Advances of Recombinant Adenoviral Vectors in Preclinical and Clinical Applications.

Adenoviruses (Ad) have the potential to induce severe infections in vulnerable patient groups. Therefore, understanding Ad biology and antiviral processes is important to comprehend the signaling cascades during an infection and to initiate appropriate diagnostic and therapeutic interventions. In addition, Ad vector-based vaccines have revealed significant potential in generating robust immune protection and recombinant Ad vectors facilitate efficient gene transfer to treat genetic diseases and are used as oncolytic viruses to treat cancer. Continuous improvements in gene delivery capacity, coupled with advancements in production methods, have enabled widespread application in cancer therapy, vaccine development, and gene therapy on a large scale. This review provides a comprehensive overview of the virus biology, and several aspects of recombinant Ad vectors, as well as the development of Ad vector, are discussed. Moreover, we focus on those Ads that were used in preclinical and clinical applications including regenerative medicine, vaccine development, genome engineering, treatment of genetic diseases, and virotherapy in tumor treatment.

Cardiopulmonary resuscitation during hyperbaric oxygen therapy: a comprehensive review and recommendations for practice.

BACKGROUND: Cardiopulmonary resuscitation (CPR) during hyperbaric oxygen therapy (HBOT) presents unique challenges due to limited access to patients in cardiac arrest (CA) and the distinct physiological conditions present during hyperbaric therapy. Despite these challenges, guidelines specifically addressing CPR during HBOT are lacking. This review aims to consolidate the available evidence and offer recommendations for clinical practice in this context. MATERIALS AND METHODS: A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, and CINAHL using the search string: "(pressure chamber OR decompression OR hyperbaric) AND (cardiac arrest OR cardiopulmonary resuscitation OR advanced life support OR ALS OR life support OR chest compression OR ventricular fibrillation OR heart arrest OR heart massage OR resuscitation)". Additionally, relevant publications and book chapters not identified through this search were included. RESULTS: The search yielded 10,223 publications, with 41 deemed relevant to the topic. Among these, 18 articles (primarily case reports) described CPR or defibrillation in 22 patients undergoing HBOT. The remaining 23 articles provided information or recommendations pertaining to CPR during HBOT. Given the unique physiological factors during HBOT, the limitations of current resuscitation guidelines are discussed. CONCLUSIONS: CPR in the context of HBOT is a rare, yet critical event requiring special considerations. Existing guidelines should be adapted to address these unique circumstances and integrated into regular training for HBOT practitioners. This review serves as a valuable contribution to the literature on "CPR under special circumstances".

The Optimal Fluid Strategy Matters in Liver Surgery: A Retrospective Single Centre Analysis of 666 Consecutive Liver Resections.

As optimal intraoperative fluid management in liver surgery has not been established, we retrospectively analyzed our fluid strategy in a high-volume liver surgery center in 666 liver resections. Intraoperative fluid management was divided into very restrictive (<10 m kg-1 h-1) and normal (≥10 mL kg-1 h-1) groups for study group characterization. The primary endpoint was morbidity as assessed by the Clavien-Dindo (CD) score and the comprehensive complication index (CCI). Logistic regression models identified factors most predictive of postoperative morbidity. No association was found between postoperative morbidity and fluid management in the overall study population (p = 0.89). However, the normal fluid management group had shorter postoperative hospital stays (p = <0.001), shorter ICU stays (p = 0.035), and lower in-hospital mortality (p = 0.02). Elevated lactate levels (p < 0.001), duration (p < 0.001), and extent of surgery (p < 0.001) were the most predictive factors for postoperative morbidity. In the subgroup of major/extreme liver resection, very low total (p = 0.028) and normalized fluid balance (p = 0.025) (NFB) were associated with morbidity. Moreover, fluid management was not associated with morbidity in patients with normal lactate levels (<2.5 mmol/L). In conclusion, fluid management in liver surgery is multifaceted and must be applied judiciously as a therapeutic measure. While a restrictive strategy appears attractive, hypovolemia should be avoided.

Impact of timing and combination of different BNT162b2 and ChAdOx1-S COVID-19 basic and booster vaccinations on humoral immunogenicity and reactogenicity in adults.

