Publications by authors named "Satoshi Hara"

186 Publications

Individualized left anterior oblique projection based on pigtail catheter visualization facilitates leadless pacemaker implantation.

J Arrhythm 2021 Jun 5;37(3):676-682. Epub 2021 May 5.

Department of Cardiovascular Medicine Tokyo Medical and Dental University Tokyo Japan.

Background: Pacemaker positioning on the right ventricular (RV) septum during implantation is conventionally conducted utilizing two fixed fluoroscopy angles, a 45° left anterior oblique (LAO) and 35° right anterior oblique projection. However, placement location can be suboptimal, especially for leadless pacemakers (LPMs).

Objective: To evaluate the safety and ease of LPM implantation using individualized LAO projection.

Methods: Consecutive patients undergoing LPM implantation were prospectively included. The angle of the RV septum was recorded for each patient by studying the angle at which an RV pigtail catheter (RV-PC) could be seen edge on. This was then used as the preferred LAO projection angle for that patient. We evaluated the success rate and safety of this method. We also compared the RV septum angle as measured by this method versus that measured by chest CT.

Results: Of the 31 patients (mean age 80.6 ± 7.0 years, 15 females), LPM implantation was successful in 30. The pacemaker was implanted on the RV septum in 29 and on the free wall in one. LPM implantation was abandoned for anatomical reasons in one. Complications were limited to a groin arteriovenous fistula and one deep vein thrombosis. The angle of RV septum as measured by pigtail catheter and chest CT was not significantly different (CT: 54.8 ± 6.0°, RV pigtail catheter: 52.9 ± 6.1°,  = .07).

Conclusions: Using an RV-PC to determine the preferred angle of LAO projection facilitates differentiation between the RV septum and free wall, which in turn facilitates optimal LPM placement.
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http://dx.doi.org/10.1002/joa3.12540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207349PMC
June 2021

Phenotypically concordant but epigenetically discordant monozygotic dichorionic diamniotic twins with Beckwith-Wiedemann syndrome.

Am J Med Genet A 2021 May 26. Epub 2021 May 26.

Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.

Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by (epi)genetic alterations. The incidence of monozygotic (MZ) twins in BWS is higher than in the general population. Most MZ twins with BWS are female and have phenotypical discordance: one twin is clinically diagnosed with BWS, while the other shows a mild or normal phenotype. The most frequent (epi)genetic alteration in MZ twins is loss of methylation of imprinting control region 2 (ICR2-LOM) at 11p15.5. Intriguingly, ICR2-LOM is usually found in the peripheral blood leukocytes (PBL) of both twins, even if they are clinically discordant. Here, we present a rare pair of MZ dichorionic diamniotic female twins with BWS and concordant phenotypes (a Beckwith-Wiedemann spectrum score of 5 in each twin). Molecular analysis of genomic DNA from PBL revealed ICR2-LOM in one twin but not the other. Our analyses suggest that ICR2-LOM occurred between days 1 and 3 after fertilization, followed by twinning. We speculate that during embryogenesis, ICR2-LOM cells were distributed to the hematopoietic stem cells in different ratios in the two fetuses, and also to commonly affected tissues, such as the tongue, in similar ratios, although we were unable to analyze any tissues other than PBL.
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http://dx.doi.org/10.1002/ajmg.a.62364DOI Listing
May 2021

Guideline adherence for radical cystectomy significantly affects survival outcomes in non-muscle-invasive bladder cancer patients.

Jpn J Clin Oncol 2021 May 3. Epub 2021 May 3.

Department of Urology, Keio University School of Medicine, Tokyo, Japan.

Background: The relationship between guideline adherence for radical cystectomy of non-muscle-invasive bladder cancer and patient prognoses currently remains unclear. We investigated whether guideline adherence at the time of non-muscle-invasive bladder cancer affects the oncological outcomes of bladder cancer patients who underwent radical cystectomy.

Methods: Among 267 cTa-4N0-2M0 bladder cancer patients, 70 who underwent radical cystectomy under the non-muscle-invasive bladder cancer or muscle-invasive bladder cancer status that progressed from non-muscle-invasive bladder cancer were identified. Patients who followed the guidelines from initial transurethral resection of bladder tumors to radical cystectomy were defined as the guideline adherent group (n = 52), while those who did not were the guideline non-adherent group (n = 18).

Results: In the guideline non-adherent group, 8 (44.4%) out of 18 were diagnosed with highest risk non-muscle-invasive bladder cancer for Bacillus Calmette Guérin-naïve patients and 7 (38.9%) had a Bacillus Calmette Guérin unresponsive tumor status. Five-year recurrence-free survival and cancer-specific survival rates for the guideline non-adherent group vs guideline adherent group were 38.9% vs 69.8% (P = 0.018) and 52.7% vs 80.1% (P = 0.006), respectively. A multivariate analysis identified guideline non-adherence as one of independent indicators for disease recurrence (hazard ratio = 2.81, P = 0.008) and cancer-specific death (hazard ratio = 4.04, P = 0.003). In a subgroup analysis of 49 patients with cT1 or less non-muscle-invasive bladder cancer at the time of radical cystectomy, guideline non-adherence remained an independent prognostic factor for cancer-specific survival (hazard ratio = 3.46, P = 0.027).

Conclusions: Guideline adherence during the time course of the non-muscle-invasive bladder cancer stage may result in a favorable prognosis of patients who receive radical cystectomy. Even under non-muscle-invasive bladder cancer status, radical cystectomy needs to be performed with adequate timing under guideline recommendations.
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http://dx.doi.org/10.1093/jjco/hyab060DOI Listing
May 2021

Laparoendoscopic single-site simple nephrectomy and reduced port procedure for inflammatory nonfunctioning kidney.

IJU Case Rep 2021 May 17;4(3):184-187. Epub 2021 Mar 17.

Department of Uro-Oncology Saitama Medical University International Medical Center Hidaka Saitama Japan.

Introduction: To describe laparoendoscopic single-site simple nephrectomy and reduced port simple nephrectomy for inflammatory nonfunctioning kidney.

