Guillain-Barré syndrome AMSAN variant in a 90-year-old woman after COVID-19: a case report.

BACKGROUND: Guillain-Barré syndrome (GBS) is an inflammatory disease of the peripheral nervous system characterized by rapidly evolving polyneuropathy caused by autoimmune demyelination and/or axonal degeneration. Since SARS-CoV-2 outbreak, several GBS cases following exposure to coronavirus disease-2019 (COVID-19) have been reported in literature, raising the concern of the latter being a potential trigger event for GBS. CASE PRESENTATION: We report the case of a 90-year-old Caucasian woman who was admitted to our hospital because of fatigue, worsening gait and leg strength, dysphonia, dysarthria and dysphagia, started 3 weeks after being exposed to COVID-19. Based on clinical presentation GBS was suspected, so she performed a lumbar puncture and electromyography, which confirmed the diagnosis of acute motor and sensory axonal neuropathy (AMSAN) variant. We administered high dose of intravenous immunoglobulin with slight neurological improvement. However, after 2 weeks of hospitalization with maximization of care, her physical condition worsen, manifesting severe frailty. The patient was discharged with home support services for managing parenteral nutrition and intense scheduled physiotherapy. A few days later, the patient experienced a further decline in her clinical condition and died at home. CONCLUSIONS: To the best of our knowledge, we report the oldest woman with GBS AMSAN variant after COVID-19 described in the existing literature. Our case supports further research aimed at improving recognition, characterization and prompt management of neurological diseases related to COVID-19 in older patients.

Assessing the mortality risk in older patients hospitalized with a diagnosis of sepsis: the role of frailty and acute organ dysfunction.

BACKGROUND: A prognostic stratification of mortality risk in older patients with sepsis admitted to medical wards is often challenging. AIMS: To evaluate the ability of the Sequential Organ Failure Assessment (SOFA) score, serum biomarkers (lactate and C-Reactive Protein, CRP), and measures of comorbidity and frailty in predicting in-hospital and 6-month mortality in a cohort of older patients admitted to an Acute Geriatric Unit (AGU) with a diagnosis of sepsis. METHODS: All patients aged 70 years and over consecutively admitted to our AGU with sepsis in the study period were included. At admission, a Comprehensive Geriatric Assessment including two measures of frailty (Clinical Frailty Scale [CFS], Frailty Index [FI]) was obtained. To assess the predictivity of candidate prognostic markers, the Area Under the Receiver-Operating Characteristic (AUROC) curves were analyzed. A multivariate logistic regression analysis was also performed. RESULTS: We included 240 patients (median age = 85, IQR = 80-89, 40.8% women), of whom 33.8% died before discharge, and 60.4% at 6 months. The SOFA score (AUROC = 0.678, 95% CI 0.610-0.747) and CRP serum levels (AUROC = 0.606, 95% CI 0.532-0.680) were good predictors of in-hospital mortality. The CFS (AUROC = 0.703, 95% CI 0.637-0.768) and the FI (AUROC = 0.677, 95% CI 0.607-0.746) better predicted 6-month mortality. Results of the regression analysis confirmed the findings of the AUROC study. The combined assessment of SOFA and measures of frailty improved the performance of the model both in the short and the long term. CONCLUSIONS: Both the severity of organ dysfunction and frailty scores should be addressed on AGU admission to establish the short- and long-term outcomes of older patients with sepsis.

Frailty predicts failure to discharge patients home from a subacute-care unit: a 3-year Italian experience.

BACKGROUND: The primary purpose of Subacute Care Units (SCU) is to decongest acute hospital wards and facilitate the return of older patients to home. AIMS: We analyzed the clinical characteristics and outcomes of patients admitted to an Italian SCU, and we explored factors associated with discharge to locations other than home (outcome). METHODS: This retrospective observational cohort study was conducted at a medium-sized suburban hospital, enrolling all patients consecutively admitted to one SCU from October 2017 to February 2020. We collected demographics, cause of admission, comorbidities, cognition, Barthel Index (BI), nutritional status, Clinical Frailty Scale (CFS), length of stay, and discharge destination. Delirium was screened with the 4AT score. We adopted a multivariable conditional logistic regression model to identify the factors associated with the outcome. RESULTS: Frail subjects accounted for 58.6% of 406 patients (mean age 78.2 years, SD 11.6), while 61% were classified as functionally dependent. More than half of patients had relevant comorbidity, approximately 80% had a poor nutritional status, and 25% had pre-existing dementia. The overall prevalence of delirium was 14.5%. Most patients came from a hospital setting; recurrent reasons for admission were infections (70.5%) and heart failure (12.7%). Having a urinary bladder catheter at discharge, being overtly frail (CFS > 8), and low BI score were factors independently associated with not being discharged home. DISCUSSION AND CONCLUSION: The routine assessment of frailty, as expressed by the CFS, may help redirecting the patients eligible for SCU admission.

