Structurally diverse zinc(II) complexes containing tripodal tetradentate phenoxido-amines with promising antiproliferative effects.

Structurally diverse zinc(II) complexes with tripodal tetradentate phenolic-amines of variable substituents in the phenol and amine moieties were synthesized and thoroughly characterized. The two dinuclear [Zn2(L1)2](ClO4)2·MeOH (1), [Zn2(L2)2](ClO4)2 (2), and four mononuclear [Zn(L3)(H2O)]·MeOH (3), [Zn(L4)] (4), [Zn(L5)] (5) and [Zn(L6)] (6) complexes revealed distorted octahedral, trigonal-bipyramidal or tetrahedral geometries. The free HL1 and H2L3-6 ligands, and complexes 1-6 were evaluated for in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3 and 22Rv1) and normal healthy MRC-5 cells. Overall results revealed high-to-moderate cytotoxicity (with the best IC50 values for complex 6 ranging from 2.4 to 4.5 µM), which is however, significantly higher than that of the reference drug cisplatin. The moderately active complexes 1-4 showed considerable selectivity on A2780 cells (IC50 ≈ 16.3-19.5 µM) over MRC-5 ones (with IC50 >50 µM for 1, 2 and 4, and with IC50 >25 µM for 3). The complexes 1, 2, and 6 and the ligand H2L6 were chosen for subsequent deeper biological evaluations. Their time-resolved cellular uptake and other cellular effects in A2780 cells were studied, such as cell cycle profile, intracellular ROS production, induction of apoptosis and activation of caspases 3/7. Complexes 1 and 2 caused significant G0/G1 cell cycle arrest in A2780 cells and antioxidant effects at normal conditions. They showed only limited effects on cellular processes connected with cytotoxicity, i.e. induction of apoptosis, depletion of mitochondrial membrane potential, and autophagy. These findings can be at least partly attributed to the low ability of the complexes to enter the A2780 cells and the depression of metabolic activity of the target cancer cells.

Tumor necrosis factor alpha induced protein 3, interleukin 10, tumor necrosis factor alpha, and interleukin 17 F genes polymorphisms in Algerian patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation. Its pathogenesis involves immunological, genetic, and environmental factors. We investigate the association between Tumor Necrosis Factor α Protein 3 (TNFAIP3), Interleukin 10 (IL10), Tumor Necrosis Factor α (TNF α), and Interleukin 17 F (IL17F) polymorphisms with susceptibility to RA. METHODS AND RESULTS: 191 patients with RA diagnosed according to the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification and 190 healthy subjects were recruited. Rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and C-reactive protein (CRP) were measured. Genotyping of the polymorphisms was performed by real-time PCR. Analysis of the allelic frequencies of TNFAIP3 showed a positive association OR (95% CI) = 1.46 (1.01-2.09); p = 0.04, but failed to meet the criteria of significance after Bonferroni Correction. The genotypic and allelic distribution of the IL10, IL17F, and TNFα showed no significant difference when comparing the RA group with controls. Furthermore, the genotype codominant model shows a moderate positive association in the presence of ACPA (OR (95% CI) = 2.82 (1.22-6.24); p = 0.01. None of the polymorphisms studied was associated with RF and CRP production. CONCLUSION: Our results show that there is a tendency for the AG genotype of IL10-1082 to be associated with the production of ACPA in patients with RA. None of the variants studied were associated with RA susceptibility in Algerians.

B-scan measurements of intraocular tumor heights intraoperatively, before and after radioactive plaque application: A comparative prospective study.

PURPOSE: To assess the difference in intraocular tumors height measurements intraoperatively before and after radioactive plaque application. METHODOLOGY: Twenty-four eyes of 24 patients with intraocular tumors, candidates for radioactive therapy, were included. Each tumor was measured at the same setting before and after plaque application independently by 3 sonographers, using a 20-MHz B-scan transducer. Mean pre-plaque and post-plaque measurements were calculated and recorded. An A-scan vector aided in identification of the inner and outer tumor surfaces. RESULTS: Each patient was examined independently three times by three experienced ultrasonographers within the same setting to assess interobserver variability. There was no statistically significant difference between the 3 examiners' readings, with P-value 0.99 for pre-plaque height and 0.97 for post-plaque height. Mean pre-plaque height was 5.16±2.11mm, while post-plaque height was 5.51±2.1mm (P-value 0.001). The Spearman correlation test showed that initial tumor height was negatively correlated with the difference between both heights, but with no statistical significance. CONCLUSION: Intraocular tumor height measurement differs significantly before and after plaque application. Use of the pre-plaque height is advised until further studies are performed to assess the effect of this difference on treatment outcomes.