Case Presentation: Case 1: a 58-year-old female with fever was referred to our hospital. Computed tomography demonstrated a markedly atrophic right kidney and mild hydronephrosis. Case 2: a 64-year-old male with a history of several intra-abdominal surgeries visited our hospital with a complaint of left back pain and fever. Computed tomography demonstrated left marked hydronephrosis, thinning of renal parenchyma, and duplicated inferior vena cava. After antibiotic treatment, transperitoneal reduced port simple nephrectomy and retroperitoneal laparoendoscopic single-site simple nephrectomy were performed in Case 1 and 2, respectively, because the function of the affected kidney was almost lost on renography. Although adhesion was slightly noted around the renal hilum in Case 1, neither conversion to laparotomy nor placement of additional ports was needed.

Conclusion: Laparoendoscopic single-site simple nephrectomy and reduced port simple nephrectomy for inflammatory nonfunctioning kidney may be options for experienced laparoscopic surgeons.
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http://dx.doi.org/10.1002/iju5.12278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088899PMC
May 2021

Factors contributing to discrepant estimated glomerular filtration values measured by creatinine and cystatin C in patients with rheumatoid arthritis.

Sci Rep 2021 May 10;11(1):9884. Epub 2021 May 10.

Department of Rheumatology, Kanazawa University Hospital, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.

This study aimed to clarify the factors underlying the discrepancy that has been noted between estimated glomerular filtration ratio (eGFR) measured using serum creatinine (Cr) and eGFR using serum cystatin C (CysC) in patients with rheumatoid arthritis (RA) and to identify those patients whose renal function should be evaluated using CysC. We retrospectively evaluated clinical features, disease activity, Steinbrocker radiological staging, and co-morbidities (diabetes mellitus, hypertension, dyslipidemia) in 238 RA patients. eGFR using serum creatinine (eGFR-Cr) and eGFR using serum cystatin C (eGFR-CysC) were calculated using the new Japanese coefficient-modified Modification of Diet in Renal Disease study equation. To clarify the cause(s) of differences of 20% or more between the two eGFRs, we divided our RA patients into Group A (eGFR-Cr/eGFR-CysC ≥ 1.2) and Group B (eGFR-Cr/eGFR-CysC < 1.2), and searched for factors independently related to Group A. Forty-five patients (18.9%) were assigned to Group A, and 193 (81.1%) to Group B. BMI (Odds Ratio [OR] 0.820, 95% confidence interval [CI] 0.675-0.996), Hb (OR 0.633, 95% CI 0.433-0.926), CK (OR 0.773 per 10 units, 95% CI 0.644-0.933), NSAID use (OR 0.099, 95% CI 0.020-0.494), diabetes mellitus (OR 6.024, 95% CI 1.508-24.390) and stage 4 Steinbrocker radiological stage (OR 10.309, 95% CI 2.994-35.714) were identified as independent relevant factors for Group A by a multifactorial analysis. Renal function in RA patients with low BMI, diabetes, anemia and low CK may be overestimated using eGFR-Cr alone, and such patients need to be evaluated using eGFR-CysC.
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http://dx.doi.org/10.1038/s41598-021-89303-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110572PMC
May 2021

Corrigendum to "A Case of Epistaxis as the First Sign of Acute Idiopathic Thrombocytopenic Purpura".

Case Rep Otolaryngol 2021 12;2021:9804515. Epub 2021 Apr 12.

Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.

[This corrects the article DOI: 10.1155/2021/6612939.].
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http://dx.doi.org/10.1155/2021/9804515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057897PMC
April 2021

Superior vena cava isolation with 50 W high power, short duration ablation strategy.

J Cardiovasc Electrophysiol 2021 Jun 5;32(6):1602-1609. Epub 2021 May 5.

Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

Introduction: The optimal ablation strategy is unknown regarding a superior vena cava isolation (SVCI). This study aimed to examine the feasibility and safety and to analyze the lesion characteristics of the SVCI using high-power, short-duration (HPSD) ablation.

Methods And Results: A total of 100 patients underwent an index SVCI using HPSD (n = 50, HPSD group) or conventional lower-power and longer-duration (n = 50, LPLD group) ablation, using the Thermocool Smarttouch SF. In the HPSD group, ablation was performed with a power of 50 W for 7 s, and was limited to 4 s at the lateral segment close to the right phrenic nerve. The ablation setting used in the LPLD group was 20-25 W for 20-30 s and was limited to 10-20 W for 15-30 s at the lateral segment when diaphragmatic capture was seen. An electrical SVCI was achieved in all patients. The HPSD group required a significantly shorter procedure time (10.8 ± 3.2 vs. 14.8 ± 6.4 min; p < .01), shorter radiofrequency duration (49 ± 16 vs. 282 ± 124 s; p < .01), fewer lesions (8.3 ± 2.5 vs. 10.4 ± 4.4; p < .01), and lower ablation index (316 ± 38 vs. 356 ± 62; p < .001) than the LPLD group. The incidence of a postprocedural asymptomatic mild diaphragmatic elevation was comparable (2% in the HPSD group vs. 6% in the LPLD group; p = .61).

Conclusion: The 50-W HPSD ablation strategy allowed for a successful, fast, and safe SVCI with the fewer ablation lesions and the lower ablation index.
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http://dx.doi.org/10.1111/jce.15060DOI Listing
June 2021

Cholesteatoma Surgery With a Dehiscent High Jugular Bulb Treated With Surgery Assisted With Underwater Endoscopy: A Case Report.

Ear Nose Throat J 2021 Apr 29:1455613211009135. Epub 2021 Apr 29.

Department of Otorhinolaryngology, 12847Juntendo University Faculty of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.

