Citations

AimsCeramic-on-ceramic (CoC) articulations in total hip arthroplasty (THA) have the advantage of low wear but the unique risk of fracture. After revision for CoC-bearing fracture, third-body ceramic particles can lead to massive wear of cobalt-chrome (CoCr) bearings, causing extremely elevated blood cobalt. We present a multicentre series of five cases where patients sustained fractures of ceramic liners, were revised using a CoCr articulation, and rapidly developed severe cobalt toxicity.MethodsWe identified five cases of cobalt toxicity after fractured CoC THA treated with revision to CoCr on polyethylene bearings. Mean follow-up was three years (5 to 72 months) after re-revision to remove the CoCr bearing.ResultsSymptoms of cobalt toxicity occurred at a mean ten months (6 to 12) after revision for ceramic fracture. All patients developed vision and hearing loss, balance difficulties, and peripheral neuropathy. Several had cardiomyopathy, endocrine abnormalities, and local skin discolouration. Only two reported hip pain. Repeat revision for recognized cobalt toxicity occurred at a mean 22 months after revision for ceramic fracture. Mean serum cobalt level at re-revision was 991 ng/ml (normal value < 1 ng/ml; 734 to 1,302). All CoCr femoral heads exhibited massive wear, and deep tissues showed prominent metal staining. Treatment consisted of debridement and revision to a ceramic femoral head with highly cross-linked polyethylene (HXLPE) liner. Serum cobalt improved to a mean 25 μg/l (1 to 76) at final follow-up. All patients reported partial improvement in vision and hearing, however their peripheral neuropathy and balance difficulties did not recover.ConclusionSystemic cobalt toxicity is a devastating complication of ceramic-bearing fracture in THA treated with CoCr bearings, which may not present with hip symptoms. The diagnosis of this syndrome of systemic cobalt toxicity was significantly delayed following systemic symptoms in this series. Debridement and re-revision to a ceramic-on-HXLPE bearing leads to improvement, but not full resolution, of cobalt toxicity complications.Cite this article: Bone Joint J 2025;107-B(6 Supple B):92–100.

Abstract Purpose With cancer ranking as the third leading cause of death in the Philippines and a disparity in healthcare resources across regions, this research aimed to assess the state of radiotherapy medical physics in the country. Methodology The study utilized a comprehensive online survey with 94 structured questions answered by 19 clinics. Results Most of the participants were within 1–3 years of training (41%), with a slight majority working in private hospitals (55%). linear accelerators (LINACs) were universally used with one Co‐60 unit available, and High Dose Rate (HDR) brachytherapy was common. Intensity‐Modulated Radiotherapy (IMRT) and 3D‐Conformal Radiotherapy (3D‐CRT) are practiced in all 19 clinics, with advanced techniques like Stereotactic Body Radiotherapy (SBRT), Stereotactic Radiosurgery (SRS), and Intraoperative Radiotherapy (IORT) limited to NCR, while modalities such as Volumetric Modulated Arc Therapy (VMAT) (21%) and 2D RT (68%) are more widely practiced. Imaging modalities included the wide adoption of Computed Tomography (CT), though only 64% of respondents had dedicated CT simulators in their clinics. Gynecologic and breast cancers were frequently treated, while bone marrow transplants (total body irradiation) were rare. For quality assurance (QA) devices, Solid Water Phantoms and Scanning Water Tanks (86%) were the most common devices for dosimetry and measurement. 82% reported performing patient‐specific QA (PSQA), with EPID dosimetry being the most common (55%) PSQA device used. Quality management practices varied between Qualified Medical Physicists and Medical Physics Trainees, with most Qualified Medical Physicists performing routine checks. Treatment interruptions were mainly due to staffing and machine downtime, rather than power outages or natural disasters. Most clinics had their own systems (86%) to document safety incidents, but only a few reported incidents (32%) to the IAEA SAFRON program. Lastly, participants expressed a willingness to collaborate in research despite limited time. Conclusion This study provides an understanding of the current landscape of radiation therapy physics in the Philippines, highlighting the need to address workforce disparities, ensure equitable cancer treatment access, optimize dosimetric tools and QA devices, and prioritize resource allocation and research collaboration to advance radiation oncology practices.

