Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57). CONCLUSIONS: The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).

Blind spots on western blots: Assessment of common problems in western blot figures and methods reporting with recommendations to improve them.

Western blotting is a standard laboratory method used to detect proteins and assess their expression levels. Unfortunately, poor western blot image display practices and a lack of detailed methods reporting can limit a reader's ability to evaluate or reproduce western blot results. While several groups have studied the prevalence of image manipulation or provided recommendations for improving western blotting, data on the prevalence of common publication practices are scarce. We systematically examined 551 articles published in the top 25% of journals in neurosciences (n = 151) and cell biology (n = 400) that contained western blot images, focusing on practices that may omit important information. Our data show that most published western blots are cropped and blot source data are not made available to readers in the supplement. Publishing blots with visible molecular weight markers is rare, and many blots additionally lack molecular weight labels. Western blot methods sections often lack information on the amount of protein loaded on the gel, blocking steps, and antibody labeling protocol. Important antibody identifiers like company or supplier, catalog number, or RRID were omitted frequently for primary antibodies and regularly for secondary antibodies. We present detailed descriptions and visual examples to help scientists, peer reviewers, and editors to publish more informative western blot figures and methods. Additional resources include a toolbox to help scientists produce more reproducible western blot data, teaching slides in English and Spanish, and an antibody reporting template.

Mechanical Thrombectomy Workshops Improve Procedural Knowledge and Skills Among Neurointerventional Teams in Low- to Middle-Income Countries.

BACKGROUND: While mechanical thrombectomy (MT) is proven to be lifesaving and disability sparing, there remains a disparity in its access in low- to middle-income countries. We hypothesized that team-based MT workshops would improve MT knowledge and skills. METHODS: We designed a 22-hour MT workshop, conducted as 2 identical events: in English (Jamaica, January 2022) and in Spanish (Dominican Republic, May 2022). The workshops included participating neurointerventional teams (practicing neurointerventionalists, neurointerventional nurses, and technicians) focused on acute stroke due to large vessel occlusion. The course faculty led didactic and hands-on components, covering topics from case selection and postoperative management to device technology and MT surgical techniques. Attendees were evaluated on stroke knowledge and MT skills before and after the course using a multiple choice exam and simulated procedures utilizing flow models under fluoroscopy, respectively. Press conferences for public education with invited government officials were included to raise stroke awareness. RESULTS: Twenty-two physicians and their teams from 8 countries across the Caribbean completed the didactic and hands-on training. Overall test scores (n=18) improved from 67% to 85% (P<0.002). Precourse and postcourse hands-on assessments demonstrated reduced time to completion from 36.5 to 21.1 minutes (P<0.001). All teams showed an improvement in measures of good MT techniques, with 39% improvement in complete reperfusion. Eight teams achieved a Thrombolysis in Cerebral Infarction score of 3 on pre-course versus 15 of 18 teams on post-course. There was a significant reduction in total potentially dangerous maneuvers (70% pre versus 20% post; P<0.002). Universally, the workshop was rated as satisfactory and likely to change practice in 93% Dominican Republic and 75% Jamaica. CONCLUSIONS: A team-based hands-on simulation approach to MT training is novel, feasible, and effective in improving procedural skills. Participants viewed these workshops as practice-changing and instrumental in creating a pathway for increasing access to MT in low- to middle-income countries.

Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

Esophageal Versus Rectal Temperature Monitoring During Whole-Body Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy: Association with Short- and Long-Term Outcomes.