A dehiscent high jugular bulb would be a pitfall in middle ear surgery especially for cholesteatoma. We report a case of cholesteatoma attached to a dehiscent high jugular bulb successfully treated with surgery assisted with underwater endoscopy. To the best of our knowledge, no previous study has reported a case of cholesteatoma with dehiscent high jugular bulb treated with surgery assisted with underwater endoscopy. Owing to the risk of jugular bulb injury, underwater endoscopy is a good indication for middle ear cases with a dehiscent high jugular bulb to obtain a clear operative field and avoid an unexpected air embolism.
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http://dx.doi.org/10.1177/01455613211009135DOI Listing
April 2021

A Case of Aspiration Pneumonia Caused by Cerebrospinal Fluid Leaks Associated with Delayed Identification of Iatrogenic Skull Base Injury during Endoscopic Sinus Surgery.

Case Rep Otolaryngol 2021 8;2021:5532194. Epub 2021 Apr 8.

Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Cerebrospinal fluid (CSF) leaks associated with endoscopic sinus surgery (ESS) are a rare complication affecting approximately 0.09% of patients. Although meningitis is a well-known complication of CSF leaks, the case we present is a rare and cautionary case of CSF leakage associated with ESS leading to aspiration pneumonia. A 43-year-old man with CSF leaks after ESS was referred to our hospital. After the operation, sometimes, he reported having a serous nasal discharge from the right side when he bent over, and he woke up choking on something every day. He also experienced headache, fever, fatigue, and cough. Interestingly, chest computed tomography (CT) showed a consolidation and ground-glass opacity in the posterior segments of the right upper lobes and superior segments of the bilateral lower lobes. These CT imaging findings were similar to those of aspiration pneumonia in bedridden patients who are always in a supine position. These findings suggest that CSF caused aspiration pneumonia. To the best of our knowledge, no case of aspiration pneumonia caused by CSF during endoscopic sinus surgery has been reported until now. If a patient with CSF leakage after ESS experiences fever, cough, or fatigue, physicians should consider aspiration pneumonia in addition to meningitis.
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http://dx.doi.org/10.1155/2021/5532194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052149PMC
April 2021

Glomerulonephritis with severe nephrotic syndrome induced by immune complexes composed of galactose-deficient IgA1 in primary Sjögren's syndrome: a case report.

BMC Nephrol 2021 Mar 25;22(1):108. Epub 2021 Mar 25.

Department of Rheumatology, Kanazawa University Hospital, Kanazawa University Graduate School of Medical Science, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.

Background: Primary Sjögren's syndrome (pSS) is an auto-immune disease characterized by sialadenitis and dacryoadenitis with lymphoplasmacytic cell infiltration. In pSS, not only sicca symptoms, but also extra-glandular involvement induced by immune abnormalities based on pSS occurs. Renal involvement is one such important life-threatening extra-glandular involvement. Although the aberrant glycosylated IgA in pSS as a product of over-activated B cells is a risk factor of renal involvement, its association has not been clarified. Here we report a case of glomerulonephritis (GN) induced by immune complexes (IC) composed of galactose-deficient IgA1 (Gd-IgA1) in a patient with pSS.

Case Presentation: A 48-year-old Japanese woman with pSS was admitted to our hospital because of a two-month history of nephrotic syndrome. Seven years before she had been diagnosed with pSS from keratoconjunctivitis sicca, elevation of serum anti-Ro/SSA antibody titer and lymphoplasmacytic cell infiltration around salivary ducts of the small salivary glands. Renal biopsy revealed diffuse bubbling appearance in glomerular basement membrane (GBM) with scarce mesangial proliferation. Immunofluorescence showed granular IgA, C3 and Gd-IgA1 staining of GBM. Light chain staining showed no monoclonality. Electron microscopy showed electron dense deposits mainly in the intra-membranous and paramesangial areas and slightly in the subepithelial area. Additional serum analysis confirmed elevation of Gd-IgA1 (13.5 μg/mL), which was comparable with that seen in IgA nephropathy, and qualitative enzyme-linked immunosorbent assay of IgA-containing circulating immune complex (IgA-CIC) was positive. Thus, we diagnosed GN induced by IC composed of Gd-IgA1. Furthermore, retrospectively performed immunofluorescence of the small salivary gland evaluated at the diagnosis of pSS showed positive Gd-IgA1 staining of infiltrating lymphoplasmacytic cells. Therefore, we concluded that Gd-IgA1 produced by over-activated B cells in pSS formed circulating IC and thereby induced GN. After induction therapy with high dose prednisolone and mycophenolate mofetil, the nephrotic syndrome remitted within 3 weeks, the serum Gd-IgA1 level decreased to the normal range (3.8 μg/mL), and serum IgA-CIC disappeared in the 6th month after induction therapy.

Conclusions: Our findings clearly demonstrate an association between aberrant glycosylated IgA and the renal involvement seen in pSS, thereby helping to clarify the renal significance of aberrant glycosylated IgA in pSS.
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http://dx.doi.org/10.1186/s12882-021-02306-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992980PMC
March 2021

Tyrosine hydroxylase conditional knockout mice reveal peripheral tissue-dependent differences in dopamine biosynthetic pathways.

J Biol Chem 2021 Mar 15:100544. Epub 2021 Mar 15.

School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan. Electronic address:

Dopamine (DA) exerts well-known functions in the brain as a neurotransmitter. In addition, it plays important physiological roles in peripheral organs, but it is largely unknown how and where peripheral DA is synthesized and regulated. Catecholamines (CAs) in peripheral tissues are either produced within the tissue itself and/or derived from sympathetic neurons, which release neurotransmitters for uptake by peripheral tissues. To evaluate DA-producing ability of each peripheral tissue, we generated conditional KO mice (cKO mice) in which the tyrosine hydroxylase (TH) gene is ablated in the sympathoadrenal system, thus eliminating sympathetic neurons as a DA source. We then examined the alterations in the noradrenaline (NA), DA, and DOPA contents in peripheral organs and performed immunohistochemical analyses of TH-expressing cells. In the heart and pancreas of cKO mice, both the TH protein and NA levels were significantly decreased, and the DA contents were decreased in parallel with NA contents, indicating that the DA supply originated from sympathetic neurons. We found TH-immunoreactive cells in the stomach and lung, where the TH protein showed a decreasing trend but the DA levels were not decreased in cKO mice. Moreover, we found a significant correlation between the DA content in the kidney and the plasma DOPA concentration, suggesting that the kidney takes up DOPA from blood to make DA. The above data unravel differences in the DA biosynthetic pathway among tissues and support the role of sympathetic neurons as a DA supplier.
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http://dx.doi.org/10.1016/j.jbc.2021.100544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076703PMC
March 2021

Association Between Earwax-Determinant Genotypes and Acquired Middle Ear Cholesteatoma in a Japanese Population.

