Inferior Healing Rate in Isolated Meniscal Repair than that in Meniscal Repair with Concomitant ACL Reconstruction Evaluated with MRI.

Introduction: Isolated meniscal repair has been suggested as one of the contributing factors in unhealed meniscal repair. The purpose of this study was to compare the healing rate between isolated meniscal repair and meniscal repair with concomitant anterior cruciate ligament reconstruction (ACLR) using a standardised assessment method after propensity score matching. Materials and methods: Accuracy of the Crues' grading system for meniscal healing was validated using second-look arthroscopy as the reference standard in 17 patients. Propensity score matching (one-to-one) was performed between 26 patients who underwent isolated meniscal repair and 98 patients who underwent meniscal repair with concomitant ACLR. Patients were matched for sex, age, side and zone of the meniscal repair, and number of sutures. Healing rates at one year which were evaluated with magnetic resonance imaging (MRI) were compared between the two groups. Results: The sensitivity and specificity of the Crues' grading system on multiple plane MRI for meniscal healing were 100% and 83.3%, respectively. Both the isolated meniscal repair group and the meniscal repair with concomitant ACLR group included 21 patients after propensity score matching. Baseline characteristics did not differ significantly between the two groups. The healing rate was significantly lower in the isolated meniscal repairs group (14.3%) than in the meniscal repair concomitant with ACLR group (47.6%, P=0.04). Conclusion: The healing rate for isolated meniscal repair using a standardised MRI assessment method was inferior to that of meniscal repair with concomitant ACLR after propensity score matching.

Inferior Healing Rate in Isolated Meniscal Repair than that in Meniscal Repair with Concomitant ACL Reconstruction Evaluated with MRI

@#Introduction: Isolated meniscal repair has been suggested as one of the contributing factors in unhealed meniscal repair. The purpose of this study was to compare the healing rate between isolated meniscal repair and meniscal repair with concomitant anterior cruciate ligament reconstruction (ACLR) using a standardised assessment method after propensity score matching. Materials and methods: Accuracy of the Crues' grading system for meniscal healing was validated using second-look arthroscopy as the reference standard in 17 patients. Propensity score matching (one-to-one) was performed between 26 patients who underwent isolated meniscal repair and 98 patients who underwent meniscal repair with concomitant ACLR. Patients were matched for sex, age, side and zone of the meniscal repair, and number of sutures. Healing rates at one year which were evaluated with magnetic resonance imaging (MRI) were compared between the two groups. Results: The sensitivity and specificity of the Crues' grading system on multiple plane MRI for meniscal healing were 100% and 83.3%, respectively. Both the isolated meniscal repair group and the meniscal repair with concomitant ACLR group included 21 patients after propensity score matching. Baseline characteristics did not differ significantly between the two groups. The healing rate was significantly lower in the isolated meniscal repairs group (14.3%) than in the meniscal repair concomitant with ACLR group (47.6%, P=0.04). Conclusion: The healing rate for isolated meniscal repair using a standardised MRI assessment method was inferior to that of meniscal repair with concomitant ACLR after propensity score matching.

Immunological inflammatory biomarkers as prognostic predictors for advanced hepatocellular carcinoma.

BACKGROUND: The immunological inflammatory biomarkers for advanced hepatocellular carcinoma are unclear. We aimed to investigate the association of immunity and inflammatory status with treatment outcomes in patients with advanced hepatocellular carcinoma who received molecular-targeted agents as primary treatment. PATIENTS AND METHODS: We enrolled 728 consecutive patients with advanced hepatocellular carcinoma who received sorafenib (n = 554) or lenvatinib (n = 174) as primary treatment in Japan between May 2009 and June 2020. Changes in the neutrophil-to-lymphocyte ratio before and 1 month after treatment and their impact on survival were evaluated. The cut-off values of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for predicting overall and progression-free survival were calculated using receiver operating characteristic curves. RESULTS: The neutrophil-to-lymphocyte ratio, but not the platelet-to-lymphocyte ratio, was an independent prognostic factor. Patients with decreased neutrophil-to-lymphocyte ratio survived significantly longer than patients with increased neutrophil-to-lymphocyte ratio (median overall survival: 14.7 versus 10.4 months, P = 0.0110). Among patients with a low pre-treatment neutrophil-to-lymphocyte ratio, the overall survival did not differ significantly between those with decreased and those with increased neutrophil-to-lymphocyte ratio after 1 month (median: 19.0 versus 14.8 months, P = 0.1498). However, among patients with high pre-treatment neutrophil-to-lymphocyte ratio, those whose neutrophil-to-lymphocyte ratio decreased after 1 month showed significantly longer survival than those whose neutrophil-to-lymphocyte ratio increased (median: 12.7 versus 5.5 months, P < 0.0001). The therapeutic effect was not correlated with pre-treatment neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio. CONCLUSIONS: The neutrophil-to-lymphocyte ratio is a prognostic factor, along with liver function and tumor markers, in patients with advanced hepatocellular carcinoma who received molecular-targeted agents as primary treatment. Thus, the neutrophil-to-lymphocyte ratio could be a prognostic biomarker for advanced hepatocellular carcinoma primarily treated with immunotherapy.

Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model.

OBJECTIVE: We have reported that fibrotic changes in infrapatellar fat pad (IFP) after acute joint inflammation are closely associated with persistent pain in rats. In this study, to examine the effects of anti-fibrotic treatment on persistent pain, we used C-type natriuretic peptides (CNP) at the recovery phase after acute joint inflammation. DESIGN: Thirty-two male Wistar rats were used in this study. Monoiodoacetic acid (MIA) was injected intra-articularly to induce IFP fibrosis and persistent pain. CNP was injected after acute inflammatory phase in the same knee joint. Time-course pain-avoidance behavior tests and histological analyses were performed to examine the effects of CNP. RESULTS: Histological evaluations indicated that intra-articular injection of CNP inhibited fibrotic changes in IFP after acute inflammation. Incapacitance tests indicated that MIA injection into rat knee joint quickly decreased the percent weight on ipsilateral limb. In the vehicle group, the decrease was maintained up to day 28, suggesting that pain persistence occurred after acute inflammation (Day 0/Day 28, Est Dif -8.15, CI -10.78∼-5.53, Linear mixed-effect model). In contrast, the pain was alleviated in the CNP group after day 14 (Day0/Day 14, -0.51, -2.62-1.59). In addition, we observed significant improvement in the degree of articular cartilage degeneration at day 14 in the CNP group (OARSI score: vehicle 16.14 ± 4.37 vs CNP 6.87 ± 3.44, P < 0.01; Wilcoxon rank sum test). CONCLUSION: Fibrotic changes in IFP may play important roles in both persistent pain and articular cartilage degeneration.

In prenatally diagnosed CPAM, does the affected lobe influence the timing of symptom onset?

PURPOSE: We investigated the relationship between the affected lobe and symptom onset in prenatally diagnosed congenital pulmonary airway malformation (CPAM). METHODS: 53 CPAM patients diagnosed prenatally were reviewed retrospectively by creating 2 groups according to symptom onset. Group Sneo: (symptomatic during the neonatal period; n = 13) and group S > neo: (symptomatic after the neonatal period; n = 40) were compared for type of CPAM, affected lobes, types of symptoms/infections, treatment, duration of follow-up, and histopathology. Requirement for surgery (Sx) was then used to create three subgroups: Sneo + Sx, S > neo + Sx, and Sx-. RESULTS: Some cases had multiple affected lobes. In Sneo, symptoms developed in 55.6%, 50.0%, 0%, 0%, and 36.8% of right upper lobes (RUL), right middle lobes (RML), right lower lobes (RLL), left upper lobes (LUL), and left lower lobes (LLL) diagnosed with CPAM, prenatally. In S > neo, symptoms developed in 0%, 0%, 6.3%, 55.6%, and 33.3% of RUL, RML, RLL, LUL, and LLL diagnosed with CPAM, prenatally. CONCLUSION: In prenatally diagnosed CPAM, RUL and RML lesions are more likely to become symptomatic in neonates, and LUL lesions in infants. Surgery is recommended before the onset of respiratory infections after 1 year of age.

Detection of anti-type VII collagen IgE antibodies in epidermolysis bullosa acquisita.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare pemphigoid disease involving autoantibodies to type VII collagen (COL7), a major structural component of anchoring fibrils. IgE autoantibodies to type XVII collagen (BP180) have been identified in bullous pemphigoid (BP), the prototype of pemphigoid diseases. Although the pathogenic relevance of IgG anti-COL7 has been investigated, that of IgE in EBA remains unclear. OBJECTIVES: To reveal the presence and pathogenic relevance of IgE anti-COL7 in EBA. METHODS: We examined IgE antibodies in 109 patients with EBA by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). RESULTS: IIF with normal human skin revealed IgE reactivity in the basement membrane zone in 29 (26·6%) cases. To verify whether the IgE antibodies were specific to COL7, we performed IIF with 21 clearly positive cases and the skin of a patient with dystrophic EBA, which does not involve COL7. All cases showed negative results, indicating that IgE antibodies were specific to COL7. In a modified IgG COL7 ELISA for IgE, 16 (14·7%) cases were positive (three and 13 cases were negative and positive on IIF, respectively). We compared anti-COL7 IgG and IgE, and found a weak but significant correlation (r = 0·459, P < 0·001). EBA is clinically divided into a mechanobullous (MB; noninflammatory) type and an inflammatory (INF) type resembling BP. Of the IIF-positive cases, 11 of 30 (37%) had INF and nine of 48 (19%) had MB. CONCLUSIONS: This study is the first to demonstrate the presence of circulating anti-COL7 IgE in patients with EBA, which may correlate with the clinical phenotype.

