Anteromedial plating without filling the gap in open wedge high tibial osteotomy may increase the risk of screw breakage, which can be reduced by medial plating and bone-substitute insertion.

BACKGROUND: Open wedge high tibial osteotomy (OWHTO) brings new complications such as screw breakages with or without correction loss and time-dependent increased posterior tibial slopes (PTS) due to the opening gap. For preventive purposes, we changed our OWHTO procedure from anteromedial plating without filling the gap (non-grafted group, n = 40, 2009-2012) to medial plating with bone-substitute insertion (grafted group, n = 45, 2012-2015). The objectives of this study were to evaluate the complication patterns and the effects of the modifications. METHODS: Patients undergoing OWHTO with TomoFix plates were included in this retrospective study. Demographics, clinical outcomes (flexion range and Japanese Orthopaedic Association score) and radiological outcomes (femorotibial angle) were assessed in both groups pre-operatively and 2-years postoperatively. The plate installation angle [PIA] and screw insertion depth [SID] were measured on computed tomographic slices at 6 months. PIA/SID was defined as the angle between the tibial anteroposterior axis and plate-width axis/the distance between the proximal screw tip and the proximal tibiofibular joint. The non-grafted group was further divided into complication and non-complication subgroups. Screw breakages were assessed during plate removal (1.5-2.5 years postoperatively). RESULTS: There were no differences in baseline characteristics or radiological/clinical outcomes between the non-grafted and grafted groups. There were 0 and 11 complications in the grafted and non-grafted groups, respectively. Complications included 7 screw breakages, 4 correction losses, and 5 time-dependent increased PTS with some overlaps. PIA and SID were significantly lower (p < 0.001) and higher (p < 0.001), respectively, in the grafted group and significantly lower (p = 0.018) and higher (p = 0.040), respectively, in the non-complication subgroup within the non-grafted group. The cutoff value of PIA for complications was calculated at 48.0°. CONCLUSIONS: Medial plating OWHTO (PIA<48°) using bone-substitute with deeper screw insertion reinforces the opening gap for better angular stability compared with anteromedial plating without bone-substitute.

A spreading roots sign: Characteristic sign of the preliminary stage of medial meniscus posterior root tear on magnetic resonance imaging.

BACKGROUND: Medial meniscus posterior root tears (MMPRTs) can result in the development of osteoarthritis or osteonecrosis. Clinical experience suggests that symptoms such as dull pain or discomfort in the popliteal area or the calf area, which are sometimes misdiagnosed as sciatic nerve pain, may precede impending rupture. We found that bone marrow edema emanating from the meniscal root on magnetic resonance imaging (MRI) scans-spreading roots sign-may indicate the preliminary stage of an MMPRT. The purpose of this study was to evaluate the efficacy of the spreading roots sign as an MMPRT-predictor. METHODS: In a retrospective study, we reviewed the chart data and MRI results of patients who had required surgery for an acute MMPRT. We grouped patients by whether or not they had reported the above-mentioned precursory symptoms prior to acute rupture (precursory symptom group/non-precursor group), and when possible, we examined MRI scans to identify with which events the appearance/disappearance of the spreading roots sign coincided. Sex, age, body mass index, bone mineral density, radiological parameters, and MRI parameters were compared between groups. RESULTS: Data from 24 patients (precursory symptom group, n = 17 [70.8 %]; non-precursor group, n = 7 [29.2 %]) were included; data from 5 patients included MRI scans prior to acute rupture. There were no significant differences between precursory symptom and non-precursor groups, except for the ratio of the presence of the spreading roots sign (p = 0.005). The appearance of the spreading roots sign on MRI scans coincided with the onset of precursory symptoms, and its disappearance coincided with acute rupture and the appearance of other MRI signs typical of MMPRT (white meniscus/truncation/meniscal extrusion/giraffe neck signs). CONCLUSIONS: Our findings suggest that the spreading roots sign can be used as a unique precursory sign for MMPRT.

