Circulatory Stability Research Articles

Ciprofol versus propofol for anesthesia induction in cardiac surgery: a randomized double-blind controlled clinical trial

BackgroundCiprofol, a novel intravenous general anesthetic with a chemical structure similar to propofol, exhibits significantly enhanced potency. It offers a rapid onset, reduced incidence of injection pain, and has comparable effects on heart rate and blood pressure to propofol. However, clinical data on its use for anesthesia induction in cardiac surgery remain limited.MethodsSeventy-eight patients undergoing coronary artery bypass grafting or valve replacement surgery were randomly assigned to receive either ciprofol (N = 40) or propofol (N = 38) for anesthesia induction. Variables recorded included changes in mean arterial pressure and heart rate during anesthesia, alterations in the oxygenation index and lactic acid concentration before and 10 min after anesthesia induction, and the incidence of adverse events such as bradycardia, hypotension, and injection pain.ResultsThe incidence of anesthesia-induced injection pain was significantly lower in the ciprofol group compared to the propofol group (3% vs. 18%, P < 0.05). The incidence of other adverse events was similar between the groups. No significant differences in hemodynamics or oxygenation index were observed during anesthesia induction between ciprofol and propofol.ConclusionsCiprofol demonstrated a significantly lower incidence of injection pain compared to propofol, potentially improving patient comfort during anesthesia induction. Additionally, ciprofol showed comparable circulatory stability to propofol during anesthesia induction in cardiac surgery, suggesting it may be a suitable alternative to propofol for this application.Trial registrationThe trial was registered at the ClinicalTrials.gov on 03/10/2024 (NCT06312345).

Exo-Cleavable Linkers: Enhanced Stability and Therapeutic Efficacy in Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) combine cytotoxic payloads with monoclonal antibodies through chemical linkers. Finding linkers that both enhance circulatory stability and enable effective tumor payload release remains a challenge. The conventional valine-citrulline (Val-Cit) linker is associated with several inherent drawbacks, including hydrophobicity-induced aggregation, a limited drug-antibody ratio (DAR), and premature payload release. This study introduces an exolinker approach, repositioning the cleavable peptide linker at the exo position of the p-aminobenzylcarbamate moiety, as an advancement over conventional linear linkers. This design, which incorporates hydrophilic glutamic acid, addresses the limitations of the Val-Cit platform and improves the ADC in vivo profiles. In vitro and in vivo evaluations showed that exolinker ADCs reduced premature payload release, increased drug-to-antibody ratios, and avoided significant aggregation, even with hydrophobic payloads. Furthermore, the payload remained stably attached to the ADC even in the presence of enzymes like carboxylesterases and human neutrophil elastase, indicating the potential for a favorable safety profile.

Severe sepsis induced by zoledronic acid: A case report.

Zoledronic acid is one of the most commonly used intravenous, highly potent amino diphosphonate salts worldwide and is commonly used in patients with primary or secondary osteoporosis, most of whom are well tolerated. There are currently no reports of severe sepsis induced by zoledronic acid. Here we present the first case of severe sepsis induced by zoledronic acid. We reviewed the literature and found that there is currently a lack of reports on severe sepsis induced by zoledronic acid or other diphosphonates. A 58-year-old woman with severe osteoporosis and Behcet disease developed severe sepsis after treatment with zoledronic acid. Sepsis, septic shock, acute kidney injury, intestinal infection, Behcet disease. The patient was given intensive care immediately after admission, and massive fluid infusion to expand blood volume could not maintain normal blood pressure. Metaraminol was added to maintain circulatory stability, piperacillin-tazobactam was used to strengthen anti-infection, and glucocorticoids were used for anti-inflammatory treatment. The patient was discharged with improvement and followed up in the outpatient clinic. The inducing mechanism of zoledronic acid is not clear, but when the patient has immunosuppression, the use of zoledronic acid should be cautious and monitored. In conclusion, severe sepsis induced by zoledronic acid is a rare but serious complication, and physicians should be aware of this adverse event in time to avoid serious consequences.