Helmet CPAP to treat hypoxic pneumonia outside the ICU: an observational study during the COVID-19 outbreak.

BACKGROUND: Respiratory failure due to COVID-19 pneumonia is associated with high mortality and may overwhelm health care systems, due to the surge of patients requiring advanced respiratory support. Shortage of intensive care unit (ICU) beds required many patients to be treated outside the ICU despite severe gas exchange impairment. Helmet is an effective interface to provide continuous positive airway pressure (CPAP) noninvasively. We report data about the usefulness of helmet CPAP during pandemic, either as treatment, a bridge to intubation or a rescue therapy for patients with care limitations (DNI). METHODS: In this observational study we collected data regarding patients failing standard oxygen therapy (i.e., non-rebreathing mask) due to COVID-19 pneumonia treated with a free flow helmet CPAP system. Patients' data were recorded before, at initiation of CPAP treatment and once a day, thereafter. CPAP failure was defined as a composite outcome of intubation or death. RESULTS: A total of 306 patients were included; 42% were deemed as DNI. Helmet CPAP treatment was successful in 69% of the full treatment and 28% of the DNI patients (P < 0.001). With helmet CPAP, PaO2/FiO2 ratio doubled from about 100 to 200 mmHg (P < 0.001); respiratory rate decreased from 28 [22-32] to 24 [20-29] breaths per minute, P < 0.001). C-reactive protein, time to oxygen mask failure, age, PaO2/FiO2 during CPAP, number of comorbidities were independently associated with CPAP failure. Helmet CPAP was maintained for 6 [3-9] days, almost continuously during the first two days. None of the full treatment patients died before intubation in the wards. CONCLUSIONS: Helmet CPAP treatment is feasible for several days outside the ICU, despite persistent impairment in gas exchange. It was used, without escalating to intubation, in the majority of full treatment patients after standard oxygen therapy failed. DNI patients could benefit from helmet CPAP as rescue therapy to improve survival. TRIAL REGISTRATION: NCT04424992.

Frailty, post-operative delirium and functional status at discharge in patients with hip fracture.

OBJECTIVE: To explore the effect of frailty, alone and in combination with post-operative delirium (POD), on the risk of poor function at discharge in patients with hip fracture (HF). METHODS: This is a prospective cohort study of patients with HF admitted to an Orthogeriatric Unit (OGU) between October 1, 2011 and March 15, 2019. POD was assessed using the 4AT and the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5-edition criteria. A 22-items Frailty Index (FI) was created using the data collected on admission. The outcome measure was the Cumulated Ambulation Score (CAS) score at discharge. A log-binomial regression model was used to assess the effect of frailty and POD on CAS. RESULTS: A total of 988 patients (median age = 84.9 years, Interquartile range = 80.6-89.2) were included: 360 patients (36.4%) were frail and 411 (42%) developed POD. Poor functional status at discharge (CAS score ≤2) was more common in frail than non-frail patients (68.3% vs. 53.8%, p < 0.001) In a regression adjusted for confounders, frailty alone (Relative Risk, RR = 1.33, 95% Confidence Intervals, CI = 1.14-1.55) and POD alone (RR 1.38, 95% CI = 1.2-1.59) were associated with poor functional status at discharge; when combined, frailty and POD had an interaction, yielding a mild increase in the risk of poor outcome (RR 1.47, 95% CI = 1.28-1.69). CONCLUSIONS: In older patients undergoing HF surgery, frailty, POD and their combination, are associated with poor functional status at discharge.

The relationship between frailty and delirium: insights from the 2017 Delirium Day study.

BACKGROUND: although frailty and delirium are among the most frequent and burdensome geriatric syndromes, little is known about their association and impact on short-term mortality. OBJECTIVE: to examine, in hospitalized older persons, whether frailty is associated with delirium, and whether these two conditions, alone or in combination, affect these patients' 30-day survival. DESIGN: observational study nested in the Delirium Day project, with 30-day follow-up. SETTING: acute medical wards (n = 118) and rehabilitation wards (n = 46) in Italy. SUBJECTS: a total of 2,065 individuals aged 65+ years hospitalized in acute medical (1,484 patients, 71.9%) or rehabilitation (581 patients, 28.1%) wards. METHODS: a 25-item Frailty Index (FI) was created. Delirium was assessed using the 4AT test. Vital status was ascertained at 30 days. RESULTS: overall, 469 (22.7%) patients experienced delirium on the index day and 82 (4.0%) died during follow-up. After adjustment for potential confounders, each FI score increase of 0.1 significantly increased the odds of delirium (odds ratio, OR: 1.66 [95% CI: 1.45-1.90]), with no difference between the acute (OR: 1.65 [95% CI: 1.41-1.93]) and rehabilitation ward patients (OR: 1.71 [95% CI: 1.27-2.30]). The risk of dying during follow-up also increased significantly for every FI increase of 0.1 in the overall population (OR: 1.65 [95% CI: 1.33-2.05]) and in the acute medical ward patients (OR: 1.61 [95% CI: 1.28-2.04]), but not in the rehabilitation patients. Delirium was not significantly associated with 30-day mortality in either hospital setting. CONCLUSIONS: in hospitalized older patients, frailty is associated with delirium and with an increased risk of short-term mortality.

