Second Child After Pregnancy and Lactation-Related Osteoporosis (PLO) Treated With Teriparatide: A Case Report.

Pregnancy and lactation-associated osteoporosis (PLO) is one of the rarest and most serious primary osteoporotic conditions that develops during the third trimester of gestation and/or early postpartum period. A history of PLO often causes individuals to hesitate when considering an additional child due to anxiety about recurrence risk. Reported here are details of a 29-year-old patient with PLO given aggressive treatment for osteoporosis with teriparatide who subsequently gave birth to a healthy child at age 33 without PLO recurrence. Further case studies are needed to examine the efficacy and safety of PLO treatment and to provide beneficial results for those who wish to have another pregnancy.

A Case of Adult-onset Still's Disease (AOSD) with Gastrointestinal Lesions.

A 51-year-old woman with fever was admitted to our hospital. A computed tomography (CT) scan showed thickened colonic walls. Colonoscopy revealed erosion in the ileum and colon. Adult-onset Still's disease (AOSD) was diagnosed due to a subsequent sore throat and skin rash. Following AOSD treatment, methylprednisolone pulse therapy, followed by prednisolone and cyclosporine, was initiated. Despite achieving a temporary improvement, relapse occurred with fever, abdominal pain, with worsening CT and endoscopic findings. The reappearance of a skin rash confirmed an exacerbation of AOSD. Tocilizumab treatment alleviated the symptoms and improved the endoscopic findings. Considering their correlation with the symptoms and endoscopic findings, the observed gastrointestinal lesions may be linked to AOSD.

Lymphoproliferative disorder progressing after partial remission following immunosuppressive drugs withdrawal in a patient with rheumatoid arthritis.

Lymphoproliferative disorders (LPDs) are serious complications that arise in patients with rheumatoid arthritis (RA) receiving immunosuppressive drugs (ISDs). Here, we reported a 73-year-old woman diagnosed with RA at 60 years of age and treated with methotrexate, bucillamine, prednisolone, and infliximab. She was referred to our hospital, Osaka Metropolitan University Hospital, with general malaise, pancytopenia, a right adrenal mass, and enlarged periaortic lymph nodes. Epstein-Barr virus was detected in serum. We suspected LPD development and performed a bone marrow biopsy, on which no malignant cells could be detected. Upon ISDs withdrawal, her symptoms and blood counts improved, and the right adrenal mass and enlarged lymph nodes regressed. The patient was followed up for clinical LPD. However, 7 months after the initial visit to our hospital, she developed fever and pancytopenia. A repeat bone marrow biopsy confirmed the diagnosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma complicated by haemophagocytic syndrome. After pulse steroid therapy, the patient received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, which resulted in a complete response. In conclusion, when LPDs develop in patients with RA during ISD treatment, LPDs can progress and complicate haemophagocytic syndrome after partial remission following ISDs withdrawal. Therefore, we should carefully follow up RA patients with LPDs, and aim to achieve an early diagnosis of LPD and promptly initiate chemotherapy.

N-Aryl Indoles as a Novel Class of Potent NaV1.7 Inhibitors.

A novel class of potent NaV1.7 inhibitors has been discovered. The replacement of diaryl ether in compound I was investigated to enhance mouse NaV1.7 inhibitory activity, which resulted in the discovery of N-aryl indoles. The introduction of the 3-methyl group is crucial for high NaV1.7 in vitro potency. The adjustment of lipophilicity led to the discovery of 2e. Compound 2e (DS43260857) demonstrated high in vitro potencies against both human and mouse NaV1.7 with high selectivity over NaV1.1, NaV1.5, and hERG. In vivo evaluations revealed 2e demonstrating potent efficacy in PSL mice with excellent pharmacokinetics.

Phase II Prospective Study of Trastuzumab in Combination with S-1 and Oxaliplatin (SOX100) Therapy for HER2-Positive Advanced Gastric Cancer.

