Spleen Length Research Articles

Presentation and Outcome of 199 Patients with 2016 Who Diagnosis of Early and Overt Primary Myelofibrosis Treated with Ruxolitinib

Presentation and Outcome of 199 Patients with 2016 Who Diagnosis of Early and Overt Primary Myelofibrosis Treated with Ruxolitinib

Beyond JAK2 Inhibitors: A Systematic Review of Management Strategies for Myelofibrosis

IntroductionDrugs that target activating mutations of Janus Kinase 2 (JAK2) have been the backbone of myelofibrosis (MF) management. With recent advancements in our understanding of the underlying molecular mechanisms involved in myelofibrosis (MF) pathogenesis, numerous novel agents have been developed in the last decade. We have systematically reviewed the mechanisms of actions, efficacy and safety of these drugs.MethodsA comprehensive literature research was performed using PubMed, Cochrane, EMBASE, Web of Science and Clinicaltrials.gov. We included all trials that were under development in phase I/II/III trials. Our search identified 1642 full-length manuscripts or abstracts with published results in the last decade were screened for relevant studies. Of these, 212 articles were finalized for our final analyses.ResultsHedgehog inhibitors (saridegib, glasdegib and sonidegib) targets signaling membrane protein, smoothened. The combination of sonidegib + ruxulotinib (RUX) elicited the best response. Spleen volume reduction (SVR) ≥35% and spleen length reduction (SLR) ≥50% was reported in 15 (55.6%) and 25 (92.6%) patients.Histone deacetylase inhibitors (panobinostat, pracinostat, vorinostat, givinostat) target JAK2-H3Y41-HP1 pathway involved in hematopoiesis and leukemogenesis. The combination of pracinostat + RUX demonstrated the best response in a phase II trial (n=22), with clinical improvement (IWG-MRT) in splenomegaly, symptoms and both were reported in four (18%), two (9%), and ten (45%) patients that were durable for a median of 7.5 months.Immunomodulators: Lenalidomide has shown anemia responses in 32% of patients in combination with prednisone, in a phase II trial (n=40). Improvement in bone marrow fibrosis (10/11 patients with G4 reduced to G2 or better) was also seen. Pomalidomide with or without prednisone has shown anemia responses varying from 17-24% across different trials. However, a recent phase III trial (n=32) comparing pomalidomide vs. placebo, found no difference in transfusion independence rates (16% vs. 16%, p=1.00).Azacytidine (AZA) and decitabine (DCB) are hypomethylating agents. An objective response rate (ORR) of 69% (n=39) with AZA+RUX was noted. DCB+RUX demonstrated an ORR of 57% with a median overall survival of 10.4 months, in a phase I trial (n=21).Imetelstat is a telomerase inhibitor that has shown an ORR of 21% among 33 MF patients. Responses were characterized by BMF improvement (n=4) and transfusion independence (3/7 responders).Anti Fibrotics: PRM 151, a recombinant pentraxin-2, has shown an ORR of 35% in a phase II trial (n=27). Anemia response was noted in 6/15 (40%) patients and BMF improvement in two patients, durable up to 72 weeks. Simtuzumab, an antibody lysysl oxidase like-2 (LOXL2) enzyme, failed to show any clinical benefit in a phase II study of 54 patients.Sotatercept and luspatercept are ligand “traps” that limit the activity of TGF-B superfamily ligands, involved in erythroid differentiation. Sotatercept monotherapy achieved transfusion independence (TI) in six (35%) of 17 evaluable patients. Luspatercept has recently been under investigation in patients with MF (NCT03194542).LCL-161 is a second mitochondrial activator of caspases (Smac)-mimetic, A phase II clinical trial (n=33) found an ORR of 30% (n=9). Five (56%) of the nine responders achieved anemia responses.Buparilisib and everolimus targets the PI3K/mTOR pathway. Buparilisib, a PI3K inhibitor, demonstrated a SLR ≥ 50% in 72% patients whereas everolimus, an mTOR inhibitor, showed an ORR of 23%.ConclusionThe combination of ruxolitinib with some of these novel agents such as hedgehog inhibitors and hypomethylating agents have shown promising efficacy with response rates of more than 40%. LCL-161 and sotatercept has been reassuring with respect to anemia management, achieving response rates of more than 30%. PRM-151 has shown durable responses and will be the first antifibrotic for MF, if approved. Even though initial results with some of these novel agents have been ground breaking, there is a need to further explore pathways that can be targeted to help prolong survival and modify the disease course in MF patients. DisclosuresNo relevant conflicts of interest to declare.

