Germline genetic variants in Turkish familial multiple myeloma/monoclonal gammopathy of undetermined significance cases.

Multiple myeloma (MM) is a haematological malignancy primarily affecting the elderly, with a striking male predilection and ethnic disparities in incidence. Familial predisposition to MM has long been recognized, but the genetic underpinnings remain elusive. This study aimed to investigate germline variants in Turkish families with recurrent MM cases. A total of 37 MM-affected families, comprising 77 individuals, were included. Targeted next-generation sequencing analysis yielded no previously reported rare variants. Whole exome sequencing analysis in 11 families identified rare disease-causing variants in various genes, some previously linked to familial MM and others not previously associated. Notably, genes involved in ubiquitination, V(D)J recombination and the PI3K/AKT/mTOR pathway were among those identified. Furthermore, a specific variant in BNIP1 (rs28199) was found in 13 patients across nine families, indicating its potential significance in MM pathogenesis. While this study sheds light on genetic variations in familial MM in Turkey, its limitations include sample size and the absence of in vivo investigations. In conclusion, familial MM likely involves a polygenic inheritance pattern with rare, disease-causing variants in various genes, emphasizing the need for international collaborative efforts to unravel the intricate genetic basis of MM and develop targeted therapies.

Analysis of Treatment Strategies and Outcomes in Malignant Peritoneal Mesothelioma: Insights From a Multi-Center Study.

BACKGROUND: This study aimed to evaluate the demographic," clinicopathologic, and prognostic characteristics of malignant peritoneal mesothelioma (MPeM), as well as the treatment options for the rare and heterogeneous MPeM population. METHODS: A retrospective multi-center observational cohort study was conducted to evaluate patients with MPeM. Due to the heterogeneity of the study population, the study divided them into two main groups in terms of treatments, follow-up periods, and prognostic features. The first group comprised the patients who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and the second group included the patients with metastatic disease for whom curative intent surgery was not possible. The patients' diagnostic procedures and treatments were identified from medical records. Patients older than 18 years old were included in the study regardless of asbestos exposure. Well-differentiated papillary and multicystic mesothelioma histologic types were not included in the study. RESULTS: The study evaluated 118 patients from five centers. Survival times, prognosis, and treatment responses were analyzed in both groups. The study showed that CRS-HIPEC was associated with longer overall survival (OS) and progression-free survival (PFS). Perioperative therapy was evaluated in subgroup analyses of this population and shown to provide survival benefits. The patients treated with chemotherapy (metastatic and medically inoperable patients and those for whom complete cytoreduction was not achievable) had a poorer prognosis than the surgery group. The study showed that life expectancy decreased significantly for the patients not suitable to undergo surgery for any reason. CONCLUSIONS: According to data from experienced centers, CRS-HIPEC is a treatment option recognized as effective, cost-effective, and safe, with better OS and PFS , as well as low morbidity and mortality rates similar to those in the literature. In addition, the platinum-pemetrexed combination continues to be an effective and acceptable treatment option for metastatic patients, those who are medically inoperable, and those for whom complete or near-complete cytoreduction is not achievable.

Safety and efficacy of mesenchymal stromal cell therapy for multi-drug-resistant acute and late-acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.

Graft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (n = 46) or late aGvHD (n = 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) × 106/kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) × 106/kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3-4, and three had ≥ 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3-4, and one had ≥ 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9% of the patients had a complete response (CR), 23.9% had a partial response (PR), and 65.2% had no response (NR). On the other hand, in the late aGvHD group, 23.3% of the patients had CR, 36.7% had PR, and the remaining 40% had NR. These findings were statistically significant (p = 0.031). Also, at the 2-year follow-up, the cumulative incidence of NRM was significantly lower in patients with late aGvHD than in patients with aGvHD at 40% (95% CI, 25-62%) versus 71% (95% CI, 59-86%), respectively (p = 0.032). In addition, the probability of survival at 2 years was significantly higher in patients with late aGvHD than in the aGvHD group at 59% (95% CI, 37-74%) versus 28% (95% CI, 13-40%), respectively (p = 0.002). To our knowledge, our study is the first to compare the safety and efficacy of MSC infusion(s) for the treatment of steroid-resistant late aGVHD and aGVHD. There were no infusion-related adverse effects in either group. The response rate to MSC therapy was significantly higher in the late aGvHD group than in the aGvHD group. In addition, at the 2-year follow-up, the survival and NRM rates were more favorable in patients with late aGVHD than in those with aGVHD. Thus, the results are encouraging and warrant further studies to optimize MSC-based treatment for late aGVHD.

