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Breast cancer (BC), the most commonly diagnosed malignancy, frequently metastasizes to the bone, lungs, brain and liver at advanced stages, whereas the thyroid gland represents a rare target site for secondary disease. We examined the most recent literature about thyroid metastasis (TM) from BC after we encountered a peculiar case of a 71-year-old woman who developed sudden dysphagia, severe hypothyroidism and hypoparathyroidism due to TM 18 years after the diagnosis of her primary cancer. Based on published data, the prevalence of TM in BC ranges from 3% to 34%, with a median onset time of 48.2 months, although longer time intervals are not infrequent. TM negatively impacts the prognosis of these patients, however thyroid surgery can limit the local disease burden. Therefore, we suggest that clinicians involved in the follow-up care of BC patients should consider a differential diagnosis of secondary thyroid malignancy when incidental lesions are diagnosed during radiological evaluations or local symptoms affect the cervical region, even many years after the diagnosis of the primary cancer.

Abstract Disclosure: P. Fallahi: None. F. Ragusa: None. A. Patrizio: None. V. Mazzi: None. C. Botrini: None. G. Elia: None. E. Balestri: None. E. Barozzi: None. L. Rugani: None. E. Palmisano: None. M. Cosenza: None. G. Varricchi: None. S. Ulisse: None. S. Benvenga: None. S. Ferrari: None. A. Antonelli: None. We have conducted an observational and retrospective study, by enrolling patients with hypothyroidism and gastric diseases in treatment with liquid L-T4 (L-LT4) or tablet L-T4 (T-LT4). The aim of the study was to compare the stability of TSH in these patients. Eighty-four patients were in treatment with L-LT4, and 120 patients with T-LT4; all of them assumed L-T4 30 minutes before breakfast. The patients were affected by different types of gastric disease: a) in T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) in L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). In the T-LT4 group 66% of the patients were chronically treated with PPI, against 51% in the L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the two groups (p>0.05). The mean L-T4 dosage in the T-LT4 group at the basal evaluation was 1.22+/-0.27 μg/kg/die, in the L-LT4 group was 1.36+/-0.22 μg/kg/die (p>0.05). At the basal evaluation the prevalence of patients with a TSH > 3.5 μIU/mL in the T-LT4 group was 36%, whereas in the L-LT4 group was of 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the patients were re-evaluated with an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of patients with a TSH>3.5 μIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of patients with a TSH > 3.5 μIU/mL in the T-LT4 group was 26%, and of 13% in the L-LT4 group (p<0.05). At the third re-evaluation, the prevalence of patients with TSH>3.5 μIU/mL in the T-LT4 group was 19%, and of 9% in the L-LT4 group (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH > 3.5 μIU/mL in the T-LT4 group was 18%, and of 5% in the L-LT4 group (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit. These data highlight a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up, by using a liquid L-T4 formulation therapy with respect to a tablet L-T4. Presentation: 6/3/2024

Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) may induce hepatitis B virus (HBV) reactivations in co-infected patients, whose dynamics and outcomes could depend on the phase of HBV infection. We investigated HBsAg and HBV-DNA kinetics in fifteen untreated HBeAg Negative Infection (ENI) (4F-11M, 62.1y) and eight Nucleos(t)ide Analogs (NAs) treated Chronic Hepatitis B (CHB) (3F-6M, 54.8y) with HCV co-infection, receiving DAAs-regimens including Sofosbuvir (13) or not (10). All achieved a sustained virologic response (SVR) and normalized alanine-aminotransferase (ALT). At the direct acting antivirals’ (DAAs) baseline (BL), the HBV-DNA was undetectable (<6 IU/mL) in eight ENI and all CHB, the mean Log-HBsAg was lower in ENI than CHB (0.88 vs. 2.42, p = 0.035). During DAAs, HBV-DNA increased in untreated ENI by >1 Log in five and became detectable in two. Accordingly, mean BL Log-HBV-DNA (0.89) increased at week-4 (1.78; p = 0.100) and at the end of therapy (1.57; p = 0.104). Mean Log-HBsAg decreased at week-4 in ENI (from 0.88 to 0.55; p = 0.020) and CHB (from 2.42 to 2.15; p = 0.015). After DAAs, the HBsAg returned to pre-treatment levels in CHB, but not in ENI (six cleared HBsAg). Female gender and SOF were associated with a greater HBsAg decline. In conclusion, HBV reactivations during DAAs in HCV co-infected ENI caused moderate increases of HBV-DNA without ALT elevations. The concomitant HBsAg decline, although significant, did not modify individual pre-treatment profiles.

