Long-term Insights: Histopathological Assessment in Polyurethane Implant Capsules up to 24 Years.

BACKGROUND: Polyurethane (PU)-coated breast implants are known for their strong integration into breast tissue and the formation of capsules around them. However, capsular contracture can pose both aesthetic and clinical challenges. OBJECTIVES: To analyze the biological and morphological characteristics of the capsular tissue surrounding PU-coated implants, irrespective of their contracture status, and to assess their potential suitability as a flap in revision breast surgery for capsular contracture. METHODS: A total of 23 tissue samples were harvested from the capsules surrounding PU-coated breast implants in 12 female patients during replacement or revision surgery. We evaluated collagen abundance, cellular and vascular density, inflammation, collagen band types and alignment, synovial metaplasia, capsule thickness, and the expression of inflammatory biomarkers and myofibroblasts using immunohistochemical techniques. Scanning electron microscopy was used to assess implant surface characteristics over time. RESULTS: We found a significant association of capsule contraction with longer implantation durations and greater implant surface roughness (p = 0.018 and p = 0.033, respectively). Synovial metaplasia was significantly more frequent in noncontracted capsules (p = 0.0049). Both capsule types consisted of paucicellular, type I collagen-rich compact fibrous tissue with low vascularization. There was a marked reduction in inflammatory cells within the foreign body granuloma. The expression of inflammatory biomarkers in the capsular tissue was negligible. CONCLUSIONS: Given the reduced levels of inflammatory and vascular components within the dense, fibrous capsular tissue, we consider them to be viable alternatives for use as capsular flaps in revision surgery. This strategy has the potential to mimic the reconstruction achieved with acellular dermal matrix.

Micellar solution of [223Ra]RaCl2: Reaching renal excretion, potent efficacy in osteoblastic osteosarcoma in PDX model, biochemistry alterations and pharmacokinetics.

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.

Characterization of the Masquelet Induced Membrane Technique in a Murine Segmental Bone Defect Model.

Objective To reproduce in an animal model the surgical technique of Masquelet used in the treatment of critical bone defects and to analyze the characteristics of the membrane formed around the bone cement. Methods A 10mm critical defect was created in the femoral shaft of 21 Sprague-Dawley rats. After resection of the central portion of the diaphysis, the defect was stabilized with a Kirschner wire introduced through the medullary canal and with the interposition of a bone cement spacer. After 2, 4, and 6 weeks of the surgical procedure, the animals were euthanized and evaluated on radiographs of the posterior limb regarding the size of the defect, alignment and stability of the osteosynthesis. The membranes formed around the spacer were subjected to histological analysis to assess thickness, connective tissue maturation and vascular density. Results Over time, the membranes initially made up of loose connective tissue were replaced by membranes represented by dense connective tissue, rich in thick collagen fibers. At six weeks, membrane thickness was greater (565 ± 208µm) than at four (186.9 ± 70.21µm, p = 0.0002) and two weeks (252.2 ± 55.1µm, p = 0.001). All membranes from the initial time showed foci of osteogenic differentiation that progressively reduced over time. Conclusion In addition to the structural and protective function of the membrane, its intrinsic biological characteristics can actively contribute to bone regeneration. The biological activity attributed by the presence of foci of osteogenesis confers to the membrane the potential of osteoinduction that favors the local conditions for the integration of the bone graft.

Characterization of the Masquelet Induced Membrane Technique in a Murine Segmental Bone Defect Model / Caracterização da membrana induzida pela técnica de Masquelet em modelo murino de defeito ósseo segmentar

Abstract Objective To reproduce in an animal model the surgical technique of Masquelet used in the treatment of critical bone defects and to analyze the characteristics of the membrane formed around the bone cement. Methods A 10mm critical defect was created in the femoral shaft of 21 Sprague-Dawley rats. After resection of the central portion of the diaphysis, the defect was stabilized with a Kirschner wire introduced through the medullary canal and with the interposition of a bone cement spacer. After 2, 4, and 6 weeks of the surgical procedure, the animals were euthanized and evaluated on radiographs of the posterior limb regarding the size of the defect, alignment and stability of the osteosynthesis. The membranes formed around the spacer were subjected to histological analysis to assess thickness, connective tissue maturation and vascular density. Results Over time, the membranes initially made up of loose connective tissue were replaced by membranes represented by dense connective tissue, rich in thick collagen fibers. At six weeks, membrane thickness was greater (565 ± 208μm) than at four (186.9 ± 70.21μm, p = 0.0002) and two weeks (252.2 ± 55.1μm, p = 0.001). All membranes from the initial time showed foci of osteogenic differentiation that progressively reduced over time. Conclusion In addition to the structural and protective function of the membrane, its intrinsic biological characteristics can actively contribute to bone regeneration. The biological activity attributed by the presence of foci of osteogenesis confers to the membrane the potential of osteoinduction that favors the local conditions for the integration of the bone graft.