Low relapse rate in patients with giant cell arteritis in a multi-centre retrospective Turkish Registry.

OBJECTIVES: Glucocorticoids (GC) are widely accepted as the standard first-line treatment for giant cell arteritis (GCA). However, relapse rates are reported up to 80% on GC-only protocol arms in controlled trials of tocilizumab and abatacept in 12-24 months. Herein, we aimed to assess the real-life relapse rates retrospectively in patients with GCA from Turkey. METHODS: We assembled a retrospective cohort of patients with GCA diagnosed according to ACR 1990 criteria from tertiary rheumatology centres in Turkey. All clinical data were abstracted from medical records. Relapse was defined as any new manifestation or increased acutephase response leading to the change of the GC dose or use of a new therapeutic agent by the treating physician. RESULTS: The study included 330 (F/M: 196/134) patients with GCA. The mean age at disease onset was 68.9±9 years. The most frequent symptom was headache. Polymyalgia rheumatica was also present in 81 (24.5%) patients. Elevation of acute phase reactants (ESR>50 mm/h or CRP>5 mg/l) was absent in 25 (7.6%) patients at diagnosis. Temporal artery biopsy was available in 241 (73%) patients, and 180 of them had positive histopathological findings for GCA. For remission induction, GC pulses (250-1000 methylprednisolone mg/3-7 days) were given to 69 (20.9%) patients, with further 0.5-1 mg/kg/day prednisolone continued in the whole group. Immunosuppressives as GC-sparing agents were used in 252 (76.4%) patients. During a follow-up of a median 26.5 (6-190) months, relapses occurred in 49 (18.8%) patients. No confounding factor was observed in relapse rates. GC treatment could be stopped in only 62 (23.8%) patients. Additionally, GC-related side effects developed in 64 (24.6%) patients, and 141 (66.2%) had at least one Vasculitis Damage Index (VDI) damage item present during follow-up. CONCLUSIONS: In this first multi-centre series of GCA from Turkey, we observed that only one-fifth of patients had relapses during a mean follow-up of 26 months, with 76.4% given a GC-sparing IS agent at diagnosis. At the end of follow-up, GC-related side effects developed in one-fourth of patients. Our results suggest that patients with GCA had a low relapse rate in real-life experience of a multi-centre retrospective Turkish registry, however with a significant presence of GC-associated side effects during follow-up.

The impact of diabetes mellitus on hematopoietic stem cell mobilization, a-single center cohort study.

BACKGROUND: Factors such as age, underlying hematological disease, chemotherapy and radiotherapy used, and bone marrow infiltration may cause mobilization failure. Several preclinical observed that diabetes mellitus (DM) leads to profound remodeling of the hematopoietic stem cell (HSC) niche, resulting in the impaired release of HSCs. We aim to examine the effect of DM on HSC mobilization and to investigate whether there is a relationship between complications developing in the DM process and drugs used to treat DM and mobilization failure. METHODS: In Erciyes University Bone Marrow Transplantation Unit, 218 patients who underwent apheresis for stem cell mobilization between 2011 and 2021 were evaluated retrospectively. One hundred and nine patients had a diagnosis of DM, and 109 did not. RESULTS: Mobilization failure developed in 17 (15.6 %) of the patients in the DM group, while it developed in 7 (6.4 %) patients in the non-DM group (p = 0.03). CD34+ stem cell count was 8.05 (1.3-30.2) × 106/kg in the DM group, while it was 8.2 (1.7-37.3) × 106/kg in the other group (p = 0.55). There was no statistically significant relationship between glucose and hemoglobin A1c levels and the amount of CD34+ cells (p = 0.83 and p = 0.14, respectively). Using sulfonylurea was the only independent predictor of mobilization failure (OR 5.75, 95 % CI: 1.38-24.05, p = 0.02). CONCLUSION: DM should be considered a risk factor for mobilization failure. Further research is needed fully to understand the mechanisms underlying the mobilization failure effects of sulfonylureas and to develop strategies to improve stem cell mobilization in diabetic patients.

Fludarabine-induced bradycardia in allogeneic hematopoietic stem cell transplantation: A retrospective study.

