Multiple myeloma patients with a long remission after autologous hematopoietic stem cell transplantation.

Autologous stem cell transplantation (autoHCT) is considered standard of care for newly diagnosed multiple myeloma (MM). Although most patients eventually progress after autoHCT, a small proportion achieve a durable response. In this retrospective study we included 1576 patients, 244 (15%) of whom were long-term responders (LTR), defined as having a progression-free survival (PFS) of ≥8 years after transplant. Patients in the LTR group were younger than the non-LTR group (median age 58.4 vs. 59.5 years; p = 0.012), less likely to have high-risk cytogenetics (4% vs. 14%; p < 0.001), more often had <50% bone marrow plasma cells (67% vs. 58%; p = 0.018) and R-ISS stage I disease (43% vs. 34%). More patients in the LTR group received post-transplant maintenance (63% vs. 52%; p = 0.002). Patients in the LTR group had higher rates of complete response (CR) at day100 (41% vs. 27%; p < 0.001) and at best post-transplant response (70% vs. 37%; p < 0.001), compared to the non-LTR group. Patients in the LTR groups had a median PFS of 169.3 months and the median overall survival (OS) had not been reached. The leading cause of death in the LTR was disease progression. In conclusion, 15% of patients in the cohort were LTR after upfront autoHCT, with distinct characteristics and a median PFS of more than 14 years.

Receipt of Diabetes Specialty Care and Management Services by Older Adults With Diabetes in the United States, 2015-2019: An Analysis of Medicare Fee-for-Service Claims.

OBJECTIVE: We characterized the receipt of diabetes specialty care and management services among older adults with diabetes. RESEARCH DESIGN AND METHODS: Using a 20% random sample of fee-for-service Medicare beneficiaries aged ≥65 years, we analyzed cohorts of type 1 diabetes (T1D) or type 2 diabetes (T2D) with history of severe hypoglycemia (HoH), and all other T2D annually from 2015 to 2019. Outcomes were receipt of office-based endocrinology care, diabetes education, outpatient diabetes health services, excluding those provided in primary care, and any of the aforementioned services. RESULTS: In the T1D cohort, receipt of endocrinology care and any service increased from 25.9% and 29.2% in 2015 to 32.7% and 37.4% in 2019, respectively. In the T2D with HoH cohort, receipt of endocrinology care and any service was 13.9% and 16.4% in 2015, with minimal increases. Age, race/ethnicity, residential setting, and income were associated with receiving care. CONCLUSIONS: These findings suggest that many older adults may not receive specialty diabetes care and underscore health disparities.

Early and rapid development of bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation.

Bronchiolitis obliterans (BO) is a form of graft-versus-host disease (GVHD) in the lung and manifests as moderate to severe airflow obstruction after hematopoietic stem cell transplantation (HCT). New-onset airflow obstruction on spirometry is considered diagnostic of bronchiolitis obliterans syndrome (BOS). BOS affects about 5% of all HCT recipients. In general, BO is thought of as a late complication of HCT, usually occurring after day 100 post-transplantation. However, the onset of airflow obstruction can be rapid and is most often irreversible even with treatment. We describe a patient who rapidly developed severe airflow obstruction less than one month after transplantation following the development of upper airway symptoms. Despite aggressive immunosuppression, the patient had no improvement in airflow obstruction. We hypothesize that early screening and treatment may help prevent BOS after HCT.

Coordinated nasal mucosa-mediated immunity accelerates recovery from COVID-19.

Introduction: Understanding the interplay of immune mediators in relation to clinical outcomes during acute infection has the potential to highlight immune networks critical to symptom recovery. The objective of the present study was to elucidate the immune networks critical to early symptom resolution following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: In a community-based randomised clinical trial comparing inhaled budesonide against usual care in 139 participants with early onset SARS-CoV-2 (the STOIC study; clinicaltrials.gov identifier NCT04416399), significant clinical deterioration (reported need for urgent care, emergency department visit, hospitalisation: the primary outcome), self-reported symptom severity (Influenza Patient-Reported Outcome questionnaire) and immune mediator networks were assessed. Immune mediator networks were determined using pre-defined mathematical modelling of immune mediators, determined by the Meso Scale Discovery U-Plex platform, within the first 7 days of SARS-CoV-2 infection compared to 22 healthy controls. Results: Interferon- and chemokine-dominant networks were associated with high viral burden. Elevated levels of the mucosal network (chemokine (C-C motif) ligand (CCL)13, CCL17, interleukin (IL)-33, IL-5, IL-4, CCL26, IL-2, IL-12 and granulocyte-macrophage colony-stimulating factor) was associated with a mean 3.7-day quicker recovery time, with no primary outcome events, irrespective of treatment arm. This mucosal network was associated with initial nasal and throat symptoms at day 0. Conclusion: A nasal immune network is critical to accelerated recovery and improved patient outcomes in community-acquired viral infections. Overall, early prognostication and treatments aimed at inducing epithelial responses may prove clinically beneficial in enhancing early host response to virus.

