Dynamic study of the finger interphalangeal joint volar plate-motion analysis with magnetic resonance cinematography and histologic comparison.

OBJECTIVE: We aimed to further improve knowledge about volar plate (VP) motion of the finger proximal interphalangeal joint (PIP), by analyzing the dynamic VP shape during a full range of finger flexion using magnetic resonance cinematography of the fingers (MRCF), and to compare the results with anatomical cross sections from cadaver specimens. MATERIALS AND METHODS: The dynamic sagittal VP shape was visualized with MRCF in a total number of 23 healthy volunteers. The length, angle, and thickness as well as the contact length of the VP to the PIP joint base were measured. Statistical analysis included t-test or rank-sum testing. Anatomical cross sections with differing degrees of PIP joint flexion were obtained from 12 cadaver specimens (fingers) for comparison. RESULTS: Significant positive correlations between PIP joint flexion angle and VP area, length, depth and the VP contact length were found. This matched histologically to fiber rearrangements especially within the loose third VP layer. CONCLUSION: Our study analyzed the full range of motion dynamic VP shape of the PIP joint using MRCF. This contributes to a more precise understanding of the complex interaction of the VP with the PIP joint and may facilitate evaluation of clinical cases such as VP avulsion or pulley rupture.

DAPK-HSF1 interaction as a positive-feedback mechanism stimulating TNF-induced apoptosis in colorectal cancer cells.

Death-associated protein kinase (DAPK) is a serine-threonine kinase with tumor suppressor function. Previously, we demonstrated that tumor necrosis factor (TNF) induced DAPK-mediated apoptosis in colorectal cancer. However, the protein-protein interaction network associated with TNF-DAPK signaling still remains unclear. We identified HSF1 as a new DAPK phosphorylation target in response to low concentrations of TNF and verified a physical interaction between DAPK and HSF1 both in vitro and in vivo. We show that HSF1 binds to the DAPK promoter. Transient overexpression of HSF1 protein led to an increase in DAPK mRNA level and consequently to an increase in the amount of apoptosis. By contrast, treatment with a DAPK-specific inhibitor as well as DAPK knockdown abolished the phosphorylation of HSF1 at Ser230 (pHSF1(Ser230)). Furthermore, translational studies demonstrated a positive correlation between DAPK and pHSF1(Ser230) protein expression in human colorectal carcinoma tissues. Taken together, our data define a novel link between DAPK and HSF1 and highlight a positive-feedback loop in DAPK regulation under mild inflammatory stress conditions in colorectal tumors. For the first time, we show that under TNF the pro-survival HSF1 protein can be redirected to a pro-apoptotic program.

A novel missense mutation in the gene EDARADD associated with an unusual phenotype of hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (HED) is a rare disorder characterized by deficient development of structures derived from the ectoderm including hair, nails, eccrine glands, and teeth. HED forms that are caused by mutations in the genes EDA, EDAR, or EDARADD may show almost identical phenotypes, explained by a common signaling pathway. Proper interaction of the proteins encoded by these three genes is important for the activation of the NF-κB signaling pathway and subsequent transcription of the target genes. Mutations in the gene EDARADD are most rarely implicated in HED. Here we describe a novel missense mutation, c.367G>A (p.Asp123Asn), in this gene which did not appear to influence the interaction between EDAR and EDARADD proteins, but led to an impaired ability to activate NF-κB signaling. Female members of the affected family showed either unilateral or bilateral amazia. In addition, an affected girl developed bilateral ovarian teratomas, possibly associated with her genetic condition.

FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal stromal tumors.

