Completion pneumonectomy via sternotomy and complete intrathoracic liver migration in metastatic osteosarcoma.

Pulmonary metastasectomy is the well-accepted surgical management for recurrent osteosarcoma in the lung. A pneumonectomy is seldom performed, even more so via a sternotomy. We report an unusual case of a pneumonectomy via median sternotomy for a pulmonary metastasis with complete migration of the liver into the intrathoracic space, a complication rarely observed. The patient remains disease-free on follow-up, 21 years following the initial diagnosis. Aggressive approaches for metastasectomy, despite clinician hesitation in the age of minimally invasive surgery, can yield excellent outcomes for a cancer with otherwise poor prognosis.

Market Analysis of Video Laryngoscopy Equipment for the Role 1 Setting.

INTRODUCTION: Airway compromise is the second leading cause of potentially preventable prehospital combat death. Endotracheal intubation (ETI) remains the most common role 1 airway intervention. Video laryngoscopy (VL) is superior to direct laryngoscopy (DL) for first-attempt intubation, especially in less-experienced providers and for trauma patients. The cost has been a major challenge in pushing VL technology far-forward; however, the cost of equipment continues to become more affordable. We conducted a market analysis of VL devices under $10,000 for possible options for role 1. MATERIALS AND METHODS: We searched Google, PubMed, and the Food and Drug Administration database from August 2022 to January 2023 with a combination of several keywords to identify current VL market options under $10,000. After identifying relevant manufacturers, we then reviewed individual manufacturer or distributor websites for pricing data and system specifications. We noted several characteristics regarding VL device design for comparison. These include monitor features, size, modularity, system durability, battery life, and reusability. When necessary, we requested formal price quotes from respective companies. RESULTS: We identified 17 VL options under $10,000 available for purchase, 14 of which were priced below $5,000 for individual units. Infium (n = 3) and Vimed Medical (n = 4) provided the largest number of unique models. VL options under $10,000 exist in both reusable and disposable modalities. These modalities included separate monitors as well as monitors attached to the VL handle. Disposable options, on a per-unit basis, cost less than reusable options. CONCLUSIONS: Several VL options exist within our goal price point in both reusable and disposable options. Clinical studies assessing the technology performance of ETI and deliberate downselection are needed to identify the most cost-effective solution for role 1 dispersion.

Fatal granulomatous amebic encephalitis initially presenting with a cutaneous lesion.

We present a case of a 66-year-old man with a cutaneous Balamuthia mandrillaris lesion that progressed to fatal granulomatous amoebic encephalitis. We provide a summary of Australian cases and describe the clinical features and approach to diagnosing this rare but devastating condition, including the importance of PCR for diagnosis.

Noise in cesarean deliveries: a comprehensive analysis of noise environments in the Labor and Delivery operating room and evaluation of a visual alarm noise abatement program.

BACKGROUND: Cesarean delivery is the most common major surgery worldwide. Noise in healthcare settings leads to impaired communication and concentration, and stress among healthcare providers. Limited information is available about noise at cesarean delivery. OBJECTIVE: This study aimed to achieve a comprehensive analysis of noise that occurs during cesarean deliveries. Sound level meters are used to determine baseline noise levels and to describe the frequency of acute noise generated during a cesarean delivery that will cause a human startle response. Secondarily, we aimed to evaluate the effectiveness of a visual alarm system in mitigating excessive noise. STUDY DESIGN: We completed a preintervention/postintervention observational study of noise levels during cesarean deliveries before and after introduction of a visual alarm system for noise mitigation between February 15, 2021 and August 26, 2021. There were 156 cases included from each study period. Sound pressure levels were analyzed by overall case median decibel levels and by time epoch for relevant phases of the operation. Rapid increases in noise events capable of causing a human startle response, "startle events," were detected by retrospective analysis, with quantification for baselines and analysis of frequency by case type. Median noise levels with interquartile ranges are presented. Data are compared between epochs and case characteristics with nonparametric 2-tailed testing. RESULTS: The median acoustic pressure for all cesarean deliveries was 61.8 (58.8-65.9) (median [interquartile range]) dBA (A-weighted decibels). The median dBA for the full case time period was significantly higher in cases with neonatal intensive care unit team presence (62.1 [60.5-63.9]), admission to the neonatal intensive care unit (62.0 [60.4-63.9]), 5-minute Apgar score <7 (62.2 [61.1-64.3]), multiple gestations (62.6 [62.0-64.2]), and intraoperative tubal sterilization (62.8 [61.5-65.1]). The use of visual alarms was associated with a statistically significant reduction of median noise level by 0.7 dBA, from 61.8 (60.6-63.5) to 61.1 (59.8-63.7) dBA (P<.001). CONCLUSION: The noise intensities recorded during cesarean deliveries were commonly at levels that affect communication and concentration, and above the safe levels recommended by the World Health Organization. Although noise was reduced by 0.7 dBA, the reduction was not clinically significant in reaching a discernible amount (a 3-dB change) or in reducing "startle events." Isolated use of visual alarms during cesarean deliveries is unlikely to be a satisfactory noise mitigation strategy.

