The 2023 Guidelines for the management and treatment of glucocorticoid-induced osteoporosis.

INTRODUCTION: Although synthetic glucocorticoids (GCs) are commonly used to treat autoimmune and other diseases, GC induced osteoporosis (GIOP) which accounts for 25% of the adverse reactions, causes fractures in 30-50% of patients, and markedly decreases their quality of life. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) published the revised guidelines for the management and treatment of steroid-induced osteoporosis, providing the treatment criteria based on scores of risk factors, including previous fractures, age, GC doses, and bone mineral density, for patients aged ≥18 years who are receiving GC therapy or scheduled to receive GC therapy for ≥3 months. MATERIALS AND METHODS: The Committee on the revision of the guidelines for the management and treatment of GIOP of the JSBMR prepared 17 clinical questions (CQs) according to the GRADE approach and revised the guidelines for the management and treatment of GIOP through systematic reviews and consensus conferences using the Delphi method. RESULTS: Bisphosphonates (oral and injectable formulations), anti-RANKL antibody teriparatide, eldecalcitol, or selective estrogen receptor modulators are recommended for patients who has received or scheduled for GC therapy with risk factor scores of ≥3. It is recommended that osteoporosis medication is started concomitantly with the GC therapy for the prevention of fragility fractures in elderly patients. CONCLUSION: The 2023 guidelines for the management and treatment of GIOP was developed through systematic reviews and consensus conferences using the Delphi method.

Work-related psychosocial factors and inflammatory markers: A systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the prospective effect of adverse work-related psychosocial factors on increases in inflammatory markers. METHODS: A systematic literature search was conducted in PubMed, Embase, PsycINFO, PsycARTICLES, and the Japan Medical Abstracts Society database. Studies were eligible for inclusion if they examined associations between work-related psychosocial factors and inflammatory markers (interleukin-6, tumor necrosis factor-alpha, and C-reactive protein), used longitudinal or prospective cohort designs, were conducted among workers, were original articles written in English or Japanese, and were published up to 2017 for the first search, October 2020 for the second, and November 2022 for the third. A meta-analysis was conducted using a random-effects model to assess the pooled effect size for the associations. A meta-regression analysis was used to estimate the association between length of follow-up and effect size. The ROBINS-I tool was used to assess risk of bias. RESULTS: Of the 11,121 studies identified in the first search, 29,135 studies from the second, and 9448 studies from the third, eleven were eligible for this review and meta-analysis. The pooled coefficient between adverse work-related psychosocial factors and inflammatory markers was significant and positive (ß = 0.014, 95% confidence interval: 0.005-0.023). However, a clear association was only observed for interleukin-6, and all the studies included had serious risks of bias. Meta-regression showed the effect size decreased depending on the follow-up period. CONCLUSION: This study revealed a weak positive association between adverse work-related psychosocial factors and increases in inflammatory markers. TRIAL REGISTRATION: PROSPERO CRD42018081553 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=81553).

Regional Variance of the Early Use of Tolvaptan for Autosomal Dominant Polycystic Kidney Disease.

Background: The development and prompt dissemination of the first drug against a particular disease can contribute to improvements in national health status and medical economy end points and are assumedly affected by socioeconomic factors that have yet to be analyzed. Tolvaptan, a vasopressin receptor 2 antagonist, was developed to treat hyponatremia, congestive heart failure, and cirrhosis ascites, although the approved indications may differ among countries. In Japan, high-dose tolvaptan tablets were approved as the first drug for autosomal dominant polycystic kidney disease (ADPKD) in 2014. This study aimed to better understand the factors that influence the total number of regional prescriptions of tolvaptan for ADPKD since its launch. Methods: The National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data was used as a national claim-based database. In each of the 47 prefectures in Japan, the total prescribed number of 30 mg tolvaptan tablets between 2015 and 2017 was examined. The parameters explaining the prescription variation among regions were then examined by correlation analysis. Results: Prescriptions for high-dose tolvaptan increased substantially 2 years after the drug's approval; however, the increase differed by approximately 21-fold between regions. Population density was positively associated with prescribed 30 mg tolvaptan tablets per 1000 population in 2015 (r=0.47, P<0.001). In addition, the increase in prescribed number of tablets per 1000 population was correlated with population density in 2016-2017 (r=0.30, P=0.04). Conclusions: This macro perspective analysis revealed an urban-rural inequity in prescriptions for the newly approved drug for ADPKD. Further studies are needed to elucidate the factors affecting the geographic variation.

