Andrew Choi

Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection Fraction: Importance of Left Atrial Strain.

Background—Left atrial (LA) enlargement is associated with adverse events in heart failure with preserved ejection fraction (HFpEF). However, the role of LA mechanics (ie, LA strain measures) in HFpEF has not been well studied. We hypothesized that in HFpEF, reduced (worse) LA strain is a key pathophysiologic abnormality and is a stronger correlate of adverse events than left ventricular or right ventricular longitudinal strain. Methods and Results—We evaluated baseline LA function in 308 patients with HFpEF who were followed up longitudinally for adverse outcomes. All patients underwent speckle-tracking echocardiography for measurement of left ventricular longitudinal strain, right ventricular free wall strain, and LA booster, conduit, and reservoir strains. The clinical and prognostic significance of left ventricular, right ventricular, and LA strain measures was assessed by regression analyses. The mean age was 65±13 years, 64% were women, 26% had atrial fibrillation, and LA enlargement was present in the majority of patients (67%). Decreased LA reservoir strain was associated with increased pulmonary vascular resistance (P<0.0001) and decreased peak oxygen consumption (P=0.0001). Of the left ventricular, right ventricular, and LA strain measures, LA reservoir strain was the strongest correlate of adverse events and was independently associated with the composite outcome of cardiovascular hospitalization or death (adjusted hazard ratio per 1-SD decrease in LA strain, 1.54; 95% CI, 1.15–2.07; P=0.006). Conclusions—Abnormal indices of LA mechanics (particularly LA reservoir strain) are powerful clinical and prognostic factors in HFpEF. Unloading the LA and augmentation of LA function may be important future therapeutic targets in HFpEF. Registration Information—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01030991.

Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis.

BACKGROUND Chronic rhinosinusitis (CRS) is a multifactorial disease of unknown cause characterized by sinonasal inflammation, increased mucus production, and defective mucociliary clearance. Expression of Pendrin, an epithelial anion transporter, is increased in asthma and chronic obstructive pulmonary disease. Pendrin increases mucus production and regulates mucociliary clearance. OBJECTIVES We sought to investigate the expression of pendrin and the mucus-related protein Muc5AC in sinonasal tissues of control subjects and patients with CRS and to evaluate the regulation of pendrin expression in nasal epithelial cells (NECs) in vitro. METHODS The expression and distribution of pendrin in sinonasal tissues was analyzed by using real-time PCR, immunoblot analysis, and immunohistochemistry. Differentiated NECs were used to study the regulation of pendrin expression. RESULTS Increased pendrin expression was observed in nasal polyp (NP) tissue of patients with CRS. Immunohistochemistry analysis revealed that pendrin was largely restricted to the epithelial layer. Pendrin expression significantly correlated with inflammatory cell markers, suggesting that the factors made by these cells might induce pendrin expression. Furthermore, both pendrin and periostin levels (a biomarker in asthma) correlated with IL-13 levels, suggesting that pendrin can be induced by this cytokine in sinonasal tissues. Expression of the mucus component protein Muc5AC correlated weakly with pendrin expression, indicating that pendrin might modulate mucus production in NPs. In cultured NECs pendrin expression was induced by TH2 cytokines and induced synergistically when TH2 cytokines were combined with IL-17A. Interestingly, human rhinovirus had a potentiating effect on IL-13-induced pendrin expression. Dexamethasone suppressed pendrin expression, suggesting that the therapeutic benefit of dexamethasone in asthmatic patients and those with CRS might involve regulation of pendrin expression. CONCLUSIONS TH2-mediated pendrin expression is increased in NPs of patients with CRS and might lead to increased inflammation, mucus production, and decreased mucociliary clearance.

Male adolescent fertility preservation

Until the 1960s, few adolescents and young adults (AYAs) survived their initial cancer diagnoses. Now, ∼12,400 AYA patients are diagnosed with cancer each year, and almost 80% will now achieve a long-term cure. This dramatic improvement in survival is primarily due to multimodal treatments and combined chemotherapeutic regimens. Unfortunately, the increase in survival is often accompanied by treatment-related toxicities due to chemotherapy, radiation therapy, and surgical procedures. Despite guidelines published by the American Society of Clinical Oncology and numerous other professional organizations, high percentages of male AYA oncology patients are not properly counseled regarding their fertility preservation options before cancer treatment. Although administering fertility preservation care to adolescent males can be challenging in many ways, numerous studies show that this care can be delivered with high degrees of success and high levels of patient and parent satisfaction. The key to this success at many institutions has been the implementation of formalized integrated fertility preservation programs with infrastructure geared toward the delivery of comprehensive expedited care.

Regional differences in the expression of innate host defense molecules in sinonasal mucosa.

