Glomus tumor with malignant features: A case report and review of the literature.

Glomus tumors are rare mesenchymal neoplasms of the subcutaneous tissue, most frequently found in the distal extremities. They are typically benign, but malignant glomus tumors have been described in the literature. Here we present a patient found to have a unilateral renal mass with pathology displaying a primary renal glomus tumor with malignant features. Review of the literature reveals only three cases of malignant glomus tumors and five glomus tumors with malignant potential. As such, previous initial presentations, current criteria for glomus tumor malignancy, and previous treatment outcomes of these cases were reviewed.

Intramedullary Threaded Nail Fixation of Distal Ulnar Fractures: The Surgical Technique and Case Series.

BACKGROUND:  To describe the surgical technique of non-compressive intramedullary threaded nail (IMTN) fixation of distal ulnar neck fractures and present the clinical and radiographic outcomes of four patients treated with this novel technique. METHODS: At a single Level 1 Trauma Center, a retrospective review was conducted for patients with distal ulnar neck fractures treated with retrograde IMTN between 2022 and 2024. Exclusion criteria included inadequate follow-up. A single surgeon performed all procedures using percutaneous retrograde IMTN fixation through the central disc of the triangular fibrocartilage complex (TFCC). Patients initiated a range of motion (ROM) protocol two weeks post-operatively. Post-operative radiographic images were used to calculate the ratio of IMTN diameter to the distal ulnar medullary isthmus diameter proximal to the fracture site. Radiographic changes in displacement, angulation, and ulnar variance were calculated between the first and last follow-up radiographs. Functional outcomes including grip strength and ROM were collected. RESULTS: Four patients with distal ulnar neck fractures were treated with retrograde IMTN between 2022 and 2024. They were followed for a minimum of three months post-operatively. All were female with an average age of 65 years. All distal ulna fractures were associated with operatively treated intraarticular distal radius fractures. All patients were treated with 75 mm length and 4.5 mm diameter IMTNs. IMTN-to-Isthmus ratio was greater than 60% in all cases. Average radiographic displacement and angulation were unchanged at the final follow-up. The average ulnar variance increased by 1.2 mm. At the final follow-up, there were no post-operative complications. No cases demonstrated ulnar-sided wrist pain, nonunion, or required revision surgery. CONCLUSIONS: Retrograde IMTN fixation is a novel surgical technique for the treatment of distal ulnar neck fractures. We found limited but promising post-operative radiographic and functional outcomes in our patients without reported ulnar-sided wrist pain, nonunion, or need for hardware removal.

Molecular Mechanisms for Iron Uptake and Homeostasis in Marine Eukaryotic Phytoplankton.

The micronutrient iron is essential for phytoplankton growth due to its central role in a wide variety of key metabolic processes including photosynthesis and nitrate assimilation. As a result of scarce bioavailable iron in seawater, marine primary productivity is often iron-limited with future iron supplies remaining uncertain. Although evolutionary constraints resulted in high cellular iron requirements, phytoplankton evolved diverse mechanisms that enable uptake of multiple forms of iron, storage of iron over short and long timescales, and modulation of their iron requirement under stress. Genomics continues to increase our understanding of iron-related proteins that are homologous to those characterized in other model organisms, while recently, molecular and cell biology is revealing unique genes and processes with connections to iron acquisition or use. Moreover, there are an increasing number of examples showing the interplay between iron uptake and extracellular processes such as boundary layer chemistry and microbial interactions.

Metatranscriptomic response of deep ocean microbial populations to infusions of oil and/or synthetic chemical dispersant.

