scholarly journals FEATURES OF THE CLINICAL COURSE OF ROTAVIRUS INFECTION IN CHILDREN INFECTED WITH HERPES VIRUSES AND THEIR BLOOD INTERLEUKIN REACTIONS

2019 ◽  
Vol 6 (2) ◽  
pp. 101-105
Author(s):  
Margaryta Sliepchenko
Keyword(s):  
Time Course ◽  
Clinical Course ◽  
Economic Damage ◽  
Herpes Viruses ◽  
Social Significance ◽  
Immunological Parameters ◽  
Rotavirus Infection ◽  
Negative Effect ◽  
Group 2 ◽  
Herpes Group

FEATURES OF THE CLINICAL COURSE OF ROTAVIRUS INFECTION IN CHILDREN INFECTED WITH HERPES VIRUSES AND THEIR BLOOD INTERLEUKIN REACTIONS Sliepchenko M.Yu. Background. The widespread prevalence of intestinal infections of rotavirus etiology, the economic damage caused by it and the difficulties of treating patients cause the medical and social significance of this pathology. Along with this, a herpes virus infection and its negative effect on the immune response of the human body is a pressing problem. The purpose of the study is to identify the characteristics of presentation and the course of rotavirus infection in children infected with herpes viruses, and to establish the characteristics of the reaction of interleukins in their blood. Subjects and Methods. 38 children aged one to three years with moderate and severe forms of intestinal infection rotavirus etiology, who received appropriate treatment were examined. The children were divided into two groups: Group 1 included 18 children who did not have a background infection and Group 2 comprised 20 patients with acute rotavirus infection who were infected with herpes viruses. Along with the generally accepted clinical and laboratory examination, the levels of interleukins 1β, 4, TNFα in the blood serum in the time course of the disease were determined by an ELISA method for all children. Results. Assessment of clinical and immunological parameters of rotavirus infection in children showed that infection with viruses of the herpes group contributed to a less severity of symptoms of the disease at the initial stage, but longer persistence, which was probably due to insufficient reaction of proinflammatory interleukins in blood in the acute period at relatively high levels during the course of the disease. Keywords: clinic, children, cytokines, herpes and rotavirus infections.   Резюме. ОСОБЛИВОСТІ КЛІНІЧНОГО ПЕРЕБІГУ РОТАВІРУСНОЇ ІНФЕКЦІЇ У ДІТЕЙ, ІНФІКОВАНИХ ГЕРПЕСВІРУСАМИ, І РЕАКЦІЇ ІНТЕРЛЕЙКІНІВ ЇХ КРОВІ Слєпченко М.Ю.Вступ. Широка розповсюдженість кишкових інфекцій ротавірусної етіології, спричинені нею економічні збитки і труднощі терапії хворих обумовлюють медичне і соціальне значення зазначеної патології. Поряд з цим, актуальною проблемою є герпесвірусна інфекція і її негативний вплив на імунну відповідь організму людини. Мета дослідження полягає у виявленні особливостей клінічної картини і перебігу ротавірусної інфекції у дітей, інфікованих герпесвирусами, а також, встановлення особливостей