Chronic kidney disease (CKD) is a clinical condition characterized by the loss of kidney function over time, as well as several complications affecting gastrointestinal, cardiovascular, and ...musculoskeletal systems. Physical exercise seems to induce positive adaptations in CKD patients, without side effects. Usually, these patients show a reduced physical activity and physical performance. The aim of this case-report was to evaluate the effects of an online training protocol on functional capacity and on muscle mass, in CKD stage III patients. Methods: Two CKD (stage III according to KDIGO guidelines) participants (1 female, Patient A; 1 male, Patient B) were enrolled and they performed an online tailored-supervised combined training lasting 12 weeks, including multi-joint strength exercises using TheraBand and an aerobic session at 65-70% of the patients' heart rate reserve. Results: Both patients showed an improving trend on functional capacity (6 min walking test: Patient A = +3%; Patient B = +5.3%) and on strength of the upper arms (handgrip strength test-right: Patient A = +13.4%; Patient B = +19.1%; handgrip strength test-left: Patient A = +42.8%; Patient B= +12.9%), as well as a reduction in inflammation and oxidative stress biomarkers. The protocol was feasible, and no side effects were evidenced. These case studies suggest that the online combined training can produce beneficial effects in CKD patients under conservative therapy, by reducing the CKD-related complications and improving the adherence to exercise of this population of patients, overcoming logistic barriers such as transportation, availability of facilities, and working and personal-life schedule.
Liver injury in COVID-19 patients has progressively emerged, even in those without a history of liver disease, yet the mechanism of liver pathogenicity is still controversial. COVID-19 is frequently ...associated with increased serum ferritin levels, and hyperferritinemia was shown to correlate with illness severity. The liver is the major site for iron storage, and conditions of iron overload have been established to have a pathogenic role in development of liver diseases. We presented here six patients who developed severe COVID-19, with biochemical evidence of liver failure. Three cases were survived patients, who underwent liver biopsy; the other three were deceased patients, who were autopsied. None of the patients suffered underlying liver pathologies. Histopathological and ultrastructural analyses were performed. The most striking finding we demonstrated in all patients was iron accumulation into hepatocytes, associated with degenerative changes. Abundant ferritin particles were found enclosed in siderosomes, and large aggregates of hemosiderin were found, often in close contact with damaged mitochondria. Iron-caused oxidative stress may be responsible for mitochondria metabolic dysfunction. In agreement with this, association between mitochondria and lipid droplets was also found. Overall, our data suggest that hepatic iron overload could be the pathogenic trigger of liver injury associated to COVID-19.
Abstract
Background
Even with contemporary treatment strategies, more than 10% of HER2-positive early stage breast cancer patients may experience distant metastasis as first event during follow-up. ...Tools for predicting unique patterns of metastatic spread are needed to plan personalized surveillance. We evaluated how molecular heterogeneity affects the pattern of distant relapse in HER2-positive breast cancer.
Methods
A total of 677 HER2-positive stage I-III breast cancer patients from ShortHER trial, Cher-LOB trial, and 2 institutional cohorts were included. PAM50 molecular subtypes and research-based HER2DX scores were evaluated. The cumulative incidence of distant relapse as the first event (any site and site specific) was evaluated using competing risk analysis. Median follow-up was 8.4 years. Tests of statistical significance are 2-sided.
Results
Stage III and high HER2DX risk score identified patients at the highest risk of distant relapse as first event (10-year incidence 24.5% and 19.7%, respectively). Intrinsic molecular subtypes were associated with specific patterns of metastatic spread: compared with other subtypes, HER2-enriched tumors were more prone to develop brain metastases (10-year incidence 3.8% vs 0.6%, P = .005), basal-like tumors were associated with an increased risk of lung metastases (10-year incidence 11.1% vs 2.6%, P = .001), and luminal tumors developed more frequently bone-only metastases (10-year incidence 5.1% vs 2.0%, P = .042). When added to stage or HER2DX risk score in competing risk regression models, intrinsic subtype maintained an independent association with site-specific metastases.
Conclusions
The integration of intrinsic molecular subtypes with stage or HER2DX risk score predicts site-specific metastatic risk in HER2-positive breast cancer, with potential implications for personalized surveillance and clinical trials aimed at preventing site-specific recurrence.
Cardiovascular malformations (CVM) represent the most common structural anomalies, occurring in 0.7% of live births. The CVM prenatal suspicion should prompt an accurate investigation with fetal ...echocardiography and the assessment through genetic counseling and testing. In particular, chromosomal microarray analysis (CMA) allows the identification of copy number variations. We performed a systematic review and meta-analysis of the literature, studying the incremental diagnostic yield of CMA in fetal isolated CVM, scoring yields for each category of heart disease, with the aim of guiding genetic counseling and prenatal management. At the same time, we report 59 fetuses with isolated CVM with normal karyotype who underwent CMA. The incremental CMA diagnostic yield in fetuses with isolated CVM was 5.79% (CI 5.54–6.04), with conotruncal malformations showing the higher detection rate (15.93%). The yields for ventricular septal defects and aberrant right subclavian artery were the lowest (2.64% and 0.66%). Other CVM ranged from 4.42% to 6.67%. In the retrospective cohort, the diagnostic yield was consistent with literature data, with an overall CMA diagnostic yield of 3.38%. CMA in the prenatal setting was confirmed as a valuable tool for investigating the causes of fetal cardiovascular malformations.