Assessment of Open Surgery Suturing Skill: Image-based Metrics Using Computer Vision.

OBJECTIVE: This paper presents a computer vision algorithm for extraction of image-based metrics for suturing skill assessment and the corresponding results from an experimental study of resident and attending surgeons. DESIGN: A suturing simulator that adapts the radial suturing task from the Fundamentals of Vascular Surgery (FVS) skills assessment is used to collect data. The simulator includes a camera positioned under the suturing membrane, which records needle and thread movement during the suturing task. A computer vision algorithm processes the video data and extracts objective metrics inspired by expert surgeons' recommended best practice, to "follow the curvature of the needle." PARTICIPANTS AND RESULTS: Experimental data from a study involving subjects with various levels of suturing expertise (attending surgeons and surgery residents) are presented. Analysis shows that attendings and residents had statistically different performance on 6 of 9 image-based metrics, including the four new metrics introduced in this paper: Needle Tip Path Length, Needle Swept Area, Needle Tip Area and Needle Sway Length. CONCLUSION AND SIGNIFICANCE: These image-based process metrics may be represented graphically in a manner conducive to training. The results demonstrate the potential of image-based metrics for assessment and training of suturing skill in open surgery.

Exploring Anabolic Androgenic Steroid Use Among Cisgender Gay, Bisexual, and Queer Men.

Importance: Anabolic androgenic steroids (AAS) are disproportionately used by sexual minority men, with the physical and mental health implications of AAS use incompletely understood. Objective: To understand the reasons for use and health care needs of gay, bisexual, and queer cisgender men using AAS. Design, Setting, and Participants: This qualitative study was conducted from November 2021 to May 2023 using self-administered questionnaires and semistructured interviews that were transcribed and coded using reflexive thematic analysis. Participants were recruited through convenience and snowball sampling from lesbian, gay, bisexual, transgender, and queer clinical centers in New York, New York, as well as through online platforms. All patients self-identified as cisgender and gay, bisexual, or queer. Exposures: History of nonprescribed AAS use for a minimum of 8 consecutive weeks was required. Main Outcomes and Measures: The primary outcomes were reasons for and health implications of AAS use and interactions with health care practitioners, as determined through interviews. Interview transcripts were collected and analyzed. Results: Thematic saturation was reached after interviews with 12 male participants (mean [SD] age, 44 [11] years), with the majority of participants identifying as gay (10 participants [83%]), White non-Hispanic (9 participants [75%]), being in their 30s and 40s (9 participants [75%]), holding a bachelor's degree or higher (11 participants [92%]), and having used steroids for a mean (SD) of 7.5 (7.1) years. One participant (8%) self-identified as Black, and 2 (17%) identified as Hispanic. Seven men (58%) met the criteria for muscle dysmorphia on screening. Nine overarching themes were found, including internal and external motivators for initial use, continued use because of effectiveness or fear of losses, intensive personal research, physical and emotional harms experienced from use, using community-based harm reduction techniques, frustration with interactions with the medical community focused on AAS cessation, and concerns around the illegality of AAS. Conclusions and Relevance: In this qualitative study, AAS use among cisgender gay, bisexual, and queer men was found to be associated with multifactorial motivators, including a likely AAS use disorder and muscle dysmorphia. Despite all participants experiencing harms from use, men seeking medical help found insufficient support with practitioners insistent on AAS cessation and, thus, developed their own harm reduction techniques. Further research is needed to assess the utility of practitioner education efforts, the safety and efficacy of community-developed harm reduction methods, and the impact of AAS decriminalization on health care outcomes for this patient population.

Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.

A rapid host-protein test for differentiating bacterial from viral infection: Apollo diagnostic accuracy study.

Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC). Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up. Results: Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99). Conclusions: MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making.

Ligand Effects on the Spin Relaxation Dynamics and Coherent Manipulation of Organometallic La(II) Potential Qudits.

We present pulsed electron paramagnetic resonance (EPR) studies on three La(II) complexes, [K(2.2.2-cryptand)][La(Cp')3] (1), [K(2.2.2-cryptand)][La(Cp″)3] (2), and [K(2.2.2-cryptand)][La(Cptt)3] (3), which feature cyclopentadienyl derivatives as ligands [Cp' = C5H4SiMe3; Cp″ = C5H3(SiMe3)2; Cptt = C5H3(CMe3)2] and display a C3 symmetry. Long spin-lattice relaxation (T1) and phase memory (Tm) times are observed for all three compounds, but with significant variation in T1 among 1-3, with 3 being the slowest relaxing due to higher s-character of the SOMO. The dephasing times can be extended by more than an order of magnitude via dynamical decoupling experiments using a Carr-Purcell-Meiboom-Gill (CPMG) sequence, reaching 161 µs (5 K) for 3. Coherent spin manipulation is performed by the observation of Rabi quantum oscillations up to 80 K in this nuclear spin-rich environment (1H, 13C, and 29Si). The high nuclear spin of 139La (I = 7/2), and the ability to coherently manipulate all eight hyperfine transitions, makes these molecules promising candidates for application as qudits (multilevel quantum systems featuring d quantum states; d >2) for performing quantum operations within a single molecule. Application of HYSCORE techniques allows us to quantify the electron spin density at ligand nuclei and interrogate the role of functional groups to the electron spin relaxation properties.

The impact of emotion regulation and dyadic coping within posttraumatic stress symptoms and risky drinking patterns on relationship distress among trauma-exposed individuals.

Individuals with posttraumatic stress symptoms (PTSS) often consume alcohol to manage PTSS-related discomfort, which can negatively impact individual and interpersonal functioning. Processes including emotion regulation and dyadic coping may influence the effects of PTSS and drinking patterns on relationship functioning. The present study examined how PTSS and risky drinking may function through the associations between maladaptive individual and interpersonal coping strategies and relationship distress among trauma-exposed individuals. Participants were 237 adults in a romantic relationship who endorsed lifetime trauma exposure and alcohol consumption within the past year and completed an online battery of self-report measures. Path analyses showed mixed support for the hypothesized theoretical causal model. PTSS was associated with maladaptive emotion regulation, ß = .537, p = .010, and negative dyadic coping, ß = .264, p = .009, whereas risky drinking was only related to negative dyadic coping, ß = .193, p = .024. Negative dyadic coping was significant in the pathways between PTSS and relationship distress, ß = .021, p = .009, and risky drinking and relationship distress, ß = .030, p = .014. Exploratory analyses based on trauma type did not significantly change the overall model; however, a direct path suggested PTSS may have a stronger negative impact on relationship distress among individuals who experienced assault trauma (e.g., physical or sexual assault), ß = .340, p = .012. Findings highlight the interrelations among intra- and interpersonal regulation and provide clinical targets of maladaptive emotion regulation and dyadic coping strategies for individuals with PTSS and harmful drinking.

Intranasal insulin treatment ameliorates spatial memory, muscular strength, and frailty deficits in 5xFAD mice.

The 5xFAD mouse model shows age-related weight loss as well as cognitive and motor deficits. Metabolic dysregulation, especially impaired insulin signaling, is also present in AD. This study examined whether intranasal delivery of insulin (INI) at low (0.875 U) or high (1.750 U) doses would ameliorate these deficits compared to saline in 10-month-old female 5xFAD and B6SJL wildtype (WT) mice. INI increased forelimb grip strength in the wire hang test in 5xFAD mice in a dose-dependent manner but did not improve the performance of 5xFAD mice on the balance beam. High INI doses reduced frailty scores in 5xFAD mice and improved spatial memory in both acquisition and reversal probe trials in the Morris water maze. INI increased swim speed in 5xFAD mice but had no effect on object recognition memory or working memory in the spontaneous alternation task, nor did it improve memory in the contextual or cued fear memory tasks. High doses of insulin increased the liver, spleen, and kidney weights and reduced brown adipose tissue weights. P-Akt signaling in the hippocampus was increased by insulin in a dose-dependent manner. Altogether, INI increased strength, reduced frailty scores, and improved visual spatial memory. Hypoglycemia was not present after INI, however alterations in tissue and organ weights were present. These results are novel and important as they indicate that intra-nasal insulin can reverse cognitive, motor and frailty deficits found in this mouse model of AD.

Impact of the COVID-19 pandemic on type 2 diabetes care and factors associated with care disruption in Kenya and Tanzania.

