Cardioprotective Effects of Sodium-Glucose Cotransporter Subtype Inhibition on Ischemic and Pharmacological Preconditioning.

BACKGROUND: Sodium-glucose cotransporter (SGLT) 2 inhibitors partially inhibit SGLT1 expression; however, whether a clinical dose of SGLT2 inhibitor abrogates ischemic preconditioning (IPC) is unknown, and the pharmacological cardioprotective effect under SGLT1 inhibition has not been examined. In this study, we investigated whether a clinical dose of tofogliflozin abrogates IPC and whether pharmacological preconditioning with olprinone has cardioprotective effects under SGLT1 inhibition. METHODS: Male Wistar rats were divided into seven groups (seven rats per group) and subjected to the following treatments before inducing ischemia/reperfusion (I/R; 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion): saline infusion control treatment (Con); ischemic preconditioning (IPC); IPC after phlorizin infusion (IPC+Phl); IPC after low-dose tofogliflozin infusion (IPC+L-Tof); IPC after high-dose tofogliflozin infusion (IPC+H-Tof); olprinone infusion (Olp); and Olp infusion after phlorizin infusion (Olp+Phl). RESULTS: The infarct size was significantly decreased in the IPC group, but not in the IPC+Phl group. In contrast, the infarct size decreased in the IPC+L-Tof and IPC+H-Tof groups. Additionally, Olp reduced the infarct size, and the effect was preserved in Olp+Phl groups. Phosphorylated AMP-activated protein kinase (AMPK) expression was lower in the IPC+Phl group compared to that in the IPC group. CONCLUSION: The cardioprotective effect of IPC was attenuated by strong SGLT1 inhibition, but the effect was preserved under a clinical dose of highly selective SGLT2 inhibitor. Olprinone exerts a cardioprotective effect even under strong SGLT1 inhibition.

Amniotic fluid embolism rescued using venoarterial extracorporeal membrane oxygenation without initial anticoagulation: A case report and literature review.

RATIONALE: Amniotic fluid embolism (AFE) is a fatal obstetric condition that often rapidly leads to severe respiratory and circulatory failure. It is complicated by obstetric disseminated intravascular coagulation (DIC) with bleeding tendency; therefore, the introduction of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is challenging. We report the case of a patient with AFE requiring massive blood transfusion, rescued using VA-ECMO without initial anticoagulation. PATIENTS CONCERNS: A 39-year-old pregnant patient was admitted with a complaint of abdominal pain. An emergency cesarean section was performed because a sudden decrease in fetal heart rate was detected in addition to DIC with hyperfibrinolysis. Intra- and post-operatively, the patient had a bleeding tendency and required massive blood transfusions. After surgery, the patient developed lethal respiratory and circulatory failure, and VA-ECMO was introduced. DIAGNOSIS: Based on the course of the illness and imaging findings, the patient was diagnosed with AFE. INTERVENTIONS: By controlling the bleeding tendency with a massive transfusion and tranexamic acid administration, using an antithrombotic ECMO circuit, and delaying the initiation of anticoagulation and anti-DIC medication until the bleeding tendency settled, the patient was managed safely on ECMO without complications. OUTCOMES: By day 5, both respiration and circulation were stable, and the patient was weaned off VA-ECMO. Mechanical ventilation was discontinued on day 6. Finally, she was discharged home without sequelae. LESSONS: VA-ECMO may be effective to save the lives of patients who have AFE with lethal circulatory and respiratory failure. For safe management without bleeding complications, it is important to start VA-ECMO without initial anticoagulants and to administer anticoagulants and anti-DIC drugs after the bleeding tendency has resolved.

Improved Reliability of Electromyography-Based Neuromuscular Monitoring During Laparoscopic Surgery Achieved by the Modified Attachment Method for Nihon-Kohden NM-345Y™ Stimulating Electrodes: A Case Report.