This trial compared surgery with physical therapy (followed by surgery as needed) in patients with a meniscal tear and mild-to-moderate knee osteoarthritis. Functional outcomes and pain were similar in the two groups at 6 months; 30% of the PT group crossed over to surgery. Symptomatic, radiographically confirmed osteoarthritis of the knee affects more than 9 million people in the United States. 1 Meniscal tears are also highly prevalent, with imaging evidence of a meniscal tear observed in 35% of persons older than 50 years of age; two thirds of these tears are asymptomatic. 2 Meniscal damage is especially prevalent among persons with osteoarthritis 3 , 4 and is frequently treated surgically with arthroscopic partial meniscectomy. This procedure, in which the surgeon trims the torn meniscus back to a stable rim, is performed for a range of indications in more than 465,000 persons annually in the United States. 5 The . . .

The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV. In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity. Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed. MTX may be effective and safe for remission-maintenance in AAV. clinicaltrials.gov NCT00751517.

Myocarditis Disease Unit (MDU) is a functional multidisciplinary network designed to offer multidisciplinary assistance to patients with myocarditis. More than 300 patients coming from the whole Country are currently followed up at a specialized multidisciplinary outpatient clinic. Following the pandemic outbreak of the SARS-CoV-2 infection in Italy, we present how the MDU rapidly evolved to a “tele-MDU”, via a dedicated multitasking digital health platform. [Display omitted]

A large multicentric cohort study showed that adding plasma donor-derived cell-free DNA (dd-cfDNA) to a standard of care prediction model improves discrimination for acute rejection in kidney transplant recipients (KTRs) [4]. [...]interest in alternative biomarkers of TCMR, including urinary chemokines CXCL9 and CXCL10, is growing [5, 8, 9]. [...]the predictive performance of the model might deteriorate upon validation in external and completely independent cohorts that use different labs. Herein, we aimed to externally validate the model in a consecutive series of KTRs who underwent a for-cause or surveillance kidney biopsy at the University Hospital of Parma, Parma, Italy. [...]discriminatory capacity was identical to that estimated in the original cohorts (AUC of the ROC curve 81.2% [95 percent confidence interval: 69.1 to 93.2] vs. 81.3% of the original study). [...]our findings on an independent cohort of patients support the utility of this model for identifying patients at low risk of AR in whom biopsy can be safely avoided.

Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis. Once in axonal endosomes, active NOX2 is retrogradely transported to the cell body through an importin-β1–dynein-dependent mechanism. Endosomal NOX2 oxidizes PTEN, which leads to its inactivation, thus stimulating PI3K–phosporylated (p-)Akt signalling and regenerative outgrowth. Challenging the view that ROS are exclusively involved in nerve degeneration, we propose a previously unrecognized role of ROS in mammalian axonal regeneration through a NOX2–PI3K–p-Akt signalling pathway. Hervera et al. show that extracellular vesicles containing NOX2 complexes are released from macrophages and incorporated into injured axons, leading to axonal regeneration through PI3K–p-Akt signalling.

We aimed to assess the role of computerized tomography attenuation values (Hounsfield unit—HU) for differentiating pyonephrosis from hydronephrosis and for predicting postoperative infectious complications in patients with obstructive uropathy. We analysed data from 122 patients who underwent nephrostomy tube or ureteral catheter placement for obstructive uropathy. A radiologist drew the region of interest for quantitative measurement of the HU values in the hydronephrotic region of the affected kidney. Descriptive statistics and logistic regression models tested the predictive value of HU determination in differentiating pyonephrosis from hydronephrosis and in predicting postoperative sepsis. A HU cut-off value of 6.3 could diagnose the presence of pyonephrosis with 71.6% sensitivity and 71.5% specificity (AUC 0.76; 95%CI: 0.66–0.85). At multivariable logistic regression analysis HU ≥ 6.3 ( p  ≤ 0.001) was independently associated with pyonephrosis. Patients who developed sepsis had higher HU values ( p  ≤ 0.001) than those without sepsis. A HU cut-off value of 7.3 could diagnose the presence of sepsis with 76.5% sensitivity and 74.3% specificity (AUC 0.79; 95%CI: 0.71–0.90). At multivariable logistic regression analysis, HU ≥ 7.3 ( p  ≤ 0.001) was independently associated with sepsis, after accounting for clinical and laboratory parameters. Measuring HU values of the fluid of the dilated collecting system may be useful to differentiate pyonephrosis from hydronephrosis and to predict septic complications in patients with obstructive uropathy.

Background The 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease. Methods During an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021. Results Ninety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach. Conclusions Our study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency. High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic. Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas.