Conditioned medium of human mesenchymal stem cells affects stem cell senescence in osteoporosis.

Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine effects of early (P5) and late (P17) passage hMSCs in vitro, as well as the preventive benefits of early passage hMSCs-CM in osteoporosis model triggered by ovariectomy. Our results indicate that long-term cultured hMSCs contributed to the progression of inflammatory transcriptional programs in P5 hMSCs, ultimately impairing their functionality and enhancing senescence-related characteristics. Conversely, early passage hMSCs reversed these alterations. Moreover, early passage hMSCs-CM infused intravenously in a postmenopausal osteoporosis mouse model suppressed bone degeneration and prevented osteoporosis by reducing ovariectomy-induced senescence in bone marrow MSCs and reducing the expression of senescence-associated secretory phenotype-related cytokines. Our findings highlight the high translational value of early passage hMSCs-CM in antiaging intervention and osteoporosis prevention.

NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.

Renal Embolism Associated with the Atrial Myxoma: A Case Report and Literature Review.

Renal embolisms due to cardiac myxomas are extremely rare; the clinical course, treatment, and prognosis of this disease are not established. A 69-year-old Japanese woman who underwent a nephrectomy for renal cell carcinoma 3 years earlier was hospitalized with a right occipital lobe cerebral infarction. Her renal function suddenly worsened 3 days post-admission: her serum creatinine rose from 1.46 mg/dL to 6.57 mg/dL and then to 8.03 mg/dL the next day, and hemodialysis therapy was started. Abdominal computed tomography (CT) scans showed patchy non-contrasted low-density areas in the right kidney, and chest CT scans and transesophageal ultrasonography revealed a left atrial tumor. We diagnosed renal infarction due to a left atrial myxoma. Hemodialysis and anticoagulant therapy (heparin) were continued, followed by the cardiac myxoma's resection. The patient's renal function gradually improved post-surgery, and the hemodialysis was discontinued. Considering our patient and 19 other case reports of renal infarction associated with cardiac myxoma, the treatment for such a renal infarction and the outcomes differ depending on the embolus site. The poor outcome of abdominal aortic embolism requires a prompt embolectomy, whereas a branch renal artery embolism requires anticoagulation therapy to prevent thrombosis formation around the myxoma.

[Attempts for salt reduction in workers through specific food service facility guidance by public health center: A case study at a worksite in Kawagoe City, Saitama Prefecture].

Objective　The Kawagoe City Public Health Center implemented a project to reduce salt intake through specific food service facility guidance in workplace cafeterias. Here, we report the study results.Methods　The target worksite was company A, with approximately 270 employees, located in Kawagoe City, Saitama Prefecture. There were 214 participants (approximately 80%). The project was conducted from November 2019 to November 2021. The long-term goal was to decrease the number of hypertensive cases in the city. Project outcomes included decreased salt intake, urinary sodium/potassium ratio, and average blood pressure. The project aimed to improve the cafeteria menu, focusing on salt reduction by offering Smart Meals® and reducing the salt equivalents in all menus. The project output indicators included reduced amount of salt in cafeteria menu items, increased frequency of cafeteria use, increased positive evaluations of the cafeteria, and increased daily awareness of the need for salt reduction. Spot urine samples, blood pressure measurements, and self-administered questionnaire data were collected during annual physical examinations. The amount of salt in the cafeteria menu was evaluated by receiving monthly data from the food service company to which company A outsourced its cafeteria operations.Results　The analysis included 102 individuals with complete data from to 2019-2021. Estimated salt intake (g/day) from spot urine decreased from 10.3±2.1 in 2019 to 9.8±2.4 in 2020 and 9.5±2.0 in 2021 (P=0.003). Systolic blood pressure (mmHg) decreased from 114.7±12.5 in 2019 to 111.7±12.1 in 2020 and 110.6±12.0 in 2021 (P=0.010). Compared to 2019, changes in dietary salt equivalents in cafeteria menus in 2020 and 2021decreased for set meals A and B, curries, and noodles (P<0.001).Conclusion　We offered Smart Meals® and reduced salt equivalents in all workplace cafeteria menus. After 1-2 years, employees' salt intake and blood pressure levels were lower. These results provide implications for the implementation of food environment improvements in public health centers and other local government agencies to promote the Health Japan 21 (third term) strategy.

