Efficacy of daratumumab in newly diagnosed multiple myeloma patients with 1q21 gain.

BACKGROUND: Gain and amplification of 1q21 (1q21+) are adverse chromosomal aberrations of multiple myeloma (MM) that lead to refractoriness to a variety of therapies. While it is known that daratumumab, an anti-cancer monoclonal antibody, cannot overcome the disadvantage of 1q21+in relapsed/refractory MM patients, its benefit in newly diagnosed MM (NDMM) patients with 1q21+has not been clarified. PATIENTS: We retrospectively evaluated 11 (55%) 1q21+patients (3 copies: 6, > 4 copies: 5) among 20 NDMM patients (median age, 74 years) who received daratumumab-containing regimens at Shibukawa Medical Center from October 2019 to October 2022. RESULTS: The overall response rate was 82% for patients with 1q21+and 78% for patients without 1q21+. Median progression-free survival (PFS) and median overall survival (OS) were not reached in either group. Neither 1q21 copy number nor co-existence of other high-risk cytogenetic abnormalities significantly affected PFS or OS. CONCLUSION: Our preliminary data suggests that outcomes of daratumumab treatment in NDMM 1q21+patients might be non-inferior to those in non-1q21+patients.

NK and T-lymphocyte Kinetics Predict Outcome in Myeloma Patients Treated With Elotuzumab, Lenalidomide Plus Dexamethasone.

Background/Aim: Elotuzumab, an anti-SLAMF7 monoclonal antibody, can enhance immune activity via elevated antibody-dependent cellular cytotoxicity and reduced SLAMF7+CD8+CD57+ regulatory T-cells (Tregs). This multicenter observational study investigated the kinetics of lymphocytes in myeloma patients treated with elotuzumab, lenalidomide, and dexamethasone (ERd) by two-color flow cytometry using peripheral blood samples. Patients and Methods: Twenty-one patients were included in this study. The median duration of ERd was 22.6 months, and the cutoff time for long-duration ERd was two years. Results: The CD2+CD16+ and CD16+CD57- NK cells were significantly increased over time in the long-duration ERd group compared to those in the short-duration ERd group (p=0.035 and p<0.001). The CD8+ and CD16-CD57+ lymphocytes, identified as low-activity NK cells or SLAMF7+ Tregs, were significantly increased in the patients whose ERd outcome was progressive disease (PD) compared to those in the non-PD group (p=0.023 and p<0.001). The mean CD4/CD8 ratio and CD19+ lymphocyte counts in the long-duration ERd group were significantly lower than those in the short-duration ERd group, although the kinetics of them did not change over time (p=0.016 and p=0.011). When the cutoff value of CD4/CD8 ratio was 0.792 according to ROC curves, the two-year time to next treatment (TTNT) in the low CD4/CD8 group was significantly longer than that in the high CD4/CD8 group (80.0% vs. 15.0%, p=0.024). Conclusion: The change in NK cells and CD8+ Tregs predicted long-duration ERd and PD, and maintaining low CD4/8 ratio predicted long TTNT, suggesting that these lymphocyte fractions might be biomarkers for a durable therapeutic effect of ERd in myeloma patients.

Bilateral Upper Arm Granulomas Induced by Leuprorelin Acetate Injection Mimicking Malignant Soft Tissue Tumors: A Case Report.

Leuprorelin acetate is a common anticancer medication used for prostate cancer treatment. One of the local adverse reactions after leuprorelin injection is the development of reactive granulomas, typically presenting as subcutaneous nodules. In this case report, we describe a 73-year-old patient with prostate cancer who developed unusually large sized intramuscular reactive granulomas, which mimicked malignant soft tissue tumors. The patient, who had been receiving leuprorelin acetate treatment for the past 12 months, noticed painful masses in both upper arms. Based on the findings of magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography/computed tomography, a diagnosis of malignant soft tissue tumor was strongly suggested. However, further investigation through needle biopsy ultimately led us to the final diagnosis of reactive granuloma. The masses spontaneously resolved after discontinuation of leuprorelin injection. While reactive granulomas after leuprorelin injections are not rare, intramuscular cases are relatively uncommon. Despite using imaging studies as a rational initial approach in the diagnostic process, as we did in our case, their results turned out to be indistinguishable from those of malignant soft tissue tumors, thus highlighting the importance of pathological examination in confirming diagnosis, especially when a patient presents with atypical clinical manifestations.