OBJECTIVE: To compare the short- and long-term outcomes of infants with hypoxic-ischemic encephalopathy (HIE) treated with whole-body therapeutic hypothermia (TH), monitored by esophageal vs rectal temperature. STUDY DESIGN: We conducted a secondary analysis of the multicenter High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial. All infants had moderate or severe HIE and were treated with whole-body TH. The primary outcome was death or neurodevelopmental impairment (NDI) at 22-36 months of age. Secondary outcomes included seizures, evidence of brain injury on magnetic resonance imaging, and complications of hypothermia. Logistic regression was used with adjustment for disease severity and site as clustering variable because cooling modality differed by site. RESULTS: Of the 500 infants who underwent TH, 294 (59%) and 206 (41%) had esophageal and rectal temperature monitoring, respectively. There were no differences in death or NDI, seizures, or evidence of injury on magnetic resonance imaging between the 2 groups. Infants treated with TH and rectal temperature monitoring had lower odds of overcooling (OR 0.52, 95% CI 0.34-0.80) and lower odds of hypotension (OR 0.57, 95% CI 0.39-0.84) compared with those with esophageal temperature monitoring. CONCLUSIONS: Although infants undergoing TH with esophageal monitoring were more likely to experience overcooling and hypotension, the rate of death or NDI was similar whether esophageal monitoring or rectal temperature monitoring was used. Further studies are needed to investigate whether esophageal temperature monitoring during TH is associated with an increased risk of overcooling and hypotension.

Time to Reaching Target Cooling Temperature and 2-year Outcomes in Infants with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To determine if time to reaching target temperature (TT) is associated with death or neurodevelopmental impairment (NDI) at 2 years of age in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Newborn infants ≥36 weeks of gestation diagnosed with moderate or severe HIE and treated with therapeutic hypothermia were stratified based on time at which TT was reached, defined as early (ie, ≤4 hours of age) or late (>4 hours of age). Primary outcomes were death or NDI. Secondary outcomes included neurodevelopmental assessment with Bayley Scales of Infant and Toddler Development, third edition (BSID-III) at age 2. RESULTS: Among 500 infants, the median time to reaching TT was 4.3 hours (IWR, 3.2-5.7 hours). Infants in early TT group (n = 211 [42%]) compared with the late TT group (n = 289 [58%]) were more likely to be inborn (23% vs 13%; P < .001) and have severe HIE (28% vs 19%; P = .03). The early and late TT groups did not differ in the primary outcome of death or any NDI (adjusted RR, 1.05; 95% CI, 0.85-0.30; P = .62). Among survivors, neurodevelopmental outcomes did not differ significantly in the 2 groups (adjusted mean difference in Bayley Scales of Infant Development-III scores: cognitive, -2.8 [95% CI, -6.1 to 0.5], language -3.3 [95% CI, -7.4 to 0.8], and motor -3.5 [95% CI, -7.3 to 0.3]). CONCLUSIONS: In infants with HIE, time to reach TT is not independently associated with risk of death or NDI at age 2 years. Among survivors, developmental outcomes are similar between those who reached TT at <4 and ≥4 hours of age. TRIAL REGISTRATION: High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL); NCT02811263; https://beta. CLINICALTRIALS: gov/study/NCT02811263.

Relationship of Neonatal Seizure Burden Before Treatment and Response to Initial Antiseizure Medication.

OBJECTIVE: To assess among a cohort of neonates with hypoxic-ischemic encephalopathy (HIE) the association of pretreatment maximal hourly seizure burden and total seizure duration with successful response to initial antiseizure medication (ASM). STUDY DESIGN: This was a retrospective review of data collected from infants enrolled in the HEAL Trial (NCT02811263) between January 25, 2017, and October 9, 2019. We evaluated a cohort of neonates born at ≥36 weeks of gestation with moderate-to-severe HIE who underwent continuous electroencephalogram monitoring and had acute symptomatic seizures. Poisson regression analyzed associations between (1) pretreatment maximal hourly seizure burden, (2) pretreatment total seizure duration, (3) time from first seizure to initial ASM, and (4) successful response to initial ASM. RESULTS: Among 39 neonates meeting inclusion criteria, greater pretreatment maximal hourly seizure burden was associated with lower chance of successful response to initial ASM (adjusted relative risk for each 5-minute increase in seizure burden 0.83, 95% CI 0.69-0.99). There was no association between pretreatment total seizure duration and chance of successful response. Shorter time-to-treatment was paradoxically associated with lower chance of successful response to treatment, although this difference was small in magnitude (relative risk 1.007, 95% CI 1.003-1.010). CONCLUSIONS: Maximal seizure burden may be more important than other, more commonly used measures in predicting response to acute seizure treatments.