реакції інтерлейкінів їх крові. Суб’єкт та методи. Для реалізації мети нами було обстежено 38 дітей у віці одного - трьох років, хворих на середньотяжкі і тяжкі форми кишкової інфекції ротавірусної етіології, з приводу якої вони отримували відповідне лікування. Діти були розділені на дві групи: перша група - 18 дітей не мали фонового інфікування і друга група- 20 хворих, що переносили РВИ на тлі інфікування їх різними герпесвирусами. Поряд із загальноприйнятим клініко-лабораторним обстеженням усім дітям визначалися рівні інтерлейкінів 1β, 4, ФНО в сироватці крові в динаміці хвороби імуноферментним методом. Результати. При аналізі клініко-імунологічних параметрів ротавірусної інфекції у дітей встановлено, що інфікування вірусами групи герпес сприяє меншій виразності симптомів хвороби на початковому етапі, але більш тривалого їх збереження, що, ймовірно, обумовлено недостатньо вираженою реакцією прозапальних інтерлейкінів крові дітей в гострий період, і збереженням їх на відносно високому рівні протягом хвороби.Ключові слова: діти, герпес- і ротавірусна інфекції, клініка, цитокіни.   Резюме. ОСОБЕННОСТИ КЛИНИЧЕСКОГО ТЕЧЕНИЯ РОТАВИРУСНОЙ ИНФЕКЦИИ У ДЕТЕЙ, ИНФИЦИРОВАННЫХ ГЕРПЕСВИРУСАМИ, И РЕАКЦИИ ИНТЕРЛЕЙКИНОВ ИХ КРОВИ.  Слепченко М.Ю. Вступление. Широкая распространенность кишечных инфекций ротавирусной этиологии, наносимый ею экономический ущерб и трудности терапии больных обуславливают медицинское и социальное значение указанной патологии.  Наряду с этим, актуальной проблемой является герпесвирусная инфекция и ее негативное влияние на имунный ответ организма человека. Цель исследования заключается в выявлении особенностей клинической картины и течения ротавирусной инфекции у детей, инфицированных герпесвирусами, а также, установлении особенностей реакции интерлейкинов их крови. Субъект и методы. Для реализации цели  нами было обследовано 38  детей в возрасте одного - трех лет, больных  среднетяжелыми и тяжелыми формами кишечной инфекции ротавирусной этиологии, по поводу которой они получали соответствующее лечение. Дети были разделены на две группы: первая группа - 18 детей не имели фонового инфицирования и вторая группа - 20  пациентов, переносили РВИ на фоне инфицирования их различными герпесвирусами. Наряду с общепринятым клинико-лабораторным обследованием всем детям определялись уровни интерлейкинов 1β, 4, ФНОα в сыворотке крови в динамике болезни иммуноферментным методом. Результаты. При анализе клинико-иммунологических параметров ротавирусной инфекции у детей установлено, что инфицирование вирусами группы герпес способствует меньшей выраженности симптомов болезни на начальном этапе, но более длительному их сохранению, что, вероятно, обусловлено недостаточно выраженной реакцией провоспалительных интерлейкинов крови детей в острый период, и сохранением их на относительно высоких цифрах в течении болезни. Ключевые слова: дети, герпес- и ротавирусная инфекции, клиника, цитокины.

