Impact of C-reactive Protein on Anticoagulation Monitoring in Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective single-center cohort study. SETTING: University-affiliated tertiary care academic medical center. PARTICIPANTS: Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001). CONCLUSIONS: Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

The Year in Thoracic Anesthesia: Selected Highlights from 2022.

This article reviews research highlights in the field of thoracic anesthesia. The highlights of this year included new developments in the preoperative assessment and prehabilitation of patients requiring thoracic surgery, updates on the use of devices for one-lung ventilation (OLV) in adults and children, updates on the anesthetic and postoperative management of these patients, including protective OLV ventilation, the use of opioid-sparing techniques and regional anesthesia, and outcomes using enhanced recovery after surgery, as well as the use of expanding indications for extracorporeal membrane oxygenation, specialized anesthetic techniques for airway surgery, and nonintubated video-assisted thoracic surgery.

A Rare Case of a Solitary Fibrous Tumor in a Child, Presenting as a Congenital Mass, Displaying NAB2ex4::STAT6ex2 Gene Fusion with an Incidental Ganglioneuroblastoma.

A solitary fibrous tumor (SFT) is a ubiquitous tumor that occurs across all ages. It is rarely reported in pediatric patients, especially as a congenital mass. A 1 year 7-month old male child presented with a slow-growing gluteal mass since birth along with a recent episode of bleeding. Magnetic resonance imaging (MRI) showed a well-defined, T1-hypointense and T2-hyperintense mass in the skin and the subcutaneous plane. Subsequently, he underwent a surgical resection that revealed a 5.7 cm-sized fleshy mass. On histopathologic examination, there was a fairly well-circumscribed, cellular spindle cell tumor, with cells arranged in intersecting fascicles and hemangiopericytomatous pattern with areas of hemorrhage and fibrinoid necrosis. Cells revealed mild nuclear atypia. Mitotic figures were up to 8/10 hpf. Immunohistochemically, the tumor cells were diffusely positive for CD34 and STAT6. Furthermore, the tumor revealed NAB2 exon 4:: STAT6 exon 2 fusion by RT-PCR and Sanger sequencing. Post-excision, during follow-up, the patient developed an adrenal mass that was histopathologically proven as a neuroblastic tumor, not further specified on biopsy and finally as ganglioneuroblastoma, intermixed type on excision. This constitutes one of the rare cases of SFT in a pediatric patient, presenting as a congenital mass, confirmed by STAT6 immunostaining and further, molecular testing. A review of literature of similar cases, including treatment-related implications, is presented.

Inhibitory deficits and symptoms of attention-deficit hyperactivity disorder: How are they related to effortful control?

Separate studies with clinical and community-based samples have identified an association between symptoms of attention-deficit hyperactivity disorder (ADHD) and inhibitory control deficits and ADHD and weak effortful control. We tested whether differences in effortful control explained the associations between ADHD symptoms and inhibitory control deficits, controlling for conduct problems. In a community sample, parents rated ADHD symptoms, conduct problems, effortful control, surgency and negative affect in 77 4-7-year-olds (47 girls), who performed an inhibitory control task. ADHD symptoms, deficient inhibitory control and low effortful control were correlated. Controlling for conduct problems, path analysis showed the ADHD symptoms - inhibitory control link was mediated statistically by effortful control. This focuses attention on cognitive-energetic factors associated with ADHD-related executive deficits.

Corrigendum to "Correlation of Clinicopathological Profile, Prognostic Factors, and Survival Outcomes with Baseline Alfa-Fetoprotein Levels in Patients with Hepatocellular Carcinoma: A Biomarker that is Bruised but Not Broken" [J Clin Exp Hepatol 12 (2022) 841-852].

[This corrects the article DOI: 10.1016/j.jceh.2021.11.006.].

Severe COVID-19 disease in a 2nd trimester pregnancy: Successful ECMO and mechanical ventilation management.