Oil spills are a frequent perturbation to the marine environment that has rapid and significant impacts on the local microbiome. Previous studies have shown that exposure to synthetic dispersant alone did not enhance heterotrophic microbial activity or oxidation rates of specific hydrocarbon components but increased the abundance of some taxa (e.g., Colwellia). In contrast, exposure to oil, but not dispersants, increased the abundance of other taxa (e.g., Marinobacter) and stimulated hydrocarbon oxidation rates. Here, we advance these findings by interpreting metatranscriptomic data from this experiment to explore how and why specific components of the microbial community responded to distinct organic carbon exposure regimes. Dispersant alone was selected for a unique community and for dominant organisms that reflected treatment- and time-dependent responses. Dispersant amendment also led to diverging functional profiles among the different treatments. Similarly, oil alone was selected for a community that was distinct from treatments amended with dispersants. The presence of oil and dispersants with added nutrients led to substantial differences in microbial responses, likely suggesting increased fitness driven by the presence of additional inorganic nutrients. The oil-only additions led to a marked increase in the expression of phages, prophages, transposable elements, and plasmids (PPTEPs), suggesting that aspects of microbial community response to oil are driven by the "mobilome," potentially through viral-associated regulation of metabolic pathways in ciliates and flagellates that would otherwise throttle the microbial community through grazing.IMPORTANCEMicrocosm experiments simulated the April 2010 Deepwater Horizon oil spill by applying oil and synthetic dispersants (Corexit EC9500A and EC9527A) to deep ocean water samples. The exposure regime revealed severe negative alterations in the treatments' heterotrophic microbial activity and hydrocarbon oxidation rates. We expanded these findings by exploring metatranscriptomic signatures of the microbial communities during the chemical amendments in the microcosm experiments. Here we report how dominant organisms were uniquely associated with treatment- and time-dependent trajectories during the exposure regimes; nutrient availability was a significant factor in driving changes in metatranscriptomic responses. Remarkable signals associated with PPTEPs showed the potential role of mobilome and viral-associated survival responses. These insights underscore the time-dependent environmental perturbations of fragile marine environments under oil and anthropogenic stress.

Welcoming a new Main Editor of Journal of Synchrotron Radiation.

Introducing a new Main Editor of JSR.

Outcomes Following Surgical Fixation of Distal Radius Fractures in Patients With Chronic Kidney Disease.

Purpose: Moderate-to-severe chronic kidney disease (CKD, stages III-IV) and end-stage renal disease (ESRD or CKD stage V) are known to be independent risk factors for fragility fracture. Altered bone and mineral metabolism contributes to greater complications and mortality rates in the setting of fractures, although most existing literature is limited to hip fractures. We hypothesized that patients with moderate-to-severe CKD or ESRD would have greater complication rates after surgical treatment of distal radius fractures compared with those without CKD. Methods: We retrospectively identified all patients at a level 1 trauma center between 2008 and 2018 who had a diagnosis of stage III-IV CKD or ESRD at the time of operative fixation of a distal radius fracture. We recorded demographic data, comorbidities, and surgical complications. Data for readmissions within 90 days and 1-year mortality were collected. A 2:1 sex-matched control group without CKD who underwent distal radius fixation was selected for comparison, with age-adjusted analysis. Results: A total of 32 patients with CKD (78.1% CKD stage III/IV, 21.9% ESRD) and 62 without CKD were identified. The mean age was 67 ± 12 years in the CKD group and 55 ± 15 years in the control group. The CKD group had a higher Charlson Comorbidity Index (5.7 vs 2.0). Surgical complication rate in the CKD group was 12.5% (12.0% CKD III/IV; 14.3% ESRD). Neither early nor late surgical complication rates were statistically different from those in patients without CKD. Reoperation rate as well as 30- and 90-day readmission rates were similar between groups. Overall, 1-year mortality was greater in the CKD group (9.4% vs 0%). Conclusions: Surgical complications and readmission rates are similar in patients with and without CKD after distal radius fracture fixation. However, 1-year mortality rate is significantly higher after distal radius fixation in patients with moderate-to-severe CKD or ESRD. Type of study/level of evidence: Prognostic IIIa.

Outcomes Following Surgical Fixation of Upper Extremity Fractures in Patients with Chronic Kidney Disease.

