The Impact of Delirium on Recovery in Geriatric Rehabilitation after Acute Infection.

OBJECTIVES: Delirium is common during acute infection in older patients and is associated with functional decline. Geriatric rehabilitation (GR) can help older patients to return to their premorbid functional level. It is unknown whether delirium affects GR outcomes in patients with acute infection. We evaluated whether delirium affects trajectories of activities of daily living (ADL) and quality of life (QoL) recovery in GR after COVID-19 infection. DESIGN: This study was part of the EU-COGER study, a multicenter cohort study conducted between October 2020 and October 2021. SETTING AND PARTICIPANTS: Participants were recruited after COVID-19 infection from 59 GR centers in 10 European countries. METHODS: Data were collected at GR admission, discharge, and at the 6-week and 6-month follow-ups. Trajectories of ADL [using the Barthel index (BI)] and QoL [using the EuroQol-5 Dimensions-5 Level (EQ-5D-5L)] recovery were examined using linear mixed models. RESULTS: Of the 723 patients included (mean age 75.5 ± 9.9 years; 52.4% male), 28.9% had delirium before or during GR admission. Participants with delirium recovered in ADL at approximately the same rate as those without (linear slope effect = -0.13, SE 0.16, P = .427) up to an estimated BI score of 16.1 at 6 months. Similarly, participants with delirium recovered in QoL at approximately the same rate as those without (linear slope effect = -0.017, SE 0.015, P = .248), up to an estimated EQ-5D-5L score of 0.8 at 6 months. CONCLUSIONS AND IMPLICATIONS: Presence of delirium during the acute phase of infection or subsequent GR did not influence the recovery trajectory of ADL functioning and QoL.

Patients with Covid-19 exhibit different immunological profiles according to their clinical presentation.

OBJECTIVES: A novel beta coronavirus has been identified as responsible for the 2019 coronavirus infection (Covid-19). Clinical presentations range from asymptomatic cases to acute respiratory distress syndrome with fatal outcome. Such a broad spectrum of disease expression calls for an investigation of immune response characteristics. METHODS: We identified subjects admitted for Covid-19 in whom a large panel of immunological markers were measured, including B- and T- and NK-lymphocyte phenotypes, T-lymphocyte subpopulation cells and plasma cytokines. Patients were divided according to symptom severity during hospitalisation, in those with uncomplicated and complicated infection. Differences between groups were analyzed. RESULTS: Seventeen patients were included (mean age: 83 years; 9 women; mean delay of symptoms onset: 4 days). Six had uncomplicated infection, while 11 developed complicated forms during hospitalization. CD10 + B lymphocyte levels were inversely correlated with clinical severity (5.8% vs 2.0%, p = 0.04) and CD10+ levels above 3% were independently associated with uncomplicated forms [Odds Ratio 0.04 (CI 0.002-0.795, p = 0.034)]. TNF-alpha, IL-1, Il-6 and Il-8 measurements upon admission differed between patients who died and those who survived (p < 0.01 for all comparisons). CONCLUSIONS: In a population of elderly patients recently infected with Covid-19, CD10 + B cell levels were inversely correlated with clinical severity. Cytokine values upon admission were highly predictive of fatal outcome during hospitalisation. These findings could explain differences in the clinical presentation and allow rapid identification of patients at risk for complications.

The pulmonary rehabilitation regimen: a treatment for frailty and 'inflammaging'?

Pulmonary rehabilitation is an exercise-based intervention that improves walking endurance, strength, functional independence, wellbeing and the risk of re-admission to hospital. It was developed for patients recovering from acute exacerbations of chronic obstructive pulmonary disease, and sometimes other long-term inflammatory lung diseases. Many other conditions have a chronic inflammatory component, including type 2 diabetes, obesity, osteoarthritis and old age. Such background inflammation is linked to a range of adverse outcomes, including all-cause mortality, sarcopenia and other markers of frailty. Exercise, including pulmonary rehabilitation, has an anti-inflammatory effect on innate immune chemistry, and improves outcomes in a variety of conditions, although for most diagnostic groups there is no consistent structured programme similar to pulmonary rehabilitation. The authors contend that the pulmonary rehabilitation model could be used generically to treat other chronic and post-acute inflammatory states and thereby reduce the risk of frailty and other adverse outcomes.

Phenotyping of subjects for large scale studies on patients with IBS.

BACKGROUND: Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. PURPOSE: The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu).

