Does Integrated Fixation Provide Benefit in the Reconstruction of Posttraumatic Tibial Bone Defects?

BACKGROUND: Limb salvage in the presence of posttraumatic tibial bone loss can be accomplished using the traditional Ilizarov method of distraction osteogenesis with circular external fixation. Internal fixation placed at the beginning of the consolidation phase, so-called integrated fixation, may allow for earlier removal of the external fixator but introduces concerns about cross-contamination from the additional open procedure and maintenance of bone regenerate stability. QUESTIONS/PURPOSES: Among patients deemed eligible for integrated fixation, we sought to determine: (1) Does integrated fixation decrease the time in the external fixator? (2) Is there a difference in the rate of complications between the two groups? (3) Are there differences in functional and radiographic results between integrated fixation and the traditional Ilizarov approach of external fixation alone? METHODS: Between January 2006 and December 2012, we treated 58 patients (58 tibiae) with posttraumatic tibial bone loss using the Ilizarov method. Of those, 30 patients (52%) were treated with the "classic technique" (external fixator alone) and 28 (48%) were treated with the "integrated technique" (a combination of an external fixator and plating or insertion of an intramedullary nail). During that period, the general indications for use of the integrated technique were closed physes, no active infection, and a healed soft tissue envelope located at the intended internal fixation site; the remainder of the patients were treated with the classic technique. Followup on 30 (100%) and 28 (100%) patients in the classic and integrated techniques, respectively, was achieved at a minimum of 1 year (mean, 3 years; range, 1-8 years). Adverse events were reported as problems, obstacles, and complications according to the publication by Paley. Problems and obstacles are managed by nonoperative and operative means, respectively; in addition, they resolve completely with treatment. Complications, according to the Paley classification, result in permanent sequelae. Functional and radiographic results were reported using the Association for the Study and Application of Methods of Ilizarov scoring system. RESULTS: Overall, there was a mean of four (range, 2-5) surgical procedures to complete the tibial reconstruction with a similar incidence of unplanned surgical procedures (obstacles) between the two groups (p = 0.87). Patients treated with integrated fixation spent less time in the external fixator, 7 months (range, 5-20 months) versus 11 months (range, 1-15 months; p < 0.001). There were seven problems, 15 obstacles, and zero complications in the classic group. Ten problems, 15 obstacles, and one complication occurred in the integrated fixation group. There was no difference in the severity (p = 0.87) or number (p = 0.40) of complications between both groups. Good to excellent Association for the Study and Application of Methods of Ilizarov function and bone scores were obtained in 100% and 98% of patients, respectively. CONCLUSIONS: The integrated fixation method allows for a more efficient limb salvage surgical reconstruction in patients carefully selected for that approach, whereas the frequency of adverse events and ability to restore limb lengths was not different between the groups with the numbers available. Careful placement of external fixation pins is critical to decrease cross-contamination with planned internal fixation constructs. In this study of posttraumatic tibial bone defect reconstruction, good/excellent results were found in all patients after a mean of four surgical procedures; however, a larger multicenter prospective study would allow for more robust and generalizable conclusions. LEVEL OF EVIDENCE: Level III, therapeutic study.

Treatment of Post-Ablation Bronchopleural Fistula Using Percutaneous Synthetic Hydrogel Surgical Sealant: Initial Experience of Safety and Efficacy.

Purpose Bronchopleural fistula is a rare but serious complication of lung ablation, as it is difficult to treat and is associated with a high mortality rate. Standard therapy often relies on surgical pleurodesis, which can be particularly problematic in patients with poor baseline lung function. A minimally invasive treatment option for bronchopleural fistula may offer an alternative to surgery for appropriate patients. This case series describes the technique, safety and efficacy of percutaneously administered synthetic hydrogel surgical sealant in the treatment of post-ablation bronchopleural fistula in five patients. Materials and methods Retrospective chart review was carried out in five consecutive patients identified to have had BPF after lung ablation between 2009 and 2017 who were treated with percutaneous administration of synthetic hydrogel surgical sealant using CT guidance. Results The procedure was successfully carried out in all patients without immediate complications, and complete resolution of air leak was achieved in four of five patients (80%). Up to the most recent follow-up, no evidence of delayed complications or recurrent air leak was present (follow-up range 1 week-8 years). Conclusion The authors' initial experience shows that targeted surgical sealant is a potentially safe and effective alternative treatment of post-ablation persistent air leak.

Technical Feasibility and Safety of Repeated Computed Tomography-Guided Transthoracic Intratumoral Injection of Gene-Modified Cellular Immunotherapy in Metastatic NSCLC.