The ability to escape apoptosis is a hallmark of cancer-initiating cells and a key factor of resistance to oncolytic therapy. Here, we identify FAM96A as a ubiquitous, evolutionarily conserved apoptosome-activating protein and investigate its potential pro-apoptotic tumor suppressor function in gastrointestinal stromal tumors (GISTs). Interaction between FAM96A and apoptotic peptidase activating factor 1 (APAF1) was identified in yeast two-hybrid screen and further studied by deletion mutants, glutathione-S-transferase pull-down, co-immunoprecipitation and immunofluorescence. Effects of FAM96A overexpression and knock-down on apoptosis sensitivity were examined in cancer cells and zebrafish embryos. Expression of FAM96A in GISTs and histogenetically related cells including interstitial cells of Cajal (ICCs), "fibroblast-like cells" (FLCs) and ICC stem cells (ICC-SCs) was investigated by Northern blotting, reverse transcription-polymerase chain reaction, immunohistochemistry and Western immunoblotting. Tumorigenicity of GIST cells and transformed murine ICC-SCs stably transduced to re-express FAM96A was studied by xeno- and allografting into immunocompromised mice. FAM96A was found to bind APAF1 and to enhance the induction of mitochondrial apoptosis. FAM96A protein or mRNA was dramatically reduced or lost in 106 of 108 GIST samples representing three independent patient cohorts. Whereas ICCs, ICC-SCs and FLCs, the presumed normal counterparts of GIST, were found to robustly express FAM96A protein and mRNA, FAM96A expression was much reduced in tumorigenic ICC-SCs. Re-expression of FAM96A in GIST cells and transformed ICC-SCs increased apoptosis sensitivity and diminished tumorigenicity. Our data suggest FAM96A is a novel pro-apoptotic tumor suppressor that is lost during GIST tumorigenesis.

Post-Operative Outcomes Associated With Open Versus Robotic Thymectomy: A Propensity Matched Analysis.

To compare post-operative outcomes associated with thymectomy performed using either open or robotic approaches. Retrospective cohort study from a single-center prospective registry consisting of patients undergoing thymectomy between 2000 and 2020. Patients were grouped according to surgical approach (open vs robotic). A propensity-score matching analysis was performed in a 2:1 open to robotic ratio, and surgical outcomes were evaluated. We analyzed 234 thymectomies (155 open; 79 robotic). Myasthenia gravis was present in 23.2% and 32.9% (P = 0.249) in the open and in the robotic group, respectively. All covariates were balanced in the matched groups (open n = 114; robotic n =5 9), except lesion size. The robotic approach was significantly associated with shorter surgical time (median 95 vs 65 minutes, P < 0.001), lesser clinical (21.1% vs 6.8%, P = 0.016) and surgical (11.4% vs 1.7%, P = 0.036) complications during the same hospitalization, less Clavien-Dindo grade 2 or higher complication rates (28.1 vs 15.3%, P = 0.048), chest tube duration (median: 3 vs 0 days, P < 0.001) and in-hospital length of stay (median: 5 vs 0 days, P < 0.001). Bleeding (P = 0.214), ICU length of stay (P = 0.167), reoperation rate (open, 1.8% vs robotic 0%), 90-day mortality (P = 0.341) and readmission rate post discharge (P = 0.277) were similar between the groups. In the matched population with primary thymic epithelial tumors, the completeness of resection rate was similar (open, 92.1% vs robotic 96.8%, P = 0.66.). Robotic thymectomy is associated with improved post-operative outcomes when compared to open thymectomy, without compromising the goals of oncologic surgery. Longer follow-up is needed to ensure oncologic equivalence.

Trepopnea may explain right-sided pleural effusion in patients with decompensated heart failure.

BACKGROUND: Physicians often overlook trepopnea as a symptom, and its prevalence and clinical repercussions are not usually described. We propose that trepopnea is a common symptom in heart failure (HF) and, because of patient avoidance of left lateral decubitus position, contributes to the greater prevalence of right-sided pleural effusion in patients with HF. Accordingly, this study aimed to determine trepopnea prevalence and to evaluate the association of trepopnea and the laterality of pleural effusion in decompensated HF. METHODS: Consecutive patients (n = 37) with decompensated HF and evidence of pleural effusion by chest x-ray were included. Data were collected at the emergency department by a standard clinical examination in which patients were specifically asked about the presence of trepopnea and preferred decubitus position while recumbent. Chest x-ray and echocardiographic parameters were recorded. RESULTS: Of the 37 patients, 19 (51%) reported trepopnea. Most patients presented with right-sided pleural effusion; only 2 patients (5.4%) presented with left-sided pleural effusion. Patients who reported trepopnea had predominant right-sided pleural effusion more frequently than patients without this symptom (73.7% vs 26.3%; P = .049). The participants that reported trepopnea or avoidance of left lateral decubitus position while recumbent or both had a greater probability of having predominant right-sided pleural effusion (likelihood ratio, 1.85; 95% confidence interval, 1.02-3.35). CONCLUSIONS: Trepopnea is a common symptom in patients with decompensated HF and is associated with predominant right-sided pleural effusion in this population. Our results indicate that trepopnea may be a contributory factor for pleural effusion laterality in patients with decompensated HF.