scholarly journals CLINICAL AND IMMUNOLOGICAL FEATURES OF ROTAVIRUS GASTROENTERITIS IN CHILDREN INFECTED WITH HERPES VIRUSES

World Science ◽  
2019 ◽  
Vol 1 (12(52)) ◽  
pp. 20-24
Author(s):  
Sergiy Kuznecov ◽  
Marharyta Sliepchenko
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Comparative Analysis ◽  
Herpes Viruses ◽  
Immunological Parameters ◽  
Rotavirus Infection ◽  
Long Period ◽  
Rotavirus Gastroenteritis

The article presents the results of a comparative analysis of clinical and immunological parameters in children with rotavirus gastroenteritis without background infection and those infected by herpes viruses. It was established that in children with rotavirus infection (RVI) on the background of infection by herpes viruses occurs with less pronounced symptoms of intoxication and a less frequency of vomiting at the onset of the disease, in combination with longer duration (more long period) of fever and diarrheal syndrome. Such features are probably associated with the formation of a hypergical regime of the functioning of the immune response in the group of patients with background infection by herpes viruses, in contrast to patients with mono- RVI, in whom the immune system functions in a normal compensation mode.

Different Morphology of Neuritic Plaques in the Archicortex of Alzheimer’s Disease with Comorbid Synucleinopathy: A Pilot Study

2020 ◽  
Vol 17 ◽  
Author(s):  
Nikol Jankovska ◽  
Tomas Olejar ◽  
Jaromir Kukal ◽  
Radoslav Matej
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pilot Study ◽  
Time Course ◽  
Clinical Course ◽  
Lewy Bodies ◽  
Dystrophic Neurites ◽  
Neuritic Plaques ◽  
Structural Differences ◽  
Lewy Body Variant

Background: Bulbous neuritic changes in neuritic plaques have already been described, and their possible effect on the clinical course of the disease has been discussed. OBJECTIVE: In our study, we focused on the location and density of these structures in patients with only Alzheimer’s disease (AD) and patients with AD in comorbidity with synucleinopathies. Methods: Utilizing immunohistochemistry and confocal microscopy, we evaluated differences of neocortical and archicortical neuritic plaques and the frequency of bulbous changes in the archicortex of 14 subjects with Alzheimer’s disease (AD), 10 subjects with the Lewy body variant of Alzheimer's disease (AD/DLB), and 4 subjects with Alzheimer's disease with amygdala Lewy bodies (AD/ALB). Also, the progression and density of neuritic changes over the time course of the disease were evaluated. Results: We found structural differences in bulbous dystrophic neurites more often in AD/DLB and AD/ALB than in pure AD cases. The bulbous neuritic changes were more prominent in the initial and progressive phases and were reduced in cases with a long clinical course. Conclusion: Our results indicate that there is a prominent difference in the shape and composition of neocortical and archicortical neuritic plaques and, moreover, that bulbous neuritic changes can be observed at a higher rate in AD/DLB and AD/ALB subjects compared to pure AD subjects. This observation probably reflects that these subacute changes are more easily seen in the faster clinical course of AD patients with comorbidities.

Cytomegalovirus-Associated Hemophagocytic Syndrome

PEDIATRICS ◽  
1985 ◽  
Vol 75 (2) ◽  
pp. 280-283
Author(s):  
ELIZABETH H. DANISH ◽  
BEVERLY B. DAHMS ◽  
MARY L. KUMAR
Keyword(s):  
Viral Infection ◽  
Epstein Barr Virus ◽  
Hemophagocytic Syndrome ◽  
Clinical Course ◽  
Underlying Disease ◽  
Barr Virus ◽  
Pathologic Findings ◽  
Immunosuppressed Patients ◽  
Epstein Barr ◽  
Herpes Group

Virus-associated hemophagocytic syndrome, first described by Risdall and co-workers in 1979,1 is a rare histiocytic proliferative syndrome characterzed by fever, hepatosplenomegaly, pancytopenia, and erythrophagocytosis by histiocytes that appear benign by histologic criteria. The clinical course and pathologic findings may be identical with another histiocytic disorder, familial erythrophagocytic lymphohistiocytosis, which occurs predominantly in infants. Diagnosis of virus-associated hemophagocytic syndrome depends entirely on evidence of concurrent viral infection, usually of the herpes group. Epstein-Barr virus has been associated with this syndrome in the few cases reported in children without underlying disease, whereas cytomegalovirus (CMV) has been implicated in immunosuppressed patients. We report a case of fatal CMV-associated hemophagocytic syndrome which occurred in a previously healthy infant.

Mathematical Examination of Dual Individualization Principles (III): Development of a Scoring System for Pneumonia Staging and Quantitation of Response to Antibiotics: Results in Cefmenoxime-Treated Patients

1992 ◽  
Vol 26 (11) ◽  
pp. 1358-1365 ◽  
Author(s):  
Aileen Luzier ◽  
Thomas F. Goss ◽  
Thomas J. Cumbo ◽  
Jerome J. Schentag
Keyword(s):  
Clinical Improvement ◽  
Antimicrobial Therapy ◽  
Scoring System ◽  
Time Course ◽  
Clinical Course ◽  
Clinical Status ◽  
Gram Stain ◽  
Retrospective Data Collection ◽  
The Mean ◽  
Important Time

