Acute Humoral Rejection of Human Lung Allografts and Elevation of C4d in Bronchoalveolar Lavage Fluid

Antibody-mediated rejection is well established for renal allografts but remains controversial for lung allografts. Cardinal features of antibody-mediated rejection in renal allografts include antibodies to donor human leukocyte antigen (HLA) and evidence for antibody action, such as complement activation demonstrated by C4d deposition. We report a lung allograft recipient with circulating antibodies to donor HLA who failed treatment for acute cellular rejection but responded to therapy for humoral rejection. To address the second criteria for antibody-mediated rejection, we determined whether complement activation could be detected by measuring C4d in bronchoalveolar lavage fluid (BALF) by ELISA. Airway allergen challenge of asthmatics activates the complement pathway; therefore, we used BALF from asthmatics pre- and post-allergen challenge to measure C4d. These controls demonstrated that ELISA could detect increases in C4d after allergen challenge. BALF from the index patient had elevated C4d concomitant with graft dysfunction and anti-donor HLA in the absence of infection. Analysis of BALF from 25 additional lung allograft recipients showed that C4d concentrations >100 ng/mL were correlated with anti-HLA antibodies (p = 0.006), but were also observed with infection and in asyptomatic patients. The findings support the occurrence of anti-HLA-mediated lung allograft rejection and suggest that C4d measurement in BALF may be useful in diagnosis.     

A contemporary evaluation of cytoreductive nephrectomy with tumor thrombus: Morbidity and long-term survival

BACKGROUND: Metastatic renal cell carcinoma (RCC) is an aggressive entity that frequently invades the venous system. We evaluated the morbidity and survival of patients with tumor thrombus who undergo cytoreductive nephrectomy. MATERIALS AND METHODS: We identified 56 patients from our institution's database who had a primary renal tumor in place and documented metastases at the time of surgery. We reviewed demographic and pathologic characteristics from these patients as well as complications and overall survival. RESULTS: Median age was 58 (37-77). There were 33 patients (59%) who had tumor thrombus with 21 (64%) involving the renal vein, 10 (30%) involving the infradiaphragmatic inferior vena cava (IVC), and 2 (6%) involving the supradiaphragmatic IVC. Median tumor size for thrombus patients was 12 cm (5-29). There were 8 (14.2%) who had complications, including 1 death. Thrombus patients were significantly more likely to have a complication (P = 0.008). Median survival for all patients was 10.7 months (0.3-61). There was no significant difference in overall survival between patients with and without thrombus (P = 0.76). CONCLUSIONS: Patients who undergo cytoreductive nephrectomy with a tumor thrombus have a higher rate of complications as compared to patients undergoing cytoreductive nephrectomy without tumor thrombus. The long-term survival, however, was not statistically different and thus aggressive surgery for select metastatic RCC patients is warranted.     

Premature Aging in Male Alcoholics: “Accelerated Aging” or “Increased Vulnerability”?

This study involved an evaluation of two versions of the "premature aging" theory of chronic alcoholism: the accelerated aging and increased vumerabHty versions. The major dependent measures used were the tests included in Reitan's brain age quotient (BAO), a series of neuropsychological tests known to be sensitive to the effects of alcoholism and aging. Subjects were 40 chronic alcoholic inpatients and 40 matched controls, divided into age groups by; decade, ranging from the 30s to the 60s. It was proposed that an j interaction between age and presence or absence of alcoholism, with BAO test differences between alcoholics and controls widening as age increases, would support the increased vulnerability version, while the absence of such aw interaction would support the accel-] erated aging version. The results dearty favored the accelerated aging version, with merited BAO test differences between alcoholics, and controls appearing even in the 30-year-old groups. It was concluded that chronic ateohoftcs tend to perform at levels found for nonalconoiics 10 years their senior, but the discrepancy between, alcoholics and nonalcohoics does not increase with age.     

Telerehabilitation of anomia in primary progressive aphasia

Background: The efficacy of telerehabilitation-based treatment for anomia has been demonstrated in post-stroke aphasia, but the efficacy of this method of anomia treatment delivery has not been established within the context of degenerative illness.

Aims: The current study evaluated the feasibility and efficacy of a telerehabilitation-based approach to anomia treatment within the three subtypes of primary progressive aphasia (PPA).

