Bone Pain Research Articles

Percutaneous vertebroplasty/kyphoplasty contributes to the improved outcome in patients with newly diagnosed multiple myeloma: A single center cohort study

ObjectiveTo evaluate the efficacy and prognosis of percutaneous vertebroplasty/kyphoplasty (PVP/PKP) in patients with newly diagnosed multiple myeloma (NDMM). MethodsClinical data of NDMM patients who underwent PVP/PKP during front-line regimen at Peking Union Medical College Hospital from January 1, 2003, to June 30, 2023, were analyzed. Patients with comparable bone diseases not receiving orthopedic surgery were selected as controls. Visual analogue scale (VAS) score, progression-free survival (PFS), and overall survival (OS) were compared. ResultsBaseline characteristics were matched between the surgical group (n = 51 with 56 surgeries) and non-surgical group (n = 102), including demographics, tumor load, International Staging System (ISS), bone diseases, cytogenetic abnormalities, first-line treatment, and autologous stem-cell transplantation (ASCT). Bone lesions for PVP/PKP were located at thoracic vertebrae (53.6 %, 30/56) or lumbosacral vertebrae (46.4 %, 26/56). The postoperative VAS score was significantly improved (2.25 ± 0.81 vs 5.92 ± 1.05, P < 0.001). The median follow-up time was 51[38–70] months. Kaplan-Meier survival analysis suggested that both PFS (37[17–89] vs 23[12–61] months, HR 0.648, 95 %CI 0.431–0.973, P = 0.047) and OS (not reached vs 66[28-NR] months, HR 0.519, 95 %CI 0.296–0.910, P = 0.045) were significantly prolonged in the surgical group. COX multivariate analysis suggested that PVP/PKP was an independent prognostic factor for PFS (P = 0.021, HR 0.589, 95 %CI 0.376–0.922) and OS (P = 0.038, HR 0.496, 95 %CI 0.255–0.963). Subgroup analysis confirmed that patients with ISS II/III or non-ASCT achieved better PFS and OS in the surgical group (PFS: P = 0.033, P = 0.040; OS: P = 0.024, P = 0.018 respectively), while similar survival outcome was observed in patients with ISS I or ASCT between two groups. ConclusionFor NDMM patients, not only does PVP/PKP alleviate bone pain, meanwhile, it improves the PFS and OS in advanced subpopulation or non-transplant myeloma patients, which suggests that shortening the gap from symptom onset to diagnosis by orthopedic surgery favors clinical prognosis.

The Risk of Medication-Related Osteonecrosis of the Jaw in Children: Guidance for Antiresorptive Use in Pediatric Patients

Antiresorptive targeted cancer therapies, such as denosumab and bisphosphonates, are used in adults, but their application in pediatric cancer is more recent. Side effects such as osteonecrosis of the jaw (ONJ) observed in adults have curtailed use of these medications in the pediatric population. This study assesses the frequency of ONJ, other side effects, and the indications for use of denosumab versus bisphosphonates in pediatric subjects. A retrospective cohort study of pediatric subjects who underwent bisphosphonate or denosumab therapy at our institution from 2007-2023 was conducted. Subjects aged ≥ 18years at therapy initiation were excluded. The independent variable was antiresorptive therapy divided into 2 groups, treatment with intravenous bisphosphonates or denosumab. Primary outcomes were development of bisphosphonate-related and denosumab-related ONJ. Secondary outcomes included additional side effects. ONJ risk factors, subject demographics, indications for use, timing, duration, and cumulative dose of antiresorptive therapy were abstracted. Univariate and bivariate statistics were computed to describe the sample and measure associations between antiresorptive therapy and outcomes. P values < .05 conferred statistical significance. The sample was composed of 178 subjects with a mean age of 11.7±6.1years. There were 14 (7.9%) and 164 (92.1%) subjects treated with denosumab and bisphosphonate therapies, respectively. There were 0 cases of ONJ across all subjects. The most common indication for treatment was adjuvant targeted therapy for aggressive tumors and malignancy (39.3%) followed by osteoporosis (14.6%). Subjects treated with denosumab had higher frequencies of hypercalcemia and severe bone pain than subjects treated with bisphosphonates, 28.6% versus 1.2% (P<.001) and 14.3% versus 0.00% (P<.001), respectively. While invasive dental procedures are ideally performed before antiresorptive treatment, our data suggest that bisphosphonates may be used safely in the pediatric population with low concern for ONJ. Our data also demonstrated bisphosphonates may have a more tolerable side effect profile than denosumab. If the perceived benefits are similar, we recommend using bisphosphonates as first-line therapy in children while reserving denosumab for refractory cases. Future studies will help determine long-term side effects and differences in efficacies of these medications.

PANCYTOPENIA: Epidemiological and Etiological Profile in Adult Patients of the Internal Medicine Department, CHU Hassan II, Fès.