Handgrip strength as a predictor of 1­year mortality after hip fracture surgery in the Colombian Andes Mountains.

Hip fracture is a public health problem recognized worldwide and a potentially catastrophic threat for older persons, even carrying a demonstrated excess of mortality. Handgrip strength (HGS) has been identified as a predictor of different outcomes (mainly mortality and disability) in several groups with hip fracture. PURPOSE: The aim of this study was to determine the association between low HGS and 1-year mortality in a cohort of older patients over 60 years old with fragility hip fractures who underwent surgery in the Colombian Andes Mountains. METHODS: A total of 126 patients (median age 81 years, women 77%) with a fragility hip fracture during 2019-2020 were admitted to a tertiary care hospital. HGS was measured using dynamometry upon admission, and data about sociodemographic, clinical and functional, laboratory, and surgical intervention variables were collected. They were followed up until discharge. Those who survived were contacted by telephone at one, three, and 12 months. Bivariate, multivariate, and Kaplan-Meier analyses with survival curves were performed. RESULTS: The prevalence of low HGS in the cohort was 71.4%, and these patients were older, had poorer functional and cognitive status, higher comorbidity, higher surgical risk, time from admission to surgery > 72 h, lower hemoglobin and albumin values, and greater intra-hospital mortality at one and three months (all p < 0.01). Mortality at one year in in patients with low HGS was 42.2% and 8.3% in those with normal HGS, with a statistically significant difference (p = 0.000). In the multivariate analysis, low HGS and dependent gait measured by Functional Ambulation Classification (FAC) were the factors affecting postoperative 1-year mortality in older adults with hip fractures. CONCLUSION: In this study of older people with fragility hip fractures, low HGS and dependent gait were independent predictive markers of 1-year mortality.

Perinatal arterial ischemic stroke diagnosed in infants receiving therapeutic hypothermia for hypoxic-ischemic encephalopathy.

BACKGROUND: Both perinatal arterial ischemic stroke (PAIS) and hypoxic-ischemic encephalopathy (HIE) can present with neonatal encephalopathy. We hypothesized that among infants undergoing therapeutic hypothermia, presence of PAIS is associated with a higher risk of seizures and a lower risk of persistent encephalopathy after rewarming. METHODS: We studied 473 infants with moderate or severe HIE enrolled in the HEAL Trial who received a brain MRI. We defined PAIS as focal ischemic infarct(s) within an arterial distribution, and HIE pattern of brain injury as central gray, peripheral watershed, or global injury. We compared the risk of seizures (clinically suspected or electrographic), and of an abnormal 5-day Sarnat exam, in infants with and without PAIS. RESULTS: PAIS was diagnosed in 21(4%) infants, most of whom (16/21, 76%) also had concurrent HIE pattern of brain injury. Infants with PAIS were more likely to have seizures (RR 2.4, CI 2.8-3.3) and persistent moderate or severe encephalopathy on 5-day Sarnat exam (RR 2.5, 95% CI 1.9-3.4). CONCLUSION: Among infants undergoing therapeutic hypothermia, PAIS typically occurs with concurrent HIE pattern brain injury. The higher rate of encephalopathy after rewarming in infants with PAIS may be due to the frequent co-existence of PAIS and HIE patterns of injury.

Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series).

The survival of preterm infants has steadily improved thanks to advances in perinatal and neonatal intensive clinical care. The focus is now on finding ways to improve morbidities, especially neurological outcomes. Although antenatal steroids and magnesium for preterm infants have become routine therapies, studies have mainly demonstrated short-term benefits for antenatal steroid therapy but limited evidence for impact on long-term neurodevelopmental outcomes. Further advances in neuroprotective and neurorestorative therapies, improved neuromonitoring modalities to optimize recruitment in trials, and improved biomarkers to assess the response to treatment are essential. Among the most promising agents, multipotential stem cells, immunomodulation, and anti-inflammatory therapies can improve neural outcomes in preclinical studies and are the subject of considerable ongoing research. In the meantime, bundles of care protecting and nurturing the brain in the neonatal intensive care unit and beyond should be widely implemented in an effort to limit injury and promote neuroplasticity. IMPACT: With improved survival of preterm infants due to improved antenatal and neonatal care, our focus must now be to improve long-term neurological and neurodevelopmental outcomes. This review details the multifactorial pathogenesis of preterm brain injury and neuroprotective strategies in use at present, including antenatal care, seizure management and non-pharmacological NICU care. We discuss treatment strategies that are being evaluated as potential interventions to improve the neurodevelopmental outcomes of infants born prematurely.

