Complications post renal transplantation: literature focus on BK virus nephropathy and diagnostic tools actually available

Clinical diagnosis of kidney transplants related illnesses is not a simple task. Several studies were conducted to define diseases and complications after renal transplantation, but there are no comprehensive guidelines about diagnostic tools for their prevention and detection

Spinal ependymoma in adults: from molecular advances to new treatment perspectives

Ependymomas are rare glial tumors with clinical and biological heterogeneity, categorized into supratentorial ependymoma, posterior fossa ependymoma, and spinal cord ependymoma, according to anatomical localization. Spinal ependymoma comprises four different types: spinal ependymoma, spinal ependymoma MYCN-amplified, myxopapillary ependymoma, and subependymoma. The clinical onset largely depends on the spinal location of the tumor. Both non-specific and specific sensory and/or motor symptoms can be present. Owing to diverse features and the low incidence of spinal ependymomas, most of the current clinical management is derived from small retrospective studies, particularly in adults. Treatment involves primarily surgical resection, aiming at maximal safe resection. The use of radiotherapy remains controversial and the optimal dose has not been established; it is usually considered after subtotal resection for WHO grade 2 ependymoma and for WHO grade 3 ependymoma regardless of the extent of resection. There are limited systemic treatments available, with limited durable results and modest improvement in progression-free survival. Thus, chemotherapy is usually reserved for recurrent cases where resection and/or radiation is not feasible. Recently, a combination of temozolomide and lapatinib has shown modest results with a median progression-free survival (PFS) of 7.8 months in recurrent spinal ependymomas. Other studies have explored the use of temozolomide, platinum compounds, etoposide, and bevacizumab, but standard treatment options have not yet been defined. New treatment options with targeted treatments and immunotherapy are being investigated. Neurological and supportive care are crucial, even in the early stages. Post-surgical rehabilitation can improve the consequences of surgery and maintain a good quality of life, especially in young patients with long life expectancy. Here, we focus on the diagnosis and treatment recommendations for adults with spinal ependymoma, and discuss recent molecular advances and new treatment perspectives

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective real-world experience with 200 cases outside of controlled clinical trials

In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved a superior clinical benefit over Pd with a manageable toxicity profile, leading to its approval in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI). We report here a real-world experience of 200 RRMMs treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was 2, with 51% of cases undergoing autologous stem cell transplant (ASCT) and 73% exposed to daratumumab. After a median follow-up of 9 months, 126 patients stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate (ORR) was 55.4%, in line with the pivotal trial results. Regarding adverse events, our cohort experienced a toxicity profile similar to the ELOQUENT-3 trial, with no significant differences between younger (<70 years) and older patients. The median progression-free survival (PFS) was 7 months, shorter than that observed in the ELOQUENT-3, probably due to the different clinical characteristics of the two cohorts. Interestingly, the ISS stage III (HR:2.55) was associated with worse PFS. Finally, our series's median overall survival (OS) was shorter than that observed in the ELOQUENT-3 trial (17.5 versus 29.8 months). In conclusion, our real-world study confirms EloPd as a safe and possible therapeutic choice for RRMM who received at least two prior therapies, including lenalidomide and a PI

Inter-society consensus for the use of inhaled corticosteroids in infants, children and adolescents with airway diseases

Background: In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. Methods: Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. Results: The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. Conclusions: We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research

Primary Effusion Lymphoma Cell Death Induced by Bortezomib and AG 490 Activates Dendritic Cells through CD91

To understand how cytotoxic agent-induced cancer cell death affects the immune system is of fundamental importance to stimulate immune response to counteract the high mortality due to cancer. Here we compared the immunogenicity of Primary Effusion Lymphoma (PEL) cell death induced by anticancer drug Bortezomib (Velcade) and Tyrphostin AG 490, a Janus Activated Kinase 2/signal trasducer and activator of transcription-3 (JAK2/STAT3) inhibitor. We show that both treatments were able to induce PEL apoptosis with similar kinetics and promote dendritic cells (DC) maturation. The surface expression of molecules involved in immune activation, namely calreticulin (CRT), heat shock proteins (HSP) 90 and 70 increased in dying cells. This was correlated with DC activation. We found that PEL cell death induced by Bortezomib was more effective in inducing uptake by DC compared to AG 490 or combination of both drugs. However the DC activation induced by all treatments was completely inhibited when these cells were pretreated with a neutralizing antiboby directed against the HSP90/70 and CRT common receptor, CD91. The activation of DC by Bortezomib and AG 490 treated PEL cells, as seen in the present study, might have important implications for a combined chemo and immunotherapy in such patients

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

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

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

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