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Tracheal intubation in the critically ill is associated with serious complications, mainly cardiovascular collapse and severe hypoxemia. In this narrative review, we present an update of interventions aiming to decrease these complications. MACOCHA is a simple score that helps to identify patients at risk of difficult intubation in the intensive care unit (ICU). Preoxygenation combining the use of inspiratory support and positive end-expiratory pressure should remain the standard method for preoxygenation of hypoxemic patients. Apneic oxygenation using high-flow nasal oxygen may be supplemented, to prevent further hypoxemia during tracheal intubation. Face mask ventilation after rapid sequence induction may also be used to prevent hypoxemia, in selected patients without high-risk of aspiration. Hemodynamic optimization and management are essential before, during and after the intubation procedure. All these elements can be integrated in a bundle. An airway management algorithm should be adopted in each ICU and adapted to the needs, situation and expertise of each operator. Videolaryngoscopes should be used by experienced operators., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Our study aimed to provide consensus and expert clinical practice statements related to airway management in critically ill adults with a physiologically difficult airway (PDA)., Methods: An international Steering Committee involving seven intensivists and one Delphi methodology expert was convened by the Society of Critical Care Anaesthesiologists (SOCCA) Physiologically Difficult Airway Task Force. The committee selected an international panel of 35 expert clinician-researchers with expertise in airway management in critically ill adults. A Delphi process based on an iterative approach was used to obtain the final consensus statements., Results: The Delphi process included seven survey rounds. A stable consensus was achieved for 53 (87%) out of 61 statements. The experts agreed that in addition to pathophysiological conditions, physiological alterations associated with pregnancy and obesity also constitute a physiologically difficult airway. They suggested having an intubation team consisting of at least three healthcare providers including two airway operators, implementing an appropriately designed checklist, and optimizing hemodynamics prior to tracheal intubation. Similarly, the experts agreed on the head elevated laryngoscopic position, routine use of videolaryngoscopy during the first attempt, preoxygenation with non-invasive ventilation, careful mask ventilation during the apneic phase, and attention to cardiorespiratory status for post-intubation care., Conclusion: Using a Delphi method, agreement among a panel of international experts was reached for 53 statements providing guidance to clinicians worldwide on safe tracheal intubation practices in patients with a physiologically difficult airway to help improve patient outcomes. Well-designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This case-control study investigated the long-term evolution of multidrug-resistant bacteria (MDRB) over a 5-year period associated with the use of selective oropharyngeal decontamination (SOD) in the intensive care unit (ICU). In addition, effects on health care-associated infections and ICU mortality were analysed., Methods: We investigated patients undergoing mechanical ventilation > 48 h in 11 adult ICUs located at 3 campuses of a university hospital. Administrative, clinical, and microbiological data which were routinely recorded electronically served as the basis. We analysed differences in the rates and incidence densities (ID, cases per 1000 patient-days) of MDRB associated with SOD use in all patients and stratified by patient origin (outpatient or inpatient). After propensity score matching, health-care infections and ICU mortality were compared., Results: 5034 patients were eligible for the study. 1694 patients were not given SOD. There were no differences in the incidence density of MDRB when SOD was used, except for more vancomycin-resistant Enterococcus faecium (0.72/1000 days vs. 0.31/1000 days, p < 0.01), and fewer ESBL-producing Klebsiella pneumoniae (0.22/1000 days vs. 0.56/1000 days, p < 0.01). After propensity score matching, SOD was associated with lower incidence rates of ventilator-associated pneumonia and death in the ICU but not with ICU-acquired bacteremia or urinary tract infection., Conclusions: Comparisons of the ICU-acquired MDRB over a 5-year period revealed no differences in incidence density, except for lower rate of ESBL-producing Klebsiella pneumoniae and higher rate of vancomycin-resistant Enterococcus faecium with SOD. Incidence rates of ventilator-associated pneumonia and death in the ICU were lower in patients receiving SOD., (© 2022. The Author(s).)

