Daniel Eastwood

Enteric defensins are essential regulators of intestinal microbial ecology.

Antimicrobial peptides are important effectors of innate immunity throughout the plant and animal kingdoms. In the mammalian small intestine, Paneth cell α-defensins are antimicrobial peptides that contribute to host defense against enteric pathogens. To determine if α-defensins also govern intestinal microbial ecology, we analyzed the intestinal microbiota of mice expressing a human α-defensin gene (DEFA5) and in mice lacking an enzyme required for the processing of mouse α-defensins. In these complementary models, we detected significant α-defensin-dependent changes in microbiota composition, but not in total bacterial numbers. Furthermore, DEFA5-expressing mice had striking losses of segmented filamentous bacteria and fewer interleukin 17 (IL-17)-producing lamina propria T cells. Our data ascribe a new homeostatic role to α-defensins in regulating the makeup of the commensal microbiota.

Preventing Leg Amputations in Critical Limb Ischemia With Below-the-Knee Drug-Eluting Stents: The PaRADISE (PReventing Amputations using Drug eluting StEnts) Trial

OBJECTIVES We investigated the efficacy and safety of using balloon expandable drug-eluting stents (DES) to prevent amputations in patients with below-the-knee critical limb ischemia. BACKGROUND Critical limb ischemia patients have a 1-year amputation rate of 30% and a mortality rate of 25%. Most patients with critical limb ischemia have severe below-the-knee arterial disease that limits the use of bypass surgery or balloon angioplasty. METHODS In all, 106 patients (118 limbs) were treated with DES in this prospective, nonrandomized trial. No patients were excluded because of comorbidities or unfavorable anatomy. Primary end points were major amputation and mortality, each stratified by Rutherford category. RESULTS The mean patient age was 74 +/- 9 years. There were 228 DES implanted (83% Cypher [Cordis, Johnson & Johnson, Warren, New Jersey], 17% Taxus [Boston Scientific, Maple Grove, Minnesota]). The number of stents per limb was 1.9 +/- 0.9, and 35% of limbs received overlapping DES (length of 60 +/- 13 mm). There were no procedural deaths, and 96% of patients were discharged within 24 h. The 3-year cumulative incidence of amputation was 6 +/- 2%, survival was 71 +/- 5%, and amputation-free-survival was 68 +/- 5%. Only 12% of patients who died had a preceding major amputation. Rutherford category, age, creatinine level, and dialysis (p <or= 0.001 to 0.04) were predictors of death but not amputation. Target limb revascularization occurred in 15% of patients, and repeat angiography in 35% of patients revealed a binary restenosis in 12%. CONCLUSIONS Treating below-the-knee critical limb ischemia with DES is an effective and safe means of preventing major amputation and relieving symptoms. Procedural complications and limb revascularization rates were low. Limb salvage and survival rates in patients treated with DES exceed those of historic controls.

Multivariate analysis suggests improved perioperative outcome in Crohn's disease patients receiving immunomodulator therapy after segmental resection and/or strictureplasty.

BACKGROUND Medical management of moderate to severe Crohns disease (CD) using immunomodulator agents has not eliminated surgical treatment of disease complications. The effect of improved medical treatment on perioperative CD surgical outcome is not known. We analyzed the impact of immunomodulator therapy on the rate of intraabdominal septic complications (IASC) in CD patients undergoing bowel reanastomosis or strictureplasty. METHODS Surgical outcome was reviewed in 100 consecutive CD patients who underwent segmental resection with primary anastomosis or strictureplasty between 1998 and 2002. Multivariate analysis was performed to determine the effect of immunomodulator therapy on rate of IASC (intraabdominal abscess, anastomotic leak, or enterocutaneous fistulae). Immunomodulator agents included azathioprine, 6-MP, methotrexate, and infliximab. RESULTS IASC developed in 11 of 100 (11%) operations. Immunomodulator use was associated with fewer IASC (4/72 procedures; 5.6%), compared with 7/28 (25%) cases with patients not on therapy (P<.01). IASC were not influenced by steroid use, smoking status, preoperative abscess, or fistula or albumin levels. Immunomodulator use did not affect the length of resection or the rate and number of strictureplasties. CONCLUSION Medical management with immunomodulator therapy is safe and significantly decreases postoperative IASC in CD patients undergoing surgical procedures requiring bowel anastomosis or strictureplasty.