INTRODUCTION: Fludarabine, a purine analog, is getting more attention with the increasing use of reduced intensive conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The side effect of bradycardia was observed in only a few cases reported in the literature. In clinical practice, bradycardia can be asymptomatic or cause syncope and cardiac arrest. This study aimed to evaluate the bradycardia side effect of fludarabine used in the conditioning regimen in allo-HSCT recipients and to increase awareness of this issue. METHODS: This retrospective study included 73 patients who received fludarabine in the allo-HSCT conditioning regimen between January 2015 and January 2021. Patients with and without bradycardia were compared regarding demographic data, allo-HSCT characteristics, electrolyte values, fludarabine administration dose and duration, and survival. Univariate and multivariate analyzes were performed to evaluate independent predictors for fludarabine-induced bradycardia. RESULTS: Fludarabine administration doses and days were higher in the bradycardia group, but no statistically significant difference was observed. In the multivariate analysis, age was the only independent predictor of fludarabine-induced bradycardia (odds ratio (OR) 0.93, 95% confidence interval (CI): 0.89-0.98, p = 0.007). The median age in the group with bradycardia was 19 years younger than those without bradycardia (34 (19-49) vs 53 (19-69), p = 0.005). In 11 (84.6%) of the patients who had bradycardia, bradycardia improved with the discontinuation of fludarabine alone, but atropine was administered in 2 (15.4%) patients. CONCLUSION: Age was the only independent predictor of fludarabine-induced bradycardia; therefore, close heart rate monitoring is recommended during fludarabine administration, especially in younger patients.

Does proton pump inhibitor reduce the antiaggregant efficacy of aspirin in ischemic stroke?

OBJECTIVE: To evaluate the effect of using acetylsalicylic acid (aspirin) together with lansoprazole in the secondary prevention of ischemic stroke. MATERIALS AND METHODS: 199 patients with a diagnosis of ischemic stroke and transient ischemic attack (TIA) using 100 mg aspirin regularly were included in the study. All patients were evaluated for the presence of aspirin resistance before starting the study. 57 patients with aspirin resistance were excluded from the study. The remaining 142 patients were divided into two groups: the 1st group consisted of those with stomach discomfort and the 2nd group consisted of those without stomach discomfort. Patients in group 1 were given 30 mg of lansoprazole taken before breakfast in addition to aspirin therapy. All patients were re-evaluated for the presence of aspirin resistance at a one-month follow-up. The antiaggregant activity was evaluated by the impedance aggregometry method in both groups. RESULTS: Of 142 patients, 75 were in group 1, and 67 were in group 2. There was no difference between the two groups in terms of age and gender distribution of vascular risk factors. There was no statistically significant difference between the two groups in terms of aspirin efficacy. The dose of aspirin was increased in patients with aspirin resistance (AR). CONCLUSION: The combination of 30 mg lansoprazole and 100 mg aspirin does not cause a decrease in antiaggregant activity in the early period, but chronic use was not evaluated in this study. Patients with AR may benefit from an increase in the dose of aspirin.

Identifying disease-causing mutations with privacy protection.

MOTIVATION: The use of genome data for diagnosis and treatment is becoming increasingly common. Researchers need access to as many genomes as possible to interpret the patient genome, to obtain some statistical patterns and to reveal disease-gene relationships. The sensitive information contained in the genome data and the high risk of re-identification increase the privacy and security concerns associated with sharing such data. In this article, we present an approach to identify disease-associated variants and genes while ensuring patient privacy. The proposed method uses secure multi-party computation to find disease-causing mutations under specific inheritance models without sacrificing the privacy of individuals. It discloses only variants or genes obtained as a result of the analysis. Thus, the vast majority of patient data can be kept private. RESULTS: Our prototype implementation performs analyses on thousands of genomic data in milliseconds, and the runtime scales logarithmically with the number of patients. We present the first inheritance model (recessive, dominant and compound heterozygous) based privacy-preserving analyses of genomic data to find disease-causing mutations. Furthermore, we re-implement the privacy-preserving methods (MAX, SETDIFF and INTERSECTION) proposed in a previous study. Our MAX, SETDIFF and INTERSECTION implementations are 2.5, 1122 and 341 times faster than the corresponding operations of the state-of-the-art protocol, respectively. AVAILABILITY AND IMPLEMENTATION: https://gitlab.com/DIFUTURE/privacy-preserving-genomic-diagnosis. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PAMOGK: a pathway graph kernel-based multiomics approach for patient clustering.

