Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disorder characterized by progressive and profoundly disabling heterotopic ossification (HO). Here we show that ...fibro/adipogenic progenitors (FAPs) are a major cell-of-origin of HO in an accurate genetic mouse model of FOP (Acvr1
). Targeted expression of the disease-causing type I bone morphogenetic protein (BMP) receptor, ACVR1(R206H), to FAPs recapitulates the full spectrum of HO observed in FOP patients. ACVR1(R206H)-expressing FAPs, but not wild-type FAPs, activate osteogenic signaling in response to activin ligands. Conditional loss of the wild-type Acvr1 allele dramatically exacerbates FAP-directed HO, suggesting that mutant and wild-type ACVR1 receptor complexes compete for activin ligands or type II BMP receptor binding partners. Finally, systemic inhibition of activin A completely blocks HO and restores wild-type-like behavior to transplanted Acvr1
FAPs. Understanding the cells that drive HO may facilitate the development of cell-specific therapeutic approaches to inhibit catastrophic bone formation in FOP.
Abstract Objectives Gynecologic oncology patients undergoing surgery are at an increased risk for venous thromboembolism (VTE). We attempted to validate a VTE risk assessment model in gynecologic ...oncology patients. Methods All gynecologic oncology patients who underwent a laparotomy for the diagnosis or suspicion of gynecologic malignancy from 2004 to 2010 were included. Demographic, surgicopathologic, and complication data were collected. VTE was based on the symptomatic diagnosis. Data for the Caprini risk assessment model (RAM) was used to score and stratify patients on their risk for VTE. Results 1123 gynecologic oncology patients were included within this study. Ovarian cancer was the most common diagnosis (39%) with a median age of 56.1. All patients received SCDs with 40% receiving double prophylaxis. The overall incidence of VTE was 3.3%, with lower extremity deep venous thrombosis (DVT) n = 17 and pulmonary embolism (PE) n = 20. Complication rates were similar in each group. Based on the Caprini scoring model 92% of patients scored in the “Highest Risk” category. The Caprini RAM accurately predicted all 37 VTEs, all of which scored in the “Highest Risk” category. The percentage of patients that received double prophylaxis increased with time from 12% in 2004 to 63% in 2010. Importantly, 25 of the 37 VTEs (68%) did not receive double prophylaxis. Conclusions The use of the Caprini RAM accurately predicted patients at the highest risk of experiencing VTE. Considering accurate identification of patients allows proper administration of double prophylaxis, we recommend the use of this scoring model preoperatively in patients undergoing surgery for gynecologic malignancies.
IMPORTANCE: There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of ...Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE: To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. DESIGN, SETTING, AND PATIENTS: The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. INTERVENTIONS: Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). MAIN OUTCOMES AND MEASURES: The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. RESULTS: The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = −0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. CONCLUSIONS AND RELEVANCE: Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00449865
Despite its relatively common occurrence and life‐threatening potential, the management of angioedema in the emergency department (ED) is lacking in terms of a structured approach. It is paramount to ...distinguish the different etiologies of angioedema from one another and more specifically differentiate histaminergic‐mediated angioedema from bradykinin‐mediated angioedema, especially in lieu of the more novel treatments that have recently become available for bradykinin‐mediated angioedema. With this background in mind, this consensus parameter for the evaluation and management of angioedema attempts to provide a working framework for emergency physicians (EPs) in approaching the patient with angioedema in terms of diagnosis and management in the ED. This consensus parameter was developed from a collaborative effort among a group of EPs and leading allergists with expertise in angioedema. After rigorous debate, review of the literature, and expert opinion, the following consensus guideline document was created. The document has been endorsed by the American College of Allergy, Asthma & Immunology (ACAAI) and the Society for Academic Emergency Medicine (SAEM).
