Knowledge, attitudes and adherence towards influenza and other vaccinations among healthcare workers at the University Hospital of Palermo, Italy, during the first COVID-19 pandemic season (2020/2021).

Background: Increasing adherence to influenza vaccination among healthcare workers is a public health priority, stated that actually remains far below than international recommendations. During the 2020/2021 pandemic season, COVID-19 vaccines were not yet available until the end of December 2020, and influenza vaccines were the only one available to protect against seasonal respiratory diseases. The main objective of the present study was to assess knowledge, attitudes and adherence to influenza and other vaccinations recommended by the National Immunization Plan 2017-2021 for healthcare workers. Methods: Enrollment lasted from October and December 2020 at the vaccination unit of the University Hospital of Palermo. Data were collected through an anonymous and self-administered questionnaire, divided into 5 sections and 31 items. Results: Among 734 healthcare professionals that completed the survey, a significantly higher adherence to influenza vaccination was observed among healthcare workers that were more prone to receive COVID-19 vaccination (OR=4.02; 95% CI: 1.63-9.91). Moreover, higher influenza vaccination rates were observed among healthcare professionals that received influenza vaccination during previous 2019/2020 season (OR=15.3; 95% CI: 5.17-45.1) and that were favorable to the possible impact on increasing adherence of influenza mandatory vaccination (OR=4.88; 95% CI: 2.43-9.80). Conclusions: Propensity of healthcare workers to undergo vaccinations recommended in the National Immunization Plan increased during the first pandemic season. At the end of the vaccination season, flu vaccination coverage reached highest rates ever at the University Hospital of Palermo (around 60%), remaining anyway below the recommended minimum value of 75%. During next seasonal flu vaccination campaigns, it becomes essential to promote communication and information strategies to increase flu vaccination among healthcare workers, also focusing on co-administration with the anti-COVID-19 booster/seasonal doses.

Emergency surgery during the COVID-19 pandemic: what you need to know for practice.

INTRODUCTION: Several articles have been published about the reorganisation of surgical activity during the COVID-19 pandemic but few, if any, have focused on the impact that this has had on emergency and trauma surgery. Our aim was to review the most current data on COVID-19 to provide essential suggestions on how to manage the acute abdomen during the pandemic. METHODS: A systematic review was conducted of the most relevant English language articles on COVID-19 and surgery published between 15 December 2019 and 30 March 2020. FINDINGS: Access to the operating theatre is almost exclusively restricted to emergencies and oncological procedures. The use of laparoscopy in COVID-19 positive patients should be cautiously considered. The main risk lies in the presence of the virus in the pneumoperitoneum: the aerosol released in the operating theatre could contaminate both staff and the environment. CONCLUSIONS: During the COVID-19 pandemic, all efforts should be deployed in order to evaluate the feasibility of postponing surgery until the patient is no longer considered potentially infectious or at risk of perioperative complications. If surgery is deemed necessary, the emergency surgeon must minimise the risk of exposure to the virus by involving a minimal number of healthcare staff and shortening the occupation of the operating theatre. In case of a lack of security measures to enable safe laparoscopy, open surgery should be considered.

The introduction of radioactive seed localisation improves the oncological outcome of image guided breast conservation surgery.