Nasal mucosal epithelial cells form the first line of defense by maintaining a barrier to restrict potentially harmful airborne substances and pathogens. To aid in host defense, specialized epithelial cells in submucosal glands as well as on the mucosal surface secrete mucous that helps to immobilize pathogens and other harmful substances. Beneath this mucous blanket resides an aqueous surface liquid layer, which allows proper ciliary function to clear mucous and entrapped pathogens. In concert with maintenance of a physical barrier, airway epithelium secretes dozens of antimicrobial peptides and proteins that become incorporated into the mucous and aqueous lining fluids1, 2. It has become clear that proper functioning of the epithelium is essential for suppressing the growth of pathogenic organisms and promoting healthy upper airway physiology. Dysfunction in innate immune expression of host defense molecules has been linked to many airway diseases3-8. Surprisingly, the regional distribution of important epithelial derived antimicrobial proteins secreted into upper airways has not been studied in detail. In this study, we analyzed the expression of select antimicrobial proteins that are known to be secreted into the lining fluids of the upper airways in two different anatomical sites of the sinonasal mucosa in healthy human subjects, namely the inferior region (inferior turbinate - IT), and the superior region (uncinate tissue - UT). We chose IT, as it is the proximal point of contact of inhaled air containing particulate matter and potential pathogens. Moreover, studies of CRS and other diseases of the upper airways routinely use IT tissue as a control tissue to make comparisons with nasal polyps. UT was chosen for its important role in the drainage pathways of maxillary, frontal and anterior ethmoid sinuses. We chose to study the expression of S100A7 (S100 family), hBD2 (β-Defensin family), SPLUNC1 (PLUNC family), and lactoferrin, as they represent broad families of antimicrobial proteins, which are either constitutively present or induced by inflammation triggered by pathogens and collectively have antimicrobial effects against a variety of pathogens (bacteria, fungi and viruses). Sinonasal tissue samples from IT and UT were collected from subjects undergoing surgery to correct non-inflammatory conditions, including facial anatomical defects (deformity, trauma etc.), to improve airflow and during the course of skull base surgery to remove tumors. The subjects were not diagnosed with any upper or lower airway diseases at the time of sample collection. Detailed patient characteristics are provided in table EI. The Investigational Review Board of Northwestern University approved all methods for the present study, and all patients provided informed consent. At the time of surgery, tissues and nasal epithelial scraping cells were collected and stored for further analysis. Tissue samples and epithelial cells were analyzed for mRNA expression by real time PCR. Protein expression and localization were analyzed using ELISA and immunohistochemistry, respectively. AB/PAS staining was performed to characterize the glandular differences between IT and UT. Details of the methods used can be found in the online repository and our other publications5, 7.

Abciximab-induced alveolar hemorrhage treated with rescue extracorporeal membranous oxygenation

We describe a case of a 75‐year‐old woman presenting emergently with an anterior S‐T elevation myocardial infarction that deteriorated into ventricular fibrillation requiring prompt resuscitation, resulting in cardiogenic shock. Emergency primary percutaneous coronary intervention of the left anterior descending coronary artery with adjunctive abciximab and heparin resulted in adequate coronary flow, and intra‐aortic balloon pump was used to support hemodynamics. Within one hour of intervention, she developed acute respiratory distress with four‐quadrant opacification of lung fields, difficulty with oxygenation, and hypotension. Emergency bronchoscopy revealed diffuse erythematous proximal airways with bloody secretions bilaterally confirming diffuse alveolar hemorrhage. An emergency veno‐arterial extracorporeal membranous oxygenation (ECMO) circuit was placed at the bedside, acutely improving oxygenation and hemodynamics. She survived the hospitalization with multiple complications related to access site and prolonged intensive care unit stay, was discharged to acute rehabilitation. She is currently thriving 18 months post‐procedure. This case highlights the use of ECMO in the often‐fatal condition of diffuse alveolar hemorrhage related to glycoprotein inhibitor use.

Scrotal Ultrasound for Pain: Low Frequency of Absolute Surgical Indications

OBJECTIVE To examine the results of scrotal ultrasounds (US) conducted for scrotal or testicular pain and review the pathologic findings of orchiectomies done for lesions that were suspicious for malignancy on US. MATERIALS AND METHODS We retrospectively reviewed the indications and findings of all scrotal US completed at our institution from 2002 to 2014. If a patient underwent an orchiectomy for an intratesticular lesion that was concerning for malignancy on US, the pathology report was also reviewed. RESULTS There were 18,593 scrotal US performed, with 7,668 (41.2%) conducted for scrotal pain. Of the US performed for pain, 80.4% revealed benign or normal findings, and only 2.2% demonstrated a finding that is an absolute indication for surgery (intratesticular lesion suspicious for malignancy 0.8%, abscess 0.7%, torsion 0.6%, infiltrative process such as lymphoma 0.1%). For those patients undergoing an orchiectomy, 75% had malignancy on pathologic analysis. CONCLUSION The majority of the 7668 US performed to evaluate scrotal or testicular pain reveal normal or benign findings. A low percentage demonstrates a finding that necessitates urgent or emergent surgery.