OBJECTIVE: In order to quantitatively express the important, time-related aspects of response to antimicrobial therapy in patients with pneumonia, we required validated measures of the time course of events during the infection. To quantitate the changes in clinical status in relation to changes in cultures, we developed a scoring system to be used for patient assessment during therapy. DESIGN: Retrospective data collection, prospective analysis of factors. SETTING: Intensive care unit, Millard Fillmore Hospital. PATIENTS: Twenty-eight patients with nosocomial pneumonia. MAIN OUTCOME MEASURES: Clinical parameters were assessed daily for the duration of antimicrobial therapy. Using linear regression, the rate of clinical change in each patient treated was quantified. Eradication of the pathogen was determined by serial cultures of the infection site. RESULTS: Seventeen of the patients demonstrated eradication of the organism, and 11 demonstrated persistence of the pathogen (7 were considered colonization). The system described the patients at baseline in that the mean baseline scores were similar in both groups of patients (p=0.79). Patients in whom the pathogen was eradicated showed a rate of clinical improvement significantly different from those who had persistence of the organism (p=0.04). In patients demonstrating eradication, the time to eradication inversely correlated with the rate of clinical improvement (p<0.05). Of the ten parameters descriptive of the disease, those most sensitive to change after eradication of bacteria were body temperature, bacterial Gram stain, white blood cell Gram stain, and volume of sputum. CONCLUSIONS: In this set of pneumonia patients, the scoring system effectively quantified both baseline and time-related changes in clinical status. The system distinguished between the clinical course of the patient with organism eradication versus organism persistence. A shorter time to eradication was associated with a better clinical response. Prospective study of the system will determine its sensitivity.

scholarly journals The toxicity of fumonisin B1on some biochemical and immunological parameters and its detoxification by red cabbage and garlic

2021 ◽  
pp. 1467-1476
Author(s):  
Mohanad S. Al-Fayyadh ◽  
Shatha Abdul Wadood
Keyword(s):  
Thyroid Gland ◽  
Fumonisin B1 ◽  
Garlic Extract ◽  
Protective Effects ◽  
Male Mice ◽  
Immunological Parameters ◽  
Red Cabbage ◽  
Group 2 ◽  
Cabbage Extract ◽  
Biochemical Examination

The protective effects of red cabbage and garlic extracts against liver, kidney and thyroid gland  damage induced by fumonisin B1 (FB1) in male mice were studied. Sixty mice divided in to six groups. Group one are the healthy mice, Group two are mice that received a daily oral dose of only FB-1 (100 µg/kg.b.w) for 1 month, Group three: are mice that received   red cabbage extract (500 mg/kg.bw) plus FB1, Group four: are mice that received  red cabbage extracts, Group five: are mice that received  garlic extract (500mg/kg.bw) plus FB1, group 6:are mice that received only garlic extract. After finishing   the experiments, samples of blood  were used for biochemical examination. The results indicated that group (2) mice treated with fumonisin B1 had significantly increased levels of immunoglobulins (IgG and IgM), kidney function parameters (urea  and creatinine), proteins (albumin and total protein (TP)), and thyroid hormones (T3 and T4), along with significantly decreased level of TSH (p < 0.05). In the LD50 experiment, we are choose concentration (100 µg/kg.b.w) gavage to the mice. Oral administration    red cabbage  garlic extracts produced significantl reduction the levels  serum  IgG, IgM, T3, T4, urea, creatinine, TP and albumin and with a significant increase in TSH.

scholarly journals Optimization of Therapeutic Measurements in Rotavirus Infection in Infants with Perinatal Exposure to HIV

2016 ◽  
Vol 22 (2) ◽  
pp. 2016213
Author(s):  
Hryhoriy Trotskyy
Keyword(s):  
Serum Level ◽  
Antibiotic Therapy ◽  
Antimicrobial Therapy ◽  
Clinical Course ◽  
Inflammatory Activity ◽  
Perinatal Exposure ◽  
Procalcitonin Level ◽  
Rotavirus Infection ◽  
Basic Treatment

The features of the clinical course of rotavirus infection in infants with perinatal exposure to HIV were studied. Serum level of procalcitonin as a marker of inflammatory activity and the need for antimicrobial therapy was determined. The efficiency of the proposed additions to basic treatment (low-lactose mixture for two months, antibiotic therapy in case of elevated procalcitonin level) was demonstrated.