Otolaryngol Head Neck Surg 2021 Mar 16:1945998211000374. Epub 2021 Mar 16.

Department of Otorhinolaryngology, Faculty of Medicine, Juntendo University, Tokyo, Japan.

Objective: A single-nucleotide polymorphism 538G>A in the human gene is a determinant of the earwax morphotype. 538GG and GA correspond to wet earwax and 538AA to dry earwax. Despite a putative positive correlation between the frequency of the 538G allele and the prevalence of cholesteatoma, minimal clinical information is currently available. We aimed to evaluate this association between the genotypes and acquired middle ear cholesteatoma.

Study Design: Case-control study.

Setting: Single-center academic hospital.

Methods: We recruited 67 Japanese patients with acquired middle ear cholesteatoma (cholesteatoma group) and 100 Japanese controls with no history of middle ear cholesteatoma. We assessed the genotypes for all participants. Clinical information was collected from the cholesteatoma group. The genotype data of 104 Japanese people from the 1000 Genomes Project who represent the general population were used.

Results: The proportion of participants with 538GG or GA was significantly higher in the cholesteatoma group than in the control group or general Japanese population ( < .001). The 538G allele frequency was also significantly higher in the cholesteatoma group than in the control group or general Japanese population ( < .001). Multivariate logistic regression analyses revealed a significant association between the genotype and acquired middle ear cholesteatoma (odds ratio, 5.49; 95% CI, 2.61-11.5; < .001).

Conclusion: Our results suggest that the genotypes could be associated with the development of acquired middle ear cholesteatoma among Japanese people.
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http://dx.doi.org/10.1177/01945998211000374DOI Listing
March 2021

Pure laparoscopic total ureterectomy for urothelial carcinoma that occurred in the ureteral stump after nephrectomy: A case report.

Urol Case Rep 2021 Jul 26;37:101618. Epub 2021 Feb 26.

Department of Urology, Kawasaki Municipal Hospital, 12-1 Shinkawadori, Kawasaki-ku, Kawasaki-city, Kanagawa, Japan.

Primary carcinoma of the ureteral stump following a radical nephrectomy is rare, and it is even rarer that the cause of the nephrectomy is renal cell carcinoma (RCC). Treatment by complete ureterectomy with a bladder cuff is considered as the standard treatment. We report a case of a 70-year-old female with urothelial carcinoma with glandular differentiation that occurred in the ureteral stump after nephrectomy for left RCC. We performed a novel technique of pure laparoscopic resection of the ureteral stump with a bladder cuff.
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http://dx.doi.org/10.1016/j.eucr.2021.101618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932898PMC
July 2021

Humanization of a tandem repeat in IG-DMR causes stochastic restoration of paternal imprinting at mouse Dlk1-Dio3 domain.

Hum Mol Genet 2021 May;30(7):564-574

Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.

The Dlk1-Dio3 imprinted domain, regulated by an intergenic differentially methylated region (IG-DMR), is important for mammalian embryonic development. Although previous studies have reported that DNA methylation of a tandem repeated array sequence in paternal IG-DMR (IG-DMR-Rep) plays an essential role in the maintenance of DNA methylation in mice, the function of a tandem repeated array sequence in human IG-DMR (hRep) is unknown. Here, we generated mice with a human tandem repeated sequence, which replaced the mouse IG-DMR-Rep. Mice that transmitted the humanized allele paternally exhibited variable methylation status at the IG-DMR and were stochastically rescued from the lethality of IG-DMR-Rep deficiency, suggesting that hRep plays a role in human IG-DMR for the regulation of imprinted expression. Moreover, chromatin immunoprecipitation analysis showed that TRIM28 was enriched in hypermethylated paternal hRep without ZFP57. Our results suggest that hRep contributes to the maintenance of human IG-DMR methylation imprints via the recruitment of TRIM28.
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http://dx.doi.org/10.1093/hmg/ddab071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120134PMC
May 2021

Urinary abnormality in mixed connective tissue disease predicts development of other connective tissue diseases and decrease in renal function.

Mod Rheumatol 2021 Mar 30:1-8. Epub 2021 Mar 30.

Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan.

Objective: To clarify the clinical significance of development of urinary abnormality in mixed connective tissue disease (MCTD).

Methods: Forty-one patients with an initial diagnosis of MCTD, followed at five hospitals between April 1, 2000 and December 31, 2013, were included. The relationship between urinary abnormality and various clinical parameters were retrospectively analyzed. Urinary abnormality was defined as proteinuria and/or hematuria detected by urinalysis. Development of other connective tissue diseases (CTDs) was defined as satisfaction of the criteria of each respective disease.

Results: Of 41 patients (34 females, 7 males, mean age at diagnosis 42.2 ± 15.2 years), 16 developed urinary abnormality (UrA(+) patients). The total incidences of development of other CTDs were higher in the UrA(+) patients than UrA(-) (62.5% versus 16.0%,  = .01). In the comparison between UrA(+) and UrA(-) patients, there were no significant differences in follow-up duration or last determined estimated glomerular filtration rate (eGFR), although eGFR decreased more significantly in the UrA(+) patients than UrA(-). (-20.2 ± 17.2 vs -6.1 ± 13.8 ml/min/1.73m,  = .01; -21.0 ± 18.9 vs -6.7 ± 14.1%,  = .03).

Conclusion: Urinary abnormality during the clinical course in MCTD is predictive of a higher incidence of developing other CTDs. Furthermore, it might also predict long-term renal prognosis in patients with an initial diagnosis of MCTD.
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http://dx.doi.org/10.1080/14397595.2021.1899602DOI Listing
March 2021

A Case of Epistaxis as the First Sign of Acute Idiopathic Thrombocytopenic Purpura.