Purpose: Moderate to severe (stage III-IV) chronic kidney disease (CKD) and end stage renal disease (ESRD) have been shown to be independent risk factors for sustaining a fragility fracture. High rates of complications and mortality are associated with fracture fixation in patients with CKD, but existing literature is limited. It is unknown how CKD stage III-IV or ESRD affects outcomes in upper-extremity fractures. We hypothesize that patients with CKD stage III-IV or ESRD will have high complication rates after surgical fixation of upper extremity fractures. Methods: We identified all patients between 2008 and 2018 who underwent operative fixation of an upper extremity fracture proximal to the distal radius with a diagnosis of CKD stage III-IV or ESRD at the time of injury. Those with an acute kidney injury at the time of injury or a history of a kidney transplant were excluded. Demographics, medical complications, and surgical complications were collected retrospectively. Data on readmissions within 90 days and mortality within 1 year were also collected. Results: Thirty-five patients were identified. Three patients had ESRD. Fractures included two clavicle, twelve proximal humerus, one humeral shaft, ten distal humerus, five olecranon, two ulnar shaft, one radial shaft, and two both-bone forearm fractures. In total, 91.4% of fractures were closed injuries. Surgical complications occurred in 40% of patients. The reoperation rate was 11.4%, and all cases of reoperation involved hardware removal. The all-cause 90-day readmission rate was 34.3%. The 1-year mortality rate was 8.6%. Conclusions: Surgical complications occurred in 40% of patients with CKD stage III-IV or ESRD who underwent fixation for an upper extremity fracture. It is important to counsel these patients regarding their high risk for complications. Further research is needed to investigate and identify how to mitigate risk. Type of study/level of evidence: Prognostic IV.

Iron limitation of heterotrophic bacteria in the California Current System tracks relative availability of organic carbon and iron.

Iron is an essential nutrient for all microorganisms of the marine environment. Iron limitation of primary production has been well documented across a significant portion of the global surface ocean, but much less is known regarding the potential for iron limitation of the marine heterotrophic microbial community. In this work, we characterize the transcriptomic response of the heterotrophic bacterial community to iron additions in the California Current System, an eastern boundary upwelling system, to detect in situ iron stress of heterotrophic bacteria. Changes in gene expression in response to iron availability by heterotrophic bacteria were detected under conditions of high productivity when carbon limitation was relieved but when iron availability remained low. The ratio of particulate organic carbon to dissolved iron emerged as a biogeochemical proxy for iron limitation of heterotrophic bacteria in this system. Iron stress was characterized by high expression levels of iron transport pathways and decreased expression of iron-containing enzymes involved in carbon metabolism, where a majority of the heterotrophic bacterial iron requirement resides. Expression of iron stress biomarkers, as identified in the iron-addition experiments, was also detected insitu. These results suggest iron availability will impact the processing of organic matter by heterotrophic bacteria with potential consequences for the marine biological carbon pump.

A Comparison of Patient Characteristics and Outcomes Between Patients Receiving Flexor Digitorum Superficialis Slip Excision or Isolated A1 Pulley Release for Trigger Finger.

PURPOSE: Resection of the radial or ulnar slip of the flexor digitorum superficialis (FDS) tendon is a known treatment option for persistent trigger finger. Risk factors for undergoing FDS slip excision are unclear. We hypothesized that patients who underwent A1 pulley release with FDS slip excision secondary to persistent triggering would have a higher comorbidity burden compared to those receiving A1 pulley release alone. METHODS: We identified all adult patients who underwent A1 pulley release with FDS slip excision because of persistent triggering either intraoperatively or postoperatively from 2018 to 2023. We selected a 3:1 age- and sex-matched control group who underwent isolated A1 pulley release. Charts were retrospectively reviewed for demographics, selected comorbidities, trigger finger history, and postoperative course. We performed multivariable logistic regression to assess the probability of FDS slip excision after adjusting for several variables that were significant in bivariate comparisons. RESULTS: We identified 48 patients who underwent A1 pulley release with FDS slip excision and 144 controls. Our multivariable model showed that patients with additional trigger fingers and a preoperative proximal interphalangeal (PIP) joint contracture were significantly more likely to undergo FDS slip excision. CONCLUSIONS: Patients who underwent A1 pulley release with FDS slip excision were significantly more likely to have multiple trigger fingers or a preoperative PIP joint contracture. Clinicians should counsel patients with these risk factors regarding the potential for FDS slip excision in addition to A1 pulley release to alleviate triggering of the affected digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results.

