Obstructive Sleep Apnea and Stroke: Determining the Mechanisms Behind their Association and Treatment Options.

Sleep-disordered breathing (SDB) can be a sequela of stroke caused by vascular injury to vital respiratory centers, cerebral edema, and increased intracranial pressure of space-occupying lesions. Likewise, obstructive sleep apnea (OSA) contributes to increased stroke risk through local mechanisms such as impaired ischemic cerebrovascular response and systemic effects such as promoting atherosclerosis, hypercoagulability, cardiac arrhythmias, vascular-endothelial dysfunction, and metabolic syndrome. The impact of OSA on stroke outcomes has been established, yet it receives less attention in national guidelines on stroke management than hyperglycemia and blood pressure dysregulation. Furthermore, whether untreated OSA worsens stroke outcomes is not well-described in the literature. This scoping review provides an updated investigation of the correlation between OSA and stroke, including inter-relational pathophysiology. This review also highlights the importance of OSA treatment and its role in stroke outcomes. Knowledge of pathophysiology, the inter-relationship between these common disorders, and the impact of OSA therapy on outcomes affect the clinical management of patients with acute ischemic stroke. In addition, understanding the relationship between stroke outcomes and pre-existing OSA will allow clinicians to predict outcomes while treating acute stroke.

Lung transplant in chronic HIV infection.

Lung transplantation is the treatment of choice for many end-stage chronic lung conditions. Chronic Human Immunodeficiency Virus (HIV) infection is considered a relative contraindication for lung transplantation. In the era of Highly Active Antiretroviral Therapy (HAART), there has been an increase in the number of HIV-positive patients living with chronic lung conditions. In this paper, we aim to summarise the available literature in the field of lung transplantation in HIV-positive patients. We also present our experience of an HIV-positive woman who underwent lung transplantation for chronic interstitial lung disease from an HIV-negative donor.Careful candidate selection, along with management focused on closer monitoring, may result in favourable outcomes, including improved longevity among HIV-positive patients with chronic lung disease.

Functional imaging for assessing regional lung ventilation in preclinical and clinical research.

Dynamic heterogeneity in lung ventilation is an important measure of pulmonary function and may be characteristic of early pulmonary disease. While standard indices like spirometry, body plethysmography, and blood gases have been utilized to assess lung function, they do not provide adequate information on regional ventilatory distribution nor function assessments of ventilation during the respiratory cycle. Emerging technologies such as xenon CT, volumetric CT, functional MRI and X-ray velocimetry can assess regional ventilation using non-invasive radiographic methods that may complement current methods of assessing lung function. As a supplement to current modalities of pulmonary function assessment, functional lung imaging has the potential to identify respiratory disease phenotypes with distinct natural histories. Moreover, these novel technologies may offer an optimal strategy to evaluate the effectiveness of novel therapies and therapies targeting localized small airways disease in preclinical and clinical research. In this review, we aim to discuss the features of functional lung imaging, as well as its potential application and limitations to adoption in research.

Coronary vasospasm as an etiology of recurrent ventricular fibrillation in the absence of coronary artery disease: a case report.

Background: Vasospastic angina (VA), or Prinzmetal's angina, is characterized by symptoms of coronary angina caused by coronary vasospasm, usually in the absence of atherosclerotic changes. It typically presents with chest pain, which can be accompanied by transient electrocardiographic changes, if visualized during the attack. It can also rarely present with severe manifestations of acute myocardial angina, ventricular fibrillation, or cardiac arrest. Case presentation: We present a case of a 50-year-old Caucasian male who initially presented to the hospital with chest pain and was diagnosed with VA. Later, he was brought to the hospital by emergency medical services later with ventricular fibrillation, despite normal coronary anatomy on angiogram. He was managed with placement of an intra-cardiac defibrillator (ICD) for secondary prevention. The patient continued to have recurrent episodes of ventricular fibrillation with associated ICD shocks, and had multiple admissions to the hospital with similar presentations. Symptoms and arrhythmia improved after optimizing antianginal therapy. Conclusions: Ventricular fibrillation can be an uncommon but severe manifestation during VA crises. In cases with normal coronary vasculature, it is important to recognize VA as a cause of recurrent ventricular fibrillation in order to optimize medical management for prevention of fatal arrhythmias.

Hypoalbuminemia is associated with increased risk of acute kidney injury in hospitalized patients: A meta-analysis.

