Mortality, Analgesic Use, and Care Requirements After Vertebral Compression Fractures: A Retrospective Cohort Study of 18,392 Older Adult Patients.

BACKGROUND: Vertebral compression fractures (VCFs) in older adults cause considerable health and socioeconomic burdens due to worsening ability to perform activities of daily living. The long-term effects of VCFs on patient outcomes, particularly prolonged analgesic use and functional decline, remain unknown. The aims of this study were to examine long-term clinical outcomes and to determine the risk factors for persistent pain and functional disability after VCFs. METHODS: This retrospective cohort study evaluated mortality, duration of analgesic use, and changes in care requirements in older adults with VCFs using claims data from a suburban prefecture in the Greater Tokyo Area. Patients were included if they were ≥65 years of age and had been diagnosed with a VCF between June 2014 and February 2019, as determined on the basis of International Classification of Diseases, Tenth Revision (ICD-10) codes; we also used claims data that could determine whether the patients underwent imaging examinations. Patients who discontinued outpatient visits within 1 month after the VCF diagnosis were excluded. RESULTS: We included 18,392 patients with VCFs and a mean age of 80 years. Seventy-six percent of patients were women, and the median follow-up period was 670 days. At the index VCF diagnosis, 3,631 patients (19.7%) were care-dependent. Overall, 968 patients (5.3%) died within 1 year. Among the 8,375 patients who received analgesics, 22% required analgesics for >4 months. Factors associated with prolonged analgesic use for >1 year were female sex (odds ratio [OR], 1.39 [95% confidence interval (CI), 1.16 to 1.65]) and VCFs in the thoracolumbar region (OR, 1.95 [95% CI, 1.50 to 2.55]) or lumbar region (OR, 1.59 [95% CI, 1.23 to 2.04]) (the reference was the thoracic region). The care needs of 1,510 patients (8.2%) increased within 1 year. Patients with a preexisting care dependency had a 10 times higher risk of increased care need (30.2% [1,060 of 3,509]) than those who had been independent at the time of the index diagnosis (3.0% [450 of 14,761]) (p < 0.001). CONCLUSIONS: Individuals with preexisting care dependency were more likely to experience functional decline following VCFs than those who were independent, which underscores the need for intensive and appropriate allocation of health-care resources to care-dependent patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Cholecystocutaneous Fistula Associated with Edwardsiella tarda as a Result of Aggressive Lymphoma Development.

A cholecystocutaneous fistula is a type of external biliary fistula that occurs when there is an abnormal connection between the gallbladder and skin. We report the first case of a cholecystocutaneous fistula that occurred in association with the development of lymphoma in the gallbladder. A 76-year-old woman who was under observation for follicular lymphoma with a low tumor burden presented with fatigue and abdominal pain. Imaging studies revealed cholecystitis associated with an abdominal subcutaneous abscess, and lymphoma transformation was confirmed by a lymph node biopsy. Edwardsiella tarda was cultured from both the abdominal subcutaneous abscess and percutaneous transhepatic gallbladder drainage, demonstrating cholecystocutaneous fistula, and open cholecystectomy revealed lymphoma cell infiltration into the gallbladder. Our case showed unique complications, and its successful management was associated with aggressive lymphoma development.

The Usefulness of Posterior Shiny Corner Lesions in the Early Diagnosis of Medial Meniscus Posterior Root Tears.

