Publications by authors named "Hiroaki Inoue"

95 Publications

Decreased expression of T-cell-associated immune markers predicts poor prognosis in patients with follicular lymphoma.

Cancer Sci 2021 Nov 27. Epub 2021 Nov 27.

Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osaka-sayama, Japan.

We previously examined the utility of rituximab-bendamustine (RB) in patients with follicular lymphoma (FL) exhibiting less than optimal responses to 2 cycles of the R-CHOP chemotherapy regimen. The aim of this study was to identify molecular biomarkers that can predict prognosis in RB-treated patients in the context of the prospective cohort. We first analyzed the mutational status of 410 genes in diagnostic tumor specimens by target capture and Sanger sequencing. CREBBP, KMT2D, MEF2B, BCL2, EZH2, and CARD11 were recurrently mutated as reported before, however none was predictive for progression-free survival (PFS) in the RB-treated patients (n = 34). A gene expression analysis by nCounter including 800 genes associated with carcinogenesis and/or the immune response showed that expression levels of CD8 T-cell markers and half of the genes regulating Th1 and Th2 responses were significantly lower in progression of disease within the 24-mo (POD24) group (n = 8) than in the no POD24 group (n = 31). Collectively, we selected 10 genes (TBX21, CXCR3, CCR4, CD8A, CD8B, GZMM, FLT3LG, CD3E, EOMES, GZMK), and generated an immune infiltration score (IIS) for predicting PFS using principal component analysis, which dichotomized the RB-treated patients into immune IIS (n = 19) and IIS (n = 20) groups. The 3-y PFS rate was significantly lower in the IIS group than in the IIS group (50.0% [95% CI: 27.1-69.2%] vs. 84.2% [95% CI: 58.7-94.6%], P = .0237). Furthermore, the IIS was correlates with absolute lymphocyte counts at diagnosis (r = 0.460, P = .00355). These results suggest that the T-cell-associated immune markers could be useful to predict prognosis in RB-treated FL patients. (UMIN:000 013 795, jRCT:051 180 181).
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http://dx.doi.org/10.1111/cas.15224DOI Listing
November 2021

Tibial Condyle Valgus Osteotomy for Ipsilateral Knee Osteoarthritis after Hip Arthrodesis.

Case Rep Orthop 2021 29;2021:6443618. Epub 2021 Oct 29.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajiicho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, Kyoto 602-8566, Japan.

We report a case of tibial condylar valgus osteotomy (TCVO) for ipsilateral knee osteoarthritis (OA) after hip arthrodesis. A 58-year-old woman developed right purulent hip arthritis at one month of age and underwent right hip fusion at 16 years old. She visited our department at the age of 57 because her right knee joint pain worsened. The range of motion for her right knee was 80° and -5° of flexion and extension, respectively, and she experienced medial weight-bearing pain. A plain X-ray image showed that the right knee joint had end-stage knee OA with a bone defect inside the tibia, and the tibial plateau shape was the pagoda type. There was a marked instability in her right knee with a valgus of 9° and varus of 7° on stress photography. She underwent TCVO on her right knee and was allowed full load four weeks after surgery. Computed tomography imaging showed bone union nine months after surgery. Two years after the operation, there was no correction loss, and she could walk independently without pain. In general, total knee arthroplasty (TKA) is indicated for end-stage knee OA; however, there are problems, such as early loosening due to the increased mechanical load on the knee after hip OA. In this case, since a good course was obtained, TCVO is considered a treatment option for terminal knee OA after hip arthrodesis.
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http://dx.doi.org/10.1155/2021/6443618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570898PMC
October 2021

Treadmill running prevents atrophy differently in fast- versus slow-twitch muscles in a rat model of rheumatoid arthritis.

J Muscle Res Cell Motil 2021 12 23;42(3-4):429-441. Epub 2021 Oct 23.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.

To investigate the effects of treadmill running on two different types of skeletal muscle, we established a rat model of collagen-induced arthritis (CIA). The skeletal muscles studied were the extensor digitorum longus (EDL), which is rich in fast-twitch muscle fibers, and the soleus, which is rich in slow-twitch muscle fibers. The histological and transcriptional changes in these muscles at 14 and 44 days after immunosensitization were compared between rats that were forced to exercise (CIA ex group) and free-reared CIA rats (CIA no group). Change in protein expression was examined on day 14 after a single bout of treadmill running. Treadmill running had different effects on the relative muscle weight and total and fiber cross-sectional areas in each muscle type. In the soleus, it prevented muscle atrophy. Transcriptional analysis revealed increased eukaryotic translation initiation factor 4E (Eif4e) expression on day 14 and increased Atrogin-1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression on day 44 in the soleus in the CIA ex group, suggesting an interaction between muscle type and exercise. A single bout of treadmill running increased the level of Eif4e and p70S6K and decreased that of Atrogin-1 in the soleus on day 14. Treadmill running prevented muscle atrophy in the soleus in a rat model of rheumatoid arthritis via activation of mitochondrial function, as evidenced by increased PGC-1α expression.
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http://dx.doi.org/10.1007/s10974-021-09610-0DOI Listing
December 2021

Onset of Stevens-Johnson syndrome and toxic epidermal necrolysis overlap due to tirabrutinib.

J Dermatol 2021 Nov 4;48(11):e536-e537. Epub 2021 Aug 4.

Department of Dermatology, Kishiwada City Hospital, Kishiwada, Japan.

