Morbidity following salvage esophagectomy for squamous cell carcinoma: the MD Anderson experience.

The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Diabetic ketoacidosis complicating pregnancy.

BACKGROUND: Although diabetic ketoacidosis (DKA) in pregnancy can result in significant adverse consequences for both mother and fetus, the response to treatment, time course of recovery, and perinatal outcomes have not been well studied in pregnancy. OBJECTIVE: We examined the precipitating factors, laboratory abnormalities, treatment strategies, and clinical recovery in pregnancies complicated by DKA. STUDY DESIGN: This is a retrospective cohort study of pregnancies complicated by DKA between October 1999 and June 2015. The diagnosis was verified by hyperglycemia; anion gap >12 mEq/L, pH <7.3, HCO3 <15 mEq/L; and the presence of ketones. Each episode of DKA was reviewed and subsequent perinatal outcomes analyzed. RESULTS: During this period, we identified 33 women with 40 admissions (incidence: 0.2%). The majority of women had type 1 diabetes (67%), and almost all presented with nausea and vomiting (97%). Over half had poor compliance with prescribed insulin. The initial mean blood glucose was 380 mg/dL, within 6 hours, it was <200 mg/dL. By 12 hours, the acidosis had resolved in 90% of patients. CONCLUSION: Nausea and vomiting is a prominent presenting feature of DKA in pregnancy. With aggressive insulin and resuscitation, hyperglycemia and acidosis improve rapidly. With current treatment, good perinatal outcomes can be expected.

Crisaborole and its potential role in treating atopic dermatitis: overview of early clinical studies.

Atopic dermatitis (AD), a chronic, relapsing, inflammatory skin disease that is characterized by intense pruritus and eczematous lesions with up to 90% of patients presenting with mild to moderate disease. Current topical treatments for AD have not changed in over 15 years and are associated with safety concerns. In AD, overactivity of phosphodiesterase 4 (PDE4), leads to inflammation and disease exacerbation. Crisaborole Topical Ointment, 2%, is a novel, nonsteroidal, topical anti-inflammatory PDE4 inhibitor currently being investigated for the treatment of mild to moderate AD. Preliminary studies in children and adults demonstrated favorable efficacy and safety profiles. Crisaborole may represent an anti-inflammatory option that safely minimizes the symptoms and severity of AD and that can be used for both acute and long-term management.

Risk factors for severe delayed postpolypectomy bleeding.

BACKGROUND AND STUDY AIMS: Postpolypectomy bleeding is a rare but serious adverse event. The aim of this study was to identify factors associated with the risk of severe delayed postpolypectomy bleeding. PATIENTS AND METHODS: This was a case-control study, comparing cases who developed hematochezia and required medical evaluation 6 hours to 14 days after colonoscopic polypectomy, and control patients who underwent polypectomy without delayed bleeding, and who were selected in approximately a 3 : 1 ratio. The following risk factors were specified a priori: resuming anticoagulation (within 1 week following polypectomy), aspirin use, hypertension, and polyp diameter. RESULTS: Of the 4592 patients who underwent colonoscopy with polypectomy, 41 patients (0.9 %) developed delayed postpolypectomy bleeding (cases), and 132 patients were selected as controls. The mean age was 64.3 years for cases and 65.4 years for controls. Cases presented on average 6 days after polypectomy (range 1 - 14 days), and 48 % required blood transfusion (average 4.2 units, range 0 - 17). Two patients required surgery. Anticoagulation was resumed following polypectomy in 34 % of cases compared with 9 % of controls (OR 5.2; 95 % CI 2.2 - 12.5; P < 0.001). For every 1 mm increase in polyp diameter, the risk of hemorrhage increased by 9 % (OR 1.09; 95 % CI 1.0 - 1.2; P = 0.008). Hypertension (OR 1.1) and aspirin use (OR 1.1) did not increase the risk of postpolypectomy bleeding. In exploratory analysis, diabetes (OR 2.5) and coronary artery disease (OR 3.0) were associated with postpolypectomy hemorrhage, but the association was no longer statistically significant once adjusted for the use of anticoagulation. CONCLUSIONS: Resuming anticoagulation following polypectomy and polyp diameter were strongly associated with increased risk of severe delayed postpolypectomy bleeding.

Placental infection with human papillomavirus is associated with spontaneous preterm delivery.