Prognostic Role of Neutrophil to Lymphocyte Ratio (NLR) in Myelofibrosis Patients Treated with Ruxolitinib: A Multi-Center Experience

Prognostic Role of Neutrophil to Lymphocyte Ratio (NLR) in Myelofibrosis Patients Treated with Ruxolitinib: A Multi-Center Experience

Esplenectomía laparoscópica, una opción eficaz en un hospital de segundo nivel

Laparoscopic splenectomy was reserved for selected cases, however and because of the improvement in surgical technique and laparoscopic instruments, nowadays, there are few contraindications. Retrospective and observational study of patients surgically treated of laparoscopic splenectomy secondary to hematologic diseases in a period span of 6 years. We analyzed demographic, preoperative, transoperative and postoperative variables. We studied eight patients, 62.5% were men with a mean age of 47.5 years. The most frequent hematologic diagnosis was idiopathic thrombocytopenic purpura (50%). The approach was laparoscopic in 100%. Median surgical time was 129.87 min and median transoperative bleeding was 396.25 cc. Median length of resected spleen was 15 cm. Median time for oral feeding was 20.62 h and total hospital stay was 4 days. There was only one reported complication. Laparoscopic splenectomy represents a safe and feasible option with rapid recovery and few complications.

Role of liver and spleen stiffness in predicting the recurrence of hepatocellular carcinoma after resection

Hepatocellular carcinoma (HCC) is a frequent complication of liver disease. When feasible, hepatic resection is the first-choice therapy. However, tumor recurrence complicates at least 2/3 hepatic resections at 5 years. Early recurrences are mainly tumor or treatment-related, but predictors of late recurrences are undefined. We aimed to evaluate the factors related to HCC recurrence after curative resection, with liver and spleen stiffness measurement (LSM and SSM) as markers of severity and duration of the underlying liver disease. We enrolled patients with chronic liver disease and primary HCC suitable for hepatic resection. We followed up patients for at least 30 months or until HCC recurrence. We performed uni- and multivariate analyses to evaluate the predictive role of tumor characteristics, laboratory data, LSM and SSM for both early and late recurrence of HCC. We prospectively enrolled 175 patients. Early HCC recurrence at multivariate analysis was associated with viral etiology, HCC grading (3 or 4), resection margins <1 cm and being beyond the Milan criteria. HCC late recurrence at univariate analysis was associated with esophageal varices (hazard ratio [HR] 3.321, 95% CI 1.564-7.053), spleen length (HR 3.123, 95% CI 1.377-7.081), platelet/spleen length ratio if <909 (HR 2.170, 95% CI 1.026-4.587), LSM (HR 1.036, 95% CI 1.005-1.067), SSM (HR 1.046, 95% CI 1.020-1.073). HCC late recurrence at multivariate analysis was independently associated only with SSM (HR 1.046, CI 1.020-1.073). Late HCC recurrence-free survival was significantly different according to the SSM cut-off of 70 kPa (p = 0.0002). SSM seems to be the only predictor of late HCC recurrence, since it is directly correlated with the degree of liver disease and portal hypertension, both of which are involved in carcinogenesis. The main result of this study is that spleen stiffness measurement, evaluated by transient elastography, seems to be the only predictor of the late recurrence of hepatocellular carcinoma, defined as recurrence after 24 months from liver resection. Indeed, spleen stiffness measurement is directly correlated with the degree of liver disease and portal hypertension, which are both involved in carcinogenesis.

