Addition of nitrous oxide and oxygen to carbon dioxide pneumoperitoneum during laparoscopic surgery for pain reduction: A double-blinded randomized controlled trial.

OBJECTIVE: To examine if peritoneal conditioning with an altered insufflation gas mixture is associated with reduced postoperative pain intensity compared to the standard insufflation gas (i.e., 100% CO2). DESIGN: A prospective, single-centre, randomized, double-blind, superiority trial was performed. SETTING: This study was conducted between 4 April 2019 and 10 February 2022 at the Jessa Hospital, Hasselt, Belgium. POPULATION: Patients scheduled for elective gynaecologic laparoscopic surgery. METHODS: Seventy-four patients scheduled for elective gynaecologic laparoscopic surgery were randomised to receive either the standard insufflation gas with 100 CO2 (n = 37; control group) or the altered gas mixture of 86% CO2, 10% N2O and 4% O2 (n = 37; experimental group). MAIN OUTCOME MEASURES: Postoperative pain was assessed at 4, 8 and 24 hours after surgery and on postoperative day (POD) 7 by an 11-point Numeric Rating Scale, with 0 indicating no pain and 10 indicating worst imaginable pain. RESULTS: No significant differences were found between the control and experimental groups regarding postoperative pain at 4, 8 and 24 h after surgery, as well as on POD7. In addition, the median (25% and 75%) total amount of IV piritramide consumption during the first 24 h after surgery was not significantly different between groups (control group: 18.0 [10.0, 27.0] mg vs. experimental group: 17.0 [10.0, 34.0] mg, p = 0.62). CONCLUSION: The alternative insufflation gas mixture comprising 86% CO2, 10% N2O and 4% O2 used for the pneumoperitoneum during gynaecologic laparoscopic surgery does not appear to reduce postoperative pain compared to the standard insufflation gas of 100% CO2.

Additive or synergistic analgesic effect of metamizole on standard pain treatment at home after arthroscopic shoulder surgery: A randomised controlled superiority trial.

BACKGROUND: There is growing evidence that the analgesic effect of metamizole is mediated at least partly by central mechanisms, including the endocannabinoid/endovanilloid system. Consequently, metamizole may have additive or even synergistic analgesic effects with paracetamol and nonsteroidal anti-inflammatory drugs (NSAID). OBJECTIVE: This study aimed to assess if triple therapy with metamizole, ibuprofen and paracetamol (MIP) is superior to double therapy with ibuprofen and paracetamol (i.p.) in treating pain at home after ambulatory arthroscopic shoulder surgery. DESIGN/SETTING/PATIENTS/INTERVENTION: In this double-blind, controlled, high-volume single centre, superiority trial, 110 patients undergoing elective ambulatory arthroscopic shoulder surgery were randomised to receive either MIP ( n  = 55) or i.p. ( n  = 55) orally for 4 days between December 2019 and November 2021. Pain intensity at movement and rest, using a numeric rating scale (NRS), perceived pain relief, use of rescue medication and adverse effects of study medication were recorded at the post-anaesthesia care unit (PACU) and on postoperative day (POD) 1 to 4 and 7. Quality of Recovery (QoR) and satisfaction with study medication were measured at POD 7 with telephone follow-up. MAIN OUTCOME MEASURE: The primary outcome measure was postoperative pain intensity on movement measured by an 11-point NRS (where 0 = no pain and 10 = worst pain imaginable) on POD 1. RESULTS: For the primary outcome, superiority of MIP in reducing postoperative pain at movement on POD 1 was not confirmed: mean difference NRS [95% confidence interval (CI), -0.08 (-1.00 to 0.84)]. For pain on movement and at rest, no significant differences were found between groups in the PACU nor on POD 1 to 4 or day 7. Nausea was reported significantly more frequently in the metamizole group (22.6 vs. 58.5; P  < 0.001). Other adverse effects of study medication, rescue opioid consumption, perceived pain relief, QoR at POD 7, and overall patient satisfaction were similar in both groups. CONCLUSION: Clinically, triple oral treatment with metamizole, paracetamol and ibuprofen is not superior to oral paracetamol and ibuprofen in multimodal pain treatment at home after ambulatory arthroscopic shoulder surgery. TRIAL REGISTRATION: European Union Clinical Trials Register 2019-002801-23 and Clinicaltrials.gov NCT04082728.

