Determining optimal length of coracoid graft in the modified Bristow procedure for anterior shoulder instability: A three-dimensional finite element analysis.

BACKGROUND: There is a lack of consensus concerning the coracoid graft length in the modified Bristow procedure. OBJECTIVE: We attempted to determine the optimal graft length using the three-dimensional finite element method. METHODS: In a shoulder model with a 25% anterior glenoid defect, a coracoid graft of varying lengths (5, 10, 15, and 20 mm) was fixed using a half-threaded screw. First, a compressive load of 500 N was applied to the screw head to determine the graft failure load during screw tightening. Next, a tensile load (200 N) was applied to the graft to determine the failure load due to biceps muscle traction. RESULTS: In the screw compression, the failure loads in the 5-, 10-, 15-, and 20-mm models were 252, 370, 377, and 331 N, respectively. In the tensile load applied to the coracoid graft, the failure load exceeded 200 N for both the 5- and 10-mm models. CONCLUSION: The 5-mm graft had a high risk of fracture during intraoperative screw tightening. As for the biceps muscle traction, the 5- and 10-mm-grafts had a lower failure risk than the 15- and 20-mm-grafts. Therefore, we believe that the optimal length of the coracoid graft is 10 mm in the modified Bristow procedure.

Intra-articular biomechanical environment following modified Bristow and Latarjet procedures in shoulders with large glenoid defects: relationship with postoperative complications.

BACKGROUND: Although coracoid transfers including the modified Bristow and Latarjet procedures are widely used to treat anterior shoulder instability, the influence of the choice of procedure on the biomechanical outcomes is not well characterized. We aimed to clarify the intra-articular stress distribution following these 2 procedures using 3-dimensional finite-element analysis and to investigate the role of stress distribution in the pathophysiology of postoperative complications. METHODS: Overall, 6 male patients aged 17-47 years with unilateral anterior shoulder instability were recruited. Computed tomographic digital imaging and communications in medicine (CT-DICOM) data of the contralateral (healthy) shoulder of each patient was obtained and used for developing the 3-dimensional normal glenohumeral joint model. A 25% bony defect was created in the anterior glenoid rim where the coracoid process was transferred in the standing and lying-down positions to create the Bristow and Latarjet models, respectively. The arm position was set as 0° or 90° abduction. The Young moduli of the humerus and scapula were calculated using CT data, and set as 35.0 MPa and 113.8 GPa for the articular cartilage and inserted screw, respectively. A compressive load (50 N) was applied to the greater tuberosity toward the center of the glenoid, and a tensile load (20 N) was applied to the tip of the coracoid in the direction of conjoint tendon. Elastic analysis was used to determine the equivalent stress distribution. RESULTS: A significant reduction in mean equivalent stress was observed within the glenoid cartilage for both models (P = .031); however, a new stress concentration appeared within the grafted coracoid-facing region of the humeral-head cartilage in both models. The proximal half of the coracoid graft exhibited lower equivalent stress than the distal half in 5 of the 6 Latarjet models, whereas the proximal half showed higher equivalent stress than the distal half in all 6 Bristow models. High stress concentration was identified at the midpoint of the inserted screw in Bristow models. DISCUSSION AND CONCLUSIONS: Intra-articular stress distribution may explain the different rates of postoperative complications associated with the modified Bristow and Latarjet procedures. New stress concentration within the humeral-head cartilage might contribute to the development of glenohumeral osteoarthritis following both procedures. Stress shielding in the proximal part of the coracoid graft might contribute to osteolysis following the Latarjet procedure. Surgeons should be aware of the risk of breakage of the inserted screw following the modified Bristow procedure.

Comparison between single and double suture passing techniques in the suture bridge rotator cuff repair with a 2-mm tape: A simulation study using a three-dimensional finite element method.