All lactate are not equal substudy of the BOX trial

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The BOX trial was supported by a grant (NNF17OC0028706) from the Novo Nordisk Foundation. Dr. Hassager's work is funded by a grant (R186-2015-2132) from the Lundbeck Foundation. Background Lactate levels following out-of-hospital cardiac arrest (OHCA) are associated with arrest duration (time to ROSC) and mortality. However, given the complexity of lactate generation and clearance, lactate levels assessed at hospital arrival represent not only time to ROSC but also the quality of resuscitation, circulatory stability following ROSC, dose of epinephrine administered, kidney, liver, and mitochondrial function in the early post-cardiac arrest phase. Accordingly, we describe the lactate levels at hospital arrival according to time to ROSC and one-year mortality. Method In this sub-study of the randomized clinical BOX trial, blood lactate levels were measured immediately at hospital arrival. Time to ROSC was registered in the medical records. Patients were divided into two groups according to median time to ROSC (≤ 18 min or &amp;gt; 18 min). The primary outcome was one-year mortality. Results The study included 768 (97% of the randomized population) patients of which 386 (50%) patients had ≤ 18 min and 382 (50%) patients had &amp;gt; 18 min to ROSC. The median age (64 (54-73) years) and sex distribution (81% men) was similar in both groups. One-year mortality was 76 (20%) and 199 (52%) in the ≤ 18 min and &amp;gt; 18 min to ROSC groups respectively. Mean lactate levels were 3.8 mmol/L (95%CI: 3.5-4.1) and 5.9 mmol/L (95%CI: 5.4-6.2), respectively. Lactate levels differed significantly between one-year survivors and non-survivors in the patients with ≤ 18 min to ROSC (mean difference: 1.9 mmol/L, 95%CI: 1.0 - 2.8) but not for patients with &amp;gt; 18 min to ROSC (mean difference: 0.6 mmol/L, 95%CI: -0.1-1.3), Figure 1. Further, lactate’s ability to predict one-year mortality was fair in the ≤ 18 min group with an Area Under Receiver Operating Characteristic Curve (AUC) of 0.68 (95%CI: 0.62-0.75) but poor for the &amp;gt; 18 min groups with an AUC of 0.55 (95%CI: 0.50-0.61) (DeLong's test for two ROC curves, p = 0.004), Figure 2. Conclusion Lactate's predictive value for one-year mortality decreases with increasing time to ROSC in OHCA. This highlights the importance of individualized clinical approaches based on lactate dynamics in OHCA patients.Figure 1Figure 2

Analysis of the application effect and safety of transnasal humidified rapid insufflation ventilatory exchange technique in hysteroscopic diagnostic and therapeutic surgery

Objective: To investigate the effect and safety of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) technique in hysteroscopic diagnostic and therapeutic surgery. Methods: This study was a randomized controlled trial. A total of 100 female patients undergoing hysteroscopy surgery at Beijing Tongren Hospital from September to December 2023 were selected and randomly divided into two groups by the random number table method: the THRIVE group and the mask oxygen group, with 50 patients in each group. Patients in both groups were given total intravenous anesthesia with propofol combined with remifentanil and preserved spontaneous respiration. The THRIVE group was given oxygen by the THRIVE device with an oxygen flow rate of 50 L/min, while the mask oxygen group was given oxygen by the mask with an oxygen flow rate of 5 L/min; the oxygen concentration of both groups was set at 100%. The general condition of the patients, vital signs during the operation, the amount of anesthesia drugs used and the operation time were recorded. The primary observation index was the incidence of hypoxic events in the two groups; the secondary observation indexes were the incidence and time of intraoperative apnea as well as the corresponding oxygenation interventions and the incidence of non-hypoxic adverse events. Results: The age of the THRIVE group was (42±14) years, and the age of the mask oxygen group was (43±15) years. The duration of surgery in the THRIVE group was (15.9±3.4) min, which was statistically lower than that of the mask oxygen group (16.3±4.5) min (P=0.041), and there were no differences observed in the duration of awakening time and anesthesia time (both P>0.05). There was no significant difference in the dosage of propofol, remifentanil, and intraoperative vasoactive drugs between the two groups (all P>0.05). The SpO2 of the patients in the THRIVE group at the end of the operation was (99.7±1.1) %, which was higher than that of the mask-oxygen group (99.1±1.1) % (P<0.05). There was no difference in SpO2 of the two groups at the other time points (all P>0.05). There were no differences in HR and MAP of two group patients at each time point (all P>0.05). The incidence of hypoxic events in the THRIVE group was 12.0% (6/50), which was lower than that of 28.0% (14/50) in the mask oxygen group (P=0.045). The difference in the incidence and duration of apnea between the two groups was not statistically significant (all P>0.05). There were no cases of temporary need for laryngeal mask or tracheal intubation during surgery in both groups. There was no statistically significant difference in the incidence of intraoperative body movement, dizziness, nausea and vomiting between the two groups (all P>0.05), and no cardiac, cerebral, renal or other important organ insufficiency occurred in the two weeks after surgery. Conclusion: THRIVE technology can provide effective oxygenation for patients undergoing hysteroscopic diagnosis and treatment, maintain patients' circulatory stability, and improve the safety and efficiency of surgery.