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http://dx.doi.org/10.1111/1346-8138.16093DOI Listing
November 2021

Mechanical stimulation of chondrocytes regulates HIF-1α under hypoxic conditions.

Tissue Cell 2021 Aug 19;71:101574. Epub 2021 Jun 19.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Electronic address:

We investigated the effects of hypoxia-inducible factor (HIF)-1α on articular cartilage under mechanical stimulation and the associated mechanisms. Chondrocytes, isolated from articular cartilage from the knee, hip, and shoulder joints of Wistar rats, were subjected to 20 % tensile stress under hypoxic (5% O) conditions for 24 h. HIF-1α and aggrecan expression was significantly enhanced with mechanical stimulation under hypoxia but not significantly altered with mechanical stimulation under normoxia. The nuclear translocation of HIF-1α was enhanced by mechanical stress under hypoxia. Under both normoxia and hypoxia, a disintegrin and metalloproteinase with thrombospondin motifs (ADAM-TS) 5 expression was significantly reduced with mechanical stimulation compared to that in the group without mechanical stimulation. However, HIF-1α knockdown mitigated changes in aggrecan and ADAM-TS5 expression mediated by mechanical stimulation under hypoxia. The effects of treadmill running on HIF-1α production in the articular cartilage of rat knee joints were also analyzed. HIF-1α production increased in the moderate running group and decreased to the same levels as those in the control group in the excessive running group. This suggests that HIF-1α regulates aggrecan and ADAM-TS5 expression in response to mechanical stimulation under hypoxia and general mechanical stimulation in articular cartilage under hypoxia, while controlling cartilage homeostasis.
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http://dx.doi.org/10.1016/j.tice.2021.101574DOI Listing
August 2021

Sustained Hypoxia Suppresses Joint Destruction in a Rat Model of Rheumatoid Arthritis via Negative Feedback of Hypoxia Inducible Factor-1α.

Int J Mol Sci 2021 Apr 9;22(8). Epub 2021 Apr 9.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

Hypoxia inducible factor (HIF)-1α has been implicated in the pathogenesis of rheumatoid arthritis (RA). HIF-1α, which is expressed in hypoxia, is reversely suppressed in sustained hypoxia. Here, we investigated the inhibitory effect of hypoxia on arthritis by controlling HIF-1α. Rheumatoid fibroblast-like synoviocyte MH7A cells were cultured in a hypoxic incubator for up to 72 h to evaluate the expression of HIF-1. Furthermore, collagen-induced arthritis (CIA) model rats were maintained under 12% hypoxia in a hypoxic chamber for 28 days to evaluate the effect on arthritis. In MH7A cells, HIF-1α protein level increased at 3 h, peaked at 6 h, and subsequently decreased in a time-dependent manner. The transcription of pro-inflammatory cytokines increased at 1 h; however, they decreased after 3 h ( < 0.05). Deferoxamine-mediated activation of HIF-1α abolished the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines. In the rat CIA model, the onset of joint swelling was delayed and arthritis was suppressed in the hypoxia group compared with the normoxia group ( < 0.05). Histologically, joint destruction was suppressed primarily in the cartilage. Thus, sustained hypoxia may represent a new safe, and potent therapeutic approach for high-risk patients with RA by suppressing HIF-1α expression.
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http://dx.doi.org/10.3390/ijms22083898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068944PMC
April 2021

Low absolute lymphocyte count is a poor prognostic factor for untreated advanced follicular lymphoma treated with rituximab plus bendamustine: results of the prospective phase 2 CONVERT trial.

Int J Hematol 2021 Aug 17;114(2):205-216. Epub 2021 Apr 17.

Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, 377-2, Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.

The aim of this trial is to evaluate the utility of rituximab-bendamustine (R-B) for untreated advanced follicular lymphoma (FL) showing non-optimal response (nOR) to R-CHOP, and to identify clinical prognostic factors for FL patients receiving R-B. Patients who failed to achieve complete response/complete response unconfirmed (CR/CRu) [nOR-group] after 2 cycles of R-CHOP subsequently received 6 cycles of R-B. The primary endpoint was the 3-year progression-free survival (PFS) rate. Secondary endpoints included determination of prognostic factors. Fifty-six patients initially received R-CHOP, 43/56 patients (76.8%) were judged as nOR, and 33/43 patients (76.7%) completed 6 cycles of R-B. At a median follow-up of 50.6 months in the nOR-group, the 3-year PFS rate was 69.0%, and the 3-year overall survival (OS) rate was 92.7%. The most common toxicities associated with R-B were grade 3-4 lymphopenia (93.0%) and neutropenia (74.4%), both of which were manageable. A multivariate analysis including dose intensity, serum soluble interleukin-2 receptor, and FL international prognostic index-2 revealed low absolute lymphocyte count (<  869/μL) at diagnosis was an independent poor prognostic factor for both PFS and OS in the R-B-treated nOR-group. This result was further confirmed in validation cohorts including R-B-treated de novo (n = 40) and relapsed (n = 49) FL patients.
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http://dx.doi.org/10.1007/s12185-021-03148-0DOI Listing
August 2021

Adjustable-Loop Devices Promote Graft Revascularization in the Femoral Tunnel After ACL Reconstruction: Comparison With Fixed-Loop Devices Using Magnetic Resonance Angiography.

Orthop J Sports Med 2021 Feb 26;9(2):2325967121992134. Epub 2021 Feb 26.

Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: Hamstring tendon grafts are usually fixed in anterior cruciate ligament (ACL) reconstruction using either an adjustable-loop device (ALD) or a fixed-loop device (FLD). The contact area between the graft and the tunnel wall is different between the 2 devices.

Purpose: To determine using magnetic resonance angiography (MRA) whether ALD and FLD result in different blood flow of the graft in the femoral tunnel during the early postoperative period.

Study Design: Cohort study; Level of evidence, 3.

Methods: Between 2008 and 2018, a total of 42 patients (17 men and 25 women) underwent MRA at 3 months after ACL reconstruction. All surgical procedures were performed using semitendinosus tendon autografts folded into 4 strands. Overall, 23 patients underwent the FLD procedure and 19 patients underwent the ALD procedure. The signal intensity of the superior portion of the graft in the femoral tunnel was evaluated using transverse MRA images perpendicular to the femoral tunnel axis.

Results: MRA images showed high signal intensity in the superior portion of the graft in the femoral tunnel in 94.7% and 60.9% of the ALD patients and FLD patients, respectively, a statistically significant difference ( = .03).

Conclusion: MRA images at 3 months after surgery revealed that blood flow reached the superior end of the tendon graft in the femoral tunnel in more patients who underwent ACL reconstruction with an ALD compared with an FLD.
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http://dx.doi.org/10.1177/2325967121992134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934042PMC
February 2021

Therapeutic significance of D3 dissection for low rectal cancer: a comparison of dissections between the lateral pelvic lymph nodes and the lymph nodes along the root of the inferior mesenteric artery in a multicenter retrospective cohort study.

Int J Colorectal Dis 2021 Jun 3;36(6):1263-1270. Epub 2021 Feb 3.

Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: D3 dissection is the standard treatment modality for locally advanced low rectal cancer in Japan. The benefit of lateral pelvic lymph node (LPLN) dissection (LPLND) and lymph nodes along the root of inferior mesenteric artery (253 LN) dissection (253 LND) for low rectal cancer has often been studied separately, and few studies have investigated their benefit in the same cohort. This study aimed to clarify the therapeutic significance of dissection of the LPLN in comparison to that of dissection of the 253 LN for low rectal cancer.

Methods: We retrospectively evaluated 3508 patients with treatment-naïve stage I-III low rectal cancer who underwent mesorectal excision between 1997 and 2012. They were identified from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database. The rates of metastasis, survival, and therapeutic value index (5-year overall survival (OS) rate multiplied by metastatic rate for lymph node metastasis) were compared between LPLN and 253 LN.

Results: The rates of LPLN metastasis and 253 LN metastasis were 17.9% and 1.5%, respectively. The 5-year OS was significantly different between patients with and without LPLN metastasis (55.0% vs 85.5%, P < 0.0001) and between patients with and without 253 LN metastasis (36.2% vs 83.3%, P < 0.0001). The therapeutic value indexes of LPLN and 253 LN were 9.85 and 0.54, respectively.

Conclusions: LPLND may have more therapeutic value than 253 LND for patients with treatment-naïve low rectal cancer, although both the patients with LPLN metastasis and those with 253 LN metastasis remained to have poor prognosis.
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http://dx.doi.org/10.1007/s00384-021-03858-1DOI Listing
June 2021

[Ⅲ.N-1 Study].

Gan To Kagaku Ryoho 2020 Dec;47(12):1681-1686

Dept. of Thoracic, Endocrine Surgery and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School.

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December 2020

Radiologic results of additional single screw fixation with lateral locking plate after hybrid closed-wedge high tibial osteotomy.

Knee Surg Relat Res 2020 Dec 14;32(1):65. Epub 2020 Dec 14.

Department of Sports and Para-Sports Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Background: Hybrid closed-wedge high tibial osteotomy (hybrid CWHTO) is an effective surgical treatment for medial compartment osteoarthritis of the knee. Our study investigated whether the combination of a lateral locking plate and a single medial screw promoted bone union after hybrid CWHTO.

Methods: The study cohort consisted of 30 patients (15 men and 15 women) who underwent hybrid CWHTO for medial compartment osteoarthritis or spontaneous osteonecrosis of the knee. Sixteen knees were fixed with a lateral locking plate (LP group), and 17 were fixed with both a lateral locking plate and a cannulated cancellous screw on the medial side of the tibia (LPS group). The times to bone union, radiolucency, and callus formation at the osteotomy site were evaluated radiographically.

Results: The mean postoperative time to radiographic confirmation of bone union was 5.5 ± 2.6 months in the LP group and 3.4 ± 1.5 months in the LPS group. Radiolucency at the osteotomy site and excess callus formation on the posterior side of the tibia were lower in the LPS group than in the LP group.

Conclusions: This modified hybrid CWHTO combining a lateral locking plate and a cannulated cancellous screw on the medial side of the tibia improves the stability of the osteotomy site and shortens the period of bone union.
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http://dx.doi.org/10.1186/s43019-020-00085-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734755PMC
December 2020

Arthroscopic Fixation Technique for Avulsion Fracture of the Posterior Cruciate Ligament From the Tibia.