Endoscopic retrograde cholangiopancreatography in the elderly: results of a retrospective study and a geriatricians' point of view.

BACKGROUND: The incidence of biliary tract pathology is growing with an age-related trend, and progresses as the population ages. Endoscopic Retrograde Cholangiopancreatography (ERCP) represents the gold standard for treatment in these cases, but evidence about its safety in the elderly is still debated. METHODS: We retrospectively analyzed the clinical records of all patients aged ≥65 undergoing ERCP between July 2013 and July 2015. Of 387 ERCP cases, 363 (~ 94%) were completed entirely. The mean age of the study population (n = 363) was 79.9 years old (range 70-95), with 190 subjects aged 70-79 and 173 older than 80. We recorded demographics, Charlson Comorbidity index (CCI), American Society of Anesthesiologists (ASA) physical status classification score, indication for the use of the ERCP procedure, and clinical outcomes. Then, we tested all variables to identify the potential risk factors for complications associated with the procedure. RESULTS: The older group (those ≥80 years old) showed significantly more patients with ASA Classes III-IV than the younger one (those ≤79 years old). Interestingly, the CCI was higher in the younger group (p = 0.009). The overall complication rate was 17.3% without inter-group differences. Older age, sex, CCI and intra-ERCP procedures were not related to a higher risk of complications, and the multivariate regression did not identify any of the considered variables to be an independent risk factor for complications. CONCLUSION: ERCP appears as safe in the patients aged 80 years and older, as it is in those aged 70-79 years old in our study, however, a selection bias may affect these findings. A study including a comprehensive geriatric assessment will contribute to shedding light on this issue.

The impact of psychomotor subtypes and duration of delirium on 6-month mortality in hip-fractured elderly patients.

OBJECTIVE: Studies exploring the incidence and impact of the psychomotor subtypes of postoperative delirium (POD) on the survival of hip fracture patients are few, and results are inconsistent. We sought to assess the incidence of POD subtypes and their impact, in addition to delirium duration, on 6-month mortality in older patients after hip-fracture surgery. METHODS: This is a prospective study involving 571 individuals admitted to an Orthogeriatric Unit within a 5-year period with a diagnosis of hip fracture. Survival status was assessed 6 months after posthip fracture surgery. Postoperative delirium was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders. Postoperative delirium subtypes were classified according to Lipowski's criteria. Cox regressions were used to evaluate the associations between POD subtypes, POD duration, and 6-month mortality, adjusting for covariates. RESULTS: The incidence of psychomotor POD subtypes was hypoactive 57 (10.0%), hyperactive 84 (14.7%), and mixed 79 (13.8%). Six-month mortality rates were 8.3%, 10.7%, 36.8%, and 29.1% in the no-delirium, hyperactive, hypoactive, and mixed-delirium subgroups, respectively. In adjusted models, the hypoactive subgroup (Hazard Ratio, HR = 3.14, 95% Confidence Intervals, CI, 1.63-6.04) and mixed subgroup (HR = 2.89, 95% CI, 1.49-5.62) showed high mortality rates and a significantly increased risk of mortality associated with POD duration as well. CONCLUSIONS: Hyperactive delirium was the most common POD psychomotor subtype, but hypoactive and mixed POD were associated with 6-month mortality risk. Moreover, the risk of death 6 months after surgery increased for both subgroups (hypoactive and mixed) with increasing duration of POD.

Management, prognosis and predictors of unfavourable outcomes in patients newly hospitalized for transient ischemic attack: a real-world investigation from Italy.

BACKGROUND: Understanding the gap between evidence-based recommendations and real-world management is important to inform priority setting and health service planning. METHODS: The 7,776 residents in the Italian Lombardy Region who were newly hospitalized for transient ischemic attack (TIA) during 2008-2009 entered into the cohort and were followed until 2012. Exposure to medical care including selected drugs, diagnostic procedures and laboratory tests was recorded. A composite outcome was employed taking into account all-cause death and hospitalization for stroke and acute myocardial infarction. A multivariable proportional hazards model was fitted to estimate hazard ratio, and 95% confidence intervals (CI), for the exposure-outcome association. RESULTS: During the first year after discharge, 8.6, 49.7 and 48.5% of patients did not use any drugs, diagnostic procedures and laboratory tests respectively. Patients exposed to medical care had 59% reduced risk (95% CI, 50 to 66%) with respect to those who did not use any of these services. CONCLUSIONS: Although the Italian National Health System supplies universal coverage for healthcare, several TIA patients receive suboptimal care. Systematic improvements are necessary in order to improve patient outcomes.