Resumo Objetivo Reproduzir em modelo animal a técnica cirúrgica de Masquelet utilizada no tratamento de defeitos ósseos críticos e analisar as características da membrana formada em torno do cimento ósseo. Métodos Um defeito crítico de 10mm foi realizado na diáfise femoral de 21 ratos Sprague-Dawley. Após a ressecção da porção central da diáfise o defeito foi estabilizado com fio de Kirschner introduzido pelo canal medular e com a interposição de espaçador de cimento ósseo. Após 2, 4, e 6 semanas do procedimento cirúrgico os animais foram eutanasiados e avaliados em radiografias do membro posterior quanto ao tamanho do defeito, o alinhamento e a estabilidade da osteossíntese. As membranas formadas em torno do espaçador foram submetidas a análise histológica para avaliação da espessura, da maturação do tecido conjuntivo e da densidade vascular. Resultados Ao longo do tempo as membranas inicialmente constituídas por tecido conjuntivo frouxo foram substituídas por membranas representadas por tecido conjuntivo denso, rico em fibras colágenas espessas. Com seis semanas a espessura das membranas foi maior (565 ± 208μm) do que com quatro (186,9 ± 70,21μm, p = 0,0002) e duas semanas (252,2 ± 55,1μm, p = 0,001). Todas as membranas do tempo inicial apresentaram focos de diferenciação osteogênica que reduziram progressivamente ao longo do tempo. Conclusão Além da função estrutural e protetora da membrana, suas características biológicas intrínsecas podem contribuir ativamente para a regeneração óssea. A atividade biológica atribuída pela presença de focos de osteogênese confere à membrana potencial de osteoindução que favorece as condições locais para a integração do enxerto ósseo.

Concepções e práticas dos agentes comunitários de saúde direcionadas a demanda de álcool e outras drogas no território da Borborema potiguar / Community Health agents' practices and conceptions regarding alcohol and other drugs in the potiguar Borborema

Resumo É possível perceber que na história múltiplas substâncias psicoativas foram usadas por indivíduos devido a diversos motivos, sentidos e contextos. Ao abordar essa temática, torna-se imprescindível compreender de que modo essa demanda chega aos serviços do Sistema Único de Saúde, especialmente na Atenção Primária à Saúde, e como estabelece ligação com a Redução de Danos. Diante disso, esta pesquisa tem como objetivo analisar como essa demanda impacta na Atenção Primária à Saúde diante da perspectiva dos Agentes Comunitários de Saúde. A pesquisa ocorreu em uma Unidade Básica de Saúde em uma cidade do interior do Rio Grande do Norte. Para abordar e interpretar os dados, optou-se por uma abordagem qualitativa, na perspectiva teórico metodológica da Análise Institucional, com ênfase na pesquisa-intervenção. Os instrumentos utilizados foram roda de conversa, entrevistas individuais e diário de pesquisa. Conforme os resultados, constatou-se o cuidado direcionado pelo saber biomédico, hospitalocêntrico, restritivo e segregador do cuidado, os quais envolvem processos fragmentados de trabalho num contexto imerso por desigualdades sociais e muita violência. Ademais, foi exposto como esses profissionais percebem a procura dos usuários no serviço em que atuam, com limites de diversas ordens, repletos de medos, tensões e silenciamentos em torno da complexidade da atuação no território.

