Biceps-incorporating rotator cuff repair with footprint medialization in large-to-massive rotator cuff tears.

PURPOSE: In large-to-massive rotator cuff tears (MRCTs), incorporating the long head of the biceps tendon (LHBT) with arthroscopic partial rotator cuff and margin convergence can improve clinical outcomes and preserve the acromio-humeral interval (AHI) during mid-term follow-up. The purpose of this study was to evaluate mid-term clinical and radiological outcomes of arthroscopic biceps-incorporating rotator cuff repair with partial release of the LHBT and footprint medialization through the Neviaser portal in MRCTs. METHODS: This study enrolled 107 patients (38 males and 69 females, mean age: 64.9 ± 8.6 years) with MRCTs. A novel arthroscopic biceps-incorporating repair was performed by footprint medialization, with a partially released biceps tendon covering central defects. Clinical outcomes such as pain VAS, KSS, ASES, UCLA, SST and CS scores and ROM were evaluated at a mean follow-up time of 35 months (range 12-132 months). Serial radiographs with a mean postoperative MRI follow-up duration of 33 months were used to evaluate AHI, tendon integrity, fatty infiltration (FI) and muscle hypotrophy. RESULTS: Postoperative pain VAS, KSS, ASES, UCLA, SST, and CS scores and ROM (except external rotation) were improved significantly. AHI also improved significantly from 8.6 to 9.3 mm. According to Sugaya's classification, type I, II, III, IV, or V healing status was found in 30 (28.0%), 29 (27.1%), 26 (24.3%), 14 (13.1%), and 8 (7.5%) patients, respectively. The retear rate was 22 (20.6%). CONCLUSIONS: Novel biceps-incorporating cuff repair with footprint medialization yielded satisfactory outcomes in MRCT patients at the 3-year follow-up. A partially released, repaired biceps tendon provided superior stability with preserved AHI similar to that of anterior cable reconstruction. LEVEL OF EVIDENCE: IV.

Influence of increased pain sensitivity on patient-reported outcomes following total knee arthroplasty.

PURPOSE: The purpose of this study was to discover whether increased pain sensitivity was associated with postoperative pain and patient-reported outcome measures (PROMs) after total knee arthroplasty (TKA). METHODS: Pain sensitivity was evaluated preoperatively using a pain sensitivity questionnaire (PSQ). Resting, walking, nighttime, and average pain visual analog scale (VAS) were measured before surgery and 6 weeks, 3 months, 6 months, and 1 year after surgery. PROMs were also evaluated based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and patient satisfaction. The association between pain VAS average score, WOMAC total score, and PSQ score (minor, moderate, and total score) was assessed at each stage. RESULTS: There were 59 patients with a high PSQ score (≥ 5.2) and 53 with a low PSQ score (< 5.2). Up to 1 year postoperatively, the group with high PSQ scores had higher resting, walking, nighttime, and average pain VAS scores than the group with low scores (all p < 0.05). Worse preoperative WOMAC pain, function, and total scores continued until 1 year after surgery in the high-scoring PSQ group (all p < 0.05). The group with low PSQ scores was more satisfied with surgery than the group with high scores (p = 0.027). There was a positive correlation between preoperative PSQ score and pain VAS average score at all time points (all p < 0.05). A relationship between PSQ score and WOMAC total score was also observed (all p < 0.05). CONCLUSION: Increased pain sensitivity is a factor related to higher postoperative pain levels and inferior PROMs in patients undergoing primary TKA. LEVEL OF EVIDENCE: Case-controlled study, III.

Bone Mineral Density and Osteoporotic Vertebral Fractures in Traditional, Unassisted, Free-Diving Women (Haenyeos).

