Development and patient acceptance of Preanestes@s, a web-based application and electronic questionnaire for preoperative assessment. A prospective cohort study.

BACKGROUND AND OBJECTIVES: We describe the development of Preanestes@s, a web-based application for preoperative assessment, which incorporates PreQuest, a smart computer-based self-assessment questionnaire for the automated management of information. Preanestes@s potentially enables remote non-telephonic preoperative assessment. The main objective of this work was the identification of factors that independently predict adequate completion of PreQuest. As a secondary objective, we assessed patient experience using the application. MATERIAL AND METHODS: To assess the influence of patient conditions on PreQuest completion, our sample included 880 adult patients scheduled to undergo surgery at our institution between February 2020 and February 2021. We evaluated patient satisfaction and acceptability with the use of the application and PreQuest. RESULTS: A total of 573 participants (65.1%) successfully completed the PreQuest. Age below 65 years and higher educational attainment were identified as independent predictors for PreQuest completion (p = 0.04 and p = 0.001, respectively). Most (89.4%) participants agreed that Preanestes@s was intuitive and easy to use, with over 85% showing high levels of acceptance of PreQuest prototype's communication improvement and ease of use. The final version of Preanestes@s and PreQuest was evaluated by 218 participants, many of whom (>74%) affirmed its ease of use. CONCLUSIONS: The use of Preanestes@s for preoperative assessment is supported by high levels of satisfaction with the prototype and by an eQuest completion rate greater than 65% in a non-selective population. In our sample, younger age and higher education attainment predicted higher rates PreQuest completion. Trial registration number NCT04259268.

Utility of preoperative polymerase chain reaction testing during SARS-CoV-2 pandemic: The challenge of evolving incidence.

INTRODUCTION: Due to its high transmissibility, measures aimed at reducing the spread of SARS CoV2 have become mandatory. Different organizations have recommended performing polymerase chain reaction tests (PCR) as part of the preoperative screening of surgical patients. We aimed to determine the performance of PCR testing to detect asymptomatic carriers. METHODS: Observational study carried out at a tertiary care center. We compared the results of preoperative real-time reverse-transcription-PCR test (RT-PCR) performed on a cohort of patients pending surgery with the results we would have expected assuming the epidemiological data released by government offices. RESULTS: We registered no positives in the 2,722 preoperative RT-PCR tests performed in our health care area between epidemiological Weeks 18 to 21, meaning a cumulative incidence trending to zero. Assuming public epidemiological data, the probabilistic projection of potential asymptomatic individuals ranged from 0.27 × 10e-4 (according to official data of new cases diagnosed by PCR) to 4.69 × 10e-4 if we assumed cases confirmed by IgG test in our province. Assuming a RT-PCR sensitivity of 95%, to obtain a positive result we should perform 38,461 and 2,028 tests respectively. CONCLUSIONS: In scenarios of very low prevalence and despite high sensitivity scores, indiscriminate preoperative RT-PCR screening is of a questionable effectiveness for detecting asymptomatic carriers. Our findings evidence the difficulty of establishing reliable predictive models for the episodic and rapidly evolving incidence of infections such as has characterized the SARS CoV2 pandemic.

Utility of preoperative polymerase chain reaction testing during SARS-CoV-2 pandemic: The challenge of evolving incidence. / Utilidad de la prueba de reacción en cadena de la polimerasa preoperatoria durante la pandemia por SARS-CoV-2: el desafío de la incidencia cambiante.

INTRODUCTION: Due to its high transmissibility, measures aimed at reducing the spread of SARS CoV2 have become mandatory. Different organizations have recommended performing polymerase chain reaction tests (PCR) as part of the preoperative screening of surgical patients. We aimed to determine the performance of PCR testing to detect asymptomatic carriers. METHODS: Observational study carried out at a tertiary care center. We compared the results of preoperative real-time reverse-transcription-PCR test (RT-PCR) performed on a cohort of patients pending surgery with the results we would have expected assuming the epidemiological data released by government offices. RESULTS: We registered no positives in the 2,722 preoperative RT-PCR tests performed in our health care area between epidemiological Weeks 18 to 21, meaning a cumulative incidence trending to zero. Assuming public epidemiological data, the probabilistic projection of potential asymptomatic individuals ranged from 0.27*10e -4 (according to official data of new cases diagnosed by PCR) to 4.69*10e -4 if we assumed cases confirmed by IgG test in our province. Assuming a RT-PCR sensitivity of 95%, to obtain a positive result we should perform 38,461 and 2,028 tests respectively. CONCLUSIONS: In scenarios of very low prevalence and despite high sensitivity scores, indiscriminate preoperative RT-PCR screening is of a questionable effectiveness for detecting asymptomatic carriers. Our findings evidence the difficulty of establishing reliable predictive models for the episodic and rapidly evolving incidence of infections such as has characterized the SARS CoV2 pandemic.