Abstract Historically, humans have used multiple psychoactive substances for a myriad of reasons, meanings, and in different contexts. When discussing this topic, it is essential toone must understand how this demand reaches Brazilian National Health System services, especially in Primary Health Care, and how it relates to Harm Reduction. Thus, this research analyzes how this demand impacts Primary Health Care as perceived by Community Health Agents. An intervention research was conducted in a Basic Health Unit in a municipality from Rio Grande do Norte, Brazil. Data were collected by means of conversation circles, individual interviews and a research diary and examined by Institutional Analysis. Results showed a hospital-centered, biomedical, restrictive and segregating care involving fragmented work processes in a context social inequalities and violence. Moreover, professionals perceived user demand as limited by various elements such as fear, tensions and silencing regarding the complexity of acting in the territory.

Correlation Between Implant Positioning and Functional Outcomes in Partial Shoulder Resurfacing.

Objective The present study aimed to correlate functional outcomes and implant positioning in a case series of partial shoulder resurfacing arthroplasties. Methods A total of 25 patients were assessed for range of motion, functional outcome per the University of California at Los Angeles (UCLA) score and radiographic findings. Pre- and postoperative data were compared. In addition, patients were grouped according to the cervical-diaphyseal angle (CDA) determined by an anteroposterior radiography and to the retroversion angle (RVA) determined by an axillary radiography. A CDA from 130° to 140° and a RVA from 20° to 40° consisted in ideal positioning (anatomical standard). Data were analyzed using the Wilcoxon signed-rank test, analysis of variance (ANOVA) followed by the Kruskal-Wallis test or the Mann-Whitney test as appropriate. Results The mean follow-up time was 48.3 months (12 to 67 months). The postoperative functional score (31.5) was higher than the preoperative score (15.5) ( p < 0.001). In 6 patients, the implant was in anatomical positioning, while implant positioning was considered "nonstandard" in 19 subjects. Seven patients had a CDA < 130°, and 14 patients had a CDA ranging from 130° to 140°; in addition, the CDA was > 140° in 4 subjects. The RVA was up to 20° in 15 patients and ranged from 20° to 40° in 10 subjects. Using these criteria to group patients, the postoperative clinical-functional parameters were not statistically different from the preoperative findings ( p > 0.05). Conclusion Partial shoulder resurfacing results in significant postoperative functional recovery in patients with degenerative joint diseases. However, implant positioning assessed by CDA and RVA does not correlate with clinical-functional outcomes and, therefore, it is an inaccurate indicator of surgical success. Level of Evidence IV; Case Series.

Behavioral manifestations in rodent models of autism spectrum disorder: protocol for a systematic review and network meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with severe social communication, interaction, and sensory processing impairments. Efforts to understand its etiology and pathophysiology are crucial for improving treatment and prevention measures. Preclinical models of ASD are essential for investigating the biological mechanisms and should present translatability potential. We aim to evaluate the consistency of the most commonly used rodent models of ASD in displaying autistic-like behavior through a systematic review and meta-analysis. METHODS: This review will focus on the most frequently used autism models, surveying studies of six genetic (Ube3a, Pten, Nlgn3, Shank3, Mecp2, and Fmr1), three chemically induced (valproic acid (VPA), lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly(I:C))), and one inbred model (BTBR T+ Itpr3tf/J mouse strain). Two independent reviewers will screen the records. Data extraction of behavioral outcomes and risk of bias evaluation will be performed. We will conduct a meta-analysis whenever at least five studies investigate the same model and behavioral outcome. We will also explore the heterogeneity and publication bias. Network meta-analyses are planned to compare different models. DISCUSSION: By shortening the gap between animal behavior and human endophenotypes or specific clinical symptoms, we expect to help researchers on which rodent models are adequate for research of specific behavioral manifestations of autism, which potentially require a combination of them depending on the research interest. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021226299 .

Correlation Between Implant Positioning and Functional Outcomes in Partial Shoulder Resurfacing / Correlação entre posicionamento do implante das artroplastias parciais de recobrimento do ombro e os resultados funcionais

