Irreversible Intrathecal Chemotherapy-induced Myelopathy in a Patient with Diffuse Large B-cell Lymphoma.

Intrathecal chemotherapy is often administered for prophylaxis and treatment of central nervous system involvement in hematological malignancies. However, it may rarely cause neurotoxicity as a side effect. We herein report a 74-year-old woman with diffuse large B-cell lymphoma including a spinal lesion. She received systemic and intrathecal chemotherapy. After five doses of intrathecal chemotherapy, she developed intrathecal chemotherapy-induced myelopathy. Intrathecal treatment was discontinued, and she was administered vitamin B12 and folic acid, along with steroid pulses. However, her symptoms did not improve. Intrathecal chemotherapy-induced myelopathy is rare, but may be irreversible; therefore, clinicians should be aware of this potential complication.

Reduced plasma coagulation factor XIII in patients with acute leukemia in remission during consolidation chemotherapy cycles.

Acute leukemia (AL) is a malignancy from hematologic stem cells (HSC). Consolidation with intensive chemotherapy is required after induced remission and repeatedly causes treatment-related bleeding that is usually attributed to chemotherapy-induced thrombocytopenia (CIT). However, our previous study demonstrated that severe deficiency of plasma coagulation factor XIII (pFXIII) also participated in the bleeding of CIT in AL. However, the relationship between pFXIII deficiency and consolidation chemotherapy was unknown. Here, we observed the concentration of pFXIII in patients with AL before and after consolidation chemotherapy and reevaluated the correlation to bleeding in myelosuppression. Thus, we found that the concentration of pFXIII before chemotherapy in all patients was markedly lower than in the control data and was further decreased by chemotherapy, related to bleeding in myelosuppression. These findings indicated that chemotherapy-induced pFXIII deficiency should be of concern and explored in depth.

[Efficacy and Safety of Decitabine Combined with Modified EIAG Regimen in the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome].

OBJECTIVE: To investigate the efficacy, prognosis and safety of decitabine combined with modified EIAG regimen in the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). METHODS: The clinical data of 44 patients with relapsed/refractory AML and high-risk MDS admitted to our hospital from January 2017 to December 2020 were analyzed retrospectively. The patients were equally divided into D-EIAG group (decitabine combined with EIAG regimen) and D-CAG group (decitabine combined with CAG regimen) according to clinical treatment regimen. The complete response (CR), CR with incomplete hematologic recover (CRi), morphologic leukemia-free state (MLFS), partial response (PR), overall response rate (ORR), modified composite complete response (mCRc), overall survival (OS) time, 1-year OS rate, myelosuppression and adverse reactions between the two groups were compared. RESULTS: In D-EIAG group, 16 patients (72.7%) achieved mCRc (CR+CRi+MLFS), 3 patients (13.6%) achieved PR, and ORR (mCRc+PR) was 86.4%. In D-CAG group, 9 patients (40.9%) achieved mCRc, 6 patients (27.3%) achieved PR, and ORR was 68.2%. Difference was observed in mCRc rate between the two groups (P=0.035), but not in ORR (P>0.05). The median OS time of D-EIAG group and D-CAG group was 20 (2-38) months and 16 (3-32) months, and 1-year OS rate was 72.7% and 59.1%, respectively. There was no significant difference in 1-year OS rate between the two groups (P>0.05). After induction chemotherapy, the median time for absolute neutrophil count recovery to 0.5×109/L in D-EIAG group and D-CAG group was 14 (10-27) d and 12 (10-26) d, for platelet count recovery to 20×109/L was 15 (11-28) d and 14 (11-24)d, the median red blood cell suspension transfusion volume was 8 (6-12) U and 6 (6-12) U, and the median apheresis platelet transfusion volume was 4 (2-8) U and 3 (2-6) U, respectively. There were no statistically significant differences in comparison of the above indicators between the two groups (P>0.05). The hematological adverse reactions of patients were mainly myelosuppression. Grade III-IV hematological adverse events occurred in both groups (100%), with no increase in the incidence of non-hematological toxicities such as gastrointestinal reactions or liver function damage. CONCLUSION: Decitabine combined with EIAG regimen in the treatment of relapsed/refractory AML and high-risk MDS can improve remission rate, provide an opportunity for subsequent therapies, and have no increase in adverse reactions compared with D-CAG regimen.

