Cardiopulmonary exercise testing before and after intravenous iron in preoperative patients: a prospective clinical study.

BACKGROUND: Anemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery. METHODS: A prospective clinical study was undertaken in patients having routine cardiopulmonary exercise testing (CPET) with a hemoglobin concentration ([Hb]) < 130 g.l-1 and iron deficiency/depletion. Patients underwent CPET and tHb-mass measurements before and a minimum of 14 days after receiving intravenous (i.v.) Ferric derisomaltose (Monofer®) at the baseline visit. Comparative analysis of hematological and CPET variables was performed pre and post-iron treatment. RESULTS: Twenty-six subjects were recruited, of whom 6 withdrew prior to study completion. The remaining 20 (9 [45%] male; mean ± SD age 68 ± 10 years) were assessed 25 ± 7 days between baseline and the final visit. Following i.v. iron, increases were seen in [Hb] (mean ± SD) from 109 ± 14 to 116 ± 12 g l-1 (mean rise 6.4% or 7.3 g l-1, p = < 0.0001, 95% CI 4.5-10.1); tHb-mass from 497 ± 134 to 546 ± 139 g (mean rise 9.3% or 49 g, p = < 0.0001, 95% CI 29.4-69.2). Oxygen consumption at anerobic threshold ([Formula: see text] O2 AT) did not change (9.1 ± 1.7 to 9.8 ± 2.5 ml kg-1 min-1, p = 0.09, 95% CI - 0.13 - 1.3). Peak oxygen consumption ([Formula: see text] O2 peak) increased from 15.2 ± 4.1 to 16 ± 4.4 ml.kg.-1 min-1, p = 0.02, 95% CI 0.2-1.8) and peak work rate increased from 93 [67-112] watts to 96 [68-122] watts (p = 0.02, 95% CI 1.3-10.8). CONCLUSION: Preoperative administration of intravenous iron to iron-deficient/deplete anemic patients is associated with increases in [Hb], tHb-mass, peak oxygen consumption, and peak work rate. Further appropriately powered prospective studies are required to ascertain whether improvements in tHb-mass and performance in turn lead to reductions in perioperative morbidity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT 033 46213.

Venous thromboembolism in benign esophageal surgery patients: potential cost effectiveness of Caprini risk stratification.

BACKGROUND: The Caprini risk assessment model (RAM) stratifies surgical patients for prescription of post-discharge extended heparin prophylaxis to reduce post-operative venous thromboembolism (VTE) events. The average cost for treatment of a VTE event is $15,123. The 30-day post-operative VTE rate after benign esophageal procedures is < 0.8% per the Society of Thoracic Surgeons database. We hypothesized that the financial cost of selective extended prophylaxis in patients undergoing surgery for benign esophageal disease would exceed the cost of treating these rare events and therefore use of risk stratification for extended prophylaxis would not be beneficial. METHODS: All patients undergoing operations for benign esophageal pathology from July 2014 to May 2019 were reviewed. Patients designated as moderate or high risk for VTE were prescribed a 10- or 30-day post-operative course of extended prophylaxis with low-molecular weight heparin (LMWH). VTE and adverse bleeding events were recorded for the 60-day post-operative period. The cost of LMWH was provided by the institution pharmacy. RESULTS: Records from 154 patients were eligible for review. Caprini RAM was used for all patients with the following distribution of risk categories: low = 64.9% (100/154); moderate = 31.8% (49/154); and high = 3.2% (5/154). The average cost of extended prophylaxis at discharge for the moderate-risk group was $121.23, while the high-risk group was $446.46. There were no 60-day VTE or adverse bleeding events recorded. CONCLUSIONS: The majority of patients undergoing surgical therapy were at low risk of post-operative VTE event, with only 35% requiring extended VTE prophylaxis at time of discharge. When compared with the average cost of treatment for a VTE event, the cost of extended prophylaxis per patient in moderate or high-risk groups is substantially lower. In the era of cost-containment, risk stratification and extended prophylaxis may reduce healthcare costs and warrant future investigations.

A carbon monoxide 'single breath' method to measure total haemoglobin mass: a feasibility study.