Abstract Objective The present study aimed to correlate functional outcomes and implant positioning in a case series of partial shoulder resurfacing arthroplasties. Methods A total of 25 patients were assessed for range of motion, functional outcome per the University of California at Los Angeles (UCLA) score and radiographic findings. Preand postoperative data were compared. In addition, patients were grouped according to the cervical-diaphyseal angle (CDA) determined by an anteroposterior radiography and to the retroversion angle (RVA) determined by an axillary radiography. A CDA from 130° to 140° and a RVA from 20° to 40° consisted in ideal positioning (anatomical standard). Data were analyzed using the Wilcoxon signed-rank test, analysis of variance (ANOVA) followed by the Kruskal-Wallis test or the Mann-Whitney test as appropriate. Results The mean follow-up time was 48.3 months (12 to 67 months). The postoperative functional score (31.5) was higher than the preoperative score (15.5) (p < 0.001). In 6 patients, the implant was in anatomical positioning, while implant positioning was considered "nonstandard" in 19 subjects. Seven patients had a CDA < 130°, and 14 patients had a CDA ranging from 130° to 140°; in addition, the CDA was > 140° in 4 subjects. The RVA was up to 20° in 15 patients and ranged from 20° to 40° in 10 subjects. Using these criteria to group patients, the postoperative clinical-functional parameters were not statistically different from the preoperative findings (p > 0.05). Conclusion Partial shoulder resurfacing results in significant postoperative functional recovery in patients with degenerative joint diseases. However, implant positioning assessed by CDA and RVA does not correlate with clinical-functional outcomes and, therefore, it is an inaccurate indicator of surgical success. Level of Evidence IV; Case Series.

Resumo Objetivo O objetivo do presente estudo é correlacionar os resultados funcionais de uma série de casos de artroplastias parciais de recobrimento do ombro com o posicionamento do implante. Métodos Um total de 25 pacientes foram avaliados em relação à amplitude de movimentos, à avaliação funcional pelo escore de Universidade da Califórnia Los Angeles (UCLA) e por análise radiográfica. Os dados pré- e pós-operatórios foram comparados. Adicionalmente, os pacientes foram agrupados quanto ao ângulo cérvico-diafisário (ACD) avaliado na radiografia em anteroposterior e quanto ao ângulo de retroversão (ARV) avaliado na radiografia em posição axilar. Foi considerado como posicionamento ideal (padrão anatômico) um ACD entre 130° e 140° e um ARV entre 20° e 40°. Os dados foram analisados pelo teste pareado de Wilcoxon, pela análise de variância (ANOVA, na sigla em inglês) seguida pelo pós-teste de Kruskal-Wallis ou pelo teste de Mann-Whitney, quando apropriado. Resultados O seguimento médio foi de 48,3 meses (12 a 67 meses). A avaliação funcional pós-operatória (31,5) foi melhor do que a pré-operatória (15,5) (p < 0,001). Seis pacientes apresentaram posicionamento anatômico do implante, enquanto 19 pacientes foram considerados "fora do padrão." Sete pacientes apresentaram um ACD < 130°, quatorze apresentaram um ACD entre 130° e 140°, e quatro apresentaram um ACD >140°. Quinze pacientes apresentaram um ARV ≤ 20°, e 10 entre 20° e 40°. Utilizando esses critérios para agrupar os pacientes, a comparação dos parâmetros da avaliação clínico-funcional pós-operatória não foi estatisticamente diferente (p > 0,05). Conclusão A artroplastia parcial de recobrimento do ombro oferece significativa recuperação funcional pós-operatória em pacientes com doenças degenerativas articulares. Entretanto, o posicionamento do implante avaliado pelos ACD e ARV não se correlaciona com o resultado clínico-funcional, sendo, portanto, uma medida imprecisa de sucesso da cirurgia. Nível de Evidência IV, Série de Casos.

In vivo evaluation of skin integration with ventricular assist device drivelines.