PURPOSE: The standard first-line treatment for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer (AGC) is trastuzumab in combination with cisplatin and fluoropyrimidines. We evaluated the efficacy and safety of S-1 and oxaliplatin (100 mg/m2) (SOX100) combined with trastuzumab, a monoclonal antibody against HER2 for HER2-positive AGC. METHODS: In this single-arm, multicenter phase II study, patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, oxaliplatin (100 mg/m2) intravenously on day 1, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. RESULTS: A total of 25 patients from six centers were enrolled from December 2015 to March 2020. In the 25 patients evaluable for analysis, the 1-year survival rate was 70.8% [90% confidence interval (CI) = 55.5-86.1%], whereas the median OS, PFS, and ORR were 17.8 (95% CI 10.5-22.9) months, 7.6 (95% CI 5.0-10.9) months, and 75.0% (95% CI 53.3-90.2), respectively. Major grade 3/4 adverse events included anorexia (20%), anemia (16%), peripheral sensory neuropathy (16%), and diarrhea (15%). CONCLUSION: SOX100 combined with trastuzumab was effective with a favorable safety profile in patients with HER2-positive AGC.

Long-term outcomes of nasogastric tube with Gastrografin for adhesive small bowel obstruction.

BACKGROUND: We had previously reported that the administration of Gastrografin through a nasogastric tube (NGT-G) followed by long tube (LT) strategy could be a novel standard treatment for adhesive small bowel obstruction (ASBO); however, the long-term outcomes after initial improvement remain unknown. This study aimed to analyze the long-term outcomes of first-line NGT-G. METHODS: Enrolled patients with ASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018. Thereafter, the cumulative surgery rate, cumulative recurrence rate, and overall survival (OS) rate were analyzed. In addition, subset analysis was conducted to determine the cumulative recurrence rate according to colonic contrast with Gastrografin at 24 h. RESULTS: A total of 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed over a median follow-up duration of 550 days. The cumulative 1-year surgery rates, cumulative 1-year recurrence rates, and 1-year OS rates in the LT and NGT-G groups were 18.8% and 18.1%, 30.0% and 31.7%, and 99.1% and 96.6%, respectively; no significant differences were observed between both groups. In the NGT-G group, a negative colonic contrast at 24 h demonstrated a higher tendency for future recurrence compared with a positive colonic contrast at 24 h (1-year recurrence rate: negative contrast, 46.9% vs positive contrast, 27.6%). CONCLUSIONS: Gastrografin through a nasogastric tube followed by LT can be a promising treatment strategy for ASBO, with long-term efficacies equivalent to initial LT placement.

Eosinophilic pancreatitis presenting as rupture of a pancreatic cystic lesion into the chest cavity.

A 71-year-old man was receiving follow-up examination because of a retention cyst in the pancreatic body that extended to the dorsal extrahepatic area, but presented to the Emergency Department at our hospital with dyspnea and cough. Chest X-ray showed a large amount of left-sided pleural effusion and abdominal computed tomography (CT) showed reduction in size of the cystic lesion. Biochemical testing of the pleural effusion revealed high levels of pancreatic enzymes. We, therefore, diagnosed rupture of the pancreatic cystic lesion into the chest cavity. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated stenosis of the pancreatic duct and leakage of contrast medium at the cystic lesion. CT after ERCP revealed leakage of contrast medium from the cystic lesion through the dorsal extrahepatic area into the chest cavity. Endoscopic naso-pancreatic drainage was performed, but the cystic lesion and pleural effusion remained unimproved. Distal pancreatectomy was, therefore, performed. Microscopic examination revealed eosinophilic infiltration of the pancreatic parenchyma, leading to a diagnosis of eosinophilic pancreatitis (EP). Pancreatic retention cyst secondary to chronic pancreatitis associated with eosinophilic infiltration was considered to have ruptured into the chest cavity. EP is a rare etiology of pancreatitis and few cases have been reported. This case was thus considered valuable.

Longitudinal Bidirectional Relationships Between Maternal Depressive/Anxious Symptoms and Children's Tic Frequency in Early Adolescence.

Background: Previous studies have revealed an association between maternal depressive/anxious symptoms and children's tics. However, the longitudinal relationships between these symptoms remain unclear. We examined the longitudinal relationships between maternal depressive/anxious symptoms and children's tic frequency in early adolescence with a population-based sample. Methods: The participants consisted of 3,171 children and their mothers from the Tokyo Teen Cohort (TTC) study, a population-representative longitudinal study that was launched in Tokyo in 2012. Maternal depressive/anxious symptoms and children's tics were examined using self-report questionnaires at the ages of 10 (time 1, T1) and 12 (time 2, T2). A cross-lagged model was used to explore the relationships between maternal depressive/anxious symptoms and children's tic frequency. Results: Higher levels of maternal depressive/anxious symptoms at T1 were related to an increased children's tic frequency at T2 (ß = 0.06, p < 0.001). Furthermore, more frequent children's tics at T1 were positively related to maternal depressive/anxious symptoms at T2 (ß = 0.06, p < 0.001). Conclusions: These findings suggest a longitudinal bidirectional relationship between maternal depressive/anxious symptoms and children's tic frequency in early adolescence that may exacerbate each other over time and possibly create a vicious cycle. When an early adolescent has tics, it might be important to identify and treat related maternal depressive/anxious symptoms.