Neuromuscular monitoring is crucial during the administration of neuromuscular blocking agents owing to individual variations in their effects. In electromyography (EMG)-based neuromuscular monitoring using the EMG electrodes (NM-345Y™, Nihon-Kohden Corporation, Tokyo, Japan) following the manufacturer-recommended attachment method, the accuracy of neuromuscular monitoring may be reduced when forearm limb position is changed. We previously devised a novel attachment method for NM-345Y™ stimulating electrodes in adult volunteers to maintain stable monitoring accuracy despite changes in forearm position. Its effectiveness in clinical practice was evaluated by conducting a descriptive study on a 52-year-old woman undergoing laparoscopic uterine surgery. NM-345Y™ electrodes were attached to each forearm following the manufacturer's recommendations (Pattern N) and our novel method (Pattern C). In Pattern C, NM-345Y™ was attached without ultrasound guidance so that the ulnar nerve crossed the line connecting the centers of the anode and cathode of the stimulating electrode. Pattern C exhibited consistent EMG-based monitoring accuracy even with changes in forearm position despite a smaller stimulus current value at calibration. Additionally, Pattern C displayed reliable recovery of the train-of-four (TOF) response after sugammadex administration in the original forearm position, with no observed adverse events. In contrast, Pattern N showed unstable monitoring accuracy after forearm position changes, highlighting the danger of imprecise EMG-based neuromuscular monitoring during the administration of neuromuscular blocking agents. The study's strength lies in identifying Pattern C, where the ulnar nerve crosses the line connecting the anode and cathode, significantly enhancing monitoring accuracy. This novel attachment method holds promise to improve EMG-based neuromuscular monitoring precision in surgery involving forearm limb position changes, although further research is required to assess its utility comprehensively.

Platypnoea-orthodeoxia syndrome in COVID-19 pneumonia patients: An observational study.

This retrospective observational study aimed to assess the clinical characteristics of platypnea-orthodeoxia syndrome in patients with coronavirus disease 2019 (COVID-19) treated using mechanical ventilation or high-flow nasal canula. We analyzed 42 consecutive patients with COVID-19 from January 2020 to March 2022. The primary outcomes were the incidence of platypnea-orthodeoxia syndrome, the time with required long-term oxygen therapy, and short-term prognosis. Additionally, we examined the relationships between platypnea-orthodeoxia syndrome and COVID-19 severity, the time with long-term oxygen therapy, and short-term prognosis. Of the 42 included patients, 15 (35.7 %) had platypnea-orthodeoxia syndrome. Although mortality was not significantly different between both groups, the oxygen withdrawal rate in the platypnea-orthodeoxia syndrome group was significantly lower than that in the group without this syndrome. Clinical staff should be aware of the possibility of platypnea-orthodeoxia syndrome during positional changes in patients with COVID-19. Recognizing POS can improve early detection, countermeasures, and safety during physiotherapy.

The lesion site in malignant psoas syndrome influences the cancer pain intensity.

BACKGROUND: Malignant psoas syndrome (MPS) is characterized by pain and hip flexion fixation due to tumor infiltration of the iliopsoas muscle. However, the dose of opioid required to control pain varies markedly among MPS patients. As the ability to predict whether an MPS patient will need a higher opioid dose in the early period of pain control is clinically meaningful, we retrospectively evaluated the relationship between lesion site in MPS and the opioid dose required for pain control. METHODS: Fourteen patients received opioid control of cancer pain due to MPS between January 2014 and December 2018. Two patients with paraplegia who died during pain control were excluded from this study. The remaining 12 patients were divided into group of muscle attachment (group MA) (n=6), with the lesion in the iliopsoas MA to the spine, and group of muscle belly (group MB) (n=6), with the lesion in the iliopsoas MB. We compared opioid doses for pain control between groups. RESULTS: No significant differences in background characteristics were seen between groups. Opioid dose (in oral morphine equivalents) was significantly higher in group MB (1,374.3±504.5 mg/day) than in group MA (92±67.9 mg/day; P=0.0007). CONCLUSIONS: MPS patients with the lesion in the MB appear to need a higher opioid dose for pain control than patients with the lesion in the MA.

Acute Amelioration of Inflammatory Activity Caused by Endothelin-2 Deficiency during Acute Lung Injury.