Factors Associated with Dose Modification of Lenalidomide Plus Dexamethasone Therapy in Multiple Myeloma.

Long-term combination treatment with lenalidomide and low-dose dexamethasone is important to achieve a curative effect in patients with multiple myeloma (MM). In this study, the plasma concentration of lenalidomide was measured at 3 h after oral administration, when the drug is in the elimination phase and can be easily measured in outpatients, to identify factors that may lead to the discontinuation of this combination therapy. Patients were assigned to continuation or discontinuation of therapy groups, and the baseline characteristics of patients, lenalidomide concentration, and concentration/dose (C/D) ratios reflecting oral clearance were compared between the two groups. The efficacy and severity of adverse events were also compared. The results showed that patients who discontinued or modified treatment had low plasma concentrations of lenalidomide and C/D ratios, indicating high oral clearance of lenalidomide. The estimated creatinine clearance rate was negatively correlated with the C/D ratio. The plasma concentrations of lenalidomide were independent from kidney function and differed significantly among patients. Taken together, the results indicate that low plasma concentrations of lenalidomide and low C/D ratios may lead to discontinuation of combination therapy in patients with MM. This suggests that early measurement of lenalidomide plasma continuation would help to prevent discontinuation of therapy or a delay in modifying the dose of lenalidomide.

[Successful treatment of relapse/refractory multiple myeloma with carfilzomib, lenalidomide, and dexamethasone combination therapy following allogeneic bone marrow transplantation].

A 50-year-old male was diagnosed with multiple myeloma (MM) and treated by high-dose melphalan followed by autologous stem cell transplantation in April 2014. However, he relapsed and received non-myeloablative bone marrow transplantation from an unrelated HLA-matched donor (UR-BMT) in July 2016. After 100 days of UR-BMT, the disease remained stable disease and the patient was treated with carfilzomib, lenalidomide, and dexamethaonse (KRd) therapy. After 10 cycles of KRd, he obtained stringent complete response without exacerbation of graft-versus-host disease. We concluded that KRd after allogeneic stem cell transplantation is one of the useful treatment regimens for relapsed refractory MM.

[Agranulocytosis during therapy of chronic myeloid leukemia lymphoid blast crisis with dasatinib].

A 61-year-old female was diagnosed with a lymphoid crisis of chronic myeloid leukemia (CML) in February 201X and started chemotherapy combined with dasatinib (DAS). After 1 month of initiating second consolidation therapy, the neutrophils decreased to 1%, bone marrow examination revealed large granular lymphocytes (LGL) at 13%, and complete cytogenetic remission was attained (CCyR). Suspecting DAS-induced agranulocytosis, DAS was discontinued. After 2 weeks, LGL disappeared and neutrophils recovered. In this case, CCyR was attained for the first time when LGL increased. We considered that the expansion of LGL correlated with the clinical efficacy, and agranulocytosis was an off-target effect of DAS.

[Possible contribution of disseminated Mycobacterium shigaense infection to development of splenic marginal zone lymphoma].

A 73-year-old male who underwent splenectomy was diagnosed with splenic non-caseating granuloma in May 201X, and sarcoidosis was disregarded from the differential diagnosis. Owing to the persisting inflammation, the patient was carefully followed up with no treatment. Four months post splenectomy, the patient was hospitalized due to progressive dyspnea. Chest computed tomography revealed an encapsulated pleural effusion and lymphocytic infiltration in the left lower lung, with subclavian and mediastinal lymphadenopathy. Although the patient was treated with antibiotics, his condition showed no improvement; therefore, prednisolone 40 mg was administered, resulting in lung lesion improvement. A re-examination of the tissue obtained from the previously removed spleen revealed splenic marginal zone lymphoma (SMZL), a specific low-grade, small B-cell lymphoma. As a result, the patient was treated with rituximab combined with chemotherapy. During the fifth course of the chemotherapy, a subcutaneous abscess appeared in the cervical region, and Mycobacterium shigaense was isolated from the pus discharge, suggesting that the splenic granulomatous lesion formed due to M.shigaense, and dissemination of the Mycobacterium infection occurred following splenectomy and chemotherapy, when the patient was immunosuppressed. Overall, we consider that SMZL developed because of chronic inflammation resulting from a nontuberculous mycobacterial infection.

