The role of surgical resection in Unicentric Castleman’s disease: a systematic review

Introduction: Castleman’s disease is a rare benign lymphoproliferative disorder of unknown etiology. The disease occurs in twoclinical forms with different prognoses, treatments and symptoms: a unicentric form (UCD), which is solitary, localized, and a multicentricform characterized by generalized lymphadenopathy and systemic symptoms. This article aims to review the currentliterature to consolidate the evidence surrounding the curative potential of surgical treatment to the unicentric type.Material and methods: A systematic review of English-language literature was performed and databases (Medline, Pubmed,the Cochrane Database and grey literature) were searched to identify articles pertaining to the treatment of unicentric form ofCastleman’s disease. Each article was critiqued by two authors using a structured appraisal tool, and stratified according to thelevel of evidence.Results: After application of inclusion criteria, 14 studies were included. There were no prospective randomized control studiesidentified. One meta-analysis including 278 patients with UCD reported that resective surgery is safe and should be consideredthe gold standard for treatment. Seven retrospective studies enhance this standpoint. Radiotherapy (RT) has been used in sixstudies with controversial results.Conclusions: We conclude that surgical resection appears to be the most effective treatment for Unicentric Castleman’s Diseaseof the thoracic cavity. Radiotherapy can also achieve clinical response and cure in selected patients

Out-of-Plane Biphilic Surface Structuring for Enhanced Capillary-Driven Dropwise Condensation

Rapid and sustained condensate droplet departure from a surface is key towards achieving high heat transfer rates in condensation, a physical process critical to a broad range of industrial and societal applications. Despite progress in enhancing condensation heat transfer through inducing its dropwise mode with hydrophobic materials, sophisticated surface engineering methods that can lead to further enhancement of heat transfer are still highly desirable. Here, by employing a three-dimensional, multiphase computational approach, we present an effective out-of-plane biphilic surface topography, that reveals an unexplored capillarity-driven departure mechanism of condensate droplets. This texture consists of biphilic diverging micro-cavities wherein a matrix of small hydrophilic spots is placed at their bottom, that is, amongst the pyramid-shaped, superhydrophobic micro-textures forming the cavities. We show that an optimal combination of the hydrophilic spots and the angles of the pyramidal structures can achieve high deformational stretching of the droplets, eventually realizing an impressive slingshot-like droplet ejection process from the texture. Such a droplet departure mechanism has the potential to reduce the droplet ejection volume and thus enhance the overall condensation efficiency, compared to coalescence-initiated droplet jumping from other state-of-the-art surfaces. Simulations have shown that optimal pyramid-shaped biphilic micro-structures can provoke droplet self-ejection at low volumes, up to 56% lower compared to superhydrophobic straight pillars, revealing a promising new surface micro-texture design strategy towards enhancing condensation heat transfer efficiency and water harvesting capabilities

Rola resekcji chirurgicznej w leczeniu zlokalizowanej postaci choroby Castlemana — przegląd systematyczny

