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Abstract First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014–2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72–1.09) and OS (HR = 0.93; 95% CI, 0.73–1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, −0.4%−34.1% and OS = 12.1%; 95% CI, −5.4–29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research.

Background: Flatback deformity, or lumbar hypolordosis, can cause sagittal imbalance, causing back pain, fatigue, and functional limitation. Surgical correction through osteotomies and interbody fusion techniques can restore sagittal balance and relieve pain. This study investigated sagittal vertical alignment (SVA) and lumbar lordosis correction achieved through sequential procedures on human spine specimens. Methods: Human T10-sacrum specimens were stratified into 2 groups: degenerative flatback specimens had smaller L1-S1 lordosis compared to the iatrogenic group (26.1°±15.0° vs. 47.8°±19.3°, p

Objective Acute myeloid leukaemia (AML) prognosis is enhanced with intensive remission induction chemotherapy (ICT) in eligible patients. However, ICT eligibility perceptions may differ among healthcare professionals. This nationwide, population-based study aimed to explore regional variation in ICT application and its relation with overall survival (OS).Methods and analysis We compared nine Dutch regional networks using data from the Netherlands Cancer Registry. Regional variance was assessed for the entire population and age subgroups (ie, ≤60 years and >60 years) using multivariable mixed effects logistic and Cox proportional hazard regression analyses, expressed via median OR (MOR) and median HR (MHR).Results Including all adult AML patients from 2014 to 2018 (N=4060 patients; 58% males; median age, 70 years), 1761 (43%) received ICT. ICT application varied from 36% to 57% (MOR 1.36 (95% CI 1.11 to 1.58)) across regions, with minor variations for patients aged ≤60 years (MOR 1.16 (95% CI 1.00 to 1.40)) and more extensive differences for those aged >60 years (MOR 1.43 (95% CI 1.16 to 1.63)). Median OS spanned 4.9–8.4 months across regions (MHR 1.11 (95% CI 1.00 to 1.15)), with pronounced differences in older patients (MHR 1.12 (95% CI 1.08 to 1.20)) but negligible differences in the younger group (MHR 1.02 (95% CI 1.00 to 1.14)). Survival differences for the total population and the older patients decreased to respectively, MHR 1.09 (95% CI 1.00 to 1.13) and 1.10 (95% CI 1.04 to 1.18), after additional adjustment for the probability of receiving ICT within a region, indicating approximately 10% unexplained differences.Conclusion Regional disparities in ICT application and survival exist, especially in older AML patients. However, ICT application differences partially explain survival disparities, indicating the need for more standardised ICT eligibility criteria and a better understanding of underlying causes of outcome disparities.

Abstract Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission rates as more intensive chemotherapy regimens in literature. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed MYC-R DLBCL patients in the Netherlands. Eligible patients from the observational cohort that were not included in the interventional trial served as control group in the present risk-adjusted comparison. R2CHOP treated patients from the interventional trial (n = 77) were younger than patients in the R-CHOP control cohort (n = 56) (median age 63 versus 70 years, p = 0.018) and they were more likely to have a lower WHO performance score (p = 0.013). We adjusted for differences at baseline using 1:1 matching, multivariable analysis, and weighting using the propensity score to reduce treatment-selection bias. These analyses consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.51, and 0.59, respectively, for OS, and 0.53, 0.59, and 0.60 for PFS. Thus, this non-randomized risk-adjusted comparison supports R2CHOP as an additional treatment option for MYC-R DLBCL patients.

