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There are several eponyms used in the assessment and management of calcaneus fractures. However, the origin of these eponyms is no longer widely known. Named for orthopaedic surgeons who made substantial contributions to the management of calcaneus fractures as well as the field of orthopaedic surgery, understanding the context of how these descriptors were derived helps give context to their use in the present day. The purpose of this review is to provide a historical perspective and comprehensive collection of the most common eponyms related to calcaneus fractures.

The aim of the study is to assess the security of information systems during an influence of advanced persistent threats. The article shows the need to build a threat model during an analyzing the security of information systems. Various approaches to modeling threats in information systems are considered, their advantages and disadvantages are noted, requirements for the developed methodology are formed. As a result of the study, a method for modeling computer attack scenarios and assessing the security of information systems under the influence of advanced persistent threats is formed, based on the use of risk matrix models. A method for determining categorical variables characterizing the probability and damage as a result of the implementation of information threats using clustering methods is also proposed. The example demonstrates the use of a graph of threat matrices for modeling scenarios of targeted computer attacks on information system assets. The scientific novelty of the work consists in the proposal of a method for analyzing the security of information systems, which takes into account the possibility of changing the probability of the implementation of information threats during the life cycle of an advanced persistent threat, the dependence of information threats and the value of information assets for the intruder and their owner, which makes it possible to predict various scenarios of computer attacks.

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Purpose: The purpose of this study was to investigate if early postoperative ambulation metrics affect hospital quality measures and 1-year outcomes in operative hip fracture patients.Methods: A consecutive series of hip fracture patients [OTA/AO 31A, 31B, 32A-C] who underwent operative treatment were reviewed for demographic and clinical data. Chart review was performed to determine participation with physical therapy [PT] and ambulation distance on postoperative day (POD) 1, 3, and 5. POD1 ambulators and non-ambulators were statistically compared. Outcome correlates of postoperative ambulation distance were investigated by univariate and multivariate linear and logistic regression.Results: 1044 patients were identified with 546 (52.3%) able to ambulate on POD1. Those able to ambulate on POD1 were significantly younger (78.4 ± 10.9 vs. 82.1 ± 10.4, p<0.001), had fewer co-morbidities (CCI 1.22 ± 1.60 vs. 1.73 ± 1.82, p<0.001), and were more likely to be preoperative community ambulators (82.2% vs. 68.3%, p<0.001). Patients unable to ambulate on POD1 had significantly higher rate of inpatient mortality (2.8% vs. 0.5%, p= 0.004), 1-year mortality (14.6% vs. 6.9%, p<0.001), and a longer length of stay (7.94 ± 4.73 vs. 6.43 ± 4.02 days, p<0.001). Non-ambulators more often required the intensive care unit postoperatively (18.7% vs. 7.1%, p<0.001), and had increased rates of major complications (15.5% vs. 5.7%, p<0.001). Patients with OTA 31B or 32A fractures were 1.63 times more likely to ambulate on POD1 while patients with an assistive device at baseline were 0.51 times less likely to ambulate on POD1. Increasing postoperative ambulation distance correlated with shorter length of stay (p<0.001 for POD1, 3, and 5) and every foot walked was associated with 0.57% decreased odds of a hospital complication (p= 0.0353).Conclusions: Failure to ambulate on POD1 following hip fracture surgery in >55 years is associated with an increased risk of in-hospital complications and mortality. Every effort should be made address this modifiable risk factor and mobilise patients on POD1 to improve patient outcomes.

Survey results on employee perceptions of distributive and procedural justice, underlying principles of equality, equity, and need are examined. Findings demonstrate that need and self interest bias are important factors influencing perceptions. Recommendations for designing benefit plans that increase justice perceptions are provided.

THE HEALTH CARE INDUSTRY HAS undergone several changes over the past several years that have created many challenges for hospital board members, administrators, and staff. These events are reducing profit [...]

New therapies are needed for patients with relapsed/refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) who do not benefit from or are ineligible for stem cell transplant and chimeric antigen receptor therapy. The CD30-targeted, antibody-drug conjugate brentuximab vedotin (BV) and the immunomodulator lenalidomide (Len) have demonstrated promising activity as single agents in this population. We report the results of a phase 1/dose expansion trial evaluating the combination of BV/Len in rel/ref DLBCL. Thirty-seven patients received BV every 21 days, with Len administered continuously for a maximum of 16 cycles. The maximum tolerated dose of the combination was 1.2 mg/kg BV with 20 mg/d Len. BV/Len was well tolerated with a toxicity profile consistent with their use as single agents. Most patients required granulocyte colony-stimulating factor support because of neutropenia. The overall response rate was 57% (95% CI, 39.6-72.5), complete response rate, 35% (95% CI, 20.7-52.6); median duration of response, 13.1 months; median progression-free survival, 10.2 months (95% CI, 5.5-13.7); and median overall survival, 14.3 months (95% CI, 10.2-35.6). Response rates were highest in patients with CD30+ DLBCL (73%), but they did not differ according to cell of origin (P = .96). NK cell expansion and phenotypic changes in CD8+ T-cell subsets in nonresponders were identified by mass cytometry. BV/Len represents a potential treatment option for patients with rel/ref DLBCL. This combination is being further explored in a phase 3 study (registered on https://clinicaltrials.org as NCT04404283). This trial was registered on https://clinicaltrials.gov as NCT02086604.

