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Background Although the use of rotator interval closure is frequently advocated as a useful supplement to shoulder instability repairs, the addition of a rotator interval closure after arthroscopic instability repair has not been fully investigated. Purpose The objective of this study was to investigate whether a rotator interval closure improves glenohumeral stability in an anterior and posterior instability shoulder model. Study Design Controlled laboratory study. Methods Fourteen fresh-frozen cadaveric shoulder specimens were dissected free of soft tissues, leaving the rotator cuff intact with simulated cuff loading. All specimens were mounted in a custom testing apparatus using infrared sensors to document glenohumeral translation and rotation. The specimens were then tested for stability in the following order: vented/subluxated state, after arthroscopic anterior (Group 1; 7 specimens) or posterior (Group 2; 7 specimens) instability repair with suture anchors, and then after rotator interval closure. For each of the 3 testing conditions, the following were measured: (1) external and internal rotation at neutral, (2) external and internal rotation at 90° of abduction, (3) posterior and anterior translation at neutral rotation (15 N and 25 N), (4) anterior translation at 90° of abduction and external rotation (Group 1; 15 N and 25 N), (5) posterior translation at 90° of flexion and internal rotation (Group 2; 15 N and 25 N), and (6) sulcus testing in neutral (7.5 N). Results Posterior stability was only improved after anchor capsulolabral repair (8.0 to 5.0 mm; P = .017, 25 N), but there was no improvement after rotator interval closure (5.0 to 4.6 mm; P = .453). However, anterior stability was improved after capsulolabral repair (8.6 to 4.0 mm; P = .016, 25 N) and also improved further by rotator interval closure (4.0 to 2.4 mm; P = .007). The mean loss of external rotation was significantly increased by the addition of the rotator interval closure in both neutral and abducted glenohumeral positions, with a mean external rotation loss of 28° in neutral ( P = .013). The addition of a rotator interval closure did not improve sulcus stability ( P = .4). Conclusion The addition of an arthroscopic rotator interval closure after posterior capsulolabral repair did not improve posterior stability; however, anterior stability was improved further after a rotator interval closure. Inferior stability was not improved. Arthroscopic rotator interval closure significantly decreased external rotation at both neutral and abducted arm positions. Clinical Relevance Arthroscopic closure may be beneficial in certain cases of anterior shoulder instability; however, posterior instability was not improved. Predictable losses of external rotation after rotator interval closure are of concern.

The current paradigm surrounding allergen-mediated T helper type 2 (Th2) immune responses in the lung suggests an almost hegemonic role for T cells. Our studies propose an alternative hypothesis implicating eosinophils in the regulation of pulmonary T cell responses. In particular, ovalbumin (OVA)-sensitized/challenged mice devoid of eosinophils (the transgenic line PHIL) have reduced airway levels of Th2 cytokines relative to the OVA-treated wild type that correlated with a reduced ability to recruit effector T cells to the lung. Adoptive transfer of Th2-polarized OVA-specific transgenic T cells (OT-II) alone into OVA-challenged PHIL recipient mice failed to restore Th2 cytokines, airway histopathologies, and, most importantly, the recruitment of pulmonary effector T cells. In contrast, the combined transfer of OT-II cells and eosinophils into PHIL mice resulted in the accumulation of effector T cells and a concomitant increase in both airway Th2 immune responses and histopathologies. Moreover, we show that eosinophils elicit the expression of the Th2 chemokines thymus- and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in the lung after allergen challenge, and blockade of these chemokines inhibited the recruitment of effector T cells. In summary, the data suggest that pulmonary eosinophils are required for the localized recruitment of effector T cells.

ObjectStabilization of the atlantoaxial complex has proven to be very challenging. Because of the high mobility of the C1–2 motion segment, fusion rates at this level have been substantially lower than those at the subaxial spine. The set of potential surgical interventions is limited by the anatomy of this region. In 2001 Jürgen Harms described a novel technique for individual fixation of the C-1 lateral mass and the C-2 pedicle by using polyaxial screws and rods. This method has been shown to confer excellent stability in biomechanical studies. Cadaveric and radiographic analyses have indicated that it is safe with respect to osseous and vascular anatomy. Clinical outcome studies and fusion rates have been limited to small case series thus far. The authors reviewed the multicenter experience with 102 patients undergoing C1–2 fusion via the polyaxial screw/rod technique. They also describe a modification to the Harms technique.MethodsOne hundred two patients (60 female and 42 male) with an average age of 62 years were included in this analysis. The average follow-up was 16.4 months. Indications for surgery were instability at the C1–2 level, and a chronic Type II odontoid fracture was the most frequent underlying cause. All patients had evidence of instability on flexion and extension studies. All underwent posterior C-1 lateral mass to C-2 pedicle or pars screw fixation, according to the method of Harms. Thirty-nine patients also underwent distraction and placement of an allograft spacer into the C1–2 joint, the authors' modification of the Harms technique. None of the patients had supplemental sublaminar wiring.ResultsAll but 2 patients with at least a 12-month follow-up had radiographic evidence of fusion or lack of motion on flexion and extension films. All patients with an allograft spacer demonstrated bridging bone across the joint space on plain x-ray films and computed tomography. The C-2 root was sacrificed bilaterally in all patients. A postoperative wound infection developed in 4 patients and was treated conservatively with antibiotics and local wound care. One patient required surgical debridement of the wound. No patient suffered a neurological injury. Unfavorable anatomy precluded the use of C-2 pedicle screws in 23 patients, and thus, they underwent placement of pars screws instead.ConclusionsFusion of C1–2 according to the Harms technique is a safe and effective treatment modality. It is suitable for a wide variety of fracture patterns, congenital abnormalities, or other causes of atlantoaxial instability. Modification of the Harms technique with distraction and placement of an allograft spacer in the joint space may restore C1–2 height and enhance radiographic detection of fusion by demonstrating a graft–bone interface on plain x-ray films, which is easier to visualize than the C1–2 joint.

