Increased procoagulant platelet levels are predictive of death in COVID-19.

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death. Coated-platelet levels were assayed after admission and repeated weekly in COVID-19 patients, and in COVID-19 negative controls. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including baseline coated-platelets to predict death. Kaplan-Meier and Cox proportional hazards analysis was used to predict risk for death at 90 days. We enrolled 33 patients (22 with moderate and 11 with severe infection) and 20 controls. Baseline coated-platelet levels were lower among moderate (mean ± SD; 21.3 ± 9.8%) and severe COVID-19 patients (28.5 ± 11.9%) compared to controls (38.1 ± 10.4%, p < 0.0001). Coated-platelet levels increased during follow-up in COVID-19 patients by 7% (relative) per day from symptom onset (95% CI 2-12%, p = 0.007). A cut-off of 33.9% for coated-platelet levels yielded 80% sensitivity and 96% specificity for death at 90 days, with resulting AUC of 0.880 (95% CI 0.680-1.0, p = 0.0002). The adjusted hazard ratio for death in patients with coated-platelet levels > 33.9% was 40.99 when compared to those with levels ≤ 33.9% (p < 0.0001). Platelet procoagulant potential is transiently decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Defining the mechanisms involved and potential links with aging may yield novel treatment targets.

Effect of CFTR modulator therapy on cystic fibrosis-related diabetes.

BACKGROUND: Half of adults with cystic fibrosis (CF) develop CF-related diabetes (CFRD). CFRD contributes to worsened pulmonary function and malnutrition. We undertook this study to determine the effect of cystic fibrosis transmembrane regulator (CFTR) modulators on CRFD. METHODS: We reviewed the medical records of adults with CF who followed in the CF clinic at Oklahoma University Medical Center. We collected data for age at diagnosis of CF and CFRD, CF mutations present, first date of ivacaftor therapy either alone or in combination, insulin use, pulmonary function, body mass index data, and home glucose monitoring results. Clinical resolution of CFRD was taken as discontinuation of routine insulin and resolution of high interstitial home glucose values. RESULTS: We identified 69 adult CF patients, of whom 31 had CFRD. Among these 14 CFRD patients taking ivacaftor alone or in combination, four patients completely stopped using insulin. Another patient went from three times a day pre-prandial insulin to using insulin once a week. Home blood glucose and hemoglobin A1c values supported resolution of CFRD. Three patients continued to have hypoglycemia despite stopping insulin. No CFRD patient not taking CFTR modulators markedly changed the insulin regimen. Pulmonary function was preserved in those patients with resolved CFRD (FEV1 +6.75% ±7.6), whereas it worsened in CFRD patients who either were not taking CFTR modulators (FEV1 -2.09% ±3.9) or who had no response of CFRD status (FEV1 -4.9% ±7.6). CONCLUSIONS: About one-third of patients on CFTR modulator therapy had resolution or near resolution of CFRD.

The effect of baclofen on objective and subjective sleep measures in a model of transient insomnia.

STUDY OBJECTIVES: Insomnia is a common medical complaint. Current pharmacologic treatments have modest efficacy and numerous side effects. Baclofen is a gamma-aminobutyric acid (GABA)b receptor agonist used to treat spasticity in various medical conditions. Several studies noted that baclofen, when used to treat sleep related disorders, resulted in improvement in sleep parameters. Measures of insomnia, however, were not assessed in those studies. To date, baclofen has not been assessed for efficacy in the treatment of insomnia. METHODS: We randomized 20 healthy subjects to baclofen or placebo in a cross over design. All subjects underwent two polysomnograms (PSG) assessing sleep parameters. Baclofen or placebo was given 90 min prior to lights out in random order for each subject. Lights out occurred two hours earlier than the subject's median habitual bedtime. RESULTS: Baclofen resulted in significantly less objective wake after sleep onset and stage 1 sleep, and significantly increased total sleep time (TST), sleep efficiency, and stage 3/4 sleep. There was no effect on sleep onset latency (SOL). Self-report variables indicated significantly less subjective awakenings from sleep and increased subjective sleep quality. There was no effect on subjective TST or subjective SOL. CONCLUSIONS: This study showed that baclofen was superior to placebo with regard to several objective and subjective measures used to assess sleep quality. These data support the notion that baclofen shows promise as an effective hypnotic drug.