Secondary infection in COVID-19 critically ill patients: a retrospective single-center evaluation.

BACKGROUND: Patients infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2) can develop severe illness necessitating intensive care admission. Critically ill patients are susceptible for the development of secondary bacterial infections. Due to a combination of virus- and drug-induced immunosuppression, critically ill patients with corona virus disease 2019 (COVID-19) may even have a higher risk of developing a secondary infection. These secondary infections can aggravate the severity of illness and increase the risk of death. Further research on secondary infections in COVID-19 patients is essential. Therefore, the objective of this study was to investigate the incidence and associated risk factors of secondary bacterial infections and to identify the most common groups of pathogens in critically ill COVID-19 patients. METHODS: This mono-center, retrospective observational cohort study was performed at the intensive care unit (ICU) of the Jessa Hospital, Hasselt, Belgium. All adult COVID-19 patients admitted to the ICU from 13th March 2020 until 17th October 2020, were eligible for inclusion in the study. Data from the resulting 116 patients were prospectively entered into a customized database. The resulting database was retrospectively reviewed to investigate three types of secondary bacterial infections (secondary pneumonia, bloodstream infections of unknown origin, catheter-related sepsis). RESULTS: Of 94 included patients, 68% acquired at least one of the studied secondary bacterial infections during their ICU stay. Almost two thirds of patients (65.96%, n = 62) acquired a secondary pneumonia, whereas 29.79% (n = 28) acquired a bacteremia of unknown origin and a smaller proportion of patients (14.89%, n = 14) acquired a catheter-related sepsis. Male gender (P = 0.05), diabetes mellitus (P = 0.03) and the cumulative dose of corticosteroids (P = 0.004) were associated with increased risk of secondary bacterial infection. The most common pathogens detected in the cultures of patients with secondary pneumonia were Gram-negative bacilli. Bacteremia of unknown origin and catheter-related sepsis were mostly caused by Gram-positive cocci. CONCLUSION: This study confirms that the incidence of secondary bacterial infections is very high in critically ill COVID-19 patients. These patients are at highest risk of developing secondary pneumonia. Male gender, a history of diabetes mellitus and the administration of corticosteroids were associated with increased risk of secondary bacterial infection.

Predictors of poor outcome in critically ill patients with COVID-19 pneumonia treated with extracorporeal membrane oxygenation.

INTRODUCTION: We aimed to identify risk factors associated with ICU mortality in critically ill patients with COVID-19 pneumonia treated with Extracorporeal membrane oxygenation (ECMO). We also aimed to assess protocol violations of the local eligibility criteria of ECMO initiation. METHODS: All 31 consecutive adult patients with confirmed COVID-19 pneumonia admitted to ICU and treated with ECMO from March 13th 2020 to 8 December 2021 were enrolled. Eligibility criteria for ECMO initiation were: P/F-ratio<50 mmHg >3 hours, P/F-ratio<80 mmHg >6 hours or pH<7.25 + PaCO2>60 mmHg >6 hours, despite maximal protective invasive ventilation. Primary outcome was ICU mortality. Univariate logistic regression analyses were performed to identify predictors of ICU mortality. RESULTS: 12 out of 31 patients (38.7%) did not survive ECMO treatment in ICU. Half of the non-survivors suffered from acute kidney failure compared to 3 out of 19 survivors (15.79%) (p = .04). Half of the non-survivors required CRRT treatment versus 1 patient in the survivor group (5.3%) (p < .01). Higher age (2.45 (0.97-6.18), p = .05), the development of AKI (5.33 (1.00-28.43), p = .05), need of CRRT during ICU stay (18.00 (1.79-181.31), p = .01) and major bleeding during ECMO therapy (0.51 (0.19-0.89), p < .01) were identified to be predictors of ICU mortality. CONCLUSION: Almost 60% of patients could be treated successfully with ECMO with sustained results at 3 months. Predictors for ICU mortality were development of AKI and need of CRRT during ICU stay, higher age category and major bleeding. Inadvertent ECMO allocation was noted in almost one in five patients.