Infrared Thermography and Ultrasonography of the Hands in Rheumatoid Arthritis Patients.

Ultrasonography (US) and power Doppler US (PDUS) are used worldwide for diagnosing rheumatoid arthritis (RA). Superb microvascular imaging (SMI) is a good tool for evaluating inflammatory activity. Thermal imaging is a noncontact, noninvasive procedure using skin temperature measurement. We report a case wherein the thermal and ultrasound images of the hand are compared and evaluated for inflammatory activity in patients with RA. Case: US imaging of the left hand of a 75-year-old woman with RA revealed a hypoechoic lesion of the left wrist joint. PDUS and SMI evaluated blood flow according to the blood flow at Grade 2. The temperature of the hypoechoic lesion with high blood flow was higher than that of the same location on the opposite side. This study shows that combining thermal and blood flow images may be useful for detecting inflammatory activity levels in RA patients.

Weather sensitivity associated with quality of life in patients with fibromyalgia.

BACKGROUND: Fibromyalgia is characterized by chronic widespread pain, and more than half of patients with fibromyalgia report that weather-related variables aggravate their symptoms. However, the differences in actual symptoms have not been measured between those with and without weather sensitivity. The present study aimed to investigate whether weather sensitivity associated with the minimal clinically important difference values of quality of life in patients with fibromyalgia, between those with and without weather sensitivity. METHODS: Sixty-four consecutive outpatients with fibromyalgia on their first visit to our tertiary center were included. Weather sensitivity was measured using self-perceived symptoms. Pain intensity was measured using the 0-10 Numerical Rating Scale (NRS). Quality of life was measured using the Euro Quality of life-5 Dimensions-3 level (EQ-5D-3L) scale. The variables were subjected to univariable and multivariable analysis using the EQ-5D-3L scale. RESULTS: The mean age of the patients was 50 years. Forty-eight patients (75%) were women. The mean EQ-5D-3L score was 0.55. Thirty-seven patients (58%) reported weather sensitivity. In univariable analysis, the welfare recipient, weather sensitivity, and NRS values were associated with EQ-5D-3L scale scores. In multivariable analysis, NRS value and weather sensitivity were independently associated with EQ-5D-3L scale scores. The NRS and EQ-5D-3L scale scores were significantly worse in those with weather sensitivity than those without weather sensitivity. The difference in NRS values was less than 1.5 points between groups. The differences in EQ-5D-3L scale scores were 0.16 points between groups. CONCLUSIONS: Weather sensitivity was significantly associated with quality of life in patients with fibromyalgia. There was an association with weather sensitivity and the minimal clinically important difference values of quality of life in patients with fibromyalgia. The presence of weather sensitivity could have a key role in the quality of life in patients with fibromyalgia.

Optimal definition of coagulation syndrome after colorectal endoscopic submucosal dissection: a post hoc analysis of randomized controlled trial.

PURPOSE: Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition. METHODS: In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air. RESULTS: A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups. CONCLUSION: Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031). TRIAL REGISTRATION NUMBER: UMIN000027031 DATE OF REGISTRATION: April 18, 2017.

Etelcalcetide decreases the PTH-calcium setpoint without changing maximum and minimum PTH secretion in mice with primary hyperparathyroidism.

