Prognostication: A fading Hippocratic art?

Over the past 75 years modern medicine has advanced in its ability to diagnose and treat many diseases. However, the medical profession's ability to prognosticate the course and outcome of an illness has not satisfied the needs of many patients. Physicians must not lose the ability, or desire, to consider the whole person in relation to a patient's disease. We need to ask ourselves what person has the disease, not what disease the person has. Here I endeavor to demonstrate why Hippocrates valued prognostication highly, how its importance may have faded from the consciousness of current medical practice, and how modern technology is attempting to reinvent or revise it.

Hippocrates, the first aphorism, and decorum: A personal view of caution and guidance regarding Generation Z students.

Generation Z students can be challenging. The Internet, the Covid-19 epidemic, its political aftermath, and the substantial online educational content they have been required to endure, has left them with a perspective towards a work-life balance to which we older, more experienced faculty are not accustomed. Here, I give caution and guidance to my colleagues regarding their interactions with this cohort through my reading of the Hippocratic corpus.

Apelin-13 reverses bupivacaine-induced cardiotoxicity: an experimental study.

INTRODUCTION: Cardiac arrest or arrhythmia caused by bupivacaine may be refractory to treatment. Apelin has been reported to directly increase the frequency of spontaneous activation and the propagation of action potentials, ultimately promoting cardiac contractility. This study aimed to investigate the effects of apelin-13 in reversing cardiac suppression induced by bupivacaine in rats. METHODS: A rat model of cardiac suppression was established by a 3-min continuous intravenous infusion of bupivacaine at the rate of 5 mg.kg-1.min-1, and serial doses of apelin-13 (50, 150 and 450 µg.kg-1) were administered to rescue cardiac suppression to identify its dose-response relationship. We used F13A, an inhibitor of Angiotensin Receptor-Like 1 (APJ), and Protein Kinase C (PKC) inhibitor chelerythrine to reverse the effects of apelin-13. Moreover, the protein expressions of PKC, Nav1.5, and APJ in ventricular tissues were measured using Western blotting and immunofluorescence assay. RESULTS: Compared to the control rats, the rats subjected to continuous intravenous administration of bupivacaine had impaired hemodynamic stability. Administration of apelin-13, in a dose-dependent manner, significantly improved hemodynamic parameters in rats with bupivacaine-induced cardiac suppression (p < 0.05), and apelin-13 treatment also significantly upregulated the protein expressions of p-PKC and Nav1.5 (p < 0.05), these effects were abrogated by F13A or chelerythrine (p < 0.05). CONCLUSION: Exogenous apelin-13, at least in part, activates the PKC signaling pathway through the apelin/APJ system to improve cardiac function in a rat model of bupivacaine-induced cardiac suppression.

Facilitating Lung Collapse for Thoracoscopic Surgery Utilizing Endobronchial Airway Occlusion Preceded by Pleurotomy and One-minute Suspension of Two-lung Ventilation.

OBJECTIVES: To assess when and whether clamping the double-lumen endobronchial tube (DLT) limb of the non-ventilated lung is more conducive to a rapid and effective lung deflation than simply allowing the open limb of the DLT to communicate with the atmosphere. DESIGN: This was a single-center, single-blind, randomized, controlled trial. SETTING: The trial was performed in a single institutional setting. PARTICIPANTS: The participants were 60 patients undergoing elective video-assisted thoracoscopic surgery. INTERVENTIONS: Patients were randomized to the open-clamp airway technique (OCAT group) or control group. Patients in the control group had one-lung ventilation initiated upon being placed in the lateral decubitus position. The OCAT group had two-lung ventilation maintained until the pleural cavity was opened with the introduction of a planned thoracoscopic access port to allow the operated lung to fall away from the chest wall. Thereafter, ventilation was suspended (temporarily ceased) for 1 minute before the DLT lumen of the isolated lung was clamped. The primary outcome of the trial was the time to complete lung collapse scored as determined from video clips taken during surgery. The secondary outcomes were (1) lung collapse score at 30 minutes after pleural incision, (2) surgeon satisfaction with surgery, and (3) intraoperative hypoxemia. MEASUREMENTS AND MAIN RESULTS: The median time to reach complete lung collapse in the OCAT group was 10 minutes (odds ratio 10.0, 95% CI 6.3-13.7), which was much shorter than that of the control group (25 minutes [odds ratio 25.0, 95% CI 13.6-36.4]). The difference in complete lung collapse at 30 minutes between the 2 groups was significant (p < 0.001). The surgeon's satisfaction with surgery was higher in the OCAT group than in the control group (8.5 ± 0.2 vs 6.8 ± 0.2; p < 0.001). There was no difference regarding intraoperative hypoxemia. CONCLUSIONS: Suspending ventilation of both DLT limbs for 1 minute after pleural cavity opening and then clamping the DLT lumen of the isolated lung resulted in a more rapid deflation of the surgical lung. This open-clamp airway technique is an effective technique for rapid surgical lung collapse during thoracoscopic surgery.

