N-acetyl-cysteine in Intensive Care Unit Patients with Acute Respiratory Distress Syndrome due to COVID-19: A Retrospective Cohort Study.

PURPOSE: We assessed the potential association between N-acetyl-cysteine (NAC) and clinical outcomes in critically ill subjects with COVID-19-related ARDS. MATERIAL AND METHODS: We included subjects with confirmed COVID-19 who were admitted to our ICU between March 1, 2020, and January 31, 2021, due to ARDS and necessitating invasive mechanical ventilation (IMV). Subjects who received standard of care (SOC) were compared with subjects who additionally received NAC 600 mg bid orally. RESULTS: A total of 243 subjects were included in this study. The results indicate significantly improved survival rates in the NAC plus SOC group, both in the unadjusted analysis and after adjusting for confounding factors such as ARDS severity (HR 0.48, 95% CI 0.32-0.70). CONCLUSIONS: We found that oral administration of NAC was associated with reduced mortality in critically ill patients with COVID-19 related ARDS.

Brain and Pharyngeal Responses Associated with Pharmacological Treatments for Oropharyngeal Dysphagia in Older Patients.

Impaired pharyngo-laryngeal sensory function is a critical mechanism for oropharyngeal dysphagia (OD). Discovery of the TRP family in sensory nerves opens a window for new active treatments for OD. To summarize our experience of the action mechanism and therapeutic effects of pharyngeal sensory stimulation by TRPV1, TRPA1 and TRPM8 agonists in older patients with OD. Summary of our studies on location and expression of TRP in the human oropharynx and larynx, and clinical trials with acute and after 2 weeks of treatment with TRP agonists in older patients with OD. (1) TRP receptors are widely expressed in the human oropharynx and larynx: TRPV1 was localized in epithelial cells and TRPV1, TRPA1 and TRPM8 in sensory fibers mainly below the basal lamina. (2) Older people present a decline in pharyngeal sensory function, more severe in patients with OD associated with delayed swallow response, impaired airway protection and reduced spontaneous swallowing frequency. (3) Acute stimulation with TRP agonists improved the biomechanics and neurophysiology of swallowing in older patients with OD TRPV1 = TRPA1 > TRPM8. (4) After 2 weeks of treatment, TRPV1 agonists induced cortical changes that correlated with improvements in swallowing biomechanics. TRP agonists are well tolerated and do not induce any major adverse events. TRP receptors are widely expressed in the human oropharynx and larynx with specific patterns. Acute oropharyngeal sensory stimulation with TRP agonists improved neurophysiology, biomechanics of swallow response, and safety of swallowing. Subacute stimulation promotes brain plasticity further improving swallow function in older people with OD.

A Systematic and Universal Artificial Intelligence Screening Method for Oropharyngeal Dysphagia: Improving Diagnosis Through Risk Management.

Oropharyngeal dysphagia (OD) is underdiagnosed and current screening is costly. We aimed: (a) to develop an expert system (ES) based on machine learning that calculates the risk of OD from the electronic health records (EHR) of all hospitalized older patients during admission, and (b) to implement the ES in a general hospital. In an observational, retrospective study, EHR and swallowing assessment using the volume-viscosity swallow test for OD were captured over 24 months in patients > 70 yr admitted to Mataró Hospital. We studied the predictive power for OD of 25,000 variables. ES was obtained using feature selection, the final prediction model was built with non-linear methods (Random Forest). The database included 2809 older patients (mean age 82.47 ± 9.33 yr), severely dependent (Barthel Index 47.68 ± 31.90), with multiple readmissions (4.06 ± 7.52); 75.76% had OD. The psychometrics of the ES built with a non-linear model were: Area under the ROC Curve of 0.840; sensitivity 0.940; specificity, 0.416; Positive Predictive Value 0.834; Negative Predictive Value 0.690; positive likelihood ratio (LH), 1.61 and negative LH, 0.146. The ES screens in 6 s all patients admitted to a 419-bed hospital, identifies patients at greater risk of OD, and shows the risk for OD in the clinician's workstation. It is currently in use at our institution. Our ES provides accurate, systematic and universal screening for OD in real time during hospital admission of older patients, allowing the most appropriate diagnostic and therapeutic strategies to be selected for each patient.

