Jefferson Hospital

BACKGROUND: mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown. METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival. RESULTS: Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred. CONCLUSIONS: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).

RSNA, 2017.

It has been shown that the type of Colles' fracture incurred bears a definite relationship to the end result obtained. A fairly high percentage of unsatisfactory end results was found in the two groups with comminuted fractures. In adidition, in a comminuted Colles' fracture the threat of traumatic arthritis is always present. The basic nature of the fracture must therefore be considered a factor in the prognosis. The study of the fracture components themselves has demonstrated that the original reduction in all cases has been inadequate. The importance of this factor in influencing end results is illustrated by the fact that those cases showing the most complete reductions have been listed among the excellent end results. Among the fracture components, residual dorsal tilt has a more direct influence on an unfavorable end result than either residual radial deviation, residual shortening, or loss of integrity of the distal radio-ulnar joint. The method of immobilization used in this series was inefficient and inadequate. Sixty per cent. of our cases, when re-examined eighteen months after injury, showed a fracture healed in a position typical of a fresh unreduced Colles' fracture. In spite of incomplete reduction and inadequate immobilization the functional results at the time of the follow-up examination were found to be surprisingly good. Satisfactory functional end results were obtained in 68.3 per cent. of cases in this series. The chief credit for this percentage must be given to the innate ability of the wrist joint to overcome and compensate for residual bony deformity, rather than to the original treatment. Studies of function have shown that a great deal of bony deformity must be present before any of the motions at the wrist are compromised. A total of 31.7 per cent. of unsatisfactory results, however, is much too high for a fracture which continues to he lightly regarded and for which treatment tends to follow a routine pattern. The fruits of this attitude are apparent when the entire course of the fracture is reviewed. We believe that, aside from tile specific type of fracture incurred, insufficient reduction and present inadequate methods of immobilization are the factors responsible for unsatisfactory functional end results in the healed Colles' fractures in this series.

BACKGROUND: Breast carcinomas in African-American patients appear to be more aggressive than in Caucasian patients due to multifactorial differences. METHODS: The authors compiled pathology data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database regarding stage, histologic grade, and estrogen receptor (ER) expression in breast carcinomas diagnosed in 197,274 African-American and Caucasian patients between 1990 and 2000, and the same information, along with nuclear grade, Ki-67, c-erb-B2, and p53 expression, in 2230 African-American and Caucasian patients diagnosed at Thomas Jefferson University Hospital between 1995 and 2002. Immunohistochemical markers were assayed in paraffin-embedded, formalin-fixed tissue stained with hematoxylin and eosin using antibodies to these proteins, with differences in expression analyzed by the chisquare test. RESULTS: In both databases, more African-American patients presented with advanced stage tumors and higher histologic (P < .001) and nuclear grade (P < .001) than Caucasian patients. African-American patients had less ER positivity (51.9% vs 63.1%; P < .001) but significantly higher Ki-67 (42.4% vs 28.7%; P < .001) and p53 expression (19.4% vs 13.1%; P < .05) than Caucasian patients with all stages of disease. In addition, the basal or "triple-negative" breast cancer phenotype was more common in African-American patients than in Caucasian patients (20.8% vs 10.4%; P < .0001), and was associated with higher histologic and nuclear grade (P < .0001). CONCLUSIONS: African-American patients with breast carcinomas are more likely than Caucasian patients to present with tumors that are of a later stage and higher grade, with higher Ki-67 expression and more ER negativity, thereby highlighting a greater need for early screening among African-American women. Molecular studies that may explain these differences, and correlations with survival, have been proposed to identify therapeutic targets.

