Restricted kinematically aligned total knee arthroplasty with an anatomically designed implant can restore constitutional coronal lower limb alignment.

PURPOSE: Restricted kinematically aligned total knee arthroplasty (rKA-TKA) may not restore the constitutional varus alignment in most patients with knee osteoarthritis. This study aimed to investigate (1) the extent to which constitutional lower limb alignment can be restored by rKA-TKA using an anatomically designed implant and (2) which lower limb alignment parameters are associated with patient-reported outcome measures (PROMs). METHODS: This study included 60 patients who underwent rKA-TKA using an anatomically designed implant. Radiographic alignment parameters, including mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), coronal hip-knee-ankle angle (HKA), coronal joint line obliquity (JLO), posterior tibial slope (PTS), single-leg standing knee flexion angle (KFA), sagittal JLO, and arithmetic HKA (aHKA), were evaluated preoperatively and postoperatively. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used for clinical evaluation. RESULTS: The mLDFA, MPTA, and aHKA showed no significant differences before and after surgery. Coronal HKA and PTS have significantly changed from 8.1 ± 8.7° and 9.9 ± 8.6° preoperatively to 3.5 ± 3.1° and 2.5 ± 2.0° postoperatively, respectively (p < 0.001 for each comparison). The postoperative WOMAC total score was significantly correlated with the KFA (r = 0.4063, p = 0.0034) and sagittal JLO (r = -0.3435, p = 0.0157). Postoperative KFA is a causal factor for the increased postoperative WOMAC total score (r = 1.416, 95% confidence interval: 0.491-2.342, p = 0.003). CONCLUSION: rKA-TKA using an anatomically designed implant can restore constitutional coronal lower limb alignment, while postoperative KFA and sagittal JLO were associated with poor PROMs. Care should be taken for the postoperative KFA because it is a risk factor for poor PROMs. LEVEL OF EVIDENCE: Level III, case-control study.

Clinical characteristics and risk factors of pneumococcal diseases in recipients of allogeneic hematopoietic stem cell transplants in the late phase: A retrospective registry study.

Pneumococcal diseases are one of the most important infectious complications in the late period following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The importance of long-term follow-up care is increasing, as the number of long-term survivors following allo-HSCT increases, but there has been a dearth of research specifically focusing on pneumococcal diseases during the late post-transplant period (day >100). Using a transplant registry database between January 1, 2001 and December 31, 2011, we aimed to assess the clinical spectrum and risk factors for pneumococcal diseases in the late post-transplant period. Among the 22,514 recipients who received allo-HSCT over an 11-year period and could be followed for ≥100 days, 43 patients developed 49 episodes of pneumococcal diseases. Six of the 43 patients died from pneumococcal diseases, and four of these six patients died within a week, despite having undergone allo-HSCT two or more years ago. A history of chronic graft-versus-host disease (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.15-4.66; P = 0.02), viral infection (OR, 3.38; 95% CI, 1.70-6.72; P < 0.01), and complete remission of the underlying disease at the time of transplantation (OR, 2.38; 95%CI, 1.10-5.14; P = 0.03) were identified as risk factors. Given the risk of sudden death and the high mortality rate, attention should be paid to pneumococcal diseases in providing long-term follow-up care, even several years after allo-HSCT.

Joint gap produced by manual stress is dependent on the surgeon's experience and is smaller in flexion in robotic-assisted total knee arthroplasty.

