3D Printing for the Development of Palatal Defect Prosthetics.

Background: Three-dimensional (3D) printing has emerged as a promising new technology for the development of surgical prosthetics. Research in orthopedic surgery has demonstrated that using 3D printed customized prosthetics results in more precise implant placements and better patient outcomes. However, there has been little research on implementing customized 3D printed prosthetics in otolaryngology. The program sought to determine whether computed tomography (CT) serves as feasible templates to construct 3D printed palatal obturator prosthetics for defects in patients who have been treated for head and neck cancers. Observations: A retrospective review of patients with palatal defects was conducted and identified 1 patient with high quality CTs compatible with 3D modeling. CTs of the patient's craniofacial anatomy were used to develop a 3D model and a Formlabs 3B+ printer printed the palatal prosthetic. We successfully developed and produced an individualized prosthetic using CTs from a veteran with head and neck deformities caused by cancer treatment who was previously treated at the Veterans Affairs Palo Alto Health Care System. This project was successful in printing patient-specific implants using CT reproductions of the patient's craniofacial anatomy, particularly of the palate. The program was a proof of concept and the implant we created was not used on the patient. Conclusions: Customized 3D printed implants may allow otolaryngologists to enhance the performance and efficiency of surgeries and better rehabilitate and reconstruct craniofacial deformities to restore appearance and function to patients. Additional research will strive to enhance the therapeutic potential of these prosthetics to serve as low-cost, patient-specific implants.

Range of motion measurements do not correlate with patient reported outcome measures in the early post-operative period following ankle fracture.

BACKGROUND: Early mobilization following ankle fracture open reduction and internal fixation (ORIF) improves long-term patient functionality. Because of this, numerous resources have been spent to increase patient adherence to post-operative mobilization, with range of motion (ROM) measurements generally considered an important outcome in patient recovery. In this study we investigated how ankle ROM correlates to patient function, self-sufficiency in performing activities of daily living (ADLs), and pain in the early post-operative period. METHODS: This was a prospective, observational study on patients undergoing ORIF of ankle fractures. We collected patient reported outcome measures (PROMs) and ROM measurements at the 2-week, 6-week, 12-week, and 6 month post-operative visit. We collected three PROMs: pain intensity (VAS), pain self-efficacy questionnaire (PSEQ-2), and foot and ankle ability measurement (FAAM). ROM of the ankle was measured by goniometer. ANOVA and post-hoc Tukey tests were used to examine statistical differences in PROMs over time. Pearson correlation tests were used to examine the association between ROM and PROMs. RESULTS: One-hundred and twenty-three participants enrolled in this study in the perioperative period. Pain intensity was higher at enrollment compared to week 6 (post-hoc p = 0.006), after which pain intensity did not differ significantly. FAAM scores for activities or daily living (ADL) were increased at all study visits compared to enrollment (post-hoc p < 0.001). FAAM-Sports scores were higher compared to enrollment at the week 12 and 6 month visits (post-hoc p < 0.001). No significant improvements in goniometer measurements were noted across any timepoints. There were no significant correlations between ROM and PROMs at any of the study visits. CONCLUSION: In our cohort of patients, there was no correlation between ROM and patient pain, self-efficacy or functionality in the early post-operative period following ankle ORIF. The lack of correlation between PROMs and ROM indicates that ROM may be both a poor indicator of patient improvement for physicians to guide post-operative treatment as well as a poor motivator for patient adherence to post-operative exercises. In the future, it is important to study reliable outcome measures in early recovery that can be utilized to track patient recovery from ankle ORIF.

Factors affecting residency selection for underrepresented minorities pursuing orthopaedic surgery.

BACKGROUND: The United States is increasingly diverse and there are many benefits to an equally diverse physician workforce. Despite this, the percentage of under-represented minorities in orthopaedic surgery has remained stagnant. The purpose of this study was to describe the characteristics underrepresented minorities pursuing orthopaedic surgery value most when evaluating residency programs. METHODS: The contact information of current underrepresented minority orthopaedic surgery residents were obtained through professional society databases, residency program coordinators and residency program websites. Individuals were sent a survey through which they evaluated the importance of a variety of program characteristics. RESULTS: The most influential program characteristics were resident happiness and camaraderie, program reputation, geographic location, and relationships between residents and attendings. The least influential characteristics were sub-internship scholarship opportunities for minorities, program affiliation with diversity organizations, word of mouth from others, number of fellows, and centralized training sites. CONCLUSIONS: There is a need to diversify the field of orthopaedic surgery, which begins by selecting more diverse trainees. This study demonstrates that underrepresented applicants are most influenced by many of the same characteristics as their well-represented peers. However, diversity-related factors still play an important role in the decision-making process. Many residents highlighted the impact microaggressions and mistreatment played in their residency experience, emphasizing the need for residency programs to focus not only on recruitment, but also on the successes and retention of their residents. Only once this is done will the field of orthopaedic surgery find sustained improvement in its diversification efforts.