MOTIVATION: Accurate classification of patients into molecular subgroups is critical for the development of effective therapeutics and for deciphering what drives these subgroups to cancer. The availability of multiomics data catalogs for large cohorts of cancer patients provides multiple views into the molecular biology of the tumors with unprecedented resolution. RESULTS: We develop Pathway-based MultiOmic Graph Kernel clustering (PAMOGK) that integrates multiomics patient data with existing biological knowledge on pathways. We develop a novel graph kernel that evaluates patient similarities based on a single molecular alteration type in the context of a pathway. To corroborate multiple views of patients evaluated by hundreds of pathways and molecular alteration combinations, we use multiview kernel clustering. Applying PAMOGK to kidney renal clear cell carcinoma (KIRC) patients results in four clusters with significantly different survival times (P-value =1.24e-11). When we compare PAMOGK to eight other state-of-the-art multiomics clustering methods, PAMOGK consistently outperforms these in terms of its ability to partition KIRC patients into groups with different survival distributions. The discovered patient subgroups also differ with respect to other clinical parameters such as tumor stage and grade, and primary tumor and metastasis tumor spreads. The pathways identified as important are highly relevant to KIRC. AVAILABILITY AND IMPLEMENTATION: github.com/tastanlab/pamogk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Design of the VIALE-M phase III trial of venetoclax and oral azacitidine maintenance therapy in acute myeloid leukemia.

Prevention of relapse is a major therapeutic challenge and an unmet need for patients with acute myeloid leukemia (AML). Venetoclax is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis in AML cells. When combined with azacitidine, it leads to prolonged overall survival and rapid, durable remissions in treatment-naive AML patients ineligible for intensive chemotherapy. VIALE-M is a randomized, double-blind, two-arm study to evaluate the safety and efficacy of venetoclax in combination with oral azacitidine (CC-486) as maintenance therapy in patients in complete remission with incomplete blood count recovery after intensive induction and consolidation therapies. The primary end point is relapse-free survival. Secondary outcomes include overall survival, minimal residual disease conversion and improvement in quality-of-life. Trial Registration Number: NCT04102020 (ClinicalTrials.gov).

Evaluation of COVID-19 fear and quality of life in patients with haematopoietic stem cell transplantation during the COVID-19 pandemic.

OBJECTIVE: We aimed to determine the coronavirus disease 2019 (COVID-19) fear state in haematopoietic stem cell transplant patients and to examine its relationship with quality of life. METHODS: In this prospective study, 64 patients who underwent HSCT during the pandemic were included. The COVID-19 fear situation was evaluated with the Fear of COVID-19 Scale (FCV-19S). Quality of life was evaluated with the European Organisation for Quality of Life Research and Treatment Core Questionnaire (EORTC QLQ-C30) (Version 3). RESULTS: The median FCV-19S score was 16.5 (12.0-22.0). The FCV-19S score was significantly higher in urban residents than rural residents. The general health score was 59.64 ± 20.04. The strongest positive correlation between fear level and life quality was found in emotional function. A weak, significant, positive correlation was observed between role function, nausea-vomiting, pain, appetite loss and fear level. CONCLUSION: FCV-19S is a quick, safe and valid tool that can be used to determine the COVID-19 fear level in vulnerable patient groups such as HSCT patients and to direct them to the necessary psycho-oncological support.

A comparison of four drug-drug interaction databases for patients undergoing haematopoietic stem cell transplantation.

WHAT IS KNOWN AND OBJECTIVE: Patients who have undergone haematopoietic stem cell transplantation are prone to drug-drug interactions due to polypharmacy. Drug-drug interaction databases are essential tools for identifying interactions in this patient group. However, drug-drug interaction checkers, which help manage interactions, may have disagreements about assessing the existence or severance of the interactions. The study aimed to determine differences among popular drug-drug interaction databases from several angles for patients who underwent haematopoietic stem cell transplantation. METHODS: The 21-day treatment sheets of one hundred patients who underwent haematopoietic stem cell transplantation were examined in two subscription-based (Uptodate and Micromedex) and two open-access databases (Drugs.com and Epocrates) in terms of several categories two years in a row. Statistical analysis was utilized to understand the compatibility of databases in terms of severity scores, evidence levels, given references, and word counts in interaction reports. Fleiss' and Cohen's kappa statistics were used to analyse the databases' agreement levels. RESULTS AND DISCUSSION: A total of 1393 and 1382 different drug-drug interactions were detected in subsequent versions of the databases, namely the 2021 and 2022 versions. The Fleiss kappa overall agreement among databases was slight. Uptodate and Micromedex showed fair agreement, and other database pairs showed slight agreement in severity ratings. CONCLUSION: There was a poor agreement among databases for interactions seen in bone marrow transplantation patients. Therefore, it would be safer to use more than one database in daily practice. Further work needs to be done to understand the agreement level of databases for different types of interactions.

