Rheumatoid elbow

The elbow is often involved in the progression of rheumatoid arthritis. Because of the elbow's unique role in maneuvering and positioning the hand in space, loss of normal elbow motion, loss of stability, or increased pain with the use of the elbow are all significant sources of impairment in patients with rheumatoid arthritis. The improvements in disease-modifying medications have greatly diminished the prevalence of severe elbow degeneration among patients with rheumatoid arthritis. However, it hasn't been eliminated. In this article the authors discuss strategies for managing it.     

Generation and Large‐Scale Expansion of Human Inducible Regulatory T Cells That Suppress Graft‐Versus‐Host Disease

Adoptive transfer of thymus‐derived natural regulatory T cells (nTregs) effectively suppresses disease in murine models of autoimmunity and graft‐versus‐host disease (GVHD). TGFß induces Foxp3 expression and suppressive function in stimulated murine CD4+25‐ T cells, and these induced Treg (iTregs), like nTreg, suppress auto‐ and allo‐reactivity in vivo. However, while TGFß induces Foxp3 expression in stimulated human T cells, the expanded cells lack suppressor cell function. Here we show that Rapamycin (Rapa) enhances TGFß‐dependent Foxp3 expression and induces a potent suppressor function in naive (CD4+ 25–45RA+) T cells. Rapa/TGFß iTregs are anergic, express CD25 at levels higher than expanded nTregs and few cells secrete IL‐2, IFNγ or IL‐17 even after PMA and Ionomycin stimulation in vitro. Unlike other published methods of inducing Treg function, Rapa/TGFß induces suppressive function even in the presence of memory CD4+ T cells. A single apheresis unit of blood yields an average ～240 × 10⁹ (range ～70–560 × 10⁹) iTregs from CD4+25‐ T cells in ≤2 weeks of culture. Most importantly, Rapa/TGFß iTregs suppress disease in a xenogeneic model of GVHD. This study opens the door for iTreg cellular therapy for human diseases.     

Delayed hepatic CT scanning: increased confidence and improved detection of hepatic metastases

Fifty oncologic patients with suspected hepatic metastases were prospectively evaluated by dynamic sequential hepatic computed tomography (DSHCT) and by delayed iodine hepatic computed tomography (DICT) scanning. DICT scanning was performed 4-6 hours following administration of 60 g of intravenous iodine. Both techniques were evaluated for lesion definition relative to the adjacent hepatic parenchyma and for numbers of metastases detected. Metastases were detected by both techniques in 26 patients. Fifteen patients (58%) had lesions better defined by DICT. DICT scanning detected more metastases in seven of these 15 patients. In eight patients (31%), there was no difference between the two techniques in numbers of masses detected or lesion definition. In three cases (11%), metastases were more confidently identified on the initial or DSHCT scan. DICT scanning, as described, is useful in defining and detecting hepatic metastases, especially where there is questionable hepatic involvement or better quantification of size is necessary.     

Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

Diagnosis of scaphoid fracture displacement with radiography and computed tomography

BACKGROUND: Displacement is an important risk factor for nonunion of scaphoid wrist fractures. We compared computed tomography with radiographs with regard to their ability to detect displacement. METHODS: Six blinded observers rated thirty scaphoid fractures (ten displaced and twenty nondisplaced) with use of radiographs and computed tomography. The radiographs were evaluated separately from the computed tomography scans and then, in a third evaluation, the two imaging studies were reviewed simultaneously. The evaluations were repeated four weeks later. Observers were asked to evaluate specific measures of fracture displacement and then to judge the fracture as being displaced or nondisplaced. RESULTS: Intraobserver reliability was better for computed tomography alone and the combination of radiographs and computed tomography than it was for radiographs alone (kappa values, 0.65, 0.63, and 0.54, respectively; all p<0.001). The interobserver reliability was also better for computed tomography alone and the combination of radiographs and computed tomography than it was for radiographs alone (kappa values, 0.43, 0.48, and 0.27, respectively; all p<0.001). The average sensitivity was 75% for radiographs alone, 72% for computed tomography alone, and 80% for both; the average specificity was 64%, 80%, and 73%, respectively; the average accuracy was 68%, 77%, and 75%, respectively. The positive predictive values (assuming a 5% prevalence of fracture displacement) were low (0.10, 0.13, and 0.16) and the negative predictive values were high (0.97, 0.98, and 0.99) for the radiographs, computed tomography, and combined modality. CONCLUSIONS: Computed tomography improves the reliability of detecting scaphoid fracture displacement but has a more limited effect on accuracy, which remains <80%. The utility of computed tomography scans for diagnosing scaphoid fracture displacement is affected by the low prevalence of fracture displacement. This study suggests that computed tomography scans are useful for ruling out displacement but not for diagnosing it. We recommend that all scaphoid fractures be evaluated with computed tomography in order to rule out displacement.     