Meeting Calorie and Protein Needs in the Critical Care Unit: A Prospective Observational Pilot Study.

BACKGROUND: Inadequate calorie and protein intake during critical illness is associated with poor clinical outcomes. Unfortunately, most critically ill patients do not consume adequate levels of these nutrients. An enteral formula with appropriate macronutrient composition may assist patients in meeting nutritional goals. DESIGN: This study was a single center, prospective, observational study of 29 adults in the medical intensive care unit who required enteral nutrition for at least 3 days. Subjects received a calorically dense, enzymatically hydrolyzed 100% whey peptide-based enteral formula for up to 5 days to assess the ability to achieve 50% of caloric goals within the first 3 days (primary outcome), the daily percentage of protein goals attained and gastrointestinal tolerance (secondary outcomes). RESULT: A total of 29 subjects consented and began the study. Four subjects dropped out before first day and 25 subjects were included in analyses. Subjects were aged 55.5 ± 16.9 years with mean body mass index (BMI) of 27.9 ± 7.5 kg/m2. Most (92%) subjects were on a mechanical ventilator and experienced organ failure. At least 50% of caloric and protein goals were achieved in 78.9% and 73.7% of the subjects, respectively, during the first 3 days. Overall, 75.0 ± 26.3% and 69.3 ± 26.7% of calorie and protein goals were achieved using the study formula. CONCLUSIONS: Subjects fed enterally with a calorically dense, enzymatically hydrolyzed 100% whey peptide-based enteral formula exceeded 50% of caloric and protein goals in most critically ill subjects included in this study. Use of study formula did not lead to severe gastrointestinal intolerance.

Metastatic Pleural Effusion: An Unusual Presentation of Urothelial Bladder Carcinoma.

Pleural effusions are frequently encountered in clinical practice. In the United States, malignancy is the third leading cause of pleural effusion after heart failure and pneumonia. The most common cause of malignant pleural effusion (MPE) is lung cancer, followed by breast cancer, lymphoma, and mesothelioma. Genitourinary cancers rarely metastasize to the pleura. Although several atypical patterns of thoracic metastasis from genitourinary cancers have been described in the literature, genitourinary cancers rarely give rise to MPEs. We describe a case where the workup of a unilateral pleural effusion led to the diagnosis of high-grade urothelial bladder carcinoma.

Fluid management in Acute Respiratory Distress Syndrome: A narrative review.

Acute Respiratory Distress Syndrome remains a major source of morbidity and mortality in the modern intensive care unit (ICU). Major advances in the understanding and management of this condition were made in the last two decades. The use of low tidal ventilation is a well-established therapy. Conservative fluid management is now another cornerstone of management. However, much remains to be understood in this arena. Assessing volume status in these patients may be challenging and the tools available to do so are far from perfect. Several dynamic measures including pulse pressures variation are used. Ultrasound of the lungs and the vascular system may also have a role. In addition, the type of fluid to administer when needed is still open to debate. Finally, supportive measures in these patients, early during their ICU stay and later after discharge continue to be crucial for survival and adequate recovery.

Sustained Glycemic Control With Ivacaftor in Cystic Fibrosis-Related Diabetes.

Cystic fibrosis-related diabetes (CFRD) is a common comorbidity in cystic fibrosis with pancreatic insufficiency occurring early in the disease process. Current treatment is exogenous insulin therapy as CFRD is due to impaired insulin secretion. Recent small studies have shown improvement in endogenous insulin secretion with a short period of ivacaftor therapy in primarily pediatric patients with cystic fibrosis transmembrane conductance regulator mutations amenable to potentiation. In this article, we present the case of an adult patient with long-standing CFRD who developed sustained improvement in glycemic control after initiation of ivacaftor.

