High Rates of Aseptic Loosening in Modern Posterior-stabilized Femoral Components From a Single Manufacturer.

Background: Total knee arthroplasty (TKA) is one of the most commonly performed surgical procedures in the United States. There are concerns and reports of early aseptic loosening due to debonding at the cement-implant interface in a specific posterior-stabilized femoral design. This study describes failure at the cement-implant interface with 2 femoral implant designs produced by a single manufacturer. Methods: This is a review of failed primary total knee arthroplasties performed with Optetrak Logic and Truliant posterior-stabilized femoral components between 2010 and 2020. Cases with revision surgery performed for femoral component loosening were reviewed. Results: Seventeen of 896 knees were revised for femoral component loosening. The mean time from index arthroplasty to revision was 73 months. Patients presented with knee pain and recurrent aseptic effusions. More than half of patients had no evidence of component loosening on plain radiographs. Bone scans were positive in 77% of patients with loosening. Femoral components were easily disimpacted from the cement mantle at the time of revision surgery. Patients were treated with femoral only revision or femoral and tibial revision. Two complications occurred in this series. Conclusions: Providers should maintain vigilance in the surveillance of patients with these implants. Clinicians should have a low threshold for additional diagnostic testing if these patients develop pain and/or recurrent effusions. Isolated femoral or complete revision both seem to be acceptable treatment strategies for this failure mechanism.

Patient-reported outcomes in CD30-directed CAR-T cells against relapsed/refractory CD30+ lymphomas.

Chimeric antigen receptor (CAR)-T cells targeting CD30 have demonstrated high response rates with durable remissions observed in a subset of patients with relapsed/refractory CD30+ hematologic malignancies, particularly classical Hodgkin lymphoma. This therapy has low rates of toxicity including cytokine release syndrome with no neurotoxicity observed in our phase 2 study. We collected patient-reported outcomes (PROs) on patients treated with CD30 directed CAR-T cells to evaluate the impact of this therapy on their symptom experience. We collected PROs including PROMIS (Patient-Reported Outcomes Measurement Information System) Global Health and Physical Function questionnaires and selected symptom questions from the NCI PRO-CTCAE in patients enrolled on our clinical trial of CD30-directed CAR-T cells at procurement, at time of CAR-T cell infusion, and at various time points post treatment. We compared PROMIS scores and overall symptom burden between pre-procurement, time of infusion, and at 4 weeks post infusion. At least one PRO measurement during the study period was found in 23 out of the 28 enrolled patients. Patient overall symptom burden, global health and mental health, and physical function were at or above baseline levels at 4 weeks post CAR-T cell infusion. In addition, PROMIS scores for patients who participated in the clinical trial were similar to the average healthy population. CD30 CAR-T cell therapy has a favorable toxicity profile with patient physical function and symptom burden recovering to at least their baseline pretreatment health by 1 month post infusion. Trial registration number: NCT02690545.

Drugs Are Not Microchips: Whither Industrial Policy In The Life Sciences?

Events such as Russia's invasion of Ukraine in February 2022 have heightened global awareness of the potential for sudden market upheaval and the need for proactive measures to protect supply chains, including in the life sciences. But advancing an industrial policy on drugs requires several unique conditions-including a continued sense of acute threat among the US and its allies, ample public-sector funding, real-time data, industry buy-in, and bipartisan support in Congress-that are currently not present in the US.

Do improvements in clinical practice guidelines alter pregnancy outcomes in asthmatic women? A single-center retrospective cohort study.