Bezafibrate attenuates immobilization-induced muscle atrophy in mice.

Muscle atrophy due to fragility fractures or frailty worsens not only activity of daily living and healthy life expectancy, but decreases life expectancy. Although several therapeutic agents for muscle atrophy have been investigated, none is yet in clinical use. Here we report that bezafibrate, a drug used to treat hyperlipidemia, can reduce immobilization-induced muscle atrophy in mice. Specifically, we used a drug repositioning approach to screen 144 drugs already utilized clinically for their ability to inhibit serum starvation-induced elevation of Atrogin-1, a factor related to muscle atrophy, in myotubes in vitro. Two candidates were selected, and here we demonstrate that one of them, bezafibrate, significantly reduced muscle atrophy in an in vivo model of muscle atrophy induced by leg immobilization. In gastrocnemius muscle, immobilization reduced muscle weight by an average of ~ 17.2%, and bezafibrate treatment prevented ~ 40.5% of that atrophy. In vitro, bezafibrate significantly inhibited expression of the inflammatory cytokine Tnfa in lipopolysaccharide-stimulated RAW264.7 cells, a murine macrophage line. Finally, we show that expression of Tnfa and IL-1b is induced in gastrocnemius muscle in the leg immobilization model, an activity significantly antagonized by bezafibrate administration in vivo. We conclude that bezafibrate could serve as a therapeutic agent for immobilization-induced muscle atrophy.

Influence of thoracolumbar kyphosis on postoperative spinal alignment in patients with Lenke type 5C adolescent idiopathic scoliosis.

PURPOSE: This study aimed to examine the changes in thoracolumbar kyphosis (TLK) following correction surgery in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS) and to evaluate its influence on postoperative spinal alignment and clinical outcomes. METHODS: Sixty-six patients with Lenke type 5C AIS were included and followed up for a minimum of 5 years after surgery. First, the patients were divided into two groups according to the preoperative TLK angle (Study 1; Kyphosis and Lordosis group). The patients were further classified into two groups according to the presence or absence of postoperative changes in TLK (Study 2; Changed and Maintained groups). Finally, the outcome variables were compared between these groups and analyzed for spinal alignment and clinical outcomes. RESULTS: In Study 1, patients demonstrated a significant kyphotic change in the Lordosis group and a significant lordotic change in the Kyphosis group postoperatively. No statistically significant differences were found between the two groups when comparing the pre- and postoperative coronal and sagittal alignment. In Study 2, there were no statistically significant differences between the Changed and the Maintained groups in each spinal alignment pre- and postoperatively. Each domain of the Scoliosis Research Society 22-item questionnaire remained unchanged at 5 years postoperation. CONCLUSION: In many patients with Lenke type 5C AIS, TLK changed significantly and approached 0° after surgery. However, the magnitude of the preoperative TLK and the presence or absence of improvement did not affect postoperative spinal alignment. Furthermore, the patients had satisfactory clinical outcomes irrespective of TLK modification. LEVEL OF EVIDENCE: III.

How coronal malalignment affects the surgical outcome in corrective spine surgery for adult symptomatic lumbar deformity.

