Rapid Mortality Review in the Intensive Care Unit: An In-Person, Multidisciplinary Improvement Initiative.

BACKGROUND: Significant resources have been allocated to decreasing the number of preventable deaths in hospitals, but identifying preventable factors and then leveraging them to effect system-wide change remains challenging. OBJECTIVE: To determine the ability of a novel in-person, multidisciplinary "rapid mortality review" process to identify deaths that are preventable and action items that lead to improvements in care. METHODS: Rapid mortality review sessions were conducted weekly for patients who died in the medical intensive care unit. Patient data and clinician opinions regarding preventable deaths were discussed and recorded. Bivariate analyses were done to detect associations between case variables and the formation of an action item. RESULTS: From 2013 to 2018, 542 patient deaths were reviewed; of those, 36 deaths (7%) were deemed potentially preventable. Facilitators identified issues in 294 cases (54%). A total of 253 action items were identified for 175 cases (32%); 60% of those action items were subsequently completed and led to tangible systemic change in 29 instances (11%). Action items were more likely to be identified for patients who had not been receiving comfort care (P < .001), for patients who had received cardiopulmonary resuscitation (P < .001), when the treatment team (P < .001) or the rapid mortality review facilitator (P < .001) had care-related concerns, and when the patient's death had been preventable (P < .001). CONCLUSIONS: Even in settings with low reported rates of preventable deaths, an in-person multidisciplinary mortality review can successfully identify areas where care can be improved, leading to systemic change.

Fatal Rhabdomyolysis in a COVID-19 Patient on Rosuvastatin.

It is well-established by now that COVID-19 can have a wide variety of neuromuscular manifestations, including rhabdomyolysis. Weakness and elevated creatinine kinase (CK) have been documented as the initial presentation of COVID-19. Myopathy from statin use has also been well-established since the introduction of this class of medication, and the common pathologic mechanism of both entities may have been mitochondrial dysfunction. We present here the case of a COVID-19 patient on rosuvastatin who developed rhabdomyolysis with CK above 1,000,000 units/L. The patient did not present with any respiratory difficulty and responded poorly to treatment, resulting in his untimely demise. COVID-19 may have accentuated an otherwise survivable condition by means of extra stress on mitochondrial homeostasis. Understanding the actual mechanism will be important in the development and utilization of medications in the fight against COVID-19.

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension.

OBJECTIVE: We sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH). METHODS: Two pulmonary pathologists blindly evaluated 360 histologic slides from lungs of 31 SSc-PF explants or autopsies with (n = 22) and without (n = 9) PH. The presence of abnormal small arteries, veins, and capillaries (pulmonary microcirculation) was semiquantitatively assessed in areas of preserved lung architecture. Capillary proliferation (CP) within the alveolar walls was measured by its distribution, extent (CP % involvement), and maximum number of layers (maximum CP). These measures were then evaluated to determine the strength of their association with right heart catheterization-proven PH. RESULTS: Using consensus measures, all measures of CP were significantly associated with PH. Maximum CP had the strongest association with PH (P = 0.013; C statistic 0.869). Maximum CP 2 or more layers and CP % involvement 10% or greater were the optimal thresholds that predicted PH, both with a sensitivity of 56% and specificity of 91%. The CP was typically multifocal rather than focal or diffuse and was associated with a background pattern of usual interstitial pneumonia. There was a significant but weaker relationship between the presence of abnormal small arteries and veins and PH. CONCLUSION: In the setting of advanced SSc-PF, the histopathologic feature of the pulmonary microcirculation best associated with PH was capillary proliferation in architecturally preserved lung areas.

A review of exercise pulmonary hypertension in systemic sclerosis.