OBJECTIVE: Asthma occurs in ∼17% of Australian pregnancies and is associated with adverse perinatal outcomes, which worsen with poor asthma control. Consequently, the South Australian 'Asthma in Pregnancy' perinatal guidelines were revised in 2012 to address management according to severity. This study investigated if these revised guidelines reduced the impact of maternal asthma on risks of adverse perinatal outcomes before (Epoch 1, 2006-2011) and after the revision (Epoch 2, 2013-2018). METHODS: Routinely collected perinatal and neonatal datasets from the Women's and Children's Hospital (Adelaide, Australia) were linked. Maternal asthma (prevalence:7.5%) was defined as asthma medication use or symptoms described to midwives. In imputation (n = 59131) and complete case datasets (n = 49594), analyses were conducted by inverse proportional weighting and multivariate logistic regression, accounting for confounders. RESULTS: Overall, maternal asthma was associated with increased risks of any antenatal corticosteroid treatment for threatened preterm birth (aOR 1.319, 95% CI 1.078-1.614), any Cesarean section (aOR 1.196, 95% CI 1.059-1.351), Cesarean section without labor (aOR 1.241, 95% CI 1.067-1.444), intrauterine growth restriction (IUGR, aOR 1.285, 95% CI 1.026-1.61), and small for gestational age (aOR 1.324, 95% CI 1.136-1.542). After guideline revision, asthma-associated risks of any Cesarean section (p < 0.001), any antenatal corticosteroids (p = 0.041), and small for gestational age (p = 0.050), but not IUGR and Cesarean section without labor, were reduced. CONCLUSIONS: Clinical practice guidelines based on the latest evidence do not guarantee clinical efficacy. Since adverse perinatal outcomes did not all improve, this work highlights the need to evaluate the ongoing impact of guidelines on clinical outcomes.

A flexible proton beam imaging energy spectrometer (PROBIES) for high repetition rate or single-shot high energy density (HED) experiments (invited).

The PROBIES diagnostic is a new, highly flexible, imaging and energy spectrometer designed for laser-accelerated protons. The diagnostic can detect low-mode spatial variations in the proton beam profile while resolving multiple energies on a single detector or more. When a radiochromic film stack is employed for "single-shot mode," the energy resolution of the stack can be greatly increased while reducing the need for large numbers of films; for example, a recently deployed version allowed for 180 unique energy measurements spanning ∼3 to 75 MeV with <0.4 MeV resolution using just 20 films vs 180 for a comparable traditional film and filter stack. When utilized with a scintillator, the diagnostic can be run in high-rep-rate (>Hz rate) mode to recover nine proton energy bins. We also demonstrate a deep learning-based method to analyze data from synthetic PROBIES images with greater than 95% accuracy on sub-millisecond timescales and retrained with experimental data to analyze real-world images on sub-millisecond time-scales with comparable accuracy.

Compact high repetition rate Thomson parabola ion spectrometer.

We present the development of a compact Thomson parabola ion spectrometer capable of characterizing the energy spectra of various ion species of multi-MeV ion beams from >1020W/cm2 laser produced plasmas at rates commensurate with the highest available from any of the current and near-future PW-class laser facilities. This diagnostic makes use of a polyvinyl toluene based fast plastic scintillator (EJ-260), and the emitted light is collected using an optical imaging system coupled to a thermoelectrically cooled scientific complementary metal-oxide-semiconductor camera. This offers a robust solution for data acquisition at a high repetition rate, while avoiding the added complications and nonlinearities of micro-channel plate based systems. Different ion energy ranges can be probed using a modular magnet setup, a variable electric field, and a varying drift-distance. We have demonstrated operation and data collection with this system at up to 0.2 Hz from plasmas created by irradiating a solid target, limited only by the targeting system. With the appropriate software, on-the-fly ion spectral analysis will be possible, enabling real-time experimental control at multi-Hz repetition rates.

MDT practice determines treatment pathway for patients with advanced ovarian cancer: A multi-centre observational study.

OBJECTIVE: To investigate decision making for patients with advanced ovarian cancer as a possible explanation of geographical variation in treatment patterns. METHODS: We carried out a multi-centre observational study in multidisciplinary teams meetings for five major UK cancer centres. All patients presenting to five cancer centres with advanced ovarian cancer over a six-week period. The GO-MDT-MODe tool was used to provide a measure of participation and quality of case discussion for all cases of advanced ovarian cancer. MDT scores were correlated with surgical data extracted from national audit data. Data were recorded for overall MDT performance. RESULTS: A total of 870 case discussions, including 145 cases of advanced ovarian cancer, were observed. MDTs varied in structure, format and time allocation between centres. Cluster analysis showed significant variation in quality and participation of discussion between centres (p < 0.0025) and this correlated with the proportion of patients in the wider cancer alliance undergoing surgery. CONCLUSIONS: We have shown that at least part of the variation in practice seen in the UK correlates with different behaviours within MDTs. Increasing time for discussion and encouraging participation from all staff groups may increase proportions of patients undergoing optimal treatment regimens.