Severe Recurrent Nocturnal Hypoglycemia During Chemotherapy With 6-mercaptopurine in 2 Children With Acute Lymphoblastic Leukemia.

Mercaptopurine (6MP) and methotrexate are the cornerstones of maintenance therapy in pediatric patients with acute lymphoblastic leukemia. However, although bone marrow suppression and liver dysfunction are common side effects of these antimetabolites, 6MP-induced hypoglycemia during the maintenance phase is rare. Guidelines and international protocols are well established for the management of bone marrow suppression and liver dysfunction, but promptly identifying 6MP-induced hypoglycemia is the key to its control. Here we report 2 cases of leukemia that developed hypoglycemia during the maintenance phase. Both patients were boys younger than 6 years of age and both suffered symptomatic morning hypoglycemia induced by 6MP (which was diagnosed after excluding all other possible causes). Successful management included changing the time of 6MP administration from evening to morning. Other management options are also discussed.

Combined subchondral and intra-articular injections of bone marrow aspirate concentrate provide stable results up to 24 months.

PURPOSE: The aim of this study was to evaluate the clinical and imaging findings up to 24 months of follow-up in patients treated with combined subchondral and intra-articular bone marrow aspirate concentrate (BMAC) injections for the treatment of knee osteoarthritis (OA). METHODS: Thirty consecutive patients (19 males, 11 females) aged between 40 and 75 years (mean age 56.4 ± 8.1 years) with unilateral symptomatic knee OA (Kellgren-Lawrence 2-3) were included in the study. Patients were treated with combined intra-articular and subchondral bone BMAC injections (total 9 ml) under fluoroscopic control. IKDC subjective score, VAS for pain, KOOS, and EQ-VAS were prospectively evaluated up to 24 months. Radiographs were performed at baseline and at 24 months after the procedure. MRI was evaluated with the WORMS score at baseline, 6-12 months, and 24 months of follow-up. The statistical analysis was performed using SPSS v.19.0 and for all tests p < 0.05 was considered significant. RESULTS: No major complications and a 13% failure rate were reported. The IKDC subjective score remained stable from 62.6 ± 19.4 at 12 months to 63.4 ± 17.1 at 24 months (both p < 0.0005 compared to baseline, 40.5 ± 12.5). Similar improvements were reported for all KOOS subscales, while EQ-VAS did not report any significant improvement. VAS pain worsened from 3.0 ± 1.9 at 12 months to 4.4 ± 1.8 at the final follow-up (p = 0.0001), although remaining lower compared to the baseline value of 6.3 ± 1.8 (p = 0.002). The radiographic evaluation did not reveal signs of improvement or deterioration of the OA grade. The MRI findings showed a worsening in marginal osteophytes and synovitis, but a significant reduction of bone marrow edema at 24 months (p < 0.0005). CONCLUSION: Combined intra-articular and subchondral BMAC injections provided clinical and imaging benefits up to 24 months for the treatment of symptomatic knee OA, with durable clinical results, a low failure rate, and a significant reduction of bone marrow edema.