BACKGROUND: Although low-dose aspirin has been reported to reduce the incidence of preeclampsia among women at high risk for this complication, its efficacy and safety in healthy, nulliparous pregnant women are not known. METHODS: We studied 3135 normotensive nulliparous women who were 13 to 26 weeks pregnant to determine whether treatment with aspirin reduced the incidence of preeclampsia. Of this group, 1570 women received 60 mg of aspirin per day and 1565 received placebo for the remainder of their pregnancies. We also evaluated the effect of aspirin on maternal and neonatal morbidity. RESULTS: Of the original group of 3135 women, 2985 (95 percent) were followed throughout pregnancy and the immediate puerperium. The incidence of preeclampsia was lower in the aspirin group (69 of 1485 women [4.6 percent]) than in the placebo group (94 of 1500 women [6.3 percent]) (relative risk, 0.7; 95 percent confidence interval, 0.6 to 1.0; P = 0.05), whereas the incidence of gestational hypertension was 6.7 and 5.9 percent, respectively. There were no significant differences in the infants' birth weight or in the incidence of fetal growth retardation, postpartum hemorrhage, or neonatal bleeding problems between the two groups. Subgroup analysis showed that preeclampsia occurred primarily in women whose initial systolic blood pressure was 120 to 134 mm Hg (incidence among such women, 5.6 percent in the aspirin group vs. 11.9 percent in the placebo group; P = 0.01). The incidence of abruptio placentae was greater among the women who received aspirin (11 women, vs. 2 in the placebo group; P = 0.01). CONCLUSIONS: Low-dose aspirin decreases the incidence of preeclampsia among nulliparous women, primarily through its effect in those who have elevated systolic blood pressure initially. This treatment does not decrease perinatal morbidity but increases the risk of abruptio placentae.

Abstract Arabinosyl cytosine (ara-C), a synthetic pyrimidine nucleoside related to the normal metabolites cytidine and deoxycytidine, has been found capable of producing marrow remission at tolerable doses in acute myelocytic and acute lymphocytic leukemia in adults. There were 16 per cent remissions complete in all aspects, 3 per cent complete except for hemoglobin level, and 6 per cent partial remissions among 180 adults with acute myelocytic leukemia treated with any one of 8 variants of infusion duration or daily dose of ara-C. Twenty-four per cent of 37 adults with acute lymphocytic or unclassified leukemia had complete or partial remissions. The comparison of 1, 4, 12 and 24 hours infusion of ara-C (to total dose tolerated) does not show significant superiority for any one group. The complete remission rate with 1 or 12 hour infusions, however, is 25 per cent (superior to that obtained with 6-mercaptopurine) and the recommended schedule of treatment for ara-C based on these data is, therefore, daily infusions of 100 or 50 mg./m.2 in one hour for approximately 3 to 6 weeks followed by maintenance therapy of once weekly subcutaneous injection of 30 mg./m.2 of ara-C. Platelet transfusions should be available when ara-C is used.