Evaluation of deployment capability of a novel outside-the-scope, detachable catheter system for ablation of lung lesions in ex vivo human lung models.

Objectives: Effective transbronchial ablation of lung nodules requires precise catheter delivery to the target lesion and freedom from the bronchoscope for safety throughout the procedure and to allow for multiple catheter insertions. A fully detachable, outside-the-scope (OTS) probe system was developed that attaches to a flexible bronchoscope. Using this system, the operator can deploy the probe in the target and completely detach it from the scope. Our aim was to demonstrate the endobronchial deployment accuracy and feasibility of an OTS, detachable, simulated ablation catheter driven to peripheral lung targets in ex vivo-ventilated human lung models. Methods: A balloon catheter inflated with radiopaque contrast was used as a simulated peripheral target in freshly explanted lungs from lung transplant recipients. A simulated ablation catheter was positioned outside and aligned to the tip of the bronchoscope using the OTS system. Under fluoroscopic guidance, the bronchoscope and the catheter were driven toward the target in mechanically ventilated lungs. Once the catheter tip was confirmed within the target, the OTS system was released and the probe was detached from the scope. The bronchoscope was retracted and fluoroscopy was used to confirm the position of the catheter. Results: Twelve peripheral targets were simulated. The ablation catheter was successfully deployed with its tip positioned within 5 mm from the target and confirmed stability during multiple cycles of ventilation. Conclusions: A novel, detachable, OTS system can be successfully deployed in peripheral lung targets with potential clinical applications for multiple procedures in advanced bronchoscopy where scope freedom is advantageous.

Inpatient Management of the Acutely Decompensating Lung Transplant Candidate.

Lung allocation in the US changed nearly 15 years ago from time accrued on the waiting list to disease severity and likelihood of posttransplant survival, represented by the lung allocation score (LAS). Notably, the risk of death within a year plays a stronger role on the score calculation than posttransplant survival. While this change was associated with the intended decrease in waitlist mortality (most recently reported at 14.6%), it was predictable that transplant teams would have to care for increasingly older and complex candidates and recipients. This urgency-based allocation also led centers to routinely consider transplanting patients with higher acuity, often hospitalized and, not infrequently, in the intensive care unit (ICU). According to the Scientific Registry for Transplant Recipients, from 2009 to 2019, the proportion of lung recipients hospitalized and those admitted to the ICU at the time of transplant increased from 18.9% to 26.8% and from 9.2% to 16.5%, respectively..

Endosonography-Guided Biopsy as a First Test in the Diagnosis of Lymphoma.

To evaluate the diagnostic accuracy of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration (EBUS-TBNA) and Endoscopic Ultrasound-guided Fine Needle Aspiration (EUS-FNA) in the diagnosis of lymphoma. A retrospective analysis of patients with suspected mediastinal lymphoproliferative disorders who underwent EBUS-TBNA, EUS-FNA or combined procedures from 2009 to 2019 was conducted using a prospectively maintained interventional thoracic endoscopy database. Demographic data, imaging, needle size, surgical biopsy, complications rate and pathology reports were reviewed. Over a 10-year period, a total of 444 patients were investigated with endosonography as the first diagnostic procedure for mediastinal adenopathy suspicious for lymphoma. Lymphoma was diagnosed in 77 patients (17.3%). In total, 68 patients (88.3%) were diagnosed using endosonographic mediastinal tissue sampling. Four patients had both lymphoproliferative disorders and lung cancer. Nine patients (11.7%) required a surgical biopsy to confirm the lymphoma diagnosis (6 non-diagnostic; 3 inadequate samples from endosonographic biopsies). In patients with adequate biopsies via endosonography, the sensitivity for the diagnosis of lymphoma, was 91.9% (n = 68/74). The histopathologic subtype of lymphoma was determined by endosonographic biopsies in 61 patients (89.7%) with an increased sensitivity (92.6%) for low grade Non-Hodgkin lymphoma (NHL). No acute complication related to endosonography was observed. Endosonographic biopsy (EBUS and/or EUS) of mediastinal adenopathy in patients with suspected lymphoma is a highly sensitive and safe diagnostic test. Endosonography should be the first test in the diagnosis of suspicious mediastinal lymphoma and should be followed by surgical biopsy in cases of insufficient sampling or indefinite diagnosis.