Flood-Related Multimedia Benchmark Evaluation: Challenges, Results and a Novel GNN Approach.

This paper discusses the importance of detecting breaking events in real time to help emergency response workers, and how social media can be used to process large amounts of data quickly. Most event detection techniques have focused on either images or text, but combining the two can improve performance. The authors present lessons learned from the Flood-related multimedia task in MediaEval2020, provide a dataset for reproducibility, and propose a new multimodal fusion method that uses Graph Neural Networks to combine image, text, and time information. Their method outperforms state-of-the-art approaches and can handle low-sample labelled data.

Point of care transthoracic echocardiography for the prediction of post - spinal anesthesia hypotension in elderly patients with cardiac diseases and left ventricular dysfunction : Inferior vena cava and post-spinal anesthesia hypotension in elderly patients.

In elderly patients with cardiac diseases, changes in cardiovascular physiology diminish cardiovascular reserve and predispose to hemodynamic instability after spinal anesthesia; hence, such patients could be at risk of postoperative complications. Additionally, transthoracic echocardiography (TTE) is used in clinical practice to evaluate cardiovascular hemodynamics. Therefore, we hypothesized that echocardiographic measurements could display significant diagnostic power in the prediction of post - spinal anesthesia hypotension in elderly patients with cardiac diseases and reduced left ventricular ejection fraction (LV-EF). Therefore, sixty-one elderly orthopedic-trauma patients were recruited. Prior to spinal anesthesia a TTE examination was performed. The LV-EF, the stroke volume index (SVI), the peripheral vascular resistance (PVR), the LV filling pressures (E/Em ratio), the right ventricular function [tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TASV) and fractional area change (FAC)], as well as inferior vena cava (IVC) measurements, such as IVCCI (collapsibility index of the IVC) and dIVCmax (maximum diameter of IVC)-to-IVCCI ratio were assessed. Twenty-six out of sixty-one patients manifested hypotension. Preoperative dIVCmax-to-IVCCI ratio demonstrated the greatest performance amongst echocardiographic indices in predicting post - spinal anesthesia hypotension. The dIVCmax-to-IVCCI ratio < 48 had significantly higher diagnostic power than IVCCI > 0.28, FAC > 42, E/Em ratio < 9 and SVI < 32 (receiver operator characteristic curve analysis). The gray zone for the dIVCmax-to-IVCCI ratio (40-49) showed the lowest number of inconclusive measurements among echocardiographic variables. The preoperative dIVCmax-to-IVCCI ratio could be a reliable echocardiographic index to predict post - spinal anesthesia hypotension in elderly patients with left ventricular dysfunction.

Continuous renal replacement therapy and extracorporeal membrane oxygenation: implications in the COVID-19 era.