Semen leukocytes and oxidative-dependent DNA damage of spermatozoa in male partners of subfertile couples with no symptoms of genital tract infection.

The influence of seminal leukocytes on generation of oxidative damage to sperm DNA was here investigated on male partners of subfertile couples asymptomatic for a genital tract infection. The study included 111 ejaculates from men attending the Andrology Centre at University of L'Aquila. Semen leukocytes subset included round cells expressing pan-leukocyte CD45 antigen, monocyte/macrophage lineage antigen CD14, and activated macrophages HLA-DR antigen. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression identified spermatozoa with DNA oxidative adducts while terminal deoxynucleotidyl transferase (TdT)-mediated fluorescein-dUTP nick end labeling (TUNEL) assay detected spermatozoa with DNA fragmentation. Flow cytometry and immunocytochemistry was used for determinations. Main outcome measure was the association of semen leukocyte subpopulations with spermatozoa showing oxidative-related DNA damage and with routine semen parameters. Leukocyte subpopulations were strictly correlated (p < 0.0001), but no association was found between the concentration of leukocytes, semen parameters, the percentage of TUNEL-positive and of 8-OHdG-positive spermatozoa. The percentage of 8-OHdG-positive spermatozoa was positively correlated with the percentage of TUNEL-positive spermatozoa (r = 0.48; p < 0.0001) and negatively correlated with sperm concentration (r = -0.44; p < 0.0001). Sperm concentration and the percentage of TUNEL-positive spermatozoa independently contributed (ß = -0.25, p = 0.008; ß = 0.23, p = 0.05, respectively) to the variation in percentage of 8-OHdG-positive spermatozoa after adjusting for age, abstinence time, and smoking. In conclusion, oxidative-dependent DNA damage in spermatozoa was associated to poor semen quality but not to different leukocyte subpopulations in ejaculates of men asymptomatic for a genital tract infection.

Severe community-acquired pneumonia and positive urinary antigen test for S. pneumoniae: amoxicillin is associated with a favourable outcome.

Positive urinary antigen tests (UAT) for pneumococcal infection in community-acquired pneumonia (CAP) may lead to targeted antibiotic therapy. We report an audit aimed at defining the link between mortality and targeted therapy. We conducted a retrospective multicentre audit of patients with severe CAP for whom a UAT was positive for S. pneumoniae. Patients admitted from January 2010 to December 2013 to 8 medical centres (from A to H) were included. Co-morbidities were defined by the specific treatment administered before hospital care, or if the diagnosis was newly established during the hospital stay. We used the Pneumonia Severity Index (PSI) to assess disease severity. Only patients with PSI > 90 were included. Antibiotic treatments and the PSI were extracted from patients' charts. Amoxicillin had to be prescribed as a targeted antibiotic treatment or at the time of antibiotic reassessment. A total of 389 patients were included. The mean (±STD) PSI score was 128 ± 29; 38.9% of the patients had a class 5 PSI score. Intensive care was required for 36.6% of the patients. Amoxicillin was initially prescribed in 47 cases (12.1%) and in 34 cases after reassessment (8.7%). In logistic regression analysis, we found three parameters associated with mortality: being hospitalised in institution D, class 5 PSI score, and metastatic cancer. In contrast, three antibiotic regimens were protective factors, including targeted therapy: OR = 0.09, p < 0.001. In the context of severe CAP with positive UAT for S. pneumoniae, targeted therapy was associated with a reduction in mortality.

Antimicrobial stewardship policy: time to revisit the strategy?

Recent data indicate that both the overall numbers of antibiotic prescription and the frequency of multidrug-resistant bacteria are increasing significantly. These threatening features are observed, despite national antimicrobial stewardship (AMS) policies aimed at decreasing antibiotic use. AMS should also focus on the initial steps leading to antibiotic prescription. Physicians and their patients should benefit from the structured clinical pathways, the latter being adapted to regional epidemiological data and resources. Continuous evaluation of these predefined clinical paths through a computerized medical dashboard will allow a critical review and finally the optimization of medical practices. These innovative behavioural approaches for clinicians will supply precise information on the relationship among the diagnosis, therapeutics and outcome. This changing environment will carry out the adapted therapeutic procedures, and appropriate antibiotic use will inherently improve.

Virologically suppressed patients with asymptomatic and symptomatic HIV-associated neurocognitive disorders do not display the same pattern of immune activation.

OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. METHODS: Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. RESULTS: Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/µL, the mean nadir CD4 count was 240 cells/µL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/µL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level. CONCLUSIONS: Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.

Evaluation of the probiotic properties of new Lactobacillus and Bifidobacterium strains and their in vitro effect.

Probiotic ingestion is recommended as a preventive approach to maintain the balance of the intestinal microbiota and to enhance the human well-being. During the whole life of each individual, the gut microbiota composition could be altered by lifestyle, diet, antibiotic therapies and other stress conditions, which may lead to acute and chronic disorders. Hence, probiotics can be administered for the prevention or treatment of some disorders, including lactose malabsorption, acute diarrhoea, irritable bowel syndrome, necrotizing enterocolitis and mild forms of inflammatory bowel disease. The probiotic-mediated effect is an important issue that needs to be addressed in relation to strain-specific probiotic properties. In this work, the probiotic properties of new Lactobacillus and Bifidobacterium strains were screened, and their effects in vitro were evaluated. They were screened for probiotic properties by determining their tolerance to low pH and to bile salts, antibiotic sensitivity, antimicrobial activity and vitamin B8, B9 and B12 production, and by considering their ability to increase the antioxidant potential and to modulate the inflammatory status of systemic-miming cell lines in vitro. Three out of the examined strains presenting the most performant probiotic properties, as Lactobacillus plantarum PBS067, Lactobacillus rhamnosus PBS070 and Bifidobacterium animalis subsp. lactis PBSO75, were evaluated for their effects also on human intestinal HT-29 cell line. The obtained results support the possibility to move to another level of study, that is, the oral administration of these probiotical strains to patients with acute and chronic gut disorders, by in vivo experiments.

Correlates of low testosterone in men with chronic spinal cord injury.

Although high rates of serum testosterone deficiency have been reported in men with spinal cord injury (SCI), its determinants and attributes are not yet established. The aim of this study was to recognize, among putative determinants and attributes of androgen deficiency, those significantly associated to low testosterone after adjustment for confounders recognizable in men with chronic SCI. A biochemical androgen deficiency (total testosterone <300 ng/dL) was exhibited by 18 of 51 patients (35.3%). Significant correlates of testosterone levels were as follows: weekly leisure time physical activity (LTPA) explored by the LTPA Questionnaire for people with SCI, body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR), triglycerides and sexual symptoms, explored by the aging males' symptom (AMS) questionnaire. At the multiple linear regression analysis, among putative determinants of low testosterone, only weekly LTPA and BMI exhibited a significant association with testosterone levels, explaining 54.2 and 9.0% of testosterone variability respectively. At the linear regression models, among various putative attributes of androgen deficiency, only lower sexual desire and, at a lesser extent, higher HOMA-IR, exhibited significant associations with lower testosterone levels, after adjustment for BMI, age, comorbidities and weekly LTPA. In conclusion, poor LTPA, high BMI and low sexual desire are independent predictors of low testosterone in men with chronic SCI. This is relevant to clinical practice, as all these features are routinely assessed in rehabilitation settings for SCI. As poor LTPA and high BMI are modifiable life-style related risk factors, prospective studies could clarify whether life-style modification could increase the level of testosterone and improve the low sexual desire, relevant clinical attribute of low testosterone in men with SCI.

Involvement of cannabinoid receptor-1 activation in mitochondrial depolarizing effect of lipopolysaccharide in human spermatozoa.

Gram-negative bacteria frequently involved in urogenital tract infections release the endotoxin lipopolysaccharide (LPS); its receptor, toll-like receptor-4 (TLR4), has been recently identified in human spermatozoa, and its direct activation has been suggested in mediating adverse effects of LPS on human spermatozoa. However, the underlying signal transduction remains to be clarified. In other cell types, LPS induces the generation of endocannabinoids, which are involved in mediating endotoxin effects. In human spermatozoa, which exhibit a completely functional endocannabinoid system, the activation of cannabinoid receptor-1 (CB1) inhibited sperm mitochondrial membrane potential (ΔΨm). In this study, we tested the hypothesis of a contribution of CB1 activation by sperm-generated endocannabinoids in the adverse effects exerted by LPS on human spermatozoa. The exposure of motile sperm suspensions to E. coli LPS produced a significant decrease in sperm ΔΨm, assessed at flow cytometry with JC-1, similar to that induced by Metanandamide (Met-AEA), a non-hydrolyzable analogue of the endocannabinoid AEA. The LPS-induced inhibition of ΔΨm was prevented by the selective CB1 cannabinoid receptor antagonist, SR141716. However, the inhibition of ΔΨm induced by either LPS or Met-AEA did not affect sperm motility. Consistent with this finding, the CB1-mediated inhibition of ΔΨm was neither associated to mitochondrial generation of reactive oxygen species as evaluated by flow cytometry with MytoSox Red nor to apoptosis pathway activation as evaluated with cytoflorimetric assay for activated caspase-9 and caspase-3. Any oxidative genomic damage was also ruled out with the cytoflorimetric quantification of the oxidized base adduct 8-hydroxy-2'-deoxyguanosine. In conclusion, E. coli LPS inhibited sperm ΔΨm through the activation of CB1, but this effect was not accompanied to the activation of mitochondrial dysfunction-related apoptotic/oxidative mechanisms, which could affect sperm motility and genomic integrity.