No AccessJournal of Urology1 May 1967Clinical Use of Long-Term Indwelling Silicone Rubber Ureteral Splints Inserted Cystoscopically Paul D. Zimskind, Theodore R. Fetter, and J. Louis Wilkerson Paul D. ZimskindPaul D. Zimskind Markle Scholar in Academic Medicine More articles by this author , Theodore R. FetterTheodore R. Fetter Died January 19, 1967. More articles by this author , and J. Louis WilkersonJ. Louis Wilkerson More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)63130-6AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 1967 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byIbilibor C, Grand R, Daneshfar C, deRiese W and Smith C (2019) Impact of Retained Ureteral Stents on Long-Term Renal FunctionUrology Practice, VOL. 6, NO. 2, (107-111), Online publication date: 1-Mar-2019.Jain R, Chaparala H, Omar M, Ganesan V, Sivalingam S, Noble M and Monga M (2017) Retained Ureteral Stents at a Tertiary Referral Stone Center—Who is at Risk?Urology Practice, VOL. 5, NO. 6, (452-457), Online publication date: 1-Nov-2018.Fiuk J, Bao Y, Calleary J, Schwartz B and Denstedt J (2018) The Use of Internal Stents in Chronic Ureteral ObstructionJournal of Urology, VOL. 193, NO. 4, (1092-1100), Online publication date: 1-Apr-2015.Yakoubi R, Lemdani M, Monga M, Villers A and Koenig P (2018) Is There a Role for α-Blockers in Ureteral Stent Related Symptoms? 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(1135-1138), Online publication date: 1-Feb-2002.OLWENY E, PORTIS A, AFANE J, BREWER A, SHALHAV A, LUSZCZYNSKI K, McDOUGALL E and CLAYMAN R (2018) FLOW CHARACTERISTICS OF 3 UNIQUE URETERAL STENTS:: INVESTIGATION OF A POISEUILLE FLOW PATTERNJournal of Urology, VOL. 164, NO. 6, (2099-2103), Online publication date: 1-Dec-2000.GOTWALD T, PESCHEL R, FRAUSCHER F, NEURURER R, NEDDEN D and BARTSCH G (2018) INDWELLING URETERAL STENT FRAGMENTATION WITH SEVERE ENCRUSTATION AND STONE FORMATIONJournal of Urology, VOL. 162, NO. 3 Part 1, (788-788), Online publication date: 1-Sep-1999.PEARLE M, PIERCE H, MILLER G, SUMMA J, MUTZ J, PETTY B, ROEHRBORN C, KRYGER J and NAKADA S (2018) OPTIMAL METHOD OF URGENT DECOMPRESSION OF THE COLLECTING SYSTEM FOR OBSTRUCTION AND INFECTION DUE TO URETERAL CALCULIJournal of Urology, VOL. 160, NO. 4, (1260-1264), Online publication date: 1-Oct-1998.Pantuck A, Weiss R and Cummings K (2018) Routine Stentograms are not Necessary Before Stent Removal Following Radical CystectomyJournal of Urology, VOL. 158, NO. 3, (772-775), Online publication date: 1-Sep-1997.Roth S, Semjonow A, Waldner M and Hertle L (2018) Anuria Due to Intrarenal Blood Clots in Solitary Kidney After Change of Ureteral Stent: Resolution with Minimally Invasive EvacuationJournal of Urology, VOL. 154, NO. 1, (195-196), Online publication date: 1-Jul-1995.Mykulak D, Herskowitz M and Glassberg K (2018) Use of Magnetic Internal Ureteral Stents in Pediatric Urology: Retrieval without Routine Requirement for Cystoscopy and General AnesthesiaJournal of Urology, VOL. 152, NO. 3, (976-977), Online publication date: 1-Sep-1994.Alvarez-Vijande R (2018) A Simple Method for the Removal of Indwelling Ureteral Stents in WomenJournal of Urology, VOL. 150, NO. 1, (149-150), Online publication date: 1-Jul-1993.Witjes J (2018) Breakage of a Silicone Double Pigtail Ureteral Stent as a Long-Term ComplicationJournal of Urology, VOL. 150, NO. 6, (1898-1899), Online publication date: 1-Dec-1993.Nishimura T, Terashima Y, Kondo Y, Ohba S, Yoshida K and Akimoto M (2018) Long-Term Indwelling Bilateral Ureteral Stents for Bilateral Hydronephrosis of Unknown EtiologyJournal of Urology, VOL. 149, NO. 1, (96-99), Online publication date: 1-Jan-1993.Hübner W, Plas E and Stoller M (2018) The Double-J Ureteral Stent: In Vivo and in Vitro Flow StudiesJournal of Urology, VOL. 148, NO. 2 Part 1, (278-280), Online publication date: 1-Aug-1992.Pryor J, Langley M and Jenkins A (2018) Comparison of Symptom Characteristics of Indwelling Ureteral CathetersJournal of Urology, VOL. 145, NO. 4, (719-722), Online publication date: 1-Apr-1991.Docimo S and Dewolf W (2018) High Failure Rate of Indwelling Ureteral Stents in Patients with Extrinsic Obstruction: Experience at 2 InstitutionsJournal of Urology, VOL. 142, NO. 2 Part 1, (277-279), Online publication date: 1-Aug-1989.Wegenke J (2018) Exchange/Retrograde Ureteral Stent SetJournal of Urology, VOL. 140, NO. 3, (550-551), Online publication date: 1-Sep-1988.Pollard S and Macfarlane R (2018) Symptoms Arising from Double-J Ureteral StentsJournal of Urology, VOL. 139, NO. 1, (37-38), Online publication date: 1-Jan-1988.Spirnak J and Resnick M (2018) Stone Formation as a Complication of Indwelling Ureteral Stents: A Report of 5 CasesJournal of Urology, VOL. 134, NO. 2, (349-351), Online publication date: 1-Aug-1985.Gibbons R (2018) Editorial CommentsJournal of Urology, VOL. 134, NO. 2, (351-351), Online publication date: 1-Aug-1985.Finney R (2018) Editorial CommentsJournal of Urology, VOL. 134, NO. 2, (351-351), Online publication date: 1-Aug-1985.Gardiner R (2018) Endoscopic Transvesical UreterotomyJournal of Urology, VOL. 134, NO. 4, (729-732), Online publication date: 1-Oct-1985.Andriole G, Bettmann M, Garnick M and Richie J (2018) Indwelling Bouble-J Ureteral Stents for Temporary and Permanent Urinary Drainage: Experience With 87 PatientsJournal of Urology, VOL. 131, NO. 2, (239-241), Online publication date: 1-Feb-1984.Gerber W and Narayana A (2018) Failure of the Double-Curved Ureteral StentJournal of Urology, VOL. 127, NO. 2, (317-319), Online publication date: 1-Feb-1982.Gibbons R (2018) Editorial CommentJournal of Urology, VOL. 127, NO. 2, (319-319), Online publication date: 1-Feb-1982.Raghavaiah N (2018) New Self-Retaining Ureteral CatheterJournal of Urology, VOL. 126, NO. 1, (29-30), Online publication date: 1-Jul-1981.Finney R (2018) Editorial CommentJournal of Urology, VOL. 126, NO. 1, (30-30), Online publication date: 1-Jul-1981.Solomon M and Macgregor R (2018) Ureterocutaneous Fistula Following Hip SurgeryJournal of Urology, VOL. 124, NO. 3, (427-428), Online publication date: 1-Sep-1980.Singh B, Kim H and Wax S (2018) Stent Versus Nephrostomy: Is There a Choice?Journal of Urology, VOL. 121, NO. 3, (268-270), Online publication date: 1-Mar-1979.J.J.M. (2018) Editorial CommentJournal of Urology, VOL. 121, NO. 3, (270-270), Online publication date: 1-Mar-1979.Finney R (2018) Experience with New Double J Ureteral Catheter StentJournal of Urology, VOL. 120, NO. 6, (678-681), Online publication date: 1-Dec-1978.Hepperlen T, Mardis H and Kammandel H (2018) Self-Retained Internal Ureteral Stents: A New ApproachJournal of Urology, VOL. 119, NO. 6, (731-733), Online publication date: 1-Jun-1978.Gibbons R (2018) Editorial CommentJournal of Urology, VOL. 119, NO. 6, (733-734), Online publication date: 1-Jun-1978.Gibbons R, Correa R, Cummings K and Mason J (2018) Experience with Indwelling Ureteral Stent CathetersJournal of Urology, VOL. 115, NO. 1, (22-26), Online publication date: 1-Jan-1976.Gibbons R, Mason J and Correa R (2018) Experience with Indwelling Silicone Rubber Ureteral CathetersJournal of Urology, VOL. 111, NO. 5, (594-599), Online publication date: 1-May-1974.Orikasa S, Tsuji I, Siba T and Ohashi N (2018) A New Technique for Transurethral Insertion of a Silicone Rubber Tube into an Obstructed UreterJournal of Urology, VOL. 110, NO. 2, (184-187), Online publication date: 1-Aug-1973.Funkhouser J and Sacher E (2018) The Contiguous Helix Ureteral Lengthening Flap for Repair of Distal Ureteral InjuryJournal of Urology, VOL. 107, NO. 4, (567-571), Online publication date: 1-Apr-1972. Volume 97Issue 5May 1967Page: 840-844 Advertisement Copyright & Permissions© 1967 by The American Urological Association Education and Research, Inc.MetricsAuthor Information Paul D. Zimskind Markle Scholar in Academic Medicine More articles by this author Theodore R. Fetter Died January 19, 1967. More articles by this author J. Louis Wilkerson More articles by this author Expand All Advertisement PDF downloadLoading ...