The Impact of Periventricular Leukoaraiosis in Post-stroke Oropharyngeal Dysphagia: A Swallowing Biomechanics and MRI-Based Study.

Oropharyngeal dysphagia is a highly prevalent post-stroke complication commonly associated with topographically specific gray-matter damage. In contrast, the role of damage to the extensive white matter brain network (leukoaraiosis) in post-stroke oropharyngeal dysphagia has not yet been clarified. We aim to assess the role of leukoaraiosis in post-stroke oropharyngeal dysphagia. We designed a cross-sectional study and retrospectively collected from our database patients with dysphagia affected by a recent stroke and on whom both a brain 1.5 T-MRI and a videofluoroscopy had been performed. Leukoaraiosis was assessed in brainstem and in cerebral regions (periventricular or deep) with Fazekas scale. Penetration-Aspiration-Scale and time to laryngeal vestibule closure and to upper esophageal sphincter opening were analyzed. Study population (n = 121; 57% men, 75.5 ± 9.4y) presented mostly supratentorial ischemic PACI-type strokes. Of the patients, 86% had unsafe swallows (PAS = 3.97 ± 2.04); 94.2% had cerebral leukoaraiosis (Fazekas = 3.36 ± 1.7) and 42.1% had brainstem-leukoaraiosis, hypertension being the main risk factor. We found both significant positive associations between degree of periventricular-leukoaraiosis and total-leukoaraiosis and presence of risk of aspirations (p = 0.016 and p = 0.023, respectively); and a correlation between periventricular-leukoaraiosis and PAS scale severity (r = 0.179, p = 0.049). No correlations/associations were found between stroke volume and dysphagia in this study. Our study supports a role for leukoaraiosis in the pathophysiology of dysphagia. Stroke is associated with chronic short-connection/circuit injury and damage to periventricular white matter long connections is a relevant neuro-pathophysiological mechanism contributing to impaired safety of swallow in post-stroke oropharyngeal dysphagia patients.

Discovering Potential Compounds for Venous Disease Treatment through Virtual Screening and Network Pharmacology Approach.

Peripheral venous hypertension has emerged as a prominent characteristic of venous disease (VD). This disease causes lower limb edema due to impaired blood transport in the veins. The phlebotonic drugs in use showed moderate evidence for reducing edema slightly in the lower legs and little or no difference in the quality of life. To enhance the probability of favorable experimental results, a virtual screening procedure was employed to identify molecules with potential therapeutic activity in VD. Compounds obtained from multiple databases, namely AC Discovery, NuBBE, BIOFACQUIM, and InflamNat, were compared with reference compounds. The examination of structural similarity, targets, and signaling pathways in venous diseases allows for the identification of compounds with potential usefulness in VD. The computational tools employed were rcdk and chemminer from R-Studio and Cytoscape. An extended fingerprint analysis allowed us to obtain 1846 from 41,655 compounds compiled. Only 229 compounds showed pharmacological targets in the PubChem server, of which 84 molecules interacted with the VD network. Because of their descriptors and multi-target capacity, only 18 molecules of 84 were identified as potential candidates for experimental evaluation. We opted to evaluate the berberine compound because of its affordability, and extensive literature support. The experiment showed the proposed activity in an acute venous hypertension model.

Assessing three industrially produced fungi for the bioremediation of diclofenac.

Diclofenac is an emerging pollutant: toxic, persistent, and bioaccumulative, present in several environmental niches in a concentration of parts per million. This pharmaceutical's biological removal was reported with various fungal species, showing promissory results. This work aimed at diclofenac removal by individually challenging the fungal species Pleurotus ostreatus, Aspergillus niger, and Penicillium roquefortii but triying to lower the biosorption nature of cell walls by NaCl addition. P. ostreatus removed 100% of the initial diclofenac concentration, whereas A. niger and P. roqueforti removed 74% and 32%, respectively. In all three cases, biosorption by polar interactions was negligible. We demonstrated that stressful environments, such as mineral media, force the fungus to take advantage of its metabolic tools to survive, hence showing higher removal capacity when limiting growth conditions. Bioremediation is an excellent alternative to give residual fungal biomass a secondary use.

Oropharyngeal Dysphagia in Older People is Associated with Reduced Pharyngeal Sensitivity and Low Substance P and CGRP Concentration in Saliva.

