Non-palpable breast lesions localization techniques - A new priority: Results of a Senonetwork survey among breast centers in Italy.

INTRODUCTION: Non palpable breast tumors are increasingly diagnosed because of screening programs, and their localization during surgery is essential to ensure an adequate resection. Little is known regarding which techniques are used in "real world". MATERIALS AND METHODS: A national web-based survey, with a 21-items questionnaire, was conducted among Breast Centers (BCs) in Italy in 2023. RESULTS: Among 153 BCs, 110 (72 %) participated. Wire-guided localization was reported to be the most used technique, regardless of the volume of malignant tumors treated by each Center (N = 36, 33 %). However, newer techniques such as Radioactive occult lesion localization and magnetic seeds, were reported to be employed in 34 (31 %) BCs, and more often among high-volume BCs (>300 cases/year) (N = 32, 29 % vs. N = 13, 12 %; p = 0.02). Logistic problems of localization were reported to cause delays to the scheduled surgery at least once or in multiple occasions in 26 (24 %) and in 4 (3.5 %) BCs, respectively. Although the majority of BCs declared they were satisfied (N = 48, 44 %) or somewhat satisfied (N = 41, 37 %) with the procedure used in their center, responders stated that they would change their technique, or that they were strongly considering this possibility in 24 (22 %) and in 38 (35 %) cases, respectively. The main barrier to introducing a new technique was associated with procedure costs (90 BCs, 82 %). CONCLUSIONS: There are several critical issues regarding localization techniques at a national level. This should be recognized as a priority because of its impact on both patients and clinical practices.

2-pentadecyl-2-oxazoline prevents cognitive and social behaviour impairments in the Amyloid ß-induced Alzheimer-like mice model: Bring the α2 adrenergic receptor back into play.

The 2-pentadecyl-2-oxazoline (PEA-OXA) is a natural compound with protective action in neuro-inflammation. We have previously shown that PEA-OXA behaves as an α2 adrenergic receptor (α2AR) antagonist and a putative protean agonist on histamine H3 receptors. Recently, neuroinflammation and monoaminergic neurotransmission dysfunction has drawn particular attention in Alzheimer Disease (AD) pathophysiology. In this context, the objective of this study was to investigate the effects of the dual-acting PEA-OXA in an AD-like model in mice. A combined computational and experimental approach was used to evaluate the ability of PEA-OXA to bind α2A-AR subtype, and to investigate the effects of PEA-OXA treatment on neuropathological (behavioural and functional) effects induced by soluble Amyloid ß 1-42 (sAß1-42) intracerebroventricular injection. Computational analysis revealed the PEA-OXA ability to bind the α2A-AR, a pharmacological target for AD, in two alternative poses, one overlapping the Na+ binding site. In vivo studies indicated that chronic treatment with PEA-OXA (10 mg/kg, os) restored the cognitive (discriminative and spatial memory) deficits and social impairments induced by sAß injection. Consistently, electrophysiological analysis showed a recovery of the long-term potentiation in the hippocampus (Lateral Entorhinal Cortex-Dentate Gyrus pathway), while neuroinflammation, i.e., increased pro-inflammatory cytokines levels and microglia cells density were reduced. These data provide the basis for further investigation of the pro-cognitive aptitude of PEA-OXA by proposing it as an adjuvant in the treatment in AD, for which the available pharmacological approaches remain unsatisfactory. Moreover, this study offers new future direction in research investigating the role of α2AR in neuropsychiatric illness and therapies.

An overview of COVID-19 related to fungal infections: what do we know after the first year of pandemic?

In 2019, severe acute respiratory syndrome caused by CoV-2 virus became a pandemic worldwide, being the fast spread of the disease due to the movement of infected people from one country to another, from one continent to another, or within the same country. Associated comorbidities are important factors that predispose to any fungal coinfections. Because of the importance of fungal infections in COVID-19 patients, the aim of this work was to collect data of the more encountered mycoses related to patients undergoing this disease. Aspergillosis was the first COVID-19-related fungal infection reported, being A. fumigatus the most frequent species for CAPA. Other fungal infections related include mainly candidiasis and mucormycosis, being Rhizopus spp. the more prevalent species found. Influenza-associated pulmonary aspergillosis is well documented; thus, similar complications are expected in severe forms of COVID-19 pneumonia. Therefore, in patients with COVID-19, it is important to take special attention to the surveillance and suspicion of fungal coinfections that might worsen the patient's prognosis.