Introduction: The purpose is to investigate the incidence of wound complications for total knee arthroplasty (TKA) following tibial plateau open reduction and internal fixation (ORIF). Materials and Methods: A prospective arthroplasty registry was queried for patients with CPT codes for primary TKA, tibial plateau ORIF, removal of hardware (ROH), and diagnosis of post-traumatic arthritis. Patients were included if they had undergone tibial plateau ORIF and subsequent TKA. Chart review was performed to obtain demographic, clinical and post-operative information. Results: Twenty-one patients were identified, with average age of 56.23 ± 13.2 years at time of tibial plateau ORIF and 62.91 ± 10.8 years at time of TKA. Seven (33.3%) patients had a tibial plateau fracture-related infection (FRI). Eight (38.1%) patients underwent ROH prior to TKA. Seven (33.3%) patients’ TKA incision incorporated the prior plateau incisions. Eight (36.4%) patients developed wound complications following TKA and 5 (23.8%) developed an acute periprosthetic joint infection (PJI) following TKA and had the plateau incision incorporated into the TKA incision. FRI history did not increase the rate of wound complications but did increase the rate of ROH prior to TKA. Conclusions: Previous FRI involving tibial plateau repair surgery doesn’t correlate with PJI after conversion TKA for post traumatic OA. Surgeon-controlled factors such as staged ROH and incision placement can help reduce the rate of wound complications following TKA performed after tibial plateau ORIF. Level of Evidence: Prognostic Level IV.

Introduction: The purpose of this study was to investigate the effect of delayed closures, whether delayed primary closure (DPC) or split-thickness skin grafting (STSG), of operatively treated forearm fractures on short-term soft tissue outcomes. Methods: In this retrospective cohort comparative study of two academic-level one trauma centers from 2010 to 2020, adult patients with diaphyseal forearm fractures who underwent open reduction and internal fixation (ORIF) were either closed primarily at index surgery, or underwent delayed closure, either with DPC or with a STSG. Primary outcome measures were soft-tissue outcomes as measured by wound healing (delayed healing, dehiscence, or skin breakdown) and fracture-related infection (FRI) at time of final follow-up. Results: Eighty-one patients with 81 diaphyseal forearm fractures underwent ORIF with a mean follow-up of 14.3 months. Forty-one fractures (50.6%) were open injuries. Thirteen patients (16.0%) were unable to be closed primarily and underwent an average of 2.46 ± 0.7 surgeries including final coverage, with an average of 4.31 ± 2.8 days to final coverage. Four patients (30.8%) underwent DPC and 9 (69.2%) underwent STSG. Five (6.6%) patients in the delayed closure group had pre-operative compartment syndrome and underwent formal two-incision fasciotomies. There were no significant differences between delayed versus primary closure in wound healing complication rates, FRI, or radiographic union. Conclusions: Diaphyseal forearm fractures that undergo ORIF have equivalent short-term soft tissue outcomes when closed primarily at index surgery or when closed in a delayed fashion.

ABSTRACTIntroduction: The use of potentially inappropriate medications (PIM) is an alarming social risk factor in cardiovascular patients. PIM administration may result in iatrogenic disorders and adverse consequences may be attenuated by limiting PIM intake.Areas covered: The goal of this review article is to discuss the trends, risks, and concerns regarding PIM administration with focus on cardiovascular patients. To find data, we searched literature using electronic databases (Pubmed/Medline 1966–2021 and Web of Science 1975–2021). The data search terms were cardiovascular diseases, potentially inappropriate medication, potentially harmful drug–drug combination, potentially harmful drug–disease combination, drug interaction, deprescribing, and electronic health record.Expert opinion: Drugs for heart diseases are the most commonly prescribed medications in older individuals. Despite the availability of explicit and implicit PIM criteria, the incidence of PIM use in cardiovascular patients remains high ranging from 7 to 85% in different patient categories. Physician-induced disorders often occur when PIM is administered and adverse effects may be reduced by limiting PIM intake. Main strategies promising for addressing PIM use include deprescribing, implementation of systematic electronic records, pharmacist medication review, and collaboration among cardiologists, internists, geriatricians, clinical pharmacologists, pharmacists, and other healthcare professionals as basis of multidisciplinary assessment teams.

Based on a theoretical analysis, the most urgent problems of labor migration as a legal phenomenon that is global in nature and carries both positive and negative features that depend on the subjective and objective factors of the region of each country are characterized. The relationship of labor migration to the potential for economic development of the country is shown. The focus is on the need for the legislative attention of the national legislator to the mechanisms of legal protection of labor rights of migrants.