Substance P (SP) and Calcitonine gene-related peptide (CGRP) are released by sensory nerve fibers in the oropharynx. Patients with oropharyngeal dysphagia (OD) present reduced oropharyngeal sensitivity and low SP concentration in saliva. We aimed to assess the concentration of salivary SP and CGRP in healthy volunteers, and older people without and with OD, and the relationship with pharyngeal sensory threshold. We included 15 healthy volunteers, 14 healthy elderly and 14 elderly with OD. Swallow function was assessed by videofluoroscopy (VFS). Pharyngeal sensory threshold was assessed by intrapharyngeal electrical stimulation. Hydration and phase angle were assessed by bioimpedance. Saliva samples were collected with a Salivette® to determine SP and CGRP concentration by ELISA. Elderly patients with OD presented impaired safety of swallow (PAS 4.38 ± 0.77 p < 0.0001 vs. healthy volunteers = 1 and healthy elderly = 1.43 ± 0.51). Healthy elderly and elderly with OD presented a reduction in intracellular water and saliva volume (healthy elderly, 592.86 ± 327.79 µl, p = 0.0004; elderly with OD, 422.00 ± 343.01 µl, p = 0.0001 vs healthy volunteers, 1333.33 ± 615.91 µl, r = 0.6621, p < 0.0001). Elderly patients with OD presented an impairment in pharyngeal sensory threshold (10.80 ± 3.92 mA vs. healthy volunteers, 5.74 ± 2.57 mA; p = 0.007) and a reduction in salivary SP (129.34 pg/ml vs. healthy volunteers: 173.89 pg/ml; p = 0.2346) and CGRP levels (24.17 pg/ml vs. healthy volunteers: 508.18 pg/ml; p = 0.0058). There was a negative correlation between both SP and CGRP concentrations and pharyngeal sensory threshold (r = - 0.450, p = 0.024; r = - 0.4597, p = 0.036, respectively), but only SP identified elderly patients with OD with higher pharyngeal sensory threshold. Elderly patients with OD presented hydropenia and sarcopenia, reduced salivary SP and CGRP and impaired pharyngeal sensitivity. Our study suggests SP levels in saliva as a potential biomarker to monitor pharyngeal sensitivity in elderly patients with OD.

A Comparative Study on the Effect of Acute Pharyngeal Stimulation with TRP Agonists on the Biomechanics and Neurophysiology of Swallow Response in Patients with Oropharyngeal Dysphagia.

Fluid thickening is the main compensatory strategy for patients with oropharyngeal dysphagia (OD) associated with aging or neurological diseases, and there is still no pharmacological treatment. We aimed to compare the effects of increasing bolus viscosity with that of acute stimulation with TRPV1, TRPA1 or TRPM8 agonists on the biomechanics and neurophysiology of swallow response in patients with OD. We retrospectively analyzed seven studies from our laboratory on 329 patients with OD. The effect of increasing shear viscosity up to 3682 mPa·s was compared by videofluoroscopy and pharyngeal sensory evoked potentials (pSEP) with that of adding to the bolus: capsaicin (TRPV1, 150 µM/10 µM), piperine (TRPA1/V1, 1 mM/150 µM), menthol (TRPM8, 1 mM/10 mM), cinnamaldehyde-zinc (TRPA1, 100 ppm−70 mM), citral (TRPA1, 250 ppm) or citral-isopulegol (TRPA1-TRPM8, 250 ppm−200 ppm). Fluid thickening improved the safety of swallow by 80% (p < 0.0001) by delaying bolus velocity by 20.7 ± 7.0% and time to laryngeal vestibule closure (LVC) by 23.1 ± 3.7%. Capsaicin 150µM or piperine 1 mM significantly improved safety of swallow by 50% (p < 0.01) and 57.1% (p < 0.01) by speeding time to LVC by 27.6% (p < 0.001) and 19.5% (p < 0.01) and bolus velocity by 24.8% (p < 0.01) and 16.9% (p < 0.05), respectively. Cinnamaldehyde-zinc shortened the P2 latency of pSEPs by 11.0% (p < 0.01) and reduced N2-P2 amplitude by 35% (p < 0.01). In conclusion, TRPV1 and TRPV1/A1 agonists are optimal candidates to develop new pharmacological strategies to promote the recovery of brain and swallow function in patients with chronic OD.