Arthrosc Tech 2020 Nov 23;9(11):e1819-e1824. Epub 2020 Oct 23.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

This study describes an arthroscopic pullout fixation technique for small and comminuted avulsion fractures of the posterior cruciate ligament from the tibia. Intra-articular surgery required 3 arthroscopic portals, the anterolateral, anteromedial, and posteromedial portals. To simplify surgery, the posterolateral portal was omitted. A 2.4-mm K-wire was inserted through the anterior incision to the center of the bone fragment. This central guidewire was subsequently overdrilled with a 4.0-mm cannulated drill. The fixation material consisted of Pass Telos artificial ligaments inserted through the fiber loop of a fixed suspensory device such as RIGIDLOOP. The leading end of the thread of the RIGIDLOOP was pulled out through the anteromedial portal. The button of RIGIDLOOP was gradually advanced through the bone tunnel. The button was pulled out and flipped over the bony fragment. The artificial ligament was pulled distally to reduce the bony fragment, and fixed onto the tibia using a ligament button while applying anterior drawer force to the proximal tibia with the knee flexed at 90°. This minimally invasive procedure was successful in treating small and comminuted avulsion fracture of the tibial attachment of the posterior cruciate ligament.
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http://dx.doi.org/10.1016/j.eats.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695752PMC
November 2020

Relationship of alignment in the lower extremity with early degeneration of articular cartilage after resection of the medial meniscus: Quantitative analysis using T2 mapping.

Medicine (Baltimore) 2020 Oct;99(44):e22984

Department of Rehabilitation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan,.

The objective of this study was to examine the relationship between cartilage degeneration early after partial medial meniscectomy and abnormal alignment in the lower extremity.The subjects were 34 patients (37 knees) with medial meniscal tear who underwent arthroscopic partial meniscectomy. MRI was performed before and 6 months after surgery. T2 mapping images in sagittal sections of medial femoral condyle were produced and 10 regions of interest were set at intervals of 10° in the articular cartilage in the femur. Subjects with an increase in T2 of ≥6% at a flexion angle of 30° were assigned to the degeneration group. Patient background, hip-knee-ankle (HKA) angle, and total resection of meniscal segments were compared between this group and the other patients to identify factors involved in degeneration of articular cartilage.T2 values 6 months after surgery in 3 ROIs at flexion angles of 30° to 50° were significantly longer than those before surgery. The preoperative HKA angle was significantly higher in the degeneration group. T2 values in articular cartilage of the femoral condyle increased earlier after meniscectomy with abnormal alignment in the lower extremity.Meniscectomy in cases with abnormal alignment may have a risk of early onset of osteoarthritis.Level of evidence: Level IV.
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http://dx.doi.org/10.1097/MD.0000000000022984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598867PMC
October 2020

Outcomes of arthroscopic repair using the all-inside inter-leaf vertical suture technique for horizontal meniscal tears sustained in sports.

Medicine (Baltimore) 2020 Oct;99(41):e22609

Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.

The aim of the study was to evaluate the outcomes of arthroscopic repair using the all-inside inter-leaf vertical suture arthroscopic technique for sports-related horizontal meniscal tears.The inter-leaf vertical suture procedure was performed to repair sports-related horizontal tears in the middle and posterior segments of the medial (11 cases) and lateral (2 cases) menisci in 13 patients (mean age: 30 ± 14 years). Pre- and post-operative Barrett criteria, Lysholm scores, and patient ability to resume sports were assessed. Magnetic resonance imaging (MRI) grades and signal intensity changes near the joint capsule were evaluated in the 9 cases among which pre- and post-operative MRI images were available.All Barrett criteria items were negative following surgery; Lysholm scores increased from 70.2 ± 13.1 before surgery to 98.9 ± 2.64 after surgery (P < .01). All patients were able to resume their sport. Preoperative MRI grade of tears was 3 for all patients; postoperative MRI grades were 1 in 3 cases, 2 in 4 cases, and 3 in 2 cases (P < .05). Importantly, MRI signal intensity at the repaired menisci near the joint capsule was reduced in 8 of these 9 cases postoperatively.The inter-leaf vertical suture procedure is associated with good outcomes for horizontal tears in the middle and posterior segments of the medial and lateral menisci. The procedure is useful and convenient.
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http://dx.doi.org/10.1097/MD.0000000000022609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544389PMC
October 2020

Revascularization to the bone tunnel wall after anterior cruciate ligament reconstruction may relate to the distance from the vessels.

Knee Surg Relat Res 2020 Oct 6;32(1):53. Epub 2020 Oct 6.

Department of Rehabilitation Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajiicho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, Kyoto, 602-8566, Japan.

Purpose: We use magnetic resonance angiography to evaluate the difference of vascular ingrowth to the bone tunnel on the anterior and posterior walls quantitatively after anterior cruciate ligament reconstruction.

Materials And Methods: One hundred patients underwent anterior cruciate ligament reconstruction with multi-stranded semitendinosus tendons. They were retrospectively divided into those who underwent magnetic resonance angiography 2, 3, 4 to 6, and ≥ 7 months after surgery. The mean signal-to-noise ratios of the bone tunnel walls in the femur and tibia from the digital data were measured and compared for the anterior and posterior walls.

Results: The signal-to-noise ratio of the posterior wall of the femoral bone tunnel was significantly higher than that of the anterior wall in each group. On the tibial side, the signal-to-noise ratio of the anterior wall was significantly higher than that of the posterior wall at ≥4 months after surgery.

Conclusions: This study showed that the blood flow after anterior cruciate ligament reconstruction to the femoral bone tunnel is maintained from the posterior wall, and is maintained to the tibial side from the anterior wall 4 months postoperatively. Revascularization to the bone tunnel wall after anterior cruciate ligament reconstruction may relate to the distance from the vessels.
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http://dx.doi.org/10.1186/s43019-020-00070-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541268PMC
October 2020

Evaluation of Legiolert for Quantification of Legionella pneumophila from Bath Water Samples.