In this single-center observational study with 1,206 participants, we prospectively evaluated SARS-CoV-2-antibodies (anti-S RBD) and vaccine-related adverse drug reactions (ADR) after basic and booster immunization with BNT162b2- and ChAdOx1-S-vaccines in four vaccination protocols: Homologous BNT162b2-schedule with second vaccination at either three or six weeks, homologous ChAdOx1-S-vaccination or heterologous ChAdOx1-S/BNT162b2-schedule, each at 12 weeks. All participants received a BNT162b2 booster. Blood samples for anti-S RBD analysis were obtained multiple times over a period of four weeks to six months after basic vaccination, immediately before, and up to three months after booster vaccination. After basic vaccination, the homologous ChAdOx1-S-group showed the lowest anti-S RBD levels over six months, while the heterologous BNT162b2-ChAdOx1-S-group demonstrated the highest anti-S levels, but failed to reach level of significance compared with the homologous BNT162b2-groups. Antibody levels were higher after an extended vaccination interval with BNT162b2. A BNT162b2 booster increased anti-S-levels 11- to 91-fold in all groups, with the homologous ChAdOx1-S-cohort demonstrated the highest increase in antibody levels. No severe or serious ADR were observed. The findings suggest that a heterologous vaccination schedule or prolonged vaccination interval induces robust humoral immunogenicity with good tolerability. Extending the time to boost-immunization is key to both improving antibody induction and reducing ADR rate.

AT 1 inhibition mediated neuroprotection after experimental traumatic brain injury is dependent on neutrophils in male mice.

After traumatic brain injury (TBI) cerebral inflammation with invasion of neutrophils and lymphocytes is a crucial factor in the process of secondary brain damage. In TBI the intrinsic renin-angiotensin system is an important mediator of cerebral inflammation, as inhibition of the angiotensin II receptor type 1 (AT1) reduces secondary brain damage and the invasion of neutrophil granulocytes into injured cerebral tissue. The current study explored the involvement of immune cells in neuroprotection mediated by AT1 inhibition following experimental TBI. Four different cohorts of male mice were examined, investigating the effects of neutropenia (anti-Ly6G antibody mediated neutrophil depletion; C57BL/6), lymphopenia (RAG1 deficiency, RAG1-/-), and their combination with candesartan-mediated AT1 inhibition. The present results showed that reduction of neutrophils and lymphocytes, as well as AT1 inhibition in wild type and RAG1-/- mice, reduced brain damage and neuroinflammation after TBI. However, in neutropenic mice, candesartan did not have an effect. Interestingly, AT1 inhibition was found to be neuroprotective in RAG1-/- mice but not in neutropenic mice. The findings suggest that AT1 inhibition may exert neuroprotection by reducing the inflammation caused by neutrophils, ultimately leading to a decrease in their invasion into cerebral tissue.

Evaluation of the Effectiveness of the Separate Anesthesia Induction Rooms on Multidisciplinary Work Flow in Operating Rooms.

Introduction: Operating suites are multidisciplinary units par excellence, and mostly they are the most expensive units in hospitals. Interdisciplinary workflow and efficiency are therefore crucial, which is influenced by floor plans varying from hospital to hospital. Most operating rooms are equipped with adjacent induction rooms, allowing preparation and anesthesia induction of the next patient, while the previous patient is still in the operating room. Parallelizing the working steps is thought to improve turn-over time, thus increasing throughput, number of cases and finally revenue. However, this assumption has never been challenged. Methods: We analyzed workflow during regular working hours in an operating suite equipped with a mixture of operating rooms (OR) with next door induction rooms and operating rooms without induction rooms. This allows a direct comparison of both structural elements for efficiency using utilization data over a 24-months period. Both settings were used for gynecological operations. Results: Key result is that induction rooms do not improve perioperative workflow including turn-over time. Instead, ORs without adjacent induction rooms have a significantly shorter turn-over time and OR occupancy duration per case, although surgical time and staffing were similar. Discussion: Adjacent induction rooms require extra space, funding, and high maintenance costs, but they do not speed up peri-operative processes. Modern anesthetic techniques allow for fast induction of and emergence from anesthesia. Induction rooms adjacent to the OR are no longer needed if general anesthesia without extended monitoring is used for the majority of cases.

Early DNase-I therapy delays secondary brain damage after traumatic brain injury in adult mice.