INTRODUCTION: Etelcalcetide binds to the extracellular domain of the calcium-sensing receptor (CaSR), while cinacalcet binds to the 7-transmembrane domain of the CaSR; however, it is unknown, whether etelcalcetide has similar effects to cinacalcet on parathyroid hormone (PTH) secretion. MATERIALS AND METHODS: The PTH-calcium setpoint and maximum and minimum PTH secretion were determined using an 'in vivo setpoint analyses.' The PTH-calcium setpoint was obtained in a mouse model of primary hyperparathyroidism (PC) and wild-type (WT) mice, with PC mice divided into two groups. The setpoint was obtained after 7 days of etelcalcetide (3.0 mg/kg BW/day) or vehicle administration via anosmotic pump. After 7 days of crossover administration, the setpoint was obtained again. Parathyroid glands were obtained after crossover administration, and CaSR expression was analyzed by immunohistochemistry. RESULTS: Etelcalcetide administration significantly decreased the setpoint from 9.03 ± 0.56 mg/dL to 6.80 ± 0.28 mg/dL, which was restored to 8.81 ± 0.38 mg/dL after vehicle administration. In the second group of mice, vehicle administration did not alter the setpoint (8.84 ± 0.69 mg/dL to 8.98 ± 0.63 mg/dL), but subsequent etelcalcetide administration significantly decreased it to 7.10 ± 0.72 mg/dL. There was no significant change in maximum and minimum PTH secretion. Expression levels of parathyroid CaSR were lower in PC mice than in WT mice; however, no significant differences were observed between the two mouse groups. CONCLUSION: Etelcalcetide decreased the PTH-calcium setpoint without changing maximum and minimum PTH secretion in PC mice, suggesting that like cinacalcet, etelcalcetide has calcimimetic potency.

Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient-derived primary parathyroid cells.

INTRODUCTION: Etelcalcetide (Parsabiv®, AMG 416/ONO-5163) is a novel allosteric modulator for the calcium-sensing receptor approved for hemodialysis patients with secondary hyperparathyroidism of uremia. Etelcalcetide reduced parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism of uremia in clinical studies. However, its direct effect on parathyroid hormone secretion in human parathyroid cells remains unknown. This study aimed to determine if etelcalcetide suppresses parathyroid hormone secretion by human parathyroid cells in vitro. MATERIALS AND METHODS: We prepared primary cell cultures from human parathyroid tissue and determined calcium-sensing receptor expression levels by immunohistochemistry. Pathyroid tumors were removed from fourteen patients with primary hyperparathyrodism. Parathyroid tissue was dispersed with collagenase, resuspended in culture medium, incubated for 2 h with etelcalcetide and Ca2+, and the medium was then collected. Final etelcalcetide concentrations in the medium were 0.005-50 µmol/L. Levels of human parathyroid hormone in the medium were determined by enzyme-linked immunosorbent assay. RESULTS: In eight of the fourteen parathyroid cell cultures, extracellular Ca2+ reduced parathyroid hormone levels. In four of the eight parathyroid cell cultures which responded extracellular Ca2+, etelcalcetide reduced hormone secretion with the 50% effective concentrations of 0.57, 20.8, 0.42, and 0.57 µmol/L. Expression levels of the calcium-sensing receptor were significantly lower in primary hyperparathyroidism patient-derived parathyroid tissues compared with controls. CONCLUSION: This is the first report that etelcalcetide directly reduced parathyroid hormone secretion from the primary cultured human parathyroid cells from patients with primary hyperparathyroidism. To verify this conclusion, further studies are needed using secondary hyperparathyroidism patient-derived parathyroid cells.

The first management using intubation of a nasogastric tube with Gastrografin enterography or long tube for non-strangulated acute small bowel obstruction: a multicenter, randomized controlled trial.

BACKGROUND: Gastrointestinal decompression is generally applied to a non-strangulated acute small bowel obstruction (NSASBO). Although long tube (LT) placement and administration of Gastrografin through a nasogastric tube (NGT-G) have shown advantages over NGT alone in previous studies, no studies appear to have compared LT and NGT-G. METHODS: In this multicenter, randomized controlled trial, patients with NSASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018 at 11 Japanese institutions. The primary endpoint was non-inferiority of NGT-G compared to LT for non-surgery rate, and the lower limit of the 95% confidence interval for the non-surgery rate (-15%) was set as the lower margin for inferiority of NGT-G compared to LT. RESULTS: In total, 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed in the present trial. The non-surgery rate was 87.4% in the LT group and 91.1% in the NGT-G group, with a 3.7% difference between NGT-G and LT (95.3%CI - 5.55 to 12.91; non-inferiority P = 0.00002923). On the other hand, the non-surgery rate with pure NGT-G alone (76.8%) that represents non-cross-over NGT-G without subsequent LT was significantly lower than that with LT (P = 0.039). Median procedure time was significantly shorter with NGT-G (1 min) than with LT (25 min; P < 0.001), whereas no significant differences in mortality or hospital stay were noted between groups. CONCLUSION: NGT-G is an effective alternative to LT as a first-line treatment for NSASBO. A sequential strategy comprising NGT-G followed by LT might offer a new standard for NSASBO. CLINICAL TRIALS REGISTRATION: This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (umin.ac.jp/ctr Identifier: UMIN000022669) prior to the start of this trial.