Giant right ventricular thrombus as the revealing form of Behçet's disease.

BACKGROUND: Behçet's disease BD is a rare multisystemic disease, with rare cardiac involvement. This case illustrates a rare cardiac involvement as a giant intracavitary thrombus which was the revealing form of Behçet disease. CASE PRESENTATION: An 15-year-old male admitted to the emergency department for progressive dyspnoea, hemoptysis for which an echocardiogram displayed a large echogenic mass in the right ventricle and angio CT revealed associated bilateral pulmonary embolism. The patient was then proposed for surgery for removal and pathological study the later confirmed its fibrin thrombotic nature. Behçet disease was suspected based on past history of recurrent oral aphthosis and confirmed with a positive pathergy test. Further management by anticoagulants, immunosuppressants and corticosteroids seemed effective to avoid relapse. CONCLUSIONS: Cardiac involvement during BD can be life-threatening as it is not always diagnosed in timely manner. However, intracardiac thrombus is uncommon with only few case reports. Echocardiography is the key tool for the diagnosis of intracardiac thrombus.

miRNAs role in cervical cancer pathogenesis and targeted therapy: Signaling pathways interplay.

Cervical cancer (CC) is the primary cause of cancer deaths in underdeveloped countries. The persistence of infection with high-risk human papillomavirus (HPV) is a significant contributor to the development of CC. However, few women with morphologic HPV infection develop invasive illnesses, suggesting other mechanisms contribute to cervical carcinogenesis. MicroRNAs (miRNAs, miRs) are small chain nucleic acids that can regulate wide networks of cellular events. They can inhibit or degrade their target protein-encoding genes. They had the power to regulate CC's invasion, pathophysiology, angiogenesis, apoptosis, proliferation, and cell cycle phases. Further research is required, even though novel methods have been developed for employing miRNAs in the diagnosis, and treatment of CC. We'll go through some of the new findings about miRNAs and their function in CC below. The function of miRNAs in the development of CC and its treatment is one of these. Clinical uses of miRNAs in the analysis, prediction, and management of CC are also covered.

Overview of Optical Biosensors for Early Cancer Detection: Fundamentals, Applications and Future Perspectives.

Conventional cancer detection and treatment methodologies are based on surgical, chemical and radiational processes, which are expensive, time consuming and painful. Therefore, great interest has been directed toward developing sensitive, inexpensive and rapid techniques for early cancer detection. Optical biosensors have advantages in terms of high sensitivity and being label free with a compact size. In this review paper, the state of the art of optical biosensors for early cancer detection is presented in detail. The basic idea, sensitivity analysis, advantages and limitations of the optical biosensors are discussed. This includes optical biosensors based on plasmonic waveguides, photonic crystal fibers, slot waveguides and metamaterials. Further, the traditional optical methods, such as the colorimetric technique, optical coherence tomography, surface-enhanced Raman spectroscopy and reflectometric interference spectroscopy, are addressed.

Productive performance, lipid profile, immunity, and antioxidant parameters of quail breeders fed low protein diets supplemented with different zinc sources.

The current study was conducted to study the impact of low-CP protein diets with different sources of zinc (zinc oxide-ZnO and zinc methionine-Zn-Met) on performance, lipid profile, immune and antioxidant parameters of quail breeders. A total number of 216 Japanese quail at 8 weeks of age were randomly distributed into nine (3 × 3) groups, with four replicates, each of six quails (four females and two males). Quails were fed three levels of CP (16, 18, and 20%) and three sources of Zn (0, 0.1 g ZnO, and 0.1 g Zn-Met/kg diets). No significant differences in daily feed intake (FI), feed conversion ratio (FCR), and egg mass are due to the main effect of protein levels or zinc sources at all ages. Dietary CP (16 and 20%) in growing quail diets increased SOD and GSH, while IgG levels were improved by 18%. Finally, it can be recommended that 16% CP and zinc source (Zn-Met or ZnO) can maintain egg mass, as well as lipid profile, immunological and antioxidant parameters in Japanese quails breeders. This level (16% CP) is enough during the production stage and a valuable way for mitigating ammonia pollution and reducing feeding costs.