Multidetector Computerized Tomography Urography as the Primary Imaging Modality for Detecting Urinary Tract Neoplasms in Patients With Asymptomatic Hematuria

PURPOSE We determined whether multidetector computerized tomography urography is sensitive and specific for detecting urinary tract neoplasms when used as the primary imaging modality for evaluating patients with hematuria. MATERIALS AND METHODS A retrospective review was performed of the radiological, urological and pathological records of 468 patients without a history of urinary neoplasms who presented with hematuria. All patients underwent multidetector computerized tomography urography and complete urological evaluation, including cystoscopy. Laboratory urinalysis and cytology were done in 350 and 318 of the 468 patients, respectively. Multivariate logistic regression analysis was performed using the variables multidetector computerized tomography urography diagnosis, worst urine cytology, number of red blood cells per high power field, gross hematuria, age and gender to predict urinary tract neoplasm. RESULTS A total of 50 urinary neoplasms were diagnosed in 468 patients. Multidetector computerized tomography urography detected 32 of 50 neoplasms for a sensitivity of 64%, specificity of 98%, positive predictive value of 76% and negative predictive value of 96%. There were 10 false-positive and 18 false-negative multidetector computerized tomography urography studies. Multivariate logistic regression showed that abnormal multidetector computerized tomography urography findings, ie neoplasm (p <0.0001), and suspicious or positive urine cytology (p = 0.0009) were significant. Patients with an abnormal multidetector computerized tomography urography diagnosis and suspicious or positive urine cytology had 44 and 47 times greater odds, respectively, of having urinary neoplasms compared to the odds in those with normal examinations. CONCLUSIONS Multidetector computerized tomography urography is relatively sensitive and highly specific for detecting urinary neoplasms. It may serve as the primary imaging modality to evaluate patients with hematuria. Multidetector computerized tomography urography does not eliminate the role of cystoscopy in the evaluation of hematuria.

Subtenon’s depot corticosteroid injections in patients with a history of corticosteroid-induced intraocular pressure elevation☆

PURPOSE To determine whether a history of intraocular pressure elevation from local corticosteroid administration could predict subsequent intraocular pressure elevation after posterior subtenons corticosteroid injection. METHODS A retrospective review was performed of 64 consecutive patients (64 eyes) receiving posterior subtenons corticosteroid injection. Patients were categorized as either historical corticosteroid responders or nonresponders based on intraocular pressure response to topical corticosteroid drops in the same eye or to previous posterior subtenons corticosteroid injection of the fellow eye. Historical responders were defined as having a relative intraocular pressure increase of 5 mm Hg and absolute intraocular pressure greater than 24 mm Hg with an anatomically open angle. Relative risk of intraocular pressure elevation was evaluated based on historical response and presenting diagnosis. RESULTS Nine eyes were historical responders, and 55 eyes were historical nonresponders. A higher rate of recurrent intraocular pressure elevation developed in historical responder eyes (4 of 9, 44%) compared with nonresponders (7 of 55, 13%) after posterior subtenons injection (P = .04, Fishers test; P = .07, Kaplan-Meier analysis). Historical responders with uveitis were at significantly higher risk of intraocular pressure elevation than nonresponders without uveitis (hazard ratio = 10.8, P = .04, Cox proportional hazards). All but one eye that developed intraocular pressure elevation from posterior subtenons injection was adequately controlled with topical antiglaucoma therapy. CONCLUSION In nonglaucomatous eyes, a previous history of corticosteroid-induced intraocular pressure elevation is a relative, not absolute, contraindication to posterior subtenons corticosteroid injection, because the risk of intraocular pressure elevation is not absolute, and because it can usually be well controlled with topical antiglaucoma therapy.