Impact of Volume on Mortality and Hospital Stay After Lung Cancer Surgery in a Single-Payer System.

BACKGROUND: There is a literature gap for hospitals in single-payer health care systems quantifying the influence of hospital volume on outcomes after major lung cancer resection. We aimed to determine the effect of hospital volume on mortality and length of stay. METHODS: A retrospective cohort study using administrative, population-based data from a single-payer universal health care system was performed in adults with non-small cell lung cancer who underwent lobectomy or pneumonectomy between 2008 and 2017. Hospital volume was defined as the average annual number of major lung resections performed at each institution. Length of stay and postoperative mortality were compared using multivariable linear and nonlinear regression between hospital volume categories and continuously. Adjusted association between hospital volume and postoperative mortality was determined by multivariable logistic regression. RESULTS: In all, 10 831 lung resections were performed: 1237 pneumonectomies and 9594 lobectomies. Patients undergoing lobectomy at high-volume hospitals had shorter median length of stay (6 vs 8 days, P = .001) compared with low-volume hospitals. After adjusting for confounders, surgery at a high-volume center was significantly associated with shorter length of stay after lobectomy and overall resections (P ≤ .001), but not after pneumonectomy (P = .787). Surgery at a high-volume center was positively associated with improved 90-day mortality in lobectomy and overall procedures (odds ratio 0.607 [95% confidence interval, 0.399 to 0.925], and 0.632 [95% confidence interval, 0.441 to 0.904], respectively). Volume was not a predictor of 90-day mortality after pneumonectomy (odds ratio 0.533 [95% confidence interval, 0.257 to 1.104], P = .090). CONCLUSIONS: Surgery at a high-volume center was positively correlated with improved 90-day survival and shorter hospital length of stay. The results support regionalized lung cancer care in a single-payer health care system.

Accuracy of multidetector computed tomography with maximum intensity projection technique in the assessment of fissure integrity.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) is a potential treatment for patients with severe emphysema, performed through the placement of unidirectional endobronchial valves (EBVs). Their benefits are only achieved in patients that significantly reduce lobar volume, and it is mandatory that the fissures are complete. Fissure evaluation is preferably done by computed tomography, but little is known if its evaluation corresponds to the anatomical findings. The aim of this study is to evaluate the accuracy of thoracic radiologists in the identification of complete fissures by multidetector computed tomography (MDCT) using maximum intensity projection (MIP) technique, compared with direct anatomical evaluation. METHODS: Prospective study, conducted in a single institution. Patients submitted to thoracic surgery had their fissures classified as complete or incomplete by thoracic surgeons and their preoperative chest scans evaluated by three radiologists, blinded for surgical evaluation. With the intraoperative categorization as a reference, the accuracy and concordance of the three thoracic radiologists' evaluation were calculated. The most experienced radiologist evaluated the fissures at two different moments to estimate the intra-observer agreement. RESULTS: There were included 67 patients, being 37 (55%) males, with a mean age of 64 years. The accuracy of radiological identification of complete fissures ranged from 76.8% for left posterior oblique fissure to 85.1% for left anterior oblique fissure, with the best performance achieved by the most experienced radiologist. The concordance of the radiological evaluation for fissure integrity compared to the surgical assessment (k) was 0.53-0.68. Intra-observer agreement ranged from 0.74 to 0.87. CONCLUSIONS: The evaluation of the fissure integrity by MDCT analysis using MIP technique by thoracic radiologists had high accuracy among the thoracic radiologists.