PURPOSES: Previous systematic review suggested that hypoalbuminemia is associated with increased risk of acute kidney injury (AKI). However, pooled sample size was small, and there was no universal definition for AKI. MATERIALS AND METHODS: vid MEDLINE, EMBASE, the Cochrane Library and Database of Abstracts of Reviews of Effects (DARE) were search up to December 2019. Inclusion criteria include: observational studies, age ≥ 18 years, non-end-stage kidney disease, AKI, or mortality are outcomes of interest. Only articles utilizing multivariate analysis were included. RESULTS: A total of 39 studies were included in hypoalbuminemia and AKI cohort (n = 168,740), and 15 studies were included in mortality cohort (n = 5693). Each 1.0 g/dL decrement of serum albumin was associated with increased AKI (OR 1.685; 95% CI, 1.302-2.179). The risk remained significant across sensitivity analyses. Furthermore, subgroup analyses showed that age ≥ 70 years and baseline serum albumin level > 3.2 g/dL were significant risk factors for AKI. In mortality cohort, patients with AKI and hypoalbuminemia had significantly higher death (OR 1.183; 95% CI, 1.085-1.288). However, there was potential publication bias to this analysis. CONCLUSIONS: Hypoalbuminemia is associated with AKI in hospitalized patients. However, the effect on mortality is subjected to publication bias.

A 31-Year-Old Man with COVID-19-Associated Empyema and Lupus Anticoagulant.

BACKGROUND COVID-19 was declared a pandemic in March 2020 in the United States. It has been associated with high mortality and morbidity all over the world. COVID-19 can cause a significant inflammatory response leading to coagulopathy and this hypercoagulable state has been associated with worse clinical outcomes in these patients. The published data regarding the presence of lupus anticoagulant in critically ill COVID-19-positive patients is limited and indicates varying conclusions so far. CASE REPORT Here, we present a case of a 31-year-old man who was admitted to the hospital with COVID-19 pneumonia, complicated with superadded bacterial empyema and required video-assisted thoracoscopic surgery with decortication. This patient also had prolonged prothrombin time on preoperative labs, which was not corrected with mixing study. Further workup detected positive lupus anticoagulant and anti-cardiolipin IgM along with alteration in other coagulation factor levels. The patient was treated with fresh frozen plasma and vitamin K before surgical intervention. He had an uneventful surgical course. He received prophylactic-dose low molecular weight heparin for venous thromboembolism prophylaxis and did not experience any thrombotic events while hospitalized. CONCLUSIONS COVID-19 infection creates a prothrombotic state in affected patients. The formation of micro-thrombotic emboli results in significantly increased mortality and morbidity. Routine anticoagulation with low molecular weight heparin can prevent thrombotic events and thus can improve patient outcomes. In patients with elevated prothrombin time, lupus anticoagulant/anti-cardiolipin antibody-positivity should be suspected, and anticoagulation prophylaxis should be continued perioperatively for better outcomes.

Pancytopenia as a Complication of Low-Dose Methotrexate in a Septuagenarian: A Rare Presentation.

Methotrexate (MTX) is an antimetabolite that was initially developed as a chemotherapeutic agent to treat malignancies but later used extensively to treat rheumatological conditions. MTX-induced toxicity is dose- and duration-dependent. Myelosuppression is a rare but fatal complication of MTX that can occur even with low doses used for inflammatory conditions. Multiple factors such as age, renal impairment, and nutritional status increase the risk of developing MTX toxicity. Frequent monitoring of symptoms and lab values are the hallmarks of prompt diagnosis and prevention of complications. Clinicians should have a high degree of suspicion to diagnose pancytopenia secondary to MTX especially in patients with multiple confounding comorbidities. We present the case of a 79-year-old male who presented with mucositis and pancytopenia diagnosed to be secondary to weekly MTX for giant cell arteritis leading to anemia and septic shock causing death.

Metformin Associated Lactic Acidosis in the Intensive Care Unit: A Rare Condition Mimicking Sepsis.

