Individualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the ...complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness.
A systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards.
Out of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively.
CPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential. Trial registration number PROSPERO- CRD42022301715 . Registered 05 February, 2022.
Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory ...failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited-in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.
Abstract Background Respiratory effort should be closely monitored in mechanically ventilated ICU patients to avoid both overassistance and underassistance. Surface electromyography of the diaphragm ...(sEMGdi) offers a continuous and non-invasive modality to assess respiratory effort based on neuromuscular coupling (NMCdi). The sEMGdi derived electrical activity of the diaphragm (sEAdi) is prone to distortion by crosstalk from other muscles including the heart, hindering its widespread use in clinical practice. We developed an advanced analysis as well as quality criteria for sEAdi waveforms and investigated the effects of clinically relevant levels of PEEP on non-invasive NMCdi. Methods NMCdi was derived by dividing end-expiratory occlusion pressure (Pocc) by sEAdi, based on three consecutive Pocc manoeuvres at four incremental (+ 2 cmH2O/step) PEEP levels in stable ICU patients on pressure support ventilation. Pocc and sEAdi quality was assessed by applying a novel, automated advanced signal analysis, based on tolerant and strict cut-off criteria, and excluding inadequate waveforms. The coefficient of variations (CoV) of NMCdi after basic manual and automated advanced quality assessment were evaluated, as well as the effect of an incremental PEEP trial on NMCdi. Results 593 manoeuvres were obtained from 42 PEEP trials in 17 ICU patients. Waveform exclusion was primarily based on low sEAdi signal-to-noise ratio (N tolerant = 155, 37%, N strict = 241, 51% waveforms excluded), irregular or abrupt cessation of Pocc (N tolerant = 145, 35%, N strict = 145, 31%), and high sEAdi area under the baseline (N tolerant = 94, 23%, N strict = 79, 17%). Strict automated assessment allowed to reduce CoV of NMCdi to 15% from 37% for basic quality assessment. As PEEP was increased, NMCdi decreased significantly by 4.9 percentage point per cmH 2 O. Conclusion Advanced signal analysis of both Pocc and sEAdi greatly facilitates automated and well-defined identification of high-quality waveforms. In the critically ill, this approach allowed to demonstrate a dynamic NMCdi (Pocc/sEAdi) decrease upon PEEP increments, emphasising that sEAdi-based assessment of respiratory effort should be related to PEEP dependent diaphragm function. This novel, non-invasive methodology forms an important methodological foundation for more robust, continuous, and comprehensive assessment of respiratory effort at the bedside.
Aim
To assess the added value of Near InfraRed Fluorescence (NIRF) imaging during laparoscopic cholecystectomy.
Methods
This international multicentre randomized controlled trial included ...participants with an indication for elective laparoscopic cholecystectomy. Participants were randomised into a NIRF imaging assisted laparoscopic cholecystectomy (NIRF-LC) group and a conventional laparoscopic cholecystectomy (CLC) group. Primary end point was time to ‘Critical View of Safety’ (CVS). The follow-up period of this study was 90 postoperative days. An expert panel analysed the video recordings after surgery to confirm designated surgical time points.
Results
A total of 294 patients were included, of which 143 were randomized in the NIRF-LC and 151 in the CLC group. Baseline characteristics were equally distributed. Time to CVS was on average 19 min and 14 s for the NIRF-LC group and 23 min and 9 s for the CLC group (
p
0.032). Time to identification of the CD was 6 min and 47 s and 13 min for NIRF-LC and CLC respectively (
p
< 0.001). Transition of the CD in the gallbladder was identified after an average of 9 min and 39 s with NIRF-LC, compared to 18 min and 7 s with CLC (
p
< 0.001). No difference in postoperative length of hospital stay nor occurrence of postoperative complications was found. ICG related complications were limited to one patient who developed a rash after injection of ICG.
Conclusion
Use of NIRF imaging in laparoscopic cholecystectomy provides earlier identification of relevant extrahepatic biliary anatomy: earlier achievement of CVS, cystic duct visualisation and visualisation of both cystic duct and cystic artery transition into the gallbladder.
It is shown that manganese complexes derived from 1,4,7-trimethyl-1,4,7-triazacyclononane and related ligand systems act as highly effective catalysts for the bleaching of stains by hydrogen peroxide.
The influence of orbital precession on early Paleogene climate and ocean circulation patterns in the southeast Pacific region is investigated by combining environmental analyses of cyclic Middle ...Eocene sediments and palynomorph records recovered from ODP Hole 1172A on the East Tasman Plateau with climate model simulations. Integration of results indicates that in the marine realm, direct effects of precessional forcing are not pronounced, although increased precipitation/runoff could have enhanced dinoflagellate cyst production. On the southeast Australian continent, the most pronounced effects of precessional forcing were fluctuations in summer precipitation and temperature on the Antarctic Margin. These fluctuations resulted in vegetational changes, most notably in the distribution of
Nothofagus (subgenus
Brassospora). The climate model results suggest significant fluctuations in sea ice in the Ross Sea, notably during Austral summers. This is consistent with the influx of Antarctic heterotrophic dinoflagellates in the early part of the studied record. The data demonstrate a strong precessionally driven climate variability and thus support the concept that precessional forcing could have played a role in early Antarctic glaciation via changes in runoff and/or precipitation.