Efficacy and Safety of Decitabine Combined with Modified EIAG Regimen in the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, prognosis and safety of decitabine combined with modified EIAG regimen in the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).@*METHODS@#The clinical data of 44 patients with relapsed/refractory AML and high-risk MDS admitted to our hospital from January 2017 to December 2020 were analyzed retrospectively. The patients were equally divided into D-EIAG group (decitabine combined with EIAG regimen) and D-CAG group (decitabine combined with CAG regimen) according to clinical treatment regimen. The complete response (CR), CR with incomplete hematologic recover (CRi), morphologic leukemia-free state (MLFS), partial response (PR), overall response rate (ORR), modified composite complete response (mCRc), overall survival (OS) time, 1-year OS rate, myelosuppression and adverse reactions between the two groups were compared.@*RESULTS@#In D-EIAG group, 16 patients (72.7%) achieved mCRc (CR+CRi+MLFS), 3 patients (13.6%) achieved PR, and ORR (mCRc+PR) was 86.4%. In D-CAG group, 9 patients (40.9%) achieved mCRc, 6 patients (27.3%) achieved PR, and ORR was 68.2%. Difference was observed in mCRc rate between the two groups (P=0.035), but not in ORR (P>0.05). The median OS time of D-EIAG group and D-CAG group was 20 (2-38) months and 16 (3-32) months, and 1-year OS rate was 72.7% and 59.1%, respectively. There was no significant difference in 1-year OS rate between the two groups (P>0.05). After induction chemotherapy, the median time for absolute neutrophil count recovery to 0.5×109/L in D-EIAG group and D-CAG group was 14 (10-27) d and 12 (10-26) d, for platelet count recovery to 20×109/L was 15 (11-28) d and 14 (11-24)d, the median red blood cell suspension transfusion volume was 8 (6-12) U and 6 (6-12) U, and the median apheresis platelet transfusion volume was 4 (2-8) U and 3 (2-6) U, respectively. There were no statistically significant differences in comparison of the above indicators between the two groups (P>0.05). The hematological adverse reactions of patients were mainly myelosuppression. Grade III-IV hematological adverse events occurred in both groups (100%), with no increase in the incidence of non-hematological toxicities such as gastrointestinal reactions or liver function damage.@*CONCLUSION@#Decitabine combined with EIAG regimen in the treatment of relapsed/refractory AML and high-risk MDS can improve remission rate, provide an opportunity for subsequent therapies, and have no increase in adverse reactions compared with D-CAG regimen.

[Effect of Chemotherapy Course Delay on the Relapse of Paediatric B-cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the effect of course delay of CCLG-ALL-2008 regimen on the relapse of paediatric B-cell acute lymphoblastic leukemia (B-ALL) patients. METHODS: Paediatric B-ALL patients newly diagnosed and treated with CCLG-ALL-2008 regimen in the Children's Hospital of Soochow University from January 2011 to December 2014 were retrospectively analyzed to clarify the relationship between chemotherapy course delay and relapse, and explore the causes of course delay which led to relapse. Patients were followed up until July 2019. RESULTS: The correlation between treatment delay (number of weeks) and relapse rate was statistically significant (P=0.034), and hazard ratio indicated that longer than 4 weeks had a significant effect. The effect of positive minimal residual disease (MRD) (1×10-4≤MRD≤1×10-2) at the 12th week on the relapse rate was also statistically significant (P=0.041). Among the causes of treatment delay, the effect of myelosuppression on the relapse rate was statistically significant (P=0.01). CONCLUSION: Treatment delay exceeding 4 weeks, positive MRD at the 12th week, and myelosuppression are independent prognostic factors for relapse.

The Efficacy of Conservative Treatment of Bone Marrow Edema Syndrome: A Scoping Review of the Last Ten Years of Literature.