BACKGROUND: Suture bridge repair has been widely used as one of the standard procedures in the arthroscopic rotator cuff repair. We compared the intratendinous stress distribution between single and double suture passing techniques in the suture bridge repair using a 2-mm tape and clarified the roles of tensioning in this procedure. METHODS: A board-like model of the supraspinatus tendon and humeral head was used in order to standardize conditions and exclude the influence of anatomical variations between individuals. Reattachment of the supraspinatus tendon to the bone was simulated using both single and double suture passing techniques for the suture bridge repair using a 2-mm tape. A tensile load was applied to the medial end of the tendon, and the stress distribution pattern was observed. Elastic analysis enabled comparison of the von Mises equivalent and maximum principal stresses between the single and double suture passing techniques. The tape configuration was subsequently translated 1 mm toward the insertion points of lateral anchors to simulate the tensioning maneuver. RESULTS: Although the distribution pattern of both the equivalent and the maximum principal stresses was similar for both models, areas with a high stress concentration were smaller in the single suture passing model than those in the double suture passing model. The equivalent stress concentrated within the tendon beneath the tapes as well as in the area between the crossing tapes and the lateral end of the tendon, whereas the maximum principal stress concentrated medial to the sites of suture penetration. CONCLUSIONS: Single suture passing technique can reduce the extent of intratendinous stress concentration compared with double suture passing technique, which might be beneficial to reduce the incidence of type 2 retear after suture bridge repair of rotator cuff tendon using a 2-mm tape.

Proximal-medial part in the coracoid graft demonstrates the most evident stress shielding following the Latarjet procedure: a simulation study using the 3-dimensional finite element method.

BACKGROUND: Although the osteolysis of the coracoid graft is frequently observed after the Latarjet procedure particularly in its proximal part, its pathomechanism is not well understood. METHODS: Three-dimensional finite element glenohumeral joint models were developed using CT-DICOM data of 10 normal shoulders. A 25% bony defect was created on the anterior glenoid rim, and the coracoid process was transferred flush with the glenoid cartilage using 2 half-threaded screws. In the hanging arm as well as in the 90° abducted positions, a compressive load (50 N) was applied to the greater tuberosity toward the center of the glenoid and a tensile force (20 N) was applied to the coracoid tip along the direction of the conjoint tendon. Next, elastic analysis was performed, and the distribution patterns of the equivalent stress as well as the maximum principal stress were compared among 4 parts (proximal/distal and medial/lateral) of the coracoid graft. RESULTS: Both the equivalent stress and the maximum principal stress were reduced in the proximal half of the coracoid graft. A high stress concentration was observed in the lateral aspect of the coracoid graft particularly in the 90° abducted position. The proximal-medial part demonstrated the lowest equivalent stress as well as the maximum principal stress for both arm positions, which were significantly lower than those in the distal 2 parts. CONCLUSION: In the Latarjet procedure, the proximal-medial part of the coracoid graft demonstrated the most evident stress shielding, which may play an important role in postoperative osteolysis.

Single Rectal Neuroendocrine Tumor Associated with Multiple Endocrine Cell Micronests.

Although a few reports of neuroendocrine tumor (NET) in the stomach or appendix with surrounding micronests have been published, cases of rectal NET are rare. We herein report a unique case of a patient with single rectal NET treated endoscopically. A pathological examination revealed multiple endocrine cell micronests (ECMs) in the submucosal layer around the main NET lesion. Neither lymph node metastasis nor distant metastasis in computed tomography was observed six years after the treatment. Because case reports of multiple ECM are very rare, the significance of malignancy is unclear. It therefore appears to be necessary to accumulate similar cases.

Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis.

