Fifteen-year symptomatic outcome of patients with nonactionable motor findings on high-resolution manometry.

BACKGROUND: High-resolution manometry (HRM) is performed for evaluation of esophageal symptoms, but patient outcome is unclear when no actionable motor disorder is identified. We evaluated long-term symptomatic outcome of patients with nonactionable HRM findings. METHODS: Patients who underwent (HRM) studies in 2006-2008 were tracked. Patients with achalasia spectrum disorders, foregut surgery before or after HRM, and incomplete symptom documentation were excluded. Symptom questionnaires assessing dominant symptom intensity (DSI, product of symptom severity and frequency recorded on 5-point Likert scales) and global symptom severity (GSS, from 10 cm visual analog scale) were repeated. Change in symptom burden was compared against HRM motor findings using Chicago Classification 4.0 (CCv4.0), applied retroactively to 2006-2008 data. KEY RESULTS: Overall, 134 patients (median age 68 years, 64.5% female) could be contacted. The majority (73.1%) had normal motility; others had ineffective esophageal motility (8.2%), esophagogastric junction outflow obstruction (13.4%), hypercontractile esophagus (3.0%), or absent contractility (2.2%), none managed invasively. Over 15 years of follow-up, DSI decreased from 8.0 (4.0-16.0) to 1.0 (0.0-6.0) (p < 0.001) and GSS improved from 5.5 (3.3-7.7) to 2.0 (0.0-4.0) (p < 0.001); improvement was consistent across CCv4.0 diagnoses and subgroups. The majority (82.8%) reported improvement over time, and antisecretory medication was the most effective intervention (83.0% improvement). There was no difference in medication efficacy (p = 0.75) or improvement in symptoms (p = 0.20) based on CCv4 diagnosis. CONCLUSIONS AND INFERENCES: Esophageal symptoms improve with conservative symptomatic management over long-term follow-up when no conclusive obstructive motor disorders or achalasia spectrum disorders are found on HRM.

Examining the effects of training on young and older adult implementation of spaced retrieval strategies.

Although the benefits of spaced retrieval are well established, research suggests that young and older adults often fail to optimally implement this strategy. The present study examined how task experience with feedback influenced participant-implemented spaced retrieval and its effect on short and long-term memory retention. Young and older adults were instructed to either equally space or expand their retrieval of face-name associations throughout an ongoing reading task. Participants were then provided feedback on the accuracy with which they implemented experimenter instructions. Results showed that feedback improved utilization of retrieval practice in both young and older adults. Moreover, both age groups successfully produced a pattern of expanded retrieval when instructed to do so, but failed to properly implement equal spacing. Consistent with extant research utilizing experimenter-determined spaced retrieval schedules, our study showed that the inclusion of a longer spacing interval immediately following acquisition resulted in reduced forgetting across the retention interval.

Intranasal Fentanyl and Midazolam Use in Children 3 Years of Age and Younger in the Emergency Department.

BACKGROUND: Although the efficacy and safety profiles of both intranasal fentanyl and midazolam are well studied in pediatric patients, few studies examine their use in younger children. OBJECTIVES: To examine and report our experiences in a pediatric emergency department (ED) with intranasal fentanyl and midazolam in children aged 3 years and younger. METHODS: This retrospective study investigated intranasal fentanyl and midazolam administration, alone and in combination, in children 3 years and younger treated in a pediatric ED. RESULTS: Of 6198 patients included, 1762 received intranasal fentanyl alone, 1115 received intranasal midazolam alone, and 3321 received combination therapy. The median (interquartile range [IQR]) patient age was 2.2 (1.5-3) years. Initial median (IQR) fentanyl dose was 2.7 (2-3) µg/kg, with 13.3% receiving a repeat dose. Initial median (IQR) midazolam dose was 0.3 (0.2-0.3) mg/kg, with 3.3% receiving a second dose. Children receiving both fentanyl and midazolam had median (IQR) initial doses of 2.8 (2.1-3) µg/kg and 0.3 (0.2-0.3) mg/kg, respectively. Of these, 3.2% received repeat doses of both medications. Laceration repairs (33.8%) and incision and drainage (22.2%) accounted for the majority of indications. Only 2.9% (n = 178) received additional opioids. No serious adverse events requiring a reversal agent or respiratory support were reported. CONCLUSIONS: Intranasal fentanyl and midazolam, alone and in combination, can provide analgesia and anxiolysis to children aged 3 years and younger in the ED setting. Further prospective studies are needed to better evaluate their safety and efficacy in this younger population.