Improvement following restoration of inline flow argues against comprehensive thrombus removal strategies and for selective stenting in acute symptomatic iliofemoral venous thrombosis.

OBJECTIVE: Randomized trials have demonstrated the benefit of thrombus removal strategies in iliofemoral deep venous thrombosis (IFDVT) in providing early symptom relief and decreasing the incidence of post-thrombotic syndrome (PTS), especially severe PTS. However, the impact of quantum of residual thrombus burden (RTB) on PTS as determined by intravascular ultrasound examination and the role of venous stenting in the acute setting have not been evaluated and represent the focus of this study. METHODS: Sixty-nine limbs (65 patients) undergoing thrombus removal for acute symptomatic IFDVT between 2015 and 2021 formed the study cohort. The Venous Clinical Severity Score (VCSS) (range, 0-27) grade of swelling (GOS) (range, 0-4), and visual analog scale (VAS) pain scores (range, 0-10) were evaluated initially and at 6, 12, and 24 months after thrombus removal. Quality of life was appraised using the CIVIQ-20 instrument. The extent of initial and RTB after the intervention was estimated using intravascular ultrasound examination. Grading was done as less than 50% (1), 50% to 99% (2), or 100% (3) of luminal thrombus fill within each segment (common femoral vein, external iliac vein, and common iliac vein) by a blinded rater and then combined to generate a total score. The use of stenting, both concurrent (severe residual stenosis/persistent occlusion) and delayed (quality of life impairing residual or recurrent symptoms), was evaluated. RESULTS: Of the 69 limbs, 53 underwent pharmacomechanical/mechanical thrombectomy (PMT), whereas 16 patients underwent PMT and catheter-directed thrombolysis with restoration of inline flow in all limbs. Post-intervention VCSS improved from 6 to 2 at 24 months (P < .0001). GOS improved from 4 to 0 at 24 months (P < .0001). The VAS pain score went from 5 to 0 at 6 months (P < .0001) and remained at 0 at 12 months (P < .0001), but increased to 3 at 24 months (P = .02). The CIVIQ-20 score improved from 38 to 22 (P = .001) over a median follow-up of 19 months. The median RTB total score improved from 9 to 4 (P < .0001). There was no impact of RTB total score (<3 vs >3) on VCSS (P = NS), GOS (P = NS), VAS pain score (P = NS) or CIVIQ-20 score (P = NS) at the various time points. Concurrent stenting was used in 23 limbs (33%) and delayed stenting was carried out in 10 limbs (14%). The median time to delayed stenting was 4 months after the initial thrombus removal intervention. CONCLUSIONS: In patients undergoing PMT or PMT with catheter-directed thrombolysis for acute symptomatic IFDVT, the restoration of inline flow seems to be adequate to provide symptom relief and decrease the incidence of PTS. The extent of RTB does not seem to impact the VCSS, GOS, VAS pain score, or quality of life after such restoration. Stenting can be pursued selectively in the acute setting to help restore inline flow.