In Silico Modeling of Novel Drug Ligands for Treatment of Concussion Associated Tauopathy.

The objective of this study was to develop an in silico screening model for characterization of potential novel ligands from commercial drug libraries able to functionally activate certain olfactory receptors (ORs), which are members of the class A rhodopsin-like family of G protein couple receptors (GPCRs), in the brain of murine models of concussion. We previously found that concussions may significantly influence expression of certain ORs, for example, OR4M1 in subjects with a history of concussion/traumatic brain injury (TBI). In this study, we built a 3-D OR4M1 model and used it in in silico screening of potential novel ligands from commercial drug libraries. We report that in vitro activation of OR4M1 with the commercially available ZINC library compound 10915775 led to a significant attenuation of abnormal tau phosphorylation in embryonic cortico-hippocampal neuronal cultures derived from NSE-OR4M1 transgenic mice, possibly through modulation of the JNK signaling pathway. The attenuation of abnormal tau phosphorylation was rather selective since ZINC10915775 significantly decreased tau phosphorylation on tau Ser202/T205 (AT8 epitope) and tau Thr212/Ser214 (AT100 epitope), but not on tau Ser396/404 (PHF-1 epitope). Moreover, no response of ZINC10915775 was found in control hippocampal neuronal cultures derived from wild type littermates. Our in silico model provides novel means to pharmacologically modulate select ubiquitously expressed ORs in the brain through high affinity ligand activation to prevent and eventually to treat concussion induced down regulation of ORs and subsequent cascade of tau pathology. J. Cell. Biochem. 117: 2241-2248, 2016. © 2016 Wiley Periodicals, Inc.

Simultaneous bilateral femoral neck fracture and end-stage renal disease in a 76-year-old woman: a case report.

Hip fracture is a common occurrence in the elderly. Due to the growing demand for the specific care of these patients, we established the Orthogeriatric Unit (OGU) at San Gerardo University Hospital (Italy) in 2007. However, simultaneous bilateral femoral neck fractures among the geriatric population (those aged ≥65 years) are rarely reported in the literature. Reporting the rare case of a frail 76-year-old woman admitted with bilateral hip fracture and end-stage renal disease, we explain the important role played by the OGU and its flexible multidisciplinary approach for providing comprehensive care to patients with multimorbidity and clinical complexity. The team of geriatricians, orthopedic surgeons, anesthesiologists, and, in this case, a nephrologist, helped in the careful planning and timing of the single-step surgical repair, decided the appropriate type of anesthesia, and optimized outcomes. After a prompt evaluation of the patient, the OGU approach can achieve clinical stabilization prior to intervention. Along with a strict follow-up in the postoperative phase, this could result in a significant reduction of complications and mortality rates and an early start to a tailored rehabilitation process. We strongly suggest employing facilities with multidisciplinary teams for cases involving complex patients at short-term high risk for poor clinical outcomes. Indeed, the usual single-specialist model of care is gradually being abandoned worldwide.

Postoperative delirium and pre-fracture disability predict 6-month mortality among the oldest old hip fracture patients.

BACKGROUND: Age is one of the most robust risk factors for hip fracture. Recent projections indicate that almost half of hip fractures are occurring with an increasing trend among the "oldest old" (i.e., in those aged >85 years). AIMS: To compare clinical characteristics, outcomes, and risk factors for 6-month mortality in two groups of "oldest old" patients (group 1 = 85-89, group 2 > 90 years), after hip fracture surgery. METHODS: Observational prospective cohort study with 6-month follow-up, performed in an Orthogeriatric Unit of an academic hospital between March 2007 and November 2012. RESULTS: Two hundred seventy-five patients (group 1: N = 171; group 2: N = 104) underwent a comprehensive geriatric assessment, including demographics, clinical, functional, nutritional, and mental status. The 6-month rehospitalization and mortality rates after surgery were assessed through structured telephone interviews with patient's caregivers. Multivariate logistic regression models were used to evaluate predictors of 6-month mortality, adjusting for relevant covariates. Fifty-eight patients died at follow-up. The in-hospital and 6-month mortality rates were significantly higher for patients of group 2 than for those of group 1. After adjusting for covariates, the multivariate logistic regressions showed that severe disability (OR 2.24, 95 % CI 1.08-4.65) and postoperative delirium (POD) (OR 3.80, 95 % CI 1.72-8.39) were predictors of 6-month mortality. CONCLUSIONS: Patients aged >90 years who underwent hip fracture surgery are more likely to die at 6 months than those aged 85-89 years. Pre-fracture disability and POD are predictors of this excess of mortality.