Introduction: Pancytopenia is a fairly common hematological condition encountered in routine clinical practice. Since there is a wide variation in the etiologies of pancytopenia, even in different populations of the same geographical region, the identification of underlying etiologies is important. With this in mind, our study was undertaken to investigate the epidemiological and clinico-hematological profile of pancytopenic adults with the aim of identifying the different etiologies of pancytopenia. Materials and Methods: This is a retrospective study including all adult patients with pancytopenia admitted to the internal medicine department at Hassan II University Hospital in Fez, Morocco, from January 1, 2019 to December 31, 2022. Pancytopenia is defined by the simultaneous presence of a hemoglobin level &lt; 13.0g/dL in men and 12.0g/dL in women, a total leukocyte count &lt; 4.0 × 10^9 /L and a platelet count &lt; 150 ×10^9 /L. Each patient included in the study underwent a series of investigations, including: blood count and reticulocyte count; peripheral blood smear examination; vitamin assays; bone marrow aspiration; immunophenotyping; osteomedullary biopsy (OMB) and serologies. Patients already diagnosed and under treatment, as well as patients under 18 years of age, were excluded from the study. Results: A total of 164 patients with pancytopenia were identified during our study period. The mean age of our patients was 48 years [extremes 18y-89y], with a preponderance of women (87women/77men). Mucocutaneous pallor was present in 100% of our patients, hepatosplenomegaly in 22.56% and hemorrhagic syndrome in 18.29%. Infectious syndrome and bone pain were observed in 12 patients (7.31%) and 05 patients (3.04%) respectively. Nineteen (19) patients had microcytic anemia, 85 had normocytic anemia and 60 patients had macrocytosis. Vitamin assays revealed vitamin B12 deficiency in 43 patients (26.91%), while 15 patients (9%) had folate deficiency. Combined B12 and folate def

Clinical Spectrum of Celiac Disease among Adult Population: Experience from Largest Tertiary Care Hospital in Karachi, Pakistan.

Celiac disease (CD) is a systemic autoimmune enteropathy triggered by dietary gluten in genetically susceptible individuals. Celiac disease affects 0.6-1.0% of the population worldwide. The prevalence of CD in Pakistan is yet unknown due to under diagnosis and lack of awareness. To determine a vast variety of presenting features in subtypes of CD to overcome the burden of disease. This was a prospective, comparative, cross-sectional study conducted at Gastroenterology department of Jinnah Postgraduate Medical Center, Karachi from December 2022 till June 2023. This study included all adult patients ≥18 years diagnosed with CD on the basis of clinical presentation, positive IgA and IgG anti-transglutaminase antibodies (value >12 IU/mL detected by ELISA followed by small intestinal biopsy classified as per Marsh criteria. The data obtained were analyzed on the statistical software SPSS version 23. Descriptive statistics were obtained by frequencies and percentages. About 142 patients were enrolled in the study, 103 (91.5%) had classical CD (CCD) whereas 36 (25%) had non-classical (NCCD). About 89 (62.7%) were females and 53 (37.3%) were males. The mean age was found to be 23 ± 6 years. Nutritional deficiencies including anemia, B12, folate, osteopenia and low body mass index (BMI) <18 was found more in CCD group as compared with NCCD group with significant p-values. Titers of anti-TTG between CCD and NCCD were not statistically significant. Hypothyroidism and PCOS were the most common associated conditions observed in adult CD patients. In conclusion, CD in adults and has diverse presentations. Adults with unexplained extra-intestinal symptoms like anemia and bone pain should be investigated for CD. Butt N, Shahid B, Butt S, et al. Clinical Spectrum of Celiac Disease among Adult Population: Experience from Largest Tertiary Care Hospital in Karachi, Pakistan. Euroasian J Hepato-Gastroenterol 2024;14(1):24-29.

Optimal production and purification of n.c.a.143Pr as a promising palliative agent for the treatment of metastatic bone pain

This study proposes the beta-emitting radioisotope 143Pr as a promising candidate for palliative treatment of metastatic bone pain due to its desirable physical decay characteristics. An optimized process was developed for the production and purification of non-carrier-added 143Pr using a medium flux research reactor. Calculations were performed to determine the optimal irradiation time and cooling period for irradiating 1 mg of natural cerium oxide to indirectly produce 143Pr through the decay of 143Ce. Following irradiation and cooling, extraction chromatography was employed to efficiently isolate 143Pr from the irradiated target material. A column containing Ln-resin was used along with nitric acid as the mobile phase and an optional oxidation step with NaBrO3/ascorbic acid to separate 143Pr from impurities such as 143Ce and 141Ce. Radionuclidic purity of over 99.995% was achieved as confirmed through gamma spectroscopy, demonstrating effective separation of 143Pr. Additional quality control analyses established the chemical and radiochemical purity of the purified 143Pr nitrate product. With a half-life of 13.6 days and maximum beta energy of 0.937 MeV, 143Pr exhibits favorable properties for palliative bone pain therapy. This study therefore provides a viable method for producing high-purity 143Pr through the optimized irradiation and purification processes described. Further investigation is warranted to explore potential clinical applications of 143Pr for palliation of metastatic bone cancer pain.

A review of botany, phytochemistry, pharmacology, and applications of the herb with the homology of medicine and food: Ligustrum lucidum W.T. Aiton.