Salvage treatment of acute respiratory failure after autogenous tissue flap transplantation for chronic empyema with chest wall sinus: a case report and literature review

BackgroundChronic empyema with chest wall sinus is a difficult and complex disease caused by multiple causative factors. It is difficult to control local infection due to its possible combination of bronchopleural fistula (BPF) and residual bone.The relevant literature emphasizes some risk factors for empyema progression after pneumonectomy, while the correlation between empyema and BPF after pneumonectomy increases mortality by infecting the remaining lungs. After pneumonectomy, the lung function of the contralateral side is particularly important.Case presentationThis paper reports a 62-year-old male patient who underwent right pneumonectomy for squamous cell carcinoma of the lung 12 years ago and began to develop empyema with anterior chest wall sinus 3 years ago. After admission, chest computed tomography (CT) showed right pleural effusion and formation of chest wall sinus. According to his clinical symptoms and imaging examination, he was diagnosed as chronic empyema with chest wall sinus.Due to the huge residual cavity of the patient,the clinical effect of using free vastus lateralis myocutaneous flap combined with pedicled pectoralis major muscle flap to fill the abscess cavity was satisfactory,but acute respiratory failure occurred due to left lung aspiration pneumonia after operation.ConclusionsAfter a series of treatment measures such as tracheal cannula, tracheotomy, anti-infection, maintenance of circulatory stability, and rehabilitation training, the patient was ultimately rescued and cured. Postoperative follow-up showed that the muscle flaps survived and empyema was eliminated.

Recent progress of porphyrin metal-organic frameworks for combined photodynamic therapy and hypoxia-activated chemotherapy.

Nanoscale metal-organic frameworks integrated with porphyrins (Por-nMOFs) have emerged as efficient nanoplatforms for photodynamic therapy (PDT), which relies on the conversion of molecular oxygen into cytotoxic singlet oxygen. However, the hypoxic microenvironment within tumors significantly limits the efficacy of PDT. To address this challenge, researchers have explored various strategies to either alter or exploit the hypoxic conditions in tumors. One such strategy involves leveraging the porous structure of Por-nMOFs to load hypoxia-activated prodrugs (HAPs) like tirapazamine (TPZ), thereby utilizing the tumor's intrinsic hypoxic environment to trigger a chemotherapeutic effect that synergizes with PDT. Advances in nanoscience have enabled the development of porphyrin-based nMOFs capable of simultaneously loading both porphyrin photosensitizers and TPZ, ensuring effective release within cancer cells under high-phosphate conditions. The subsequent activation of co-loaded TPZ, by the tumor's own hypoxic microenvironment, and that created during PDT, facilitates a combined PDT and chemotherapy approach. This method not only enhances the suppression of cancer cell proliferation but also improves control over tumor metastasis while mitigating the negative impact of hypoxia on singular Por-nMOFs in PDT. This review summarizes recent advances in Por-nMOFs research, focusing on the design strategies for enhancing water dispersibility, circulatory stability, and targeting specificity through post-synthetic modifications. Additionally, this review highlights the bioapplication of Por-nMOFs by integrating TPZ chemotherapy and other therapeutic modalities to combat hypoxic and metastatic malignancies. We anticipate that this review will inspire further research into Por-nMOFs and advance their application in biomedicine.