Discovery of DS-1971a, a Potent, Selective NaV1.7 Inhibitor.

A highly potent, selective NaV1.7 inhibitor, DS-1971a, has been discovered. Exploration of the left-hand phenyl ring of sulfonamide derivatives (I and II) led to the discovery of novel series of cycloalkane derivatives with high NaV1.7 inhibitory potency in vitro. As the right-hand heteroaromatic ring affected the mechanism-based inhibition liability of CYP3A4, replacement of this moiety resulted in the generation of 4-pyrimidyl derivatives. Additionally, GSH adducts formation, which can cause idiosyncratic drug toxicity, was successfully avoided by this modification. An additional optimization led to the discovery of DS-1971a. In preclinical studies, DS-1971a demonstrated highly potent selective in vitro profile with robust efficacy in vivo. DS-1971a exhibited a favorable toxicological profile, which enabled multiple-dose studies of up to 600 mg bid or 400 mg tid (1200 mg/day) administered for 14 days to healthy human males. DS-1971a is expected to exert potent efficacy in patients with peripheral neuropathic pain, with a favorable safety profile.

Social withdrawal and testosterone levels in early adolescent boys.

Social withdrawal may lead to mental health problems and can have a large impact on a life course, particularly among boys. To support adolescents with social withdrawal, an integrative understanding of the biological bases would be helpful. Social dominance, a possible opposite of social withdrawal, is known to have positive associations with testosterone levels. A previous study suggested that social withdrawal has a negative relationship with sexual maturity among adolescent boys. However, the relationship between social withdrawal and testosterone in adolescence is unknown. This study aimed to examine whether social withdrawal was negatively associated with testosterone levels in early adolescent boys. Salivary samples were collected from 159 healthy early adolescent boys (mean age [standard deviation]: 11.5 [0.73]) selected from participants of the "population-neuroscience study of the Tokyo Teen Cohort" (pn-TTC). Social withdrawal and confounding factors, such as the secondary sexual characteristics and their age in months, were evaluated by self-administered questionnaires completed by the primary parents. The degree of social withdrawal was assessed with the Child Behaviour Checklist (CBCL). Levels of salivary testosterone, and cortisol as a control, were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Logistic regression was conducted to examine the association between social withdrawal and testosterone levels. A higher risk of social withdrawal was associated with a lower salivary testosterone level after adjustment for age in months (odds ratio 0.55, 95 % confidence interval 0.33-0.94), and the association remained significant after adjusting for body mass index, the degree of anxiety/depression and pubertal stage. Thus, we found a negative relationship between social withdrawal and testosterone levels in early adolescent boys. These findings may help to clarify the biological foundations of and to develop support for social withdrawal.

Crystal structure of the mineralocorticoid receptor ligand-binding domain in complex with a potent and selective nonsteroidal blocker, esaxerenone (CS-3150).

Activation of the mineralocorticoid receptor (MR) has long been considered a risk factor for cardiovascular diseases. It has been reported that the novel MR blocker esaxerenone shows high potency and selectivity for MR in vitro as well as great antihypertensive and renoprotective effects in salt-sensitive hypertensive rats. Here, we determined the cocrystal structure of the MR ligand-binding domain (MR-LBD) with esaxerenone and found that esaxerenone binds to MR-LBD in a unique manner with large side-chain rearrangements, distinct from those of previously published MR antagonists. This structure also displays an antagonist form that has not been observed for MR previously. Such a unique binding mode of esaxerenone provides great insight into the novelty, potency, and selectivity of this novel antihypertensive drug.

Estimation of short-circuit current induced by ELF uniform electric fields in grounded humans with different body shapes based on a semi-ellipsoidal model.

