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Objective: The first pandemic phase of COVID-19 in Italy was characterized by high in-hospital mortality ranging from 23% to 38%. During the third pandemic phase there has been an improvement in the management and treatment of COVID-19, so mortality and predictors may have changed. A prospective study was planned to identify predictors of mortality during the third pandemic phase. Patients and methods: From 15 December 2020 to 15 May 2021, 208 patients were hospitalized (median age: 64 years; males: 58.6%); 83% had a median of 2 (IQR,1-4) comorbidities; pneumonia was present in 89.8%. Patients were monitored remotely for respiratory function and ECG trace for 24 hours/day. Management and treatment were done following the timing and dosage recommended by international guidelines. Results: 79.2% of patients necessitated O2-therapy. ARDS was present in 46.1% of patients and 45.4% received non-invasive ventilation and 11.1% required ICU treatment. 38% developed arrhythmias which were identified early by telemetry and promptly treated. The in-hospital mortality rate was 10%. At multivariate analysis independent predictors of mortality were: older age (R-R for≥70 years: 5.44), number of comorbidities ≥3 (R-R 2.72), eGFR ≤60 ml/min (RR 2.91), high d-Dimer (R-R for≥1,000 ng/ml:7.53), and low PaO2/FiO2 (R-R for

Innate immune mechanisms are central players in response to the binding of pathogens to pattern-recognition receptors providing a crucial initial block on viral replication. Moreover, innate immune response mobilizes cells of the cellular-mediated immune system, which develop into effector cells that promote viral clearance. Here, we observed circulating leukocyte T cell response in healthy subjects, COVID-19 infected, and in healthy vaccinated subjects. We found a significant CD8+ T cells (p < 0,05) decrease and an augmented CD4+/CD8+ ratio (p < 0,05) in COVID-19 infected group compared with vaccinated subjects. In addition, healthy vaccinated subjects have a significant increased expression of CD8+ T cells, and a reduction of CD4+/CD8+ ratio with respect to subjects previously COVID-19 infected. Central Memory and Terminal Effector Memory cells (TEMRA) increased after vaccine but not among groups.

Background RAS mutations are the only validated biomarkers in metastatic colorectal cancer (mCRC) for anti-epidermal growth factor receptor (EGFR) therapy. Limited clinical information is available on AXL expression, marker of epithelial to mesenchymal transition, in mCRC. Methods AXL was retrospectively assessed by immunohistochemistry in 307 patients. RAS wild-type (WT) patients (N = 136) received first-line anti-EGFR–based therapy; RAS mutant patients (N = 171) received anti-angiogenic–based regimens. Preclinical experiments were performed using human RAS WT CRC cell lines and xenograft models. AXL RNA levels were assessed in a cohort of patients with available samples at baseline and at progression to anti-EGFR treatment and in the GSE5851 dataset. Results AXL was expressed in 55/307 tumour tissues, correlating with worse survival in the overall population (AXL-positive, 23.7 months; AXL-negative, 30.8 months; HR, 1.455, P = 0.032) and in RAS WT patients (AXL-positive, 23.0 months; AXL-negative, 35.8 months; HR,1.780, P = 0.032). Progression-free survival (PFS) in the RAS WT cohort was shorter in the AXL-positive cohort (6.2 months versus 12.1 months; HR, 1.796, P = 0.013). Three-dimensional cultures obtained from a patient following anti-EGFR therapy resulted AXL-positive, showing resistance to anti-EGFR drugs and sensitivity to AXL inhibition. AXL transfection in CRC cell lines induced AXL overexpression and resistance to the EGFR blockade. At progression to cetuximab, 2/10 SW48-tumour xenograft mice showed AXL expression. Consistently, AXL RNA levels increased in 5/7 patients following anti-EGFR therapy. Moreover, in the GSE5851 dataset higher AXL RNA levels correlated with worse PFS with cetuximab in KRAS-exon2 WT chemorefractory patients. Conclusions AXL is a marker of poor prognosis in mCRC with consistent clinical and preclinical evidences of involvement in primary and acquired resistance to anti-EGFR drugs in RAS WT patients.

OBJECTIVE: To evaluate 2 different techniques of myomectomy by comparing laparoscopy with 3 or 2 suprapubic ports, with regard to operative parameters and outcomes. STUDY DESIGN: This was a retrospective nonrandomized study (Canadian Task Force classification II-2) set at the Second University of Naples, involving 67 patients who underwent laparoscopic myomectomy between January 2010 and March 2014. Patients were divided into 2 groups: Group A (n=37) underwent laparoscopic myomectomy with 3 operative ports, and Group B (n=30) underwent laparoscopic myomectomy with 2 operative ports. RESULTS: Significant differences were observed in operative times and intraoperative blood loss. No significant difference was observed in number of removed myomas, although a significantly greater number of isthmic and infraligamentary myomas and a greater diameter of removed myomas were observed in the patients of Group A as compared to those in Group B. The degree of surgical difficulty, evaluated by visual analog scale, was higher in Group A. CONCLUSION: Laparoscopic myomectomy with 2 operative trocars is, in our opinion, an effective and safe surgical approach with lower or at least comparable intraoperative difficulties and similar outcome. However, the technique with 3 operative trocars remains the best choice for large and difficult myomas.