Exploring the Social Impact of Foreign Direct Investment on Institutional Change

2016 ◽  
pp. 198-214
Author(s):  
Natalya Smith ◽  
Ekaterina Thomas
Keyword(s):  
Foreign Direct Investment ◽  
Institutional Change ◽  
Direct Investment ◽  
Multinational Firms ◽  
Social Impact ◽  
Positive Impact ◽  
Social Significance ◽  
The Social ◽  
Negative Effect ◽  
Positive Direct

Despite the vast and growing literature on the economic impact of foreign direct investment (FDI), its social significance is somewhat a neglected issue. Focusing on Russia, this chapter examines the effect of FDI and (formal) institutions (proxied, alternatively, by the [1] accumulated stock of small and medium sized firms or SMEs and [2] number of economic crimes per 100,000 population or corruption) on (informal) institutional change (proxied by the change in the number of violent and property crimes per 100,000 population). The empirical findings provide robust support for a significantly positive direct impact of SMEs, whilst observing a significantly negative effect of corruption and either significantly positive impact of FDI or insignificant effect of multinational firms in this context.

scholarly journals Different Visual Weighting due to Fast or Slow Vestibular Deafferentation: Before and after Schwannoma Surgery

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Fredrik Tjernström ◽  
Per-Anders Fransson ◽  
Babar Kahlon ◽  
Mikael Karlberg ◽  
Sven Lindberg ◽  
...  
Keyword(s):  
Postural Control ◽  
Spatial Orientation ◽  
Visual Cues ◽  
Time Course ◽  
Vestibular Function ◽  
Sensory Systems ◽  
Vestibular Loss ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background. Feedback postural control depends upon information from somatosensation, vision, and the vestibular system that are weighted depending on their relative importance within the central nervous system. Following loss of any sensory component, the weighting changes, e.g., when suffering a vestibular loss, the most common notion is that patients become more dependent on visual cues for maintaining postural control. Dizziness and disequilibrium are common after surgery in schwannoma patients, which could be due to interpretation of the remaining sensory systems involved in feedback-dependent postural control and spatial orientation. Objective. To compare visual dependency in spatial orientation and postural control in patients suffering from unilateral vestibular loss within different time frames. Methods. Patients scheduled for schwannoma surgery: group 1 (n=27) with no vestibular function prior to surgery (lost through years), group 2 (n=12) with remaining vestibular function at the time of surgery (fast deafferentation), and group 3 (n=18) with remaining function that was lost through gentamicin installations in the middle ear (slow deafferentation). All patients performed vibratory posturography and rod and frame investigation before surgery and 6 months after surgery. Results. Postural control improved after surgery in patients that suffered a slow deafferentation (groups 1 and 3) (p<0.001). Patients that suffered fast loss of remaining vestibular function (group 2) became less visual field dependent after surgery (p≤0.035) and were less able to maintain stability compared with group 1 (p=0.010) and group 3 (p=0.010). Conclusions. The nature and time course of vestibular deafferentation influence the weighting of remaining sensory systems in order to maintain postural control and spatial orientation.

Effect of the Adminstration of Rituximab between Mobilization Chemotherapy and Leukapheresis on Stem Cell Collection Parameters: A Study of Fifty NHL Patients Mobilized Using Intermediate Dose Cyclophosphamide and Sequential GM-CSF and G-CSF.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2874-2874
Author(s):  
Asad Bashey ◽  
Lin Liu ◽  
Anita Ihasz ◽  
Ewa Carrier ◽  
Januario Castro ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Time Course ◽  
Cumulative Probability ◽  
Gm Csf ◽  
Cd34 Cells ◽  
Group 2 ◽  
Stem Cell Collection ◽  
Intermediate Dose ◽  
Group 1

