A New Marker for the Diagnosis of Acute Pelvic Inflammatory Disease: Immature Granulocyte.

BACKGROUND: The goal is to assess the role of immature granulocytes (IG) in the diagnosis of acute pelvic-inflammatory-disease (PID) and to determine whether they are useful for discriminating mild/moderate and severe PID. METHODS: Patients admitted with the diagnosis of acute PID were retrospectively assessed. Diagnosis was based on CDC criteria. Patients were grouped as severe and mild/moderate PID based on need for hospitalization. Control group consisted of patients in whom PID was excluded by laparoscopy. Sample size was calculated with statistical methods. IGs were compared within the groups. Cutoff values were determined for prediction of diagnosis and severity of acute PID. RESULTS: There were 74 severe, 32 mild/moderate acute PID, and 41 control patients. Thirty patients had surgery following no response to antibiotic treatment or tubo-ovarian abscess. IGs were significantly higher in the severe group compared to mild/moderate and control groups. ROC analysis showed IG counts (≥ 0.035 µL) and percentages (≥ 0.35%) were significantly effective in predicting acute PID and were associated with severity when they were ≥ 0.055 µL and ≥ 0.42%, respectively. IG count ≥ 0.085 was found to have 58.6% sensitivity and 63.1% speci-ficity for prediction of surgical intervention need. CONCLUSIONS: IGs are components of simple CBC tests and are easily obtainable, cheap markers. They were found to be elevated in acute PID and correlated significantly with the severity of the disease. These markers may serve as adjunctive markers for the diagnosis of acute PID and may be useful in discrimination between mild/moderate and severe PID.

Significance of Lymphocyte Count, Monocyte Count, and Lymphocyte-To-Monocyte Ratio in Predicting Molecular Response in Patients with Chronic Myeloid Leukemia: a Single-Centre Experience.

BACKGROUND: Chronic myeloid leukemia (CML) is a disease resulting from BCR-ABL gene fusion. It is possible to monitor treatment by molecular testing for BCR-ABL. The lymphocyte-to-monocyte ratio (LMR) is a commonly used marker associated with prognosis in various neoplasms. This study was performed to evaluate the relevance of absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR in predicting molecular response status in patients with chronic phase CML. METHODS: Samples submitted to our hematology laboratory for BCR-ABL testing between April 2012 and October 2018 were retrospectively reviewed. Concurrent hemogram testing together with the results of quantitative reverse transcriptase-polymerase chain reaction were noted. Data were grouped according to molecular response status and the ALC, AMC, and LMR were compared among patient groups. RESULTS: A total of 224 samples from 95 patients were included in the study. Analysis revealed differences between groups when newly diagnosed patients were compared with patients undergoing treatment, regardless of response status. However, analyzing the groups according to molecular response status failed to reveal differences in ALC, AMC, or LMR. CONCLUSIONS: ALC, AMC, and LMR are not potential biomarkers for predicting molecular response status in patients with chronic phase CML.

The Impact of the Ferric Carboxymaltose on Hemoglobin and Ferritin Levels.

BACKGROUND: Anemia is a frequent disorder worldwide. Iron deficiency anemia (IDA) is the most common form of anemia. Although oral iron is the first choice for treatment, the efficacy of oral iron preparations may be limited. Ferric carboxymaltose (FCM) is a novel parenteral iron preparation which can rapidly replenish iron stores. The aim of the present study is to investigate the impact of FCM dose on hemoglobin (Hb) and ferritin levels and the frequency of hypersensitivity reactions. METHODS: This study was conducted with 765 IDA patients between September 1, 2016 and September 1, 2018. He-moglobin (Hb), serum ferritin, transferrin saturation values were examined at the time of diagnosis, Hb and ferritin values at first month. RESULTS: Post-treatment Hb and ferritin levels significantly increased. The mean Hb level alteration was 2.43 ± 1.2 g/dL, the median ferritin level alteration was 157.3 ng/mL. The mean Hb level was lower and the mean change in Hb level was higher in higher doses. Allergic reactions were more frequent in higher doses. CONCLUSIONS: Ferric carboxymaltose is a novel treatment option with a low risk of hypersensitivity reactions and well tolerated even in high doses.

Granulocyte-colony stimulating factor administration among hemoglobin S trait donors: A single center experience from the Eastern Mediterranean region.