How does cognitive impairment impact on functional improvement following the rehabilitation of elderly patients?

AIMS: It has been suggested that patients with cognitive impairment do not benefit from rehabilitation or that rehabilitation gains are reduced. Most studies focus on absolute gain rather than gains in individual functional areas. The Barthel activities of daily living (ADL) score is a tool, which is used widely and comprises 10 functional domains. This study aimed to assess the response to rehabilitation based on improvement or deterioration on the Barthel ADL score for patients with different cognitive abilities METHODS: This independence measure was assessed at specific time periods in an observational study of 241 patients undergoing in-patient rehabilitation. Therapy was delivered formally by physiotherapists and occupational therapists and also informally by nursing staff. Patients were divided into four groups according to cognition. Group 1 (MMSE, mini-mental state examination 27-30), normal cognition, Group 2 (MMSE 21-26) mild impairment, Group 3 (MMSE 11-20) moderate impairmentand Group 4 (MMSE 0-10) severe impairment. RESULTS: Statistically significant improvement was made in most of the functional domains by patients with normal cognition and mild cognitive impairment (p < 0.0025). The exception to this for both groups was in the areas of feeding and bowels because of the fact that most patients were independent with these aspects on admission. Group 3 patients made improvements in the domains of grooming, dressing, toileting, transferring and mobility. Group 4 patients did not demonstrate statistically significant improvement in any domain although there were trends for improvement in mobility and transferring. CONCLUSIONS: This study demonstrated that cognitive impairment did have an impact on the ADL that patients improved in following rehabilitation. However, even patients with moderate cognitive impairment made significant gains with many ADL.

Involvement of mitochondrial dysfunction in the adverse effect exerted by seminal plasma from men with spinal cord injury on sperm motility.

The aetiology of severe asthenozoospermia in men with spinal cord injury includes an adverse impact of seminal plasma (SP) on sperm motility. In this study we investigated the effect exerted by SP from men with SCI on donor sperm mitochondrial activity and its reflection on motility. Donor spermatozoa were exposed (1 h) to SP from 22 ejaculates of men with SCI. Only SP from samples exhibiting both a low fructose level and an inhibitory effect on mitochondrial membrane potential (ΔΨm), assessed at flow cytometry with JC-1, affected donor sperm motility when evaluated 1 h after co-incubation. This effect was reverted by washing from SP and sperm re-suspension in medium containing glucose, in spite of persistently depressed ΔΨm. In the same samples, sperm motility and vitality dramatically decreased when evaluated 6 h after washing and re-suspension in the glucose-containing medium. Seminal plasmas which induced a disruption of ΔΨm, also enhanced a mitochondrial ROS generation, as assessed by MitoSOX red. The enhanced mitochondrial ROS generation was associated with a late induction of sperm membrane lipid peroxidation, as assessed by BODIPY C11 , when evaluated at 6 h, but not at 1 h, after washing from SP. Furthermore, activation of caspase-9 and caspase-3 accompanied the loss of ΔΨm. In conclusion, a double energetic blockage (glycolysis and mitochondrial respiration) can represent a metabolic determinant of the early adverse effect exerted by SP from men with SCI on sperm motility. Mitochondrial dysfunction-related oxidative/apoptotic mechanisms can account for later consequences on sperm motility/vitality.

Changes in microvascular blood flow during coupled plasma filtration and adsorption.