The Relationship between Acute and Chronic Pancreatitis with Pancreatic Adenocarcinoma: Review.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with poor prognosis, leading to significant cancer-related mortality and an overall five-year survival rate of about nine percent. Acute and chronic pancreatitis have been associated with PDAC through common risk factors based on multiple epidemiological studies. Acute pancreatitis (AP) might be one of the earliest manifestations of PDAC, but evolving chronic pancreatitis (CP) following recurrent bouts of AP has been proposed as a risk factor for cancer development in the setting of persistent inflammation and ongoing exposure to carcinogens. This review aims to highlight the evidence supporting the relationship between acute and chronic pancreatitis with PDAC.

Renal Cell Carcinoma Presenting With Combined Cervical Lymphadenopathy and Cardiac Metastasis Without Inferior Vena Cava Involvement.

Renal cell cancer is the third most common urological malignancy following prostate and bladder malignancies. Cardiac metastases to the right side of the heart without inferior vena cava (IVC) involvement are exceedingly rare, with only a handful of cases described in the literature. Metastasis to the head and neck region is also rare, occurring in an estimated 1% of cases. Here we present a case of a patient with recurrent syncopal events secondary to renal cell carcinoma without IVC involvement, with metastases both to the right ventricle and cervical lymph nodes. To our knowledge, this is the first case that presents with both of these rare findings together and that highlights cancer screening in patients with high risk factors and new exam findings in patients with syncopal events having negative initial workup.

A Case Report of Disseminated Blastomycosis With Thyroid Involvement in a Pregnant Patient.

Blastomyces dermatitidis is the causal agent of blastomycosis, an invasive and often serious fungal infection. Blastomycosis typically presents as a pulmonary infection, but common extrapulmonary manifestations of blastomycosis include the skin, bones, and reticuloendothelial systems. Disseminated blastomycosis occurs more prominently in immunocompromised individuals, such as organ transplant recipients, HIV patients, and pregnant women. We report here a rare case of disseminated blastomycosis to the thyroid in a pregnant patient. This case emphasizes the unique challenges of diagnosing and treating disseminated fungal infections in pregnancy.

Left ventricular diastolic dysfunction in liver transplantation: a stronger association with non-alcoholic steatohepatitis.

AIM OF THE STUDY: Cardiovascular death is an important cause of mortality in end stage liver disease (ESLD) patients undergoing orthotopic liver transplant (OLT). Left ventricular diastolic dysfunction (LVDD) is often the early manifestation and only measurable manifestation of cirrhotic cardiomyopathy. Therefore, it is important to understand the risk factors for LVDD in ESLD patients undergoing OLT and its immediate impact post-operatively. MATERIAL AND METHODS: Electronic medical records (EMR) of 100 consecutive patients who underwent OLT were reviewed at the University of Tennessee/Methodist University Hospital in Memphis, Tennessee, USA. Transthoracic echocardiogram (TTE) reports were accessed to evaluate for LVDD based on the latest 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines. The clinical and demographic variables were obtained and variable quality measures, incidence of cardiac arrhythmias, and 30-day all-cause mortality were compared. RESULTS: Patients with LVDD were older (62.7 ±6.3 years vs. 55.9 ±12.3 years, p = 0.017) and were more often female (57% vs. 31%, p = 0.026). In addition, patients with non-alcoholic steatohepatitis (NASH) were more likely to have LVDD (48% vs. 12%, p = 0.001). In contrast, patients with alcoholic liver disease were less likely to have LVDD (10% vs. 33%, p = 0.032). In a multivariate logistic regression analysis, NASH (OR = 4.4 [95% CI: 1.33-14.5], p = 0.015) and female gender (OR = 3.31 [95% CI: 1.09-9.99], p = 0.033) were independent predictors of LVDD. CONCLUSIONS: In our cohort of patients, the presence of NASH was associated with a higher risk of LVDD. However, presence of LVDD did not influence immediate post-transplant outcome or 30-day all-cause mortality.

Dermatomyositis Developed After Exposure to Epstein-Barr Virus Infection and Antibiotics Use.

Dermatomyositis is an inflammatory disorder involving muscle and skin. Similar to many other autoimmune diseases, environmental factors appear to trigger the onset of disease in some cases. Many drugs have been reported to be associated with dermatomyositis, and rarely infections have been described as potential triggering agents. Here we are describing a case of dermatomyositis that developed after doxycycline and levofloxacin use, who also had recent Epstein-Barr virus infection. Dermatomyositis associated with doxycycline or levofloxacin use has not yet been described in the literature, while reports of dermatomyositis after Epstein-Barr virus infection have been rare and limited to juvenile dermatomyositis or in association with cancer. It is important for clinicians to be aware of this rare association so that the diagnosis and treatment can be exercised promptly.