INTRODUCTION: Radioactive seed localisation (RSL) has become increasingly popular for localisation of non-palpable breast tumours. This is largely due to advantages it offers in terms of practicality and convenience when compared to guide wire localisation (WL). This institute switched from using WL to RSL in September 2014. The primary aim was to assess whether this change improved the accuracy of excision with regards to inadequate margin rates and weight of excision specimens. The secondary aim was to establish whether there is a "learning curve" associated with RSL technique. METHODS: Retrospective data collection was performed for 333 consecutive cases of unifocal non-palpable invasive breast cancers undergoing excision with WL or RSL. An inadequate margin was defined as tumour <1 mm from an inked radial margin. Patient demographics, tumour characteristics and clinical outcomes were compared between WL and RSL cases. RESULTS: 100 WL and 233 RSL cases were included. Patient demographics and tumour characteristics were similar for both groups. Inadequate margin rates were 18% with WL and 8.6% with RSL (p = 0.013). Median specimen weights were 33.3 g with WL and 28.7 g with RSL (p = 0.014). Subdividing the RSL group into the first 100 cases performed (RSL1) and the subsequent 133 cases (RSL2), inadequate margin rates were 13.0% and 5.3% respectively (p = 0.037). Mean specimen weights were similar. CONCLUSION: Switching from WL to RSL results in a significant reduction in both inadequate margin rates and specimen weights. A procedure-specific learning curve is present on first implementation of RSL and following this, inadequate margin rates are further reduced.

A systematic review of generic and breast cancer specific life expectancy models in the elderly.

INTRODUCTION: The use of primary endocrine therapy (PET) in managing breast cancer in the elderly has become common practice. Whilst there appears to be no difference in overall survival in comparison with surgery, PET has been found to be inferior in local disease control with a limited duration of efficacy (2-3 years). The International Society of Geriatric Oncology (SIOG) state that PET may be considered in patients with a short life expectancy (<2 years) or considered unfit for surgery. Frequently, decision making for PET allocation is a subjective process by the clinician. METHOD: A systematic literature review was performed to establish what prediction models are available for all-cause mortality in the elderly, and what breast-specific models have been produced. RESULTS: 18 prognostic models were deemed eligible from 15 papers. 1 breast-specific model was found, 2 nursing home related and 15 for community-dwelling elders. Accuracy (as defined by discrimination; c-statistic or AUROC) ranged from 0.69 (moderate) to 0.86 (very good). CONCLUSIONS: This review highlighted a variety of validated prognostic indexes. Several models with very good accuracy were identified but most were validated in US-populations and relied on information from administrative datasets. One breast specific model by Stotter et al. was identified, specifically to aid treatment planning for frail elderly patients but had limited accuracy. The strength of an index will ultimately be on its clinical impact and influence on treatment decisions rather than its accuracy and as of yet no trials exploring this have been carried out.

Cross-helicity in rotating homogeneous shear-stratified turbulence.

We consider homogeneous shear-stratified turbulence in a rotating frame, that exhibits complex nonlinear dynamics. Since the analysis of relative orientation between coupled fluctuating fields helps us to understand turbulence dynamics, we focus on the alignment properties of both the velocity and gravity fields with the potential vorticity gradient. With the help of statistical mechanics, we define a vector field which plays a role in the analogous so-called cross-helicity in magnetohydrodynamics. High-resolution direct numerical simulations of developed homogeneous baroclinic turbulence are performed, and a detailed analysis of probability density functions for cross-helicity is provided. A net preference for positive cross-helicity is shown to be related to a new alignment mechanism. We argue that the analysis of cross-helicity is crucial for understanding the dynamics of buoyancy driven flows.

Genetic factors regulating inflammation and DNA methylation associated with prostate cancer.

BACKGROUND: Prostate cancer (PCa) displays a strong familiarity component and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions and ultimately carcinogenesis. The enzyme glycine-N-methyltransferase (GNMT) contributes to S-adenosylmethionine level regulation and, by affecting DNA methylation, influences gene expression. The genotype and allele distribution of single-nucleotide polymorphisms (SNPs) in the promoter regions of vascular endothelial growth factor (VEGF), interleukin (IL)-10, IL-1ß, alpha-1-antichymotrypsin (ACT) and GNMT genes, the level of global DNA methylation and the influence of GNMT SNP upon DNA methylation in a PCa case-control study have been investigated. METHODS: SNPs of VEGF (rs699947), ACT (rs1884082), IL-1ß (rs16944), IL-10 (rs1800896) and GNMT (rs9462856) genes were assessed by PCR or by real-time PCR methods. DNA methylation was assessed by an ELISA assay. RESULTS: Frequencies of the VEGF AA genotype, the IL-10 A allele and GNMT T allele were higher in PCa. The concomitant presence of the AA genotype of VEGF, the A allele of IL-10 and T allele of GNMT increased the risk of PCa. Total DNA methylation was decreased in PCa; control GNMT T carriers (T+) showed the highest level of DNA methylation. CONCLUSIONS: SNPs in VEGF, IL-10 and GNMT genes might have a synergistic role in the development of PCa. The GNMT T allele may influence PCa risk by affecting DNA methylation and prostate gene expression. Our observations might help implement the screening of unaffected subjects with an increased susceptibility to develop PCa.

