Medicine

Previously, we demonstrated that a submerged fermentation culture ofAntrodia camphorata(AC) promotes cell-cycle arrest and apoptosis in human estrogen receptor-positive/negative breast cancer cells. However, whether AC is effective against HER-2/neu-overexpressing breast cancers has not been thoroughly elucidated. In the present study, we showed that AC exhibited a significant cytotoxic effect against HER-2/neu-overexpressing MDA-MB-453 and BT-474 cells. Immunoblot analysis demonstrated that HER-2/neuand their tyrosine phosphorylation were inhibited by AC in a dose-dependent manner. An increase in intracellular reactive oxygen species (ROS) was observed in AC-treated cells, whereas antioxidantN-acetylcysteine (NAC) significantly prevented AC induced HER-2/neudepletion and cell death, which directly indicates that AC-induced HER-2/neudepletion and cell death was mediated by ROS generation. Also, AC significantly downregulated the expression of cyclin D1, cyclin E, and CDK4 followed b...

Introduction. Although residents frequently lead end-of-life (EOL) discussions in the intensive care unit (ICU), training in EOL care during residency has been required only recently, and few educational interventions target EOL communication in the ICU. This study evaluated a simulation-based intervention designed to improve resident EOL communication skills with families in the ICU.Methods. Thirty-four second-year internal medicine residents at a large urban teaching hospital participated in small group sessions with faculty trained in the “VitalTalk” method. A Likert-type scale questionnaire measured self-assessed preparedness before, immediately following, and approximately 9 months after intervention. Data were analyzed using Wilcoxon rank-sum analysis.Results. Self-assessed preparedness significantly improved for all categories surveyed (preintervention mean; postintervention mean;pvalue), including discussing bad news (3.3; 4.2;p<0.01), conducting a family conference (3.1;...

A 48-year-old woman with a past medical history of seizures and end-stage renal disease secondary to obstructive uropathy from retroperitoneal fibrosis presented to the emergency department with seizures and altered mental status. A Glasgow Coma Scale of 4 prompted intubation, and she was subsequently admitted to the intensive care unit. Magnetic resonance imaging of the brain performed to elucidate the aetiology of her seizure showed a dural-based mass within the left temporoparietal lobe as well as mass lesions within the orbits. Further imaging showed extensive retroperitoneal fibrosis extending to the mediastinum with involvement of aorta and posterior pleural space. Imaging of the long bones showed bilateral sclerosis and cortical thickening of the diaphyses. Imaging of the maxillofacial structures showed osseous destructive lesions involving the mandible. These clinical and radiological features were consistent with a diagnosis of Erdheim-Chester disease; however, the patient’...

Objectives Develop and validate a template for patient handoffs from the hospital to hospice. Create an interactive didactic to teach this handoff to physicians and nurses in training. Develop a direct observation evaluation tool for hospital to hospice handoffs that meets ACGME requirements for handoff assessment.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease of the pulmonary vascular bed that is characterized by elevations in the mean pulmonary artery pressure in the setting of perfusion defects on ventilation-perfusion scan, and subsequently confirmed by pulmonary angiography. CTEPH, or World Health Organization (WHO) group 4 pulmonary hypertension, is a result of unresolved thromboembolic obstruction in the pulmonary arteries. Pulmonary endarterectomy (PEA) is the treatment of choice for CTEPH as it is a potentially curative therapy. However, up to one-third of patients are not candidates for the surgery, either due to distal and inaccessible nature of the lesions or comorbid conditions. Due to remodeling that occurs in nonobstructed pulmonary vessels, a portion of patients who have undergone PEA have residual CTEPH after the procedure, attributable to high shear stress prior to PEA. This phenomenon has led to the understanding of a so-called "two-compartment mode...

Pulmonary arterial hypertension (PAH) is a rare disease characterized by elevated pulmonary vascular resistance. Macitentan is an endothelin receptor antagonist indicated for the long-term treatment of PAH. This study presents consensus recommendations for managing macitentan and associated adverse events in PAH patients.

