Postmetastasis survival in high-grade extremity osteosarcoma: A retrospective analysis of prognostic factors in 126 patients.

BACKGROUND AND OBJECTIVES: Prognostic factors predictive of postmetastasis survival (PMS) in metastatic osteosarcoma are poorly understood. Our aims were to evaluate PMS in patients with high-grade osteosarcoma in extremities, and to identify prognostic factors related to PMS. METHODS: A retrospective review of data for 126 patients with metastatic osteosarcoma was conducted. The study population consisted of 70 men and 56 women, with a mean age of 21 years (range: 4-75 years). The mean postmetastasis follow-up period was 37 months (range: 1-245 months). RESULTS: The 5-year PMS rate was 31% and median PMS duration was 22 months. In the multivariate analyses, no metastasectomy (P < 0.001), local recurrence prior to metastasis (P = 0.016), extrapulmonary metastasis (P = 0.006), and poor histologic response to preoperative chemotherapy (P = 0.047) were significant poor prognostic factors. The 5-year PMS without any negative prognostic factor was 60.2%; with one factor, 31.6%; and with more than two factors, 3.6%. CONCLUSIONS: PMS in osteosarcoma patients was influenced by primary tumor-related factors such as histologic response to chemotherapy, as well as metastasis-related factors such as complete metastasectomy and metastasis site. A certain group of patients without such poor prognostic factors could be cured even after the development of metastasis.

Reconstruction using a perforator free flap after malignant melanoma resection of the ankle and foot.

BACKGROUND: Surgical excision with adequate margin is the treatment of choice to provide best chance for survival. However, tumors located on distal lower extremity may require reconstruction to salvage the limb which may affect prognosis and quality of life. This retrospective study aimed to evaluate the effect of free flap on overall outcomes of patients with primary malignant melanoma located on the foot and ankle. METHODS: Patients with primary malignant melanoma on the leg and foot who required free flap coverage between August 2005 and January 2014 were evaluated. The reconstruction and oncological outcomes were assessed. RESULTS: The cohort of 59 patients showed 96.7% successful reconstructive outcomes. The mean duration from surgery to partial weight bearing was 9 days. The 5-year overall survival and 5-year progression-free survival rates were 73.2% and 44%, respectively. The overall VAS-FA score was 94.1 implying excellent functional recovery. CONCLUSION: The use of free flaps to close defects after cancer resection can help preserve maximal extremity length and function. This approach does not have negative impact on overall outcome and further provide an increased quality of life with better function. Reconstruction using free flaps should be considered primarily when defects cannot be covered by conventional methods.

TLR2 signaling in tubular epithelial cells regulates NK cell recruitment in kidney ischemia-reperfusion injury.

Damage-associated molecular patterns released from damaged kidney cells initiate postischemic inflammation, an essential step in the progression of kidney ischemia-reperfusion injury (IRI). However, the mechanism that coordinates this highly specific process in ischemic kidneys remains to be clarified. Previously, we demonstrated that CD137 from NK cells specifically stimulates CD137 ligand (CD137L) on tubular epithelial cells (TECs) such that TECs produced the high CXCR2 chemokine levels required for neutrophil chemotaxis. We report in the present study that endogenous TLR2 ligands released from ischemic TECs induce CCR5 chemokine expression, which is critical to promoting NK cell recruitment. By implanting CD137L(-/-) TECs into the kidney capsule of TLR2(-/-) mice, we further showed that TLR2-mediated NK cell recruitment is an uncoupled event that can occur independently of CD137L signaling in TECs, which is responsible for recruiting neutrophils. Therefore, our findings identify TECs as both a target for kidney damage and also as a master regulator that actively modulates stepwise signaling, leading to the initiation and amplification of acute sterile inflammation that inflicts kidney IRI. Being clinically important, the signaling pathway of innate receptors in epithelial cells may therefore be a good target to block acute sterile inflammation resulting from tissue damage, including kidney IRI.

Reverse signaling through the costimulatory ligand CD137L in epithelial cells is essential for natural killer cell-mediated acute tissue inflammation.

Renal ischemia-reperfusion injury (IRI) after kidney transplantation is a major cause of delayed graft function. Even though IRI is recognized as a highly coordinated and specific process, the pathways and mechanisms through which the innate response is activated are poorly understood. In this study, we used a mouse model of acute kidney IRI to examine whether the interactions of costimulatory receptor CD137 and its ligand (CD137L) are involved in the early phase of acute kidney inflammation caused by IRI. We report here that the specific expressions of CD137 on natural killer cells and of CD137L on tubular epithelial cells (TECs) are required for acute kidney IRI. Reverse signaling through CD137L in TECs results in their production of the chemokine (C-X-C motif) receptor 2 ligands CXCL1 and CXCL2 and the subsequent induction of neutrophil recruitment, resulting in a cascade of proinflammatory events during kidney IRI. Our findings identify an innate pathogenic pathway for renal IRI involving the natural killer cell-TEC-neutrophil axis, whereby CD137-CD137L interactions provide the causal contribution of epithelial cell dysregulation to renal IRI. The CD137L reverse signaling pathway in epithelial cells therefore may represent a good target for blocking the initial stage of inflammatory diseases, including renal IRI.