BACKGROUND: Ventricular assist device (VAD) driveline exit site infection is a common complication. 3D scaffolds manufactured with highly homogeneous pores via melt electro-writing (MEW) may generate an improved skin-driveline interface which permits cellular in-growth and creates a barrier to prevent bacterial migration along the driveline tissue tunnel. This study investigated skin integration on segments of Heartmate 3 driveline: smooth polyurethane, velour, and on a custom MEW scaffold in a small animal model. METHODS: Drivelines with surfaces consisting of smooth polyurethane, velour bonded to smooth polyurethane, and smooth polyurethane with a MEW scaffold sleeve were implanted percutaneously in the dorsum of 42 rats. Each rat was implanted with 2 pieces of driveline of 2 cm in length. Skin integration was assessed after 7 and 14 days. RESULTS: Macroscopically, velour and MEW scaffold surfaces were anchored at the driveline-skin interface while smooth polyurethane samples were not attached. The histology analyses showed epidermal migration throughout the thickness of the velour and MEW scaffold groups. Evident tissue growth around single MEW scaffold fibers resulted in full coverage of the pores, while areas of compacted fibers were apparent in the velour group. Tissue ingrowth was significantly higher in the MEW group compared to the velour group after 7 (p < 0.0001) and 14 days (p < 0.0001). Marsupialization was observed in the smooth polyurethane samples. Mechanical pull-out forces were similar between velour and MEW scaffold groups at 7 and 14 days (p > 0.05). CONCLUSIONS: Velour and MEW scaffolds promoted epidermal integration while smooth polyurethane drivelines did not. Fine control of MEW scaffold structure production resulted in full cellular coverage and may reduce driveline infection.

A humanised rat model of osteosarcoma reveals ultrastructural differences between bone and mineralised tumour tissue.

Current xenograft animal models fail to accurately replicate the complexity of human bone disease. To gain translatable and clinically valuable data from animal models, new in vivo models need to be developed that mimic pivotal aspects of human bone physiology as well as its diseased state. Above all, an advanced bone disease model should promote the development of new treatment strategies and facilitate the conduction of common clinical interventional procedures. Here we describe the development and characterisation of an orthotopic humanised tissue-engineered osteosarcoma (OS) model in a recently genetically engineered x-linked severe combined immunodeficient (X-SCID) rat. For the first time in a genetically modified rat, our results show the successful implementation of an orthotopic humanised tissue-engineered bone niche supporting the growth of a human OS cell line including its metastatic spread to the lung. Moreover, we studied the inter- and intraspecies differences in ultrastructural composition of bone and calcified tissue produced by the tumour, pointing to the crucial role of humanised animal models.

Cuidado pré-operatório para pacientes em estágio terminal de doença na perspectiva dos enfermeiros / Preoperative care for patients in terminal stage of disease from the perspective of nurses

RESUMO Objetivo compreender os significados atribuídos pelos enfermeiros à assistência pré-operatória prestada a pacientes em estágio terminal de doenças. Métodos pesquisa qualitativa que utilizou como referencial metodológico a Teoria Fundamentada nos Dados e foi realizada nas enfermarias cirúrgicas de um hospital universitário. Resultados participaram da pesquisa onze enfermeiros. Elaborou-se uma teoria para o fenômeno central: Os enfermeiros cuidando de pacientes em estágio terminal de doença no período pré-operatório no contexto de uma enfermaria cirúrgica. Conclusão os enfermeiros atribuem significados a este cuidado que tem particularidades próprias, que requer preparo do profissional e que demanda, ainda, mais de uma comunicação efetiva dentro da equipe multidisciplinar e na relação com paciente e família. Contribuições para a prática: a teoria apresentada permite a reflexão do profissional sobre sua práxis, a compreensão das condições intervenientes para os dilemas éticos e conflitos envolvidos e consequências, além de estratégias para melhorar a assistência neste cenário.

ABSTRACT Objective to understand the meanings attributed by nurses to preoperative care provided to terminal disease patients. Methods qualitative research that used the Grounded Theory as methodological reference and was conducted in the surgical wards of a university hospital. Results eleven nurses participated in the research. A theory was elaborated for the central phenomenon: Nurses caring for terminal disease patients in the preoperative period in the context of a surgical ward. Conclusion nurses attribute meanings to this care that has its own particularities, that requires professional preparation and that demands, even more, an effective communication within the multidisciplinary team and in the relationship with the patient and family. Contributions to practice: the theory presented allows professionals to reflect on their praxis, understand the intervening conditions for ethical dilemmas and conflicts involved and consequences, as well as strategies to improve care in this scenario.

Infection after primary total knee arthroplasty: a randomized controlled prospective study of the addition of antibiotics to bone cement.

