Invasive Pulmonary Aspergillosis in Hospitalized Hematopoietic Stem Cell Transplantation Recipients: Outcomes Based on the United States National Readmission Database.

BACKGROUND AND OBJECTIVE: Hematopoietic stem cell transplant (HSCT) is a well-established treatment for hematologic malignancies and certain autoimmune and congenital conditions. HSCT is associated with immunocompromise and increased risk of infections. This study assessed whether invasive pulmonary aspergillosis (IPA) affects in-hospital mortality and 30-day readmission among HSCT patients. A secondary objective was to examine potential differences in complications between HSCT with and without IPA. MATERIALS AND METHODS: A retrospective study of a nationally representative cohort of hospital admissions was conducted, with data collected from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database between 2013 and 2019. The International Classification of Diseases, 10th revision (ICD-10), and 9th revision (ICD-9) diagnostic codes were used to identify patients with IPA and HSCT. All adult patients ≥18 years were included in the study. RESULTS: There were 90,451 hospitalizations for HSCT from 2013 to 2019; 89,331 (98.8%) had HSCT without IPA, while 1092 (1.2%) hospitalizations had HSCT with IPA. The in-hospital mortality for HSCT-IPA was higher compared to HSCT without IPA (18.3% vs. 4.2%; p < 0.001). HSCT-IPA had a significantly higher 30-day readmission rate (36.2%) than that of HSCT without IPA (24.0%). HSCT-IPA also had a higher mean cost of admission ($303,437) than that of HSCT without IPA ($57,587).The HSCT-IPA group had higher multi-organ complications, including respiratory failure (51.3% vs. 13.5%, p < 0.001), sepsis (38.2% vs. 18.5%, p < 0.001), septic shock (16.1% vs. 5.1%, p < 0.001), need for mechanical ventilation (21.1% vs. 5.1% p < 0.001), non-invasive positive pressure ventilation (4.9% vs. 2.5%, p < 0.001), and intensive-care unit admission (21.8% vs. 6.1% p < 0.001). CONCLUSION: IPA is a rare but severe complication associated with HSCT, with higher in-hospital mortality, complications due to multi-organ failure, readmission rates, and cost of hospitalization when compared to HSCT without IPA.

Diagnostic Dilemma: A Patient With Pulmonary Fibrosis Who Presented for Severe Tracheal Stenosis After COVID-19 Pneumonia.

A 44-year-old man with pulmonary fibrosis presented to our pulmonary hypertension clinic with biphasic stridor and dyspnea. He was sent to the emergency department, where he was found to have 90% subglottic tracheal stenosis and was successfully treated with balloon dilation. Seven months prior to the presentation, he required intubation for coronavirus disease 2019 (COVID-19) pneumonia complicated by hemorrhagic stroke. He was discharged after percutaneous dilatational tracheostomy, which was decannulated after three months. Our patient possessed several risk factors for tracheal stenosis, including endotracheal intubation, tracheostomy, and airway infection. Furthermore, our case is of great importance given the developing literature on COVID-19 pneumonia and its subsequent complications. Additionally, his history of interstitial lung disease may have confounded his presentation. Therefore, it is important to understand stridor, as it is an important exam finding that clinically distinguishes upper and lower airway disease. Our patient's biphasic stridor is consistent with the diagnosis of severe tracheal stenosis.

ST-Elevation Myocardial Infarction Outcomes: A United States Nationwide Emergency Departments Cohort Study.