What are the resection accuracy and guide-fitting errors associated with 3D-printed, patient-specific resection guides for bone tumour resections?

AIMS: This study aimed to analyze the accuracy and errors associated with 3D-printed, patient-specific resection guides (3DP-PSRGs) used for bone tumour resection. METHODS: We retrospectively reviewed 29 bone tumour resections that used 3DP-PSRGs based on 3D CT and 3D MRI. We evaluated the resection amount errors and resection margin errors relative to the preoperative plans. Guide-fitting errors and guide distortion were evaluated intraoperatively and one month postoperatively, respectively. We categorized each of these error types into three grades (grade 1, < 1 mm; grade 2, 1 to 3 mm; and grade 3, > 3 mm) to evaluate the overall accuracy. RESULTS: The maximum resection amount error was 2 mm. Out of 29 resection amount errors, 15 (51.7%) were grade 1 errors and 14 (38.3%) were grade 2 errors. Complex resections were associated with higher-grade resection amount errors (p < 0.001). The actual resection margins correlated significantly with the planned margins; however, there were some discrepancies. The maximum guide-fitting error was 3 mm. There were 22 (75.9%), five (17.2%), and two (6.9%) grade 1, 2, and 3 guide-fitting errors, respectively. There was no significant association between complex resection and fitting error grades. The guide distortion after one month in all patients was rated as grade 1. CONCLUSION: In terms of the accurate resection amount according to the preoperative planning, 3DP-PSRGs can be a viable option for bone tumour resection. However, 3DP-PSRG use may be associated with resection margin length discrepancies relative to the planned margins. Such discrepancies should be considered when determining surgical margins. Therefore, a thorough evaluation of the preoperative imaging and surgical planning is still required, even if 3DP-PSRGs are to be used.Cite this article: Bone Joint J 2023;105-B(2):190-197.

Thermal Transport Evolution Due to Nanostructural Transformations in Ga-Doped Indium-Tin-Oxide Thin Films.

We report on a comprehensive theoretical and experimental investigation of thermal conductivity in indium-tin-oxide (ITO) thin films with various Ga concentrations (0-30 at. %) deposited by spray pyrolysis technique. X-ray diffraction (XRD) and scanning electron microscopy have shown a structural transformation in the range 15-20 at. % Ga from the nanocrystalline to the amorphous phase. Room temperature femtosecond time domain thermoreflectance measurements showed nonlinear decrease of thermal conductivity in the range 2.0-0.5 Wm-1 K-1 depending on Ga doping level. It was found from a comparison between density functional theory calculations and XRD data that Ga atoms substitute In atoms in the ITO nanocrystals retaining Ia-3 space group symmetry. The calculated phonon dispersion relations revealed that Ga doping leads to the appearance of hybridized metal atom vibrations with avoided-crossing behavior. These hybridized vibrations possess shortened mean free paths and are the main reason behind the thermal conductivity drop in nanocrystalline phase. An evolution from propagative to diffusive phonon thermal transport in ITO:Ga with 15-20 at. % of Ga was established. The suppressed thermal conductivity of ITO:Ga thin films deposited by spray pyrolysis may be crucial for their thermoelectric applications.

The effect of a sequential compression device on hemodynamics in arthroscopic shoulder surgery using beach-chair position.

PURPOSE: This study investigated the effect of intermittent compression by a sequential compression device (SCD) on the incidence of hypotension and other hemodynamic variables in the beach-chair position. METHODS: Fifty healthy patients undergoing elective shoulder arthroscopy under general anesthesia were randomly assigned to either the control group (n = 25) or SCD group (n = 25). A standardized protocol for pre-hydration and anesthetic technique was followed. Hemodynamic variables were measured before (pre-induction values) and 5 minutes after the induction of anesthesia in the supine position (baseline values) and 1, 3, and 5 minutes after the patient was raised to a 70 degrees sitting position. The incidence of hypotension was recorded and treated with ephedrine. RESULTS: The incidence of hypotension was significantly higher in the control group (16 of 25) than that in the SCD group (7 of 25) (P = .022; odds ratio, 0.219; 95% confidence interval, 0.066 to 0.723). Between the groups, mean arterial pressure, cardiac index, and stroke volume index were significantly higher in the SCD group compared with values in the control group at 1 minute after patients were raised to a 70 degrees sitting position (P = .035, P = .046, and P = .011, respectively). CONCLUSIONS: This study showed that the use of an SCD could reduce the incidence of hypotension from 64% to 28% and supports hemodynamic variables such as mean arterial pressure and stroke volume index when patients were changed from the supine to the beach-chair position in those undergoing shoulder arthroscopy. LEVEL OF EVIDENCE: Level I, therapeutic randomized controlled trial.