Surgical site infections (SSIs) represent a potential complication in surgical procedures, mainly because clean/contaminated surgery involves organs that are normally colonized by bacteria. Dental, ...maxillo-facial and ear-nose-throat (ENT) surgeries are among those that carry a risk of SSIs because the mouth and the first respiratory tracts are normally colonized by a bacterial flora. The aim of this consensus document was to provide clinicians with recommendations on surgical antimicrobial prophylaxis in neonates (<28 days of chronological age) and pediatric patients (within the age range of 29 days−18 years) undergoing dental, maxillo-facial or ENT surgical procedures. These included: (1) dental surgery; (2) maxilla-facial surgery following trauma with fracture; (3) temporo-mandibular surgery; (4) cleft palate and cleft lip repair; (5) ear surgery; (6) endoscopic paranasal cavity surgery and septoplasty; (7) clean head and neck surgery; (8) clean/contaminated head and neck surgery and (9) tonsillectomy and adenoidectomy. Due to the lack of pediatric data for the majority of dental, maxillo-facial and ENT surgeries and the fact that the recommendations for adults are currently used, there is a need for ad hoc studies to be rapidly planned for the most deficient areas. This seems even more urgent for interventions such as those involving the first airways since the different composition of the respiratory microbiota in children compared to adults implies the possibility that surgical antibiotic prophylaxis schemes that are ideal for adults may not be equally effective in children.
Pediatric neurosurgery is a highly specialized branch of surgery in which surgical site infections (SSIs) are potentially serious complications that can also adversely affect a good surgical outcome, ...compromising functional recovery and, in some cases, even putting the patient’s life at risk. The main aim of this consensus document is to provide clinicians with a series of recommendations on antimicrobial prophylaxis for neonates and children undergoing neurosurgery. The following scenarios were considered: (1) craniotomy or cranial/cranio-facial approach to craniosynostosis; (2) neurosurgery with a trans-nasal-trans-sphenoidal approach; (3) non-penetrating head injuries; (4) penetrating head fracture; (5) spinal surgery (extradural and intradural); (6) shunt surgery or neuroendoscopy; (7) neuroendovascular procedures. Patients undergoing neurosurgery often undergo peri-operative antibiotic prophylaxis, with different schedules, not always supported by scientific evidence. This consensus provides clear and shared indications, based on the most updated literature. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies, and represents, in our opinion, the most complete and up-to-date collection of recommendations on the behavior to be held in the peri-operative setting in this type of intervention, in order to guide physicians in the management of the patient, standardize approaches and avoid abuse and misuse of antibiotics.
Lessons Learned
The androgen receptor (AR) is present in most breast cancers (BC), but its exploitation as a therapeutic target has been limited.
This study explored the activity of ...dehydroepiandrosterone (DHEA), a precursor being transformed into androgens within BC cells, in combination with an aromatase inhibitor (to block DHEA conversion into estrogens), in a two‐stage phase II study in patients with AR‐positive/estrogen receptor‐positive/human epidermal growth receptor 2‐negative metastatic BC.
Although well tolerated, only 1 of 12 patients obtained a prolonged clinical benefit, and the study was closed after its first stage for poor activity.
Background
Androgen receptors (AR) are expressed in most breast cancers, and AR‐agonists have some activity in these neoplasms. We investigated the safety and activity of the androgen precursor dehydroepiandrosterone (DHEA) in combination with an aromatase inhibitor (AI) in patients with AR‐positive metastatic breast cancer (MBC).
Methods
A two‐stage phase II study was conducted in two patient cohorts, one with estrogen receptor (ER)‐positive (resistant to AIs) and the other with triple‐negative MBC. DHEA 100 mg/day was administered orally. The combination with an AI aimed to prevent the conversion of DHEA into estrogens. The main endpoint was the clinical benefit rate. The triple‐negative cohort was closed early.
Results
Twelve patients with ER‐positive MBC were enrolled. DHEA‐related adverse events, reported in four patients, included grade 2 fatigue, erythema, and transaminitis, and grade 1 drowsiness and musculoskeletal pain. Clinical benefit was observed in one patient with ER‐positive disease whose tumor had AR gene amplification. There was wide inter‐ and intra‐patient variation in serum levels of DHEA and its metabolites.
Conclusion
DHEA showed excellent safety but poor activity in MBC. Although dose and patient selection could be improved, high serum level variability may hamper further DHEA development in this setting.