Remimazolam tosilate infusion has a lower incidence of hypotension than propofol infusion during painless colonoscopy

Background: Remimazolam tosilate is an ultra-short-acting sedative drug with the advantages of rapid onset and recovery, mild respiratory, and circulatory inhibition. This study primarily investigated the effect of remimazolam on incidence of intraoperative hypotension compared to the widely used propofol in patients undergoing outpatient painless colonoscopy. Methodology: This was a double-blinded, randomized, controlled trial. We randomly divided the eligible patients with outpatient appointment for painless colonoscopy in our hospital into the remimazolam group and the propofol group. The modified observer’s assessment of alert/sedative was used to evaluate the depth of the patient's sedation. The Narcotrend score was monitored throughout the whole process. In the propofol group, propofol 0.5-1.5 mg/kg was infused intravenously as a loading dose, followed by 3-5 mg/kg/h to maintain a satisfied sedation depth during operation. While, with regarding to the patients in remimazolam group, remimazolam 0.05-0.15 mg/kg was induced intravenously as a loading dose, and continuously pumped at a rate of 0.3-0.5 mg/kg/h. SPSS 23.0 software was used to analyze the data. Results: From December 2020 to March 2021, we enrolled 116 eligible patients. The incidence of hypotension during sedation (13.8%) in the remimazolam group was significantly lower than that in propofol (37.9%), and the success rate of remimazolam (98.3%) was slightly lower than propofol (100.0%), but the awakening time was significantly shorter (P &lt; 0.001); The incidence of respiratory inhibition, nausea, vomiting and other adverse events during colonoscopy, remimazolam was significantly lower than that of propofol (P &lt; 0.05). Conclusion: Remimazolam tosilate still has higher circulatory stability than propofol in painless colonoscopy under continuous administration with a loading dose. Trial registration: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2000040557), data of registration: December 2020. Abbreviations: BMI- Body Mass Index; MOAA/S- Modified Observer’s Assessment of Alert Scale; MAP- Mean Arterial Pressure; Rem- Remimazolam; Pro- Propofol Key words: Remimazolam tosilate; Propofol; Painless Colonoscopy; Hypotension Citation: Li S, Zhang Y, Wang H, Ye G, Yao N, Zhu X. Continuous remimazolam tosilate infusion has a lower incidence of hypotension than propofol infusion for sedation in painless colonoscopy. Anaesth. pain intensive care 2022;27(6):697−705; DOI: 10.35975/apic.v27i6.2341 Received: Aug 27, 2023; Revised: October 16, 2023; Accepted: October 16, 2023

Alleviating morphine-induced itching while sustaining its analgesic efficacy: Esketamine as a potential co-administrating choice

Morphine is one of the most commonly used and effective analgesic drugs in clinical practice. Morphine injected directly into the epidural and subarachnoid space acts directly on the central nervous system compared to oral or intravenous administration. This route of morphine delivery requires only a small dose to achieve satisfactory analgesia and greatly reduces the risk of adverse effects. However, morphine-induced itching significantly limits the clinical use of morphine and the maximization of its analgesic effects. Drugs commonly used worldwide to treat morphine-induced pruritus have different degrees of limitations. N-Methyl-D-aspartate (NMDA) receptors are involved in the mechanisms associated with morphine-induced itching. Theoretically, esketamine, an NMDA antagonist, which is commonly used in clinical practice to exert analgesic and sedative effects and contributes to circulatory stability, has the potential to effectively relieve morphine-induced itching without compromising its analgesic effects. In this paper, we discuss the possibility of co-administration of esketamine in cases of morphine-induced pruritus based on the current clinical situation and relevant mechanisms, with the intention of developing novel therapeutic options for morphine-induced pruritus.