Extracorporeal membrane oxygenation (ECMO) is an invasive support strategy for cardiac, respiratory, or combined cardiorespiratory failure. ECMO has become increasing utilized in patients with severe respiratory failure due to COVID-19 infection. To our knowledge there is no report of successful ECMO utilization in second trimester of pregnancy leading to a successful outcome. We present a case of severe COVID-19 infection in a patient causing respiratory failure in the second trimester pregnancy. With diligent utilization of ECMO and mechanical ventilation we were able to support the patient's respiratory needs to allow her pregnancy to continue. Ultimately, the patient underwent successful caesarean section in the third trimester. This case highlights excellent lung injury protection and lung recovery can be achieved through optimal utilization of ECMO support together with a careful and closely monitored lung protective ventilation strategy, even while also supporting the patient through the increasing metabolic circumstances of a progressing pregnancy.

Correlation of Clinicopathological Profile, Prognostic Factors, and Survival Outcomes with Baseline Alfa-Fetoprotein Levels in Patients With Hepatocellular Carcinoma: A Biomarker that is Bruised but Not Broken.

Background and aims: The role of Alfa-fetoprotein (AFP) in the management of hepatocellular carcinoma (HCC) is still debated, with differences in recommendations between international guidelines. We analyzed the relationship of the clinicopathological profile, prognostic features, and survival outcomes with baseline serum AFP levels in patients with HCC. Methods: Retrospective analysis of a prospectively accrued dataset of consecutive HCC patients was done. Results: 508 treatment naive patients were included in the analysis. AFP at presentation was normal (<10 ng/ml) in 18% patients. Patients with very high AFP (>400 ng/ml) had poor hepatic reserves (higher mean serum bilirubin, AST, ALT, INR, and lower mean albumin) and advanced disease at presentation (higher incidence of extrahepatic metastasis, and less proportion of patients with well-differentiated tumors). AFP >400 ng/ml was an independent predictor for presence of portal vein tumor thrombosis (PVTT) (OR, 4.08; 95% CI, 2.34-7.12; P < 0.001), higher tumor size (OR, 2.19; 95% CI, 1.36-3.54, P = 0.001) and advanced BCLC stage (OR, 4.19; 95% CI, 2.51-7.03; P < 0.001). Two-third of patients with small HCC (MTD <3 cm) and more than half with early-stage HCC (BCLC stage 0/A) had elevated AFP levels. No significant relationship was seen between overall survival (OS) and baseline AFP in patients who underwent surgery, but median OS in patients subjected to nonsurgical therapies was 19.4,10.5 and 5.7 months in patients having AFP <10 ng/ml, 10-400 ng/ml and >400 ng/ml respectively (P = 0.003). AFP >400 ng/ml was an independent predictor of survival in patients receiving any form of therapy (HR = 2.23; 95% CI = 1.19-4.18, P = 0.012). Conclusion: AFP as a biomarker still has a significant role to play in the management of HCC patients and is here to stay till the search for an ideal biomarker in HCC is over.

The Effect of Povidone-Iodine Nasal Spray on Nasopharyngeal SARS-CoV-2 Viral Load: A Randomized Control Trial.