Healthcare costs of post-stroke oropharyngeal dysphagia and its complications: malnutrition and respiratory infections.

BACKGROUND AND PURPOSE: The healthcare economic costs of post-stroke oropharyngeal dysphagia (OD) are not fully understood. The purpose of this study was to assess the acute, subacute and long-term costs related to post-stroke OD and its main complications (malnutrition and respiratory infections). METHODS: A cost of illness study of patients admitted to Mataró Hospital (Catalonia, Spain) from May 2010 to September 2014 with a stroke diagnosis was performed. OD, malnutrition and respiratory infections were assessed during hospitalization and follow-up (3 and 12 months). Hospitalization and long-term costs were measured from hospital and healthcare system perspectives. Multivariate linear regression analysis was performed to assess the independent effect of OD, malnutrition and respiratory infections on healthcare costs during hospitalization, and at 3 and 12 months' follow-up. RESULTS: In all, 395 patients were included of whom 178 had OD at admission. Patients with OD incurred major total in-hospital costs (€5357.67 ± €3391.62 vs. €3976.30 ± €1992.58, p < 0.0001), 3-month costs (€8242.0 ± €5376.0 vs. €5320.0 ± €4053.0, p < 0.0001) and 12-month costs (€11,617.58 ± €12,033.58 vs. €7242.78 ± €7402.55, p < 0.0001). OD was independently associated with a cost increase of €789.68 (p = 0.011) during hospitalization and of €873.5 (p = 0.084) at 3 months but not at 12 months. However, patients with OD who were at risk of malnutrition or malnourished and suffered respiratory infections incurred major mean costs compared with those patients without OD (€19,817.58 ± €13,724.83 vs. €7242.8 ± €7402.6, p < 0.0004) at 12 months' follow-up. CONCLUSION: Oropharyngeal dysphagia causes significant high economic costs during hospitalization that strongly and significantly increase with the development of malnutrition and respiratory infections at long-term follow-up.

Synthesis and immunogenicity assessment of a gold nanoparticle conjugate for the delivery of a peptide from SARS-CoV-2.

The development of vaccines is a crucial response against the COVID-19 pandemic and innovative nanovaccines could increase the potential to address this remarkable challenge. In the present study a B cell epitope (S461-493) from the spike protein of SARS-CoV-2 was selected and its immunogenicity validated in sheep. This synthetic peptide was coupled to gold nanoparticles (AuNP) functionalized with SH-PEG-NH2 via glutaraldehyde-mediated coupling to obtain the AuNP-S461-493 candidate, which showed in s.c.-immunized mice a superior immunogenicity (IgG responses) when compared to soluble S461-493; and led to increased expression of relevant cytokines in splenocyte cultures. Interestingly, the response triggered by AuNP-S461-493 was similar in magnitude to that induced using a conventional strong adjuvant (Freund's adjuvant). This study provides a platform for the development of AuNP-based nanovaccines targeting specific SARS-CoV-2 epitopes.

The Potential of Algal Biotechnology to Produce Antiviral Compounds and Biopharmaceuticals.

The emergence of the Coronavirus Disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has led to an unprecedented pandemic, which demands urgent development of antiviral drugs and antibodies; as well as prophylactic approaches, namely vaccines. Algae biotechnology has much to offer in this scenario given the diversity of such organisms, which are a valuable source of antiviral and anti-inflammatory compounds that can also be used to produce vaccines and antibodies. Antivirals with possible activity against SARS-CoV-2 are summarized, based on previously reported activity against Coronaviruses or other enveloped or respiratory viruses. Moreover, the potential of algae-derived anti-inflammatory compounds to treat severe cases of COVID-19 is contemplated. The scenario of producing biopharmaceuticals in recombinant algae is presented and the cases of algae-made vaccines targeting viral diseases is highlighted as valuable references for the development of anti-SARS-CoV-2 vaccines. Successful cases in the production of functional antibodies are described. Perspectives on how specific algae species and genetic engineering techniques can be applied for the production of anti-viral compounds antibodies and vaccines against SARS-CoV-2 are provided.

