Investigation on the site of coronal deformities in Hallux valgus.

Hallux valgus (HV) is a common foot deformity that is more prevalent in females, characterised by abnormal adduction of the first metatarsal (MT) and valgus deviation of the phalanx on the transverse plane. Increasing evidence indicates that HV is more than a 2D deformity but a 3D one with rotational malalignment. Pronation deformity is seen during clinical examination for HV patients, but the exact origin of this rotational deformity is still unknown. Some attribute it to first tarsometatarsal (TMT) joint rotation, while others attribute it to intra-metatarsal bony torsion. In addition, the correlation between the rotational and transverse plane deformity is inconclusive. Identifying the origin of the rotational deformity will help surgeons choose the optimal surgical procedure while also enhancing our understanding of the pathophysiology of HV. This study aims to (1) develop an objective method for measuring the first MT torsion and first TMT joint rotation; (2) investigate the exact location of the coronal deformity in HV; (3) investigate the relationship between the severity of deformity on the transverse and coronal planes as well as the correlation between deformity severity and foot function/symptoms in HV. Age-matched females with and without HV were recruited at the Foot and Ankle Clinic of the Department of Orthopaedics and Traumatology. Computed tomography was conducted for all subjects with additional weight-bearing dorsal-plantar X-ray examination for HV subjects. Demographic information of all subjects was recorded, with symptoms and functions related to HV evaluated. The intra-class correlation was used to explore the relationship between deformities on different planes and the deformity severity and functional outcomes, respectively. An Independent t-test was used to compare joint rotation and bone torsion degrees. TMT joint rotation is significantly correlated with foot function. HV patients had more TMT joint rotation but not MT torsion compared to normal controls. No relationship was found between the coronal rotation and the 1,2-intermetatarsal angle (IMA) or Hallux valgus angle (HVA) on the transverse plane. Our results indicate that coronal deformities in HV may originate from TMT joint rotation. In addition, the severity of the TMT joint coronal rotation correlates with worse foot function; thus, multi-plane assessment and examination will be necessary for more precise surgical correction.

Improving Our Maternity Care Now Through Midwifery.

This contribution reprints the Executive Summary from a technical report issued by the National Partnership for Women & Families within its larger Improving Our Maternity Care Now project. This project identifies the priority of continuing the long, challenging work of maternity care system transformation, while also increasing access to high-performing care models that can help meet current urgent, dire needs for equitable high-quality care now. The Midwifery report is the first in a series of four reports on these care models, which share distinctive features. They reliably provide highly appropriate services that minimize both underuse of beneficial practices and overuse of unneeded, often harmful practices. They prioritize relationship-based, whole person care that builds trust, confidence and resilience and helps meet the varied needs of birthing families. They incorporate skills and knowledge to support the innate physiologic processes of birthing people and their fetuses/newborns. They achieve remarkable results for consequential outcomes relative to standard maternity care. And childbearing people greatly desire access to these forms of care relative to current access and use. Community-based versions offering trustworthy, respectful, culturally-congruent care are especially powerful. The midwifery report includes recommendations for federal policymakers, state policymakers, and private sector decision makers to increase access to midwifery care. It was carried out in partnership with the American College of Nurse-Midwives, the National Association of Certified Professional Midwives, and the National Black Midwives Alliance. Access the full project through https://www.nationalpartnership.org/improvingmaternitycare/. The project is supported by the Yellow Chair Foundation and is reprinted with permission. Reproduced with permission of the National Partnership for Women & Families.

Improving Our Maternity Care Now Through Community Birth Settings.