OBJECTIVES/HYPOTHESIS: To determine the effect of povidone-iodine (PVP-I) nasal sprays on nasopharyngeal (NP) viral load as assessed by cycle threshold (Ct) on quantitative polymerase chain reaction (qPCR) of SARS-CoV-2 in outpatients. STUDY DESIGN: Three arm, triple blinded, randomized, placebo-controlled clinical trial. METHODS: Participants were randomized within 5 days of testing positive for COVID-19 to receive nasal sprays containing placebo (0.9% saline), 0.5% PVP-I, or 2.0% PVP-I. NP swabs for qPCR analysis were taken at baseline, 1-hour post-PVP-I spray (two sprays/nostril), and 3 days post-PVP-I spray (20 sprays/nostril). Symptom and adverse event questionnaires were completed at baseline, day 3, and day 5. University of Pennsylvania Smell Identification Tests (UPSIT) were completed at baseline and day 30. RESULTS: Mean Ct values increased over time in all groups, indicating declining viral loads, with no statistically significant difference noted in the rate of change between placebo and PVP-I groups. The 2.0% PVP-I group showed statistically significant improvement in all symptom categories; however, it also reported a high rate of nasal burning. Olfaction via UPSIT showed improvement by at least one category in all groups. There were no hospitalizations or mortalities within 30 days of study enrollment. CONCLUSIONS: Saline and low concentration PVP-I nasal sprays are well tolerated. Similar reductions in SARS-CoV-2 NP viral load were seen over time in all groups. All treatment groups showed improvement in olfaction over 30 days. These data suggest that dilute versions of PVP-I nasal spray are safe for topical use in the nasal cavity, but that PVP-I does not demonstrate virucidal activity in COVID-19 positive outpatients. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:2089-2095, 2022.

Venous thromboembolism rates and risk factors following endoscopic skull base surgery.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal perioperative complication. The objective of this study was to assess the rate and risk factors for VTE in endoscopic skull base surgery (ESBS). METHODS: This was a retrospective review of adults undergoing ESBS at a tertiary academic center. Incidence of VTE in the 30-day postoperative period was recorded. Logistic regression analyses identified factors associated with VTE. RESULTS: A total of 1122 ESBS cases performed at Stanford University School of Medicine between 2009 and 2019 were studied. Almost all cases (96.1%) did not employ perioperative VTE chemoprophylaxis. The overall incidence of VTE was 2.3% (26/1122). Malignant pathologies had a higher rate of VTE compared with nonmalignant pathologies (4.5% vs 2.0%, odds ratio [OR] 2.85, 95% confidence interval [CI] 1.22-6.66). Factors associated with an increased risk of VTE included a Caprini score greater than 5 (OR 1.53, 95% CI 1.28-1.83); multiple preoperative endocrinopathies such as the syndrome of inappropriate antidiuretic hormone secretion (SIADH) (OR 22.48, 95% CI 3.93-128.70), adrenal insufficiency (OR 5.24, 95% CI 1.82-15.03), hypercortisolism (OR 4.46, 95% CI 1.47-13.56), and hypothyroidism (OR 3.69, 95% CI 1.66-8.20); each 10-hour increment of lumbar drain duration (OR 1.16, 95% CI 1.08-1.25); and each 10-hour increment for duration of hospitalization (OR 1.05, 95% CI 1.03-1.06). CONCLUSIONS: The incidence of VTE following ESBS is relatively low at 2.3%. Factors with a higher association of VTE include malignancy, preoperative endocrinopathies, higher Caprini score, prolonged lumbar drain duration, and prolonged hospitalization. Larger, multi-institutional studies are needed to validate these findings and to better refine clinical decision-making regarding perioperative VTE prophylaxis.

Validation of a Portable Whole-Slide Imaging System for Frozen Section Diagnosis.