In acute lung injury (ALI), a severe insult induces a hyperinflammatory state in the lungs. The mortality rate of severe ALI remains high, and novel mechanistic insights are required to improve therapeutic strategies. Endothelin-2 (Edn2), the least studied isoform of endothelin, is involved in lung physiology and development and can be affected by various factors. One of them is inflammation, and another isoform of endothelin, endothelin-1 (Edn1), affects lung inflammatory responses. Considering the importance of Edn2 in the lungs and how Edn2 works through the same receptors as Edn1, we postulated that Edn2 may affect inflammatory responses that are central to ALI pathophysiology. In this study, we performed 24 hours intratracheal lipopolysaccharide (LPS) instillation or PBS control as an in vivo ALI model in eight-week-old conditional Edn2 knockout mice (Edn2-iKO), with Edn2-floxed mice as controls. Bronchoalveolar lavage (BAL) fluid and tissue were collected after exsanguination and analyzed for its cellular, molecular, functional, and histological inflammatory phenotypes. We found that Edn2-iKO mice displayed a reduced pro-neutrophilic inflammatory phenotype even after acute LPS treatment, shown by the reduction in the overall protein concentration and neutrophil count in bronchoalveolar lavage fluids. Further investigation revealed a reduction in mRNA interferon gamma (IFNγ) level of Edn2-iKO lungs and suppression of its downstream signaling, including phosphorylated level of STAT1 and IL-1ß secretion, leading to reduced NFĸB activation. To conclude, Edn2 deletion suppressed acute lung inflammation by reducing neutrophil-mediated IFNγ/STAT1/IL-1ß/NFĸB signaling cascade. Targeting Edn2 signaling may be beneficial for the development of novel treatment options for ALI.

Living donor liver transplantation for a patient with acute liver failure following thyroid storm: a case report.

BACKGROUND: Thyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest. CASE REPORT: The patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications-including intra-abdominal hemorrhaging and ischemic changes in the intestine-her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function. CONCLUSIONS: To our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

Hyperoxia but not high tidal volume contributes to ventilator-induced lung injury in healthy mice.

BACKGROUND: Mechanical ventilation is a supportive therapy used to maintain respiratory function in several clinical and surgical cases but is always accompanied by lung injury risk due to improper treatment. We investigated how tidal volume and oxygen delivery would contribute independently or synergistically to ventilator-induced lung injury (VILI). METHODS: Under general anesthesia and tracheal intubation, healthy female C57BL/6 N mice (9 weeks old) were randomly ventilated for 2 h by standard (7 ml/kg) or high (14 ml/kg) tidal volume at positive end-expiratory pressure (PEEP) of 2 cmH2O, with room air, 50% O2 (moderate hyperoxia), or 100% O2 (severe hyperoxia); respectively. Mice were sacrificed 4 h after mechanical ventilation, and lung tissues were collected for experimental assessments on lung injury. RESULTS: Compared with the healthy control, severe hyperoxia ventilation by either standard or high tidal volume resulted in significantly higher wet-to-dry lung weight ratio and higher levels of IL-1ß and 8-OHdG in the lungs. However, moderate hyperoxia ventilation, even by high tidal volume did not significantly increase the levels of IL-1ß and 8-OHdG in the lungs. Western blot analysis showed that the expression of RhoA, ROCK1, MLC2, and p-MLC2 was not significantly induced in the ventilated lungs, even by high tidal volume at 2 cmH2O PEEP. CONCLUSION: Severe hyperoxia ventilation causes inflammatory response and oxidative damage in mechanically ventilated lungs, while high tidal volume ventilation at a reasonable PEEP possibly does not cause VILI.

Venoarterial extracorporeal membrane oxygenation for group B streptococcal toxic shock syndrome: A case report and literature review.

RATIONALE: Streptococcal toxic shock syndrome (STSS) rapidly leads to refractory shock and multiple organ failure. The mortality rate among patients with STSS is 40%; however, most deaths occur within a few days of onset. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) may help avoid acute death in adult patients with STSS. However, the effectiveness of VA-ECMO is unclear. In this study, we report a case of group B STSS, which was successfully treated with VA-ECMO despite cardiopulmonary arrest (CPA) owing to rapidly progressive refractory shock. PATIENT CONCERNS: A 60-year-old woman was hospitalized because of diarrhea and electrolyte abnormalities owing to chemoradiation therapy for rectal cancer. A sudden deterioration of her condition led to CPA. Conventional cardiopulmonary resuscitation was immediately performed but was ineffective. Therefore, VA-ECMO was initiated. Contrast-enhanced computed tomography revealed duodenal perforation. Hence, septic shock owing to peritonitis was diagnosed, and emergency surgery was performed under VA-ECMO. However, the patient had progressive multiple organ failure and required organ support therapy in the intensive care unit (ICU). DIAGNOSES: On day 2 in the ICU, blood and ascites fluid culture tests revealed beta-hemolytic streptococci, and the patient was finally diagnosed as having STSS caused by Streptococcus agalactiae. INTERVENTIONS: Clindamycin was added to meropenem, vancomycin, and micafungin, which had been administered since the sudden deterioration. In addition, VA-ECMO, mechanical ventilation, blood purification therapy, and treatment for disseminated intravascular coagulation were continued. OUTCOMES: Thereafter, hemodynamics improved rapidly, and the patient was weaned off VA-ECMO on day 5 of ICU admission. She was transferred to a general ward on day 22 in the ICU. LESSONS: In patients with fatal STSS and rapid progressive refractory shock or CPA, VA-ECMO may help to avoid acute death and improve prognosis by ameliorating tissue oxygenation and providing extra time to treat invasive streptococcal infection.

Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction.

Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin ßA. We demonstrate that activin A, a homodimer of inhibin ßA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin ßA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target.

Effects of the attachment method of the stimulating electrodes Nihon-Kohden NM-345Y™ and changes in forearm position on stimulus current values during calibration in electromyography-based neuromuscular monitoring: a single-center experimental study.

PURPOSE: The traditionally recommended method for attaching electromyography (EMG) electrodes (NM-345Y™) during EMG-based neuromuscular monitoring developed by Nihon-Kohden may decrease the monitoring accuracy when forearm limb position changes. This study investigated methods for attaching stimulating electrodes that maintained stable EMG-based neuromuscular monitoring accuracy, regardless of forearm limb position changes. METHODS: This single-center experimental study recruited 28 healthy adults from October 2022 to December 2022. The NM-345Y™ was attached to the forearm using three patterns: Pattern N, electrodes attached according to the attachment pattern recommended by Nihon-Kohden; Pattern U, electrodes attached along the ulnar nerve identified using an ultrasound device; Pattern C, electrodes attached where the ulnar nerve crosses the line connecting the centers of the anode and cathode of the stimulating electrodes. The stimulus current values during calibration were measured at three forearm positions for each attachment pattern: supination 90 degrees; pronation 0 degrees; pronation 90 degrees. The differences in stimulus current values caused by forearm position changes were calculated as the difference between values at supination 90 degrees and pronation 0 degrees and between values at supination 90 degrees and pronation 90 degrees. RESULTS: Pattern C showed significantly smaller differences than Pattern N between the stimulus current values at supination 90 degrees and pronation 0 degrees (p = 0.018) and between the stimulus current values at supination 90 degrees and pronation 90 degrees (p = 0.008). CONCLUSION: Crossing the ulnar nerve with the line connecting the anode and cathode of the stimulating electrodes may stabilize EMG-based neuromuscular monitoring accuracy.

Refractory cardiac arrest caused by type I Kounis syndrome treated with adrenaline and nicorandil: A case report.

RATIONALE: Kounis syndrome is a rare but life-threatening anaphylactic reaction that can lead to acute coronary syndrome and cardiac arrest, and requires prompt diagnosis. Adrenaline, which is used to treat anaphylaxis, may cause coronary vasoconstriction and worsen ischemia, whereas coronary vasodilators may dilate systemic vessels and exacerbate hypotension. Delayed diagnosis of Kounis syndrome and inadequate therapeutic intervention may thus lead to a poor outcome. PATIENT CONCERNS: A 59-year-old man was treated for sepsis due to a liver abscess. Following administration of daptomycin, the patient developed severe anaphylactic shock leading to refractory cardiac arrest. Because conventional cardiopulmonary resuscitation was ineffective, extracorporeal cardiopulmonary resuscitation was considered as an alternative approach. DIAGNOSES: On bedside monitoring during cardiopulmonary resuscitation, unexpected ST-segment elevation was found on lead II electrocardiogram. Accordingly, the patient was clinically diagnosed with Kounis syndrome. INTERVENTIONS: Nicorandil (6 mg/h), a coronary vasodilator with minimal blood pressure effects, was administered along with high doses of vasopressors, including adrenaline 0.2 µg/kg/min. OUTCOMES: After the initiation of nicorandil administration, the patient achieved return of spontaneous circulation and did not require extracorporeal cardiopulmonary resuscitation. Based on the elevated serum tryptase level, normal creatine kinase-MB range, and lack of stenosis on coronary angiography, the patient was definitively diagnosed with type I (coronary vasospasm) Kounis syndrome. He was subsequently transferred to the referring hospital without neurological sequelae. LESSONS: If anaphylaxis leads to refractory shock and cardiac arrest, ischemic changes on the electrocardiogram should be investigated to identify underlying Kounis syndrome. In addition to adrenaline, coronary dilators are the definitive treatment. Nicorandil may be a useful treatment option because of its minimal effect on blood pressure.