INTRODUCTION:  Posterior shiny corner lesions (PSCLs) have been reported to be useful for the early diagnosis of medial meniscus posterior root tears (MMPRTs) in surgical patients. However, the usefulness of PSCLs in outpatients, particularly regarding the optimal timing of magnetic resonance imaging (MRI) examinations after injury, remains unknown. We hypothesized that PSCLs would normally be observed in patients with MMPRTs within one month of injury. MATERIALS AND METHODS:  This study included 144 patients with knee pain who visited our hospital between January 2021 and May 2023. MRI findings within and after one month were examined. Fisher's exact test was performed for PSCLs, cleft signs, ghost signs, radial tear signs, bone cysts, and medial meniscus extrusion (MME), which are findings used for the diagnosis of MMPRTs. Time-dependent receiver operating characteristic (ROC) curve analysis was performed for each MRI finding. A binomial logistic regression analysis was performed for age, sex, PSCL, ghost sign, and MME. RESULTS: PSCLs were observed on 82.6% of the MRI scans within one month, but the positivity rate decreased after one month. After one month, a high percentage of patients had cleft signs and ghost signs. The results of a time-dependent ROC curve analysis showed that the PSCL had better diagnostic ability than the cleft sign, ghost sign, radial tear sign, and MME at a relatively early stage. Additionally, the area under the curve (AUC) of PSCL peaks around 35 days and then declines, reaching 0.8 or less around 40 days. On the other hand, the AUC of the cleft sign and ghost sign began to increase around 30 days after injury, and it exceeded 0.8 after approximately 100 days. The results of the binomial logistic regression analysis revealed significant PSCLs and ghost signs. Independent associations between the PSCL, or ghost sign, and the MMPRT were demonstrated. CONCLUSION:  This study suggests that PSCLs have a superior diagnostic capability for MMPRT during the early stages of injury compared with other MRI findings in outpatients. In particular, PSCLs have a high positivity rate within one month after injury and a high diagnostic capacity up to 40 days after injury.

Unique bile acid profiles in the bile ducts of patients with primary sclerosing cholangitis.

BACKGROUND: The relationship between primary sclerosing cholangitis (PSC) and biliary bile acids (BAs) remains unclear. Although a few studies have compared PSC biliary BAs with other diseases, they did not exclude the influence of cholestasis, which affects the composition of BAs. We compared biliary BAs and microbiota among patients with PSC, controls without cholestasis, and controls with cholestasis, based on the hypothesis that alterations in BAs underlie the pathophysiology of PSC. METHODS: Bile samples were obtained using endoscopic retrograde cholangiopancreatography from patients with PSC (n = 14), non-hepato-pancreato-biliary patients without cholestasis (n = 15), and patients with cholestasis (n = 13). RESULTS: The BA profiles showed that patients with PSC and cholestasis controls had significantly lower secondary BAs than non-cholestasis controls, as expected, whereas the ratio of cholic acid/chenodeoxycholic acid in patients with PSC was significantly lower despite cholestasis, and the ratio of (cholic acid + deoxycholic acid)/(chenodeoxycholic acid + lithocholic acid) in patients with PSC was significantly lower than that in the controls with or without cholestasis. The BA ratio in the bile of patients with PSC showed a similar trend in the serum. Moreover, there were correlations between the alteration of BAs and clinical data that differed from those of the cholestasis controls. Biliary microbiota did not differ among the groups. CONCLUSIONS: Patients with PSC showed characteristic biliary and serum BA compositions that were different from those in other groups. These findings suggest that the BA synthesis system in patients with PSC differs from that in controls and patients with other cholestatic diseases. Our approach to assessing BAs provides insights into the pathophysiology of PSC.

Prevalence and factors associated with lateral epicondylitis among hospital healthcare workers.

Background: Hospital healthcare workers have been reported to have a high prevalence of musculoskeletal disorders, but their association with lateral epicondylitis (LE) is unknown. This study aimed to clarify the prevalence of LE and its associated factors among hospital healthcare workers. Methods: The present study included all staff members of a secondary emergency hospital who provided their consent to participate. Participants with a history of elbow joint trauma were excluded from this study. The diagnostic criteria for definite LE were: (1) pain in the elbow joint within 2 weeks of the study; (2) pain in the lateral epicondyle region on resisted extension of the wrist with the elbow extended; and (3) tenderness in the lateral epicondyle. The diagnosis of LE was defined by meeting all criteria. Age, height, weight, sex, dominant hand, occupation, years of employment, smoking history, drinking history, personal computer usage history, and smartphone usage history were investigated using a questionnaire. A physical examination, in addition to evaluation of pain in the lateral epicondyle, grip strength and wrist extension strength were measured. A statistical analysis was used to assess the prevalence of LE and its associated factors. All investigations, including the diagnosis of LE, were performed by a single orthopedic specialist. Results: We evaluated 544 individuals, corresponding to approximately 80% of all staff members. The median age was 39 years (interquartile range, 30-48). The study population included 154 males and 390 females. The occupations of the participants were as follows: nurses (n = 265), doctors (n = 47), clerks (n = 93), therapists (n = 27), certified care workers (n = 23), medical technologists (n = 22), pharmacists (n = 19), and others (n = 48). LE was diagnosed in 30 limbs/30 individuals with a prevalence of approximately 5.5%. There was no difference in the prevalence of LE among occupations (P = .85). A logistic regression analysis revealed that age (odds ratio, 1.05; 95% confidence interval 1.01-1.1; P = .01) and smoking history (odds ratio, 2.94; 95% confidence interval 1.01-8.56; P = .04) were independently associated with LE. Conclusion: This study was conducted to evaluate the prevalence of LE among hospital healthcare workers. The prevalence of LE was 5.5%, and LE was independently associated with age and smoking history.