Traumatic brain injury (TBI) causes the release of danger-associated molecular patterns (DAMP) from damaged or dead cells, which contribute to secondary brain damage after TBI. Cell-free DNA (cfDNA) is a DAMP known to cause disruption of the blood-brain barrier (BBB), promote procoagulant processes, brain edema, and neuroinflammation. This study tested the hypothesis that administration of deoxyribonuclease-I (DNase-I) has a beneficial effect after TBI. Mice (n = 84) were subjected to controlled cortical impact (CCI) and posttraumatic intraperitoneal injections of low dose (LD) or high dose (HD) of DNase-I or vehicle solution at 30 min and 12 h after CCI. LD was most effective to reduce lesion volume (p = 0.003), brain water content (p < 0.0001) and to stabilize BBB integrity (p = 0.019) 1 day post-injury (dpi). At 6 h post injury LD-treated animals showed less cleavage of fibrin (p = 0.0014), and enhanced perfusion as assessed by micro-computer-tomography (p = 0.027). At 5 dpi the number of Iba1-positive cells (p = 0.037) were reduced, but the number of CD45-positive cells, motoric function and brain lesion volume was not different. Posttraumatic-treatment with DNase-I therefore stabilizes the BBB, reduces the formation of brain edema, immune response, and delays secondary brain damage. DNase-I might be a new approach to extend the treatment window after TBI.

Influence of traumatic brain injury on ipsilateral and contralateral cortical perfusion in mice.

Traumatic brain injury (TBI) is one of the most important causes of death in young adults. After brain injury cortical perfusion is impaired by cortical spreading depression, cerebral microvasospasm or microvascular thrombosis and contributes to secondary expansion of lesion into surrounding healthy brain tissue. The present study was designed to determine the regional cortical perfusion pattern after experimental TBI induced by controlled cortical impact (CCI) in male C57/BL6N mice. We performed a longitudinal time series analysis by Laser speckle contrast imaging (LSCI). Measurements were carried out before, immediately and 24 h after trauma. Immediately after CCI cortical perfusion in the lesion core dropped to 10 % of before injury (baseline; %BL) and to 21-24 %BL in the cortical area surrounding the core. Interestingly, cortical perfusion was also significantly reduced in the contralateral non-injured hemisphere (41-58 %BL) matching the corresponding brain region of the injured hemisphere. 24 h after CCI perfusion of the contralateral hemisphere returned to baseline level in the area corresponding to the lesion core, whereas the lateral area of the parietal cortex was hyperperfused (125 %BL). The lesion core region itself remained severely hypoperfused (18 to 26 %BL) during the observation period. TBI causes a maldistribution of both ipsi- and contralateral cerebral perfusion immediately after trauma, which persist for at least 24 h. Higher perfusion levels in the lesion core 24 h after trauma were associated with increased tissue damage, which supports the role of reperfusion injury for secondary brain damage after TBI.

COVID-19 CPR-Impact of Personal Protective Equipment during a Simulated Cardiac Arrest in Times of the COVID-19 Pandemic: A Prospective Comparative Trial.

Background: Guidelines of cardiopulmonary resuscitation (CPR) recommend the use of personal protective equipment (PPE) during the resuscitation of COVID-19 patients. Data on the effects of PPE on rescuers' stress level and quality of CPR are sparse and conflicting. This trial investigated the effects of PPE on team performance in simulated cardiac arrests. Methods: During the pandemic period, 198 teams (689 participants) performed CPR with PPE in simulated cardiac arrests (PPE group) and were compared with 423 (1451 participants) performing in identical scenarios in the pre-pandemic period (control group). Video recordings were used for data analysis. The primary endpoint was hands-on time. Secondary endpoints included a further performance of CPR and the perceived task load assessed by the NASA task-load index. Results: Hands-on times were lower in PPE teams than in the control group (86% (83−89) vs. 90% (87−93); difference 3, 95% CI for difference 3−4, p < 0.0001). Moreover, PPE teams made fewer change-overs and delayed defibrillation and administration of drugs. PPE teams perceived higher task loads (57 (44−67) vs. 63 (53−71); difference 6, 95% CI for difference 5−8, p < 0.0001) and scored higher in the domains physical and temporal demand, performance, and effort. Leadership allocation had no effect on primary and secondary endpoints. Conclusions: Having to wear PPE during CPR is an additional burden in an already demanding task. PPE is associated with an increase in perceived task load, lower hands-on times, fewer change-overs, and delays in defibrillation and the administration of drugs. (German study register number DRKS00023184).