BACKGROUND: Water pressure and muscle contraction may influence bone mineral density (BMD) in a positive way. However, divers experience weightlessness, which has a negative effect on BMD. The present study investigated BMD difference in normal controls and woman free-divers with vertebral fracture and with no fracture. METHODS: Between January 2010 and December 2014, traditional woman divers (known as Haenyeo in Korean), and non-diving women were investigated. The study population was divided into osteoporotic vertebral fracture and non-fracture groups. The BMD of the lumbar spine and femoral neck was measured. The radiological parameters for global spinal sagittal balance were measured. RESULTS: Thirty free-diving women and thirty-three non-diving women were enrolled in this study. The mean age of the divers was 72.1 ± 4.7 years and that of the controls was 72.7 ± 4.0 years (P = 0.61). There was no statistical difference in BMD between the divers and controls. In divers, cervical lordosis and pelvic tilt were significantly increased in the fracture subgroup compared to the non-fracture subgroup (P = 0.028 and P = 0.008, respectively). Sagittal vertical axis was statistically significantly correlated with cervical lordosis (Spearman's rho R = 0.41, P = 0.03), and pelvic tilt (Spearman's rho R = 0.46, P = 0.01) in divers. CONCLUSION: BMD did not differ significantly between divers and controls during their postmenopausal period. When osteoporotic spinal fractures develop, compensation mechanisms, such as increased cervical lordosis and pelvic tilt, was more evident in traditional woman divers. This may be due to the superior back muscle strength and spinal mobility of this group of women.

Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation.

OBJECTIVE: To investigate the efficacy of human adipose tissue-derived mesenchymal stem cell (AD-MSC) transplantation in systemic lupus erythematosus (SLE) and to determine the optimal transplantation window for stem cells either before or after disease onset. METHODS: (NZB×NZW)F1 mice with SLE were administered human AD-MSCs (5×10(5)) intravenously every 2 weeks from age 6 weeks until age 60 weeks, while the control group received saline vehicle on the same schedule. Another experiment was carried out with a different initiation time point for serial transplantation (age 6 weeks or age 32 weeks). RESULTS: Long-term serial administration (total of 28 times) of human AD-MSCs ameliorated SLE without any adverse effects. Compared with the control group, the human AD-MSC-treated group had a significantly higher survival rate with improvement of histologic and serologic abnormalities and immunologic function, and also had a decreased incidence of proteinuria. Anti-double-stranded DNA antibodies and blood urea nitrogen levels decreased significantly with transplantation of human AD-MSCs, and serum levels of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), and IL-10 increased significantly. A significant increase in the proportion of CD4+FoxP3+ cells and a marked restoration of capacity for cytokine production were observed in spleens from the human AD-MSC-treated group. In the second experiment, an early stage treatment group showed better results (higher survival rates and lower incidence of proteinuria) than an advanced stage treatment group. CONCLUSION: Serial human AD-MSC transplantation had beneficial effects in the treatment of SLE, without adverse effects. Transplantation of human AD-MSCs before disease onset was preferable for amelioration of SLE and restoration of immune homeostasis.

Comparison of Locking Plate Fixation and Coracoclavicular Ligament Reconstruction for Neer Type 2B Distal Clavicle Fractures.