Kinematic analysis of pressing situations in female collegiate football games: New insight into anterior cruciate ligament injury causation.

The most common events during which anterior cruciate ligament (ACL) injuries occur in football are pressing situations. This study aimed to describe the knee and hip joint kinematics during pressing situations in football games to identify kinematic patterns in actions with a high risk for ACL injuries. We filmed 5 female collegiate football matches and identified 66 pressing situations. Five situations with a large distance between the trunk and foot placements in the sagittal plane were analyzed using a model-based image-matching technique. The mean knee flexion angle at initial contact (IC) was 13° (range, 8°-28°) and increased by 11° (95% confidence interval [CI], 3°-14°) at 40 ms after IC. As for knee adduction and rotation angles, the knee positions were close to neutral at IC, and only minor knee angular changes occurred later in the sequences. The mean hip flexion was 25° (range, 8°-43°) at IC and increased by 22° (95% CI, 11°-32°) after 100 ms. The hip was also externally rotated by 7° (range, -19° to 3°) at IC, and gradually rotated internally, reaching 10° of internal rotation (range, -5° to 27°) at 100 ms after IC. This study suggests that the observed knee valgus, internal hip and knee rotation, and static hip flexion previously reported in non-contact ACL injury events are unique to injury situations. In contrast, neither rapid knee valgus nor increased internal rotation was seen in non-injury pressing maneuvers.

A clinical and serological study of linear IgA bullous dermatosis without linear immunoglobulin deposition other than IgA at the basement membrane zone using direct immunofluorescence.

BACKGROUND: Linear IgA bullous dermatosis (LABD) is a heterogeneous disease. Different diagnostic criteria have been used in different reports. OBJECTIVES: To reappraise the characteristic features of LABD with only IgA deposition at the basement membrane zone (BMZ) with direct immunofluorescence (DIF). METHODS: We retrospectively collected data from 101 patients from our archival records from 1 January 1996 to 31 December 2014 who had: (i) blisters on the skin and/or mucous membranes; (ii) subepidermal blisters in a biopsy specimen; and (iii) linear IgA deposition along the BMZ with/without linear C3 deposition at the BMZ with DIF. Most patients were referred for serological evaluation. Patients who showed concurrent linear IgG and/or IgM deposition at the BMZ under DIF were excluded. Clinical manifestations and serological findings were analysed. RESULTS: Heterogeneity of autoantigens in LABD was confirmed. Fifty-four of 101 patients (53%) had IgG antibodies detected either by indirect immunofluorescence, immunoblotting or enzyme-linked immunosorbent assays (ELISA). No statistical difference in clinical manifestations was found between patients in the IgG antibody-possessing group and patients in the other group. CONCLUSIONS: An association of IgG anti-BMZ antibodies with LABD may increase if new IgG immunoblotting or ELISA techniques become available. Consensus for diagnostic criteria for LABD is desired for prospective data storage, although it may be arbitrary.

Methodological Issues in Conducting Pilot Trials in Chronic Pain as Randomized, Double-blind, Placebo-controlled Studies.

BACKGROUND: The efficacy of tapentadol extended release (ER) for managing chronic pain has been demonstrated in large-scale, randomized, controlled, phase 3 studies (N=318-1,030) in patients with chronic osteoarthritis (OA) pain, low back pain (LBP), and pain related to diabetic peripheral neuropathy (DPN), which led to registration in many regions, including the United States and Europe. 2 pilot 12-week, randomized, double-blind, placebo-controlled phase 2 studies of tapentadol ER for chronic pain (OA knee pain or LBP, n=91; DPN or peripheral herpetic neuralgia [PHN] pain; n=91) were conducted in Japan. These small exploratory studies were substantially underpowered compared with the registration trials. METHODS: Patients in both studies were randomized (2:1) to tapentadol ER (25-250 mg) or placebo for 12 weeks (≤6-week titration plus maintenance periods). RESULTS: For the primary efficacy endpoint (change in pain intensity from baseline to last week of treatment; last observation carried forward), both studies failed to differentiate between tapentadol ER and placebo; least-squares mean differences (95% confidence intervals) for tapentadol ER vs. placebo were -0.1 (-1.04, 0.80) in the OA/LBP study and -0.1 (-1.10, 0.99) in the DPN/PHN study. More than 80% of patients took concomitant analgesics during these studies. Tapentadol was well tolerated. CONCLUSIONS: Both studies were associated with methodological issues, including populations with different disease entities, small sample sizes, use of concomitant analgesics, and possible placebo effect that may have led to the failure to differentiate between tapentadol ER and placebo.