A phase 2 study of ruxolitinib in combination with azacitidine in patients with myelofibrosis

AbstractRuxolitinib (RUX)-based combinations may provide benefit for patients with myelofibrosis (MF). In this open-label, nonrandomized, prospective phase 2 study, patients with MF initially received RUX twice per day continuously in 28-day cycles for the first 3 cycles. Azacitidine (AZA) 25 mg/m2 (days 1-5) was added starting with cycle 4 and could be subsequently increased to 75 mg/m2 (days 1-5). Forty-six patients were enrolled with a median follow-up of 28 months (range, 4-50+ months). An International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) response was achieved in 33 patients (72%), with a median time to response of 1.8 months (range, 0.7-19.0 months). One-fourth (7 of 33) of the IWG-MRT responses occurred after the addition of AZA. A reduction of >50% in palpable spleen length at 24 weeks and at any time on the study was achieved in 62% and 71% of the evaluable patients, respectively. Among patients who achieved a >50% reduction in spleen length at 24 weeks, 95% had maintained it at 48 weeks. Notably, improvements in bone marrow reticulin fibrosis grade occurred in 57% of the patients at 24 months. Treatment discontinuations as a result of drug-related toxicities occurred in 4 patients (9%), all as a result of cytopenias. New onset grade 3 to 4 anemia and thrombocytopenia occurred in 35% and 26% of patients, respectively. RUX and AZA were safe, with encouraging spleen response rates and improvement in bone marrow fibrosis in patients with MF. This trial was registered at www.clinicaltrials.gov as #NCT01787487.

Local Reference of splenic volume in Healthy Sudanese Subjects Sonographically

This study was carried out to estimate normal linear dimensions and volume of the spleen in Sudanese using ultrasonography, and to keep it as standards reference for diagnostic purposes.This prospective study was done at Radiology Department, National Ribat University Hospital, Khartoum, Sudan, conducted on 108 volunteers (72 males and 36 females). All linear dimensions of spleen were measured, and splenic volume was calculated using ultrasonography. The splenic volume was then analyzed with age and body parameters using the Pearson’s correlation coefficient. Results of this study revealed that the mean values of the age, height, weight of subjects, spleen length (SL), spleen width (SW), spleen thickness (ST) and spleen volume were calculated were found to be 38.74±18.898years,163.11±17.747mm,65.33±15.431kg,91.07±11.330mm,37.59±7.440mm, 37.78±8.085mm and 70.63±31.924cm3 respectively. Age had no significant effect on spleen volume (p=0. 684). There was a significant positive correlation, using Pearson’s correlation coefficient, between the spleen volume, and other parameters (height p=0.000, and weight p=0.002. The present study concluded that a local reference of spleen dimensions was established with a different range of values reported previously.

Effects of endoscope combined with drug therapy on the hemorrhage of esophageal varicose veins in cirrhosis

Objective To observe the clinical effect of endoscope combined with drug therapy in the treatment of hemorrhage of esophageal and gastric varices in patients with cirrhosis, thus to provide reference for clinical diagnosis and treatment. Methods From January 2017 to January 2018, 58 liver cirrhosis patients with ruptured esophageal gastric varices bleeding in Tongji Huangzhou Hospital of Huazhong University of Science and Technology were selected and divided into two groups by random number table method, with 29 cases in each group.The control group was treated with somatostatin alone.The observation group was treated with somatostatin combined with endoscopic therapy.The clinical efficacy of the two groups was compared, and the clinical indicators and the changes of indices of TCM syndromes before and after treatment were compared between the two groups. Results The total effective rate of the observation group was 89.8%, which was higher than 79.3% of the control group, and the difference was statistically significant(χ2=9.75, P<0.01). After treatment, the pain, abdominal distention, poor appetite, nausea, weakness of the body tired, depression, boredom, loose stool and other syndromes index scores of two groups were improved obviously, the improvements in the observation group was better than those in the control group, and the differences were statistically significant(t=8.847, 9.470, 7.833, 8.120, 9.029, 8.120, 9.029, all P<0.05). After treatment, the white blood cells, platelets of the two groups were increased, the spleen length to diameter, thickness of spleen, portal venous trunk, spleen vein diameter of the two groups were reduced, the improvements in the observation group was better than those in the control group, and the differences were statistically significant(t=8.934, 8.923, 8.933, 9.463, 9.478, 9.463, all P<0.05). Conclusion Endoscope combined with drugs in the treatment of cirrhotic esophageal variceal hemorrhage has significant clinical efficacy, and can effectively improve the patients' TCM syndrome score and clinical indicators. Key words: Endoscopy; Somatostatin; Liver cirrhosis; Esophageal and gastric varices; Hemorrhage

Correlation Between Liver Stiffness Measured by Shear Wave Elastography and Child-Pugh Classification.