BACKGROUND: Literature regarding trends in incidence and mortality of ST-elevation myocardial infarction (STEMI) in emergency departments (EDs) is limited. OBJECTIVE: To study the trends of incidence and mortality of STEMI. METHODS: Using the National Emergency Department Sample database in the United States, we identified all ED encounters for patients presenting with STEMI using International Classification of Diseases codes. A linear p-trend was used to assess the trends. RESULTS: Out of the 973 million ED encounters represented, 641,762 (65/100,000; mean age 69 [59-81] years, 35.8% female) adult patients were recorded with STEMI. Among the major complications associated with STEMI, a total of 49,401 (7.7%) had cardiac complications, which included acute heart failure (n = 9361, 1.6%), ventricular tachycardia or fibrillation (n = 12,267, 1.91%), conduction block (n = 20,165, 3.1%), and cardiogenic shock (n = 7608, 1.2%). There were 5675 (0.9%) patients recorded with cerebrovascular events, which included acute ischemic stroke among 5205 (0.8%) patients and 470 (0.1%) with transient ischemic attack. Acute kidney injury was recorded for 10,082 (1.6%) patients. The trend for incidence of STEMI in the ED had decreased from 7.76/10,000 in 2011 to 4.07/10,000 in 2018 (linear p-trend 0.0006). However, the yearly mortality of STEMI related to ED encounters had remained relatively steady: 7.56% in 2011 to 7.50% in 2018 (linear p-trend 0.2364). CONCLUSION: Despite the fact that the number of patients presenting to the ED with STEMI has been decreasing, the mortality trends have remained steady. Further research of in-hospital STEMI may yield opportunities to reduce the risk of complications, improve patient outcomes and decrease health care burden.

Mortality outcomes associated with invasive aspergillosis among acute exacerbation of chronic obstructive pulmonary disease patient population.

BACKGROUND: Literature regarding trends of mortality, and complications of aspergillosis infection among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is limited. METHODS: Data from the National Readmissions Database (NRD) that constitutes 49.1% of the stratified sample of all hospitals in the United States (US), representing more than 95% of the national population were analyzed for hospitalizations with aspergillosis among AECOPD. Predictors and trends related to aspergillosis in AECOPD were evaluated. A Linear p-trend was used to assess the trends. RESULTS: Out of the total 7,282,644 index hospitalizations for AECOPD (mean age 69.17 ± 12.04years, 55.3% females), 8209 (11.2/10,000) with primary diagnosis of invasive aspergillosis were recorded in the NRD for 2013-2018. Invasive aspergillosis was strongly associated with mortality (OR 4.47, 95%CI 4.02-4.97, p < 0.001) among AECOPD patients. Malignancy and organ transplant status were predominant predictors of developing aspergillosis among AECOPD patients. The IA-AECOPD group had higher rates of multi-organ manifestations including ACS (3.7% vs 0.44%; p-value0.001), AF (20% vs 18.4%; p-value0.001), PE (4.79% vs1.87%; p-value0.001), AKI (22.3% vs17.5%; p-value0.001), ICU admission (16.5% vs11.9%; p-value0.001), and MV (22.3% vs7.31%; p-value0.001) than the AECOPD group. The absolute yearly trend for mortality of aspergillosis was steady (linear p-trend 0.22) while the yearly rate of IA-AECOPD had decreased from 15/10,000 in 2013 to 9/10,000 in 2018 (linear p-trend 0.02). INTERPRETATION: Aspergillosis was related with high mortality among AECOD hospitalizations. There has been a significant improvement in the yearly rates of aspergillosis while the mortality trend was steady among aspergillosis subgroups. Improved risk factor management through goal-directed approach may improve clinical outcomes.

Trends in Incidence, and Mortality of Acute Exacerbation of Chronic Obstructive Pulmonary Disease in the United States Emergency Department (2010-2018).