Case Rep Otolaryngol 2021 6;2021:6612939. Epub 2021 Feb 6.

Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Tokyo 113-8421, Japan.

Idiopathic thrombocytopenic purpura (ITP) is an acquired thrombocytopenia caused by the action of autoantibodies against platelet antigens. It is traditionally defined by a platelet count of less than 10 × 10/L. Most patients with ITP are asymptomatic; however, symptoms have been confirmed in some cases. Conversely, it is very rare to find epistaxis as the first sign of ITP. We report the case of an 84-year-old man who came to the ear, nose, and throat department with severe and repeated epistaxis. We decided to keep him hospitalized as it was very difficult to stop the nasal bleeding. A full blood count showed a platelet level of only 1000/L. Hematologic results confirmed the diagnosis of ITP. The patient underwent treatment with intravenous gamma-globulin, platelet transfusions, and romiplostim with a favorable response.
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http://dx.doi.org/10.1155/2021/6612939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884150PMC
February 2021

Antiphospholipid antibody syndrome-associated renal thrombotic microangiopathy improved not with rivaroxaban but with warfarin in a systemic lupus erythematosus patient without lupus nephritis.

CEN Case Rep 2021 Feb 17. Epub 2021 Feb 17.

Department of Rheumatology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.

A 34-year-old Japanese woman with systemic lupus erythematosus (SLE) was admitted to our hospital for exacerbation of renal dysfunction, hemolytic anemia and thrombocytopenia. Twenty-two years before admission, she was diagnosed with SLE. Eight years before, lupus anticoagulant (LAC) positivity was detected without any thrombotic findings. Fourteen months before, renal function started to worsen. Three months before, unprovoked left leg swelling appeared. She was diagnosed with deep vein thrombosis (DVT) by ultrasonography. Blood examination revealed mild anemia, thrombocytopenia, and renal dysfunction. Rivaroxaban was started after which the left leg swelling subsided. When she was referred to our hospital, LAC was positive, but hypocomplementemia nor elevation of serum anti-double-stranded DNA antibodies was detected. Renal biopsy showed acute and chronic thrombotic microangiopathy (TMA) without concurrent lupus nephritis. Brain magnetic resonance imaging showed new small multiple cerebral infarcts. Antiphospholipid antibody syndrome (APS), causing renal TMA, new cerebral infarction, and DVT was diagnosed. Rivaroxaban was changed to warfarin. Two months after admission, renal impairment improved, and the complete disappearance of DVT and brain infarcts was confirmed. This case suggests that warfarin may be more effective than direct oral anticoagulants in the treatment of APS-associated renal TMA.
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http://dx.doi.org/10.1007/s13730-021-00581-2DOI Listing
February 2021

Interdisciplinary groups perform better than intradisciplinary groups in online group discussion activities.

Med Educ Online 2021 Dec;26(1):1886649

Division of Health Sciences, Graduate School of Pharmaceutical Science, Kanazawa University , Kanazawa, Japan.

Online classes have been provided for health-care pre-licensure learners during the novel coronavirus disease 2019 pandemic. The purpose of this study was to evaluate the utility of online group work in interprofessional education. A total of 209 students were assigned to 50 groups (18 medical student groups, 13 nursing student groups, and 19 mixed medical/nursing student groups). Learners performed group work during the orientation for the course, which was hosted using an online video conferencing system. The learners first performed the activity individually (10 min) and then engaged in a group discussion to reach consensus on their answers (30 min). We calculated the scores before and after the group discussion and shared the results with the students. Scores were improved after the group discussion (mean ± SEM, 23.7 ± 0.9) compared with before (37.3 ± 1.3) (P < .0001). Lower scores after the group discussion, which indicated the effect of the group discussion on making better decisions, were observed most in the mixed medical/nursing student groups, followed by the nursing student and medical student groups. We noted only 3 groups in which the group discussion showed a negative effect on decision-making: all 3 of these groups were mixed (3 of 19 groups; 16%). These data demonstrated the power of group discussion for solving tasks when the participants' professional fields were mixed. However, the small size of the interdisciplinary groups might have resulted in less effective discussion, which might be due in part to psychological barriers arising from professional differences. Online group work is effective for facilitating discussion and building consensus about decisions in interprofessional education for medical and nursing students. Potential psychological barriers may exist in about 16% of mixed group students at the start, which should be kept in mind by instructors. : COVID-19: coronavirus disease 2019; IPE: Interprofessional Education; NASA: National Aeronautics and Space Administration; SD: standard deviation; WHO: World Health Organization.
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http://dx.doi.org/10.1080/10872981.2021.1886649DOI Listing
December 2021

Pneumonia and central nervous system infection caused by reactivation of varicella-zoster virus in a living-donor kidney transplantation patient: case report and review of the literature.

CEN Case Rep 2021 Jan 27. Epub 2021 Jan 27.

Department of Rheumatology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.

Varicella-zoster virus (VZV) typically causes herpes zoster in the elderly due to reactivation, but immunocompromised individuals may develop organ damage such as pneumonia with a poor prognosis. We herein report a case of pneumonia and central nervous system (CNS) infection caused by reactivation of VZV in a 50-year-old man who had received a living-donor kidney transplant. We also conducted a literature review of adult cases with pneumonia or CNS infection caused by VZV after kidney transplantation. It showed that there are cases in which eruptions appeared upto 21 days after the onset of the disease and others in which eruptions did not appear at any time during the clinical course. Furthermore, there may be a wide variety of intervals from kidney transplantation to VZV infection (including both primary infection and reactivation of VZV), ranging from 2 weeks to 11 years. Therefore, it should be kept in mind that kidney transplant patients are always at high risk of VZV infection, as early recognition and treatment of the disease improves its prognosis. Although the diagnosis of varicella pneumonia is generally made by PCR test of bronchoalveolar lavage fluid, our case experience suggests that the less invasive PCR test of sputum may be useful for rapid and accurate diagnosis. The efficacy of inactivated recombinant zoster vaccine in immunocompromised individuals at high risk of reactivation of VZV also needs to be examined in the future.
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http://dx.doi.org/10.1007/s13730-021-00576-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838850PMC
January 2021

Involvement of two or more sets of lacrimal glands and/or major salivary glands is related to greater systemic disease activity due to multi-organ involvement in IgG4-related dacryoadenitis/sialadenitis.