Calreticulin (CALR) exon 9 frameshift mutations, commonly detected in essential thrombocythemia (ET) and primary myelofibrosis patients, activate signal transducer and activator of transcription (STAT) proteins in the presence of Myeloproliferative Leukemia Virus (MPL) and induce ET in vivo. Loss of the KDEL motif, an endoplasmic reticulum retention signal, and generation of many positively charged amino acids (AAs) in the mutated C-terminus are thought to be important for disease induction. To test this hypothesis, we generated mice harboring a Calr frameshift mutation using the CRISPR/Cas9 system. Deletion of 19-base pairs in exon 9 (c.1099-1117del), designated the del19 mutation, induced loss of the KDEL motif and generated many positively charged AAs, similar to human mutants. Calr del19 mice exhibited mild thrombocytosis, slightly increased megakaryocytes, and mild splenomegaly. In vitro experiments revealed that the murine CALR del19 mutant had a weaker ability to combine with murine MPL than the human CALR del52 mutant. Consequently, STAT5 activation was also very weak downstream of the murine mutant and murine MPL, and may be the reason for the mild disease severity. In summary, loss of the KDEL motif and positively charged AAs in the C-terminus of CALR is insufficient for MPL binding and ET development.

Capsule endoscopy findings for the diagnosis of Crohn's disease: a nationwide case-control study.

BACKGROUND: Capsule endoscopy can be used to identify the early stage of small bowel Crohn's disease (CD). We evaluated significant small bowel capsule endoscopy (SBCE) findings that can lead to early diagnosis of CD. METHODS: We retrospectively accumulated clinical and SBCE data of 108 patients (63 with and 45 without CD). Types of small bowel mucosal injuries, including erosion, ulceration, and cobblestone appearance, and the alignment of diminutive lesions were compared between patients with and without CD. Inter- and intra-observer agreement in the determination of lesions was assessed in 25 pairs of SBCE from the two groups. RESULTS: Under SBCE, cobblestone appearance (33% vs. 2%, p < 0.0001), longitudinal ulcers (78% vs. 20%, p < 0.0001), and irregular ulcers (84% vs. 60%, p < 0.01) were more frequently found in patients with CD. Linear erosion (90% vs. 38%, p < 0.0001) and irregular erosion (89% vs. 64%, p < 0.005) were also more frequent in patients with CD. Furthermore, circumferential (75% vs. 9%, p < 0.0001) and longitudinal (56% vs. 7%, p < 0.0001) alignment of diminutive lesions, mainly observed in the 1st tertile of the small bowel, was more frequent in patients with CD. Good intra-observer agreement was found for ulcers, cobblestone appearance, and lesion alignment. However, inter-observer agreement of SBCE findings differed among observers. CONCLUSIONS: Circumferential or longitudinal alignment of diminutive lesions, especially in the upper small bowel, may be a diagnostic clue for CD under SBCE, while inter-observer variations should be cautiously considered when using SBCE.

Loss of Tyrosine Kinase 2 Does Not Affect the Severity of Jak2V617F-induced Murine Myeloproliferative Neoplasm.

BACKGROUND/AIM: In myeloproliferative neoplasms (MPN), Janus kinase 2 (JAK2) is activated by mutations including JAK2V617F (JAK2VF). It is unclear whether JAK kinases [i.e. JAK1, JAK2, JAK3, or tyrosine kinase 2 (TYK2)] other than JAK2 have cooperative actions such as enhancement or suppression of JAK2. If other kinases enhance activation, therapies that co-target them could have a therapeutic efficacy. We examined the role of TYK2 in Jak2VF-induced murine MPN. MATERIALS AND METHODS: We crossed Jak2VF transgenic mice and Tyk2-knockout (Tyk2KO) mice to generate Jak2VF/Tyk2KO mice. The disease severity and treatment effect with a JAK2 inhibitor was compared between Jak2VF and Jak2VF/Tyk2KO mice. RESULTS: Both types of mice developed MPN, and there were no differences in peripheral blood counts, spleen weight, or survival period. Upon JAK2 inhibitor therapy, both types of mice had equally improved leukocytosis and splenomegaly. CONCLUSION: TYK2 does not have cooperative effects with JAK2VF upon MPN onset nor in the presence of a JAK2 inhibitor.

Tight medial knot tying may increase retearing risk after transosseous equivalent repair of rotator cuff tendon.