Ligustrum lucidum W.T. Aiton is an outstanding herb with the homology of medicine and food. Its ripe fruits are traditionally used as an important tonic for kidneys and liver in China. Ligustrum lucidum W.T. Aiton is rich in nutritional components and a variety of bioactive ingredients. A total of 206 compounds have been isolated and identified, they mainly include flavonoids, phenylpropanoids, iridoid glycosides, and triterpenoids. These compounds exert anti-osteoporosis, anti-tumor, liver protective, antioxidant, anti-inflammatory, and immunomodulatory effects. Ligustrum lucidum W.T. Aiton has been traditionally used to treat many complex diseases, including osteoporotic bone pain, rheumatic bone, cancer, related aging symptoms, and so on. In the 2020 Edition of Chinese Pharmacopoeia, there are more than 100 prescriptions containing L. lucidum W.T. Aiton. Among them, some classical preparations including Er Zhi Wan and Zhenqi fuzheng formula, are used in the treatment of various cancers with good therapeutic effects. Additionally, L. lucidum W.T. Aiton has also many excellent applications for functional food, ornamental plants, bioindicator of air pollution, algicidal agents, and feed additives. Ligustrum lucidum W.T. Aiton has rich plant resources. However, the application potential of it has not been fully exploited. We hope that this paper provides a theoretical basis for the high-value and high-connotation development of L. lucidum W.T. Aiton in the future.

Burosumab treatment of X-linked hypophosphatemia patients: interim analysis of the SUNFLOWER longitudinal, observational cohort study.

X-linked hypophosphatemia (XLH) is a genetic disease that results in excessive FGF23, chronic hypophosphatemia, and musculoskeletal abnormalities, with affected patients experiencing symptoms such as bone pain, bone deformity, fracture, and pseudofracture. Burosumab is a fully human monoclonal antibody that binds to FGF23, improving lowered serum 1,25(OH)2D and phosphate levels in patients with XLH. There are insufficient data on the use of burosumab, its safety, and the outcomes of treated patients in a real-world setting. The SUNFLOWER (Study of longitUdinal observatioN For patients with X-Linked hypOphosphatemic rickets/osteomalacia in collaboration With Asian partnERs) study is an ongoing longitudinal, observational cohort study of patients with XLH in Japan and South Korea. Enrollment occurred between April 2018 and December 2020. This interim analysis compared the background characteristics of patients who received burosumab with those who did not, and assessed improvements in biomarkers, physical and motor function, health-related quality-of-life (HRQOL) and other patient-reported outcome (PRO) measures, as well as the safety of burosumab treatment in 143 Japanese patients from 15 institutions over 6mo. The patients had a median [interquartile range] age of 17.5 [11.0, 38.8] yr and 98 (68.5%) were female. Among patients aged <18 and ≥18yr, 40/73 (54.8%) and 25/70 (35.7%) received burosumab, respectively. More patients aged ≥18 who received burosumab had bone pain at baseline vs those not treated with burosumab (6/25, 24.0% vs 2/45, 4.4%, p=.021). Patients treated with burosumab had improved serum phosphate and 1,25(OH)2D levels; moreover, rickets severity and HRQOL/PRO measures, such as pain, appeared to improve over 6mo of burosumab treatment, and no new safety concerns were identified. This study identified trends in the background characteristics of patients with XLH who receive burosumab in real-world clinical practice. Furthermore, the results support the use of burosumab therapy in real-world settings.

Schnitzler's Syndrome-Diagnostic Experience, Approaches to Therapy, and Patient Management according to a Multicenter Russian Cohort.