Real-life assessment of chronic rhinosinusitis patients using mobile technology: The mySinusitisCoach project by EUFOREA.

BACKGROUND: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socioeconomic burden. Monitoring of patient-reported outcomes by mobile technology offers the possibility to better understand real-life burden of CRS. METHODS: This study reports on the cross-sectional evaluation of data of 626 users of mySinusitisCoach (mSC), a mobile application for CRS patients. Patient characteristics of mSC users were analysed as well as the level of disease control based on VAS global rhinosinusitis symptom score and adapted EPOS criteria. RESULTS: The mSC cohort represents a heterogeneous group of CRS patients with a diverse pattern of major symptoms. Approximately half of patients reported nasal polyps. 47.3% of all CRS patients were uncontrolled based on evaluation of VAS global rhinosinusitis symptom score compared to 40.9% based on adapted EPOS criteria. The impact of CRS on sleep quality and daily life activities was significantly higher in uncontrolled versus well-controlled patients. Half of patients had a history of FESS (functional endoscopic sinus surgery) and reported lower symptom severity compared to patients without a history of FESS, except for patients with a history of more than 3 procedures. Patients with a history of FESS reported higher VAS levels for impaired smell. CONCLUSION: Real-life data confirm the high disease burden in uncontrolled CRS patients, clearly impacting quality of life. Sinus surgery improves patient-reported outcomes, but not in patients with a history of more than 3 procedures. Mobile technology opens a new era of real-life monitoring, supporting the evolution of care towards precision medicine.

Comparison of Intracranial Pressure and Pressure Reactivity Index Obtained Through Pressure Measurements in the Ventricle and in the Parenchyma During and Outside Cerebrospinal Fluid Drainage Episodes in a Manipulation-Free Patient Setting.

OBJECTIVE: We investigated the effect of cerebrospinal fluid (CSF) drainage on the intracranial pressure (ICP) signal measured in the parenchyma and the ventricle as well as the effect on the pressure reactivity index (PRx) calculated from both signals. METHODS: Ten patients were included in this prospective study. All patients received a parenchymal ICP sensor and an external ventricular drain (EVD) for CSF drainage. ICP signals (ICP-p and ICP-evd) were captured. Part of the study was a period of 90 min during which the patient was free from any manipulation, consisting of 30 min of drainage (O1), 30 min EVD closed (C) and 30 min of drainage (O2). RESULTS: Mean ICP-evd and mean AMP-evd increased (3.03 and 0.46 mmHg) from O1 to C and decreased (2.12 and 0.43 mmHg) from C to O2. ICP-p and AMP-p changes were less pronounced (closing EVD: +0.81 mmHg/+0.22 mmHg; opening EVD: -0.22 mmHg/-0.05 mmHg). Mean difference between PRx-evd and PRx-p was 0.12 for O1, 0.02 for C and -0.02 for O2. The intraclass correlation coefficient for absolute agreement of single measures was 0.66 for O1, 0.77 for C and 0.69 for O2. Mean PRx differences demonstrated a significant difference between O1 versus C and O1 versus O2 but not between C versus O2. CONCLUSION: Drainage of CSF reduces ICP magnitude and amplitude through the EVD. This effect was only marginal in parenchymal ICP measurements. In manipulation-free circumstances, agreement of PRx obtained through parenchymal and ventricular measurements was moderate to good, depending on the statistical method, and was not necessarily influenced by drainage.

Enhanced chemosensory sensitivity in patients with idiopathic rhinitis and its reversal by nasal capsaicin treatment.