The novel severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (coronavirus Disease 19 (COVID-19)) was identified as the causative agent of viral pneumonias in Wuhan, China in December 2019, and has emerged as a pandemic causing acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. Interim guidance by the World Health Organization states that extracorporeal membrane oxygenation (ECMO) should be considered as a rescue therapy in COVID-19-related ARDS. International registries tracking ECMO in COVID-19 patients reveal a 21%-70% incidence of acute renal injury requiring renal replacement therapy (RRT) during ECMO support. The indications for initiating RRT in patients on ECMO are similar to those for patients not requiring ECMO. RRT can be administered during ECMO via a temporary dialysis catheter, placement of a circuit in-line hemofilter, or direct connection of continuous RRT in-line with the ECMO circuit. Here we review methods for RRT during ECMO, RRT initiation and timing during ECMO, anticoagulation strategies, and novel cytokine filtration approaches to minimize COVID-19's pathophysiological impact.

Anterior Quadratus Lumborum block area comparison in the three different volumes of Ropivacaine: a double-blind, randomized controlled trial in healthy volunteers.

BACKGROUND: In abdominal surgery, ultrasound-guided anterior quadratus lumborum blocks (QLB) are performed to induce analgesia. However, no study reported suitable volumes of the anterior QLB for the different postoperative analgesia regions. Therefore, this prospective randomized controlled study assessed the dermatomal spread and analgesic effects of the three different volumes of a local anesthetic for anterior QLB. METHODS: Ultrasound-guided anterior QLB was performed at the L2 level on 30 healthy volunteers. The volunteers were randomized to receive 20 ml (n = 10), 30 ml (n = 10), and 40 mL (n = 10) of 0.375% ropivacaine. The cutaneous sensory blocked area (CSBA), the number of block dermatomes, and the block duration time were measured by determining the extent of the cold sensation. RESULTS: The CSBA was significantly larger in the 40 ml group than in the 30 (P = 0.001; 1350.6 ± 234.4 vs. 1009.5 ± 151.6 cm2) and 20 ml groups (P < 0.001; 1350.6 ± 234.4 vs. 808.1 ± 120.5 cm2). Similarly, the number of blocked dermatomes was significantly higher in the 40 ml group than in the 30- and 20-ml groups. However, no significant difference was observed in block duration among the groups. CONCLUSIONS: No difference was observed in block duration with the various volumes of 0.375% ropivacaine. However, the larger volume for anterior QLB contributed to a larger area of cutaneous sensory blockade. Appropriate volumes in anterior QLB can create suitable postoperative analgesia levels for the different operative sites. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registration Center on www.chictr.org.cn on 27th April 2018 (registration number: ChiCTR-IOR-17010853).

Contributing Factors to Operating Room Delays Identified from an Electronic Health Record: A Retrospective Study.

The operating room (OR) is considered a major cost center and revenue generator for hospitals. Multiple factors contribute to OR delays and impact patient safety, patient satisfaction scores, and hospital financial performance. Reducing OR delays allows better utilization of OR resources and staffing and improves patient satisfaction while decreasing operating costs. Accurate scheduling can be the basis to achieve these goals. The objective of this initial study was to identify factors not normally documented in the electronic health record (EHR) that may contribute to or be indicators of OR delays. Materials and Methods. A retrospective data analysis was performed analyzing 67,812 OR cases from 12 surgical specialties at a small university medical center from 2010 through the first quarter of 2017. Data from the hospital's EHR were exported and subjected to statistical analysis using Statistical Analysis System (SAS) software (SAS Institute, Cary, NC). Results. Statistical analysis of the extracted EHR data revealed factors that were associated with OR delays including, surgical specialty, preoperative assessment testing, patient body mass index, American Society of Anesthesiologists (ASA) physical status classification, daily procedure count, and calendar year. Conclusions. Delays hurt OR efficiency on many levels. Identifying those factors may reduce delays and better accommodate the needs of surgeons, staff, and patients thereby leading to improved patient's outcomes and patient satisfaction. Reducing delays can decrease operating costs and improve the financial position of the operating theater as well as that of the hospital. Anesthesiology teams can play a key role in identifying factors that cause delays and implementing mitigating efficiencies.

A Lumbar Paravertebral Space Ultrasound Lumbar Plexus Block Technique for Hip Fracture Surgery in the Elderly.

