Sex Differences in Ischemic Stroke Readmission Rates and Subsequent Outcomes After Coronary Artery Bypass Graft Surgery.

BACKGROUND AND PURPOSE: Prior studies examining sex-related risk of readmission for ischemic stroke (IS) after coronary artery bypass grafting (CABG) did not adjust for preoperative comorbidities and used small study samples that were single-center or otherwise poorly generalizable. We assessed risk of readmission for IS after CABG for females compared to males in a nationwide sample. METHODS: The 2013 Nationwide Readmissions Database contains data on 49% of all U.S. hospitalizations. We used population weighting to determine national estimates. Using all follow-up data up to 1 year after discharge from CABG hospitalization, we estimated Kaplan-Meier cumulative risk of IS, stratified by sex, using the log-rank test for significance. We created Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for IS readmission, with sex as the main independent variable. We ran unadjusted models and models adjusted for age, vascular risk factors, estimated severity of illness and risk of mortality, hospital characteristics, and income quartile of patient's zip code. RESULTS: An estimated 53,270 females and 147,396 males survived index CABG admission in 2013. There was a consistently elevated cumulative risk of readmission for IS after CABG for females versus males (log-rank p-value = 0.0014). In the unadjusted Cox model, the HR of IS in females vs. males was 1.35 (95% CI 1.12-1.62, p = 0.0015). The elevated risk for females remained after adjusting for severity of illness (1.30 [1.08-1.56], p = 0.0056) and risk of mortality (1.28 [1.07-1.54], p = 0.0086). This elevated risk persisted after adjusting for multiple vascular risk factors, hospital characteristics, and income quartile of patient's zip code (1.23 [1.02-1.48], p = 0.03). CONCLUSIONS: We found a 23% increased risk of readmission for IS up to 1 year after CABG for females compared to males in a fully adjusted model utilizing a large, contemporary, nationwide database. Further research would clarify mechanisms of this increased risk among women.

A Successful Pharmacist-Based Quality Initiative to Reduce Inappropriate Stress Ulcer Prophylaxis Use in an Academic Medical Intensive Care Unit.

Stress ulcer prophylaxis (SUP) is often inappropriately utilized, particularly in critically ill patients. The objective of this study is to find an effective way of reducing inappropriate SUP use in an academic medical intensive care unit (ICU). Medical ICU patients receiving SUP were identified over a 1-month period, and their charts were reviewed to determine whether American Society of Health-System Pharmacists guidelines were followed. Inappropriate usage was calculated as inappropriate patient-days and converted to incidence per 100 patient-days. Two interventions were implemented: (1) Pharmacists reviewed indications for SUP on each patient during daily team rounds and daily medication reconciliation and (2) residents rotating on ICU services were educated on a bimonthly basis. Postintervention data were obtained in a similar fashion. Prior to intervention, the incidence of inappropriate SUP usage was calculated to be 26.75 per 100 patient-days (n = 1099 total patient-days). Total cost attributable to the inappropriate use was $2433. Post intervention, we were able to decrease the inappropriate incidence of SUP usage to 7.14 per 100 patient-days (n = 1149 total patient-days). In addition, total cost of inappropriate use was reduced to $239.80. Our study highlights an effective multidisciplinary approach to reduce the inappropriate use of SUP in an academic medical ICU. We were able to reduce the incidence of inappropriate use of SUP by 73.31% ( P < .001). Furthermore, we were able to decrease the costs by approximately $2200/month.

Gangrene and osteomyelitis of the toe in a previously healthy patient due to undiagnosed essential thrombocythemia.

We report a case of gangrene and osteomyelitis of the toe in a young, previously healthy male with undiagnosed essential thrombocythemia (ET). The patient experienced persistent right fifth toe pain, discolouration and ulceration for 3-4 months, unresponsive to antibiotics. Despite multiple normal X-rays, 2 months later, MRI revealed osteomyelitis. On inpatient admission, testing revealed thrombocytosis and abnormal blood flow to right fourth and fifth toes without thrombus, consistent with vasospasm. This ultimately resulted in ischemia, gangrene and osteomyelitis of the toe, necessitating amputation. The patient was subsequently treated with hydroxyurea for ET. This unusual presentation underscores the importance of a broad differential in cases when conventional treatments fail to yield improvement.

Synchronous Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Metastatic Squamous Cell Carcinoma of the Cervix Involving the Coronary Arteries Leading to Acute Myocardial Infarction.