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The anti-CD19 chimeric antigen receptor (CAR)–T cell therapy tisagenlecleucel was evaluated in the global, phase 2 JULIET study in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We correlated tisagenlecleucel cellular kinetics with clinical/product parameters in 111 patients treated in JULIET. Tisagenlecleucel persistence in responders and nonresponders, respectively, was demonstrated for 554 and 400 days maximum by flow cytometry and for 693 and 374 days maximum by quantitative polymerase chain reaction (qPCR). No relationships were identified between cellular kinetics (qPCR) and product characteristics, intrinsic/extrinsic factors, dose, or immunogenicity. Most patients with 3-month response had detectable transgene at time of response and continued persistence for ≥6 months. Expansion (maximal expansion of transgene/CAR-positive T-cell levels in vivo postinfusion [Cmax]) was potentially associated with response duration but this did not reach statistical significance (hazard ratio for a twofold increase in Cmax, 0.79; 95% confidence interval, 0.61-1.01). Tisagenlecleucel expansion was associated with cytokine-release syndrome (CRS) severity and tocilizumab use; no relationships were observed with neurologic events. Transgene levels were associated with B-cell levels. Dose was associated with CRS severity, but this was not statistically significant after adjusting for baseline tumor burden. In contrast to the results from B-cell precursor acute lymphoblastic leukemia (B-ALL) and chronic lymphocytic leukemia, similar exposure was observed in DLBCL in this study regardless of response and expansion was lower in DLBCL than B-ALL, likely from differences in cancer location and/or T-cell intrinsic factors. Relationships between expansion and CRS severity, and lack of relationships between dose and exposure, were similar between DLBCL and B-ALL. Tisagenlecleucel cellular kinetics in adult relapsed/refractory DLBCL improve current understanding of in vivo expansion and its relationships with safety/efficacy endpoints. This trial was registered at www.clinicaltrials.gov as #NCT02445248.

ABSTRACTOne possible predictor of treatment outcome in cognitive-behavioral therapy (CBT) is executive functioning (EF; i.e., planning, initiating, and maintaining goal-directed behavior), but the role of EF in treatment outcome has not been studied in pediatric anxiety disorders. The current study examines the predictive role of pre-treatment EF and change in EF over treatment (EF change) in the Resilience Builder Program® (RBP), a manualized, 12-week CBT group intervention implemented in a private practice. The RBP targets social competence and resilience skills.The current study examines 73 children ages 7–13 years (mean age = 9.95 ± 1.53 years, 69.86% male, 79.45% White) diagnosed with an anxiety disorder who completed the RBP. The studied outcome variables included anxiety symptomatology, social competence, and resilience. Hierarchical linear modeling and hierarchical linear regressions were used to examine if pre-treatment EF and EF change predicted post-treatment symptomatology, controlling for pre-treatment functioning and ADHD diagnosis. Pre-treatment EF was not significantly related to any of the outcome variables. EF change was significantly related to improved anxiety and resilience, but not social competence. Adding EF change to the model significantly improved model fit when predicting resilience. Change in EF predicted parent-reported reductions in anxiety symptomatology and increases in resilience over and above pre-treatment EF levels. EF change was particularly important for predicting resilience outcomes. Results indicate that, for children with anxiety, pre-treatment EF is not an important predictor of outcome, but improvement in EF during treatment may improve treatment response as measured by anxiety symptomatology and resilience.

Dr. Ruan and colleagues provide an excellent summary of available treatment options, as well as new drugs on the horizon, for the management of relapsed mantle cell lymphoma (MCL). As [...]

Therapeutic gene delivery to hematopoietic stem cells (HSCs) holds great potential as a life-saving treatment of monogenic, oncologic, and infectious diseases. However, clinical gene therapy is severely limited by intrinsic HSC resistance to modification with lentiviral vectors (LVs), thus requiring high doses or repeat LV administration to achieve therapeutic gene correction. Here we show that temporary coapplication of the cyclic resveratrol trimer caraphenol A enhances LV gene delivery efficiency to human and nonhuman primate hematopoietic stem and progenitor cells with integrating and nonintegrating LVs. Although significant ex vivo, this effect was most dramatically observed in human lineages derived from HSCs transplanted into immunodeficient mice. We further show that caraphenol A relieves restriction of LV transduction by altering the levels of interferon-induced transmembrane (IFITM) proteins IFITM2 and IFITM3 and their association with late endosomes, thus augmenting LV core endosomal escape. Caraphenol A-mediated IFITM downregulation did not alter the LV integration pattern or bias lineage differentiation. Taken together, these findings compellingly demonstrate that the pharmacologic modification of intrinsic immune restriction factors is a promising and nontoxic approach for improving LV-mediated gene therapy.