BACKGROUND AND OBJECTIVES: Serum creatinine (Scr) does not allow for early diagnosis of acute kidney injury (AKI). The diagnostic utility of urinary kidney injury molecule-1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG), and neutrophil gelatinase associated lipocalin (NGAL) was evaluated for the early detection of postoperative AKI in a prospective study of 90 adults undergoing cardiac surgery. Designs, setting, participants, & measurements: Urinary KIM-1, NAG, and NGAL were measured at 5 time points for the first 24 h after operation and normalized to the urinary creatinine concentration after cardiac surgery. Receiver-operating characteristic curves were generated and the areas under the curve (AUCs) compared for performance of biomarkers in detection of postoperative AKI. RESULTS: Thirty-six patients developed AKI, defined as an increase in Scr of > or =0.3 mg/dl within 72 h after surgery. The AUCs for KIM-1 to predict AKI immediately and 3 h after operation were 0.68 and 0.65; 0.61 and 0.63 for NAG; and 0.59 and 0.65 for NGAL, respectively. Combining the three biomarkers enhanced the sensitivity of early detection of postoperative AKI compared with individual biomarkers: the AUCs for the three biomarkers combined were 0.75 and 0.78. The performance of combining biomarkers was even better among 16 early postoperative AKI patients with AUCs of 0.80 and 0.84, respectively. CONCLUSIONS: The results of this study support that a combination of urinary biomarkers may allow for early detection of postoperative AKI after cardiac surgery before a rise in Scr.