Objective: The objective of this study was to quantitatively determine intervertebral motions and changes in the intervertebral foramen (IVF) area, height, and width in the lumbar spine during the application of a chiropractic procedure. Methods: Eight unembalmed cadavers (five male and three female, age range 43?87 years) were procured for these experiments. Infrared light emitting markers were attached to L4, L5, and sacrum using metal rods to track the three-dimensional motion using the OPTOTRAK system. Five 4-sec cycles of flexion?distraction were performed over a 20-sec period by three clinicians. Vertebral movement data were collected using the marker data in three dimensions and the IVF by digitizing the IVF and computing the changes in area, height, and width. Vertebral motions were computed using three-dimensional kinematics in flexion, lateral bending, twisting, axial traction, and by digitizing the IVF contours; the dimensional changes in terms of height, length, and width were computed. Results: The flexion?distraction procedure created vertebral motions. Mean and standard deviation (SD) values of movements at L4?L5 were (1) 4.2? (0.78) in flexion and mean and SD values of vertebral separations were 1.10 (0.20) mm, respectively. Mean and SD values of vertebral movements at L5?S1 were 3.68? (0.69) in flexion and mean and SD values of vertebral separations were 0.80 (0.15) mm, respectively. Clinicians have created similar movements. Increases were observed in IVF dimensions in terms of area, height, and width at the L4?L5 and L5?S1. Mean and SD values of IVF changes in area, height, and width at L4?L5 were 21.12 (3.87)%, 12.13 (1.89)%, and 5.12 (1.88)%, respectively. Mean and SD values of IVF changes in area, height, and width at L5?S1 were 18.02 (2.97)%, 8.11 (1.68)%, and 4.11 (1.40)%, respectively. Conclusions: Intervertebral motions and IVF dimensional increases were noticed during the flexion?distraction procedure.

Abstract The longevity of patients with chronic lymphocytic leukemia (CLL) has improved progressively over the past decades, making it essential to understand long-term health outcomes, such as second primary malignancies (SPMs). Therefore, this nationwide, population-based study assessed the risk of SPM development in CLL patients diagnosed during 1989-2019 in the Netherlands compared to the expected number of malignancies in an age-, sex-, and period-matched group from the general Dutch population. In 24,815 CLL patients followed for 162,698.49 person-years, 4369 SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.63 (95% confidence interval [CI] 1.59–1.68). This elevated risk was observed for solid (SIR, 1.67; 95% CI, 1.65–1.75) and hematological SPMs (SIR 1.42; 95% CI, 1.24–1.62). The highest risk for SPMs was noted beyond five years post-diagnosis (SIR, 1.70; 95% CI, 1.62–1.77), for male individuals (SIR, 1.70; 95% CI, 1.64–1.77), and patients aged 18–69 years (SIR, 1.92; 95% CI, 1.79–2.05). The risk of SPMs was higher in CLL patients who received anti-neoplastic therapy (SIR, 2.12; 95% CI, 1.96–2.28), as compared with those who did not (SIR, 1.58; 95% CI, 1.53–1.63). Routine surveillance activities and tailored interventions to counteract the increased morbidity and excess mortality associated with SPMs are essential for improving long-term outcomes in CLL patients.

Objective: The study objective was to quantify the changes in intradiscal pressure (IDP) during the application of a chiropractic procedure known as the Cox flexion-distraction technique. Materials and Methods: Pressure sensors were inserted into lumbar intervertebral discs of eight unembalmed cadavers (five male and three female, age range 43?75 years). Five 4-second cycles of flexion distraction were performed for a 20-sec period. Pressure data were collected while the discs were in an unpressurized state as well as a pressurized state (with water). The pressure data were collected during three separate applications of the flexion-distraction procedure with transducers inserted into the L2-L3, L3-L4, and L4-L5 intervertebral discs. The mean pressure values were documented before, during (in the distracted position), and after the treatment procedure (calculated). Pressure differences were compared using the paired t-test for significance in pressure changes from initial prone position to distracted treatment position. Results: The IDPs significantly decreased in both pressurized and unpressurized discs at all studied disc levels. The average IDP decreases in unpressurized discs were as follows: 5.6?kPa at L2-L3, 20.6?kPa at L3-L4, and 22.0?kPa at L4-L5. The IDP decrease range in pressurized-in-the-initial-prone-position discs were as follows: 17.8?kPa at L2-L3, 35.2?kPa at L3-L4, and 122.0?kPa at L4-L5. Conclusions: IDP was found to decrease during the flexion-distraction procedure, which is consistent with the hypothesis that this procedure may be able to draw a protruded nucleus pulposus back toward the intervertebral disc's center and allow for the nutrients flow into the disc.