Biocontrol Sci 2020 ;25(3):179-182

Tsukuba Research Laboratories, Aquas Corporation.

Testing for Legionella spp. in public bath water samples is regulated in Japan. In this study, we used a total of 132 public bath water samples to compare the performance of Legiolert® and the conventional plate culture method for the enumeration of Legionella pneumophila. When Legiolert and plate culturing were performed at the same detection limit, L. pneumophila was detected in 26.5% of 132 samples by Legiolert, while 12.9% contained Legionella spp. (11.4% contained L. pneumophila) based on the plate culture method. Moreover, results of 83.3% of the total samples were consistent between the two methods, meaning that they were both positive or both negative. In this study, we demonstrated that Legiolert is a simpler and more effective method of monitoring for L. pneumophila in bath water samples.
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http://dx.doi.org/10.4265/bio.25.179DOI Listing
June 2021

Interpreting the Results of the Conventional Plate Culture and Gene Detection Methods for Legionella Detection in Environmental Water Samples.

Authors:
Hiroaki Inoue

Biocontrol Sci 2020 ;25(3):121-129

Tsukuba Research Laboratories, Aquas Corporation.

The conventional plate culture method is widely used as a method for detection of Legionella in environmental water samples, but to obtain results takes more than a week. Because it is much quicker, the gene detection method has become widespread as an alternative detection method. However, the results of gene detection and plate culture methods may differ even when the same sample is examined; the gene detection method shows a higher detection ratio than the plate culture method. The reason for this difference is that the plate culture method detects Legionella cells that have the ability to form colonies on an agar plate, whereas the gene detection method detects any Legionella genes present regardless of the state of the Legionella. In this paper, we consider the factors that cause differences between the results of the plate culture and gene detection methods, and how to interpret the results of each.
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http://dx.doi.org/10.4265/bio.25.121DOI Listing
June 2021

Clinical outcomes after medial patellofemoral ligament reconstruction: an analysis of changes in the patellofemoral joint alignment.

Int Orthop 2021 05 7;45(5):1215-1222. Epub 2020 Aug 7.

Department of Rehabilitation Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Purpose: Medial patellofemoral ligament (MPFL) reconstruction using the hamstring tendon is widely performed to treat recurrent patellar dislocation. MPFL reconstruction includes a post-operative process of necrosis and reperfusion of the hamstring tendon graft. We hypothesise that the patella gradually shifts laterally because of this process, ultimately affecting the patellofemoral joint alignment. This study aimed to analyse the chronological changes in the patellofemoral joint alignment and the outcomes of MPFL reconstruction.

Methods: In this retrospective case-series study, the Knee Society, Lysholm, and Kujala scores were evaluated in 24 consecutive patients (27 knees). To evaluate patellar tracking defects, radiographic indices including the tilting angle, the lateral shift ratio, and the congruence angle were measured before, immediately after, and three, 12, and 36 months after MPFL reconstruction.

Results: Post-operative Kujala, Knee Society, and Lysholm scores for the study population significantly improved relative to the pre-operative scores. The tilting and congruence angles at three months after the operation significantly increased relative to those recorded immediately after the operation. The tilting and congruence angles were not significantly different at three, 12, and 36 months after the operation.

Conclusions: The post-operative outcomes of MPFL reconstruction for recurrent patellar dislocation were favourable. Insufficient union between the bone tunnel and tendon graft, along with an elongation of the necrotic tendon graft, may change the alignment of the patellofemoral joint within three months after the operation. Therefore, we believe it is necessary to refrain from knee rotation that places lateral stress on the patella until three months after the operation.
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http://dx.doi.org/10.1007/s00264-020-04765-wDOI Listing
May 2021

Effect of adjuvant chemotherapy in patients with ER + /HER2- breast cancer, assessed by propensity score matching: significance of nuclear grade and nodal status.

Breast Cancer 2021 Jan 26;28(1):40-47. Epub 2020 Jun 26.

Department of Breast Surgery, Tokyo Women's Medical University Medical Center East, 2-1-10 Nishi-ogu, Arakawa-ku, Tokyo, 116-8567, Japan.

Background: Survival benefits of chemotherapy (CT) differ among patients with estrogen receptor-positive (ER +) breast cancer. This study investigated the survival benefits of CT for ER + and human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) patients by propensity score matching (PSM).

Methods: Patients with stages I-IIIER + /HER2- BC were enrolled in this study. The primary endpoints were 5-year recurrence-free survival (RFS) and overall survival (OS) in the non-CT and CT groups of the selected population matched by PS. The PS was analyzed by a logistic regression model with factors those influence provided indication of chemotherapy [tumor size, nuclear grade (NG), progesterone receptor, and nodal status].

Results: This study enrolled 895 patients between 2000 and 2015. The median follow-up period was 5.7 years. Overall, the 5-year RFS was 94.3% and 90.1% in the non-CT and CT-treated groups, respectively (p = 0.106). The 5-year OS was 97.5% in the non-CT group and 95.6% in the CT group (p = 0.047). Using PSM, 236 patients were selected. After matching, both the 5-year RFS and the 5-year OS were higher in the CT group than in the non-CT group (96.8% vs. 82.7%, p = 0.003 and 100% vs. 91.9%, p < 0.001, respectively). Particularly in the case of the node negative/NG3 and 1-3 node positive/NG2 patients after PSM, the 5-year RFS was significantly higher in the CT group than in the non-CT group (p = 0.041 and p = 0.006, respectively).