Chest radiography predictor of COVID-19 adverse outcomes. A lesson learnt from the first wave.

AIM: To assess the role of a severity score based on chest radiography (CXR) in predicting the risk of adverse outcomes in coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Of the patients who presented to L. Sacco Hospital (Milan, Italy) between 21 February and 31 March 2020, patients with a laboratory confirmation of COVID-19 who also underwent a CXR were included in the study. To quantify the extent of lung involvement, each CXR image was given a score (Milan score), ranging from 0 to 24, depending on the presence of reticular pattern and/or ground-glass opacities and/or extensive consolidations in each of the 12 areas in which the lungs were divided. The score was calculated by an expert radiologist, blinded to laboratory tests. The ability of the Milan score to predict hospital admission and mortality, after adjusting for some variables (age; gender; comorbidities; time between symptoms onset and admission), using univariate and multivariate statistical analysis was investigated retrospectively. RESULTS: Among the 554 patients, 115 of which (21%) had a negative CXR, the in-hospital mortality was 16% (90/554). At univariate analysis, age, gender, and comorbidities were significant predictors of mortality and hospital admission. At multivariate analysis, adjusting for age and gender, the Milan score was an independent predictor of mortality and hospitalisation. In particular, patients with a Milan score ≥ 9 had a mortality risk five-times higher than those with a lower score. Other independent predictors of mortality were gender and age. CONCLUSIONS: The CXR Milan score was an independent predictive factor of both in-hospital mortality and hospital admission.

ANOVA-Simultaneous Component analysis modelling of low-level-fused spectroscopic data: A food chemistry case-study.

Ripening is a crucial step to guarantee the high commercial value of cheddar cheese, one of the dairy products the European Union exports the most. Although several methods have lately been proposed to assess its ageing process from a chemical point of view, the majority of them is not particularly time-efficient and implies destructive analytical tests, thus, exhibiting limitations for, e.g., industrial applications. Here, a fast approach based on combining Raman and Mid-InfraRed (MIR) spectroscopy with ANOVA-Simultaneous Component Analysis (ASCA) is proposed in a low-level data fusion framework. This approach allowed to evaluate how storage temperature and time (as well as their interaction) influence cheddar ripening in a relatively cheap, rapid and green fashion.

Combination of Amphotericin B and Terbinafine against Melanized Fungi Associated with Chromoblastomycosis.

Our in vitro studies showed that a combination of amphotericin B and terbinafine had synergistic effects against the majority of melanized fungi associated with chromoblastomycosis (CBM) and similar infections, including those with Cladophialophora carrionii, Cladophialophora arxii, Exophialadermatitidis, Exophialaspinifera, Fonsecaea monophora, Fonsecaea nubica, Fonsecaea pedrosoi, and Phialophora verrucosa. This drug combination could provide an option for the treatment of severe or unresponsive cases of CBM, particularly in cases due to species of Fonsecaea and Cladophialophora.

MR Micro-Neurography and a Segmentation Protocol Applied to Diabetic Neuropathy.

The aim of this study was to assess with MRI morphometric ultrastructural changes in nerves affected by diabetic peripheral neuropathy (DPN). We used an MR micro-neurography imaging protocol and a semiautomated technique of tissue segmentation to visualize and measure the volume of internal nerve components, such as the epineurium and nerve fascicles. The tibial nerves of 16 patients affected by DPN and of 15 healthy volunteers were imaged. Nerves volume (NV), fascicles volume (FV), fascicles to nerve ratio (FNR), and nerves cross-sectional areas (CSA) were obtained. In patients with DPN the NV was increased and the FNR was decreased, as a result of an increase of the epineurium (FNR in diabetic neuropathy 0,665; in controls 0,699, p = 0,040). CSA was increased in subjects with DPN (12,84 mm2 versus 10,22 mm2, p = 0,003). The FV was increased in patients with moderate to severe DPN. We have demonstrated structural changes occurring in nerves affected by DPN, which otherwise are assessable only with an invasive biopsy. MR micro-neurography appears to be suitable for the study of microscopic changes in tibial nerves of diabetic patients.

Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis.

Primary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungiCladophialophora bantiana,Rhinocladiella mackenziei, andExophiala dermatitidis.Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Ourin vitrostudies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the orderChaetothyriales Furtherin vivostudies and clinical investigations to elucidate and confirm these observations are warranted.

Spectroelectrochemistry of Fe(III)- and Co(III)-mimochrome VI artificial enzymes immobilized on mesoporous ITO electrodes.

UV-visible absorption spectroelectrochemistry elucidated the different redox behaviours of Fe(III)- and Co(III)-mimochrome VI artificial enzymes, adsorbed on mesoporous conductive films of ITO. The reduction of the ferric complex was rapid and reversible, while the cobaltic complex exhibited irreversible processes probably related to multiple coordination states.

Effect of immunosuppressive therapy on patients with inflammatory bowel diseases and hepatitis B or C virus infection.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

Lipid fingerprints of intact viruses by MALDI-TOF/mass spectrometry.

A number of viruses contain lipid membranes, which are in close contact with capsid proteins and/or nucleic acids and have an important role in the viral infection process. In this study membrane lipids of intact viruses have been analysed by MALDI-TOF/MS with a novel methodology avoiding lipid extraction and separation steps. To validate the novel method, a wide screening of viral lipids has been performed analysing highly purified intact bacterial and archaeal viruses displaying different virion architectures. Lipid profiles reported here contain all lipids previously detected by mass spectrometry analyses of virus lipid extracts. Novel details on the membrane lipid composition of selected viruses have also been obtained. In addition we show that this technique allows the study of lipid distribution easily in subviral particles during virus fractionation. The possibility to reliably analyse minute amounts of intact viruses by mass spectrometry opens new perspectives in analytical and functional lipid studies on a wider range of viruses including pathogenic human ones, which are difficult to purify in large amounts.

La coccidioidomicosis en Argentina, 1892-2009 / Coccidioidomycosis in Argentina, 1892-2009

Los casos clínicos de coccidioidomicosis en Argentina son pocos y han tenido lugar fundamentalmente en la extensa región árida precordillerana. Este trabajo tiene como objetivos realizar una revisión retrospectiva del total de casos de coccidioidomicosis documentados en Argentina desde el año 1892 hasta 2009 y describir una serie de casos ocurridos en los últimos 4 años. En 117 años se documentaron 128 casos. Desde la primera descripción de la enfermedad en 1892 hasta 1939 se registraron 6 casos; desde 1940 hasta 1999, 59 casos (6-14 casos cada 10 años); y los 63 casos restantes (49% del total histórico) se produjeron en el último decenio. La mediana de edad de los 34 pacientes registrados en el período 2006-2009 fue de 31 años (rango: 7-89), la relación hombre:mujer fue 1,3:1; 12 de estos individuos eran inmunocomprometidos. Veintiséis casos se confirmaron por examen microscópico, por cultivo o por ambos procedimientos; los casos restantes se confirmaron por serología. Todos los aislamientos recuperados fueron identificados como Coccidioides posadasii. Treinta pacientes residían en una amplia área geográfica con epicentro en el valle de Catamarca. Entre 2006 y 2009, la tasa de incidencia en la provincia de Catamarca se incrementó desde valores históricos inferiores a 0,5 casos cada 100 000 habitantes hasta 2,0 casos cada 100 000 habitantes. Este aumento sugiere una emergencia de la coccidioidomicosis en el área.

Clinical cases of coccidioidomycosis are rare in Argentina and are generally found in the large arid precordilleran area of the country. This study aims to perform a retrospective review of all coccidioidomycosis cases documented in the country from 1892 to 2009, and to describe those occurring in the last 4 years. One hundred and twenty eight cases were documented in the 117 year-period. Since the original description of the disease in 1892 until 1939, only 6 cases were registered; between 1940 and 1999, 59 (6-14/10 yrs) and the remaining 63 (49% of total cases) occurred in the last decade. The median age of 34 patients registered in 2006-2009 was 31 years (range: 7-89), male/female ratio was 1.3:1 and 12 patients were immunocompromised. Twenty-six cases were confirmed by direct microscopy and/or culture whereas the remaining ones by serology. All isolates were identified as Coccidioides posadasii. Thirty patients lived in a vast geographic region with epicenter in Catamarca Valley. Between 2006 and 2009, annual disease incidence rates in Catamarca Province increased from historical values below 0.5/100,000 to 2/100,000 inhabitants. Such increase suggests an emergency of coccidioidomycosis in that region.