TWENTY years ago Drs. Seymour Kety and Carl Schmidt first described the inert-gas technic for the quantitative measurement of cerebral blood flow. Conceived and developed in the Pharmacology Laboratory of the University of Pennsylvania and carried out on the wards of the Philadelphia General Hospital, the nitrous oxide method was first reported in 1945 in the American Journal of Physiology. 1 Since then, and on the basis of this method, a remarkable number of data have accumulated on the physiology of the cerebral circulation. Normal brain metabolism has been elucidated, along with alterations produced by drugs and disease.2 , 3 In the ensuing . . .

Iorio, Richard MD; Robb, William J. MD; Healy, William L. MD; Berry, Daniel J. MD; Hozack, William J. MD; Kyle, Richard F. MD; Lewallen, David G. MD; Trousdale, Robert T. MD; Jiranek, William A. MD; Stamos, Van P. MD; Parsley, Brian S. MD Author Information

The Interaural Time Difference for High-Pass Filtered Noise and Its Relationship With Brainstem Dysfunction and Disability in Multiple Sclerosis,

Rupture of the posterior tibial tendon has been postulated to occur, in part, as a result of degenerative changes to the tendon. This possibility was examined by a review of 67 patients (average age 57 years) diagnosed with rupture of the posterior tibial tendon. Forty-five of the 67 patients (60%) had one or more of the following positive medical histories: (1) hypertension, (2) obesity, (3) diabetes mellitus, (4) previous surgery or trauma about the medial aspect of the foot, or (5) steroid exposure. Thirty-five patients (52%) had either hypertension, diabetes mellitus, or obesity. A statistical correlation was demonstrated between rupture of the posterior tibial tendon and obesity (P = .005) and to a lesser extent hypertension (P = .025). These disorders have been uniformly associated with an acceleration of the degenerative processes associated with aging, commonly via an acceleration of microvascular and macrovascular diseases. An additional vascular risk is implicated by the known zone of hypovascularity of the posterior tibial tendon and risk of rupture secondary to systemic or local injections of corticosteroids. The prevalence of posterior tibial tendon rupture parallels the degenerative processes of aging, hypertension, diabetes mellitus, and obesity. Additionally, the effects of corticosteroids and local surgical procedures may further be associated with local vascular impairment and eventual rupture.