Conclusion: After PSM, CT significantly improved both the RFS and OS of ER + / HER2- BC patients, especially for node negative/NG3 and 1-3 node positive/NG2 patients.
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http://dx.doi.org/10.1007/s12282-020-01125-9DOI Listing
January 2021

Tumour-immune microenvironment in duodenal-type follicular lymphoma.

Br J Haematol 2020 10 8;191(2):243-252. Epub 2020 May 8.

Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University Hospital, Osakasayama, Japan.

Despite duodenal-type follicular lymphoma (DTFL) being morphologically, immunophenotypically and genetically indistinguishable from nodal FL (nFL), this entity typically shows a significantly better prognosis. Here, we analysed the tumour immune microenvironments of diagnostic specimens from patients with DTFL (n = 30), limited-stage FL (LSFL; n = 19) and advanced-stage FL (ASFL; n = 31). The mean number of CD8 tumour-infiltrating lymphocytes (TILs) in the neoplastic follicles was higher in DTFL (1,827/mm ) than in LSFL (1,150/mm ) and ASFL (1,188/mm ) (P = 0·002, P = 0·002, respectively). In addition, CD8 PD1  T cells with non-exhausting phenotype were more abundant in the peripheral blood (PB) of DTFL than in LSFL and ASFL, indicating that DTFL may exhibit a better and longer-lasting T cell-mediated immune response. Moreover, whereas FOXP3 CTLA-4 effector regulatory T cells (eTregs) were rarely observed in the neoplastic follicles of DTFL (mean: 12/mm ), they were more abundant in LSFL (78/mm ) and ASFL (109/mm ) (P = 2·80 × 10 , P = 4·74 × 10 , respectively), and the numbers of eTregs correlated inversely with those of CD8 TILs (r = -0267; P = 0·018). Furthermore, DTFL showed significantly fewer circulating FOXP3 CD45RA CD25 eTregs (0·146%) than ASFL (0·497%) and healthy controls (0·639%) (P = 0·0003, P = 6·79 × 10 , respectively). These results suggest that the augmented anti-tumour immune reactions may contribute to a better prognosis on DTFL.
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http://dx.doi.org/10.1111/bjh.16715DOI Listing
October 2020

Survival Rate of Cells Sent by a Low Mechanical Load Tube Pump: The "Ring Pump".

Micromachines (Basel) 2020 Apr 23;11(4). Epub 2020 Apr 23.

Department of Mechanical Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

A ring pump (RP) is a useful tool for microchannels and automated cell culturing. We have been developing RPs (a full-press ring pump, FRP; and a mid-press ring pump, MRP). However, damage to cells which were sent by the RP and the MRP was not investigated, and no other studies have compared the damage to cells between RPs and peristaltic pumps (PPs). Therefore, first, we evaluated the damage to cells that were sent by a small size FRP (s-FRP) and small size MRPs (s-MRPs; gap = 25 or 50 μm, respectively). "Small size" means that the s-FRP and the s-MRPs are suitable for microchannel-scale applications. The survival rate of cells sent by the s-MRPs was higher than those sent by the s-FRP, and less damage caused by the former. Second, we compared the survival rate of cells that were sent by a large size FRP (l-FRP), a large size MRP (l-MRP) (gap = 50 μm) and a PP. "Large size" means that the l-FRP and the l-MRP are suitable for automated cell culture system applications. We could not confirm any differences among the cell survival rates. On the other hand, when cells suspended in Dulbecco's phosphate-buffered saline solution were circulated with the l-MRP (gap = 50 μm) and the PP, we confirmed a difference in cell survival rate, and less damage caused by the former.
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http://dx.doi.org/10.3390/mi11040447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231339PMC
April 2020

Epstein-Barr Virus-Induced Post-Transplant Lymphoproliferative Disorder of the Central Nervous System Successfully Treated with Chemo-immunotherapy.

Viruses 2020 04 8;12(4). Epub 2020 Apr 8.

Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.

Aplastic anemia is a rare blood disease characterized by the destruction of the hematopoietic stem cells (HSC) in the bone marrow that, in the majority of cases, is caused by an autoimmune reaction. Patients with aplastic anemia are treated with immunosuppressive drugs and some of them, especially younger individuals with a donor available, can be successfully treated with hematopoietic stem cell transplantation (HSCT). We report here a rare case of post-transplant lymphoproliferative disorder (PTLD) associated with Epstein-Barr virus (EBV) reactivation in a 30-year-old female patient who underwent allogeneic HSCT for severe aplastic anemia. The PTLD, which was diagnosed 230 days after transplantation, was localized exclusively in the central nervous system (specifically in the choroid plexus) and manifested with obvious signs of intracranial hypertension. After receiving three cycles of high dose methotrexate (HD-MTX) combined with rituximab, the patient achieved a complete clinical recovery with normalization of blood cell counts, no evidence of EBV reactivation, and no associated neurotoxicity.
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http://dx.doi.org/10.3390/v12040416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232501PMC
April 2020

Extensor hallucis longus tendon is a new distal landmark for coronal tibial component alignment in total knee arthroplasty: A study of magnetic resonance imaging.