EGFR Inhibitors and Cutaneous Complications: A Practical Approach to Management

Epidermal growth factor receptor inhibitors (EGFRIs) are increasingly being used for malignancies of epithelial origin. Though these therapies are better tolerated than conventional chemotherapy, they have unique side-effect profiles that are related to their mechanism of action. Given the function of the epidermal growth factor receptor in the skin, nails, and hair, dermatologic side effects are commonly seen with the use of EGFRIs. This review includes a practical approach to recognizing and treating the most common dermatologic side effects seen with EGFRIs, including papulopustular eruptions, nail changes, xerosis and pruritus, hair changes, mucositis, and radiation dermatitis exacerbations.

Assessment of the diameter of pigmented skin lesions with and without a ruler

lier presentation may be attributable to carcinogenic occupational exposures; however, non–work-related ultraviolet light exposure may also contribute. Better understanding of these carcinogens is needed to inform best practices for protection. For most skin cancer screening and sun protection practices, firefighters with a history of skin cancer had higher rates of adherence than firefighters without a history of skin cancer. This firefighter sample showed a higher rate of skin checks compared with state-wide statistics on skin cancer screening.5 Compared with the US national average, firefighters reported a lower proportion of ever using a tanning bed, yet the rate is still high representing an opportunity for education and behavior modification.6 Despite the potentially increased skin cancer risk, skin cancer screening and sun protection habits could be improved for firefighters with and without skin cancer diagnoses. Future research is warranted to further investigate skin cancer risk and mortality among firefighters and to identify occupational hazards associated with this excess risk.

Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection FractionCLINICAL PERSPECTIVE: Importance of Left Atrial Strain

Background—Left atrial (LA) enlargement is associated with adverse events in heart failure with preserved ejection fraction (HFpEF). However, the role of LA mechanics (ie, LA strain measures) in HFpEF has not been well studied. We hypothesized that in HFpEF, reduced (worse) LA strain is a key pathophysiologic abnormality and is a stronger correlate of adverse events than left ventricular or right ventricular longitudinal strain. Methods and Results—We evaluated baseline LA function in 308 patients with HFpEF who were followed up longitudinally for adverse outcomes. All patients underwent speckle-tracking echocardiography for measurement of left ventricular longitudinal strain, right ventricular free wall strain, and LA booster, conduit, and reservoir strains. The clinical and prognostic significance of left ventricular, right ventricular, and LA strain measures was assessed by regression analyses. The mean age was 65±13 years, 64% were women, 26% had atrial fibrillation, and LA enlargement was present in the majority of patients (67%). Decreased LA reservoir strain was associated with increased pulmonary vascular resistance (P<0.0001) and decreased peak oxygen consumption (P=0.0001). Of the left ventricular, right ventricular, and LA strain measures, LA reservoir strain was the strongest correlate of adverse events and was independently associated with the composite outcome of cardiovascular hospitalization or death (adjusted hazard ratio per 1-SD decrease in LA strain, 1.54; 95% CI, 1.15–2.07; P=0.006). Conclusions—Abnormal indices of LA mechanics (particularly LA reservoir strain) are powerful clinical and prognostic factors in HFpEF. Unloading the LA and augmentation of LA function may be important future therapeutic targets in HFpEF. Registration Information—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01030991.

Prognostic Utility and Clinical Significance of Cardiac Mechanics in Heart Failure With Preserved Ejection FractionCLINICAL PERSPECTIVE

Background—Left atrial (LA) enlargement is associated with adverse events in heart failure with preserved ejection fraction (HFpEF). However, the role of LA mechanics (ie, LA strain measures) in HFpEF has not been well studied. We hypothesized that in HFpEF, reduced (worse) LA strain is a key pathophysiologic abnormality and is a stronger correlate of adverse events than left ventricular or right ventricular longitudinal strain. Methods and Results—We evaluated baseline LA function in 308 patients with HFpEF who were followed up longitudinally for adverse outcomes. All patients underwent speckle-tracking echocardiography for measurement of left ventricular longitudinal strain, right ventricular free wall strain, and LA booster, conduit, and reservoir strains. The clinical and prognostic significance of left ventricular, right ventricular, and LA strain measures was assessed by regression analyses. The mean age was 65±13 years, 64% were women, 26% had atrial fibrillation, and LA enlargement was present in the majority of patients (67%). Decreased LA reservoir strain was associated with increased pulmonary vascular resistance (P<0.0001) and decreased peak oxygen consumption (P=0.0001). Of the left ventricular, right ventricular, and LA strain measures, LA reservoir strain was the strongest correlate of adverse events and was independently associated with the composite outcome of cardiovascular hospitalization or death (adjusted hazard ratio per 1-SD decrease in LA strain, 1.54; 95% CI, 1.15–2.07; P=0.006). Conclusions—Abnormal indices of LA mechanics (particularly LA reservoir strain) are powerful clinical and prognostic factors in HFpEF. Unloading the LA and augmentation of LA function may be important future therapeutic targets in HFpEF. Registration Information—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01030991.