Therapeutic vaccines that elicit cytotoxic T cell responses targeting tumor-specific neoantigens hold promise for providing long-term clinical benefit to patients with cancer. Here we evaluated safety and tolerability of a therapeutic vaccine encoding 20 shared neoantigens derived from selected common oncogenic driver mutations as primary endpoints in an ongoing phase 1/2 study in patients with advanced/metastatic solid tumors. Secondary endpoints included immunogenicity, overall response rate, progression-free survival and overall survival. Eligible patients were selected if their tumors expressed one of the human leukocyte antigen-matched tumor mutations included in the vaccine, with the majority of patients (18/19) harboring a mutation in KRAS. The vaccine regimen, consisting of a chimp adenovirus (ChAd68) and self-amplifying mRNA (samRNA) in combination with the immune checkpoint inhibitors ipilimumab and nivolumab, was shown to be well tolerated, with observed treatment-related adverse events consistent with acute inflammation expected with viral vector-based vaccines and immune checkpoint blockade, the majority grade 1/2. Two patients experienced grade 3/4 serious treatment-related adverse events that were also dose-limiting toxicities. The overall response rate was 0%, and median progression-free survival and overall survival were 1.9 months and 7.9 months, respectively. T cell responses were biased toward human leukocyte antigen-matched TP53 neoantigens encoded in the vaccine relative to KRAS neoantigens expressed by the patients' tumors, indicating a previously unknown hierarchy of neoantigen immunodominance that may impact the therapeutic efficacy of multiepitope shared neoantigen vaccines. These data led to the development of an optimized vaccine exclusively targeting KRAS-derived neoantigens that is being evaluated in a subset of patients in phase 2 of the clinical study. ClinicalTrials.gov registration: NCT03953235 .

CHF6297: a novel potent and selective p38 MAPK inhibitor with robust anti-inflammatory activity and suitable for inhaled pulmonary administration as dry powder.

Inhibition of p38 mitogen-activated protein kinase (MAPKs) is a potential therapeutic approach for the treatment of acute and chronic pulmonary inflammatory conditions. Here, we report the in vitro and in vivo characterization of the anti-inflammatory effects of CHF6297, a novel potent and selective p38α inhibitor designed for inhalation delivery as a dry powder formulation. CHF6297 has been proven to inhibit p38α enzymatic activity with sub-nanomolar potency (IC50 = 0.14 ± 0.06 nM), with >1,000-fold selectivity against p38γ and p38δ. In human peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharides (LPS), as well as in human bronchial epithelial cells (BEAS2B) stimulated with TNF-α or cigarette smoke extract (CSE), CHF6297 inhibited interleukin (IL)-8 release with low nanomolar potency. CHF6297 administered to rats by using a nose-only inhalation device as a micronized dry powder formulation blended with lactose dose-dependently inhibited the LPS-induced neutrophil influx in the bronchoalveolar lavage fluid (BALF). CHF6297 administered intratracheally to rats dose-dependently counteracted the IL-1ß (0.3 mg/kg)-induced neutrophil influx (ED50 = 0.22 mg/kg) and increase in IL-6 levels (ED50 = 0.82 mg/kg) in the BALF. In mice exposed to tobacco smoke (TS), CHF6297, administered intranasally (i.n.) for 4 days at 0.03 or 0.3 mg/kg, dose-dependently inhibited the corticosteroid-resistant TS-induced neutrophil influx in the BALF. In a murine house dust mite (HDM) model of asthma exacerbated by influenza virus A (IAV) (H3N3), CHF6297 (0.1 mg/kg, i.n.) significantly decreased airway neutrophilia compared to vehicle-treated IAV/HDM-challenged mice. When CHF6297, at a dose ineffective per se (0.03 mg/kg), was added to budesonide, it augmented the anti-inflammatory effects of the steroid. Overall, CHF6297 effectively counteracted lung inflammation in experimental models where corticosteroids exhibit limited anti-inflammatory activity, suggesting a potential for the treatment of acute exacerbations associated with chronic obstructive pulmonary disease (COPD) and asthma, acute lung injury (ALI), and viral-induced hyperinflammation.

