Single Bolus Research Articles

Maternal and fetal serum concentrations of magnesium after administration of a 6-g bolus dose of magnesium sulfate (MgSO4 ) to women with imminent preterm delivery.

Magnesium sulfate is used world-wide to treat pregnant women at imminent risk of preterm delivery in order to protect the brain of the premature infant. Previous research has shown that magnesium sulfate decreases the risk of cerebral palsy by ~30% in infants born preterm. Despite this, the dosage required for optimal neuroprotection remains unknown. We aimed to investigate whether 6 g magnesium sulfate given as a single bolus dose was tolerable for the women and infants and whether the desired target concentration in the mother's blood was reached and non-toxic level in the infant could be ensured. In total, 49 women who were at risk of delivery prior to 32 weeks of gestation were recruited. They received a bolus dose of 6 g magnesium sulfate intravenously between 1 and 24h prior to giving birth and were closely monitored during and after infusion. Blood samples from the patients were analyzed at different time-points (20-30min after start of infusion, 1, 2, 6 and 24h) post-administration. Blood samples from the umbilical cord were also taken directly after birth to assess the concentration of magnesium in the infant. None of the women who received magnesium sulfate reached serum magnesium concentrations >3.3 mmol/L. In all, 72% of the women showed serum magnesium levels within the therapeutic interval (2.0-3.5 mmol/L) and no adverse events were observed during the infusion. The serum magnesium levels in the mothers declined to pre-bolus-levels within 24h after delivery. Serum magnesium levels in the umbilical cord samples ranged from 0.87 to 1.4 mmol/L, which means that all but two were within the normal expected range for a newborn premature infant. A bolus dose of 6 g magnesium sulfate was well tolerated and without any serious side effects in either mother or infant. Most of our women reached the targeted concentration range of serum magnesium levels after infusion was completed. Their infants had magnesium levels within acceptable levels, regardless of gestational week or mother's body mass index.

Ampakine CX717 Stimulates Diaphragm Activity following Mid‐cervical Spinal Contusion Injury

Cervical spinal cord injuries result in significant respiratory compromise and there is a need to develop therapies to counter respiratory insufficiency in this patient population. Ampakines are positive allosteric modulators of AMPA receptors, and can stimulate breathing during states of hypoventilation, such as following opioid overdose or in neuromuscular disorders. Our laboratory has previously shown that acute treatment with ampakine CX717 can stimulate phrenic activity in spinally injured animals under urethane anesthesia. Recently, we extended these findings by showing that a low dose of CX717 was sufficient to enhance diaphragm electromyography (EMG) activity and tidal volume in unanaesthetized animals with a C2 hemisection injury. The next step in the translational pathway, and the goal of the current study, was to test the efficacy of ampakines in a model of contusion injury that is more similar to the injuries typically experienced by humans. The C4 contusion injury used in the current study results in direct phrenic motor neuron loss and significant damage of the spinal pathways innervating respiratory motor pools. This model is also associated with strong spontaneous recovery of diaphragm function, such that pronounced deficits are likely to be detected only in the initial week following injury. Animals were implanted with in‐dwelling bilateral diaphragm EMG electrodes and ventilation was measured using whole body plethysmography. At 4 and 14 days following a 150 kDy C4 unilateral contusion injury (C4Ct), male and female rats were given a single intravenous bolus of CX717 (5 mg/kg, n=4) or vehicle (2‐hydroxypropyl‐beta‐cyclodextrin; HPCD; n=4). At the 4‐day time point, infusion of CX717 increased peak diaphragm EMG (recorded ipsilateral to C4Ct) by 40‐50% when compared to vehicle group. Respiratory rate was also elevated in the CX717 group by 80% post‐infusion, indicating a likely supraspinal mechanism of the impact of ampakines. In the CX717 group, tidal volume was increased by 25±13% during infusion, 20±16% at 5 min post infusion and returned to baseline levels by 15 mins post CX717 infusion. There was no change in tidal volume in the vehicle group. During an acute respiratory challenge with hypoxia (10% O2), CX717 treated animals were able to increase diaphragm EMG (100±15%) to a greater extent as compared to vehicle (50 ± 23%, P=0.004). Similarly, during a combined hypoxia‐hypercapnia challenge (10% O2, 7% CO2), CX717 treated animals displayed an increased diaphragm EMG response (200±44%) compared to vehicle (100 ± 55%, P=0.0144). In contrast to the 4‐day data, there was no discernable impact of ampakines on baseline or challenged breathing at 14 days post C4Ct. This is perhaps not surprising because prior work establishes that in this injury model, robust compensation has occurred after 2 weeks, and deficits in diaphragm activation are difficult to detect. In summary, our data indicate that low dose, low impact ampakine treatment can increase diaphragm muscle output at an acute timepoint following mid‐cervical contusion type injuries. These studies pave the path for future experiments to test if ampakine treatment can be combined with rehabilitation techniques to further enhance the therapeutic effect of ampakines in this injury model.

