Citations

Abstract The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

Abstract Cardiac toxicity is one of the most concerning side effects of anti-cancer therapy. The gain in life expectancy obtained with anti-cancer therapy can be compromised by increased morbidity and mortality associated with its cardiac complications. While radiosensitivity of the heart was initially recognized only in the early 1970s, the heart is regarded in the current era as one of the most critical dose-limiting organs in radiotherapy. Several clinical studies have identified adverse clinical consequences of radiation-induced heart disease (RIHD) on the outcome of long-term cancer survivors. A comprehensive review of potential cardiac complications related to radiotherapy is warranted. An evidence-based review of several imaging approaches used to detect, evaluate, and monitor RIHD is discussed. Recommendations for the early identification and monitoring of cardiovascular complications of radiotherapy by cardiac imaging are also proposed.

SummaryNearly all information about patients with chronic lymphocytic leukaemia (CLL) who develop diffuse large B‐cell lymphoma [Richter syndrome (RS)] is derived from retrospective case series or patients treated on clinical trials. We used the Mayo Clinic CLL Database to identify patients with newly diagnosed CLL between January 2000 and July 2011. Individuals who developed biopsy‐proven RS during follow‐up were identified. After a median follow‐up of 4 years, 37/1641 (2·3%) CLL patients developed RS. The rate of RS was approximately 0·5%/year. Risk of RS was associated with advanced Rai stage at diagnosis (P < 0·001), high‐risk genetic abnormalitites on fluorescence in situ hybridization (P < 0·0001), unmutated IGHV (P = 0·003), and expression of ZAP70 (P = 0·02) and CD38 (P = 0·001). The rate of RS doubled in patients after treatment for CLL (1%/year). Stereotyped B‐cell receptors (odds‐ratio = 4·2; P = 0·01) but not IGHV4‐39 family usage was associated with increased risk of RS. Treatment with combination of purine analogues and alkylating agents increased the risk of RS three‐fold (odds‐ratio = 3·26, P = 0·0003). Median survival after RS diagnosis was 2·1 years. The RS prognosis score stratified patients into three risk groups with median survivals of 0·5 years, 2·1 years and not reached. Both underlying characteristics of the CLL clone and subsequent CLL therapy influence the risk of RS. Survival after RS remains poor and new therapies are needed.

AbstractAimMost patients presenting with rectourethral fistula acquire it as a complication of radiotherapy for prostate cancer, as a result of injury to the rectum during prostatectomy, through trauma or from Crohn's disease. This study examined whether choice of operation and results of surgery for rectourethral fistula are influenced by prior radiotherapy.MethodMale patients undergoing surgery for rectourethral fistula were identified from a prospectively maintained database. Data regarding aetiology, surgical treatment and outcomes were analysed.ResultsFifty patients (median age = 65.5 years) were identified. Radiation was received by 29 patients for prostate or rectal cancer, and 21 patients developed a fistula following prostatectomy, Crohn's disease or pelvic fracture (without radiation). Prior to definitive surgery, 30 patients underwent fecal diversion and 37 underwent urinary diversion. In total, 57 repairs were performed (44 patients had one repair, five patients had two and one patient had three). Definitive surgery was approached predominantly abdominally in radiated patients (90.6 vs 9.3%, P < 0.001) and perineally in nonradiated patients (80 vs 20%, P < 0.001). Successful primary fistula repair was more frequent in the nonradiated group compared with the radiated group (80.9 vs 0%, P < 0.001). Permanent colostomy and urinary diversion were more often required in radiated patients than in nonradiated patients (colostomy: 83 vs 0%, P < 0.001; urorostomy: 100 vs 19%, P < 0.001).ConclusionFew patients with radiation‐induced rectourethral fistula avoid permanent colostomy and urostomy. In contrast, most patients with nonradiation‐related fistulae undergo successful perineal repair without permanent faecal and urinary diversion.

The Fontan procedure represents the final stage of the transition to single ventricle physiology. Conversion of very complex congenital heart anatomy, such as hypoplastic left heart syndrome, double-outlet right ventricle or double-inlet left ventricle, to a single ventricle has grown in popularity as morbidity and mortality have improved. As these patients grow, survivors are at risk for impaired ventricular dysfunction, plastic bronchitis, protein-losing enteropathy and late failure. Late failing Fontan patients represent a particularly vexing scenario for clinicians, as the only durable treatment option is cardiac transplantation. However, in the short-term, some of these patients require support beyond medical management, with mechanical circulatory support via extracorporeal life support or a ventricular assist device. We report the successful bridge of an adolescent female post-Fontan conversion with late severe cardiac failure. The patient was initially resuscitated with extracorporeal life support, transitioned to a single Berlin Heart EXCOR® ventricular assist device and, subsequently, underwent successful cardiac transplantation.

AbstractBackgroundLiver biopsy has been the reference standard when evaluating fibrosis due to recurrent hepatitis after liver transplantation. Magnetic resonance elastography estimates liver stiffness, correlating to fibrosis.AimTo investigate the utility of elastography in staging liver fibrosis in transplant recipients with hepatitis C.MethodsFifty‐four patients, ≥12 months post‐transplant, underwent elastography within three months of biopsy. Discriminatory capability for METAVIR fibrosis stages F0–2 vs. F3–4 and receiver operating characteristic curve (ROC) analysis were determined.ResultsOn biopsy, 27 patients had METAVIR fibrosis score 0–1; 12 had a 3 or 4. There was significant correlation between histologic fibrosis and shear stiffness (R² = 0.588, p < 0.0001). Using a cutoff value of 3.5 kPa, elastography was 91% sensitive and 72% specific in differentiating fibrosis scores of ≥3 from 0 to 1. The AUC of elastography in predicting a fibrosis score of ≥3 was 0.92. Multivariate analysis revealed no correlation between the grade of histologic inflammation and liver stiffness measured by magnetic resonance elastography (R² = 0.265, p = 0.47).ConclusionMagnetic resonance elastography is an accurate non‐invasive technique for excluding stage ≥3 graft in recipients with hepatitis C.

BACKGROUND Friedreich ataxia (FRDA) is caused by reduced frataxin (FXN) concentrations. A clinical diagnosis is typically confirmed by DNA-based assays for GAA-repeat expansions or mutations in the FXN (frataxin) gene; however, these assays are not applicable to therapeutic monitoring and population screening. To facilitate the diagnosis and monitoring of FRDA patients, we developed an immunoassay for measuring FXN. METHODS Antibody pairs were used to capture FXN and an internal control protein, ceruloplasmin (CP), in 15 μL of whole blood (WB) or one 3-mm punch of a dried blood spot (DBS). Samples were assayed on a Luminex LX200 analyzer and validated according to standard criteria. RESULTS The mean recovery of FXN from WB and DBS samples was 99%. Intraassay and interassay imprecision (CV) values were 4.9%–13% and 9.8%–16%, respectively. The FXN limit of detection was 0.07 ng/mL, and the reportable range of concentrations was 2–200 ng/mL. Reference adult and pediatric FXN concentrations ranged from 15 to 82 ng/mL (median, 33 ng/mL) for DBS and WB. The FXN concentration range was 12–22 ng/mL (median, 15 ng/mL) for FRDA carriers and 1–26 ng/mL (median 5 ng/mL) for FRDA patients. Measurement of the FXN/CP ratio increased the ability to distinguish between patients, carriers, and the reference population. CONCLUSIONS This assay is applicable to the diagnosis and therapeutic monitoring of FRDA. This assay can measure FXN and the control protein CP in both WB and DBS specimens with minimal sample requirements, creating the potential for high-throughput population screening of FRDA.