Catheter ablation in atrial fibrillation: is there a mortality benefit in patients with diabetes and heart failure?

Atrial fibrillation (AF) is the most commonly sustained arrhythmia, and patients with diabetes mellitus (DM) exhibit an increased incidence of AF. Besides DM, heart failure (HF) shares pathophysiological links with AF, mainly related to the pathological remodeling of hearts affected by structural disease. As in a vicious circle, AF may contribute to HF worsening and increased mortality in patients with structural heart diseases, and the outcome may be further impaired when concomitant DM is present. Although no data directly referring to DM patients with HF are available, indirect information can be drawn from large studies on patients with HF and AF. The present review discusses the outcome of AF ablation in patients with DM and HF, focusing on safety, efficacy, and most particularly on hard endpoints such as mortality and thromboembolic event incidence.

Clinical and radiological study of sternal fractures in pediatrics. / Estudio clínico radiológico de las fracturas esternales en edad pediátrica.

Sternal fractures are considered uncommon in pediatric patients. Classically, they have been described as fractures secondary to high-energy trauma that have a risk of associated lesions. OBJECTIVE: To describe the clinical and imaging features of sternal fractures in patients less than 18 years of age. MATERIAL AND METHODS: We retrospectively reviewed 79 pediatric patients diagnosed with sternal fractures after trauma. RESULTS: We found that 92.4% of the fractures were caused by low-energy trauma and that associated lesions were present in only 3 (4%) patients. CONCLUSION: Our results suggest that sternal fractures in children are often due to lesser trauma and that associated lesions are rare.

Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study.

BACKGROUND: Dimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (MS) in randomized clinical trials. OBJECTIVES: To track and evaluate post-market DMF profile in real-world setting. MATERIALS AND METHODS: Patients receiving DMF referred to Italian MS centres were enrolled and prospectively followed, collecting demographic clinical and radiological data. RESULTS: Among the 735 included patients, 45.4% were naïve to disease-modifying therapies, 17.8% switched to DMF because of tolerance, 27.4% switched to DMF because of lack of efficacy, and 9.4% switched to DMF because of safety concerns. Median DMF exposure was 17 months (0-33). DMF reduced the annual relapse rate (ARR) by 63.2%. At 12 and 24 months, 85 and 76% of patients were relapse-free. NEDA-3 status after 12 months of DMF treatment was maintained by 47.5% of patients. 89 and 70% of patients at 12 and 24 months regularly continued DMF. Most frequent adverse events (AEs) were flushing (37.2%) and gastro-enteric AEs (31.1%). CONCLUSION: Our post-market study corroborated that DMF is a safe and effective drug. Additionally, the study suggested that naïve patients strongly benefit from DMF and that DMF improved ARR also in patients who were horizontally switched from injectable therapies due to tolerability and efficacy issues.

Predictors of Cardiovascular Autonomic Neuropathy Onset and Progression in a Cohort of Type 1 Diabetic Patients.

AIM: The prevalence of cardiovascular autonomic neuropathy (CAN) in diabetes mellitus is well documented. However, the rate and predictors of both the development and progression of CAN have been less studied. Hereby, we assessed the rate and the major risk factors for CAN initiation and progression in a cohort of type 1 diabetic patients followed over a three-year period. METHODS: 175 type 1 diabetic patients (mean age: 50 ± 11 years; female/male: 76/99) with positive bedside screening for CAN were included and underwent 2 standardized autonomic testings using 4 standardized tests (deep breathing, Valsalva maneuver, 30/15 ratio, and changes in blood pressure during standing), separated by 3 ± 1 years. CAN staging was achieved according to the Toronto Consensus Panel on Diabetic Autonomic Neuropathy into 4 categories: absent, possible, confirmed, or severe CAN. RESULTS: Out of the 175 patients included, 31.4% were free of CAN, 34.2% had possible CAN, 24.6% had confirmed CAN, and 9.7% exhibited severe CAN at the first assessment. Among the 103 patients with nonsevere CAN at inclusion, forty-one (39.8%) had an increase of at least one category when reassessed and 62 (60.2%) remained stable. A bivariate analysis indicated that only BMI and exposure to selective serotonin reuptake inhibitors (SSRIs) were significantly different in both groups. A multivariate analysis indicated that lower BMI (OR: 0.15, CI 95%: 0.05-0.48, p = 0.003) and SSRI exposure (OR: 4.18, CI 95%: 1.03-16.97, p = 0.04) were the sole predictors of CAN deterioration. In the 55 patients negative for CAN at the first laboratory assessment, 12 became positive at the second assessment. CONCLUSION: No clear predictive factor for CAN onset was identified. However, once present, CAN progression was related to low BMI and SSRI exposure.