Comparing the Outcomes and Complication Rates of Biologic vs Synthetic Meshes in Implant-Based Breast Reconstruction: A Systematic Review.

OBJECTIVE: This systematic review evaluates all published studies comparing biologic and synthetic meshes in implant-based breast reconstruction (IBBR), to determine which category of mesh produces the most favorable outcomes. SUMMARY BACKGROUND DATA: Breast cancer is the most common cancer in women globally. Implant-based breast reconstruction is currently the most popular method of postmastectomy reconstruction, and recently, the use of surgical mesh in IBBR has become commonplace. Although there is a long-standing belief among surgeons that biologic mesh is superior to synthetic mesh in terms of surgical complications and patient outcomes, few studies exist to support this claim. METHODS: A systematic search of the EMBASE, PubMed, and Cochrane databases was performed in January 2022. Primary literature studies comparing biologic and synthetic meshes within the same experimental framework were included. Study quality and bias were assessed using the validated Methodological Index for Non-Randomized Studies criteria. RESULTS: After duplicate removal, 109 publications were reviewed, with 12 meeting the predetermined inclusion criteria. Outcomes included common surgical complications, histological analysis, interactions with oncologic therapies, quality of life measures, and esthetic outcomes. Across all 12 studies, synthetic meshes were rated as at least equivalent to biologic meshes for every reported outcome. On average, the studies in this review tended to have moderate Methodological Index for Non-Randomized Studies scores. CONCLUSION: This systematic review offers the first comprehensive evaluation of all publications comparing biologic and synthetic meshes in IBBR. The consistent finding that synthetic meshes are at least equivalent to biologic meshes across a range of clinical outcomes offers a compelling argument in favor of prioritizing the use of synthetic meshes in IBBR.

Preneoplastic stromal cells promote BRCA1-mediated breast tumorigenesis.

Women with germline BRCA1 mutations (BRCA1+/mut) have increased risk for hereditary breast cancer. Cancer initiation in BRCA1+/mut is associated with premalignant changes in breast epithelium; however, the role of the epithelium-associated stromal niche during BRCA1-driven tumor initiation remains unclear. Here we show that the premalignant stromal niche promotes epithelial proliferation and mutant BRCA1-driven tumorigenesis in trans. Using single-cell RNA sequencing analysis of human preneoplastic BRCA1+/mut and noncarrier breast tissues, we show distinct changes in epithelial homeostasis including increased proliferation and expansion of basal-luminal intermediate progenitor cells. Additionally, BRCA1+/mut stromal cells show increased expression of pro-proliferative paracrine signals. In particular, we identify pre-cancer-associated fibroblasts (pre-CAFs) that produce protumorigenic factors including matrix metalloproteinase 3 (MMP3), which promotes BRCA1-driven tumorigenesis in vivo. Together, our findings demonstrate that precancerous stroma in BRCA1+/mut may elevate breast cancer risk through the promotion of epithelial proliferation and an accumulation of luminal progenitor cells with altered differentiation.

Effectiveness of melatonin treatment for sleep disturbance in orthopaedic trauma patients: A prospective, randomized control trial.

OBJECTIVES: Explore sleep disturbance in postoperative orthopedic trauma patients and determine the impact of melatonin supplementation on postoperative sleep, pain, and quality of life. MATERIALS AND METHODS: In this prospective, randomized controlled trial at a Level I trauma center, 84 adult orthopedic trauma patients with operative fracture management were randomized 2-weeks postoperatively to either the melatonin or placebo group. Patients randomized to the melatonin group (42 subjects, mean age 41.8 ± 15.5 years) received 5 mg melatonin supplements. Patients in the placebo group (42 subjects, mean age 41.3 ± 14.0 years) received identical glucose tablets. Both groups were instructed to take the tablets 30 minutes before bed for 4 weeks and received sleep hygiene education and access to the Cognitive Behavioral Therapy for Insomnia (CBT-I) Coach app. MAIN OUTCOME MEASURES: Our primary outcome was sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes were pain measured by the Visual Analog Scale (VAS), quality of life measured by the 36-Item Short Form Survey (SF-36), and opioid use. RESULTS: Patients in both groups had significant sleep disturbance (PSQI ≥ 5) at 2-weeks (83%) and 6-weeks (67%) postoperatively. PSQI improved by 3.3 points (p<0.001) at follow-up, but there was no significant difference between groups (melatonin PSQI = 5.6, placebo PSQI = 6.1, P = 0.615). Compared to placebo, melatonin did not affect VAS, SF-36, or opioid use significantly. CONCLUSION: Sleep disturbance is prevalent in orthopedic trauma patients. Melatonin treatment did not significantly improve subjective sleep quality, pain, quality of life or opioid use. LEVEL OF EVIDENCE: Therapeutic Level I.

