Breakthrough invasive fungal infections on isavuconazole prophylaxis in hematologic malignancy & hematopoietic stem cell transplant patients.

BACKGROUND: Isavuconazole (ISA) is a newer antifungal used in patients with history of hematologic malignancies and hematopoietic transplant and cellular therapies (HM/TCT). Although it has a more favorable side-effect profile, breakthrough invasive fungal infections (bIFIs) while on ISA have been reported. METHODS: In this single-center retrospective study evaluating HM/TCT patients who received prophylactic ISA for ≥7 days, we evaluated the incidence and potential risk factors for bIFIs. RESULTS: We evaluated 106 patients who received prophylactic ISA. The patients were predominantly male (60.4%) with median age of 65 (range: 21-91) years. Acute myeloid leukemia (48/106, 45.3%) was the most common HM, with majority having relapsed and/or refractory disease (43/106, 40.6%) or receiving ongoing therapy (38/106, 35.8%). Nineteen patients (17.9%) developed bIFIs-nine proven [Fusarium (3), Candida (2), Mucorales plus Aspergillus (2), Mucorales (1), Colletotrichum (1)], four probable invasive pulmonary Aspergillus, and six possible infections. Twelve patients were neutropenic for a median of 28 (8-253) days prior to bIFI diagnosis. ISA levels checked within 7 days of bIFI diagnosis (median: 3.65 µg/mL) were comparable to industry-sponsored clinical trials. All-cause mortality among the bIFI cases was 47.4% (9/19).We also noted clinically significant cytomegalovirus co-infection in 5.3% (1/19). On univariate analysis, there were no significant differences in baseline comorbidities and potential risk factors between the two groups. CONCLUSION: ISA prophylaxis was associated with a significant cumulative incidence of bIFIs. Despite the appealing side-effect and drug-interaction profile of ISA, clinicians must be vigilant about the potential risk for bIFIs.

A Data-Driven and Personalized Stance Symmetry Controller for Robotic Ankle-Foot Prostheses: A Preliminary Investigation.

People with unilateral transtibial amputation generally exhibit asymmetric gait, likely due to inadequate prosthetic ankle function. This results in compensatory behavior, leading to long-term musculoskeletal impairments (e.g., osteoarthritis in the joints of the intact limb). Powered prostheses can better emulate biological ankles, however, control methods are over-reliant on non-disabled data, require extensive amounts of tuning by experts, and cannot adapt to each user's unique gait patterns. This work directly addresses all these limitations with a personalized and data-driven control strategy. Our controller uses a virtual setpoint trajectory within an impedance-inspired formula to adjust the dynamics of the robotic ankle-foot prosthesis as a function of stance phase. A single sensor measuring thigh motion is used to estimate the gait phase in real time. The virtual setpoint trajectory is modified via a data-driven iterative learning strategy aimed at optimizing ankle angle symmetry. The controller was experimentally evaluated on two people with transtibial amputation. The control scheme successfully increased ankle angle symmetry about the two limbs by 24.4% when compared to the passive condition. In addition, the symmetry controller significantly increased peak prosthetic ankle power output at push-off by 0.52 W/kg and significantly reduced biomechanical risk factors associated with osteoarthritis (i.e., knee and hip abduction moments) in the intact limb. This research demonstrates the benefits of personalized and data-driven symmetry controllers for robotic ankle-foot prostheses.

Using Deep Learning Models to Predict Prosthetic Ankle Torque.

Inverse dynamics from motion capture is the most common technique for acquiring biomechanical kinetic data. However, this method is time-intensive, limited to a gait laboratory setting, and requires a large array of reflective markers to be attached to the body. A practical alternative must be developed to provide biomechanical information to high-bandwidth prosthesis control systems to enable predictive controllers. In this study, we applied deep learning to build dynamical system models capable of accurately estimating and predicting prosthetic ankle torque from inverse dynamics using only six input signals. We performed a hyperparameter optimization protocol that automatically selected the model architectures and learning parameters that resulted in the most accurate predictions. We show that the trained deep neural networks predict ankle torques one sample into the future with an average RMSE of 0.04 ± 0.02 Nm/kg, corresponding to 2.9 ± 1.6% of the ankle torque's dynamic range. Comparatively, a manually derived analytical regression model predicted ankle torques with a RMSE of 0.35 ± 0.53 Nm/kg, corresponding to 26.6 ± 40.9% of the ankle torque's dynamic range. In addition, the deep neural networks predicted ankle torque values half a gait cycle into the future with an average decrease in performance of 1.7% of the ankle torque's dynamic range when compared to the one-sample-ahead prediction. This application of deep learning provides an avenue towards the development of predictive control systems for powered limbs aimed at optimizing prosthetic ankle torque.

