Electric Cell-Substrate Impedance Sensing (ECIS) as a Platform for Evaluating Barrier-Function Susceptibility and Damage from Pulmonary Atelectrauma.

Biophysical insults that either reduce barrier function (COVID-19, smoke inhalation, aspiration, and inflammation) or increase mechanical stress (surfactant dysfunction) make the lung more susceptible to atelectrauma. We investigate the susceptibility and time-dependent disruption of barrier function associated with pulmonary atelectrauma of epithelial cells that occurs in acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI). This in vitro study was performed using Electric Cell-substrate Impedance Sensing (ECIS) as a noninvasive evaluating technique for repetitive stress stimulus/response on monolayers of the human lung epithelial cell line NCI-H441. Atelectrauma was mimicked through recruitment/derecruitment (RD) of a semi-infinite air bubble to the fluid-occluded micro-channel. We show that a confluent monolayer with a high level of barrier function is nearly impervious to atelectrauma for hundreds of RD events. Nevertheless, barrier function is eventually diminished, and after a critical number of RD insults, the monolayer disintegrates exponentially. Confluent layers with lower initial barrier function are less resilient. These results indicate that the first line of defense from atelectrauma resides with intercellular binding. After disruption, the epithelial layer community protection is diminished and atelectrauma ensues. ECIS may provide a platform for identifying damaging stimuli, ventilation scenarios, or pharmaceuticals that can reduce susceptibility or enhance barrier-function recovery.

Characteristics of aspiration pneumonia patients in acute care hospitals: A multicenter, retrospective survey in Northern Japan.

BACKGROUND: Pneumonia is a common cause of illness and death of the elderly in Japan. Its prevalence is escalating globally with the aging of population. To describe the latest trends in pneumonia hospitalizations, especially aspiration pneumonia (AP) cases, we assessed the clinical records of pneumonia patients admitted to core acute care hospitals in Miyagi prefecture, Japan. METHODS: A retrospective multi-institutional joint research was conducted for hospitalized pneumonia patients aged ≥20 years from January 2019 to December 2019. Clinical data of patients were collected from the medical records of eight acute care hospitals. RESULTS: Out of the 1,800 patients included in this study, 79% of the hospitalized pneumonia patients were aged above 70 years. The most common age group was in the 80s. The ratio of AP to total pneumonia cases increased with age, and 692 out of 1,800 patients had AP. In univariate analysis, these patients had significantly older ages, lower body mass index (BMI), a lower ratio of normal diet intake and homestay before hospitalization, along with more AP recurrences and comorbidities. During hospitalization, AP patients had extended fasting periods, more swallowing assessments and interventions, longer hospitalization, and higher in-hospital mortality rate than non-AP patients. A total of 7% and 2% AP patients underwent video endoscopy and video fluorography respectively. In multivariate analysis, lower BMI, lower C-reactive protein, a lower ratio of homestay before hospitalization, a higher complication rate of cerebrovascular disease, dementia, and neuromuscular disease were noted as a characteristic of AP patients. Swallowing interventions were performed for 51% of the AP patients who had been hospitalized for more than two weeks. In univariate analysis, swallowing intervention improved in-hospital mortality. Lower AP recurrence before hospitalization and a lower ratio of homestay before hospitalization were indicated as characteristics of AP patients of the swallowing intervention group from multivariate analysis. Change in dietary pattern from normal to modified diet was observed more frequently in the swallowing intervention group. CONCLUSION: AP accounts for 38.4% of all pneumonia cases in acute care hospitals in Northern Japan. The use of swallowing evaluations and interventions, which may reduce the risk of dysphagia and may associate with lowering mortality in AP patients, is still not widespread.

Outcomes of elderly patients with organophosphate intoxication.

This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (P < 0.001), shock (P < 0.001) and kidney injury (P = 0.001) than survivors did. Kaplan-Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test, P < 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045-166.667, P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.

Association of early antibiotic therapy and in-hospital mortality in adult mild-to-moderate acute aspiration pneumonitis: a cohort study.