Hemorrhagic Cerebral Insults and Secondary Takotsubo Syndrome: Findings in a Novel In Vitro Model Using Human Blood Samples.

Intracranial hemorrhage results in devastating forms of cerebral damage. Frequently, these results also present with cardiac dysfunction ranging from ECG changes to Takotsubo syndrome (TTS). This suggests that intracranial bleeding due to subarachnoid hemorrhage (SAH) disrupts the neuro-cardiac axis leading to neurogenic stress cardiomyopathy (NSC) of different degrees. Following this notion, SAH and secondary TTS could be directly linked, thus contributing to poor outcomes. We set out to test if blood circulation is the driver of the brain-heart axis by investigating serum samples of TTS patients. We present a novel in vitro model combining SAH and secondary TTS to mimic the effects of blood or serum, respectively, on blood-brain barrier (BBB) integrity using in vitro monolayers of an established murine model. We consistently demonstrated decreased monolayer integrity and confirmed reduced Claudin-5 and Occludin levels by RT-qPCR and Western blot and morphological reorganization of actin filaments in endothelial cells. Both tight junction proteins show a time-dependent reduction. Our findings highlight a faster and more prominent disintegration of BBB in the presence of TTS and support the importance of the bloodstream as a causal link between intracerebral bleeding and cardiac dysfunction. This may represent potential targets for future therapeutic inventions in SAH and TTS.

AT2 activation does not influence brain damage in the early phase after experimental traumatic brain injury in male mice.

Antagonism of the angiotensin II type 1 receptor (AT1) improves neurological function and reduces brain damage after experimental traumatic brain injury (TBI), which may be partly a result of enhanced indirect angiotensin II type 2 receptor (AT2) stimulation. AT2 stimulation was demonstrated to be neuroprotective via anti-inflammatory, vasodilatory, and neuroregenerative mechanisms in experimental cerebral pathology models. We recently demonstrated an upregulation of AT2 after TBI suggesting a protective mechanism. The present study investigated the effect of post-traumatic (5 days after TBI) AT2 activation via high and low doses of a selective AT2 agonist, compound 21 (C21), compared to vehicle-treated controls. No differences in the extent of the TBI-induced lesions were found between both doses of C21 and the controls. We then tested AT2-knockdown animals for secondary brain damage after experimental TBI. Lesion volume and neurological outcomes in AT2-deficient mice were similar to those in wild-type control mice at both 24 h and 5 days post-trauma. Thus, in contrast to AT1 antagonism, AT2 modulation does not influence the initial pathophysiological mechanisms of TBI in the first 5 days after the insult, indicating that AT2 plays only a minor role in the early phase following trauma-induced brain damage.

Manual and Mechanical Induced Peri-Resuscitation Injuries-Post-Mortem and Clinical Findings.

(1) Background: Injuries related to resuscitation are not usually systematically recorded and documented. By evaluating this data, conclusions could be drawn about the quality of the resuscitation, with the aim of improving patient care and safety. (2) Methods: We are planning to conduct a multicentric, retrospective 3-phased study consisting of (1) a worldwide literature review (scoping review), (2) an analysis of anatomical pathological findings from local institutions in North Rhine-Westphalia, Germany to assess the transferability of the review data to the German healthcare system, and (3) depending on the results, possibly establishing potential prospective indicators for resuscitation-related injuries as part of quality assurance measures. (3) Conclusions: From the comparison of literature and local data, the picture of resuscitation-related injuries will be focused on and quality indicators will be derived.

Simulation-based randomized trial of medical emergency cognitive aids.