Central and peripheral delivered AAV9-SMN are both efficient but target different pathomechanisms in a mouse model of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the SMN1 gene and low SMN protein levels. Although lower motor neurons are a primary target, there is evidence that peripheral organ defects contribute to SMA. Current SMA gene therapy and clinical trials use a single intravenous bolus of the blood-brain-barrier penetrant scAAV9-cba-SMN by either systemic or central nervous system (CNS) delivery, resulting in impressive amelioration of the clinical phenotype but not a complete cure. The impact of scAAV9-cba-SMN treatment regimens on the CNS as well as on specific peripheral organs is yet to be described in a comparative manner. Therefore, we injected SMA mice with scAAV9-cba-SMN either intravenously (IV) for peripheral SMN restoration or intracerebroventricularly (ICV) for CNS-focused SMN restoration. In our system, ICV injections increased SMN in peripheral organs and the CNS while IV administration increased SMN in peripheral tissues only, largely omitting the CNS. Both treatments rescued several peripheral phenotypes while only ICV injections were neuroprotective. Surprisingly, both delivery routes resulted in a robust rescue effect on survival, weight, and motor function, which in IV-treated mice relied on peripheral SMN restoration but not on targeting the motor neurons. This demonstrates the independent contribution of peripheral organs to SMA pathology and suggests that treatments should not be restricted to motor neurons.

The Effects of Remifentanil and Fentanyl on Emergence Agitation in Pediatric Strabismus Surgery.

Emergence agitation (EA) is one of the main concerns in the field of pediatric anesthesia using sevoflurane. We investigated the effects of remifentanil and fentanyl on the incidence of EA in pediatric patients undergoing strabismus surgery. Ninety children were randomly allocated into two groups and received either remifentanil (group R: intraoperatively remifentanil 0.2 μg/kg/min) or fentanyl (group F: fentanyl 2 μg/kg at anesthetic induction) intraoperatively. After surgery, EA incidence was assessed using a four-point agitation scale and Pediatric Anesthesia Emergence Delirium (PAED) scale in the post-anesthesia care unit. Face, leg, activity, cry, and consolability (FLACC) scores for postoperative pain were also assessed. The incidence of EA using the four-point agitation scale (scores ≥ 3) was similar in both groups (remifentanil group, 28.89% vs. fentanyl group, 24.44%). Similar results were obtained using the PAED scale (scores > 12), with an incidence of 33.33% in the remifentanil group and 26.67% in the fentanyl group. Differences in FLACC scores were not found to be statistically significant. A single bolus administration of fentanyl during anesthetic induction and continuous infusion of remifentanil during surgery had similar effects on the EA incidence in these pediatric patients.

A human coronavirus OC43-derived polypeptide causes neuropathic pain.