Ultra-rare genetic variation in relapsing polychondritis: a whole-exome sequencing study.

OBJECTIVE: Relapsing polychondritis (RP) is a systemic inflammatory disease of unknown aetiology. The objective of this study was to examine the contribution of rare genetic variations to RP. METHODS: We performed a case-control exome-wide rare variant association analysis that included 66 unrelated European American cases with RP and 2923 healthy controls (HC). Gene-level collapsing analysis was performed using Firth's logistics regression. Exploratory pathway analysis was performed using three different methods: Gene Set Enrichment Analysis, sequence kernel association test and higher criticism test. Plasma DCBLD2 levels were measured in patients with RP and HC using ELISA. RESULTS: In the collapsing analysis, RP was associated with a significantly higher burden of ultra-rare damaging variants in the DCBLD2 gene (7.6% vs 0.1%, unadjusted OR=79.8, p=2.93×10-7). Plasma DCBLD2 protein levels were significantly higher in RP than in HC (median 4.06 ng/µL vs 0.05 ng/µL, p<0.001). The pathway analysis revealed a statistically significant enrichment of genes in the tumour necrosis factor signalling pathway driven by rare damaging variants in RELB, RELA and REL using higher criticism test weighted by eigenvector centrality. CONCLUSIONS: This study identified specific rare variants in the DCBLD2 gene as a putative genetic risk factor for RP. These findings should be validated in additional patients with RP and supported by future functional experiments.

Single-nucleus DNA sequencing reveals hidden somatic loss-of-heterozygosity in Cerebral Cavernous Malformations.

Cerebral Cavernous Malformations (CCMs) are vascular malformations of the central nervous system which can lead to moderate to severe neurological phenotypes in patients. A majority of CCM lesions are driven by a cancer-like three-hit mutational mechanism, including a somatic, activating mutation in the oncogene PIK3CA, as well as biallelic loss-of-function mutations in a CCM gene. However, standard sequencing approaches often fail to yield a full complement of pathogenic mutations in many CCMs. We suggest this reality reflects the limited sensitivity to identify low-frequency variants and the presence of mutations undetectable with bulk short-read sequencing. Here we report a single-nucleus DNA-sequencing approach that leverages the underlying biology of CCMs to identify lesions with somatic loss-of-heterozygosity, a class of such hidden mutations. We identify an alternative genetic mechanism for CCM pathogenesis and establish a method that can be repurposed to investigate the genetic underpinning of other disorders with multiple somatic mutations.

Short-term acidification promotes diverse iron acquisition and conservation mechanisms in upwelling-associated phytoplankton.

Coastal upwelling regions are among the most productive marine ecosystems but may be threatened by amplified ocean acidification. Increased acidification is hypothesized to reduce iron bioavailability for phytoplankton thereby expanding iron limitation and impacting primary production. Here we show from community to molecular levels that phytoplankton in an upwelling region respond to short-term acidification exposure with iron uptake pathways and strategies that reduce cellular iron demand. A combined physiological and multi-omics approach was applied to trace metal clean incubations that introduced 1200 ppm CO2 for up to four days. Although variable, molecular-level responses indicate a prioritization of iron uptake pathways that are less hindered by acidification and reductions in iron utilization. Growth, nutrient uptake, and community compositions remained largely unaffected suggesting that these mechanisms may confer short-term resistance to acidification; however, we speculate that cellular iron demand is only temporarily satisfied, and longer-term acidification exposure without increased iron inputs may result in increased iron stress.

Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens.

Clinical response to adoptive T cell therapies is associated with the transcriptional and epigenetic state of the cell product. Thus, discovery of regulators of T cell gene networks and their corresponding phenotypes has potential to improve T cell therapies. Here we developed pooled, epigenetic CRISPR screening approaches to systematically profile the effects of activating or repressing 120 transcriptional and epigenetic regulators on human CD8+ T cell state. We found that BATF3 overexpression promoted specific features of memory T cells and attenuated gene programs associated with cytotoxicity, regulatory T cell function, and exhaustion. Upon chronic antigen stimulation, BATF3 overexpression countered phenotypic and epigenetic signatures of T cell exhaustion. Moreover, BATF3 enhanced the potency of CAR T cells in both in vitro and in vivo tumor models and programmed a transcriptional profile that correlates with positive clinical response to adoptive T cell therapy. Finally, we performed CRISPR knockout screens that defined cofactors and downstream mediators of the BATF3 gene network.