Calcium sustained release, pH changes and cell viability induced by chitosan-based pastes for apexification.

We explored chitosan-based sustained release pastes for apexification. The study aimed to formulate chitosan-based pastes loaded with calcium hydroxide (CH) or with calcium chloride (CC), and to evaluate the sustained release of Ca2+ and pH changes in deionized water as well as the effect of the pastes on cell viability. The pastes were formulated by dissolution of the chitosan in 1% or 2% acetic acid (AAC) plus the addition of CH or CC, then were suspended in deionized water for 50 days; the released Ca(II) and pH were measured with an electrode probe. The effect of the pastes on viability of human dental pulp cells was evaluated with a MTS assay. The results showed that the pastes prepared with 1% and 2% AAC and loaded with CH released a 74.9% and a 76.1% of the Ca2+ content, respectively, while the pastes prepared with 1% and 2% AAC loaded with CC released a content of Ca2+ of 90.8% and 76.6%, respectively. A control paste (CH and polyethylene glycol) released a 95.4%; significant statistical differences were found between the percentage of the experimental pastes and the control. The CH-loaded pastes caused an alkaline pH at the starting of the study, but the pH became neutral at the ending. The pH of the CC-loaded pastes was neutral at the starting and was acid at the ending. The pastes no affected on the cell viability. The chitosan-based pastes showed a suitable sustained release profile and cytocompatibility.

A Comparative Study Between Two Sensory Stimulation Strategies After Two Weeks Treatment on Older Patients with Oropharyngeal Dysphagia.

Oropharyngeal dysphagia (OD) is a prevalent geriatric syndrome. Treatment is based on compensatory strategies to avoid complications. New treatments based on sensory stimulation to promote the recovery of the swallowing function have proved effective in acute studies but prolonged treatment needs further research. Our aim was to evaluate and compare the effect of two, longer-term sensory treatment strategies on older patients with OD. 38 older patients (≥70 years) were studied with videofluoroscopy (pre/posttreatment) and randomized into two 10-day treatment groups: Group A-transient receptor potential vanilloid 1 (TRPV1) agonist (capsaicin 1 × 10(-5) M) and Group B-transcutaneous sensory electrical stimulation (TSES) (Intelect VitalStim, biphasic pulses, 300 µs, 80 Hz). Patients were analyzed for treatment response. Patients were old (80.47 ± 5.2 years), with comorbidities (3.11 ± 1.59 Charlson Index), polymedication (8.92 ± 3.31 drugs/patient), and mild functional impairment (86.84 ± 17.84 Barthel Index), and 28.9 % were at risk of malnutrition (MNA-sf). Overall, all patients had videofluoroscopic signs of impaired safety of swallow (ISS) with delayed oropharyngeal swallow response (OSR). After sensory stimulation, prevalence of ISS decreased to 68.42 % in both groups (P = 0.019). There were 68.42 % responders in Group A (TRPV1) and 42.11 % in Group B (TSES). Group A responders showed an improvement in the penetration-aspiration scale (PAS, 5.23 ± 2.04 to 3 ± 1.47; P = 0.002), and the same was true for those of Group B (4.63 ± 1.41 to 2.13 ± 0.64; P = 0.007). 10-day sensory stimulation with either therapy improved safety of swallow and OSR in older patients with OD, reducing the severity of OD in a significant subgroup of these patients.

Production and purification of recombinant hypocholesterolemic peptides.

Elevated concentrations of cholesterol in plasma are associated with increased risk for heart diseases in humans. Bioactive peptides can be considered as an option to prevent or treat this condition. Currently, there are wide sources of bioactive peptides with hypocholesterolemic activities; however, most researches are focused in bioactive peptides derived from soybean and milk protein. Although there are several preparation methods for these peptides, it is a novel process to prepare bioactive peptides by genetic engineering techniques. In this review, after a general introduction on approaches and advances in bioactive peptides, recombinant strategies to generate hypocholesterolemic peptides and their purification are discussed as well as their application in food and drug design.

Oral health in older patients with oropharyngeal dysphagia.