BACKGROUND: Medical emergencies are complex and stressful, especially for the young and inexperienced. Cognitive aids (CA) have been shown to facilitate management of simulated medical emergencies by experienced teams. In this randomized trial we evaluated guideline adherence and treatment efficacy in simulated medical emergencies managed by residents with and without CA. METHODS: Physicians attending educational courses executed simulated medical emergencies. Teams were randomly assigned to manage emergencies with or without CA. Primary outcome was risk reduction of essential working steps. Secondary outcomes included prior experience in emergency medicine and CA, perceptions of usefulness, clinical relevance, acceptability, and accuracy in CA selection. Participants were grouped as "medical" (internal medicine and neurology) and "perioperative" (anesthesia and surgery) regarding their specialty. The study was designed as a prospective randomized single-blind study that was approved by the ethical committee of the University Duisburg-Essen (19-8966-BO). TRIAL REGISTRATION: DRKS, DRKS00024781. Registered 16 March 2021-Retrospectively registered, http://www.drks.de/DRKS00024781 . RESULTS: Eighty teams participated in 240 simulated medical emergencies. Cognitive aid usage led to 9% absolute and 15% relative risk reduction. Per protocol analysis showed 17% absolute and 28% relative risk reduction. Wrong CA were used in 4%. Cognitive aids were judged as helpful by 94% of the participants. Teams performed significantly better when emergency CA were available (p < 0.05 for successful completion of critical work steps). Stress reduction using CA was more likely in "medical" than in "perioperative" subspecialties (3.7 ± 1.2 vs. 2.9 ± 1.2, p < 0.05). CONCLUSIONS: In a high-fidelity simulation study, CA usage was associated with significant reduction of incorrect working steps in medical emergencies management and was characterized by high acceptance. These findings suggest that CA for medical emergencies may have the potential to improve emergency care.

Influence of intraoperative fluid replacement on ampicillin serum levels and surgical site infections.

BACKGROUND: Surgical site infections (SSI) occur despite antimicrobial prophylaxis and increase postoperative morbidity and mortality. This could be caused by an intraoperative decrease in antibiotic serum concentrations such as ampicillin after major abdominal surgery due to blood loss and fluid therapy, which possibly promotes SSI. This hypothesis was tested in the present study. METHODS: This pilot study was performed as a prospective observational trial between March 2018 and May 2019. Ampicillin/sulbactam was administered intravenously during anesthesia induction. Fluid replacement was guided based on hemodynamic variables, including analysis of pulse pressure variation. The primary outcome was ampicillin serum level (ASL), measured after administration and hourly within 4 hours. The incidence of SSI at hospital discharge was the secondary outcome. Linear mixed and logistic regression models were used for statistical analyses. RESULTS: After screening of 133 adult patients, 129 were enrolled, and 102 completed the study protocol. No correlation was found between the volume of intraoperative fluids and ASL, nor was any association found between ASL and SSI. Based on 5 SSI cases, SSI were associated with higher intraoperative fluid volume. ASL was sufficient to provide intraoperative coverage for all potential bacterial strains. CONCLUSION: Intraoperative fluid replacement had no effect on ASL up to 4 hours after ampicillin/sulbactam administration. SSI were within an acceptable range, indicating adequate antimicrobial prophylaxis, so intraoperative control of ASL does not seem necessary. In conclusion, contrary to our initial hypothesis, ASL is not influenced by volume turnover or blood loss during major surgery and therefore does not affect SSI.

A beginner's view of end of life care on German intensive care units.

BACKGROUND: Little is known about importance and implementation of end-of-life care (EOLC) in German intensive care units (ICU). This survey analyses preferences and differences in training between "medical" (internal medicine, neurology) and "surgical" (surgery, anaesthesiology) residents during intensive care rotation. METHODS: This is a point-prevalence study, in which intensive care medicine course participants of one educational course were surveyed. Physicians from multiple ICU and university as well as non-university hospitals and all care levels were asked to participate. The questionnaire was composed of a paper and an electronic part. Demographic and structural data were prompted and EOLC data (48 questions) were grouped into six categories considering importance and implementation: category 1 (important, always implemented), 2 (important, sometimes implemented), 3 (important, never implemented) and 4-6 (unimportant, implementation always, sometimes, never). The trial is registered at the "Deutsches Register für klinische Studien (DRKS)", Study number DRKS00026619, registered on September 10th 2021, www.drks.de . RESULTS: Overall, 194/ 220 (88%) participants responded. Mean age was 29.7 years, 55% were female and 60% had scant ICU working experience. There were 64% medical and 35% surgical residents. Level of care and size of ICU differed significantly between medical and surgical (both p < 0.001). Sufficient implementation was stated for 66% of EOLC questions, room for improvement (category 2 and 3) was seen in 25, and 8% were classified as irrelevant (category 6). Areas with the most potential for improvement included prognosis and outcome and patient autonomy. There were no significant differences between medical and surgical residents. CONCLUSIONS: Even though EOLC is predominantly regarded as sufficiently implemented in German ICU of all specialties, our survey unveiled still 25% room for improvement for medical as well as surgical ICU residents. This is important, as areas of improvement potential may be addressed with reasonable effort, like individualizing EOLC procedures or setting up EOLC teams. Health care providers as well as medical societies should emphasize EOLC training in their curricula.