Metformin-associated lactic acidosis (MALA) is a rare but serious complication of metformin use, associated with high mortality. MALA can occur any time a patient on metformin suffers disruption in renal function resulting in the accumulation of metformin. A 63-year-old man with a history of non-insulin-dependent type 2 diabetes mellitus, alcohol abuse, and hypothyroidism was brought to the emergency department with altered mental status, nausea, vomiting, and abdominal pain. He was found to be in respiratory distress, was hypotensive and hypoglycemic (48 mg/dL), and required emergent intubation. Blood work was significant for pH<6.69, undetectable bicarbonate, anion gap 37.2 mEq/L, lactate >12 mmol/L, creatinine 15.95 mg/dL, blood urea nitrogen (BUN) 112 mg/dL, glomerular filtration rate (GFR), 3 ml/min/1.73sqm, and potassium 7 mmol/L. He suffered cardiac arrest, underwent cardiopulmonary resuscitation (CPR), and was admitted to the intensive care unit (ICU) where he required multiple vasopressors, bicarbonate infusion, and bicarbonate pushes. He was started on continuous renal replacement therapy with a high flux membrane. A high dose of pre- and post- filter fluids was used to improve conductive clearance. His pH corrected to normal in less than 24 hours, and hemodialysis was initiated the following day for a total of four days. Head/chest/abdomen/pelvis CT, urine, and blood cultures did not reveal any pathology that would explain lactic acidosis. The patient's dose of metformin was 1 gr twice daily and sitagliptin, 100 mg daily. Blood metformin that had been tested on admission was 29 mcg/ml (therapeutic range, 1-2 mcg/ml). Methanol, ethanol, ethylene glycol, propylene glycol, and isopropanol levels were negative. He had been started on lisinopril 5 mg and amitriptyline 25 mg four weeks prior to admission and had normal creatinine at that time. He was discharged to an acute rehabilitation facility on day seven of hospitalization. MALA generally presents with nausea, vomiting, and fatigue-often mimicking sepsis. It is possible that our patient progressively developed alcoholic ketoacidosis and acute renal failure from dehydration and excessive drinking in the setting of newly started Angiotensin-converting-enzyme (ACE) inhibitor. Recommendations for the optimal treatment of MALA mostly depend on expert opinion and case reports. Treatment is restricted to supportive measures, although hemodialysis may offer a protective effect. Our case demonstrates that even in extreme cases of MALA, prompt and adequate supportive measures can produce a favorable outcome.

A meta-analysis of clinical predictors for renal recovery and overall mortality in acute kidney injury requiring continuous renal replacement therapy.

PURPOSE: To determine clinical predictors for continuous renal replacement therapy (CRRT) discontinuation in patients with acute kidney injury (AKI). MATERIALS AND METHODS: Ovid MEDLINE, EMBASE, and Cochrane Library were searched. The protocol is registered on researchregistry.com (reviewregistry909). Our criteria included non-end-stage kidney disease adults who required CRRT for AKI. Renal recovery was defined by CRRT discontinuation. Risk of bias was assessed using ROBINS-I tool. RESULTS: We classified our analyses into renal recovery cohort and overall mortality cohort. All studies were observational. For renal recovery cohort, increasing urine output at time of CRRT discontinuation, elevated initial SOFA score and serum creatinine at CRRT initiation were predictive of renal recovery with OR 1.021 (95%CI = 1.011-1.031), 0.869 (95%CI = 0.811-0.932) and 0.995 (95%CI = 0.996-0.999), respectively. For overall mortality cohort, age and presence of sepsis were significantly associated with overall mortality with OR of 1.028 (95%CI = 1.008-1.048) and 2.160 (95%CI = 0.973-1.932), respectively. CONCLUSIONS: Urine output at CRRT discontinuation, lower initial SOFA score, and lower serum creatinine levels at CRRT initiation were associated with higher likelihood of renal recovery. Increasing age and the presence of sepsis were associated with increased overall mortality from AKI on CRRT. However, there were limited data on co-morbidities which might preclude their inclusion in our analysis.

Takotsubo Cardiomyopathy in a Nonagenarian With Urosepsis.

Takotsubo cardiomyopathy (TCM) is a rare but reversible myocardial left ventricular (LV) dysfunction, which mimics acute coronary syndrome (ACS) without the presence of significant coronary artery disease (CAD). Emotional stressors may include the death of kin or a life-threatening medical diagnosis whereas physical stressors include infections, endoscopic procedures, exacerbation of asthma, or systemic disorders. A 90-year-old female presented to the ED with nausea, intermittent chest heaviness, and generalized weakness for a duration of three days. Her troponin-I was elevated and an electrocardiogram (EKG) showed T-wave inversions in leads V2-V6 and no ST-segment changes. An echocardiogram (ECHO) revealed an ejection fraction (EF) of 35%-40% with anteroapical hypokinesis. She underwent cardiac catheterization showing nonobstructive CAD. She was diagnosed with pan-sensitive Escherichia coli urosepsis and started on ceftriaxone. She improved clinically and was discharged. A repeat ECHO done a month later showed normal EF. Urosepsis-induced TCM has rarely been reported in the literature. Physicians should have a high index of suspicion of TCM in patients with symptoms mimicking ACS in the presence of a physical stressor like an infection. We report the case of TCM, which resulted from a urinary tract infection (UTI) in an elderly female.