Distal junctional failure after corrective surgery without pelvic fixation for thoracolumbar junctional kyphosis due to osteoporotic vertebral fracture.

BACKGROUND: Thoracolumbar junctional kyphosis (TLJK) due to osteoporotic vertebral fracture (OVF) negatively impacts patients' quality of life. The necessity of pelvic fixation in corrective surgery for TLJK due to OVF remains controversial. This study aimed to: 1) evaluate the surgical outcomes of major corrective surgery for thoracolumbar junctional kyphosis due to osteoporotic vertebral fracture, and 2) identify the risk factors for distal junctional failure to identify potential candidates for pelvic fixation. METHODS: Patients who underwent surgical correction (fixed TLJK>40°, OVF located at T11-L2, the lowermost instrumented vertebra at or above L5) were included. Sagittal vertical axis, pelvic tilt, pelvic incidence, thoracic kyphosis, lumbar lordosis (L1-S1), local kyphosis, and lower lumbar lordosis (L4-S1) were assessed. Proximal and distal junctional kyphosis (P/DJK) and failures (P/DJF) were evaluated. Pre/postoperative spinopelvic parameters were compared between DJF and non-DJF patients. RESULTS: Thirty-one patients (mean age: 72.3 ± 7.9 years) were included. PJK was observed in five patients (16.1%), while DJK in 11 (35.5%). Twelve cases (38.7%) were categorized as failure. Among the patients with PJK, there was only one patient (20%) categorized as PJF and required an additional surgery. Contrary, all of eleven patients with DJK were categorized as DJF, among whom six (54.5%) required additional surgery for pelvic fixation. In comparisons between DJF and non-DJF patients, there was no significant difference in pre/postoperative LK (pre/post, p = 0.725, p = 0.950). However, statistically significant differences were observed in the following preoperative alignment parameters: SVA (p = 0.014), LL (p = 0.001), LLL (p = 0.006), PT (p = 0.003), and PI-LL (p < 0.001). CONCLUSIONS: Spinopelvic parameters, which represent the compensatory function of lumbar hyperlordosis and pelvic retroversion, have notable impacts on surgical outcomes in correction surgery for TLJK due to OVF. Surgeons should consider each patient's compensatory function when choosing a surgical approach.

The Immunobiological Agents for Treatment of Antiglomerular Basement Membrane Disease.

Combination therapy with glucocorticoids, cyclophosphamide, and plasmapheresis is recommended as the standard treatment for anti-glomerular basement membrane (anti-GBM) disease, but the prognosis of this disease remains poor. Several immunobiological agents have been administered or are expected to be useful for anti-GBM disease in light of refractory disease or the standard treatments' tolerability. Many data regarding the use of biologic agents for anti-GBM disease have accumulated, verifying the effectiveness and potential of biologic agents as a new treatment option for anti-GBM disease. Tumor necrosis factor (TNF) inhibitors were shown to be useful in animal studies, but these agents have no clinical use and were even shown to induce anti-GBM disease in several cases. Although the efficacy of the TNF-receptor antagonist has been observed in animal models, there are no published case reports of its clinical use. There are also no published reports of animal or clinical studies of anti-B-cell-activating factor, which is a member of the TNF family of agents. Anti-interleukin (IL)-6 antibodies have been demonstrated to have no effect on or to exacerbate nephritis in animal models. Anti-C5 inhibitor was observed to be useful in a few anti-GBM disease cases. Among the several immunobiological agents, only rituximab has been demonstrated to be useful in refractory or poor-tolerance patients or small uncontrolled studies. Rituximab is usually used in combination with steroids and plasma exchange and is used primarily as an alternative to cyclophosphamide, but there is insufficient evidence regarding the efficacy of rituximab for anti-GBM disease, and thus, randomized controlled studies are required.

Comparison of pedicle screw placement accuracy between two types of imaging support (Artis Zeego versus two-dimensional fluoroscopy): a cross-sectional observational study.