Dinuclear doubly bridged phenoxido copper(II) complexes as efficient anticancer agents.

Two cationic [Cu2(L1-2)2](ClO4)2 (1, 2), and four neutral doubly bridged-phenoxido-copper(II) complexes [Cu2(L3-4)2] (3, 4) and [Cu2(L5-6)2(H2O)]‧2H2O (5, 6) as well as 1D polymeric catena-[Cu(L7)] (7), where HL1-2 and H2L3-7 represent tripodal tetradentate pyridyl or aliphatic-amino groups based 2,4-disubstituted phenolates, were synthesized and thoroughly characterized by various spectroscopic methods and single crystal X-ray analysis. The molecular structures of the complexes exhibited diverse geometrical environments around the central Cu(II) atoms. The in vitro antiproliferative activity of the isolated complexes and selected parent free ligands were screened against some human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, MCF-7). The most promising cytotoxicity against cancer cells were obtained for 1-6, while complex 6 was found as the best performing as compared to the reference drug cisplatin. The cytotoxicity study of complex 6 was therefore extended to wider variety of cancer cell lines (HOS, A549, PANC-1, CaCo2, HeLa) and results revealed its significant cytotoxicity on all investigated human cancer cells. The cell uptake study showed that cytotoxicity of 6 (3 µM concentration and 24 h of incubation) against A2780 cells was almost independent from the intracellular levels of copper. The effect of complexes 4, 6 and 7 on cell cycle of A2780 cells indicates that the mechanism of action in these complexes is not only different from that of cisplatin but also different among them. Complex 7 was able to induce apoptosis in A2780 cells, while complexes 4 and 6 did not and on the other hand, they showed considerable effect on autophagy induction and there are some clues that these complexes were able to induce cuproptosis in A2780 cells.

Clinical characteristics and treatment outcomes of germ cell tumor in Jordan: A tertiary center experience.

Objective: In the Middle East, there is a paucity of data regarding germ cell tumor characteristics and treatment outcomes. Herein, we aim to present the largest series in Jordan reporting our cancer center experience managing GCT. Methods: Between 2010 and 2020, a total of 241 patients with a pathological diagnosis of GCT were treated at our cancer center. Demographic, epidemiologic, and pathological data were retrospectively collected. In addition, survival and relapse outcomes based on tumor stage and adjuvant treatment were collected. Results: A total of 241 patients were diagnosed with GCT, of whom 108 (44.8%) had seminoma and 133 (55.2%) had non-seminoma tumors (NSGCT). Median age (interquartile range) at diagnosis was 31 years (25-36). Patients with seminoma (68.5%) had pT1 disease post orchiectomy, while only 37.5% of patients with NSGCT had pT1 on final pathology. Elevated tumor markers such as beta-human chorionic gonadotropin were present in 10% of seminomas. Following radical orchiectomy and staging, 88 (36.5%) went for active surveillance while 153 patients (63.5%) received adjuvant treatment. With regard to pathology slides read outside, rereading by our genitourinary pathologist yielded a discrepancy on GCT type in 41 (19.3%) out of 212 patients. The median follow-up was 36 (24-48) months. Twenty-two patients relapsed after an average follow-up time of 39 months. The 5-year overall survival for stage I, II, and III was 98%, 94%, and 87%, respectively, and 3-year recurrence-free survival for stage I, II, and III was 94.8%, 78%, and 67%, respectively. Conclusion: Our data on testicular GCT including demographic, histological, and treatment outcomes were comparable to that of developed countries. In light of the pathology discrepancy rate revealed in our study, authors recommend a second review by expert genitourinary pathologists to ensure proper classification and management of GCT.

Separation of Soluble Benzene from an Aqueous Solution by Pervaporation Using a Commercial Polydimethylsiloxane Membrane.