Since the 1970s, intramuscular triamcinolone (IMT) has been available as an option for systemic corticosteroid use in dermatology. Although shown to be safe and effective in early studies, this method of systemic corticosteroid delivery fell out of favor in the 1980s in many United States residency programs. To identify factors associated with US dermatologists' preferences for and use of IMT we surveyed a random sample of US board-certified dermatologists to assess knowledge, attitudes, and practices regarding IMT in dermatologists' daily clinical practice. A total of 844 out of 2000 dermatologists completed the survey (42.2%). Only 55.0% reported feeling comfortable using IMT for steroid-responsive dermatoses, while 90.4% felt comfortable using oral corticosteroids for steroid-responsive dermatoses. Most participants (59.2%) did not prefer IMT over oral corticosteroids when both were indicated. One third (33.3%) of the participants reported that none of the faculty during their residency advocated using IMT. Receiving education on IMT indications (OR = 1.96 [95% CI: 1.46-2.63]) and encouragement to use IMT (OR = 4.29 [95% CI: 3.01-6.11]) during residency were positively associated with use of IMT at least once a month in current practice. Current knowledge, attitudes, and practices surrounding IMT vary amongst practicing dermatologists. Modifiable factors such as training could improve comfort with use of this short-term systemic steroid treatment modality., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pseudoxanthoma elasticum (PXE (OMIM 264800)) is an autosomal recessive connective tissue disorder mainly caused by mutations in the ABCC6 gene. PXE results in ectopic calcification primarily in the skin, eye and blood vessels that can lead to blindness, peripheral arterial disease and stroke. Previous studies found correlation between macroscopic skin involvement and severe ophthalmological and cardiovascular complications. This study aimed to investigate correlation between skin calcification and systemic involvement in PXE. Ex vivo nonlinear microscopy (NLM) imaging was performed on formalin fixed, deparaffinized, unstained skin sections to assess the extent of skin calcification. The area affected by calcification (CA) in the dermis and density of calcification (CD) was calculated. From CA and CD, calcification score (CS) was determined. The number of affected typical and nontypical skin sites were counted. Phenodex + scores were determined. The relationship between the ophthalmological, cerebro- and cardiovascular and other systemic complications and CA, CD and CS, respectively, and skin involvement were analyzed. Regression models were built for adjustment to age and sex. We found significant correlation of CA with the number of affected typical skin sites (r = 0.48), the Phenodex + score (r = 0.435), extent of vessel involvement (V-score) (r = 0.434) and disease duration (r = 0.48). CD correlated significantly with V-score (r = 0.539). CA was significantly higher in patients with more severe eye (p = 0.04) and vascular (p = 0.005) complications. We found significantly higher CD in patients with higher V-score (p = 0.018), and with internal carotid artery hypoplasia (p = 0.045). Significant correlation was found between higher CA and the presence of macula atrophy (β = - 0.44, p = 0.032) and acneiform skin changes (β = 0.40, p = 0.047). Based on our results, the assessment of skin calcification pattern with nonlinear microscopy in PXE may be useful for clinicians to identify PXE patients who develop severe systemic complications., (© 2023. The Author(s).)

T cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive malignancy of progenitor T cells. Despite significant improvements in survival of T-ALL/LBL over the past decades, treatment of relapsed and refractory T-ALL (R/R T-ALL/LBL) remains extremely challenging. The prognosis of R/R T-ALL/LBL patients who are intolerant to intensive chemotherapy remains poor. Therefore, innovative approaches are needed to further improve the survival of R/R T-ALL/LBL patients. With the widespread use of next-generation sequencing in T-ALL/LBL, a range of new therapeutic targets such as NOTCH1 inhibitors, JAK-STAT inhibitors, and tyrosine kinase inhibitors have been identified. These findings led to pre-clinical studies and clinical trials of molecular targeted therapy in T-ALL/LBL. Furthermore, immunotherapies such as CD7 CAR T cell therapy and CD5 CAR T cell therapy have shown profound response rate in R/R T-ALL/LBL. Here, we review the progress of targeted therapies and immunotherapies for T-ALL/LBL, and look at the future directions and challenges for the further use of these therapies in T-ALL/LBL., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The relationship between cognitive demands and postural control is controversial. Mental fatigue paradigms investigate the attentional requirements of postural control by assessing balance after a prolonged cognitive task. However, a majority of mental fatigue research has focused on cognition and sports performance, leaving balance relatively underexamined. The purpose of this paper was to systematically review the existing literature on mental fatigue and balance control. We conducted a comprehensive search on PubMed and Web of Science databases for studies comparing balance performance pre- to post-mental fatigue or between a mental fatigue and control group. The literature search resulted in ten relevant studies including both volitional (n = 7) and reactive (n = 3) balance measures. Mental fatigue was induced by various cognitive tasks which were completed for 20-90 min prior to balance assessment. Mental fatigue affected both volitional and reactive balance, resulting