Sleep-Disordered Breathing and Cerebral Oxygenation During Sleep in Adults With Mild Cognitive Impairment.

The current study examined relationships between laterality in cerebral oxygenation (L-COX), sleep-disordered breathing (SDB), and daytime function in 16 adults with mild cognitive impairment (MCI). All participants underwent two nights of diagnostic polysomnography. Using dual-cerebral oximetry, L-COX was defined by differences ≥4% in right- versus left-sided percent cerebral oxyhemoglobin saturation. Eight patients had SDB. L-COX was found in five patients, but only on nights with SDB. Greater L-COX was associated more severe SDB: higher frequency of apneas + hypopneas per hour (r = 0.66, p < 0.01), desaturations per hour (r = 0.73, p < 0.01), and percent time with oxygen saturation <88% (r = 0.65, p < 0.01). Greater laterality, but not severity of SDB, was associated with poorer functional ability (Lawton Instrumental Activities of Daily Living Scale: r = -0.83, p = 0.02), lower cognitive function (Mini-Mental State Examination: r = -0.76, p = 0.03), and greater daytime sleepiness (Epworth Sleepiness Scale: r = 0.85, p < 0.001). L-COX associated with SDB suggests disruptions in cerebral autoregulation and need for aggressive treatment of SDB in individuals with MCI. [Res Gerontol Nurs. 2018; 11(6):282-292.].

The impact of continuous positive airway pressure on radiation dose to heart and lung during left-sided postmastectomy radiotherapy when deep inspiration breath hold technique is not applicable: a case report.

Deep inspiration breathing hold (DIBH) compared to free-breathing (FB) during radiotherapy (RT) has significantly decreased radiation dose to heart and has been one of the techniques adopted for patients with breast cancer. However, patients who are unable to make suitable deep inspiration breath may not be eligible for DIBH, yet still need to spare the heart and lung during breast cancer RT (left-sided RT in particular). Continuous positive airway pressure (CPAP) is a positive airway pressure ventilator, which keeps the airways continuously open and subsequently inflates the thorax resembling thoracic changes from DIBH. In this report, authors applied CPAP instead of FB during left-sided breast cancer RT including internal mammary node in a patient who was unable to tolerate DIBH, and substantially decreased radiation dose the heart and lung with CPAP compared to FB.

Metastatic Lung Carcinoma Involving the Maxillary Gingiva.

Metastatic spread of malignant tumors to the oral soft tissue is rare and account for 0.1% of all oral malignancies. Metastatic spread to the oral soft tissue can present as dental infections, which in turn can create a diagnostic challenge. Metastasis to the oral soft tissue from lung cancer is a rare situation. Here we describe a 52 year-old male patient treated initially with antibiotics for presumed oral abscess, who later was found to have metastatic lung cancer involving the maxillary gingiva.

Review and Outcome of Prolonged Cardiopulmonary Resuscitation.

The maximal duration of cardiopulmonary resuscitation (CPR) is unknown. We report a case of prolonged CPR. We have then reviewed all published cases with CPR duration equal to or more than 20 minutes. The objective was to determine the survival rate, the neurological outcome, and the characteristics of the survivors. Measurements and Main Results. The CPR data for 82 patients was reviewed. The median duration of CPR was 75 minutes. Patients mean age was 43 ± 21 years with no significant comorbidities. The main causes of the cardiac arrests were myocardial infarction (29%), hypothermia (21%), and pulmonary emboli (12%). 74% of the arrests were witnessed, with a mean latency to CPR of 2 ± 6 minutes and good quality chest compression provided in 96% of the cases. Adjunct therapy included extracorporeal membrane oxygenation (18%), thrombolysis (15.8%), and rewarming for hypothermia (19.5%). 83% were alive at 1 year, with full neurological recovery reported in 63 patients. Conclusion. Patients undergoing prolonged CPR can survive with good outcome. Young age, myocardial infarction, and potentially reversible causes of cardiac arrest such as hypothermia and pulmonary emboli predict a favorable result, especially when the arrest is witnessed and followed by prompt and good resuscitative efforts.

