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Introduction: Acute appendicitis (AA) requires a prompt diagnosis. According to postoperative pathological results, a significant number of appendectomies are performed on a normal appendix (NA). The aim of this study is to evaluate the role of preoperative inflammatory markers in supporting and improving the clinical diagnosis of AA, extracting more information from CBC parameters. Methods: The study is a retrospective one. The histopathological results of operated appendix from 102 patients, who underwent appendectomy for clinically suspected AA, were extracted from the Galilee Medical Center systems. Two patient groups (NA and true AA) were compared for neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR) and mean platelet volume (MPV). The obtained data were statistically analyzed, using the independent sample t test and Mann–Whitney test. Category data have been compared among groups with the chi‐squared test. The primary endpoint of our research was to assess the predictive power of blood biomarkers. Results: Patients with suspected AA, based on clinical picture and contrast enhanced computed tomography (CECT), and with MLR‐value ≥0.3357 were 5.25 times more likely than normal to have AA. Patients with NLR‐value ≥3.2223 were 7 times more likely than normal to have AA. The differences in PLR and MPV values were not statistically significant. Conclusions: The NLR and MLR biomarkers can assist in diagnosis of AA. This can be particularly helpful in cases where CECT is contraindicated, as in pregnant women or children. [ABSTRACT FROM AUTHOR]

Several studies showed ethnic disparities in multiple myeloma (MM) incidence and prognosis. In order to compare prognosis and overall survival between different ethnic groups, a multicenter retrospective study was conducted in Northern Israel. A total of 145 patients suffering from MM were included (72% Jewish, and 28% Arabs) who were treated between 2008–2018. A difference was found in the stage of the disease at the time of diagnosis, patients of Arab origin were diagnosed at a more advanced stage (III), (53.7% vs. 33.7%, respectively). A mortality rate of 48.9% was found in the study, regardless of population ethnic origin. No significant differences in rates of MGUS, MM symptoms, treatments, or progression-free survival (PFS) and overall survival (OS) were observed between ethnic groups. This suggests that raising awareness of MM may result in an earlier diagnosis, especially among patients of Arab origin, preventing unnecessary suffering from these patients. [ABSTRACT FROM AUTHOR]

• Infectious complications post-cladribine treatment remain high. • Primary peg-filgrastim prophylaxis compared to filgrastim given on demand. • Both types of G-CSF are justifiable, and the choice remains at the physician's discretion. Major advances in the treatment of patients with hairy cell leukemia (HCL) have been made following the introduction of purine analogues. The major significant short-term toxicity of cladribine therapy are neutropenia and neutropenic fever (NF) which may be life-threatening. In this retrospective study, we compared the incidence and duration of neutropenia and hospitalization in patients with HCL treated with cladribine followed by peg-filgrastim as primary prophylaxis versus daily filgrastim given "on demand" according to absolute neutrophil count (ANC). Medical records of patients with HCL diagnosed and followed in 12 medical centers in Israel during 1985–2015 were examined for details of disease at diagnosis. The efficacy of peg-filgrastim and filgrastim was assessed by evaluating the incidence of neutropenia (ANC < 1.0 × 10 [ 9 ]/L), number and length of hospitalizations, and number of days from the last day of therapy to recovery of ANC to >1.0 × 10 [ 9 ]/L. The study population included 202 patients with HCL, 159 of whom (80.7%) were treated with cladribine; 78 patients (49%) required hospitalization for the administration of broad-spectrum antibiotics due to NF. Twenty-eight (19%) patients were treated with peg-filgrastim as primary prophylaxis, while 74 (64%) received filgrastim "on demand" due to neutropenia. Median length of hospitalization, and nadir duration were 8 and 18 days respectively (p = 0.71, p = 0.44). Infectious complications post-cladribine treatment remain high. No difference was found in terms of incidence of NF, number of febrile days, and nadir duration in patients receiving primary peg-filgrastim prophylaxis compared to filgrastim given on demand. Both approaches are justifiable, and the choice remains at the physician's discretion. [ABSTRACT FROM AUTHOR]