PURPOSE: This study aimed to retrospectively investigate (1) the reproducibility of gap measurements by manual stress using the Z-shaped retractor depending on the surgeon's experience with this maneuver and (2) the consistency of the gap distraction force produced by manual stress throughout the range of motion (ROM) in the robotic-assisted total knee arthroplasty (TKA). It was hypothesized that the joint gap produced by manual stress is not reproducible depending on the surgeon's experience, and the distraction force applied by manual stress throughout the ROM is not constant. METHODS: Medial and lateral joint gaps were obtained throughout the ROM by manual stress or a tensioner by two surgeons with different levels of experience in robotic-assisted TKA. The association between the differences in gap measurement by the two surgeons and the preoperative radiographic parameters, including the hip-knee-ankle (HKA) angle and absolute and relative varus/valgus laxities were analyzed. RESULTS: The experienced surgeon produced significantly greater gaps than the inexperienced surgeon from 0° to 100° flexion, with a mean difference of 0.35 ± 0.12 mm in the medial gap (p < 0.0001), and from 10° to 120° flexion with a mean difference of 0.57 ± 0.13 mm in the lateral gap (p < 0.0001). The tensioner produced a significantly greater medial gap from 70° to 110° flexion with a mean difference of 0.32 ± 0.01 mm in the medial gap (p < 0.0001) and from 0° to 110° flexion with a mean difference of 1.12 ± 0.26 mm in the lateral gap (p < 0.0001). The differences in gap distance by manual stress between experienced and inexperienced surgeons were moderately correlated with the HKA angle in the lateral gap (r = 0.40, p = 0.01). The gap differences due to manual stress and a tensioner showed moderate negative correlation with the HKA angle in the medial gap (r = - 0.50, p = 0.001) and weak negative correlation with the absolute valgus laxity in the lateral gap (r = - 0.35, p = 0.03). CONCLUSIONS: The joint distraction force by manual stress may differ depending on the surgeon's experience and tended to be smaller in deep flexion; therefore, the flexion gap may be underestimated. Surgeons should determine implant positioning considering gap balance by manual stress, taking into account these characteristics of the manual stress maneuver. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Spontaneous morphological remodelling of the O-C1 joint after posterior fusion for occipitocervical dislocation.

BACKGROUND: Traumatic occipitocervical dislocation (OCD) occurs due to fatal high-energy injury. Modern screw-based constructs enable successful reduction and stabilisation. In view of this, there are no previous reports on the spontaneous remodelling of the O-C1 joint after posterior fusion. We report the first case of postoperative spontaneous remodelling and stabilisation of the O-C1 joint after traumatic OCD.Case description: A 9-year-old girl suffered from traumatic OCD, accompanied by complete rupture of the O-C1-C2 ligamentous complex. Halo-vest fixation, and subsequently posterior fusion surgery from the occipital bone to C2, with autologous iliac crest bone graft and an allograft were performed. However, we could not achieve complete reduction of the O-C1 joint during surgery owing to extremely severe instability.Postoperative X-ray and computed tomography scan showed incomplete reduction of the O-C1 joint. Insufficient congruity of the O-C1 joint persisted. Afterwards, gradual spontaneous remodelling of the O-C1 joint occurred, both anteriorly and posteriorly 3 months postoperatively. Solid union was achieved 6 months postoperatively. Two years later, bilateral O-C1 joints in the patient were completely reformed and restabilised by incredible vigorous remodelling. Insufficient reduction and persisting poor joint congruence after surgery for OCD was probably restabilised by further spontaneous remodelling of articular morphology in such a young patient. CONCLUSIONS: Postoperative spontaneous remodelling of the O-C1 joint after posterior reconstruction for OCD may occur in young patients. Incomplete reduction of the O-C1 joint during surgery may be acceptable due to the possibility of postoperative bone remodelling and restabilisation.

Medial proximal tibial angle at the posterior tibial plateau represents the pre-arthritic constitutional medial proximal tibial angle in anterior cruciate ligament-intact, advanced osteoarthritis of the knee.

PURPOSE: In kinematically aligned total knee arthroplasty (TKA), it is necessary to infer the pre-arthritic constitutional medial proximal tibial angle (MPTA) in advanced osteoarthritis (OA) of the knee with bone loss. The aim of this study was to investigate whether MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA in anterior cruciate ligament (ACL)-intact, advanced OA knees. It was hypothesized that MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA of ACL-intact, advanced knee OA. METHODS: One hundred varus, anterior cruciate ligament (ACL)-intact, advanced OA knees were analysed. The hip-knee-ankle (HKA) angle and MPTA were assessed on computed radiography (CR) and MPTAs at the anterior, middle, and posterior part of the tibial plateau were assessed on computed tomography (CT) images. The association between these parameters was also analysed. RESULTS: CR images showed an HKA angle of 172.4 ± 4.1° and MPTA of 84.3 ± 2.5°. CT images showed different MPTAs in the three regions, ranging from 83.9 ± 2.4° to 85.9 ± 2.8°. The middle MPTA was the lowest at 83.9 ± 2.4°. HKA angle correlated with the middle MPTA (r = 0.3355, 95% confidence interval [CI] 0.1489-0.4991, p = 0.0006) and ΔMPTA (Middle-Posterior) (r = 0.5128, 95% CI 0.3518-0.6443, p < 0.0001). CONCLUSION: The MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA in ACL-intact, advanced OA knees. LEVEL OF EVIDENCE: III, retrospective cohort study.

Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways.

Lubricin is a secreted proteoglycan encoded by the Prg4 locus that is abundantly expressed by superficial zone articular chondrocytes and has been noted to both be sensitive to mechanical loading and protect against the development of osteoarthritis. In this study, we document that running induces maximal expression of Prg4 in the superficial zone of knee joint articular cartilage in a COX-2-dependent fashion, which correlates with augmented levels of phospho-S133 CREB and increased nuclear localization of CREB-regulated transcriptional coactivators (CRTCs) in this tissue. Furthermore, we found that fluid flow shear stress (FFSS) increases secretion of extracellular PGE2, PTHrP, and ATP (by epiphyseal chondrocytes), which together engage both PKA- and Ca(++)-regulated signaling pathways that work in combination to promote CREB-dependent induction of Prg4, specifically in superficial zone articular chondrocytes. Because running and FFSS both boost Prg4 expression in a COX-2-dependent fashion, our results suggest that mechanical motion may induce Prg4 expression in the superficial zone of articular cartilage by engaging the same signaling pathways activated in vitro by FFSS that promote CREB-dependent gene expression in this tissue.

Fracture of the tibial tubercle does not affect clinical outcomes in medial opening wedge high tibial osteotomy with distal tibial tubercle osteotomy.

PURPOSE: To investigate whether tibial tubercle fracture affected clinical outcomes and bony union in medial opening wedge high tibial osteotomy with distal tibial tubercle osteotomy (DTO) and to determine the anatomical risk factors for tibial tubercle fracture. MATERIALS AND METHODS: All patients who underwent DTO were retrospectively reviewed, and 104 successive patients were included. The Knee Society Score and complications including tibial tubercle fracture were recorded. On radiographs and computed tomography scans, the length, thickness, width, height, and bony union of the osteotomized tibial tubercle and the posterior tibial slope were statistically analysed. RESULTS: Fracture of the tibial tubercle occurred intraoperatively in 11 patients (10.6%) and in the postoperative period in 1 (1.0%). The case of postoperative fracture showed non-union. There was no significant difference in the Knee Society Score between the non-fracture and fracture groups. There were significant differences in the posterior tibial slope and the height of the tibial tubercle between the groups (p < 0.0001 for each comparison). The logistic regression analysis showed that the height of the tibial tubercle was associated with a higher risk of the fracture of the tibial tubercle (p < 0.01; OR, 1.548; 95% CI, 1.149-2.085). However, there were no significant differences in the bony union rate of the tibial tubercle at 6 months after surgery between the groups. CONCLUSIONS: Tibial tubercle fracture did not affect the clinical outcome and bony union in spite of the relatively high occurrence rate. Anatomical risk factors for the fractures was a lower tibial tubercle position. LEVEL OF EVIDENCE: Level IV.

Relationship Between Corticosteroid Dose and Muscle Oxygen Consumption in Recipients of Hematopoietic Stem-Cell Transplantation.