BACKGROUND: We sought to determine if human papillomavirus (HPV) infection of extravillous trophoblast cells reduces cell invasion and if placental infection is associated with adverse reproductive outcomes attributed to placental dysfunction. METHODS: We conducted apoptosis and invasion assays using extravillous trophoblast (HTR-8/SVneo) cells that were transfected with a plasmid (pAT-HPV-16) containing the entire HPV-16 genome. In order to associate HPV infection with reproductive outcomes, we conducted a case-control study to detect HPV DNA in the extravillous trophoblast region of placentas from cases of spontaneous preterm delivery, severe pre-eclampsia requiring delivery at <37 weeks and controls who delivered at term. RESULTS: Rates of apoptosis were 3- to 6-fold greater in transfected cells than in non-transfected cells or cells transfected with an empty plasmid. Invasion of transfected cells through extracellular matrices was 25-58% lower than that of the controls. HPV was detected more frequently in placentas from spontaneous preterm deliveries than in placentas from controls (P = 0.03). Identification of HPV in placentas from cases of pre-eclampsia was not significantly different to controls. CONCLUSIONS: HPV infection of extravillous trophoblast induces cell death and may reduce placental invasion into the uterine wall. Thus, HPV infection may cause placental dysfunction and is associated with adverse pregnancy outcomes, including spontaneous preterm delivery.

Adverse reproductive outcomes in urban women with adeno-associated virus-2 infections in early pregnancy.

BACKGROUND: We demonstrated recently that adeno-associated virus-2 (AAV-2) DNA was detected significantly more frequently in placental trophoblast cells from cases of severe pre-eclampsia than from normal term deliveries. Here, we sought to determine if maternal AAV-2 infection early in pregnancy preceded adverse outcomes resulting from placental dysfunction. METHODS: We collected first trimester maternal serum samples and compared anti-AAV-2 IgM antibody levels (indicating primary infection or reactivation of latent AAV-2) between controls delivered at term (n = 106) and three groups of cases: spontaneous abortions (n = 34), spontaneous preterm deliveries (n = 24) and women with at least one outcome usually attributed to placental dysfunction, including pre-eclampsia, intrauterine growth restriction (IUGR) or stillbirth (n = 20). The seroprevalence of immunoglobulin G (IgG) antibodies against AAV-2 and IgM antibodies against viruses that promote AAV-2 replication [adenovirus and cytomegalovirus (CMV)] were also determined. RESULTS: First trimester maternal IgM seropositivity was 5.6 times more prevalent among pre-eclampsia/IUGR/stillbirth cases (P = 0.0004) and 7.6 times more prevalent among preterm deliveries (P < 0.0001) than among controls. CMV and adenovirus IgM antibodies and chronic AAV-2 infections (IgG seropositivity) were not associated with adverse pregnancy outcomes. CONCLUSIONS: Primary or reactivated AAV-2 infection (maternal IgM seropositivity) early in pregnancy was associated with adverse reproductive outcomes associated with placental dysfunction, including pre-eclampsia, stillbirth and spontaneous preterm delivery.

Vaginal symptoms and bacterial vaginosis (BV): how useful is self-report? Development of a screening tool for predicting BV status.

Vaginal complaints compel an evaluation of bacterial vaginosis (BV), however, many cases of BV are asymptomatic. We evaluated the sensitivity and specificity of vaginal symptoms in the diagnosis of BV and examined the utility of creating a BV screening tool using clinical, behavioural and demographic characteristics. A total of 1916 pregnant women were included in this analysis. In total, 757 women screened positive for BV and over one third of BV-positive women presented without any lower genital tract symptoms (39.4%). African American race, abnormal vaginal odour, and smoking were independently related to BV positivity. A BV screening tool including these three factors was fairly predictive of BV status with the area under the ROC curve equal to 0.669. This three-item prediction rule may be useful in identifying high- risk pregnant women in need of BV screening and, given the high specificity, accurately identify the group of BV-negative pregnant women.

A trial of education, prompts, and opinion leaders to improve prescription of lipid modifying therapy by primary care physicians for patients with ischemic heart disease.

BACKGROUND: Recent clinical trials indicate that treatment with lipid modifying therapy improves outcomes in patients with ischemic heart disease (IHD) and low levels of high density lipoprotein (HDL) cholesterol. The results of these trials, however, have not been widely implemented in clinical practice. OBJECTIVES: To develop and test an intervention designed to increase the rate of prescription of lipid modifying therapy and to determine the relative effectiveness of three different prompts (progress notes, patient letters, or computer chart reminders). METHODS: The study was conducted in 11 US Department of Veterans Affairs Medical Centers. The effect of the intervention on the proportion of eligible patients receiving lipid modifying therapy was compared between five intervention sites and six matched control sites using a controlled before and after study design. Additionally, 92 providers within the intervention clinics were randomized to receive one of the three prompts. Data were analyzed using logistic regression modeling which incorporated terms to account for the clustered nature of the data. RESULTS: At the intervention sites the prescription rate increased from 8.3% during the pre-intervention period to 39.1% during the intervention (OR = 6.5, 95% CI 5.2 to 8.2, p<0.0001) but remained unchanged at the control sites. The interaction between group (control v intervention) and time period was highly significant (p<0.0001). The adjusted odds of receiving a prescription during the intervention period was 3.1 times higher at the intervention sites than at the control sites (95% CI 2.1 to 4.7). Overall, there was no significant difference in prescription rates among the three prompt groups. However, there was a significant interaction between prompt group and site, indicating that the efficacy of the prompts differed by site. CONCLUSION: An intervention for primary care providers consisting of an educational workshop, opinion leader influence, and prompts substantially increased the prescription rate of lipid modifying therapy.