Imaging, histopathological degree of degeneration and clinical findings - Do these correlate in patients with temporomandibular joint disorders.

The gold standard for temporomandibular joint imaging is magnetic resonance imaging, although there are still pathological findings that cannot be seen in MRI but in surgery and the subsequent histological analysis only. The main goal of this investigation was to validate the MRI score used by histopathological findings as well as clinical findings. In this retrospective study 39 patients were included; 38 of which underwent unilateral and 1 underwent bilateral discectomy. MRI findings were graded according to the score by Wurm. Histopathological analysis was performed in hematoxylin-eosin staining and graded in accordance with the scores by Krenn and by Leonardi. For valuation of preoperative pain values of the temporomandibular joint operated on the numeric rating scale was utilized. Correlations were verified by Spearman-Rho. The MRI scores on average showed significantly lower scores for the discs of the operated temporomandibular joint than for the discs of the non-operated side(p<.01). No significant correlations between MRI findings, histopathological findings and pain intensities could be observed. Thus unsuspicious morphology of the TMJ and the articular disc in MRI is no guarantee for the absence of cartilage-degeneration. Further investigations utilizing T2 cartilage mapping could possibly show better correlations between the temporomandibular joint's degree of degeneration and imaging results.

Surgical Cost Awareness Program Study: Impact of a Novel, Real-Time, Cost Awareness Intervention on Operating Room Expenses in Thoracoscopic Lobectomy.

BACKGROUND: For surgical patients, operating room expenses are significant drivers of overall hospitalization costs. Surgical teams often lack awareness of the costs associated with disposable surgical supplies, which may lead to unnecessary expenditures. The aim of this study is to evaluate whether a Surgical Cost Awareness Program would reduce operating room costs. STUDY DESIGN: A prototype software displays the types and costs of disposable instruments used in real-time during surgery and generates insight-driven operative cost reports, which are automatically sent to the surgeons. A prospective pre-post controlled trial of thoracoscopic lobectomy procedures performed by 7 surgeons at a single academic center was conducted. Control and intervention groups consisted of consecutive cases from February 2nd through June 23, 2021, and from June 28th through December 22, 2021, respectively. The primary outcome was mean per case surgical disposables cost. RESULTS: Three hundred twenty-two lobectomies were evaluated throughout the study period (control: n = 164; intervention: n = 158). Baseline characteristics were comparable between groups. Mean disposables cost per case was $3,320.73 ± $814.83 in the control group compared with $2,567.64 ± $594.59 in the intervention group, representing a mean cost reduction of $753.08 (95% CI, $622.29 to $883.87; p < 0.001). All surgeons experienced a reduction in disposable costs after the intervention. Intraoperative and postoperative outcomes did not differ between the cohorts. CONCLUSIONS: Providing real-time educational feedback to surgical teams significantly reduced costs associated with disposable surgical equipment without compromising perioperative outcomes for lobectomy. Integrating the novel AssistIQ software across other procedural settings may generate further data insights with the potential for significant cost savings on a larger scale.

Single-Stage Posterior Approach for the En Bloc Resection and Spinal Reconstruction of T4 Pancoast Tumors Invading the Spine.

STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to evaluate the outcomes of patients who had T4 Pancoast tumors invading the spine and underwent en bloc resection and spinal stabilization through a single-stage posterior approach. OVERVIEW OF LITERATURE: Surgical resection for Pancoast tumors affecting the spine has been successfully performed in two stages involving spinal reconstruction and tumor resection. However, reports have rarely presented the results of en bloc resection combined with spinal stabilization for T4 Pancoast tumors invading the spine through a single-stage posterior approach. METHODS: Patients who had T4N0M0 Pancoast tumors invading the spine and underwent a single-stage posterior approach were retrospectively recruited. The following data were obtained and examined: demographics, tumor histology, preoperative and postoperative therapy, complications, spinal reconstruction technique, tumor resection extent, survival time, and disease recurrence. RESULTS: Eighteen patients were included. The mean population age was 61±17 years, and the most common pathological type was adenocarcinoma (61.1%). Complete resection (R0) was obtained in 15 patients (83.3%), positive surgical margins (R1) were found in three patients (16.7%), and the 90-day mortality rate was 0%. Postoperative major complications were detected in 12 patients (66.7%), who required reoperation. The mean survival time was 67±24 months, but the median survival time was not reached. Among the patients, 10 (55.6%) are still alive at the end of the study. The 2- and 5-year actual survival rates were 59% (95% confidence interval [CI], 35.7%-82.3%) and 52.5% (95% CI, 28.4%-76.6%), respectively. CONCLUSIONS: En bloc resection and spinal stabilization through a single-stage posterior approach might be effective for T4 Pancoast tumors invading the spine.