Human coronaviruses have been recently implicated in neurological sequelae by insufficiently understood mechanisms. We here identify an amino acid sequence within the HCoV‐OC43 p65‐like protein homologous to the evolutionarily conserved motif of myelin basic protein (MBP). Because MBP‐derived peptide exposure in the sciatic nerve produces pronociceptive activity in female rodents, we examined whether a synthetic peptide derived from the homologous region of HCoV‐OC43 (OC43p) acts by molecular mimicry to promote neuropathic pain. OC43p, but not scrambled peptides, induces mechanical hypersensitivity in rats following intrasciatic injections. Transcriptome analyses of the corresponding spinal cords reveal upregulation of genes and signaling pathways with known nociception‐, immune‐, and cellular energy‐related activities. Affinity capture shows the association of OC43p with an Na+/K+‐transporting ATPase, providing a potential direct target and mechanistic insight into virus‐induced effects on energy homeostasis and the sensory neuraxis. We propose that HCoV‐OC43 polypeptides released during infection dysregulate normal nervous system functions through molecular mimicry of MBP, leading to mechanical hypersensitivity. Our findings might provide a new paradigm for virus‐induced neuropathic pain.

Pharmacokinetic Evaluation of a Single 5-Gram Bolus of Creatine Monohydrate Versus Two Other Creatine-Containing Investigational Products.

The purpose of this study was to determine the relative pharmacokinetics of creatine monohydrate delivered as a formula or as a pure powder (all mixed in solution). A single 5 g bolus of creatine monohydrate was ingested as CreaBev 1, CreaBev 2, or creatine monohydrate. Participants we assigned a test product and monitored in a supervised laboratory setting for ingestion and all blood draws starting 30 min post-ingestion to the 6-h mark. Standard pharmacokinetic analysis was undertaken to determine relative maximum concentration (Cmax), time to maximum concentration (Tmax), and area under the curve (AUC) for the products. Cmax data indicate that CreaBev 1 10.55±4.10, CreaBev 2 15.45±5.48, and creatine monohydrate 12.77±4.0 nmol/h/μL. The Tmax analysis demonstrated CreaBev 1 1.20±1.01, CreaBev 2 1.23±0.65, and creatine monohydrate 0.91±0.2 h. The AUC data indicate that CreaBev 1 22.90±9.17, CreaBev 2 33.92±9.52, and creatine monohydrate 29.58±11.93 nmol/h/μL. When examining the data for pharmacokinetics, the AUC and Cmax pharmacokinetics were greatest for CreaBev 2 (p<0.021 and 0.020). Within the confines of this study, CreaBev 2 produced the highest blood concentrations of creatine as compared to creatine monohydrate and CreaBev 1.

Comparison between use of fentanyl and rocuronium on outpatient undergoing ultra-short duration gynecologic surgery: a randomized, double-blind, controlled trial

Background: There has been a steady increase in outpatient-based ultra-short duration gynecology surgeries. However, there are no detailed studies on anesthesia regimens for these surgeries. The aim of this study was to compare the effects of low-dose rocuronium and fentanyl single bolus for their suitability with these patients. Methods: A total of 60 patients were randomly divided into three groups: a control group (group C, n = 20) that received 3 mL of normal saline; a fentanyl group (group F, n = 19) that received 1 mcg/kg of fentanyl; and a low-dose rocuronium group (group R, n = 20) that received 0.3 mg/kg of rocuronium. We collected hemodynamic data during anesthetic induction and the intraoperative period. We also investigated supraglottic airway (SGA) insertion condition, patient’s gross movements, and surgeon’s satisfaction. In addition, we evaluated the incidence of postoperative nausea and vomiting, pruritus, first voiding time and discharge time from the postanesthetic care unit. Results: Systolic, diastolic, and mean blood pressure were significantly lower in group F after SGA insertion (p = 0.031, p = 0.046 and p = 0.048). SGA insertion conditions scores were significantly worse in group C than in group F and group R for total score (p &lt; 0.001). Also, the number of patient movements during surgery and the number of rescue fentanyl injections were significantly higher in group C than group F and group R (p = 0.005 and p &lt; 0.001). Conclusion: Fentanyl administration at 1 mcg/kg has advantages compared with rocuronium and is a more suitable single agent regimen for outpatient-based ultra-short duration gynecology surgeries.

