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Background Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18–88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82–1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74–0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78–1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information ISRCTN 81261306; EudraCT Number: 2006-005505-64

Objective To characterize communication strategies of labor and delivery nurses and their physician colleagues during perinatal decisions. Design A quantitative descriptive design was used. Setting A perinatal setting in an urban acute care facility. Participants Twenty‐nine perinatal nurses and 11 attending physicians. Methods A model of team communication derived from research on cockpit crew communication served as a framework for this analysis. Data were taken from transcriptions of audio‐taped conversations and discourse analysis. Results Findings indicated that nurses and physicians tended to use status‐based communication styles and rarely employed team‐centered communication strategies. Conclusion Nurse and physician status‐based communication styles may hinder optimal patient outcomes.

William Tomison, in charge of the Hudson's Bay Company's Cumberland House on the Saskatchewan River, described the devastating smallpox epidemic of 1781 and 1782. He understood contagion, practised isolation and disinfection, and provided mortality statistics during a 'virgin soil' epidemic. Above all, he showed remarkable compassion. He and his men took dying Indians into their already crowded quarters, and provided them with food, shelter and 24 h care. This article describes the epidemic and its aftermath.

BACKGROUND Dramatic reductions in plasma HIV RNA levels are possible with current antiretroviral regimens; the effect of potent therapies and "undetectable" viral load on the perceived risk of HIV transmission and need for safer practices remains unknown. METHODS A questionnaire was developed to examine perceptions of HIV transmission risk and need for safer practices with unprotected anal, vaginal, and oral sex and intravenous drug use with needle sharing for HIV-discordant couples in which the HIV-infected partner was receiving no therapy, was receiving reverse transcriptase inhibitor therapy, and protease inhibitor (PI)-based therapy with viral load "undetectable". This was applied anonymously to 147 unselected HIV-infected individuals attending a university-based HIV clinic. RESULTS Almost all respondents believed that all sexual activities except oral sex were "very risky" and that safer practices were "extremely important" for those not receiving antiretroviral agents. Significantly fewer considered that anal or vaginal sex was "very risky" for those receiving PI therapy (90.9% and 86.0%, respectively), and fewer thought that safer practices for anal or vaginal sex were "very important" for those receiving PI therapy (93.0% and 91.6%, respectively). In total, 20.4% thought the risk of HIV transmission for at least one activity was reduced for those receiving PI therapy, and 19.0% believed that the need for safer practices was reduced by PI therapy. CONCLUSION A small but significant proportion of HIV-infected people perceive the need for safer practices to be reduced during antiretroviral therapy, particularly those containing PIs. Even if the risk is truly reduced, the importance of safer practices should be conveyed consistently and terms such as "undetectable" to describe HIV RNA responses should be avoided.

Tendon transfers are used to restore balance and function to a paralyzed, injured, or absent neuromuscular-motor unit. In general, tendon transfer is indicated for restoration of muscle function after peripheral nerve injury, injury to the brachial plexus or spinal cord, or irreparable injury to tendon or muscle. The goal is to improve the balance of a neurologically impaired hand. In the upper extremity, tendon transfers are most commonly used to restore function following injury to the radial, median, and ulnar nerves. An understanding of the general principles of tendon transfer is important to maximize the outcome.

It has been pointed out that an adenomatous formation composed of either tubal epithelium or endometrium, or in a few cases of both simultaneously, occurs rather frequently in the region of the uterine cornu and tubal isthmus. A previous operative trauma of this region is not essential for the production of such an adenomatous formation, nor is it necessarily associated with any previous inflammatory process. It may be considered then as a truly neoplastic formation or primary adenomyoma. From the types of epithelium described in these adenomyomas it is evident that they may arise from tubal epithelium as well as endometrium. The presence in a few cases of spaces lined by tubal epithelium as well as islands of true endometrium in the same specimen suggests the possibility of a metaplasia of one of these types of mucosa into the other. The finding of gland-like spaces lined by tubal epithelium but surrounded by endometrial stroma is even more suggestive of this possibility. The finding of ten cases in which the interstitial or isthmic portion of the tube is lined by endometrium rather than tubal mucosa is further evidence of the histologic variability of this region, and suggests again the possibility of a metaplasia of one of these types of mucosa into the other. Evidence gathered from the literature, particularly from the work of Sampson, tends to show that a number of cases reported as endometriosis are really cases of aberrant tubal epithelium. It is noted, however, that Sampson has called attention to this fact from time to time, and in a more recent work on “Endometriosis Following Salpingectomy” has stressed the probability of a metaplasia of tubal mucosa into endometrium. In a review of 24 cases diagnosed as endometriosis in our own laboratory it has been found that in a third of them the epithelial elements were definitely tubal in type. In some of them there was in addition to the tubal epithelium an endometrial-like stroma. In a few instances cysts lined by tubal epithelium and others with real endometrium occurred in the same case. In one very striking case the same hemorrhagic cyst of an ovary was lined in part by tubal epithelium, while another area of the cyst wall showed real endometrium with stroma and glands. Such cases lend additional evidence to the hypothesis that tubal epithelium may, by metaplasia, be transformed into endometrium.

