Citations

Abstract Background: Blood-based testing can be used as a noninvasive method to recover and analyze circulating tumor-derived cells for clinical use. Circulating cancer-associated macrophage-like cells (CAML) are specialized myeloid cells found in peripheral blood and associated with the presence of solid malignancies. We measured CAMLs prospectively in peripheral blood to ascertain their prevalence, specificity, and sensitivity in relation to breast disease status at clinical presentation. Methods: We report on two related but separate studies: 1) CellSieve microfilters were used to isolate CAMLs from blood samples of patients with known malignant disease (n = 41). Prevalence and specificity was compared against healthy volunteers (n = 16). 2) A follow-up double-blind pilot study was conducted on women (n = 41) undergoing core-needle biopsy to diagnose suspicious breast masses. Results: CAMLs were found in 93% of known malignant patients (n = 38/41), averaging 19.4 cells per sample, but none in the healthy controls. In subjects undergoing core biopsy for initial diagnosis, CAMLs were found in 88% of subjects with invasive carcinoma (n = 15/17) and 26% with benign breast conditions (n = 5/19). Conclusion: These preliminary pilot studies suggest that the presence of CAMLs may differentiate patients with malignant disease, benign breast conditions, and healthy individuals. Impact: We supply evidence that this previously unidentified circulating stromal cell may have utility as a screening tool to detect breast cancer in various malignancies, irrespective of disease stage. Cancer Epidemiol Biomarkers Prev; 25(7); 1037–42. ©2016 AACR.

Purpose: To describe a bailout technique for use during branched/fenestrated thoracoabdominal aortic aneurysm (TAAA) repair to address celiac artery (CA) dissection. Technique: The technique is demonstrated in a 69-year-old man who underwent fenestrated stent-graft repair of a 6-cm type III TAAA. The main fenestrated stent-graft was positioned without difficulty, and the renal and superior mesenteric arteries were stented. A stent-graft was placed in the CA, but angiography showed the vessel to be occluded by dissection beyond the stent-graft. Wire manipulations to regain access to the true lumen culminated in perforation. At this point, the gastroduodenal artery was catheterized with a 0.035-inch guidewire, which was advanced in retrograde fashion into the CA true lumen and then snared back to the left brachial artery forming a loop. After exchange for a 0.014-inch system, self-expanding stents were deployed into the hepatic artery. Postoperative recovery was uneventful, and the patient was discharged on day 6. At 1-year follow-up, the patient was doing very well. Imaging demonstrated no endoleak, no graft migration, and sac shrinkage to a diameter of 5.1 cm. Conclusion: The “loop technique” can be a very useful and effective bailout maneuver in regaining access to the true lumen of a dissected CA in patients undergoing branched/fenestrated thoracoabdominal aortic aneurysm repair.

Background: Advance care planning (ACP) is an instrumental mechanism aimed at preserving patient autonomy. Numerous interventions have been proposed to facilitate the implementation of ACP; however, rates of completed advance directives (ADs) are universally low. Patient electronic portal messaging is a newer tool in patient–provider communication which has not been studied as a method to promote ACP. In this study, we hypothesized that the use of ACP-specific patient electronic messages would increase rates of AD completion in patients aged 65 years and older in an academic primary care practice. Methods: All primary care patients, aged 65+, who had previously enrolled in a patient electronic messaging system, within an academic primary care practice, were included for randomization. Two hundred patients were randomized to receive an electronic message. The primary outcome was the proportion of patients in each group who completed an AD, 3 months after intervention. Secondary outcomes included clinical utility of the completed ADs and proportion of patients who viewed their electronic messages. Results: The intervention group completed an AD 5.5% of the time when compared to 2% in the control group (odds ratio 3.2 [1.6-6.3]). Up to 74.5% of patients opened their electronic messages. Conclusion: Among primary care patients aged 65 years and older, use of AD-specific electronic messaging statistically significantly increased the rate of AD completion, but the absolute number of completed AD remained relatively low. These data suggest that this valuable communication tool holds opportunities for further improvement. Older, frailer adults were more likely to complete an AD, and prompted directives were more likely to include a written expression of the individual’s health-care values and preference.