ABSTRACTObjectiveThe study’s purpose was to investigate readiness for an increase in the congenital Zika infection (CZI) by describing the distribution of pediatric subspecialists needed for the care of children with CZI.MethodsWe applied county-level subspecialist counts to US maps, overlaying the geocoded locations of children’s hospitals to assess the correlation of hospital and subspecialist locations. We calculated travel distance from census tract centroids to the nearest in-state children’s hospital by state (with/without > 100 reported adult Zika virus cases) and by regions corresponding to the likely local Zika virus transmission area and to the full range of the mosquito vector. Travel distance percentiles reflect the population of children < 5 years old.ResultsOverall, 95% of pediatric subspecialists across the United States are located in the same county or neighboring county as a children’s hospital. In the states where Zika virus transmission is likely, 25% of children must travel more than 50 miles for subspecialty care; in one state, 50% of children must travel > 100 miles.ConclusionThe travel distance to pediatric subspecialty care varies widely by state and is likely to be an access barrier in some areas, particularly states bordering the Gulf of Mexico, which may have increasing numbers of CZI cases. (Disaster Med Public Health Preparedness. 2019;13:476-486)

Background:Reduced-intensity induction (RII) with imatinib yields comparable outcomes to HyperCVAD with imatinib with fewer induction deaths and an improved CR rate in Ph+ ALL (Chalandon. Blood. 2015). Dasatinib with steroids also produces excellent responses with little toxicity (Foa. Blood. 2011). Allogeneic bone marrow transplant (AlloBMT) remains the goal of therapy in Ph+ ALL based on contemporary trials with TKIs demonstrating improved survival in patients transplanted in CR1, and we have shown that transplant following induction with dasatinib yields better outcomes than with imatinib. Thus we implemented RII with dasatinib for the treatment of Ph+ ALL and compared to patients who received HyperCVAD with a 2nd generation TKI.

Published reports suggest that immune checkpoint inhibitors (ICIs) before allogeneic blood or marrow transplantation (alloBMT) may increase the incidence of graft-versus-host disease (GvHD), immune-related adverse events, and nonrelapse mortality (NRM); this led to the US Food and Drug Administration issuing a “Warning and Precaution” regarding the potential for life-threatening immune-mediated complications associated with alloBMT after nivolumab and pembrolizumab. We retrospectively reviewed the outcomes of 14 consecutive patients who received ICIs as their final salvage therapy before T-cell–replete alloBMT using reduced-intensity conditioning. All patients received posttransplant cyclophosphamide (PTCy), which significantly limits severe GvHD, even in the mismatched-donor setting. There was no grade 3-4 acute GvHD (aGvHD), and all 6 cases of grade 2 aGvHD readily resolved with immunosuppression. No patient experienced veno-occlusive disease of the liver, other immune-related adverse events, chronic GvHD, or NRM. There have been 2 relapses (15-month median follow-up), with 12 of 14 patients remaining alive, well, and progression-free. The only death was a result of disease relapse. Although more experience is needed, our data suggest that concerns over immunologic complications associated with ICIs should not preclude allogeneic bone marrow transplantation with PTCy as GvHD prophylaxis.

Registry-based studies report an increased risk for end-stage kidney disease after hypertensive disorders of pregnancy (HDPs). It is unclear whether HDPs lead to an increased incidence of chronic kidney disease (CKD) and/or progression of kidney function decline.

Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice. Biodistribution analysis with radiolabeled hHSCs showed that after intrasplenic injection, the majority of transplanted cells rapidly translocated to the liver. GFP-immunohistochemistry demonstrated that transplanted hHSCs engrafted alongside hepatic sinusoids. Prior permeabilization of the sinusoidal endothelial layer with monocrotaline enhanced engraftment of hHSCs. Transplanted hHSCs remained engrafted without relevant proliferation in the healthy liver. However, after CCl4or bile duct ligation-induced liver damage, transplanted hHSCs expanded and contributed to extracellular matrix production, formation of bridging cell-septae and cirrhosis-like hepatic pseudolobules. CCl4-induced injury recruited hHSCs mainly to zone 3, whereas after bile duct ligation, hHSCs were mainly in zone 1 of the liver lobule. Transplanted hHSCs neither transdifferentiated into other cell types nor formed tumors in these settings. In conclusion, a humanized mouse model was generated by transplanting hHSCs, which proliferated during hepatic injury and inflammation, and contributed to liver fibrosis. The ability to repopulate the liver with transplanted hHSCs will be particularly significant for mechanistic studies of cell-cell interactions and fibrogenesis within the liver.

During antifungal drug treatment and hypoxia, genetic and epigenetic changes occur to maintain sterol homeostasis and cellular function. In this study, we show that SET domain-containing epigenetic factors govern drug efficacy to the medically relevant azole class of antifungal drugs. Upon this discovery, we determined that Set4is induced when Saccharomyces cerevisiaeare treated with azole drugs or grown under hypoxic conditions; two conditions that deplete cellular ergosterol and increase sterol precursors. Interestingly, Set4induction is controlled by the sterol-sensing transcription factors, Upc2and Ecm22. To determine the role of Set4on gene expression under hypoxic conditions, we performed RNA-sequencing analysis and showed that Set4is required for global changes in gene expression. Specifically, loss of Set4led to an upregulation of nearly all ergosterol genes, including ERG11and ERG3, suggesting that Set4functions in gene repression. Furthermore, mass spectrometry analysis revealed that Set4interacts with the hypoxic-specific transcriptional repressor, Hap1, where this interaction is necessary for Set4recruitment to ergosterol gene promoters under hypoxia. Finally, an erg3Δ strain, which produces precursor sterols but lacks ergosterol, expresses Set4under untreated aerobic conditions. Together, our data suggest that sterol precursors are needed for Set4induction through an Upc2-mediated mechanism. Overall, this new sterol-signaling pathway governs azole antifungal drug resistance and mediates repression of sterol genes under hypoxic conditions.