Objective The present prospective, randomized and controlled study was conducted with 286 patients submitted to primary total knee arthroplasty (TKA) with the objective of evaluating the efficacy of the addition of antibiotics to bone cement as a way to prevent post arthroplasty infection (PAI). Methods The patients were randomized into two groups: bone cement without antibiotic (No ATB, n = 158) or cement with antibiotic (ATB, n = 128), in which 2 g of vancomycin was added to 40 g of cement. The patients were followed up for 24 months after surgery. Results Regarding preoperative demographic data, the distribution of patients between groups was homogeneous ( p < 0.05). In the 24-month period, the overall infection rate was of 2.09% (6/286), with no difference (odds ratio [OR] = 1.636; 95% confidence interval [CI]: 0.294-9.080; p = 0.694) between the ATB group (1.56%; 2/128) and the No ATB group (2.53%; 4/158). In the No ATB group, the infection was caused by methicillin-resistant Staphylococcus aureus (MRSA) ( n = 2), methicillin-sensitive S. aureus (MSSA) ( n = 1) and Eschirichia coli ( n = 1). Proteus mirabilis and MSSA were isolated from patients in the ATB group. Among the comorbidities, all patients with PAI were hypertensive and nondiabetic. Two rheumatoid arthritis patients who developed PAI were from the ATB group. Conclusion The use of cement with ATB reduced the absolute number of infections, but without statistical difference between the groups; thus, routine use should not be encouraged.

PTH1-34 improves devitalized allogenic bone graft healing in a murine femoral critical size defect.

The treatment of large segmental defects of long bones resulting from trauma, infection, or bone tumor resections is a major challenge for orthopedic surgeons. The reconstruction of bone defects with acellular allografts can be used as an osteoconductive approach. However, devitalized allografts are associated with high rates of clinical failure as a result of poor intrinsic osteoinduction properties and a lack of further remodeling. Nevertheless, evidence suggests that due to its anabolic properties, teriparatide (PTH1-34) could be effective as an adjuvant therapy for massive allograft healing. Therefore, our goal was to investigate in a murine critical-sized defect model whether the intermittent administration of PTH1-34 improves the incorporation and revitalization of acellular structural bone allografts. Thus, a 2.5-mm critical-sized defect was established in the right femur of C57BL/6 mice, followed by the reconstruction with a devitalized cortical structural allograft. A titanium micro locking plate was applied to the anterior femoral surface and secured in place with self-tapping locking screws. Subsequently, daily doses of PTH1-34 (30, and 40 µg/kg) or saline were administered to the mice for 14 days after surgery. The mice were maintained without PTH1-34 therapy for an additional 7 days before being euthanized at 3 weeks post-surgery. Bone graft consolidation was assessed on radiographic images and by histomorphometric analysis. Additionally, to determine the frequency of osteoprogenitor cells in the bone marrow and their in vitro osteogenic capacity, stromal cells were isolated from the bone marrow of animals treated with 30 or 40 µg/kg/day of PTH1-34 following the same protocol used for the experimental animals. Our results suggest that intermittent PTH1-34 treatment at 30 µg/kg/day after femoral allograft reconstruction surgery accelerated the healing process as evidenced by new bone formation induced on endosteal and periosteal surfaces, enhanced revitalization of allogeneic graft, and increased frequency and osteogenic capacity of bone marrow stromal cells (BMSC). These findings should encourage further studies aimed at investigating the potential therapeutic use of intermittent PTH1-34, specifically with regards to the optimal dosing regimen in clinically challenging orthopedic scenarios.

Poly(2-allylamidopropyl-2-oxazoline)-Based Hydrogels: From Accelerated Gelation Kinetics to In Vivo Compatibility in a Murine Subdermal Implant Model.

A rapid photo-curing system based on poly(2-ethyl-2-oxazoline-co-2-allylamidopropyl-2-oxazoline) and its in vivo compatibility are presented. The base polymer was synthesized from the copolymerization of 2-ethyl-2-oxazoline (EtOx) and the methyl ester containing 2-methoxycarboxypropyl-2-oxazoline (C3MestOx) followed by amidation with allylamine to yield a highly water-soluble macromer. We showed that spherical hydrogels can be obtained by a simple water-in-oil gelation method using thiol-ene coupling and investigated the in vivo biocompatibility of these hydrogel spheres in a 28-day murine subdermal model. For comparison, hydrogel spheres prepared from poly(ethylene glycol) were also implanted. Both materials displayed mild, yet typical foreign body responses with little signs of fibrosis. This is the first report on the foreign body response of a poly(2-oxazoline) hydrogel, which paves the way for future investigations into how this highly tailorable class of materials can be used for implantable hydrogel devices.