Aims An angular proximal femoral deformity, in association with osteoarthritis (OA) of the hip, considerably increases the technical complexity of primary total hip arthroplasty (THA). The aims of this study were to determine the long-term implant survival, the risk factors for failure, complications, and clinical outcomes of contemporary primary THA in this difficult group of patients. Methods Our institutional total joint registry was used to identify 119 primary THAs performed in 108 patients with an angular proximal femoral deformity, between January 1997 and September 2017. The deformity was related to a previous femoral osteotomy in 102 THAs (86%), and developmental or metabolic disorders in 17 THAs (14%). A total of 62 hips (53%) had a predominantly varus deformity. The mean age of the patients was 44 years (SD 13), their mean BMI was 29 kg/m 2 (SD 6), and 70 (59%) were female. An uncemented femoral component with metaphyseal fixation was used in 35 THAs (30%), an uncemented femoral component with diaphyseal fixation in 34 (29%), an uncemented modular femoral component with a metaphyseal fixation sleeve in 29 (24%), and a cemented femoral component in 21 (18%). Simultaneous corrective femoral osteotomy was performed in 22 THAs (18%). Kaplan-Meier survival and Harris Hip Scores (HHSs) were reported. The mean follow-up was eight years (2 to 22). Results The ten-year survival free of femoral loosening, any femoral revision, any revision and any reoperation was 95%, 93%, 90%, and 88%, respectively. A total of 13 revisions were undertaken, for aseptic femoral loosening in three, fracture of the femoral component in two, dislocation in two, aseptic acetabular loosening in two, polyethylene liner exchange in two, and infection in two. A preoperative varus deformity was associated with a higher risk of any revision (hazard ratio (HR) 12.5, p = 0.020), and those with a simultaneous osteotomy had a higher risk of any reoperation (HR 3.6, p = 0.023). The mean HHSs improved significantly from 52 preoperatively to 82 at ten years (p < 0.001). Conclusion In the largest series to date of primary THAs in patients with hip OA and an angular proximal femoral deformity, we found a good ten-year survival free from any revision. Varus deformities, particularly those treated with a simultaneous osteotomy due to the magnitude or location of the deformity, had a higher rate of further surgery. Cite this article: Bone Joint J 2025;107-B(6 Supple B):101–108.

ABSTRACTPrimary lymphedema (i.e., a chronic condition characterized by the accumulation of protein‐rich fluid in the interstitial spaces due to impaired lymphatic drainage) and lipomatosis of nerve (LN) (i.e., a congenital lesion characterized by the presence of fat interspersed within nerve) can involve a significant overgrowth of the affected limb, but their pathophysiology and treatment are totally different. This report addresses the misdiagnosis of both entities. The purpose is to highlight how both entities can be differentiated through two case reports. The first patient, a 69‐year‐old man, presented in our lymphedema clinic with multiple debulking operations; he was diagnosed with right upper extremity lymphedema during childhood. The thumb, index, and middle fingers had previously been amputated due to sequelae from the bony overgrowth. MRI of the right upper extremity showed pathognomonic features of LN affecting the median nerve associated with soft tissue fatty overgrowth. He had a 3 months follow‐up for this condition in our institution during which his symptoms remained stable. The second patient, an 81‐year‐old man, presented in our lymphedema clinic. He carried a long time diagnosis of primary left lower extremity lymphedema and had been followed at our institution for more than 25 years. Physical examination revealed overgrowth (increased volume) affecting the entire leg and foot. MRI showed pathognomonic features of LN of the left sciatic nerve. No surgical interventions were performed. At the last follow‐up, his extremity showed slightly worsened diameter measurements. Based on our 2 cases presented and 2 additional cases identified in the literature, we believe that primary lymphedema and LN are two different entities that could be confused. Plastic surgeons treating patients with lymphedema should be aware of LN and rule out this condition clinically and with imaging (US or MRI).

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.

PURPOSE Continued improvement in outcomes is needed for advanced cutaneous squamous cell carcinoma (cSCC). Methods Alliance A091802 is a randomized phase II trial of avelumab (800 mg IV once every 2 weeks) plus cetuximab (500 mg/m 2 IV once every 2 weeks) versus avelumab alone once every 2 weeks for up to 2 years. Cetuximab was given for 1 year in the avelumab + cetuximab arm. Crossover at progression to avelumab + cetuximab was allowed. Randomization was 1:1, stratified by PD-L1 and HIV status. Patients had distant metastatic or unresectable locally advanced cSCC, were anti–PD-1/PD-L1 monoclonal antibody–naive, had no previous cetuximab in the advanced setting, had an Eastern Cooperative Oncology Group performance status of 0-2, and could be HIV+ (CD4 >200, viral load <200). Patients with chronic lymphocytic leukemia, immunosuppression, or active autoimmune diseases were excluded. The primary end point was progression-free survival (PFS; null hypothesis: median = 12 months v alternative hypothesis: 21 months or a 75% improvement, power of 80% with one-sided alpha .2, n = 57, 37 PFS events required). Secondary end points were overall survival, objective response rates (ORRs), clinical benefit rate, and toxicity. RESULTS Sixty patients were enrolled; 57 patients were evaluable. The median age was 72 years, all were HIV–; 75.4% was PD-L1+, 84.2% had head/neck origin, 47.4% had distant metastasis, and there were no differences in baseline characteristics by arm. Avelumab + cetuximab significantly improved PFS versus avelumab (median, 11.1 [7.6-not reached (NR)] v 3.0 months [2.7-13.6] hazard ratio, 0.48 [95% CI, 0.23 to 0.97], P = .018). Avelumab patients who crossed over (n = 9) to combination had a median PFS after crossover of 11.3 months (5.8-NR). The confirmed ORR was 27.6% with avelumab + cetuximab and 21.4% with avelumab. Grade 3 treatment-related adverse events occurred in 48.3% and 21.5% of patients with avelumab + cetuximab (most common: rash [20.7%], infusion reaction [20.7%]) and avelumab, respectively. CONCLUSION Avelumab + cetuximab significantly improved PFS versus avelumab alone in patients with advanced cSCC. Alliance A091802 supports a larger confirmatory study with the combination of cetuximab and PD-1:PD-(L)1 blockade.