Choroba Castlemana jest rzadką, łagodną chorobą limfoproliferacyjną o nieznanej etiologii. Schorzenie występuje w dwóch postaciach klinicznych o różnym rokowaniu, sposobie leczenia i objawach: postaci zlokalizowanej (UCD) oraz wieloogniskowej, charakteryzującej się powiększeniem węzłów chłonnych oraz objawami ogólnymi. Celem pracy był przegląd piśmiennictwa, a także analiza dowodów na skuteczność resekcji chirurgicznej w zlokalizowanej postaci choroby. Przeprowadzono przegląd systematyczny piśmiennictwa angielskojęzycznego oraz baz danych (Medline, Pubmed, Cochrane i źródeł dodatkowych) w poszukiwaniu artykułów dotyczących leczenia zlokalizowanej postaci choroby Castlemana. Każdy artykuł oceniony był przez dwóch autorów przy użyciu ustrukturyzowanego narzędzia oceny, a następnie skategoryzowany zgodnie z siłą dowodu. Zgodnie z kryteriami włączenia, do badania zakwalifikowano 14 badań. Nie znaleziono prospektywnych, randomizowanych badań z grupą kontrolną. W jednej metaanalizie, obejmującej 278 chorych na UCD, stwierdzono, że resekcja chirurgiczna jest bezpieczna i powinna być traktowana jako „złoty standard” w leczeniu. Wnioski zawarte w siedmiu badaniach retrospektywnych potwierdzały ten punkt widzenia. Radioterapia (RT) była stosowana w sześciu badaniach, z różnym efektem. W leczeniu choroby Castlemana zlokalizowanej w klatce piersiowej resekcja chirurgiczna wydaje się metodą o najwyższej skuteczności. Ponadto, pozytywną odpowiedź kliniczną można w niektórych przypadkach osiągnąć przy zastosowaniu radioterapii.Choroba Castlemana jest rzadką, łagodną chorobą limfoproliferacyjną o nieznanej etiologii. Schorzenie występuje w dwóch postaciach klinicznych o różnym rokowaniu, sposobie leczenia i objawach: postaci zlokalizowanej (UCD) oraz wieloogniskowej, charakteryzującej się powiększeniem węzłów chłonnych oraz objawami ogólnymi. Celem pracy był przegląd piśmiennictwa, a także analiza dowodów na skuteczność resekcji chirurgicznej w zlokalizowanej postaci choroby. Przeprowadzono przegląd systematyczny piśmiennictwa angielskojęzycznego oraz baz danych (Medline, Pubmed, Cochrane i źródeł dodatkowych) w poszukiwaniu artykułów dotyczących leczenia zlokalizowanej postaci choroby Castlemana. Każdy artykuł oceniony był przez dwóch autorów przy użyciu ustrukturyzowanego narzędzia oceny, a następnie skategoryzowany zgodnie z siłą dowodu. Zgodnie z kryteriami włączenia, do badania zakwalifikowano 14 badań. Nie znaleziono prospektywnych, randomizowanych badań z grupą kontrolną. W jednej metaanalizie, obejmującej 278 chorych na UCD, stwierdzono, że resekcja chirurgiczna jest bezpieczna i powinna być traktowana jako „złoty standard” w leczeniu. Wnioski zawarte w siedmiu badaniach retrospektywnych potwierdzały ten punkt widzenia. Radioterapia (RT) była stosowana w sześciu badaniach, z różnym efektem. W leczeniu choroby Castlemana zlokalizowanej w klatce piersiowej resekcja chirurgiczna wydaje się metodą o najwyższej skuteczności. Ponadto, pozytywną odpowiedź kliniczną można w niektórych przypadkach osiągnąć przy zastosowaniu radioterapii

The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial

The aim of this prospective study was to evaluate the long-term efficacy and safety of hydroxyurea (HU) in patients with sickle cell disease (SCD). Thirty-four patients with sickle cell anemia (hemoglobin S [HbS]/HbS), 131 with HbS/␤ 0 -thal, and 165 with HbS/␤ ؉ -thal participated in this trial. HU was administered to 131 patients, whereas 199 patients were conventionally treated. The median follow-up period was 8 years for HU patients and 5 years for non-HU patients. HU produced a dramatic reduction in the frequency of severe painful crises, transfusion requirements, hospital admissions, and incidence of acute chest syndrome. The probability of 10-year survival was 86% and 65% for HU and non-HU patients, respectively (P ‫؍‬ .001), although HU patients had more severe forms of SCD. The 10-year probability of survival for HbS/ HbS, HbS/␤ 0 -thal, and HbS/IVSI-110 patients was 100%, 87%, and 82%, respectively, for HU patients and 10%, 54%, and 66%, for non-HU patients. The multivariate analysis showed that fetal hemoglobin values at baseline and percentage change of lactate dehydrogenase between baseline and 6 months were independently predicted for survival in the HU group. These results highlight the beneficial effect of HU, which seems to modify the natural history of SCD and raise the issue of expanding its use in all SCD patients. (Blood

Stem cell factor is implicated in microenvironmental interactions and cellular dynamics of chronic lymphocytic leukemia