The objectives of the study were to present the experience of diagnosis, management, and therapy with IL-1 inhibitors in patients with Schnitzler's syndrome (SchS) according to a multicenter Russian cohort. An observational retrospective study for a 10-year period (2012-2022) involved 17 patients with SchS who were admitted to the hospital or were observed on an outpatient basis (eight women and nine men). The diagnosis of all of them corresponded to the Strasbourg diagnostic criteria. The age of patients ranged from 25 to 81 years (Me 53[46; 56]). The age at the time of the onset of the disease ranged from 20 to 72 years (Me 46[39; 54]), the duration of the disease before diagnosis ranged from 1 to 35 years (Me 6.5[3; 6]), in three patients it exceeded 10 years, in the rest it ranged from 1 to 8 years. Infectious and lymphoproliferative diseases, monogenic AIDs (CAPS, TRAPS, and HIDS) were excluded from all patients at the prehospital stage. The referral diagnosis for all of them was Still 's disease in adults. Clinical manifestations of the disease in all patients included fatigue, lethargy, fatigue, rash, and fever. In all patients, skin elements were urticular and were accompanied by itching in 6 (37.5%) patients. Bone pain was observed in 12 (70.6%) patients; arthralgias, in 16 (94.1%); arthritis, in 9 (52.9%); myalgia, in 7 (41.2%); and weight loss, in 4 (23.5%). Lymphadenopathy was detected in 6 (35.3%) patients; enlarged liver, in 6 (35.3%); pericarditis, in 4 (23.5%); angioedema, in 6(35.3); redness and dryness in the eyes, in 3 (17.6%); sore throat, in 2 (11.8%); abdominal pain, in 1 (5.9%), distal polyneuropathy, in 2 (11.8%); paraesthesia, in 1 (5.9%); and chondritis of the auricles, in 1 (5.9%). Monoclonal gammopathy was detected in all patients with a secretion level of 2.9-15.1 g/L: IgMk (n = 10, 64.7%), less often IgMλ (n = 2), IgGk (n = 2), IgGλ (n = 1), and IgAλ (n = 1). Ben-Jones protein was not detected in any of them. All patients had an increased level of ESR and CRP. Before inclusion in the study, 16 patients received GCs (94.1%) with a temporary effect that disappeared with dose reduction or cancellation. Seven patients received cDMARDs, including methotrexate (5), hydroxychloroquine (2), and cyclophosphamide (1). All patients received NSAIDs and antihistamines, as well as biologics, including the anti-B-cell drug rituximab (1), monoclonal ABs to IgE omalizumab (2, 1 without effect and 1 with partial effect), IL-1i canakinumab (n = 10, 58.8%) subcutaneously once every 8 weeks, and anakinra (n = 4, 23.5%) subcutaneously daily. The duration of taking anakinra, which was prescribed in the test mode, ranged from 1 week to 2.5 months with a further switch to canakinumab in 3 patients. The duration of taking canakinumab at the time of analysis ranged from 7 months to 8 years. Against the background of treatment with IL-1i, 10 out of 11 (90.9%) patients received a complete response in terms of the clinical manifestations of the disease and a decrease in the level of ESR and CRP within a few days. In one patient, a partial response to the administration of anakinra was detected; however, after switching to canakinumab, the effect of treatment was finally lost. One patient received IL-6i for 8 months with an incomplete effect and a positive dynamics after switching to anakinra. Thus, anakinra was initially prescribed to four patients and changed to canakinumab in two of them; canakinumab was started as the first drug in seven patients. Treatment with anakinra was continued in two patients; with canakinumab, in nine patients. In one patient, due to the persistent absence of relapses, the interval between canakinumab injections was increased to 5 months without signs of reactivation; however, subsequently, against the background of stress and relapses of the disease, the intervals were reduced to 4 months. A healthy child was born by the same patient on the background of treatment. The tolerability of therapy was satisfactory in all patients, no SAEs were noted. SchS is a rare multifactorial/non-monogenic AID that should be differentiated from a number of rheumatic diseases and other AIDs. The onset in adulthood, the presence of recurrent urticarial rashes in combination with fever and other manifestations of a systemic inflammatory response are indications for examination for monoclonal secretion. The use of short- or long-acting IL-1i is a highly effective and safe option in the treatment of such patients.

Detection of novel PPP1R1B::STARD3 fusion transcript in acute myeloid leukemia: a case report

BackgroundAcute myeloid leukemia (AML) is the second most common type of leukemia in children. Although prognostic and diagnostic tests of AML patients have improved, there is still a great demand for new reliable clinical biomarkers for AML. Read-through fusion transcripts (RTFTs) are complex transcripts of adjacent genes whose molecular mechanisms are poorly understood. This is the first report of the presence of the PPP1R1B::STARD3 fusion transcript in an AML patient. Here, we investigated the presence of PPP1R1B::STARD3 RTFT in a case of AML using paired-end RNA sequencing (RNA-seq).Case presentationA Persian 12-year-old male was admitted to Dr. Sheikh Hospital of Mashhad, Iran, in September 2019 with the following symptoms, including fever, convulsions, hemorrhage, and bone pain. The patient was diagnosed with AML (non-M3-FAB subtype) based on cell morphologies and immunophenotypical features. Chromosomal analysis using the G-banding technique revealed t (9;22) (q34;q13).ConclusionsSingle-cell RNA sequencing (scRNA-seq) analysis suggested that the PPP1R1B promoter may be responsible for the PPP1R1B::STARD3 expression. Alterations in the level of lipid metabolites implicate cancer development, and this fusion can play a crucial role in the cholesterol movement in cancer cells. PPP1R1B::STARD3 may be considered a candidate for targeted therapies of the cholesterol metabolic and the PI3K/AKT signaling pathways involved in cancer development and progression.

Current Novel Targeted Therapeutic Strategies in Multiple Myeloma.

Multiple myeloma (MM) is a hematologic malignancy caused by the clonal expansion of immunoglobulin-producing plasma cells in the bone marrow and/or extramedullary sites. Common manifestations of MM include anemia, renal dysfunction, infection, bone pain, hypercalcemia, and fatigue. Despite numerous recent advancements in the MM treatment paradigm, current therapies demonstrate limited long-term effectiveness and eventual disease relapse remains exceedingly common. Myeloma cells often develop drug resistance through clonal evolution and alterations of cellular signaling pathways. Therefore, continued research of new targets in MM is crucial to circumvent cumulative drug resistance, overcome treatment-limiting toxicities, and improve outcomes in this incurable disease. This article provides a comprehensive overview of the landscape of novel treatments and emerging therapies for MM grouped by molecular target. Molecular targets outlined include BCMA, GPRC5D, FcRH5, CD38, SLAMF7, BCL-2, kinesin spindle protein, protein disulfide isomerase 1, peptidylprolyl isomerase A, Sec61 translocon, and cyclin-dependent kinase 6. Immunomodulatory drugs, NK cell therapy, and proteolysis-targeting chimera are described as well.