A 66-year-old woman presented to the hospital with a one-month history of shortness of breath, fatigue, and postmenopausal vaginal bleeding and a one-week history of chest pain. This case report discusses the rare synchronous occurrence of two different malignancies in the setting of non-ST segment elevation myocardial infarction and the relation between these unfortunate events. Besides the case presented in this report, there have been only 13 reported cases of synchronous chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) associated with metastatic squamous cell carcinoma. While it is well known that malignancy causes a hypercoagulable state, there are other mechanisms which may have contributed to the patient's myocardial ischemia including external vascular compression, tumor lysis syndrome, and anemia. This case report discusses the rarity of synchronous malignancies but the importance of understanding and consideration of cardiac events in this population.

Manganese Neurotoxicity as a Complication of Chronic Total Parenteral Nutrition.

Manganese accumulation in the central nervous system creates clinical symptoms of cognitive dysfunction, behavioral changes, and movement disorders resembling Parkinson's disease. Radiographic features of this rare clinical entity include symmetric T1 hyperintensities in the bilateral globus pallidi, with corresponding hypointensities on T2-weighted images. Total parenteral nutrition (TPN) is an increasingly used potentially lifesaving therapy for patients who cannot tolerate enteral nutrition. However, when used over a period of several weeks to months, its associated risks and complications carry significant morbidity and mortality. One of the more rare complications of TPN use is manganese toxicity. We provided care for a 38-year-old female on chronic TPN who presented to the hospital with Parkinsonian features, confusion, falls, and lethargy. MRI brain showed T1 hyperintensities in the bilateral globus pallidi, which were attributed to manganese toxicity from chronic TPN use. Supporting evidence for this rare entity included decreased signal intensity in the bilateral globus pallidi on T2-weighted images and T1 hyperintensities in the substantia nigra. With antifungal treatment and permanent cessation of TPN, her mentation and neurological symptoms began to improve within a week. Repeat MRI brain performed one month after discontinuation of TPN revealed improvement of the T1 hyperintensities in the bilateral globus pallidi. Our objective in presenting this case is to highlight manganese neurotoxicity as a rare complication of TPN in a patient without known hepatic dysfunction and to emphasize the importance of routinely monitoring patients for the possible adverse effects of chronic TPN. Our case is among the handful of published cases in which a patient without known liver dysfunction, which is the primary organ responsible for manganese elimination from the body, developed manganese neurotoxicity.

Miller Fisher syndrome with bilateral vocal cord paralysis: a case report.

BACKGROUND: Miller Fisher syndrome is a variant of acute inflammatory demyelinating polyneuropathy classically characterized by ataxia, ophthalmoplegia, and areflexia. Miller Fisher syndrome can present with uncommon symptoms such as bulbar, facial, and somatic muscle palsies and micturition disturbance. CASE PRESENTATION: We describe the case of a 76-year-old white man with new-onset ataxia, stridor, areflexia, and upper and lower extremity weakness who required intubation at presentation. An initial work-up including imaging studies and serum tests was inconclusive. Eventually, neurophysiological testing and cerebrospinal fluid analysis suggested a diagnosis of Miller Fisher syndrome. Our patient responded to treatment with intravenous immunoglobulin and supportive therapy. CONCLUSION: The occurrence of acute or subacute descending paralysis with involvement of bulbar muscles and respiratory failure can often divert clinicians to a diagnosis of neuromuscular junction disorders (such as botulism or myasthenia gravis), vascular causes like stroke, or electrolyte and metabolic abnormalities. Early identification of Miller Fisher syndrome with appropriate testing is essential to prompt treatment and prevention of further, potentially fatal, deterioration.

Usefulness of a metronome to improve quality of chest compressions during cardiopulmonary resuscitation.

The objective of this study was to improve the quality of chest compressions after the introduction of a metronome during cardiopulmonary resuscitation (CPR). A retrospective analysis of Zoll® compression data of 219 in-hospital adult participants who received CPR from January 2017 to December 2018 was done. A metronome was introduced during chest compressions in January 2018, and the 2017 data served as the control. The main outcome measure compared the overall quality of chest compressions measured by the rate (100 to 120 compressions per minute), depth (2.0 to 2.4 inches), and mean release velocity (≥400 mm/sec) on chest recoil. Compared to control, the metronome group had a statistically significant improvement of the mean percent compression rate within 100 to 120 beats per minute: 28.16% vs. 71.14% (P < 0.001) and a statistically significant improvement of the mean percent compression depth within 2.0 to 2.4 inches: 29.35% vs. 34.84% (P = 0.03). However, there was no statistically significant improvement of mean percent release velocity ≥400 mm/second: 47.41% vs. 51.09% (P = 0.38). Our data suggest that an inexpensive and widely available intervention may improve the quality of CPR. We suggest that further research be conducted to measure patient clinical outcomes.