CCR5-mediated Recruitment of NK Cells to the Kidney Is a Critical Step for Host Defense to Systemic Candida albicans Infection.

C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5-/- mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5-/- mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c+ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.

Inhibition of kidney ischemia-reperfusion injury through local infusion of a TLR2 blocker.

Kidney ischemia-reperfusion injury (IRI) occurs as a result of complex interactions of kidney parenchymal cells and immune cells that are initiated by hypoxic damage of parenchymal cells. In particular, tubular epithelial cells (TECs) not only are susceptible to ischemia but also have an auto-loop system to amplify renal inflammation caused by ischemia and reperfusion. Since endogenous TLR2 ligands released from TECs trigger renal inflammation leading to kidney IRI in an autocrine manner, we hypothesized that local infusion of TLR2 blockers would prevent kidney IRI. In this study, we demonstrated that injection of antagonist anti-TLR2 mAb through the renal vein after cross-clamping significantly reduced the recruitment of NK cells to the kidney after IRI, a phenomenon that is governed by TLR2 signaling in TECs. In addition, intrarenal blocking of TLR2 signaling was shown to inhibit NK cell-mediated neutrophil infiltration and subsequent renal damage. Overall, our simple experiment system will be of help in testing the efficacy of candidate blockers targeting kidney parenchymal cells in inhibition of kidney IRI.

Prurigo pigmentosa in Korea: clinicopathological study.

BACKGROUND: Prurigo pigmentosa (PP) is an inflammatory dermatosis characterized by recurrent pruritic erythematous papules, mainly located on the trunk. It was first described by Nagashima in 1971 in Japan. Since then, more than 300 cases have been reported in Japan, but reports from other parts of the world are quite rare. MATERIALS AND METHODS: We studied clinical and histopathological data from six patients with PP diagnosed in our hospital and 43 patients (18 reports) who were diagnosed with PP in Korea between 1988 and 2008. RESULTS: The number of Korean patients reported in recent years is higher than the number of other non-Japanese patients reported. Clinicopathological characteristics in Korean patients were not significantly different from those previously reported. Therapeutic results with minocycline were successful in our patients. CONCLUSIONS: We suspect that PP is not uncommon in Korea, and the disease may be underestimated. Strict restriction of diet as well as known associated factors like wet condition are suggested as one of the important factors contributing to the occurrence of PP in Korea.

Serum C-reactive protein level is a predictive factor for 14-day mortality of patients with advanced cancer who present to the emergency department with acute symptoms.

OBJECTIVES: This study aimed to investigate the potential of C-reactive protein (CRP) as a predictor of death within 14 days in acutely symptomatic patients with advanced cancer admitted to the emergency department (ED). METHODS: A prospective observational study was conducted of 126 consecutive patients with advanced cancer who were admitted to the ED because of acute symptoms. The patients were categorized into two groups according to serum CRP levels (cutoff 9.2 mg/dL). Demographic characteristics, disease-related factors, clinical symptoms and signs, and laboratory data were collected. Univariate and multivariate analyses were performed to evaluate the relationship between clinical findings and 14-day mortality. RESULTS: Median survival was 26.5 days (interquartile range = 8.0-79.5 days). In univariate analysis, serum CRP level (≥9.2 mg/dL), chemotherapy, age (≥65 years), altered mental status, hypotension, and leukocytosis were significant. Multivariate regression analysis revealed that among these variables, serum CRP level (hazard ratio [HR] = 2.444, 95% confidence interval [CI] = 1.298 to 4.603, p = 0.006) and chemotherapy (HR = 0.452, 95% CI = 0.236 to 0.863, p = 0.016) were independent prognostic factors for 14-day mortality. CONCLUSIONS: Serum CRP levels may provide information on death within 14 days after the ED visit in patients with advanced cancer.

Isoflurane depresses baroreflex control of heart rate in decerebrate rats.

BACKGROUND: Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression. METHODS: The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 microg/kg) and nitroprusside (1-60 microg/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, beta-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically. RESULTS: Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups. CONCLUSIONS: Isoflurane depresses HR baroreflex control by actions that do not require suprapontine central nervous system sites. Isoflurane actions seem to inhibit HR baroreflex primarily by the sympathetic nervous system.