Negative Pressure Wound Therapy for Extremity Open Wound Management: A Review of the Literature.

SUMMARY: Negative pressure wound therapy (NPWT) with reticulated open cell foam is used commonly in orthopaedic trauma, particularly in the management of complex open fracture wounds. This article reviews the literature to date regarding this adjunctive treatment, particularly in regard to removal of infectious material, temporary management of wounds pending soft tissue reconstruction, combat wounds, and over split-thickness skin grafts. Mechanism of action is also reviewed, including stabilization of the wound environment, edema control, macrodeformation, and microdeformation effects. Use of NPWT as an adjunct in management of open fractures along with operative debridement, systemic antibiotics, and early soft tissue reconstruction are the highest yield interventions for managing open fracture wounds with infection. NPWT as an adjunct therapy in the protocol for open fractures seems to add additional clinical benefit for patients with severe open fracture wounds not amenable to primary, immediate closure.

Anticancer potential of new 3-nitroaryl-6-(N-methyl)piperazin-1,2,4-triazolo[3,4-a]phthalazines targeting voltage-gated K+ channel: Copper-catalyzed one-pot synthesis from 4-chloro-1-phthalazinyl-arylhydrazones.

A series of six 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines were prepared through a facile and efficient one-pot copper-catalyzed procedure from 4-chloro-1-phthalazinyl-arylhydrazones with relatively good yields (62-83%). The one-pot copper-catalytic procedure consists of two simultaneous reactions: (i) a direct intramolecular dehydrogentaive cyclization between ylidenic carbon and adjacent pyrazine nitrogen to form 1,2,4-triazolo ring and, (ii) a direct N-amination on carbon-chlorine bond. Then, an in vitro anticancer evaluation was performed for the synthesized compounds against five selected human cancer cells (A549, MCF-7, SKBr3, PC-3 and HeLa). The nitro-derivatives were significantly more active against cancer strains than against the rest of tested compounds. Specifically, compound 8d was identified as the most promising anticancer agent with significant biological responses and low relative toxicities on human dermis fibroblast. The cytotoxic effect of compound 8d was more significant on PC3, MCF-7 and SKBr3 cancer cells with low-micromolar IC50 value ranging from 0.11 to 0.59 µM, superior to Adriamycin drug. Mechanistic experimental and theoretical studies demonstrated that compounds 8d act as a K+ channel inhibitor in cancer models. Further molecular docking studies suggest that the EGFR Tyrosine Kinase enzyme may be a potential target for the most active 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines.

Estudio comparativo de la distancia coracohumeral en pacientes con patología degenerativa del subescapular y una población voluntaria asintomática / Comparative analysis of the coracohumeral distance between patients with degenerative subscapularis tendon pathology and a normal age-matched population

INTRODUCCIÓN: El pinzamiento subcoracoideo secundario a una distancia coracohumeral (DCH) disminuida, ha sido descrito como una posible etiología de las lesiones degenerativas del tendón del Subescapular (SSC), sin embargo, esa teoría aún es controversial. OBJETIVO: Evaluar si existe una diferencia significativa entre la DCH promedio de pacientes con patología degenerativa del SSC y un grupo control. MATERIALES Y MÉTODOS: Se diseñó un estudio de casos-controles y se estableció un tamaño muestral mínimo de 36 casos por grupo. De nuestra base de datos, y dentro de un periodo de 6 meses, se rescataron 46 Resonancias Magnéticas (RM) de hombro con patología degenerativa avanzada y/o roturas del SSC (grupo SSC). El grupo control fue conformado por 36 RM realizadas a voluntarios asintomáticos sin patología del mango rotador. Se incluyeron en ambos grupos solo pacientes entre 40 y 60 años. Se utilizó prueba de t para determinar las diferencias entre 2 grupos con un nivel de confianza del 95%. RESULTADOS: La edad promedio del grupo SSC fue 50,1 6,1 años y del grupo control 51,7 6,8 años, no existiendo diferencia estadísticamente significativa entre ambos (p » 0.43). La DCH promedio en el grupo SSC fue 8,58 mm [IC: 7,95­9,21 mm], y en el grupo control fue 11,04 mm [IC: 10,05­12,04 mm]. Al comparar la DCH, se encontró una diferencia estadísticamente significativa entre grupos (p » 0,00048). CONCLUSIÓN: Nuestros resultados respaldan la existencia de una asociación estadísticamente significativa entre una DCH disminuida y la presencia de patología degenerativa del SSC. NIVEL DE EVIDENCIA: III (Estudio de casos y controles).