in increased postural sway, decreased accuracy on volitional tasks, delayed responses to perturbations, and less effective balance recovery responses. These effects could have been mediated by the depletion of attentional resources or impaired sensorimotor perception which delayed appropriate balance-correcting responses. However, the current literature is limited by the number of studies and heterogeneous mental fatigue induction methods. Future studies are needed to confirm these postulations and examine the effects of mental fatigue on different populations and postural tasks. This line of research could be clinically relevant to improve safety in occupational settings where individuals complete extremely long durations of cognitive tasks and for the development of effective fall-assessment and fall-prevention paradigms., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cognitive fatigue (CF) can result from sustained mental effort, is characterized by subjective feelings of exhaustion and cognitive performance deficits, and is associated with slowed simple reaction time (RT). This study determined whether declines in motor preparation underlie this RT effect. Motor preparation level was indexed using simple RT and the StartReact effect, wherein a prepared movement is involuntarily triggered at short latency by a startling acoustic stimulus (SAS). It was predicted that if decreased motor preparation underlies CF-associated RT increases, then an attenuated StartReact effect would be observed following cognitive task completion. Subjective fatigue assessment and a simple RT task were performed before and after a cognitively fatiguing task or non-fatiguing control intervention. On 25% of RT trials, a SAS replaced the go-signal to assess the StartReact effect. CF inducement was verified by significant declines in cognitive performance (p = 0.003), along with increases in subjective CF (p < 0.001) and control RT (p = 0.018) following the cognitive fatigue intervention, but not the control intervention. No significant pre-to-post-test changes in SAS RT were observed, indicating that RT increases resulting from CF are not substantially associated with declines in motor preparation, and instead may be attributable to other stages of processing during a simple RT task., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The present study aimed to investigate the hepatoprotective effect of sesamol (SML), a nutritional phenolic compound obtained from sesame seeds, in liver fibrosis induced by thioacetamide (TAA) in rats and to explore the underlying mechanisms. Thirty-two male Sprague-Dawley rats were equally divided into four groups: control, TAA, TAA + SML 50 mg/kg, and TAA + SML 100 mg/kg groups. Liver functions and hepatic contents of glutathione (GSH) and malondialdehyde (MDA) were measured colorimetrically. Gene expressions of lysophosphatidic acid receptor (LPAR)-1 and -3, connective tissue growth factor (CTGF), transforming growth factor (TGF)-β1, small mothers against decapentaplegic (Smad)-3 and -7, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK19) were analyzed by qRT-PCR. Moreover, phosphorylated Smad3 (pSmad3) was quantified by ELISA. Additionally, TGF-β1, α-SMA, CK19, and vascular endothelial growth factor (VEGF) protein concentrations were semi-quantitatively analyzed by immunostaining of liver sections. SML treatment markedly improved liver index and liver functions. Moreover, SML protected against liver fibrosis in a dose-dependent manner as indicated by down-regulation of LPAR1, LPAR3, CTGF, TGF-β1/Smad3, and α-SMA expressions and a decrease in pSmad3 level, as well as an up-regulation of Smad7 expression. In addition, SML suppressed ductular reaction hinted by the decrease in CK19 expression. These results reveal the anti-fibrotic effect of SML against liver fibrosis that might be attributed to down-regulation of LPAR1/3 expressions, inhibition of TGF-β1/Smad3 pathway, and ductular reaction., (© 2022. The Author(s).)

Microsurgical free flap transfer plays a key role in soft tissue reconstruction of the lower extremities. Through close cooperation between plastic and orthopedic surgery, great progress and success in limb salvage could be achieved over the last decades. The risk for extremity malperfusion is especially high in older patients and after trauma. To maximize the success rate for free flap transfer there is need for interdisciplinary clinical examination and diagnostics. In addition to clinical methods radiological procedures are necessary to evaluate and optimize lower extremity perfusion before surgery.Vascular ultrasound provides important information about the arterial and venous status; however, DSA, CTA and MRA are well-established and exact methods to evaluate arterial inflow. The use of less invasive methods makes it much more feasible, economic and comfortable to perform preoperative selection of patients requiring interventional procedures.In the case of intraluminal stenosis without any option for PTA, a vascular surgeon can be involved at an early stage to evaluate further surgical options. In some cases, similar surgical revascularization and free flap transfer can be performed in a single surgery. The aim of this study is to implement a standardized algorithm for preoperative examination and radiological diagnostics before reconstructive surgery of the lower extremity., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Aims/hypothesis: Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR., Methods: We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration., Results: We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024)., Conclusions/interpretation: These results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.