Prognostic factors of idiopathic hypereosinophilic syndrome: A nationwide survey in Japan.

Idiopathic hypereosinophilic syndrome (iHES) is a condition wherein persistent hypereosinophilia associated with end-organ damage occurs without any known causes. Due to the rarity of the disease, insufficient knowledge has been accumulated. We therefore conducted a retrospective, multicentre, nationwide survey on iHES in Japan. A total of 57 patients were identified. For 43 patients who received any treatment, all cases were first treated with corticosteroids. An eosinophil percentage of less than 30% in the bone marrow and the absence of oedema were identified as factors associated with steroid dependency. The 5-year overall survival was 88.2%, and five patients died during follow-up; factors associated with worse overall survival were age >50, haemoglobin <12 g/dL, activated partial thromboplastin time >34 s, the presence of dyspnoea, the presence of thrombotic tendency and the presence of renal failure. Given the rarity of fatalities in our cohort, time-to-next-treatment (TTNT) was further analysed; the presence of renal failure, splenomegaly and lung abnormalities were associated with worse TTNT. Our nationwide study not only demonstrated clinical characteristics and the outcome of patients with iHES but also for the first time revealed clinical factors associated with steroid dependency and duration of first-line corticosteroid efficacy.

Long-term remission after upfront autologous hematopoietic stem cell transplant for CD5+ diffuse large-B cell lymphoma.

CD5+ diffuse large B-cell lymphoma (DLBCL) is a rare subtype characterized by an inferior outcome. While dose-dense therapy shows promising activity, the optimal management remains to be determined. To evaluate the benefit of consolidative autologous hematopoietic stem cell transplantation (ASCT), we retrospectively reviewed the medical records of 47 consecutive patients with newly diagnosed de novo CD5+ DLBCL. Of 19 patients ≤ 70 of age with age-adjusted International Prognostic Index 2-3, eight underwent upfront ASCT, and nine did not, despite preserved organ function and response after induction therapy. The remaining two, ineligible for ASCT due to early progression or comorbidities, had a dismal clinical course. Among younger 17 high-risk patients eligible for ASCT, ASCT was associated with better overall (p = 0.0327) and progression-free survival (p = 0.0184). Younger patients without ASCT demonstrated similar outcomes to older patients with similar risk profiles. ASCT could be considered for high-risk CD5+ DLBCL with a response after induction therapy.

Isolated massive pleural effusion as a manifestation of chronic graft versus host disease successfully treated with corticosteroid.

Isolated pleural effusion is a rare manifestation of chronic graft versus host disease (cGVHD) after hematopoietic stem cell transplantation (HSCT). We herein report a 58-year-old woman presenting with massive pleural effusion approximately 1 year after allogeneic HSCT, who was successfully treated with corticosteroid. She had discontinued tacrolimus approximately 1 month before she presented with pleural effusion, which was attributed to cGVHD after a thorough exclusion process. This case illustrates a unique manifestation of atypical cGVHD and highlights the need for prompt therapy initiation.

Usefulness of the preoperative thoracic inlet angle in comparison to the T1 slope for predicting cervical kyphosis after laminoplasty.