Injectable biocompatible poly(2-oxazoline) hydrogels by strain promoted alkyne-azide cycloaddition.

Poly(2-alkyl-2-oxazoline) (PAOx) hydrogels are tailorable synthetic materials with demonstrated biomedical applications, thanks to their excellent biocompatibility and tunable properties. However, their use as injectable hydrogels is challenging as it requires invasive surgical procedures to insert the formed hydrogel into the body due to their nonsoluble 3D network structures. Herein, we introduce cyclooctyne and azide functional side chains to poly(2-oxazoline) copolymers to induce in situ gelation using strain promoted alkyne-azide cycloaddition. The gelation occurs rapidly, within 5 min, under physiological conditions when two polymer solutions are simply mixed. The influence of several parameters, such as temperature and different aqueous solutions, and stoichiometric ratios between the two polymers on the structural properties of the resultant hydrogels have been investigated. The gel formation within tissue samples was verified by subcutaneous injection of the polymer solution into an ex vivo model. The degradation study of the hydrogels in vitro showed that the degradation rate was highly dependent on the type of media, ranging from days to a month. This result opens up the potential uses of PAOx hydrogels in attempts to achieve optimal, injectable drug delivery systems and tissue engineering.

Tranexamic acid use in high-risk blood transfusion patients undergoing total hip replacement: a randomised controlled trial.

INTRODUCTION: We hypothesised that a single preoperative intravenous dose of tranexamic acid (TXA) is effective in patients who undergo total hip arthroplasty (THA) and are at high risk of blood transfusion (preoperative haemoglobin level <13.0 g/dL). METHODS: A prospective, randomised controlled study of 308 patients who underwent primary THA was conducted. 256 participants remained in the study and were divided into 2 major groups: high-risk group comprising 116 patients with preoperative Hb < 13.0 g/dL (57 of whom were treated with a 15 mg/kg intravenous bolus of TXA, and 59 of whom did not receive the medication) and low-risk group comprising 140 patients with Hb ⩾ 13.0 g/dL (71 of whom received the same dose of TXA, and 69 of whom did not). Participants were followed up at 3 weeks, 3 months, 6 months, and 1 year after surgery. RESULTS: The use of TXA in both groups of patients significantly increased the levels of postoperative Hb and Ht. TXA protected high-risk patients from blood loss and from transfusion. In low-risk patients the use of TXA reduced blood loss but did not protect from blood transfusion. The median length of stay was significantly affected for high-risk patients. No thromboembolic event was recorded in either group. CONCLUSIONS: TXA reduces intra- and postoperative bleeding, transfusion rates, and the length of hospital stays in patients with low preoperative Hb. The use of TXA in patients with normal preoperative Hb reduces blood loss but does not affect the transfusion rate.ClinicalTrials.gov Identifier: NCT03019198.

Convergence of 3D printed biomimetic wound dressings and adult stem cell therapy.

Biomimetically designed medical-grade polycaprolactone (mPCL) dressings are 3D-printed with pore architecture and anisotropic mechanical characteristics that favor skin wound healing with reduced scarring. Melt electrowritten mPCL dressings are seeded with human gingival tissue multipotent mesenchymal stem/stromal cells and cryopreserved using a clinically approved method. The regenerative potential of fresh or frozen cell-seeded mPCL dressing is compared in a splinted full-thickness excisional wound in a rat model over six weeks. The application of 3D-printed mPCL dressings decreased wound contracture and significantly improved skin regeneration through granulation and re-epithelialization compared to control groups. Combining 3D-printed biomimetic wound dressings and precursor cell delivery enhances physiological wound closure with reduced scar tissue formation.

Occurrence of multiple genotype infection caused by Leishmania infantum in naturally infected dogs.