CEA-producing multiple myeloma with meningeal invasion during relapse.

Here we describe the case of a 62-year-old woman diagnosed with multiple myeloma (IgA-κ type) who had a high serum CEA level of 27.7 ng/ml. Upper and lower gastrointestinal endoscopy and PET/CT scan showed no abnormality. After two courses of VAD therapy, the serum CEA level decreased to 5.7 ng/ml, with a decrease in the IgA level, suggesting the diagnosis of CEA-producing myeloma. After 4 years and 1 month, she had a relapse with an increase in the LDH level and myeloma cells in the blood, followed by cognitive loss and convulsion. She died 1 month after the onset of neurological symptoms. Several myeloma cells were detected in the cerebral spinal fluid, which suggested the diagnosis of myelomatous meningitis. Myelomatous meningitis is a rare disease and accounts for 1% of all myelomas. This is the fourth reported case of CEA-producing myeloma.

Renal artery stenosis following nilotinib administration in a patient with chronic myelogenous leukemia.

A 63-year-old male was diagnosed as having chronic phase CML in 2001. He obtained a major molecular response with imatinib (IM). In 2012, amulodipin was started for hypertension. In January 2013, IM was switched to nilotinib (NIL) in a clinical trial, and in February 2015, NIL was discontinued because MR4.5 had been maintained for two years. One month later, he was admitted to our hospital because of headache and high blood pressure (194/108 mmHg). His urine test showed protein 3+ and occult blood 2+. His eGFR rapidly deteriorated from 45.6 to 28.5 after admission. MR angiography showed left renal artery stenosis. He thus underwent angioplasty of the left renal artery with a stent implantation. His renal function subsequently improved. Cardiovascular events such as PAOD (peripheral artery occlusive disease) during NIL treatment were recently reported. However, to date, only four cases including our present patient with renal artery stenosis associated with NIL have been reported. These observations suggest assessment of risk factors for cardiovascular events at the start of NIL and careful monitoring to be important during tyrosine kinase inhibitor treatment of CML patients.

Quincke's edema and hypersensitivity pneumonitis induced by lenalidomide for multiple myeloma.

A 64-year-old man with recurrent multiple myeloma (BJP-κ type) was treated with 15 mg of lenalidomide (LEN) and dexamethasone. He developed Quincke's edema on his eyelid on day 4. Since the edema improved after withdrawal of LEN, the drug was subsequently re-administered at a decreased dose. However, the edema developed again on day 4. After withdrawal of LEN, the drug was administered again with gradually dose escalation, while confirming the absence of eyelid edema. Although edema did not develop, eosinophils and basophils were increased, and the CRP level was elevated. During the third course of LEN administration, his chest CT showed bilateral ground-glass opacity, and LEN-induced hypersensitivity pneumonitis was diagnosed. The pneumonitis resolved after LEN withdrawal and prednisolone administration. These observations suggested that Quincke's edema, eosinophilia and basophilia, CRP elevation, and hypersensitivity pneumonitis might occur due to the immunological effects of LEN, which is classified as an immunomodulatory drug.

[Transition to aggressive phase in a multiple myeloma patient with IgH/CCND1 translocation and diffuse osteosclerotic lesions].