Mod Rheumatol 2021 Feb 11:1-10. Epub 2021 Feb 11.

Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan.

Objectives: In IgG4-related dacryoadenitis and/or sialadenitis (IgG4-DS), involvement of two or more sets of lacrimal glands (LGs) and/or major salivary glands (MSGs) is regarded as a specific finding with diagnostic significance. This study aimed to clarify the influence of this factor on the overall clinical picture of IgG4-DS.

Methods: We retrospectively reviewed the medical records of 130 patients with IgG4-related disease, 97 of whom were diagnosed with IgG4-DS. We determined their clinical features according to the presence/absence of involvement of ≥2 sets of LGs and/or MSGs and compared the results with those obtained in 33 DS-limited patients.

Results: The IgG4-DS patients comprised 60 men and 37 women (median age 65 years). The median serum IgG4 level at diagnosis was 548 mg/dL. The patients with involvement of ≥2 sets ( = 44) had significantly more affected organs, lower serum C3 and C4 levels, and a tendency to have higher serum IgG levels and IgG4-RD responder index than did those without it ( = 53). In the 33 DS-limited patients, these two groups had no significant differences in clinical features.

Conclusions: Involvement of ≥2 sets of LGs and/or MSGs suggests greater systemic disease activity mainly reflected by involvement of more organs.
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http://dx.doi.org/10.1080/14397595.2021.1878623DOI Listing
February 2021

Tertiary lymphoid tissue in early-stage IgG4-related tubulointerstitial nephritis incidentally detected with a tumor lesion of the ureteropelvic junction: a case report.

BMC Nephrol 2021 01 19;22(1):34. Epub 2021 Jan 19.

Division of Rheumatology, Department of Internal Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa, Japan.

Background: IgG4-related kidney disease causes renal impairment of unknown pathogenesis that may progress to kidney failure. Although ectopic germinal centers contribute to the pathogenesis of the head and neck lesions of IgG4-related disease, the presence of tertiary lymphoid tissue (TLT) containing germinal centers in IgG4-RKD has rarely been reported.

Case Presentation: We report a 72-year-old Japanese man who had IgG4-related tubulointerstitial nephritis (TIN) with TLT formation incidentally detected in a resected kidney with mass lesion of IgG4-related ureteritis in the ureteropelvic junction. During follow-up for past surgical resection of a bladder tumor, renal dysfunction developed and a ureter mass was found in the right ureteropelvic junction, which was treated by nephroureterectomy after chemotherapy. Pathology revealed no malignancy but abundant IgG4-positive cell infiltration, obliterative phlebitis and storiform fibrosis, confirming the diagnosis of IgG4-related ureteritis. In the resected right kidney, lymphoplasmacytes infiltrated the interstitium with focal distribution in the renal subcapsule and around medium vessels without storiform fibrosis, suggesting the very early stage of IgG4-TIN. Lymphocyte aggregates were also detected at these sites and consisted of B, T, and follicular dendritic cells, indicating TLT formation. IgG4-positive cells infiltrated around TLTs.

Conclusions: Our case suggests that TLT formation is related with the development of IgG4-TIN and our analysis of distribution of TLT have possibility to elucidate IgG4-TIN pathophysiology.
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http://dx.doi.org/10.1186/s12882-021-02240-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816437PMC
January 2021

Influence of prostate cancer status on the prevalence of medication-related osteonecrosis of the jaw.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Mar 26;131(3):312-318. Epub 2020 Dec 26.

Department of Dentistry and Oral Surgery, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Japan.

Objective: The aim of this study was to evaluate the risk of osteonecrosis of the jaw (ONJ) in patients with prostate cancer, particularly the relationship between prostate cancer progression and ONJ development.

Study Design: This single-center, retrospective, observational study included 113 patients who received zoledronic acid or denosumab for prostate cancer with bone metastasis between January 2012 and March 2020. The risk of ONJ was evaluated regarding age; antiresorptive drugs; duration of antiresorptive treatment; prostate cancer status, including castration-resistant prostate cancer (CRPC) and prostate-specific antigen level; chemotherapy; radium-223 treatment; corticosteroid treatment; diabetes mellitus; and dental extractions.

Results: Overall, 28 patients had ONJ; 10 patients received zoledronic acid and 18 patients received denosumab. Multiple logistic regression analysis demonstrated that CRPC (odds ratio = 6.01; 95% confidence interval, 1.76-20.05; P = .004) and dental extractions (odds ratio = 12.40; 95% confidence interval, 3.42-44.70; P < .001) were significantly associated with ONJ. In addition, antiresorptive treatment lasting more than 1 year partially mediated between CRPC and development of ONJ.

Conclusion: CRPC and dental extraction are risk factors for developing ONJ, and antiresorptive treatment lasting more than 1 year is a partial mediator between CRPC and ONJ.
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http://dx.doi.org/10.1016/j.oooo.2020.12.018DOI Listing
March 2021

Efficacy of Osimertinib Plus Bevacizumab vs Osimertinib in Patients With EGFR T790M-Mutated Non-Small Cell Lung Cancer Previously Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor: West Japan Oncology Group 8715L Phase 2 Randomized Clinical Trial.

JAMA Oncol 2021 Mar;7(3):386-394

Internal Medicine III, Wakayama Medical University, Wakayama, Japan.

Importance: Although treatment with first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) plus antiangiogenic inhibitor has shown promising efficacies in patients with EGFR-mutated lung adenocarcinoma, recent single-arm studies have suggested that osimertinib plus antiangiogenic inhibitor might not work synergistically.

Objective: To explore the efficacy and safety of osimertinib plus bevacizumab compared with osimertinib alone in patients with lung adenocarcinoma with EGFR T790M mutation.