INTRODUCTION: After hematopoietic stem-cell transplantation (HSCT), patients exhibit decreased muscle strength and muscle oxygen consumption. Furthermore, total corticosteroid dose affects the reduction in muscle strength after HSCT. However, to date, no studies have investigated the relationship between corticosteroid dose and muscle oxygen consumption and saturation in these patients. The purpose of this study was to investigate the relationship between steroid dose and deoxyhemoglobin (ΔHHb) and muscle oxyhemoglobin saturation (ΔSmO2) in patients undergoing HSCT. METHODS: This study included 17 men with hematologic disease who underwent allogeneic HSCT. We evaluated ankle dorsiflexor muscle force, ΔHHb, and ΔSmO2 in skeletal muscles by near-infrared spectroscopy (NIRS) in patients before and after HSCT. RESULTS: Peak ankle dorsiflexion, ΔHHb, and ΔSmO2 decreased significantly after transplantation as compared to measurements taken before transplantation (p < 0.01). The change in peak ankle dorsiflexion from before to after HSCT was not significantly correlated with total steroid dose. However, ΔHHb and ΔSmO2 from before to after HSCT were significantly correlated with total steroid dose (p < 0.01). CONCLUSION: This study showed that higher corticosteroid doses are associated with diminished skeletal muscle O2 consumption and skeletal muscle O2 demand relative to supply. Therefore, rehabilitation staff, nurses, and physicians should take note of these findings in patients undergoing HSCT. Moreover, physiotherapists should be carefully measuring muscle oxidative metabolism on skeletal muscle when planning physical exercise in such patients.

Correlation between mutated genes and forearm deformity in patients with multiple osteochondroma.

BACKGROUNDS: Exostosin-1 (EXT1) and exostosin-2 (EXT2) cause multiple osteochondromas (MO). In this study, we investigated the correlation between forearm deformity and mutant EXTs in Japanese families with MO. METHODS: We evaluated 112 patients in 71 families with MO. Genomic DNA was isolated from peripheral blood leucocytes. Of these, 28 patients were selected and underwent radiography for their forearms since they had gross forearm deformities. We measured the radial articular angle (RAA), ulna variance (UV), carpal slip (CS), and percentage of radial bowing (%RB) to compare between patients with mutant EXT1 or EXT2 and those with missense or other mutations using Student's t-test. RESULTS: Twenty-two (78.6%) and 6 (11.4%) out of 28 patients had mutations in EXT1 and EXT2, respectively. Nine (32.1%) and 19 (67.9%) of the 28 patients had missense and other mutations, respectively. The mean age of patients with EXT1 and EXT2 were 25.9 ± 20.3 and 33.5 ± 25.4 years, respectively and those with missense mutation and other mutations were 28.7 ± 27.0 and 24.6 ± 17.0 years, respectively. There were no significant differences in RAA, UV, and RB between patients harbouring mutant EXT1 or EXT2 (RAA, 40.1 ± 8.7 and 31.5 ± 13.9°; UV, -2.7 ± 5.7 and -3.1 ± 3.7 mm; %RB, 8.6 ± 1.5 and 8.3 ± 2.0%). CS was significantly greater in patients with mutant EXT1 than that in those with mutant EXT2 (EXT1, 44.1 ± 16.8%; EXT2, 18.6 ± 14.0%). There were no significant differences in RAA, UV, CS and %RB between patients with missense and other mutations. CONCLUSIONS: Patients with mutant EXT1 displayed greater CS than patients with mutant EXT2, indicating that patients with MO harbouring EXT1 mutations sustain more severe ulnar drift deformities than those with EXT2 mutations.

Relationship Between Exercise Capacity and Muscle O2Hb Saturation in Patients Before Hematopoietic Stem-Cell Transplantation.

Patients with hematological malignancy might already have decreased muscle oxygen saturation at rest and exercise capacity before undergoing hematopoietic stem cell transplantation (HSCT). However, to date, no studies have investigated the relationship between exercise capacity and muscle oxygen saturation at rest in these patients. Therefore, purpose of this study was to investigate the relationship between exercise capacity and muscle oxygen-hemoglobin (O2Hb) saturation (SmO2) at rest and patients' hemoglobin level before undergoing HSCT. METHODS: This study included 60 men with hematologic disease who underwent allo-HSCT. Patients performed a 6-minute walk test (6MWT) to determine exercise capacity, and muscle O2Hb saturation at rest was evaluatabed using near-infrared spectroscopy (BOM-L1TRW, Omegawave Inc., Japan); hemoglobin levels in hematological malignancy patients before undergoing HSCT were also evaluated. RESULTS: There was a significant correlation between the 6MWT and muscle O2Hb saturation at rest in hematological malignancy patients (p < 0.05). Additionally, the 6MWT was significantly correlated to the hemoglobin level (p < 0.05). Furthermore, muscle O2Hb saturation at rest was significantly related to hemoglobin level (p < 0.05). CONCLUSION: In patients with hematological malignancy, a relationship exists between exercise capacity, muscle O2Hb saturation, and hemoglobin level before they undergo HSCT. Therefore, rehabilitation staff, nurses, and physicians should recognize these relationships in patients who undergo allo-HSCT. Moreover, physiotherapists may need to promote muscle oxidative metabolism through exercise to increase exercise capacity in these patients.