Impact of wrist-ankle acupuncture on propofol dosage under the dual monitoring of density spectrum array and anesthesia consciousness index in elderly patients undergoing urologic surgery: a sham-controlled randomized clinical trial.

Propofol is a widely used intravenous anesthetic in clinic. However, it is easy to cause serious circulatory fluctuation in elderly patients, so the dose should be reduced as appropriate. Studies have shown that wrist-ankle acupuncture (WAA) can reduce the dosage of propofol in patients undergoing painless endoscopy. Unfortunately, there is no report on whether WAA will reduce the dosage of propofol when used for anesthesia in elderly patients. The purpose of this study is to observe the effect of WAA on propofol dosage in elderly patients, and to provide a new method for maintaining circulatory stability in elderly patients under general anesthesia. From October 2022 to December 2022, Hebei Provincial Hospital of Traditional Chinese Medicine was selected. Forty-four elderly patients undergoing general anesthesia in urology department were randomly divided into two groups according to the complete random method with WAA group, consisting of 22 individuals, and non-WAA (NWAA) group, also consisting of 22 individuals. Both groups were treated with WAA or false needle acupuncture at the same site before anesthesia, respectively, and the needle was kept until the operation was finished. During the operation, the dosage of propofol was adjusted according to the depth of field monitoring density spectrum array (DSA) and anesthesia consciousness index (Ai) with anesthesia monitor. A total of 44 patients participated in this study, and all of them completed the experiment. There were no significant difference in sex, age, height, weight, duration of anesthesia, liver and kidney function, score of Fried frailty scale, activity of daily living (ADL), age-adjusted Charlson comorbidity index (aCCI) and mini-cognitive test (Mini-Cog) between the two groups (P>0.05), but the total dose of propofol (WAA =121.5, NWAA =170.5) mg and maintenance dose (WAA =1.02±0.55, NWAA =1.76±0.67) mg/kg/h, utilization rate of vasoactive drugs during operation, recovery time after anesthesia (WAA =2, NWAA =3) min and surgeon satisfaction (WAA =9, NWAA =8.5) had significant differences (P<0.05). Compared with NWAA group, WAA group could reduce the dosage of propofol in anesthesia for elderly patients with exocrine secretion and was beneficial to circulatory stability. Chinese Clinical Trial Registry (ID: ChiCTR2100054132).

A Collection of Studies on Anesthesia Modalities, Anesthetic Drugs and Circulatory Stability in Elderly Patients

With the increase in the proportion of elderly population in the society, China is gradually entering an aging society. Elderly patients may require anesthesia during medical treatment, and considering the relatively high surgical risk of elderly patients, comprehensive consideration must be given to the selection of anesthesia and the use of anesthetic drugs. Induction of general anesthesia is a process in which patients undergo reversible drug inhibition from a physiological state to a surgically operable anesthesia state within a short period of time, but tracheal intubation and anesthesia inhibition can trigger cardiovascular reactions, especially in elderly patients with poor circulatory function, which can lead to hemodynamic fluctuations and affect the stability of circulatory function. As elderly patients age, their organ function decreases, and their reserve function deficiency under anesthetic stress can increase the risk of adverse cardiovascular events. The hemodynamic fluctuations of patients during the induction period of general anesthesia are large, and it is important to reduce the hemodynamic fluctuations and maintain the stability of circulatory function to improve the safety of surgery. At present, the commonly used methods for induction of general anesthesia include manual intravenous push, target-controlled infusion and constant-rate infusion by infusion pump, and the commonly used drugs for induction of general anesthesia include intravenous sedative anesthetics, intravenous analgesics, muscle relaxants and inhaled anesthetics. Based on this paper, we analyze the effects of general anesthesia, epidural anesthesia, lumbar anesthesia, and epidural anesthesia in the application of surgery in elderly patients and general anesthesia induction in the circulatory stability of elderly patients for a review, in order to more accurately and better guide further clinical anesthesia research.