BACKGROUND: Patients with aspiration pneumonitis often receive empiric antibiotic therapy despite it being due to a non-infectious, inflammatory response. OBJECTIVE: To study the benefits of early antibiotic therapy in patients with suspected aspiration pneumonitis in an acute care hospital. DESIGN: Retrospective cohort study using electronic medical records from Teine Keijinkai Hospital. PARTICIPANTS: Adults aged over 18 years admitted with a diagnosis of aspiration pneumonitis to the Department of General Internal Medicine or Emergency Department between January 1, 2008, and May 31, 2019. A diagnosis of aspiration pneumonitis was defined as a documented macro-aspiration event and a chest radiograph demonstrating new radiographic infiltrates. MAIN MEASURES: Patients were classified into the "early antibiotic treatment" group and the "no or late treatment" group depending on whether they received antibiotic therapy for respiratory bacterial pathogens within 8 h of arrival. The primary outcome was in-hospital all-cause mortality. Secondary outcomes included length of hospital stay, antibiotic-free days, duration of fever, readmission within one month, and incidence of complications. KEY RESULTS: Of the 146 patients enrolled, 52 (35.6%) did not receive early antibiotic therapy, while the remaining 94 (64.4%) did. There was no difference in in-hospital mortality rates between the groups after adjustment for potential confounding variables using Cox proportional hazards analysis (hazard ratio 2.78; 95% confidence interval, 0.57-13.50, p = 0.20). Patients in the no or late treatment group had more antibiotic-free days (p < 0.001) and a shorter length of hospital stay among survivors (p = 0.040) than did those in the early antibiotic treatment group. There were no statistically significant differences between the groups with respect to other secondary outcomes. CONCLUSIONS: Early antibiotic therapy for acute aspiration pneumonitis was not associated with in-hospital mortality, but was associated with a longer hospital stay and prolonged use of antibiotics.

Premature oral pre-shaping for feeding in elderly population with risk of aspiration pneumonia.

The aim of this study was to determine the abnormal hand and mouth behavior before actual swallowing for eating in elderly people with high risk of aspiration pneumonia. Ten elderly people with a diagnosis of aspiration pneumonia (EAP), 15 healthy elderly (HE) people, and 21 young adults (YA) were enrolled. The feeding time and the timing of the maximum distance between the upper and lower lips were extracted using a motion analyzer during self-feeding and assisted-feeding. The results showed that feeding time in EAP was significantly longer than that for the other groups in self- and assisted-feeding. In self-feeding, the timing of mouth-preparation in the EAP group was significantly earlier than that in the other groups; conversely, in assisted-feeding, the timing in EAP was significantly delayed. Our results indicate that abnormal preparation of mouth-shape and movement time of hand before actual swallowing in both self- and assisted-feeding may exist in elderly people with previous experience of aspiration pneumonia.

Risk factors for aspiration pneumonia in patients with dysphagia undergoing videofluoroscopic swallowing studies: A retrospective cohort study.

Prediction of aspiration pneumonia development in at-risk patients is vital for implementation of appropriate interventions to reduce morbidity and mortality. Unfortunately, studies utilizing a comprehensive approach to risk assessment are still lacking. The objective of this study was to analyze the clinical features and videofluoroscopic swallowing study (VFSS) findings that predict aspiration pneumonia in patients with suspected dysphagia.Medical records of 916 patients who underwent VFSS between September 2014 and June 2018 were retrospectively analyzed. Patients were divided into either a pneumonia group or a non-pneumonia group based on diagnosis of aspiration pneumonia. Clinical information and VFSS findings were evaluated.One hundred seven patients (11.7%) were classified as having pneumonia. Multivariate analysis indicated that aspiration during the 2- cubic centimeter thick-liquid trial of VFSS (odds ratio [OR] = 3.23, 95% confidence interval [CI]: 1.93-5.41), smoking history (OR = 2.63, 95% CI: 1.53-4.53), underweight status (OR = 2.27, 95% CI: 1.31-3.94), abnormal pharyngeal delay time (OR = 1.60, 95% CI: 1.01-2.53), and a Penetration-Aspiration Scale level of 8 (OR = 3.73, 95% CI: 2.11-6.59) were significantly associated with aspiration pneumonia development. Integrated together, these factors were used to develop a predictive model for development of aspiration pneumonia (DAP), with a sensitivity of 82%, specificity of 56%, and an area under the receiver operating characteristic curve of 0.73.The best predictors for DAP included videofluoroscopic findings of aspiration during a 2-cubic centimeter thick-liquid trial, prolonged pharyngeal delay time, a Penetration-Aspiration Scale level of 8, history of smoking, and underweight status. These 5 proposed determinants and the associated DAP score are relatively simple to assess and may constitute a clinical screening tool that can readily identify and improve the management of patients at risk for aspiration pneumonia.