BACKGROUND: The therapeutic action of capsaicin treatment in patients with idiopathic rhinitis (IR) is based on ablation of the transient receptor potential cation channel subfamily V, receptor 1 (TRPV1)-substance P nociceptive signaling pathway. However, the functional consequences of capsaicin treatment on nasal nerve activation and the association between the reduction in nasal hyperreactivity (NHR) and response to capsaicin treatment remain unknown. OBJECTIVE: We sought to study the effects of capsaicin nasal spray on the afferent innervation of the nasal mucosa by monitoring trigeminal nerve activity in patients with IR and healthy control (HC) subjects. METHODS: A double-blind, placebo-controlled randomized trial with capsaicin nasal spray was performed involving 33 patients with IR and 12 HC subjects. Before and at 4, 12, and 26 weeks after treatment, nasal mucosal potentials (NMPs) were measured while exposing the nasal mucosa of patients with IR and HC subjects to aerosols with increasing doses of the chemical irritants allyl isothiocyanate (AITC; also known as mustard oil) or capsaicin. The threshold for each compound was determined for each subject. The results of the NMP measurements were evaluated in parallel with the therapeutic response, visual analog scale scores for nasal symptoms, self-reported NHR, and mRNA expression of PGP9.5; TRPV1; transient receptor potential cation channel subfamily A, receptor 1 (TRPA1); TRPV4; transient receptor potential cation channel subfamily M, member 8 (TRPM8); and nerve growth factor (NGF) in nasal biopsy specimens. RESULTS: AITC turned out to be the best stimulus because the coughing induced by capsaicin interfered with measurements. At baseline, the threshold for evoking changes in NMPs based on AITC was significantly lower for patients with IR compared with HC subjects (P = .0423). Capsaicin treatment of IR patients increased the threshold for the response to AITC at 4 and 12 weeks compared with placebo (P = .0406 and P = .0325, respectively), which returned to baseline by week 26 (P = .0611). This increase correlated with changes in visual analog scale major symptom (P = .0004) and total symptom (P = .0018) scores. IR patients with self-reported NHR at baseline showed a trend to being better responders to capsaicin treatment compared with patients with IR but without NHR (P = .10). CONCLUSION: The lower threshold for AITC based on NMPs in patients with IR compared with HC subjects and the increased threshold for AITC after capsaicin treatment in patients with IR demonstrate the crucial role of TRPA1 and TRPV1 in IR pathophysiology. The strong correlation between the increase in AITC threshold in patients with IR and symptom reduction after capsaicin treatment demonstrates the clinical relevance of these findings.

Crucial role of transient receptor potential ankyrin 1 and mast cells in induction of nonallergic airway hyperreactivity in mice.

RATIONALE: Airway hyperreactivity (AHR) is a key feature of bronchial asthma, and inhalation of irritants may facilitate development of nonallergic AHR. Swimmers exposed to hypochlorite (ClO(-))-containing water show a higher risk of developing AHR. We developed a mouse model in which instillation of ClO(-) before ovalbumin (OVA) induces AHR without bronchial inflammatory cells. OBJECTIVES: To investigate the mechanisms of ClO(-)-OVA-induced nonallergic AHR. METHODS: The involvement of the transient receptor potential ankyrin (TRPA)1 channel was checked in vivo by the use of TRPA1(-/-) mice and in vitro by Ca(2+) imaging experiments. The role of substance P (SP) was investigated by pretreating animals with the receptor antagonist RP67580, by replacing ClO(-) with SP in vivo, and by immunofluorescent staining of large airways of exposed mice. The role of mast cells was evaluated by exposing mast cell-deficient Kit(Wh)/Kit(Wsh) mice to ClO(-)-OVA with or without mast cell reconstitution. MEASUREMENTS AND MAIN RESULTS: ClO(-)-OVA did not induce AHR in TRPA1(-/-) mice, and ClO(-) generates a Ca(2+) influx in TRPA1-transfected cells. Pretreatment with RP67580 reduces ClO(-)-OVA-induced AHR, although no increased SP expression was shown in the airways. SP-OVA exposure resulted in the same AHR as induced by ClO(-)-OVA. Kit(Wsh)/Kit(Wsh) mice did not develop AHR in response to ClO(-)-OVA unless they were reconstituted with bone marrow-derived mast cells. CONCLUSIONS: Induction of AHR by exposure to ClO(-)-OVA depends on a neuroimmune interaction that involves TRPA1-dependent stimulation of sensory neurons and mast cell activation.