Abstract We have previously reported that intermediate dose cyclophosphamide followed by sequential GM-CSF and G-CSF (iCy/GM/G) provides efficient mobilization for patients undergoing autografting. Furthermore, the predictable time course of mobilization with this regimen obviates the need for weekend leukaphereses (Blood 2003: 957a). Recently, the addition of rituximab to mobilization regimens for B-cell NHL has been shown to be effective at depleting contaminating B-cells from the leukapheresis product. However, the effect of rituximab administered for in-vivo purging, on mobilization and stem cell collection parameters is unclear. We compared leukapheresis (LP) yield parameters, and the time course of stem cell mobilization in 23 consecutive B-cell NHL patients mobilized with iCy/GM/G plus rituximab (group 1) with 27 consecutive B-cell NHL patients mobilized with the same regimen without rituximab (group 2). The iCy/GM/G regimen consisted of cyclophosphamide 1.5g/m2 (d1), GM-CSF 500 mcg/d (d 3–7), G-CSF (d 8 until completion of LP) 600mcg/d for weight ≤80kg, 960 mcg for weight &gt; 80 kg. Rituxan was administered at 375mg/m2 as a single dose on d8. LP was begun on d 11 irrespective of WBC. D1 was usually a Friday in order to avoid weekend LP. Patients underwent up to 20 liter LP for ≤ 5 days (median =3, range 1–5 for both groups) with a target collection of &gt; 5 x 10e6 CD34+ cells/kg. The groups were well matched for median age, gender, number of prior chemotherapy regimens (median=2 for both groups), prior pelvic XRT and histological subtype of B-NHL (p=NS in all cases). The estimated (Kaplan-Meier) cumulative probability of achieving a target collection of 2 x 10e6 CD34+ cells/kg on d 1–5 was 0.43, 0.70, 0.78, 0.84, 0.84 respectively for group 1 and 0.22, 0.69, 0.77, 0.84, 0.84 respectively for group 2. The corresponding probabilites of achieving 5 x 10e6 CD34+ cells/kg on d 1–5 were 0.22, 0.39, 0.57, 0.57, 0.57 (group 1) and 0.11, 0.30, 0.46, 0.59, 0.59 (group 2) (p=NS Log-rank test). Percentage of CD34+ cells in the LP product (LP CD34%) was measured daily. Maximums LP CD34% was seen on LP d1 for both groups with a fall on subsequent days (p=NS between groups 1 and 2). Toxicities experienced were generally mild consisting mostly of bone pain and fevers and were similar in both gropups. No patient required admission for febrile neutropenia. The number of CD34+ cells infused were similar for both groups (median 5.9 vs.5.7 x10e6 CD 34+ cells/kg). Median time to reach ANC &gt; 500/mm3 and platelets &gt; 20,000/mm3 were identical between groups 1 and 2 (d11 and d 10 respectively). These data show that the addition of rituximab administered on d 8 to the iCy/GM/G regimen in patients with B-NHL does not impair the yield of CD34+ cells, or the tolerability of the regimen. Furthermore, the time course of the mobilization and therefore the predictbility of the collection is not compromised. Maximum cumulative yield of CD34+ cells is achieved within 4 days of LP with no patient benefitting from a fifth day of collection. The additional cost and inconvenience of weekend leukapheresis can be avoided in all cases using this regimen.