PURPOSE: The purpose of this review was to conduct a literature search assessing the efficacy of various conservative treatments of BMES. METHODS: According to the PRISMA guidelines, a literature search was conducted in April 2021 in MEDLINE database via PubMed and Embase to identify original articles describing the results of conservative treatments for BMES of hip and knee published in the last ten years. For each study, information regarding study characteristics, description of the treatment, patient's demographic and clinical data, length of follow-up, clinical outcome measure, disability, adverse events, classification, and extent and of edema on MRI, were extracted. RESULTS: A total of 12 studies were identified. Two studies described treatment with iloprost, three with hyperbaric oxygen (HBO), two with bisphosphonates, five with extracorporeal shockwave therapy (ESWT). The total number of patients was 351: 34 treated with iloprost, 64 with hyperbaric oxygen, 37 with bisphosphonates, 216 with ESWT. In ESWT studies, treatment with a higher flux density and a higher number of therapy sessions lead to better clinical and radiological scores. In iloprost studies, a more remarkable improvement in the VAS scale was observed in the study on hip patients. CONCLUSIONS: The treatment of idiopathic bone marrow edema is currently not standardized, making it difficult to find data that can be compared in a highly reliable way. The studies available in the literature show promising results as for the possibility to cure bone marrow edema efficiently. Standardized radiological scores for evaluating bone marrow edema area are needed in future studies.

Successful treatment of acquired amegakaryocytic thrombocytopenia with eltrombopag and immunosuppressant.

Acquired amegakaryocytic thrombocypenia (AAMT) is an extremely rare hematologic disorder and standard treatment strategy has not been established. We described herein two cases of AAMT who were fully responded to eltrombopag and immunosuppressant. Patient 1 was refractory to steroid, IVIG and recombinant human thrombopoietin (rhTPO). Patient 2 did not respond to high dosage of steroid, IVIG, rhTPO and rituximab. Moreover, his AAMT progressed to aplastic anemia in 5 months. Both patients took eltrombopag and immunosuppressant, then they achieved long-term remission without obvious side effects. Our findings suggest that this combination can be a valuable alternative in AAMT.

Subjective loss of clinical response to TNFi in axSpA relates to recurrence of MRI bone marrow oedema particularly with long-acting agents.

OBJECTIVES: Subjective loss of response immediately prior to routine TNFi therapy can occur in axial spondyloarthritis (axSpA). We investigated clinical outcomes in patients taking the first three licenced TNFis and correlated this with recurrence of MRI bone marrow oedema (MRI-BMO). METHODS: Proof-of-concept study including axSpA patients established on etanercept (ETA), adalimumab (ADA) or infliximab (IFX) reporting symptom deterioration prior to next dose. MRI/clinical data were collected prior to scheduled dose (v1), 4 days post-dose (v2) and at the time of patient-reported symptom return (v3). MRI spine/sacroiliac joints utilizing 3 T were scored using the semi-quantitative Leeds MRI scoring system. RESULTS: A total of 113 clinical assessments and MRIs were performed in 38 participants (ADA = 16, ETA = 12, IFX = 10), mean age 42.1 years ± 24.4(2SD, n = 38), 71.1% male (n = 27/38), 69.7% HLA-B27 positive (n = 23/33). At v1, all patients had high disease activity [ASDAS-CRP = 3 (2.7-3.7)] and 57.9% had MRI-BMO (number of MRI-BMO: ETA = 26, ADA = 59, IFX = 28). Improved clinical responses were seen at v2 [ASDAS-CRP -0.41(-0.81 - 0.30), P =0.018; BASDAI -0.58(-2.2 - 0.52), P =0.024]. Despite just a 4-day interval between v1 and v2, a numerical reduction in MRI-BMO lesions between v1/v2 was observed (ETA = -6, ADA = -10, IFX = -3). By v3, comparatively fewer new BMO lesions were detected in the ETA and ADA groups compared with IFX (ETA = -1, ADA = +3, IFX = +8), although the numbers were too small to enable testing for statistical significance. CONCLUSIONS: Short-lived fluctuations in MRI-BMO were commoner with longer-acting agents and corresponded with subjective loss of clinical response before next scheduled TNFi dose. Larger studies are needed to confirm the possible pathogenic implications of this phenomenon.

Haematological profiles after Intensive phase of Anti Koch Treatment with special emphasis on bone marrow changes.