Ultra-compact x-ray spectrometer for high-repetition-rate laser-plasma experiments.

We present in this work the development of an ultra-compact, multi-channel x-ray spectrometer (UCXS). This diagnostic has been specially built and adapted to perform at high-repetition-rate (>1 Hz) for high-intensity, short-pulse laser plasma experiments. X-ray filters of varying materials and thicknesses are chosen to provide spectral resolution up to ΔE ≈ 1 keV over the x-ray energy range of 1-30 keV. These filters are distributed over a total of 25 channels, where each x-ray filter is coupled to a single scintillator. The UCXS is designed to detect and resolve a large variety of laser-driven x-ray sources such as low energy bremsstrahlung emission, fluorescence, and betatron radiation (up to 30 keV). Preliminary results from commissioning experiments at the ABL laser facility at Colorado State University are provided.

Placenta Accreta Spectrum: A 2-year Retrospective Observational Study.

Aims To assess the management and outcomes of Placenta Accreta Spectrum disorders and highlight the important management recommendations from international guidelines. Methods A retrospective audit of women diagnosed with Placenta Accreta Spectrum disorder from January 2018 to December 2019. Results Nine cases (0.16%) of placenta accreta from 5695 births were identified. All women received caesarean section under general anaesthesia. Caesarean hysterectomy occurred in seven cases (78%). Mean (±SD) age of women was (34.4 ± 3.9 years) and mean parity score was (3.2 ± 1.2). Mean gestational age at birth was 35.1 ± 0.8 weeks. Bilateral iliac artery balloon occlusion occurred in eight (89%) cases. Median estimated blood loss [range] was 1700 mL [1000-7000] with only 11% of patients (1/9) experiencing more than 3L of blood loss. Intraoperative red blood cell transfusion occurred in six cases (67%). Median number of units of red cell transfusion [range] was four units [0-10]. Mean hospital length of stay was (6.7 ± 1.1 days) and there were no maternal deaths. Multidisciplinary team involvement of senior anaesthetists and obstetricians was noted in all cases. Discussion Placenta accreta spectrum is increasing in incidence in obstetric practice and is associated with significant maternal morbidity and mortality. Implementing national guidelines can improve patient outcomes.

Stabilized Radiation Pressure Acceleration and Neutron Generation in Ultrathin Deuterated Foils.

Premature relativistic transparency of ultrathin, laser-irradiated targets is recognized as an obstacle to achieving a stable radiation pressure acceleration in the "light sail" (LS) mode. Experimental data, corroborated by 2D PIC simulations, show that a few-nm thick overcoat surface layer of high Z material significantly improves ion bunching at high energies during the acceleration. This is diagnosed by simultaneous ion and neutron spectroscopy following irradiation of deuterated plastic targets. In particular, copious and directional neutron production (significantly larger than for other in-target schemes) arises, under optimal parameters, as a signature of plasma layer integrity during the acceleration.

Absolute calibration of Fujifilm BAS-TR image plate response to laser driven protons up to 40 MeV.

Image plates (IPs) are a popular detector in the field of laser driven ion acceleration, owing to their high dynamic range and reusability. An absolute calibration of these detectors to laser-driven protons in the routinely produced tens of MeV energy range is, therefore, essential. In this paper, the response of Fujifilm BAS-TR IPs to 1-40 MeV protons is calibrated by employing the detectors in high resolution Thomson parabola spectrometers in conjunction with a CR-39 nuclear track detector to determine absolute proton numbers. While CR-39 was placed in front of the image plate for lower energy protons, it was placed behind the image plate for energies above 10 MeV using suitable metal filters sandwiched between the image plate and CR-39 to select specific energies. The measured response agrees well with previously reported calibrations as well as standard models of IP response, providing, for the first time, an absolute calibration over a large range of proton energies of relevance to current experiments.

Factors associated with body weight of young surplus dairy calves on arrival to a calf rearing facility.