To explore the association between liver stiffness and the Child-Pugh classification of liver function by shear wave elastography (SWE). A total of 116 patients with liver cirrhosis were divided into 3 groups according to the Child-Pugh classification prospectively. Conventional ultrasound imaging and SWE were performed for all patients. The associations of liver stiffness measured by SWE with ultrasound measurements, serum biochemical indicators, and the Child-Pugh classification were analyzed. Receiver operating characteristic curves were analyzed and compared to determine the ability of liver stiffness to diagnose cirrhosis. Liver stiffness measured by SWE increased with an increasing Child-Pugh classification, internal diameter of the hepatic portal and splenic veins, spleen thickness, spleen length, total bilirubin level, and prothrombin time, which were positively correlated with the Child-Pugh classification (all P < .05). The albumin level and liver stiffness showed higher areas under the curve in comparison with other parameters for evaluating the Child-Pugh classification. Albumin and cholinesterase levels were negatively correlated with the Child-Pugh classification (P < .05). All of these indicators were significantly different between each pair of groups (all P < .05), except for the internal diameter of the hepatic portal vein, prothrombin time, and total bilirubin, and cholinesterase levels between groups B and C (P > 0.05) and the thickness and length of spleen and internal diameter of the splenic vein between groups A and B (P > 0.05). There were no differences among the groups for alanine aminotransferase, aspartate aminotransferase, and globulin levels. Liver stiffness measured by SWE was correlated with the Child-Pugh classification, and it may be able to help evaluate liver function in patients with cirrhosis.

Sonographic determination of liver and spleen sizes in patients with sickle cell disease at Gombe, Nigeria

Background: Ultrasonography is a safe, reproducible, and accurate diagnostic imaging modality in the evaluation of the effects of sickle cell anemia (SCA) on the sizes of liver and spleen. The study is aimed at determining the size of liver and spleen in SCA patients compared with that of healthy age-matched known normal hemoglobin genotype (HbAA) volunteers and also to correlate with some hematological parameters. Materials and Method: This is a prospective cross-sectional study conducted over a period of 1 year. A total number of 237 SCA patients attending the outpatient sickle cell clinic of Federal Teaching Hospital, Gombe and an equal number of apparently healthy known age-matched HbAA from the general public were recruited by a convenient sampling technique. Results: The mean size of liver span and spleen length in SCA patients was 13.12 ± 2.05 cm and 6.50 ± 1.75 cm, respectively, while that of the controls was 11.77 ± 1.491 cm and 7.62 ± 1.827 cm, respectively (P = 0.00 for both liver and spleen). The liver span in SCA patients was higher among all the ages, while the spleen length reduces after the first 10 years of age. There was a strong positive correlation between liver span and the age, weight, and height (r = 0.767, 0.830, and 0.826, respectively) in SCA patients. The liver span showed a significant relationship with packed cell volume, red blood cell, white blood cells, mean corpuscular hemoglobin (MCH), MCH concentration, and mean corpuscular volume (r = −0.181, −0.266,−0.299, 0.316, 0.206, and 0.309). There was no correlation between spleen size and hematological parameter. Conclusion: Ultrasound is a veritable tool in the estimation of liver and spleen sizes in SCA patients.

Ultrasonographic parameters of the liver, spleen and kidneys among a cohort of school children in Sri Lanka