Opioid antidote induced pulmonary edema and lung injury.

INTRODUCTION: Opioid overdose emergencies are increasing every year, naloxone is the antidote for the treatment of opioid overdose. Naloxone is being dispensed to even lay persons through some programs to prevent opioid overdose deaths. CASE: 23 year old patient presented with naloxone treated opioid overdose complained of chest pain, pink frothy sputum production and shortness of breath. Physical exam showed tachycardia, tachypnea and coarse breath sounds. Imaging of the lungs showed diffuse pulmonary edema. Within an hour after the administration of naloxone patient developed pulmonary edema and lung injury. Patient was managed with non-invasive positive pressure ventilation which improved patient's symptoms in less than 6 hours confirmed by radiological improvement in 24-36 hrs. DISCUSSION: There are no specific observation guidelines post naloxone treatment in opiate overdose patients. We recommend early treatment of naloxone induced pulmonary complications during the observation period with non-invasive positive pressure ventilation to reduce the morbidity.

Vitamin D and Stroke: Effects on Incidence, Severity, and Outcome and the Potential Benefits of Supplementation.

Vitamin D serum level has been positively associated with improved cardiovascular health, especially with reduction of stroke risk. This systemic review summarizes and synthesizes findings from studies relevant to the relationship between vitamin D and stroke risk, severity, and outcome; potential mechanisms explaining such a relationship; and outcomes from vitamin D supplementation. The literature shows that vitamin D deficiency is a significant risk factor for ischemic stroke, with sun exposure, sex, age, race, diabetes, and genetics playing a role as well. Stroke severity and short- and long-term outcomes also worsen with vitamin D deficiency. The neuroprotective mechanisms by which vitamin D operates to mitigate stroke onset and outcomes have yet to be fully studied, but researchers have proposed several pathways, including promotion of certain neuroprotective growth factors, reduction of arterial pressure through vasodilation, and inhibition of reactive oxygen species. There is some evidence that vitamin D supplementation could lower stroke risk and improve recovery, though outcomes can also be negligible or negative. Although results are mixed and the limitations of vitamin D supplementation merit some caution, vitamin D overall plays a significant role in stroke health. Future research should further develop understanding of the neuroprotective mechanisms of vitamin D and study how supplementation could be administered effectively in stroke treatment.

Extremely High Creatine Kinase Activity in Rhabdomyolysis without Acute Kidney Injury.

BACKGROUND Elevation of creatine kinase (CK) activity has been shown to be predictive of acute kidney injury (AKI) in rhabdomyolysis. Patients with extremely high CK activity with preserved renal function are uncommon. This report describes a case of non-traumatic rhabdomyolysis, with a markedly elevated CK activity, without associated AKI. CASE REPORT A 22-year-old male presented with severe generalized myalgias and darkened urine for 1 week prior to his admission. The patient presented to the Emergency Department with initial CK activity of >40 000 U/L and a serum creatinine level of 0.77 mg/dL. Urinalysis was positive for myoglobinuria. Serum cystatin C confirmed an estimated glomerular filtration rate of 144 mL/min/1.73 m². Several causes of rhabdomyolysis, including viral infections, Lyme disease, viral hepatitis, hypothyroidism, and cocaine abuse were investigated; however, all were negative. He was given a bolus of 2 liters of normal saline and continued on intravenous normal saline at 250 mL/hour throughout his hospital stay. Urine output remained adequate. We were able to quantify his serum CK activity by dilution method, which revealed a serum CK activity of >150 000 U/L. His CK levels consistently trended down with treatment. CONCLUSIONS An extremely high CK activity in rhabdomyolysis may lead to AKI. However, preserved kidney function is possible. Young age, no concurrent cocaine use, and adequate oral fluid hydration may prevent AKI in rhabdomyolysis. Physicians need to remain vigilant for cases of rhabdomyolysis that have not yet caused renal compromise.

Pot smokers puffing away lung health.

BACKGROUND: Marijuana is the second most commonly used inhalational agent after tobacco. It has been used for therapeutic benefits in cancer, epilepsy, inflammation and pain. Inhalation of marijuana causes reversible and irreversible lung injury. CASE: We present a 26-year-old female with cough, chest pain, epistaxis, hemoptysis, night sweats and breathlessness few hours after smoking marijuana. Physical exam was positive for tachycardia, tachypnea, and diminished coarse breath sounds. Further investigation revealed elevated white blood cell count, chest X-ray, computed tomography of the chest showed bilateral patchy infiltrates. The patient was managed with short term steroid, as antibiotics alone did not work. Radiological improvement of lung injury was noted within 36-48 h. CONCLUSION: There is a paucity of treatment guidelines for acute lung injury secondary to marijuana inhalation. We advocate early use of short-term steroids and also more awareness on quitting marijuana smoking to prevent life-threatening complications like myocardial infarction, diffuse alveolar hemorrhage and acute respiratory distress syndrome.