Ribonuclease-1 treatment after traumatic brain injury preserves blood-brain barrier integrity and delays secondary brain damage in mice.

Traumatic brain injury (TBI) involves primary mechanical damage and delayed secondary damage caused by vascular dysfunction and neuroinflammation. Intracellular components released into the parenchyma and systemic circulation, termed danger-associated molecular patterns (DAMPs), are major drivers of vascular dysfunction and neuroinflammation. These DAMPs include cell-free RNAs (cfRNAs), which damage the blood-brain barrier (BBB), thereby promoting edema, procoagulatory processes, and infiltration of inflammatory cells. We tested the hypothesis that intraperitoneal injection of Ribonuclease-1 (RNase1, two doses of 20, 60, or 180 µg/kg) at 30 min and 12 h after controlled-cortical-impact (CCI) can reduce secondary lesion expansion compared to vehicle treatment 24 h and 120 h post-CCI. The lowest total dose (40 µg/kg) was most effective at reducing lesion volume (- 31% RNase 40 µg/kg vs. vehicle), brain water accumulation (- 5.5%), and loss of BBB integrity (- 21.6%) at 24 h post-CCI. RNase1 also reduced perilesional leukocyte recruitment (- 53.3%) and microglial activation (- 18.3%) at 120 h post-CCI, but there was no difference in lesion volume at this time and no functional benefit. Treatment with RNase1 in the early phase following TBI stabilizes the BBB and impedes leukocyte immigration, thereby suppressing neuroinflammation. RNase1-treatment may be a novel approach to delay brain injury to extend the window for treatment opportunities after TBI.

Posttraumatic midazolam administration does not influence brain damage after experimental traumatic brain injury.

BACKGROUND: The benzodiazepine midazolam is a γ-aminobutyric acid (GABA)-A receptor agonist frequently used for sedation or stress control in patients suffering from traumatic brain injury (TBI). However, experimental studies on benzodiazepines have reported divergent results, raising concerns about its widespread use in patients. Some studies indicate that benzodiazepine-mediated potentiation of GABAergic neurotransmission is detrimental in brain-injured animals. However, other experimental investigations demonstrate neuroprotective effects, especially in pretreatment paradigms. This study investigated whether single-bolus midazolam administration influences secondary brain damage post-TBI. METHODS: Two different midazolam dosages (0.5 and 5 mg/kg BW), a combination of midazolam and its competitive antagonist flumazenil, or vehicle solution (NaCl 0.9%) was injected intravenously to mice 24 h after experimental TBI induced by controlled cortical impact. Mice were evaluated for neurological and motor deficits using a 15-point neuroscore and the rotarod test. Histopathological brain damage and mRNA expression of inflammatory marker genes were analyzed using quantitative polymerase chain reaction three days after insult. RESULTS: Histological brain damage was not affected by posttraumatic midazolam administration. Midazolam impaired functional recovery, and this effect could not be counteracted by administering the midazolam antagonist flumazenil. An increase in IL-1ß mRNA levels due to postinjury application of midazolam was reversible by flumazenil administration. However, other inflammatory parameters were not affected. CONCLUSIONS: This study merely reports minor effects of a postinjury midazolam application. Further studies focusing on a time-dependent analysis of posttraumatic benzodiazepine administration are required.

Adaptive Mechanisms of Somatostatin-Positive Interneurons after Traumatic Brain Injury through a Switch of α Subunits in L-Type Voltage-Gated Calcium Channels.