A 51-year-old man with septic shock underwent three consecutive sessions of coupled plasma filtration-adsorption each lasting 12 hours. Sublingual microvascular perfusion was assessed using the orthogonal polarisation spectral imaging technique at three different times: immediate pre-coupled plasma filtration-adsorption phase, two hours following commencement and two hours after its termination. The video images of the sublingual microcirculation were analysed by an investigator blinded to the time of image acquisition. The De Backer's score was calculated. During the coupled plasma filtration-adsorption, the number of perfused vessels increased compared with the pre-coupled plasma filtration-adsorption period, but decreased again after its termination. It is arguable that the elimination of septic mediators during the procedure could account for the observed variations.

Arteriolopatía cálcica urémica: comunicación de un caso y revisión de la literatura / Calcific uremic arteriolopathy. A case report and review of the literature

Introducción. La arteriolopatía cálcica urémica se define como un síndrome constituido por úlceras cutáneas isquémicas, debido a la calcificación de la pared de las arteriolas del tejido celular subcutáneo como consecuencia del hiperparatiroidismo en pacientes urémicos. Caso clínico. Paciente femenina de 55 años, hipertensa, con insuficiencia cardíaca e insuficiencia renal, tratada con hemodiálisis, quien presenta dolor en miembros inferiores e hipercalcemia. Al examen físico se encontraron lesiones cutáneas con pulsos periféricos presentes y simétricos en extremidades. Los exámenes de laboratorio revelaron hipercalcemia, hiperfosfatemia y niveles de paratohormona muy elevados. Se le realizó paratiroidectomía y biopsia de lesiones cutáneas presentando una evolución tórpida, por lo cual fallece. Se realizó la autopsia con hallazgos morfológicos propios de arteriolopatía cálcica urémica. Conclusiones. La arteriolopatía cálcica urémica o calcifilaxis es una enfermedad compleja, variable, difícil de diagnosticar y de manejo muy complicado. A pesar de los esfuerzos de los investigadores aún existen muchas interrogantes en cuanto a su patogenia, lo cual sirve de incentivo para futuras investigaciones con el fin de establecer la conducta más adecuada para mantener una mejor calidad de vida del paciente y evitar complicaciones que en algunas instancias desencadenen la muerte(AU)

Background. Calcific uremic arteriolopathy is defined as a syndrome consisting of ischemic skin ulceration due to calcification of the wall of the arterioles of the subcutaneous tissue as a result of hyperparathyroidism in uremic patients. Case report. A 55-year old female patient, hypertense, with heart failure and kidney failure treated with hemodialysis, who presented lower limb pain and hypercalcemia. On physical examination, skin lesions with symmetrical peripheral pulses present in the limbs. Laboratory tests revealed hypercalcemia, hyperphosphatemia, and very high parathyroid hormone levels. Parathyroidectomy was performed and biopsy of skin lesions, the patient having a torpid course causing exitus. Autopsy was performed, with histologic features characteristic of calcific uremic arteriolopathy. Conclusions. Calcific calcium uremic arteriolopathy or calciphylaxis is a complex and variable disease that is difficult to diagnose and whose treatment is complicated. Despite the efforts of the investigators, there are still many questions regarding its pathogenesis. This acts as an incentive for further research to establish the most appropriate actions to take to maintain an adequate quality of life for the patients and avoid complications that trigger death in some cases(AU)

[Calcific uremic arteriolopathy. a case report and review of the literature]. / Arteriolopatía cálcica urémica: comunicación de un caso y revisión de la literatura.

BACKGROUND: Calcific uremic arteriolopathy is defined as a syndrome consisting of ischemic skin ulceration due to calcification of the wall of the arterioles of the subcutaneous tissue as a result of hyperparathyroidism in uremic patients. CASE REPORT: A 55-year old female patient, hypertense, with heart failure and kidney failure treated with hemodialysis, who presented lower limb pain and hypercalcemia. On physical examination, skin lesions with symmetrical peripheral pulses present in the limbs. Laboratory tests revealed hypercalcemia, hyperphosphatemia, and very high parathyroid hormone levels. Parathyroidectomy was performed and biopsy of skin lesions, the patient having a torpid course causing exitus. Autopsy was performed, with histologic features characteristic of calcific uremic arteriolopathy. CONCLUSIONS: Calcific calcium uremic arteriolopathy or calciphylaxis is a complex and variable disease that is difficult to diagnose and whose treatment is complicated. Despite the efforts of the investigators, there are still many questions regarding its pathogenesis. This acts as an incentive for further research to establish the most appropriate actions to take to maintain an adequate quality of life for the patients and avoid complications that trigger death in some cases.