Lumbar malignant peripheral nerve sheath tumor: a rare case in a young patient

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma that originate from peripheral nerves or from cells associated with the nerve sheath. We report the case of a 30‑year‑old male patient with a history of neurofibromatosis type I (NF-1) and a MPNST located in the lumbar region. The mass was resecated but surgical margins weren't clear. Recurrence of disease was observed after few months. A close monitoring of subjects with NF-1 is crucial to diagnose MPNST at an earlier stage and allow a complete surgical resection

Chemokine fractalkine/CX3CL1 negatively modulates active glutamatergic synapses in rat hippocampal neurons

We examined the effects of the chemokine fractalkine (CX3CL1) on EPSCs evoked by electrical stimulation of Schaffer collaterals in patch-clamped CA1 pyramidal neurons from rat hippocampal slices. Acute application of CX3CL1 caused a sustained reduction of EPSC amplitude, with partial recovery after washout. CX3CL1-induced EPSC depression is postsynaptic in nature, because paired-pulse ratio was maintained, amplitude distribution of spontaneous excitatory postsynaptic currents shifted to lower values, and whole-cell current responses to AMPA were reversibly inhibited. EPSC depression by CX3CL1 is mediated by CX3CL1 receptor (CX3CR1), because CX3CL1 was unable to influence EPSC amplitude in CA1 pyramidal neurons from CX3CR1 knock-out mice. CX3CL1-induced depression of both EPSC and AMPA current was not observed in the absence of afferent fiber stimulation or AMPA receptor activation, respectively, indicating the requirement of sustained receptor activity for its development. Findings obtained from hippocampal slices, cultured hippocampal neurons, and transfected human embryonic kidney cells indicate that a Ca2+-, cAMP-, and phosphatase-dependent process is likely to modulate CX3CL1 effects because of the following: (1) CX3CL1-induced depression was antagonized by intracellular BAPTA, 8Br-cAMP, phosphatase inhibitors, and pertussis toxin (PTX); (2) CX3CL1 inhibited forskolin-induced cAMP formation sensitive to PTX; and (3) CX3CL1 inhibited forskolin-induced Ser845 GluR1 phosphorylation, which was sensitive to PTX and dependent on Ca2+ and phosphatase activity. Together, these findings indicate that CX3CL1 negatively modulates AMPA receptor function at active glutamatergic synapses through cell-signaling pathways by influencing the balance between kinase and phosphatase activity

Prostate Multiparametric MRI: Common Pitfalls in Primary Diagnosis and How to Avoid Them

Abstract Purpose of Review To provide the radiologist with basic knowledge about normal and abnormal findings in the prostatic mp-MRI, taking a look at the possible diagnostic pitfalls commonly seen in daily clinical practice, allowing him to recognize and consequently avoid them. Recent Findings Prostate mp-MRI has now become commonly used in most diagnostic imaging centers, as a precise, accurate and above all non-invasive tool, useful in the diagnosis, staging and follow-up of prostate diseases, first of all prostatic carcinoma. For this reason, it is important to take into account the existence of numerous possible anatomic and pathologic processes which can mimick or masquerade as prostate cancer. Summary Through the combination of anatomical (T2WI) and functional sequences (DWI/ADC and DCE), the mp-MRI of the prostate provides all the information necessary for a correct classification of patients with prostate disease, cancer in particular. It is not uncommon, however, for the radiologist to make errors in the interpretation of imaging due to conditions, pathological or otherwise, that mimic prostate cancer and that, consequently, affect the diagnostic/therapeutic process of patients. The strategy, and what this pictorial review aims at, is to learn to recognize the potential pitfalls of the prostatic mp-MRI and avoid them

The Current State of Validation of Administrative Healthcare Databases in Italy: A Systematic Review