Delayed immune-related hepatitis after 24 months of pembrolizumab treatment: a case report and literature review.

Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1) pathway have revolutionized cancer immunotherapy by enhancing the immune system's ability to combat cancer cells. However, this innovative approach comes with a distinctive set of challenges, as these therapies can lead to immune-related adverse events (irAEs) due to their mechanism of action. The most common irAEs involve the skin, gastrointestinal tract, liver, endocrine system, and lungs. These events can range from mild skin rashes to severe colitis, pneumonitis, or even autoimmune organ damage. These adverse effects usually appear with an average of 5-15 weeks from the start of treatment depending on the affected organ. This article presents a case report of a delayed related-mediated hepatitis, after 24 months of treatment with pembrolizumab and almost 3 months after its termination, and a review of the scientific literature on cases of delayed immune-related hepatitis caused by anti-PD1. This case highlights the importance of monitoring patients treated with immune checkpoint inhibitors after cessation as a growing number of patients stop treatment due to achieving durable responses.

Ethnic diversity in Chilean blood groups: A comprehensive analysis of genotypes, phenotypes, alleles and the immunogenic potential of antigens in northern, southern and central regions.

BACKGROUND AND OBJECTIVES: The available information on blood groups in the Chilean population is derived from studies on aboriginal cohorts and routine serological test results. The purpose of this study is to conduct a comprehensive analysis of genotypes, phenotypes and blood group alleles in donors from northern, central and southern Chile using molecular methods. MATERIALS AND METHODS: Overall, 850 samples from donors in northern, central and southern Chile were genotyped. Allelic, genotypic and antigenic frequencies were calculated and compared among regions. Of these, 602 samples were analysed by haemagglutination, and discrepancies found between phenotypes and genotypes were investigated. The immunogenic potential of antigens was calculated by the Giblett equation, using the antigenic frequencies of donors from Santiago and the alloantibody frequencies of patients from the same region. RESULTS: Alleles of low prevalence, variant alleles and those responsible for the absence of high-prevalence antigens were found. Significant differences were observed between the antigenic frequencies of the three regions. Discrepancies between serologic and molecular results were mostly attributed to the molecular background affecting antigen expression. In the calculation of the immunogenic potential of antigens, the highest value was attributed to the Dia antigen. CONCLUSION: These findings represent the first molecular characterization of blood group antigens in Chileans. Our results highlight the necessity of using molecular tools to explore the genotypes underlying variant phenotypes, low-frequency antigens and antigens lacking specific antisera that cannot be detected by haemagglutination. Additionally, they emphasize the importance of understanding the distribution of blood groups among different populations.

Biosensing strategies using recombinant luminescent proteins and their use for food and environmental analysis.

Progress in synthetic biology and nanotechnology plays at present a major role in the fabrication of sophisticated and miniaturized analytical devices that provide the means to tackle the need for new tools and methods for environmental and food safety. Significant research efforts have led to biosensing experiments experiencing a remarkable growth with the development and application of recombinant luminescent proteins (RLPs) being at the core of this boost. Integrating RLPs into biosensors has resulted in highly versatile detection platforms. These platforms include luminescent enzyme-linked immunosorbent assays (ELISAs), bioluminescence resonance energy transfer (BRET)-based sensors, and genetically encoded luminescent biosensors. Increased signal-to-noise ratios, rapid response times, and the ability to monitor dynamic biological processes in live cells are advantages inherent to the approaches mentioned above. Furthermore, novel fusion proteins and optimized expression systems to improve their stability, brightness, and spectral properties have enhanced the performance and pertinence of luminescent biosensors in diverse fields. This review highlights recent progress in RLP-based biosensing, showcasing their implementation for monitoring different contaminants commonly found in food and environmental samples. Future perspectives and potential challenges in these two areas of interest are also addressed, providing a comprehensive overview of the current state and a forecast of the biosensing strategies using recombinant luminescent proteins to come.