BACKGROUND: With the recent trend toward minimally invasive total joint arthroplasty and the increased emphasis on faster recovery and shorter hospital stays, it has become increasingly important to recognize the timing and severity of the various complications associated with elective total joint arthroplasty to ensure that early patient discharge is a safe practice. METHODS: We evaluated the systemic and local complications associated with primary unilateral lower-extremity arthroplasties performed during one year in 1636 patients. A total of 966 patients had a primary total hip arthroplasty, and 670 had a primary total knee arthroplasty. All complications that occurred in the hospital and for six weeks following the index surgery were recorded. The circumstances leading to the complications and the details of the therapeutic intervention for each complication were recorded. Analyses were performed to predict the factors that predispose patients to serious complications. RESULTS: One patient (0.06%) in the cohort died during the hospital stay. There were a total of 104 major (life-threatening) complications, including cardiac arrest (one), tachyarrhythmia (thirty-three), pulmonary edema or congestive heart failure (ten), myocardial infarction (six), hypotensive crisis (four), pulmonary embolus (twenty-five), acute renal failure (fourteen), stroke (six), bowel obstruction or perforation (three), and pneumothorax (one). There were seventeen major local complications. Ninety-four (90%) of the major complications occurred within four days after the index surgery. Although older age, increased body mass, and preexistent comorbidities were important predisposing factors for serious medical complications, 58% of the patients who had life-threatening complications develop had no identifiable predisposing factors. CONCLUSIONS: This study demonstrated that most of the complications of lower-extremity total joint replacement occur within the time-frame of the typical hospital stay. Given the serious nature of some of these complications and the inability to identify many of the patients who may be at risk, we caution against early discharge of patients from the hospital after elective total joint arthroplasty in the lower extremity.

Abstract The effect of 6-MP therapy on the duration of remissions induced by adrenal corticosteroids has been studied as a model for testing of new agents. Ninetytwo patients under age 20 entered the study and were accepted for analysis. Sixty-two (67 per cent) had complete or partial remissions induced by corticosteroids. Patients in remission were randomly assigned to maintenance therapy with either 6-MP or placebo. The median duration of 6-MP-maintained complete remissions was 33 weeks and for placebo, 9 weeks. A sequential experimental design was used to analyze remission times while the study was in progress. This resulted in the study being stopped after analysis of the remission times of 21 pairs of patients (42 patients). Overall survival was not significantly different for the two treatment programs, since patients maintained on placebo were treated with 6-MP when relapse occurred. The activity of the known active antileukemic compound 6-MP was readily detected by this experimental design without compromise of optimal survival. Such a design should prove useful for the evaluation of new agents and also permit study of the remission maintenance activity of a compound separately from its remission inducing activity.

PURPOSE Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services. METHODS A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (&gt; 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider). RESULTS Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing—initial testing of priority genes followed by expanded testing—was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches. CONCLUSION This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

Abstract Purpose: To evaluate the results of the randomized, double-blind, placebo-controlled phase II clinical trial of ICT-107 in patients with newly diagnosed glioblastoma. Patients and Methods: We conducted a double-blinded randomized phase II trial of ICT-107 in newly diagnosed patients with glioblastoma (GBM) and tested efficacy, safety, quality of life (QoL), and immune response. HLA-A1+ and/or -A2+–resected patients with residual tumor ≤1 cm3 received radiotherapy and concurrent temozolomide. Following completion of radiotherapy, 124 patients, randomized 2:1, received ICT-107 [autologous dendritic cells (DC) pulsed with six synthetic peptide epitopes targeting GBM tumor/stem cell–associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL13Rα2] or matching control (unpulsed DC). Patients received induction ICT-107 or control weekly × 4 followed by 12 months of adjuvant temozolomide. Maintenance vaccinations occurred at 1, 3, and 6 months and every 6 months thereafter. Results: ICT-107 was well tolerated, with no difference in adverse events between the treatment and control groups. The primary endpoint, median overall survival (OS), favored ICT-107 by 2.0 months in the intent-to-treat (ITT) population but was not statistically significant. Progression-free survival (PFS) in the ITT population was significantly increased in the ICT-107 cohort by 2.2 months (P = 0.011). The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher immune response (via Elispot). HLA-A2 patients achieved a meaningful therapeutic benefit with ICT-107, in both the MGMT methylated and unmethylated prespecified subgroups, whereas only HLA-A1 methylated patients had an OS benefit. Conclusions: PFS was significantly improved in ICT-107–treated patients with maintenance of QoL. Patients in the HLA-A2 subgroup showed increased ICT-107 activity clinically and immunologically.