Examination of stabilization of sedation by Nasal High Flow in patients with endoscopic retrograde cholangiopancreatography during sedation using Dexmedetomidine.

INTRODUCTION: Dexmedetomidine is used for the sedation method in the case of endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of relieving patient anxiety. It has been reported that CO2 accumulated during sedation causes an arousal reaction, so how to normalize CO2 during sedation can be improved by administration of the minimum necessary sedative.Nasal High Flow oxygen therapy (NHF) uses a mild positive pressure load that improves carbon dioxide washout and reduces rebreathing to improve respiratory function and therefore is widely used to prevent hypoxemia and hypercapnia. In this study, we will investigate whether the upper airway patency would be maintained and the hypercapnia and hypoxemia during sedation would be prevented, by applying NHF as a respiratory management method to patients undergoing ERCP under sedation. METHODS/DESIGN: In a randomized comparative study of 2 groups, the NHF device use group and the nasal cannula use group, for adult patients who visited the Nagasaki University Hospital and underwent ERCP examination under sedation. For sedation, Dexmedetomidine will be used in combination with and Midazolam and evaluation by anesthesiologist. In addition, as an analgesic, pethidine hydrochloride was administered intravenously. The total dose of the analgesic pethidine hydrochloride used in combination is used as the primary endpoint. As a secondary evaluation item, the percutaneous CO2 concentration is evaluated with a TCO2 monitor to examine whether it is effective in preventing hypercapnia. Furthermore, we will evaluate the incidence of hypoxemia with a percutaneous oxygen saturation value of 90% or less, and examine whether the use of equipment is effective in preventing the occurrence of hypercapnia and hypoxemia. DISCUSSION: The purpose of this study was to obtain evidence for the utility of NHF as a potential therapeutic device for patients undergoing an ERCP under sedation, assessed by determining if the incidence rates of hypercapnia and hypoxemia decreased in the NHF device group, compared to the control group that did not use of this device.

Acute mesenteric ischemia diagnosed using the aquarium sign: A case report.

RATIONALE: The diagnosis of mesenteric ischemia in critically ill patients remains challenging; however, the aquarium sign, comprising a large number of bubble images in the right cardiac chambers on echocardiography, may be used as a point-of-care ultrasound finding to diagnose acute mesenteric ischemia (AMI). PATIENT CONCERNS: A 65-year-old woman diagnosed with lymphoma was urgently admitted to the intensive care unit with suspected tumor lysis syndrome. High-dose vasopressor and inotropic agents were required to manage the patient's shock with marked lactic acidosis and peripheral hypoperfusion with mottled skin, and multidisciplinary treatment was initiated. By day 6, the lactate levels normalized and there were no abnormal abdominal findings. An echocardiogram was performed to examine the mass lesion associated with lymphoma in the right atrium and evaluate the hemodynamics; it revealed an "aquarium sign." Similar findings were found in the inferior vena cava and portal vein. DIAGNOSES: Contrast-enhanced computed tomography of the abdomen revealed hepatic portal vein gas, poor contrast of the colon wall, and intramural emphysema, and a diagnosis of AMI was made. Lower gastrointestinal endoscopy showed necrosis of the colon. INTERVENTIONS: The patient underwent urgent subtotal colorectal resection. OUTCOMES: Although a tracheostomy was required, the patient's general condition improved after surgery, and she was discharged to the ward without mechanical ventilatory support in the intensive care unit on Day 19. LESSONS: In patients with risk factors for AMI, repeated evaluation for the presence of aquarium signs by echocardiography may be warranted, even if there are no abdominal findings or abnormalities in biomarkers, such as lactate levels and trends. When the aquarium sign is found, AMI should be aggressively suspected, and a definitive diagnosis should be made to initiate early therapeutic intervention.

Modifications of peripheral perfusion in patients with vasopressor-dependent septic shock treated with polymyxin B-direct hemoperfusion.