PURPOSE: The importance of coronal alignment is unclear, while the importance of sagittal alignment in the treatment of adult patients with spinal deformities is well described. This study sought to elucidate the impact of global coronal malalignment (GCMA) in surgically treated adult symptomatic lumbar deformity (ASLD) patients. METHODS: A multicentre retrospective analysis of a prospective ASD database. GCMA was defined as GCA (C7PL-CSVL) ≥ 3 cm. GCMA is categorized based on the Obeid-Coronal Malalignment Classification (O-CM). Demographic, surgical, radiographic, HRQOL, and complication data were analysed. The risk for postoperative GCMA was analysed by univariate and multivariate analyses. RESULTS: Of 230 surgically treated ASLD patients, 96 patients showed GCMA preoperatively and baseline GCA was correlated with the baseline SRS-22 pain domain score (r = - 30). Postoperatively, 62 patients (27%, O-CM type 1: 41[18%], type 2: 21[9%]) developed GCMA. The multivariate risk analysis indicated dementia (OR 20.1[1.2-304.4]), diabetes (OR 5.9[1.3-27.3]), and baseline O-CM type 2 (OR 2.1[1.3-3.4]) as independent risk factors for postoperative GCMA. The 2-year SRS-22 score was not different between the 2 groups, while 4 GCMA patients required revision surgery within 1 year after surgery due to coronal decompensation (GCMA+ vs. GCMA- function: 3.6 ± 0.6 vs. 3.7 ± 0.7, pain: 3.7 ± 0.8 vs. 3.8 ± 0.8, self-image: 3.6 ± 0.8 vs. 3.6 ± 0.8, mental health: 3.7 ± 0.8 vs. 3.8 ± 0.9, satisfaction: 3.9 ± 0.9 vs. 3.9 ± 0.8, total: 3.7 ± 0.7 vs. 3.7 ± 0.7). Additionally, the comparisons of 2-yr SRS-22 between GCMA ± showed no difference in any UIV and LIV level or O-CM type. CONCLUSIONS: In ASLD patients with corrective spine surgery, GCMA at 2 years did not affect HRQOL or major complications at any spinal fusion extent or O-CM type of malalignment, whereas GCA correlated with pain intensity before surgery. These findings may warrant further study of the impact of GCMA on HRQOL in the surgical treatment of ASLD patients.

Determinants of Gait Parameters in Patients With Severe Hip Osteoarthritis.

OBJECTIVE: To investigate the characteristics and symptoms of patients with hip osteoarthritis that are associated with spatiotemporal gait parameters, including their variability and asymmetry. DESIGN: A retrospective, cross-sectional study. SETTING: University hospital. PARTICIPANTS: The study analyzed the gait analysis data of 155 patients (N=155) with hip osteoarthritis who were admitted to a university hospital for total hip replacement and were able to walk on a treadmill without a handrail. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The dependent variables were gait parameters during treadmill walking. These included gait speed, stride length, cadence, coefficient of variation of stride length and stride time, swing time symmetry index, and step symmetry index. Single and multiple regression analyses were conducted using independent variables of the characteristics and symptoms of the patients, including age, sex, height, pain, leg-length discrepancy, and muscle strength of the affected and normal sides measured with a hand-held dynamometer (iliopsoas, gluteus medius, and quadriceps). RESULTS: In the analysis, gait speed and stride were the dependent variables, whereas age, height, and muscle strength on the affected side were the significant independent variables (P<.05). Additionally, pain demonstrated a marginal association with gait speed (P=.053). Only the leg-length discrepancy correlated with cadence. When the coefficient of variation of the stride length was the dependent variable, age and muscle strength on the affected side were significant. For the swing time symmetry index, only the muscle strength on the affected side was significant. Furthermore, the step symmetry index only correlated with leg-length discrepancy. The muscle strength on the affected side was the only significant independent variable for the coefficient of variation of the stride time. CONCLUSIONS: The results revealed that each of the frequent clinical symptoms of hip osteoarthritis, such as pain, muscle weakness, and leg-length discrepancy, can explain different aspects of gait performance.

Cost-Effectiveness of Universal Asymptomatic Preoperative SARS-CoV-2 Polymerase Chain Reaction Screening: A Cost-Utility Analysis.

BACKGROUND: An early report has shown the clinical benefit of the asymptomatic preoperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening test, and some clinical guidelines recommended this test. However, the cost-effectiveness of asymptomatic screening was not evaluated. We aimed to investigate the cost-effectiveness of universal preoperative screening of asymptomatic patients for SARS-CoV-2 using polymerase chain reaction (PCR) testing. METHODS: We evaluated the cost-effectiveness of asymptomatic screening using a decision tree model from a payer perspective, assuming that the test-positive rate was 0.07% and the screening cost was 8500 Japanese yen (JPY) (approximately 7601 US dollars [USD]). The input parameter was derived from the available evidence reported in the literature. A willingness-to-pay threshold was set at 5 000 000 JPY/quality-adjusted life-year (QALY). RESULTS: The incremental cost of 1 death averted was 74 469 236 JPY (approximately 566 048 USD) and 291 123 368 JPY/QALY (approximately 2 212 856 USD/QALY), which was above the 5 000 000 JPY/QALY willingness-to-pay threshold. The incremental cost-effectiveness ratio fell below 5 000 000 JPY/QALY only when the test-positive rate exceeded 0.739%. However, when the probability of developing a postoperative pulmonary complication among SARS-CoV-2-positive patients was below 0.22, asymptomatic screening was never cost-effective, regardless of how high the test-positive rate became. CONCLUSIONS: Asymptomatic preoperative universal SARS-CoV-2 PCR screening is not cost-effective in the base case analysis. The cost-effectiveness mainly depends on the test-positive rate, the frequency of postoperative pulmonary complications, and the screening costs; however, no matter how high the test-positive rate, the cost-effectiveness is poor if the probability of developing postoperative pulmonary complications among patients positive for SARS-CoV-2 is sufficiently reduced.

