Non-polypoidal, synchronous mantle- cell lymphoma of small intestine: a rare case

Herein is reported the case of a mantle cell lymphoma (MCL) with synchronous double intestinal location. A 74 - year old male presented with mild abdominal pain. CT scan imaging indicated invasion of lateral intestinal cavity by large mass formation. Exploratory laparotomy was performed and two solid extra-mural masses were isolated and excised. Histology revealed non- polypoid double synchronous lymphoma of mantle cell origin, an unusual presentation of the disease

Early signs of memory impairment among multiple sclerosis patients with clinically isolated syndrome

Abstract. The study investigates primary and secondary verbal memory and motor/executive functions (response inhibition and strategy shifting ability) in multiple sclerosis (MS) patients with clinically isolated syndrome (CIS). We studied 44 CIS patients and compared them to 49 patients with relapsing remitting MS (RR-MS) displaying mild disability and to a large cohort of ageand education level-matched healthy volunteers (n = 230). Results showed that both CIS and RR-MS patients evidenced a disproportionate impairment in the immediate and delayed recall of the second (as compared to the first) of two short narratives of the Logical Memory WMS-III subtest, and reduced performance on the Memory for Digits-Forward. Performance of either group on the executive tasks was not impaired, showing evidence of a reversed speed-accuracy trade-off. Illness duration emerged as a significant predictor of memory and executive task performance. Clinical, psychoemotional, and brain imaging findings were also examined as potential correlates of memory deficits and disease progression among CIS patients. These findings may signify early-onset decline of specific cognitive functions in CIS, which merits regular follow-up assessments and monitoring of psychoemotional adaptation and everyday functioning

Correlation of Serum and Urine Midazolam Levels with Consciousness Tests after Discontinuation of Sedation in the Intensive Care Unit

Title: Correlation of serum and urine midazolam levels with observed level of consciousness after discontinuation of midazolam sedation in the intensive care unit   Marilena Papadaki1, Maria Pratikaki2, Achilleas Giannopoulos1, Theodora Ntaidou1, Eleftheria Mizi1, Marios Kougias1, Georgios Bouboulis1, Aikaterini Sarri1 and Charikleia S Vrettou1   1  1st Department of Intensive Care, Evangelismos Hospital, University of Athens Medical School, 45-47 Ipsilantou Str., 106 76 Athens, Greece 2 Department of Clinical Biochemistry, Evangelismos Hospital, Athens, Greece   Introduction: Continuous infusion of midazolam is related to prolonged activity and delayed awakening in the critically ill. Serum benzodiazepine levels can be helpful in differentiating residual benzodiazepine activity from other causes of impaired level of consciousness (LOC) [1]. Although benzodiazepine levels can also be measured in the urine, the relationship between serum and urine levels with the observed LOC has not been studied in clinical practice. Objectives: To investigate the correlation between serum and urine benzodiazepine levels in the critically ill and their correlation with the observed level of consciousness estimated with the Glasgow Coma Scale (GCS) and the Full Outline of UnResponsiveness Score (FOUR score). Patients and Methods: This prospective observational study involved patients admitted to a 30 bed General Intensive Care Unit, who were intubated and mechanically ventilated, with GCS prior to intubation > 8. Midazolam infusion was discontinued for at least 12 hours before sampling. Serum and urine sampling and clinical evaluation to calculate the GCS and FOUR score were done simultaneously. Gathered data included age, sex, weight and height, reason for admission to intensive care, renal function, daily fluid balance, daily and hourly urine output, liver function, serum proteins, hemoglobin and the application of renal replacement therapy. Serum benzodiazepine measurements were performed on the Integra system (Roche), which is suitable for semiquantitative detection of benzodiazepines in the serum. Urine benzodiazepine levels were measured with the Cobas C501 system, which is suitable for semiquantitative detection of benzodiazepines in human urine. The Scientific and Ethics committee of Evangelismos hospital approved the study protocol. Results: Twenty patients were included in the study, 10 male and 10 female. Reasons for ICU admission were septic shock (n=7), respiratory failure and ARDS (n=7), and acute surgery and trauma (n=6). Patients’ age ranged from 20 to 90 years old (median 66 years) and their weight from 45 to 160 Kg  (median 77.5 Kg). The SOFA score ranged from 4 to 15 (median 8). The GCS score from 3 to 14 (median 7) and the FOUR score from 3 to 15 (median 10). Six patients were on continuous veno-venous haemodiafiltration (CVVHD) at sampling time. Serum benzodiazepine levels correlate moderately with the GCS (R =-0.496, p=0.026) and better with the FOUR score (R =-0.685, p=0.001), but did not correlate with measured levels in the urine (R =-0.029 p=0.904), even when patients without AKI were analysed separately (n= 12, R = 0.173, p=0.572). Figure 1 presents the scatter plot of measured urine and serum benzodiazepine levels in our sample. Conclusions: In patients treated in the intensive care unit, after discontinuation of midazolam sedation, the LOC (GCS and FOUR score) correlate significantly with the benzodiazepine levels measured in the serum. Urine benzodiazepine levels do not correlate with serum levels or with the observed LOC and therefore cannot be helpful in the differential diagnosis of drowsiness or coma in this population. References: (1) Rosich Andreu et al. Intensive Care Medicine Experimental 2015, 3(Suppl 1):A330     &nbsp

Visible-Light Active Sulfur-Doped Titania Nanoparticles Immobilized on a Silica Matrix: Synthesis, Characterization and Photocatalytic Degradation of Pollutants