BACKGROUND: The pedicle screw system is widely used in spine surgery, and it provides rigid fixation and leads to successful subsequent deformity correction and bony fusion. The standard imaging technique for pedicle screw insertion is two-dimensional images obtained from C-arm-type X-ray fluoroscopy. Artis Zeego is an emerging intraoperative imaging technique that can provide conventional two-dimensional fluoroscopic images and rapid three-dimensional fluoroscopic computed tomography reconstruction imaging. The aim of this study is to compare the insertion accuracies of PS placement using Artis Zeego and conventional 2D X-ray fluoroscopy. METHODS: In this study, we retrospectively reviewed the postoperative images of thoracolumbar fusion patients who underwent surgery using pedicle screws between 2013 and 2018. Pedicle screw malplacement was assessed using a four-grade classification by Rao et al. Misplacement rates were compared between pedicle screws assisted with Artis Zeego and two-dimensional fluoroscopy. RESULTS: A total of 1107 pedicle screws in 153 patients were inserted using Artis Zeego, and 427 pedicle screws in 80 patients were inserted using fluoroscopy. The overall perforation rate was 4.2% (46 perforations of 1106 pedicle screws) in the Artis Zeego group and 7.7% (33 perforations of 427 pedicle screws) in the fluoroscopy group. In the Artis Zeego group, 43 (3.9%) screws were classified as grade 1, and three (0.3%) screws were classified as grade 2. In the fluoroscopy group, 21 (4.9%) screws were classified as grade 1, 10 (2.3%) screws were classified as grade 2, and 2 (0.5%) screws were classified as grade 3. The use of Artis Zeego was associated with a significantly lower screw malplacement rate than was the use of fluoroscopy (p < 0.001). CONCLUSIONS: Our results demonstrated that pedicle screw placement with Artis Zeego was associated with a lower malplacement rate than was conventional two-dimensional fluoroscopy. No severe malplacement was observed in the Artis Zeego group. Thus, Artis Zeego could be a good option for improving pedicle screw accuracy.

[A Case of Advanced Gastric Cancer Successfully Treated with FOLFOX].

The Japanese gastric cancer clinical practice guideline recommends FOLFOX as one of the first-line chemotherapy for advanced gastric cancer. Since FOLFOX is administered intravenously, it is helpful for patients who have difficulty in oral intake. Herein, we report a patient in which FOLFOX was significantly effective after failure to treatment with S-1 plus CDDP. A 75-year-old gastric cancer patient with paraaortic lymph node metastasis and multiple liver metastases(Stage ⅣB)was treated. Severe stomatitis and impaired consciousness due to dehydration appeared after administration of S-1 plus CDDP. After his general condition recovered, we changed his regimen to FOLFOX. No serious adverse events were observed, and partial response was achieved after 4 courses of treatment. Partial response was maintained until the onset of oxaliplatin drug allergy in the 10th course. FOLFOX is a promising option for patients with difficulties in oral intake.

Dental pulp stem cell-derived small extracellular vesicle in irradiation-induced senescence.

Small extracellular vesicles (sEV) facilitate signaling molecule transfer among cells. We examined the therapeutic efficacy of human dental pulp stem cell-derived sEV (hDPSC-sEV) against cellular senescence in an irradiated-submandibular gland mouse model. Seven-week-old mice were exposed to 25 Gy radiation and randomly assigned to control, phosphate-buffered saline (PBS), or hDPSC-sEV groups. At 18 days post-irradiation, saliva production was measured; histological and reverse transcription-quantitative PCR analyses of the submandibular glands were performed. The salivary flow rate did not differ significantly between the PBS and hDPSC-sEV groups. AQP5-expressing acinar cell numbers and AQP5 expression levels in the submandibular glands were higher in the hDPSC-sEV group than in the other groups. Furthermore, compared with non-irradiated mice, mice in the 25 Gy + PBS group showed a high senescence-associated-ß-galactosidase-positive cell number and upregulated senescence-related gene (p16INK4a, p19Arf, p21) and senescence-associated secretory phenotypic factor (MMP3, IL-6, PAI-1, NF-κB, and TGF-ß) expression, all of which were downregulated in the hDPSC-sEV group. Superoxide dismutase levels were lower in the PBS group than in the hDPSC-sEV group. In summary, hDPSC-sEV reduced inflammatory cytokine and senescence-related gene expression and reversed oxidative stress in submandibular cells, thereby preventing irradiation-induced cellular senescence. Based on these results, we hope to contribute to the development of innovative treatment methods for salivary gland dysfunction that develops after radiotherapy for head and neck cancer.