A case of multiple myeloma misdiagnosed as seronegative rheumatoid arthritis: a rare case report

Introduction: Multiple myeloma (MM) is a malignant plasma cell proliferation producing large numbers of monoclonal immunoglobulins. Typical MM symptoms include anemia, bone pain, hypercalcemia, and renal failure. Atypical presentations like joint involvement were rarely reported in the literature and may cause significant delays in treatment and adverse outcomes. Case presentation: The authors report a case of a 54-year-old female who presented with symmetrical polyarthritis and was misdiagnosed with rheumatoid arthritis. The diagnosis of MM was made after failing many treatments of rheumatoid arthritis and with further laboratory tests and procedures. Conclusion: This rare manifestation of MM carries a diagnostic challenge and causes a significant delay in treating such patients. Here, the authors report this unusual initial presentation with a review of several cases in the literature describing similar presentations.

Patient (pt) interview–based content validation of the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0).

e23106 Background: Pts with myelofibrosis (MF) often experience debilitating symptoms that negatively impact health-related quality of life and functioning. The MFSAF v4.0 is a 7-item questionnaire assessing the burden of MF symptoms, including fatigue, night sweats, pruritus, abdominal discomfort, pain under left ribs, early satiety, and bone pain. Each item is evaluated on an 11-point numeric rating scale (NRS) from 0 (absent) to 10 (worst imaginable). We sought to evaluate the content validity of the MFSAF v4.0 in Janus kinase inhibitor–experienced pts with MF. Methods: Qualitative interviews were conducted remotely by trained interviewers with 20 Janus kinase inhibitor–experienced and symptomatic (MFSAF Total Symptom Score [TSS] ≥10) pts with MF from the US (n = 5) and UK, Germany, Italy, Poland, and Spain (n = 3 each). The interview began with a concept elicitation section to allow spontaneous reporting of important concepts prior to content validation of the MFSAF v4.0 items and NRS as relevant, important, and understandable to pts. Results: Mean pt age was 59.4 years; 50% were male, 55% were diagnosed within the past year, 95% were on any treatment for MF, and 75% were anemic. On average, pts had 2.1 transfusions within the past 3 mo. Mean MFSAF v4.0 TSS was 28.6.The top spontaneously endorsed symptoms were tired (70%), bone/muscle pain (70%), fatigue (55%), night sweats (45%), and pruritis (45%), many of which are also items in the MFSAF v4.0. An additional 18 symptoms were spontaneously mentioned by pts prior to completion of the MFSAF v4.0. Many of these other symptoms were endorsed by ≤10% of pts (1 or 2 pts each), and 90% of pts felt that the measure represented their experience and did not recommend inclusion of additional symptoms after reviewing the measure. Overall, pts showed a clear understanding of the MFSAF v4.0 (Table). No more than 3 pts (15%) mentioned that a given item was not relevant to their individual experience. Pts consistently felt that it was easy to select an answer on the response scale and were able to differentiate response options. When describing meaningful change in terms of NRS, pts most often suggested that an improvement of 2 to 4 points would be meaningful. Conclusions: Based on the findings from this study, the MFSAF v4.0 is a content-valid measure for pts with MF and captures the most important concepts. All items are comprehensible and relevant, with the NRS endorsed as an appropriate response scale. [Table: see text]

Predictors of symptom scores in myeloproliferative neoplasms: A real-world retrospective cohort study.