Alterations in 18F-FDG accumulation into neck-related muscles after neck dissection for patients with oral cancers.

BACKGROUND: 18F-fluoro-2-deoxy-D-glucose (18F-FDG) accumulations are commonly seen in the neck-related muscles of the surgical and non-surgical sides after surgery with neck dissection (ND) for oral cancers, which leads to radiologists having difficulty in diagnosing the lesions. To examine the alterations in 18F-FDG accumulation in neck-related muscles of patients after ND for oral cancer. MATERIAL AND METHODS: 18F-FDG accumulations on positron emission tomography (PET)-computed tomography (CT) in neck-related muscles were retrospectively analyzed after surgical dissection of cervical lymph nodes in oral cancers. RESULTS: According to the extent of ND of cervical lymph nodes, the rate of patients with 18F-FDG-PET-positive areas increased in the trapezius, sternocleidomastoid, and posterior neck muscles of the surgical and/or non-surgical sides. In addition, SUVmax of 18F-FDG-PET-positive areas in the trapezius and sternocleidomastoid muscles were increased according to the extent of the ND. CONCLUSIONS: In evaluating 18F-FDG accumulations after ND for oral cancers, we should pay attention to the 18F-FDG distributions in neck-related muscles including the non-surgical side as false-positive findings.

Summary of results of serological tests and diagnoses for 4774 cases of various autoimmune bullous diseases consulted to Kurume University.

BACKGROUND: Although many new disease entities of autoimmune bullous disease (AIBD) have recently been recognized, satisfactory immunological diagnostic methods and comprehensive classifications for various AIBDs have not been established. OBJECTIVES: To identify immunological diagnostics and comprehensive classifications for AIBDs. METHODS: We selected and examined 4774 patients with various AIBDs from our cohort of 5063 patients with difficult AIBDs, whose sera and information were sent for our diagnostic method from other institutes in either Japan or other countries over the last 19 years. We examined the sera by our immunological diagnostic methods including various immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay tests to make final diagnoses. RESULTS: By our immunological diagnostic methods, we successfully made final diagnoses for approximately three-quarters of the difficult cases of AIBD, although the remaining cases could not be diagnosed. Using the results, we suggest the most extensive and newest classification of AIBDs, and also propose the most efficient algorithm of immunological tests for the diagnosis of various AIBDs. CONCLUSIONS: The results in this study of 4774 patients with various AIBDs indicate that our immunological diagnostic method is useful for making diagnoses for most patients with AIBD. However, we need further improvements including new immunological techniques to establish more satisfactory methods.

Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats.

OBJECTIVE: We investigated the effects of single or repetitive intra-articular injections of synovial mesenchymal stem cells (MSCs) on a rat osteoarthritis (OA) model, and elucidated the behaviors and underlying mechanisms of the stem cells after the injection. DESIGN: One week after the transection of the anterior cruciate ligament (ACL) of wild type Lewis rats, one million synovial MSCs were injected into the knee joint every week. Cartilage degeneration was evaluated with safranin-o staining after the first injection. To analyze cell kinetics or MSC properties, luciferase, LacZ, and GFP expressing synovial MSCs were used. To confirm the role of MSCs, species-specific microarray and PCR analyses were performed using human synovial MSCs. RESULTS: Histological analysis for femoral and tibial cartilage showed that a single injection was ineffective but weekly injections had significant chondroprotective effects for 12 weeks. Histological and flow-cytometric analyses of LacZ and GFP expressing synovial MSCs revealed that injected MSCs migrated mainly into the synovium and most of them retained their undifferentiated MSC properties though the migrated cells rapidly decreased. In vivo imaging analysis revealed that MSCs maintained in knees while weekly injection. Species-specific microarray and PCR analyses showed that the human mRNAs on day 1 for 21 genes increased over 50-fold, and increased the expressions of PRG-4, BMP-2, and BMP-6 genes encoding chondroprotective proteins, and TSG-6 encoding an anti-inflammatory one. CONCLUSION: Not single but periodic injections of synovial MSCs maintained viable cells without losing their MSC properties in knees and inhibited osteoarthritis (OA) progression by secretion of trophic factors.