Ultrasound imaging of peripheral nerves is challenging in elderly population. In cases involving the lumbar plexus (LP), we have employed ultrasound imaging and neurostimulation guidance for successful localization and block of the LP. The postero-medial segment of the psoas muscle (PSM), superior to the vertebral body and anterior to the transverse process ("corner pocket") was used as an imaging landmark for the implementation of the LP block. By advancing the needle through the lateral abdominal wall into the "corner pocket" we were afforded a seamless advancement of the needle into the postero-medial segment of the PSM, which is the standard anatomic position of LP in the PSM. Forty-eight patients in whom ultrasound imaging of the LP was not feasible, but the "corner pocket" was clearly depicted were included in the study. LP block characteristics and adverse events were recorded. The LP was localized in 43/48 patients. The average imaging, needling, and performance times to complete the block were 51 sec (range, 6-180 sec), 81 sec (range, 16-236 sec), and 132 sec (range, 24-270 sec), respectively. The median number of needle redirections per patient was 5.5 (range, 1-13). The local anesthetic spread was visualized in the postero-medial segment of the PSM in 39/43 patients. No complications were recorded. The imaging, needling, and performance times, as well as the number of needle passes did not significantly differ between obese and non-obese patients. In conclusion, in cases with challenging ultrasound imaging of the LP, ultrasound-assisted LP block can be accomplished through the lateral abdominal wall by using as an imaging landmark the "corner pocket" at the postero-medial quadrant of the PSM.

Dexmedetomidine prolongs the duration of local anesthetics when used as an adjuvant through both perineural and systemic mechanisms: a prospective randomized double-blinded trial.

BACKGROUND: To study the respective peripheral and systemic mechanisms of action of dexmedetomidine, as adjuvant to regional anesthesia, we compared dexmedetomidine added to ropivacaine for mid-forearm nerve blocks, to either systemic-only dexmedetomidine, and to a control with no dexmedetomidine. METHODS: Sixty patients undergoing hand surgery were randomly divided into three groups (n = 20 per group). Each group underwent a triple-nerve (median, radial and ulnar) mid-forearm blocks with 0.75% ropivacaine. In the DexP group, 60 µg of dexmedetomidine were added to the anesthetic mixture, while in the DexIV group, they were intravenously infused. Normal saline as a placebo was used, either as adjuvant, or intravenously. All patients underwent also a supraclavicular block with 1.5% lidocaine for tourniquet pain. The main outcomes were the duration of analgesia and the duration of sensory blockade separately for each nerve termination of the upper limb, and the duration of motor blockade of the upper limb. Tolerance was assessed by blood pressure and heart rate, and the report of adverse events. RESULTS: Duration of analgesia was longer in the DexP group, in comparison to the two other groups (P < 0.001), while it was similar in the DexIV and the control group. For cutaneous territories targeted by the three mid-forearm blocks, the between-group differences behaved similarly. For the other cutaneous territories (musculocutaneous and posterior brachial cutaneous nerves), duration of sensory blockade was shorter in the control group than in the two dexmedetomidine groups. For duration of motor blockade, the between-group differences behaved similarly. Both blood pressure and heart rate were reduced in the DexP and the DexIV groups, compared to the control. CONCLUSIONS: Dexmedetomidine used as an adjuvant to regional anesthesia may act mostly though a perineural mechanism, especially for the sensory aspects of anesthesia. A systemic action might however explain other clinical effects. TRIAL REGISTRATION: ChiCTR-IOR-17011149 , date of registration: 16/04/2017.

Inferior vena cava ultrasonography in the assessment of intravascular volume status and fluid responsiveness in the emergency department and intensive care unit: A critical analysis review.

Rapid evaluation of intravascular volume status is vital; either excessive or limited fluid administration may result in adverse patient outcomes. In this narrative review, critical analysis of pertinent diagnostic accuracy studies is developed to delineate the role of inferior vena cava ultrasound measurements in the assessment of both intravascular volume status and fluid responsiveness in the emergency department and intensive care unit. In addition, limitations, and technical considerations of inferior vena cava ultrasound measurements as well as directions for future research are thoroughly discussed.