Mid-term functional outcomes following reoperation after total ankle arthroplasty: A retrospective cohort study.

BACKGROUND: Despite a significant reported rate of non-revision reoperation after total ankle arthroplasty (TAA), it is uncertain if these subsequent procedures have an impact on the longer term outcomes. This study aimed to compare minimum five-year functional outcomes of patients who had undergone reoperation after TAA to those who did not require reoperation. METHODS: Seventy-six ankles (74 patients) who underwent TAA with the Salto Talaris fixed bearing system between 2007 and 2014 were allocated into two groups based on presence (n = 16) or absence of reoperation (n = 60). Reoperations included all secondary procedures after index TAA, excluding revision surgeries requiring removal or exchange of the original prosthesis. The foot and ankle outcome score (FAOS) at preoperative and minimum five-year follow-up was compared between the groups. Additionally, improvements in FAOS subscales were compared. Preoperative deformity, postoperative implant alignment, number of periprosthetic cysts, and subsidence between groups were compared using standard weightbearing radiographs. RESULTS: The most common cause of reoperation was gutter impingement (n = 11), followed by stress fracture of the medial malleolus (n = 2), tarsal tunnel syndrome (n = 1), periprosthetic cyst (n = 1), and infection (n = 1). In comparison to the non-reoperation group, all FAOS subscales except for the Sports and Recreational Activities subscale were significantly lower in the reoperation group at final follow-up. The reoperation group exhibited significantly less improvement in the Pain, Symptoms, and Quality of Life subscales at final follow-up (p < 0.05). There were no statistical differences in the radiographic parameters between both groups. CONCLUSIONS: Patients who underwent reoperation after TAA demonstrated inferior functional outcomes at mid-term follow-up. An emphasis should be placed on preventing possible causes of reoperations to achieve favorable patient outcomes. Additionally, if a reoperation is deemed necessary, a thorough evaluation and surgical correction of underlying causes should be achieved.

Clinical Outcomes of Revision Surgery Using a Dorsal Approach After Failed Primary Interdigital Neuroma Excision.

BACKGROUND: Revision neurectomy may be approached with either a dorsal or a plantar incision. Although a plantar approach is more commonly described, few studies have investigated outcomes following a dorsal revision neuroma excision. In this study, we performed a case series on a group of patients who underwent revision neuroma excision through a dorsal approach and reported complications and outcomes using validated patient-reported outcome measures (PROMs). METHODS: This retrospective case series included 10 patients who underwent a dorsal-approach revision neuroma excision and had preoperative and minimum 1-year postoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores. Complications including neuroma recurrence and continued unresolved pain were obtained from the electronic medical record. Preoperative and postoperative PROMIS scores were compared to assess improvement in PROMs. RESULTS: There were significant improvements in the PROMIS pain interference (P = .026), pain intensity (P = .008), and global physical health (P = .017) domains. One patient experienced recurrence of their neuroma 4 years after surgery. CONCLUSION: This case series provides preliminary data indicating that revision neurectomy using a dorsal approach leads to satisfactory outcomes in pain-related PROMs. Further research with comparative study designs is necessary to determine if one approach is superior to the other. LEVELS OF EVIDENCE: Level IV: Retrospective.

Early Radiographic and Clinical Outcomes of a Novel, Fixed-Bearing Fourth-Generation Total Ankle Replacement System.