Matrix biochemistry and cell biology of dedifferentiated chondrosarcomas.

Dedifferentiated chondrosarcoma is an uncommon mesenchymal neoplasm comprised of two different components, low-grade conventional chondrosarcoma and high-grade non-cartilaginous sarcoma. In order to gain better insight into the biology of this tumor, we investigated a large series of dedifferentiated chondrosarcomas by looking at the composition of the extracellular tumor matrix within each of the distinct histological components. Our results showed that the well-differentiated portion of the tumors showed matrix components largely similar to conventional chondrosarcomas or enchondromas. In contrast, the high-grade portions showed a variety of staining patterns related to the matrix being formed. Cartilage-specific proteoglycans and collagens were consistently absent, except in areas showing a chondroblastic osteosarcoma histomorphology. Instead, the most dominant immunostaining was received for type I collagen. Type III and VI collagens were concentrated in the areas showing a fibroblastic phenotype. Our results lend further support to the notion that dedifferentiated chondrosarcoma represents transdifferentiation of a cell towards various blastic mesenchymal cell lineages, most commonly osteoblastic and fibroblastic, but occasionally chondroblastic as well. There was no difference in the clinical outcome of patients with differing high-grade tumor types, emphasizing that grade is a more important predictor of biological behavior than the direction of tumor differentiation.

Craniofacial Osteosarcoma-Pilot Study on the Expression of Osteobiologic Characteristics and Hypothesis on Metastasis.

Background: Craniofacial osteosarcomas (COS) and extracranial osteosarcomas (EOS) show distinct clinical differences. COS show a remarkably lower incidence of metastases and a better survival. However, in contrast to EOS, they show a poor response to neoadjuvant chemotherapy. Tumor-associated macrophages and their polarization as well as developmental biological signaling pathways are possible candidates for explaining the clinical differences between COS and EOS. The aim of the study was to analyze differential expression of macrophage markers and important regulators of these pathways. Methods: Twenty osteosarcoma cases (10 COS and 10 EOS) were immunohistochemically stained to assess CD68, CD11c, CD163, MRC1, Gli1, and Gli2 expression. Statistical differences between COS and EOS were tested using the Mann-Whitney U test. Additionally, the paper describes an example of multidisciplinary treatment of a patient suffering from COS and discusses the surgical challenges in treatment and rehabilitation of COS. Results: COS showed a significantly (p < 0.05) increased infiltration of CD11c-positive M1 macrophages and a shift toward M1 polarization compared to EOS. Additionally, COS revealed a significantly (p < 0.05) lower Gli1 expression than EOS. Conclusion: The reduced Gli1 expression in COS can be interpreted as reduced activation of the Hedgehog (Hh) signaling pathway. The increased M1 polarization and reduced Hh activation in COS could explain the low incidence of metastases in these osteosarcomas.

Is Ovarian Tissue Transport at Supra-zero Temperatures Compared to Body Temperature Optimal for Follicle Survival?