The objective of this study was to identify factors present on the source dairy farm and during transport, that are associated with low body weight of young dairy calves at arrival to a calf rearing facility. A total of 195 surplus dairy calves from five farms in southern Ontario, Canada were examined from October 2020 to June 2021. Calves were continuously enrolled at birth on participating source dairy farms for three weeks until the day of transport and followed until arrival at the calf rearing facility. Calf sex, breed, calving difficulty, and birth weight were recorded at enrollment and blood samples were collected between 24 and 48 h after birth to determine serum total protein. From the day of birth through arrival at the calf rearing facility, each calf received a daily health examination which included a fecal consistency score, respiratory score, and navel score. On the day of transport, calves were randomly assigned to 1 of 3 transport treatments: 6 h, 12 h, or 16 h of continuous transportation by road. Age on the day of transport was recorded, and body weight was measured immediately before and after transportation. Two mixed linear regression models were built to determine the effect of these variables on body weight at arrival. The mean (± SD) birth weight, body weight before transport and body weight at arrival were 45 kg (± 6.9), 51 kg (± 6.6), and 47 kg (± 5.9), respectively, and age on the day of transport ranged from 1 to 22 d. Breed, birth weight, age at transport, body weight immediately before transport, and transport duration were associated with body weight at arrival. Holstein calves had greater body weights at arrival compared to Holstein-beef calves. Additionally, calves with greater birth weights and greater body weights immediately before transport had greater body weights at arrival. Calves over 5 d of age at transport had greater body weights at arrival compared to calves transported at 5 d of age or less. Calves transported for 6 h had a greater body weight at arrival compared to 12 h or 16 h, and those transported for 12 h had a greater body weight at arrival compared to 16 h. Future studies should evaluate approaches and policies to increase body weight of surplus dairy calves at arrival as it is consistently associated with improved health and productivity at calf rearing facilities.

Pretherapy metabolic tumor volume is associated with response to CD30 CAR T cells in Hodgkin lymphoma.

Our group has recently demonstrated that chimeric antigen receptor T-cell therapy targeting the CD30 antigen (CD30.CAR-T) is highly effective in patients with relapsed and refractory (r/r) classical Hodgkin lymphoma (cHL). Despite high rates of clinical response, relapses and progression were observed in a subset of patients. The objective of this study was to characterize clinical and correlative factors associated with progression-free survival (PFS) after CD30.CAR-T cell therapy. We evaluated correlatives in 27 patients with r/r cHL treated with lymphodepletion and CD30.CAR-T cells. With a median follow-up of 9.5 months, 17 patients (63%) progressed, with a median PFS of 352 days (95% confidence interval: 116-not reached), and 2 patients died (7%) with a median overall survival of not reached. High metabolic tumor volume (MTV, >60 mL) immediately before lymphodepletion and CD30.CAR-T cell infusion was associated with inferior PFS (log rank, P = .02), which persisted after adjusting for lymphodepletion and CAR-T dose (log rank, P = .01 and P = .006, respectively). In contrast, receiving bridging therapy, response to bridging therapy, CD30.CAR-T expansion/persistence, and percentage of CD3+PD-1+ lymphocytes over the first 6 weeks of therapy were not associated with differences in PFS. In summary, this study reports an association between high baseline MTV immediately before lymphodepletion and CD30.CAR-T cell infusion and worse PFS in patients with r/r cHL. This trial was registered at www.clinicaltrials.gov as #NCT02690545.

Placental growth factor in assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a stepped wedge cluster randomised control trial (PARROT Ireland).

OBJECTIVE: To determine whether the addition of placental growth factor (PlGF) measurement to current clinical assessment of women with suspected pre-eclampsia before 37 weeks' gestation would reduce maternal morbidity without increasing neonatal morbidity. DESIGN: Stepped wedge cluster randomised control trial from 29 June 2017 to 26 April 2019. SETTING: National multisite trial in seven maternity hospitals throughout the island of Ireland PARTICIPANTS: Women with a singleton pregnancy between 20+0 to 36+6 weeks' gestation, with signs or symptoms suggestive of evolving pre-eclampsia. Of the 5718 women screened, 2583 were eligible and 2313 elected to participate. INTERVENTION: Participants were assigned randomly to either usual care or to usual care plus the addition of point-of-care PlGF testing based on the randomisation status of their maternity hospital at the time point of enrolment. MAIN OUTCOMES MEASURES: Co-primary outcomes of composite maternal morbidity and composite neonatal morbidity. Analysis was on an individual participant level using mixed-effects Poisson regression adjusted for time effects (with robust standard errors) by intention-to-treat. RESULTS: Of the 4000 anticipated recruitment target, 2313 eligible participants (57%) were enrolled, of whom 2219 (96%) were included in the primary analysis. Of these, 1202 (54%) participants were assigned to the usual care group, and 1017 (46%) were assigned the intervention of additional point-of-care PlGF testing. The results demonstrate that the integration of point-of-care PlGF testing resulted in no evidence of a difference in maternal morbidity-457/1202 (38%) of women in the control group versus 330/1017 (32%) of women in the intervention group (adjusted risk ratio (RR) 1.01 (95% CI 0.76 to 1.36), P=0.92)-or in neonatal morbidity-527/1202 (43%) of neonates in the control group versus 484/1017 (47%) in the intervention group (adjusted RR 1.03 (0.89 to 1.21), P=0.67). CONCLUSIONS: This was a pragmatic evaluation of an interventional diagnostic test, conducted nationally across multiple sites. These results do not support the incorporation of PlGF testing into routine clinical investigations for women presenting with suspected preterm pre-eclampsia, but nor do they exclude its potential benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT02881073.