Prevalence and significance of clonal hematopoiesis of indeterminate potential in lung transplant recipients.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition of somatic mutations that leads to an expanded blood cell clone, has been associated with development of a pro-inflammatory state. An enhanced or dysregulated inflammatory response may contribute to rejection after lung transplantation, however the prevalence of CHIP in lung recipients and influence of CHIP on allograft outcomes is unknown. METHODS: We analyzed whole-exome sequencing data in 279 lung recipients to detect CHIP, defined by pre-specified somatic mutations in 74 genes known to promote clonal expansion of hematopoietic stem cells. We compared the burden of acute rejection (AR) over the first post-transplant year in lung recipients with vs. without CHIP using multivariable ordinal regression. Multivariate Cox proportional hazards models were used to assess the association between CHIP and CLAD-free survival. An exploratory analysis evaluated the association between the number of CHIP-associated variants and chronic lung allograft dysfunction (CLAD)-free survival. RESULTS: We detected 64 CHIP-associated mutations in 45 individuals (15.7%), most commonly in TET2 (10.8%), DNMT3A (9.2%), and U2AF1 (9.2%). Patients with CHIP tended to be older but did not significantly differ from patients without CHIP in terms of race or native lung disease. Patients with CHIP did not have a higher incidence of AR over the first post-transplant year (p = 0.45) or a significantly increased risk of death or CLAD (adjusted HR 1.25, 95% CI 0.88-1.78). We did observe a significant association between the number of CHIP variants and CLAD-free survival, specifically patients with 2 or more CHIP-associated variants had an increased risk for death or CLAD (adjusted HR 3.79, 95% CI 1.98-7.27). CONCLUSIONS: Lung recipients have a higher prevalence of CHIP and a larger variety of genes with CHIP-associated mutations compared with previous reports for the general population. CHIP did not increase the risk of AR, CLAD, or death in lung recipients.

Techniques and Fixation of Olecranon Osteotomy: A Systematic Review.

Purpose: We aimed to characterize the incidence of complications regarding olecranon osteotomy, looking more specifically at the type of osteotomy and the fixation construct used to repair the osteotomy. Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a comprehensive search was performed. A study was included if it was an adult clinical study, a transverse or chevron olecranon osteotomy was performed, and the study explicitly states the fixation construct used to repair the osteotomy. A quality assessment was performed in each study prior to data extraction. Results: We included 39 studies with a total of 1,445 patients. Most studies included patients who were being treated primarily for a distal humerus fracture. The overall incidence of delayed union was 27/643 (4.2%), with a higher rate in transverse osteotomy than in chevron osteotomy (5/49 (10.2%) vs 22/595 (3.7%)). Nonunion occurred in 43/811 (5.4%) of patients, with a higher rate in transverse osteotomy (6/73 (8.2%) vs. 37/712 (5.2%)). Implant failure or loss of reduction occurred in 44/746 (5.9%) of patients, with a higher rate in transverse osteotomy (11/49 (22.4%) vs 33/688 (4.8%)). The removal of implants occurred in 236/1078 (21.9%) of all patients, with the highest rate in those studies that used plate fixation 44/99 (44.4%). Conclusions: Compared with chevron osteotomy, patients who underwent transverse osteotomy had a higher incidence of delayed union, nonunion, and implant failure or loss of reduction requiring revision surgery. The incidence of implant removal indicates that patients should be informed that nearly half of the osteotomy fixed with a plate was removed after implantation. Type of study/level of evidence: Therapeutic III.

Ultra-Rare Genetic Variation in Relapsing Polychondritis: A Whole-Exome Sequencing Study.