BACKGROUND: The Cadence Total Ankle System is a 2-component, fixed-bearing fourth-generation total ankle arthroplasty (TAA) system that was introduced for clinical use in 2016. The purpose of this study was to report non-inventor, non-industry funded survivorship, radiographic and clinical outcomes, and early complications following use of this implant at a minimum of 2 years. METHODS: This single-center retrospective study included patients who underwent TAA by 2 surgeons with this novel fixed-bearing system between January 2017 and September 2018. Forty-eight patients were evaluated at an average of 33.6 months. Radiographic outcomes included preoperative and postoperative tibiotalar angle on anteroposterior radiographs of the ankle, sagittal tibial angle (STA) on lateral radiographs of the ankle, and periprosthetic lucency formation and location. Revision and reoperation data were collected, and patient-reported outcomes were assessed using Patient Reported Outcomes Measurement Information System (PROMIS). Subgroup analysis assessed associations between preoperative deformity, postoperative implant alignment, PROMIS scores, and periprosthetic lucency formation. RESULTS: Survivorship of implant was 93.7%, with 3 revisions, 1 due to infection and 2 due to loosening of the implant (1 tibial and 1 talar component). Three patients had reoperations (6.3%): 2 for superficial infection and 1 for gutter debridement due to medial gutter impingement. Fifteen patients (35.8%) developed periprosthetic lucencies, all on the tibial side. PROMIS scores improved after surgery in all domains except Depression. Patients with significant postoperative periprosthetic lucency had worse postoperative PROMIS Physical function scores than patients without lucency (P < .05). CONCLUSION: This study demonstrated excellent minimum 2-year clinical and radiographic outcomes and low revision and reoperation rates of this new fourth-generation TAA system. Future studies with longer follow-up, especially on patients with periprosthetic lucency, are necessary to investigate the long-term complications and understand the long-term functional and radiographic outcomes of this implant.

Relationship Between Preoperative PROMIS Scores and Postoperative Outcomes in Hallux Rigidus Patients Undergoing Cheilectomy.

BACKGROUND: Previous studies have demonstrated that preoperative patient-reported outcome measures are associated with postoperative outcomes in foot and ankle surgery, and also in specific procedures such as bunionectomy, flatfoot reconstruction, and total ankle replacement. The primary purpose of this study was to determine if preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) physical function, pain interference, pain intensity, and depression scores were associated with the ability of patients undergoing cheilectomy for hallux rigidus to achieve a minimal clinically important difference (MCID) of improvement. METHODS: This retrospective study included preoperative and ≥2-year postoperative PROMIS physical function, pain interference, pain intensity, and depression scores for 125 feet in 118 patients undergoing cheilectomy collected from an institutional review board (IRB)-approved foot and ankle registry database. MCIDs were established using distribution-based methods to determine clinical significance of improvements in PROMIS scores. Receiver operating characteristic (ROC) curves and area under the curve analyses were used to determine which preoperative PROMIS scores were associated with patients meeting the MCID. RESULTS: ROC analysis found statistically significant areas under the curve (AUCs) for the physical function domain (AUC 0.71), pain intensity (AUC 0.70), and depression (AUC 0.79) PROMIS domains. Subsequent analyses were unable to identify clinically useful 95% sensitivity and specificity preoperative thresholds, with the exception of the 95% sensitivity PROMIS physical function threshold. A preoperative physical function score of greater than 53.2 resulted in a 63% probability of achieving the MCID. The pain interference PROMIS domain did not demonstrate a statistically significant AUC. CONCLUSION: Preoperative PROMIS physical function, pain interference, pain intensity, and depression scores are minimally associated with preoperative to 2-year postoperative improvement in patients undergoing cheilectomy. It may be difficult to determine which patients improve from a cheilectomy based on the severity of symptoms they exhibit preoperatively. LEVEL OF EVIDENCE: Level IV, retrospective case series.

The influence of concomitant hammertoe correction on postoperative outcomes in patients undergoing hallux valgus correction.