6582 Background: Although high symptom burden indicates poor survival and informs treatment decisions, little is known about the impact of demographic, clinical, and laboratory features on total symptom score (TSS) in patients with myeloproliferative neoplasms (MPN). Methods: Patients with MPN (polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF)) were identified from the retrospective chart review. TSS, individual symptom scores (fatigue, early satiety, abdominal discomfort, inactivity, concentration problems, fever, night sweats, itching, bone pain, weight loss), demographic characteristics (race, ethnicity, age, gender), clinical features (time since diagnosis, depression status, obesity status, spleen size), laboratory results and season at the time of visit were recorded from the clinical encounter when index assessment of TSS was performed for each patient. Normality was assessed using visual inspection of data distribution, whereas multicollinearity was assessed using various inflation factors. A univariable regression followed by a multivariable regression analysis was conducted using a backward selection approach. A p-value &lt;0.05 indicated a statistically significant association of a given feature with TSS. Results: The chart review identified 252 patients (PV: 78; ET: 81; MF: 93). Mean age was 59 (SD: 17.7), 67 (SD: 13.0), and 68 (SD: 10.9) years for ET, PV, and MF respectively. Most patients were white (PV, MF: 92%; ET: 83%) and females (ET: 75%; PV: 60%; MF: 53%). The TSS of patients was highest with PV (mean: 18.5; SD: 16.9) followed by MF (mean: 18.1; SD: 15.4) and ET (mean: 14.3; SD: 15.9). Fatigue was the most reported symptom whereas the least reported symptoms were fever and weight loss. Univariable regression analyses showed depression (B: 17.7; p=0.02), female gender (B: 10.6; p=0.01), platelet count (B: 0.03; p=0.03), and hemoglobin (Hb) (B: -2.6; p=0.01) in PV patients, depression (B: 19.8, p=2x10-5) in ET patients and depression (B: 11.0, p=0.03), white blood cell (WBC) count (B: 0.2; p=0.01), neutrophil count (B: 0.3, p=0.01), and non-neutrophil WBC count (B: 0.6; p=0.02) in MF patients to have significant association with TSS. Multivariable regression analyses ( Table) showed Hb (B: -2.5; p=0.01) and platelet count (B: 0.02; p=0.03) in PV patients, depression (B: 19.7; p=2x10-5) in ET patients and depression (B: 12.3, p=0.01) and WBC count (B: 0.3; p=0.002) in MF patients to have a significant association with TSS. Conclusions: Depression in ET and MF and low Hb in PV were identified as significant drivers of symptom burden. Identifying and managing patients with these comorbidities could improve their quality of life with a potential survival benefit. [Table: see text]

Baseline PSMA PET/CT as a predictive biomarker for toxicity and patient-reported outcomes in mCRPC patients undergoing 177Lu-PSMA radioligand therapy.

e17058 Background: The phase III VISION trial demonstrated that 177Lu-PSMA-617 (PSMA-RLT) prolonged overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Common side effects of PSMA-RLT include xerostomia, bone pain, and myelosuppression. The objective of this study is to evaluate the role of baseline PSMA PET/CT (bPET) in predicting hematologic toxicity and patient-reported outcomes in mCRPC patients undergoing PSMA-RLT. Methods: Patients treated with 177Lu-PSMA-617 in the Expanded Access Program at UCLA with available bPET, toxicity data, and patient-reported outcomes (BPI, FACT-P, and Xerostomia Questionnaire) were included in this retrospective analysis. TRAQinform IQ technology (AIQ Solutions-Madison, WI) was used to conduct region of interest (ROI)-based analyses at bPET. SUVmean, SUVmax, volume (cm3), and total lesion PSMA (TLP; SUVmean x volume) of the whole-body tumor burden, healthy bone, and the salivary glands were extracted. We evaluated the following associations: 1) Whole-body tumor parameters on bPET with time to worsening of FACT-P scores (defined as a decrease of &gt;10 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 2) Healthy bone parameters on bPET with time to worsening of BPI Pain Severity and Pain Interference scores (defined as a 30% increase or at least 2 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 3) Salivary gland parameters on bPET with Xerostomia Questionnaire scores (Mixed-effect linear regression model). Results: 61 mCRPC patients were included. When evaluating associations between healthy bone SUVmean, SUVmax, and TLP with time to first occurrence of Grade 3 or 4 hematologic toxicity, baseline hemoglobin was associated with a longer time to first occurrence (HR = 0.61, p = 0.005; HR = 0.59, p = 0.002; HR = 0.62, p = 0.005 respectively). When evaluating associations between bPET and time to worsening of FACT-P scores, whole-body tumor SUVmean, SUVmax, and TLP were associated with a longer time to worsening (HR = 0.74, p = 0.033; HR = 0.82, p = 0.01; HR = 0.91, p = 0.028 respectively). When evaluating associations between salivary gland SUVmean, volume, SUVmax, and TLP with Xerostomia Questionnaire scores, the number of cycles was associated with higher scores (mean estimate: 0.63, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.63, p = 0.003 respectively). Conclusions: In this retrospective analysis of 61 mCRPC patients treated with PSMA-RLT, bPET parameters were generally not predictive of hematologic toxicity or patient-reported outcomes. Of note, whole-body tumor SUV was associated with a longer time to worsening of FACT-P scores. Validation in a larger, prospective cohort is warranted.

Primary prophylaxis with pegylated-granulocyte colony-stimulating factor for patients with unresectable pancreatic cancer treated with modified-FOLFIRINOX: A randomized phase II trial.