Management of hypertrophic scars and keloids has advanced from crude, invasive methods such as gross excision and radiation to intralesional or topical agents that act on a cellular level. There is no universally accepted treatment regimen and no evidence-based literature to guide management. Our objectives are to present a list of available treatment regimens, their proposed mechanisms of action, and supporting evidence and to perform a meta-analysis of clinical trials to identify treatments with a better-than-even likelihood of improvement. We conducted a PubMed search through October 2005, identifying clinical studies of various treatments for hypertrophic scars and keloids. We graded the quality of each study, delineated the results into favorable vs nonfavorable, and calculated the statistical significance of the findings. The meta-analysis of 70 treatment series for various clinical measures showed a 70% chance of improvement with treatment; however, the mean amount of improvement to be expected was around 60%. There was no statistically significant difference between treatments. Most treatments for keloidal and hypertrophic scarring offer minimal likelihood of improvement. The magnitude of likely permanent improvement in any sign or symptom may be clinically meaningful but far short of cure. Novel therapies deserve further investigation but remain without proven benefit to date.

DEPALMA, ANTHONY F. M.D.; MCKEEVER, C. DICKSON M.D.; SUBIN, DAVID K. M.D. Author Information

Abstract The efficacy of three therapeutic programs for acute leukemia were compared. These programs included (1) Methotrexate (Phase I) followed by 6-mercaptopurine (Phase II); (2) 6-mercaptopurine (Phase I) followed by Methotrexate (Phase II); and (3) Combination Therapy, i.e., 6-mercaptopurine given in combination with Methotrexate. In children with acute lymphocytic leukemia the remission rate was 59 per cent for combination therapy, 47 per cent for 6-mercaptopurine, and 29 per cent for Methotrexate. The better remission rate for combination therapy is consistent with that predicted if it is assumed that 6-mercaptopurine and Methotrexate act independently. The median duration of complete remissions for the three treatments was not different (4 to 5 months). However, long lasting remissions were more frequent in patients receiving combination therapy. The median survival from the onset of therapy to death was 9 months. There were no differences between the three treatment programs as regards survival. In adults the remission rate was 15 per cent for combination therapy, 21 per cent for 6-mercaptopurine and 7 per cent for Methotrexate. As regards survival in adults, early deaths were more common in patients who received MTX as initial therapy, whereas after 5 months survival was somewhat better in those patients receiving combination therapy. In both children and adults there was no evidence that prior treatment with one of the antimetabolites altered response to the other antimetabolite. This result differs from those in animal models, and its effect on our concept of the mechanism of resistance is discussed. Responsiveness to the second course of antimetabolite therapy (Phase II) was as good as that to the first course of treatment. This was true for the remission rate, remission duration, and even for survival when appropriate corrections were made. Thus, responsiveness to drug therapy is maintained as the disease progresses temporally. It may be concluded therefore that new agents can be effectively studied in patients with "late" disease. Responsiveness to Phase II therapy was independent of responsiveness to Phase I. The most common and severe toxic manifestations related to the bone marrow and gastrointestinal tract. There were no major differences quantitatively in the toxicity for the three treatment programs in children in spite of the fact that the drugs were given in full dosage in the combination program. Oral ulcers and a generalized erythematous rash occurred significantly more frequently in patients receiving Methotrexate. Jaundice was significantly more frequent in adults and in patients receiving 6-MP.

UNLABELLED: The association between wound drainage and subsequent periprosthetic infection is well known. However, the most appropriate treatment of wound drainage is not well understood. We retrospectively reviewed the records of 10,325 patients (11,785 procedures), among whom 300 patients (2.9%) developed persistent (greater than 48 hours postoperatively) wound drainage. Wound drainage stopped spontaneously between 2 and 4 days in 217 patients treated with local wound care and oral antibiotics. The remaining 83 patients (28%) underwent further surgery. A single débridement resulted in cessation of drainage without subsequent infection in 63 of 83 patients (76%), whereas 20 (24%) patients continued to drain and underwent additional treatment (repeat débridement, resection arthroplasty, or long-term antibiotics). Timing of surgery and the presence of malnutrition predicted failure of the first débridement. There were no differences between the success and failure groups with regard to all other examined parameters, including demographic or surgical factors. LEVEL OF EVIDENCE: Level III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.