Caring for Patients with Spinal Cord Injuries.

The column in this issue is supplied by Juan Jose Olivero, MD, who was a nephrologist at Houston Methodist Hospital and a member of the hospital's Nephrology Training Program before his retirement in 2019. Dr. Olivero obtained his medical degree from the University of San Carlos School of Medicine in Guatemala, Central America, and completed his residency and nephrology fellowship at Baylor College of Medicine in Houston, Texas. He currently serves on the journal's editorial board and is editor of the "Points to Remember" section.

Does our swallow go to sleep? Changes in swallow function during sleep and implications for symptoms.

PURPOSE OF REVIEW: Swallowing is a vital function and the clearance of the pharynx by deglutition, which removes matter that could be aspirated, and the respiratory phase patterns associated with deglutition are important in protecting the airways and lungs against aspiration. This article reviews swallowing and respiratory phase patterns associated with deglutition during sleep and their implications for pathophysiology. RECENT FINDINGS: During sleep, swallowing is infrequent and absent for long periods. The deeper the sleep stage, the lower the mean deglutition frequency. However, in healthy younger adults, sleep-related deglutition is almost always followed by arrested breathing and expiration, reducing the risk of aspiration. Deglutition is extremely infrequent as well as absent for long periods in the aged. Consequently, clearance of the pharynx and esophagus by deglutition was extremely reduced during sleep in the aged. Furthermore, respiratory phase patterns associated with deglutition displayed adverse patterns during sleep in the aged. SUMMARY: Due to the complexity of swallowing processes, many adverse health conditions can influence swallowing functions during sleep, especially in the aged. Sleep-related deglutition and respiratory phase patterns may adversely influence aspiration-related diseases such as aspiration pneumonia, especially in the aged not only with primary but also with secondary presbyphagia.

Fiberoptic endoscopic evaluation of swallowing in early-to-advanced stage Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor disturbances, cognitive decline, and behaviour changes. A well-recognized feature of advanced HD is dysphagia, which leads to malnutrition and aspiration pneumonia, the latter being the primary cause of death in HD. Previous studies have underscored the importance of dysphagia in HD patients with moderate-to-advanced stage disease, but it is unclear whether dysphagia affects patients already at an early stage of disease and whether genetic or clinical factors can predict its severity. We performed fiberoptic endoscopic evaluation of swallowing (FEES) in 61 patients with various stages of HD. Dysphagia was found in 35% of early-stage, 94% of moderate-stage, and 100% of advanced-stage HD. Silent aspiration was found in 7.7% of early-stage, 11.8% of moderate-stage, and 27.8% of advanced-stage HD. A strong correlation was observed between disease progression and dysphagia severity: worse dysphagia was associated with worsening of motor symptoms. Dysphagia severity as assessed by FEES correlated with Huntington's Disease Dysphagia Scale scores (a self-report questionnaire specific for evaluating swallowing in HD). The present findings add to our understanding of dysphagia onset and progression in HD. A better understanding of dysphagia onset and progression in HD may inform guidelines for standard clinical care in dysphagia, its recognition, and management.

[Severe pneumonia and delirium in a 90-year-old male patient with postdeglutition regurgitation]. / Schwere Pneumonie und Delir bei einem 90-jährigen Patienten mit postdeglutitivem Aufstoßen.