INTRODUCTION: To assess the technical feasibility and safety of repeated percutaneous computed tomography (CT)-guided transthoracic biopsies and intratumoral injections of gene-modified dendritic cells in metastatic NSCLC. METHODS: A total of 15 patients with 15 NSCLC lesions measuring greater than 1.0 cm underwent two cycles of intratumoral biopsies and CCL21 dendritic cell injections separated by 7 days. All needle placements and injections were done under CT guidance. Clinical and imaging follow-up was done approximately 4 weeks after the first procedure. Safety and feasibility were determined as: (1) safety and feasibility similar to that of single-needle biopsy, and (2) an absence of serious adverse events defined as grade greater than or equal to three according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 30 percutaneous, transthoracic intratumoral biopsies and injections into the lung cancer were performed, two cycles (at d 0 and 7) received by each patient (311 biopsies and 96 intratumoral injections). All percutaneous cases achieved technical success with respect to needle placement for both biopsy and injection of CCL21 dendritic cells. Only minor complications were observed (grade <3), including pneumothorax (n = 10, 33%) and small postbiopsy hemorrhage (n = 2, 7%). Pneumothorax was moderate (n = 1) or trace (n = 9), with resolution of the moderate pneumothorax after manual aspiration without chest tube placement. No patient required chest tube placement. No other complications or serious adverse effects related to the biopsy or dendritic cell injection were noted. All patients were in stable condition after up to 4 hours in the recovery unit and were discharged home on the same day. No procedure-related complications were observed on imaging or clinical follow-up at 4 weeks. CONCLUSIONS: Repeated percutaneous, transthoracic CT-guided biopsies and intratumoral gene-modified cell-based immunotherapy injections into lung cancers are technically feasible, safe, and reproducible. There were no procedure-related serious (defined as grade ≥3) adverse events.

Cancer immunotherapy and the PD-1/PD-L1 checkpoint pathway. / Inmunoterapia contra el cáncer y la ruta del punto de control PD-1/PD-L1.

Long-term survival for patients with advanced bladder cancer is precarious, with a 5-year survival of just 5% in metastatic cases. Normally, the binding of PD-L1 to PD-1 alters the immune activity by modulating it to inhibit autoimmune diseases or chronic inflammation. However, some cancers use this route to block the immune response of the patient and continue growing. The new immunotherapy against bladder cancer aims to block the ability of tumor cells to resist patient' immune response by acting on the checkpoints of immune cells. These drugs are able to block the PD-1 receptor present on the surface of the lymphocytes, or the PD-L1 and PD-L2 ligands expressed by the cancer cells; this would prevent the binding of both blocking the immunomodulatory signal and allowing the T cells continue active against the tumor. The therapeutic target of Pembrolizumab and Nivolumab is PD-1, the receptor protein of PD-L1 in immune cells. The rest of molecules approved for different types of cancer such as Atezolizumab, Avelumab or Durvalumab act on the PD-L1 protein that is expressed in high concentrations in some cancer cells. The checkpoint inhibitors offer an effective alternative for patients for whom previously there were few options for durable responses, including those who are ineligible for cisplatin-based regimens or who are at risk of significant toxicity. This review describes the most recent data on agents that inhibit PD-L1, found on the surface of tumor cells, and PD-1 found on activated T and B cells and macrophages. Research is ongoing to further categorize responses, define ideal patient populations, and investigate combinations of checkpoint inhibitors to address multiple pathways in the functioning immune system.

A Comparison of Femoral Lengthening Methods Favors the Magnetic Internal Lengthening Nail When Compared with Lengthening Over a Nail.

BACKGROUND: Bone lengthening with an internal lengthening nail (ILN) avoids the need for external fixation and requires one less surgical procedure than lengthening over a nail (LON). However, LON has been shown to be superior to femoral internal lengthening using a mechanical nail. The magnetic ILN, a remote-controlled and magnet-driven device, may have overcome the weaknesses of earlier internal lengthening technology and may be superior to LON. QUESTIONS/PURPOSES: (1) Is the magnetic ILN more accurate than LON for femoral lengthening? (2) Does the magnetic ILN demonstrate more precise distraction rate control than LON? (3) Does the magnetic ILN result in faster regenerate site healing, with more robust callus, than LON? (4) Does the magnetic ILN result in fewer complications, including impediments to knee motion, than LON? METHODS: We conducted a retrospective comparison of the records and radiographs of 21 consecutive patients with 22 femoral lengthenings using LONs and 35 consecutive patients with 40 femoral lengthenings using remote-controlled magnetic ILNs. Primary outcomes measured included accuracy, distraction rate precision, time to bony union, final knee range of motion, regenerate quality, and complications. The minimum follow-up times for the LON and ILN cohorts were 13 and 21 months, respectively. RESULTS: Patients treated with ILN had a lower post-treatment residual limb-length discrepancy (0.3 mm) than those treated with LON (3.6 mm). The rate of distraction was closer to the goal of 1 mm/day and more tightly controlled for the ILN cohort (1 mm/day) than that for the LON group (0.8 mm/day; SD, 0.2). Regenerate quality was not significantly different between the cohorts. Bone healing index for ILN was not statistically significant. Time to union was shorter in the ILN group (3.3 months) than that in the LON group (4.5 months). A lower percentage of patients experienced a complication in the ILN group (18%) than in the LON group (45%). Knee flexion at the end of distraction was greater for ILN patients (105°) than that for LON patients (88.8°), but this difference was no longer observed after 1 year. CONCLUSIONS: Femoral lengthening with magnetic ILN was more accurate than with LON. The magnetic ILN comports the additional advantage of greater precision with distraction rate control and fewer complications. Both techniques afford reliable healing and do not significantly affect knee motion at the final follow-up. The magnetic ILN method showed no superiority in regenerate quality and healing rate.