Efficacy of Alkaline Phosphatase in Critically Ill Patients with COVID-19: A Multicentre Investigator-Initiated Double-Blind Randomised Placebo-Controlled Trial.

BACKGROUND: Efforts to identify therapies to treat hospitalised patients with COVID-19 are being continued. Alkaline phosphatase (AP) dephosphorylates pro-inflammatory adenosine triphosphate (ATP) into anti-inflammatory adenosine. METHODS: In a randomised controlled trial, we investigated the safety and efficacy of AP in patients with SARS-CoV-2 infection admitted to the ICU. AP or a placebo was administered for four days following admission to the ICU. The primary outcome was the duration of mechanical ventilation. Mortality in 28 days, acute kidney injury, need for reintubation, safety, and inflammatory markers relevant to the described high cytokine release associated with SARS-CoV-2 infection were the secondary outcomes. RESULTS: Between December 2020 and March 2022, 97 patients (of the intended 132) were included, of which 51 were randomised to AP. The trial was terminated prematurely based on meeting the threshold for futility. Compared to the placebo, AP did not affect the duration of mechanical ventilation (9.0 days vs. 9.3 days, p = 1.0). No safety issues were observed. After 28 days, mortality was 9 (18%) in the AP group versus 6 (13%) in the placebo group (p = 0.531). Additionally, no statistically significant differences between the AP and the placebo were observed for the other secondary outcomes. CONCLUSIONS: Alkaline phosphatase (AP) therapy in COVID-19 ICU patients showed no significant benefits in this trial.

Serratus plane block versus standard of care for pain control after totally endoscopic aortic valve replacement: a double-blind, randomized controlled, superiority trial.

INTRODUCTION: Serratus anterior plane block has been proposed to reduce opioid requirements after minimally invasive cardiac surgery, but high-quality evidence is lacking. METHODS: This prospective, double-blinded, randomized controlled trial recruited patients undergoing totally endoscopic aortic valve replacement. Patients in the intervention arm received a single-injection serratus anterior plane block on arrival to the intensive care unit added to standard of care. Patients in the control group received routine standard of care, including patient-controlled intravenous analgesia. Primary outcome was piritramide consumption within the first 24 hours after serratus anterior plane block placement. We hypothesized that compared with no block, patients in the intervention arm would consume 25% less opioids. RESULTS: Seventy-five patients were analyzed (n=38 in intervention arm, n=37 in control arm). When comparing the serratus anterior plane group with the control group, median 24-hour cumulative opioid use was 9 (IQR 6-19.5) vs 15 (IQR 11.3-23.3) morphine milligram equivalents, respectively (p<0.01). Also, pain scores at 4, 8 and 24 hours were lower in the intervention arm at 4, 8 and 24 hours, respectively. CONCLUSION: Combined deep and superficial single-injection serratus anterior plane block is superior to standard of care in reducing opioid requirements and postoperative pain intensity up to 24 hours after totally endoscopic aortic valve replacement. TRIAL REGISTRATION NUMBER: NCT04699422.

Extracorporeal Membrane Oxygenation to Support COVID-19 Patients: A Propensity-Matched Cohort Study.