Off-flavors generated during long-term ambient storage of pasteurized drinking yogurt from skim milk.

Few studies have examined sensory quality changes during the storage of pasteurized drinking yogurt (PDY), and the cause of off-flavor development is unclear. Off-flavors generated during 90-d ambient storage (25 °C) of PDY from reconstituted skim milk were investigated by sensory evaluation, volatile component analysis with gas chromatography-mass spectroscopy, and gas chromatography-olfactometry. Rancid off-flavor was induced by increased fatty acid concentration due to fat decomposition by heat-stable lipase. Masking of off-flavors was inhibited by degradation of diacetyl, which originally contributed to yogurt-like flavors. Maillard reaction particular to ambient storage of PDY resulted in changes in the furaneol and sotolon levels, which may be involved in enhancement of off-flavors. Finally, our findings indicated that production of 4-vinylguaiacol may be involved in off-flavor development. The results of this study will contribute to the development of PDY with a longer shelf life and superior flavor.

Prediction of portal vein thrombosis after hepatectomy for hepatocellular carcinoma.

PURPOSE: Portal vein thrombosis (PVT) following hepatectomy is potentially life-threatening. We aimed to evaluate the incidence of PVT after hepatectomy for hepatocellular carcinoma and identify coagulation and fibrinolytic factors that could predict early-stage postoperative PVT. METHODS: A retrospective analysis was conducted on 65 hepatocellular carcinoma patients who underwent radical hepatectomy. The risk factors for postoperative PVT were identified based on univariate and multivariate analyses, and the levels of coagulation and fibrinolytic factors were measured during the perioperative period. RESULTS: The incidence of PVT after hepatectomy was 20.0%. The patients were divided into two groups: those with PVT (n=13; PVT group) and those without PVT (n=52; no-PVT group). The frequency of the use of the Pringle maneuver during surgery was higher in the PVT group than in the no-PVT group, and the postoperative/preoperative ratios of thrombin-antithrombin III complex (TAT) and of D-dimer were significantly higher in the PVT group. CONCLUSION: A high incidence of PVT was found in hepatocellular carcinoma patients after hepatectomy. The frequency of the Pringle maneuver is a potential risk factor for postoperative PVT, and the postoperative/preoperative TAT and D-dimer ratios may be used as early predictors of PVT after hepatectomy for hepatocellular carcinoma.

Radiological features of cervical spine in dropped head syndrome: a matched case-control study.

PURPOSE: Dropped head syndrome (DHS) is presumably caused by focal myopathy in the cervical posterior muscles; however, distinguishable radiological features of the cervical spine in DHS remain unidentified. This study investigated the radiological features of the cervical spine in dropped head syndrome. METHODS: The records of DHS patients and age- and sex-matched cervical spondylotic myelopathy (CSM) patients were reviewed. Cervical spinal parameters (C2-7, C2-4, and C5-7 angles) were assessed on lateral cervical spine radiographs. Quantitative radiographic evaluation of cervical spine degeneration was performed using the cervical degenerative index (CDI), which consists of four elements: disk space narrowing (DSN), endplate sclerosis, osteophyte formation, and listhesis. RESULTS: Forty-one DHS patients were included. Statistically significant differences were noted between the upper and lower cervical spine in the sagittal angle parameters on the neutral, flexion, and extension radiographs in DHS group, whereas no significant differences were observed in CSM group. CDI comparison showed significantly higher scores of DSN in C3/4, C4/5, C5/6, and C6/7; sclerosis in C5/6 and C6/7; and osteophyte formation in C4/5, C5/6, and C6/7 in DHS group than in CSM group. Comparison of listhesis scores revealed significant differences in the upper levels of the cervical spine (C2/3, C3/4, and C4/5) between two groups. CONCLUSION: Our results demonstrated that the characteristic radiological features in the cervical spine of DHS include lower-level dominant severe degenerative change and upper-level dominant spondylolisthesis. These findings suggest that degenerative changes in the cervical spine may also play a role in the onset and progression of DHS.