The effect of inhalational anaesthesia during deceased donor organ procurement on post-transplantation graft survival.

Many deceased by neurologic criteria donors are administered inhalational agents during organ recovery surgery-a process that is characterised by warm and cold ischaemia followed by warm reperfusion. In certain settings, volatile anaesthetics (VA) are known to precondition organs to protect them from subsequent ischaemia-reperfusion injury. As such, we hypothesised that exposure to VA during organ procurement would improve post-graft survival. Lifebanc (organ procurement organisation [OPO] for NE Ohio) provided the investigators with a list of death by neurologic criteria organ donors cared for at three large tertiary hospitals in Cleveland between 2006 and 2016-details about the surgical recovery phase were extracted from the organ donors' medical records. De-identified data on graft survival were obtained from the United Network for Organ Sharing (UNOS). The collated data underwent comparative analysis based on whether or not VA were administered during procurement surgery. Records from 213 donors were obtained for analysis with 138 exposed and 75 not exposed. Demographics, medical histories, and organ procurement rates were similar between the two cohorts. For the primary endpoint, there were no significant differences observed in either early (30-day) or late (five-year) graft survival rates for kidney, liver, lung, or heart transplants. Our findings from this retrospective review of a relatively small cohort do not support the hypothesis that the use of VA during the surgical procurement phase improves graft survival. Reviews of larger datasets and/or a prospective study may be required to provide a definitive answer.

Chemokine Patterns in Children with Acute Bacterial Infections.

Chemokines are chemotactic cytokines that are mainly involved in the migratory patterns of immune cells. Few studies have evaluated the levels of chemokines in children with acute bacterial infections. The aim of this study was to evaluate the serum levels of chemokines MCP-1, RANTES, MIG and IP-10 in children with sepsis, community-acquired pneumonia (CAP) and skin abscess. Serum levels of MCP-1, RANTES, MIG and IP-10 were measured in 37 children with sepsis, 27 children with CAP, 25 children with skin abscess and 20 controls with no signs of infection. Patients with sepsis, CAP and skin abscess had higher concentrations of RANTES compared to controls (P = 0.0057, P = 0.0004 and P = 0.0108, respectively). IP-10 values were higher in patients with sepsis compared to children with skin abscess (P = 0.0075). However, MCP-1 levels were lower in septic patients compared to controls (P = 0.0136). There was no difference on MIG concentrations between the groups. Our original findings observed that RANTES was consistently elevated in all types of infections suggesting this chemokine may play an important role in the pathogenesis of bacterial infection. Additionally, patients with sepsis had a unique pattern of response with high levels of IP-10 but low levels of MCP-1, which should be further explored as the markers of disease severity.

Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity.

BACKGROUND: The approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients. The aim of our study was to describe Sativex effectiveness and adverse events profile in a large population of Italian patients with MS in the daily practice setting. METHODS: We collected data of all patients starting Sativex between January 2014 and February 2015 from the mandatory Italian medicines agency (AIFA) e-registry. Spasticity assessment by the 0-10 numerical rating scale (NRS) scale is available at baseline, after 1 month of treatment (trial period), and at 3 and 6 months. RESULTS: A total of 1615 patients were recruited from 30 MS centres across Italy. After one treatment month (trial period), we found 70.5% of patients reaching a ≥20% improvement (initial response, IR) and 28.2% who had already reached a ≥30% improvement (clinically relevant response, CRR), with a mean NRS score reduction of 22.6% (from 7.5 to 5.8). After a multivariate analysis, we found an increased probability to reach IR at the first month among patients with primary and secondary progressive MS, (n=1169, OR 1.4 95% CI 1.04 to 1.9, p=0.025) and among patients with >8 NRS score at baseline (OR 1.8 95% CI 1.3-2.4 p<0.001). During the 6 months observation period, 631(39.5%) patients discontinued treatment. The main reasons for discontinuation were lack of effectiveness (n=375, 26.2%) and/or adverse events (n=268, 18.7%). CONCLUSIONS: Sativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.