Resumen
A pesar de su ocurrencia relativamente común y su potencial riesgo vital, el manejo del paciente con angioedema en el servicio de urgencias está falto de una aproximación estructurada. Es primordial distinguir las diferentes etiologías del angioedema y más específicamente diferenciar el angioedema mediado por histamina del mediado por bradicinina, especialmente en relación con los tratamientos que recientemente están disponibles para el angioedema mediado por bradicinina. Con este escenario en mente, este parámetro consenso para la evaluación y el manejo del angiodema intenta proporcionar un marco de trabajo para los urgenciólogos en la aproximación del paciente con angiodema en términos de diagnóstico y tratamiento en el servicio de urgencias. Este esquema consenso fue desarrollado a través de un esfuerzo de colaboración entre un grupo de urgenciólogos y alergólogos expertos líderes en angiodema. Tras un riguroso debate, una revisión de la literatura y la opinión de los expertos, se creó el siguiente documento de guía clínica de consenso. En reconocimiento a la importancia de este tema, este documento de consenso ha sido respaldado por el American College of Allergy, Asthma, and Immunology (ACAAI) y la Society for Academic Emergency Medicine (SAEM).
Abstract Background Palliative and supportive care services provide excellent care to patients near the end of life. It is estimated that enrollment in such services can reduce end-of-life costs; ...however, there is limited data available regarding the impact of palliative services in end-of-life care in gynecologic oncology patients. We examined the use of palliative services in gynecologic oncology patients during the last six months of life. Methods After IRB approval, a retrospective chart review of patients with a diagnosis of a gynecologic malignancy who died between June 2007 and June 2010 was performed. Abstracted data included demographics, admission and procedural history, use of anti-cancer therapy, and palliative care utilization during the last six months of life. Results 268 patients were identified. Most patients were white (76.9%) and had ovarian cancer (56.7%). During the last six months of life, 155 (57.8%) patients underwent anti-cancer therapy with chemotherapy, 19 (7.1%) patients were treated with radiation therapy, and 17 patients (6.3%) underwent treatment with both. 218 patients (81.3%) had at least one admission during this time (range 0–14). The most common reason for admission was gastrointestinal complaints (37.1%), followed by admissions for procedures (18.3%). The median time between the last admission and death was 32 days. 157 patients (58.6%) underwent at least one procedure during the last six months of life (range 0–11). The most common procedure performed was paracentesis (22.6%). 198 (73.9%) patients died at home or in a palliative care unit. 189 (70.5%) patients were referred to hospice or palliative care. 3.2% underwent a procedure or treatment with chemotherapy or radiation after hospice enrollment. The median time between hospice enrollment and death was 22 days. 55% of patients were enrolled in hospice less than 30 days before death. Of the 79 patients not referred to hospice, only 16.5% had documentation of refusing hospice services. Conclusions During the last six months of life, the majority of gynecologic oncology patients receive anticancer therapy and many have repeated hospital admissions. While the majority of patients are referred for palliative care, it appears that most patients spend less than 30 days on hospice. Earlier referral could decrease the number of hospital admissions and procedures while providing invaluable support during this end of life transition.
Abstract Objective Relative dose intensity (RDI) is the ratio of delivered dose intensity of chemotherapy to standard dose intensity. In this study, we sought to determine the prognostic significance ...of RDI in patients with epithelial ovarian cancer (EOC). Methods A retrospective analysis of chemotherapy naïve patients treated between 2001 and 2008 with intravenous taxane and platinum was performed. RDI was calculated as the delivered dose intensity (total dose delivered/total time of therapy) divided by standard dose intensity calculated for each regimen and compared to progression-free survival (PFS). Multivariate recursive partitioning survival analysis was utilized. Results 138 EOC patients completed initial taxane/platinum-based chemotherapy following surgical cytoreduction. The most common reasons for dose delays and reductions were thrombocytopenia (38%) and neutropenia (31%). 24% of treatment delays were due to social reasons such as transportation constraints or scheduling conflicts. The average RDI was 90% (range, 24–126%). The mean PFS was 31 months (range, 3–117). Patients that achieved an RDI between 70% and 110% had a mean PFS of 32 months compared to 20 months in patients with an RDI of < 70% or > 110% (p = 0.046). 14 patients (10%) had a RDI of < 70%. Conclusions RDI is a significant predictor of survival in patients with EOC. Effort should be made to achieve an RDI of at least 70%. Dose reductions and treatment delays could be minimized by utilizing prophylactic colony stimulating factors and educating patients about the importance of adhering to their treatment schedule.