Background: In patients with severe respiratory failure from COVID-19, extracorporeal membrane oxygenation (ECMO) treatment can facilitate lung-protective ventilation and may improve outcome and survival if conventional therapy fails to assure adequate oxygenation and ventilation. We aimed to perform a confirmatory propensity-matched cohort study comparing the impact of ECMO and maximum invasive mechanical ventilation alone (MVA) on mortality and complications in severe COVID-19 pneumonia. Materials and Methods: All 295 consecutive adult patients with confirmed COVID-19 pneumonia admitted to the intensive care unit (ICU) from March 13th, 2020, to July 31st, 2021 were included. At admission, all patients were classified into 3 categories: (1) full code including the initiation of ECMO therapy (AAA code), (2) full code excluding ECMO (AA code), and (3) do-not-intubate (A code). For the 271 non-ECMO patients, match eligibility was determined for all patients with the AAA code treated with MVA. Propensity score matching was performed using a logistic regression model including the following variables: gender, P/F ratio, SOFA score at admission, and date of ICU admission. The primary endpoint was ICU mortality. Results: A total of 24 ECMO patients were propensity matched to an equal number of MVA patients. ICU mortality was significantly higher in the ECMO arm (45.8%) compared with the MVA cohort (16.67%) (OR 4.23 (1.11, 16.17); p=0.02). Three-month mortality was 50% with ECMO compared to 16.67% after MVA (OR 5.91 (1.55, 22.58); p < 0.01). Applied peak inspiratory pressures (33.42 ± 8.52 vs. 24.74 ± 4.86 mmHg; p < 0.01) and maximal PEEP levels (14.47 ± 3.22 vs. 13.52 ± 3.86 mmHg; p=0.01) were higher with MVA. ICU length of stay (LOS) and hospital LOS were comparable in both groups. Conclusion: ECMO therapy may be associated with an up to a three-fold increase in ICU mortality and 3-month mortality compared to MVA despite the facilitation of lung-protective ventilation settings in mechanically ventilated COVID-19 patients. We cannot confirm the positive results of the first propensity-matched cohort study on this topic. This trial is registered with NCT05158816.

Comprehensive antibody and cytokine profiling in hospitalized COVID-19 patients in relation to clinical outcomes in a large Belgian cohort.

The immune response in patients with Coronavirus Disease 2019 (COVID-19) is highly variable and is linked to disease severity and mortality. However, antibody and cytokine responses in the early disease stage and their association with disease course and outcome are still not completely understood. In this large, multi-centre cohort study, blood samples of 434 Belgian COVID-19 hospitalized patients with different disease severities (ranging from asymptomatic/mild to critically ill) from the first wave of the COVID-19 pandemic were obtained. Baseline antibody and cytokine responses were characterized and associations with several clinical outcome parameters were determined. Anti-spike immunoglobulin (Ig)G and IgM levels were elevated in patients with a more severe disease course. This increased baseline antibody response however was associated with decreased odds for hospital mortality. Levels of the pro-inflammatory cytokines IL-6, IP-10 and IL-8, the anti-inflammatory cytokine IL-10 and the antiviral cytokines IFN-α, IFN-ß and IFN-λ1 were increased with disease severity. Remarkably, we found significantly lower levels of IFN-λ2,3 in critically ill patients compared to patients of the moderate and severe disease category. Finally, levels of IL-8, IL-6, IP-10, IL-10, IFN-α, IFN-ß, IFN-γ and IFN-λ1 at baseline were positively associated with mortality, whereas higher IFN-λ2,3 levels were negatively associated with mortality.

Placental growth factor contributes to bronchial neutrophilic inflammation and edema in allergic asthma.

Placental growth factor (PlGF) and its receptor vascular endothelial growth factor receptor 1 (VEGFR1) play an important role in pathological conditions related to angiogenesis, vascular leakage, and inflammation. This study investigated their contributions to inflammation and the formation of edema in allergic asthma. The expression of PlGF and VEGFR1 was measured in induced sputum of patients with asthma (n = 11) and healthy subjects (n = 11), and in bronchial biopsies of house dust mite (HDM)-allergic patients stimulated with HDM allergens. The effects of the endonasal administration of human PlGF-2 and PlGF deficiency on inflammation and edema were evaluated in a murine model of allergic asthma. The migration of human neutrophils in response to hPlGF-2 was tested in vitro. The expression of PlGF and VEGFR1 was significantly higher in the sputum of patients with asthma, and in Der p 1-induced PlGF in biopsies from HDM-allergic patients. PlGF was increased in the bronchi of ovalbumin (OVA)-challenged mice compared with control mice (65 ± 17 pg/mg versus 18 ± 1 pg/mg, respectively; P < 0.01), and VEGFR1 was expressed in bronchial epithelium, endothelium (control mice), and inflammatory cells (OVA-challenged mice). The endonasal instillation of hPlGF-2 in wild-type, OVA-challenged mice led to an increase in bronchial neutrophils, lung tissue wet/dry ratio, and IL-17. PlGF-deficient mice showed lower numbers of BAL-infiltrating neutrophils, a reduced lung wet/dry ratio, and lower production of IL-17, macrophage inflammatory protein-2, and granulocyte chemotactic protein-2/LPS-induced chemokine compared with wild-type, OVA-challenged mice. hPlGF-2 induced the migration of human neutrophils in vitro in a VEGFR1-dependent way. PlGF and its receptor VEGFR1 are up-regulated in allergic asthma and play a proinflammatory role by inducing tissue edema, and increasing tissue neutrophilia and the production of IL-17.