Everyday non-partisan fake news: Sharing behavior, platform specificity, and detection.

Concern over the impact of fake news on major socio-political events is growing. The use of deliberate misinformation is thought to have played a role in the outcome of the UK EU referendum, the 2016 US presidential election, and in the effectiveness of COVID-19 public health messaging. As a result, recent research has tended to focus on hyper-partisan (e.g., US politics; Democrat/Republican), person specific (e.g., Hillary Clinton/Donald Trump) content that incorporates emotive and hyperbolic language. However, in this study, we focus on an alternative form of fake news, across a variety of topics (e.g., Crime, Immigration, and Health), that avoids these characteristics, and which may therefore be more pervasive and difficult to detect. In a three-part study, we examined participants sharing intentions for fake news (including platform preference; Facebook, Twitter, Instagram, and WhatsApp), their ability to explicitly detect fake news, and whether individual differences on psychological measures of critical thinking ability, rational thinking, and emotional stability predict sharing behavior and detection ability. The results show that even our well-informed sample (political science students) were not immune to the effects of fake news, some issues (e.g., health and crime) were more likely to be shared than others (e.g., immigration), and on specific platforms (e.g., Twitter, Facebook). In addition, we show that individual differences in emotional stability appears to be a key factor in sharing behavior, while rational thinking aptitude was key to fake news detection. Taken together, this study provides novel data that can be used to support targeted fake news interventions, suggesting possible news topic, sharing behavior, and platform specific insights. Such interventions, and implications for government policy, education, and social media companies are discussed.

Successful restoration of protective immunity against measles, mumps, and rubella following MMR vaccination in adult hematopoietic cell transplant recipients.

BACKGROUND: The optimal number of doses as well as the role for measurement of postvaccination titers after measles, mumps, rubella (MMR) vaccination in adult hematopoietic cell transplantation (HCT) recipients remains unknown. METHODS: In the present study, we assessed humoral immunity against measles, mumps and rubella before and after MMR vaccination in 187 adults who received at least one dose of the MMR vaccine after HCT. RESULTS: Among those with baseline titers, posttransplant prevaccination seroprotection rates were 56%, 30%, and 54% for measles, mumps, and rubella, respectively; and significantly lower in allogeneic versus autologous HCT recipients for measles (39% vs. 80%, p = .0001), mumps (22% vs. 41%; p = .02) and rubella (48% vs. 62%, p = .12). Among those who were seronegative at baseline, seroconversion rates after one dose of MMR were 69%, 56%, and 97% for measles, mumps, and rubella, respectively. Seronegative patients after one dose of MMR (i.e., nonresponders) seroconverted for measles and mumps after a second MMR vaccine dose. CONCLUSION: Our findings demonstrate successful restoration of protective immunity against measles, mumps, and rubella after vaccination in adult HCT recipients; one dose of MMR elicited protective titers in the majority of patients, and a second vaccine dose was immunogenic in nonresponders.

Early administration of SARS-CoV-2 monoclonal antibody reduces the risk of mortality in hematologic malignancy and hematopoietic cell transplant patients with COVID-19.