4145 Background: Pancreatic cancer patients treated with FOLFIRINOX often suffer from severe neutropenia leading to dose reductions and sometimes fatal outcomes. However, there is no high-level evidence for primary prophylaxis of peg-GCSF for those patients. We report the result of a multi-institutional, open-label, randomized phase II trial of the peg-GCSF for unresectable pancreatic cancer patients treated with first-line modified-FOLFIRINOX. Methods: Treatment-naïve patients with histologically confirmed locally advanced or metastatic pancreatic cancer from two Korean cancer centers were enrolled. Patients received oxaliplatin 85mg/m2 D1 + leucovorin 400mg/m2 D1 + irinotecan 150mg/m2 D1 + 5-FU 2,400mg/m2 46h continuous infusion, every other week. After 1:1 randomization, peg-GCSF (pegteograstim 6 mg, GC Biopharma Corp.) was administered on day 4 for initial 8 cycles for primary prophylaxis group, where no G-CSF was given for control group. Crossover to administer peg-GCSF was permitted if patients in control group developed grade 3-4 neutropenia during initial 8 cycles. Co-primary endpoints were grade 3-4 neutropenia or febrile neutropenia during initial 8 cycles of mFOLFIRINOX. Secondary endpoints included relative dose intensity (RDI), patient reported quality of life, bone pain, and survival. Results: Between Feb 2022 and Jan 2024, 38 patients were randomized to peg-GCSF primary prophylaxis group and 39 patients were randomized to control group. Peg-GCSF group patients had significantly less grade 3-4 neutropenia during initial 8 cycles of mFOLFIRINOX, compared to the control (1/38, 2.6% vs 15/39, 38.5%, P=0.0001). None of peg-GCSF group patients experienced febrile neutropenia, where 5 patients (12.8%) experienced febrile neutropenia in control group. Cumulative RDIs of mFOLFIRINOX until progression or 8th cycles were similar between two groups with 93%. Although this trial was not powered for survival comparison, median PFS (9.0 vs 7.3 months) was numerically longer for peg-GCSF group compared to control. OS was not reached for both arms, but hazard ratio was 0.48 for peg-GCSF group. Conclusions: Primary prophylaxis with peg-GCSF significantly reduced grade 3-4 neutropenia and febrile neutropenia in patients with locally advanced or metastatic pancreatic cancer treated with mFOLFIRINOX events. Considering the study design of permitting the crossover, cumulative RDI was similar. Further follow-up of survival and quality of life results will be presented. Clinical trial information: KCT0006536 .

Kerala Ayurveda Ostoact Tablet treats osteoporosis in ovariectomized rat model via regulating RANKL/OPG pathway

Background and aimKerala Ayurveda Ostoact Tablet (OAT) is a traditional Ayurvedic preparation that might use for the management of joint pain, bone pain and arthritis. The goal of present research was to evaluate the activity of OAT in improving postmenopausal osteoporosis (PMO) in ovariectomized (OVX) rats. Experimental proceduresFemale rats were ovariectomized bilaterally and distributed into 6 groups (n = 8) as Sham control (SC), Ovariectomy control (OVX), OVX with OAT (50 mg/kg, p.o.), OVX with OAT (100 mg/kg, p.o.) and OVX with OAT (150 mg/kg, p.o.) and Standard group (17β-estradiol, 30 μg/kg, s.c.). SC group rats went through a sham operation procedure. The animals were treated with an oral dose of OAT (50, 100 and 150 mg/kg) for 90 days. Body weight, tail skin temperature (TST) Serum hormones, bone turnover parameters, proinflammatory cytokines, bone physical parameters, histopathological analysis (uterus, vagina, and femur) and microcomputed tomography of the femur were measured on the 90th day of treatment. A new high performance thin layer chromatography (HPTLC) process has been established for the standardization of OAT. Results and conclusionOVX rats treated with OAT exhibited a significant decrease in TST, improved serum hormonal and lipid profile, bone turnover markers and pro-inflammatory cytokines, bone physical properties, increased bone density, and enhanced cytological and histological alterations with significant improvement in rat's body weight. In addition, OAT administration enhanced the weakening of trabecular bone microarchitecture triggered by OVX confirmed by microcomputed tomography (micro-CT). These findings imply that OAT may help treat osteoporosis in women brought on by menopause.

Safety and efficacy of PEG-rhG-CSF as primary prophylaxis against neutropenia induced by combination chemotherapy regimens involving oral chemotherapy agents in gastrointestinal cancer patients: A prospective, exploratory, non-randomized controlled study.