Communication skills training with simulated patients is used by many academic centers, but how to translate skills learned in simulated settings to improve communication in real encounters has not been described. We developed a communications bundle to facilitate skill transfer from simulation to real encounters and improve patient and/or family satisfaction with physician communication. We tested the feasibility of its use in our hospital's medical intensive care unit (MICU). This prospective cohort 2-week feasibility study included patients admitted to the MICU with APACHE IV predicted mortality >30% and/or single organ failure. The communications bundle included simulation communication training for MICU physicians, scheduling a family meeting within 72 hours of MICU admission, standardized pre and post meeting team huddles with the aid of a mobile app to set an agenda, choose a communication goal, and get feedback, and documentation of meeting in the electronic medical r...

In patients treated with macitentan (Opsumit®, Actelion Pharmaceuticals Ltd., Basel, Switzerland) for pulmonary arterial hypertension (PAH), prevention and/or effective management of treatment-related adverse events may improve adherence. However, management of these adverse events can be challenging and the base of evidence and clinical experience for macitentan is limited. In the absence of evidence, consensus recommendations from physicians experienced in using macitentan to treat PAH may benefit patients and physicians who are using macitentan. Consensus recommendations were developed by a panel of physicians experienced with macitentan and PAH using a modified Delphi process. Over three iterations, panelists developed and refined a series of statements on the use of macitentan in PAH and rated their agreement with each statement on a Likert scale. The panel of 18 physicians participated and developed a total of 118 statements on special populations, add-on therapy, drug-drug in...

Patients are often reluctant to assert their interests in the presence of clinicians, whom they see as experts. The higher the stakes of a health decision, the more entrenched the socially sanctioned roles of patient and clinician can become. As a result, many patients are susceptible to "hostage bargaining syndrome" (HBS), whereby they behave as if negotiating for their health from a position of fear and confusion. It may manifest as understating a concern, asking for less than what is desired or needed, or even remaining silent against one's better judgment. When HBS persists and escalates, a patient may succumb to learned helplessness, making his or her authentic involvement in shared decision making almost impossible. To subvert HBS and prevent learned helplessness, clinicians must aim to be sensitive to the power imbalance inherent in the clinician-patient relationship. They should then actively and mindfully pursue shared decision making by helping patients trust that it is safe to communicate their concerns and priorities, ask questions about the available clinical options, and contribute knowledge of self to clinical decisions about their care. Hostage bargaining syndrome is an insidious psychosocial dynamic that can compromise quality of care, but clinicians often have the power to arrest it and reverse it by appreciating, paradoxically, how patients' perceptions of their power as experts play a central role in the care they provide.

A critical care physician returning to medicine after her own critical illness experiences a crisis of orientation. She finds she can no longer serve as the Voice of Medicine. She replaces the former construct with a more humble model, in which the physician serves as an intermediary. She equates this new role to that of the Sherpas of Nepal. Maslow's hierarchy of needs forms the mountain, as she reimagines her role in her patients' lives.

As guest editor of this issue, Dr Chakinala organized a group of individuals who each had different perspectives and relationships to Pulmonary Hypertension Care Centers. In conversation among the physicians, nurse, social worker, and patient, they touch on the evolution of care of pulmonary hypertension patients over the past 20 years and the complexity of care that new medications and their side effects create. They discuss the advantages that centers of care can bring to the patients and to the field as a whole from access to experts to multidisciplinary care and clinical research during their lively conversation.

Pulmonary arterial hypertension has evolved from a fatal disease with few treatment options to a chronic condition with improved survival. This improvement is possible through development of effective therapies as well as the expansion of risk stratification scores to assist clinical decision making. Despite improved disease control, quality of life, and overall prognosis, many challenges remain. The treatment itself is burdensome, with significant impact on quality of life. Many patients with pulmonary arterial hypertension still present with advanced, often end-stage disease. Increased use of mechanical circulatory support and catheter-based interventions have expanded use of extracorporeal life support and right ventricle assist devices. For these reasons as well as the long-term relationships pulmonary hypertension physicians have with patients and their families, navigating the course of the illness in a considered, proactive way is essential. Understanding individual goals a...