This contribution reprints the Executive Summary from a technical report issued by the National Partnership for Women & Families within its larger Improving Our Maternity Care Now project. This project identifies the priority of continuing the long, challenging work of maternity care system transformation, while also increasing access to high-performing care models that can help meet current urgent, dire needs for equitable high-quality care now. The Community Birth Settings report (encompassing birth center and planned home birth care) is the second in a series of four reports on these care models, which share distinctive features. They reliably provide highly appropriate services that minimize both underuse of beneficial practices and overuse of unneeded, often harmful practices. They prioritize relationship-based, whole person care that builds trust, confidence and resilience and helps meet the varied needs of birthing families. They incorporate skills and knowledge to support the innate physiologic processes of birthing people and their fetuses/newborns. They achieve remarkable results for consequential outcomes relative to standard maternity care. And childbearing people greatly desire access to these forms of care relative to current access and use. Community-based versions offering trustworthy, respectful, culturally-congruent care are especially powerful. The community birth settings report includes recommendations for federal policymakers, state policymakers, and private sector decision makers to increase access to these settings. It was carried out in partnership with the American Association of Birth Centers, American College of Nurse-Midwives, Birth Center Equity, National Association of Certified Professional Midwives, and National Black Midwives Alliance. Access the full project through https://www.nationalpartnership.org/improvingmaternitycare/. The project is supported by the Yellow Chair Foundation. Reproduced with permission of the National Partnership for Women & Families.

PLD1 promotes reactive oxygen species production in vascular smooth muscle cells and injury-induced neointima formation.

Phospholipase D (PLD) generates the signaling lipid phosphatidic acid (PA) and has been known to mediate proliferation signal in vascular smooth muscle cells (VSMCs). However, it remains unclear how PLD contributes to vascular diseases. VSMC proliferation directly contributes to the development and progression of cardiovascular disease, such as atherosclerosis and restenosis after angioplasty. Using the mouse carotid artery ligation model, we find that deletion of Pld1 gene inhibits neointima formation of the injuried blood vessels. PLD1 deficiency reduces the proliferation of VSMCs in both injured artery and primary cultures through the inhibition of ERK1/2 and AKT signals. Immunohistochemical staining of injured artery and flow cytometry analysis of VSMCs shows a reduction of the levels of reactive oxygen species (ROS) in Pld1-/- VSMCs. An increase of intracellular ROS by hydrogen peroxide stimulation restored the reduced activities of ERK and AKT in Pld1-/- VSMCs, whereas a reduction of ROS by N-acetyl-l-cysteine (NAC) scavenger lowered their activity in wild-type VSMCs. These results indicate that PLD1 plays a critical role in neointima, and that PLD1 mediates VSMC proliferation signal through promoting the production of ROS. Therefore, inhibition of PLD1 may be used as a therapeutic approach to suppress neointimal formation in atherosclerosis and restenosis after angioplasty.

Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma.

Zanubrutinib, a highly selective Bruton tyrosine kinase inhibitor, was evaluated in a phase 1/2 study in patients with various B-cell malignancies. In the subgroup of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), zanubrutinib was administered as 160 mg twice daily (n = 14), 320 mg once daily (n = 18), or ≤160 mg total dose (n = 5). Herein, we report results for patients receiving a total daily dose of 320 mg (N = 32). Median study follow-up was 18.8 months. Eighteen patients discontinued treatment, 10 because of progressive disease and 8 because of adverse events (AEs); 1 AE (peripheral edema) was considered to be related to zanubrutinib treatment. The most common AEs were diarrhea (43.8%), contusion (37.5%), constipation (31.3%), and upper respiratory tract infection (31.3%). Infection was the most commonly reported AE of interest (18.8% of patients experienced grade ≥3 infection). At least 1 AE of grade ≥3 was reported in 59.4% of patients; grade ≥3 AEs that were reported in >2 patients were anemia (12.5%), pneumonia (9.4%), and myalgia (9.4%). Overall response rate was 84%, with 25% achieving a complete response. Median duration of response was 18.5 months. Median progression-free survival (PFS) was 21.1 months. Zanubrutinib was well tolerated and demonstrated activity in patients with R/R MCL. The trial is registered at www.clinicaltrials.gov as #NCT02343120.

Running biomechanics before and after Pose® method gait retraining in distance runners.