NEW FINDINGS: What is the central question of this study? Is it possible to modify the CO-rebreathing method to acquire reliable measurements of haemoglobin mass in ventilated patients? What is the main finding and its importance? A 'single breath' of CO with a subsequent 30 s breath hold provides almost as exact a measure of haemoglobin mass as the established optimized CO-rebreathing method when applied to healthy subjects. The modified method has now to be checked in ventilated patients before it can be used to quantify the contributions of blood loss and of dilution to the severity of anaemia. ABSTRACT: Anaemia is defined by the concentration of haemoglobin (Hb). However, this value is dependent upon both the total circulating haemoglobin mass (tHb-mass) and the plasma volume (PV) - neither of which is routinely measured. Carbon monoxide (CO)-rebreathing methods have been successfully used to determine both PV and tHb-mass in various populations. However, these methods are not yet suitable for ventilated patients. This study aimed to modify the CO-rebreathing procedure such that a single inhalation of a CO bolus would enable its use in ventilated patients. Eleven healthy volunteers performed four CO-rebreathing tests in a randomized order, inhaling an identical CO volume. In two tests, CO was rebreathed for 2 min (optimized CO rebreathing; oCOR), and in the other two tests, a single inhalation of a CO bolus was conducted with a subsequent breath hold of 15 s (Procnew 15s) or 30 s (Procnew 30s). Subsequently, the CO volume in the exhaled air was continuously determined for 20 min. The amount of CO exhaled after 7 and 20 min was respectively 3.1 ± 0.3 and 5.9 ± 1.1 ml for oCOR, 8.7 ± 3.6 and 12.0 ± 4.4 ml for Procnew 15s and 5.1 ± 2.0 and 8.4 ±2.6 ml for Procnew 30s. tHb-mass was 843 ± 293 g determined by oCOR, 821 ± 288 g determined by Procnew 15s (difference: P < 0.05) and 849 ± 311 g determined by Procnew 30s. Bland-Altman plots demonstrated slightly lower tHb-mass values for Procnew 15s compared with oCOR (-21.8 ± 15.3 g) and similar values for Procnew 30s. In healthy volunteers, a single inhalation of a CO bolus, preferably followed by a 30 s breath hold, can be used to determine tHb-mass. These results must now be validated for ventilated patients.

Type 2 diabetes is associated with failure of non-operative treatment for sternoclavicular joint infection.

BACKGROUND: A standardized treatment algorithm for sternoclavicular joint infection management is lacking in the literature. While major risk factors for sternoclavicular joint infection, including immunosuppression, rheumatoid arthritis, type 2 diabetes, indwelling catheters, and intravenous drug use have been identified, clear association with treatment outcome has not been established. As our safety net hospital treats a patient population with high incidence of intravenous drug use, we sought to identify risk factors associated with failure of non-operative management of sternoclavicular joint infection. METHODS: We conducted a retrospective cohort study, reviewing charts of patients diagnosed with sternoclavicular joint infection between January 2001 and December 2017 to collect demographic information as well as clinical risk factors and treatment patterns. A chi-square test was performed to determine any association between clinical variables and management, as well as relation to treatment outcome. RESULTS: The study cohort consisted of 35 patients with diagnosis of sternoclavicular joint infection and complete follow-up. Intravenous drug use was prevalent, seen in 45.6% (16/35) of subjects, though there was no association with failure of non-operative management (P=0.50). Operative management was the initial treatment for 25.7% (9/35) of subjects and was associated with abscess on presentation (P=0.03). Failure of non-operative management was seen in 26.9% (7/26). Type 2 diabetes was associated with failed initial non-operative management, present in 42.9% (3/7) of patients (P=0.03) experiencing failure. CONCLUSIONS: This study constitutes the largest series of sternoclavicular joint infection with intravenous drug use. While intravenous drug use was not associated with failure of non-operative management, we observed that type 2 diabetes is associated with failure of non-operative management and could be considered in determining management of sternoclavicular joint infection patients.

Metagenomic Analysis Reveals Clinical SARS-CoV-2 Infection and Bacterial or Viral Superinfection and Colonization.

BACKGROUND: More than 2 months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence. METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, WA were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. RESULTS: Within 36 h our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients' respiratory symptoms. CONCLUSION: Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.

Application of the optimized carbon monoxide rebreathing method for the measurement of total haemoglobin mass in chronic liver disease.

BACKGROUND: Anemia is common in liver cirrhosis. This generally infers a fall in total hemoglobin mass (tHb-mass). However, hemoglobin concentration ([Hb]) may fall due to an expansion in plasma volume (PV). The "optimized carbon monoxide rebreathing method" (oCOR) measures tHb-mass directly and PV (indirectly using hematocrit). It relies upon carboxyhemoglobin (COHb) distribution throughout the entire circulation. In healthy subjects, such distribution is complete within 6-8 min. Given the altered circulatory dynamics in cirrhosis, we sought in this pilot study, to assess whether this was true in cirrhosis. The primary aim was to ascertain if the standard timings for the oCOR were applicable to patients with chronic liver disease and cirrhosis. The secondary aim was to explore the applicability of standard CO dosing methodologies to this patient population. METHODS: Sixteen patients with chronic liver parenchymal disease were studied. However, tHb-mass was determined using the standard oCOR technique before elective paracentesis. Three subjects had an inadequate COHb% rise. In the remaining 13 (11 male), mean ± standard deviation (SD) age was 52 ± 13.8 years, body mass 79.1 ± 11.4 kg, height 175 ± 6.8 cm. To these, mean ± SD dose of carbon monoxide (CO) gas administered was 0.73 ± 0.13 ml/kg COHb values at baseline, 6 and 8 min (and "7-min value") were compared to those at 10, 12, 15 and 20 min after CO rebreathing. RESULTS: The "7-min value" for median COHb% (IQR) of 6.30% (6.21%-7.47%) did not differ significantly from those at subsequent time points (8 min: 6.30% (6.21%-7.47%), 10 min: 6.33% (6.00%-7.50%), 12 min: 6.33% (5.90%-7.40%), 15 min: 6.37% (5.80%-7.33%), 20 min: 6.27% (5.70%-7.20%)). Mean difference in calculated tHb-mass between minute 7 and minute 20 was only 4.1 g, or 0.6%, p = .68. No subjects reported any adverse effects. CONCLUSIONS: The oCOR method can be safely used to measure tHb-mass in patients with chronic liver disease and ascites, without adjustment of blood sample timings. Further work might refine and validate appropriate dosing regimens.

Hemoglobin concentration, total hemoglobin mass and plasma volume in patients: implications for anemia.

In practice, clinicians generally consider anemia (circulating hemoglobin concentration < 120 g.l-1 in non-pregnant females and < 130 g.l-1 in males) as due to impaired hemoglobin synthesis or increased erythrocyte loss or destruction. Rarely is a rise in plasma volume relative to circulating total hemoglobin mass considered as a cause. But does this matter? We explored this issue in patients, measuring hemoglobin concentration, total hemoglobin mass (optimized carbon monoxide rebreathing method) and thereby calculating plasma volume in healthy volunteers, surgical patients, and those with inflammatory bowel disease, chronic liver disease or heart failure. We studied 109 participants. Hemoglobin mass correlated well with its concentration in the healthy, surgical and inflammatory bowel disease groups (r=0.687-0.871, P<0.001). However, they were poorly related in liver disease (r=0.410, P=0.11) and heart failure patients (r=0.312, P=0.16). Here, hemoglobin mass explained little of the variance in its concentration (adjusted R2=0.109 and 0.052; P=0.11 and 0.16), whilst plasma volume did (R2 change 0.724 and 0.805 in heart and liver disease respectively, P<0.0001). Exemplar patients with identical (normal or raised) total hemoglobin masses were diagnosed as profoundly anemic (or not) depending on differences in plasma volume that had not been measured or even considered as a cause. The traditional inference that anemia generally reflects hemoglobin deficiency may be misleading, potentially resulting in inappropriate tests and therapeutic interventions to address 'hemoglobin deficiency' not 'plasma volume excess'. Measurement of total hemoglobin mass and plasma volume is now simple, cheap and safe, and its more routine use is advocated.

pH Responsive Release of Doxorubicin to the Cancer Cells by Functionalized Multi-Walled Carbon Nanotubes.

The main aim of the current study is to formulate the Doxorubicin loaded functionalized carbon nanotubes to deliver the drug only to the cancer cells by using pH difference. Multi walled Carbon Nanotubes (MWNTs) have been identified as an efficient drug carrier through π-π linkage, because this covalent bond is sensitive to tumor microenvironments. This bond is acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective release near the acidic tumor microenvironment and thus reduces its overall systemic toxicity. Doxorubicin was released at low pH and taken up by tumor cells via adenosine triphosphate (ATP)-dependent endocytosis. By varying the Concentration of MWNTs with the Doxorubicin, it forms a conjugate. It is due to supra molecular interactions between the drug and MWNTs, so it shows high loading, prolonged release and improved cytotoxicity against cancer cells. This study shows the phenomenal pH responsive drug release to the cancerous microenvironment and prolonged release. This study suggests that MWNTs have a great potential as a drug carrier; the efficient formulation strategy requires further study.