Cystatin C has been suggested to be a more accurate glomerular filtration rate (GFR) surrogate than creatinine in patients with acquired immunodeficiency syndrome (AIDS) because it is unaffected by skeletal muscle mass and dietary influences. However, little is known about the utility of this marker for monitoring medications in the critically ill. We describe the case of a 64-year-old female with opportunistic infections associated with a new diagnosis of AIDS. During her course, she experienced neurologic, cardiac, and respiratory failure; yet her renal function remained preserved as indicated by an eGFR ≥ 120 mL/min and a urine output > 1 mL/kg/hr without diuresis. The patient was treated with nephrotoxic agents; therefore cystatin C was assessed to determine if cachexia was resulting in a falsely low serum creatinine. Cystatin C measured 1.50 mg/L which corresponded to an eGFR of 36 mL/min. Given the >60 mL/min discrepancy, serial 8-hour urine samples were collected and a GFR > 120 mL/min was confirmed. It is unclear why cystatin C was falsely elevated, but we hypothesize that it relates to the proinflammatory state with AIDS, opportunistic infections, and corticosteroids. More research is needed before routine use of cystatin C in this setting can be recommended.

The discovery of a series of genetic and serological markers associated with disease susceptibility and phenotype in inflammatory bowel disease has led to the prospect of an integrated classification system involving clinical, serological and genetic parameters. The Working Party has reviewed current clinical classification systems in Crohn’s disease, ulcerative colitis and indeterminate colitis, and provided recommendations for clinical classification in practice. Progress with respect to integrating serological and genetic markers has been examined in detail, and the implications are discussed. While an integrated system is not proposed for clinical use at present, the introduction of a widely acceptable clinical subclassification is strongly advocated, which would allow detailed correlations among serotype, genotype and clinical phenotype to be examined and confirmed in independent cohorts of patients and, thereby, provide a vital foundation for future work.

Objective: To establish evidence-based guidelines for the use of bedside cardiac ultrasound, echocardiography, in the ICU and equivalent care sites. Methods: Grading of Recommendations, Assessment, Development and Evaluation system was used to rank the “levels” of quality of evidence into high (A), moderate (B), or low (C) and to determine the “strength” of recommendations as either strong (strength class 1) or conditional/weak (strength class 2), thus generating six “grades” of recommendations (1A–1B–1C–2A–2B–2C). Grading of Recommendations, Assessment, Development and Evaluation was used for all questions with clinically relevant outcomes. RAND Appropriateness Method, incorporating the modified Delphi technique, was used in formulating recommendations related to terminology or definitions or in those based purely on expert consensus. The process was conducted by teleconference and electronic-based discussion, following clear rules for establishing consensus and agreement/disagreement. Individual panel members provided full disclosure and were judged to be free of any commercial bias. Results: Forty-five statements were considered. Among these statements, six did not achieve agreement based on RAND appropriateness method rules (majority of at least 70%). Fifteen statements were approved as conditional recommendations (strength class 2). The rest (24 statements) were approved as strong recommendations (strength class 1). Each recommendation was also linked to its level of quality of evidence and the required level of echo expertise of the intensivist. Key recommendations, listed by category, included the use of cardiac ultrasonography to assess preload responsiveness in mechanically ventilated (1B) patients, left ventricular (LV) systolic (1C) and diastolic (2C) function, acute cor pulmonale (ACP) (1C), pulmonary hypertension (1B), symptomatic pulmonary embolism (PE) (1C), right ventricular (RV) infarct (1C), the efficacy of fluid resuscitation (1C) and inotropic therapy (2C), presence of RV dysfunction (2C) in septic shock, the reason for cardiac arrest to assist in cardiopulmonary resuscitation (1B–2C depending on rhythm), status in acute coronary syndromes (ACS) (1C), the presence of pericardial effusion (1C), cardiac tamponade (1B), valvular dysfunction (1C), endocarditis in native (2C) or mechanical valves (1B), great vessel disease and injury (2C), penetrating chest trauma (1C) and for use of contrast (1B–2C depending on indication). Finally, several recommendations were made regarding the use of bedside cardiac ultrasound in pediatric patients ranging from 1B for preload responsiveness to no recommendation for RV dysfunction. Conclusions: There was strong agreement among a large cohort of international experts regarding several class 1 recommendations for the use of bedside cardiac ultrasound, echocardiography, in the ICU. Evidence-based recommendations regarding the appropriate use of this technology are a step toward improving patient outcomes in relevant patients and guiding appropriate integration of ultrasound into critical care practice.