BACKGROUND: Retearing mechanism after transosseous equivalent (TOE) rotator cuff repair has not been fully clarified yet. OBJECTIVE: The purposes of this study were to compare the stress distribution pattern in the tendon stump between knotted and knotless TOE repair and to investigate the role of suture tension applied during medial knot tying using a 3-dimensional finite element (3D-FE) method. METHODS: Both knotted and knotless TOE repairs were simulated on the 3D-FE human rotator cuff tear model. Elastic analysis was performed to compare the stress distribution pattern inside the tendon between the two models. The amount of compressive load applied to the medial-row sutures was then changed as 0, 20, 40, 60, 80, and 100 N in the knotted model. RESULTS: Knotted model demonstrated more distinct stress concentration inside the tendon around medial-row sutures than the knotless model. Mean von Mises equivalent stress in this area in the 0, 20, 40, 60, 80, and 100 N models was 0.26, 0.35, 0.50, 0.70, 1.11, and 1.14 MPa, respectively. CONCLUSIONS: In the knotted TOE repair, tight medial knot tying might cause a high stress concentration around medial knots, which may constitute one of the pathogenetic factors of postoperative retearing at this site.

TET2 mutation in diffuse large B-cell lymphoma.

Ten-eleven translocation-2 (TET2) mutation is frequently observed in myeloid malignancies, and loss-of-function of TET2 is essential for the initiation of malignant hematopoiesis. TET2 mutation presents across disease entities and was reported in lymphoid malignancies. We investigated TET2 mutations in 27 diffuse large B-cell lymphoma (DLBCL) patients and found a frameshift mutation in 1 case (3.7%). TET2 mutation occurred in some populations of DLBCL patients and was likely involved in the pathogenesis of their malignancies.

Comparison of fixation properties between coil-type and screw-type anchors for rotator cuff repair: A virtual pullout testing using 3-dimensional finite element method.

BACKGROUND: Pullout of inserted anchor constitutes one of the pathomechanisms of re-tearing after rotator cuff repair. The purpose of the present study was to investigate the fixation properties of suture anchors using 3-dimensional finite element method. METHODS: The computer models of three types of anchors (TwinFix Ti, HEALICOIL PK and HEALICOIL RG) were inserted into the isotropic cube model that simulated cancellous bone. In the virtual pullout testing, a tensile load (500 N) along the long axis of the inserted anchor was applied to the site of suture thread attachment to simulate a traction force. The distribution of von Mises equivalent stress, the failure patterns of elements inside the cube and the anchor displacement were compared among the three anchors. RESULTS: In TwinFix Ti, the highest stress concentration was seen around the anchor threads close to the surface of the cube, which caused element failure at this site. On the other hand, both HEALICOIL PK and HEALICOIL RG demonstrated a high stress concentration as well as element failure around the anchor tip. Comparing the anchor displacement, HEALICOIL RG showed the smallest displacement among the three anchors. The tensile loads that required a 0.1-mm displacement for TwinFix Ti, HEALICOIL PK and HEALICOIL RG were 400 N, 370 N, and greater than 500 N, respectively. CONCLUSIONS: The bony structures close to the footprint surface may be damaged during surgery due to preparation for the bony bed as well as the insertion of anchors. Thus, we assumed that HEALICOIL RG represented the best initial fixation properties among the three anchors tested. Virtual pullout testing using 3-dimensional finite element method could reveal the detailed biomechanical characteristics of each suture anchor, which would be important for shoulder surgeons to improve the clinical outcomes of rotator cuff repair.

Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer.