Design, Setting, And Participants: Patients with advanced lung adenocarcinoma that progressed with prior EGFR-TKI treatment (other than third-generation TKI) and acquired EGFR T790M mutation were enrolled. This study comprises a lead-in part with 6 patients and a subsequent phase 2 part. In phase 2, patients were randomized to osimertinib plus bevacizumab or osimertinib alone in a 1:1 ratio.

Interventions: The combination arm received oral osimertinib (80 mg, every day) plus intravenous bevacizumab (15 mg/kg, every 3 weeks) until progression or unacceptable toxic effects. The control arm received osimertinib monotherapy.

Main Outcomes And Measures: The primary end point was progression-free survival (PFS) assessed by investigators. Secondary end points consisted of overall response rate, time to treatment failure, overall survival, and safety.

Results: From August 2017 through September 2018, a total of 87 patients were registered (6 in the lead-in part and 81 in the phase 2 part [intention-to-treat population]). Among those randomized, the median (range) age was 68 (41-82) years; 33 (41%) were male; 37 (46%) had an Eastern Cooperative Oncology Group performance status of 0; and 21 (26%) had brain metastasis. Although the overall response rate was better with osimertinib plus bevacizumab than osimertinib alone (68% vs 54%), median PFS was not longer with osimertinib plus bevacizumab (9.4 months vs 13.5 months; adjusted hazard ratio, 1.44; 80% CI, 1.00 to 2.08; P = .20). Median time to treatment failure was also shorter in the combination arm vs the osimertinib arm (8.4 months vs 11.2 months; P = .12). Median overall survival was not different in the combination arm vs osimertinib arm (not reached vs 22.1 months; P = .96). In the combination arm, common adverse events of grade 3 or higher were proteinuria (n = 9; 23%), hypertension (n = 8; 20%).

Conclusions And Relevance: In this randomized clinical trial comparing osimertinib plus bevacizumab vs osimertinib alone, the combination arm failed to show prolongation of PFS in patients with advanced lung adenocarcinoma with EGFR T790M mutation.

Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000023761.
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http://dx.doi.org/10.1001/jamaoncol.2020.6758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791398PMC
March 2021

Durvalumab for patients with unresectable stage III non-small cell lung cancer and grade 1 radiation pneumonitis following concurrent chemoradiotherapy: a multicenter prospective cohort study.

Invest New Drugs 2021 Jun 6;39(3):853-859. Epub 2021 Jan 6.

Internal Medicine III, Wakayama Medical University, 811-1, Kimiidera, Wakayama, Wakayama, Japan.

Introduction/Background Durvalumab demonstrated a good efficacy and safety in patients with unresectable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT) in the PACIFIC trial. Although a history of radiation pneumonitis (RP) has been reported to increase the risk of pneumonitis associated with programmed death-1 inhibitors, the safety and efficacy of durvalumab in patients with baseline Grade 1 RP have not been assessed. Therefore, we carried out a multicenter prospective cohort study to evaluate the efficacy and safety of durvalumab in these patients. Patients and Methods This was a multicenter prospective cohort study of 35 patients with Grade 1 RP after CCRT and before durvalumab initiation. This study was a first prespecified analysis for the first 20 patients with the primary objective of assessing the short-term safety; it was assessed 3 months after durvalumab initiation. Results Twenty patients were enrolled in this study between March 1, 2019, and September 3, 2019. Three patients (15%) experienced drug-related Grade ≥3 adverse events, while three patients (15%) had Grade ≥2 pneumonitis/RP within 3 months after durvalumab initiation. Three months after durvalumab initiation, all the patients were alive and four patients (20%) experienced disease progression. Conclusion Durvalumab can be a feasible treatment option for patients with stage III NSCLC with baseline Grade 1 RP following CCRT.(Trial registration number: UMIN000036061. The registration period was between March 2019 and December 2019.).
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http://dx.doi.org/10.1007/s10637-020-01060-8DOI Listing
June 2021

Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific?

BMC Nephrol 2021 01 4;22(1). Epub 2021 Jan 4.

Division of Rheumatology, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan.

Background: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients.

Methods: Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed.

Results: Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6-53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected.

Conclusions: Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.
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http://dx.doi.org/10.1186/s12882-020-02169-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784305PMC
January 2021

Long-term follow-up comparing salvage radiation therapy and androgen-deprivation therapy for biochemical recurrence after radical prostatectomy.

Int J Clin Oncol 2021 Apr 2;26(4):744-752. Epub 2021 Jan 2.

Department of Urology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo, 160-8582, Japan.

Background: The salvage treatments for biochemical recurrence (BCR) include local external beam radiation therapy (RT) and systemic androgen-deprivation therapy (ADT).

Methods: We reviewed patients who underwent radical prostatectomy (RP) and developed BCR at three institutions. After excluding patients whose nadir prostate-specific antigen (PSA) was higher than 0.2 ng/mL, those who received neoadjuvant/adjuvant therapy, and those whose BCR was not treated until their PSA exceeded 4.0 ng/mL, the remaining 335 patients comprised the cohort of this study. Salvage RT and ADT were performed for 154 and 181 patients, respectively. After the failure of salvage RT, all patients received subsequent ADT. The starting point of this study was the timing of BCR and the endpoint was the development of castration-resistant prostate cancer (CRPC).

Results: During the mean follow-up period of 8.5 years after BCR, CRPC was observed in 13 patients administered RT and 24 patients administered ADT. Kaplan-Meier curves demonstrated no significant difference in CRPC-free survival between the RT and ADT groups (10-year CRPC-free survival 89.9 vs. 86.3%, p = 0.199). On the other hand, we found a significant difference in CRPC-free survival between the RT and ADT groups in 50 high-risk patients with two risk factors of Grade Group ≥ 4 and PSA-doubling time  < 6 months (10-year CRPC-free survival 73.4 vs. 40.3%, p = 0.040).