Background: There remains no consensus regarding which repair technique provides the most optimal results for unstable distal clavicle fractures. Purpose: To compare radiologic and clinical outcomes between locking plate fixation and anatomic coracoclavicular (CC) ligament reconstruction for patients with unstable distal clavicle fractures. Study Design: Cohort study; Level of evidence, 3. Methods: The study included 41 patients with Neer type 2B distal clavicle fracture. In group A (n = 15), patients were treated using CC ligament reconstruction with autologous palmaris longus tendon, artificial tape, and Steinmann pin fixation; in group B (n = 26), patients were treated using anatomic locking plate fixation. All patients had a minimum 2 years of follow-up. CC distance and arthrosis of the acromioclavicular joint were assessed radiographically. Clinical outcomes-including range of motion, visual analog scale for pain, American Shoulder and Elbow Surgeons rating scale, and Constant score-were compared between the groups using the paired Student t test and Fisher exact test. Results: Bone union was attained in all patients. In both groups, the CC distance decreased significantly from presurgery to final follow-up: group A, from 16.25 ± 4.75 to 7.66 ± 2.61 mm (P < .001); group B, from 17.3 ± 4.07 to 9.33 ± 2.01 mm (P < .001). The final CC distance was significantly greater in group B (7.66 vs 9.33 mm in groups A and B, respectively; P = .028). Osteoarthritis of the acromioclavicular joint occurred in 13 of 41 patients (3 in group A and 10 in group B). At final follow-up, there was no statistical significance between the groups in range of motion, and clinical outcome scores were satisfactory in both groups, with no statistical difference between them. Conclusion: Anatomic locking plate and anatomic reconstruction of the CC ligament showed good clinical results, so both techniques can be considered reliable for restoring stability. However, CC ligament reconstruction had better CC distance on radiologic assessment and did not require removal surgery, so it may be the preferable surgical option to treat unstable distal clavicle fractures (Neer type 2B).

Transplantation of CTLA4Ig gene-transduced adipose tissue-derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis.

BACKGROUND: Autoimmune thyroiditis is one of common organ-specific autoimmune disease. The aim of this study was to observe the effect of adipose tissue derived mesenchymal stem cells (ATMSC) and CTLA4Ig gene-transduced ATMSC on autoimmune thyroiditis. METHODS: Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Animals were divided into three groups: (i) a half million of human ATMSC, (ii) a half million of murine CLTA4Ig gene-transduced human ATMSC (CTLA4Ig-MSC), or (iii) normal saline (as control), which were administered intravenously four times within a 3-week period. Blood and tissue samples were collected 1 week after the last cell transplantation. RESULTS: The absorbance of serum thyroglobulin autoantibody (TgAA) in the CTLA4Ig-MSC group was considerably lower than those in other groups. In culture supernatant of LPS-stimulated spleen cells, both of the MSC-treated groups showed significantly lower absorbances of TgAA than the control. Flow cytometric analysis of spleen cells revealed a significant decrease in the proportion of CD3+ and CD11b in the CTLA4Ig-MSC group compared to the other groups. Lymphocyte infiltration in the thyroid glands was also dramatically decreased in both of MSC-treated groups. Cytokine analysis showed that ATMSC decreased the production of proinflammatory cytokines and improved the Th1/Th2 balance by down-regulating Th1 cytokines. CONCLUSION: Although CTLA4Ig-MSC transplantation had better result in reduction of serum TgAA, both of ATMSC and CTLA4Ig-MSC transplantations are promising treatments for autoimmune thyroiditis judging from the results of histopathology and cytokine analysis. They may be attractive candidates for treating organ-specific autoimmune disease.

Risk factors for intraoperative endplate injury during minimally-invasive lateral lumbar interbody fusion.

During lateral lumbar interbody fusion (LLIF), unintended intraoperative endplate injury (IEPI) can occur and thereafter lead cage subsidence. The aim of this study was to investigate the incidence of IEPI during LLIF, and its predisposing factors. A retrospective review was conducted on consecutive patients (n = 186; mean age, 70.0 ± 7.6 years) who underwent LLIF at 372 levels. Patient's demographic and surgical data were compared between patients with and without IEPI. Also, the radiographic data of each level were compared between intact and IEPI segments. IEPI was identified at 76 levels (20.4%) in 65 patients. The incidences of IEPI at every 100 consecutive segments were not different. When 372 segments were analyzed independently, sagittal disc angle (DA) in the extended position (4.3° ± 3.6° at IEPI segments vs. 6.4° ± 4.0° at intact segments), the difference between sagittal DA in the extended position and cage angle (- 2.2° ± 4.0° vs. 0.0° ± 3.9°), and the difference between preoperative disc height and cage height (- 5.4 mm ± 2.4 mm vs. - 4.7 mm ± 2.0 mm) were different significantly. Also, endplate sclerosis was more common at intact segments than IEPI segments (33.2% vs. 17.3%). Multivariate analysis showed that male sex (odds ratio [OR] 0.160; 95% confidence interval [CI] 0.036-0.704), endplate sclerosis (OR 3.307; 95% CI 1.450-8.480), and sagittal DA in the extended position (OR 0.674; 95% CI 0.541-0.840) were significant associated factors for IEPI. IEPI was correlated not with surgeon's experience, but with patient factors, such as sex, preoperative disc angle, and endplate sclerosis. Careful surgical procedures should be employed for patients with these predisposing factors.