Abstract This study benchmarks the robustness and resilience of computational deconvolution methods for estimating cell-type proportions in bulk tissues, with a focus on comparing reference-based and reference-free methods. Robustness is evaluated by generating in silico pseudo-bulk tissue RNA sequencing data from cell-level gene expression profiles derived from four different tissue types, with simulated cellular composition at varying levels of heterogeneity. To assess resilience, we intentionally alter single-cell RNA profiles to create pseudo-bulk tissue RNA-seq data. Deconvolution estimates are compared with ground truth using Pearson’s correlation coefficient, root mean squared deviation, and mean absolute deviation. The results show that reference-based methods are more robust when reliable reference data are available, whereas reference-free methods excel in scenarios lacking suitable reference data. Furthermore, variations in cell-level transcriptomic profiles and cell composition have emerged as critical factors influencing the performance of deconvolution methods. This study provides significant insights into the factors affecting bulk tissue deconvolution performance, which are essential for guiding users and advancing the development of more powerful and reliable algorithms in the future.

Background: Evaluation of the performance of Cobas ® Pulse (Roche Diagnostics GmbH, Mannheim, Germany), a new blood glucose (BG) monitoring system (BGMS; referred to here as BGMSA) intended for point-of-care testing using samples from patients in diverse clinical settings by intended point-of-care test operators. Methods: Arterial, capillary, venous, or heel stick whole blood (WB) samples from patients in non-critical and critical care settings were collected and analyzed using BGMSA and the Nova StatStrip ® BGMS (Nova Biomedical, Waltham, MA; referred to here as BGMSB), and a hexokinase comparator (Cobas 6000 Analyzer Series; Roche Diagnostics GmbH). The blood glucose measurement accuracy was assessed by the Food and Drug Administration guidance criteria. Results: Two studies are presented. In the first, 2678 samples (622 arterial, 706 capillary, 1203 venous, 147 heel stick) were collected from 1577 patients in 14 US and three European sites. All accuracy criteria were met for arterial and venous samples considering all data combined. BGMSA showed better accuracy than BGMSB for arterial, venous, and heel stick, and similar results to BGMSB for capillary WB vs venous comparator. No endogenous interference from pO 2 , hematocrit, and sodium was identified. BGMSA was also accurate when analyzing contrived samples used to show accuracy over a wide range of glucose concentrations, alone and when combined with extreme hematocrit. In the second study, 117 capillary fingerstick samples collected at one US site were measured on both BGMSA and the comparator, and all accuracy criteria were met. No clinically significant medical risks were observed via Diabetes Technology Society Error Grids. Conclusions: BGMSA was effective for determining blood glucose in venous, arterial, neonatal arterial, neonatal heel stick, and capillary WB samples.

Palliative care (PC) has been shown to improve quality of life (QoL), reduce symptom burden, and align care with patient goals in those with serious illnesses. However, its integration into the emergency department (ED), where many patients with advanced illness present, remains underexplored and inconsistently applied. This narrative review evaluates several recent studies on ED-based palliative care, aiming to clarify whether the early benefits in symptom management and QoL are associated with reduced healthcare utilization and cost. A comprehensive literature search identified five new key studies with significant methodological differences, including variations in patient populations, outcome measures, and study designs. Some studies demonstrated short-term symptom relief, yet only one showed significant improvements in QoL at long-term follow-up. For healthcare utilization, still only one of these new studies reported substantial cost savings, underscoring the need for further research to validate financial benefits. We suggest how future work should be designed to explore both clinical and economic outcomes in tandem to establish a clear value proposition for ED-based palliative care. By addressing this lack of cohesion, we can determine the merit of ED-palliative care integrations with the goal of improving patient care and optimizing resource utilization.

The liver stores substantial numbers of neutral lipid organelles termed lipid droplets (LDs) that accumulate within hepatocytes in response to chronic ethanol (EtOH) consumption leading to hepatic steatosis. Mass spectrometry analysis of LDs isolated from EtOH-damaged rat livers revealed a substantial reduction in the valosin-containing protein ATPase (VCP/p97) that acts to remove targeted proteins from cellular membranes for degradation. Experimental disruption of VCP function resulted in an increase in LD content in hepatocytes and mouse livers along with a marked increase in LD-associated hydroxysteroid dehydrogenase (HSD17β13) known to contribute to hepatic steatosis. Surprisingly, treatment of hepatocytes with the proteasome inhibitor MG132 had no effect on HSD17β13 levels, while a disruption of lysosome function and chaperone-mediated autophagy increased cellular HSD17β13 levels substantially. These findings provide new insights into the cellular mechanisms by which the liver regulates its lipid stores and how this is disrupted by chronic EtOH exposure.