BACKGROUND: Data on severe acute respiratory distress syndrome coronavirus 2 monoclonal antibody (SARS-CoV-2-specific mAb) use in hematologic malignancy and hematopoietic cell transplantation (HM/HCT) patients are limited. Here, we describe our experience with the use of casirivimab-imdevimab or bamlanivimab for the treatment of coronavirus disease 2019 (COVID-19) in HM/HCT patients. METHODS: This was a retrospective chart review at the University of Miami Hospital and Sylvester Comprehensive Cancer Center for HM/HCT patients with COVID-19 who received casirivimab-imdevimab or bamlanivimab from November 21, 2020, to September 30, 2021. Outcomes measured were mortality, hospital admission, and infusion reaction to SARS-CoV-2-specific mAbs. RESULTS: We identified 59 HM/HCT patients with mild to moderate COVID-19 who received casirivimab-imdevimab or bamlanivimab. Median age was 57 years (interquartile range [IQR]: 45-65). Among the 59 patients, 25 (42%) received cellular therapy: 14 (24%) had undergone allogeneic HCT, nine (15%) autologous HCT, and two (3%) received chimeric antigen receptor T-cell therapy. The median time from COVID-19 symptom onset to SARS-CoV-2-specific mAb administration was 4 (IQR: 3-6) days. Forty-six (78%) patients received SARS-CoV-2-specific mAbs as outpatients and 13 (22%) patients received SARS-CoV-2-specific mAbs during hospitalization. Among patients who received SARS-CoV-2-specific mAbs as outpatients, only four (9%) visited the emergency department at days 10, 11, 15, and 35 after SARS-CoV-2-specific mAb administration. None of these four patients required hospital admission. Among the hospitalized patients, five (38%) were admitted to the hospital with neutropenic fever, four (31%) were already hospitalized for transplantation and cellular therapy, three (23%) were admitted for monitoring of COVID-19 symptoms, and one (8%) was admitted with acute kidney injury. Three hospitalized patients (23%) died at 14, 35, and 59 days after SARS-CoV-2-specific mAb administration; two of these three deaths were attributed to COVID-19 infection. One patient developed an immediate infusion reaction to bamlanivimab, and no infusion reactions were reported to casirivimab-imdevimab use. CONCLUSION: During the alpha and delta variant surges, early administration of bamlanivimab or casirivimab-imdevimab prevented hospitalization and death when given in the outpatient setting. Among patients who received mAbs at or after hospital admission, the risk of COVID-19 disease progression and death remains significant. Larger studies of the use of mAb therapy to treat COVID-19 in this population are needed.

Full body musculoskeletal model for simulations of gait in persons with transtibial amputation.

This paper describes the development, properties, and evaluation of a musculoskeletal model that reflects the anatomical and prosthetic properties of a transtibial amputee using OpenSim. Average passive prosthesis properties were used to develop CAD models of a socket, pylon, and foot to replace the lower leg. Additional degrees of freedom (DOF) were included in each joint of the prosthesis for potential use in a range of research areas, such as socket torque and socket pistoning. The ankle has three DOFs to provide further generality to the model. Seven transtibial amputee subjects were recruited for this study. 3 D motion capture, ground reaction force, and electromyographic (EMG) data were collected while participants wore their prescribed prosthesis, and then a passive prototype prosthesis instrumented with a 6-DOF load cell in series with the pylon. The model's estimates of the ankle, knee, and hip kinematics comparable to previous studies. The load cell provided an independent experimental measure of ankle joint torque, which was compared to inverse dynamics results from the model and showed a 7.7% mean absolute error. EMG data and muscle outputs from OpenSim's Static Optimization tool were qualitatively compared and showed reasonable agreement. Further improvements to the muscle characteristics or prosthesis-specific foot models may be necessary to better characterize individual amputee gait. The model is open-source and available at (https://simtk.org/projects/biartprosthesis) for other researchers to use to advance our understanding and amputee gait and assist with the development of new lower limb prostheses.

Design and Evaluation of a Knee Flexion Assistance Exoskeleton for People with Transtibial Amputation.

People with below-knee amputation walk with asymmetric gaits that over time can lead to further musculoskeletal disorders and decreased quality of life. While prosthesis technology is improving, prosthetic ankles may be fundamentally limited in their ability to restore healthy walking patterns because they do not assist the residual knee joint. The knee on the residual limb has muscular deficits due to the loss of the gastrocnemius, a biarticular muscle that crosses both the ankle and knee. Here we present the design, development, and preliminary evaluation of a robotic knee exoskeleton for people with transtibial amputation. The device is intended to restore gastrocnemius-like flexion moments to the knee on the residual limb. The exoskeleton uses a custom offboard actuation and control system to allow for a simple and lightweight design with high torque capabilities. A preliminary walking experiment with one person with transtibial amputation was conducted. The exoskeleton provided a range of knee flexion torque profiles and had an RMS tracking error of 1.9 Nm across four assistance conditions. This device will be used in future studies to explore the effects of providing knee flexion assistance to people with transtibial amputation during walking. Long term, findings from studies with this exoskeleton could motivate future assistive device designs that improve walking mechanics and quality of life for people with limb loss.