Impact of postoperative remote infection on length of stay and medical costs in hospitals in Japan.

PURPOSE: To analyze the impact of postoperative remote infections (PRIs) on medical expenditure. METHODS: The subjects of this retrospective study were 338 patients who had undergone gastroenterological surgery at one of the 20 Japanese institutions within the Japan Society for Surgical Infection (JSSI) and mainly authorized as educational institutions. The patients were allocated to 169 pairs of those with a PRI (PRI (+) group) matched with those without a PRI (PRI (-) group). PRIs included pneumonia, urinary tract infection (UTI), catheter-associated blood stream infection (CA-BSI), and antibiotic-associated enteritis. RESULTS: SSI developed in 74 of the 338 patients (22 without PRI and 52 with PRI). The SSI incidence was significantly higher in the PRI (+) group (p < 0.001). The difference in the median postoperative length of hospital stay was 15 days, indicating a significant prolongation in the PRI (+) group (p < 0.001). The PRI (+) group also had a higher rate of inter-hospital transfer (p < 0.01) and mortality (p < 0.001). Similarly, the difference in median postoperative medical fees was $6832.3, representing a significant increase in the PRI (+) group (p < 0.001). CONCLUSIONS: The postoperative length of hospital stay is longer and the postoperative medical expenditure is higher for patients with a PRI than for those without a PRI.

Impact of Spinopelvic sagittal alignment on the surgical outcomes of dropped head syndrome: a multi-center study.

BACKGROUND: Most of the previous studies about the surgical treatment of dropped head syndrome (DHS) are small case series, and their primary outcome measures were cervical alignment parameters. Therefore, little is known about the associations between pre- and postoperative global sagittal alignment in the whole spine and the clinical outcomes of the surgical treatment of DHS. In this study, we investigated the surgical outcomes of DHS, including correction of cervical and global spinal sagittal alignment. METHODS: This study was a retrospective observational study. Fifteen patients with DHS who had undergone correction surgery were enrolled. Surgical outcomes, including complications and implant failures, were investigated. We assessed cervical alignment parameters as well as spinopelvic global alignment parameters, including pelvic incidence (PI), lumbar lordosis (LL), and C7-sacral sagittal vertical axis (SVA). We examined the changes in these parameters using pre- and posoperative whole spine lateral radiographs. The parameters were compared between the failure and nonfailure groups. RESULTS: Recurrence of sagittal imbalance and horizontal gaze difficulty was observed in 6 cases (40%). In all, 3 cases (20%) exhibited a distal junctional failure and required multiple surgeries with extension of fusion. Of all the radiographic parameters compared between the failure and nonfailure groups, significant differences were only observed in pre and postoperative SVA and PI-LL. CONCLUSIONS: Our results suggest that the global sagittal alignment parameters, including PI-LL and SVA, were different between the patients with failure and non failure, and these parameters might have notable impacts on surgical outcomes. Surgeons should consider PI-LL and SVA while determining the surgical course for patients with DHS.

Lateral lumbar interbody fusion in revision surgery for restenosis after posterior decompression.

