Remdesivir for the treatment of COVID-19.

BACKGROUND: Remdesivir is an antiviral medicine approved for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19). This led to widespread implementation, although the available evidence remains inconsistent. This update aims to fill current knowledge gaps by identifying, describing, evaluating, and synthesising all evidence from randomised controlled trials (RCTs) on the effects of remdesivir on clinical outcomes in COVID-19. OBJECTIVES: To assess the effects of remdesivir and standard care compared to standard care plus/minus placebo on clinical outcomes in patients treated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies, without language restrictions. We conducted the searches on 31 May 2022. SELECTION CRITERIA: We followed standard Cochrane methodology. We included RCTs evaluating remdesivir and standard care for the treatment of SARS-CoV-2 infection compared to standard care plus/minus placebo irrespective of disease severity, gender, ethnicity, or setting. We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for outcomes that were reported according to our prioritised categories: all-cause mortality, in-hospital mortality, clinical improvement (being alive and ready for discharge up to day 28) or worsening (new need for invasive mechanical ventilation or death up to day 28), quality of life, serious adverse events, and adverse events (any grade). We differentiated between non-hospitalised individuals with asymptomatic SARS-CoV-2 infection or mild COVID-19 and hospitalised individuals with moderate to severe COVID-19. MAIN RESULTS: We included nine RCTs with 11,218 participants diagnosed with SARS-CoV-2 infection and a mean age of 53.6 years, of whom 5982 participants were randomised to receive remdesivir. Most participants required low-flow oxygen at baseline. Studies were mainly conducted in high- and upper-middle-income countries. We identified two studies that are awaiting classification and five ongoing studies. Effects of remdesivir in hospitalised individuals with moderate to severe COVID-19 With moderate-certainty evidence, remdesivir probably makes little or no difference to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 6 more; 4 studies, 7142 participants), day 60 (RR 0.85, 95% CI 0.69 to 1.05; RD 35 fewer per 1000, 95% CI 73 fewer to 12 more; 1 study, 1281 participants), or in-hospital mortality at up to day 150 (RR 0.93, 95% CI 0.84 to 1.03; RD 11 fewer per 1000, 95% CI 25 fewer to 5 more; 1 study, 8275 participants). Remdesivir probably increases the chance of clinical improvement at up to day 28 slightly (RR 1.11, 95% CI 1.06 to 1.17; RD 68 more per 1000, 95% CI 37 more to 105 more; 4 studies, 2514 participants; moderate-certainty evidence). It probably decreases the risk of clinical worsening within 28 days (hazard ratio (HR) 0.67, 95% CI 0.54 to 0.82; RD 135 fewer per 1000, 95% CI 198 fewer to 69 fewer; 2 studies, 1734 participants, moderate-certainty evidence). Remdesivir may make little or no difference to the rate of adverse events of any grade (RR 1.04, 95% CI 0.92 to 1.18; RD 23 more per 1000, 95% CI 46 fewer to 104 more; 4 studies, 2498 participants; low-certainty evidence), or serious adverse events (RR 0.84, 95% CI 0.65 to 1.07; RD 44 fewer per 1000, 95% CI 96 fewer to 19 more; 4 studies, 2498 participants; low-certainty evidence). We considered risk of bias to be low, with some concerns for mortality and clinical course. We had some concerns for safety outcomes because participants who had died did not contribute information. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data. Effects of remdesivir in non-hospitalised individuals with mild COVID-19 One of the nine RCTs was conducted in the outpatient setting and included symptomatic people with a risk of progression. No deaths occurred within the 28 days observation period. We are uncertain about clinical improvement due to very low-certainty evidence. Remdesivir probably decreases the risk of clinical worsening (hospitalisation) at up to day 28 (RR 0.28, 95% CI 0.11 to 0.75; RD 46 fewer per 1000, 95% CI 57 fewer to 16 fewer; 562 participants; moderate-certainty evidence). We did not find any data for quality of life. Remdesivir may decrease the rate of serious adverse events at up to 28 days (RR 0.27, 95% CI 0.10 to 0.70; RD 49 fewer per 1000, 95% CI 60 fewer to 20 fewer; 562 participants; low-certainty evidence), but it probably makes little or no difference to the risk of adverse events of any grade (RR 0.91, 95% CI 0.76 to 1.10; RD 42 fewer per 1000, 95% CI 111 fewer to 46 more; 562 participants; moderate-certainty evidence). We considered risk of bias to be low for mortality, clinical improvement, and safety outcomes. We identified a high risk of bias for clinical worsening. AUTHORS' CONCLUSIONS: Based on the available evidence up to 31 May 2022, remdesivir probably has little or no effect on all-cause mortality or in-hospital mortality of individuals with moderate to severe COVID-19. The hospitalisation rate was reduced with remdesivir in one study including participants with mild to moderate COVID-19. It may be beneficial in the clinical course for both hospitalised and non-hospitalised patients, but certainty remains limited. The applicability of the evidence to current practice may be limited by the recruitment of participants from mostly unvaccinated populations exposed to early variants of the SARS-CoV-2 virus at the time the studies were undertaken.  Future studies should provide additional data on the efficacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for different population subgroups.