A case series to examine the perinatal outcomes of infants conceived by intravaginal culture (IVC).

PURPOSE: In vitro fertilization (IVF) has been a well-established method for treating infertility for over four decades. The mainstay method of culture of oocytes and embryos has been in gas incubators. More recently, the novel use of a gas-permeable closed vessel to culture oocytes and embryos in the vagina, intravaginal culture (IVC), has been introduced as a viable lower-cost option for infertility patients. Several studies have studied the efficacy of IVC; however, there is no data on the perinatal outcomes of the babies born using this newer technology. METHODS: Our study is a retrospective case series (n = 66) from a single center, uniquely examining the perinatal outcomes of infants born after IVC. RESULTS: There were 50 singleton and 16 twin gestations in this case series. For singleton infants conceived via IVC (n = 50), the mean gestational age at delivery was 38 weeks and 4 days, and the mean birth weight was 3159.1 + / - 501.5 g. Four infants were born with low birth weight, three were born preterm, and one was born macrosomic. The twin pregnancies had a mean gestational age at delivery of 33 weeks 4 days and a mean birth weight of 1992.9 + / - 620.7 g. Twenty-seven infants met the criteria for low birthweight, and twenty-four infants delivered preterm. No twin infants met the criteria for macrosomia. CONCLUSION: This case series provides an initial description of the perinatal outcomes of IVC conceived infants, which shows no concerning trends in adverse birth outcomes for singleton infants. As expected, IVC twin gestations had a high rate of low birth weight and preterm delivery. Continued larger studies are essential to provide more comprehensive data on perinatal outcomes of infants conceived by this new technology.

Successful Treatment of Disseminated Disease Due to Highly Resistant Aspergillus calidoustus with a Novel Antifungal Therapy.

Invasive aspergillosis is the most common invasive mold infection following a hematopoietic cell transplant. Widespread use of antifungal prophylaxis has led to the increasing incidence of cryptic Aspergillus species. Aspergillus calidoustus is one of those emerging species and is notorious for multidrug resistance to antifungals. Here, we report a case of disseminated A. calidoustus infection in a hematopoietic stem cell transplant recipient who was successfully treated with combination therapy that included a novel antifungal.

Correction: Detecting fake news on Facebook: The role of emotional intelligence.

[This corrects the article DOI: 10.1371/journal.pone.0246757.].

Lower Incidence of Cytomegalovirus Reactivation Following Post-Transplantation Cyclophosphamide HLA-Mismatched Unrelated Donor Transplantation.

The use of haploidentical or HLA-mismatched unrelated donors (MMUD) allows allogeneic hematopoietic cell transplantation in individuals without suitable matched donors. Post-transplantation cyclophosphamide (PTCy) is used routinely for prevention of graft-versus-host disease in recipients of haploidentical transplants, and its use has been recently explored in MMUD transplantation. We compared the incidence of cytomegalovirus (CMV) reactivation and rate of lymphocyte recovery between PTCy MMUD and alternative transplantation modalities. Single-center retrospective study of 22 consecutive PTCy MMUD recipients transplanted between April 2017 and January 2019. Patients undergoing anti-thymocyte globulin (ATG) MMUD (n = 37) and PTCy haploidentical transplantation (n = 19) between January 2015 and July 2018 served as historical controls. We assessed the incidence of CMV (any viremia) and clinically significant CMV reactivation (cs-CMVi; defined as CMV disease or CMV viremia leading to preemptive treatment) in these 3 groups. Immune reconstitution was assessed by absolute lymphocyte count (ALC) at days 30, 90, 180, and 360 after transplantation. Statistical analyses included Kaplan-Meier plots with a log-rank test, Kruskal-Wallis test, and Fisher's exact test where appropriate, and logistic regression analyses. For PTCy MMUD, PTCy haploidentical and ATG MMUD groups, the 100-day and 200-day incidence of CMV (any viremia) were 41%, 63%, and 77% (P = .02), and 64%, 68%, and 86% (P = .049), respectively. The rate of cs-CMVi was also lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (14% versus 53% and 54% at day 100 [P = .01] and 25% versus 53% and 58% at day 200 [P = .03]). There was a trend toward lower 200-day incidence of cs-CMVi in PTCy MMUD compared to ATG MMUD, even after excluding letermovir-treated patients from the analysis (25% versus 58% [P = .06]). The association between PTCy MMUD and lower risk of cs-CMVi remained significant even after adjusting for letermovir prophylaxis (odds ratio = 0.23, 95% confidence interval, 0.07-0.81 [P = .02]). Day 30 ALC was lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (0.14, 0.33, 0.44 × 109/L, respectively [P = .005) but similar across groups at other time points. PTCy MMUD transplantation was associated with lower incidence of CMV events, independent of the use of CMV prophylaxis. Larger studies are needed.