Pose® Method gait retraining has been claimed to modify running form and prevent injury. This study examined the running biomechanics before and after Pose® Method gait retraining. Fourteen runners underwent a 4-week Pose® Method gait retraining program delivered by a certified coach. Paired t-tests were employed to compare vertical average (VALR) and instantaneous loading rates (VILR), lower limb kinematics, footstrike angle and trunk flexion in the sagittal plane before and after the training. Kinetically, there were no significant differences in the VALR (p= 0.693) and VILR (p= 0.782) before and after the training. Kinematically, participants exhibited greater peak hip flexion (p= 0.008) and knee flexion (p= 0.003) during swing. Footstrikeangle also reduced significantly (p= 0.008), indicating a footstrike pattern switch from rearfoot strike to midfoot strike. There was no significant difference in the trunk flexion in the sagittal plane after training (p= 0.658). After a course of Pose® Method gait retraining, runners demonstrated a footstrike pattern switch and some kinematics changes at the hip and knee joint during swing. However, injury-related biomechanical markers (e.g., VALR and VILR) and the trunk kinematics remained similar after training. Runners may consider other gait retraining programs for impact loading reduction.

Effect of minimalist and maximalist shoes on impact loading and footstrike pattern in habitual rearfoot strike trail runners: An in-field study.

Running-related injuries among trail runners are very common and footwear selection may modulate the injury risk. However, most previous studies were conducted in a laboratory environment. The objective of this study was to examine the effects of two contrasting footwear designs, minimalist (MIN) and maximalist shoes (MAX), on the running biomechanics of trail runners during running on a natural trail. Eighteen habitual rearfoot strike trail runners completed level, uphill and downhill running at their preferred speeds in both shod conditions. Peak tibial acceleration, strike index and footstrike pattern were compared between the two footwear and slopes. Interactions of footwear and slope were not detected for all the selected variables. There was no significant effect from footwear (F = 1.23, p = 0.27) and slope (F = 2.49, p = 0.09) on peak tibial acceleration and there was no footwear effect on strike index (F = 3.82, p = 0.056). A significant main effect of slope on strike index (F = 13.24, p < 0.001) was found. Strike index during uphill running was significantly greater (i.e. landing with a more anterior foot strike) when compared with level (p < 0.001, Cohen's d = 1.72) or downhill running (p < 0.001, Cohen's d = 1.44) in either MIN or MAX. The majority of habitual rearfoot strike runners switched to midfoot strike during uphill running while maintaining a rearfoot strike pattern during level or downhill running. In summary, wearing either one of the two contrasting footwear (MIN or MAX) demonstrated no effect on impact loading and footstrike pattern in habitual rearfoot strike trail runners running on a natural trail with different slopes.

Difference in the running biomechanics between preschoolers and adults.

BACKGROUND: High vertical loading rate is associated with a variety of running-related musculoskeletal injuries. There is evidence supporting that non-rearfoot footstrike pattern, greater cadence, and shorter stride length may reduce the vertical loading rate. These features appear to be common among preschoolers, who seem to experience lower running injury incidence, leading to a debate whether adults should accordingly modify their running form. OBJECTIVE: This study sought to compare the running biomechanics between preschoolers and adults. METHODS: Ten preschoolers (4.2±1.6 years) and ten adults (35.1±9.5 years) were recruited and ran overground with their usual shoes at a self-selected speed. Vertical average (VALR) and vertical instantaneous loading rate (VILR) were calculated based on the kinetic data. Footstrike pattern and spatiotemporal parameters were collected using a motion capture system. RESULTS: There was no difference in normalized VALR (p=0.48), VILR (p=0.48), running speed (p=0.85), and footstrike pattern (p=0.29) between the two groups. Preschoolers demonstrated greater cadence (p<0.001) and shorter normalized stride length (p=0.01). CONCLUSION: By comparing the kinetic and kinematic parameters between children and adults, our findings do not support the notion that adults should modify their running biomechanics according to the running characteristics in preschoolers for a lower injury risk.

Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase.

PURPOSE: Mantle-cell lymphoma (MCL) is an incurable mature B-cell neoplasm with high initial response rates followed almost invariably by relapse. Prognosis for patients following relapse is poor, and treatment choices are limited. We evaluated the efficacy and safety of zanubrutinib, an investigational selective Bruton's tyrosine kinase (BTK) inhibitor. PATIENTS AND METHODS: Patients with relapsed/refractory MCL were enrolled in this ongoing phase II, single-arm, open-label study, and treated with oral zanubrutinib 160 mg twice daily. The primary endpoint is overall response rate (ORR) assessed by an independent review committee (per Lugano 2014 classification); secondary endpoints include duration of response (DOR), time to response, progression-free survival (PFS), and safety. RESULTS: Eighty-six patients (median age, 60.5 years) were enrolled after a median of 2 prior lines of therapy, received ≥1 dose of the study drug, and were evaluable for safety and efficacy. After a median follow-up of 18.4 months, 72 (84%) patients achieved an objective response, with 59 (68.6%) achieving a complete response (CR). Median DOR and PFS were 19.5 and 22.1 months, respectively; 12-month event-free estimates for DOR and PFS are 78% and 76%, respectively. Most common grade ≥3 adverse events (AE) were neutropenia (19.8%) and lung infection/pneumonia (9.3%). Three patients experienced major bleeding events, and there were no reports of atrial fibrillation. Eight (9.3%) patients discontinued zanubrutinib for AEs. CONCLUSIONS: These results demonstrate high and durable ORR and CR rates in patients with relapsed/refractory MCL. Zanubrutinib was generally well tolerated; grade ≥3 BTK inhibitor-associated toxicities (hemorrhage, rash, hypertension, diarrhea, atrial fibrillation) were uncommon.

Ideal implant choice for proximal interphalangeal joint arthrodesis in hammer toe/claw toe deformity correction: A systematic review.

Intramedullary devices have been developed to reduce the problems associated with Kirschner (K)-wire fixation in proximal interphalangeal joint (PIPJ) arthrodesis. The purpose of this systematic review is to compare the surgical outcomes of K-wires versus novel internal fixation devices in PIPJ arthrodesis in claw/hammer toe surgery. The databases searched were PubMed, Scopus, Cochrane, and Embase with keywords "claw toe OR hammer toe" AND "proximal interphalangeal OR PIP" AND "fusion OR arthrodesis." Clinical trials published in English with evidence levels I, II, and III were included. Five studies, including one randomized controlled trial and four case-controlled studies, were identified to meet the inclusion criteria. Overall, the studies showed promising results in union rates using the novel internal devices compared to K-wires. However, the novel internal devices seem not to present advantages in clinical parameters such as pain levels, patient satisfaction, foot-related function, or surgical complication rates.

Phosphatidic acid generated by PLD2 promotes the plasma membrane recruitment of IQGAP1 and neointima formation.

Very little is known about how lipid signaling regulates intima hyperplasia after vascular injury. Herein, we report that deletion and pharmacological inhibition of phospholipase D (PLD)2, which generates the signaling lipid phosphatidic acid (PA), reduced neointimal formation in the mouse carotid artery ligation model. PLD2 deficiency inhibits migration of vascular smooth muscle cells (VSMCs) into the intima in mice as well as migration and formation of membrane ruffles in primary VSMCs. PA specifically binds to the IQ motif-containing guanosine triphosphatase-activating protein 1 (IQGAP1) scaffold protein. The binding between PA and IQGAP is required for the plasma membrane recruitment of IQGAP1. Similar to PLD2 inhibition, knockdown of IQGAP1 blocks ruffle formation and migration in VSMCs, which are rescued by expression of the exogenous IQGAP1 but not the PA binding-deficient mutant. These data reveal that the PLD2-PA-IQGAP1 pathway plays an important role in VSMC migration and injury-induced vascular remodeling, and implicate PLD2 as a candidate target for therapeutic interventions.-Wang, Z., Cai, M., Tay, L. W. R., Zhang, F., Wu, P., Huynh, A., Cao, X., Di Paolo, G., Peng, J., Milewicz, D. M., Du, G. Phosphatidic acid generated by PLD2 promotes the plasma membrane recruitment of IQGAP1 and neointima formation.