Background and Aim. It is difficult to master the skill of discriminating gastric adenoma from early gastric cancer by conventional endoscopy or magnifying endoscopy combined with narrow-band imaging, because the colors and morphologies of these neoplasms are occasionally similar. We focused on the surrounding gastric mucosa findings in order to determine how to discriminate between early gastric cancer and gastric adenoma by analyzing the characteristics of the gastric background mucosa. Methods. We retrospectively examined 146 patients who underwent endoscopic submucosal dissection for gastric neoplasm between October 2009 and January 2015. The boundary of atrophic gastritis was classified endoscopically according to the Kimura-Takemoto classification system. Of 146 lesions, 63 early gastric cancers and 21 gastric adenomas were ultimately evaluated and assessed. Results. Almost all gastric adenomas were accompanied by open-type gastritis, whereas 47 and 16 early gastric cancers were accompanied by open-type and closed-type gastritis, respectively (p = 0.037). Conclusions. The evaluation of the boundary of atrophic gastritis associated with gastric neoplasms appears to be useful for discrimination between early gastric cancer and gastric adenoma. When gastric neoplasm is present in the context of surrounding localized gastric atrophy, gastric cancer is probable but not certain.

Gene expression profiling of loss of TET2 and/or JAK2V617F mutant hematopoietic stem cells from mouse models of myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are clinically characterized by the chronic overproduction of differentiated peripheral blood cells and the gradual expansion of malignant intramedullary/extramedullary hematopoiesis. In MPNs mutations in JAK2 MPL or CALR are detected mutually exclusive in more than 90% of cases [1,2]. Mutations in them lead to the abnormal activation of JAK/STAT signaling and the autonomous growth of differentiated cells therefore they are considered as "driver" gene mutations. In addition to the above driver gene mutations mutations in epigenetic regulators such as TET2 DNMT3A ASXL1 EZH2 or IDH1/2 are detected in about 5%-30% of cases respectively [3]. Mutations in TET2 DNMT3A EZH2 or IDH1/2 commonly confer the increased self-renewal capacity on normal hematopoietic stem cells (HSCs) but they do not lead to the autonomous growth of differentiated cells and only exhibit subtle clinical phenotypes [4,6-8,5]. It was unclear how mutations in such epigenetic regulators influenced abnormal HSCs with driver gene mutations how they influenced the disease phenotype or whether a single driver gene mutation was sufficient for the initiation of human MPNs. Therefore we focused on JAK2V617F and loss of TET2-the former as a representative of driver gene mutations and the latter as a representative of mutations in epigenetic regulators-and examined the influence of single or double mutations on HSCs (Lineage(-)Sca-1(+)c-Kit(+) cells (LSKs)) by functional analyses and microarray whole-genome expression analyses [9]. Gene expression profiling showed that the HSC fingerprint genes [10] was statistically equally enriched in TET2-knockdown-LSKs but negatively enriched in JAK2V617F-LSKs compared to that in wild-type-LSKs. Double-mutant-LSKs showed the same tendency as JAK2V617F-LSKs in terms of their HSC fingerprint genes but the expression of individual genes differed between the two groups. Among 245 HSC fingerprint genes 100 were more highly expressed in double-mutant-LSKs than in JAK2V617F-LSKs. These altered gene expressions might partly explain the mechanisms of initiation and progression of MPNs which was observed in the functional analyses [9]. Here we describe gene expression profiles deposited at the Gene Expression Omnibus (GEO) under the accession number GSE62302 including experimental methods and quality control analyses.

Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator.

Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms (MPNs). We examined the individual and cooperative effects of these mutations on MPN development. Recipients of JAK2V617F cells developed primary myelofibrosis-like features; the addition of loss of TET2 worsened this JAK2V617F-induced disease, causing prolonged leukocytosis, splenomegaly, extramedullary hematopoiesis, and modestly shorter survival. Double-mutant (JAK2V617F plus loss of TET2) myeloid cells were more likely to be in a proliferative state than JAK2V617F single-mutant myeloid cells. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the second recipients, which did not develop MPNs. In marked contrast, cooperation between JAK2V617F and loss of TET2 developed and maintained MPNs in the second recipients by compensating for impaired hematopoietic stem cell (HSC) functioning. In-vitro sequential colony formation assays also supported the observation that JAK2V617F did not maintain HSC functioning over the long-term, but concurrent loss of TET2 mutation restored it. Transcriptional profiling revealed that loss of TET2 affected the expression of many HSC signature genes. We conclude that loss of TET2 has two different roles in MPNs: disease accelerator and disease initiator and sustainer in combination with JAK2V617F.