Opacification of the Genitourinary Collecting System During MDCT Urography with Enhanced CT Digital Radiography: Nonsaline Versus Saline Bolus

OBJECTIVE The purpose of this study was to determine whether a saline bolus during CT urography improves urinary collecting system opacification and whether the addition of enhanced CT digital radiography (CTDR) improves urinary collecting system visualization with or without a saline bolus. MATERIALS AND METHODS One hundred eight CT urography and enhanced CTDR examinations were reviewed. Fifty-four patients were given a saline bolus during CT urography, and 54 patients underwent CT urography without a saline bolus. Urinary collecting system opacification was evaluated by group (saline vs nonsaline), imaging technique (CT urography alone vs CT urography plus enhanced CTDR), number of enhanced CTDR images, and site of nonopacified urinary segments. Using a multivariate logistic regression model, we determined significance of variables and odds of complete opacification. RESULTS In the saline group, 248 nonopacified sites were identified on CT urography alone and 95 sites with CT urography plus enhanced CTDR. In the nonsaline group, 185 nonopacified sites were identified on CT urography alone and 59 sites with CT urography plus enhanced CTDR. Combining both groups, 433 nonopacified sites were identified with CT urography alone and 154 sites with CT urography plus enhanced CTDR. Multivariate logistic regression showed significance for group (p = 0.010), imaging method (p < 0.0001), number of enhanced CTDR images (p = 0.048), and site of segment opacification (p < 0.0001). The renal pelvis shows the greatest odds and the distal ureter the lowest odds for complete opacification by group or imaging method. CONCLUSION The addition of a saline bolus offers no improvement, whereas the addition of enhanced CTDR offers significant improvement in collecting system opacification during CT urography.

Long-Term Outcome Evaluation in Young Adults Following Clubfoot Surgical Release

Background The aim of this study was to evaluate the long-term outcome of a comprehensive surgical release for congenital talipes equinovarus (CTEV). Methods Gait, strength, segmental foot motion, and outcomes questionnaire data were collected on 24 adults (21.8±2.3 y) who were surgically treated for CTEV as infants. These data were statistically compared with of 48-age group matched controls (23.2±2.4 y). Results The clubfoot group was functional in activities of daily living, although most patients did experience foot pain after a day of typical activities, such as walking, standing, using stairs and doing exercise. Lower extremity gait kinematics was similar to the control group. There were differences in segmental foot motion with the hindfoot in a more plantarflexed position relative to the tibia and the forefoot dorsiflexed, and adducted relative to the hindfoot. Ankle plantarflexion and inversion strength and range of motion was reduced in the clubfoot group in association with an increase in hip power generation during the preswing and initial swing phases of the gait cycle. Conclusions Surgical correction of CTEV was successful in providing a functional plantigrade foot as the patients reached adulthood. However, limitations included foot pain, limited foot range of motion, and weakness. Level of Evidence Level III.

Longitudinal Quality of Life Assessment of Patients with Hepatocellular Carcinoma after Primary Transarterial Chemoembolization