Abnormal peripheral perfusion (PP) worsens the prognosis of patients with septic shock. Polymyxin B-direct hemoperfusion (PMX-DHP) increases blood pressure and reduces vasopressor doses. However, the modification of PP following administration of PMX-DHP in patients with vasopressor-dependent septic shock have not yet been elucidated. A retrospective exploratory observational study was conducted in patients with septic shock treated with PMX-DHP. Pulse-amplitude index (PAI), vasoactive inotropic score (VIS), and cumulative fluid balance data were extracted at PMX-DHP initiation (T0) and after 24 (T24) and 48 (T48) h. Changes in these data were analyzed in all patients and two subgroups (abnormal PP [PAI < 1] and normal PP [PAI ≥ 1]) based on the PAI at PMX-DHP initiation. Overall, 122 patients (abnormal PP group, n = 67; normal PP group, n = 55) were evaluated. Overall and in the abnormal PP group, PAI increased significantly at T24 and T48 compared with that at T0, with a significant decrease in VIS. Cumulative 24-h fluid balance after PMX-DHP initiation was significantly higher in the abnormal PP group. PMX-DHP may be an effective intervention to improve PP in patients with abnormal PP; however, caution should be exercised as fluid requirements may differ from that of patients with normal PP.

Practical guide for safe sedation.

This practical guide has been developed to ensure safe and effective sedation performed in adult patients outside of the operating room, for instance in intensive care units and dental treatment rooms and in the field of palliative care. Sedation levels are classified based on level of consciousness, airway reflex, spontaneous ventilation, and cardiovascular function. Deep sedation induces loss of consciousness and protective reflexes, and can cause respiratory depression and pulmonary aspiration. Invasive medical procedures necessitating deep sedation include cardiac ablation, endoscopic submucosal dissection, and internal radiation therapy. Appropriate analgesia is necessary for procedures that require deep sedation. The sedationist should evaluate the risks of the planned procedure, explain the sedation process to the patient, and obtain the patient's informed consent. Major parameters to be evaluated preoperatively are the patient's airway and general condition. Equipment, instruments, and drugs necessary for emergency situations should be defined and routinely maintained. To prevent aspiration, patients scheduled for moderate or deep sedation should fast preoperatively. In both inpatients and outpatients, biological monitoring should be continued until the discharge criteria are met. Anesthesiologists should be involved in management systems that ensure safe and effective sedation even if they do not personally perform all sedation procedures.

Inactivating the Uninhibited: The Tale of Activins and Inhibins in Pulmonary Arterial Hypertension.

Advances in technology and biomedical knowledge have led to the effective diagnosis and treatment of an increasing number of rare diseases. Pulmonary arterial hypertension (PAH) is a rare disorder of the pulmonary vasculature that is associated with high mortality and morbidity rates. Although significant progress has been made in understanding PAH and its diagnosis and treatment, numerous unanswered questions remain regarding pulmonary vascular remodeling, a major factor contributing to the increase in pulmonary arterial pressure. Here, we discuss the role of activins and inhibins, both of which belong to the TGF-ß superfamily, in PAH development. We examine how these relate to signaling pathways implicated in PAH pathogenesis. Furthermore, we discuss how activin/inhibin-targeting drugs, particularly sotatercep, affect pathophysiology, as these target the afore-mentioned specific pathway. We highlight activin/inhibin signaling as a critical mediator of PAH development that is to be targeted for therapeutic gain, potentially improving patient outcomes in the future.

Management of Combined Cardiac Surgery Using Cardiopulmonary Bypass With Acute Normovolemic Hemodilution in a Jehovah's Witness: A Case Report.

Combined cardiac surgery under cardiopulmonary bypass (CPB) has a high risk of requiring blood transfusion. Performing this surgery on Jehovah's Witnesses (JWs) is challenging as they strictly refuse allogeneic blood transfusions due to their religious beliefs. A 73-year-old female JW patient underwent combined surgery involving coronary artery bypass grafting and mitral valvuloplasty under CPB. Preoperative hematopoiesis maintained the hemoglobin (Hb) level at >12 g/dL preoperatively; the Hb level was maintained at >7 g/dL during CPB for effective acute normovolemic hemodilution (ANH). Compared with the values obtained immediately after CPB weaning, the Hb level and coagulation functions (measured using viscoelastic tests) improved after autologous transfusion at the end of the surgery. When cardiac surgery under CPB is performed on JWs, ANH can be useful for maintaining postoperative Hb levels and coagulation factors. Sufficient preoperative hematopoiesis and determination of an appropriate volume for intraoperative ANH may be important for effective ANH.