BACKGROUND: The incidence of subscapularis tears is increasing as diagnostic imaging and arthroscopic technology improves. Decreased coracohumeral distance (CHD) with associated Subcoracoid Impingement is thought to be one, potential etiology for these lesions. OBJECTIVE: The purpose of this study was to identify the association between reduced CHD and degenerative pathology of the subscapularis tendon. METHODS: A comparative case-control study was performed. The sample size required to determine significance was calculated to be 36 cases. In total, 46 patients with severe degenerative SSC tendinopathy or subscapularis tears on magnetic resonance imaging (MR) were collected consecutively from our database (SSC group). The control group consisted of 36 asymptomatic volunteers undergoing shoulder MR. Only patients between 40 and 60 years of age were included. An independent t-test was used to determine the statistical significance between the two groups (with a 95% level of confidence). RESULTS: No statistically relevant difference was found between the average age of the two groups (50.1 6.1 and 51.7 6.8; p » 0.43). In the control group, the mean CHD was found to be 11.04 mm [CI:10.05­12.04 mm] and was 8.58 mm [CI: 7.95­9.21 mm] in the subscapularis group. The statistical analysis, comparing the CHD showed a significant difference between groups (p » 0.00048). CONCLUSION: This study supports the conclusion that degenerative subscapularis pathology is associated with narrowed coracohumeral distance, when compared with an asymptomatic age-matched group. LEVEL OF EVIDENCE: III (case-control study).

Identification of dehydroxy isoquine and isotebuquine as promising anticancer agents targeting K+ channel.

Traditional antimalarial drugs based on 4-aminoquinolines have exhibited good antiproliferative activities against human tumor cells; however, their low relative efficacy has limited their corresponding clinical uses. In order to identify new potent anticancer agents based on 4-aminoquinoline, we evaluated the antiproliferative activity of a series of dehydroxy isoquines and isotebuquines against five human cancer lines. HeLa and SKBr3 were significantly more sensitive to the action of tested quinolines than the A549, MCF-7, and PC-3 cancer lines. Compound 2h was by far the most potent derivative against four of the tested lines (except to PC3 line), exhibiting low micromolar or nanomolar IC50 values superior to adriamycin reference, low toxicities on dermis human fibroblasts (LD50  > 250 µM), and excellent selectivity indexes against the mentioned cancer cells. A structure-activity relationship analysis put in evidence that a pyrrolidine or morpholine moiety as N-alkyl terminal substitution and the incorporation of the extra phenyl attached to aniline ring are pharmacophore essentials for improvement the anticancer activity of the studied dehydroxy isoquines and isotebuquines. From the results, compound 2h emerged as a promising anticancer candidate for further in vitro assays against resistant-strain and in vivo studies as well as pharmacokinetic and genotoxicity studies. Mechanistic assays suggested that the most active quinoline 2h act as calcium-activated potassium channel activator.

Cardiovascular responses to hyperoxic withdrawal of arterial chemosensory drive.

Searching for an arterial chemosensory drive exerted upon the cardiovascular system under eucapnic normoxia, we performed experiments on spontaneously ventilated, pentobarbitone-anesthetized cats, in which ventilatory flow through a pneumo-tachograph, instantaneous respiratory frequency, end-tidal pressure of CO(2), arterial pressure, and instantaneous heart frequency were simultaneously recorded. Repeated exposures to 100% O(2) breathing for 5 to 60 s caused the well-known transient decreases in tidal ventilatory volume and instantaneous respiratory frequency, after which minor decreases in systolic, diastolic and mean arterial pressures, as well as in instantaneous heart frequency were observed. After selective bilateral denervation of carotid sinuses (barodenervation), hyperoxia-induced falls in arterial pressure and heart rate became more evident. Subsequent bilateral section of the carotid nerves (with or without section of the aortic nerves) suppressed these effects. Present results indicate the presence of a chemosensory drive of the cardiovascular system under eucapnic normoxia, although considerably smaller than that exerted upon ventilation. The small magnitude of the decreases in arterial pressure and heart rate observed under control conditions suggests that cardiovascular effects elicited by hyperoxic challenges are normally buffered by carotid baroreflexes.

Intoxicación por caústico: revisión / Caustic poisoning: review

La incidencia de intoxicaciones por cáustico ha ido aumentando en los últimos años a pesar de las indicaciones que se imparten de mantener estas sustancias fuera del alcance de los niños. Por esta razón se procede a realizar esta bibliografía con el objetivo de actualizar conocimientos sobre el tema a fin de prevenir lesiones en muchos casos, irreversibles.

Caustic poisoning incidence has increased in the last few years in spite of warnings given to keep this substances out of the reach of children. This is why we are developing this bibliography aiming to update the knowledge about this subject in order to prevent injuries, which in most cases are irreversible.