METHODS FOR FIXATION OF BONE FRAGMENTS IN LOWER JAW FRACTURES

Thing. A review of the literature devoted to the topical problem of maxillofacial surgery and surgical dentistry – methods of treating patients with mandibular fractures was carried out. The aim of the study is to review the materials of publications on the methods of treatment of patients with mandibular fractures. Methodology. The publications of domestic and foreign authors, considering methods of fixation of bone fragments in lower jaw fractures, have been studied. Results. Publications indicate that there are many treatments for mandibular fractures. Research results demonstrate the importance of bone stabilization for bone fusion. A common disadvantage of conservative and surgical methods of treatment is unstable fixation of bone fragments, which is the most common cause of delayed consolidation of a mandibular fracture. The presented studies show that bone osteosynthesis with metal plates is considered the most appropriate method for treating mandibular fractures. Conclusions. Splinting as a method of treating fractures of the lower jaw has a large number of disadvantages. A common disadvantage of methods for splinting the lower jaw is that these structures do not always provide anatomical reduction and stability for the entire period of consolidation or require mandatory intermaxillary fixation, the lower jaw is fixed in the central occlusion position, which is not a position of physiological rest, and leads to passive muscle tension. depriving them of active function. The main disadvantage of the methods of osteosynthesis using a suture and using wires is that it is difficult to achieve stable fixation of fragments using these techniques. Combined methods of fixation of bone fragments (use of a bone suture and dental splints) provide a stronger fixation of the fragments. In the past two decades, in the treatment of mandibular fractures, there has been an increase in the trend towards rigid or semi-rigid osteosynthesis using plates. The disadvantages of compression osteosynthesis is that significant compression can lead to ischemia and slow down the formation of callus. A common disadvantage of conservative and surgical methods of treatment is unstable fixation of bone fragments, which is the most common reason for their delayed consolidation. Bone osteosynthesis with metal plates is considered a more progressive method of treating mandibular fractures.

Osteopetrosis. Presentación de dos casos [Non-surgical management of osteopetrosis: two case reports an review of the literature]

Las osteopetrosis (enfermedad de Albers-Schönberg) es un síndrome con cuatro tipos clásicos e instituye una displasia ósea secundaria a la falta de resorción de hueso por anormalidad de los osteoclastos, lo cual provoca un tejido óseo duro y quebradizo,propenso a fracturas difíciles de tratar quirúrgicamente. Se han publicado escasos artículos sobre el tema; por este motivo, decidimos presentar a dos pacientes con fracturas diafisarias de húmero con osteopetrosis, ambas tratadas en forma incruenta.Los objetivos son comunicar nuestra experiencia y el método de tratamiento de dicha afección y realizar una revisión bibliográfica acerca del tema. Creemos que el tratamiento de elección para las fracturas diafisarias de húmero en pacientes con osteopetrosises el incruento, ya que su tipo de tejido óseo dificulta la implementación de cualquier osteosíntesis. Además, la colocación de implantes puede provocar algunas complicaciones, como infecciones, retraso de la consolidación y seudoartrosis. La cirugía se reserva para ciertos casos, como en pacientes con riesgo de desarrollar deformidades incapacitantes, aquellos que han sufrido fracturas repetidas, con retraso de la consolidación, seudoartrosis, quienes no responden al tratamiento incruento o con unadeformidad previa.AbstractOsteopetrosis (also known as Albers-Schönberg disease) is a syndrome that includes four classic types and is characterized by bone dysplasia and lack of bone resorption due to abnormal osteoclastic activity and consequent development of brittle and hard bone that is prone to fractures that are difficult to treat surgically. Herein we present two cases of osteopetrosis with diaphyseal fractures of the humerus, both managed with non-surgical treatment. The objectives of our manuscript are to document our experience in the management of these cases and review the literature. The non-invasive treatment provides the best outcome for dyaphyseal fractures on the humerus in patients with osteopetrosis, given that the quality of the bone in these patients impairs the implementation of osteosynthesis. In addition, the placement of implants can lead to complications such as infections, delayed consolidation and pseudoarthrosis, among others. Surgical treatment should reserved for certain patients such as those with delayed consolidation, pseudoarthrosis, a history of repeated fractures, pre-existing deformity and those who are at risk for the development of disabling deformities or do not respond to non-surgical treatment.