Establishment of a Simple and Versatile Evaporation Compensation Model for in vitro Chronic Ethanol Treatment: Impact on Neuronal Viability.

Alcohol overconsumption is a major cause of preventable mental disorders and death in the United States and around the world. The pathogenesis of alcohol dependence, abuse, and toxicity to the central nervous system remains incompletely understood. In vitro and cell culture-based models have been highly valuable in studying the molecular and cellular mechanisms underlying the contribution of individual CNS cell types to ethanol's effects on the brain. However, conventional cell culture model systems carry the inherent disadvantage of rapid loss of ethanol due to evaporation following a bolus addition at the start of the treatment. We have established a multi-well cell culture plate-based ethanol evaporation compensation model that utilizes the inter-well space as a reservoir to compensate for the evaporative loss of ethanol in the cell treatment wells. Following a single bolus addition at the start of the treatment, ethanol concentration rapidly decreased over time. Through compensation using the multi-well plate platform, maintenance of ethanol concentrations ranging from 10-100 mM was achieved for up to 72 hours in a cell-free system. Greater effects in ethanol-induced decrease in neuronal cell viability were observed with than without compensation. Our method effectively compensates for the evaporative loss of ethanol typically observed in the traditional method. This method provides an economic, simple and effective in vitro model system for ethanol treatment over an extended timeframe where maintenance of a relatively constant concentration of ethanol is desired.

Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit—TASTE-A): protocol for a prospective randomised, open-label, blinded endpoint, phase II superiority trial of tenecteplase versus alteplase for ischaemic stroke patients presenting within 4.5 hours of symptom onset to the mobile stroke unit

IntroductionMobile stroke units (MSUs) equipped with a CT scanner are increasingly being used to assess and treat stroke patients’ prehospital with thrombolysis and transfer them to the most appropriate hospital...

Feasibility of prehospital esmolol for refractory ventricular fibrillation.

BackgroundEsmolol may increase survival for patients with refractory ventricular fibrillation (RVF); however, information related to esmolol use in the prehospital environment is limited. We aimed to assess the feasibility of prehospital bolus dose esmolol for patients with RVF treated by a high‐volume, ground‐based emergency medical services (EMS) agency.Methods Esmolol (0.5 mg/kg single bolus) was added to the RVF protocol on December 10, 2018. Feasibility was defined as esmolol administration in >75% of RVF cases. Secondarily, we compared the proportion of patients with prehospital return of spontaneous circulation (ROSC), 24‐hour survival, and survival to hospital discharge during the intervention period (December 10, 2018–June 10, 2020) to a historical control period (June 10, 2017–December 9, 2018) using chi‐square tests.ResultsBefore the protocol change, 63 patients with RVF were identified. After esmolol was added, 70 patients with RVF were identified and 61 (87%) received esmolol. Prehospital ROSC was higher in the esmolol group compared to the historical control group, though statistical significance was not reached (38% versus 24%, P = 0.09). Overall, few patients survived to 24 hours (esmolol n = 15, pre‐esmolol n = 16) and fewer survived to hospital discharge (esmolol n = 5, pre‐esmolol n = 5), precluding stable statistical comparisons.ConclusionCollectively, these findings suggest that EMS clinicians are able to accurately identify RVF and administer esmolol in the prehospital setting and that ROSC may be increased. Further large‐scale studies are needed to determine the effect of prehospital esmolol for RVF as it relates to neurologically intact hospital discharge.

Intravenous hypertonic saline to reduce intraocular pressure: the effect of splitting the bolus