Tigecycline-induced acute pancreatitis in a cystic fibrosis patient: A case report and literature review.

PURPOSE: The purpose of this case report is to increase awareness of tigecycline-associated pancreatitis, specifically in patients who may be predisposed to develop pancreatitis. CASE SUMMARY: A 22-year-old male with cystic fibrosis developed acute bronchitis, with sputum cultures significant for Mycobacterium chelonae. He was started on tigecycline on two separate occasions, in each case developing pancreatitis as evidenced by symptomatology, elevated pancreatic enzymes and, in one case, by CT imaging. On both occasions, symptomatology improved and enzymes normalized after discontinuation of tigecycline. DISCUSSION: Current literature including two recent review pieces is discussed. The unique aspects of the case are highlighted, including the particular risk of drug-associated pancreatitis in those with cystic fibrosis. CONCLUSION: The results of this case, in the context of current literature, suggest that clinicians should be aware of the potential for pancreatitis when using tigecycline. Clinicians should be particularly mindful of this complication in patients with comorbidities that might increase the risk of pancreatitis above that of the general population.

STOP-BANG questionnaire as a screening tool for diagnosis of obstructive sleep apnea by unattended portable monitoring sleep study.

The Snoring, Tiredness, Observed apnea, high blood Pressure (STOP)-Body mass index (BMI), Age, Neck circumference, and Gender (BANG) questionnaire is a well validated screening tool for diagnosis of Obstructive sleep apnea (OSA) by an in- lab sleep study. However, performance of STOP-BANG as a screening tool for diagnosis of OSA in patients undergoing portable monitoring (PM) sleep study has not been well validated. We conducted a retrospective chart review of patients older than 18 years who had unattended portable monitoring sleep study done at a VA medical center between June 2012 and October 2014. STOP-BANG questionnaire and Epworth sleepiness scale (ESS) were routinely done prior to study. Sensitivity, specificity, and positive predictive value (PPV) various STOP-BANG score thresholds were calculated for diagnosis of OSA defined by Apnea Hypopnea Index (AHI) ≥5. Out of 502 unattended portable monitoring sleep studies, there were 465 males and 37 females. STOP-BANG thresholds of ≥2 and 3 have high sensitivity of 99.8 and 98.9 %, respectively, but very low specificity. Higher score thresholds of ≥7 and 8 have high specificity of 95 and 98.3 %, and PPV of 98.1 and 98.5 %, respectively, but very low sensitivity. A threshold of ≥7 in patients with BMI ≥30 was 100 % specific. The false negative rate for unattended portable monitoring sleep study compared to in-lab study was 80 %. STOP-BANG score thresholds of ≥7 and 8 are highly specific and have high PPV and therefore can potentially reduce need of diagnostic sleep studies in selected patients. Score thresholds of ≤2 or 3 are highly sensitive for AHI ≥5 by unattended portable monitoring sleep study but have high false negative rates. Therefore, in-lab sleep study should be performed to rule out OSA.

Gas-Forming Pyogenic Liver Abscess with Septic Shock.

The pyogenic liver abscess caused by Clostridium perfringens (C. perfringens) is a rare but rapidly fatal infection. The main virulence factor of this pathogen is its α-toxin (lecithinase), which decomposes the phospholipid in cell membranes leading to cell lysis. Once the bacteria are in blood stream, massive intravascular hemolysis occurs. This can present as anemia on admission with evidence of hemolysis as indicated by low serum haptoglobin, high serum lactate dehydrogenase (LDH), elevated indirect bilirubin, and spherocytosis. The clinical course of C. perfringens septicemia is marked by rapidly deteriorating course with a mortality rate ranging from 70 to 100%. The very rapid clinical course makes it difficult to diagnose on time, and most cases are diagnosed at autopsy. Therefore it is important to consider C. perfringens infection in any severely ill patient with fever and evidence of hemolysis. We present a case of seventy-seven-year-old male with septic shock secondary to pyogenic liver abscess with a brief review of existing literature on C. perfringens.