Relationship Between Muscle Oxygen Saturation and Exercise Load in Patients with Malignant Hematopoietic Disease.

Our previous research confirmed that patients with malignant hematopoietic disease already had a low hemoglobin level before allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no study has determined whether a correlation exists between exercise load, hemoglobin level, and muscle oxygen saturation (SmO2), during exercise. Therefore, the purpose of this study was to investigate whether near-infrared spectroscopy (NIRS)-derived SmO2 is associated with exercise load, as determined by a dynamometer, before allo-HSCT. This study included 19 male patients who received allo-HSCT in Hyogo College of Medicine Hospital (Japan) between November 2009 and October 2012. Patients performed isometric repeated dorsiflexion at 50% maximum voluntary contraction for 180 s to determine exercise load, and SmO2 was evaluated during exercise at the same time using NIRS (BOM-L1TRW, Omega Wave, Inc., Japan). The hemoglobin level was also evaluated before allo-HSCT. Patients with hematopoietic disease before allo-HSCT already had a low hemoglobin level. There was a significant correlation between exercise load and ∆SmO2; however, the hemoglobin level was not correlated with exercise load. In these patients, exercise load might be affected by muscle oxygen consumption rather than by the hemoglobin level. This finding shows that NIRS can used to assess fatigue in patients with malignant hematopoietic disease.

Radiographic characteristics of the hip joint in skeletally mature patients with multiple hereditary exostoses.

OBJECTIVE: To elucidate the radiological characteristics of the hips, especially in proximal femur, of skeletally mature patients with multiple hereditary exostoses (MHE). MATERIALS AND METHODS: Fifty eligible patients (100 hips) were included in the study and assigned to the MHE group. The control group included age- and sex-matched individuals, and the radiographs of 100 hips were used as controls. We examined the anatomical characteristics of the acetabulum and the proximal femur, including the acetabular depth-width ratio (ADR), Sharp's angle, femoral neck-shaft angle (NSA), Wiberg's centre-edge angle (CEA), femoral neck axis length (FNAL), femoral head diameter, (FHD), femoral neck width (FNW), femoral shaft width (FSW), femoral neck-shaft angle (NSA), and femoral head-neck ratio (FHNR = FHD/FNW). p value < 0.05 was considered significant. RESULTS: Osteochondroma was frequently observed in the medial femoral neck (79%), but it was rarely found in the femoral head (1%). ADR and Sharp's angle were not significantly different between the MHE and control groups (p = 0.2056, p = 0.5025). CEA was significantly different between the two groups (p < 0.0001). FNW was significantly larger in the MHE group than in the control group (p < 0.0001). FHNR was significantly different between the two groups (p < 0.0001). NSA was significantly larger than the MHE group (141.8° ± 9.7° vs 129.5° ± 5.6°, p < 0.0001). CONCLUSIONS: Hip dysplasia in the pelvic side was not commonly observed in skeletally mature MHE patients. However, they showed femoral neck widening and coxa valga. The occurrence of osteochondroma around the femoral neck affects the degree of valgus deformity. These facts could be useful for orthopaedic surgeons treating MHE patients.

Arthroscopic repair of horizontal cleavage meniscus tears provides good clinical outcomes in spite of poor meniscus healing.