Two cases of arrhenoblastoma of the ovary have been reported. Both occurred in relatively young women and in the right ovary. One was associated with rather marked virulism and microscopically was of the intermediate cell type. The other tumor, which was associated with only slight masculinization, was microscopically highly differentiated and resembled a tubular adenoma of Pick. The 17-ketosteroid exeretion was studied in one case and proved to be elevated preoperatively, falling to normal within twelve days postoperatively. Noopregnanediol was present in the urine in this case. A simple salpingo-oophorectomy was performed in one case, and the patient is well one year postoperatively with some regression of masculinization and regular menses. The other patient had a bilateral salpingo-oophorectomy and hysterectomy, and is well six months postoperatively.

s I N c E 1929 one of us (H. S. E.) has been interested in the urinary tract complications resulting from various types of gynecologic disease and from the methods of treatment of some of these disease entities. This interest was stimulated by 2 patients: one with a right ureteroperitoneal fistula and urinary ascites resulting from a surgical injury to the right ureter during hysterectomy for fibroids, the other with a vesicovaginal fistula, enormous hydroureters, terminal chronic pyelonephritis, and urinary ascites resulting from spontaneous perforation of the dilated left ureter, all of which followed irradiation therapy for carcinoma of the cervix. Reports of both of these cases were published in collaboration with Hunner,r, ’ and since that time a number of papers dealing with various aspects of such urologic complications have been presented and/or published either alone or with other members of our staff. The first of these reports resulting from a systematic study of the subject was pre

Acute gonorrhea/ urethritis in women has become rare, but chronic nonspecific granular urethritis is now frequent. Polyps are most often found associated with the latter, and may be responsible for the appearance of blood toward the end of each urination. Caruncles near the urethral meatus at times cause bleeding and pain, but they are usually symptomless and rarely undergo malignant degeneration. Obstruction of the urethra in children by folds of mucous membrane can cause symptoms of all degrees of severity including intractable enuresis and persistent infection; removal of such folds by fulguration or resection has often relieved these symptoms completely, but must be done with care to avoid producing incontinence and fistulas. The treatment of strictures is very difficult; scarring leads to rigidity of the urethral wall and incontinence at the sphincter, and the latter is not relieved by repeated dilatations. Urethral diverticula can be rendered visible by positive pressure urethrography; they sometimes afford an explanation of chronic or recurrent cystitis. Malignant tumors in and about the urethra are very difficult to treat surgically. Treatment by radiation has given better results in two series of malignant tumors in this location.

Secondary anemia following excessive uterine hemorrhage constitutes a frequent and important complication of gynecologic disorders. When the bleeding is the result of such gross lesions as uterine fibroids, a severe degree of anemia may present a situation requiring considerable delicacy of judgment in its handling. A major surgical procedure is usually necessary to stop the excessive flow effectively and permanently, and before the surgeon is justified in operating the anemia must be effectively treated to an extent sufficient to render the procedure a safe risk; this must usually be accomplished in the all too brief interval between two prolonged and profuse menstrual periods. It is therefore essential that one have at one's disposal efficient and speedy methods of effecting such an improvement. For many years iron in one form or another has been the standard drug used in the treatment of such conditions, and more recently transfusion has proved to

History. —E. R., a colored woman, aged 34, was first admitted to the gynecologic service of the Johns Hopkins Hospital, Oct. 7, 1928, complaining of increased duration of the menstrual periods. There was nothing of significance in the family history so far as the present report is concerned. The past history was also irrelevant except as regarded the digestive system. The patient's appetite had always been good, but for several years she had been subject to "indigestion." at times with nausea, occurring usually at night. In the winter of 1927 she was troubled by frequent attacks of vomiting which were aggravated by eating, even when she was most careful about taking a moderate diet. There was often a feeling of fulness after eating and moderate pain, especially at night. These symptoms were associated with an obstinate chronic constipation. At this time she was treated in the gastro-intestinal division of the