BACKGROUND: The COVID-19 pandemic affected healthcare delivery globally, impacting care access and delivery of essential services. OBJECTIVES: We investigated the pandemic's impact on care for patients with type 2 diabetes and factors associated with care disruption in Kenya and Tanzania. METHODS: A cross-sectional study was conducted among adults diagnosed with diabetes pre-COVID-19. Data were collected in February-April 2022 reflecting experiences at two time-points, three months before and the three months most affected by the COVID-19 pandemic. A questionnaire captured data on blood glucose testing, changes in medication prescription and access, and healthcare provider access. RESULTS: We recruited 1000 participants (500/country). Diabetes care was disrupted in both countries, with 34.8% and 32.8% of the participants reporting change in place and frequency of testing in Kenya, respectively. In Tanzania, 12.4% and 17.8% reported changes in location and frequency of glucose testing, respectively. The number of health facility visits declined, 14.4% (p < 0.001) in Kenya and 5.6% (p = 0.001) in Tanzania. In Kenya, there was a higher likelihood of severe care disruption among insured patients (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI][1.05-2.34]; p = 0.029) and a lower likelihood among patients residing in rural areas (aOR, 0.35[95%CI, 0.22-0.58]; p < 0.001). Tanzania had a lower likelihood of severe disruption among insured patients (aOR, 0.51[95%CI, 0.33-0.79]; p = 0.003) but higher likelihood among patients with low economic status (aOR, 1.81[95%CI, 1.14-2.88]; p = 0.011). CONCLUSIONS: COVID-19 disrupted diabetes care more in Kenya than Tanzania. Health systems and emergency preparedness should be strengthened to ensure continuity of service provision for patients with diabetes.

Main findings: The COVID-19 pandemic disrupted diabetes care in Kenya and Tanzania resulting in changes in place and frequency of blood glucose testing, medication prescribed (less oral hypoglycaemics and more insulin), fewer health facility visits and more difficulty accessing healthcare providers.Added knowledge: This study quantifies the impact of the COVID-19 pandemic on diabetes care in Kenya and Tanzania, and describes the factors associated with care disruption in both countries.Global health impact for policy and action: Evidence on diabetes care disruption is useful in making plans and policies responsive to the needs of diabetes patients during pandemics or related emergency situations.

Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.

The spectinamides are novel, narrow-spectrum semisynthetic analogs of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis . Spectinamides, including lead MBX-4888A (Lee-1810), exhibit promising therapeutic profiles in mice, as single drugs and as partner agents with other anti-tuberculosis antibiotics including rifampin and/or pyrazinamide. To demonstrate that this translates to more effective cure, we first confirmed the role of rifampin, with or without pyrazinamide, as essential to achieve effective bactericidal responses and sterilizing cure in the current standard of care regimen in chronically infected C3HeB/FeJ mice compared to BALB/c mice. Thus, demonstrating added value in testing clinically relevant regimens in murine models of increasing pathologic complexity. Next we show that MBX-4888A, given by injection with the front-line standard of care regimen, is treatment shortening in multiple murine tuberculosis infection models. The positive treatment responses to MBX-4888A combination therapy in multiple mouse models including mice exhibiting advanced pulmonary disease can be attributed to favorable distribution in tissues and lesions, retention in caseum, along with favorable effects with rifampin and pyrazinamide under conditions achieved in necrotic lesions. This study also provides an additional data point regarding the safety and tolerability of spectinamide MBX-4888A in long-term murine efficacy studies.

Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

Characterisation of the morphology of surface-assembled Au nanoclusters on amorphous carbon.

In this study, aberration-corrected scanning transmission electron microscopy is employed to investigate the morphology of Au clusters formed from the aggregation of single atoms sputtered onto an amorphous carbon surface. The morphologies of surface-assembled clusters of N > 100 atoms are referenced against the morphologies of size-selected clusters determined from previously published results. We observe that surface-assembled clusters (at the conditions employed here) are approximately spherical in shape. The structural isomers of the imaged clusters have also been identified, and the distribution of structural types is broadly in agreement with those from size-selected cluster deposition sources. For clusters of approximately 147 atoms, we find a preference for icosahedra over decahedra and truncated octahedra, but at this size there is a high proportion of unidentified/amorphous structures. At around 309 atoms, we find a preference for decahedra over icosahedra and truncated octahedra, but over half the structures remain unidentifiable/amorphous. For sizes above approximately 561 atoms we are able to identify most of the structures, and find decahedra are still the most favoured, although in competition with single-crystal fcc morphologies. The similarity in structure between surface-assembled and size-selected clusters from a cluster source provides evidence of the relevance of size-selected cluster studies to clusters synthesised by other, industrially relevant, methodologies.