A developed polydimethylsiloxane (PDMS) membrane was used to separate soluble benzene compounds (C6H6) from an aqueous solution via a pervaporation (PV) process. This membrane was characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, contact angle (CA), and energy-dispersive spectroscopy (EDS). To evaluate the performance of the membrane, the separation factor and permeation flux were estimated in various operating conditions, including the feed temperature, initial benzene concentration, and feed flow rate. The experiments to maximize the separation factor and permeation flux were designed using the response surface method (RSM) that is built into Minitab 18. A quadratic model (nonlinear regression equation) was suggested to obtain mathematical expressions to predict the benzene permeation flux and the separation factor according to the effect of the parameters' interaction. The optimization of the PV was performed using an RSM that was based on the analysis of variance (ANOVA). The optimal values of the benzene permeation flux and separation factor were 6.7 g/m2·h and 39.8, respectively, at the optimal conditions of temperature (30 °C), initial concentration of benzene (1000 ppm), and feed flow rate (3.5 L/min). It was found that the feed concentration was the most influential parameter, leading to a significant increase in the permeation flux and separation factor of the PDMS membrane.

Terrible triad injury of the elbow: A PROCESS-compliant surgical case series from Eastern Morocco.

Introduction: The terrible triad of the elbow (TTE) is a lesion associating a dislocation of the elbow, a fracture of the radial head, and a fracture of the coronoid process, with a high potential of complication. The treatment is based on the restoration of bone lesions and external capsular ligament repair. The systematic repair of the medial collateral ligament (MCL) is still debated in the literature. The aim of this study is to evaluate the clinical and functional results of the surgical treatment in a real-world series from Easter Morocco. Patients and methods: This was a retrospective study of 6 cases of TTE operated by isolated external approach or combined approach (internal or anterior) of the elbow in the department of Traumatology-Orthopedics of the Mohammed VI University Hospital (Oujda Morocco), over a period of 7 years from 2013 to 2020. Radial head and coronoid process fractures were classified according to the Mason and Morrey-Regan classifications, respectively. The following clinical parameters were evaluated: Mayo Clinic Elbow Performance Score (MEPS), Quick Disabilities of the Arm, Shoulder and Hand (DASH), Visual Analog Scale (VAS), and arc of mobility in flexion-extension and prono-supination. Results: 6 male patients treated between May 2013 and December 2020 were included. The median follow-up was 48 months. All patients had frontal and lateral standard X-ray of over and under joints, and computed tomography (CT)-scan was delivered for 5 cases. The elbow dislocation was posterolateral in five cases, and posteromedial in only one patient. Radial head fractures were classified as type I in one case, type II in two cases, and type III in three cases. Coronoid fractures were type I in three cases, type II in one case, and type III in two cases. At the last follow up, the mean MEPS, Quick DASH, and VAS was 81, 28, 0.8, respectively. The mean arc of mobility in flexion was 120° and it was deficient by 20° in extension. In addition, the mean arc of mobility in protonation was 80°, while in supination it was 75°. Regarding complications, we noticed an instability of the elbow on valgus in a single case, elbow stiffness with heterotopic ossification in a single case, ulnar nerve damage in a single case during medial collateral ligament anchoring, and elbow hygroma in one single case. Conclusion: The surgical management of TTE can provide good and long-term functional results after restoration of the stabilization of bone structures and the lateral ligament complex, without the need to repair the medial collateral ligament.

Evaluation of novel coagulation and platelet function assays in patients with chronic kidney disease.