The potential use of birds as bioindicators of suspended atmospheric microplastics and artificial fibers.

Microplastics (MPs) and artificial fibers (AFs) have been detected suspended tens of meters above ground level in the atmosphere, yet empirical data on them remain scarce. This study aimed to investigate the presence of MPs and AFs in the digestive and respiratory systems of two abundant bird species, the Common House Martin (Delichon urbicum) and the Common Swift (Apus apus), within the Community of Madrid, Spain. Given that these birds spend the majority of their lives airborne, engaging in activities such as mating and sleeping during flight, the research sought to assess the potential of using these bird species as bioindicators for suspended atmospheric MPs and AFs. Samples were obtained from necropsies of birds (N = 24) collected primarily between spring and summer from 2021 to 2023. Only individuals that died within the initial 24-hour period and had not been fed were selected for examination to avoid contamination. MPs and AFS were identified by micro-FTIR, characterized and quantified. Results revealed that 75 % of the sampled birds exhibited at least one MPs in their respiratory and/or digestive system. All identified MPs were fibers, with polyester (PES) being the most predominant (48 %), followed by acrylic fibers (ACR; 28 %), and polyethylene (PE; 18 %). The average concentrations in the respiratory system were 1.12 ± 0.45 MPs/specimen and 2.78 ± 1.04 AFs/specimen for Common Swift and 0.75 ± 0.30 MPs/specimen and 0.75 ± 0.36 AFs/specimen for House Martin. In the digestive system, these were 1.92 ± 0.72 MPs/specimen and 3.42 ± 0.69 AFs/specimen for Common Swift, and 1.34 ± 0.50 MPs/specimen and 1.39 ± 0.47 AFs/specimen for House Martin. Birds collected areas with high population density located in the direction of the prevailing winds showed a concentration of MPs significantly higher in the digestive system. Taken together, these findings confirmed the potential use of these birds as bioindicators for monitoring of suspended atmospheric MPs and AFs.

Contribution of the Medial Iliofemoral Ligament to Hip Stability After Total Hip Arthroplasty Through the Direct Anterior Approach.

BACKGROUND: Dislocation after total hip arthroplasty (THA) is a primary reason for THA revision. During THA through the direct anterior approach (DAA), the iliofemoral ligament, which provides the main resistance to external rotation (ER) of the hip, is commonly partially transected. We asked: (1) what is the contribution of the medial iliofemoral ligament to resisting ER after DAA THA? and (2) how much resistance to ER can be restored by repairing the ligament? METHODS: A fellowship-trained surgeon performed DAA THA on 9 cadaveric specimens. The specimens were computed tomography scanned before and after implantation. Prior to testing, the ER range of motion of each specimen to impingement in neutral and 10° of extension was computationally predicted. Each specimen was tested on a 6-degrees-of-freedom robotic manipulator. The pelvis was placed in neutral and 10° of extension. The femur was externally rotated until it reached the specimen's impingement target. Total ER torque was recorded with the medial iliofemoral ligament intact, after transecting the ligament, and after repair. Torque at extremes of motion was calculated for each condition. To isolate the contribution of the native ligament, the torque for the transected state was subtracted from both the native and repaired conditions. RESULTS: The medial iliofemoral ligament contributed an average of 68% (range, 34 to 87) of the total torque at the extreme of motion in neutral and 80% (58 to 97) in 10° of extension. The repaired ligament contributed 17% (1 to 54) of the total torque at the extreme of motion in neutral and 14% (5 to 38) in 10° of extension, restoring on average 18 to 25% of the native resistance against ER. CONCLUSIONS: The medial iliofemoral ligament was an important contributor to the hip torque at the extreme of motion during ER. Repairing the ligament restored a fraction of its ability to generate torque to resist ER.