Esketamine opioid-free intravenous anesthesia versus opioid intravenous anesthesia in spontaneous ventilation video-assisted thoracic surgery: a randomized controlled trial.

Opioid-free anesthesia (OFA) provides adequate analgesia and can reduce postoperative opioid consumption, but its efficacy in spontaneous ventilation video-assisted thoracic surgery (SV-VATS) has not been demonstrated. We aimed to investigate the hypothesis that OFA could provide the same perioperative pain control as opioid anesthesia (OA), maintain safe and stable respiration and hemodynamics during surgery, and improve postoperative recovery. Sixty eligible patients (OFA group: n=30; OA group: n=30) treated between September 15, 2022, and December 15, 2022, at The First Hospital of Guangzhou Medical University were included. They were randomized to receive standard balanced OFA with esketamine or OA with remifentanil combined with sufentanil. The primary outcome was the pain numeric rating score (NRS) at postoperative 24 h, and the secondary outcomes were intraoperative respiratory and hemodynamic data, opioid consumption, vasoactive drug dosage, and recovery in the post-anesthesia care unit and ward. There was no significant difference in the postoperative pain scores and recovery quality between the two groups. The OFA group had a significantly lower dose of phenylephrine (P=0.001) and a lower incidence of hypotension (P=0.004) during surgery. The OFA group resumed spontaneous respiration faster (P<0.001) and had a higher quality of lung collapse (P=0.02). However, the total doses of propofol and dexmetomidine were higher (P=0.03 and P=0.02), and the time to consciousness was longer (P=0.039) in the OFA group. OFA provides the same level of postoperative pain control as OA, but it is more advantageous in maintaining circulatory and respiratory stability and improving the quality of pulmonary collapse in SV-VATS.

A Patient with Extremely Severe Constrictive Pericarditis Underwent Emergency Pericardiectomy Without Cardiopulmonary Bypass

We report a case of a 58-year-old man admitted to hospital with severe constrictive pericarditis. An emergency pericardiectomy was planned due to the patient's orthopnea associated with hemodynamic instability. The patient performed pericardiectomy without cardiopulmonary bypass. The patient was found to be orthopnea and began to experience disturbance of consciousness after entering the operating room. Non-invasive blood pressure was 100/54 mmHg, accompanied by atrial fibrillation, the ventricular rate was 158 beats/min, and arterial oxygen saturation was 90% with air inhalation. After intubation, the ventricular rate rose to 187 beats/min, the blood pressure dropped to 65/45 mmHg, and vasopressors were urgently administered to maintain circulatory stability. At the same time, the internal jugular vein cannula was placed ultrasound-guided. During the operation, the central venous pressure (CVP) increased to 41.2 cmH₂O, and cerebral oxygen saturation dropped to 47.6%. Although the patient with severe constrictive pericarditis, we still performed pericardiectomy without cardiopulmonary bypass. The operation time was about 3 hours, and the patient was successfully transferred to the Intensive Care Unit (ICU) to continue monitoring and treatment, and the tracheal intubation was removed 48 hours after the operation and he was discharged 19 days after the operation. Real-time transesophageal echocardiography (TEE) monitoring played a crucial role in intraoperative management.

Effect of targeted coagulopathy management and 5% albumin as volume replacement therapy during lung transplantation on allograft function: a secondary analysis of a randomized clinical trial