New trends in bio/nanotechnology: stable proteins as advanced molecular tools for health and environment.

In this work the thermophilic trehalose/maltose-binding protein from Thermococcus litoralis is presented as a probe for the design of a high stable fluorescence biosensor for glucose. In particular, we show the possibility of modulating the protein specificity by changing temperature. In addition to glucose sensing, we also report on the possibility of utilizing odorant-binding proteins as a probe for the development of optical sensors for analytes of environmental interests.

[Coccidioidomycosis in Argentina, 1892-2009]. / La coccidioidomicosis en Argentina, 1892-2009.

Clinical cases of coccidioidomycosis are rare in Argentina and are generally found in the large arid precordilleran area of the country. This study aims to perform a retrospective review of all coccidioidomycosis cases documented in the country from 1892 to 2009, and to describe those occurring in the last 4 years. One hundred and twenty eight cases were documented in the 117 year-period. Since the original description of the disease in 1892 until 1939, only 6 cases were registered; between 1940 and 1999, 59 (6-14/10 yrs) and the remaining 63 (49% of total cases) occurred in the last decade. The median age of 34 patients registered in 2006-2009 was 31 years (range: 7-89), male/female ratio was 1.3:1 and 12 patients were immunocompromised. Twenty-six cases were confirmed by direct microscopy and/or culture whereas the remaining ones by serology. All isolates were identified as Coccidioides posadasii. Thirty patients lived in a vast geographic region with epicenter in Catamarca Valley. Between 2006 and 2009, annual disease incidence rates in Catamarca Province increased from historical values below 0.5/100,000 to 2/100,000 inhabitants. Such increase suggests an emergency of coccidioidomycosis in that region.

In vitro activity of antifungal drugs against Cladophialophora species associated with human chromoblastomycosis.

The antifungal activity of six drugs was evaluated against 41 clinical and environmental isolates of Cladophialophora carrionii and its sister species C. yegresii. Drugs tested, including their ranges, were: 16-0.016 microg/ml for amphotericin B (AMB), itraconazole (ITZ) and voriconazole (VCZ), 8-0.008 microg/ml for terbinafine (TBF), and 64-0.063 microg/ml for flucytosin (5-FC) and fluconazole (FCZ). Strains were tested according to the CLSI guidelines (M38A). The MIC Gmeans for clinical strains in microg/ml were; 0.02 for TBF and ITZ, 0.07 microg/ml for VCZ, 0.49 for 5FC, 6.14 for FCZ and 9.42 for AMB. The MFC Gmeans in microg/ml were; 0.04 for TBF, 0.13 for ITZ, 0.72 for VCZ, 18.83 for 5FC, 36.16 for FCZ and 31.35 for AMB. The most active drugs against the fungi were TBF, ITZ, VCZ and 5FC. However, for all drugs more than two dilution steps were noted between the MIC and the MFC, indicating fungistatic activity. Despite in vitro susceptibility of C. carrionii to antifungal agents, the efficacy of therapy was shown to be not optimal.

Tinea nigra palmaris: presentación de un caso clínico en la República Argentina

Se presenta el caso clínico de una paciente que consultó por una mancha oscura en la palma izquierda. El examen micológico permitió determinar que la infección había sido producida por un hongo pigmentado, Hortaea werneckii, agente etiológico de la tinea nigra palmaris. Esta es una infección benigna que puede ser rápidamente diagnosticada y tiene tratamiento eficaz. La paciente fue tratada con econazol durante un mes, con remisión completa de las lesiones. Frente a la sospecha de una infección fúngica por la presencia de manchas de color pardo es muy importante practicar el estudio micológico, ya que mediante una técnica no invasora es posible establecer un diagnóstico diferencial y descartar fácilmente otras patologías más graves con las que puede confundirse en el examen clínico.