The extraordinary nature of COVID-19 has presented, and will likely continue to present, unique challenges for care delivery systems; not only in respect to delivery of care to patients, but also in respect to the ways in which health systems care for, and facilitate safe working environments for their employees. It was identified early on that COVID-19 would challenge our Health System, Henry Ford, in its ability to provide an optimal experience of care for our patients. We realized that the feelings of isolation experienced by patients, anxieties experienced by their families and impacts to the well-being of our employees would be significant. Communication was fraught, yet the need for communication had never been greater. Providing difficult news, only to be delivered by phone, injured morale for providers, nurses and support staff. Prior to COVID-19, Henry Ford Health System paired physician and administrative leaders to create high performing dyad partnerships. Clinical and administrative leaders were paired based on their diverse skill sets, competencies and representation. The goals of the Care Experience dyad are to 1) build connectivity; demonstrate support for work being done in times of complex and evolving situations, 2) provide psychological first aid through diffusion and debrief of real time situational stress, utilizing coaching resources, developed by Chief Wellness Officer, 3) assess needs and concerns; assist teams with interpretation and operationalization of rapidly evolving guidelines and protocols; co-discover solutions and escalate concerns, 4) listen with non-judgmental curiosity; normalize and validate feelings and 5) identify and link to resources; identify families who need crisis-level communication.

When people think about trust in the context of health care, they typically focus on whether patients trust the competence of doctors and other health professionals. But for health care to reach its full potential as a service, trust must also include the notion of partnership, whereby patients see their clinicians as reliable, caring, shared decision-makers who provide ongoing "healing" in its broadest sense. Four interrelated service-quality concepts are central to fostering trust-based partnerships in health care: empathetic creativity, discretionary effort, seamless service, and fear mitigation. Health systems and institutions that prioritize trust-based partnerships with patients have put these concepts into practice using several concrete approaches: investing in organizational culture; hiring health professionals for their values, not just their skills; promoting continuous learning; attending to the power of language in all care interactions; offering patients "go-to" sources for timely assistance; and creating systems and structures that have trust built into their very design. It is in the real-world implementation of trust-based partnership that health care can reclaim its core mission.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown. Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy. Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response. Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting. Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening. Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Copyright © 2015 Shahzaib Nabi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 48-year-old woman with a past medical history of seizures and end-stage renal disease secondary to obstructive uropathy from retroperitoneal fibrosis presented to the emergency department with seizures and altered mental status. A Glasgow Coma Scale of 4 prompted intubation, and she was subsequently admitted to the intensive care unit. Magnetic resonance imaging of the brain performed to elucidate the aetiology of her seizure showed a dural-based mass within the left temporoparietal lobe as well as mass lesions within the orbits. Further imaging showed extensive retroperitoneal fibrosis extending to the mediastinum with involvement of aorta and posterior pleural space. Imaging of the long bones showed bilateral sclerosis and cortica...

e met in a frigid Connecticut conference room during a late March Nor'easter. The obliterative storm had delayed our flights and made mockery of the lightweight clothing we had each packed. We thought it was Spring. Tiffany was a regular on the speaking circuit and had been invited by the state's hospital association to deliver a talk on the lessons of her second double lung transplant, as a patient advocate. I was presenting on my own critical illness and recovery, as a critical care physician. My invitation was based on an essay I had recently published in the New England Journal of Medicine, and public speaking was new to me.

Mortality in pulmonary arterial hypertension (PAH) remains high and referral to palliative or supportive care (P/SC) specialist services is recommended when appropriate. However, access to P/SC is frequently a challenge for patients with a noncancer diagnosis and few patients living with PAH report P/SC involvement in their care. A modified Delphi process of three questionnaires completed by a multidisciplinary panel (N = 15) was used to develop expert consensus statements regarding the use of P/SC to support patients with PAH. Panelists rated their agreement with each statement on a Likert scale. There was a strong consensus that patients should be referred to P/SC when disease symptoms become unmanageable or for end-of-life care. Services that achieved consensus were pain