Unilateral traumatic brain injury (TBI) causes cortical dysfunctions spreading to the primarily undamaged hemisphere. This phenomenon, called transhemispheric diaschisis, is mediated by an imbalance of glutamatergic versus GABAergic neurotransmission. This study investigated the role of GABAergic, somatostatin-positive (SST) interneurons in the contralateral hemisphere 72 h after unilateral TBI. The brain injury was induced to the primary motor/somatosensory cortex of glutamate decarboxylase 67-green fluorescent protein (GAD67-GFP) knock-in mice at postnatal days 19-21 under anesthesia in vivo. Single GFP+ interneurons of the undamaged, contralateral cortex were isolated by fluorescence-activated cell sorting and analyzed by mass spectrometry. TBI caused a switch of 2 α subunits of pore-forming L-type voltage-gated calcium channels (VGCC) in GABAergic interneurons, an increased expression of CaV1.3, and simultaneous ablation of CaV1.2. This switch was associated with 1) increased excitability of single SST interneurons in patch-clamp recordings and (2) a recovery from early network hyperactivity in the contralateral hemisphere in microelectrode array recordings of acute slices. The electrophysiological changes were sensitive to pharmacological blockade of CaV1.3 (isradipine, 100 nM). These data identify a switch of 2 α subunits of VGCCs in SST interneurons early after TBI as a mechanism to counterbalance post-traumatic hyperexcitability.

U SO CARE-The Impact of Cardiac Ultrasound during Cardiopulmonary Resuscitation: A Prospective Randomized Simulator-Based Trial.

BACKGROUND: Actual cardiopulmonary resuscitation (CPR) guidelines recommend point-of-care ultrasound (POCUS); however, data on POCUS during CPR are sparse and conflicting. This randomized trial investigated the effects of POCUS during CPR on team performance and diagnostic accuracy. METHODS: Intensive Care and Emergency Medicine residents performed CPR with or without available POCUS in simulated cardiac arrests. The primary endpoint was hands-on time. Data analysis was performed using video recordings. RESULTS: Hands-on time was 89% (87-91) in the POCUS and 92% (89-94) in the control group (difference 3, 95% CI for difference 2-4, p < 0.001). POCUS teams had delayed defibrillator attachments (33 vs. 26 sec, p = 0.017) and first rhythm analysis (74 vs. 52 sec, p = 0.001). Available POCUS was used in 71%. Of the POCUS teams, 3 stated a POCUS-derived diagnosis, with 49 being correct and 42 followed by a correct treatment decision. Four teams made a wrong diagnosis and two made an inappropriate treatment decision. CONCLUSIONS: POCUS during CPR resulted in lower hands-on times and delayed rhythm analysis. Correct POCUS diagnoses occurred in 52%, correct treatment decisions in 44%, and inappropriate treatment decisions in 2%. Training on POCUS during CPR should focus on diagnostic accuracy and maintenance of high-quality CPR.

The Recovery Room: Transition from a Sleepy Postoperative Unit to a Vibrant and Cost-Effective Multipurpose Perioperative Care Unit.

The anesthesiologist, who traditionally was solely responsible for the intra- and postoperative care of patients, has undergone a transformation over the last decades and has emerged as a specialist for perioperative medicine. This includes preoperative assessment, preoperative stabilization of emergent cases, pre- or postoperative initiation of regional blocks, postoperative recovery and if needed postoperative intensive care outside the intensive care unit. A traditional recovery room, designated to take care of patients emerging from anesthesia only, no longer matches the modern anesthesiologist's demands. However, a traditional recovery room can easily be transformed into a vibrant multi-purpose perioperative care unit. Especially in smaller hospitals, this serves to match the anesthesiologist's demands without the financial burden of separate units for each task. On the contrary, it allows to transform the recovery room from a mandatory, but costly postoperative unit into a highly productive and demanding perioperative unit, allowing for extra revenues without corresponding costs. Worldwide, operating rooms are linked to an adjacent recovery room allowing patients to emerge from anesthesia until they fulfill the criteria to be transferred either to the regular ward or, in case of outpatient surgery, to be discharged home. Running these recovery rooms, however, is expensive due to the required technical equipment and the monthly costs of highly qualified anesthesia personnel. Despite these financial burdens, such recovery rooms are still mandatory to ensure full recovery after anesthesia and surgery. In most countries, there is no (full) reimbursement for providing recovery rooms, turning them into fiscally deficient units in most hospitals. However, recovery rooms can be further developed allowing hospitals to improve their caseloads, reduce turnover times in the operating room, and even help to manage a shortage of beds in the intensive care unit. In this paper, we describe the potential transformation from a traditional recovery room to a multi-purpose perioperative high-tech unit.