Pneumonia and in particular aspiration pneumonia, is a common disease in geriatrics. These aspirations are often due to dysphagia, which is frequently first noticed in the context of a geriatric assessment. The reasons for dysphagia are manifold. In this geriatric department several patients have been detected in recent months in whom a Zenker diverticulum was the cause of recurrent aspiration pneumonia. The swallowing disorder was already apparent during the logopedic examination on admission to hospital. A supplementary fiber optic endoscopic evaluation of swallowing (FEES) revealed a postswallow hypopharyngeal reflux (PSHR), which is typical for a Zenker diverticulum. A supplementary contrast esophagography confirmed the findings. In the present case the treatment of choice was a myotomy with a flexible endoscope performed by gastroenterologists. After successful treatment, swallowing was again possible with no indications of penetration or aspiration in the FEES control. The case highlights the importance of logopedic diagnostics and treatment in geriatric patients with recurrent pneumonia. With the aid of early diagnostics it was possible to quickly recognize the finding of a PSHR that is typical for a Zenker diverticulum. The findings in this case could be clearly demonstrated based on the images of the FEES and contrast esophagography.

A Comparative Study of Two Tube Feeding Methods in Patients with Dysphagia After Stroke: A Randomized Controlled Trial.

BACKGROUND: Dysphagia is a common symptom seen in stroke patients, it not only affects patients' nutrition supply, but also causes aspiration pneumonia. To solve the problem of nutritional support for patients with dysphagia after stroke, nasogastric tubes are routinely indwelling to provide nutrition in China. However, this feeding method sometimes causes food reflux, aspiration, pneumonia, and often affects the patients' comfort and self-image acceptance. AIM: The aim of this study was to determine whether a new feeding method called intermittent oroesophageal (IOE) tube feeding compared with continuous nasogastric tube feeding as a practical and beneficial mean of decreasing the rate of stroke associated pneumonia (SAP), and improving patients' swallowing function, comfort, psychological status. DESIGN: This was an assessor-blinded, single-center, randomized controlled trial. METHODS: Ninety-seven hospitalized stroke patients with dysphagia in the rehabilitation department from January to December 2018 were randomized to a control group and an intervention group. Patients in both groups received routine nursing, rehabilitation treatment and swallowing therapy. Patients in the intervention group were given IOE tube feeding, while those in the control group were fed by indwelling nasogastric tube. Outcomes were assessed at admission, discharge or the end of the tube feeding. RESULTS: The incidence of SAP in the intervention group was 16.33% lower than that (31.25%) in the control group; the comfort score (2.08 ± .64), anxiety score (10.98 ± 2.28), depression score (7.39 ± 2.16) were lower than those (3.02 ± .70), (12.10 ± 2.18), (8.42 ± 2.34) in the control group. The improvement rate of swallowing function in the intervention group was 83.67% higher than that (66.67%) in the control group (all P < .05). CONCLUSIONS: The IOE tube feeding compared with continuous tube feeding may reduce the incidence of SAP, and improve patients' swallowing function, comfort, psychological status in patients with dysphagia after stroke.

Association between sarcopenia and pneumonia in older people.

Pneumonia is a major cause of death in older people, and the number of such deaths is increasing. Present guidelines for pneumonia management are based on a pathogen-oriented strategy that relies on the optimal application of antibiotics. Older pneumonia inpatients show the high incidence of aspiration pneumonia. The main cause of aspiration pneumonia is an impairment in the swallowing and cough reflexes. These facts suggest a limitation of present management strategies and a requirement for new strategies for aspiration pneumonia. Sarcopenia is the loss of muscle strength and mass, and declining physical function with aging. Recently, a decrease in the mass or strength of the swallowing muscles was suggested to be associated with reduced swallowing function. Accordingly, dysphagia caused by sarcopenia of the systemic and swallowing-related muscles was named sarcopenic dysphagia. Presently, few studies have shown associations between aspiration pneumonia and sarcopenic dysphagia. As for the cough reflex, strong cough prevents aspiration pneumonia, and its strength is regulated by respiratory muscles. A few studies have reported a relationship between muscles and pneumonia in older people. Sarcopenia is a risk factor for pneumonia in older people, and aspiration pneumonia inpatients with low muscle mass show high mortality rates. Aspiration pneumonia induced muscle atrophy in respiratory, swallowing, and skeletal muscles in an animal model and humans. Associations between respiratory muscle strength and pneumonia are currently under investigation. Evaluation and management of sarcopenia could potentially become a new strategy to prevent and treat pneumonia in older patients, and research has only recently been launched. Geriatr Gerontol Int 2020; 20: 7-13.