Follicular phase hormone levels and menstrual bleeding status in the approach to menopause.

OBJECTIVE: (1) Characterize the relationship between follicular phase hormone levels and menstrual bleeding patterns in the approach to menopause; (2) identify racial differences in hormone levels; (3) determine independent contributions of menstrual status, race, age, BMI, and smoking to hormone levels. DESIGN: Randomly identified, population-based cohort, stratified to obtain equal numbers of African American and Caucasian women, prospectively followed for 5 years. SETTING: Women in Philadelphia County, PA, identified by random-digit telephone dialing. PARTICIPANT(S): Women aged 35 to 47 years with regular menstrual cycles at enrollment (N = 436). DATA COLLECTION: Blood sampling twice in each of 7 assessment periods during days 1-6 of the cycle, menstrual dates identified through structured interview and daily symptom reports, anthropometric measures and standardized questionnaires at each assessment period. MAIN OUTCOME MEASURE(S): Serum levels of follicular E(2), FSH, inhibin B, and LH. RESULT(S): The mean levels of E(2), FSH, inhibin B, and LH were differentially associated with the 5 menstrual status groups defined by changes in bleeding patterns. Significant changes in hormone levels occurred prior to missed menstrual cycles for inhibin B, FSH, and LH. All hormones had a highly significant interaction between menstrual status and BMI. African American women had significantly lower levels of E(2) and LH compared to Caucasian women in univariate analyses. The interaction of race, menstrual status, and BMI was highly significant (P<.001) for E(2), with African American women having lower E(2) levels until postmenopause, when E(2) levels were higher in AA women with BMI > or =25 and BMI > or =30. CONCLUSION(S): Levels of E(2), FSH, LH, and inhibin B are significantly associated with menstrual bleeding patterns in late reproductive age women and differentiate the earliest stages of the menopausal transition. Racial differences in mean levels of E(2) appear strongly mediated by BMI.

Disability after clinical fracture in postmenopausal women with low bone density: the fracture intervention trial (FIT).

Relatively little is known about outcomes following clinical osteoporotic fractures at nonhip, nonvertebral skeletal sites. To address this issue, we prospectively assessed post-fracture disability at multiple skeletal sites in a population of 909 older (aged 55-81 years), community-dwelling women with low femoral neck bone mineral density who had experienced a fracture while enrolled in the Fracture Intervention Trial (FIT). FIT is a randomized, double-masked, placebo-controlled trial that was designed to determine the effect of alendronate on fracture incidence, and the current study was conducted as a secondary analysis of FIT data. Following incident clinical fractures, FIT participants were followed prospectively for assessment of site-specific, fracture-related disability. Measures of disability were self-reported days hospitalized or confined to bed because of the fracture ('bed days') and days of reduced usual activities because of the fracture ('limited activity days'). Of fracture types evaluated, those of the hip resulted in the highest percentage of subjects with any bed days or limited activity days after fracture (94% with any bed days and 100% with any limited activity days), though the mean number of bed days and limited activity days appeared highest after lumbar vertebral fractures (25.8 mean bed days and 158.5 mean limited activity days). Substantial disability also was reported after fractures of thoracic vertebrae, humerus, distal forearm, ankle and foot. Within fracture types, post-fracture disability was highly variable, ranging from none to more than 6 months.

Sex hormones, hemostasis and early pregnancy loss.

AIMS: This study was designed to determine the association between coagulation factors and spontaneous abortion adjusting for sex steroids and to examine the influence of sex hormones on coagulation factors early in pregnancy. METHODS: Pregnant women presenting to the emergency department at the Hospital of the University of Pennsylvania were recruited and followed through 22 weeks gestation. Cases were women who experienced a spontaneous abortion (n=29) and controls were women who maintained their pregnancy to 22 weeks gestation (n=89). Participants completed a baseline questionnaire to assess demographic, reproductive, and drug use information. Blood samples measured estradiol, progesterone, fibrinogen, and factor VII antigen. RESULTS: Cases of spontaneous abortion had significantly lower levels of estradiol, progesterone, fibrinogen and factor VII antigen compared to controls. The relationship between low levels of fibrinogen and factor VII antigen was diminished adjusting for the sex steroids. Regression analyses found low progesterone was the primary prospective marker for early pregnancy loss among our study population. CONCLUSIONS: The relationship between coagulation factors and spontaneous abortion was reduced after adjustment for progesterone suggesting that progesterone mediates the relationship between low levels of coagulation factors and spontaneous abortion. Progesterone seems to be the primary marker for a spontaneous abortion among women seeking emergent care.