Pharmacological treatment of mechanical edema: a randomized controlled trial about the effects of mesoglycan.

AIM: Mechanical edema (MO) is frequently found in a lot of the lower extremities' orthopedic diseases. In absence of deep vein thrombosis, MO is caused by the change in the dynamics of calf muscle pump with venous hypertension and by the change in capillary permeability which offsets the extra-vascular fluid balance resulting in edema formation. The correct treatment includes specific training for musculo-skeletal and gait recovery, together with medical treatment focused on venous endothelium. Little information is available about pharmacological treatment of this condition. Some studies suggest the efficacy of mesoglycan in venous pathology. Aim of this study was to evaluate the clinical efficacy of the pharmacological treatment (mesoglycan 50 mg p.o., twice a day) in patients affected by MO. METHODS: Forty-four patients with MO, aged 20-89 years, were randomized in two treatment groups: specific physiotherapy (Fkt) alone or physiotherapy plus mesoglycan 50 mg twice a day, per os. The patients were evaluated before treatment (t0), and after 1 month of treatment (t1), measuring ankle joint range of motion (degrees), calf circumference and malleolar circumference (cm), pain Borg CR10 Scale and adapted lymphedema Weiss Scale. Statistical analysis was performed by the Pearson's c2 test and the Mann-Whitney-Wilcoxon test. RESULTS: At the final evaluation of the objective and subjective parameters, the mesoglycan effect combined to the Fkt provided statistical differences on nearly all the parameters in comparison with the patients randomised to Fkt alone. CONCLUSIONS: The present study suggest that mesoglycan treatment (50 mg p.o., twice a day) can improve the recovery of MO, and it is well tolerated by the patients. Specific physiotherapy remains the first treatment for the recovery of both muscular pump and correct walking, but the optimal treatment of MO seems to be a synergic approach, including both pharmacological and mobilization programs.

-Dual nucleoside therapy for HIV infection: analysis of results and factors influencing viral response and long term efficacy.

We performed a retrospective analysis of our experience with dual nucleoside regimens to look for predictors of long term benefit. The study evaluated a cohort of 68 HIV-infected patients treated at 3 Italian hospital-based facilities. The results were evaluated using univariate and multivariate statistical analysis. Fourty-three males and 25 females were treated for 22 +/- 14 months. Sixty three patients (92.6%) suffered no or low-grade side-effects. Thirty-four patients (50%) reached a viral load <400 copies/ml (undetectable). Viremia remained persistently undetectable in 9 cases (13.2%). Variable relapses of viremia were seen in 13 patients (19.1%) even though their therapys were not modified. Eight patients (11.8%) showed relapsing viremias persistently around or below 10,000 copies/ml. All patients reaching undetectable viremia but one showed increasing or stable CD4+ cell counts. Factors predicting favourable response were: pre-treatment CD4+ T-cells >150/microl, pre-treatment viremia <50,000 copies/ml, pre-treatment lymphocytes >1,500/microl, and no previous exposure to NRTI. Total lymphocyte counts and CD4+ T-cells showed a significant correlation. Dual NRTI regimens may be still considered for patients unable to tolerate HAART regimens and presenting with favourable predictors of response.