OBJECTIVE: The purpose of this study was to compare the clinical results of revision interbody fusion surgery between lateral lumbar interbody fusion (LLIF) and posterior lumbar interbody fusion (PLIF) or transforaminal lumbar interbody fusion (TLIF) with propensity score (PS) adjustments and to investigate the efficacy of indirect decompression with LLIF in previously decompressed segments on the basis of radiological assessment. METHODS: A retrospective study of patients who underwent revision surgery for recurrence of neurological symptoms after posterior decompression surgery was performed. Postoperative complications and operative factors were evaluated and compared between LLIF and PLIF/TLIF. Moreover, postoperative improvement in cross-sectional areas (CSAs) in the spinal canal and intervertebral foramen was evaluated in LLIF cases. RESULTS: A total of 56 patients (21 and 35 cases of LLIF and PLIF/TLIF, respectively) were included. In the univariate analysis, the LLIF group had significantly more endplate injuries (p = 0.03) and neurological deficits (p = 0.042), whereas the PLIF/TLIF group demonstrated significantly more dural tears (p < 0.001), surgical site infections (SSIs) (p = 0.02), and estimated blood loss (EBL) (p < 0.001). After PS adjustments, the LLIF group still showed significantly more endplate injuries (p = 0.03), and the PLIF/TLIF group demonstrated significantly more dural tears (p < 0.001), EBL (p < 0.001), and operating time (p = 0.04). The PLIF/TLIF group showed a trend toward a higher incidence of SSI (p = 0.10). There was no statistically significant difference regarding improvement in the Japanese Orthopaedic Association scores between the 2 surgical procedures (p = 0.77). The CSAs in the spinal canal and foramen were both significantly improved (p < 0.001). CONCLUSIONS: LLIF is a safe, effective, and less invasive procedure with acceptable complication rates for revision surgery for previously decompressed segments. Therefore, LLIF can be an alternative to PLIF/TLIF for restenosis after posterior decompression surgery.

Correlation between blood cell count and outcome of melanoma patients treated with anti-PD-1 antibodies.

BACKGROUND: Anti-programmed cell death protein 1 monoclonal antibodies (αPD-1mAbs) have been shown to be effective for advanced malignant melanoma. Treatment with αPD-1mAbs can also cause immune-related adverse events (irAEs). However, clinical predictive factors for treatment responses or irAE risk remain unclear. OBJECTIVE: To identify useful blood biomarkers for response and occurrence of irAEs with αPD-1mAbs treatment. METHODS: We retrospectively collected data from patients with melanoma treated with αPD-1mAbs at the University of Tsukuba Hospital. Clinical data including age, sex, clinical type, metastatic site, treatment course, blood laboratory tests, irAEs and treatment outcome were collected. RESULTS: Multivariate logistic regression analysis showed that increased baseline neutrophil-lymphocyte ratio (NLR) was significantly associated with poor response (odds ratio [OR]: 2.638, P = 0.0227, cutoff value = 2.8). Similarly, multivariate Cox regression analysis revealed that NLR at baseline were significantly associated with shorter progression survival (hazard ratio: 1.343, P = 0.0095). As for irAEs, logistic regression analysis revealed that baseline absolute eosinophil count was positively associated with occurrence of endocrine irAEs (OR: 1.601, P = 0.045, cutoff value = 240/µL). Additionally, a higher relative eosinophil count at 1 month was significantly correlated with occurrence of endocrine irAEs (OR: 1.229, P = 0.0296, cutoff value = 3.2%). CONCLUSION: Our results suggested that NLR > 2.8 could be a useful baseline biomarker for indicating poor response to αPD-1mAbs treatment and that absolute eosinophil count >240/µL at baseline and relative eosinophil count at 1 month >3.2% could be useful biomarkers to predict endocrine irAEs in patients receiving αPD-1mAbs.

Unusual Bone Lesions with Osteonecrosis Mimicking Bone Metastasis of Squamous Cell Carcinoma in Recessive Dystrophic Epidermolysis Bullosa.

Some bone lesions are reported to mimic bone metastasis on imaging tests. Herein, we report a case of a 55-year-old Japanese man who presented with a skin tumor on the left lower extremity. He also had a history of recurrent generalized cutaneous blister and erosion formation since childhood. His skin lesions were diagnosed as cutaneous squamous cell carcinoma complicated by recessive dystrophic epidermolysis bullosa. Magnetic resonance imaging of the left lower extremity detected multiple focal bone lesions mimicking bone metastases in the left femur and tibia. However, bone biopsy revealed that the bone lesions were osteonecrosis without tumor cells. We suggest that cancer-induced osteonecrosis should be included in the differential diagnosis of bone lesions suspected of being metastases on magnetic resonance imaging.

Microscopic polyangiitis associated with thymic tumor: a case report and review of the literature.