J Orthop Surg (Hong Kong) 2020 Jan-Apr;28(1):2309499020912340

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Purpose: In total knee arthroplasty (TKA), various landmarks are generally used to ensure correct osteotomy. In this study, we examined whether the tibialis anterior tendon (TAT) or the extensor hallucis longus tendon (EHLT) could be used as a landmark of the center of the ankle joint in patients with knee osteoarthrosis (OA), using magnetic resonance imaging (MRI).

Methods: The subjects were 61 patients with OA in 79 knees (males: 8 with 9 knees and females: 53 with 70 knees). With the ankle joint secured in the intermediate position, MRI from the knee joint to the ankle joint was performed in the same foot position. We prepared individual lines connecting the center of the ankle joint with the TAT or EHLT to measure the angle difference (ΔA) from Akagi's line in the knee joint. We analyzed whether the ΔA might be affected by deformity of the knee joint or foot region, and tibial torsion.

Results: At the ankle joint level, the ΔA of EHLT was the smallest, with an average of 1.6 ± 3.4°. The ΔA for the femorotibial angle, hallux valgus angle, and varus-valgus angle showed no correlations with deformity of the knee joint and foot region, or tibial torsion.

Conclusions: MRI findings showed that EHLT would be useful as a landmark of the ankle joint center in extramedullary tibial osteotomy in TKA for medial knee OA. It was also clarified that the landmark would not be affected by severe deformity of the knee joint, deformity of the foot region, or external torsion of the tibia.
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http://dx.doi.org/10.1177/2309499020912340DOI Listing
December 2020

Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models.

Int J Mol Sci 2019 Oct 15;20(20). Epub 2019 Oct 15.

Department of Rehabilitation Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.
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http://dx.doi.org/10.3390/ijms20205100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834114PMC
October 2019

Early Clinical Results of Arthroscopically Assisted Drilling via the Radius in a Distal-to-Proximal Direction for Osteochondritis Dissecans of the Elbow.

Orthop J Sports Med 2019 Sep 6;7(9):2325967119868937. Epub 2019 Sep 6.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: We have previously reported the technique of arthroscopically assisted drilling of osteochondritis dissecans (OCD) lesions of the elbow via the radius in a distal-to-proximal direction. With this technique, the entire OCD lesion can be drilled vertically under arthroscopic guidance with pronation and supination of the forearm and flexion and extension of the elbow joint.

Purpose: To retrospectively evaluate return to sport, range of motion, and the Japanese Orthopaedic Association-Japan Elbow Society Elbow Function Score (JOA-JES score) after treatment of an elbow OCD lesion by drilling through the radius.

Study Design: Case series; Level of evidence, 4.

Methods: From November 2003 to January 2006, a total of 7 male adolescent baseball players with OCD lesions of the elbow were treated through use of arthroscopically assisted drilling via the radius. The stage of the OCD lesion was evaluated based on preoperative plain radiographs. Patients were observed for a minimum of 36 months, and clinical analysis included time for return to sport, elbow range of motion, and the JOA-JES score before intervention and at final follow-up.

Results: We evaluated all 7 patients at a mean follow-up time of 36.1 months (range, 24-68 months). The stage of the OCD lesion on plain radiography was "translucent" in 1 patient, "sclerotic" in 5 patients, and "loosening" in 1 patient. The mean range of motion before surgery was 131.2° and -4.7° in flexion and extension, respectively, and this improved to 138.6° and 1.1° at final follow-up. The improvement in extension was statistically significant ( = .04). The mean JOA-JES score of 83.0 before surgery significantly improved to 94.0 at final follow-up ( < .001). One patient required excision of a free body at 51 months postoperatively, but all patients returned to sports early and without pain at an average of 4.6 months postoperatively. No feature of osteoarthrosis was noted on radiography on the final examination in any patient.

Conclusion: The findings of this study demonstrate that arthroscopically assisted drilling of an elbow OCD lesion through the radial head allows for early return to sporting activities as well as improved motion and functional scores.
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http://dx.doi.org/10.1177/2325967119868937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732861PMC
September 2019

Nadir lymphocytopenia as a risk factor of bloodstream infection during molecular targeting pharmacotherapy in multiple myeloma.

Int J Clin Pharmacol Ther 2019 Nov;57(11):542-551

Objective: Molecular targeting pharmacotherapy (MTP) with proteasome inhibitors and immunomodulatory drugs has led to a remarkable improvement in the effectiveness of multiple myeloma (MM) therapy. However, the effect of MTP on the occurrence of infections in patients with MM remains unclear. We aimed to identify the incidence of and risk factors for bloodstream infection (BSI) in patients with MM undergoing MTP.

Materials And Methods: We conducted a retrospective cohort study. We reviewed the medical records of 108 inpatients with MM at the National Defense Medical College Hospital between January 2010 and January 2017. Univariate and multivariate analyses were conducted to identify risk factors for BSI.

Results: The incidence of BSI in patients with MM receiving MTP (n = 188) was 6.9%, which was significantly lower than the 52.6% in patients receiving cytotoxic chemotherapy (n = 57). We found that the most important risk factor for BSI in patients receiving MTP was lymphocytopenia at nadir (< 200/µL). In contrast, the risk factor for BSI in patients receiving cytotoxic chemotherapy was the number of regimens performed.

Conclusion: Our study suggests that the incidence of BSI is lower in patients with MM receiving MTP than in those receiving cytotoxic chemotherapy and that lymphocytopenia at nadir may be a risk factor for BSI in patients with MM receiving MTP. Since previous clinical trials with MTP showed that the frequency of myelosuppression and infections was high in the Japanese population, these findings might provide novel insights into MTP for Japanese patients with MM.
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http://dx.doi.org/10.5414/CP203455DOI Listing
November 2019

Breast-conserving surgery without radiation in elderly women with early breast cancer.