In general, pulmonary vascular disease has important negative prognostic implications, regardless of the associated condition or underlying mechanism. In this regard, systemic sclerosis is of particular interest as it is the most common connective tissue disease associated with pulmonary hypertension, and a well-recognized at-risk population. In the setting of systemic sclerosis and unexplained dyspnea, the concept of using exercise to probe for underlying pulmonary vascular disease has acquired significant interest. In theory, a diagnosis of systemic sclerosis-associated exercise pulmonary hypertension may allow for earlier therapeutic intervention and a favorable alteration in the natural history of the pulmonary vascular disease. In the context of underlying systemic sclerosis, the purpose of this article is to provide a comprehensive review of the evolving definition of exercise pulmonary hypertension, the current role and methodologies for non-invasive and invasive exercise testing, and the importance of the right ventricle.

Spelunking Meckel Cave: A 31-Year-Old With Diplopia and Loss of Taste and Smell.

CASE PRESENTATION: A 31-year-old woman presented to the ED with a loss of taste and smell of 2 months' duration and a frontal headache, bilateral facial numbness, photophobia, and horizontal diplopia that was worse with far vision of 2 weeks' duration. A review of systems revealed mild nausea and decreased appetite without weight loss. She denied any cardiopulmonary symptoms, specifically no cough or shortness of breath. Her medical history was notable for arthralgias. The patient was diagnosed with ankylosing spondylitis, for which she had been taking etanercept for several months. She consumed minimal alcohol and had no history of tobacco or drug use or recent travel. Her family history was unremarkable.

Forging Ahead.

The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient's case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant. This icon represents the patient's case. Each paragraph that follows represents the discussant's thoughts.

Subject review: pancreatic ductal adenocarcinoma in the setting of mutations in the cystic fibrosis transmembrane conductance regulator gene: case report and review of the literature.

BACKGROUND: Cystic fibrosis (CF) is the most commonly inherited lethal autosomal recessive genetic disease amongst Caucasians. CF results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with homozygous or compound heterozygous CFTR mutations have a risk of pancreatitis, but typically do not live long enough to develop pancreatic ductal adenocarcinoma (PDA), a disease that has an average age at diagnosis of 65 years. Little is known about the risk of the development of PDA in people who are heterozygous for mutations in the CFTR gene. PATIENTS AND METHODS: We report a case of a patient with PDA who underwent resection, who is a carrier for the W1282X nonsense mutation in the CFTR gene. The patient is of Ashkenazi Jewish ethnicity and has a family history of CF, but no family history of PDA. We reviewed the English language literature for the prevalence of PDA in CF patients (and CFTR mutations in the setting of PDA) and their significance in terms of screening, and the use of this mutation as a biomarker for an increased risk of the development of PDA. CONCLUSION: We conclude that patients with CFTR mutations, who also have other risks for the development of PDA such as a family history of the disease, should undergo screening and be educated about their risks.

Identification of novel antimicrobials using a live-animal infection model.

The alarming increase of antibiotic-resistant bacterial pathogens points to the need for novel therapeutic approaches to combat infection. To discover novel antimicrobials, we devised a screen to identify compounds that promoted the survival of the model laboratory nematode Caenorhabditis elegans infected with the human opportunistic pathogen Enterococcus faecalis. E. faecalis colonizes the nematode intestinal tract, forming a persistent lethal infection. Infected nematodes were rescued by antibiotic treatment in a dose-dependent manner, and antibiotic treatment markedly reduced the number of bacteria colonizing the nematode intestine. To facilitate high throughput screening of compound libraries, we adapted a previously developed agar-based C. elegans-E. faecalis infection assay so that it could be carried out in liquid medium in standard 96-well microtiter plates. We used this simple infection system to screen 6,000 synthetic compounds and 1,136 natural product extracts. We identified 16 compounds and 9 extracts that promoted nematode survival. Some of the compounds and extracts inhibited E. faecalis growth in vitro, but, in contrast to traditional antibiotics, the in vivo effective dose of many of these compounds was significantly lower than the minimum inhibitory concentration needed to prevent the growth of E. faecalis in vitro. Moreover, many of the compounds and extracts had little or no affect on in vitro bacterial growth. Our findings indicate that the whole-animal C. elegans screen identifies not only traditional antibiotics, but also compounds that target bacterial virulence or stimulate host defense.