Monoiodoacetic acid induces arthritis and synovitis in rats in a dose- and time-dependent manner: proposed model-specific scoring systems.

OBJECTIVE: In a rat monoiodoacetic acid (MIA)-induced arthritis model, the amount of MIA commonly used was too high, resulting in rapid bone destruction. We examined the effect of MIA concentrations on articular cartilage and infrapatellar fat pad (IFP). We also established an original system for "macroscopic cartilage and bone score" and "IFP inflammation score" specific to the rat MIA-induced arthritis model. DESIGN: Male Wistar rats received a single intra-articular injection of MIA in the knee. The amount of MIA was 0.1, 0.2, 0.5, and 1 mg respectively. Articular cartilage was evaluated at 2-12 weeks. IFP was also observed at 3-14 days. RESULTS: Macroscopically, low MIA doses induced punctate depressions on the cartilage surface, and cartilage erosion proceeded slowly over 12 weeks, while higher MIA doses already induced cartilage erosion at 2 weeks, followed by bone destruction. MIA macroscopic cartilage and bone score, OARSI histological score, and Mankin score increased in a dose- and time-dependent manner. The IFP inflammation score peaked at 5 days in low dose groups, then decreased, while in high dose groups, the IFP score continued to increase over 14 days due to IFP fibrosis. CONCLUSIONS: Punctate depressions, cartilage erosion, and bone destruction were observed in the MIA-induced arthritis model. The macroscopic cartilage and bone scoring enabled the quantification of cartilage degeneration and demonstrated that MIA-induced arthritis progressed in a dose- and time-dependent manner. IFP inflammation scores revealed that 0.2 mg MIA induced reversible synovitis, while 1 mg MIA induced fibrosis of the IFP body.

Clinical and immunological findings in 104 cases of paraneoplastic pemphigus.

BACKGROUND: Although there are many reports of sporadic patients with paraneoplastic pemphigus (PNP), only a few systematic studies on large cohorts of patients with PNP have been reported. OBJECTIVES: To analyse the clinical and immunological findings in a large cohort of patients with PNP. METHODS: This retrospective study consisted of 104 patients with PNP. Clinical and histopathological manifestations, associated neoplasms, complicating diseases, prognosis and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assays (ELISAs) were analysed. RESULTS: The clinical and histopathological findings in this study were generally similar to those in previous reports. The most common associated neoplasms included malignant lymphomas, malignant solid tumours and Castleman disease, in that order, while 12 patients had no detectable tumours. Novel ELISAs for desmocollins (Dscs) showed that 19 (18·6%), 42 (41·2%) and 62 (60·8%) of 102 patients with PNP showed antibodies to Dsc1, Dsc2 and Dsc3, respectively. Thirty-two (60%) of 53 patients had antibodies to alpha-2-macroglobulin-like protein 1 (A2ML1). We found statistically significant correlations between positive desmoglein 3 reactivity and genital lesions, and between positive desmoglein 3 reactivity and bronchiolitis obliterans. CONCLUSIONS: We consider that antibodies to Dscs and A2ML1 are useful for the diagnosis of PNP.

The BRAAFF checklist: a new dermoscopic algorithm for diagnosing acral melanoma.

BACKGROUND: The parallel ridge pattern (PRP) is considered the dermoscopic hallmark of acral melanoma (AM). However, it was recently shown that approximately one-third of AMs do not display a PRP dermoscopically, rendering their detection more troublesome. OBJECTIVES: To investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of AM. METHODS: Dermoscopic images of consecutive cases of histopathologically diagnosed AMs and acral naevi with histopathological diagnosis or with at least 1 year of follow-up were evaluated by three independent investigators for the presence of predefined criteria. Crude and adjusted odds ratios and their corresponding 95% confidence intervals were calculated by univariate and multivariate logistic regression, respectively. Receiver operating characteristic curves were used to choose among competing classification schemes. RESULTS: In total 603 lesions (472 naevi and 131 AMs) were included in the study. A scoring system (named BRAAFF) composed of six variables was associated with optimal area under the curve and sensitivity for the diagnosis of AM. This method includes four positive (irregular blotches, ridge pattern, asymmetry of structures and asymmetry of colours) and two negative predictors (furrow pattern and fibrillar pattern). CONCLUSIONS: The BRAAFF checklist significantly improves the diagnostic accuracy of dermoscopy for the diagnosis of AM.