Risk factors for post-ERCP pancreatitis: a prospective, multicenter study.

BACKGROUND: Post-ERCP pancreatitis is poorly understood. The goal of this study was to comprehensively evaluate potential procedure- and patient-related risk factors for post-ERCP pancreatitis over a wide spectrum of centers. METHODS: Consecutive ERCP procedures were prospectively studied at 11 centers (6 private, 5 university). Complications were assessed at 30 days by using established consensus criteria. RESULTS: Pancreatitis occurred after 131 (6.7%) of 1963 consecutive ERCP procedures (mild 70, moderate 55, severe 6). By univariate analysis, 23 of 32 investigated variables were significant. Multivariate risk factors with adjusted odds ratios (OR) were prior ERCP-induced pancreatitis (OR 5.4), suspected sphincter of Oddi dysfunction (OR 2.6), female gender (OR 2.5), normal serum bilirubin (OR 1.9), absence of chronic pancreatitis (OR 1.9), biliary sphincter balloon dilation (OR 4.5), difficult cannulation (OR 3.4), pancreatic sphincterotomy (OR 3.1), and 1 or more injections of contrast into the pancreatic duct (OR 2.7). Small bile duct diameter, sphincter of Oddi manometry, biliary sphincterotomy, and lower ERCP case volume were not multivariate risk factors for pancreatitis, although endoscopists performing on average more than 2 ERCPs per week had significantly greater success at bile duct cannulation (96.5% versus 91.5%, p = 0.0001). Combinations of patient characteristics including female gender, normal serum bilirubin, recurrent abdominal pain, and previous post-ERCP pancreatitis placed patients at increasingly higher risk of pancreatitis, regardless of whether ERCP was diagnostic, manometric, or therapeutic. CONCLUSIONS: Patient-related factors are as important as procedure-related factors in determining risk for post-ERCP pancreatitis. These data emphasize the importance of careful patient selection as well as choice of technique in the avoidance of post-ERCP pancreatitis.

Do clerkship experiences affect medical students' attitudes toward chronically ill patients?

PURPOSE: To measure changes in medical students' attitudes toward chronically ill patients, and to identify experiences, specifically during clerkships, that contributed to students' attitudes. METHOD: A cohort of students from five U.S. medical schools voluntarily participated in three surveys longitudinally administered before and after required clinical rotations. The first two questionnaires were identical and asked for demographic information and pre-matriculation experiences with chronically ill patients. The third was modified to include questions about clinical experiences with chronically ill patients. Responses from the first and third questionnaires were linked for analysis. RESULTS: A total of 502 of 695 students (69%) completed both the first and the third questionnaires. Many students (36%) had had pre-matriculation experiences with chronic illness. After clinical training, 25% of the respondents stated that they would seek another career specialty if the incidence of chronically ill patients increased in their chosen field, compared with the 9% who responded so before clinical training (p <.001). While 73% of the students had favorable perceptions toward chronically ill patients, and 91% felt involved in care, significantly fewer students (p <.01) had had positive patient care experiences when working with residents (57%) and attendings (59%). Gender, age, prior experiences, and school site were not associated with attitudinal changes. CONCLUSION: Students begin medical school with positive attitudes toward caring for chronically ill patients, but this perception depreciates with clinical experience, which may affect specialty decisions. Contributing factors may include adequate role modeling by residents and attendings and a perceived discrepancy in the quality of care patients receive.

Influence of hemostatic factors on spontaneous abortion.

To assess the relationship between hemostatic factors and spontaneous abortion, 134 pregnant women presenting to the emergency department were recruited and followed through 22 weeks' gestation. Cases were women experiencing a spontaneous abortion and controls were women who maintained their pregnancy. Fibrinogen, factor VII antigen, activated protein C-sensitivity ratio (APC-SR), protein S, and plasmin-antiplasmin (PAP) were measured. Cases had lower mean levels of fibrinogen and factor VII antigen compared with controls (3.1 g/L vs. 3.7 g/L and 89% of normal vs. 109% of normal, respectively). Regression analyses found that women with fibrinogen levels below 3.0 g/L had a five-fold increased risk of spontaneous abortion (OR = 5.1, 95% CI: 1.8-14.4) and women with factor VII antigen levels below 94% of normal had a threefold increased risk of spontaneous abortion normal (OR = 3.3, 95% CI: 1.2-8.5). Similar mean levels of APC-SR, protein S, and PAP were found in the two groups.