BACKGROUND: oropharyngeal dysphagia (OD), aspiration and poor oral health status are potential risk factors in elderly patients with aspiration pneumonia (AP). AIM: to assess the oral hygiene status and the prevalence of periodontal disease and dental caries in elderly patients with OD. PATIENTS AND METHODS: fifty elderly patients (79.7 ± 6.64 years) with OD associated with ageing or neurological diseases and 15 elderly patients without OD (77.01 ± 4.51 years) were enrolled in this observational-transversal study. OD and aspiration were evaluated by videofluoroscopy (VFS). Oral health was assessed by: (i) the Simplified Oral Hygiene Index (OHI-S); (ii) a complete periodontal examination, assessing the periodontal pocket depth, clinical attachment loss and bleeding on probing to study periodontal diseases (periodontitis, gingivitis); and (iii) the presence of dental caries. RESULTS: 8/50 elderly patients with OD presented VFS signs of aspiration, half of them silent; 40/50, signs of penetration into laryngeal vestibule and 16/50, oropharyngeal residue. Prevalence of edentulism and caries was higher in patients with OD. Dentate older patients with OD (30/50) presented the following complications (i) poor oral hygiene in 18 patients (OHI-S 3.1-6), (ii) gingivitis in 2 and periodontitis in 28 and (iii) caries in 16. CONCLUSIONS: older patients with OD presented polymorbidity and impaired health status, high prevalence of VFS signs of impaired safety of swallow and poor oral health status with high prevalence of periodontal diseases and caries. These patients are at great risk of developing AP. We recommend a policy of systematic oral health assessment in elderly patients with OD.

Comparing biomechanics and neurophysiology between different phenotypes of patients with oropharyngeal dysphagia.

The pathophysiology of oropharyngeal dysphagia (OD) across patient phenotypes may differ. The aim of this study was to compare the biomechanics and neurophysiology of swallowing between healthy volunteers (HVs) and patients with dysphagia as a consequence of aging (OOD), post-stroke (PSOD), Parkinson's disease (POD), or dementia (DOD). A retrospective study including 35 HVs and 109 OOD, 195 PSOD, 78 POD, and 143 DOD patients was performed. Videofluoroscopic data of signs of impaired efficacy and safety, penetration-aspiration scale (PAS) score, and the biomechanics of laryngeal vestibule closure (LVC) and opening (LVO) and of upper esophageal sphincter opening (UESO) were collected. Neurophysiology was assessed with pharyngeal sensory evoked potentials and neurotopography maps. All OD phenotypes showed signs of impaired efficacy and safety of swallowing, increased PAS score (p < 0.001), and delayed time to LVC (p < 0.0001). OOD (p < 0.0001), PSOD (p < 0.0001), and POD (p = 0.0065) patients also had delayed time to LVO, and OOD (p = 0.0062) and DOD (p = 0.0016) patients to UESO. Regarding neurophysiology, all phenotypes presented impaired pharyngeal sensitivity, a significant reduction in cortical activation, and impaired sensory input integration. Additionally, only PSOD was associated with impaired conduction of sensory stimuli. In conclusion, we found common but also specific pathophysiological elements. These results improve our understanding of OD pathophysiology and may help pave the way for phenotype-specific treatments.

Complications of oropharyngeal dysphagia in older individuals and patients with neurological disorders: insights from Mataró hospital, Catalonia, Spain.

Background: Oropharyngeal dysphagia (OD) significantly impacts older individuals and neurologically compromised patients, hindering safe ingestion of food and liquids. Despite its prevalence, OD remains underdiagnosed and undertreated, leading to severe complications such as malnutrition, dehydration, respiratory infections, and aspiration pneumonia (AP), and increases hospital readmissions. Objectives: This study analyzes the intricate relationship between OD and various clinical complications in older individuals and patients with neurological disorders. Methods: Utilizing retrospective analysis and narrative review, our work consolidates findings from prior studies on Hospital de Mataro's dysphagia patient cohort. Revisiting OD's intricate association with clinical complications, it presents data via odds ratios (OR), incidence ratios (IR), and hazard ratios (HR) from univariate and multivariate analyses. Results: Five studies (2001-2014) involving 3,328 patients were scrutinized. OD exhibited independent and significant associations with various complications among older patients. Older individuals with OD faced heightened 1-month (ODDS 3.28) and 1-year (OR 3.42) mortality risks post-pneumonia diagnosis. OD correlated with a 2.72-fold risk of malnutrition, 2.39-fold risk of lower respiratory tract infections, 1.82-fold pneumonia readmissions (IR), and 5.07-fold AP readmissions (IR). Post-stroke OD is linked to neurological impairment (OR 3.38) and respiratory (OR 9.54) and urinary infections (OR 7.77), alongside extended hospital stays (beta coefficient 2.11). Conclusion: Oropharyngeal dysphagia causes and significantly exacerbates diverse clinical complications in older and post-stroke patients, emphasizing the urgent need for proactive identification, comprehensive assessment, and tailored management. Acknowledging OD's broader implications in general medical practice is pivotal to improving patient outcomes and healthcare quality.