BACKGROUND: Hemostasis evaluation in chronic kidney disease (CKD) is critical for optimal management of thrombotic and bleeding events. Standard coagulation screens are inadequate for predicting coagulopathy in CKD. OBJECTIVE: To evaluate hemostasis parameters in patients with different stages of CKD using novel coagulation assays. PATIENTS/METHODS: Cross-sectional study of 30 healthy controls (HC) and 120 CKD patients (10 Stage 2, 20 Stage 3, 20 Stage 4, 20 Stage 5 not requiring renal replacement therapy, 20 transplant, 10 newly started on hemodialysis [HD], 20 established on HD). Standard laboratory tests were performed in addition to rotational thromboelastometry (ROTEM), multiple electrode aggregometry (MEA), thrombin generation assays, D-dimer, and markers of thrombogenesis (thrombin-antithrombin [TAT]), fibrinolysis, and endothelial activation (intercellular adhesion molecule-1 [ICAM-1]). RESULTS: D-dimer, TAT, and ICAM-1 concentrations were significantly higher in patients with CKD than HC (P < .01). ROTEM maximum clot firmness was significantly higher in patients than in HC (P < .01). In CKD Stage 5 patients (pre-HD and started HD) adenosine diphosphate and thrombin receptor activating peptide MEA tests were significantly lower than HC indicating platelet aggregation defect (P < .05). Multivariate analysis confirmed the direct effect of estimated glomerular filtration rate (eGFR) in the variance of ROTEM and MEA tests. Endogenous thrombin potential and peak thrombin were not statistically different between groups, but Stage 5 CKD patients had prolonged lag time (7.91 vs. 6.33, P < .001) and time to thrombin peak (10.8 vs. 9.5, P < .05) compared to HC. CONCLUSIONS: Patients with CKD exhibit features of concomitant hypercoagulability measured by ROTEM and platelet dysfunction measured with MEA. eGFR was an independent determinant of platelet dysfunction and hypercoagulability.

Supplementation of different zinc sources to low-CP diets and its effect on performance, carcass traits, liver and kidney functions, immunological, and antioxidant parameters of quail chicks.

The present study was performed to evaluate the influence of low crude protein (CP) levels, zinc sources (organic as zinc methionine-Zn-Met and inorganic as zinc oxide-ZnO) and their interactions on growth performance, carcass traits, and blood components of growing Japanese quail. A total of 450 one-wk-old Japanese quail with the same body weights were randomly distributed into 9 groups of 50 birds. The 9-diet treatments comprised 3 levels of CP (20, 22, and 24%) and 3 Zn source (0 g of Zn/kg diet, 0.1 g ZnO/kg diet, and 0.1 g Zn-Met/kg diet). The results obtained from this study showed that there were no significant differences among the groups, except for differences in body weight (BW) and body weight gain (BWG) at 3 to 5 - and 1 to 5 wk of age for quail supplemented with 24% and 20% CP. All the studied biochemical parameters were significantly influenced by different levels of CP and Zn, except urea and creatinine, which were affected by CP levels only. In conclusion, dietary protein level for growing Japanese quails could be reduced to 20% without negative effects on their performance, carcass traits, and blood metabolites.

Identification of potent anticancer copper(ii) complexes containing tripodal bis[2-ethyl-di(3,5-dialkyl-1H-pyrazol-1-yl)]amine moiety.

A series of heteroleptic copper(ii) complexes of the composition [Cu(L1-5)Cl]X, where X = ClO4 and/or PF6 and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(6-methyl-(2-pyridylmethyl))]amine (L1), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl))-(3,4-dimethoxy-(2-pyridylmethyl))]amine (L2), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(2-quinolymethyl)]amine (L3), [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazolyl)-(di(3,5-dimethyl-1H-pyrazol-1-yl-methyl))]amine (L4) and [bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-(5-methyl-3-phenyl-1H-pyrazol-1-yl-methyl)]amine (L5), were prepared and thoroughly characterized including single-crystal X-ray diffraction technique. The in vitro cytotoxicity of complexes against A2780, A2780R, HOS and MCF-7 human cancer cell lines was evaluated using the MTT test. The results revealed that complexes [Cu(L1)Cl]PF6 (1-PF6), [Cu(L2)Cl]ClO4 (2-ClO4) and [Cu(L3)Cl]PF6 (3-PF6) are the most effective, with IC50 values ranging from 1.4 to 6.3 µM, thus exceeding the cytotoxic potential of metallodrug cisplatin (IC50 values ranging from 29.9 to 82.0 µM). The complexes [Cu(L4)Cl]PF6 (4-PF6) and [Cu(L5)Cl]PF6 (5-PF6) showed only moderate cytotoxicity against A2780, with IC50 = 53.6 µM, and 33.8 µM, respectively. The cell cycle profile, time-resolved cellular uptake, interactions with small sulfur-containing biomolecules (cysteine and glutathione), intracellular ROS production, induction of apoptosis and activation of caspases 3/7 were also evaluated in the case of the selected complexes. It has been found that the best performing complexes 1 and 2 cause cell arrest in the G2/M phase and induce apoptosis via the increase in production of ROS, dominantly due to the overproduction of superoxide.

Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma.

BACKGROUND: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing sarcoma (ES), although studies are largely limited to paediatric populations. METHODS: We retrospectively reviewed paediatric (< 18 years) and adult patients (≥ 18 years) treated with salvage IT at two institutions. Haematologic toxicities were graded according to common terminology criteria of adverse events. Survival was estimated by the Kaplan-Meier method and compared by the Log Rank test. RESULTS: Fifty-three patients were treated with IT from Jan, 2010 to Dec, 2018 (n = 16 paediatric; n = 37 adult). IT was given as second-line (n = 34; 64%) or ≥ third-line (n = 19; 36%). There was no difference in ≥ grade 3/4 haematologic toxicity between paediatrics and adults (31% vs. 35% respectively; p = 0.76). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 12 (28%) stable disease and 19 (44%) disease progression. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.2 months, p = 0.039). CONCLUSION: Irinotecan and temozolomide (IT) chemotherapy has activity for relapsed ES, with favourable toxicity and equally observed objective responses in the paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in future studies.

A Systematic Framework for Optimizing a Sweeping Gas Membrane Distillation (SGMD).

The present work has undertaken a meticulous glance on optimizing the performance of an SGMD configuration utilized a porous poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-co-HFP) membrane. This was carried out by conducting a systematic framework for investigating and optimizing the pertinent parameters such as sweeping gas flow rate, feed temperature, feed concentration and feed flow rate on the permeate flux. For this purpose, the Taguchi method and design of experiment techniques were harnessed to statistically determine optimum operational conditions. Besides that, a comprehensive surface and permeation characterization was conducted against the hand-made membranes. Results showcased that the membrane performance was ultimately controlled by the feed temperature and was nearly (~680) % higher when the temperature raised from 45 to 65 °C. Also, to a lesser extent, the system was dominated by the feed flow rate. As the adopted feed flow rate increases (from 0.2 to 0.6 L/min), around 47.5% increment was bestowed on water permeability characteristics. In contra, 34.5% flux decline was witnessed when higher saline feed concentration (100 g/L) was utilized. In the meantime, with raising the sweeping gas flow rate (from 120 to 300 L/h), the distillate was nearly 129% higher. Based on Taguchi design, the maximum permeate flux (17.3 and 17 kg/m2·h) was secured at 35 g/L, 0.4 L/min, 65 °C and 300 L/h, for both commercial and prepared membranes, respectively.

Androgen therapy in inherited bone marrow failure syndromes: analysis from the Canadian Inherited Marrow Failure Registry.

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.

Outcomes of extraskeletal vs. skeletal Ewing sarcoma patients treated with standard chemotherapy protocol.

PURPOSE: To compare the outcomes of extraskeletal and skeletal Ewing sarcomas treated with standard chemotherapy protocol. METHODS: We retrospectively collected data on primary localized skeletal and extraskeletal ES patients. Demographics and disease characteristics were compared between the two groups. The influence of presentation (skeletal vs. extraskeletal) on overall survival (OS) and local recurrence-free survival (LRFS) was assessed and compared by the log-rank test. RESULTS: A total of 120 patients were included; 29 (24%) had extraskeletal and 91 (76%) had skeletal ES. All patients received vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE) chemotherapy, with a plan for local control at week 12. At a median follow-up of 38 months, there was no difference in OS between skeletal and extraskeletal ES; 5-year OS 70% and 67% respectively, p = 0.96. Patients with extraskeletal ES had inferior 5-year LRFS compared to skeletal ES; 74% vs. 83%; p = 0.042. Local recurrence occurred at a higher frequency in the extraskeletal group; 28% vs. 11%, p = 0.034, although more extraskeletal patients received adjuvant radiotherapy; 73% vs. 36%, p = 0.01. Among patients who underwent surgery (n = 76), there was no difference in R0 resection rate (skeletal: 89%, extraskeletal: 86%, p = 0.52, or good ( ≥ 90%) tumor necrosis; skeletal: 54%, extraskeletal: 38%, p = 0.31. CONCLUSION: Patients with localized extraskeletal ES have comparable OS outcomes to patients with skeletal ES utilizing the standard VDC-IE chemotherapy. However, extraskeletal patients are at significantly higher risk for local recurrence.