BACKGROUND: Patients with hallux valgus often develop secondary hammertoe deformities of the lesser toes. Operative management of bunions with hammertoe can be more extensive; however, it is unclear whether this affects patient-reported outcomes. The aim of this study was to compare postoperative patient-reported outcome measures and radiographic outcomes between patients who underwent isolated bunion correction and patients who underwent simultaneous bunion and hammertoe correction. METHODS: Preoperative, postoperative, and change in Patient-Reported Outcomes Measurement Information System (PROMIS) scores were compared between patients who underwent isolated hallux valgus correction and those who underwent concomitant hammertoe correction. Radiographic measures including hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal-articular angle (DMAA), and Meary's angle were also compared. Targeted minimum-loss estimation (TMLE) was used for statistical analysis to control for confounders. RESULTS: A total of 221 feet (134 isolated bunion correction, 87 concomitant hammertoe correction) with a minimum of 12 months follow-up were included in this study. Both cohorts demonstrated significant improvements in the physical function, pain interference, pain intensity, and global physical health PROMIS domains (all p < 0.001). However, patients in the concomitant hammertoe cohort had significantly less improvements in pain interference and pain intensity (p < 0.01, p < 0.05 respectively). The concomitant hammertoe cohort also had significantly higher postoperative pain interference scores than the isolated bunion cohort (p < 0.01). Radiographic outcomes did not differ between the two groups. CONCLUSION: While both isolated bunion correction and concomitant hammertoe correction yielded clinically significant improvements in patient reported outcomes and normalized radiographic parameters, patients undergoing simultaneous bunion and hammertoe correction experienced substantially less improvement in postoperative pain-related outcomes than those who underwent isolated bunion correction.

Return to Physical Activity Following Flatfoot Reconstruction.

BACKGROUND: Progressive collapsing foot deformity (PCFD) is a debilitating condition encompassing several interrelated, progressive deformities requiring a combination of reconstructive procedures. Few studies investigate returns to activity following flatfoot reconstruction, and existing studies only examine 1 or 2 of the numerous procedures employed. This study aims to provide the first generalizable assessment of returns to sports and physical activity following reconstruction surgery in patients with flexible flatfoot deformity. METHODS: Patients aged 18-60 years who underwent reconstructive surgery between February 16 and May 19 for symptomatic flexible-stage flatfoot deformity were identified by registry review. Eighty-two of 113 eligible patients (73%) were reached at a mean 2.9 years (range, 2.0-5.4) of follow-up with mean age at surgery of 48.9 years (range, 18-59). Returns to physical activity were evaluated with a sports-specific survey. Clinical outcomes were evaluated with Patient-Reported Outcomes Measurement Information System (PROMIS) scores. RESULTS: Patients reported participation in 21 specific sports and activities. One-fourth (25.6%) of patients (21/82) reported increased difficulty with physical activities postoperatively, 15.9% reported equal difficulty, and 58.5% (48/82) reported decreased difficulty. Median return times were 9-12 months for participation and 12-18 months to reach maximum preoperative participation levels. Improvements in Physical Function (P= .001), Pain Interference (P < .001), Pain Intensity (P <.001), and Global Physical Health (P = .004) were associated with increased satisfaction with respect to sports and physical activities. DISCUSSION: This study investigated participation in specific sports and physical activities following flatfoot reconstruction. Our findings suggest mixed outcomes, where many patients reported life-changing improvements but many also experienced prolonged pain and difficulty after surgery. Some patients reported increased difficulty or inability to return to their preoperative maximum level of participation, indicating that flatfoot reconstructions can lead to athletic limitations. CONCLUSION: Although flatfoot reconstruction can be a powerful tool to increase patients' capacity to engage in physical activity, in our cohort many patients had reduced physical activity outcomes. LEVEL OF EVIDENCE: Level IV, retrospective case series.

In-stent restenosis and stent compression following stenting for chronic iliofemoral venous obstruction.