Literature regarding trends of incidence, mortality, and complications of acute exacerbation of chronic obstructive pulmonary disease (COPD) in the emergency departments (ED) is limited. What are trends of COPD exacerbation in ED? Data were obtained from the Nationwide Emergency Department Sample (NEDS) that constitutes a 20% sample of hospital-owned EDs and inpatient sample in the US. All ED encounters were included in the analysis. Complications of AECOPD were obtained by using ICD codes. Out of 1.082 billion ED encounters, 5,295,408 (mean age 63.31 ± 12.63 years, females 55%) presented with COPD exacerbation. Among these patients, 353,563(6.7%) had AECOPD-plus (features of pulmonary embolism, acute heart failure and/or pneumonia) while 4,941,845 (93.3%) had exacerbation without associated features or precipitating factors which we grouped as AECOPD. The AECOPD-plus group was associated with statistically significantly higher proportion of cardiovascular complications including AF (5.6% vs 3.5%; p < 0.001), VT/VF (0.14% vs 0.06%; p < 0.001), STEMI (0.22% vs 0.11%; p < 0.001) and NSTEMI (0.65% vs 0.2%; p < 0.001). The in-hospital mortality rates were greater in the AECOPD-plus population (0.7% vs 0.1%; p < 0.001). The incidence of both AECOPD and AECOPD-plus had worsened (p-trend 0.004 and 0.0003) and the trend of mortality had improved (p-trend 0.0055 and 0.003, respectively). The prevalence of smoking for among all COPD patients had increased (p-value 0.004), however, the prevalence trend of smoking among AECOPD groups was static over the years 2010-2018. There was an increasing trend of COPD exacerbation in conjunction with smoking; however, mortality trends improved significantly. Moreover, the rising burden of AECOPD would suggest improvement in diagnostics and policy making regarding management.

Spontaneous retroperitoneal haemorrhage secondary to anticoagulation polypharmacy.

Retroperitoneal haemorrhage (RH) is not uncommon in patients with provoking events like trauma. However, spontaneous RH (SRH) is a rare and life-threatening complication described as the development of bleeding into the retroperitoneal cavity, appearing spontaneously and without a preceding history of trauma or other predisposing illness. We are reporting a case of an elderly patient with recurrent deep vein thrombosis who had developed SRH secondary to concurrent use of multiple anticoagulation agents, resulting from poor healthcare follow-up and lack of sufficient medication reconciliation. This article highlights the significance of recognising risk factors for SRH, as well as management strategies through literature review.

Infectious Mononucleosis Presenting with Loss of Taste and Smell During the SARS-CoV-2 Pandemic?

A 53-year-old woman presented during the SARS-CoV-2 pandemic with an 18-day history of pyrexia, myalgia, progressive dyspnoea and loss of taste and smell after a close contact had tested positive for SARS-CoV-2. In this period two swabs had been negative for SARS-CoV-2. Clinical examination was normal. During this admission a third SARS-CoV-2 swab was negative, and investigations showed mildly elevated inflammatory markers, mildly deranged liver function, atypical lymphocytes on a blood film and a normal chest x-ray. Her Epstein-Barr virus serology was positive and thus the diagnosis was infectious mononucleosis. LEARNING POINTS: SARS-CoV-2 is not the only virus to cause loss of taste/smell and so other differential diagnoses should be considered.Loss of taste/smell is a subjective symptom, and therefore caution should be exercised in the context of an upper respiratory tract infection.

Diaphragmatic Excursion: Does it Predict Successful Weaning from Mechanical Ventilation?

OBJECTIVE: To measure the diaphragmatic excursion and its outcome on weaning from mechanical ventilation. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: Medical Intensive Care Unit (ICU), Military Hospital (MH), Rawalpindi, Pakistan, from January to December 2014. METHODOLOGY: Diaphragmatic excursion (DE) in cm was measured through ultrasound by marking liver and spleen displacement in patients who fulfilled the criteria of removal from ventilatory support. The patients were followed up for 48 hours and classified according to the outcome as successful weaning and weaning failure. RESULTS: Out of 100 cases, 76 patients had a successful weaning while 24 had a failed weaning outcome. At a diaphragmatic excursion of 1.2 cm and more, out of 67 cases, 60 had a successful weaning (89.55%) while 7 cases (10.45%) had a weaning failure. At an excursion of less than 1.2 cm, 17 out of 33 cases (51.5%) had successful weaning while 16 (48.48%) had weaning failure. At this cut off point (1.2 cm), the sensitivity and specificity for successful weaning were 78.95% and 70.83%, respectively. The positive and negative likelihood ratio (LR) for these values being 2.70 and 0.29, respectively. The positive predictive value was 82.35% and negative predictive value 60.00%. CONCLUSION: Ultrasonographic measurement of diaphragmatic excursion is a good method for predicting weaning outcome from mechanical ventilation.