Comparison of Efficacy and Safety of Two Types of E.coli Asparaginase (Native or Pegylated) for Treatment of Adult Patients with High-Risk (HR), Philadelphia (Ph) Chromosome-Negative ALL Included in the Prospective MRD-Oriented Protocol ALL-HR-11 from the Spanish Pethema Group

Background and objective. Asparaginase (ASP) is an essential drug for ALL treatment. Two types of E.coli ASP (native and pegylated) are used in clinical trials for treatment of children and adults with ALL, but to our knowledge direct comparison between these two types of ASP in the same protocol has not been performed. This study aimed to compare the efficacy and safety of native vs. PEG-ASP in adult patients with HR, Ph-negative ALL. Patients and methods. HR ALL included one or more of the following parameters at baseline: age 30-60 yr., WBC count >30x109/L for B-cell precursor ALL or >100x109/L for thymic T-ALL, pro-B, early or mature T-ALL, 11q23 or MLL rearrangements or complex karyotype. Induction therapy consisted of vincristine, prednisone, daunorubicin and ASP (native 10,000 IU/m2, i.v., days 16-20 and 23-27 or PEG 2,000 IU/m2, iv, day 15 depending on center decision) for 4 weeks (Induction-1). FLAG-Ida was administered as intensified induction (Induction-2) in patients not achieving CR or in those in CR with MRD≥0.1% at the end of induction, and those patients proceeded to allogeneic HSCT if CR was attained. Patients in CR and MRD<0.1% proceeded to early consolidation therapy including 3 cycles with rotating cytotoxic drugs with high-dose methotrexate, high-dose ARA-C and ASP (native 20,000 IU/m2 on day 3 of each cycle or PEG 2,000 IU/m2 on day 3 of each cycle). Patients continued with delayed consolidation (identical to that of early consolidation) followed by maintenance therapy up to 2 yr. in continuous CR if MRD levels after consolidation were <0.01%, otherwise they were assigned to allogeneic HSCT. The cumulated doses of native ASP and PEG-ASP for patients who completed the induction and early+delayed consolidation were 220,000 IU/m2 and 14,000 IU/m2, respectively. No ASP levels were assessed. Results. Ninety-onepatients received native ASP and 35 PEG-ASP in Induction-1. The two groups of patients were comparable for the main clinical and hematologic ALL parameters. No differences were observed in the CR rate (86% vs. 86%), in the frequency of MRD level <0.1% after Induction-1 (63% vs. 70%), and that of MRD level <0.01% after early consolidation (74% vs. 92%, p=0.19), as well as in the proportion of patients submitted to allogeneic HSCT (20% vs. 14%). No differences were found in overall survival or disease-free survival probabilities at 3-years according to the type of ASP (OS: 60% [95%CI: 47% ; 73%] vs. 57%[95%CI: 36% ; 78%], p=0.872 and DFS: 40% [95%CI: 25% ; 55%] vs. 58% [95%CI: 36% ; 80%], p=0.302). Abnormalities in the coagulation parameters were significantly more frequent in patients receiving PEG-ASP in Induction-1 (18% vs. 35%, p=0.045). These abnormalities, together with hepatic toxicity were significantly more frequent in patients receiving PEG-ASP in early consolidation (1% vs. 13%, p=0.003, and 5% vs. 34, p<0.001, respectively). A trend for more allergic reactions was seen in patients receiving native ASP (18% vs. 5%, p=0.1) No differences in the frequency of ASP discontinuation rate were observed (6 % vs. 3%). Conclusions. In HR, Ph-negative adult ALL patients included in the PETHEMA ALL-HR 11 protocol the type of E.coli ASP (native vs. PEG) did not have impact on response and outcome. Allergic reactions were more frequently seen with native ASP and coagulation abnormalities and hepatic toxicity were most frequent with PEG-ASP. Most of the differences in toxicity can be explained by the schedule of ASP given in consolidation (single dose of native ASP vs. single dose of PEG-ASP in each cycle). Supported in part by grants RD12/0036/0029 (RTICC, FEDER), PI14/01971 FIS, Instituto Carlos III, and SGR225 (GRE), Spain Disclosures No relevant conflicts of interest to declare.