A clinical case of a female patient with a black spot on the palm of her left hand is presented. The infection was due to a black fungus identified as Hortaea werneckii, the aetiological agent of tinea nigra palmaris. This infection can be easily diagnosed and it is important to establish the differential diagnosis from other skin pathologies. Normally, the treatment has a successful outcome. In this case, the patient was treated with econazole locally applied during one month, with complete remission of the lesions. In conclusion, the early diagnosis of this disease is very important since the mycology procedures are fast and non-invasive and cure is obtained with local treatment.

[Tinea nigra palmaris: a clinical case in Argentina]. / Tinea nigra palmaris: presentacion de un caso clínico en la República Argentina.

A clinical case of a female patient with a black spot on the palm of her left hand is presented. The infection was due to a black fungus identified as Hortaea werneckii, the aetiological agent of tinea nigra palmaris. This infection can be easily diagnosed and it is important to establish the differential diagnosis from other skin pathologies. Normally, the treatment has a successful outcome. In this case, the patient was treated with econazole locally applied during one month, with complete remission of the lesions. In conclusion, the early diagnosis of this disease is very important since the mycology procedures are fast and non-invasive and cure is obtained with local treatment.

Effects of aging and anti-aging caloric restrictions on carbonyl and heat shock protein levels and expression.

Heat shock proteins (Hsps) are induced by stressful stimuli and have been shown to protect cells and organs from such stresses both in vitro and in vivo, and play a positive role in lifespan determination. An attenuated response to stress is characteristic of senescence and no Hsp induction is observed upon exposure to stress and no protective effect of a mild stress is observed in cells from aged individuals. The artificial over-expression of Hsps, can produce a protective effect against a variety of damaging stimuli in cells from aged rats or aged humans, in whom cardiovascular disease is a major cause of morbidity in older age. Here, we show that aging significantly decreases the levels of Hsp27, Hsp60, Hsp72 and Hsc70 in right atrium and left ventricle of the rat heart, both at level of protein and of mRNA. Two different caloric restriction regimens have been found to counteract in part the decrease in the levels of Hsp expression in the aged heart tissue as well as the tendency to an increase of the levels of carbonyl in cardiac proteins. Our data suggest that cardiac Hsp levels may be a determinant of longevity in rodents, and that generation of new regimens of caloric restriction may eventually show how to improve modulation of cardiac aging.

Design of a safer approach to intravenous drug infusions: failure mode effects analysis.

OBJECTIVES: A set of standard processes was developed for delivering continuous drug infusions in order to improve (1) patient safety; (2) efficiency in staff workflow; (3) hemodynamic stability during infusion changes, and (4) efficient use of resources. Failure modes effects analysis (FMEA) was used to examine the impact of process changes on the reliability of delivering drug infusions. SETTING: An 11 bed multidisciplinary pediatric ICU in the children's hospital of an academic medical center staffed by board certified pediatric intensivists. The hospital uses computerized physician order entry for all medication orders. METHODS: A multidisciplinary team characterized key elements of the drug infusion process. The process was enhanced to increase overall reliability and the original and revised processes were compared using FMEA. Resource consumption was estimated by reviewing purchasing and pharmacy records for the calendar year after full implementation of the revised process. Staff satisfaction was evaluated using an anonymous questionnaire administered to staff nurses in the ICU and pediatric residents who had rotated through the ICU. RESULTS: The original process was characterized by six elements: selecting the drug; selecting a dose; selecting an infusion rate; calculating and ordering the infusion; preparing the infusion; programming the infusion pump and delivering the infusion. The following practice changes were introduced: standardizing formulations for all infusions; developing database driven calculators; extending infusion hang times from 24 to 72 hours; changing from bedside preparation by nurses to pharmacy prepared or premanufactured solutions. FMEA showed that the last three elements of the original process had high risk priority numbers (RPNs) of >225 whereas the revised process had no elements with RPNs >100. The combined effect of prolonging infusion hang times, preparation in the pharmacy, and purchasing premanufactured solutions resulted in 1500 fewer infusions prepared by nurses per year. Nursing staff expressed a significant preference and pediatric residents unanimously expressed a strong preference for the revised process. CONCLUSIONS: Standardization of infusion delivery reduced the frequency for completing the most unreliable elements of the process and reduced the riskiness of the individual elements. Both contribute to a safer system.