BACKGROUND AND OBJECTIVE: Assessment of Hemoglobin S trait donors has gained importance together with the increased allogeneic peripheral stem cell transplant activity for sickle cell disease in the regions where the disease is prevalent. Outcomes of Granulocyte-Colony Stimulating Factor (G-CSF) administration are obscure for hemoglobin S trait donors. This study aims at investigating the incidence of hemoglobin S carrier status and outcomes of G-CSF administration among donors who live in Eastern Mediterranean region. MATERIAL AND METHOD: The cross-sectional, single-center cohort study was performed with 147 donors between January 2013 and March 2017. Prevalence of hemoglobin S trait was estimated and subjects with or without Hemogobin S trait were compared with regard to stem cell characteristics, early and late clinical outcomes after G-CSF administration. RESULTS: Eleven out of 147 donors (7.48%) were found as hemoglobin S trait. G-CSF administration was successfully completed and yielded good harvesting results in hemoglobin S trait donors. No statistically significant difference was found between groups with regard to early and late side effects, stem cell characteristics. Blood pressures and QTc values were within normal ranges in both groups. Groups were similar with regard to CD34 values. CONCLUSION: G-CSF seems safe in hemoglobin S trait donors. Their being eligible as donors would increase the chance of the patients for allogeneic stem cell transplantation in high prevalence regions. Further studies are required to reveal the safety profile of G-SCF in hemoglobin S carriers in different regions.

Role of first trimester total testosterone in prediction of subsequent gestational diabetes mellitus.

AIM: To assess the role of first trimester maternal testosterone and dehydroepiandrosterone sulfate (DHEA-S) levels in prediction of development of gestational diabetes mellitus (GDM). METHODS: Four hundred and fifty pregnant women were included in this prospective cohort study. All pregnant women with a singleton pregnancy who were not diabetic, had no family history of diabetes, had no history of previous GDM, were of white race and non-smokers were enrolled. Total testosterone and DHEA-S were measured at 11-14 weeks of gestation. The patients were called for routine pregnancy visits and followed accordingly. Forty-two patients did not come to their visits and were excluded. During gestational weeks 24-28, the remaining 408 patients were screened for GDM. The total testosterone and DHEA-S levels were compared between patients with and without GDM. Regression and receiver-operator curve analysis were performed. RESULTS: GDM developed in 22 women (5.7%). Compared with women without GDM, first trimester total testosterone levels were higher among women in whom GDM subsequently developed. The DHEA-S level did not differ. Age, total testosterone and body mass index were found to be independent predictors of GDM development. A total testosterone value of 0.45 ng/mL was found to predict development of GDM with a sensitivity of 63.6% and a specificity of 62.7%. CONCLUSION: First trimester total testosterone has a low testing power for GDM screening with low sensitivity and specificity values and cannot be used as a marker alone. It may have a role in combination with other markers.

Heart rate variability and heart rate turbulence in hypothyroidism before and after treatment.

BACKGROUND: Cardiac autonomic dysfunction may develop in patients with clinical or subclinical thyroid hormone deficiency. Heart rate variability (HRV) and heart rate turbulence (HRT) are used for evaluating changes in cardiac autonomic functions and also used to provide risk stratification in cardiac and noncardiac diseases. The aim of this study is to evaluate cardiac autonomic functions before and 6 months after thyroid replacement therapy in patients with thyroid hormone deficiency. METHODS: Forty hypothyroid patients (mean age 48 ± 13, four male) and 31 healthy controls (mean age 51 ± 12, three male) were included in the study. Twenty-four hour ambulatory electrocardiogram recordings were taken using Pathfinder Software Version V8.255 (Reynolds Medical). The time domain parameters of HRV analysis were performed using the Heart Rate Variability Software (version 4.2.0, Norav Medical Ltd, Israel). HRT parameters, Turbulence Onset (TO), and Turbulence Slope (TS) were calculated with HRT! View Version 0.60-0.1 software. RESULTS: HRV and HRT parameters were decreased in the patient group (SDNN; P < 0.001, SDANN; P < 0.009, RMSSD; P = 0.049, TO; P = 0.035, TS; P < 0.001). After 6 months of thyroid replacement therapy, there were no significant changes observed in either HRV or HRT. CONCLUSIONS: Hypothyroidism may cause cardiac autonomic dysfunction. Treating hypothyroidism with L-thyroxine therapy does not effectively restore cardiac autonomic function. HRV and HRT can be used as to help monitor cardiovascular-related risk in this population.

