. The phylogeny reconstruction suggests that ancestral BEA biosynthesis independently diverged into biosynthesis of other compounds. The divergent positioning of three Fusarium isolates raises the possibility of parallel acquisition of cyclic depsipeptide synthases in ancient complexes within Fusarium genus. Different fungi have independently evolved NRPS genes involved in depsipeptide biosynthesis, with functional adaptation towards biosynthesis of overlapping yet diversified metabolite profiles