Multiple Recurrent Atypical Lipomatous Tumors/Well-Differentiated Liposarcomas and Dedifferentiated Liposarcomas Treated with Multiple Surgical Resections: A Case Report.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) is usually a solitary adipocytic tumor. ALT/WDLPS shows no potential for metastasis unless it undergoes dedifferentiation. No case of multiple ALT/WDLPS has been reported in recent years. We present a rare case of multiple recurrent liposarcomas. A 71-year-old man with a history of scrotal ALT/WDLPS at 61 years presented with multiple large tumors spread throughout the body. The patient was bedridden and severely limited in his activities of daily living (ADL) due to multiple large tumors in the trunk and lower extremities. Radiological examination revealed multiple adipocytic tumors, mainly in the soft tissues of the trunk and extremities, with several visceral lesions. Tumors were resected in stages, starting with large tumors directly related to disability. Repeated palliative resections improved the patient's ADL; he regained ambulation and was discharged 18 months after admission. Twelve surgeries were performed to remove 44 adipocytic tumors from the testis, left chest wall, perigastric area, ileum, left inguinal region, both buttocks, thighs, and lower legs. Histological examination revealed dedifferentiated components in five tumors, while 39 tumors were diagnosed as ALT/WDLPS. At the age of 76 years, the patient developed an unresectable dedifferentiated liposarcoma between the heart and aorta, leading to fatality at 79 years. The patient's clinical course suggested multiple metastases of ALT/WDLPS of scrotal origin or ALT/WDLPS of multicentric origin. Although multicentric ALT/WDLPS or ALT/WDLPS metastases are rare, they should be considered when multiple large adipocytic tumors are found throughout the body. Despite the presence of numerous large malignant tumors, surgical treatments of the lesions can improve ADL and prolong life if the tumors are of low-grade malignancy.

Severe lactic acidosis during tenofovir disoproxil fumarate and cobicistat combination for HIV patient.

Lactic acidosis is a rare but serious side effect in individuals receiving nucleoside reverse transcriptase inhibitors. An underweight woman with HIV was admitted to our hospital because of nausea and diffuse myalgia. Her antiretroviral regimen had been changed to tenofovir disoproxil fumarate (TDF)/emtricitabine and darunavir/cobicistat 3 months prior, after which her renal function had gradually declined. After admission, she was diagnosed with lactic acidosis, and a liver biopsy suggested mitochondrial damage. Her plasma tenofovir levels were elevated at the onset of lactic acidosis. We hypothesise that the patient's low body weight, combined with the addition of cobicistat, induced renal dysfunction and led to elevated plasma tenofovir concentrations, resulting in mitochondrial damage and lactic acidosis. Careful monitoring of renal function and lactic acidosis is required during use of TDF-containing regimens for underweight HIV patients, particularly when combined with cobicistat.

Impact of Surgical Resection Without Spinal Fusion for Thoracic Dumbbell Tumors on Postoperative Global Spinal Sagittal Alignment and Clinical Outcomes.