CASE: A 71-year-old woman had been diagnosed as having osteosclerotic myeloma (BJP-λ type) three years prior to the current presentation, based on tumor biopsy from the forehead showing plasmacytoma with systemic osteosclerotic lesions. At 71 years of age, she underwent transverse colectomy for a tumor in the hepatic flexure of the large intestine, and it was diagnosed as IgH/CCND-1-positive plasmacytoma of the large intestine. Although serum vascular endothelial cell growth factor (VEGF) was not elevated, the plasmacytoma was largely positive for VEGF staining. She subsequently experienced transformation to aggressive myeloma over a short period of time. Osteosclerotic myeloma is a rare disease that accounts for less than 3% of all myelomas, and requires differentiation from POEMS syndrome. In this case, peripheral nerve symptoms, which are necessary for the diagnosis of POEMS syndrome, were not confirmed. Thus, this case was diagnosed as having osteosclerotic myeloma. By contrast, abnormal IgH/CCND-1 is confirmed in 15% of patients with myeloma, and 25% of those with POEMS syndrome. While it is unclear whether this genetic abnormality is involved in the development of an osteosclerotic lesion, it is expected that data from patients with osteosclerotic myeloma and POEMS syndrome will be accumulated in the future, allowing clarification of the relationship between the genetic abnormality and osteosclerosis.

SMY2 and SYH1 suppress defects in ribosome biogenesis caused by ebp2 mutations.

Ebp2 is an assembly factor of the 60S ribosomal subunit in yeast. We demonstrate that overexpression of SMY2 or SYH1 partially suppresses defects in growth and ribosome biogenesis of ebp2 mutants, and that smy2Δ and syh1Δ exhibit synthetic growth defects with the ebp2 allele. These results suggest that Smy2 and Syh1 may be involved in ribosome biogenesis in relation to Ebp2.

[Light chain escape followed by leukemic transformation in a patient with IgD myeloma].

A 63-year-old male with multiple myeloma (IgD-λ) received autologous peripheral blood stem cell transplantation (PBSCT) after induction of VAD in March 2008, and obtained a very good partial response. However, he required BOR/DEX and a second PBSCT for relapse, and in August 2012, treatment with LEN/DEX was started. After 4 cycles of LEN/DEX, IgD decreased but FLC-λ increased paradoxically, indicating a clonal change. In January 2013, an LCD regimen was started and after 4 cycles, IgD showed normalization, but his condition worsened as FLC-λ increased. This case showed a fulminant clinical course with light chain escape in this era of treating multiple myeloma with novel agents.

[Successful treatment with pseudo-autologous blood stem cell transplantation for an adolescent-onset multiple myeloma who relapsed after allogenic bone marrow transplantation].

A 14-year-old male with multiple myeloma (IgG-λ, ISS stage 3) received myeloablative matched unrelated bone marrow transplantation, and achieved a complete response. At 16 months after the transplantation, he relapsed. The relapse was resistant to bortezomib and thalidomide. Peripheral blood showed mixed chimerism with 10% recipient cells. Peripheral blood stem cells (PBSC) were collected and pseudo-autologous PBSC transplantation (PASCT) was performed following high-dose melphalan without graft-versus-host disease prophylaxis. Hematopoietic recovery was prompt and a partial response was obtained without graft-versus-host disease exacerbation. We have presented a rare case of adolescent-onset multiple myeloma, obtaining a transient response with PASCT following post-allogeneic transplant relapse.

Secondary MGUS following by adenovirus-induced hemorrhagic cystitis after autologous peripheral blood stem cell transplantation in a patient with multiple myeloma.

A 61-year-old man with multiple myeloma (IgG-κ) received autologous peripheral blood stem cell transplantation (PBSCT) after induction of VAD in July 2009, and obtained a very good partial response. In November 2009, he was admitted to our hospital because of adenovirus-induced hemorrhagic cystitis and pneumocystis jiroveci pneumonia. The pneumonia resolved with sulfamethoxazole and steroid pulse therapy, and cystitis subsided spontaneously. In December 2009, serum protein electrophoresis showed two abnormal protein bands (APB)(IgG-λ, IgA-λ), different from the original M-protein, and IgG thereafter increased to 2,771 mg/dl with a concomitant increase in anti-adenovirus antibody to 4,096. In October 2010, APB disappeared. To date, he has been in stable complete remission for five years since PBSCT. The emergence of APB is considered to be a surrogate marker for long-term remission. Immune reconstitution syndrome and APB after high dose chemotherapy following PBSCT are discussed herein.