Primary prevention of deep venous thrombosis and pulmonary embolism in acute spinal cord injured patients.

STUDY DESIGN: Prospective clinical trial. OBJECTIVES: To evaluate the efficacy of a specific protocol for prevention of thrombo-embolic disease occurring during the acute stage of spinal cord lesions, based on the simultaneous use of pharmacological plus mechanical procedures. SETTING: Regional Spinal Unit of Florence, Italy. INTRODUCTION: Deep venous thrombosis (DVT) is a dangerous pathology whose first clinical sign can be represented by unexpected pulmonary embolism (PE). Its incidence in acute spinal cord injured (SCI) patients is reported to range between 9% and 90%. Its prevention represents one of the major challenges for the clinicians involved in the care of such patients. METHOD: Two hundred and seventy-five SCI patients consecutively admitted to our Centre were investigated by colour doppler ultrasonography of lower limbs and pelvis on admission, after 30-45 days and whenever clinically requested. Subcutaneous Nadroparine, a low molecular weight heparin (LMWH), plus early mobilisation, permanently dressed gradient elastic stockings (PGES), and external sequential pneumatic compression (ESPC) of the lower limbs, applied during the first 30 days after injury, were given to all of them. Colour doppler ultrasonography (CDUS) complete investigations of the lower limbs and pelvis were performed on admission, after 30-45 days and whenever clinically requested. The patients were divided into two groups according to their time interval from injury to the admission to our Centre. RESULTS: The incidence of detected DVT was 2% in those patients (99) admitted early to our centre (within 72 h from the trauma), who immediately received our prophylactic protocol. No PE was reported. The other group of patients (176), all admitted between 8 and 28 days (mean 12 days) developed DVT in 26% of cases. None of these patients received ESPC before being admitted to our Centre. No patient had been admitted between 3 and 8 days interval time post injury. CONCLUSION: Early application of pharmacological plus mechanical treatment for DVT prevention produces a marked reduction in such complications. It also reduces the risks of morbidity and mortality in our patients, and, not least, reduces the hospitalization costs during the early period of rehabilitation.

An in vivo model of hyperacute rejection: characterization and evaluation of the effect of transgenic human complement inhibitors.

Hyperacute rejection (HAR) occurring after transplantation within phylogenetically distant species is a severe reaction triggered by preexisting xenoreactive antibodies and complement activation, leading to the destruction of the donor organ. Expression of human complement inhibitors in transgenic pig organs prolongs the survival of xenograft in experimental models. Moreover, the extent of protection from hyperacute rejection is dependent on the level and site of expression of the transgenic molecules and, probably, on the combination of different molecules. In this regard a small animal model to test the efficacy of expression vectors and different human molecules could be very advantageous. A murine model developed in our laboratory was characterized by measurement of several parameters characteristic of HAR in the livers of control and transgenic mice expressing transgenic human DAF (CD55) or MCP (CD46) at the end of 2 h of perfusion with human plasma and after I day. The parameters studied were heamatological values of hepatic functions (GOT and GPT), induction of pro-inflammatory molecules and histopathological evaluation. Cytokines (IL-1alpha, IL-1beta, IL-6) induction and exposure of P-selectin on the endothelial cell surface, was only observed in control animals after 2 h of perfusion, as an early event. GOT and GPT values increase dramatically after 2 h perfusion and 1 day after the treatment according to the histopathological observation of liver damage. On the contrary, the livers of hDAF or hMCP transgenic mice, under the same treatment were significantly protected although the extent of this protection is dependent on the level of expression of transgenic human molecules.

Interaction between acylphosphatase and SERCA in SH-SY5Y cells.