BACKGROUND: Frozen section (FS) diagnosis is one of the promising applications of digital pathology (DP). However, the implementation of an appropriate and economically viable DP solution for FS in routine practice is challenging. The objective of this study was to establish the non-inferiority of whole-slide imaging (WSI) versus optical microscopy (OM) for FS diagnosis using a low cost and portable DP system. MATERIALS AND METHODS: A validation study to investigate the technical performance and diagnostic accuracy of WSI versus OM for FS diagnosis was performed using 60 FS cases[120 slides i.e, 60 hematoxylin and eosin (H & E) and 60 toluidine blue (TOLB)]. The diagnostic concordance, inter- and intra-observer agreement for FS diagnosis by WSI versus OM were recorded. RESULTS: The first time successful scanning rate was 89.1% (107/120). Mean scanning time per slide for H and E and TOLB slide was 1:47 min (range; 0:22-3: 21 min) and 1:46 min (range; 0:21-3: 20 min), respectively. Mean storage space per slide for H and E and TOLB slide was 0.83 GB (range: 0.12-1.73 GB) and 0.71 GB (range: 0.11-1.66 GB), respectively. Considering major discrepancies, the overall diagnostic concordance for OM and WSI, when compared with the reference standard, was 95.42% and 95.83%, respectively. There was almost perfect intra as well as inter-observer agreement (k ≥ 0.8) among 4 pathologists between WSI and OM for FS diagnosis. Mean turnaround time (TAT) of 14:58 min was observed using WSI for FS diagnosis, which was within the College of American Pathologists recommended range for FS reporting. The image quality was average to best quality in most of the cases. CONCLUSION: WSI was noninferior to OM for FS diagnosis across various specimen types. This portable WSI system can be safely adopted for routine FS diagnosis and provides an economically viable alternative to high-end scanners.

Intraoperative Management of Adult Patients on Extracorporeal Membrane Oxygenation: an Expert Consensus Statement From the Society of Cardiovascular Anesthesiologists-Part I, Technical Aspects of Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is used to support patients with refractory cardiopulmonary failure. Given ECMO's increased use in adults and the fact that many ECMO patients are cared for by anesthesiologists, the Society of Cardiovascular Anesthesiologists ECMO working group created an expert consensus statement that is intended to help anesthesiologists manage adult ECMO patients who are cared for in the operating room. In the first part of this 2-part series, technical aspects of ECMO are discussed, and related expert consensus statements are provided.

Unexpected Interruptions in the Inhaled Epoprostenol Delivery System: Incidence of Adverse Sequelae and Therapeutic Consequences in Critically Ill Patients.

OBJECTIVES: Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients. DESIGN: Retrospective review and analysis. SETTING: Stanford University Hospital, a 605-bed tertiary care center. PATIENTS: Patients receiving inhaled epoprostenol in 2019. INTERVENTIONS: No interventions. MEASUREMENTS AND MAIN RESULTS: Clinical indication, duration of inhaled epoprostenol delivery, mode of respiratory support, and documented unexpected interruption. In 2019, there were 493 administrations of inhaled epoprostenol in 433 unique patients. Primary indications for inhaled epoprostenol were right heart dysfunction (n = 394; 79.9%) and hypoxemia (n = 92; 18.7%). Unexpected delivery interruptions occurred in 31 administrations (6.3%). Median duration of therapy prior to unexpected interruption was 2 days (interquartile range, 2-5 d). Respiratory support at the time of unexpected interruption was mechanical ventilation (61.3%), high-flow nasal cannula (35.5%), and noninvasive positive pressure ventilation (3.2%). Adverse sequelae of unexpected interruption included elevated pulmonary artery pressures (n = 12), systemic hypotension (n = 8), hypoxemia (n = 8), elevated central venous pressure (n = 4), and cardiac arrest (n = 1). Therapeutic interventions following unexpected interruption included initiation of inhaled nitric oxide (n = 21), increase in vasoactive medication (n = 2), and increase in respiratory support (n = 2). Most of the adverse events were Common Terminology Criteria for Adverse Events grade 3 and 4 (93.5%). CONCLUSIONS: A retrospective review of patients receiving inhaled epoprostenol via vibrating mesh nebulizer in 2019 revealed interruptions in 6.3% of administrations with most of these interruptions requiring therapeutic intervention. The true incidence of unexpected interruption and subsequent rate of unexpected interruption's requiring intervention is unknown due to the reliance on unexpected interruption identification and subsequent documentation in the electronic medical record. Sudden interruption in inhaled epoprostenol delivery can result in severe cardiopulmonary compromise, and on rare occasion, death.