Suppressor function of umbilical cord blood-derived CD4+CD25+ T-regulatory cells exposed to graft-versus-host disease drugs

BACKGROUND: This study examines the effects of the most commonly used graft-versus-host disease (GVHD) prophylactic drugs on inducing apoptosis and suppressor cell function of human umbilical cord blood (UCB) CD4+25+ Treg and CD4+25- cells. METHODS: Cyclosporin A (CSA), methylprednisolone (MP), methotrexate (MTX), and mycophenolic acid (MPA) were added to the final 6 days of expansion cultures of Treg or CD4+25- T-cells isolated from the same donor and each concurrently cultured under the same conditions. Cell viability was measured for CD4+25+ as compared to CD4+25- T-cells and Treg function was assessed. The effects of these immunosuppressive drugs, Treg cells, or both also were tested in a primary allogeneic mixed lymphocyte response (MLR) response. RESULTS: The cell viability percentages were lower for CD4+25- cells than for Treg cells when MP, MTX, or MPA was added for the last 6 days of an expansion culture. Under these interleukin (IL)-2 based expansion conditions, CSA had no effect. The addition of any of the four GVHD prophylactic agents to the expansion phase of culture did not reduce the MLR suppressive capacity of Treg cells. Overall MLR suppression was increased when Treg cells were added along with CSA and MP to a primary MLR culture, whereas MTX modestly reduced Treg suppression. CONCLUSION: These data indicate a general resistance of expanded UCB Treg cells to GVHD immune suppressive agents and support trials to test UCB Treg infusions under the cover of GVHD prophylactic drugs in hematopoietic cell transplantation.     

Epidemiology of musculoskeletal upper extremity ambulatory surgery in the United States

Background

Musculoskeletal disorders of the upper extremity are common reasons for patients to seek care and undergo ambulatory surgery. The objective of our study was to assess the overall and age-adjusted utilization rates of rotator cuff repair, shoulder arthroscopy performed for indications other than rotator cuff repair, carpal tunnel release, and wrist arthroscopy performed for indications other than carpal tunnel release in the United States. We also compared demographics, indications, and operating room time for these procedures.

Methods

We used the 2006 National Survey of Ambulatory Surgery to estimate the number of procedures of interest performed in the United States in 2006. We combined these data with population size estimates from the 2006 U.S. Census Bureau to calculate rates per 10,000 persons.

Results

An estimated 272,148 (95% confidence intervals (CI)?=?218,994, 325,302) rotator cuff repairs, 257,541 (95% CI?=?185,268, 329,814) shoulder arthroscopies excluding those for cuff repairs, 576,924 (95% CI?=?459,239, 694,609) carpal tunnel releases, and 25,250 (95% CI?=?17,304, 33,196) wrist arthroscopies excluding those for carpal tunnel release were performed. Overall, carpal tunnel release had the highest utilization rate (37.3 per 10,000 persons in persons of age 45–64 years; 38.7 per 10,000 persons in 65–74 year olds, and; 44.2 per 10,000 persons in the age-group 75 years and older). Among those undergoing rotator cuff repairs, those in the age-group 65–74 had the highest utilization (28.3 per 10,000 persons). The most common indications for non-cuff repair related shoulder arthroscopy were impingement syndrome, periarthritis, bursitis, and instability/SLAP tears. Non-carpal tunnel release related wrist arthroscopy was most commonly performed for ligament sprains and diagnostic arthroscopies for pain and articular cartilage disorders.

Conclusions

Our data shows substantial age and demographic differences in the utilization of these commonly performed upper extremity ambulatory procedures. While over one million upper extremity procedures of interest were performed, evidence-based clinical indications for these procedures remain poorly defined.     

The use of a single volar locking plate for AO C3-type distal radius fractures

Background

A single volar locking plate (VLP) is now frequently used for open reduction and internal fixation (ORIF) of many types of distal radius fractures. Comminuted intra-articular distal radius fractures (AO C3-type) are typically the most challenging to surgically treat. No studies directly address the adequacy of a VLP alone for maintaining reduction of AO C-type fractures. We hypothesized that a single VLP provides an effective method for maintaining reduction for these fractures.

Methods

We retrospectively evaluated radiographs of a series of AO C-type fractures. Seventy-seven patients with 77 AO C3-type fractures were identified from billing records and were eligible for the study. All patients were treated by fellowship-trained hand surgeons. Radiographs at the time of union were compared to those from immediately postoperatively.

Results

Sixty-nine of 77 (89.6 %) fractures treated with VLP fixation alone for AO C3-type distal radius fractures united without loss of reduction. Eight of 77 (10.4 %) patients treated with VLP for AO C3 fractures lost reduction. The most common fracture fragment to lose reduction was the lunate fossa (5 of 8); loss of reduction of the scaphoid fossa die-punch fragment (2 of 8) and the radial styloid (1 of 8) were also seen.

Conclusions

The majority (89.6 %) of AO C3-type fractures treated with a single volar locking plate come to union without loss of reduction.Level of evidence: Level IV.