BACKGROUND: Tuberculosis remains a major public health problem in various parts of the world. It leads to various haematological changes. Study of these haematological changes will help better patient management. OBJECTIVE & METHODS: It is to evaluate haematological changes in tuberculosis patients and compare the result with special emphasis to bone marrow changes as active case search is sharply decreasing the miliary tuberculosis. It is also to evaluate the patients with before and after the Intensive Phase of Anti Koch Treatment. Sputum positive and sputum negative tuberculosis patients confirmed by other ancillary techniques were included into this study. It is conducted at a tertiary level hospital in rural area. RESULT: In this study bone marrow hypercellularity was of erythroid series with only 1.92% patients showed granuloma in bone marrow aspiration. In addition to bone marrow changes, significant changes were evident in haemoglobin level, Erythrocyte Sedimentation Rate (ESR) Total White Blood Cell count and RBC count. DISCUSSION: In majority cases this study showed Erythroid Hyperplasia. It is sharp contrast with other study where myeloid hyperplasia was evident. This study also differs from other study where high number of bone marrow granuloma was reported. In this study only 1.92% cases showed bone marrow granuloma. This study also documented higher number of anaemic cases mostly because of the institute serves poor and tribal population. CONCLUSION: In our study the cases showing granuloma and hyperplasia of myeloid series were limited. With introduction of Directly Observed Treatment and house to house active case search helped to sharply decrease bone marrow granuloma by limiting multi-organ spread. This study showed, ESR level may be considered as prognostic parameters of tuberculosis.

The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms.

OBJECTIVE: To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA. METHODS: In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months. RESULTS: Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: -53.0mm3, 95% CI: -100.0, -6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: -8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals. CONCLUSIONS: In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms.

Bone Marrow Sarcoidosis with Pancytopenia and Renal Failure Presenting as Fever of Unknown Origin: The Pivotal Role of 18F-FDG PET/CT in Lesion Detection.

We describe a case of fever of unknown origin (FUO), renal failure, and pancytopenia. Initially, lymph proliferative disorder was suspected; therefore, bone marrow biopsy and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) were performed. Bronchoscopy and lung biopsy were performed because of abnormal FDG uptake in both lung fields. Imaging data and laboratory and histological results confirmed sarcoidosis with bone marrow invasion. The patient was discharged after favorable response to corticosteroid therapy. Sarcoidosis may present as FUO without typical specific presentations in the skin or lungs. Combined 18F-FDP PET/CT helped identify the biopsy site and confirmed the sarcoidosis diagnosis.

Pain control with ibandronate for bone marrow oedema of the knee.

INTRODUCTION: Bone marrow oedema is a disabling disease characterised by severe bone pain (with or without prior trauma), insufficient response to analgesics, and reduction of weight bearing. Several studies showed promising results after using bisphosphonates to inhibit osteoclast activity. The aim of this study was to investigate the association between ibandronate administration and pain relief in patients with bone marrow oedema of the knee, and to precisely describe its presentation in magnetic resonance imaging (MRI). METHODS: This is a single-centre, retrospective analysis of 18 patients who received intravenous ibandronate due to bone marrow oedema of the knee between April 2012 and February 2016. Information has been extracted from our clinical database and a questionnaire. Furthermore, an experienced radiologist reassessed all MRI diagnoses. RESULTS: Our results showed a significant reduction of pain from 7.4 to 3.8 points on the visual analogue scale (p = 0.0001; median follow-up 41.5 months). Furthermore, the disability in daily life also significantly decreased (p = 0.008); 55.6% of the participants stated to be pain-free in the follow-up, and the same percentage also did not use alternative therapies after completing therapy with ibandronate (e.g., regular use of analgesics, operation, or local infiltration). However, there was no significant correlation between pain and specific radiologic findings. CONCLUSIONS: Participants with bone marrow oedema of the knee showed a significant pain reduction after an administration of ibandronate, independently of the severity showed in MRI. If the first administration leads to an insufficient control of pain, the administration of a second dose may be helpful. As bone marrow oedema syndrome is a self-limiting disease, prospective studies with a comparison group are needed to distinguish between the natural course of the disease and the beneficial effects of bisphosphonates.  .