Background: Administrative healthcare databases are widely present in Italy. Our aim was to describe the current state of healthcare databases validity in terms of discharge diagnoses (according to the International Classification of Diseases, ICD-9 code) and their output in terms of research.Methods: A systematic search of electronic databases including Medline and Embase (1995-2013) and of local sources was performed. Inclusion criteria were: healthcare databases in any Italian territory routinely and passively collecting data; medical investigations or procedures at patient level data; the use of a validation process. The quality of studies was evaluated using the STARD criteria. Citations of the included studies were explored using Scopus and Google Scholar.Results: The search strategy allowed the identification of 16 studies of which 3 were in Italian. Thirteen studies used regional administrative databases from Lombardia, Piemonte, Lazio, Friuli-Venezia Giulia and Veneto. The ICD-9 codes of the following diseases were successfully validated: amyotrophic lateral sclerosis (3 studies in four different regional administrative databases), stroke (3 studies), gastrointestinal bleeding (1 study), thrombocytopenia (1 study), epilepsy (1 study), infection (1 study), chronic obstructive pulmonary disease (1 study), Guillain-Barre syndrome (1 study), and cancer diseases (4 studies). The quality of reporting was variable among the studies. Only 6 administrative databases produced further research related to the validated ICD-9 codes.Conclusion: Administrative healthcare databases in Italy need an extensive process of validation for multiple diagnostic codes to perform high quality epidemiological and health services research

Evolving knowledge in surgical oncology of pancreatic cancer: from theory to clinical practice-a fifteen-year journey at a tertiary referral centre

Pancreatic ductal adenocarcinoma (PDAC) is an increasing disease having a poor prognosis. The aim of the present study was to evaluate the effect of different models of care for pancreatic cancer in a tertiary referral centre in the period 2006-2020. Retrospective study of patients with PDAC observed from January 2006 to December 2020. The demographic and clinical data, and data regarding the imaging techniques used, preoperative staging, management, survival and multidisciplinary tumour board (MDTB) evaluation were collected and compared in three different periods characterised by different organisation of pancreatic cancer services: period A (2006-2010); period B (2011-2015) and period C (2016-2020). One thousand four hundred seven patients were analysed: 441(31.3%) in period A; 413 (29.4%) in B and 553 (39.3%) in C. The proportion of patients increased significantly, from 31.3% to 39.3% (P = 0.032). Body mass index (P = 0.033), comorbidity rate (P = 0.002) and Karnofsky performance status (P < 0.001) showed significant differences. Computed tomography scans (P < 0.001), endoscopic ultrasound (P < 0.001), fine needle aspiration, fine needle biopsy (P < 0.001), and fluorodeoxyglucose-positron emission tomography/computed tomography (P < 0.001) increased; contrast-enhanced ultrasound (P = 0.028) decreased. The cTNM was significantly different (P < 0.001). The MDTB evaluation increased significantly (P < 0.001). Up-front surgery and exploratory laparotomy decreased (P < 0.001), neoadjuvant treatment increased (P < 0.001). The present study showed the evolving knowledge in surgical oncology of pancreatic cancer at a tertiary referral centre over the time. The different models of care of pancreatic cancer, in particular the introduction of the MDTB and the institution of a pancreas unit to the decision-making process seemed to be influential

Columnar cell lesions and subsequent breast cancer risk: a nested case-control study

Introduction: Histologic and genetic evidence suggests that at least some columnar cell lesions (CCL) of the breast represent precursor lesions in the low-grade breast neoplasia pathway. However, the risk of subsequent breast cancer associated with the presence of CCL in a benign breast biopsy is poorly understood.Methods The authors examined the association between the presence of CCL and subsequent breast cancer risk in a nested case-control study of benign breast disease (BBD) and breast cancer within the Nurses' Health Studies (394 cases, 1,606 controls). Benign breast biopsy slides were reviewed by pathologists and CCL presence assessed. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association between CCL and breast cancer risk. Results: Women with CCL (140 cases, 448 controls) had an increased risk of breast cancer compared with those without CCL (OR = 1.44, 95% CI: 1.14 to 1.83), although this was attenuated and became non-significant after adjustment for the histologic category of BBD (OR = 1.20, 95% CI: 0.94 to 1.54). CCL presence was associated with the greatest risk of breast cancer for those with nonproliferative BBD (OR = 1.36, 95% CI: 0.79 to 2.37) and the lowest risk for those with atypical hyperplasia (AH) (OR = 1.10, 95% CI: 0.65 to 1.87); however, this apparent heterogeneity in risk across BBD categories was not significant (P for interaction between CCL presence and BBD category = 0.77). Conclusions: These results provide evidence that CCL may be an important marker of breast cancer risk in women with BBD but suggest that CCL do not increase breast cancer risk independently of concurrent proliferative changes in the breast

Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ

Abstract Background Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations. Methods Patients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months. Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. Results Median age of the cohort was 53 years (range 38–78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery. Conclusion Preoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women may be the best candidates for such treatment for DCIS, and whether best responders may safely avoid surgical intervention. Trial Registration ClinicalTrials.gov NCT0029074

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

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