Factors Associated With Overall Survival in Acute Myeloid Leukemia Patients Before and After Hematopoietic Stem Cell Transplant.

OBJECTIVES: Our aim was to identify factors associated with overall survival and the efficacy of postrelapse treatment protocols and to determine whether pretransplant consolidation therapy and minimal residual disease status pose a survival benefit. MATERIALS AND METHODS: Patients with acute myeloid leukemia who underwent stem cell transplant between 2007 and 2018 were enrolled retrospectively. The effects of pretransplant cytogenetic and minimal residual disease status, pretransplant consolidation therapies, development of graft-versus-host disease, postrelapse treatment protocols, and type of con-ditioning regimens on overall survival were analyzed. RESULTS: In 76 study patients, the cumulative overall 1- and 5-year relapse probabilities were 67.8% and 58.7%, respectively. Overall survival rates at 3 and 5 years in patients with and without relapse were 23.5% and 0% and 95.9% and 91.1% (P < .001), respectively. Although mean postrelapse overall survival was better with intensive salvage plus donor lymphocyte infusion, no significant differences were shown versus other therapies (intensive salvage, nonintensive salvage, intensive salvage or nonintensive salvage plus donor lymphocyte infusion, or supportive therapy). Twenty-three patients (30.3%) died during the study period with a median survival of 9.6 months. Patients with favorable, intermediate, and unfavorable cytogenetic status showed overall survival of 46.6 ± 10.4, 54.6 ± 4.4, and 36.9 ± 5.9 months (P = .807). Patients with and without minimal residual disease and patients who received or did not receive consolidation therapy had similar overall survival. Relapse was an independent predictor of overall survival (increased mortality risk of 26.22). Patients who developed graft-versus-host disease showed decreased relapse. CONCLUSIONS: Relapse is the most important predictor of overall survival and is associated with poor prognosis. Pretransplant minimal residual status and cytogenetic status showed no effect on relapse rates and overall survival, and consolidation therapy did not improve outcomes.

Comparison of Outcomes of Transplant and Nontransplant High-Risk Chronic Lymphocytic Leukemia Patients in the Novel Targeted Therapy Era.

OBJECTIVES: Our aim was to compare patients with high-risk chronic lymphocytic leukemia referred to our transplant center who underwent allogeneic stem cell transplant with those who did not receive this treatment. Factors compared included demographics, clinical characteristics, and survival rates in the novel targeted therapy era. MATERIALS AND METHODS: All 33 patients with high-risk chronic lymphocytic leukemia who were referred to the hematopoietic stem cell transplant center were enrolled in this retrospective, single-center nonrandomized study. Outcomes of patients who received allogeneic stem cell transplant were compared with those of nontransplant patients. Chemoimmunotherapy and ibrutinib were given when indicated. Factors related to overall and progression-free survival were assessed. RESULTS: Thirteen patients underwent allotransplant, and transplant was not done in 20 patients for various reasons. Demographic and clinical features of the transplant and nontransplant groups were similar. The estimated cumulative overall survival was 72.6 ± 15 and 84.3 ± 13 months in the nontransplant and transplant groups, respectively. The 5-year overall and progression-free survival rates in the transplant and nontransplant groups were 57.3%/36.0% and 40%/20.6%, respectively. In the nontransplant group, overall survival of those who used ibrutinib was longer than overall survival in patients in the transplant group who used the same drug, but the difference was not statistically significant. Although not significant, overall survival in patients who did not use ibrutinib was longer in the transplant group than in the nontransplant group. Cox regression analyses showed that transplant, relapse, and Binet stage were independent predictors of overall survival. CONCLUSIONS: In patients who do not use ibrutinib, allogeneic stem cell transplant improved survival compared with nontransplant patients. Addition of ibrutinib provided comparable life expectancies, showing that allogeneic stem cell transplant and ibrutinib may have complementary roles. Transplant is still an independent predictor of overall survival.