An Anterior Spike Decreases Bone-Implant Micromotion in Cementless Tibial Baseplates for Total Knee Arthroplasty: A Biomechanical Study.

BACKGROUND: Cementless tibial baseplates in total knee arthroplasty include fixation features (eg, pegs, spikes, and keels) to ensure sufficient primary bone-implant stability. While the design of these features plays a fundamental role in biologic fixation, the effectiveness of anterior spikes in reducing bone-implant micromotion remains unclear. Therefore, we asked: Can an anterior spike reduce the bone-implant micromotion of cementless tibial implants? METHODS: We performed computational finite element analyses on 13 tibiae using the computed tomography scans of patients scheduled for primary total knee arthroplasty. The tibiae were virtually implanted with a cementless tibial baseplate with 2 designs of fixation of the baseplate: 2 pegs and 2 pegs with an anterior spike. We compared the bone-implant micromotion under the most demanding loads from stair ascent between both designs. RESULTS: Both fixation designs had peak micromotion at the anterior-lateral edge of the baseplate. The design with 2 pegs and an anterior spike had up to 15% lower peak micromotion and up to 14% more baseplate area with micromotions below the most conservative threshold for ingrowth, 20 µm, than the design with only 2 pegs. The greatest benefit of adding an anterior spike occurred for subjects who had the smallest area of tibial bone below the 20 µm threshold (ie, most at risk for failure to achieve bone ingrowth). CONCLUSIONS: An anteriorly placed spike for cementless tibial baseplates with 2 pegs can help decrease the bone-implant micromotion during stair ascent, especially for subjects with increased bone-implant micromotion and risk for bone ingrowth failure.

Clinical and Biomechanical Evaluation of Mid-Level Constrained and Posterior-Stabilized Polyethylene Inserts in Primary Total Knee Arthroplasty: An Analysis of 12,674 Cases.

BACKGROUND: Mid-level constraint polyethylene designs provide additional stability in total knee arthroplasty (TKA). The purposes of this study were to (1) compare the survivorship and reason for revision between mid-level inserts and posterior-stabilized (PS) used in primary TKA and (2) evaluate the biomechanical constraint characteristics of mid-level inserts. METHODS: We reviewed all cases of primary TKA performed at our institution from 2016 to 2019 using either PS or mid-level constrained inserts from 1 of 6 manufacturers. Data elements included patient demographics, implants, reasons for revision, and whether a manipulation under anesthesia was performed. We performed finite element analyses to quantify the varus/valgus and axial-rotation constraint of each mid-level constrained insert. A one-to-one propensity score matching was conducted between the patients with mid-level and PS inserts to match for variables, which yielded 2 cohorts of 3,479 patients. RESULTS: For 9,163 PS and 3,511 mid-level TKAs, survivorship free from all-cause revision was estimated up to 5 years and was lower for mid-level than PS inserts (92.7 versus 94.1%, respectively, P = .004). When comparing each company's mid-level insert to the same manufacturer's PS insert, we found no differences in all-cause revision rates (P ≥ .91) or revisions for mechanical problems (P ≥ .97). Using propensity score matching between mid-level and PS groups, no significant differences were found in rates of manipulation under anesthesia (P = .72), all-cause revision (P = .12), revision for aseptic loosening (P = .07), and revision for instability (P = .45). Finite element modeling demonstrated a range in varus/valgus constraint from ±1.1 to >5°, and a range in axial-rotation constraint from ±1.5 to ±11.5° among mid-level inserts. CONCLUSIONS: Despite wide biomechanical variations in varus/valgus and axial-rotation constraint, we found minimal differences in early survivorship rates between PS and mid-level constrained knees.

Is Tibial Bone Mineral Density Related to Sex, Age, Preoperative Alignment, or Fixation Method in Primary Total Knee Arthroplasty?