It has been reported that when a grounded human is exposed to an electric field at power frequency, a short-circuit current flowing from the feet to the ground is proportional to the square of his or her height. The current, however, should also vary with the body surface area, that is, body shape, even in people with the same height. In the present study, we confirmed this hypothesis using an analytical solution derived from a semi-ellipsoidal model. The short-circuit currents were calculated for various numerical human body models in which the horizontal length of a voxel was varied from 1.8 to 3.0 mm, and the results for different body shapes were compared. Finally, we derived an approximate expression for estimating the short-circuit current from the left-right width (2b), frontal thickness (2c), and height (a) of a human from the analytical solution. The short-circuit currents obtained from the approximate expression are consistent with those obtained from numerical calculations for 48 differently shaped human body models with a correlation coefficient of 0.9942. Hence, we concluded that the short-circuit current can be determined depending on the similarity ratio (a/b) and the ellipticity ratio (c/b) of the human body as well as the height. This finding is consistent with the numerical human body models that have been used previously, in which the similarity and ellipticity ratios were very close. Therefore, we can make the limited conclusion that the short-circuit current is proportional only to the square of the height. Additionally, numerical calculations showed that the short-circuit current is the same whether one foot or both feet are grounded.

Denosumab Improves Glomerular Filtration Rate in Osteoporotic Patients With Normal Kidney Function by Lowering Serum Phosphorus.

Higher serum phosphorus (Pi) increases the risk for chronic kidney disease (CKD). It was reported that a single administration of denosumab or zoledronate significantly suppressed serum Pi levels as well as those of bone resorption markers in serum. Also, previous evidences suggest a link between bone anti-resorptive therapy and vasoprotective/renoprotective effects through mechanisms that remain unexplored. The aim of this study is to assess the renoprotective effect of denosumab and involvement of denosumab-induced reduction in serum Pi in osteoporotic patients. Osteoporotic patients (n = 73) without overt proteinuria in dipstick test results were treated with denosumab (60 mg) every 6 months during the study period (24 months). Estimated glomerular filtration rate based on serum cystatin C (eGFRcys) was used as a filtration marker and tartrate-resistant acid phosphatase-5b (TRACP-5b) as a bone resorption marker. For analysis of non-CKD patients (n = 56), those with eGFRcys <60 mL/min/1.73 m2 were excluded. A single injection of denosumab suppressed serum Pi as well as TRACP-5b during the first 6 months, whereas age-related decline in eGFRcys was significantly reversed, with an increase of 2.75 ± 1.2 mL/min/1.73 m2 after 24 months noted. Multivariate analysis showed that serum Pi reduction following the initial denosumab injection was positively associated with serum TRACP-5b suppression during that same period (ß = 0.241, p = 0.049). In addition, a positive association of serum Pi suppression, but not of corrected calcium or TRACP-5b, with eGFRcys increase after 24 months (ß = 0.321, p = 0.014) was found after adjustments for gender, age, BMI, antihypertensive drug use, albumin, and eGFRcys. The same was observed in osteoporotic cases restricted to non-CKD patients. In conclusion, serum Pi reduction resulting from phosphorus load decrement from bone induced by denosumab is a determinant for eGFRcys increase. Early introduction of bone antiresorptive therapy can retain glomerular filtration in osteoporosis cases, including non-CKD patients. © 2019 American Society for Bone and Mineral Research.

Efficacy of Mucosal Cutting Biopsy for the Histopathological Diagnosis of Gastric Submucosal Tumors.

BACKGROUND: Gastrointestinal stromal tumors occur frequently. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed commonly for diagnosis. However, the success rate of histological diagnosis is insufficient when the submucosal tumor (SMT) is small. Recently, another technique, mucosal cutting biopsy (MCB) has been reported. The aim of this study is to evaluate the efficacy and safety of MCB. METHOD: Between January 2012 and August 2018, MCB and EUS-FNA were performed 16 and 31 times for diagnosing gastric SMT. The diagnostic rate, the rate of successful immunohistochemistry, and the safety were reviewed. Difficult locations for EUS-FNA were also evaluated. RESULTS: The mean SMT sizes measured on MCB and EUS-FNA were 21.2 and 36.2 mm. The diagnostic rates of MCB and EUS-FNA were almost the same (88 vs. 81%), but successful immunohistochemistry was significantly higher in the MCB group (93 vs. 59%, p = 0.03). In the subgroup of SMTs < 20 mm, the successful histological diagnosis rate from EUS-FNA was relatively low. There were no complications. Failures of EUS-FNA were more frequent in the middle third of the stomach. CONCLUSIONS: MCB was an effective procedure for diagnosing gastric SMT, especially in the case of small SMTs located at the middle third of the stomach.