Viral kinetics and outcomes of adenovirus viremia following allogeneic hematopoietic cell transplantation.

BACKGROUND: Adenovirus (AdV) is a serious infection following hematopoietic cell transplantation (HCT). Little is known about AdV viral kinetics and optimal threshold for initiation of pre-emptive therapy. METHODS: Single-center retrospective study of 16 consecutive adult HCT recipients with detectable AdV identified over a 5-year period. RESULTS: Median time to AdV reactivation after HCT was 176 days (IQR 86-408). Nine patients received cidofovir, although 14/16 had no tissue-invasive disease. Among treated patients, median duration of viremia was shorter when initiating treatment at viral loads < 10,000 copies/ml (28 vs. 52 days). All-cause mortality in this cohort was 44%. All six patients (five of which were untreated) with peak viral loads < 10,000 copies/ml survived; whereas only 30% (3/10) of patients with peak viral loads greater than this threshold survived, despite most (n = 8; 80%) of them receiving cidofovir (P = .01). Three-month survival following diagnosis of AdV viremia was significantly lower with peak viremia > 10,000 copies/ml (100 vs. 17%; P = .005). CONCLUSION: AdV is associated with high all-cause mortality, especially for viremia > 10,000 copies/ml. Delaying therapy until viremia reaches AdV levels ≥10,000 copies/ml was associated with more protracted infection and poor outcomes. Larger studies are needed.

Evaluation of a quasi-passive biarticular prosthesis to replicate gastrocnemius function in transtibial amputee gait.

Lower limb amputees experience gait impairments, in part due to limitations of prosthetic limbs and the lack of a functioning biarticular gastrocnemius (GAS) muscle. Energy storing prosthetic feet restore the function of the soleus, but not GAS. We propose a transtibial prosthesis that implements a spring mechanism to replicate the GAS. A prototype Biarticular Prosthesis (BP) was tested on seven participants with unilateral transtibial amputation. Participants walked on an instrumented treadmill with motion capture, first using their prescribed prosthesis, then with the BP in four different spring stiffness conditions. A custom OpenSim musculoskeletal model, including the BP, was used to estimate kinematics, joint torques, and muscle forces. Kinematic symmetry was evaluated by comparing the amputated and intact angles of the ankle, knee, and hip. The BP knee and ankle torques were compared to the intact GAS. Finally, work done by the BP spring was calculated at the ankle and knee. There were no significant differences between conditions in kinematic symmetry, indicating that the BP performs similarly to prescribed prostheses. When comparing the BP torques to intact GAS, higher spring stiffness better approximated peak GAS torques, but those peaks occurred earlier in the gait cycle. The BP spring did positive work on the knee joint and negative work on the ankle joint, and this work increased as BP spring stiffness increased. The BP has the potential to improve amputee gait compensations associated with the lack of biarticular GAS function, which may reduce their walking effort and improve quality of life.

Clinical presentation and outcomes of COVID-19 following hematopoietic cell transplantation and cellular therapy.