TET2 Mutation in Adult T-Cell Leukemia/Lymphoma.

Loss-of-function of ten-eleven translocation-2 (TET2) is a common event in myeloid malignancies, and plays pleiotropic roles, including augmenting stem cell self-renewal and skewing hematopoietic cells to the myeloid lineage. TET2 mutation has also been reported in lymphoid malignancies; 5.7～12% of diffuse large B-cell lymphomas and 18～83% of angioimmunoblastic T-cell lymphomas had TET2 mutations. We investigated TET2 mutations in 22 adult T-cell leukemia/lymphoma (ATLL) patients and identified a missense mutation in 3 cases (14%). TET2 mutation occurred in a number of ATLL patients and was likely involved in their leukemogenesis.

Possible diagnostic role of antibodies to Crohn's disease peptide (ACP): results of a multicenter study in a Japanese cohort.

BACKGROUND: Various noninvasive tests have been studied to screen for patients with Crohn's disease (CD), and were found to have limited accuracy and sensitivity, particularly in Asian populations. The aim of our study was to explore the possible diagnostic utility of antibodies to the CD peptide (ACP) in patients with CD. METHODS: In a multicenter study using enzyme-linked immunosorbent assay, serum ACP levels were determined in 196 patients with CD, 210 with ulcerative colitis, 98 with other intestinal diseases, 132 with other inflammatory diseases, and 183 healthy controls. and then examined for correlation to clinical variables. The diagnostic utility of ACP was evaluated by receiver operating characteristics analysis and compared with anti-Saccharomyces cerevisiae antibodies (ASCA). RESULTS: ACP levels were significantly elevated in the CD patients, but not in the other groups that included UC, other intestinal diseases, other inflammatory diseases and the healthy controls. Among these other groups, ACP levels were not significantly different. In the CD patients, ACP had a higher sensitivity and specificity (63.3 and 91.0 %, respectively) than ASCA (47.4 and 90.4 %). ACP levels were negatively associated with disease duration, but not with CDAI, disease location, or medical treatment. CONCLUSIONS: ACP, a newly proposed serologic marker, was significantly associated with CD and was highly diagnostic. Further investigation is needed across multiple populations of patients and ethnic groups, and more importantly, in prospective studies.

[A case study: interferon-beta-induced remission of ulcerative colitis in a patient with type C chronic hepatitis].

A 66-year-old man patient with chronic hepatitis (CH) C and complications from ulcerative colitis (UC) was treated with interferon-beta (IFN-beta). Endoscopically, the UC disease activity was moderate before IFN-beta treatment but was in remission eight week after treatment. However, a few months after stopping IFN treatment, endoscopy revealed that the UC disease activity had returned to moderate levels. This result shows that UC improved with IFN treatment.

Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats.

The role of osteoactivin (OA) in liver fibrogenesis remains unclear. After feeding wild-type (WT) and OA transgenic (OA-Tg) rats a choline-deficient, L-amino acid-defined (CDAA) diet for 12 weeks, we evaluated liver fibrosis. Hepatic fibrosis and expression of alpha-smooth muscle actin protein in OA-Tg rats were reduced in comparison to WT rats. Our examination of the expression of 31,100 genes by microarray analysis identified 177 and 256 genes that were upregulated and downregulated, respectively, by at least twofold in OA-Tg rat livers in comparison to WT rat livers. Of these genes, we confirmed a significant downregulation in the expression levels of tissue inhibitor of metalloproteinase-1 and -2, type I collagen, and platelet-derived growth factor receptor-alpha and -beta in the livers of OA-Tg rats. These results indicate that transgenic OA expression attenuates the development of hepatic fibrosis in association with the suppression of specific genes involved in its pathogenesis.