A funfair without the candy floss: engaging communities to prevent diabetes in Nepal.

OBJECTIVES: The World Health Organization estimates that 422 million people have diabetes, three-quarters of whom live in low- and middle-income countries. Global action plans to address non-communicable diseases (NCDs) recognise the centrality of community engagement to create an enabling environment within which to address risk factors. STUDY DESIGN: In this article, we describe and critically reflect on a cocreated community engagement approach to address type 2 diabetes in the southern plains of Nepal. We coproduced the engagement approach with 40 artists from the Janakpur Women's Development Centre to create an environment for dialogue about diabetes and NCD risk between artists and the general public. METHODS: We used participatory action research to produce contextually relevant interactive methods and materials. Methods included artists' peer research to inform creative workshops, a drama performed in 19 villages and a two-day funfair in a public park. We used qualitative and participatory methods to analyse the effect of this engagement and reflect on lessons learned. RESULTS: Around 2000 people saw the drama, and around 4000 people attended the funfair. Community dialogue about prevention of diabetes was facilitated by drama and through games and songs at the funfair. Artists grew confident to interact with their peers and drama audiences about the causes of diabetes and prevention strategies. Despite crowds at the funfair, it was difficult to reach women because the venue was often used by men and boys, and patriarchal norms prevent women from free movement. Village interactions were able to engage a more mixed audience. CONCLUSION: Innovative, asset-based community engagement about diabetes and other NCDs at scale is possible through locating, building on and strengthening community resources to address local health issues. Engagement could be enhanced by considering the gendered nature of community engagement spaces and by increasing opportunities for interaction between artists and the general public through more intimate and large-scale events.

Shouldice standard 2020: review of the current literature and results of an international consensus meeting.

INTRODUCTION: For many years the Shouldice technique was the gold standard for inguinal hernia repair. Nowadays mesh repair has been proven to entail better results in randomized trials. Since the first publication 1953 the Repair has been described in detail in many textbooks, articles and You Tube videos. It appears that the original technique is used almost exclusively in the Shouldice Hospital in Thornhill/ Canada and despite the success of the Shouldice Hospital many surgeons inexplicably modify this original technique in their daily practice. In the last couple of years there appears to be an increasing interest in pure tissue repairs for various reasons, often fear of mesh-related pain. The aim of the study was to review the current evidence and to define an updated standard with key principles of the Shouldice repair. METHODS: Because of unpublished evidence regarding many operative details the organizing group decided to create a technical update via a consensus meeting with 13 international designated hernia surgeons from six countries. In preparation of the meeting a review of the current literature regarding Shouldice repair was done by the organizing group. A questionnaire was prepared and sent to all participants before the meeting to get an independent answer on all critical aspects. RESULTS: All questions regarding a detailed standard of the operation technique could be outlined. As result of the consensus meeting the participants have formulated all key-points of preparation/dissection and repair of the Shouldice technique. For 5 of 6 critical technical surgical steps a strong consensus could be defined in the group. There was no consensus among the group regarding the cremaster resection and the ideal indication for Shouldice repair. CONCLUSION: After a 75-year history of the Shouldice repair the technique should continue to merit consideration by all hernia surgeons. After this consensus meeting a clear binding standard of the Shouldice technique for all interested surgeons is proposed.