Post-Remission Treatment with Chemotherapy or Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) of High-Risk (HR) Philadelphia Chromosome-Negative (Ph-neg) Adult Acute Lymphoblastic Leukemia (ALL) According to Minimal Residual Disease (MRD). Preliminary Results of the Pethema ALL-HR-11 Trial

Introduction: Recent studies have shown that young to middle-aged adults who receive a pediatric-inspired chemotherapy regimen for treatment of Ph-neg ALL do not appear to require an alloHSCT if they achieve good response on MRD testing after induction therapy. Patients (pts) who are not good MRD responders achieve better outcomes with alloHSCT than their counterparts who do not receive alloHSCT. However, it is not clear if this approach can be translated to adult ALL pts with HR features at baseline. The aim of the prospective ALL-HR-11 trial from the Spanish PETHEMA Group was to evaluate the response to a differentiated post-induction therapy (chemotherapy or alloHSCT) according to MRD levels (assessed by 8-color, centrally-performed flow cytometry at the end of induction-week 5- and consolidation therapy-week 17-) in HR Ph-neg adult ALL patients. Patients and methods: HR ALL included one or more of the following parameters at baseline: age 30-60 yr, WBC count >30x109/L for B-cell precursor ALL or >100x109/L for thymic T-ALL, pro-B, early or mature T-ALL, 11q23 or MLL rearrangements or complex karyotype. Induction therapy included vincristine, prednisone, daunorubicin and asparaginase (E coli native or PEG according to center availability) for 4 weeks (Induction-1). FLAG-Ida was administered as intensified induction (Induction-2) in pts not achieving CR or those in CR with MRD≥0.1% at the end of induction. For pts in CR and MRD<0.1% early consolidation therapy included 3 cycles with rotating cytotoxic drugs with high-dose methotrexate, high-dose ARA-C and high-dose asparaginase (E coli native or PEG). These pts continued with delayed consolidation (identical to that of early consolidation) followed by maintenance therapy up to 2 yr. in CR if MRD levels after consolidation were <0.01%, otherwise they were assigned to alloHSCT. Pts in CR after Induction-2 received one consolidation cycle and were assigned to alloHSCT. Results: On June 2015, 115 HR ALL pts were evaluable [mean (SD) age 38(13) yr, 67 males, 80/114 precursor B-ALL, 34/114 T-ALL, WBC count 56(96) x109/L]. Results of Induction-1: therapy-related death: 4(4%), resistance: 11 (10%), CR: 95(86%). MRD<0.1% at the end of induction was observed in 75% of CR patients. Induction-2 was administered to 33 patients (no CR: 11, CR and MRD≥0.1%: 22). No differences in the CR rate or in the rate of MRD clearance after induction were observed according to the type of asparaginase administered, although significantly increased hepatic toxicity in consolidation was observed in patients treated with PEG-asparaginase. The 2-yr DFS and OS probabilities for whole series were 51%±18% and 62%±13%. By intention-to treat after Induction-1 36 pts were assigned to alloHSCT and 68 to delayed consolidation and maintenance. The 2-yr DFS and OS probabilities were 54%±25% and 49%±20%, respectively, for pts assigned to alloHSCT, and 50%±22% and 73%±17%, respectively, for those assigned to chemotherapy (P=0.002 for OS comparison). Patients with MRD<0.1% at the end of induction and <0.01% at the end of consolidation (n=51) showed a 2-yr DFS and OS of 55%±25% and 81%±18%, respectively. Conclusions: The preliminary results of this trial, in which the post-induction therapy decision is only based on MRD results, suggest that in HR, Ph-neg adult ALL pts with adequate MRD response after induction and after consolidation the results of therapy are not hampered by avoiding alloHSCT. Supported by grants RD12/0036/0029 (RTICC, FEDER), PI14/01971 FIS, Instituto Carlos III, and SGR225 (GRE), Spain Disclosures No relevant conflicts of interest to declare.