BackgroundLiver, spleen and kidney dimensions on ultrasonography vary with the age, weight and ethnicity. Reference standards of these parameters for normal Sri Lankan children are not available. Our aim was to establish normative data for longitudinal length of liver, spleen and kidneys in healthy children.MethodThree hundred fifty-seven children, 5–13 years of age were selected from two randomly selected schools in the Gampaha district in the western province of Sri Lanka. A questionnaire was administered to the parents after obtaining informed written consent. Participants were screened for risk factors for organomegaly and were examined by a trained officer. Children with a past history of infective, inflammatory, haematological, malignant, congestive, collagenous or congenital conditions that can affect the size of the organs were excluded as well as those with clinically evident malnutrition, anemia, lymphadenopathy or organomegaly.Ultrasonographic assessment was done using a high resolution real-time scanner with a 3.5 MHz convex transducer by a trained officer. Children with ultrasonographic abnormalities of organs were also excluded from the study and referred for further evaluation.ResultsThe study comprised 332 children comprising 176 girls (53%). There was a significant difference in the longitudinal dimension of the liver between the two sexes with a higher value recorded among females (Mann Whitney U = 11,830.5, p = 0.037). Body weight was correlated with the dimensions of the liver, the spleen and the kidneys. On multiple regression analysis body weight significantly associated with all the organs. (p < 0.01) Percentile graphs for longitudinal length of liver, spleen, right and left kidneys were formed according to the body weight.ConclusionThe organ dimensions showed the highest correlation with body weight. We hope the normal ultrasonographic values of healthy Sri Lankan children will assist in interpretation of sonographic examinations in daily clinical practice.

Predictors of Severe Thrombocytopenia Secondary to Peginterferon Alfa-2a Treatment in Subjects With Hepatitis C Virus Infection.

In this study, we aim to identify patient characteristics that predict severe thrombocytopenia induced by peginterferon alfa-2a in hepatitis C virus-infected patients. Demographic, clinical, and genetic data collected from patients with chronic hepatitis C virus infection (n = 232; age ≥18 years) who received peginterferon alfa-2a following eltrombopag treatment. Predictors of severe thrombocytopenia (platelet count below 50 GI/L) were identified using a 2-step approach: First, univariate analysis, using χ test for categorical variables and t test for continuous variables, was performed to identify possible predictors of severe thrombocytopenia (P < 0.05). Second, a logistic regression with backward stepwise selection was then performed using predictors identified in univariate analysis step to produce final model containing independent predictors at P < 0.05. Logistic model identified several predictors of severe thrombocytopenia. Increased spleen length and increased alkaline phosphatase levels increases the likelihood of severe thrombocytopenia. However, being Central/South Asian, increased neutrophils count and increased platelet baseline count decreases the probability of developing severe thrombocytopenia. In summary, we identified several patient characteristics that predict severe thrombocytopenia induced by peginterferon alfa-2a. Early selection of individuals with high risk of developing interferon-associated severe thrombocytopenia allows early intervention (such as eltrombopag treatment). Early intervention in turn minimizes the odds of developing severe thrombocytopenia and allows the continual of antiviral therapy before patient progress into liver decompensation.

Acute Chest Syndrome as the Initial Presentation of a Patient With Hemoglobin SC

SESSION TITLE: Pulmonary Manifestations of Systemic Disease 3 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Acute Chest Syndrome (ACS) is a rare and potentially fatal complication of Hemoglobin SC disease (HbSC) that manifests by fevers, dyspnea, hypoxia, and new infiltrates on chest imaging. If recognized, treatment to reduce percentage of circulating HbS by simple red blood cell transfusion or large volume red blood cell exchange can effectively treat ACS respiratory failure. CASE PRESENTATION: A previously healthy 26-year-old man presented to the emergency department with a four day history of left sided abdominal and pleuritic chest pain. His vital signs revealed a temperature of 100.1 degree Fahrenheit, blood pressure of 160/103 mmHg, heart rate of 120/min, respiratory rate of 18/min and oxygen saturation of 97% on ambient air. Laboratory studies were significant for WBC of 33,200/uL, hemoglobin of 9.6 g/dL and serum creatinine of 2.8 mg/dL. CT chest and abdomen without contrast was significant for left lower lobe consolidation and spleen length of 17 cm. The patient was started on ceftriaxone and azithromycin and admitted to the MICU. Over the next 36 hours, patient developed worsening tachypnea and hypoxemia requiring non-invasive positive pressure ventilation. A repeat chest x-ray (CXR) (Figure A) when compared to the CXR from admission (Figure B) demonstrated diffuse airspace opacifications. A single diagnosis unifying pulmonary, renal, and hematologic systems was sought and hemoglobin electrophoresis revealed a pattern of 52% hemoglobin S and 48% hemoglobin C. Patient was transfused one unit of packed red blood cells and repeat quantitative hemoglobin S was 32%. Over the following 12-24 hours, patient’s respiratory distress resolved. DISCUSSION: This case demonstrates a rare presentation of ACS in a patient who had no known history of sickle cell. Despite being the second most common hemoglobinopathy worldwide, diagnosis of HbSC is often delayed into adulthood due to decreased frequencies of complications compared to patients with sickle cell anemia. ACS in these patients can be fatal but is responsive to bland RBC transfusions or RBC exchange. CONCLUSIONS: Respiratory failure due to a previously unrecognized congenital condition in a previously healthy adult can be a challenging diagnosis. Although rare, ACS should remain a diagnostic consideration in patients without a history of sickle cell who are presenting with respiratory failure and new consolidation on imaging. RBC transfusion is an effective treatment in patients with HbSC who have ACS. Reference #1: Francois Lionnet et al. Haematologica. 2012; 97:1136-1141 Reference #2: Orah S. Platt. N Engl J Med 2000;343(8):591 Reference #3: Elliott P Vichinksy et al. Blood. 1997 89; 1787-1792 DISCLOSURE: The following authors have nothing to disclose: Garrett Rampon, Ghassan Kamel, Soophia Naydenov No Product/Research Disclosure Information