Janus kinase inhibitors for the treatment of COVID-19.

BACKGROUND: With potential antiviral and anti-inflammatory properties, Janus kinase (JAK) inhibitors represent a potential treatment for symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. They may modulate the exuberant immune response to SARS-CoV-2 infection. Furthermore, a direct antiviral effect has been described. An understanding of the current evidence regarding the efficacy and safety of JAK inhibitors as a treatment for coronavirus disease 2019 (COVID-19) is required. OBJECTIVES: To assess the effects of systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo) on clinical outcomes in individuals (outpatient or in-hospital) with any severity of COVID-19, and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, medRxiv, and Cochrane Central Register of Controlled Trials), Web of Science, WHO COVID-19 Global literature on coronavirus disease, and the US Department of Veterans Affairs Evidence Synthesis Program (VA ESP) Covid-19 Evidence Reviews to identify studies up to February 2022. We monitor newly published randomised controlled trials (RCTs) weekly using the Cochrane COVID-19 Study Register, and have incorporated all new trials from this source until the first week of April 2022. SELECTION CRITERIA: We included RCTs that compared systemic JAK inhibitors plus standard of care to standard of care alone (plus/minus placebo) for the treatment of individuals with COVID-19. We used the WHO definitions of illness severity for COVID-19. DATA COLLECTION AND ANALYSIS: We assessed risk of bias of primary outcomes using Cochrane's Risk of Bias 2 (RoB 2) tool. We used GRADE to rate the certainty of evidence for the following primary outcomes: all-cause mortality (up to day 28), all-cause mortality (up to day 60), improvement in clinical status: alive and without need for in-hospital medical care (up to day 28), worsening of clinical status: new need for invasive mechanical ventilation or death (up to day 28), adverse events (any grade), serious adverse events, secondary infections. MAIN RESULTS: We included six RCTs with 11,145 participants investigating systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo). Standard of care followed local protocols and included the application of glucocorticoids (five studies reported their use in a range of 70% to 95% of their participants; one study restricted glucocorticoid use to non-COVID-19 specific indications), antibiotic agents, anticoagulants, and antiviral agents, as well as non-pharmaceutical procedures. At study entry, about 65% of participants required low-flow oxygen, about 23% required high-flow oxygen or non-invasive ventilation, about 8% did not need any respiratory support, and only about 4% were intubated. We also identified 13 ongoing studies, and 9 studies that are completed or terminated and where classification is pending. Individuals with moderate to severe disease Four studies investigated the single agent baricitinib (10,815 participants), one tofacitinib (289 participants), and one ruxolitinib (41 participants). Systemic JAK inhibitors probably decrease all-cause mortality at up to day 28 (95 of 1000 participants in the intervention group versus 131 of 1000 participants in the control group; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91; 6 studies, 11,145 participants; moderate-certainty evidence), and decrease all-cause mortality at up to day 60 (125 of 1000 participants in the intervention group versus 181 of 1000 participants in the control group; RR 0.69, 95% CI 0.56 to 0.86; 2 studies, 1626 participants; high-certainty evidence). Systemic JAK inhibitors probably make little or no difference in improvement in clinical status (discharged alive or hospitalised, but no longer requiring ongoing medical care) (801 of 1000 participants in the intervention group versus 778 of 1000 participants in the control group; RR 1.03, 95% CI 1.00 to 1.06; 4 studies, 10,802 participants; moderate-certainty evidence). They probably decrease the risk of worsening of clinical status (new need for invasive mechanical ventilation or death at day 28) (154 of 1000 participants in the intervention group versus 172 of 1000 participants in the control group; RR 0.90, 95% CI 0.82 to 0.98; 2 studies, 9417 participants; moderate-certainty evidence). Systemic JAK inhibitors probably make little or no difference in the rate of adverse events (any grade) (427 of 1000 participants in the intervention group versus 441 of 1000 participants in the control group; RR 0.97, 95% CI 0.88 to 1.08; 3 studies, 1885 participants; moderate-certainty evidence), and probably decrease the occurrence of serious adverse events (160 of 1000 participants in the intervention group versus 202 of 1000 participants in the control group; RR 0.79, 95% CI 0.68 to 0.92; 4 studies, 2901 participants; moderate-certainty evidence). JAK inhibitors may make little or no difference to the rate of secondary infection (111 of 1000 participants in the intervention group versus 113 of 1000 participants in the control group; RR 0.98, 95% CI 0.89 to 1.09; 4 studies, 10,041 participants; low-certainty evidence). Subgroup analysis by severity of COVID-19 disease or type of JAK inhibitor did not identify specific subgroups which benefit more or less from systemic JAK inhibitors. Individuals with asymptomatic or mild disease We did not identify any trial for this population. AUTHORS' CONCLUSIONS: In hospitalised individuals with moderate to severe COVID-19, moderate-certainty evidence shows that systemic JAK inhibitors probably decrease all-cause mortality. Baricitinib was the most often evaluated JAK inhibitor. Moderate-certainty evidence suggests that they probably make little or no difference in improvement in clinical status. Moderate-certainty evidence indicates that systemic JAK inhibitors probably decrease the risk of worsening of clinical status and make little or no difference in the rate of adverse events of any grade, whilst they probably decrease the occurrence of serious adverse events. Based on low-certainty evidence, JAK inhibitors may make little or no difference in the rate of secondary infection. Subgroup analysis by severity of COVID-19 or type of agent failed to identify specific subgroups which benefit more or less from systemic JAK inhibitors. Currently, there is no evidence on the efficacy and safety of systemic JAK inhibitors for individuals with asymptomatic or mild disease (non-hospitalised individuals).

Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID-19.

BACKGROUND: Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID-19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA). This approach is potentially associated with both advantages (e.g. a preserved diaphragmatic motility and an optimised ventilation-perfusion ratio of the ventilated lung), as well as risks (e.g. a higher rate of ventilator-induced lung injury or a worsening of pulmonary oedema due to increases in transpulmonary pressure). As a consequence, spontaneous breathing in people with COVID-19-ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists. OBJECTIVES: To assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID-19 with ARDS compared to ventilation strategies that avoid spontaneous breathing. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, Clinical Trials.gov WHO ICTRP, and medRxiv) and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies from their inception to 2 March 2022. SELECTION CRITERIA: Eligible study designs comprised randomised controlled trials (RCTs) that evaluated spontaneous breathing in participants with COVID-19-related ARDS compared to ventilation strategies that avoided spontaneous breathing (e.g. using NMBA or deep sedation levels). Additionally, we considered controlled before-after studies, interrupted time series with comparison group, prospective cohort studies and retrospective cohort studies. For these non-RCT studies, we considered a minimum total number of 50 participants to be compared as necessary for inclusion. Prioritised outcomes were all-cause mortality, clinical improvement or worsening, quality of life, rate of (serious) adverse events and rate of pneumothorax. Additional outcomes were need for tracheostomy, duration of ICU length of stay and duration of hospitalisation. DATA COLLECTION AND ANALYSIS: We followed the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently screened all studies at the title/abstract and full-text screening stage. We also planned to conduct data extraction and risk of bias assessment in duplicate. We planned to conduct meta-analysis for each prioritised outcome, as well as subgroup analyses of mortality regarding severity of oxygenation impairment and duration of ARDS. In addition, we planned to perform sensitivity analyses for studies at high risk of bias, studies using NMBA in addition to deep sedation level to avoid spontaneous breathing and a comparison of preprints versus peer-reviewed articles. We planned to assess the certainty of evidence using the GRADE approach. MAIN RESULTS: We identified no eligible studies for this review. AUTHORS' CONCLUSIONS: We found no direct evidence on whether early spontaneous breathing in SARS-CoV-2-induced ARDS is beneficial or detrimental to this particular group of patients.  RCTs comparing early spontaneous breathing with ventilatory strategies not allowing for spontaneous breathing in SARS-CoV-2-induced ARDS are necessary to determine its value within the treatment of severely ill people with COVID-19. Additionally, studies should aim to clarify whether treatment effects differ between people with SARS-CoV-2-induced ARDS and people with non-SARS-CoV-2-induced ARDS.

Remdesivir for the treatment of COVID-19.