Allopurinol use during pediatric acute lymphoblastic leukemia maintenance therapy safely corrects skewed 6-mercaptopurine metabolism, improving inadequate myelosuppression and reducing gastrointestinal toxicity.

BACKGROUND: Inadequate myelosuppression during maintenance therapy for acute lymphoblastic leukemia (ALL) is associated with an increased risk of relapse. One mechanism is skewed metabolism of 6-mercaptopurine (6MP), a major component of maintenance therapy, which results in preferential formation of the hepatotoxic metabolite (6-methyl mercaptopurine [6MMP]) with low levels of the antileukemic metabolite, 6-thioguanine nucleotides (6TGN). Allopurinol can modify 6MP metabolism to favor 6TGN production and reduce 6MMP. METHODS: Patients in maintenance were considered for allopurinol treatment who had the following features: (a) Grade ≥3 hepatotoxicity; (b) Grade ≥2 nonhepatic gastrointestinal (GI) toxicity; or (c) persistently elevated absolute neutrophil count (ANC) despite >150% protocol dosing of oral chemotherapy. RESULTS: From 2013 to 2017, 13 ALL patients received allopurinol: nine for hepatotoxicity, five for inadequate myelosuppression, and three for nonhepatic GI toxicity (four met multiple criteria). Allopurinol was well tolerated, without significant adverse events. Allopurinol resulted in a significant decrease in the average 6MMP/6TGN ratio (mean reduction 89.1, P = .0001), with a significant increase in 6TGN (mean 550.4, P = .0008) and a significant decrease in 6MMP (mean 13 755, P = .0013). Patients with hepatotoxicity had a significant decrease in transaminase elevation after starting allopurinol (alanine transaminase [ALT] mean decrease 22.1%, P = .02), and all with nonhepatic GI toxicity had improved symptoms. Those with inadequate myelosuppression had a significant increase in the time with ANC in goal (mean increase 26.4%, P = .0004). CONCLUSIONS: Allopurinol during ALL maintenance chemotherapy is a safe, feasible, and effective intervention for those who have altered metabolism of 6MP causing toxicity or inadequate myelosuppression.

Talar Avascular Necrosis After Calcium Phosphate Injection Treatment of Talar Bone Marrow Lesions: A Report of 2 Cases.

CASE: We report on 2 patients who developed avascular necrosis (AVN) of the talus and poor patient outcomes after undergoing calcium phosphate injection into talar dome bone marrow lesions. CONCLUSION: Subchondroplasty, defined as calcium phosphate injection for the treatment of articular bone marrow edema, is a recently described procedure for use in the ankle joint. In our opinion, the limited available research is of poor quality and describes equivocal improvement in patient symptoms after this procedure. Given the debilitating outcomes and extensive AVN we observed in 2 patients, we strongly advise caution in the use of this procedure in the talus.

Cost-utility analysis of antibiotic treatment in patients with chronic low back pain and Modic changes: results from a randomised, placebo-controlled trial in Norway (the AIM study).