BackgroundPrimary graft dysfunction (PGD) after lung transplantation (LuTx) contributes substantially to early postoperative morbidity. Both intraoperative transfusion of a large amount of blood products during the surgery and ischemia–reperfusion injury after allograft implantation play an important role in subsequent PGD development.MethodsWe have previously reported a randomized clinical trial of 67 patients where point of care (POC) targeted coagulopathy management and intraoperative administration of 5% albumin led to significant reduction of blood loss and blood product consumption during the lung transplantation surgery. A secondary analysis of the randomized clinical trial evaluating the effect of targeted coagulopathy management and intraoperative administration of 5% albumin on early lung allograft function after LuTx and 1-year survival was performed.ResultsCompared to the patients in the control (non-POC) group, those in study (POC) group showed significantly superior graft function, represented by the Horowitz index (at 72 h after transplantation 402.87 vs 308.03 with p < 0.001, difference between means: 94.84, 95% CI: 60.18–129.51). Furthermore, the maximum doses of norepinephrine administered during first 24 h were significantly lower in the POC group (0.193 vs 0.379 with p < 0.001, difference between the means: 0.186, 95% CI: 0.105–0.267). After dichotomization of PGD (0–1 vs 2–3), significant difference between the non-POC and POC group occurred only at time point 72, when PGD grade 2–3 developed in 25% (n = 9) and 3.2% (n = 1), respectively (p = 0.003). The difference in 1-year survival was not statistically significant (10 patients died in non-POC group vs. 4 patients died in POC group; p = 0.17).ConclusionsUtilization of a POC targeted coagulopathy management combined with Albumin 5% as primary resuscitative fluid may improve early lung allograft function, provide better circulatory stability during the early post-operative period, and have potential to decrease the incidence of PGD without negative effect on 1-year survival.Trial registrationThis clinical trial was registered at ClinicalTrials.gov (NCT03598907).

A universal GlycoDesign for lysosomal replacement enzymes to improve circulation time and biodistribution.

Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due in part to short circulation times and suboptimal biodistribution of the therapeutic enzymes. We previously engineered Chinese hamster ovary (CHO) cells to produce α-galactosidase A (GLA) with various N-glycan structures and demonstrated that elimination of mannose-6-phosphate (M6P) and conversion to homogeneous sialylated N-glycans prolonged circulation time and improved biodistribution of the enzyme following a single-dose infusion into Fabry mice. Here, we confirmed these findings using repeated infusions of the glycoengineered GLA into Fabry mice and further tested whether this glycoengineering approach, Long-Acting-GlycoDesign (LAGD), could be implemented on other lysosomal enzymes. LAGD-engineered CHO cells stably expressing a panel of lysosomal enzymes [aspartylglucosamine (AGA), beta-glucuronidase (GUSB), cathepsin D (CTSD), tripeptidyl peptidase (TPP1), alpha-glucosidase (GAA) or iduronate 2-sulfatase (IDS)] successfully converted all M6P-containing N-glycans to complex sialylated N-glycans. The resulting homogenous glycodesigns enabled glycoprotein profiling by native mass spectrometry. Notably, LAGD extended the plasma half-life of all three enzymes tested (GLA, GUSB, AGA) in wildtype mice. LAGD may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy.

Management of massive cerebral infarction as a complication of post-tonsillectomy and analysis of the risk factors: a case report

BackgroundThe majority of postoperative complications of tonsillectomy are bleeding. However, massive cerebral infarction following haemostasis is a very rare and serious complication and has rarely been reported clinically.Case presentationWe performed a left tonsillectomy on a patient with chronic tonsillitis. After that, active bleeding was found under the tonsillar fossa, so an exploratory hypopharyngeal haemostasis was performed. However, the bleeding worsened intraoperatively, so the patient was converted to a cervical angiographic embolization. The interventional procedure was completed successfully without an ectopic embolic event. After the procedure, the patient was transferred to the intensive care unit (ICU) and was diagnosed with acute massive cerebral infarction in the left cerebral hemisphere after awakening symptoms combined with cranial computed tomography angiography (CTA) results. Symptomatic treatment such as sedation and analgesia, dehydration to lower intracranial pressure, and maintenance of respiratory and circulatory stability was then administered. After treatment, the patient’s condition stabilized and he was transferred to the rehabilitation physiotherapy unit for rehabilitation.ConclusionPost-tonsillectomy haemorrhage can be augmented with a carotid arteriogram to clarify whether the tonsillar fossa is at a safe distance from the posterior internal carotid artery. Furthermore, interventional haemostasis can also be performed as early as possible to reduce the incidence of complications in cases of persistent post-tonsillectomy bleeding.