A phase 1 study of the Janus kinase 2 (JAK2)V617F inhibitor, gandotinib (LY2784544), in patients with primary myelofibrosis, polycythemia vera, and essential thrombocythemia

Mutations in Janus kinase 2 (JAK2) are implicated in the pathogenesis of Philadelphia-chromosome negative myeloproliferative neoplasms, including primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Gandotinib (LY2784544), a potent inhibitor of JAK2 activity, shows increased potency for the JAK2V617F mutation. The study had a standard 3+3 dose-escalation design to define the maximum-tolerated dose. Primary objectives were to determine safety, tolerability, and recommended oral daily dose of gandotinib for patients with JAK2V617F-positive myelofibrosis, essential thrombocythemia, or polycythemia vera. Secondary objectives included estimating pharmacokinetic parameters and documenting evidence of efficacy by measuring clinical improvement. Thirty-eight patients were enrolled and treated (31 myelofibrosis, 6 polycythemia vera, 1 essential thrombocythemia). The maximum-tolerated dose of gandotinib was 120mg daily, based on dose-limiting toxicities of blood creatinine increase or hyperuricemia at higher doses. Maximum plasma concentration was reached 4h after single and multiple doses, and mean half-life on day 1 was approximately 6h. Most common treatment-emergent adverse events were diarrhea (55.3%) and nausea (42.1%), a majority of which were of grade 1 severity. Best response of clinical improvement was achieved by 29% of myelofibrosis patients. A ≥50% palpable spleen length reduction was observed at any time during therapy in 20/32 evaluable patients. Additionally, ≥50% reduction in the Total Symptom Myeloproliferative Neoplasm Symptom Assessment Form Score was seen in 11/21 (52%) and 6/14 patients (43%) receiving ≥120mg at 12 and 24 weeks respectively. Gandotinib demonstrated an acceptable safety and tolerability profile, and findings at the maximum-tolerated dose of 120mg supported further clinical testing. Clinicaltrials.gov identifier: NCT01134120.

Sonographic Measurement of Spleen in Relation to Age: A Prospective Study among Adult Nepalese People in Western Nepal