BACKGROUND: Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID-19.  A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required. OBJECTIVES: To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS-CoV-2 infection, and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021. SELECTION CRITERIA: We followed standard Cochrane methodology. We included RCTs evaluating remdesivir for the treatment of SARS-CoV-2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting.  We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all-cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high-flow oxygen or non-invasive or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non-invasive mechanical ventilation or high-flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, adverse events (any grade), and serious adverse events. MAIN RESULTS: We included five RCTs with 7452 participants diagnosed with SARS-CoV-2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low-flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. We identified two ongoing studies, one was suspended due to a lack of COVID-19 patients to recruit. Risk of bias was considered to be of some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data. Effects of remdesivir in hospitalised individuals  Remdesivir probably makes little or no difference to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate-certainty evidence). Considering the initial severity of condition, only one study showed a beneficial effect of remdesivir in patients who received low-flow oxygen at baseline (RR 0.32, 95% CI 0.15 to 0.66, 435 participants), but conflicting results exists from another study, and we were unable to validly assess this observations due to limited availability of comparable data. Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low-certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low-certainty evidence).   We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high-flow oxygen or non-invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low-certainty evidence); new need for non-invasive mechanical ventilation or high-flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low-certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low-certainty evidence). The evidence suggests that remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low-certainty evidence).  None of the included studies reported quality of life. Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate-certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Based on the currently available evidence, we are moderately certain that remdesivir probably has little or no effect on all-cause mortality at up to day 28 in hospitalised adults with SARS-CoV-2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to validly examine the effect of remdesivir on mortality in subgroups depending on the extent of respiratory support at baseline.  Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.

Non-medical risk factors associated with postponing elective surgery: a prospective observational study.

BACKGROUND: Operation room (OR) planning is a complex process, especially in large hospitals with high rates of unplanned emergency procedures. Postponing elective surgery in order to provide capacity for emergency operations is inevitable at times. Elderly patients, residents of nursing homes, women, patients with low socioeconomic status and ethnic minorities are at risk for undertreatment in other contexts, as suggested by reports in the medical literature. We hypothesized that specific patient groups could be at higher risk for having their elective surgery rescheduled for non-medical reasons. METHODS: In this single center, prospective observational trial, we analysed 2519 patients undergoing elective surgery from October 2018 to May 2019. A 14-item questionnaire was handed out to illicit patient details. Additional characteristics were collected using electronic patient records. Information on the timely performance of the scheduled surgery was obtained using the OR's patient data management system. 6.45% of all planned procedures analysed were postponed. Association of specific variables with postponement rates were analysed using the Mann-Whitney U test and Fisher's exact test/χ2-test. RESULTS: Significantly higher rates of postponing elective surgery were found in elderly patients. No significant differences in postponing rates were found for the variables gender, nationality (Germany, EU, non-EU), native language, professional medical background and level of education. Significantly lower rescheduling rates were found in patients with ties to hospital staff and in patients with a private health insurer. CONCLUSIONS: Elderly patients, retirees and nursing home residents seem to be at higher risk for having their elective surgery rescheduled. However, owing to the study design, causality could not be proven. Our findings raise concern about possible undertreatment of these patient groups and provide data on short-term postponement of elective surgery. Trial registration DRKS00015836. Retrospectively registered.

Asymmetry in patient-related information disrupts pre-anesthetic patient briefing.

BACKGROUND: If one party has more or better information than the other, an information asymmetry can be assumed. The aim of the study was to identify the origin of incomplete patient-related preoperative information, which led to disruptions and losses of time during pre-anaesthetic patient briefing. We hypothesized that lower employees' educational level increases the amount of disruptive factors. METHODS: A prospective observational study design was used. Patient selection was depending on the current patient flow in the area of the clinic for pre-anesthetic patient briefing. Data were collected over a period of 8 weeks. A stopwatch was used to record the time of disruptive factors. Various causes of time losses were grouped to facilitate statistical evaluation, which was performed by using the U-test of Mann and Whitney, Chi-square test or the Welch-t-test, as required. RESULTS: Out of 221 patients, 130 patient briefings (58.8%) had been disrupted. Residents were affected more often than consultants (66% vs. 47%, p = 0.008). Duration of disruptions was independent of the level of training and lasted about 2,5 minutes and 10% of the total time of patient briefing. Most time-consuming disruptive factors were missing study results, incomplete case histories, and limited patient compliance. CONCLUSIONS: Disruptions during pre-anesthetic patient briefings that were caused by patient-related information asymmetry are common and account for a significant loss of time. The resultant costs justify investments in appropriate personnel allocation.

Melanotic Neuroectodermal Tumour of Infancy: Clinical Courses and Therapeutic Options-A Review of Three Cases.