Background: This phase III, controlled, patient-blinded, multicentre study in two parallel, equal-sized treatment groups compared the efficacy and safety of TISSEEL Lyo, fibrin sealant versus Manual Compression (MC) with surgical gauze pads for use as a haemostatic agent in patients who underwent vascular surgery in Russia.Methods: Adult patients, both genders, who received peripheral vascular expanded polytetrafluoroethylene conduits and had suture line bleeding after surgical haemostasis were enrolled. Patients were randomized to be treated with TISSEEL Lyo or MC. The bleeding needed additional treatment and had to be assessed as grade 1 or 2 bleeding according to the Validated Intraoperative Bleeding scale. The primary efficacy endpoint was the proportion of patients achieving haemostasis at 4 min after treatment application (T4) at the study suture line, which was maintained until the closure of the surgical wound. The secondary efficacy endpoints included the proportion of patients achieving haemostasis at 6 min (T6) and 10 min (T10) after treatment application at the study suture line, which was maintained until closure of the surgical wound, as well as the proportion of patients with intraoperative and postoperative rebleeding. Safety outcomes included incidence of adverse events (AEs), surgical site infections and graft occlusions.Results: A total of 110 patients were screened; 104 patients were randomized: (TISSEEL Lyo: 51 [49%] patients; MC: 53 [51%] patients). T4haemostasis was achieved in 43 (84.3%) patients in the TISSEEL Lyo group and in 11 (20.8%) patients in the MC group (p< 0.001). Significantly more patients in TISSEEL Lyo group achieved the haemostasis at T6(relative risk (RR) of achieving haemostasis 1.74 [95% confidence interval (CI) 1.37; 2.35]) and T10(RR 1.18 [95% CI 1.05; 1.38]) versus MC. No one had intraoperative rebleeding. Postoperative rebleeding was reported only in one patient in the MC group. No treatment-emergent serious AEs (TESAEs) related to TISSEEL Lyo/MC, TESAEs leading to withdrawal and TESAEs leading to death were reported in patients during the study.Conclusions: Data demonstrated TISSEEL Lyo had clinically and statistically significant superiority to MC as a haemostatic agent in vascular surgery at all measured time points including 4, 6 and 10 min and had proven to be safe.

PURPOSE: To characterize patients who received chemotherapy during their intensive care unit (ICU) admission in a cancer hospital over a 5-year period. METHODS: All ICU admissions between October 1998 and [...]

This study was conducted to determine whether proximal humerus fracture patterns as defined by the Orthopaedic Trauma Association (AO/OTA) classification and the Neer 4-part system predicted functional outcomes for patients treated with open reduction and internal fixation with locked plates and, if so, which system correlated better with outcomes. During a 12-year period, 213 patients with a displaced proximal humerus fracture who underwent surgical treatment with a locking plate at 1 academic institution were prospectively followed. All patients were treated in a similar way and were followed by the operating surgeon at routine intervals. Functional outcomes were measured with the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Of these patients, 164 were available for analysis. Functional outcomes based on DASH scores did not differ significantly by Neer system, AO/OTA classification, or varus/valgus humeral head alignment at more than 12 months postoperatively. However, patients with Neer 4-part fracture and AO/OTA type 11-C fracture had worse shoulder range of motion in terms of forward elevation and external rotation. Time to healing and complication rates also were not significantly different based on either classification system. Fracture classification can predict shoulder range of motion 12 months after surgical fixation, but its use is limited in predicting functional outcome scores, time to healing, and complication rates. Patients who undergo surgical repair of a proximal humerus fracture can expect good functional results independent of the initial injury pattern, but more severe fracture patterns may lead to decreased shoulder range of motion. [This study was conducted to determine whether proximal humerus fracture patterns as defined by the Orthopaedic Trauma Association (AO/OTA) classification and the Neer 4-part system predicted functional outcomes for patients treated with open reduction and internal fixation with locked plates and, if so, which system correlated better with outcomes. During a 12-year period, 213 patients with a displaced proximal humerus fracture who underwent surgical treatment with a locking plate at 1 academic institution were prospectively followed. All patients were treated in a similar way and were followed by the operating surgeon at routine intervals. Functional outcomes were measured with the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Of these patients, 164 were available for analysis. Functional outcomes based on DASH scores did not differ significantly by Neer system, AO/OTA classification, or varus/valgus humeral head alignment at more than 12 months postoperatively. However, patients with Neer 4-part fracture and AO/OTA type 11-C fracture had worse shoulder range of motion in terms of forward elevation and external rotation. Time to healing and complication rates also were not significantly different based on either classification system. Fracture classification can predict shoulder range of motion 12 months after surgical fixation, but its use is limited in predicting functional outcome scores, time to healing, and complication rates. Patients who undergo surgical repair of a proximal humerus fracture can expect good functional results independent of the initial injury pattern, but more severe fracture patterns may lead to decreased shoulder range of motion. [Orthopedics.2017; 40(6):368–374.]