Introduction: Splenomegaly is an enlargement of the spleen which is a quite common problem in any part of the world. Spleen is enlarged in various clinical disorders e.g. infections, metabolism or storage disor­ders and hematological abnormalities. Splenomegaly is an indicator of pathologic process that may be of primary splenic origin but also may be a reflection of disease in virtually any other organ system. Thus, it is important to estimate the splenic size in vivo in the diagnosis, treat­ment and prognosis of a variety of disorders.Objective: The objective of this study was to determine the normal dimension of the spleen in the adult Nepalese people.Methods: This is a prospective study in which 320 adults subjects were scanned by using 3.5 MHz curvilinear probe. We used ultrasonography to examine 160 males and 160 females, not to have any condition likely to be associated with splenic enlargement. The measurement for the length and thickness of spleen were obtained in right lateral position.Results: This study revealed the splenic dimensions for males were greater than in females. The men spleen length were (10.07 ±0.7 cm, 10.1 ±0.54 cm, 9.5 ±0.7 cm and 9.0 ±0.43 cm for age group of 16 - 30, 31 - 45, 46 - 60 and 61 - 75 years respectively). The females spleen length were (9.83 ±0.53 cm, 9.58 ±0.58cm, 9.2 ±0.64 cm and 8.8 ±0.36 cm for age group of 16 - 30, 31 - 45, 46 - 60 and 61 - 75 years respec­tively). The men spleen thickness were more (4.1 ±0.5 cm, 4.05 ±0.58 cm, 3.43 ±0.38 cm and 3.0 ±0.36 cm for age group of 16 - 30, 31 - 45, 46 - 60 and 61 - 75 years respectively). The females splenic thickness were 4.06 ±0.47 cm, 3.78 ±0.48 cm, 3.38 ±0.35 cm and 2.29 ±0.23 cm for age group of 16 - 30, 31 - 45, 46 - 60 and 61 - 75 years respectively. Thus significant differences between male and female splenic dimen­sions were found for each age group chosen (P &lt;0.05).Conclusions: The results show that the splenic length and thickness decreased with increase in age in both males and females and all the di­mensions were greater in males than in females. This study established normogram that can be more reliably used as both a complementary modality to clinical evaluation and as a more sensitive means of evalu­ating and screening patients for splenic disorders for any pathologi­cal enlargement or reduction of size in clinical practice in a Nepalese populations.Journal of Gandaki Medical College Vol. 10, No. 1, 2017, page: 11-16

Sonographic assessment of length of spleen in relation to age in the adults of Rajasthan

Sonographic assessment of length of spleen in relation to age in the adults of Rajasthan

Leishmaniasis in Turkey: Visceral and cutaneous leishmaniasis caused by Leishmania donovani in Turkey

In Turkey, the main causative agents are Leishmania tropica (L. tropica) and Leishmania infantum (L. infantum) for cutaneous leishmaniasis (CL) and L. infantum for visceral leishmaniasis (VL). In this study, we investigated leishmaniasis cases caused by L. donovani and established animal models for understanding its tropism in in vivo conditions. Clinical samples (lesion aspirations and bone marrow) obtained from CL/VL patients were investigated using parasitological (smear/NNN) and DNA-based techniques. For species identification, a real time ITS1-PCR was performed using isolates and results were confirmed by hsp70 PCR-N/sequencing and cpb gene PCR/sequencing in order to reveal Leishmania donovani and Leishmania infantum discrimination. Clinical materials from CL and VL patients were also inoculated into two experimental groups (Group CL and Group VL) of Balb/C mice intraperitoneally for creating clinical picture of Turkish L. donovani strains. After 45days, the samples from visible sores of the skin were taken, and spleens and livers were removed. Measurements of the internal organs were done and touch preparations were prepared for checking the presence of amastigotes. The strains were isolated from all patients and amastigotes were seen in all smears of the patients, and then isolates were immediately stored in liquid nitrogen. In real time ITS1-PCR, the melting temperatures of all samples were out of range of L. infantum, L. tropica and L. major. Sequencing of hsp70 PCR-N showed that all isolates highly identical to previously submitted L. donovani sequences in GenBank, and cpb gene sequencing showed five isolates had longer cpbF allele, whereas one isolate contained a mixed sequence of both cpbF and cpbE. All mice in both experimental groups became infected. Compared to controls, the length and width of both liver and spleen were significantly elevated (p<0.001) in both groups of mice. However, the weight of the liver increased significantly in all mice whereas the weight of spleen increased only in VL group. Amastigotes were also seen in all touch preparations prepared from skin sores, spleen and liver. L. donovani strain was isolated from autocutaneous a VL patient first time in Turkey. Animal models using clinical samples were successfully established and important clinical differences of the isolated strains were observed.

Ruxolitinib (RUX) in combination with azacytidine (AZA) in patients (pts) with myelodysplastic/myeloproliferative neoplasms (MDS/MPNs).