BACKGROUND: Thymic hyperplasia and thymic epithelial tumor (thymoma) have been associated with a variety of autoimmune diseases. Renal involvement has been reported in patients with thymoma. Minimal change disease and membranous nephropathy are frequently observed in glomerular lesions of thymoma patients, but ANCA-associated renal vasculitis is rare. We present a case of thymoma-associated microscopic polyangiitis with positivity for three ANCAs: MPO-ANCA, PR3-ANCA and azurocidin-ANCA. CASE PRESENTATION: An 89-year-old Japanese woman was admitted to our hospital following an episode of general fatigue, nausea, muscle weakness of the lower limbs, and ophthalmoplegia. On urinalysis, proteinuria, hematuria, and cellular casts were observed. Elevated levels of serum creatinine and C-reactive protein were also demonstrated, and MPO-, PR3- and azurocidin-ANCA were detected on serological examination. Renal biopsy showed pauci-immune crescentic glomerulonephritis. We therefore diagnosed rapidly progressive glomerulonephritis due to microscopic polyangiitis. Acetylcholine-receptor antibody was also detected. Chest computed tomography and MRI revealed a lobulated tumor in the anterior mediastinum. We thus also diagnosed myasthenia gravis with thymoma. CONCLUSION: Considering the patient's triple-ANCA positivity, thymic diseases may be associated with the pathogenesis of ANCA-associated vasculitis due to central T-cell tolerance. A further accumulation of cases is needed, because thymectomy does not always induce the remission of thymoma-associated autoimmune diseases.

Overview of dropped head syndrome (Combined survey report of three facilities).

BACKGROUND: Dropped head syndrome (DHS) is a low prevalence and the clinical features remain unclear. The purpose of the present study was to clarify the general overview of DHS. METHODS: The subjects were 67 consecutive DHS patients (17 men and 50 women; average age 72.9 ± 10.2 years) presenting difficulty of horizontal gaze in up-right position. The patients' background, global spinal alignment, clinical findings and treatment were analyzed. RESULTS: The peak population of DHS was 75-79-year-old females. The comorbidities included Parkinson's disease in 9 cases, minor trauma in 9 cases, post-cervical operation in 3 cases, mental depression in 3 cases, malignant tumor in 3 cases, diabetes mellitus in 2 cases and rheumatoid arthritis in 2 cases. The C2-C7 cervical coronal vertical axis was distributed more to the right side (2.6 ± 12.8 mm). Regarding sagittal alignment, 24 cases (35.8%) showed negative balanced DHS (N-DHS) and 43 cases (64.2%) showed positive balanced DHS (P-DHS). There were significant differences in C2-C7 angle, T1S, LL and PI-LL between the two groups. Cervical or back pain was present in 62 cases (92.5%), and average numerical rating scale was 3.0 ± 2.6. Fourteen cases (20.9%) recovered (average 11.3 months), but 29 cases (43.3%) did not recover without surgery. Twenty-four cases (35.8%) underwent surgery, 20 for cervical spine and 4 for thoraco-lumbar spine, and horizontal gaze difficulty was improved in all patients post-surgery. CONCLUSION: DHS was mainly observed in elderly women. About 20% of DHS patients recovered without surgical treatment. DHS was accompanied by scoliosis in 37.3% of the cases.

[A Case of Survival Following Fourth-Line Outpatient Chemotherapy 19 Months after Surgery for Small Intestinal Cancer with Multiple Liver Metastases in a Patient with Good General Condition].

A 59-year-old woman who complained of melena and lightheadedness visited the outpatient clinic at our hospital.According to her blood test result, she had anemia, and her tumor marker levels were high.Enhanced computed tomography(CT) findings showed small intestinal cancer with multiple liver metastases.Partial resection of the small bowel for the small intestinal cancer was performed.Following the administration of fourth-line outpatient chemotherapy containing S-1 plus irinotecan( IRIS)and IRIS plus bevacizumab(IRIS plus Bev), S-1 plus oxaliplatin plus Bev(SOX plus Bev), and weekly paclitaxel (wPAC), she survived with good condition for 19 months after the surgery.