There is an increasing awareness, interest and acceptance of the biopsychosocial (BPS) model by all health care professionals involved with patient care. The areas of spine care and pain medicine are ...no exception, and in fact, these areas of health care are a major centerpiece of the movement from the traditional biomedical model to a BPS model of patient assessment and delivery of care. The chiropractic approach to health care has a history that is grounded in key aspects of the BPS model. The profession has inherently implemented certain features of the BPS model throughout its history, perhaps without a full understanding or realization. The purpose of this paper is to present an overview of the BPS model, its relationship with spine care and pain management, and to discuss the BPS model, particularly psychosocial aspects, in the context of its historical relationship with chiropractic. We will also provide recommendations for the chiropractic profession as it relates to successful adoption of a full integration of the BPS model.
To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis.
...Prospective cohort study.
Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington.
Adult patients presenting to the ED with signs (two of four Systemic Inflammatory Response Syndrome criteria, where one must be temperature or WBC count) or suspicion (provider-ordered culture) of infection.
All patients underwent testing with the IntelliSep using ethylene diamine tetraacetic acid-anticoagulated whole blood followed by retrospective adjudication for sepsis by sepsis-3 criteria by a blinded panel of physicians.
Of 599 patients enrolled, 572 patients were included in the final analysis. The result of the IntelliSep test is reported as the IntelliSep Index (ISI), ranging from 0.1 to 10.0, divided into three interpretation bands for the risk of sepsis: band 1 (low) to band 3 (high). The median turnaround time for ISI results was 7.2 minutes. The ISI resulted band 1 in 252 (44.1%), band 2 in 160 (28.0%), and band 3 in 160 (28.0%). Sepsis occurred in 26.6% (152 of 572 patients). Sepsis prevalence was 11.1% (95% CI, 7.5-15.7%) in band 1, 28.1% (95% CI, 21.3-35.8%) in band 2, and 49.4% (95% CI, 41.4-57.4%) in band 3. The Positive Percent Agreement of band 1 was 81.6% and the Negative Percent Agreement of band 3 was 80.7%, with an area under the receiver operating characteristic curve of 0.74. Compared with band 1, band 3 correlated with adverse clinical outcomes, including mortality, and resource utilization.
Increasing ISI interpretation band is associated with increasing probability of sepsis in patients presenting to the ED with suspected infection.
Abstract Objectives We evaluated the indications and outcomes of patients with known gynecologic malignancies that underwent video-assisted thoracoscopic surgery (VATS) and pleurodesis for malignant ...pleural effusion. Methods After IRB approval was obtained, a retrospective study of patients with gynecologic malignancies who underwent planned VATS/pleurodesis between 1/2000 and 7/2010 was performed. Abstracted data included demographics, diagnosis, disease status, treatment history, indication for VATS, complications, and outcomes. Results Forty-two patients with a gynecologic malignancy underwent VATS/pleurodesis. Median age was 63 years. Twenty-nine patients (69%) had ovarian cancer. Fifty-seven percent had recurrent disease at the time of VATS and 57% were undergoing chemotherapy at the time of VATS. Eight patients (19%) underwent perioperative VATS to improve pulmonary status. Seven patients (17%) underwent a palliative VATS. The median length of stay was 7 days (range 1–53). Sixty-two percent had gross disease noted at the time of VATS. A mean of 1650 cc of fluid was drained at time of surgery (range 300–4500), and the majority (88%) of patients had a talc pleurodesis performed. Seven patients (17%) were readmitted within 30 days; 6 were for complications unrelated to their VATS. One patient was readmitted with hospital-acquired pneumonia and died during readmission. Median time to death after VATS was 104 days (range 4–1062). Patients who underwent a perioperative VATS had the longest survival (845 days). Conclusion Patients with gynecologic malignancies may require a VATS/pleurodesis for symptomatic pleural effusions. This procedure appears to be safe and effective in this patient population.
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