PURPOSE: The purpose of this study was to evaluate the clinical outcomes and meniscus healing after arthroscopic repair of horizontal-cleavage meniscus tears, compared with vertical-longitudinal meniscus tears. METHODS: This was a retrospective review of a consecutive series of 52 meniscal repairs for horizontal-cleavage tears (n = 27) or vertical-longitudinal tears (n = 25); the groups were compared with respect to clinical symptoms and meniscal healing. Arthroscopic meniscal repair was performed using the inside-out technique with a marrow-stimulating technique. Clinical symptoms were evaluated using the Lysholm score and Knee injury and osteoarthritis outcome score (KOOS). Meniscus healing was evaluated by MRI. RESULTS: The mean follow-up periods were 35.4 ± 8.9 months in the horizontal-cleavage tear group and 39.8 ± 8.3 months in the vertical-longitudinal tear group. There were no significant differences in Lysholm score and KOOS, including each subscale, between the horizontal-cleavage tear- and vertical-longitudinal tear-groups at the final follow-up. At the final follow-up, MRI meniscus grades 0 and 1 were significantly more frequent in the vertical-longitudinal tear-group than in the horizontal-cleavage tear-group, while grade 3 was significantly more frequent in the horizontal-cleavage tear group than in the vertical-longitudinal tear group (p < 0.0001). CONCLUSIONS: Although meniscus healing of horizontal-cleavage tears may be poor, arthroscopic repair should be considered for horizontal-cleavage tears because it does provide good clinical outcomes. LEVEL OF EVIDENCE: IV.

Distal tibial tubercle osteotomy is superior to the proximal one for progression of patellofemoral osteoarthritis in medial opening wedge high tibial osteotomy.

PURPOSE: To investigate the effect of proximal tibial tubercle osteotomy (PTO) and distal tibial tubercle osteotomy (DTO) in medial opening wedge high tibial osteotomy on patellofemoral alignment, patellofemoral osteoarthritis and clinical outcomes. METHODS: PTO (n = 41) and DTO (n = 43) for the same surgical indications were included. Radiographic measurements of the Caton-Deschamps index, patellar tilt and shift, and arthroscopic cartilage evaluation at the patellofemoral joint were performed at osteotomy and plate removal. The Knee Society Score (KSS) was evaluated preoperatively and at the latest follow-up. RESULTS: The follow-up period was longer in the PTO group (33.7 months; range 23-40 years) than in the DTO group (22.2 months; range 18-29 months) (p < 0.0001), whereas the period from osteotomy to plate removal was not different between the groups. The Caton-Deschamps index of the DTO group was unchanged from 0.9 (range 0.7-1.2) to 0.9 (range 0.6-1.4), whereas that of the PTO group changed from 0.9 (0.7-1.2) to 0.7 (0.5-1.0) (p < 0.0001). There were fewer deteriorated cases of cartilage status in the trochlear groove in the DTO group (20.9%) than in the PTO group (56.1%, p < 0.05). There were more improved cases in the DTO group (23.3%) than in the PTO group (4.9%, p < 0.05). Postoperative KSS was better in the DTO group than in the PTO group (p < 0.05). CONCLUSION: DTO is associated not only with reduced deterioration but also with increased improvement of cartilage status in the trochlear groove and better KSS as compared with PTO. LEVEL OF EVIDENCE: IV.

Low incidence of HHV-6 reactivation in haploidentical hematopoietic stem cell transplantation with corticosteroid as graft-vs-host disease prophylaxis compared with cord blood transplantation.

BACKGROUND: Human leukocyte antigen (HLA) mismatch and the administration of immunosuppressive agents are considered risks for human herpesvirus 6 (HHV-6) reactivation after stem cell transplantation (SCT). However, the incidence of HHV-6 reactivation in HLA-mismatched related SCT remains unknown. METHODS: We monitored plasma HHV-6 DNA loads weekly using real-time quantitative polymerase chain reaction for 5 weeks after SCT and compared serum IL-6 levels in HLA-mismatched SCT groups. RESULTS: Compared with detection in all 11 umbilical cord blood transplantation (CBT) patients (100%), plasma HHV-6 DNA was detected in only 3 of 42 haplo-SCT patients (7.1%) despite the use of methylprednisolone and antithymocyte globulin as graft-vs-host disease prophylaxis and a reduced-intensity conditioning regimen, respectively. Correspondingly, serum IL-6 levels in haplo-SCT patients were significantly lower than those in CBT patients. No HHV-6-associated encephalitis developed in either groups. CONCLUSIONS: Neither HLA disparity nor the use of methylprednisolone and antithymocyte globulin were risk factors for HHV-6 reactivation in our haplo-SCT patients. Rather than increasing risk, the administration of immunosuppressive agents potentially prevented HHV-6 reactivation after haplo-SCT by suppressing IL-6 production.