LUMiC Endoprosthetic Reconstruction of Periacetabular Tumor Defects: A Multicenter Follow-up Study.

BACKGROUND: We previously reported promising early results for periacetabular tumor reconstructions using the LUMiC prosthesis. The current study evaluates mid-term complications, revision rates, cumulative incidence of implant revision, and risk factors for complications in a multicenter cohort. METHODS: We assessed patients in whom a tumor defect after type P1b+2, P2, P2+3, or P1b+2+3 internal hemipelvectomy was reconstructed with a LUMiC prosthesis during the period of 2008 to 2022. Complications were reported according to the Henderson classification. Competing risks models were used to estimate the cumulative incidence of implant revision for mechanical and nonmechanical reasons, and reoperations for any complication. Cox models were used to study the effect of risk factors on dislocation and infection. RESULTS: One hundred and sixty-six patients (median follow-up, 4.2 years [interquartile range, 2.6 to 7.6 years]) were included. A total of 114 (69%) were treated for a primary malignant tumor, 46 (28%) for metastatic carcinoma, 5 (3%) for a benign aggressive lesion, and 1 (1%) for another reason. One hundred and sixty-five reoperations were performed in 82 (49%) of the patients; 104 (63%) of the reoperations were within 6 months. Thirty-two (19%) of 166 implants were revised: 13 (8%) for mechanical reasons, mainly dislocation (n = 5, 3%), and 19 (11%) for nonmechanical reasons, mainly periprosthetic joint infection (PJI) (n = 15, 9%). The cumulative incidences of revision for mechanical reasons and PJI (Henderson 1 to 4) at 2, 5, and 10 years were 11% (95% confidence interval [CI], 7% to 17%), 18% (12% to 25%), and 24% (16% to 33%), respectively. Previous surgery at the same site was associated with an increased dislocation risk (cause-specific hazard ratio [HRCS], 3.0 [95% CI, 1.5 to 6.4]; p < 0.01), and resections involving the P3 region were associated with an increased infection risk (HRCS, 2.5 [95% CI, 1.4 to 4.7]; p < 0.01). CONCLUSIONS: Despite a substantial reoperation risk, the LUMiC prosthesis demonstrated its durability in the mid-term, with a low mechanical revision rate and most patients retaining their primary implant. Most complications occur in the first postoperative months. Patients with previous surgery at the same site had an increased dislocation risk and might benefit from more conservative rehabilitation and aftercare. Measures should be aimed at reducing the PJI risk, especially in resections involving the P3 region. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Neither injury induced macrophages within the nerve, nor the environment created by Wallerian degeneration is necessary for enhanced in vivo axon regeneration after peripheral nerve injury.

BACKGROUND: Since the 1990s, evidence has accumulated that macrophages promote peripheral nerve regeneration and are required for enhancing regeneration in the conditioning lesion (CL) response. After a sciatic nerve injury, macrophages accumulate in the injury site, the nerve distal to that site, and the axotomized dorsal root ganglia (DRGs). In the peripheral nervous system, as in other tissues, the macrophage response is derived from both resident macrophages and recruited monocyte-derived macrophages (MDMs). Unresolved questions are: at which sites do macrophages enhance nerve regeneration, and is a particular population needed. METHODS: Ccr2 knock-out (KO) and Ccr2gfp/gfp knock-in/KO mice were used to prevent MDM recruitment. Using these strains in a sciatic CL paradigm, we examined the necessity of MDMs and residents for CL-enhanced regeneration in vivo and characterized injury-induced nerve inflammation. CL paradigm variants, including the addition of pharmacological macrophage depletion methods, tested the role of various macrophage populations in initiating or sustaining the CL response. In vivo regeneration, measured from bilateral proximal test lesions (TLs) after 2 d, and macrophages were quantified by immunofluorescent staining. RESULTS: Peripheral CL-enhanced regeneration was equivalent between crush and transection CLs and was sustained for 28 days in both Ccr2 KO and WT mice despite MDM depletion. Similarly, the central CL response measured in dorsal roots was unchanged in Ccr2 KO mice. Macrophages at both the TL and CL, but not between them, stained for the pro-regenerative marker, arginase 1. TL macrophages were primarily CCR2-dependent MDMs and nearly absent in Ccr2 KO and Ccr2gfp/gfp KO mice. However, there were only slightly fewer Arg1+ macrophages in CCR2 null CLs than controls due to resident macrophage compensation. Zymosan injection into an intact WT sciatic nerve recruited Arg1+ macrophages but did not enhance regeneration. Finally, clodronate injection into Ccr2gfp KO CLs dramatically reduced CL macrophages. Combined with the Ccr2gfp KO background, depleting MDMs and TL macrophages, and a transection CL, physically removing the distal nerve environment, nearly all macrophages in the nerve were removed, yet CL-enhanced regeneration was not impaired. CONCLUSIONS: Macrophages in the sciatic nerve are neither necessary nor sufficient to produce a CL response.