Idelalisib, a first-in-class oral inhibitor of phosphatidylinositol-3-kinase δ, has shown considerable antitumor activity as a monotherapy in recurrent indolent non-Hodgkin lymphoma (iNHL). To evaluate the safety and activity of idelalisib in combination with immunotherapy, chemotherapy, or both, 79 patients with relapsed/refractory iNHL were enrolled based on investigator preference in 3 treatment groups. Patients received continuous idelalisib in combination with (1) rituximab (IR; 375 mg/m2weekly × 8 doses), (2) bendamustine (IB; 90 mg/m2per day × 2, for 6 cycles), or (3) both bendamustine and rituximab at aforementioned doses (IBR; monthly × 6 cycles). Patients had a median age of 61 years, a median of 3 prior therapies, and 46% had refractory disease. The overall response rate was 75% (22% complete response) for IR, 88% (36%) for IB, and 79% (43%) for IBR. The median progression-free survival was 37.1 months overall: 29.7 months for IR, 32.8 for IB, and 37.1 months for IBR. The median duration of response was 28.6 months in the IR group and has not been reached in the IB and IBR groups. The most common grade ≥3 adverse events and laboratory abnormalities were neutropenia (41%), pneumonia (19%), transaminase elevations (16%), diarrhea/colitis (15%), and rash (9%). The safety and efficacy reflected in these early data, however, stand in contrast with later observations of significant toxicity in subsequent phase 3 trials in frontline chronic lymphocytic leukemia and less heavily pretreated iNHL patients. Our findings highlight the limitations of phase 1 trial data in the assessment of new regimens. This trial was registered at www.clinicaltrials.govas #NCT01088048 (an extension study was registered at www.clinicaltrials.govas #NCT01090414).

•HLA-haploidentical BMT with PTCy as upfront therapy in patients with SAA results in survival >90% and low morbidity/mortality.•More than 35% of patients were from underrepresented race/ethnic backgrounds, demonstrating accessibility to those lacking matched donors.

Background: Patient-reported allergies (PRAs) are often stigmatized as a potential nonmodifiable risk factor for increased pain and worse functional outcomes following surgery. However, there is a dearth of literature directly assessing the impact of PRAs on outcomes in sport surgeries such as medial patellofemoral ligament reconstruction (MPFLR). The purpose of our study was to determine whether PRAs were associated with worse outcomes following MPFLR. Methods: We conducted a retrospective review of patients who underwent MPFLR at our institution from 2011 to 2019. Patients were included if they had at least 12 months of follow-up. PRAs were obtained from preoperative medical assessments and categorized by drug class. Demographic and perioperative data were obtained from electronic medical records. Postoperative outcomes were measured using a telephone survey and included recurrent instability, Visual analog scale (VAS) for pain, VAS for sports, Kujala score, MPFL-Return to Sport after Injury (MPFL-RSI) score, and overall satisfaction score. Multiple linear regression was used to determine association between PRAs and outcome measures, and p-values less than 0.05 were considered significant. Results: The cohort included 141 MPFLR. Most patients were female (98, 70%) with an average age of 25 years (range 12–56 years). Average follow-up time was 47 months. Forty-seven patients (33%) reported at least one PRA. There were no significant differences in postoperative pain, functional outcomes, satisfaction, or return to sport between patients with or without PRAs (all p> 0.05). Absence of antibiotic PRAs was predictive of higher VAS (p&lt; 0.007), but there were no other differences. There were no significant differences in outcomes between patients without PRAs, PRAs without a concomitant psychiatric disorder, or PRAs with a concomitant psychiatric disorder (all p> 0.05). Conclusions: In conclusion, PRAs with or without concomitant psychiatric diagnoses are not associated with worse postoperative pain, functional outcomes, or satisfaction following MPFLR with allograft, dispelling common misconceptions that increased number of allergies or psychiatric diagnoses lead to inferior surgical outcomes. Presence of antibiotic allergies was associated with lower VAS postoperative pain score. Future research should investigate the relationship between PRAs and other surgeries in the field of sports medicine.

The article describes the role of the U.S. Department of Energy's Los Alamos National Laboratory in the implementation of the International Atomic Energy Agency's safeguards mission. It offers information on the influence of physicist G. Robert Keepin in promoting nuclear measurement techniques harnessed by the agency. Also cited are various technologies developed at the lab including the high resolution x-ray assay and laser-induced breakdown spectroscopy.