Sepsis: The evolution in definition, pathophysiology, and management.

There has been a significant evolution in the definition and management of sepsis over the last three decades. This is driven in part due to the advances made in our understanding of its pathophysiology. There is evidence to show that the manifestations of sepsis can no longer be attributed only to the infectious agent and the immune response it engenders, but also to significant alterations in coagulation, immunosuppression, and organ dysfunction. A revolutionary change in the way we manage sepsis has been the adoption of early goal-directed therapy. This involves the early identification of at-risk patients and prompt treatment with antibiotics, hemodynamic optimization, and appropriate supportive care. This has contributed significantly to the overall improved outcomes with sepsis. Investigation into clinically relevant biomarkers of sepsis are ongoing and have yet to yield effective results. Scoring systems such as the sequential organ failure assessment and Acute Physiology and Chronic Health Evaluation help risk-stratify patients with sepsis. Advances in precision medicine techniques and the development of targeted therapy directed at limiting the excesses of the inflammatory and coagulatory cascades offer potentially viable avenues for future research. This review summarizes the progress made in the diagnosis and management of sepsis over the past two decades and examines promising avenues for future research.

Reply to the Comment on: Subrat Khanal et al. The Repertoire of Adenovirus in Human Disease: The Innocuous to the Deadly. Biomedicines 2018, 6, 30.

We would like to thank Dr. Atkinson for his comments on our review article on the manifestations of adenoviral infections in humans. [...].

The Repertoire of Adenovirus in Human Disease: The Innocuous to the Deadly.

Adenoviridae is a family of double-stranded DNA viruses that are a significant cause of upper respiratory tract infections in children and adults. Less commonly, the adenovirus family can cause a variety of gastrointestinal, ophthalmologic, genitourinary, and neurologic diseases. Most adenovirus infections are self-limited in the immunocompetent host and are treated with supportive measures. Fatal infections can occur in immunocompromised patients and less frequently in the healthy. Adenoviral vectors are being studied for novel biomedical applications including gene therapy and immunization. In this review we will focus on the spectrum of adenoviral infections in humans.

A pilot study to standardize and peer-review shift handoffs in an academic internal medicine residency program: The DOCFISH method.

With increased oversight of residency work hours, there has been an increase in shift handoffs, which are prone to medical errors. To date, there are no evidence-based recommendations on essential elements of shift handoffs. We implemented a standardized shift-handoff rubric at an academic medicine residency program. Compliance, resident/faculty perceptions, and surrogate markers of patient safety were measured.Shift-handoff documents were collected January-February 2016 (control) April-June 2016 (intervention). Signouts were scored based on inclusion of seven elements: Daily events, Overnight events, Code status, Follow up tasks, If/then statements, 'sick or stable' and History present illness. The mnemonic 'DOCFISH' was taught in a grand-rounds forum then embedded into a shift-handoff tool within our electronic health record (EHR). Senior residents were assigned to supervise/provide feedback on shift handoffs from April-June 2016. Faculty and resident perceptions regarding quality of shift handoffs was measured by the annual ACGME (Accreditation Council Graduate Medical Education) program survey.Patient safety was measured by number of rapid-response teams (RRT) initiated for unstable vital signs. Handoffs were 74% complete in intervention group and 60% in control group (p < .0001). Median DOCFISH features present in patients that required RRT was 3 of 7 whereas, total post-intervention group had 5 of 7 (p < .001). 'Daily events' and 'follow -up tasks' were less frequent in patients that required RRT (20%, 67% respectively, p < .001).Academic medical centers can implement standardized shift handoffs by embedding high-yield information in an EHR with peer-review. Information during shift changes that may have significant improvement on patient safety includes: 'daily events' and 'follow -up tasks.'

The ongoing evolution of proteomics in malignancy.

The complementary fields of genomics and proteomics offer insights into the molecular mechanisms of diseases. While genomics seeks to define our genetic substrate, proteomics explores the structure and function of proteins, which are the end effectors of our genes. Proteomics has been revolutionized in the past decade by the application of techniques such as protein arrays, two-dimensional gel electrophoresis, and mass spectrometry. These techniques have tremendous potential for biomarker development, target validation, diagnosis, prognosis, and optimization of treatment in medical care, especially in the field of clinical oncology. We will discuss innovations in proteomic technologies and highlight their prospective applications to patient care.