Post-Acute COVID-19 Syndrome for Anesthesiologists: A Narrative Review and a Pragmatic Approach to Clinical Care.

Post-acute coronavirus disease 2019 (COVID-19) syndrome is a novel, poorly understood clinical entity with life-impacting ramifications. Patients with this syndrome, also known as "COVID-19 long-haulers," often present with nonspecific ailments involving more than one body system. The most common complaints include dyspnea, fatigue, brain fog, and chest pain. There currently is no single agreed-upon definition for post-acute COVID-19 syndrome, but most agree that criterion for this syndrome is the persistence of mental and physical health consequences after initial infection. Given the millions of acute infections in the United States over the course of the pandemic, perioperative providers will encounter these patients in clinical practice in growing numbers. Symptoms of the COVID-19 long-haulers should not be minimized, as these patients are at higher risk for postoperative respiratory complications and perioperative mortality for up to seven weeks after initial illness. Instead, a cautious multidisciplinary preoperative evaluation should be performed. Perioperative care should be viewed through the prism of best practices already in use, such as avoidance of benzodiazepines in patients with cognitive impairment and use of lung-protective ventilation. Recommendations especially relevant to the COVID-19 long-haulers include assessment of critical care myopathies and neuropathies to determine suitable neuromuscular blocking agents and reversal, preoperative workup of insidious cardiac or pulmonary pathologies in previously healthy patients, and, thorough medication review, particularly of anticoagulation regimens and chronic steroid use. In this article, the authors define the syndrome, synthesize the available scientific evidence, and make pragmatic suggestions regarding the perioperative clinical care of COVID-19 long-haulers.

Apelin-13 Reverses Bupivacaine-Induced Cardiotoxicity via the Adenosine Monophosphate-Activated Protein Kinase Pathway.

BACKGROUND: Cardiotoxicity can be induced by the commonly used amide local anesthetic, bupivacaine. Bupivacaine can inhibit protein kinase B (AKT) phosphorylation and activated adenosine monophosphate-activated protein kinase alpha (AMPKα). It can decouple mitochondrial oxidative phosphorylation and enhance reactive oxygen species (ROS) production. Apelin enhances the phosphatidylinositol 3-kinase (PI3K)/AKT and AMPK/acetyl-CoA carboxylase (ACC) pathways, promotes the complete fatty acid oxidation in the heart, and reduces the release of ROS. In this study, we examined whether exogenous (Pyr1) apelin-13 could reverse bupivacaine-induced cardiotoxicity. METHODS: We used the bupivacaine-induced inhibition model in adult male Sprague Dawley (SD) rats (n = 48) and H9c2 cardiomyocyte cell cultures to explore the role of apelin-13 in the reversal of bupivacaine cardiotoxicity, and its possible mechanism of action. AMPKα, ACC, carnitine palmitoyl transferase (CPT), PI3K, AKT, superoxide dismutase 1 (SOD1), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47-phox) were quantified. Changes in mitochondrial ultrastructure were examined, and mitochondrial DNA, cell viability, ROS release, oxygen consumption rate (OCR) were determined. RESULTS: Apelin-13 reduced bupivacaine-induced mitochondrial DNA lesions in SD rats (P < .001), while increasing the expression of AMPKα (P = .007) and PI3K (P = .002). Furthermore, apelin-13 blocked bupivacaine-induced depolarization of the mitochondrial membrane potential (P = .019) and the bupivacaine-induced increases in ROS (P = .001). Also, the AMPK pathway was activated by bupivacaine as well as apelin-13 (P = .002) in H9c2 cardiomyocytes. Additionally, the reduction in the PI3K expression by bupivacaine was mitigated by apelin-13 in H9c2 cardiomyocytes (P = .001). While the aforementioned changes induced by bupivacaine were not abated by apelin-13 after pretreatment with AMPK inhibitor compound C; the bupivacaine-induced changes were still mitigated by apelin-13, even when pretreated with PI3K inhibitor-LY294002. CONCLUSIONS: Apelin-13 treatment reduced bupivacaine-induced oxidative stress, attenuated mitochondrial morphological changes and mitochondrial DNA damage, enhanced mitochondrial energy metabolism, and ultimately reversed bupivacaine-induced cardiotoxicity. Our results suggest a role for the AMPK in apelin-13 reversal of bupivacaine-induced cardiotoxicity.