Cough Strength Is an Indicator of Aspiration Risk When Restarting Food Intake in Elderly Subjects With Community-Acquired Pneumonia.

BACKGROUND: The incidence of community-acquired pneumonia (CAP) is relatively high in elderly subjects. Cough peak flow (CPF) is an objective indicator of cough strength, and CPF evaluation might be useful to assess whether food intake can be restarted. We aimed to examine whether cough strength assessed with CPF can be used as an indicator of the aspiration risk when restarting food intake in elderly subjects with CAP. METHODS: This cross-sectional study included 82 elderly subjects with CAP between August 2016 and March 2018. CPF was measured using a peak flow meter, and we performed the repetitive saliva-swallowing test (RSST), which is a videoendoscopic evaluation of swallowing and is used to assess dysphagia and aspiration. Receiver operating characteristic (ROC) curve analysis was performed. The cutoff value was determined, and the area under the ROC was calculated. RESULTS: The areas under the RSST and CPF curves were 0.87 and 0.83, respectively. The RSST value for identifying the aspiration risk was 2.5 swallows. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 70.0%, 71.7%, 2.5, and 0.42, respectively. The CPF for identifying the aspiration risk was 190 L/min. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 82.6%, 69.4%, 2.7, and 0.25, respectively. CONCLUSIONS: Our findings suggest that cough strength assessed with CPF can be used as an indicator of the aspiration risk when restarting food intake in elderly subjects with CAP and that CPF evaluation is not inferior to the RSST. However, CPF evaluation should be performed together with swallowing screening tests to determine the aspiration risk.

A Simple Assessment of the Eating and Swallowing Functions in Elderly Patients with Pneumonia.

It is important to assess the eating and swallowing functions of elderly people because they often develop aspiration pneumonia due to dysphagia. The most reliable modalities for assessing the eating and swallowing functions are videofluoroscopic examinations and videoendoscopic evaluations; however, these diagnostic modalities often cannot be performed in elderly people. Therefore, we established the Assessment of Swallowing Ability for Pneumonia (ASAP), which is an assessment of eating and swallowing functions in elderly patients with pneumonia that can be conducted by all health care professionals, and examined the usefulness thereof. The subjects included 130 patients with pneumonia (58 males, 72 females, average age: 82.2 ± 13.0) who had been admitted to the internal medicine department at our hospital between January 2016 and June 2016. The coefficient of correlation between ASAP and the Mann Assessment of Swallowing Ability (MASA) was 0.97, indicating a strong correlation, and the area under the curves (AUC) between the ASAP and the degrees of severity were 0.98, 0.95, and 0.94, respectively. We suggest that ASAP can be useful as a modality for assessing the eating and swallowing functions in elderly patients with pneumonia.

A Double-Blind Randomized Controlled Trial to Determine the Preventive Effect of Hangekobokuto on Aspiration Pneumonia in Patients Undergoing Cardiovascular Surgery.