经验获取
• 虽然雄激素受体 (AR) 存在于大多数乳腺癌 (BC) 中，但是，人们将其作为治疗靶点进行的开发利用十分有限。
• 本研究探索了脱氢表雄酮(DHEA，一种可在 BC 细胞中转化为雄激素的前体)与芳香化酶抑制剂(可阻止 DHEA 转化为雌激素)在两阶段 II 期研究中联合治疗 AR‐阳性/雌激素受体‐阳性/人类表皮生长受体 2‐阴性的转移性 BC 患者的活性。
• 虽然耐受性良好，但是，在 12 名患者中仅有 1 名患者维持了长时间的临床获益，而且，研究在第一阶段之后因活性较差而关闭。
摘要
背景。雄激素受体 (AR) 存在于大多数乳腺癌中，AR‐激动剂在此类肿瘤中具有一些活性。我们研究了雄激素前体脱氢表雄酮 (DHEA) 和芳香化酶抑制剂 (AI) 联合治疗 AR‐阳性转移性乳腺癌 (MBC) 患者的安全性和活性。
方法。我们在两个患者队列中执行了一项两阶段 II 期研究，一个队列中的患者为雌激素受体 (ER)‐阳性(对 AI 耐药)，另一个队列中的患者为三阴性 MBC。按照 100 mg/天的剂量口服 DHEA。AI 联合治疗旨在防止 DHEA 转化为雌激素。主要终点为临床获益率。三阴性队列提前关闭。
结果。12 名 ER‐阳性 MBC 患者加入研究。4 名患者报告与 DHEA 相关的不良反应，包括 2 级疲劳、红斑和转氨酶升高以及 1 级困倦和肌肉骨骼痛。在 1 名 ER‐阳性疾病患者中观察到临床获益，该患者的肿瘤出现 AR 基因扩增。DHEA 及其代谢物的血清水平在患者之间和患者内部的变化较大。
结论。虽然 DHEA 显示出良好的安全性，但是，它在 MBC 中的活性较差。尽管可以改进剂量和患者的选择，但是，血清水平变化性高可能会妨碍 DHEA 在这种设定中的进一步开发。
Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most ...cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.
A 50 l Cygno prototype overground characterization Amaro, Fernando Domingues; Antonietti, Rita; Baracchini, Elisabetta ...
The European physical journal. C, Particles and fields,
10/2023, Volume:
83, Issue:
10
Journal Article
Peer reviewed
Open access
The nature of dark matter is still unknown and an experimental program to look for dark matter particles in our Galaxy should extend its sensitivity to light particles in the GeV mass range and ...exploit the directional information of the DM particle motion (Vahsen et al. in CYGNUS: feasibility of a nuclear recoil observatory with directional sensitivity to dark matter and neutrinos,
arXiv:2008.12587
, 2020). The
Cygno
project is studying a gaseous time projection chamber operated at atmospheric pressure with a Gas Electron Multiplier (Sauli in Nucl Instrum Meth A 386:531,
https://doi.org/10.1016/S0168-9002(96)01172-2
, 1997) amplification and with an optical readout as a promising technology for light dark matter and directional searches. In this paper we describe the operation of a 50 l prototype named LIME (Long Imaging ModulE) in an overground location at Laboratori Nazionali di Frascati (LNF) of INFN. This prototype employs the technology under study for the 1 cubic meter
Cygno
demonstrator to be installed at the Laboratori Nazionali del Gran Sasso (LNGS) (Amaro et al. in Instruments 2022, 6(1),
https://www.mdpi.com/2410-390X/6/1/6
, 2022). We report the characterization of LIME with photon sources in the energy range from few keV to several tens of keV to understand the performance of the energy reconstruction of the emitted electron. We achieved a low energy threshold of few keV and an energy resolution over the whole energy range of 10–20%, while operating the detector for several weeks continuously with very high operational efficiency. The energy spectrum of the reconstructed electrons is then reported and will be the basis to identify radio-contaminants of the LIME materials to be removed for future
Cygno
detectors.
The CYGNO experiment, a directional detector for direct Dark Matter searches Amaro, Fernando Domingues; Baracchini, Elisabetta; Benussi, Luigi ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
September 2023, 2023-09-00, Volume:
1054
Journal Article
Peer reviewed
Open access
The CYGNO project aims at the development of a high precision optical readout gaseous Tima Projection Chamber (TPC) for directional dark matter (DM) searches, to be hosted at Laboratori Nazionali del ...Gran Sasso (LNGS). CYGNO employs a He:CF4 gas mixture at atmospheric pressure with a Gas Electron Multiplier (GEM) based amplification structure coupled to an optical readout comprised of sCMOS cameras and photomultiplier tubes (PMTs). This experimental setup allows to achieve 3D tracking and background rejection down to O(1) keV energy, to boost sensitivity to low WIMP masses. The characteristics of the optical readout approach in terms of the light yield will be illustrated along with the particle identification properties. The project timeline foresees, in the next 2–3 years, the realisation and installation of a 0.4 m3 TPC in the underground laboratories at LNGS to act as a demonstrator. Finally, the studies of the expected DM sensitivities of the CYGNO demonstrator will be presented.
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