Binding of PLD2-Generated Phosphatidic Acid to KIF5B Promotes MT1-MMP Surface Trafficking and Lung Metastasis of Mouse Breast Cancer Cells.

Little is known about the cellular events promoting metastasis. We show that knockout of phospholipase D2 (PLD2), which generates the signaling lipid phosphatidic acid (PA), inhibits lung metastases in the mammary tumor virus (MMTV)-Neu transgenic mouse breast cancer model. PLD2 promotes local invasion through the regulation of the plasma membrane targeting of MT1-MMP and its associated invadopodia. A liposome pull-down screen identifies KIF5B, the heavy chain of the motor protein kinesin-1, as a new PA-binding protein. In vitro assays reveal that PA specifically and directly binds to the C terminus of KIF5B. The binding between PLD2-generated PA and KIF5B is required for the vesicular association of KIF5B, surface localization of MT1-MMP, invadopodia, and invasion in cancer cells. Taken together, these results identify a role of PLD2-generated PA in the regulation of kinesin-1 motor functions and breast cancer metastasis and suggest PLD2 as a potential therapeutic target for metastatic breast cancer.

Microbial Genetic Composition Tunes Host Longevity.

Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.

Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

Cancer cells reprogram their metabolism to increase the synthesis of macromolecules for rapid proliferation. Compared to fatty acids, much less is known about the synthesis of phospholipids, which is essential for membrane biogenesis in cancer cells. We found that LPIN1, which encodes lipin-1, a phosphatidic acid phosphatase (PAP) controlling the rate-limiting step in the phospholipid synthesis pathway, is highly up-regulated in basal-like triple-negative breast cancer (TNBC). Moreover, high LPIN1 expression correlates with the poor prognosis of these patients. Knockdown of LPIN1 increases apoptosis in basal-like TNBC cell lines, whereas it has minimal or less effect on normal human mammary gland epithelial cells (HMECs) and estrogen receptor-positive breast cancer cell lines. Fatty acid incorporation and lipidomics analyses showed that LPIN1 knockdown blocks phospholipid synthesis and changes membrane lipid compositions that ultimately induce the activation of 1 of the 3 branches of unfolded protein responses, the inositol-requiring enzyme-1α pathway. We also show for the first time, to our knowledge, that lipin-1 knockdown significantly inhibits tumor growth in vivo using an orthotopic xenograft breast mouse model. Our results suggest that lipin-1 is a potential target for cancer therapy.-He, J., Zhang, F., Tay, L. W. R., Boroda, S., Nian, W., Levental, K. R., Levental, I., Harris, T. E., Chang, J. T., Du, G. Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

Phospholipase D1-regulated autophagy supplies free fatty acids to counter nutrient stress in cancer cells.

Cancer cells utilize flexible metabolic programs to maintain viability and proliferation under stress conditions including nutrient deprivation. Here we report that phospholipase D1 (PLD1) participates in the regulation of metabolic plasticity in cancer cells. PLD1 activity is required for cancer cell survival during prolonged glucose deprivation. Blocking PLD1 sensitizes cancer cells to glycolysis inhibition by 2-deoxy-D-glucose (2-DG) and results in decreased autophagic flux, enlarged lysosomes, and increased lysosomal pH. Mechanistically, PLD1-regulated autophagy hydrolyzes bulk membrane phospholipids to supply fatty acids (FAs) for oxidation in mitochondria. In low glucose cultures, the blockade of fatty acid oxidation (FAO) by PLD1 inhibition suppresses adenosine triphosphate (ATP) production and increases reactive oxygen species (ROS), leading to cancer cell death. In summary, our findings reveal a novel role of PLD1 in sustaining cancer cell survival during metabolic stress, and suggest PLD1 as a potential target for anticancer metabolism therapy.