Iodinated contrast media are essential for diagnostic and interventional radiological and cardiological procedures, but may cause kidney damage. Intravenous hydration is the current cornerstone for prevention of contrast-induced acute kidney injury; however, new data from the AMACING trial suggest that this approach might not be beneficial in low-risk patients.

BACKGROUND: Fine needle cytology (FNC) of thyroid nodules is not always diagnostic. Most of FNCs undeterminated for malignancy belong to the cytological class of "follicular neoplasm/suspicious for follicular neoplasm" lesions (FN). In this group only 10-30% of cases are malignant and the most appropriate surgical management is still controversial. Here, this issue was addressed and the more reliable predictive criteria of malignancy were also evaluated. METHODS: We retrospectively evaluated 472 patients, surgically treated after a FN diagnosis in a tertiary care referral center. In patients affected by bilateral thyroid disease with a cytological diagnosis of FN, or when high-risk clinical features and familiarity for thyroid cancer were present, total thyroidectomy (TT) was performed. Conversely, hemithyroidectomy (HT) was preferred when the nodule was single and when the age was ≤ 45 years. Frozen section examination was not used, and if cancer was diagnosed by definitive pathology of the HT specimen, the remnant thyroid lobe was removed. Histological features, surgical complications, and long-term outcomes of the remnant lobe were reported. Clinical features predictivity was also evaluated. RESULTS: TT was performed in 154/472 pts (32.62%), while HT was carried out in 318/472 cases (67.37%). The overall malignancy rate (MR) was 18.85% (89/472 pts), respectively 16% (51/318pts) following HT, and 24.6% (38/154pts) following TT, with a statistically significant difference. Similarly, the rates of transient and definitive hypoparathyroidism and the mean hospital stay following TT were higher than after HT (and statistically significant). Age < 45years and female gender were more frequently associated to malignancy. The rate of complications following second surgery was comparable to that of primary HT. In the HT group incidence of unexpected contralateral papillary thyroid cancer (PTC) was 9.8% and, after 88.2 ± 30.42 months mean follow-up, completion surgery for benign pathology was carried out in 6.7% of cases. CONCLUSIONS: Our data show that histology following a cytological FN diagnosis is malignant only in a low percentage of cases (89/472, 18.85%). Following TT, a MR higher than in HT was observed. Even if some clinical features are cancer associated, malignancy cannot be reliably predicted before surgery. Thus, in solitary low-risk lesions, HT is still the standard of care. Its lower complication rates makes HT the safest procedure. In case of multiglandular disease TT may be recommended. Further investigation is warranted to achieve a better preoperative diagnostic accuracy in order to reduce the amount of surgical operations with diagnostic aim.

Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.

PURPOSE: The aim of this study was to assess bone mineral density (BMD) in a large population of children, adolescents, and young adults with epilepsy alone or in association with cerebral palsy and/or mental retardation. METHODS: Ninety-six patients were enrolled in the study. The group comprised 50 males and 46 females, aged between 3 and 25 years (mean age 11 years). The control group consisted of 63 healthy children and adolescents (23 males, 40 females), aged between 3 and 25 years (mean age 12.1 years). Patients underwent a dual-energy x-ray absorptiometry (DEXA) scan of the lumbar spine (L1-L4) and the z scores were calculated for each patient; the t score was considered for patients 18 years of age or older. RESULTS: Abnormal BMD was found in 56 patients (58.3%), with values documenting osteopenia in 42 (75%) and osteoporosis in 14 (25%). A significant difference emerged between epileptic patients and the control group in BMD, z score, and body mass index (BMI) (p =

