Challenging New Targets for CNS–HIV Infection

The central nervous system (CNS) represents an important target for HIV infection during multiple stages of the disease: early, after invasion of the host, acting as a viral reservoir; lately, subverting its function and causing peripheral neuropathies and neurocognitive disorders; and lastly, during the final stage of NeuroAIDS, triggering opportunistic infections, cancers, and dementia. Highly active antiretroviral therapy, a combination of drugs that inhibits enzymes essential for HIV replication, can reduce the viremia and the onset of opportunistic infections in most patients, and prolong the survival. Among the limits of the current treatments the most noticeable is the inability to eradicate HIV-infected cells, both, limiting the time frame in which antiretroviral therapies initiated after exposure to HIV can prevent infection, and allowing replication-competent virus that persists in infected cells to emerge rapidly after the cessation of treatments. Many strategies are currently under evaluation to improve HIV treatment, unfortunately more than 98% of drug candidates for CNS disorders never make it to the clinic; here in we report how nanoformulated strategies might be adapted and applied to the field of CNS–HIV infection

Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further

Il biofeedback preoperatorio migliora il recupero della continenza a seguito di prostatectomia radicale: una revisione sistematica con meta-analisi

BACKGROUND:  Postoperative urinary incontinence is the overall result of urethral sphincter incompetence and modifications in urethral length after radical prostatectomy. Findings for preoperative interventions targeted at preventing post-prostatectomy incontinence include preoperative pelvic floor muscle training (PFMT) and biodfeedback (BFB), which can be managed by nurses in many countries and have been used for decades to speed up continence recovery after surgery. AIM: to determine the effectiveness of preoperative biofeedback (BFB) for post-prostatectomy urinary incontinence compared to pelvic training without BFB, considering the variability between the results of the available studies.  METHODS: A systematic review and meta-analysis was conducted, analyzing the indications provided by the literature regarding preoperative biofeedback for preventing urinary incontinence after open radical prostatectomy, in terms of treatment regimens, timing for beginning the sessions, number of contraction and relaxation exercises, and scheduled work at home. Literature search on Pubmed, CINAHL, Cochrane Library, Web of Science, Scopus, EMBASE, and PEdro. RESULTS: Despite only three papers being suitable for metanalysis, our results support BFB over written instructions for continence recovery after both 3 and 6 moths from surgery. Implementing progressive programs with many different muscular exercises and including relaxation are the main recommendations. CONCLUSIONS: Preoperative biofeedback leads to improved urinary continence after 3 and 6 months from radical prostatectomy. Future studies should focus on the characteristics and number of pelvic muscle contractions required during biofeedback in order to maximize effectiveness.BACKGROUND: L'incontinenza urinaria postoperatoria è il risultato complessivo dell'incompetenza dello sfintere uretrale e delle modifiche della lunghezza dell'uretra dopo la prostatectomia radicale. I risultati degli interventi preoperatori mirati a prevenire l'incontinenza post-prostatectomia includono l'allenamento preoperatorio dei muscoli del pavimento pelvico (PFMT) e il biodfeedback (BFB), che possono essere gestiti dal personale infermieristico in molti Paesi. OBIETTIVO: determinare l'efficacia del biofeedback preoperatorio (BFB) per l'incontinenza urinaria post-prostatectomia rispetto al training pelvico senza BFB, considerando la variabilità dei risultati degli studi disponibili.  METODI: è stata condotta una revisione sistematica con meta-analisi, analizzando le indicazioni fornite dalla letteratura sul biofeedback preoperatorio per la prevenzione dell'incontinenza urinaria in termini di regimi di trattamento, tempi di inizio delle sessioni, numero di esercizi di contrazione e rilassamento e lavoro programmato a casa. La ricerca della letteratura è stata effettuata su Pubmed, CINAHL, Cochrane Library, Web of Science, Scopus, EMBASE e PEdro. RISULTATI: nonostante solo tre articoli siano stati adatti alla metanalisi, i nostri risultati supportano il BFB rispetto alle istruzioni scritte per il recupero della continenza dopo 3 e 6 mesi dall'intervento. L'implementazione di programmi progressivi con molti esercizi muscolari diversi e l'inclusione del rilassamento sono le principali raccomandazioni. CONCLUSIONI: Il biofeedback preoperatorio porta a un miglioramento della continenza urinaria dopo 3 e 6 mesi dalla prostatectomia radicale. Gli studi futuri dovrebbero concentrarsi sulle caratteristiche e sul numero di contrazioni muscolari pelviche richieste durante il biofeedback per massimizzare l'efficacia.Il biofeedback preoperatorio migliora il recupero della continenza dopo la prostatectomia aperta: una revisione sistematica e una meta-analis

Airway management in patients with suspected or confirmed cervical spine injury

Summary: Background: There are concerns that airway management in patients with suspected or confirmed cervical spine injury may exacerbate an existing neurological deficit, cause a new spinal cord injury or be hazardous due to precautions to avoid neurological injury. However, there are no evidence‐based guidelines for practicing clinicians to support safe and effective airway management in this setting. Methods: An expert multidisciplinary, multi‐society working party conducted a systematic review of contemporary literature (January 2012–June 2022), followed by a three‐round Delphi process to produce guidelines to improve airway management for patients with suspected or confirmed cervical spine injury. Results: We included 67 articles in the systematic review, and successfully agreed 23 recommendations. Evidence supporting recommendations was generally modest, and only one moderate and two strong recommendations were made. Overall, recommendations highlight key principles and techniques for pre‐oxygenation and facemask ventilation; supraglottic airway device use; tracheal intubation; adjuncts during tracheal intubation; cricoid force and external laryngeal manipulation; emergency front‐of‐neck airway access; awake tracheal intubation; and cervical spine immobilisation. We also signpost to recommendations on pre‐hospital care, military settings and principles in human factors. Conclusions: It is hoped that the pragmatic approach to airway management made within these guidelines will improve the safety and efficacy of airway management in adult patients with suspected or confirmed cervical spine injury

The nucleus reuniens: a key node in the neurocircuitry of stress and depression

Uncorrected proofThe hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC-hippocampal pathway, provokes an antidepressant-like behavioral response in the forced swim test and prevents, but does not ameliorate, anhedonia in the chronic mild stress (CMS) model of depression. Additionally, RE lesioning before CMS abrogates the well-known neuromorphological and endocrine correlates of CMS. In summary, this work highlights the importance of the reciprocal connectivity between the hippocampus and PFC in the establishment of stress-induced brain pathology and suggests a role for the RE in promoting resilience to depressive illness.Greece for providing sertraline. This work was supported by an ‘Education and Lifelong Learning, Supporting Postdoctoral Researchers’, co-financed by the European Social Fund (ESF) and the General Secretariat for Research and Technology, Greece, the Life and Health Sciences Research Institute (ICVS), ON.2—O NOVO NORTE—North Portugal Regional Operational Program 2007/2013 of the National Strategic Reference Framework (NSRF) 2007/2013 through the European Regional Development Fund (ERDF), the Portuguese Foundation for Science and Technology (FCT; grant no. NMC-113934) and an InEurope program funded by International Brain Research Organizationinfo:eu-repo/semantics/publishedVersio

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population