Considering context: Current relationship satisfaction in a second-generation model of men's physical intimate partner violence.

Despite a half-century of scholarship devoted to explicating and disrupting the intergenerational transmission of family violence, it remains a prominent and destructive social force in the United States. Theoretical models have posited a variety of historical and concurrent risk and protective factors implicated in the trajectory from childhood violence exposure to adult perpetration. Using a second-generation model of intimate partner violence (IPV), we integrated social learning and attachment conceptualizations to examine pathways from family-of-origin violence to IPV perpetration among adult men. A sample of mixed-sex couples (N = 233) completed self-report measures related to social learning and attachment-based factors (e.g., violence in past relationships, child exposure, IPV attitudes, adult attachment) and participated in a 10-min conversation about a desired area for change in their relationship. Following, each partner participated in a video-mediated-recall procedure assessing their anger volatility and eliciting attributions of their partners' behavior. We tested mediation pathways (consistent with social learning and attachment theories) between violence in men's families of origin and their adult IPV perpetration as a function of relationship satisfaction. The proposed model fit the data well (CFI = 0.95) but had notable modifications from the hypothesized model. Generally, social-learning pathways were more consistent with the data. Relationship satisfaction interacted with some parameters. Results support theoretical advances in understanding IPV. Although exposure to violence in men's family of origin confers risk for later IPV, and a social learning developmental pathway is consistent with results, some of these effects are altered by relationship context.

Effect of human H3N2 influenza virus reassortment on influenza incidence and severity during the 2017-18 influenza season in the USA: a retrospective observational genomic analysis.

BACKGROUND: During the 2017-18 influenza season in the USA, there was a high incidence of influenza illness and mortality. However, no apparent antigenic change was identified in the dominant H3N2 viruses, and the severity of the season could not be solely attributed to a vaccine mismatch. We aimed to investigate whether the altered virus properties resulting from gene reassortment were underlying causes of the increased case number and disease severity associated with the 2017-18 influenza season. METHODS: Samples included were collected from patients with influenza who were prospectively recruited during the 2016-17 and 2017-18 influenza seasons at the Johns Hopkins Hospital Emergency Departments in Baltimore, MD, USA, as well as from archived samples from Johns Hopkins Health System sites. Among 647 recruited patients with influenza A virus infection, 411 patients with whole-genome sequences were available in the Johns Hopkins Center of Excellence for Influenza Research and Surveillance network during the 2016-17 and 2017-18 seasons. Phylogenetic trees were constructed based on viral whole-genome sequences. Representative viral isolates of the two seasons were characterised in immortalised cell lines and human nasal epithelial cell cultures, and patients' demographic data and clinical outcomes were analysed. FINDINGS: Unique H3N2 reassortment events were observed, resulting in two predominant strains in the 2017-18 season: HA clade 3C.2a2 and clade 3C.3a, which had novel gene segment constellations containing gene segments from HA clade 3C.2a1 viruses. The reassortant re3C.2a2 viruses replicated with faster kinetics and to a higher peak titre compared with the parental 3C.2a2 and 3C.2a1 viruses (48 h vs 72 h). Furthermore, patients infected with reassortant 3C.2a2 viruses had higher Influenza Severity Scores than patients infected with the parental 3C.2a2 viruses (median 3·00 [IQR 1·00-4·00] vs 1·50 [1·00-2·00]; p=0·018). INTERPRETATION: Our findings suggest that the increased severity of the 2017-18 influenza season was due in part to two intrasubtypes, cocirculating H3N2 reassortant viruses with fitness advantages over the parental viruses. This information could help inform future vaccine development and public health policies. FUNDING: The Center of Excellence for Influenza Research and Response in the US, National Science and Technology Council, and Chang Gung Memorial Hospital in Taiwan.