BACKGROUND/AIM: Transportation of ovarian cortex prior to freezing is used clinically; however, basic investigations of ovarian storage are limited and the question remains what temperature is optimal for transport over long distances and time periods. The aim of this study was to evaluate the rate of follicular loss over various time periods under two different temperatures and assess whether ovarian follicle viability is affected following cryopreservation and thawing subsequent to the transportation of ovarian tissue. MATERIALS AND METHODS: Pig ovaries were transported at 4°C (n=10) or at 38°C (n=10) prior to cryopreservation. At 0, 4, 12 and 24 h tissues were fixed for histological examination and a LIVE/DEAD Assay. At the same time-points ovarian tissues were cryopreserved and analysed after thawing. RESULTS: Histological evaluation and LIVE/DEAD Assay of freshly transported ovarian tissue showed significantly better follicle survival at 4°C during transportation duration. In cryopreserved ovarian tissues the LIVE/DEAD Assay showed a significant difference in the number of intact and dead follicles at 24 h in favor of 4°C (p<0.05). CONCLUSION: Ovarian tissue transportation should be kept at a minimum to prevent potential damage.

Safety assessment of microsilver-loaded poly(methyl methacrylate) (PMMA) cement spacers in patients with prosthetic hip infections: Results of a prospective cohort study.

OBJECTIVES: Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. METHODS: A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3. RESULTS: In total, 11 of the 12 patients completed the study. No argyria or considerable differences in laboratory parameters were detected. Silver blood concentrations were below or around the detection limit of 1 ppb in ten of the 11 patients. A maximum of 5.6 ppb at 48 hours after implantation of the silver spacer, which is below the recommended maximum level of 10 ppb, was found in one patient. No silver was detected in the urine. Drainage fluids showed concentrations between 16.1 ppb and 23.3 ppb at 12 hours after implantation of the silver spacers, and between 16.8 ppb to 25.1 ppb at 48 hours after implantation. Pathohistological assessment of the periprosthetic membrane did not reveal any differences between the two groups. CONCLUSION: Microsilver-loaded gentamicin-PMMA spacers showed good biocompatibility and the broad antimicrobial activity warrants further clinical research to assess its effectivity in reducing infection rates in prosthetic joint infection.Cite this article: V. Alt, M. Rupp, K. Lemberger, T. Bechert, T. Konradt, P. Steinrücke, R. Schnettler, S. Söder, R. Ascherl. Safety assessment of microsilver-loaded poly(methyl methacrylate) (PMMA) cement spacers in patients with prosthetic hip infections: Results of a prospective cohort study. Bone Joint Res 2019;8:387-396. DOI: 10.1302/2046-3758.88.BJR-2018-0270.R1.

Response of HEK293 and CHO cells overexpressing fusiogenic syncytin-1 to mitochondrion-mediated apoptosis induced by antimycin A.

Apoptosis is essential for the regulation of cellular homeostasis in the placenta and is also involved in the pathophysiology of pregnancy-related diseases such as pre-eclampsia and intrauterine growth restriction (IUGR). Syncytin-1, a fusiogenic glycoprotein of endogenous-retroviral origin expressed in human trophoblasts, facilitates placental syncytium formation and is found reduced in pre-eclamptic placentas. We focus here on the mitochondrial apoptotic pathway and investigate whether the overexpression of syncytin-1 in HEK293-52 (human embryonic kidney cells) and CHO-52 cells influences the apoptotic response to the mitochondrial inhibitor antimycin A (AA). After the induction of apoptosis by 5 microM AA and incubation for up to 36 h in the absence of serum, the mean apoptotic rate was reduced by 15-30% in syncytin-1 transfected cells compared with mock-transfectants. After 12 h of challenge with AA we found lower cytochrome c levels in the cytoplasmic protein fraction and higher amounts in the mitochondrial fraction in syncytin-1 transfectants compared with mock-transfectants. We observed a decreased Mitotracker Red staining of mitochondria following AA challenge for 24 h in mock-treated CHO cells, in particular, compared with syncytin-1 transfectants. Moreover, we found a reduced activation of caspase 9 in syncytin-1 transfected HEK293-52 cells after 48 h of apoptotic challenge compared to mock-transfectants. However, a high expression of anti-apoptotic Bcl-x(L) was found in both cell types. Using syncytin-1 transfected HEK293-52 cells and CHO-52 cells, we provide initial evidence that syncytin-1 may exert its anti-apoptotic function at the mitochondrial level. A reduced release of cytochrome c followed by a diminished activation of caspase 9 is a possible mechanism.