A Comparison of the BEAM and MITO/MEL Conditioning Regimens for Autologous Hematopoietic Stem Cell Transplantation in Hodgkin Lymphoma: An Analysis of Efficiency and Treatment-Related Toxicity.

BACKGROUND: Approximately half of patients with relapsed chemosensitive disease achieve robust responses with BEAM (BCNU, etoposide, cytarabine, and melphalan) and autologous stem cell rescue. The scarcity of comparative studies further limits alternative treatment protocols, such as the MITO/MEL (mitoxantrone, melphalan) protocol. PATIENTS AND METHODS: In this retrospective multicenter study, we compared the BEAM and MITO/MEL regimens used before autologous hematopoietic stem cell transplantation (ASCT) in terms of efficacy and side effects in patients with Hodgkin lymphoma. Data met international accreditation rules. Before ASCT, 108 patients received the MITO/MEL, and 34 patients received the BEAM. RESULTS: The median follow-up time was 36 months in the MITO/MEL group (range, 3-178) and 23 months in the BEAM group (range, 4-99). After ASCT, the 3-year expected overall survival and disease-free survival rates were 86.1% and 86.1% for the MITO/MEL group and 91.3% and 76.5% for the BEAM group, respectively. Although 50% of patients developed febrile neutropenia attacks in the MITO/MEL group, this rate was 91.1% in the BEAM group. The grade II and higher rates of hepatic, renal, gastrointestinal, and cardiac toxicities were similar in both groups. However, the rate of pulmonary toxicity was determined to be 1.9% in the MITO/MEL group and 29.4% in the BEAM group (P < .001). CONCLUSION: The MITO/MEL conditioning regimen seems to be as effective as the BEAM regimen but has better tolerability in terms of pulmonary toxicity and may be used as an alternative option if necessary, depending on the comorbidity status of the patient.

Early Access Program Results From Turkey and a Literature Review on Daratumumab Monotherapy Among Heavily Pretreated Patients With Relapsed/Refractory Myeloma.

BACKGROUND: In countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program. PATIENTS AND METHODS: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter. RESULTS: The median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). The overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. The median duration of response was 4.9 months. The median progression-free survival (PFS) was 5.5 (95% confidence interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7% and 31.0%, respectively. The median overall survival was not reached; the 12- and 18-month overall survival rates were 64.3% and 59.5%, respectively. The depth of response had a significant effect on PFS (log-rank test, P = .026). Overall, of the 76 adverse events reported, 33 (43.4%) were grade ≥ 3; only 4 (9.52%) were grade 3 infusion-related reactions. No infusion-related reactions or adverse events led to treatment discontinuation. CONCLUSION: The present findings from our daratumumab early access program have confirmed the efficacy and safety profile of daratumumab monotherapy in heavily pretreated Turkish patients with RRMM.

A novel antibiotic, linezolid, reduces intraperitoneal adhesion formation in the rat uterine horn model.

OBJECTIVE: To examine the effects of linezolid in prevention of adhesion formation in a rat uterine horn model. DESIGN: Prospective randomized study. SETTING: University Experimental Animal Research Laboratory Center. SAMPLE: Ninety female Wistar albino rats. METHODS: A dose response study was first conducted with 60 Wistar albino rats that were randomly assigned to six equal groups by administering vehicle (control), 5 mg/kg (Group 1), 15 mg/kg (Group 2), 50 mg/kg (Group 3), 100 mg/kg (Group 4), and 150 mg/kg (Group 5) linezolid starting three days before the adhesion inducing operation and continuing for 14 days postoperatively. Adhesion was scored clinically with a scoring system. The minimum effective dose was found to be 100 mg/kg/day. With this dose time response (starting three days before the operation and continuing for seven days), only preoperative and postoperative administration studies were conducted. MAIN OUTCOME MEASURES: Extent and severity of adhesions. RESULTS: Total adhesion scores in the control and Groups 1 and 2 were significantly higher when compared with Groups 4 and 5, but not with Group 3. There were no significant differences in the adhesion scores between Groups 3, 4, and 5. In time response arm a total of 10 days treatment was not as effective as 17 days treatment. In postoperative and preoperative arms of the study, it was found that administration of linezolid only postoperatively or preoperatively did not affect adhesion formation significantly when compared with the control group. CONCLUSION: Linezolid was found to reduce intraperitoneal adhesion formation.