ABSTRACTChange detection studies using remote sensing and plot-based sampling show that Arctic vegetation is changing. Most studies have focused on the proliferation of tall shrubs, but increased productivity in areas where shrub cover is low suggests that other functional groups may also be changing. To investigate vegetation change across the Tuktoyaktuk Coastlands we analyzed high-resolution repeat air photos from 1980 and 2013. Thirty-eight image pairs were used to estimate changes in the cover of six functional groups (tall shrub, dwarf shrub, non-tussock-forming sedge, tussock-forming sedge, moss, and lichen). The spatial extent of our airphotos allowed us to investigate changes across four terrain types (high-center polygonal terrain, low-center polygonal terrain, shrub tundra, and tussock tundra). Our analysis shows that all four terrain types experienced absolute increases in shrub cover (+7.71% to 11.98%), with the expansion of dwarf shrubs playing an especially important role in regional change. Significant declines in lichen cover were also observed. While the consistency of shrub encroachment across terrain types suggests that changes were facilitated by shifts in broad-scale processes like temperature or precipitation, our data also indicate that differences in the magnitude of change were mediated by community structure and the availability of suitable microsites.

We assessed the incidence, prognostic features, and outcomes associated with transformation of follicular lymphoma (FL) among 2652 evaluable patients prospectively enrolled in the National LymphoCare Study. At a median follow-up of 6.8 years, 379/2652 (14.3%) patients transformed following the initial FL diagnosis, including 147 pathologically confirmed and 232 clinically suspected cases. Eastern Cancer Oncology Group performance status >1, extranodal sites >1, elevated lactate dehydrogenase, and B symptoms at diagnosis were associated with transformation risk. Relative to observation, patients initiating treatment at diagnosis had a reduced risk of transformation (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.46-0.75). The risk of transformation was similar in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone compared with rituximab, cyclophosphamide, vincristine, and prednisone (adjusted HR, 0.94; 95% CI, 0.62-1.42). Maintenance rituximab was associated with reduced transformation risk (HR, 0.67; 95% CI, 0.46-0.97). Five-year survival from diagnosis was significantly worse for patients with vs without transformation (75%, 95% CI, 70-79 vs 85%, 95% CI, 83-86). The median overall survival posttransformation was 5 years. Forty-seven patients with evidence of transformation at the time of diagnosis shared similar prognostic factors and survival rates to those without transformation. Improved outcomes for transformation in the modern era are suggested by this observational study. This trial is registered at www.clinicaltrials.govas #NCT00097565.

Cardiomyocytes (CMs) are terminally differentiated cells in the adult heart, and ischemia and cardiotoxic compounds can lead to cell death and irreversible decline of cardiac function. As testing platforms, isolated organs and primary cells from rodents have been the standard in research and toxicology, but there is a need for better models that more faithfully recapitulate native human biology. Hence, a new in vitromodel comprising the advantages of 3D cell culture and the availability of induced pluripotent stem cells (iPSCs) of human origin was developed and characterized. Human CMs derived from iPSCs were studied in standard 2D culture and as cardiac microtissues (MTs) formed in hanging drops. Two-dimensional cultures were examined using immunofluorescence microscopy and western blotting, while the cardiac MTs were subjected to immunofluorescence, contractility, and pharmacological investigations. iPSC-derived CMs in 2D culture showed well-formed myofibrils, cell–cell contacts positive for connexin-43, and other typical cardiac proteins. The cells reacted to prohypertrophic growth factors with a substantial increase in myofibrils and sarcomeric proteins. In hanging drop cultures, iPSC-derived CMs formed spheroidal MTs within 4 days, showing a homogeneous tissue structure with well-developed myofibrils extending throughout the whole spheroid without a necrotic core. MTs showed spontaneous contractions for more than 4 weeks that were recorded by optical motion tracking, sensitive to temperature and responsive to electrical pacing. Contractile pharmacology was tested with several agents known to modulate cardiac rate and viability. Calcium transients underlay the contractile activity and were also responsive to electrical stimulation, caffeine-induced Ca2+release, and extracellular calcium levels. A three-dimensional culture using iPSC-derived human CMs provides an organoid human-based cellular platform that is free of necrosis and recapitulates vital cardiac functionality, thereby providing a new and promising relevant model for the evaluation and development of new therapies and detection of cardiotoxicity.