BACKGROUND: Fine needle cytology (FNC) of thyroid nodules is not always diagnostic. Most of FNCs undeterminated for malignancy belong to the cytological class of "follicular neoplasm/suspicious for follicular neoplasm" lesions (FN). In this group only 10-30% of cases are malignant and the most appropriate surgical management is still controversial. Here, this issue was addressed and the more reliable predictive criteria of malignancy were also evaluated. METHODS: We retrospectively evaluated 472 patients, surgically treated after a FN diagnosis in a tertiary care referral center. In patients affected by bilateral thyroid disease with a cytological diagnosis of FN, or when high-risk clinical features and familiarity for thyroid cancer were present, total thyroidectomy (TT) was performed. Conversely, hemithyroidectomy (HT) was preferred when the nodule was single and when the age was ≤ 45 years. Frozen section examination was not used, and if cancer was diagnosed by definitive pathology of the HT specimen, the remnant thyroid lobe was removed. Histological features, surgical complications, and long-term outcomes of the remnant lobe were reported. Clinical features predictivity was also evaluated. RESULTS: TT was performed in 154/472 pts (32.62%), while HT was carried out in 318/472 cases (67.37%). The overall malignancy rate (MR) was 18.85% (89/472 pts), respectively 16% (51/318pts) following HT, and 24.6% (38/154pts) following TT, with a statistically significant difference. Similarly, the rates of transient and definitive hypoparathyroidism and the mean hospital stay following TT were higher than after HT (and statistically significant). Age < 45years and female gender were more frequently associated to malignancy. The rate of complications following second surgery was comparable to that of primary HT. In the HT group incidence of unexpected contralateral papillary thyroid cancer (PTC) was 9.8% and, after 88.2 ± 30.42 months mean follow-up, completion surgery for benign pathology was carried out in 6.7% of cases. CONCLUSIONS: Our data show that histology following a cytological FN diagnosis is malignant only in a low percentage of cases (89/472, 18.85%). Following TT, a MR higher than in HT was observed. Even if some clinical features are cancer associated, malignancy cannot be reliably predicted before surgery. Thus, in solitary low-risk lesions, HT is still the standard of care. Its lower complication rates makes HT the safest procedure. In case of multiglandular disease TT may be recommended. Further investigation is warranted to achieve a better preoperative diagnostic accuracy in order to reduce the amount of surgical operations with diagnostic aim.

Peripheral arterial disease (PAD) is a chronic condition caused by atherosclerosis and is a severe complication of type 2 diabetes (T2D). We hypothesised that chronic condition of arterial disease engenders inflammation and endothelial damage in response to circulating cytokines released in the blood stream of PAD patients. We explored the levels of circulating cytokines in PAD patients with and without diabetes by multiplex cytokine array compared with non-PAD controls. Serum from PAD patients with or without diabetes showed high levels of VEGF, IFN-gamma, TNF-alpha, MCP-1, and EGF. VEGF levels correlated with TNF-alpha and IFN-gamma, significantly. Endothelial cells (ECs) were exposed to the different altered cytokines to evaluate changes in cell growth, migration and tubule-like formation, displaying impairment on proliferation, migration and tubule formation. Our findings demonstrate that a set of cytokines is significantly increased in the serum of PAD patients. These cytokines act to induce endothelial dysfunction synergistically. VEGF strongly correlated with TNF-alpha and IFN-gamma, opening new therapeutic perspectives.

The current implementation into nephrology clinical practice of guidelines on treatment of cardiovascular (CV) risk factors in chronic kidney disease (CKD) is unknown. We designed a cross-sectional analysis to evaluate the prevalence and treatment of eight modifiable CV risk factors in 1058 predialysis CKD patients (stage 3: n =486; stage 4: n =430, stage 5: n =142) followed for at least 1 year in 26 Italian renal clinics. The median nephrology follow-up was 37 months (range: 12–391 months). From stages 3 to 5, hypertension was the main complication (89, 87, and 87%), whereas smoking, high calcium-phosphate product and malnutrition were uncommon. The prevalence of proteinuria (25, 38, and 58%), anemia (16, 32, and 51%) and left ventricular hypertrophy (51, 55, and 64%) significantly increased, while hypercholesterolemia was less frequent in stage 5 (49%) than in stages 4 and 3 (59%). The vast majority of patients received multidrug antihypertensive therapy including inhibitors of renin–angiotensin system; conversely, diuretic treatment was consistently inadequate for both frequency and dose despite scarce implementation of low salt diet (19%). Statins were not prescribed in most hypercholesterolemics (78%), and epoietin treatment was largely overlooked in anemics (78%). The adjusted risk for having a higher number of uncontrolled risk factors rose in the presence of diabetes (odds ratio 1.29, 95% confidence interval 1.00–1.66), history of CV disease (odds ratio 1.48, 95% confidence interval 1.15–1.90) and CKD stages 4 and 5 (odds ratio 1.75, 95% confidence interval 1.37–2.22 and odds ratio 2.85, 95% confidence interval 2.01–4.04, respectively). In the tertiary care of CKD, treatment of hypertension is largely inadequate, whereas therapy of anemia and dyslipidemia is frequently omitted. The risk of not achieving therapeutic targets is higher in patients with diabetes, CV disease and more advanced CKD.

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.