Methods & Procedures: Each of the three telerehabilitation participants represented a distinct subtype of PPA. Following a baseline evaluation of language and cognition, a phonological treatment and an orthographic treatment were administered to all participants over the course of 6 months. One month after the end of treatment, a post-treatment evaluation began. All treatment sessions and the majority of the evaluation sessions were administered via telerehabilitation. Treatment effects were examined within each subject, and treatment effects were also compared between each telerehabilitation participant and a group of in-person participants who had the same subtype of PPA.

Outcomes & Results: All three telerehabilitation participants exhibited positive treatment effects. CGR (nonfluent/agrammatic variant PPA) and WCH (logopenic variant PPA) showed maintenance of naming for prophylaxis items under both treatment conditions, while ACR (semantic variant PPA) demonstrated increased naming of remediation items under the phonological treatment condition. Compared to in-person participants with the same subtype of PPA, each of the telerehabilitation participants typically showed effects that were either within the expected range or larger than expected.

Conclusions: Telerehabilitation-based anomia treatment is feasible and effective in all three subtypes of PPA.     

Does the quality,accuracy, and readability of information about lateral epicondylitis on the internet vary with the search term used?

Background

Concern exists over the quality, accuracy, and accessibility of online information about health care conditions. The goal of this study is to evaluate the quality, accuracy, and readability of information available on the internet about lateral epicondylitis.

Methods

We used three different search terms (“tennis elbow,” “lateral epicondylitis,” and “elbow pain”) in three search engines (Google, Bing, and Yahoo) to generate a list of 75 unique websites. Three orthopedic surgeons reviewed the content of each website and assessed the quality and accuracy of information. We assessed each website’s readability using the Flesch–Kincaid method. Statistical comparisons were made using ANOVA with post hoc pairwise comparisons.

Results

The mean reading grade level was 11.1. None of the sites were under the recommended sixth grade reading level for the general public. Higher quality information was found when using the terms “tennis elbow” and “lateral epicondylitis” compared to “elbow pain” (p < 0.001). Specialty society websites had higher quality than all other websites (p < 0.001). The information was more accurate if the website was authored by a health care provider when compared to non-health care providers (p = 0.003). Websites seeking commercial gain and those found after the first five search results had lower quality information.

Conclusions

Reliable information about lateral epicondylitis is available online, especially from specialty societies. However, the quality and accuracy of information vary significantly with the search term, website author, and order of search results. This leaves less educated patients at a disadvantage, particularly because the information we encountered is above the reading level recommended for the general public.     

A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast‐like cells

Neurofibromatosis type 1 (NF1) is a common genetic condition caused by mutations in the NF1 gene. Patients often suffer from tissue‐specific lesions associated with local double‐inactivation of NF1. In this study, we generated a novel fracture model to investigate the mechanism underlying congenital pseudarthrosis of the tibia (CPT) associated with NF1. We used a Cre‐expressing adenovirus (AdCre) to inactivate Nf1 in vitro in cultured osteoprogenitors and osteoblasts, and in vivo in the fracture callus of Nf1^flox/flox and Nf1^flox/? mice. The effects of the presence of Nf1^null cells were extensively examined. Cultured Nf1^null‐committed osteoprogenitors from neonatal calvaria failed to differentiate and express mature osteoblastic markers, even with recombinant bone morphogenetic protein‐2 (rhBMP‐2) treatment. Similarly, Nf1^null‐inducible osteoprogenitors obtained from Nf1 mouse muscle were also unresponsive to rhBMP‐2. In both closed and open fracture models in Nf1^flox/flox and Nf1^flox/? mice, local AdCre injection significantly impaired bone healing, with fracture union being <50% that of wild type controls. No significant difference was seen between Nf1^flox/flox and Nf1^flox/? mice. Histological analyses showed invasion of the Nf1^null fractures by fibrous and highly proliferative tissue. Mean amounts of fibrous tissue were increased upward of 10‐fold in Nf1^null fractures and bromodeoxyuridine (BrdU) staining in closed fractures showed increased numbers of proliferating cells. In Nf1^null fractures, tartrate‐resistant acid phosphatase–positive (TRAP+) cells were frequently observed within the fibrous tissue, not lining a bone surface. In summary, we report that local Nf1 deletion in a fracture callus is sufficient to impair bony union and recapitulate histological features of clinical CPT. Cell culture findings support the concept that Nf1 double inactivation impairs early osteoblastic differentiation. This model provides valuable insight into the pathobiology of the disease, and will be helpful for trialing therapeutic compounds. © 2012 American Society for Bone and Mineral Research     

Active surveillance of small renal masses offers short‐term oncological efficacy equivalent to radical and partial nephrectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance of small renal masses has traditionally been reserved for elderly patients deemed unfit for surgery or ablation. There is increasing evidence showing the safety of active surveillance in the management of small renal masses. In this retrospective study we compared outcomes for patients with small renal masses managed with active surveillance, radical nephrectomy and partial nephrectomy. We showed that active surveillance was safe and appeared as effective as immediate surgery in the management of small renal tumours.