BACKGROUND: Cementless total knee arthroplasty (TKA) has regained interest for its potential for long-term biologic fixation. The density of the bone is related to its ability to resist static and cyclic loading and can affect long-term implant fixation; however, little is known about the density distribution of periarticular bone in TKA patients. Thus, we sought to characterize the bone mineral density (BMD) of the proximal tibia in TKA patients. METHODS: We included 42 women and 50 men (mean age 63 years, range: 50 to 87; mean body mass index 31.6, range: 20.5 to 49.1) who underwent robotic-assisted TKA and had preoperative computed tomography scans with a BMD calibration phantom. Using the robotic surgical plan, we computed the BMD distribution at 1 mm-spaced cross-sections parallel to the tibial cut from 2 mm above the cut to 10 mm below. The BMD was analyzed with respect to patient sex, age, preoperative alignment, and type of fixation. RESULTS: The BMD decreased from proximal to distal. The greatest changes occurred within ± 2 mm of the tibial cut. Age did not affect BMD for men; however, women between 60 and 70 years had higher BMD than women ≥ 70 years for the total cut (P = .03) and the medial half of the cut (P = .03). Cemented implants were used in 1 86-year-old man and 18 women (seven < 60 years, seven 60 to 70 years, and four ≥ 70 year old). We found only BMD differences between cemented or cementless fixation for women < 60 years. CONCLUSIONS: To our knowledge, this is the first study to characterize the preoperative BMD distribution in TKA patients relative to the intraoperative tibial cut. Our results indicate that while sex and age may be useful surrogates of BMD, the clinically relevant thresholds for cementless knees remain unclear, offering an area for future studies.

State of HIV costing in Latin America and the Caribbean: a systematic literature review.

Objectives: To summarize available data on unit costs for human immunodeficiency virus (HIV) testing, prevention, and care interventions in Latin America and the Caribbean. Methods: We conducted a systematic literature review of costing studies published between 2012 and 2024, and selected those reporting empirically measured costing data. The available data were categorized according to predefined intervention categories and compared by time and place. We also explored variations in unit costs by intervention type. Results: Of 1 746 studies identified, 22 met the inclusion criteria, which provided 103 unique unit cost estimates from nine countries. About 50% of the included studies were published between 2019 and 2021. Antiretroviral therapy services had the most cost data available (39% of unit costs), followed by inpatient care (27%) and HIV testing (24%). Considerable cost variations were observed both within and between interventions. Conclusions: Our analysis underscores the need for accurate and reliable cost data to support HIV budgeting and decision-making efforts. We identified several gaps in the availability of cost data and emphasize the importance of presenting results more effectively by incorporating key contextual variables. Given the challenges of shrinking budgets and sustainability risks, robust evidence is indispensable to inform priority setting and budget allocation for HIV services.

Carcinogenic, non-carcinogenic risk, and attributable cases to organochlorine pesticide exposure in women from Northern Mexico.

This study aimed to estimate the carcinogenic and non-carcinogenic risk as well as the attributable cases due to exposure to organochlorine pesticides (OCPs): hexachlorobenzene (HCB), dichlorophenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), heptachlor, and chlordane. From serum concentrations of pesticides of interest in a sample of 908 women from Northern Mexico, the risk for both cancer and non-cancer health effects was evaluated. The population attributable fraction (PAF) was also calculated based on summary association estimates between exposure to OCPs and different health events. Findings revealed that due to their OCP exposure slightly less than half of the women in the sample were at increased risk of developing non-cancerous diseases. Moreover, approximately 25% and 75% of participants were at risk of develop some type of cancer associated with their HCB and DDE concentrations, respectively. In addition, it was estimated that 40.5% of type 2 diabetes, 18.7% of endometriosis, and 23.1% of non-Hodgkin's lymphoma cases could have been prevented if women had not been exposed to these OCPs. Results suggest that the use of OCPs may have contributed to the disease burden in the study area and, based on the time required for these substances to be eliminated from the body, there are probably some women who are still at elevated risk of developing diseases associated to OCPs.