PURPOSE: This study aimed to assess whether hangekobokuto (HKT) can prevent aspiration pneumonia in patients undergoing cardiovascular surgery. METHODS: We performed a single-center, double-blinded, randomized, placebo-controlled study of HKT in patients undergoing cardiovascular surgery. JPS HKT extract granule (JPS-16) was used as HKT. The primary endpoint was defined as the prevention of postoperative aspiration pneumonia. The secondary endpoints included complete recovery from swallowing and coughing disorders. RESULTS: Between August 2014 and August 2015, a total of 34 patients were registered in this study. The rate of subjects with postoperative aspiration pneumonia was significantly lower in the HKT group than in the placebo group (p = 0.017). In high-risk patients for aspiration pneumonia, the rate was significantly lower in the HKT group than in the placebo group (p = 0.015). The rate of subjects with swallowing disorders tended to be lower in the HKT group than in the placebo group (p = 0.091), and in high-risk patients, the rate was significantly lower in the HKT group than in the placebo group (p = 0.038). CONCLUSIONS: HKT can prevent aspiration pneumonia in patients undergoing cardiovascular surgery. In high-risk patients for aspiration pneumonia, HKT can prevent aspiration pneumonia and improve swallowing disorders.

Long-term Swallowing Function, Pulmonary Complications, and Quality of Life after Supracricoid Laryngectomy.

OBJECTIVES: Long-term effects of supracricoid laryngectomies are nowadays under discussion. The purpose of this study was to detect the prevalence of chronic aspiration and incidence of pulmonary complications, to investigate possible influencing factors, and to analyze dysphagia-related quality of life in a cohort of patients who recovered swallowing function after undergoing supracricoid laryngectomies. STUDY DESIGN: Retrospective observational study. SETTING: San Raffaele Hospital, Vita-Salute University, Milan, Italy. METHODS: A cohort of 39 patients who recovered swallowing function free of disease after a minimum 3-year follow-up period was retrospectively investigated between October and December 2017-clinically with the Pearson's Scale and M. D. Anderson Dysphagia Inventory and instrumentally with fiberoptic endoscopic evaluation of swallowing. RESULTS: Chronic aspiration was demonstrated in a significant portion of patients (clinically in 33.3% and instrumentally in 35.9%). Aspiration was influenced by advanced age at surgery (P = .020). Type of surgical procedure, resection of 1 arytenoid cartilage, postoperative rehabilitation with a speech-language therapist, radiotherapy, age at consultation, and length of follow-up did not influence the prevalence of aspiration. Pulmonary complications affected 5 patients; incidence of pulmonary complications was related to aspiration and was favored by poor laryngeal sensation/cough reflex. Aspiration significantly affected quality of life. CONCLUSIONS: Chronic aspiration is frequent and affects patients' quality of life. However, incidence of pulmonary complications is low; therefore, oral feeding should not be contraindicated for aspirating patients. Preservation of laryngeal sensation and cough reflex is mandatory to prevent pulmonary complications.

The Mortality and the Risk of Aspiration Pneumonia Related with Dysphagia in Stroke Patients.

BACKGROUND: Dysphagia may result in poor outcomes in stroke patients due to aspiration pneumonia and malnutrition. GOAL: The aim of the study was to investigate aspiration pneumonia and the mortality rate in stroke patients with dysphagia in Taiwan. METHODS: We selected 1220 stroke patients, divided them into dysphagia and nondysphagia groups, and matched them according to age; covariates and comediations from 2000 to 2005 were identified from the NHIRD 2000 database. The date of the diagnosed stroke for each patient was defined as the index date. All patients were tracked for 5 years following their index visit to evaluate mortality and the risk of aspiration pneumonia. We estimated the adjusted hazard ratio using Cox proportional hazard regression. RESULTS: Within 1 year, the dysphagia group was 4.69 times more likely to develop aspiration pneumonia than the nondysphagia group (adjusted hazard ratio [aHR], 4.69; 95% confidence interval [CI] 2.83-7.77; P < .001). The highest significant risk of aspiration pneumonia was in the cerebral hemorrhage patients within 3 years of the index visit (aHR, 5.04; 95% CI 1.45-17.49; P = .011). The 5-year mortality rate in the dysphagia group was significantly higher than that in the nondysphagia group (aHR, 1.84; 95% CI 1.57-2.16; P < .001). CONCLUSION: Dysphagia is a critical factor in aspiration pneumonia and mortality in stroke patients. Early detection and intervention of dysphagia in stroke patients may reduce the possibility of aspiration pneumonia.