Single and Repeated Intrapleural Ropivacaine Administration: A Plasma Concentration and Pharmacodynamics Study.

BACKGROUND: Intrapleural analgesia has been increasingly recommended for postoperative analgesia after thoracic surgery. However, the analgesic effect provided by a single intrapleural administration is time limited. This study reports the efficacy and safety of repeated intrapleural 0.75% ropivacaine administration after thoracoscopic surgery. METHODS: Twenty patients were randomly divided into two groups: a single administration group receiving a single intrapleural injection of 0.75% ropivacaine 15 mL (single administration group, SA group), and a repeated administration group with an intrapleural injection of 0.75% ropivacaine 15 mL every 4h for 4 doses (repeated administration group, RA group). The primary outcomes of this study were the peak plasma concentration of ropivacaine and 24h morphine consumption. The secondary outcomes were pain score, patient satisfaction, extubation time, hospital length of stay, and adverse reactions. RESULTS: In SA group, the highest plasma concentration after intrapleural administration of 0.75% ropivacaine 15 mL was 1345±364 µg/L. The highest plasma concentration in RA group after the fourth administration was 1864±492 µg/L. The 24h morphine consumption in RA group was significantly less than that in SA group (9.0±5.66 vs 15.9±3.48 mg, P=0.004). The NRS scores at rest and while coughing of patients in RA group were significantly lower than those in SA group at 5, 9, 13, 17 and 24h after operation. The patients in RA group had higher satisfaction than those in SA group. There was no significant difference in postoperative adverse events, drainage tube placement days and hospital length of stay between the two groups. CONCLUSION: Repeated intrapleural administration with 0.75% ropivacaine, 15 mL every 4h for 4 doses after video-assisted thoracoscopic lobectomies, can provide a more durable and more effective analgesic effect than single intrapleural administration. Repeated intrapleural administration of ropivacaine is an effective postoperative method of analgesia resulting in higher patient satisfaction. Moreover, it was also able to keep the plasma concentration of ropivacaine within a possible safe range. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17010560.

Evaluation of Recombinant CYP3A4 Variants on the Metabolism of Oxycodone In Vitro.

Cytochrome P450 3A4 is a highly polymorphic enzyme and metabolizes approximately 40%-60% of therapeutic drugs. Its genetic polymorphism may significantly affect the expression and function of CYP3A4 resulting in alterations of the pharmacokinetics and pharmacodynamics of the CYP3A4-mediated drugs. The purpose of this study was to evaluate the catalytic activities of 30 CYP3A4 nonsynonymous variants and wild type toward oxycodone in vitro. CYP3A4 proteins were incubated with oxycodone for 30 min at 37 °C and the reaction was terminated by cooling to -80 °C immediately. Ultraperformance liquid chromatography tandem mass-spectrometry was used to analyze noroxycodone, and kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of noroxycodone were also determined. Compared with CYP3A4.1, 24 CYP3A4 variants (CYP3A4.2-.5, -.7-.16, -.18 and -.19, -.23 and -.24, -.28 and -.29, and -.31-.34) exhibited significantly decreased relative clearance values (from 4.82% ± 0.31% to 80.98% ± 5.08%), whereas CYP3A4.6, -.17, -.20, -.21, -.26, and -.30 displayed no detectable enzyme activity. As the first study of these alleles for oxycodone metabolism in vitro, results of this study may provide insight into establishing the genotype-phenotype relationship for oxycodone and serve as a reference for clinical administrators and advance the provision of personalized precision medicine.