Objective: Relapsing polychondritis (RP) is a systemic inflammatory disease of unknown etiology. The study objective was to examine the contribution of rare genetic variations in RP. Methods: We performed a case-control exome-wide rare variant association analysis including 66 unrelated European American RP cases and 2923 healthy controls. Gene-level collapsing analysis was performed using Firth's logistics regression. Pathway analysis was performed on an exploratory basis with three different methods: Gene Set Enrichment Analysis (GSEA), sequence kernel association test (SKAT) and higher criticism test. Plasma DCBLD2 levels were measured in patients with RP and healthy controls using enzyme-linked immunosorbent assay (ELISA). Results: In the collapsing analysis, RP was associated with higher burden of ultra-rare damaging variants in the DCBLD2 gene (7.6% vs 0.1%, unadjusted odds ratio = 79.8, p = 2.93 × 10-7). Patients with RP and ultra-rare damaging variants in DCBLD2 had a higher prevalence of cardiovascular manifestations. Plasma DCBLD2 protein levels were significantly higher in RP than healthy controls (5.9 vs 2.3, p < 0.001). Pathway analysis showed statistically significant enrichment of genes in the tumor necrosis factor (TNF) signaling pathway driven by rare damaging variants in RELB, RELA and REL using higher criticism test weighted by degree and eigenvector centrality. Conclusions: This study identified specific rare variants in DCBLD2 as putative genetic risk factors for RP. Genetic variation within the TNF pathway is also potentially associated with development of RP. These findings should be validated in additional patients with RP and supported by future functional experiments.

The Opioid Risk Tool Correlates With Increased Postsurgical Opioid Use Among Patients With Orthopedic Trauma.

The aim of this study was to determine whether the Opioid Risk Tool (ORT), which has been validated in patients with chronic pain, relates to postoperative opioid consumption. The purpose was to investigate a tool that could help identify patients with orthopedic trauma at high risk for opioid abuse. Patients 18 to 80 years old presenting between May 2018 and August 2018 to UNC Hospitals with isolated orthopedic injuries that required surgical intervention were considered for inclusion. At 2 weeks postoperatively, the ORT was administered. At 6 weeks postoperatively, total morphine milligram equivalents (MME) was determined for each patient. Each patient was also categorized as either low risk (LR) or moderate to high risk (M-HR) based on the cumulative ORT score. Finally, opioid prescriptions provided after 6 weeks postoperatively was recorded. One hundred four patients met the inclusion criteria, and 42 completed the questionnaire. Thirty patients were categorized as LR and 12 patients as M-HR. Patients who were at M-HR consumed a significantly higher MME than LR patients (LR=406 [95% CI, 287-526]; M-HR=824 [95% CI, 591-1057]; P=.001). Linear regression analysis showed that for each additional risk factor, opioid consumption increased by 61 MME, and approximately 58% of the variation in opioid consumption could be explained by the ORT (beta=61, R2=0.58, P=.02). In this study, the ORT predicted which patients would have increased opioid consumption after orthopedic trauma surgery. Each additional risk factor correlated with increased opioid use. The ORT did not predict which patients would continue to receive opioid prescriptions after 6 weeks postoperatively. [Orthopedics. 2023;46(4):e219-e222.].

Sexual quality of life following a cancer diagnosis: a qualitative study.

Sexual quality of life (SQoL) challenges are prevalent and persistent for people with a cancer diagnosis. Using a qualitative design, this study investigated the impact of a cancer diagnosis on SQoL in participants (N = 18) with a current or past cancer diagnosis of various sites and severity. Thematic analysis identified three themes: gender attachment, vulnerability, and growth vs. fixed mindset. The theme of gender attachment related to the impact of understanding SQoL based on heteronormative definitions of masculinity and femininity. The second theme of vulnerability suggested that pre-existing relational or personal challenges can amplify the impact of a cancer diagnosis on SQoL. The third theme of growth vs. fixed mindset explored how cognitive flexibility and optimism can support SQoL, while a rigid and pessimistic mindset can exacerbate SQoL challenges. The findings of this study build on the traditional medical understanding of SQoL and can inform SQoL support in cancer care settings.