Human placental trophoblast progenitor cells (hTPCs) promote angiogenesis and neurogenesis after focal cerebral ischemia in rats.

INTRODUCTION: Reduction of blood flow below a threshold value in brain regions locally or globally is called cerebral ischemia and proper treatment requires either the restoration of normal blood flow and/or the administration of neuroprotective therapies. Human trophoblast progenitor cells (hTPCs) give rise to the placenta and are responsible for the invasion and vascular remodeling of the maternal vessels within the uterus. Here, we tested whether hTPCs promoted to differentiate along neural lineages may exhibit therapeutic properties in the setting of cerebral ischemia in vivo. MATERIALS AND METHODS: Cerebral ischemia was generated in rats via middle cerebral artery occlusion and, after 24 h, hTPCs were injected systemically via tail vein. Animals were sacrified at Day 3 or 11. RESULTS: TTC staining indicated that infarct volumes were smaller in hTPC treated animals. Visible myelin recovery was observed in the hTPC injected group with Luxol Fast Blue staining. On Day 11 after hTPC transplantation, DLX5 and VEGF expression, as well as 2 and 10 d after hTPC transplantation, NKX2.2 were significantly increased; while LHX6, Olig1, PDGFRα, VEGFR1 and VEGFR2 showed trends toward improved expression in brain tissue via immunoblot analysis. Neuron-like differentiated cells were positive for both NeuN and Cresyl Violet staining. CONCLUSION: Here, we demonstrate for the first time that hTPCs enhance the expression of angiogenic and neurogenic factors in rat brain after stroke. Transplantation of hTPCs could form the basis of novel therapeutic approaches for the treatment of stroke in the clinical setting.

Alarms in a neurocritical care unit: a prospective study.

The contemporary practice of monitoring physiologic parameters in the critical care setting is based on alarm systems with high sensitivity but low specificity. A natural consequence of this approach is a massive amount of alarms, which potentially leads to fatigue in the personnel and negatively impacts the quality of care provided. The study objective is to determine the prevalence, types, and determinants of alarms in a neurological critical care unit (NCCU) prototype. During a one-month period corresponding to 272 days of monitoring in 34 patients, nursing staff recorded the type and number of sounding alarms in a university NCCU. Alarms were categorized into three types as type-A alarms that were merely handled by the nursing staff, type-B alarms that were primarily managed by nurses, but the physician was also notified, and type-C alarms that were principally handled by NCCU physicians. There were a total of 9439 alarms, with an average of daily 34.7 alarms per bed, corresponding to one alarm every 41.4 min. Most of the alarms were type-A (57.7%), followed by type-B (39.2%) and type-C (3.1%) alarms. Alarms originated from electrocardiogram (34.6%), pulse oximeter (33.7%), noninvasive blood pressure monitoring (9.8%), respiratory monitoring (9.7%), intravenous fluid pumps (4.5%), ventilator (3.9%), enteral pumps (2.1%) and invasive blood pressure systems (1.7%). A noticeable diurnal variation was observed for type-A pulse oximeter, type-A and -B ECG alarms (increase during morning shifts), and type-A ventilator alarms (decrease during morning shifts). Alarms are highly prevalent in NCCUs and can correspond to an important portion of the workload.

Assessment of Takayasu arteritis in routine practice with PETVAS, an 18F-FDG PET quantitative scoring tool.