OBJECTIVE: In-stent restenosis (ISR) and stent compression (SC) are problems encountered after stenting for chronic iliofemoral venous obstruction that are responsible for a majority of reinterventions. However, characteristics of ISR and SC, in addition to outcomes after reintervention, have not been explored in detail and represent the focus of this study. METHODS: A retrospective analysis of contemporaneously entered electronic medical record data on 578 limbs/patients with initial unilateral iliofemoral venous stents placed from 2014 to 2018 was performed. ISR was estimated from stent and flow channel diameters measured using duplex ultrasound. SC was estimated from rated stent diameter and actual stent diameter on duplex ultrasound. Characteristics evaluated included onset of ISR/SC after stent placement and progression over time. Analysis was performed to evaluate risk factors for the development of ISR and SC. Outcomes after reintervention for ISR/SC were also appraised. RESULTS: A total of 578 limbs underwent stenting for stenotic lesions (nonthrombotic iliac vein lesion/post-thrombotic syndrome). ISR was noted in 27% of limbs on post-intervention day 1. The prevalence of ISR increased to 74% by 3 months and stabilized thereafter. SC was noted in 80% of limbs on day 1 and plateaued. Of the variables evaluated as potential risk factors for ISR, intravascular ultrasound determined stent inflow luminal area and shear rate were found to be significant. For SC, asymmetric stent sizing was a significant risk factor. Over a median follow-up of 24 months, 95 of 578 (16.4%) limbs underwent reintervention for ISR, SC, or a combination. The median time to reintervention was 11 months. There was no statistically significant difference in the degree of ISR/SC among patients who underwent reintervention vs those who did not (P > .05). However, there was a statistically significant difference in the grade of swelling (P = .006) and visual analog scale pain scores (P < .0001) between those who underwent reintervention and those who did not. Primary, primary assisted, and secondary patencies at 60 months were 70%, 98%, and 84% after reintervention for ISR and 70%, 99%, and 84% for SC, respectively. CONCLUSIONS: Although ISR and SC are both common after stenting for chronic iliofemoral venous obstruction, neither are relentlessly progressive. Indication for reintervention must be a recurrence of symptoms with impairment of quality of life and not the percentage of ISR or degree of SC. After reintervention good outcomes can be expected both in terms of clinical improvement and stent patency. Further study of the impact of shear rate on stent flow is required to help reduce the incidence of ISR.

Role of laser ablation in recalcitrant instent restenosis post iliofemoral venous stenting.

Instent restenosis (ISR) represents the most common reason for recurrent symptoms requiring reintervention in patients who have undergone venous stenting for chronic iliofemoral venous obstruction. Treatment of ISR requires stent angioplasty typically using angioplasty balloons equal to or larger than the rated diameter of the stent. At times this does not yield the required result, and in these patients, utilization of a laser catheter supported by an angled sheath is helpful to ablate the ISR or make it more amenable to repeat balloon angioplasty. The authors report their experience with this technique for 18 patients with recurrent symptoms impacting quality of life as a result of recalcitrant ISR in this retrospective review of contemporaneously entered electronic medical record data. 12 (67%) limbs underwent laser ablation only, while 6 (33%) limbs underwent additional angioplasty post laser ablation. Post intervention for ISR, at 12 months, the venous clinical severity score improved from 5 to 3.5 (P = .0005) and the VAS pain score went from 7 to 5 (P = .0005). At 10 months, primary patency was 87% and primary assisted patency was 100%. There were no stent occlusions. Laser ablation of recalcitrant instent restenosis in patients presenting with recurrent chronic iliac venous obstruction post iliofemoral venous stenting is a safe and effective option. Corroboration from larger studies is warranted.

Elevated plasma factor VIII levels in a mixed patient population on anticoagulation and past venous thrombosis.