Effects of two doses of anti-T lymphocyte globulin-Fresenius given after full-match sibling stem cell transplantation in acute myeloblastic leukemia patients who underwent myeloablative fludarabine/busulfan conditioning.

OBJECTIVE/BACKGROUND: Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. METHODS: This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. RESULTS: Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III-IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667-199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5). CONCLUSION: Dose difference of rATG-F did not influence survival parameters; however, increasing the dose to 30 mg/kg seems to be effective for reducing cGVHD with an increase in infection rate requiring close monitoring of infections in AML patients who received myeloablative fludarabine/busulfan conditioning.

Organ damage mitigation with the Baskent Sickle Cell Medical Care Development Program (BASCARE).

The Eastern Mediterranean is among the regions where sickle cell disease (SCD) is common. The morbidity and mortality of this disease can be postponed to adulthood through therapies implemented in childhood. The present study focuses on the organ damage-reducing effects of the Baskent Sickle Cell Medical Care Development Program (BASCARE), which was developed by a team who lives in this region and has approximately 25 years of experience. The deliverables of the program included the development of an electronic health recording system (PRANA) and electronic vaccination system; the use of low citrate infusion in routine prophylactic automatic erythrocyte exchange (ARCE) programs including pregnant women; the use of leukocyte-filtered and irradiated blood for transfusion; the use of magnetic resonance imaging methods (T2) for the management of transfusion-related hemosiderosis; and the implementation of an allogeneic hematopoietic stem cell transplantation protocol for adult patients. The sample was composed of 376 study subjects and 249 control subjects. The hospital's Data Management System and the central population operating system were used for data collection. BASCARE enabled better analysis and interpretation of complication and mortality data. Vaccination rates against influenza and pneumococcal disease improved (21.5% vs 50.8% and 21.5% vs 49.2%, respectively). Effective and safe ARCE with low citrate infusion were maintained in 352 subjects (1003 procedures). Maternal and fetal mortality was prevented in 35 consecutive pregnant patients with ARCE. Chelating therapy rates reduced from 6.7% to 5%. Successful outcomes could be obtained in all 13 adult patients who underwent allogeneic peripheral stem cell transplantation from a fully matched, related donor. No patients died by day 100 or after the first year. Cure could be achieved without graft loss, grades III to IV acute graft versus host disease, extensive chronic graft versus host disease, or other major complications. The BASCARE program significantly improved patient care and thereby prolonged the life span of SCD patients (42 ± 13 years vs 29 ±â€Š7 years, P < .001). We may recommend using such individualized programs in centers that provide health care for patients with SCD, in accordance with holistic approach due to the benign nature but malignant course of the disease.

Changes in metabolic and cardiovascular risk factors before and after treatment in overt hypothyroidism.

AIM: Overt hypothyroidism is associated with an increased risk for developing cardiovascular disease. We aimed to assess the changes in renal function, serum lipids, vitamin B12, folic acid and homocysteine levels before and after treatment in hypothyroid patients. METHODS: The study included 54 patients (F/M=47/7) with overt hypothyroidism. All patients were assessed for demographic characteristics such as age, gender, body weight, and body mass index. Fasting blood samples were taken from the patients for analysis of chemical parameters including thyroid stimulating hormone (TSH), free thyroxine (fT4), homocysteine, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), folic acid, and vitamin B12 levels before and after L-thyroxine (LT4) treatment. RESULTS: Homocysteine levels in hypothyroidism (9.67 ± 5.24 mmol/l) were significantly higher than in euthyroid state (8.16 ± 3.38 mmol/L, p=0.038). Glomerular filtration rate (GFR) was lower before treatment. Following LT4 replacement, renal functions significantly improved. After achieving the euthyroid state, folic acid levels significantly increased although vitamin B12 levels were not changed. There was a significant reduction in serum lipid levels after LT4 replacement. It was demonstrated that there was a significant negative correlation between GFR and lipids and a positive correlation with homocysteine and lipids at hypothyroid state. After normalization of thyroid functions, the correlations became non-significant. CONCLUSION: The hypothyroidism was associated with increased serum homocysteine, lipids, and creatinine concentrations. The improvement of these parameters with LT4 replacement may be associated with the lower risk for atherosclerotic cardiovascular diseases in the patients with hypothyroidism.