ACL degeneration after an excessive increase in the medial proximal tibial angle with medial open wedge high tibial osteotomy.

PURPOSE: This study examined the influence of the mechanical medial proximal tibial angle (MPTA) on anterior cruciate ligament (ACL) degeneration following open wedge high tibial osteotomy (OWHTO). It was hypothesised that an excessive increase in MPTA would be associated with ACL degeneration following OWHTO. METHODS: Seventy-four knees treated with OWHTO were retrospectively examined. Arthroscopic ACL grading [0 (intact) to 4 (complete rupture)], anterior tibial translation (ATT) test at the time of OWHTO with the index arthroscopy and at plate removal with the second-look arthroscopy, clinical assessments using the Knee Society Score (KSS), and radiographic evaluations of MPTA were performed. The relationship between MPTA and the ACL condition was analysed using Spearman's correlation. RESULTS: The time from the index arthroscopy to the second-look arthroscopy was 15.0 ± 4.4 months; the total follow-up was 31.0 ± 6.5 months. ACL grade significantly increased from 0.6 ± 0.8 (index arthroscopy) to 1.1 ± 1.2 (second-look arthroscopy) (p < 0.0018). ATT on the operated side significantly decreased from 7.1 ± 2.6 mm preoperatively to 5.3 ± 2.3 mm at the time of plate removal (p < 0.001). No significant difference was observed in KSS for ACL grades in the steady and progression groups. Changes in MPTA from the preoperative to postoperative period were significantly higher in the progression group (p = 0.0155). Changes in ACL grades were significantly correlated with preoperative MPTA and changes in MPTA (r = - 0.365 and 0.343, respectively; p < 0.01). CONCLUSIONS: Excessively increased MPTA led to ACL degeneration following OWHTO. ACL degeneration was not associated with short-term clinical outcomes. Excessive correction of MPTA should be avoided to prevent ACL degeneration following OWHTO. LEVEL OF EVIDENCE: Therapeutic case series, Level IV.

Joint Space Width, but not Osteophyte Thickness, is a Reliable Indicator of Degeneration of Lateral Knee Joint Cartilage.

In this histologically controlled in vitro study, we evaluated the validity of plain radiography for the assessment of lateral knee joint cartilage degeneration (25 specimens). We examined the correlation between histological grade and radiography findings along with patient demographics. Our study indicated that the Mankin score had a significant inverse correlation with middle joint space width (JSW ; r=-0.19,P=0.02), but not with inner and outer JSW (inner : r=-0.11,P=0.10, outer : r=-0.14,P=0.06) under a non-weight bearing condition. The Mankin score had a significant inverse correlation with middle and outer JSW (middle : r=-0.17,P=0.04, outer : r=-0.14,P=0.04), but not with inner JSW (inner : r=-0.15,P=0.06) under valgus stress. There was no significant correlation between the Mankin score and osteophyte thickness (r=0.004,P=0.76). We also examined the correlation with patient demographics. We found that only the preoperative femorotibial angle had a significant inverse correlation with the Mankin score. These results indicate that JSW, but not osteophyte thickness, is reliable for evaluating lateral femoral cartilage degeneration.

Impact of a Low CD34+ Cell Dose on Allogeneic Peripheral Blood Stem Cell Transplantation.