To compare intraocular pressure (IOP) and pain after a single versus split bolus of intravenous hypertonic saline (IVHTS). In a prospective, randomized, interventional trial, we enrolled patients with an IOP of 22-34 mmHg. Twenty patients in Group 1 received IVHTS as a single bolus of 1 mmol/kg 23.4% sodium chloride, and 13 patients in Group 2 received two boli of 0.5 mmol/kg separated by 10 min. They graded pain at the infusion site. We measured IOP, heart rate and blood pressure before and 10 and 20 min after IVHTS. Eighteen patients (90%) in Group 1 felt pain (median, 6.5; range, 0-10). In Group 2, 11 patients (85%) felt pain after the first bolus (median, 6.0; range, 0-8) and 12 (92%) after the second one (median, 8; range, 0-10). We found no difference in pain grade between the groups after their first bolus (p = 0.33) or between the first bolus of Group 1 and the second bolus of Group 2 (p = 0.47). The median IOP reduction in Group 1 was 6.5 mmHg (range, 2-16) at 10 min and 7.0 mmHg (range, 4-16) at 20 min (p < 0.001 for both). In Group 2, the corresponding reductions after the second bolus were 9.0 mmHg (range, 4-10; p = 0.002) and 8.0 mmHg (range, 6-11; p = 0.002). The IOP reduction at 10 and 20 min was comparable between groups (p = 0.094 and p = 0.41, respectively). Splitting the bolus did not reduce pain associated with IVHTS. Single bolus is consequently recommended.

Comparison of plasma levobupivacaine concentrations with and without epinephrine following erector spinae plane block for breast cancer surgery: a randomized controlled trial

BackgroundThe erector spinae plane (ESP) block requires a large volume of local anesthetic to provide effective analgesia, which has the potential to cause local anesthetic systemic toxicity (LAST). Adjunctive epinephrine slows the entry of local anesthetic into the plasma and decreases its toxic effect on vulnerable tissues. We compared plasma levobupivacaine concentrations with and without epinephrine after ESP blocks for breast cancer surgery.MethodsIn this prospective, double-blinded, randomized controlled trial, 35 patients who underwent elective unilateral partial mastectomy with sentinel lymph node biopsy were enrolled. The patients were randomized to group L (ESP block with 2 mg/kg levobupivacaine) or LE (ESP block with 2 mg/kg levobupivacaine and 5 μg/mL epinephrine). Blood samples were obtained at 2.5, 5, 7.5, 10, 12.5, 15, 30, 60, and 120 min after the ESP block, and plasma concentrations of levobupivacaine were compared.ResultsTwenty-nine patients were included in the analysis. The maximum plasma concentration (Cmax) and the time to maximum concentration (Tmax) were, respectively, 1.24 μg/mL and 6.0 min in group L and 0.62 μg/mL and 7.2 min in group LE. The two groups showed no significant differences in the numerical rating scale scores immediately after extubation and 5 and 9 h after the ESP block, or in the interval from the ESP block to the first rescue analgesia. No patient developed symptoms suggestive of LAST.ConclusionsA single bolus of 2 mg/kg levobupivacaine in the ESP block resulted in a short Tmax with high Cmax. Adding epinephrine to levobupivacaine decreased the Cmax and delayed the Tmax after ESP blocks but had no effect on postoperative analgesia.Trial registrationUMIN Clinical Trials Registry, UMIN000034479. The trial was retrospectively registered on October 13, 2018.

Comparison of Magnesium Sulphate Loading Dose with &amp; without Maintenance Regimen for Management of Patients Presenting with Eclampsia, Randomized Control Trial

Aim: To compare the frequency of recurrence of convulsions with Magnesium Sulphate loading dose versus loading dose plus maintenance regimen for management of patients presenting with eclampsia. Methods: In this Randomized Controlled Trial, 240 pregnant female admitted in department of Obstetrics &amp; Gynaecology, LGH, Lahore. Half In group A, females were given MgSO4 in a single bolus dose i.e. 4 grams intravenously diluted in 100ml normal saline over 20 minutes and 10grams intramuscularly, while in group B, females were given complete standard regime according to the Pritchard i.e. 14 grams loading dose followed by 5gm intramuscularly every 4 hours on alternate buttock for 24 hours after the last episode of convulsion or delivery of the fetus whichever comes later. Results: In this study recurrence of convulsion was significantly higher in patients who were given MgSO4 loading dose as compared to patients who were given MgSO4 loading + maintenance regimen i.e. Group-A: 15.8% vs. Group-B: 5.8%, (p-value 0.013). The frequency of recurrence of convulsion was significantly higher in women who were given loading dose alone as that of women who were given MgSO4 loading + maintenance regimen but Age, gestational age and parity status of women although did not show any significant association.. Conclusion: Loading dose plus maintenance regimen had low frequency of recurrence convulsion when compared with loading dose of MgSO4 only. Keywords: Eclampsia, loading dose, Recurrence of convulsions, Magnesium Sulphate, Maintenance regimen