Flexion Contracture in Knee Osteoarthritis Can Be Fully Eliminated by Hybrid Closed Wedge High Tibial Osteotomy Using a Reduction-Insertion-Compression Handle.

In conventional closed-wedge high tibial osteotomy (CWHTO) with preservation of the medial hinge, flexion contracture cannot be improved because of the two-dimensional correction. Conversely, in hybrid CWHTO, for which the name is derived from a hybrid of the lateral closing and medial opening, the medial cortex is intentionally disrupted. The medial hinge disruption enables three-dimensional correction, which helps eliminate flexion contracture by decreasing posterior tibial slope (PTS). The fine adjustment of the anterior closing distance and thigh-compression technique further facilitates PTS control. In this study, we describe the use of the Reduction-Insertion-Compression Handle (RICH), which maximizes the benefits of hybrid CWHTO. This device permits accurate osteotomy reduction, easy screw insertion, and assists with providing sufficient compressive force at the osteotomy site, as well as the elimination of the flexion contracture. This Technical Note presents the details of using the RICH and the associated advantages and disadvantages in hybrid CWHTO for medial compartmental knee arthritis.

Derotational Hybrid Closed-Wedge High Tibial Osteotomy for Knee Osteoarthritis With Patellar Subluxation Caused by Tibial Torsional Deformity.

Patellar subluxation and recurrent dislocation are commonly treated with medial patellofemoral ligament reconstruction, and patients with predisposing factors for these problems often require additional bony realignment procedures. However, these procedures mainly address problems in the axial plane, and patients with medial-compartmental knee osteoarthritis may require further realignment in the coronal plane. In this Technical Note article, we introduce our technique for derotational hybrid closed-wedge high tibial osteotomy. Using this technique, simultaneous 3-dimensional realignment in the axial, coronal, and sagittal planes can be achieved in patients with medial compartmental knee osteoarthritis and patellar subluxation caused by a tibial torsional deformity. The indications for the technique and the preoperative planning assessments involving a static torsional deformity analysis on computed tomography images and a dynamic gait analysis by our walking-on-paper method are presented. This is followed by a detailed description of the surgical procedure, together with consideration of the pearls and pitfalls of the procedure. A video of the surgery performed in a representative case with medial knee osteoarthritis and patellar subluxation in the right knee owing to an outward tibial torsion deformity is also provided.

Double-Row Root Repair with Bridging Centralization Using Double Nonsliding Anchors for Medial Meniscus Posterior Root Tear.

Medial meniscal posterior root tears disrupt the "hoop" function of the meniscus and may lead to knee osteoarthritis. Although root repair could be a key to osteoarthritis prevention, this surgery does not necessarily guarantee an optimal result even when combined with meniscal centralization and high tibial osteotomy. To address this issue, we made five modifications to the original combined approach, namely two anchors to fix the root, instead of one; bridging centralization instead of single centralization; release of the meniscotibial capsule vs no release; release of valgus stress before knot tying vs no release; and prohibiting postoperative cross-legged sitting and sitting on heels. The advantages of this approach over the original approach are numerous and comprise ease of performing concurrent open wedge high tibial osteotomy, shorter fixation distance, better anatomical reattachment of the meniscal root, increased bone-meniscus contact and contact pressure, and larger contact area between the capsule and tibial rim. The disadvantages of the approach are that knot-tying is cumbersome, pie-crusting of the medial collateral ligament is necessary in patients not undergoing open wedge high tibial osteotomy, and tears >3 mm from the attachment are a contraindication. We describe the steps in this modified approach in detail.