7064 Background: Clinical trials exclusively focusing on pts with MDS/MPNs are lacking. Combining RUX and AZA may target distinct manifestations of MDS/MPNs. Methods: Pts were treated with single-agent RUX 15 mg or 25 mg (based on platelets count) orally twice daily continuously in 28-day cycles for the first 3 cycles. AZA 25 mg/m2 (day 1-5) was added on each cycle starting cycle 4 and could be increased to 75 mg/m2 (maximum) or started earlier than cycle 4 and/or at higher dose in pts with proliferative features or high blasts. Results: 35 pts with med age 70 years (range, 43-79) were enrolled (MDS/MPN-U, n = 14; CMML, n = 17; atypical CM (aCML), n = 4), 28 (80%) were Int-2/High per MF DIPSS, 14 (41%) had splenomegaly &gt; 5 cm, and 12 (34%) had EUMNET MF-2/MF-3 fibrosis. Common mutations on a 28-gene sequencing panel included JAK2 (29%), RAS (27%), ASXL1 (21%), TET2 (18%), and DNMT3A (12%). All 35 pts were evaluable for response per MDS/MPN IWG criteria and 17 (49%) responded. 6/17 (35%) IWG responses occurred after the addition of AZA (med time after AZA = 1.8 months). JAK2 mutated pts had a trend to higher responses vs those with non-mutated pts (8/10 vs 9/25, P = 0.19). Ten pts had &gt; 5% pretreatment BM blasts and 7 achieved a reduction in blasts to &lt; 5% (70%). A &gt; 50% reduction in palpable spleen length reduction at 24 weeks was seen in 9/12 (75%) pts. New grade 3/4 anemia and thrombocytopenia occurred in 18 pts (51%) and 19 (54%) pts but were manageable with dose modifications. Only one pt discontinued therapy due to cytopenias. At a med follow-up of 17.4 mo (range, 1.2-36.8+), 14 (40%) pts died: pneumonia (n = 4), sepsis (n = 4), progression to AML (n = 4), and cardiac arrest (n = 1). The med survival for all pts was 16.6 mo (1.0 - 36.8). Compared to CMML and aCML, MDS/MPN-U pts had significantly better med survival (26.4+ vs 15.0+ vs 1.5+ mo, respectively; p = 0.01). Conclusions: The combination of RUX and AZA showed an IWG-response rate of 49% in pts with MDS/MPNs, and was well-tolerated. The benefit appears more profound in pts with MDS/MPN-U. This study is ongoing. (ClinicalTrials.gov Identifier: NCT01787487).

Platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices in people with chronic liver disease or portal vein thrombosis.

Platelet count, spleen length, and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices in people with chronic liver disease or portal vein thrombosis.

Morphometric Study of Spleen in Iranian Cadavers from Razavi-Khorasan Province

Anthropologic parameters of the spleen are important because many diseases present with reduction or enlargement of the spleen. No data exists about the standard dimensions of the normal spleen in Iranian population. Therefore, the objective of the study was to investigate anthropologic parameters of the spleen in Iranian cadavers. In 2014-2015, this cross sectional study was undertaken from the Razavi Khorasan Province of Iran. Iranian cadavers (n=693, 152 female/541 male) with no history of poisoning, drug or alcohol addiction, no gross abnormality and injury of the spleen were included in the study. The length, width and thickness of spleen were measured using a Vernier caliper. The mean values of the demographic data were age= 40.28 ± 20.97 years; weight = 63.68 ± 17.40 kg; height = 160.03 ± 28.45 cm and BMI = 25.03 ± 20.46 kg/m2. The mean values of the spleen length, width, thickness, notch, weight and index in the cadavers were 11.32 ± 3.10 cm, 8.05 ± 2.35 cm, 20.12 ± 9.21 mm, 0.84 ± 1.35, 123.87 ± 82.46 g, and 2.01 ± 1.40, respectively. Accessory spleen was found in five cadavers. The anthropologic parameters of the spleen showed significant difference between males and females except for index of the spleen. Having standard data on the spleen is useful for radiologists, surgeons, anatomists and anthropologists. The results of the study may provide valuable data in the standardization of the anthropologic parameters of the spleen in the Iranian population.