Carbetocin versus Oxytocin in the Prevention of Postpartum Haemorrhage after Caesarean Section

Background: postpartum haemorrhage is one of the major contributors to maternal mortality and morbidity worldwide. There are many pharmacological options for the management of postpartum hemorrhage, oxytocin being the first line choice of treatment.Carbetocin, a long acting oxytocin agonist, appears to be a promising agent for the prevention of PPH. This comparative study was between Carbetocin Versus Oxytocin for the Prevention of Postpartum Haemorrhage in Caesarean Section&#x0D; Objective: To determine the safety and effectiveness of carbetocin and oxytocin for the prevention of post-partum haemorrhage in caesarean section.&#x0D; Methods: Randomized controlled clinical trial was done in the department of Obstetrics and Gynaecology of Sir Salimullah Medical College Mitford Hospital, Dhaka, between February to July 2015. Study population were 64 pregnant women admitted for delivery and underwent caesarean section, who were randomly selected. Women in the intervention group (group I) received injection carbetocin a bolus of 100 mgm IV; women in the standard treatment group (group II) received 10 IU of oxytocin in IV.Both administered immediately after chiidbirth.This trial was registered in SSMC MH with reference no-SSMC/2014/76.&#x0D; Result: Difference of mean age,mean gestational age and indication of C/S were not statistically significant between two groups.Regarding haemodynamic effect,both drugs were almost similar.There was no significant difference in per-operetive blood loss,uterine tone, level of uterine fundus, urine output in urobag and hemoglobin level. Need for additional oxytocics required 0(0.0%) vs 5(16.7%) patients in group I and group II respectively and was found statistically significant.Blood transfusion needed was 0(0.0%) vs 3(10.0%) patients and primary PPH 0(0.0%) vs 3(9.4%),though both were not statistically significant. No significant difference regarding side effects and total expense was found.&#x0D; Conclusion: Administration of single bolus dose of carbetocin (100 μgIV) after delivery of the baby in caesarean section immediately reduces the need for additional oxytocics, occurrence of primary PPH and further blood transfusion. Side effects are mild and similar in both the groups.&#x0D; Bangladesh J Obstet Gynaecol, 2020; Vol. 35(2): 63-67

Study of Hemodynamic Effects of Preoperative Single-Bolus Dexmedetomidine in Elective Laparoscopic Surgeries

Objective: To observe the hemodynamic effects of a single bolus dose of dexmedetomidine in patients undergoing elective laparoscopic surgeries. Methods: A total of 60 adult patients were randomized into two groups of 30 each. Group D patients were given 1 µg/kg dexmedetomidine in 50 mL of saline as a single-dose infusion over 10 min before induction. Group S patients were given a 50-mL 0.9% NS slow infusion over 10 min. Groups D and S patients were premedicated 10 min prior to surgery. Baseline vital and hemodynamic parameters were monitored during the perioperative period. Conclusion: Premedicating with a single bolus of 1 µg/kg IV dexmedetomidine has been proven safe and effective in maintaining perioperative hemodynamic stability, although few developed bradycardia and hypotension, which were managed without any adverse outcome. Furthermore, dexmedetomidine effectively reduced the incidence of shivering.

Diagnosis and management of intra-operative pulmonary embolism under general anaesthesia in a peripheral tertiary care centre with limited resources.