Although the CD34+ cell dose in allogeneic peripheral blood stem cell transplantation (PBSCT) is considered to be associated with transplantation outcomes, a lower acceptable threshold has not been defined. We retrospectively analyzed 2919 adult patients with hematologic malignancies who underwent related PBSCT in Japan between 2001 and 2014. According to the number of CD34+ cells in the graft, we categorized 2494 patients in the standard group (2 to 5 × 106 cells/kg), 377 patient in the low group (1 to 2 × 106 cells/kg), and 48 patients in the very low group (<1 × 106 cells/kg). Compared with the standard group, the low and very low groups showed delayed neutrophil recovery (93.8%, 89.5%, and 78.3%, respectively at day +28; P < .001) and platelet recovery (69.3%, 53.0%, and 45.5%, respectively at day +28; P < .001). The 2-year overall survival (OS) in the 3 groups was 45.5%, 45.3%, and 29.8%, respectively, with inferior survival in the very low group. However, a higher percentage of high-risk patients may account for the inferior survival in the very low group, and no significant difference in OS was found in a multivariate analysis. There were no differences in relapse, nonrelapse mortality, or the development of graft-versus-host disease among the 3 groups. In conclusion, allogeneic PBSCT with low CD34+ cell doses of 1 to 2 × 106 cells/kg gives acceptable results, whereas further investigations are needed to evaluate the effects of lower doses of <1 × 106 cells/kg owing to the smaller number and the higher percentage of patients with adverse prognostic factors in this cohort.

A prospective multicenter phase II study of intrabone marrow transplantation of unwashed cord blood using reduced-intensity conditioning.

Cord blood transplantation (CBT) is associated with delayed hematopoietic recovery and graft failure. To overcome these problems, we conducted a prospective, multicenter phase II study of intrabone marrow transplantation in which patients received reduced-intensity conditioning without anti-thymocyte globulin (ATG). The primary endpoint was the probability of full donor engraftment. Forty patients with hematologic malignancies were enrolled. Cord blood (CB) cells were injected without washing into 4 iliac bone sites (2 at each hemipelvis), at which approximately 6 mL of CB was administered at one site with local anesthesia. Full donor engraftment rate was 86.8%. The cumulative incidence of neutrophil and platelet engraftment was 86.4% and 85.5%, respectively. The median time to neutrophil (>0.5 × 109 /L) and platelet (2.0 × 109 /L) recovery was 17.5 and 44 days, respectively. The probability of severe acute graft-vs-host disease (GVHD) was 47.5%. The cumulative incidence of extensive chronic GVHD was 3.0%. The probability of relapse and non-relapse mortality was 30.4% and 28.0%, respectively. The survival rate at 3 years was 45.6%, although most patients were at an advanced stage. These results suggest that our intrabone marrow-CBT procedure without using ATG improves hematopoietic recovery and decreases the incidence of chronic GVHD, but does not decrease the incidence of acute GVHD.

Host Foxp3+CD4+ Regulatory T Cells Act as a Negative Regulator of Dendritic Cells in the Peritransplantation Period.

Host Foxp3+CD4+ regulatory T cells (Tregs) have been shown to suppress graft-versus-host disease (GVHD) in experimental bone marrow transplantation (BMT) models; however, the detailed mechanism is unknown. To address this issue, we established a murine MHC-haploidentical BMT model (BDF1 (H-2b/d) → B6C3F1 (H-2b/k)), in which transplantation following conditioning with high-dose (13 Gy) or low-dose (5 Gy) total body irradiation corresponds to myeloablative stem cell transplantation (MAST) or reduced-intensity stem cell transplantation (RIST) BMT. All MAST recipients died of GVHD within 70 d, whereas RIST recipients developed almost no GVHD and survived for at least 3 mo. In this BMT model, we investigated the kinetics of immune cells in the mesenteric lymph nodes because GVHD was most prominent in the intestines. Host Tregs that survived after total body irradiation could proliferate transiently by day 4. Comparing the kinetics of immune cells among MAST, RIST, and anti-CD25 mAb-treated RIST, we found that the transiently surviving host Tregs were fully functional, closely contacted with host dendritic cells (DCs), and significantly restrained the maturation (CD80 and CD86 expression) of DCs in a dose-dependent manner. There was a positive correlation between the ratio of DCs to host Tregs and the extent of maturation of DCs. Host Tregs suppressed alloresponse mainly by contact inhibition. Host Tregs are already active in lymph nodes before transplantation and restrain the maturation of host DCs, thereby dampening the ability of DCs to activate allogeneic donor T cells and consequently reducing the magnitude of graft-versus-host reaction. Thus, host Tregs are negative regulators of host DCs that act in the peritransplantation period.