BACKGROUND: The aim of this study was to evaluate the value of the PET vascular activity score (PETVAS) during the follow-up of patients with Takayasu arteritis. METHODS: Takayasu arteritis patients who underwent 18F-Fluorodeoxyglucose (FDG) PET imaging were evaluated retrospectively. In 8 patients both 1 and 2-h imagings were also performed prospectively. For PETVAS, 9 arterial areas were scored between 0-3 according to the FDG uptake. RESULTS: Forty-six images of 34 patients were evaluated. PETVAS was higher in patients with clinically active disease (p = 0.03) and in the C-reactive protein (CRP) elevated group among clinically inactive patients (p = 0.0015). PETVAS correlated with CRP (p = 0.003, r = 0.53) and erythrocyte sedimentation rate (p = 0.005, r = 0.41), whereas age, disease duration, immunosuppressive, and glucocorticoid (GC) treatments were not associated with PETVAS. First vs. 2nd-h PETVAS was similar in patients who had both 1st and 2nd h PET scans (p = 0.67). DISCUSSION: We observed higher PETVAS in patients with active disease and elevated acute phase reactants. Although scores in our study (performed at one-h) were lower compared to the original PETVAS study performed at two h, PETVAS seems to be a reliable tool to quantify FDG PET scores in routine practice.

Clinical characteristics and therapeutic outcomes of paroxysmal nocturnal hemoglobinuria patients in Turkey: a multicenter experience.

The aim of this study is to collect paroxysmal nocturnal hemoglobinuria (PNH) patient data from hematology centers all over Turkey in order to identify clinical features and management of PNH patients. Patients with PNH were evaluated by a retrospective review of medical records from 19 different institutions around Turkey. Patient demographics, medical history, laboratory findings, and PNH-specific information, including symptoms at the diagnosis, complications, erythrocyte, and granulocyte clone size, treatment, and causes of death were recorded. Sixty patients (28 males, 32 females) were identified. The median age was 33 (range; 17-77) years. Forty-six patients were diagnosed as classic PNH and 14 as secondary PNH. Fatigue and abdominal pain were the most frequent presenting symptoms. After eculizumab became available in Turkey, most of the patients (n = 31/46, 67.4%) were switched to eculizumab. Three patients with classic PNH underwent stem cell transplantation. The median survival time was 42 (range; 7-183 months) months. This study is the first and most comprehensive review of PNH cases in Turkey. It provided us useful information to find out the differences between our patients and literature, which may help us understand the disease.

Relationship between lymphovascular invasion and molecular subtypes in invasive breast cancer.

PURPOSE: The aim of this study is to evaluate the relation between LVI and molecular subtypes in invasive breast cancers and to find out whether LVI which is a histopathologic indicator has a role in subtype classification or not. METHODS: One hundred and seventy-six patients who had mastectomy for breast cancer between 2013 and 2018 in the Department of Surgical Oncology, Faculty of Medicine, Ankara University were retrospectively analysed. One hundred and thirty-two patients who had LVI, ER, PR, Her 2 and Ki-67 index status information provided in their pathology results were included in the study. The relationship between molecular subtypes and LVI was investigated. RESULTS: One hundred and thirty-two patients were analysed retrospectively. Eighty-two patients had LVI and 50 patients had not. We found a relationship between Luminal B with Her2(-) and LVI, basal like and LVI (P = .00). No significant statistical difference was found between LVI and other molecular subtypes. We confirmed these results with multiple variable analysis (%77.3 correlation). CONCLUSIONS: As a result, we found that LVI can affect molecular subtypes. This showed that a histopathological factor may affect tumour biology. In other words, breast cancer is a heterogeneous disease with many different predictors and prognostic variables.

The diagnostic value of modified systemic inflammation score in predicting post-operative outcomes of cutaneous melanoma patients who underwent isolated limb perfusion.