Kir2.3 isoform confers pH sensitivity to heteromeric Kir2.1/Kir2.3 channels in HEK293 cells.

BACKGROUND: Data on pH regulation of the cardiac potassium current I(K1) suggest species-dependent differences in the molecular composition of the underlying Kir2 channel proteins. OBJECTIVE: The purpose of this study was to test the hypothesis that the presence of the Kir2.3 isoform in heterotetrameric channels modifies channel sensitivity to pH. METHODS: Voltage clamp was performed on HEK293 cells stably expressing guinea pig Kir2.1 and/or Kir2.3 isoforms and on sheep cardiac ventricular myocytes at varying extracellular pH (pH(o)) and in the presence of CO(2) to determine the sensitivity of macroscopic currents to pH. Single-channel activity was recorded from the HEK293 stables to determine the mechanisms of the changes in whole cell current. RESULTS: Biophysical characteristics of whole-cell and single-channel currents in Kir2.1/Kir2.3 double stables displayed properties attributable to isoform heteromerization. Whole-cell Kir2.1/Kir2.3 currents rectified in a manner reminiscent of Kir2.1 but were significantly inhibited by extracellular acidification in the physiologic range (pK(a) approximately 7.4). Whole-cell currents were more sensitive to a combined extracellular and intracellular acidification produced by CO(2). At pH(o) = 6.0, unitary conductances of heteromeric channels were reduced. Ovine cardiac ventricular cell I(K1) was pH(o) and CO(2) sensitive, consistent with the expression of Kir2.1 and Kir2.3 in this species. CONCLUSION: Kir2.1 and Kir2.3 isoforms form heteromeric channels in HEK293. The presence of Kir2.3 subunit(s) in heteromeric channels confers pH sensitivity to the channels. The single and double stable cells presented in this study are useful models for studying physiologic regulation of heteromeric Kir2 channels in mammalian cells.

Proteomics as a tool for biomarker discovery.

Novel technologies are now being advanced for the purpose of identification and validation of new disease biomarkers. A reliable and useful clinical biomarker must a) come from a readily attainable source, such as blood or urine, b) have sufficient sensitivity to correctly identify affected individuals, c) have sufficient specificity to avoid incorrect labeling of unaffected persons, and d) result in a notable benefit for the patient through intervention, such as survival or life quality improvement. Despite these critical descriptors, the few available FDA-approved biomarkers for cancer do not completely fit this definition and their benefits are limited to a small number of cancers. Ovarian cancer exemplifies the need for a diagnostic biomarker of early stage disease. Symptoms are present but not specific to the disease, delaying diagnosis until an advanced and generally incurable stage in over 70% of affected women. As such, diagnostic intervention in the form of oopherectomy can be performed in the appropriate at-risk population if identified such as with a new accurate, sensitive, and specific biomarker. If early stage disease is identified, the requirement for survival and life quality improvement will be met. One of the new technologies applied to biomarker discovery is tour-de-force analysis of serum peptides and proteins. Optimization of mass spectrometry techniques coupled with advanced bioinformatics approaches has yielded informative biomarker signatures discriminating presence of cancer from unaffected in multiple studies from different groups. Validation and randomized outcome studies are needed to determine the true value of these new biomarkers in early diagnosis, and improved survival and quality of life.

Intermediate-Term Risk of Stroke Following Cardiac Procedures in a Nationally Representative Data Set.

BACKGROUND: Studies on stroke risk following cardiac procedures addressed only perioperative and long-term risk following limited higher-risk procedures, were poorly generalizable, and often failed to stratify by stroke type. We calculated stroke risk in the intermediate risk period following cardiac procedures compared with common noncardiac surgeries and medical admissions. METHODS AND RESULTS: The Nationwide Readmissions Database contains readmission data for 49% of US admissions in 2013. We compared age-adjusted stroke readmission rates up to 90 days postdischarge. We used Cox regression to calculate hazard ratios, up to 1 year, of stroke risk comparing transcatheter aortic valve replacement versus surgical aortic valve replacement and coronary artery bypass graft versus percutaneous coronary intervention. Procedures and diagnoses were identified by International Classification of Disease, Ninth Revision, Clinical Modification codes. After cardiac procedures, 90-day ischemic stroke readmission rate was highest after transcatheter aortic valve replacement (2.05%); 90-day hemorrhagic stroke rate was highest after left ventricular assist device placement (0.09%). The hazard ratio for ischemic stroke after transcatheter aortic valve replacement, compared with surgical aortic valve replacement, in fully adjusted Cox models was 1.86 (95% confidence interval, 1.12-3.08; P=0.016) and 6.17 (95% confidence interval, 1.97-19.33; P=0.0018) for hemorrhagic stroke. There was no difference between coronary artery bypass graft and percutaneous coronary intervention. CONCLUSIONS: We demonstrated elevated readmission rates for ischemic and hemorrhagic stroke in the intermediate 30-, 60-, and 90-day risk periods following common cardiac procedures. Furthermore, we found an elevated risk of stroke after transcatheter aortic valve replacement compared with surgical aortic valve replacement up to 1 year.

Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+ current.

The inwardly rectifying potassium (Kir) 2.x channels mediate the cardiac inward rectifier potassium current (I(K1)). In addition to differences in current density, atrial and ventricular I(K1) have differences in outward current profiles and in extracellular potassium ([K+]o) dependence. The whole-cell patch-clamp technique was used to study these properties in heterologously expressed Kir2.x channels and atrial and ventricular I(K1) in guinea pig and sheep hearts. Kir2.x channels showed distinct rectification profiles: Kir2.1 and Kir2.2 rectified completely at potentials more depolarized than -30 mV (I approximately 0 pA). In contrast, rectification was incomplete for Kir2.3 channels. In guinea pig atria, which expressed mainly Kir2.1, I(K1) rectified completely. In sheep atria, which predominantly expressed Kir2.3 channels, I(K1) did not rectify completely. Single-channel analysis of sheep Kir2.3 channels showed a mean unitary conductance of 13.1+/-0.1 pS in 15 cells, which corresponded with I(K1) in sheep atria (9.9+/-0.1 pS in 32 cells). Outward Kir2.1 currents were increased in 10 mmol/L [K+]o, whereas Kir2.3 currents did not increase. Correspondingly, guinea pig (but not sheep) atrial I(K1) showed an increase in outward currents in 10 mmol/L [K+]o. Although the ventricles of both species expressed Kir2.1 and Kir2.3, outward I(K1) currents rectified completely and increased in high [K+]o-displaying Kir2.1-like properties. Likewise, outward current properties of heterologously expressed Kir2.1-Kir2.3 complexes in normal and 10 mmol/L [K+]o were similar to Kir2.1 but not Kir2.3. Thus, unique properties of individual Kir2.x isoforms, as well as heteromeric Kir2.x complexes, determine regional and species differences of I(K1) in the heart.

Diagnosis and treatment of a rare sinonasal neuroendocrine tumour: adding to the evidence.

Sinonasal neuroendocrine tumours (NETs) are rare, aggressive neoplasms with a high recurrence potential. There are no robust protocols for the management of these tumours. An 81-year-old man presented with an incidental sinonasal mass visualised on CT scan of head. Over the next few weeks he developed new onset, progressively worsening headache, right eye ptosis and restricted extraocular movements. Imaging confirmed a rapidly enlarging tumour involving the right nasal cavity and the orbit. Biopsy showed a large cell neuroendocrine carcinoma of the right ethmoidal sinus. The patient was treated with concurrent cisplatin chemotherapy and radiation. Repeat imaging showed decrease in tumour volume. The patient continues to do well and follows up regularly with our oncology service. Current protocols comprising chemotherapy after radiation are based on limited studies. A regimen involving concurrent chemoradiation also appears to aid in tumour volume reduction. Additional studies are required to formulate robust clinical protocols for management of sinonasal NETs.

Walking the tightrope: Using quantitative Doppler echocardiography to optimize ventricular filling pressures in patients hospitalized for acute heart failure.

Acutely decompensated heart failure (HF), one of the most common reasons for hospitalization, places an intense economic pressure on the health care system and adversely affects outcome of HF patients. Due to lack of reliable clinical tools to assess and monitor hemodynamics, accurate judgment on cardiac preload remains a challenge and complicates current inpatient HF management. In this review, we discuss the emerging role of real-time quantitative Doppler echocardiography (DE) in identifying inappropriate cardiac preload, monitoring volume status during the management, and improving quality of care in patients with acute HF. We illustrate the utilization of DE in common clinical scenarios, propose stepwise algorithms to effectively utilize serial quantitative DE in the bedside care, and discuss obstacles and prospects of quantitative DE utilization in HF management. These efforts will further prompt the development of multi-center prospective studies to define and validate the specific roles of quantitative DE in reducing hospitalization time and improving outcome of HF patients.