OBJECTIVE: To evaluate the cost-utility of 100 days of antibiotics in patients with chronic low back pain (LBP) and type I or II Modic changes included in the Antibiotic treatment In patients with chronic low back pain and Modic changes (AIM) study. DESIGN: A cost-utility analysis from a societal and healthcare perspective alongside a double-blinded, parallel group, placebo, multicentre trial. SETTING: Hospital outpatient clinics at six hospitals in Norway. The main results from the AIM study showed a small effect in back-related disability in favour of the antibiotics group, and slightly larger in those with type I Modic changes, but this effect was below the pre-defined threshold for clinically relevant effect. PARTICIPANTS: 180 patients with chronic LBP, previous disc herniation and Modic changes type I (n=118) or type II (n=62) were randomised to antibiotic treatment (n=89) or placebo-control (n=91). INTERVENTIONS: Oral treatment with either 750 mg amoxicillin or placebo three times daily for 100 days. MAIN OUTCOME MEASURES: Quality-adjusted life years (QALYs) by EuroQoL-5D over 12 months and costs for healthcare and productivity loss measured in Euro (€1=NOK 10), in the intention-to-treat population. Cost-utility was expressed in incremental cost-effectiveness ratio (ICER). RESULTS: Mean (SD) total cost was €21 046 (20 105) in the amoxicillin group and €19 076 (19 356) in the placebo group, mean difference €1970 (95% CI; -3835 to 7774). Cost per QALY gained was €24 625. In those with type I Modic changes, the amoxicillin group had higher healthcare consumption than the placebo group, resulting in €39 425 per QALY gained. Given these ICERs and a willingness-to-pay threshold of €27 500 (NOK 275 000), the probability of amoxicillin being cost-effective was 51%. Even when the willingness-to-pay threshold increased to €55 000, the probability of amoxicillin being cost-effective was never higher than 53%. CONCLUSIONS: Amoxicillin treatment showed no evidence of being cost-effective for people with chronic LBP and Modic changes during 1-year follow-up. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02323412.

Clinical effect of intramuscular calcitonin compared with oral celecoxib in the treatment of knee bone marrow lesions: a retrospective study.

BACKGROUND: Bone marrow lesions (BMLs) are a common finding in patients with osteoarthritis (OA), which are predictors of progression and pain related to cartilage damage in OA. The objective of the present research was to compare the short-term clinical effect of intramuscular calcitonin and oral celecoxib in treating knee BMLs. PATIENTS AND METHODS: Between January 2016 and December 2018, the medical records of patients with knee BMLs treated by intramuscular calcitonin or oral celecoxib were reviewed. Visual analog scale (VAS) and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were used to assess knee pain and function, respectively. BMLs were assessed by MRI scans and were scored by the modified Whole-Organ MRI Score (WORMS). The safety of these two medications was also evaluated. RESULTS: A total of 123 eligible patients who received calcitonin treatment (n = 66) or celecoxib treatment (n = 57) were included. All patients were followed up clinically and radiographically for 3 months. The VAS and WOMAC scores were lower statistically in calcitonin group than celecoxib group at 4-week and 3-month follow-up. For BMLs, the WORMS scores in the calcitonin group were significantly lower than the celecoxib group. Besides, statistically higher MRI improvement rates were found in the calcitonin group compared with the celecoxib group at 4-week follow-up (21.21% vs. 7.01%; P = 0.039) and 3-month follow-up (37.88% vs. 15.79%; P = 0.006). CONCLUSION: Intramuscular calcitonin 50 IU once daily demonstrated a better short-term effect for knee BML patients compared with oral celecoxib 200 mg twice per day.

Clinical and clinicopathological features and outcomes of Miniature Dachshunds with bone marrow disorders.

Non-neoplastic bone marrow disorders such as non-regenerative immune-mediated anemia, pure red cell aplasia, and myelodysplastic syndrome are major causes of non-regenerative anemia in dogs. However, there has been no study on the clinical and clinicopathological features of canine non-neoplastic bone marrow disorders in Japan. Hence, we first investigated the breed disposition of non-neoplastic bone marrow disorders that induce anemia as a retrospective study and found that Miniature Dachshund (MD) was a predisposed breed. Based on this finding, we investigated the clinical and clinicopathological features of non-neoplastic bone marrow disorders in MDs as a preliminary retrospective study, and we compared them between immunosuppressive treatment-responsive and -resistant MDs. We found that treatment-resistant MDs showed thrombocytosis and increased frequencies of dysplastic features in the peripheral blood. These results indicate that bone marrow disorders in treatment-resistant MDs might manifest distinct features compared with those in treatment-sensitive MDs, and sensitivity to immunosuppressive treatments could be predicted based on thrombocytosis and dysplastic features in the peripheral blood. Further studies that examine aberrations in the genome are needed to elucidate the pathophysiology of bone marrow disorders in MDs.