Bronchial responsiveness in patients with restrictive spirometry.

BACKGROUND: Improvement in PFT after bronchodilators is characteristic of obstructive airway diseases such as COPD. However, improvement in patients with restrictive pattern is occasionally seen. We aim to determine the clinical significance of a bronchodilator responsive restrictive defect. METHODS: Patients with restrictive spirometry and a bronchodilator study were identified at the University of Oklahoma and Oklahoma City VAMC between September 2003 and December 2009. Restriction was defined as a decreased FVC and FEV1, with normal FEV1/FVC. Responsiveness to bronchodilators was defined as an improvement in FEV1 and/or FVC of at least 12% and 200 mL. Patients with lung volume measurements had their clinical and radiographic records reviewed. RESULTS: Twenty-one patients were included in the study. Most were current or ex-smokers, with most being on bronchodilators. The average FVC and FEV1 were 65 ± 11% and 62 ± 10% of the predicted, respectively. Most patients (66%) had a normal TLC, averaging 90 ± 16% of the predicted. RV, RV/TLC, and the TLC-VA values strongly suggested an obstructive defect. CONCLUSIONS: Reversible restrictive pattern on spirometry appears to be a variant of obstructive lung disease in which early airway closure results in air trapping and low FVC. In symptomatic patients, a therapeutic trial of bronchodilators may be beneficial.

Clinical outcomes of a pharmacist-managed anticoagulation service for breast cancer patients.

PURPOSE: Report descriptive outcome measures related to the quality of pharmacist-managed anticoagulation care with warfarin in patients with breast cancer since the formation of the anticoagulation management service (AMS). METHODS: Retrospective review of 145 patients with breast cancer (median age 54 years) receiving warfarin therapy for venous thromboembolism (VTE) managed by the pharmacist-run AMS between 1998 and 2005. RESULTS: The median time followed by the AMS was 151 days. Fifty three percent (n = 1651) of total lab draws (n = 3129) were within the target therapeutic INR range 2-3. Recurrent thrombosis occurred in 4.1% of patients. Minor bleeding occurred in 18.6% of patients and major bleeding occurred in three patients (2.1%, gastrointestinal, intra-abdominal, and subdural hematoma). CONCLUSION: To date, this is the largest known published database of cancer patients receiving anticoagulation in a pharmacist-managed anticoagulation service. Recurrent VTE rates, major and minor bleeding rates, and percentage of time spent within the therapeutic range are slightly different in our patient population compared to an oncology population receiving warfarin and a non-oncology population with warfarin managed by AMS. Oral anticoagulation with warfarin is an effective, albeit complicated, treatment for venous thromboembolism in the oncology population. Although low-molecular weight heparin (LMWH) therapy is now the preferred treatment for thrombosis in malignancy, warfarin is still relevant in patients who are unable to receive treatment with LMWH. This report provides valuable information supporting coordinated anticoagulation therapy with a pharmacist-managed service in a breast cancer-specific population, and contributes to the growing data supporting the challenging nature of maintaining warfarin anticoagulation in patients with cancer.

Approaches for administering chemotherapy in the intensive care unit.

Guidelines on how to treat cancer patients receiving cytotoxic chemotherapy in the intensive care unit (ICU) are very limited. Recognizing the severity of the patient, their disease may require the need for chemotherapy whether for localized, metastatic, or hematological malignancies. It may be given alone or in combination with other cancer treatments such as radiation, or hormonal therapies. Nevertheless, the toxicities associated with chemotherapy serve as the driving force for managing complications and safe handling in the ICU. Tumor lysis syndrome, nausea and vomiting, pain management, and adverse medication effects requiring antidotes are complications for patients receiving chemotherapy in the ICU. The administration and safe handling of chemotherapy by nursing is emphasized to provide additional safety precautions. A basic understanding of cytotoxic chemotherapy is reviewed for patients requiring therapy in an ICU.