Ca2+ transport by sarco/endoplasmic reticulum, tightly coupled with the enzymatic activity of Ca2+ -dependent ATPase, controls the cell cycle through the regulation of genes operating in the critical G, to S checkpoint. Experimental studies demonstrated that acylphosphatase actively hydrolyses the phosphorylated intermediate of sarco/endoplasmic reticulum calcium ATPase (SERCA) and therefore enhances the activity of Ca2+ pump. In this study we found that SH-SY5Y neuroblastoma cell division was blocked by entry into a quiescent G0-like state by thapsigargin, a high specific SERCA inhibitor, highlighting the regulatory role of SERCA in cell cycle progression. Addition of physiological amounts of acylphosphatase to SY5Y membranes resulted in a significant increase in the rate of ATP hydrolysis of SERCA. In synchronized cells a concomitant variation of the level of acylphosphatase isoenzymes opposite to that of intracellular free calcium during the G1 and S phases occurs. Particularly, during G1 phase progression the isoenzymes content declined steadily and hit the lowest level after 6 h from G0 to G1 transition with a concomitant significant increase of calcium levels. No changes in free calcium and acylphosphatase levels upon thapsigargin inhibition were observed. Moreover, a specific binding between acylphosphatase and SERCA was demonstrated. No significant change in SERCA-2 expression was found. These findings suggest that the hydrolytic activity of acylphosphatase increase the turnover of the phosphoenzyme intermediate with the consequences of an enhanced efficiency of calcium transport across endoplasmic reticulum and a subsequent decrease in cytoplasmic calcium levels. A hypothesis about the modulation of SERCA activity by acylphosphatase during cell cycle in SY5Y cells in discussed.

Oxidative stress and calcium homeostasis in dystrophic skin fibroblasts.

Muscular dystrophy is a genetic disease that affects primarily skeletal muscle. The dystrophin absence has been related to the degeneration of muscle fibres. Indirect evidences suggest that oxidative stress may play a role in the pathogenesis of the disease, but the significance and precise extent of this contribution is poorly understood. In this paper we show that Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD) skin fibroblasts are more susceptible to H2O2 treatment than are fibroblasts from unaffected persons. In particular, we found that, in growing DMD skin fibroblasts, the oxidative treatment resulted in significantly reduced growing capacity. We also investigated the concentrations of intracellular calcium during H2O2 treatment. The intracellular free calcium concentration increased by 22%, 35%, and 40% in unaffected, BMD, and DMD fibroblasts, respectively. However, the increase of the intracellular free calcium concentration is not related, as previously hypothesized, to a reduction of acylphosphatase concentrations, which seem to be unaffected by the H2O2 treatment, but rather to reduced enzyme activity.

Utility of an integrated clinical, echocardiographic, and venous ultrasonographic approach for triage of patients with suspected pulmonary embolism.

The potential role of ultrasound techniques in diagnosing acute pulmonary embolism (PE) has been investigated in severe cases with hemodynamic compromise, but is still unclear for the whole clinical spectrum of patients with suspected PE. The aim of this study was to assess the utility of an integrated bedside evaluation for PE based on the combination of a clinical score, 2-dimensional echocardiography, and color venous duplex scanning. A group of 117 consecutive patients with suspected PE was assessed using a clinical likelihood score, echocardiography, and venous duplex scanning in order to obtain a preliminary diagnosis of PE, which was subsequently compared with the final diagnosis obtained by lung perfusion scintigraphy and angiography. A preliminary diagnosis of PE was made in 70 patients; a final diagnosis of PE was made in 63 patients, of which 56 had and 7 did not have a preliminary diagnosis of PE. The preliminary diagnosis therefore showed 89% sensitivity and 74% specificity, with a total accuracy of 82%. In patients with massive PE, sensitivity and negative predictive values of the preliminary diagnosis were 97% and 98%, respectively. Echocardiography was poorly sensitive (51%) but highly specific (87%) for PE. Thus, the integration of clinical likelihood, echocardiography, and venous duplex scanning provides a practical approach to patients with suspected PE, allows the rapid implementation of appropriate management strategies, and may reduce or postpone the need for further instrumental evaluation of more limited access.