13q14 Chromosome Deletion Size and Number of Deleted Cells Influence Prognosis In Chronic Lymphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3578-3578
Author(s):  
Francesca Maria Rossi ◽  
Davide Rossi ◽  
Clara Deambrogi ◽  
Francesco Bertoni ◽  
Michele Dal Bo ◽  
...  
Keyword(s):  
Clinical Course ◽  
Lymphocytic Leukemia ◽  
Single Institution ◽  
Group 4 ◽  
Median Size ◽  
Mutational Status ◽  
Genome Wide ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Abstract 3578 Introduction: Chronic lymphocytic leukemia (CLL) patients bearing 13q14 deletion are known to experience a more favorable clinical course. Recent studies, focusing on patients with loss of 13q as the sole cytogenetic aberration at diagnosis (del13q-only cases), showed that the number of malignant cells carrying this genetic lesion correlates with a more aggressive clinical behavior. However, whether the size of the 13q deletion may also influence the clinical outcome remains to be elucidated. Patients and Methods: Probes for chromosome 13q (LSI-RB1, LSI-D13S319), 11q (LSI-ATM), 17p (LSI-p53) and chromosome 12 (CEP12) were utilized on nuclei collected at diagnosis from: i) a multi-institutional CLL cohort (342 del13q-only cases) and ii) a consecutive unselected single-institution cohort of 265 cases. RB1 deleted cases (delRB1) were defined as having at least 5% of deleted nuclei. Time to treatment (TTT) intervals, as well as Rai staging, IGHV mutational status, CD38 and ZAP70 expression, B2-microglobulin levels, all evaluated at diagnosis, were also available for all cases that entered the study. Genome wide DNA profile was performed in a pilot series of 90 CLL samples using Affymetrix GeneChip Human SNP6 arrays. Results: According to genome wide DNA analysis, delRB1 occurred in a proportion of del13q-only cases (36/90; 40%), always comprising the deleted region detected with the LSI-D13S319 probe (that covers the miR-15a/16-1 cluster and the DLEU2 gene) and characterized by a larger chromosome loss (median size 2.07 Mb vs. a median size of 0.86 Mb for the canonical del13S319). Maximally selected log-rank statistics identified the 70% of nuclei bearing del13S319 as the most appropriate cut-off value capable of separating del13q-only cases into two subgroups with different TTT distributions. Consistently, del13q-only cases with at least 70% of nuclei bearing del13S319 showed a significantly shorter TTT than del13q-only cases with less than 70% deleted nuclei (p=0.0001). Del13q-only cases were then divided in four subsets according to the percentage of nuclei bearing del13S319 with or without a concomitant delRB1: del13S319 <70% (group 1), 144 cases; del13S319 <70% + delRB1 (group 2), 95 cases; del13S319 >70% (group 3), 64 cases; del13S319 >70% + delRB1 (group 4), 39 cases. The median TTT of group 1 (not reached) was significantly longer than the median TTT of group 2 (92 months, p=0.012), group 3 (68 months, p<0.0001), and group 4 (82 months, p=0.0025; see Fig. 1A). Multivariate Cox proportional hazard analyses selected the presence of delRB1 (p=0.029), along with the IGHV mutational status (p<0.0001), as an independent negative prognosticator in the context of del13q-only cases with low/intermediate Rai risk (Rai stage of 0/I at diagnosis) and <70% of del13S319. Cases belonging to the consecutive unselected single-institution CLL cohort were divided into subsets according to the classification proposed by Döhner et al (NEJM, 2000). Notably, the presence of del13S319 in <70% of cells in the absence of delRB1 identified a patient subset with particularly stable and benign clinical course (group A in Fig. 1B, 48 cases; median TTT not reached). Conversely, patients characterized by del13S319 in <70% of cells but with a larger deletion, as determined by concomitant delRB1 (group B, 24 cases), or del13S319 in >70% of cells (with or without delRB1, group C, 25 cases) or a normal karyotype (group D, 75 cases) had shorter median TTT intervals (ranging from 105 to 129 months, p<0.01 in all the comparisons). Finally, patients affected by CLL bearing trisomy 12 (group E, 48 cases) and del11q or del17p (group F, 45 cases) experienced the worst clinical courses (p<0.0001). Conclusion: In the context of del13q-only cases, different clinical outcomes were associated to the percentage of 13q14 deleted cells, as well as to the size of the 13q14 deletion, as detected by the LSI-RB1 probe. Moreover, the presence of delRB1 emerged as a feature capable of refining the prognostic assessment in the context of CLL cases with <70% del13S319. The underlying genetic mechanisms correlated with the different clinical outcomes and associated with the size of the 13q deletion are presently under investigation. Disclosures: No relevant conflicts of interest to declare.

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