Monitoring Phosphatidic Acid Signaling in Breast Cancer Cells Using Genetically Encoded Biosensors.

Phospholipids are important signaling molecules that regulate cell proliferation, death, migration, and metabolism. Many phospholipid signaling cascades are altered in breast cancer. To understand the functions of phospholipid signaling molecules, genetically encoded phospholipid biosensors have been developed to monitor their spatiotemporal dynamics. Compared to other phospholipids, much less is known about the subcellular production and cellular functions of phosphatidic acid (PA), partially due to the lack of a specific and sensitive PA biosensor in the past. This chapter describes the use of a newly developed PA biosensor, PASS, in two applications: regular fluorescent microscopy and fluorescence lifetime imaging microscopy-Förster/fluorescence resonance energy transfer (FLIM-FRET). These protocols can be also used with other phospholipid biosensors.

A counterfactual p-value approach for benefit-risk assessment in clinical trials.

Clinical trials generally allow various efficacy and safety outcomes to be collected for health interventions. Benefit-risk assessment is an important issue when evaluating a new drug. Currently, there is a lack of standardized and validated benefit-risk assessment approaches in drug development due to various challenges. To quantify benefits and risks, we propose a counterfactual p-value (CP) approach. Our approach considers a spectrum of weights for weighting benefit-risk values and computes the extreme probabilities of observing the weighted benefit-risk value in one treatment group as if patients were treated in the other treatment group. The proposed approach is applicable to single benefit and single risk outcome as well as multiple benefit and risk outcomes assessment. In addition, the prior information in the weight schemes relevant to the importance of outcomes can be incorporated in the approach. The proposed CPs plot is intuitive with a visualized weight pattern. The average area under CP and preferred probability over time are used for overall treatment comparison and a bootstrap approach is applied for statistical inference. We assess the proposed approach using simulated data with multiple efficacy and safety endpoints and compare its performance with a stochastic multi-criteria acceptability analysis approach.

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents.

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease.

Health resource utilisation associated with skeletal-related events in European patients with lung cancer: Α subgroup analysis from a prospective multinational study.

Bone complications or skeletal-related events (SREs), typically defined as radiation to bone, pathological fractures, surgery to bone and spinal cord compression, occur frequently in patients with bone metastases. As the survival of patients with advanced lung cancer improves, preventing SREs is becoming increasingly clinically relevant. The aim of this analysis was to assess the impact of SREs on health resource utilisation (HRU) in European lung cancer patients with bone metastasis. This multinational, observational study included patients who had at least one SRE in the 97 days prior to enrolment, a life expectancy of ≥6 months and an Eastern Cooperative Oncology Group performance status of 0-2. Data on HRU were retrospectively collected for up to 97 days prior to enrolment with a planned prospective follow-up for up to 18-21 months. The HRU measures included the number and length of inpatient hospitalisations and the number of outpatient visits and procedures. The investigators determined whether each HRU was attributable to a SRE. In total, 135 patients with lung cancer, enrolled at centres in Germany, Italy, Spain and the United Kingdom, contributed 214 SREs to this analysis. The median length [quartile (Q)1, Q3] of follow-up ranged from 1.5 (0.7, 3.3) to 5.6 (2.0, 8.2) months across the countries. Overall, 41% of the SREs required an inpatient stay, with a median (Q1, Q3) duration of 19.0 (6.0, 28.0) days. Spinal cord compression and surgery to bone were the SRE types most frequently requiring inpatient stays. Radiation to bone was associated with the largest number of outpatient visits and procedures. All the SREs resulting from bone metastases in patients with lung cancer contribute considerably to HRU and efforts to minimise the incidence of bone complications in these patients through appropriate treatments may help reduce this burden.