Conclusion: This study revealed that salvage RT increases the CRPC-free survival rate compared with salvage ADT in high-risk patients with Grade Group ≥ 4 and PSA-doubling time < 6 months.
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http://dx.doi.org/10.1007/s10147-020-01839-yDOI Listing
April 2021

Positive disease-specific autoantibodies have limited clinical significance in diagnosing IgG4-related disease in daily clinical practice.

Rheumatology (Oxford) 2020 Dec 12. Epub 2020 Dec 12.

Department of Rheumatology, Kanazawa University Hospital, Kanazawa, Japan.

Objectives: The 2019 ACR/EULAR classification criteria for IgG4-related disease (IgG4-RD) have exclusion criteria including positive disease-specific autoantibodies, and these have been documented to have a high specificity. This study aimed to further validate these criteria as well as identify characteristics of patients showing false-negative results.

Methods: We retrospectively analysed 162 IgG4-RD patients and 130 mimickers. The sensitivity, specificity and fulfilment rates for each criterion were calculated, and intergroup comparisons were performed to characterize the false-negative cases.

Results: Both the IgG4-RD patients and mimickers were aged ≥65 years with male predominance. The final diagnoses of mimickers were mainly malignancy, vasculitis, sarcoidosis and aneurysm. The classification criteria had a sensitivity of 72.8% and specificity of 100%. Of the 44 false-negative cases, one did not fulfil the entry criteria, 20 fulfilled one exclusion criterion and 27 did not achieve sufficient inclusion criteria scores. The false-negative cases had fewer affected organs, lower serum IgG4 levels, and were less likely to have received biopsies than the true-positive cases. Notably, positive disease-specific autoantibodies were the most common exclusion criterion fulfilled in 18 patients, only two of whom were diagnosed with a specific autoimmune disease complicated by IgG4-RD. In addition, compared with the true-positive cases, the 18 had comparable serum IgG4 levels, number of affected organs, and histopathology and immunostaining scores despite higher serum IgG and CRP levels.

Conclusions: The ACR/EULAR classification criteria for IgG4-RD have an excellent diagnostic specificity in daily clinical practice. Positive disease-specific autoantibodies may have limited clinical significance for the diagnosis of IgG4-RD.
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http://dx.doi.org/10.1093/rheumatology/keaa783DOI Listing
December 2020

Osimertinib is associated with reversible and dose-independent cancer therapy-related cardiac dysfunction.

Lung Cancer 2021 03 16;153:186-192. Epub 2020 Nov 16.

Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.

Introduction: The use of osimertinib is associated with the risk of cancer therapy-related cardiac dysfunction (CTRCD) for EGFR-mutated non-small cell lung cancer (NSCLC) patients. In this study, we aimed to clarify the clinical features of patients with CTRCD associated with osimertinib.

Methods: A total of 183 cases of advanced EGFR-mutated NSCLC who received osimertinib monotherapy from January 2014 to December 2019 were evaluated. Longitudinal changes in LVEF were evaluated in 58 patients by serial echocardiography before and after osimertinib administration.

Results: Of 58 patients, 16 patients (8.7%) had decreased LVEF of 10 units or more and 8 patients (4.4%) met the CTRCD criteria. Overall, LVEF significantly decreased after osimertinib treatment from a mean value of 69% (range, 52-82%) at baseline to 66% (26-75%) (p < 0.001). During osimertinib treatment, LVEF remained low but did not decline any further. Discontinuation, dose reduction, or switching to another EGFR tyrosine kinase inhibitors resulted in recovery in 6 out of 8 CTRCD patients. Multivariate analysis showed that history of heart disease was a significant predictor of CTRCD (ORR, 4.97; 95% confidence interval [CI], 1.26-19.6; P = 0.022).

Conclusions: Osimertinib was associated with the risk of CTRCD, which is dose-independent and reversible with drug withdrawal.
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http://dx.doi.org/10.1016/j.lungcan.2020.10.021DOI Listing
March 2021

Hand-assisted laparoscopic ileal ureter substitution for ureteral obstruction after right ureteral rupture: A case report.

Urol Case Rep 2020 Nov 24;33:101326. Epub 2020 Jun 24.

Department of Urology, Kawasaki Municipal Hospital, 12-1 Shinkawadori, Kawasaki-ku, Kawasaki-city, Kanagawa, 210-0013, Japan.

Iatrogenic ureteral rupture is a serious complication. In the past, ileal ureter substitution was performed with open, laparoscopic, and robot-assisted procedure; however, there are problems with operation invasiveness and difficulty. We present a 72-year-old female whose ureter was completely injured at the ureteropelvic junction and torn longitudinally in full length at the time of transurethral lithotripsy. Although initially she had nephrostomy, we were able to internalize with hand-assisted laparoscopic ileal ureter substitution for obstruction over the full length of the ureter.
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http://dx.doi.org/10.1016/j.eucr.2020.101326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573837PMC
November 2020

Synthesis of computer simulation and machine learning for achieving the best material properties of filled rubber.

Sci Rep 2020 10 22;10(1):18127. Epub 2020 Oct 22.

Research and Advanced Development Division, The Yokohama Rubber Co., Ltd., 2-1 Oiwake, Hiratsuka,, Kanagawa,, 254-8601, Japan.

Molecular dynamics (MD) simulation is used to analyze the mechanical properties of polymerized and nanoscale filled rubber. Unfortunately, the computation time for a simulation can require several months' computing power, because the interactions of thousands of filler particles must be calculated. To alleviate this problem, we introduce a surrogate convolutional neural network model to achieve faster and more accurate predictions. The major difficulty when employing machine-learning-based surrogate models is the shortage of training data, contributing to the huge simulation costs. To derive a highly accurate surrogate model using only a small amount of training data, we increase the number of training instances by dividing the large-scale simulation results into 3D images of middle-scale filler morphologies and corresponding regional stresses. The images include fringe regions to reflect the influence of the filler constituents outside the core regions. The resultant surrogate model provides higher prediction accuracy than that trained only by images of the entire region. Afterwards, we extract the fillers that dominate the mechanical properties using the surrogate model and we confirm their validity using MD.
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http://dx.doi.org/10.1038/s41598-020-75038-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581745PMC
October 2020