Background: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron-overloaded RBC transfusion-dependent patients with lower risk MDSs., Methods: Adult lower risk MDS patients with a cumulative transfusion burden of &gt;20 red blood cell units and evidence of iron overload (serum ferritin &gt;1,000 ng/mL) were included in this study. DFP was administered (100 mg/kg/day) for 4 months. Blood samples for oxidative stress parameters and iron overload parameters were done at baseline and monthly: reactive oxygen species (ROS), phosphatidylserine, reduced glutathione, membrane lipid peroxidation, serum ferritin, and cellular labile iron pool. The primary efficacy variable was ROS. Tolerability and side effects were recorded as well. A paired t test was applied for statistical analyses., Results: Eighteen patients were treated with DFP. ROS significantly decreased in all cell lineages: median decrease of 58.6% in RBC, 33.3% in PMN, and 39.8% in platelets (p &lt; 0.01 for all). Other oxidative stress markers improved: phosphatidylserine decreased by 57.95%, lipid peroxidase decreased by 141.3%, and reduced gluthathione increased by 72.8% (p &lt; 0.01 for all). The iron-overload marker and cellular labile iron pool decreased by 35% in RBCs, 44.3% in PMN, and 46.3% in platelets (p &lt; 0.01 for all). No significant changes were observed in SF levels. There were no events of agranulocytosis. All AEs were grades 1-2., Conclusions: Herein, we showed preliminary evidence that DFP decreases iron-induced oxidative stress in MDS patients with a good tolerability profile (albeit a short follow-up period). No cases of severe neutropenia or agranulocytosis were reported. The future challenge is to prove that reduction in iron toxicity will eventually be translated into a clinically meaningful improvement., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Venous thromboembolism (VTE) is a serious disease, which demands a fast accurate diagnosis to begin suitable treatment. It presents a major problem in the emergency department (ED), and its confirmation requires adequate evaluation., Objectives: To evaluate a potential role of mean platelet volume (MPV) in differentiating VTE from other potential diagnosis in patients with suspected VTE., Methods: We conducted a retrospective case-controlled study of 440 consecutive patients who presented to the ED of our hospital with clinical VTE, but only 316 with proven VTE. A control group was composed of patients (124) who presented with clinical VTE but without proven VTE. We checked the MPV value in all 440 patients and the correlation with VTE occurrence in the study group vs. control group., Results: Statistical analysis of the acquired results indicated that MPV value could not aid in determining the difference of real VTE vs. patients with VTE-like clinical picture presenting to the ED. We found an inverse correlation between MPV value and proven VTE, in contrast to most researchers who have studied the same issue., Conclusions: Although MPV can be a useful diagnostic marker in many diseases, we found no definite association between low MPV and VTE.

Chronic lymphocytic leukemia (CLL) is a disease of elderly patients. The fludarabine, cyclophosphamide, and rituximab (FCR) regimen is considered the treatment of choice for young fit patients with CLL; however, this combination is toxic for older patients. At the time this study was first planned and initiated, there was no standard chemo-immunotherapy regimen regarded as standard therapy for the less fit elderly patient with CLL. Here, we conducted a single-arm, phase II trial to examine the efficacy and safety of lower-dose fludarabine and cyclophosphamide combined with a standard dose of rituximab (LD-FCR) in elderly patients with previously untreated CLL. Forty patients received LD-FCR and were included in the efficacy analysis. Two patients treated with FC alone were only included in the safety analysis. The median age was 72.7 years (range, 65.0 to 85.0). The overall response and complete response rates were 67.5% and 42.5%, respectively. Median progression-free survival (PFS) was 35.5 months (95% CI, 29.27-41.67). Two patients (4.8%) died during the study period. Hematological toxicities and infections were the most common complications encountered; grade 3 to 4 treatment-related neutropenia occurred in 20 (47.6%) patients. During the entire study follow-up, 26 patients (61.9%) had all grades of infection including six (14.3%) with neutropenic fever and eight (19%) with grade 3 to 4 non-neutropenic infections. In conclusion, LD-FCR is an effective and relatively safe regimen for previously untreated patients with CLL. It has the advantage of being both "time and cost limited" and, even in the era of novel agents, can still be considered when planning treatment for elderly patients without high-risk biomarkers. However, recent results in fit elderly patients using the combination of bendamustine and rituximab which have achieved longer PFS with good safety profile must be taken into consideration in this regard., (© 2019 John Wiley & Sons, Ltd.)