Nasal corticosteroid treatment reduces substance P levels in tear fluid in allergic rhinoconjunctivitis.

BACKGROUND: The mechanisms underlying conjunctival symptom reduction by nasal corticosteroids in allergic rhinoconjunctivitis are unknown. A naso-ocular reflex may be present. OBJECTIVE: To study the effects of nasal fluticasone furoate (FF) on conjunctival symptoms and substance P and histamine levels in tear fluid after nasal grass pollen provocation (GPP). METHODS: A double-blind placebo-controlled study was performed in 26 grass pollen-allergic patients. A selective GPP was performed during the grass pollen season after 2 weeks of FF or placebo treatment. Nasal and conjunctival symptoms were scored using a visual analog scale (VAS), and tear fluid was collected for measuring substance P and histamine using an enzyme-linked immunosorbent assay. RESULTS: Compared with placebo, FF reduced conjunctival symptom scores during the pollen season (-1.75 [-2.75, 0.20] vs 0.0 [0.0, 0.0]; P = .01) and after GPP at 15 minutes (0.05 [-0.42, 1.52] vs 2.05 [0.62, 3.62]; P < .001) and 1 hour (-0.45 [-1.75, 0.1] vs 0.05 [-0.97, 1.85]; P < .01). Treatment with FF decreased substance P levels in tear fluid (44.11 [32.81, 61.02] vs 65.26 [48.62, 79.73] pg/mg protein; P = .0098). Histamine levels in tear fluid showed a GPP-induced increase in the placebo group (7.26 [3.12, 9.69] vs 5.71 [2.05, 7.00] ng/mg protein; P = .02), but not in the FF group (6.77 [3.43, 13.00] vs 5.24 [3.18, 7.06] ng/mg protein; P = .08). CONCLUSION: FF nasal spray reduced conjunctival symptoms in grass pollen-allergic patients in parallel with lower substance P levels in tear fluid. These data help in understanding the reduction of conjunctival symptoms by intranasal anti-inflammatory therapy.

Worsening COVID-19 Disease Course After Surgical Trauma: A Case Series.

Introduction: Current guidelines from the American Society of Anesthesiologists recommend postponing elective surgery on COVID-19-positive patients for a minimum of four to twelve weeks. However, literature focusing on the outcomes of COVID-19-positive patients undergoing surgery is scarce. In this case series, the outcome of asymptomatic COVID-19 patients undergoing acute or semi-urgent surgery was evaluated. Case Presentation: A case series of four patients between 32 and 82 years old with a confirmed SARS-CoV-2 infection undergoing acute or semi-urgent surgery was presented here. All four patients were asymptomatic for COVID-19, developing severe respiratory failure following endo CABG, caesarian section, a thyroidectomy, or abdominal surgery. ICU admission, together with invasive ventilation, was necessary for all patients. Two patients required venovenous extracorporeal membrane oxygenation treatment. A mortality of 50% was observed. Conclusions: In conclusion, the present case series suggests that elective surgery in asymptomatic SARS-CoV-2 infected patients might elicit an exacerbated COVID-19 disease course. This study endorses the current international guidelines recommending postponing elective surgery for SARS-CoV-2-positive patients for seven weeks, depending on the severity of the surgery and perioperative morbidities, to minimize postoperative mortality.