Neurophysiological characterization of oropharyngeal dysphagia in older patients.

OBJECTIVE: To characterize swallowing biomechanics and neurophysiology in older patients with oropharyngeal dysphagia (OD). METHODS: Observational study in 12 young healthy volunteers (HV), 9 older HV (OHV) and 12 older patients with OD with no previous diseases causing OD (OOD). Swallowing biomechanics were measured by videofluoroscopy, neurophysiology with pharyngeal sensory (pSEP) and motor evoked-potentials (pMEP) to intrapharyngeal electrical and transcranial magnetic stimulation (TMS), respectively, and salivary neuropeptides with enzyme-linked immunosorbent assay (ELISA). RESULTS: 83.3% of OOD patients had unsafe swallows (Penetration-Aspiration scale = 4.3 ± 2.1; p < 0.0001) with delayed time to laryngeal vestibule closure (362.5 ± 73.3 ms; p < 0.0001) compared to both HV groups. OOD patients had: (a) higher pharyngeal sensory threshold (p = 0.009) and delayed pSEP P1 and N2 latencies (p < 0.05 vs HV) to electrical stimulus; and (b) higher pharyngeal motor thresholds to TMS in both hemispheres (p < 0.05) and delayed pMEPs latencies (right, p < 0.0001 HV vs OHV/OOD; left, p < 0.0001 HV vs OHV/OOD). CONCLUSIONS: OOD patients have unsafe swallow and delayed swallowing biomechanics, pharyngeal hypoesthesia with disrupted conduction of pharyngeal sensory inputs, and reduced excitability and delayed cortical motor response. SIGNIFICANCE: These findings suggest new elements in the pathophysiology of aging-associated OD and herald new and more specific neurorehabilitation treatments for these patients.

The Impact of Frailty, Oropharyngeal Dysphagia and Malnutrition on Mortality in Older Patients Hospitalized for Covid-19.

COVID-19 hospital mortality is higher among older patients through as yet little-known factors. We aimed to assess the effect of frailty (FR), oropharyngeal dysphagia (OD) and malnutrition (MN) on mortality in hospitalized COVID-19 older patients. Prospective cohort study of older patients (>70 years) with COVID-19 admitted to a general hospital from April 2020 to January 2021. Patients were evaluated on admission, discharge and at 1- and 3-months follow up. FR was assessed with FRAIL-VIG, OD with Volume-Viscosity Swallowing Test and MN with GLIM criteria. Clinical characteristics and outcomes, including intra-hospital, 1- and 3-month mortality, were analyzed. 258 patients were included (82.5±7.6 years; 58.9% women); 66.7% had FR (mild 28.7%, moderate 27.1% and severe 10.9%); 65.4%, OD and 50.6%, MN. OD prevalence increased from non-FR patients through the severity levels of FR: mild, moderate and severe (29.8%, 71.6%, 90.0%, 96.2%; p<0.0001, respectively), but not that of MN (50.6%, 47.1%, 52.5%, 56.0%). Mortality over the whole study significantly increased across FR categories (9.3% non-FR; 23.0% mild; 35.7% moderate; 75.0% severe; p<.001). Functionality (Barthel pre-admission, HR=0.983, CI-95%:0.973-0.993; p=0.001), OD (HR=2.953, CI-95%:0.970-8.989; p=0.057) and MN (HR=4.279, CI-95%:1.658-11.049; p=0.003) were independent risk factors for intra-hospital mortality. FR, OD and MN are highly prevalent conditions in older patients hospitalized with COVID-19. Functionality, OD and MN were independent risk factors for intra-hospital mortality.