STUDY DESIGN: A retrospective comparative study. OBJECTIVES: This study investigated radiographical changes in global spinal sagittal alignment (GSSA) and clinical outcomes after tumor resection without spinal fusion in patients with thoracic dumbbell tumors. METHODS: Thirty patients with thoracic dumbbell tumors who were followed up for at least 3 years were included in this study. Variations in the outcome variables were analyzed using individual GSSA parameters measured on radiography. Clinical outcomes were assessed using the modified McCormick scale (MMCS), Japan Orthopaedic Association (JOA) score, and visual analog scale (VAS). To assess the impact of the affected levels on these outcomes, we divided the patients into three groups according to the location of the tumor (upper [T1-4], middle [T5-8], or lower [T9-12] thoracic spine). RESULTS: The GSSA parameters (cervical lordosis, T1 slope, thoracic kyphosis [global, upper, middle, and lower], thoracolumbar kyphosis, lumbar lordosis, sacral slope, pelvic incidence, and pelvic tilt) of all the patients did not change significantly after surgery. Eleven of thirty patients had preoperative gait disturbances but they could walk without support (MMCS grade I or II) at the final follow-up. The JOA score and VAS showed significant postoperative improvements. No statistically significant differences were observed in each postoperative sagittal profile or clinical outcome between the upper, middle, and lower groups. CONCLUSIONS: Tumor resection without spinal fusion did not affect the various GSSA parameters and resulted in satisfactory clinical outcomes, indicating that spinal fusion may not always be necessary when resecting thoracic dumbbell tumors.

Hepatocyte growth factor pretreatment boosts functional recovery after spinal cord injury through human iPSC-derived neural stem/progenitor cell transplantation.

BACKGROUND: Human induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC)-based cell transplantation has emerged as a groundbreaking method for replacing damaged neural cells and stimulating functional recovery, but its efficacy is strongly influenced by the state of the injured spinal microenvironment. This study evaluates the impact of a dual therapeutic intervention utilizing hepatocyte growth factor (HGF) and hiPSC-NS/PC transplantation on motor function restoration following spinal cord injury (SCI). METHODS: Severe contusive SCI was induced in immunocompromised rats, followed by continuous administration of recombinant human HGF protein into the subarachnoid space immediately after SCI for two weeks. Acute-phase histological and RNA sequencing analyses were conducted. Nine days after the injury, hiPSC-NS/PCs were transplanted into the lesion epicenter of the injured spinal cord, and the functional and histological outcomes were determined. RESULTS: The acute-phase HGF-treated group exhibited vascularization, diverse anti-inflammatory effects, and activation of endogenous neural stem cells after SCI, which collectively contributed to tissue preservation. Following cell transplantation into a favorable environment, the transplanted NS/PCs survived well, facilitating remyelination and neuronal regeneration in host tissues. These comprehensive effects led to substantial enhancements in motor function in the dual-therapy group compared to the single-treatment groups. CONCLUSIONS: We demonstrate that the combined therapeutic approach of HGF preconditioning and hiPSC-NS/PC transplantation enhances locomotor functional recovery post-SCI, highlighting a highly promising therapeutic strategy for acute to subacute SCI.

Spatial heterogeneity of bone marrow endothelial cells unveils a distinct subtype in the epiphysis.

Bone marrow endothelial cells (BMECs) play a key role in bone formation and haematopoiesis. Although recent studies uncovered the cellular taxonomy of stromal compartments in the bone marrow (BM), the complexity of BMECs is not fully characterized. In the present study, using single-cell RNA sequencing, we defined a spatial heterogeneity of BMECs and identified a capillary subtype, termed type S (secondary ossification) endothelial cells (ECs), exclusively existing in the epiphysis. Type S ECs possessed unique phenotypic characteristics in terms of structure, plasticity and gene expression profiles. Genetic experiments showed that type S ECs atypically contributed to the acquisition of bone strength by secreting type I collagen, the most abundant bone matrix component. Moreover, these cells formed a distinct reservoir for haematopoietic stem cells. These findings provide the landscape for the cellular architecture in the BM vasculature and underscore the importance of epiphyseal ECs during bone and haematopoietic development.

Efficacy and safety of single-agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-3): a phase 3, open-label, randomised study.