Objectives: Hypogammaglobulinemia, commonly encountered in chronic lymphocytic leukemia (CLL), is one of the main causes of morbidity and mortality; however, its prognostic significance in patients diagnosed in early stages of disease remains uncertain. The aim of this study was to evaluate the predictive power of hypogammaglobulinemia at Bonet stage A., Methods: Using the database of the Israeli CLL Study Group, we analyzed the relationship between low serum levels of IgG, IgA, and IgM; the presence of paraproteinemia, as well as other well-recognized prognostic markers in CLL; and time to first treatment (TTT) and overall survival. A total of 1113 patients consecutively diagnosed during the last 25 yrs with Binet stage A CLL were evaluated, and baseline information on serum immunoglobulin levels was found in 857 of the cases., Results: Overall survival times correlated with age >65 yr, male gender, the presence of lymphadenopathy, high serum beta 2-microglobulin (b2m), CD38 and ZAP-70 expression, but not with low levels of immunoglobulin or the presence of paraproteinemia. By univariate analysis, patients with low IgA levels had a shorter TTT; however, on multivariate analysis, the presence of lymphadenopathy (P 0.02), b2m (P 0.04), CD38 (P < 0.001), and ZAP-70 (P < 0.001) was the only laboratory parameters with prognostic significance., Conclusions: In our cohort of patients with early-stage CLL, baseline hypogammaglobulinemia and the presence of paraproteinemia were not found to correlate with prognosis., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Bone marrow (BM) biopsies from patients with chronic lymphocytic leukemia (CLL) may show reticulin fibrosis at diagnosis, but its significance remains unclear. This study sought to assess the prognostic impact of BM reticulin fibrosis in patients with previously untreated CLL., Methods: Data was reviewed from untreated CLL patients in the national Israel CLL database, followed during 1987 to 2012. All bone marrow biopsies were graded for reticulin fibrosis using a modified scoring system containing 4 grades (0-3), based on the European consensus report. Grade of reticulin fibrosis was correlated with overall survival (OS), outcome, and a number of well-recognized prognostic factors for CLL., Results: The final cohort included 176 patients (122 males and 51 females). Median age was 63 years (range, 32-86 years) and the 5-year OS was 77.1%. Grade of BM reticulin fibrosis correlated with OS (P < .0001) and mortality (P = .001), and separated patients into 2 groups with different survival curves. Advanced reticulin fibrosis (grades 2-3) was associated with thrombocytopenia (platelet counts of < 100,000/mm(3) ) (P = .025), anemia (P = .018), elevated β2-microglobulin < 4000 μg/mL (P = .048), and the presence of 11q deletion (P = .0015)., Conclusions: There was a significant correlation between poor survival and grade of BM reticulin fibrosis. This staining procedure is easy to perform and can readily be added routinely when examining BM biopsies in CLL, because the findings do have prognostic implications., (Copyright © 2013 American Cancer Society.)

Hypomethylating agents have become the standard therapy for patients with high-risk myelodysplastic syndrome (MDS). In Israel, azacitidine (AZA) is routinely used. Yet, infectious complications are common during AZA therapy. The current study was aimed to evaluate the incidence and predisposing risk factors for infections in AZA-treated patients. This retrospective study included patients treated with AZA in 18 Israeli medical institutions between 2008 and 2011. Data on 184 patients [157 high-risk MDS and 27 acute myeloid leukemia (AML)], with a median age of 71.6 (range 29-92) were recorded. Overall, 153 infectious events were reported during 928 treatment cycles (16.5%) administered to 100 patients. One hundred fourteen, 114/153 (75%) events required hospitalization and 30 (19.6%) were fatal. In a univariate analysis, unfavorable cytogenetics, low neutrophil, hemoglobin (Hb) and platelet (PLT) counts were found to be associated with infections (24.4% vs. 12.9%, P < 0.0001; 27% vs. 13.5%, P < 0.0001; 20.4% vs. 11%, P < 0.0001 and 29.2% vs. 14.2%, P < 0.0001, respectively). In multivariate analysis, only low Hb level, low PLT count, and unfavorable cytogenetics remained significant. Prior to therapy, poor cytogenetics, PLT count below 20 × 10⁹/L and neutrophil count below 0.5 × 10⁹/L were predictive of the risk of infection during the first two cycles of therapy. In conclusion, patients with unfavorable cytogenetics, presenting with low neutrophil and PLT counts, are susceptible to infections. Evaluation of infection risk should be repeated prior to each cycle. Patients with poor cytogenetics in whom AZA is prescribed despite low PLT count are particularly at high risk for infections and infection prophylaxis may be considered., (Copyright © 2012 Wiley Periodicals, Inc.)

In the light of recent data showing survival improvement of patients with chronic lymphocytic leukemia (CLL), we investigated clinical characteristics and survival patterns of patients with CLL over the last 40 years in Israel. Demographic and clinical data collected in the database of the Israeli CLL Study Group were analyzed. Of the 1,325 patients, 221 were diagnosed during the time period 1968-1989, 456 during 1990-1999, and 639 during 2000-2010. There was shift toward older age (median, 71 vs. 68 vs. 66 years) and a higher proportion of patients at Binet stage A at diagnosis (77.6% vs. 66.7% vs. 60.3%) in the more recent time periods. Median survival for the entire cohort was 10.9 years; 12.2 years for patients diagnosed at Binet stage A, 8.5 years for stage B, and 6.4 years for stage C patients. Older age, high-beta 2-microglobulin level, and expression of ZAP-70 predicted shorter survival. There were no apparent changes over time regarding gender, age or different clinical stages. Young patients with Binet stage A had lower life expectancy than the general population; but, in older ages, the survival rates were comparable. There were increased proportions of CLL patients diagnosed in early stages, and, at older age, during the last decades, however, survival rates according to sex, age, or stage remained stable. CLL continues to be an incurable disease affecting survival even in patients diagnosed at early stages. Survival benefit shown in recent trials using chemoimmunotherapy has still to be proven in wider general practice., (Copyright © 2011 Wiley-Liss, Inc.)