Background: Soft tissue complications after Achilles tendon repair has led to increased interest in less invasive techniques. Various limited open techniques have gained popularity as an alternative to open operative repair. The purpose of this study was to biomechanically compare an open Krackow and limited open repair for Achilles tendon rupture. We hypothesized that there would be no statistical difference in load to failure, work to failure, and initial linear stiffness. Methods: A simulated Achilles tendon rupture was created 4 cm proximal to its insertion in 18 fresh-frozen cadaveric below-knee lower limbs. Specimens were randomized to open or limited open PARS Achilles Jig System repair. Repairs were loaded to failure at a rate of 25.4 mm/s to reflect loading during normal ankle range of motion. Load to failure, work to failure, and initial linear stiffness were compared between the 2 repair types. Results: The average load to failure (353.8 ± 88.8 N vs 313.3 ± 99.9 N; P = .38) and work to failure (6.4 ± 2.3 J vs 6.3 ± 3.5 J; P = .904) were not statistically different for Krackow and PARS repair, respectively. Mean initial linear stiffness of the Krackow repair (17.8 ± 5.4 N/mm) was significantly greater than PARS repair (11.8 ± 2.5 N/mm) ( P = .011). Conclusion: No significant difference in repair strength was seen, but higher initial linear stiffness for Krackow repair suggests superior resistance to gap formation, which may occur during postoperative rehabilitation. With equal repair strength, but less soft tissue devitalization, the PARS may be a favorable option for patients with risk factors for soft tissue complications.

Summary: Background: Loss of life expectancy (LOLE) may provide more intuitive information on the impact of cancer than relative survival over a fixed time horizon (e.g., 5-year relative survival). We aimed to assess the evolution of the LOLE using a nationwide, population-based cohort including patients diagnosed with one of 17 most frequent solid malignancies. Methods: From the Netherlands Cancer Registry, we selected adult patients diagnosed with one of the 17 most frequent solid malignancies in the Netherlands during 1989–2019, with survival follow-up until 2022. We used flexible parametric survival models to estimate the LOLE at diagnosis and the LOLE after surviving several years post-diagnosis (conditional LOLE; CLOLE) by cancer type, calendar year, age, sex, and disease stage. Findings: For all cancers combined, the LOLE consistently decreased from 1989 to 2019. This decrease was most pronounced for males with prostate cancer (e.g., from 6.9 [95% confidence interval [CI], 6.7–7.1] to 2.7 [95% CI, 2.5–3.0] for 65-year-olds) and females with breast cancer (e.g., from 6.6 [95% CI, 6.4–6.7] to 1.9 [95% CI, 1.8–2.0] for 65-year-olds). The LOLE among patients with cancers of the head and neck or the central nervous system remained constant over time. Overall, the CLOLE showed that the life years lost among patients with cancer decreased with each additional year survived post-diagnosis. For example, the LOLE at diagnosis for 65-year-old females diagnosed with breast cancer in 2019 was 1.9 [95% CI, 1.8–2.0] compared with 1.7 [95% CI, 1.6–1.8], 1.0 [95% CI, 0.9–1.1], and 0.5 [95% CI, 0.5–0.6] when surviving one, five, and ten years post-diagnosis, respectively. Estimates for other combinations of patient and tumour characteristics are available in a publicly available web-based application. Interpretation: Our findings suggested that the evolution of LOLE substantially varies across cancer type, age, and disease stage. LOLE estimates help patients better understand the impact of their specific cancer diagnosis on their life expectancy. Funding: None.