The photocatalytic oxidation (PCO) of pollutants using TiO(2)-based materials can significantly improve indoor air quality (IAQ), which in turn, has a significant impact on human health and life expectancy. TiO(2)-based nanoparticles (NPs) are widely used as part of building materials to function as photocatalysts in PCO. In this work, a series of sulfur-doped TiO(2) NPs immobilized on a silica matrix were synthesized by combining a sol-gel process with ball milling. The samples were structurally characterized by X-ray diffraction (XRD), UV-Vis diffuse reflectance spectroscopy (DRS), Fourier-transform infrared spectroscopy (FT-IR) and N(2) adsorption-desorption isotherms. Furthermore, the morphological characteristics were determined by dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The photocatalytic activity of the as prepared S-doped TiO(2)/SiO(2) NPs in the degradation of liquid and air pollutants under visible-light irradiation was investigated. Our results show that sulfur is an effective dopant for activating TiO(2)/SiO(2) photocatalysts under visible-light irradiation. Silica constitutes a “safe-by-design” approach and inhibits the aggregation of NPs during synthesis. The most efficient photocatalyst afforded 79% removal of methyl orange (5 h), 26% removal of acetaldehyde (1 h) and 12% oxidation of NO (1 h)

Expanded national database collection and data coverage in the FINDbase worldwide database for clinically relevant genomic variation allele frequencies

FINDbase (http://www.findbase.org) is a comprehensive data repository that records the prevalence of clinically relevant genomic variants in various populations worldwide, such as pathogenic variants leadingmostly tomonogenic disorders and pharmacogenomics biomarkers. The database also records the incidence of rare genetic diseases in various populations, all in well-distinct data modules. Here, we report extensive data content updates in all data modules, with direct implications to clinical pharmacogenomics. Also, we report significant new developments in FINDbase, namely (i) the release of a new version of the ETHNOS software that catalyzes development curation of national/ethnic genetic databases, (ii) the migration of all FINDbase data content into 90 distinct national/ethnicmutation databases, all built around Microsoft's PivotViewer (http://www.getpivot.com) software (iii) new data visualization tools and (iv) the interrelation of FINDbase with DruGeVar database with direct implications in clinical pharmacogenomics. The abovementioned updates further enhance the impact of FIND-base, as a key resource for Genomic Medicine applications

Expanded national database collection and data coverage in the FINDbase worldwide database for clinically relevant genomic variation allele frequencies

Peer reviewe

Drug Eluding Stents for Malignant Airway Obstruction: A Critical Review of the Literature

Lung cancer being the most prevalent malignancy in men and the 3rd most frequent in women is still associated with dismal prognosis due to advanced disease at the time of diagnosis. Novel targeted therapies are already on the market and several others are under investigation. However non-specific cytotoxic agents still remain the cornerstone of treatment for many patients. Central airways stenosis or obstruction may often complicate and decrease quality of life and survival of these patients. Interventional pulmonology modalities (mainly debulking and stent placement) can alleviate symptoms related to airways stenosis and improve the quality of life of patients. Mitomycin C and sirolimus have been observed to assist a successful stent placement by reducing granuloma tissue formation. Additionally, these drugs enhance the normal tissue ability against cancer cell infiltration. In this mini review we will concentrate on mitomycin C and sirolimus and their use in stent placement

Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations.

The B cell receptor immunoglobulin (BcR IG) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n=488) i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL) as well as provisional entities (n=76) according to the World Health Organization classification. The most striking IG gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different IG gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ IG sequence dataset with a large dataset of IG sequences (MZ-related or not; n=65,837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia but also rheumatoid factors and non-malignant spleen MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms, may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments.This work was supported in part by H2020 “AEGLE, An analytics framework for integrated and personalized healthcare services in Europe”, by the European Union (EU); H2020 No. 692298 project “MEDGENET, Medical Genomics and Epigenomics Network” by the EU; grant AZV 15-30015A from the Ministry of Health of the Czech Republic, and the project CEITEC2020 LQ1601 from the Ministry of Education, Youth, and Sports of the Czech Republic; Bloodwise Research Grant (15019); the Swedish Cancer Society, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Karolinska Institutet, Stockholm, the Lion’s Cancer Research Foundation, Uppsala, the Marcus Borgström Foundation and Selander’s Foundation, Uppsala

Clinical Approach to Immunotherapy-induced Type 1 Diabetes Mellitus: A Case of Pembrolizumab Associated Insulin-dependent Diabetes in a Patient with NSCLC

As the introduction of immune checkpoint inhibitors in the treatment of various cancers is now proven to be already acquired knowledge, so does a new challenge arise for clinicians; the understanding, diagnosis, and management of the rarest adverse effects of immunotherapy. We present a case of type-1 diabetes Mellitus (T1DM) in a patient with non-small cell lung carcinoma (NSCLC) treated with pembrolizumab. Following ten cycles of treatment, our patient was diagnosed with T1DM after being admitted for diabetic ketoacidosis and stayed hospitalized in the ICU. Later, they continued treatment with insulin, having shown disease response to pembrolizumab, and resumed immunotherapy while on insulin. Immunotherapy-induced T1DM can sometimes occur with PD1/PD-L1 blockage therapies. It has a rapid onset, is characterized by insulin deficiency due to the autoimmune destruction of beta-cells, and usually presents itself with diabetic ketoacidosis. Unlike most of the other adverse effects of immunotherapy, glucocorticoids don’t seem to be of therapeutic value, and insulin substitution is required. Regular glucose monitoring can be key to early diagnosis and prevention of hospitalization.&nbsp