PURPOSE: Thoracic inlet angle (TIA) is a sagittal radiographic parameter with a constant value regardless of posture and is significantly correlated with the sagittal balance of the cervical spine. However, the practical use of TIA has not been studied. This study aimed to investigate the usefulness of the preoperative TIA for predicting the development of kyphotic deformity after cervical laminoplasty in comparison to the preoperative T1 slope (T1S). METHODS: A total of 98 patients who underwent cervical laminoplasty without preoperative kyphotic alignment were included (mean age, 73.7 years; 41.8% female). Radiography was evaluated before surgery and at the 2-year follow-up examination. The cervical sagittal parameters were measured on standing radiographs, and the TIA was measured on T2-weighted MRI in a supine position. Cervical alignment with a C2-C7 angle of ≥ 0° was defined as lordosis, and that with an angle of < 0° was defined as kyphosis. RESULTS: Postoperative kyphosis occurred in 11 patients (11.2%). Preoperatively, the kyphosis group showed significantly lower values in the T1S (23.5° vs. 30.3°, p = 0.034) and TIA (76.1° vs. 81.8°, p = 0.042). We performed ROC curve analysis to clarify the impact of the preoperative TIA and T1S on kyphotic deformity after laminoplasty. The optimal cutoff angles for TIA and T1S were 68° and 19°, respectively, with similar diagnostic accuracy. CONCLUSION: This study demonstrated the clinical utility of the preoperative TIA for predicting the risk of postoperative kyphotic deformity after cervical laminoplasty. These findings suggest the importance of the preoperative assessment of thoracic inlet alignment in cervical spine surgery.

Proteinuria screening and risk of bone fracture: a retrospective cohort study using a nationwide population-based database.

Background and hypothesis: Proteinuria is associated with an increased risk of kidney function deterioration, cardiovascular disease, or cancer. Previous reports suggesting an association between kidney dysfunction and bone fracture may be confounded by concomitant proteinuria and were inconsistent regarding the association between proteinuria and bone fracture. Therefore, we aimed to evaluate the association using a large administrative claims database in Japan. Methods: Using the DeSC database, we retrospectively identified individuals with laboratory data including urine dipstick test between August 2014 and February 2021. We evaluated the association between proteinuria and vertebral or hip fracture using multivariable Cox regression analyses adjusted for various background factors including kidney function. We also performed subgroup analyses stratified by sex and kidney function and sensitivity analyses with Fine & Gray models considering death as a competing risk. Results: We identified 603 766 individuals and observed 21 195 fractures. With reference to the negative proteinuria group, the hazard ratio for hip or vertebral fracture was 1.10 [95% confidence interval (CI), 1.05-1.14] and 1.16 (95%CI, 1.11-1.22) in the trace and positive proteinuria group, respectively, in the Cox regression analysis. The subgroup analyses showed similar trends. The Fine & Gray model showed a subdistribution hazard ratio of 1.09 (95%CI, 1.05-1.14) in the trace proteinuria group and 1.15 (95% CI, 1.10-1.20) in the positive proteinuria group. Conclusions: Proteinuria was associated with an increased risk of developing hip or vertebral fractures after adjustment for kidney function. Our results highlight the clinical importance of checking proteinuria for predicting bone fractures.

Induction of CYP3A activity by dexamethasone may not be strong, even at high doses: insights from a case of tacrolimus co-administration.

BACKGROUND: Dexamethasone (DEX) induces CYP3A activity in a concentration-dependent manner. However, no study has examined changes in the blood concentration of CYP3A substrate drugs when DEX is administered at high doses. Herein, we present a case in which tacrolimus (TAC), a typical CYP3A substrate drug, was co-administered with a chemotherapy regimen that included high-dose DEX. CASE PRESENTATION: A 71-year-old woman underwent liver transplantation for hepatocellular carcinoma 18 years prior to her inclusion in this case study. She was receiving TAC orally at 2 mg/day and had a stable trough blood concentration of approximately 4 ng/mL and a trough blood concentration/dose (C/D) ratio of approximately 2. The patient was diagnosed with post-transplant lymphoproliferative disease (histological type: Burkitt's lymphoma) after admission. Thereafter, the patient received cyclophosphamide-prednisolone (CP), followed by two courses of R-HyperCVAD (rituximab, cyclophosphamide, doxorubicin, vincristine, and DEX) and R-MA (rituximab, methotrexate, and cytarabine) replacement therapy. DEX (33 mg/day) was administered intravenously on days 1-4 and days 11-14 of R-HyperCVAD treatment, and aprepitant (APR) was administered on days 1-5 in both courses. The TAC C/D ratio decreased to approximately 1 on day 11 during both courses, and then increased. Furthermore, a decreasing trend in the TAC C/D ratio was observed after R-MA therapy. The decrease in the TAC C/D ratio was attributed to APR administration rather than to DEX. CONCLUSION: The induction of CYP3A activity by a high dose of DEX may not be strong. The pharmacokinetic information on DEX and in vitro enzyme activity induction studies also suggested that CYP3A activity induction is not prominent under high-dose DEX treatment.