AbstractWe analyzed the presenting features and survival in 1689 patients with multiple myeloma aged younger than 50 years compared with 8860 patients 50 years of age and older. Of the total 10 549 patients, 7765 received conventional therapy and 2784 received high-dose therapy. Young patients were more frequently male, had more favorable features such as low International Staging System (ISS) and Durie-Salmon stage as well as less frequently adverse prognostic factors including high C-reactive protein (CRP), low hemoglobin, increased serum creatinine, and poor performance status. Survival was significantly longer in young patients (median, 5.2 years vs 3.7 years; P < .001) both after conventional (median, 4.5 years vs 3.3 years; P < .001) or high-dose therapy (median, 7.5 years vs 5.7 years; P = .04). The 10-year survival rate was 19% after conventional therapy and 43% after high-dose therapy in young patients, and 8% and 29%, respectively, in older patients. Multivariate analysis revealed age as an independent risk factor during conventional therapy, but not after autologous transplantation. A total of 5 of the 10 independent risk factors identified for conventional therapy were also relevant for autologous transplantation. After adjusting for normal mortality, lower ISS stage and other favorable prognostic features seem to account for the significantly longer survival of young patients with multiple myeloma with age remaining a risk factor during conventional therapy.

Abstract Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjögren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis.

Purpose To review the state of the science with respect to diagnostic imaging and locoregional therapy for patients with breast cancer receiving preoperative chemotherapy. Methods Published data relevant to clinical staging, monitoring of tumor response, and locoregional therapy for patients with breast cancer treated with preoperative chemotherapy were reviewed. Results High-quality data from prospective randomized trials are limited. Available data suggest that locoregional therapy decisions should be based on both the pretreatment clinical extent of disease and the pathologic extent of the disease after chemotherapy. Accordingly, physical examination and imaging studies that accurately define the initial extent of disease are required before treatment. Sentinel lymph node biopsy can be performed either before or after preoperative chemotherapy for patients with clinical N0 disease. The success of breast conservation after preoperative chemotherapy depends on careful patient selection and achieving negative surgical margins. Adjuvant breast radiation is indicated for all patients treated with breast conservation. For patients treated with mastectomy, chest-wall and regional nodal radiation should be considered for those who present with clinical stage III disease or have histologically positive lymph nodes after preoperative chemotherapy. Additional prospective studies are needed to determine the value of postmastectomy radiation for patients with stage II breast cancer who have negative lymph nodes after chemotherapy. Conclusion The increased use of preoperative chemotherapy has raised new questions concerning the optimal methods to stage and monitor disease response to treatment and how to optimize locoregional treatment. The available evidence suggests that a multidisciplinary approach improves outcomes.

Abstract Purpose: To test combination treatment schedules of reovirus and radiation in human and murine tumor cells in vitro and in vivo. Experimental Design: In vitro cytotoxicity and cell cycle effects of reovirus given alone and combined with radiotherapy were assessed by colorimetric, tissue culture infectious dose 50, and fluorescence-activated cell sorting–based assays. Interactions between the agents were evaluated using combination index analysis. The effect of different schedules of reovirus and radiotherapy on viral replication and cytotoxicity was tested in vitro and the combination was assessed in three tumor models in vivo. Results: Characterization of reovirus cytotoxicity in a panel of cell lines yielded a range of sensitivities. Combined reovirus and radiotherapy yielded statistically significantly increased cytotoxicity, particularly in cell lines with moderate susceptibility to reovirus alone. The enhanced cytotoxicity of the combination occurred independently of treatment sequence or schedule. Radiation did not affect viral replication and only reduced reoviral cytotoxicity after clinically irrelevant single doses (&gt;50 Gy). Combination index analysis revealed synergy between radiation (3-10 Gy) and reovirus at multiplicities of infection between 0.001 and 1. Combination treatment significantly increased apoptosis in tumor cells relative to either single-agent treatment. In vivo studies using xenograft and syngeneic tumors showed enhanced activity of the combination relative to reovirus or radiation alone (P &lt; 0.001). Conclusions: Combining reovirus and radiotherapy synergistically enhances cytotoxicity in a variety of tumor cells in vitro and in vivo. These results offer strong support for translational clinical trials of reovirus plus radiotherapy that have been initiated in the clinic.