Genetic polymorphisms in natural Leishmania populations have been reported in endemic areas. Microsatellite typing is a useful tool to elucidate the genetic variability of parasite strains, due to its capability for high-resolution mapping of genomic targets. The present study employed multilocus microsatellite typing (MLMT) to explore the genotypic composition of Leishmania infantum in naturally infected dogs by genotyping parasites infecting different tissues with or without in vitro expansion. Eighty-six samples were collected from 46 animals in an endemic region of visceral leishmaniasis (VL). MLMT was performed for 38 spleen samples and 48 L. infantum cultures isolated from different tissues. Of the 86 samples, 23 were effectively genotyped by MLMT, identifying nine multilocus genotypes (MLG; referred to as MLG A-I). MLGs A, B and C were detected in more than one type of tissue and in more than one sample. Conversely, MLG D-I were uniquely detected in one sample each. The results showed that multiple genotype infections occur within a single host and tissue. Paired sample analysis revealed the presence of different MLMT alleles in 14 dogs, while the same MLG allele was present in 15 animals. STRUCTURE analysis demonstrated the presence of two populations; 13 samples displayed a similar admixture of both ancestral populations, and these were not assigned to any population. Only samples for which Q ≥ 0.70 after CLUMPP alignment were considered to be part of Population 1 (POP1) or Population 2 (POP2). POP2 comprised the majority of samples (n = 54) compared to POP1 (n = 19). This study presents evidence of multiple genotype infections (caused by L. infantum) in dogs in an area with high VL transmission. Further investigations must be undertaken to determine the effects of multiple infection on the host immune response and disease dynamics and treatment.

Factors Influencing the Outcome of Osteosynthesis in the Fracture of the Femoral Neck in Young Adult Patients.

Objectives To evaluate the factors that influence the outcome of osteosynthesis after closed reduction of the fracture of the femoral neck in young adult patients. Methods A retrospective study was conducted, reviewing the data of patients operated in a large orthopedic hospital from 2003 to 2011; a total of 81 patients met the inclusion criteria. The time interval between the fracture and the surgery, the initial fracture deviation, the quality of the reduction, and the placement of the implant were evaluated. Results The present study observed a strong relationship between the quality of the reduction and therapeutic success. The degree of the initial deviation and the time elapsed between the initial trauma and the osteosynthesis did not influence the surgical outcome regarding bone consolidation. The correct positioning of the implants was associated with a satisfactory evolution in the postoperative period. Conclusion The quality of the reduction and the positioning of the implants are factors that influence the results of osteosynthesis in fractures of the femoral neck in young adult patients.

Factors Influencing the Outcome of Osteosynthesis in the Fracture of the Femoral Neck in Young Adult Patients / Fatores que influenciam o resultado da osteossíntese na fratura do colo do fêmur em pacientes adultos jovens

Abstract Objectives To evaluate the factors that influence the outcome of osteosynthesis after closed reduction of the fracture of the femoral neck in young adult patients. Methods A retrospective study was conducted, reviewing the data of patients operated in a large orthopedic hospital from 2003 to 2011; a total of 81 patients met the inclusion criteria. The time interval between the fracture and the surgery, the initial fracture deviation, the quality of the reduction, and the placement of the implant were evaluated. Results The present study observed a strong relationship between the quality of the reduction and therapeutic success. The degree of the initial deviation and the time elapsed between the initial trauma and the osteosynthesis did not influence the surgical outcome regarding bone consolidation. The correct positioning of the implants was associated with a satisfactory evolution in the postoperative period. Conclusion The quality of the reduction and the positioning of the implants are factors that influence the results of osteosynthesis in fractures of the femoral neck in young adult patients.

Resumo Objetivos Avaliar os fatores que influenciam o resultado da osteossíntese pela redução fechada da fratura do colo femoral nos pacientes jovens. Métodos Foi feito um estudo retrospectivo com revisão dos dados dos pacientes operados em um hospital ortopédico de grande porte, de 2003 a 2011, com um total de 81 pacientes que atenderam aos critérios de inclusão. O intervalo de tempo entre a fratura e a cirurgia, o desvio inicial da fratura, a qualidade da redução e o posicionamento dos implantes foram os fatores avaliados. Resultados O estudo encontrou forte relação entre a qualidade da redução e o sucesso terapêutico. O grau de desvio inicial e o tempo entre o trauma inicial e a osteossíntese não influenciaramo desfecho cirúrgico emrelação à consolidação óssea. O correto posicionamento dos implantes mostrou relação com a evolução satisfatória no pós-operatório dos pacientes. Conclusão A qualidade da redução e o posicionamento dos implantes são fatores que influenciamoresultadodaosteossíntesenafraturadocolodofêmurnopacienteadultojovem.