Influence of hometown on family physicians' choice to practice in rural settings.

OBJECTIVE: This study examines the influence of a physician's hometown location on the choice of practice location, adjusting for confounding variables. METHODS: Medical school records for 2,487 Indiana University graduates (classes of 1988--1997) were matched to the American Medical Association's Masterfile data to identify the graduates' current practice locations and specialties. Urban influence codes were assigned to each county in Indiana for the purposes of defining metro or nonmetro locations. Physician practice locations were mapped using ArcGIS software. Chi-square tests, logistic regression, and analysis of variance were used to examine the influence of hometown on choice of practice location. RESULTS: Chi-square tests revealed significant associations between physician hometown and current practice location. Logistic regression, controlling for age and gender, predicted physicians (all specialties) from nonmetro hometowns were 4.7 times as likely to locate their practice in a nonmetro location as compared to their peers from metro hometowns. Similarly, family physicians from nonmetro hometowns were 4.4 times as likely to choose a nonmetro practice location. There was not a significant difference in the mean distance between hometown and practice location for physicians from nonmetro hometowns compared to those from metro hometowns. CONCLUSIONS: This study underscores the influence of physicians' hometown on their choice of practice location.

Inmunoterapia contra el cáncer y la ruta del punto de control PD-1/PD-L1 / Cancer immunotherapy and the PD-1/PD-L1 checkpoint pathway

La supervivencia a largo plazo para pacientes con cáncer avanzado de vejiga es precaria, con una supervivencia a 5 años de apenas el 5% en los casos metastásicos. Normalmente, la unión de PD-L1 a PD-1 altera la actividad inmunitaria modulándola para inhibir enfermedades autoinmunes e inflamaciones crónicas. Sin embargo, algunos canceres utilizan esta vía para bloquear la respuesta inmune del paciente y continuar creciendo. La nueva inmunoterapia contra el cáncer vesical pretende bloquear la capacidad de las células tumorales para resistir a la respuesta inmune del paciente mediante la actuación sobre los puntos de control de las células inmunitarias. Dichos fármacos son capaces de bloquear el receptor PD-1 presente en la superficie de los linfocitos, o bien los ligandos PD-L1 y PD-L2 expresados por las células cancerosas, esto impediría la unión de ambos bloqueando la señal inmunomoduladora y permitiendo que las células T continúen activas contra el tumor. La diana terapéutica del Pembrolizumab y el Nivolumab, es PD-1, la proteína receptora de PD-L1 en células inmunitarias. El resto de moléculas aprobadas para distintos tipos de cáncer como Atezolizumab, Avelumab o Durvalumab actúan sobre la proteína PD-L1 que es expresada en concentraciones altas en algunas células cancerosas. Los inhibidores del punto de control ofrecen una alternativa efectiva para los pacientes para los que anteriormente había pocas opciones de respuestas duraderas, incluidos aquellos que no son elegibles para los regímenes basados en cisplatino o que están en riesgo de toxicidad significativa. Esta revisión describe los datos más recientes sobre los agentes que inhiben la PD-L1, que se encuentran en la superficie de las células tumorales, y la PD-1 que se encuentra en las células T y B activadas y los macrófagos. Se están llevando a cabo investigaciones para categorizar aún más las respuestas, definir poblaciones de pacientes ideales e investigar combinaciones de inhibidores de puntos de control para abordar múltiples vías en el funcionamiento del sistema inmunitario

Long-term survival for patients with advanced bladder cancer is precarious, with a 5-year survival of just 5% in metastatic cases. Normally, the binding of PD-L1 to PD-1 alters the immune activity by modulating it to inhibit autoimmune diseases or chronic inflammation. However, some cancers use this route to block the immune response of the patient and continue growing. The new immunotherapy against bladder cancer aims to block the ability of tumor cells to resist patient's immune response by acting on the checkpoints of immune cells. These drugs are able to block the PD-1 receptor present on the surface of the lymphocytes, or the PD-L1 and PD-L2 ligands expressed by the cancer cells; this would prevent the binding of both blocking the immunomodulatory signal and allowing the T cells continue active against the tumor. The therapeutic target of Pembrolizumab and Nivolumab is PD-1, the receptor protein of PD-L1 in immune cells. The rest of molecules approved for different types of cancer such as Atezolizumab, Avelumab or Durvalumab act on the PD-L1 protein that is expressed in high concentrations in some cancer cells. The checkpoint inhibitors offer an effective alternative for patients for whom previously there were few options for durable responses, including those who are ineligible for cisplatin-based regimens or who are at risk of significant toxicity. This review describes the most recent data on agents that inhibit PD-L1, found on the surface of tumor cells, and PD-1 found on activated T and B cells and macrophages. Research is ongoing to further categorize responses, define ideal patient populations, and investigate combinations of checkpoint inhibitors to address multiple pathways in the functioning immune system