BACKGROUND: Multiple myeloma remains incurable, and heavily pretreated patients with relapsed or refractory disease have few good treatment options. Belantamab mafodotin showed promising results in a phase 2 study of patients with relapsed or refractory multiple myeloma at second or later relapse and a manageable adverse event profile. We aimed to assess the safety and efficacy of belantamab mafodotin in a phase 3 setting. METHODS: In the DREAMM-3 open-label phase 3 study, conducted at 108 sites across 18 countries, adult patients were enrolled who had confirmed multiple myeloma (International Myeloma Working Group criteria), ECOG performance status of 0-2, had received two or more previous lines of therapy, including two or more consecutive cycles of both lenalidomide and a proteasome inhibitor, and progressed on, or within, 60 days of completion of the previous treatment. Participants were randomly allocated using a central interactive response technology system (2:1) to receive belantamab mafodotin 2·5 mg/kg intravenously every 21 days, or oral pomalidomide 4·0 mg daily (days 1-21) and dexamethasone 40·0 mg (20·0 mg if >75 years) weekly in a 28-day cycle. Randomisation was stratified by previous anti-CD38 therapy, International Staging System stage, and number of previous therapies. The primary endpoint was progression-free survival in all patients who were randomly allocated. The safety population included all randomly allocated patients who received one or more doses of study treatment. This trial is registered with ClinicalTrials.gov, NCT04162210, and is ongoing. Data cutoff for this analysis was Sept 12, 2022. FINDINGS: Patients were recruited between April 2, 2020, and April 18, 2022. As of September, 2022, 325 patients were randomly allocated (218 to the belantamab mafodotin group and 107 to the pomalidomide-dexamethasone group); 184 (57%) of 325 were male and 141 (43%) of 325 were female, 246 (78%) of 316 were White. Median age was 68 years (IQR 60-74). Median follow-up was 11·5 months (5·5-17·6) for belantamab mafodotin and 10·8 months (5·6-17·1) for pomalidomide-dexamethasone. Median progression-free survival was 11·2 months (95% CI 6·4-14·5) for belantamab mafodotin and 7·0 months (4·6-10·6) for pomalidomide-dexamethasone (hazard ratio 1·03 [0·72-1·47]; p=0·56). Most common grade 3-4 adverse events were thrombocytopenia (49 [23%] of 217) and anaemia (35 [16%]) for belantamab mafodotin, and neutropenia (34 [33%] of 102) and anaemia (18[18%]) for pomalidomide-dexamethasone. Serious adverse events occurred in 94 (43%) of 217 and 40 (39%) of 102 patients, respectively. There were no treatment-related deaths in the belantamab mafodotin group and one (1%) in the pomalidomide-dexamethasone group due to sepsis. INTERPRETATION: Belantamab mafodotin was not associated with statistically improved progression-free survival compared with standard-of-care, but there were no new safety signals associated with its use. Belantamab mafodotin is being tested in combination regimens for relapsed or refractory multiple myeloma. FUNDING: GSK (study number 207495).

Isolated ACTH deficiency: an uncommon cause of hyperferritinaemia.

Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder but not a known cause of hyperferritinaemia. We here report a man with IAD who presented with mild anaemia and unexpected hyperferritinaemia (serum ferritin, 1796 µg/L). He had high serum hepcidin and relatively low erythropoietin levels for his anaemia, with hepcidin and ferritin levels reducing with hydrocortisone supplementation. We speculate that low glucocorticoid levels might suppress erythropoiesis and anti-inflammatory activity, resulting in a higher hepcidin level and hyperferritinaemia. The possibility of adrenal insufficiency including IAD should be considered as a differential diagnosis in patients with unexplained hyperferritinaemia.

Analysis of the sacroiliac joint vacuum phenomenon in adolescent thoracic idiopathic scoliosis (Lenke types 1 and 2).

The sacroiliac joint (SIJ) is the largest axial joint in the human body, and the SIJ vacuum phenomenon (SIJ VP) is a common finding in computed tomography studies of the abdomen, pelvis, and lumbosacral spine in adults, with the incidence increasing with age. Adolescent idiopathic scoliosis (AIS) is an abnormal spinal curvature that appears during adolescence and places abnormal stress on the SIJs. This retrospective observational study aimed to investigate the incidence of the SIJ VP in thoracic AIS (Lenke types 1 and 2). Sixty-seven patients with AIS (age: 12-19 years) and 76 controls (age: 11-19 years) were retrospectively analyzed to investigate SIJ VP, subchondral bone cysts, and SIJ degeneration (Eno classification: type 0, no degenerative change; type 1, mild degenerative changes; type 2, substantial degenerative changes; and type 3, ankylosis). SIJ degeneration was defined as type ≥ 2. The association between SIJ VP, cysts, SIJ degeneration, and sagittal/coronal spinopelvic alignment was assessed. SIJ VP (59% vs. 35.5%, P < .01), cysts (32.8% vs. 1.3%, P < .01), and SIJ degeneration (3.2% vs. 2.6%, P = .823) differed significantly between the 2 groups. There were 0 cases of SIJ ankylosis (Eno classification type 3) in both groups. The VP was not correlated with lumbar lordosis, sacral slope, or Cobb angle. All lumbar modifier type C belonged to the VP present group, whereas none to VP absent group. Our results suggest an association between AIS and SIJ VP and SIJ cysts. SIJ VP and SIJ cysts in AIS may be caused and accelerated by abnormal mechanical stress on SIJ due to spinal deformity.