BACKGROUND: Thrombophilia conditions are associated with an increased risk of venous thromboembolism. Elevated plasma levels of factor VIII (>150 IU/dL) increase the risk of venous thrombosis. The aim of this report is to analyze a subset of patients in whom plasma factor VIII levels were investigated as part of a thrombophilia panel at a specialty venous clinic at a tertiary care hospital. METHODS: From January 2019 to December 2019, records of all patients (n = 306) who had a plasma factor VIII level assay performed as part of a thrombophilia panel were retrospectively analyzed. Group 1 (n = 92) had normal factor VIII levels (≤150 IU/dL), whereas group 2 (n = 214) had elevated factor VIII levels (>150 IU/dL). Venous thromboembolic events were classified as provoked if there was an association with surgery, trauma, immobilization, orthopedic fracture, peripartum period, or use of hormones. If there was no associated factor identifiable in the patient's history, the event was considered unprovoked. RESULTS: The median age for patients in groups 1 and 2 was 55 and 65 years, respectively. Family history of deep venous thrombosis (DVT) was noted in 6 patients in group 1 (6.5%) vs 77 patients in group 2 (36%), P value: .0001. Unprovoked DVT was more commonly noted in group 2 patients (66%) compared with group 1 patients (5%), P value: .0001. In addition, venous ulceration was more commonly encountered in group 2 (23%) than group 1 (11%), P value: .008. Factor VIII level >150 IU/dL was a significant predictor of DVT occurrence itself (odds ratio: 3.3, P value <.005). Factor VIII level >200 IU/dL was a significant predictor of occurrence of two or more episodes of DVT (odds ratio: 12.3, P value < .005). CONCLUSIONS: Factor VIII levels were found to be elevated in a significant proportion of patients in whom thrombophilia testing was performed at a specialty venous clinic. This elevation was more common in patients with venous ulceration, a positive family history of DVT, and a personal history of an unprovoked DVT. Levels above 200 IU/dL were associated with DVT recurrence. This has important implications for secondary prophylactic strategies for DVT.

The Vps13p-Cdc31p complex is directly required for TGN late endosome transport and TGN homotypic fusion.

Yeast VPS13 is the founding member of a eukaryotic gene family of growing interest in cell biology and medicine. Mutations in three of four human VPS13 genes cause autosomal recessive neurodegenerative or neurodevelopmental disease, making yeast Vps13p an important structural and functional model. Using cell-free reconstitution with purified Vps13p, we show that Vps13p is directly required both for transport from the trans-Golgi network (TGN) to the late endosome/prevacuolar compartment (PVC) and for TGN homotypic fusion. Vps13p must be in complex with the small calcium-binding protein Cdc31p to be active. Single-particle electron microscopic analysis of negatively stained Vps13p indicates that this 358-kD protein is folded into a compact rod-shaped density (20 × 4 nm) with a loop structure at one end with a circular opening ∼6 nm in diameter. Vps13p exhibits ATP-stimulated binding to yeast membranes and specific interactions with phosphatidic acid and phosphorylated forms of phosphatidyl inositol at least in part through the binding affinities of conserved N- and C-terminal domains.

CD271 Expression on Patient Melanoma Cells Is Unstable and Unlinked to Tumorigenicity.

The stability of markers that identify cancer cells that propagate disease is important to the outcomes of targeted therapy strategies. In human melanoma, conflicting data exist as to whether hierarchical expression of CD271/p75/NGFR (nerve growth factor receptor) marks cells with enriched tumorigenicity, which would compel their specific targeting in therapy. To test whether these discrepancies relate to differences among groups in assay approaches, we undertook side-by-side testing of published methods of patient-derived melanoma xenografting (PDX), including comparisons of tissue digestion procedures or coinjected Matrigel formulations. We found that CD271(-) and CD271(+) melanoma cells from each of seven patients were similarly tumorigenic, regardless of assay variations. Surprisingly variable CD271 expression patterns were observed in the analyses of sibling PDX tumors (n = 68) grown in the same experiments from either CD271(-) or CD271(+) cells obtained from patients. This indicates unstable intratumoral lineage relationships between CD271(-) and CD271(+) melanoma cells that are inconsistent with classical, epigenetically based theories of disease progression, such as the cancer stem cell and plasticity models. SNP genotyping of pairs of sibling PDX tumors grown from phenotypically identical CD271(-) or CD271(+) cells showed large pairwise differences in copy number (28%-48%). Differences were also apparent in the copy number profiles of CD271(-) and CD271(+) cells purified directly from each of the four melanomas (1.4%-23%). Thus, CD271 expression in patient melanomas is unstable, not consistently linked to increased tumorigenicity and associated with genetic heterogeneity, undermining its use as a marker in clinical studies. Cancer Res; 76(13); 3965-77. ©2016 AACR.

A Classification of Healthcare Facilities: Toward the Development of Energy Performance Benchmarks for Day Surgery Centers in Australia.