AbstractObjectiveThe objective of this study is to assess clinical and safety outcomes after laparoscopic nephrectomy with autotransplantation for loin pain‐hematuria syndrome (LPHS).MethodsWe conducted telephone interviews using structured questionnaires and retrospectively reviewed data on all patients who underwent laparoscopic nephrectomy with autotransplantation for LPHS between January 2000 and May 2014.ResultsA total of 24 laparoscopic nephrectomies with renal autotransplantation of 21 patients with LPHS were reviewed. Eighty‐three per cent were female with a mean age of 31 years. Postoperatively, graft loss resulting in subsequent nephrectomy occurred in two patients; However, no patients died (median follow‐up = 22 months, range 5 to 78 months) or required dialysis (median follow‐up = 10 months, range 0.2 to 178 months). There was no significant difference in estimated glomerular filtration rate (eGFR) before and after surgery (100 ± 22 vs. 97 ± 23 mL/min/1.73 m2; P = 0.37). Among 14 patients (16 autotransplantation) with telephone follow‐up, 14 (88%) resulted in pain relief and no operation resulted in worsening pain. All procedures resulted in immediate pain relief; pain recurrence was reported after two procedures. However, those patients had pain‐free period up to 36 months. The quality of life was better after 15 (94%) autotransplantation with higher employment rate (44% vs. 69%; P = 0.04). Two patients with graft loss reported better pain control and quality of life.ConclusionsRenal autotransplantation is a possible treatment option for LPHS refractory to conservative medical treatment. It can offer pain relief and better quality of life. Despite postoperative risk, it seems to be safe for survival and renal outcomes.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder characterized by overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Diagnosis is based on the presence of persistent (>3 months) peripheral blood monocytosis (>1 × 109/L), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ∼20–30% of patients, while >90% have gene mutations. Mutations involving TET2 (∼60%), SRSF2 (∼50%), ASXL1 (∼40%), and RAS (∼30%) are frequent; with only ASXL1 mutations negatively impacting overall survival. Two molecularly integrated, CMML‐specific prognostic models include; the Groupe Français des Myélodysplasies (GFM) and the Molecular Mayo Model (MMM). The GFM model segregates patients into 3 groups based on: age >65 years, WBC >15 × 109/L, anemia, platelets <100 × 109/L, and ASXL1 mutation status, with respective median survivals of 56 (low), 27.4 (intermediate), and 9.2 (high) months. The MMM is based on ASXL1 mutational status, absolute monocyte count >10 × 109/L, hemoglobin <10 g/dL, platelets <100 × 109/L and circulating immature myeloid cells. This model stratifies patients into four groups; high (≥3 risk factors), intermediate‐2 (2 risk factors), intermediate‐1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59, and 97 months, respectively. Hypomethylating agents such as 5‐azacitidine and decitabine are commonly used, with overall response rates of ∼30–40% and complete remission rates of ∼7–17%. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality. Individualized therapy, including epigenetic modifiers and small molecule inhibitors, are exciting prospects. Am. J. Hematol. 91:632–642, 2016. © 2016 Wiley Periodicals, Inc.