In a group of chronically dysphonic patients, a voice range profile, or phonetogram, was recorded before and after receiving voice therapy and again 3 months later. The voice range profiles took a ...wide variety of shapes. Therefore, only measures that did not depend on a smooth contour could be used to describe changes before and after therapy. The main effect of voice therapy was an enlargement on the side of low frequency and low intensity.
The monoclonal antibodies (MAbs) 323/A3 and 17-1A both recognize a 40-kDa carcinoma-associated epithelial glycoprotein (EGP40). MAb 17-1A has been used in many therapeutic trials as an ...immunotherapeutic agent to combat advanced colorectal cancer, and about 5-10% overall responses have been observed. It has been shown that MAb 323/A3 has a higher affinity than 17-1A, which might be an advantageous feature for a therapeutic agent. In our immunohistological studies different reaction patterns of these two MAbs were observed, suggesting that MAb 323/A3 reacts more intensely with carcinoma cells than MAb 17-1A. This also suggests that MAb 323/A3 might be a more effective immunotherapeutic tool. Because chimerization may reduce the immunogenicity of the murine MAb 323/A3 and increase the interaction with human effector mechanisms, we developed a chimeric form of murine MAb 323/A3. MAb 323/A3 heavy and light chain variable genes were cloned and grafted onto human C gamma 1 and C kappa domains, respectively. A chimeric antibody-producing cell line was established by transfection of the chimeric constructs into a nonproducing myeloma cell. The chimeric and murine 323/A3 MAbs were evaluated for efficacy of inducing complement-mediated cytotoxicity (CMC) and mediating antibody-dependent cellular cytotoxicity against LS 180 cells derived from human colon carcinoma. Both forms were found to mediate similar levels of CMC in the presence of human complement; however, higher levels of lysis of target cells were observed with human peripheral blood lymphocytes when the chimeric 323/A3 was used. Chimeric 323/A3 mediated higher maximal cytotoxicity than chimeric 17-1A in both CMC and antibody-dependent cellular cytotoxicity assays and was equally active as chimeric 17-1A at 100- to 1000-fold lower concentrations. The superior reactivity of chimeric 323/A3 with EGP40 on carcinoma cells and its higher cytotoxicity-mediating capacity, compared to chimeric 17-1A, are important characteristics, which support further clinical studies with chimeric MAb 323/A3 in immunotherapy of carcinomas.
In vitro as well as in vivo observations have shown that IL6 plays a key role in the pathogenesis of multiple myeloma. Therefore we started a phase I/II dose escalating study with chimeric monoclonal ...anti-IL6 antibodies (cMab) in multiple myeloma (MM) patients resistant to second-line chemotherapy. Here we describe the pharmacological data as well as a new method for calculating the endogenous IL6 production. The cMab (CLB IL6/8; Kd: 6.25 x 10(-12) M) was given in two cycles of 14 daily infusions, starting on day 1 and day 28. Daily dose: 5 mg in patients 1-3, 10 mg in patients 4-6, and 20 mg in patients 7-9 (total dose 140, 280, and 560 mg of anti-IL6, respectively). Using the pharmacokinetic data of free IL6 and the binding characteristics of the cMab, the endogenous IL6 production could be calculated from day to day using a one-compartment open model. The median half-life time of this antibody was 17.6 d. No human antichimeric antibodies were induced. Pre-treatment median endogenous IL6 production in the MM patients was 60 micrograms/d (range 13.8-230; normal controls < 7 micrograms/d). During treatment with anti-IL6 cMabs, the endogenous IL6 production immediately decreased in all patients to below 3 micrograms/d and never reached the pre-treatment value during the treatment period, except in two patients who developed an active infection, resulting in an IL6 production of 128 and 1,208 micrograms/d, respectively. We concluded that in MM patients endogenous IL6 production is 2-30 times higher than in healthy individuals. The anti-IL6 cMab strongly suppress this endogenous IL6 production, probably by blocking a positive feed-back loop, but this cMab does not prevent infection-induced IL6 production. The chimeric anti-IL6 Mabs have a long half-life time, a low immunogenicity, and are able to block IL6-dependent processes in vivo.
cG250 is an IgG1 kappa light-chain chimeric monoclonal antibody that binds to a cell surface antigen found on 95% of clear-cell renal cancer. A multicentre phase II study was performed to evaluate ...the safety and efficacy of repeated doses of cG250. Thirty-six patients with metastatic RCC were included. All patients were nephrectomized for the primary tumour. Twenty-one patients were pretreated (e.g. with IL-2, IFN-alpha). A weekly dose of 50 mg cG250 was given by i.v. infusion for 12 weeks. Patients with SD or tumour response (PR, CR) after 12 weeks of treatment could receive additional treatment for 8 more weeks. None of the 36 enrolled patients had any cG250 grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. ELISA testing gave no evidence for relevant amounts of HACA. Eleven patients presented with SD and ten were eligible for extension treatment. After the end of the study in the follow-up period, one patient demonstrated a CR in week 38 and another patient with SD showed a significant reduction of the overall tumour load in week 44. Six additional patients with progressive disease at study entry were stable for more than six months after the treatment start. The weekly schedule of i.v. cG250 in patients with metastatic RCC was safe, very well tolerated and non-immunogenic in a 12-week treatment regimen. cG250 showed anti-tumour activity.
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