PRE-HOSPITAL MANAGEMENT OF UNSTABLE TACHYCARDIA COMPLICATED BY CARDIOGENIC PULMONARY EDEMA BASED ON A CASE STUDY

Aim: This work was aimed at presenting the standard of pre-hospital management for a patient with worrying symptoms who developed pulmonary edema as a result of circulatory failure in the hospital. The complication occurred despite the use of electrical cardioversion in unstable tachycardia. Material and methods: The work was casuistic. The method of the undertaken research was based on a case study. The research material was obtained through the analysis of the Medical Rescue Card, the Departure Order Card of the Medical Rescue Team and the hospital treatment information card. Conclusions: Pulmonary edema, especially in the acute phase, belongs to a clinical situation that is directly life-threatening and requires immediate medi-cal intervention. Hospitalization of a patient with pulmonary oedema is important in order to implement appropriate diagnostics and treatment aimed at achieving circulatory and respiratory stability of the patient.

Emergency management of oral corrosive poisoning based on case study

Poisoning is one of the reasons for which Emergency Medical Teams are called. They range from mild and asymptomatic incidents to those complicated by shock and Sudden Cardiac Arrest. The causes of poisoning may be related to accidental contact with a potentially poisonous substance, but also to deliberate use or exposure to poison for suicidal purposes. Some of these events are classified as situations subject to the assessment of forensic specialists. Rescue procedures in case of poisoning depend on the type of poison, the course of poisoning and the clinical signs presented by the patient. Medical Emergency Procedures should always be based on the pursuit of circulatory and respiratory stability of the patient. Pre-hospital management is aimed at limiting further absorption of the poison and, if possible, implementing causal treatment through the supply of antidotes. In the absence of a specific antagonist, the patient should be treated symptomatically.

Advanced hitchhiking nanomaterials for biomedical applications.

Hitchhiking, a recently developed bio-inspired cargo delivery system, has been harnessed for diverse applications. By leveraging the interactions between nanoparticles and circulatory cells or proteins, hitchhiking enables efficient navigation through the vasculature while evading immune system clearance. Moreover, it allows for targeted delivery of nutrients to tissues, surveillance of the immune system, and pathogen elimination. Various synthetic nanomaterials have been developed to facilitate hitchhiking with circulatory cells or proteins. By combining the advantages of synthetic nanomaterials and circulatory cells or proteins, hitchhiking nanomaterials demonstrate several advantages over conventional vectors, including enhanced circulatory stability and optimized therapeutic efficacy. This review provides an overview of general strategies for hitchhiking, choices of cells and proteins, and recent advances of hitchhiking nanomaterials for biomedical applications.

One Stone, Two Birds: A Peptide-Au(I) Infinite Coordination Supermolecule for the Confederate Physical and Biological Radiosensitization in Cancer Radiation Therapy.

Over half of cancer patients are subjected to radiotherapy, but owing to the deficient amount of reactive oxygen radicals (ROS) and DNA double-strand breaks (DSBs), a fair number of them suffer from radiotherapy resistance and the subsequent short-term survival opportunity. To overcome it, many successes have been achieved in radiosensitizer discovery using physical strategy and/or biological strategy, but significant challenges remain regarding developing clinically translational radiosensitizers. Herein, a peptide-Au(I) infinite coordination supermolecule termed PAICS is developed that combined both physical and biological radiosensitization and possessed pharmaceutical characteristics including adequate circulatory stability, controllable drug release, tumor-prioritized accumulation, and the favorable body eliminability. As expected, monovalent gold ion endowed this supermolecule with high X-ray absorption and the subsequent radiosensitization. Furthermore, a peptide targeting CRM1, is assembled into the supermolecule, which successfully activates p53 and apoptosis pathway, thereby further sensitizing radiotherapy. As a result, PAICS showed superior ability for radiotherapy sensitization in vivo and maintained a favorable safety profile. Thus, the PAICS reported here will offer a feasible solution to simultaneously overcome both the pharmaceutical obstacles of physical and biological radiosensitizers and will enable the development of a class of nanomedicines for tumor radiotherapy sensitization.