Risk factors for early mortality in elderly patients with unstable isolated C2 odontoid fracture treated with halo-vest or surgery.

The aim of this study was to compare in-hospital mortality of three procedures -halo-vest immobilization, anterior spinal fixation (ASF), and posterior spinal fixation (PSF)- in the treatment of elderly patients with isolated C2 odontoid fracture. We extracted data for elderly patients who were admitted with C2 odontoid fracture and treated with at least one of the three procedures (halo-vest immobilization, ASF, or PSF) during hospitalization. We conducted a generalized propensity score-based matching weight analysis to compare in-hospital mortality among the three procedures. We further investigated independent risk factors for in-hospital death. The study involved 891 patients (halo-vest, n = 463; ASF, n = 74; and PSF, n = 354) with a mean age of 78 years. In-hospital death occurred in 45 (5.1%) patients. Treatment type was not significantly associated with in-hospital mortality. Male sex (odds ratio 2.98; 95% confidence interval 1.32-6.73; p = 0.009) and a Charlson comorbidity index of ≥ 3 (odds ratio 9.18; 95% confidence interval 3.25-25.92; p < 0.001) were independent risk factors for in-hospital mortality. In conclusion, treatment type was not significantly associated with in-hospital mortality in elderly patients with isolated C2 odontoid fracture. Halo-vest immobilization can help to avoid adverse events in patients with C2 odontoid fracture who are considered less suitable for surgical treatment.

Acalabrutinib and steroid for autoimmune thrombocytopenia due to relapsed chronic lymphocytic leukemia with severe bone marrow infiltration.

Thrombocytopenia is a frequent complication in chronic lymphocytic leukemia (CLL). Differentiating autoimmune thrombocytopenia from thrombocytopenia due to bone marrow infiltration is necessary for appropriate treatment, but sometimes difficult. Here we report a 60-year-old male patient with CLL who had achieved complete response after treatment with fludarabine, cyclophosphamide, and rituximab two years prior to presentation. He was admitted with severe thrombocytopenia that was unresponsive to intravenous immunoglobulin. Imaging studies revealed systemic enlarged lymph nodes and bone marrow aspiration was hypercellular with > 95% lymphocytes and scant megakaryocytes. Acalabrutinib 200 mg/day was administered for the treatment of CLL exacerbation. A gradual decrease in CLL cells and recovery of megakaryocytes in bone marrow were observed, but platelet counts remained low. Systemic administration of prednisolone 0.5 mg/kg, in addition to acalabrutinib, was started, considering the contribution of autoimmune thrombocytopenia; platelet recovery was rapid and sustained for more than a year. Even if bone marrow examination suggested thrombocytopenia due to direct leukemic infiltration, it is difficult to exclude the possibility of concomitant immunogenic thrombocytopenia. We conclude that for CLL patients with severe thrombocytopenia, repeating bone marrow examination and concurrent immunosuppressive therapies and treatment of the underlying CLL may be beneficial.