Prevalence and clinical outcomes of vitamin D deficiency among Japanese multiple myeloma patients: a single-center observational study.

PURPOSE: Vitamin D plays a crucial role in skeletal metabolism and holds significant importance in the pathophysiology of multiple myeloma (MM). This study aimed to determine the prevalence of vitamin D deficiency among Japanese MM patients and its correlation with clinical outcomes. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were assessed in 68 MM patients at a single institution in Japan, analyzing their association with clinical status, laboratory parameters including procollagen type 1 N-propeptide (P1NP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), health-related quality of life (HR-QOL) scores, and overall survival. Additionally, patients with suboptimal 25(OH)D levels received cholecalciferol supplementation (1000 IU/day), and changes in laboratory parameters were monitored. RESULTS: The median 25(OH)D level was 22 ng/ml, with 32% and 51% of patients exhibiting vitamin D deficiency (< 20 ng/ml) and insufficiency (20-29 ng/ml), respectively. The 25(OH)D levels were unrelated to sex, age, MM stage, or bone lesions, but the vitamin D-deficient group showed a tendency towards lower HR-QOL scores. Among patients achieving complete remission, vitamin D supplementation increased P1NP, while TRACP-5b remained unchanged. Overall survivals from vitamin D measurement and from MM diagnosis were significantly worse in the vitamin D-deficient group compared to the vitamin D-insufficient/-sufficient group. CONCLUSION: The study identified a considerable number of Japanese MM patients with insufficient serum vitamin D levels, with one-third being deficient. Additionally, vitamin D deficiency predicted poor overall survival in Japanese MM patients. Further investigation is required to determine whether vitamin D supplementation can improve the frailty and survival of vitamin D-deficient MM patients.

The Effect of Age-adjusted Sagittal Alignment on the Result of Posterior Decompression Surgery for Lumbar Spinal Canal Stenosis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: The aim of this study was to compare the outcomes of posterior decompression surgery for lumbar spinal canal stenosis (LSS) in patients with preoperative sagittal malalignment to those without, after adjusting for age and sex. SUMMARY OF BACKGROUND DATA: Sagittal balance is an important factor in spine surgery and is thought to affect postoperative outcomes following LSS. However, the relationship between sagittal malalignment and postoperative outcomes has not been thoroughly examined. METHODS: We included 533 patients who underwent surgical treatment for LSS and also achieved two-year follow-up. Patients were categorized into either a malalignment (MA+) group (69 patients) or a matched-alignment (MA-) group (348 patients) based on age-adjusted preoperative sagittal alignment. We compared the baseline and two-year postoperative health-related quality of life (HRQOL) using the Visual Analog Scale and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) scores. We also calculated clinical efficacy using the minimal clinically important difference (MCID) based on JOABPEQ scores, and age- and sex-adjusted JOABPEQ scores two years after surgery. Differences between groups were examined using the Mann‒Whitney U test and χ 2 analysis, where applicable. RESULTS: Both groups showed an improved HRQOL after decompression surgery. Similar proportions of patients showed substantial improvement, as estimated by the MCID, in four out of five subdomains of the JOABPEQ. A significantly smaller proportion of patients in the MA+ group showed substantial improvement in lumbar function. The age- and sex-adjusted HRQOL scores two years after surgery were lower in the MA+ group, particularly in the lumbar function and social life function subdomains of the JOABPEQ. CONCLUSION: The effects of posterior decompression surgery alone can still be observed at least two years postoperatively for patients with LSS and concomitant sagittal malalignment. Patients with sagittal malalignment may experience lower HRQOL than those without this type of malalignment.