One novel treatment strategy for the diseased heart focuses on the use of pluripotent stem cell‐derived cardiomyocytes (SC‐CMs) to overcome the heart's innate deficiency for self‐repair. However, targeted application of SC‐CMs requires in‐depth characterization of their true cardiogenic potential in terms of excitability and intercellular coupling at cellular level and in multicellular preparations. In this study, we elucidated the electrical characteristics of single SC‐CMs and intercellular coupling quality of cell pairs, and concomitantly compared them with well‐characterized murine native neonatal and immortalized HL‐1 cardiomyocytes. Firstly, we investigated the electrical properties and Ca2+signaling mechanisms specific to cardiac contraction in single SC‐CMs. Despite heterogeneity of the new cardiac cell population, their electrophysiological activity and Ca2+handling were similar to native cells. Secondly, we investigated the capability of paired SC‐CMs to form an adequate subunit of a functional syncytium and analyzed gap junctions and signal transmission by dye transfer in cell pairs. We discovered significantly diminished coupling in SC‐CMs compared with native cells, which could not be enhanced by a coculture approach combining SC‐CMs and primary CMs. Moreover, quantitative and structural analysis of gap junctions presented significantly reduced connexin expression levels compared with native CMs. Strong dependence of intercellular coupling on gap junction density was further confirmed by computational simulations. These novel findings demonstrate that despite the cardiogenic electrophysiological profile, SC‐CMs present significant limitations in intercellular communication. Inadequate coupling may severely impair functional integration and signal transmission, which needs to be carefully considered for the prospective use of SC‐CMs in cardiac repair. StemCells2015;33:2208–2218

Now the most pressing and to end unresolved question is the determination of the design parameters for the base in the conditions of formation of karst deformations. Foundation calculations made on the basis of forecasting karst manifestations sizes and the likelihood of their formation at the base of the designed construction. In paper presented the grillage calculation scheme. We calculated the grillage with four bays for four cases: excluding karst collapse, taking into account the collapse of a single support, taking into account the collapse under two not adjacent supports and taking into account the collapse at two adjacent supports. In paper presents the diagrams of bending moments and shear forces.

We consider the propagation of two photonic qubits, initially maximally entangled in their orbital angular momenta (OAM), across a weakly turbulent atmosphere. By introducing the phase correlation length of an OAM beam, we show that the photonic entanglement exhibits a universal exponential decay. [ABSTRACT FROM AUTHOR]

ABSTRACTFinding an effective human immunodeficiency virus type 1 (HIV-1) vaccine remains a major global health priority. In a phase I/II, placebo-controlled trial, healthy, HIV-1-negative adults were randomized to receive one of 5 vaccine regimens: LIPO-5 (combination of 5 lipopeptides) alone (250 µg), ALVAC-HIV (vCP1452) alone, or 3 groups of ALVAC-HIV (vCP1452) followed by ALVAC-HIV (vCP1452) plus LIPO-5 (250, 750, and 2,500 µg). Only 73/174 participants (42%) received all four vaccinations due to a study halt related to myelitis. There were no significant differences in systemic reactions between groups or in local reactogenicity between groups receiving ALVAC-HIV (vCP1452). Significant differences in local reactogenicity occurred between groups receiving LIPO-5 (P= 0.05). Gag and Env antibodies were undetectable by ELISA 2 weeks after the fourth vaccination for all but one recipient. Antibodies to Gag and Env were present in 32% and 24% of recipients of ALVAC-HIV (vCP1452) alone and in 47% and 35% of ALVAC-HIV (vCP1452)+LIPO recipients, respectively. Coadministration of LIPO-5 did not significantly increase the response rate compared to ALVAC-HIV (vCP1452) alone, nor was there a significant relationship between dose and antibody responses among ALVAC-HIV (vCP1452)+LIPO groups. Over 90% of study participants had no positive gamma interferon (IFN-?) enzyme-linked immunosorbent spot assay (ELISpot) responses to any peptide pool at any time point. The study was halted due to a case of myelitis possibly related to the LIPO-5 vaccine; this case of myelitis remains an isolated event. In general, there was no appreciable cell-mediated immunity detected in response to the vaccines used in this study, and antibody responses were limited. The clinical trial is registered on ClinicalTrials.govwith registry number NCT00076063.

Idelalisib (GS-1101, CAL-101), an oral inhibitor of phosphatidylinositol 3-kinase-δ, was evaluated in a phase I study in 64 patients with relapsed indolent non-Hodgkin lymphoma (iNHL). Patients had a median (range) age of 64 (32-91) years, 34 (53%) had bulky disease (≥1 lymph nodes ≥5 cm), and 37 (58%) had refractory disease. Patients had received a median (range) of 4 (1-10) prior therapies. Eight dose regimens of idelalisib were evaluated; idelalisib was taken once or twice daily continuously at doses ranging from 50 to 350 mg. After 48 weeks, patients still benefitting (n = 19; 30%) enrolled into an extension study. Adverse events (AEs) occurring in 20% or more patients (total%/grade ≥3%) included diarrhea (36/8), fatigue (36/3), nausea (25/3), rash (25/3), pyrexia (20/3), and chills (20/0). Laboratory abnormalities included neutropenia (44/23), anemia (31/5), thrombocytopenia (25/11), and serum transaminase elevations (48/25). Twelve (19%) patients discontinued therapy due to AEs. Idelalisib induced disease regression in 46/54 (85%) of evaluable patients achieving an overall response rate of 30/64 (47%), with 1 patient having a complete response (1.6%). Median duration of response was 18.4 months, median progression-free survival was 7.6 months. Idelalisib is well tolerated and active in heavily pretreated, relapsed/refractory patients with iNHL. These trials were registered at clinicaltrials.govas NCT00710528 and NCT01090414.