Clinical Presentation of Tubulointerstitial Nephritis Caused by Amyloid Light-chain Amyloidosis in a Patient with Sjögren's Syndrome.

We report a 70-year-old woman with Sjögren's syndrome who had severe renal dysfunction with mild proteinuria and elevated urinary low-molecular-weight proteins. Based on these clinical presentations, interstitial nephritis due to Sjögren's syndrome was strongly suspected. Unexpectedly, renal pathology revealed amyloid light-chain (AL) lambda-type depositions predominantly in the vasculatures with severe tubulointerstitial damage. Concentrated urine immunofixation was positive for Bence Jones lambda-type monoclonal proteins. Given the involvement in other organs, systemic AL amyloidosis was diagnosed. The patient underwent chemotherapy, but hemodialysis was ultimately instituted. It should be remembered that renal amyloidosis occurs as a clinical presentation of interstitial nephritis.

Therapeutic dose of acetaminophen as a possible risk factor for acute kidney injury: learning from two healthy young adult cases.

Acetaminophen overdose can lead to severe liver and kidney failure; however, the risk of therapeutic doses in healthy individuals causing acute kidney injury (AKI) is less clear. We herein describe the cases of two young adults with renal biopsy-proven acute tubular necrosis under a therapeutic dose of acetaminophen. The first patient exhibited mild reversible renal insufficiency, whereas, in the second case, the patient demonstrated a slightly increased serum creatinine level and enlarged kidneys and the administration of contrast media and antibiotics may have worsened the renal dysfunction, leading to the need for temporal hemodialysis. Physicians should be aware of the risk of acetaminophen causing AKI and avoid administering other nephrotoxic agents in such cases.

Determination of nicotine, cotinine, and related alkaloids in human urine and saliva by automated in-tube solid-phase microextraction coupled with liquid chromatography-mass spectrometry.

A simple, rapid and sensitive method for the determination of nicotine, cotinine, nornicotine, anabasine, and anatabine in human urine and saliva was developed. These compounds were analyzed by on-line in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-mass spectrometry (LC-MS). Nicotine, cotinine and related alkaloids were separated within 7 min by high performance liquid chromatography (HPLC) using a Synergi 4u POLAR-RP 80A column and 5 mM ammonium formate/methanol (55/45, v/v) as a mobile phase at a flow-rate of 0.8 mL/min. Electrospray ionization conditions in the positive ion mode were optimized for MS detection of these compounds. The optimum in-tube SPME conditions were 25 draw/eject cycles with a sample size of 40 microL using a CP-Pora PLOT amine capillary column as the extraction device. The extracted compounds could be desorbed easily from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC-MS method, the calibration curves were linear in the concentration range of 0.5-20 ng/mL of nicotine, cotinine and related compounds in urine and saliva, and the detection limits (S/N=3) were 15-40 pg/mL. The method described here showed 20-46-fold higher sensitivity than the direct injection method (5 microL injection). The within-run and between-day precision (relative standard deviations) were below 4.7% and 11.3% (n=5), respectively. This method was applied successfully to analysis of urine and saliva samples without interference peaks. The recoveries of nicotine, cotinine and related compounds spiked into urine and saliva samples were above 83%, and the relative standard deviations were below 7.1%. This method was used to analyze urinary and salivary levels of these compounds in nicotine intake and smoking.

Determination of isophorone in food samples by solid-phase microextraction coupled with gas chromatography-mass spectrometry.

A simple and sensitive method for the determination of isophorone in food samples was developed by headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). Isophorone was separated within 10 min by GC-MS using a DB-1 capillary column and detected with selective ion monitoring mode. The HS-SPME using a polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber provided effective sample enrichment, and was carried out by fiber exposition at 60 degrees C for 45 min. The extracted isophorone was easily desorbed by fiber exposition in the injection port of a capillary GC-MS system, and carryover was not observed. Using this method, the calibration curve of isophorone was linear in the range 20-1000 pg/mL, with a correlation coefficient 0.9996 (n = 18), and the detection limit (S/N = 3) was 0.5 pg/mL. The HS-SPME/GC-MS method showed 25,000-fold higher sensitivity than the direct injection method (1 microL injection). The within-day and between-day precisions (relative standard deviations) at the concentration of 1 ng/mL isophorone were 3.9% and 6.1% (n=5), respectively. This method was successfully applied to the analysis of food samples without interference peaks. The recoveries of isophorone spiked into food sample were above 84% for a 50 or 500 pg/mL spiking concentration. The analytical results of the contents of isophorone in various food samples were presented.