Internal medicine fellowship directors' perspectives on the quality and utility of letters conforming to residency program director letter of recommendation guidelines.

Background: In May 2017, the Alliance for Academic Internal Medicine (AAIM) published guidelines intending to standardize and improve internal medicine residency program director (PD) letters of recommendation (LORs) for fellowship applicants. Objectives: This study aimed to examine fellowship PDs impressions of the new guidelines, letter writers' adherence to the guidelines, and the impact of LORs that conformed to guidelines compared to non-standardized letters. Methods: The authors anonymously surveyed fellowship PDs from January to March 2018 to gather input about LORs submitted to their programs during the 2017 fellowship application cycle. Results: A total of 78% of survey respondents were satisfied with letters that followed the AAIM guidelines, whereas 48% of respondents were satisfied with letters that did not. Fellowship PDs felt that letters that followed the AAIM guidelines were more helpful than letters that did not, especially for differentiating between applicants from the same institution and for understanding residents' performance across the six core competency domains. Fellowship PDs provided several suggestions for residency PDs to make the LORs even more helpful. Conclusion: Fellowship PD respondents indicated that LORs that followed the new AAIM guidelines were more helpful than letters that did not.

Pregnancy after breast cancer: from psychosocial issues through conception.

Women face numerous issues if they either contemplate childbearing or become pregnant after the diagnosis of breast cancer. Based on a search of the English medical literature from 1966 to 1997, we make the following conclusions regarding pregnancy after breast cancer: (1) Sexual function is not affected by the decision to treat breast cancer by breast conservation vs mastectomy. (2) Infertility after breast cancer treatment is directly proportional to patient age and the use and dose of alkylating agents. There is no conclusive information on the effects of duration, dose intensity, schedule, or route of administration of chemotherapy on subsequent fertility. (3) There appears to be no increase in birth defects in children whose parents were exposed to chemotherapy earlier in life. (4) Milk production of the irradiated breast is likely to be limited. Also, breastfeeding appears to decrease the risk of breast cancer. (5) With respect to monitoring pregnant women for breast cancer recurrence, in general the recommendations made by the American Society of Clinical Oncology (ASCO) regarding monitoring in nonpregnant women should be followed. (6) Pregnancy does not increase the risk of recurrent breast cancer. (7) Adjuvant tamoxifen (Nolvadex) therapy has adverse effects on pregnancy in vivo and in laboratory animals. No reports exist on the effects of tamoxifen on human pregnancy.

Interferon alpha-2b and megestrol acetate in the treatment of advanced renal cell carcinoma: a phase II study.

Interferon-alpha has been used to treat advanced renal cell carcinoma, and megestrol acetate has been shown to improve the quality of life of patients who have cancer. We combined interferon alpha-2b, 10 million IU/m2 subcutaneously 5 consecutive days per week, with megestrol acetate, 80 mg orally twice a day, in 15 patients who had advanced renal cell carcinoma. Only 6 (40%) had a prior nephrectomy, and most had disease in the lung and other sites. There were no complete or partial responders to this treatment, although stable disease was achieved in 5 (33%) patients. The treatment was excessively toxic, with 12 (86%) patients requiring dose modification or discontinuation of treatment due to fatigue. We conclude that interferon alpha-2b and megestrol acetate is an excessively toxic, inactive regimen, at least in a group of patients who have advanced disease with a poor prognosis.

Management of patients with small cell carcinoma and the syndrome of ectopic corticotropin secretion.

BACKGROUND: Small cell carcinoma (SCC) associated with clinical evidence of tumor corticotropin (ACTH) production is common, and management of this syndrome is difficult. The purpose of this retrospective analysis is to describe clinical features, prognosis, and treatment results in patients with SCC and the syndrome of ectopic ACTH secretion to permit formulation of management guidelines for these patients. METHODS: Using tumor registry data and chart review, the authors identified patients with SCC and ectopic ACTH secretion treated over 11 years at two large teaching hospitals. They recorded clinical and laboratory data regarding the patients' tumors and their endocrine syndrome along with results of treatment for the malignancy and the hypercortisolism. RESULTS: Ten patients with SCC and ectopic ACTH secretion were identified. These patients were initially seen with adverse prognostic features, including elevations of serum lactate dehydrogenase and extensive stage disease. Cytotoxic chemotherapy and standard doses of anti-adrenal medications rarely controlled the paraneoplastic syndrome. Bacterial or opportunistic infections, although not neutropenic, developed in most patients. Median survival of patients diagnosed with the paraneoplastic syndrome at the same time as the initial diagnosis of cancer was 4 months. However, three patients whose cortisol secretion was controlled survived longer than 6 months. CONCLUSIONS: Patients with SCC and ectopic ACTH syndrome have a poor prognosis. However, in the minority of patients whose hypercortisolism can be controlled with cytotoxic chemotherapy combined with treatment to inhibit cortisol biosynthesis, effective palliation can be achieved.

Megakaryocyte and hepatocyte origins of human fibrinogen biosynthesis exhibit hepatocyte-specific expression of gamma chain-variant polypeptides.

The gamma chain of human fibrinogen is heterogeneous in length at the C-terminus due to differential RNA processing of the gamma chain-gene primary transcript. We have produced two specific monoclonal antibodies (MoAbs) against the gamma-chain epitopes generated by this alternative processing event: anti-gamma 57.5(408-416) (L2B), which reacts with gamma 57.5 and gamma 55 chains, and anti-gamma 50(337-411) (H9B7), which reacts preferentially with gamma 50 chains. Using these MoAbs we have studied the expression of gamma-chain polypeptides by immunofluorescence microscopy in the tissues of fibrinogen biosynthesis and have determined that gamma 57.5 polypeptide is expressed in hepatocytes but is absent or present in significantly reduced amounts in megakaryocytes. Therefore the gamma 50 chain is found in plasma, platelet, and megakaryocyte fibrinogens, but the gamma 57.5 chain is found only in plasma fibrinogen. The C-terminal amino acid sequence of gamma 55 includes the L2B epitope 57.5(408-416). Using MoAb L2B we have determined that gamma 55, which is a post-translationally modified gamma 57.5 chain, is found only in plasma fibrinogen and is absent or present in markedly reduced amounts in platelet or megakaryocyte fibrinogen. In addition, the conformation of the L2B epitope is preserved in gamma 55, as determined by Western blot analysis. The hepatocyte-specific expression of the gamma 57.5-chain polypeptide and the post-translational modification to gamma 55 result in a compartmentalization of gamma-chain polypeptide expression. This is suggestive of different mechanisms regulating human fibrinogen gamma-chain gene expression in hepatocytes v megakaryocytes that may operate in a tissue-specific manner at the level of 3' RNA processing events.