Sir, It is difficult to detect and diagnose acute pulmonary embolism (APE) in patients under general anaesthesia (GA) as signs and symptoms such as dyspnoea, chest pain, haemoptysis and syncope are not evident.[1] A 64-year-old male, with left sided carcinoma buccal mucosa and American Society of Anesthesiologists physical status II, was listed for left anterior hemi-mandibulectomy with bilateral multinodal neck dissection and left sided pectoral muscle musculocutaneous flap (PMMC) under GA. Preoperative contrast enhanced computed tomography (CECT) thorax was unremarkable. After induction, haemodynamics remained stable during excision of the primary lesion. Approximately, 5 hours into the surgery, while raising the PMMC, the patient developed sudden pronounced hypotension with a mean arterial pressure of 45 mmHg and a decrease in end tidal carbon di-oxide (EtCO2) 38 mmHg to 15 mmHg. This was associated with bradycardia (heart rate 44-48/min) and a gradual fall in oxygen saturation to 86-88%. Peak airway pressures gradually increased from 21 cmH2O to 32 cmH2O with an associated increase in plateau pressures from 19 cmH2O to 29 cmH2O. Central venous pressures were elevated and bilateral breath sounds were marginally reduced with no adventitious sounds. There was no significant acute blood loss, nor any evidence of sepsis. Immediately, the inhalational agent was switched off and the fraction of inspiratory oxygen increased to 100%. Intravenous mephentermine 6 mg (two boluses), hydrocortisone 100 mg and atropine 0.6 mg were administered intravenously. A single intravenous adrenaline bolus of 10 μg was subsequently administered, followed by an infusion at the rate of 0.02 μg/kg/min. Immediate arterial blood gas (ABG) analysis showed hypercarbia as well as hypoxia [Table 1a]. Transthoracic echocardiography (TTE) through subcostal four chamber view showed dilated and strained right heart chambers (McConnell sign) and distended inferior vena cava [Figure 1a and b]. A probable diagnosis of APE was made.Table 1: Arterial blood gas analysisFigure 1: (a) Echo showing dilated IVC and RA (b) Dilated RA and RV. IVC: Inferior vena cava; RA: Right atrium; RV: Right ventricleOur institute is a tertiary cancer care centre in a small town with limited resources. After adequate resuscitation, a joint consensus among operating room team members was made for pharmacological treatment. Unfractionated heparin (UFH) 5000 IU was administered intra-venously. Activated partial thromboplastin time (APTT) was maintained 1.5-2 times of the normal value. We were in the middle of the surgery (with tumour excised and the PMMC flap raised), and the haemodynamics had stabilised. Repeat blood gas analysis came normal [Table 1b]. So, we decided to complete the surgery. Post-surgery, the patient was kept on mechanical ventilation. Vitals in the postoperative period remained stable. A dose of 2500 IU of UFH was repeated as the reported APTT was 38.3 seconds. The patient underwent computed tomographic pulmonary angiography which showed no filling defect [Figure 2] and was shifted onto subcutaneous low molecular weight heparin 60 mg twice a day. On post-operative day (POD) 1, the patient was weaned off the ventilator. He was shifted to the ward on POD 2. He was found haemodynamically stable during follow-up.Figure 2: CT Pulmonary Angiography (Post Surgery)APE leads to significant separation of EtCO2 and PaCO2 values intra-operatively. It causes a sudden decrease in EtCO2 and an increase in PaCO2. This separation in EtCO2 and PaCO2 values is also an important tool to measure thrombolysis under GA.[1] TTE coupled with EtCO2 changes seems to be useful in intra-operative cardio- circulatory failure to exclude other differential diagnoses.[2] The 2019 consensus European Society of Cardiology (ESC) guidelines strongly recommend intravenous UFH as a treatment of choice in haemodynamically unstable APE.[3] Catheter-directed therapy (CDT) had been done for APE.[4] CDT is recommended by the American College of Chest Physicians as second-line therapy for massive pulmonary embolism.[5] Our case is a classic example of APE in head and neck malignancy. The involvement of a multidisciplinary team can also help in preparedness for emergent and unanticipated situations.[6] We emphasise that vigilant monitoring of EtCO2, timely use of TTE and systemic anticoagulation with adequate intraoperative haemodynamic resuscitation can lead to safe completion of surgery with minimal morbidity and mortality. Though UFH is not a recommended modality in the intra-operative period, due to the limitations of our set -up, CDT was beyond our purview. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to concealidentity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