Hyperammonemic encephalopathy associated with 5-fluorouracil in a patient with previous orthotopic liver transplantation.

5-Fluorouracil (5-FU)-based chemotherapy is the most common regimen used to treat metastatic or advanced colon cancer. Neurotoxicity is a rare but serious adverse effect of 5-FU-based therapy. We report an unusual case of 5-FU-induced hyperammonemic encephalopathy in a patient with recurrent colon cancer that metastasized to the liver and lung. Two days after receiving the third dose of FOLFOX, he presented with altered mental status, agitation, abdominal pain, nausea, and vomiting. His total ammonia level was 434 µmol/L, for which he was treated with lactulose retention enema and lactulose via nasogastric tube. Over the next 24 hours, his condition improved significantly.

Dual specificity phosphatase 5 regulates perfusion recovery in experimental peripheral artery disease.

Peripheral artery disease (PAD) is caused by atherosclerotic occlusions of vessels outside the heart, particularly those of the lower extremities. Angiogenesis is one critical physiological response to vessel occlusion in PAD, but our understanding of the molecular mechanisms involved in angiogenesis is incomplete. Dual specificity phosphatase 5 (DUSP5) has been shown to play a key role in embryonic vascular development, but its role in post-ischemic angiogenesis is not known. We induced hind limb ischemia in mice and found robust upregulation of Dusp5 expression in ischemic hind limbs. Moreover, in vivo knockdown of Dusp5 resulted in impaired perfusion recovery in ischemic limbs and was associated with increased limb necrosis. In vitro studies showed upregulation of DUSP5 in human endothelial cells exposed to ischemia, and knockdown of DUSP5 in these ischemic endothelial cells resulted in impaired endothelial cell proliferation and angiogenesis, but did not alter apoptosis. Finally, we show that these effects of DUSP5 on post-ischemic angiogenesis are a result of DUSP5-dependent decrease in ERK1/2 phosphorylation and p21 protein expression. Thus, we have identified a role of DUSP5 in post-ischemic angiogenesis and implicated a DUSP5-ERK-p21 pathway that may serve as a therapeutic target for the modulation of post-ischemic angiogenesis in PAD.

In experimental peripheral arterial disease, type 2 diabetes alters post-ischemic gene expression.

Peripheral arterial disease is characterized by impaired blood flow to tissues outside the heart due to atherosclerosis and it most frequently occurs in the lower extremities. Type 2 diabetes (T2D) is a well-known risk factor that accelerate the course and contributes to poor clinical outcomes of PAD. While there is some evidence that T2D is associated with altered expression of genes involved in regulating PAD severity, our knowledge about the specific genes and pathways involved remains incomplete. We induced experimental PAD or hind limb ischemia in T2D and non-diabetic mice and subjected the ischemic gastrocnemius muscle tissues to genome-wide mRNA transcriptome analysis. We subsequently performed pathway analysis on the top 500 genes that showed the most significant expression differences between the ischemic diabetic and ischemic non-diabetic muscle tissues. Pathway analysis of the differentially expressed genes identified pathways involved in essential biological processes such as "metabolic pathways," "phagosomes," "lysosomes," and "regulation of actin cytoskeleton". Overall, our data provides the opportunity to test hypotheses on the potential role of the altered genes/molecular pathways in poor PAD outcomes in diabetes.

Type 1 diabetes alters ischemia-induced gene expression.

Peripheral Artery Disease (PAD) is a chronic, activity-limiting disease that is caused by atherosclerotic occlusion of blood vessels outside the heart. Type 1 Diabetes (T1D) not only increases an individual's likelihood of developing PAD, but also contributes to poor clinical outcomes after PAD manifestation. Although there is some evidence suggesting that hyperglycemia might alter expression of genes involved in regulating PAD severity or outcomes, our knowledge about the specific genes and pathways involved remains incomplete. We induced experimental PAD or hind limb ischemia in T1D and non-diabetic mice and subjected the ischemic gastrocnemius muscle tissues to genome-wide mRNA transcriptome and pathway analysis. We identified 513 probe sets that represented 443 different genes with highly significant expression differences (p < 0.005) between the ischemic diabetic and ischemic non-diabetic muscle tissues. Moreover, pathway analysis of the differentially expressed genes identified pathways involved in essential biological processes such as "cell cycle," "DNA replication," "metabolic pathways," "focal adhesion," "regulation of actin cytoskeleton," and "nucleotide excision repair". Taken together, our data offer the opportunity to test hypotheses on the roles played by the altered genes/molecular pathways in poor PAD outcomes in diabetes. Such studies may lead to the development of specific therapies to improve PAD outcomes in patients with comorbid diabetes.