Impairment of Interleukin-17A Expression in Canine Visceral Leishmaniosis is Correlated with Reduced Interferon-γ and Inducible Nitric Oxide Synthase Expression.

Dogs are the primary urban reservoir of Leishmania infantum and play a crucial role in the transmission of this parasite to man via sandflies. The spleen and liver are the main target organs of L. infantum infection, but few studies have evaluated the immune response to this infection in the canine liver. To identify the immunological mediators involved in resistance and/or susceptibility to canine visceral leishmaniosis (CVL), we selected 21 dogs naturally infected by L. infantum and classified as asymptomatic or symptomatic. Immunological parameters were analysed and correlations with clinical signs were determined. Symptomatic dogs showed higher numbers of parasites and less leucocyte infiltration in the liver compared with asymptomatic dogs. The progression of this disease was characterized not only by the down regulation of T helper (Th) 1-related cytokines, such as interferon (IFN)-γ and tumour necrosis factor (TNF)-α, but also by the down regulation of genes encoding interleukin (IL)-17A, inducible nitric oxide synthase (iNOS) and IL-10 in the spleen and liver in symptomatic dogs compared with asymptomatic dogs. Importantly, IL-17A gene transcription level was positively correlated with mRNA expression for iNOS and IFN-γ. Th1- and Th17-related cytokines therefore appear to play a role in restricting parasite growth via iNOS activation and decrease susceptibility of dogs to CVL.

Reproductive biology of the Alaska skate Bathyraja parmifera, with comments on an intersexual individual.

A total of 1357 specimens of Alaska skate Bathyraja parmifera were collected in the eastern Bering Sea by fisheries observers and during scientific groundfish surveys from 2003 to 2005. Male and female gonads were examined for maturity stage and seasonal reproductive timing. Based on seasonal reproductive data, including the occurrence of egg cases, ovum size, ovum number, shell-gland width and gonado-somatic index, this species appears to reproduce continually throughout the year. Potential effects of maternal size upon the size and number of mature oocytes were also investigated, with total length having a significant, although weak, influence on both. Morphology of a single intersexual individual encountered during the collection period is also described.

Biological monitoring of IFN-ß therapy in Multiple Sclerosis.

Multiple Sclerosis (MS) is a heterogeneous disease and a variable percentage of patients are non-responders to common treatment. Early diagnosis of non-responders allows change to a more useful therapy for the patient and better allocates a large amount of financial resources. Quantification of Neutralizing antibodies (Nabs) and of biological activity of IFN-ß are recognized approaches to identify immuno-pharmacological non-responders. A consistent number of studies have demonstrated that quantification of Myxovirus-induced protein A (MxA) is a valid biomarker to detect immune-pharmacological non responders after one year of treatment. Persistent high titre of Nabs and absence of biological activity predict abolition of IFN-ß effects in disease activity measured through MRI, number of relapses and disability. Guidelines and flow-charts including both Nabs and MxA quantification are presented.

No impact of current therapeutic strategies on disease reactivation after natalizumab discontinuation: a comparative analysis of different approaches during the first year of natalizumab discontinuation.

BACKGROUND AND PURPOSE: Natalizumab discontinuation induces the recurrence of multiple sclerosis disease activity: currently no therapeutic approach has been found able to abolish disease reactivation. METHODS: The recurrence of disease activity after natalizumab discontinuation was retrospectively evaluated in 79 patients who had been treated with immunomodulating agents, other first-line therapies, fingolimod or not treated. RESULTS: No differences have been found in clinical or magnetic resonance imaging recurrence of disease activity amongst the groups. Interestingly, no disease reactivation was observed only in one patient treated for 6 months with monthly pulses of cyclophosphamide. CONCLUSION: Disease modifying treatment or 'no treatment' is unable to abolish disease activity reactivation after natalizumab discontinuation.

Primary neurolymphomatosis diagnosis and treatment: a retrospective study.

BACKGROUND: To discuss the therapeutic approach for primary neurolymphomatosis. METHODS: We report all primary neurolymphomatosis cases referred to our institution, with descriptions of clinical, radiological, electrophysiological, histological features and long-term follow-up. We treated all patients with a combination of high-dose methotrexate and alkylating agents. RESULTS: Five patients were diagnosed with histologically confirmed primary neurolymphomatosis. The majority of them presented with painful asymmetric sensory-motor neuropathy. Magnetic resonance imaging was abnormal in 4 of 5 patients, as shown with gadolinium enhancements. Electroneuromyography revealed denervation in all 4 cases with contributive examinations. All our patients received a chemotherapy combination of high-dose methotrexate and alkylating agent. Median progression-free survival was 8 months (2 complete responses and 2 partial responses), and overall survival was 24 months. CONCLUSIONS: Primary neurolymphomatosis is rare and polymorphic; it represents a difficult diagnosis of neuropathy. In our cohort, treatment with a chemotherapy combination with high-dose methotrexate showed encouraging results.