Drosophila melanogaster acylphosphatase: a common ancestor for acylphosphatase isoenzymes of vertebrate species.

An open reading frame encoding a putative acylphosphatase was found in Drosophila melanogaster. The corresponding gene product shows 40% identity and 22 additional amino acid residues at the C-terminus as compared to muscle- and common-type human acylphosphatases. Moreover, all the residues involved in the catalytic mechanism of vertebrate enzymes are conserved in the D. melanogaster acylphosphatase. The D. melanogaster protein and a deletion mutant, similar in length to vertebrate acylphosphatases, were produced by cloning the corresponding cDNA in Escherichia coli. The wild-type enzyme is a protein with a well-established three-dimensional fold and a markedly reduced conformational stability as compared to vertebrate isoenzymes. The specific activity of the enzyme is significantly lower than that found in vertebrate enzymes though the substrate binding capability is basically unaltered. The deletion of 22 residues does not cause a significant change in k(cat), while affecting the apparent binding parameters. This work suggests that the genes encoding the vertebrate enzymes originate from an ancestor gene by duplication and subsequent evolution.

Diagnosis of vertebrobasilar insufficiency: time to rethink established dogma?

As isolated symptoms, vertigo, dizziness and imbalance are not regarded by neurologists as reflections of transient ischemia in the vertebrobasilar circulation. The purpose of this retrospective study was to demonstrate that these symptoms can and do occur in isolation. To this end, we analyzed the symptoms, stroke risk factors and diagnostic algorithms in 27 patients with a diagnosis of transient vertebrobasilar ischemia. None of the 27 patients included in the review complained of any associated neurologic symptoms. Against the reference standard of brain imaging, the site of the pathologic lesion was defined in the brainstem/cerebellum with the Torok monothermal caloric test, with a sensitivity greater than 86%. Vestibular decruitment and hyperactive caloric responses were of particular diagnostic value. Thus, we recommend that the neurologic dogma with regard to brainstem cerebellar ischemia be rethought.

Alteration of intracellular free calcium and acylphosphatase levels in differentiating SH-SY5Y neuroblastoma cells.

Levels of acylphosphatase isoenzymes and free intracellular calcium have been investigated in cultured SH-SY5Y human neuroblastoma cells under stimulation with all-trans retinoic acid and phorbol-12-myristate-13-acetate. Under these conditions morphological and functional characteristics demonstrated the differentiation of SH-SY5Y cells towards neuronal phenotype. Retinoic acid treatment caused a progressive and synchronous increase of the organ common-type acylphosphatase and of free intracellular calcium but not of the muscle-type acylphosphatase. Phorbol-12-myristate-13-acetate treatment gave rise to a peak of the muscle-type acylphosphatase levels during the early differentiation stage whereas organ common-type isoenzyme and free calcium levels show a pattern similar to that observed in retinoic acid-treated cells. These evidences indicate that the two acylphosphatase isoenzymes play different roles in SH-SY5Y differentiation and that during this process the expression of organ common-type acylphosphatase increases in a synchronous way with intracellular free calcium concentration.

Alteration of free calcium levels and acylphosphatase muscular isoenzyme in cultured dystrophic skin fibroblasts.

Levels of free intracellular calcium have been measured on two cell lines of cultured human fibroblasts carrying the genetic lesions occurring in Duchenne and Becker dystrophies. Both cell lines elicited a markedly higher content of the cation (98 nM and 57 nM, respectively) than control fibroblasts (35 nM). Differences toward controls were statistically significant (p < 0.01). Dystrophic fibroblasts were also found to possess a significantly reduced amount by about 50% of muscular acylphosphatase isoenzyme as compared to normal cells. As acylphosphatase was demonstrated to be involved in the regulation of Ca2+-ATPase activity from different sources, a hypothesis was formulated that could explain the disruption of calcium homeostasis as an effect of the altered acylphosphatase activity.