PURPOSE To determine the effects of primary chemoembolization on the health-related quality of life (HRQOL) of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Single-center prospective data collection with longitudinal analysis of HRQOL scores obtained via the Short Form-36 (SF-36) assessment tool was performed before and during serial chemoembolization procedures in 73 patients with HCC. Baseline HRQOL scores were evaluated for significant (P < .05) change within the total patient population during 4, 8, and 12 months of treatment, and separately within a subset of 23 patients who underwent three or more chemoembolization procedures. RESULTS Patients had decreased pretreatment baseline scores within all eight scales of the SF-36 compared with healthy age-adjusted norms. Within the total population, mental health scores improved after 4 months of chemoembolization (rate of change, 5.6; P = .05; n = 48), but no significant change was present at 8 or 12 months. Subset patients experienced improvements of mental health scores after the first (score change, 13; P = .008; n = 21) and second procedures (score change, 12.2; P = .002; n = 23) and improvements of bodily pain scores (score change, 9.9; P = .047; n = 21) after the initial procedure. Vitality scores worsened (score change, -7.8; P = .044; n = 21) in the subset after the first chemoembolization. CONCLUSIONS Patients with HCC are likely to perceive improved mental health during the first 4 months of primary treatment with chemoembolization. In addition, if patients ultimately undergo more than two procedures, they are likely to perceive improved mental health during the first two sessions, with decreased bodily pain during the initial session. Patient-perceived vitality will likely worsen after the initial procedure.

Does breast tumor location influence success of sentinel lymph node biopsy

BACKGROUND Controversy exists regarding the influence of sentinel lymph node (SLN) mapping technique or patient variables on the success rate of SLN mapping. We undertook a prospective study in a single institution series to evaluate multiple variables that could adversely affect SLN identification rates. STUDY DESIGN Data were collected on 174 patients who underwent 177 SLN mapping procedures followed by axillary dissection from October 1996 through January 2000. Patient demographics, body mass index (BMI), biopsy method, tumor size, palpability, and location were recorded. SLNs were identified by blue dye only (n = 31), Tc-99m sulfur colloid only (n = 34), or combined techniques (n = 112). Data were analyzed by logistic regression analysis and expressed as the probability of failure to map the SLN. RESULTS SLNs were identified successfully in 150 of 177 procedures (85%) with a false negative rate of 3.7%. Mapping success reached 93% using combination blue dye and isotope. Variables found to adversely affect SLN mapping success and the odds ratio of failure (OR) included lower inner quadrant (LIQ) location (OR 35.6), blue dye only (OR 42.4), BMI >30 and upper outer quadrant (UOQ) location (OR 14.6), and nonpalpable UIQ location (OR 25). LIQ location adversely affects mapping success independent of technique, tumor size, or obesity. Obesity and nonpalpability were adverse factors when tumors were located in the UOQ and UIQ, respectively. Age, biopsy technique, and tumor diameter did not affect SLN mapping success. CONCLUSIONS SLN mapping success is influenced by technique and tumor location, with best results achieved using combined techniques and for lesions located in quadrants other than the LIQ. Obesity and tumor palpability influence success in the context of tumor location.

Engraftment syndrome after autologous hematopoietic stem cell transplant supported by granulocyte-colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor (GM-CSF)

Summary:The engraftment syndrome (ES) is a phenomenon observed in some patients undergoing autologous hematopoietic stem cell transplant (AHSCT). ES is characterized by fever, rash, capillary leak, and pulmonary infiltrates occurring at the onset of engraftment. Prior studies have suggested that the administration of hematopoietic growth factors post-transplant results in the increased frequency of ES. However, the relative contribution of granulocyte colony-stimulating factor (G-CSF) vs granulocyte-macrophage colony-stimulating factor (GM-CSF) to the development of ES remains unknown. A total of 152 consecutive patients who were treated with high-dose chemotherapy and AHSCT supported by either G-CSF or GM-CSF were analyzed retrospectively. In all, 20 patients developed ES, an incidence of 13%. ES was seen more frequently in patients who received GM-CSF (GM-CSF 24% vs G-CSF 4%, p=0.0001). The highest incidence of ES was observed in breast cancer patients (42% of breast cancer patients; 70% of all ES cases). Comparison of the incidence of ES by the priming regimen used comprising either of the growth factors revealed no significant association (p=0.8224). This study demonstrates that the incidence of ES is higher using GM-CSF, particularly in patients with breast cancer. It suggests that it might be advantageous to administer only G-CSF in breast cancer patients undergoing AHSCT to reduce ES-related morbidity.