Intraoperative Management of Adult Patients on Extracorporeal Membrane Oxygenation: An Expert Consensus Statement From the Society of Cardiovascular Anesthesiologists-Part I, Technical Aspects of Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is used to support patients with refractory cardiopulmonary failure. Given ECMO's increased use in adults and the fact that many ECMO patients are cared for by anesthesiologists, the Society of Cardiovascular Anesthesiologists ECMO working group created an expert consensus statement that is intended to help anesthesiologists manage adult ECMO patients who are cared for in the operating room. In the first part of this 2-part series, technical aspects of ECMO are discussed, and related expert consensus statements are provided.

Intraoperative Management of Adult Patients on Extracorporeal Membrane Oxygenation: An Expert Consensus Statement From the Society of Cardiovascular Anesthesiologists-Part II, Intraoperative Management and Troubleshooting.

In the second part of the Society of Cardiovascular Anesthesiologists Extracorporeal Membrane Oxygenation (ECMO) working group expert consensus statement, venoarterial (VA) and venovenous (VV) ECMO management and troubleshooting in the operating room are discussed. Expert consensus statements are provided about intraoperative monitoring, anesthetic drug dosing, and management of intraoperative problems in VA and VV ECMO patients.

Comparative Assessment of Digital Pathology Systems for Primary Diagnosis.

BACKGROUND: Despite increasing interest in whole-slide imaging (WSI) over optical microscopy (OM), limited information on comparative assessment of various digital pathology systems (DPSs) is available. MATERIALS AND METHODS: A comprehensive evaluation was undertaken to investigate the technical performance-assessment and diagnostic accuracy of four DPSs with an objective to establish the noninferiority of WSI over OM and find out the best possible DPS for clinical workflow. RESULTS: A total of 2376 digital images, 15,775 image reads (OM - 3171 + WSI - 12,404), and 6100 diagnostic reads (OM - 1245, WSI - 4855) were generated across four DPSs (coded as DPS: 1, 2, 3, and 4) using a total 240 cases (604 slides). Onsite technical evaluation revealed successful scan rate: DPS3 < DPS2 < DPS4 < DPS1; mean scanning time: DPS4 < DPS1 < DPS2 < DPS3; and average storage space: DPS3 < DPS2 < DPS1 < DPS4. Overall diagnostic accuracy, when compared with the reference standard for OM and WSI, was 95.44% (including 2.48% minor and 2.08% major discordances) and 93.32% (including 4.28% minor and 2.4% major discordances), respectively. The difference between the clinically significant discordances by WSI versus OM was 0.32%. Major discordances were observed mostly using DPS4 and least in DPS1; however, the difference was statistically insignificant. Almost perfect (κ ≥ 0.8)/substantial (κ = 0.6-0.8) inter/intra-observer agreement between WSI and OM was observed for all specimen types, except cytology. Overall image quality was best for DPS1 followed by DPS4. Mean digital artifact rate was 6.8% (163/2376 digital images) and maximum artifacts were noted in DPS2 (n = 77) followed by DPS3 (n = 36). Most pathologists preferred viewing software of DPS1 and DPS2. CONCLUSION: WSI was noninferior to OM for all specimen types, except for cytology. Each DPS has its own pros and cons; however, DPS1 closely emulated the real-world clinical environment. This evaluation is intended to provide a roadmap to pathologists for the selection of the appropriate DPSs while adopting WSI.

First lung and kidney multi-organ transplant following COVID-19 Infection.

As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.

The Year in Thoracic Anesthesia: Selected Highlights From 2020.

Selected highlights in thoracic anesthesia in 2020 include updates in the preoperative assessment and prehabilitation of patients undergoing thoracic surgery; updates in one-lung ventilation (OLV) pertaining to the devices used for OLV; the use of dexmedetomidine for lung protection during OLV and protective ventilation, recommendations for the care of thoracic surgical patients with coronavirus disease 2019; a review of recent meta-analyses comparing truncal blocks with paravertebral and thoracic epidural blocks; and a review of outcomes after initiating the enhanced recovery after surgery guidelines for lung and esophageal surgery.