The inflammatory cytokine Stem Cell Factor (SCF, ligand of c-kit receptor) has been implicated as a pro-oncogenic driver and an adverse prognosticator in several human cancers. Increased SCF levels have recently been reported in a small series of patients with chronic lymphocytic leukemia (CLL), however its precise role in CLL pathophysiology remains elusive. In this study, CLL cells were found to predominantly express the membrane isoform of SCF that is known to elicit a more robust activation of the c-kit receptor. SCF was significantly overexpressed in CLL cells compared to healthy tonsillar B cells whilst it correlated with adverse-prognostic biomarkers, shorter time-to-first treatment and shorter overall survival. Activation of immune receptors and long-term cell-cell interactions with the mesenchymal stroma led to an elevation of SCF primarily in adverse-prognostic CLL cases. On the contrary, suppression of oxidative stress and the BTK inhibitor Ibrutinib negated SCF levels. Interestingly, SCF significantly correlated with mitochondrial dynamics and HIF-1α which have previously been linked with clinical aggressiveness in CLL. SCF was able to elicit direct biological effects in CLL cells affecting redox homeostasis and cell proliferation. Overall, the aberrantly expressed SCF in CLL cells emerges as a key response regulator to microenvironmental stimuli whilst correlating with poor prognosis. On these grounds, specific targeting of this inflammatory molecule could serve as a novel therapeutic approach in CLL

Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations and clinical impact

Recent evidence suggests that complex karyotype (CK) defined by the presence of 653 chromosomal aberrations (structural and/or numerical) identified by chromosome banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges towards routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with 655 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcome, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and or TP53 mutations, TP53abs) and the expression of somatically hypermutated (M-CLL) or unmutated (U-CLL) immunoglobulin heavy variable genes (IGHV). Thus, they contrasted CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs and IGHV gene somatic hypermutation status, we propose a novel hierarchical model where patients with high-CK exhibit the worst prognosis, while M-CLL lacking CK or TP53abs as well as CK with +12,+19 show the longest overall survival. In conclusion, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with 655 chromosomal aberrations emerges as prognostically adverse, independently of other biomarkers. Prospective clinical validation is warranted before finally incorporating high-CK in risk stratification of CLL

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

Transforming scholarship in the archives through handwritten text recognition:Transkribus as a case study

Purpose: An overview of the current use of handwritten text recognition (HTR) on archival manuscript material, as provided by the EU H2020 funded Transkribus platform. It explains HTR, demonstrates Transkribus, gives examples of use cases, highlights the affect HTR may have on scholarship, and evidences this turning point of the advanced use of digitised heritage content. The paper aims to discuss these issues. - Design/methodology/approach: This paper adopts a case study approach, using the development and delivery of the one openly available HTR platform for manuscript material. - Findings: Transkribus has demonstrated that HTR is now a useable technology that can be employed in conjunction with mass digitisation to generate accurate transcripts of archival material. Use cases are demonstrated, and a cooperative model is suggested as a way to ensure sustainability and scaling of the platform. However, funding and resourcing issues are identified. - Research limitations/implications: The paper presents results from projects: further user studies could be undertaken involving interviews, surveys, etc. - Practical implications: Only HTR provided via Transkribus is covered: however, this is the only publicly available platform for HTR on individual collections of historical documents at time of writing and it represents the current state-of-the-art in this field. - Social implications: The increased access to information contained within historical texts has the potential to be transformational for both institutions and individuals. - Originality/value: This is the first published overview of how HTR is used by a wide archival studies community, reporting and showcasing current application of handwriting technology in the cultural heritage sector

Subtotal Occlusion of Left Anterior Coronary Artery in a Professional Athlete

Screening for cardiovascular disease in athletes is crucial to avoid life-threatening complications. Here, we present the case of a fairly asymptomatic young professional soccer player with several cardiovascular risk factors, who proved to have significant coronary artery disease on coronary computed tomography which was ordered based on clinical suspicion and his family history. Informed consent for publication was obtained from the patient. (C) 2018 S. Karger AG, Base