Absence of transverse tubules contributes to non-uniform Ca(2+) wavefronts in mouse and human embryonic stem cell-derived cardiomyocytes.

Mouse (m) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are known to exhibit immature Ca(2+) dynamics such as small whole-cell peak amplitude and slower kinetics relative to those of adult. In this study, we examined the maturity and efficiency of Ca(2+)-induced Ca(2+) release in m and hESC-CMs, the presence of transverse (t) tubules and its effects on the regional Ca(2+) dynamics. In m and hESC-CMs, fluorescent staining and atomic force microscopy (AFM) were used to detect the presence of t-tubules, caveolin-3, amphiphysin-2 and colocalization of dihydropyridine receptors (DHPRs) and ryanodine receptors (RyRs). To avoid ambiguities, regional electrically-stimulated Ca(2+) dynamics of single ESC-CMs, rather than spontaneously beating clusters, were measured using confocal microscopy. m and hESC-CMs showed absence of dyads, with neither t-tubules nor colocalization of DHPRs and RyRs. Caveolin-3 and amphiphysin-2, crucial for the biogenesis of t-tubules with robust expression in adult CMs, were also absent. Single m and hESC-CMs displayed non-uniform Ca(2+) dynamics across the cell that is typical of CMs deficient of t-tubules. Local Ca(2+) transients exhibited greater peak amplitude at the peripheral than at the central region for m (3.50 +/- 0.42 vs. 3.05 +/- 0.38) and hESC-CMs (2.96 +/- 0.25 vs. 2.72 +/- 0.25). Kinetically, both the rates of rise to peak amplitude and transient decay were faster for the peripheral relative to the central region. Immature m and hESC-CMs display unsynchronized Ca(2+) transients due to the absence of t-tubules and gene products crucial for their biogenesis. Our results provide insights for driving the maturation of ESC-CMs.

Early asymmetry of gene transcription in embryonic human left and right cerebral cortex.

The human left and right cerebral hemispheres are anatomically and functionally asymmetric. To test whether human cortical asymmetry has a molecular basis, we studied gene expression levels between the left and right embryonic hemispheres using serial analysis of gene expression (SAGE). We identified and verified 27 differentially expressed genes, which suggests that human cortical asymmetry is accompanied by early, marked transcriptional asymmetries. LMO4 is consistently more highly expressed in the right perisylvian human cerebral cortex than in the left and is essential for cortical development in mice, suggesting that human left-right specialization reflects asymmetric cortical development at early stages.

Expression patterns of epidermal growth factor receptor and fibroblast growth factor receptor 1 mRNA in fetal human brain.

Factors that interact with the epidermal growth factor and fibroblast growth factor receptors have numerous effects in the central nervous system (CNS), inducing the proliferation of CNS stem cells and astrocytes and the survival and differentiation of neurons. Both receptors are expressed in the embryonic rodent brain in proliferative and nonproliferative regions, suggesting roles in numerous developmental processes. However, the roles of these factors in human brain development are not known. In the current study, we examined the expression of human epidermal growth factor receptor (HEGFR) and human fibroblast growth factor receptor 1 (HFGFR1) mRNAs in the human fetal brain. The expression of both receptors is strikingly conserved relative to previously reported patterns in the rodent. In the germinal zones, the sites of cellular proliferation, HFGFR1 was expressed primarily in the ventricular zone, whereas HEGFR was expressed in the subventricular zone, suggesting different roles in CNS progenitor proliferation. Differential expression was also observed in other brain areas examined, including the hippocampus and the cerebellum. The current study suggests that HEGFR and HFGFR1 are likely to play different roles during human brain development, but that these roles will be similar to those observed in the rodent brain.