BACKGROUND: In-transit metastasis is considered a locoregional disease in cutaneous melanoma (CM) patients. Isolated limb perfusion (ILP) is among the treatment options in selected cases. The aim of this study was to determine the success of pre- and post-perfusion mSIS values in predicting the potential complications and the prognosis of the disease by investigating the early and long-term results of mSIS values calculated before and after ILP in CM cases with in-transit metastases. MATERIALS AND METHODS: Patients who underwent ILP within the period from 2014 to 2020 in our department were retrospectively scanned. A total of 20 patients were found to undergo ILP. The scores obtained from modified inflammation score (mSIS) were formulated according to albumin (Alb) and lymphocyte to monocyte ratio (LMR) scores. RESULTS: The mean follow-up time was 20.47 months. Complications requiring surgical intervention developed in three patients. According to the Wieberdink local toxicity classification, the majority (70%) of the patients were found to be grade II. Based on pre-perfusion mSIS values, 8 patients were classified as mSIS 0 while six patients were classified as mSIS 1 and 2. Based on post-perfusion mSIS values, 14 patients and one patient were classified as mSIS 2 (70%) and mSIS 0, respectively. Accordingly, univariate analysis showed that mSIS 1 and mSIS 2 were negative prognostic factors for mean survival in the pre-perfusion period (HR 0.162, 95% CI 0.036-0.729; p = 0.018 and HR: 0.223, 95% CI 0.049-1.019; p = 0.053) whereas albumin (Alb) and lymphocyte to monocyte ratio (LMR) were not independent prognostic factors for mean survival. CONCLUSION: The mSIS values calculated in the pre-perfusion period can give an opinion about the OS of the patients whereas post-perfusion mSIS values may predict potential surgical complications and local toxicities.

Contribution of Human Trophoblast Progenitor Cells to Neurogenesis in Rat Focal Cerebral Ischemia Model.

OBJECTIVE: : A decrease in the blood flow below a current level in the brain results in ischemia. Studies demonstrated that human trophoblast progenitor cells (hTPCs) contribute to the treatment of many diseases. Therefore, hTPCs might be a promising source to repair ischemia in cerebral ischemia models. For this purpose, we evaluated the expression of many neurogenesis markers by performing hTPC transplantation after focal cerebral ischemia in rats. METHODS: : hTPCs, isolated from the term placentae, were characterized by immunofluorescent staining and differentiated into neuron-like cells. Differentiation was confirmed with immunostaining of GFAP and NeuN proteins. Cerebral ischemia models were generated in rats via middle cerebral artery occlusion and, after 24 hours, hTPCs were injected via the tail vein. Animals were sacrificed on day 3 or day 11. Immunohistochemical analysis was performed with proteins associated with neurogenesis and neuronal development, such as DLX2, DLX5, LHX6, NGN1, and NGN2, Olig1, Olig2, and PDGFRα. RESULTS: : According to our results, hTPCs may alleviate ischemic damage in the brain and contribute to the neurogenesis after ischemia. CONCLUSIONS: : Based on our findings, this topic should be further investigated as the hTPC-based therapies may be a reliable source that can be used in the treatment of stroke and ischemia.

A real world multicenter retrospective study on extramedullary disease from Balkan Myeloma Study Group and Barcelona University: analysis of parameters that improve outcome.

Here, we report the outcome of 226 myeloma patients presenting with extramedullary plasmacytoma or paraosseous involvement in a retrospective study conducted in 19 centers from 11 countries. Extramedullary disease was detected at diagnosis or relapse between January 2010 and November 2017. Extramedullary plasmacytoma and paraosseous involvement were observed in 130 patients at diagnosis (92 of 38) and in 96 at relapse (84 of 12). The median time from multiple myeloma diagnosis to the development of extramedullary disease was 25.1 months (range 3.1-106.3 months) in the relapse group (median follow up: 15 months). Imaging approach for extramedullary disease was computed tomography (n=133), positron emission tomography combined with computed tomography (n=50), or magnetic resonance imaging (n=35). The entire group received a median two lines of treatment and autologous stem cell transplantation (44%) following the diagnosis of extramedullary disease. Complete response was higher for paraosseous involvement versus extramedullary plasmacytoma at diagnosis (34.2% vs 19.3%; P=NS.) and relapse (54.5% vs 9%; P=0.001). Also paraosseous involvement patients had a better progression-free survival (PFS) when recognized at initial diagnosis of myeloma than at relapse (51.7 vs 38.9 months). In addition, overall survival was better for paraosseous involvement compared to extramedullary plasmacytoma at diagnosis (not reached vs 46.5 months).Extramedullary plasmacytoma at relapse had the worst prognosis with a PFS of 9.1 months and overall survival of 11.4 months. In the multivariate analysis, paraosseous involvement, extramedullary disease at diagnosis, International Staging System (ISS-I), and undergoing autologous stem cell transplantation improved overall survival independently. This cohort demonstrated that extramedullary disease benefits from front-line autologous stem cell transplantation and extramedullary plasmacytoma differs from paraosseous involvement in terms of rate and duration of response, with even worse outcomes when detected at relapse, constituting an unmet clinical need.