OBJECTIVE: In the literature, there is no consistent classification of healthcare facilities. In order to benchmark, assess, and compare the environmental performance of these buildings, it is important to clearly identify the typology within the scope of a particular research. This article identifies the different typologies within the healthcare sector, particularly in Australia, with the aim of the development of energy performance benchmarks for day surgery/procedure centers. BACKGROUND: Healthcare buildings encompass a wide range of facilities. They all share the same purpose of healing and offering a health service for patients. However, they vary significantly in terms of patient type and service provided. These buildings consume a considerable amount of energy, and as a result of the different designs and sizes, their pattern of energy consumption varies. METHODS: The research used a systematic review of the literature to determine how the term "healthcare facility" has been employed in different contexts. In order to better understand the differences in healthcare facilities, definitions and the origin of hospitals and healthcare facilities are introduced and a framework for the classification of healthcare facilities and hospitals is proposed. RESULTS: Healthcare facilities are classified into the following six categories: patient type, care provided, management and ownership, level of care, facility size, and location. Based on these classifications, a categorization for the studies of energy performance in healthcare is introduced. CONCLUSIONS: This study provides a basis for assessment and comparison for a particular healthcare building typology that will assist researchers working in the field of design and energy assessment of healthcare facilities.

Post-appendectomy visits to the emergency department within the global period: a target for cost containment.

BACKGROUND: Postoperative visits to the emergency department (ED) instead of the surgeon's office consume enormous cost. HYPOTHESIS: Postoperative ED visits can be avoided. SETTING: Fully accredited, single-institution, 617-bed hospital affiliated with the University of Connecticut School of Medicine. PATIENTS: Retrospective analysis of 597 consecutive patients with appendectomies over a 4-year period. METHODS: Demographic and medical data, at initial presentation, surgery, and ED visit were recorded as categorical variables and statistically analyzed (Pearson chi(2) test, Fisher exact test, and linear-by-linear). Costs were calculated from the hospital's billing department. RESULTS: Forty-six patients returned to the ED within the global period with pain (n = 22, 48%), wound-related issues (n = 6, 13%), weakness (n = 4, 9%), fever (13%), and nausea and vomiting (n = 3, 6%). Thirteen patients (28%) required readmission. Predictive factors for ED visit postoperatively were perforated appendicitis (2-fold increase over uncomplicated appendicitis) and comorbidities (cardiovascular or diabetes). The cost of investigations during ED visits was $55,000 plus physician services. CONCLUSIONS: ED visits during the postoperative global period are avoidable by identifying patients who may need additional care; improving patient education, optimizing pain control, and improving patient office access.

Inhibition of furin/proprotein convertase-catalyzed surface and intracellular processing by small molecules.

Furin is a ubiquitously expressed proprotein convertase (PC) that plays a vital role in numerous disease processes including cancer metastasis, bacterial toxin activation (e.g. anthrax and Pseudomonas), and viral propagation (e.g. avian influenza and human immunodeficiency virus). To identify small molecule inhibitors of furin and related processing enzymes, we performed high-throughput screens of chemical diversity libraries utilizing both enzyme-based and cell-based assays. The screens identified partially overlapping sets of compounds that were further characterized for affinity, mechanism, and efficacy in additional cellular processing assays. Dicoumarols were identified as a class of compounds that inhibited furin non-competitively and reversibly with Ki values in the micromolar range. These compounds inhibited furin/furin-like activity both at the cell surface (protecting against anthrax toxin) and in the secretory pathway (blocking processing of the metastasis factor membrane-type 1 matrix metalloproteinase/MT1-MMP) at concentrations close to Ki values. Compounds tested exhibited distinct patterns of inhibition of other furin-family PCs (rat PACE4, human PC5/6 and human PC7), showing that dicoumarol derivatives might be developed as either generic or selective inhibitors of the PCs. The extensive clinical use, high bioavailability and relatively low toxicity of dicoumarols suggests that the dicoumarol structure will be a good starting point for development of drug-like inhibitors of furin and other PCs that can act both intracellularly and at the cell surface.