The Modified Barium Swallow Impairment Profile as a Predictor of Clinical Outcomes of Admission for Pneumonia or Choking in Dysphagic Patients with Parkinson's Disease.

Dysphagia increases risk of pneumonia in patients with Parkinson's disease (PD). However, no studies have investigated the association between objective measures of swallowing dysfunction and clinical outcomes. Therefore, we aimed to study the link between scores obtained on the modified barium swallow impairment scale profile (MBSImP) and hospital admissions for pneumonia and choking, in groups of patients with PD on different feeding modes. 157 patients who completed MBS studies were divided into three groups based on their feeding modes (oral, enteral, and rejected enteral feeding with oral feeding at own risk). Videos were analysed using the MBSImP. We evaluated the association of the oral, pharyngeal, and combined scores, with risk of admission for pneumonia and choking. Kaplan-Meier plots and log-rank tests were used to compare survival distributions among feeding groups. Cox regression models were generated to estimate hazard ratios (HRs) and 95% confidence intervals. Patients in the group that rejected enteral feeding scored the highest on the MBSImP, followed by enteral then oral feeding. Within the group that rejected enteral feeding, higher pharyngeal (HR = 3.73, p = 0.036) and combined scores (HR = 1.63, p = 0.034) significantly increased the risk of pneumonia and choking. In the enteral feeding group, higher oral subscores (HR = 2.16, p = 0.011) increased risk for the event, while higher pharyngeal (HR = 0.40, p = 0.004) subscores reduced risk for pneumonia and choking. This is the first study to analyse the association of MBSImP scores with clinical outcomes in PD patients. Patients who rejected enteral feeding had the highest risk for pneumonia and choking that could be predicted by their MBSImP scores. In the enteral feeding group, this risk was partially reversed. Compliance with feeding modes reduces the risk of pneumonia and choking.

Denture Wearing Moderates the Association between Aspiration Risk and Incident Pneumonia in Older Nursing Home Residents: A Prospective Cohort Study.

Aspiration is increasingly recognized as a major risk for pneumonia, but a potential link between wearing dentures and incident pneumonia with aspiration risk is unclear. The aim of this study was to investigate whether denture wearing moderates the association between aspiration risk and incident pneumonia in older adults. We used prospective cohort data of 156 residents aged >70 years from eight nursing homes in Aso, Japan. Aspiration risk was evaluated using the modified water swallowing test. During a 1-year follow-up (2014 to 2015), information on incident pneumonia was obtained from nursing home medical records. During follow-up, pneumonia developed in 7.1% of participants. In the multivariate-adjusted Cox proportional hazards model, after adjusting for potential confounders, aspiration risk was independently associated with a 4.4-fold higher hazard ratio (HR) of incident pneumonia (95% confidence interval, CI, 1.16⁻16.43). The difference in the risk of incident pneumonia between subjects with aspiration risk who were wearing dentures and those not at risk of aspiration was not significant, whereas those with aspiration risk without dentures had a 7.3-fold higher HR of incident pneumonia than those not at risk of aspiration (95% CI, 1.02⁻52.63). Denture wearing might partially moderate the increased risk of incident pneumonia associated with aspiration risk.

Disruption of protein function by pathogenic mutations: common and uncommon mechanisms 1.

Mutations in protein-coding regions underlie almost all Mendelian disorders, drive tumorigenesis, and contribute to susceptibility to common diseases. Despite the great diversity of diseases that are caused by coding mutations, the cellular processes that affect, and are affected by, pathogenic variants at the molecular level are fundamentally conserved. Experimental and computational approaches have revealed that a substantial fraction of disease mutations are not simple loss-of-function alleles. Rather, these pathogenic variants disrupt protein function in more subtle ways by tuning protein folding pathways, altering subcellular trafficking, interrupting signaling cascades, and rewiring highly connected interaction networks. Focusing mainly on Mendelian disorders, this review discusses the common mechanisms by which deleterious mutations disrupt protein function and how these disruptions can be exploited in the development of novel therapies.