The Clinical Outcome of Intravenous Single Bolus 0.5gm of Tranexamic Acid for Reducing Blood Loss Following an Elective Cesarean Delivery: A Randomized Controlled Trial

The Clinical Outcome of Intravenous Single Bolus 0.5gm of Tranexamic Acid for Reducing Blood Loss Following an Elective Cesarean Delivery: A Randomized Controlled Trial

89Zr]ZrDFO-CR011 PET Correlates with Response to Glycoprotein Nonmetastatic Melanoma B-targeted Therapy in Triple-negative Breast Cancer.

There is a need for prognostic markers to select patients most likely to benefit from antibody-drug conjugate (ADC) therapy. We quantified the relationship between pretreatment PET imaging of glycoprotein nonmetastatic melanoma B (gpNMB) with 89Zr-labeled anti-gpNMB antibody ([89Zr]ZrDFO-CR011) and response to ADC therapy (CDX-011) in triple-negative breast cancer. First, we compared different PET imaging metrics and found that standardized uptake values (SUV) and tumor-to-heart SUV ratios were sufficient to delineate differences in radiotracer uptake in the tumor of four different cell- and patient-derived tumor models and achieved high standardized effect sizes. These tumor models with varying levels of gpNMB expression were imaged with [89Zr]ZrDFO-CR011 followed by treatment with a single bolus injection of CDX-011. The percent change in tumor volume relative to baseline (% CTV) was then correlated with SUVmean of [89Zr]ZrDFO-CR011 uptake in the tumor. All gpNMB-positive tumor models responded to CDX-011 over 6 weeks of treatment, except one patient-derived tumor regrew after 4 weeks of treatment. As expected, the gpNMB-negative tumor increased in volume by 130 ± 59% at endpoint. The magnitude of pretreatment SUV had the strongest inverse correlation with the % CTV at 2-4 weeks after treatment with CDX-011 (Spearman ρ = -0.8). However, pretreatment PET imaging with [89Zr]ZrDFO-CR011 did not inform on which tumor types will regrow over time. Other methods will be needed to predict resistance to treatment.

Simultaneous radiomethylation of [11C]harmine and [11C]DASB and kinetic modeling approach for serotonergic brain imaging in the same individual

Simultaneous characterization of pathologies by multi-tracer positron emission tomography (PET) is among the most promising applications in nuclear medicine. Aim of this work was the simultaneous production of two PET-tracers in one module and test the relevance for human application. [11C]harmine and [11C]DASB were concurrently synthesized in a ‘two-in-one-pot’ reaction in quality for application. Dual-tracer protocol was simulated using 16 single PET scans in different orders of tracer application separated by different time intervals. Volume of distribution was calculated for single- and dual-tracer measurements using Logan’s plot and arterial input function in 13 brain regions. The ‘two-in-one-pot’ reaction yielded equivalent amounts of both radiotracers with comparable molar activities. The simulations of the dual-tracer application were comparable to the single bolus injections in 13 brain regions, when [11C]harmine was applied first and [11C]DASB second, with an injection time interval of 45 min (rxy = 0.90). Our study shows the successful simultaneous dual-tracer production leading to decreased radiation burden and costs. The simulation of dual subject injection to quantify the monoamine oxidase-A and serotonin transporter distribution proved its high potential. Multi-tracer imaging may drive more sophisticated study designs and diminish the day-to-day differences in the same individual as well as increase PET scanner efficiency.

A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D\u2014a randomised multicentre international clinical trial

BackgroundVitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed.MethodsThe COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed.ResultsIn the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0–10.5] vs. 9.5 [95%CI 9.0–10.5] days), admission to ICU (17.2% [95%CI 13.0–22.3] vs. 16.4% [95%CI 12.3–21.4]) and death rate (8.0% [95%CI 5.2–12.1] vs. 5.6% [95%CI 3.3–9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes.ConclusionsThe randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes.Trial registrationCOVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov (NCT04552951).