e24107 Background: The safety and efficacy of PEGylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for prevention of chemotherapy-induced neutropenia (CIN) in patients undergoing oral chemotherapy remain unclear. This study investigated the safety and efficacy of PEG-rhG-CSF as primary prophylaxis against CIN in gastrointestinal (GI) cancer patients receiving combination chemotherapy regimens involving oral chemotherapy agents. Methods: This is a prospective, single-center, open-label, exploratory, non-randomized controlled study. GI cancer patients receiving two consecutive cycles of IV oxaliplatin (150mg/m2 on day 1) combined with oral capecitabine 1000mg/m2 or tegafur gimeracil oteracil potassium capsule 40-60mg twice daily on days 1-14 every 3 weeks. PEG-rhG-CSF (6mg) was administered subcutaneously 24 hours post-oxaliplatin treatment in the PEG-rhG-CSF group, while the control group did not receive it. The primary endpoint was safety, and secondary endpoints included CIN incidence and neutropenic complications. The study was registered with the Chinese Clinical Trial Registry (registration number ChiCTR2100054854). Results: Between March 2022 and January 2023, a total of 49 patients was screened, and 43 patients completed the treatment (26 in PEG-rhG-CSF group and 17 in control group). The average age was 61.4 years, with 90.7% males and 83.7% having gastric cancer. Baseline characteristics were similar between the two groups. The overall adverse events (AE) did not differ statistically (88.5% vs. 88.2%, p = 1.000), with grade £2 fatigue and nausea being the most common AEs. Grade 3 platelet reduction showed no significant difference between the two groups (7.69% vs. 17.65%, p = 0.432). Four cases of bone pain (15.4%) and five cases of injection site reactions below grade 3 (19.2%) were observed in the PEG-rhG-CSF group. Grade ≥2 CIN was significantly lower in the PEG-rhG-CSF group (3.84% vs. 58.82%, p &lt; 0.001). One case in the PEG-rhG-CSF group required antibiotic treatment due to febrile neutropenia. Regarding neutropenic complications, the PEG-rhG-CSF group exhibited lower proportion of chemotherapy delay (3.85% vs. 35.29%, p &lt; 0.001) and dose reduction (1.92% vs. 23.53%, p = 0.002). Rescue treatment with rhG-CSF for grade 3/4 CIN was significantly less frequent in the PEG-rhG-CSF group (1.92% vs. 23.53%, p = 0.002). Conclusions: Primary prophylaxis with PEG-rhG-CSF in GI cancer patients undergoing oral capecitabine/tegafur gimeracil oteracil potassium may be safe, without an increased chemotherapy-related AEs, and is associated with a reduced grade ≥2 CIN. Clinical trial information: ChiCTR2100054854.

Secondary hyperparathyroidism: Update

Secondary hyperparathyroidism is a clinical condition characterized by an increase in the synthesis and secretion of parathyroid hormone (PTH). Its presentation will be conditioned by the development of stimuli such as hyperphosphatemia, hypocalcemia, vitamin D deficiency, and PTH resistance. The most common cause of secondary hyperparathyroidism is chronic kidney disease, a pathological condition in which all the afore mentioned stimuli converge. Secondary hyperparathyroidism is evidenced by an increase in the size of the parathyroid glands, favored by cellular hyperplasia and hypertrophy. At the bone level, there will be an increase in the quantity and activity of osteoblasts and osteoclasts, leading to bone with unusual structural characteristics. Symptoms related to the disease include itching, bone pain, concentration alteration, and depression. In the long term, patients have a higher risk of cardiovascular mortality. Therapeutic options include calcimimetics, phosphate binders, vitamin D supplements, and surgery.

Challenging diagnosis of a rare disease: hypophosphatemic osteomalacia – case report and literature review

Hypophosphatemic osteomalacia is a rare condition caused by different causes, all resulting in disturbances of calcium-phosphate management. One of the most common causes among adults is tumor-induced osteomalacia, which is characterized by increased secretion of fibroblast growth factor-23. Its symptoms are vague, tests necessary for diagnosis are not commonly used by clinicians and some of them are only available in highly specialized centers. Due to these reasons, patients often are misdiagnosed for more common conditions and are left without proper treatment for many years. We present a case of a patient suffering from multiple fractures, diffuse bone pain, and muscle weakness, who was previously misdiagnosed for osteoporosis, primary and secondary hyperparathyroidism. We discuss the pathophysiology of tumor-induced osteomalacia, diagnostic path, differential diagnosis, available forms of treatment and possible complications.

Brown tumors: Retrospective analysis of 26 cases.

Brown tumors are reactive osteolytic lesions caused by hyperparathyroidism. These rare lesions are non-neoplastic processes that result from bone resorption. The purpose of this study was to retrospectively review a 34-year experience with brown tumors in our institution. We retrospectively analyzed the records of 26 consecutive patients with brown tumor who were treated in our institution between May 1988 and October 2020, with a mean follow-up of 36,1 months. 17 male (65,4%) and 9 female (34,6%) patients with a mean age of 41,6 were included in the study. Localized bone pain was present in 13 cases (50,0%) as the first presenting symptom. 3 patients (11,5%) presented with diffuse bone pain. 7 patients (26,9%) were diagnosed with brown tumor while being investigated for pathological fractures. The other 3 patients (11,5%) were diagnosed while being evaluated for hypercalcemia symptoms. 7 patients (26,9%) had solitary lesions, while 19 patients (73,1%) had multiple lesions. Pelvis, femur, ribs, tibia, proximal humerus and mandible were the most common sites of localization. 23 patients (88,5%) were diagnosed with primary hyperparathyroidism, while the other 3 patients (11,5%) had secondary hyperparathyroidism. A total of the 65 lesions, 23 (35.4%) underwent orthopedic surgery, and 42 (64.6%) were followed up conservatively after parathyroidectomy. Orthopedic surgery was performed in 21 of 26 patients, the other 5 cases were followed up conservatively. Intralesional curettage was performed in 19 cases (82,6%). The resulting cavity was filled with bone cement in 11 cases (47,8%). Bone grafting was applied in 8 cases (34,8%). No recurrence was observed in any of the patients. The diagnosis of brown tumor begins with clinical suspicion. Endocrinology and general surgery consultation is important before surgery. Treatment of brown tumors requires a multidisciplinary approach.