Conserved residues in RF-NH2 receptor models identify predicted contact sites in ligand-receptor binding.

Peptides in the RF-NH2 family are grouped together based on an amidated dipeptide C terminus and signal through G-protein coupled receptors (GPCRs) to influence diverse physiological functions. By determining the mechanisms underlying RF-NH2 signaling targets can be identified to modulate physiological activity; yet, how RF-NH2 peptides interact with GPCRs is relatively unexplored. We predicted conserved residues played a role in Drosophila melanogaster RF-NH2 ligand-receptor interactions. In this study D. melanogaster rhodopsin-like family A peptide GPCRs alignments identified eight conserved residues unique to RF-NH2 receptors. Three of these residues were in extra-cellular loops of modeled RF-NH2 receptors and four in transmembrane helices oriented into a ligand binding pocket to allow contact with a peptide. The eighth residue was unavailable for interaction; yet its conservation suggested it played another role. A novel hydrophobic region representative of RF-NH2 receptors was also discovered. The presence of rhodopsin-like family A GPCR structural motifs including a toggle switch indicated RF-NH2s signal classically; however, some features of the DMS receptors were distinct from other RF-NH2 GPCRs. Additionally, differences in RF-NH2 receptor structures which bind the same peptide explained ligand specificity. Our novel results predicted conserved residues as RF-NH2 ligand-receptor contact sites and identified unique and classic structural features. These discoveries will aid antagonist design to modulate RF-NH2 signaling.

Limited impact of prognostic factors in patients with recurrent glioblastoma multiforme treated with a bevacizumab-based regimen.

Bevacizumab has demonstrated activity in patients with recurrent glioblastoma. However, the impact of prognostic factors associated with recurrent glioblastoma treated with cytotoxic agents has not been determined in patients treated with bevacizumab. To analyze the prognostic factors and clinical benefits of bevacizumab and irinotecan treatment in patients with recurrent glioblastoma. This monocentric study retrospectively analyzed all patients with recurrent glioblastoma who were treated with at least one cycle of bevacizumab and irinotecan at our institution from April 2007 to May 2010. Multivariate analysis was used to analyze prognostic factors for overall survival (OS) from the initiation of bevacizumab administration. Among the 100 patients that were identified (M/F: 65/35), the median age was 57.9 years (range: 18-76). Karnofsky Performance Status (KPS) was <70 in 44 patients and ≥ 70 in 56 patients; 83 % of the patients were on steroids. The median tumor area was 2012 mm². The median progression free survival was 3.9 months (CI 95 %: 3.4-4.3). The median OS was 6.5 months (CI 95 %: 5.6-7.4). Multivariate analysis revealed that OS was affected by KPS (p = 0.024), but not by gender, age, steroid treatment, number of previous lines of treatment, tumor size, or time from initial diagnosis. KPS was improved in 30 patients, including 14/44 patients with an initial KPS <70. The median duration of maintained functional independence (KPS ≥ 70) was 3.75 months (CI 95 %: 2.9-4.6). The median OS from initial diagnosis was 18.9 months (CI 95 %: 17.5-20.3). In patients with recurrent glioblastoma treated with bevacizumab, KPS was revealed as the only factor to impact OS. The clinical benefits associated with this regimen appear valuable. A positive impact of bevacizumab administration on OS of patients with glioblastoma multiforme is suggested.

Dengue: a newly emerging viral infection in Andaman and Nicobar Islands, India.

Prior to 2009 dengue fever had not been reported in the Andaman and Nicobar archipelago. In 2009, a few patients with dengue fever-like illness were reported, some of whom tested positive for dengue antibodies. In 2010, 516 suspected cases were reported, including some with dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS); 80 (15·5%) were positive for dengue antibodies. DENV RNA was detected in five patients and PCR-based typing showed that three of these belonged to serotype 1 and two to serotype 2. This was confirmed by sequence typing. Two clones of dengue virus, one belonging to serotype 1 and the other to serotype 2 appeared to be circulating in Andaman. Emergence of severe diseases such as DHF and DSS might be due to recent introduction of a more virulent strain or because of the enhancing effect of sub-neutralizing levels of antibodies developed due to prior infections. There is a need to revise the vector-borne disease surveillance system in the islands.