Surg Oncol 2019 Dec 22;31:22-25. Epub 2019 Aug 22.

Department of Breast Surgery, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.

Background And Objectives: Irradiation after breast-conserving surgery (BCS) decreases the incidence of ipsilateral breast tumor recurrence (IBTR) and breast cancer-related death. However, daily radiation treatments are burdensome to elderly patients, whose risk of IBTR is relatively low. Since 2001, we have offered BCS without radiation to patients meeting our selection criteria. This study assessed the prognosis of the patients who chose this option.

Methods: Between 2001 and 2014, 203 patients met the selection criteria: aged ≥60 years; pathologically node-negative, hormone-positive breast cancer; a negative surgical margin; and no lymphovascular invasion. Among these patients, 84 and 119 underwent BCS with or without radiation, respectively. IBTR, overall survival (OS), and breast cancer-specific survival (BCSS) were evaluated.

Results: The median follow-up duration was 6.2 years. There were no significant differences in tumor size or the number of patients with adjuvant therapy between the groups. The 5-year IBTR rates were 0.9% and 1.6% in the non-irradiated and irradiated groups, respectively (p = 0.308). The 5-year OS rates were 94.1% and 98.7% (p = 0.391). Similarly, the 5-year BCSS rates were 97.2% and 98.7% (p = 0.812).

Conclusion: It is suggested that the omission of irradiation could be an option for elderly breast cancer patients who satisfy our criteria.
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http://dx.doi.org/10.1016/j.suronc.2019.08.008DOI Listing
December 2019

[Ethinyl Estradiol Therapy for Postmenopausal Women with Heavily Pre-Treated Endocrine-Responsive Metastatic Breast Cancer].

Gan To Kagaku Ryoho 2019 Jul;46(7):1187-1189

Dept. of Breast Surgery, Tokyo Women's Medical University, Medical Center East.

Ethinyl estradiol(EE2)therapy has been reported to be an effective endocrine therapy for postmenopausal hormone receptor-positive advanced breast cancer, especially in the supposed acquired resistance state. The current study retrospectively investigated the efficacy and safety of EE2 therapy in postmenopausal women with hormone receptor-positive advanced breast cancer who had previously undergone multiple endocrine therapies. Twelve patients were enrolled; median lines of endocrine therapies were seven before EE2. Median PFS was 4.8 months and median overall survival was 10.0 months. Grade 3 adverse event comprised of anorexia in only one patient. EE2 therapy may be considered effective and safe in hormone receptor-positive advanced breast cancer even in late-stage endocrine therapy.
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July 2019

[Complete Remission of Advanced Gastric Cancer with Tumor Embolism in the Right Gastric Vein Treated with Radical Resection after Chemotherapy].

Gan To Kagaku Ryoho 2019 Apr;46(4):823-825

Dept. of Surgery, Onomichi Municipal Hospital.

A 74-year-old man presented to our hospital with the chief complaint of epigastric pain; upper gastrointestinal endoscopy revealed a 7-cm-sized type 3 gastric cancer in the lesser curvature of the lower part of the stomach. Abdominal contrast computed tomography revealed a tumor embolus in the right gastric vein; the preoperative diagnosis was cT4a(SE) N3aH0P0M0, cStage ⅢC. Because the cancer could spread during surgical manipulation, performing a safe radical resection was difficult; therefore, we decided to initiate chemotherapy. The patient received 3 courses of trastuzumab plus CapeOX, which led to reduction of the primarylesion, peri-gastric lymph node, and right gastric vein tumor embolus. Partial remission was achieved after chemotherapy; therefore, distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction were performed. Histopathological examination did not reveal viable tumor cells in the primarylesion, lymph nodes, or tumor embolus, and the histological effect was Grade 3. Currently, the patient is alive without relapse at 9 months post operation. Advanced gastric cancer accompanied with tumor embolism in the gastric vein is commonly observed in patients with liver metastasis and in those with severely progressed state of cancer; many of these patients have poor prognosis. Preoperative chemotherapymaybe effective in cases in which tumor embolism in the gastric vein is identified through preoperative diagnostic imaging.
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April 2019

Usefulness of Ustekinumab for Treating a Case of Myelodysplastic Syndrome-associated Inflammatory Bowel Disease.

Intern Med 2019 Jul 17;58(14):2029-2033. Epub 2019 Apr 17.

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan.

Autoimmune diseases including inflammatory bowel disease (IBD) occur in association with myelodysplastic syndrome (MDS). MDS-associated IBD frequently demonstrates a complicated course. We herein report the first case with MDS-associated IBD that was successfully treated with ustekinumab (UST), an anti-interleukin (IL) 12/23p40 monoclonal antibody. A 63-year-old man with a 7-year history of MDS was referred for examination of diarrhea, abdominal pain and fever. A blood examination revealed a marked elevation of C-reactive protein. Colonoscopy showed multiple ulcers in the terminal ileum. He was resistant to anti-tumor necrosis factor (TNF)-α antibody and azacitidine. Subsequently, UST treatment reduced colonic IL-17 and IL-6 expression and the patient currently maintains a state of remission.
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http://dx.doi.org/10.2169/internalmedicine.2495-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702013PMC
July 2019
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