BACKGROUND: Melanotic neuroectodermal tumour of infancy (MNTI) is a rare benign neoplasm. MNTI appears most often during the first year of life, arises predominantly in the maxilla and tends to recur. We discuss possible therapeutic options given in the literature and within our experience in three cases. PATIENTS: In our recent case, we used an intraoral approach to perform resection of the right-sided maxilla. Despite tumour-positive margins, there was no recurrence over the course of one year. In a previous case of MNTI, two recurrences occurred and 6 months after last resection patient received a rib graft for maxillary reconstruction. However, at the age of 7 years, the infant displayed severe maxillary hypoplasia. In a third case of MNTI, the patient was followed up after initial therapy for two decades and underwent multiple reconstruction procedures to achieve successful rehabilitation. CONCLUSION: Surgical treatment of MNTI should respect vital anatomic structures to avoid gross mutilation. The need for extended and repetitive tumour resection in early childhood can lead to growth disturbances and to further multiple reconstruction procedures in adulthood. Because of the rarity of MNTI, an international database is warranted to evaluate therapies and clinical courses over decades.

Do variations in the 5-HT3A and 5-HT3B serotonin receptor genes (HTR3A and HTR3B) influence the occurrence of postoperative vomiting?

BACKGROUND: Postoperative nausea and vomiting are unpleasant side effects of general anesthesia. Besides known risk factors (female gender, nonsmoker, history, and opioids), a genetic influence of the serotonin receptor system on the development of nausea and vomiting has repeatedly been proposed. In this pilot study, we therefore investigated the genes of the serotonin receptor subunits A and B (HTR3A and HTR3B) for genetic variants. METHODS: We included 95 patients who had suffered from postoperative vomiting (POV) after general anesthesia and 94 control patients. After DNA isolation, the entire HTR3A and HTR3B coding regions, the 5' flanking regions, and exon/intron boundaries were screened for genetic variants. Correlation of identified genetic variants with POV was determined by logistic regression. RESULTS: We identified 16 different variants in the HTR3A gene and 19 in the HTR3B gene. By using a multivariate logistic regression model that also included classical risk factors, the HTR3A variant c1377A>G was associated with a significantly higher risk (odds ratio [OR] 2.972; 95% confidence interval [CI] 1.466-6.021; P = 0.003) and the HTR3B variants c5+201_+202delCA (OR 0.421; 95% CI 0.257-0.69; P = 0.001) and c6-137C>T (OR 0.034; 95% CI 0.003-0.332; P = 0.004) were associated with a lower risk for POV. However, all significant genetic variants were located in noncoding regions of their gene. CONCLUSIONS: Genetic variations in the HTR3A and HTR3B gene seem to be associated with the individual risk of developing POV. How strong their influence is within the multifactorial genesis of POV needs to be investigated in additional studies with an appropriate sample size.

Effects of clonidine and superficial cervical plexus block on hemodynamic stability after carotid endarterectomy.

OBJECTIVES: To evaluate the effects of 2 interventions (intravenous clonidine and superficial cervical block) on hemodynamic stability after carotid endarterectomy and to identify variables associated with hemodynamic instability. DESIGN: Prospective, observational study, sequential enrollment. SETTING: University hospital. PARTICIPANTS: Two hundred seventy-five patients undergoing elective carotid endarterectomy under general anesthesia. INTERVENTIONS: Group NN (n = 50) received no intervention. In group CN (n = 85), 3 mug/kg of clonidine were administered intravenously 30 minutes before the end of the operation. Group CB (n = 140) additionally received a superficial cervical plexus block (SCB) with 20 mL of naropine 0.5% before the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Clonidine alone (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.45-3.76) and clonidine combined with an SCB (OR, 4.99; 95% CI, 3.19-7.82) resulted in a significant increase in hemodynamic stability after CEA (p < 0.001) from 53.3% (NN) to 70.0% (CN) and 83.3% (CB), respectively. The need for rescue medication decreased from 40.0% to 17.6% and 13.6% (p < 0.001). Both interventions significantly reduced the need for postoperative opioid analgesics (p < 0.01). Logistic regression analysis showed preoperative systolic blood pressure values greater than 170 mmHg (OR, 3.23; 95% CI, 1.76-5.93), previous cardiac interventions (OR, 3.3; 95% CI, 1.54-7.11), and the need for rescue medication in the awakening period (OR, 5.8; 95% CI, 2.88-11.52) to be independent risk factors for postoperative hemodynamic instability (p < or = 0.002). CONCLUSIONS: Intravenous clonidine and superficial cervical block significantly improve cardiovascular stability after carotid endarterectomy. Patients with pre-existing excessive hypertension and previous coronary interventions must be considered a high-risk group.