Successful adaptation of twinning concept for global neurosurgery collaborations-a validation study.

INTRODUCTION: Globally, many regions have an urgent, unmet need of neurosurgical care. A multi-step neurosurgical twinning technique, International Neurosurgical Twinning Modeled for Africa (INTIMA), was proved to be successful during a previous mission to Neurosurgical Unit, Enugu, Nigeria. The Swedish African Neurosurgical Collaboration (SANC) performed a developmental mission together with the local neurosurgical unit in The Gambia, adopting the INTIMA model. METHODS: A multidisciplinary team visited for a 2-week collaborative mission at the Neurosurgical Department of the Edward Francis Small Teaching Hospital in Banjul, The Gambia. The mission followed the data of neurosurgical operations during and after the mission as well as about the operations 3 months prior to and after the mission was collected. RESULTS: During the mission, a total of 22 operations was carried out, the most common being degenerative spinal conditions (n = 9). In the 3 months following the mission, 43 operations were performed compared to 24 during the 3 months leading up to the mission. The complexity of the performed procedures increased after the mission. An operating microscope (Möller-Wedel) was donated and installed and the neurosurgeons on site underwent training in microneurosurgery. The surgical nurses, nurses at the postoperative ward, and the physiotherapists underwent training. A biomedical engineer serviced multiple appliances and devices improving the patient care on site while training local technicians. CONCLUSION: This study validated the use of the INTIMA model previously described in a mission by Swedish African Neurosurgical Collaboration (SANC). The model is sustainable and produces notable results. The core strength of the model is in the multidisciplinary team securing all the aspects and steps of the neurosurgical care. Installation of an operating microscope opened for further microsurgical possibilities, improving the neurosurgical care in The Gambia.

Analgesic effects of intrathecal morphine and bupivacaine during robotic-assisted surgery: A prospective randomized controlled study.

BACKGROUND: Limited data exist concerning the management of postoperative pain after robotic-assisted surgery. The present study was performed to investigate the efficacy of intrathecal morphine and bupivacaine to treat postoperative pain in adult women undergoing robot-assisted laparoscopic hysterectomy. METHODS: The primary outcomes of this study were opioid consumption and pain scores during and after robotic surgery. 96 patients were prospectively enrolled and randomized to a nonspinal group (n = 48) and a spinal group (n = 48). The intrathecal regimen consisted of 100 µg morphine and 15 mg of bupivacaine. The numeric rating scale scores (NRS) were assessed every 15 min in the postoperative care unit (PACU) and pain was treated with iv fentanyl or morphine when NRS was above 5 and orally oxycodone when NRS was 3-5. Cumulative iv opioid-consumption and NRS scores were compared. RESULTS: Intrathecal morphine and bupivacaine resulted in a significantly lower cumulative total iv opioid (morphine equivalents) consumption (9.4 ± 3.9 vs. 22.8 ± 6.1 mg equivalents). Highest recorded NRS scores in the PACU were also significantly lower in the spinal group (2.0 ± 2.6 vs. 5.3 ± 3.2). CONCLUSION: Intrathecal morphine and bupivacaine to treat postoperative pain after robotic-assisted laparoscopic hysterectomy decrease total opioid consumption and NRS pain scores. This might be of great importance to diminish the rate of other serious disadvantages related to opioids.

The novel antidepressant ketamine enhances dentate gyrus proliferation with no effects on synaptic plasticity or hippocampal function in depressive-like rats.

AIM: Major depressive disorder is a common and debilitating condition with substantial economic impact. Treatment options, although effective, are aimed at relieving the symptoms with limited disease modification. Ketamine, a commonly used anaesthetic, has received substantial attention as it shows rapid antidepressant effects clinically. We studied the effects of ketamine on hippocampal function and dentate gyrus proliferation in rats showing a depressive-like phenotype. METHODS: Adolescent and adult animals were pre-natally exposed to the glucocorticoid analog dexamethasone, and we verified a depressive-like phenotype using behavioural tests, such as the sucrose preference. We subsequently studied the effects of ketamine on hippocampal synaptic transmission, plasticity and dentate gyrus proliferation. In addition, we measured hippocampal glutamate receptor expression. We also tested the ketamine metabolite hydroxynorketamine for NMDA-receptor independent effects. RESULTS: Surprisingly, our extensive experimental survey revealed limited effects of ketamine or its metabolite on hippocampal function in control as well as depressive-like animals. We found no effects on synaptic efficacy or induction of long-term potentiation in adolescent and adult animals. Also there was no difference when comparing the dorsal and ventral hippocampus. Importantly, however, ketamine 24 hours prior to experimentation significantly increased the dentate gyrus proliferation, as revealed by Ki-67 immunostaining, in the depressive-like phenotype. CONCLUSION: We find limited effects of ketamine on hippocampal glutamatergic transmission. Instead, alterations in dentate gyrus proliferation could explain the antidepressant effects of ketamine.

Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction

Background: In the DETO2X-AMI trial (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction), we compared supplemental oxygen with ambient air in normoxemic patients presenting with suspected myocardial infarction and found no significant survival benefit at 1 year. However, important secondary end points were not yet available. We now report the prespecified secondary end points cardiovascular death and the composite of all-cause death and hospitalization for heart failure. Methods: In this pragmatic, registry-based randomized clinical trial, we used a nationwide quality registry for coronary care for trial procedures and evaluated end points through the Swedish population registry (mortality), the Swedish inpatient registry (heart failure), and cause of death registry (cardiovascular death). Patients with suspected acute myocardial infarction and oxygen saturation of ≥90% were randomly assigned to receive either supplemental oxygen at 6 L/min for 6 to 12 hours delivered by open face mask or ambient air. Results: A total of 6629 patients were enrolled. Acute heart failure treatment, left ventricular systolic function assessed by echocardiography, and infarct size measured by high-sensitive cardiac troponin T were similar in the 2 groups during the hospitalization period. All-cause death or hospitalization for heart failure within 1 year after randomization occurred in 8.0% of patients assigned to oxygen and in 7.9% of patients assigned to ambient air (hazard ratio, 0.99; 95% CI, 0.84­1.18; P=0.92). During long-term follow-up (median [range], 2.1 [1.0­3.7] years), the composite end point occurred in 11.2% of patients assigned to oxygen and in 10.8% of patients assigned to ambient air (hazard ratio, 1.02; 95% CI, 0.88­1.17; P=0.84), and cardiovascular death occurred in 5.2% of patients assigned to oxygen and in 4.8% assigned to ambient air (hazard ratio, 1.07; 95% CI, 0.87­1.33; P=0.52). The results were consistent across all predefined subgroups. Conclusions: Routine use of supplemental oxygen in normoxemic patients with suspected myocardial infarction was not found to reduce the composite of all-cause mortality and hospitalization for heart failure, or cardiovascular death within 1 year or during long-term follow-up. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01787110.

Consistent manufacturing and quality control of a highly complex recombinant polyclonal antibody product for human therapeutic use.

The beneficial effect of antibody therapy in human disease has become well established mainly for the treatment of cancer and immunological disorders. The inherent monospecificity of mAbs present limitations to mAb therapy which have become apparent notably in addressing complex entities like infectious agents or heterogenic endogenous targets. For such indications mixtures of antibodies comprising a combination of specificities would convey more potent biological effect which could translate into therapeutic efficacy. Recombinant polyclonal antibodies (rpAb) consisting of a defined number of well-characterized mAbs constitute a new class of target specific antibody therapy. We have developed a cost-efficient cell banking and single-batch manufacturing concept for the production of such products and demonstrate that a complex pAb composition, rozrolimupab, comprising 25 individual antibodies can be manufactured in a highly consistent manner in a scaled-up manufacturing process. We present a strategy for the release and characterization of antibody mixtures which constitute a complete series of chemistry, manufacturing, and control (CMC) analytical methods to address identity, purity, quantity, potency, and general characteristics. Finally we document selected quality attributes of rozrolimupab based on a battery of assays at the genetic-, protein-, and functional level and demonstrate that the manufactured rozrolimupab batches are highly pure and very uniform in their composition.

Thermodynamic investigations on materials corrosion in some industrial and environmental processes.

For better understanding of corrosion schemes and corrosion mechanisms of a wide range of steels/Fe-alloys, Ni-/NiFe-/Co-superalloys, Al-/Mg-/Ti-/Zr-/Sn-/Cu-/Zn-alloys, electronic-packing alloys, medical-instrument alloys and other materials, under various corrosive environments (such as aqueous solutions, non-aqueous solutions, molten salts, high-temperature gases, etc.) during production/application processes and experimental observations, the Thermo-Calc software/database/programming-interface package can be used. This article is aimed at presenting some application examples of thermodynamic calculations/simulations in some specific areas: aqueous corrosions of stainless steels and other alloys, and of high-performance corrosion-resistant materials (HPCRM); molten salt corrosions of stainless steels and high-temperature alloys; high-temperature gaseous corrosions of steels/alloys; formations of oxide-coated protective layers on steel/alloy surfaces; and emergence conditions during oxidation of steels/alloys.

Development of mass spectrometry based techniques for the identification and determination of compositional variability in recombinant polyclonal antibody products.

Recombinant polyclonal antibodies are a new class of protein biologics, combining a defined number of target-specific antibodies, developed for therapeutic use across various indications. Development, manufacture, and release of recombinant polyclonal antibodies as well characterized biological products have required development of new chemistry, manufacturing, and control (CMC) technologies. Sym001 is a recombinant polyclonal antibody product containing 25 unique antibodies specific for the Rhesus D antigen. Sym001 drug substance is manufactured using a single batch technology, Sympress. Here, we describe the development of two novel mass spectrometry based methods that allows identification of individual antibodies in the Sym001 drug substance, through the determination of unique marker peptides or antibody light chains. The two methods provide an unambiguous identification of the 25 unique antibodies comprised in the Sym001 drug substance. Furthermore, the light chain liquid chromatography-mass spectrometry (LC-MS) method has been developed to allow the determination of the relative distribution of the 25 antibodies. The light chain LC-MS method has demonstrated linearity, specificity, precision, and accuracy, thus qualifying it for use in the quality control of recombinant polyclonal antibodies for human use. The development of such quantitative methods is central for the development and quality control of additional therapeutic recombinant polyclonal antibody products.