BACKGROUND: One year into the pandemic, published data on hematopoietic cell transplantation (HCT) recipients with coronavirus disease 2019 (COVID-19) remain limited. METHODS: Single-center retrospective cohort study of adult HCT recipients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: Twenty-eight consecutive transplantation and cellular therapy patients (autologous, n = 12; allogeneic, n = 15; chimeric antigen receptor T-cell therapy [CAR-T], n = 1) with COVID-19 were identified. The median age was 57 years. The median time from HCT to COVID-19 diagnosis was 656 days (interquartile range [IQR], 33-1274). Patients were followed for a median of 59 days (IQR, 40-88). Among assessable patients (n = 19), 10 (53%) had documented virological clearance; median time to clearance was 34 days (range, 21-56). Out of 28, 12 (43%), 6 (21%), and 10 (36%) patients had mild, moderate, and severe/critical disease, respectively. Overall mortality was 25%, nearly identical for autologous and allogeneic HCT, and exclusively seen in hospitalized patients, older than 50 years of age with severe COVID-19. None of the patients with mild (n = 12) or moderate (n = 6) COVID-19 died whereas 7/10 patients (70%) with severe/critical COVID-19 died (P = .0001). Patients diagnosed with COVID-19 within 12 months of HCT exhibited higher mortality (57% vs 14%; P = .04). All-cause 30-day mortality (n = 4) was 14%. A higher proportion of patients who died within 30 days of COVID-19 diagnosis (3/4) were receiving ≥2 immunosuppressants, compared with patients who survived beyond 30 days after COVID-19 diagnosis (2/24; 75% vs. 8%; P = .01). CONCLUSIONS: Mortality in COVID-19 HCT patients is higher than that of the age-comparable general population and largely dependent on age, disease severity, timing from HCT, and intensity of immunosuppression.

Detecting fake news on Facebook: The role of emotional intelligence.

The proliferation of fake news on social media is now a matter of considerable public and governmental concern. In 2016, the UK EU referendum and the US Presidential election were both marked by social media misinformation campaigns, which have subsequently reduced trust in democratic processes. More recently, during the COVID-19 pandemic, the acceptance of fake news has been shown to pose a threat to public health. Research on how to combat the false acceptance of fake news is still in its infancy. However, recent studies have started to focus on the psychological factors which might make some individuals less likely to fall for fake news. Here, we adopt that approach to assess whether individuals who show high levels of 'emotional intelligence' (EQ) are less likely to fall for fake news items. That is, are individuals who are better able to disregard the emotionally charged content of such items, better equipped to assess the veracity of the information. Using a sample of UK participants, an established measure of EQ and a novel fake news detection task, we report a significant positive relationship between individual differences in emotional intelligence and fake news detection ability. We also report a similar effect for higher levels of educational attainment, and we report some exploratory qualitative fake news judgement data. Our findings are discussed in terms of their applicability to practical short term (i.e. current Facebook user data) and medium term (i.e. emotional intelligence training) interventions which could enhance fake news detection.

Validation of Accelerometry Data to Identify Movement Patterns During Agility Testing.

Purpose: The purpose of this study was to develop an algorithm for the detection and timing of foot contact/off timing for each lateral repetition and assess the validity/reliability of the calculated timings. Methods: Participants performed a modified Edgren Side Step Test in which they moved laterally along a 4-m path as quickly as possible while wearing an accelerometer on each ankle. Time of completion of each attempt was recorded using a stopwatch and digital video was obtained. Accelerometer-based (ACC) events were determined for the start of the test (START), foot contact at the end-line (FC) and the lifting of the foot when transitioning to the other direction (FO). Based on these ACC events the Overall, Split (ST) and Lag (LT) times were determined and compared to either the stopwatch or video-based timings (p < 0.05). The ACC event criterion was then applied by independent reviewers to assess inter/intra-rater reliability of identifying the events. Results: There was no significant difference in ACC (12.37 ± 2.19 s) based Overall Time compared to the Stopwatch (12.42 ± 2.25 s, p = 0.34). Bland-Altman plots for ST and LT revealed very good agreement between the ACC time to the Video (ST: Bias = 0.11 s, LOA -0.57 to 0.79; LT: Bias = -0.11 s, LOA -0.43 to 0.22). Intra and inter-rater reliability was moderate to excellent for all reviewer identified events. Conclusions: This study demonstrates methodology to identify ACC based timings during an agility test. The inclusion of an accelerometer supplements standard timing options with the added benefit of assessing sided split and lag times.