Femoral-varus tibial-valgus osteotomy (FVTVO) for neutrally-aligned knee osteoarthritis with severe joint line obliquity enables return to sports activities: A case series study.

Background: Re-alignment surgeries for uni-compartmental knee osteoarthritis, such as high tibial osteotomy (HTO) for varus knees or distal femoral osteotomy (DFO) for valgus knees, are recognized as standard strategies. However, the treatment strategy has not been established for patients with a neutrally-aligned osteoarthritic knee with severe joint line obliquity (JLO) owing to the combination of a valgus femur and a varus tibia; i.e., type II coronal plane alignment of the knee (CPAK). total knee arthroplasty (TKA) can be an option for CPAK type II-aligned osteoarthritis in older inactive patients. Here, we hypothesized that joint line horizontalization by femoral-varus tibial-valgus osteotomy (FVTVO), which may reduce the shear stress induced by JLO, could be a treatment option for CPAK type II-aligned osteoarthritis in young active patients who wish to return to sports (RTS) activity. Our aim in this study was to evaluate the postoperative results of FVTVO with RTS. Methods: Our indications for FVTVO are as follows: JLO >5°; mechanical medial proximal tibial angle (mMPTA) < 87°; mechanical lateral distal femoral angle (mLDFA) < 87°; typical osteoarthritis patterns for CPAK type II on magnetic resonance images, namely osteoarthritic change of the lateral tibial spine, medial slip of the femur, and/or lateral meniscal extrusion from the lateral femoral condyle; and flexion contracture <10°. We enrolled patients who wished to RTS and who had a pre-symptom Tegner score ≥5 and had completed at least a 1-year follow-up. For FVTVO, closed-wedge DFO was performed in all femurs; both closed-wedge HTO and open-wedge HTO were used in the tibia, depending on the situation. Range of motion exercises began on the first postoperative day, and full weight-bearing was permitted 6 weeks postoperatively. Jogging was permitted 3 months postoperatively after confirming bone union, and patients could gradually return to their sports activity 6-12 months' postoperatively. The Japanese Orthopaedic Association (JOA) score and knee flexion range were assessed preoperatively and at the last follow-up. Tegner activity scale scores were assessed presymptom, preoperatively, and at the last follow-up. The hip-knee-ankle (HKA) angle, JLO, mMPTA, and mLDFA were evaluated radiologically, and meniscal extrusions, osteoarthritic change, and/or bone marrow edema were assessed on magnetic resonance images. Results: One man and two women were included in this case series. Two were competitive athletes and one was a mountain climber. The patients' ages were 69, 46, and 57 years (Case 1, 2, and 3, respectively). All patients' CPAK type was converted from type II to type V; i.e., neutral-aligned knee with a neutral joint line, postoperatively. All patients returned to their presymptom sports activity level by the final follow-up. The presymptom/preoperative/final follow-up Tegner scale in Case 1, 2, and 3 were 6/1/6, 5/2/5, and 7/3/7, respectively. Conclusion: Joint line horizontalization by FVTVO for patients with a neutral-aligned knee with severe JLO provided highly satisfactory clinical results and successfully led to RTS.

[Successful treatment with lenalidomide plus dexamethasone for multiple myeloma complicated with systemic amyloidosis].

A 62-year-old woman diagnosed with asymptomatic IgG multiple myeloma in 1998 received distal gastrectomy because of abdominal fullness and was diagnosed with AL amyloidosis in 2009. She was referred to our hospital and further examination revealed amyloid depositions on the tongue, submandibular glands, heart, and gastrointestinal tract. Combination therapy of melphalan with dexamethasone was ineffective. She then received 13 courses of lenalidomide at 15 mg daily with weekly dexamethasone, which resulted in complete response with no detectable M-protein by immunofixation electrophoresis. Reduced-dose lenalidomide with dexamethasone is effective for patients with multiple myeloma complicated with AL amyloidosis.