Characteristics of mouse adipose tissue-derived stem cells and therapeutic comparisons between syngeneic and allogeneic adipose tissue-derived stem cell transplantation in experimental autoimmune thyroiditis.

Previously, we found that the intravenous administration of human adipose tissue-derived mesenchymal stem cells was a promising therapeutic option for autoimmune thyroiditis even when the cells were transplanted into a xenogeneic model without an immunosuppressant. Therefore, we explored the comparison between the therapeutic effects of syngeneic and allogeneic adipose tissue-derived stem cells on an experimental autoimmune thyroiditis mouse model. Experimental autoimmune thyroiditis was induced in C57BL/6 mice by immunization with porcine thyroglobulin. Adipose tissue-derived stem cells derived from C57BL/6 mice (syngeneic) or BALB/c mice (allogeneic) or saline as a vehicle control were administered intravenously four times weekly. Blood and tissue samples were collected 1 week after the last transplantation. Adipose tissue-derived stem cells from mice were able to differentiate into multiple lineages in vitro; however, mouse adipose tissue-derived stem cells did not have immunophenotypes identical to those from humans. Syngeneic and allogeneic administrations of adipose tissue-derived stem cells reduced thyroglobulin autoantibodies and the inflammatory immune response, protected against lymphocyte infiltration into the thyroid, and restored the Th1/Th2 balance without any adverse effects. However, different humoral immune responses were observed for infused cells from different stem cell sources. The strongest humoral immune response was induced by xenogeneic transplantation, followed by allogeneic and syngeneic administration, in that order. The stem cells were mostly found in the spleen, not the thyroid. This migration might be because the stem cells primarily function in systemic immune modulation, due to being given prior to disease induction. In this study, we confirmed that there were equal effects of adipose tissue-derived stem cells in treating autoimmune thyroiditis between syngeneic and allogeneic transplantations.

Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans.

Adipose tissue-derived mesenchymal stem cells (AdMSCs) represent an attractive and ethical cell source for stem cell therapy. With the recent demonstration of MSC homing properties, intravenous applications of MSCs to cell-damaged diseases have increased. In the present study, the toxicity and tumorigenicity of human AdMSCs (hAdMSCs) were investigated for clinical application. Culture-expanded hAdMSCs showed the typical appearance, immunophenotype, and differentiation capacity of MSCs, and were genetically stable at least 12 passages in culture. Cells suspended in physiological saline maintained their MSC properties in a cold storage condition for at least 3 days. To test the toxicity of hAdMSCs, different doses of hAdMSCs were injected intravenously into immunodeficient mice, and the mice were observed for 13 weeks. Even at the highest cell dose (2.5×10(8) cells/kg body weight), the SCID mice were viable and had no side effects. A tumorigenicity test was performed in Balb/c-nu nude mice for 26 weeks. Even at the highest cell dose (2×10(8) MSCs/kg), no evidence of tumor development was found. In a human clinical trial, 8 male patients who had suffered a spinal cord injury >12 months previous were intravenously administered autologous hAdMSCs (4×10(8) cells) one time. None of the patients developed any serious adverse events related to hAdMSC transplantation during the 3-month follow-up. In conclusion, the systemic transplantation of hAdMSCs appears to be safe and does not induce tumor development.