OBJECTIVE

• ? To compare the oncological outcomes of active surveillance (AS), radical nephrectomy (RN) and partial nephrectomy (PN) in the management of T1a small renal masses (SRMs).

PATIENTS AND METHODS

• ? At present AS is used in the treatment of SRMs in elderly patients with multiple co‐morbidities or in those who decline surgery.
• ? We identified all patients with T1a SRMs managed with RN, PN or AS.
• ? Retrospective data were collected from patient case records with survival data and cause of death cross‐referenced with the Oxford Cancer Intelligence Unit.

RESULTS

• ? A total of 202 patients with 234 T1a SRMs (solid or Bosniak IV) were identified; 71 patients were managed with AS, 41 with an RN and 90 by PN.
• ? Over a median follow‐up of 34 months the mean growth rate on AS was 0.21 cm/year with 53% of SRMs managed with AS showing negative or zero growth.
• ? No statistically significant difference was observed in overall (OS) and cancer‐specific (CSS) survival for AS, RN and PN (AS‐CSS 98.6%, AS‐OS 83%; RN‐CSS 92.6%, RN‐OS 80.4%; PN‐CSS 96.6%, PN‐OS 90.0%).

CONCLUSIONS

• ? Active surveillance of SRMs offers oncological efficacy equivalent to surgery in the short/intermediate term.
• ? The results of this study support a multicentre prospective randomized controlled trial designed to compare the oncological efficacy of AS and surgery.

     

Trochanteric osteotomy and fixation during total hip arthroplasty

Once used routinely, trochanteric osteotomy in total hip arthroplasty now is usually limited to difficult primary and revision cases. There are three types: the standard trochanteric osteotomy and its variations, the trochanteric slide, and the extended trochanteric osteotomy. Each has unique indications, fixation techniques, and complications. Primary total hip arthroplasty procedures requiring the enhanced exposure provided by trochanteric osteotomy may be needed in patients with hip ankylosis or fusion, protrusio acetabuli, proximal femoral deformities, developmental dysplasia, or abductor muscle laxity. Trochanteric osteotomies in revision arthroplasties, primarily the extended trochanteric osteotomy, facilitate the removal of well-fixed femoral components, provide direct access to the diaphysis for distal fixation, and enhance acetabular exposure.     

Low-iodine diet revisited: importance in nuclear medicine imaging and management

PURPOSE: The need for a low-iodine diet (LID) to maximize the results of radioactive iodine uptake (RAIU), nuclear medicine thyroid scintigraphy, and ultimately treatment of thyroid cancer patients is widely accepted. Failure to follow the prescribed diet can alter RAIU results, thyroid scan findings, and poststudy management. OBJECTIVE: Provided is a case presentation that illustrates the need for adequate patient understanding and compliance with the LID. METHODS: We present the clinical history, laboratory values, and pertinent imaging of a 21-year-old woman with papillary thyroid cancer. The patient's post-thyroidectomy I-123 and 2 subsequent thyroid (I-123 and post-RAI ablation I-131) scintigraphy examinations are reviewed as well as the patient's urine iodine levels. RESULTS: In this case of a woman with papillary thyroid cancer, the nuclear medicine whole body and neck pinhole images revealed that compliance to an LID positively impacts the overall management. After an LID was followed, the patient's urine iodine level appropriately declined from the previously elevated level. Initial negative results on thyroid scintigraphy caused by noncompliance with the LID became positive when the patient adhered to the prescribed dietary regimen. CONCLUSION: An LID is an integral element in the management of differentiated thyroid cancer. Proper guidance and emphasis on the implementation of the diet needs to be provided to patients. Noncompliance may lead to false negative imaging results, misleading the medical professionals and patient. Potentially inadequate management of the patient's thyroid cancer may follow.