Radiographic Predictors of Subaxial Subluxation After Atlantoaxial Fusion.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to clarify preoperative radiographic predictors associated with the development of subaxial subluxation (SAS) after surgery. BACKGROUND: The incidence of atlantoaxial fusion for atlantoaxial instability has been increasing. SAS can develop after surgery despite atlantoaxial fusion with the optimal C1-C2 angle. We hypothesized that preoperative discordant angular contribution in the upper and subaxial cervical spine is associated with the occurrence of postoperative SAS. MATERIALS AND METHODS: Patients who underwent surgery for atlantoaxial instability with a minimum 5-year follow-up and control participants were included. The O-C2 angle, C2 slope (C2S), C2-C7 cervical lordosis (CL), and T1 slope (T1S) were measured. We focused on the angular contribution ratio in the upper cervical spine to the whole CL, and the preoperative C2/T1S ratio was defined as the ratio of C2S to T1S. RESULTS: Twenty-seven patients (SAS=11, no-SAS=16; mean age, 60.7 y old; 77.8% female; mean follow-up duration, 6.8 y) and 23 demographically matched control participants were enrolled. The SAS onset was at 4.7 postoperative years. Preoperatively, the O-C2 angle, C2-C7 CL, and T1S were comparable between the SAS, no-SAS, and control groups. The preoperative C2S and C2/T1S ratio were smaller in the SAS group than in the no-SAS or control group (C2S, 11.0 vs. 18.4 vs. 18.7 degrees; C2/T1S ratio, 0.49 vs. 0.77 vs. 0.78, P <0.05). The receiver operating characteristic curve analysis demonstrated that the C2/T1S ratio had higher specificity and similar sensitivity as a predictor of postoperative SAS than C2S (specificity: 0.90 vs. 0.87; sensitivity: 0.73 vs. 0.73). The estimated cutoff values of the C2S and C2/T1S ratio were 14 degrees and 0.58, respectively. CONCLUSIONS: The preoperative C2/T1S ratio was closely associated with postoperative SAS. Patients with a C2/T1S ratio <0.58 were at a high risk of SAS after atlantoaxial fusion. LEVEL OF EVIDENCE: Level 4.

Upregulation of Taurine Biosynthesis and Bile Acid Conjugation with Taurine through FXR in a Mouse Model with Human-like Bile Acid Composition.

Taurine, the end product in the sulfur-containing amino acid pathway, is conjugated with bile acids (BAs) in the liver. The rate-limiting enzymes in both taurine synthesis and BA conjugation may be regulated by a nucleus receptor, FXR, that promotes BA homeostasis. However, it is controversial because BAs act as natural FXR agonists or antagonists in humans and mice, respectively, due to the species differences in BA synthesis. The present study evaluated the influences of different BA compositions on both pathways in the liver by comparing Cyp2a12-/-/Cyp2c70-/- mice with a human-like BA composition (DKO) and wild-type (WT) mice. The DKO liver contains abundant natural FXR agonistic BAs, and the taurine-conjugated BA proportion and the taurine concentration were significantly increased, while the total BA concentration was significantly decreased compared to those in the WT liver with natural FXR antagonistic BAs. The mRNA expression levels of the enzymes Bacs and Baat in BA aminations and Cdo and Fmo1 in the taurine synthesis, as well as Fxr and its target gene, Shp, were significantly higher in the DKO liver than in the WT liver. The present study, using a model with a human-like BA composition in the liver, confirmed, for the first time in mice, that both the taurine synthesis and BA amidation pathways are upregulated by FXR activation.

Recurrent bilateral adrenal infarction with myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U): a case report.

BACKGROUND: Bilateral adrenal infarction is rare and only a small number of cases have been reported so far. Adrenal infarction is usually caused by thrombophilia or a hypercoagulable state, such as antiphospholipid antibody syndrome, pregnancy, and coronavirus disease 2019. However, adrenal infarction with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) has not been reported. CASE PRESENTATION: An 81-year-old man with a sudden severe bilateral backache presented to our hospital. Contrast-enhanced computed tomography (CT) led to the diagnosis of bilateral adrenal infarction. Previously reported causes of adrenal infarction were all excluded and a diagnosis of MDS/MPN-unclassifiable (MDS/MPN-U) was reached, which was considered to be attributed to adrenal infarction. He developed a relapse of bilateral adrenal infarction, and aspirin administration was initiated. Partial primary adrenal insufficiency was suspected as the serum adrenocorticotropic hormone level was persistently high after the second bilateral adrenal infarction. CONCLUSION: This is the first case of bilateral adrenal infarction with MDS/MPN-U encountered. MDS/MPN has the clinical characteristics of MPN. It is reasonable to assume that MDS/MPN-U may have influenced bilateral adrenal infarction development, considering the absence of thrombosis history and a current comorbid hypercoagulable disease. This is also the first case of recurrent bilateral adrenal infarction. It is important to carefully investigate the underlying cause of adrenal infarction once adrenal infarction is diagnosed, as well as to assess adrenocortical function.