Catheter-associated Hafnia alvei-induced Urosepsis.

Hafnia alvei, belonging to the Enterobacteriaceae family, is a gram-negative, facultative anaerobe. The organism predominantly colonizes the gastrointestinal tract and, less often, the tissues, urine, and catheters. A 75-year-old male presented with a dry cough, fatigue, decreased appetite, intermittent disorientation, and difficulty ambulating. He had a history of self-catheterization due to urinary retention. He was scheduled to undergo transcatheter aortic valve replacement for enterococcal endocarditis. Physical examination was not significant for any changes. Urine analysis revealed positive leukocyte esterase, the presence of red and white blood cells, urine bacteria, and hyaline casts. The patient was started on empiric intravenous ceftriaxone. Urine culture grew Hafnia alvei and he was switched over to cefepime due to greater susceptibility. On day four, he started deteriorating clinically and was treated with four pressors but remained hypotensive and eventually became anuric. The patient developed septic shock with multiple organ dysfunction syndromes. Despite all measures, his clinical condition failed to improve, and he was continued with comfort measures only. The literature on Hafnia alvei-induced urosepsis is poor and fragmentary. Our patient showed resistance to most beta-lactam antibiotics, including cefuroxime, ceftriaxone, and ceftazidime, along with intermediate susceptibility to piperacillin/tazobactam and was managed with intravenous cefepime based on the sensitivity report. Inducible Bush group 1 beta-lactamase produced by Hafnia alvei is postulated to be responsible for antibiotic resistance. Physicians should remain vigilant of Hafnia alvei-induced urosepsis in patients with long-term catheterization initiating appropriate treatment.

The role of nitric oxide in melanoma.

Nitric oxide (NO) is a small gaseous signaling molecule that mediates its effects in melanoma through free radical formation and enzymatic processes. Investigations have demonstrated multiple roles for NO in melanoma pathology via immune surveillance, apoptosis, angiogenesis, melanogenesis, and on the melanoma cell itself. In general, elevated levels of NO prognosticate a poor outcome for melanoma patients. However, there are processes where the relative concentration of NO in different environments may also serve to limit melanoma proliferation. This review serves to outline the roles of NO in melanoma development and proliferation. As demonstrated by multiple in vivo murine models and observations from human tissue, NO may promote melanoma formation and proliferation through its interaction via inhibitory immune cells, inhibition of apoptosis, stimulation of pro-tumorigenic cytokines, activation of tumor associated macrophages, alteration of angiogenic processes, and stimulation of melanoma formation itself.

Tumor-specific expression and detection of a CEST reporter gene.

PURPOSE: To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI. METHODS: Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9L(CMV-LRP) and 9L(PEG-LRP) , were established and tested for CEST contrast in vitro and in vivo. RESULTS: 9L(PEG-LRP) cells showed increased CEST contrast compared with 9L cells in vitro. Both 9L(CMV-LRP) and 9L(PEG-LRP) cells were capable of generating tumors in the brains of mice, with a similar growth rate to tumors derived from wild-type 9L cells. An increase in CEST contrast was clearly visible in tumors derived from both 9L(CMV-LRP) and 9L(PEG-LRP) cells at 3.4 ppm. CONCLUSION: The PEG-3 promoter:LRP system can be used as a cancer-specific, molecular-genetic imaging reporter system in vivo. Because of the ubiquity of MR imaging in clinical practice, sensors of this class can be used to translate molecular-genetic imaging rapidly.

Molecular-genetic imaging of cancer.

Molecular-genetic imaging of cancer using nonviral delivery systems has great potential for clinical application as a safe, efficient, noninvasive tool for visualization of various cellular processes including detection of cancer, and its attendant metastases. In recent years, significant effort has been expended in overcoming technical hurdles to enable clinical adoption of molecular-genetic imaging. This chapter will provide an introduction to the components of molecular-genetic imaging and recent advances on each component leading to safe, efficient clinical applications for detecting cancer. Combination with therapy, namely, generating molecular-genetic theranostic constructs, will provide further impetus for clinical translation of this promising technology.