Publications by authors named "Lorenzo Tofani"

51 Publications

Risk factors for difficult Laryngeal Mask Airway LMA-Supreme™ (LMAS) placement in adults: a multicentric prospective observational study in an Italian population.

Minerva Anestesiol 2021 Feb 16. Epub 2021 Feb 16.

Anaesthesia and Intensive Care, AOU Policlinico Vittorio Emanuele San Marco, Catania, Italy.

Background: Supraglottic airway Devices (SADs) are precious tools for airway management in both routine and rescue situations; few studies have analysed the risk factors for their difficult insertion.

Methods: The aim of this study was to identify the risk factors for difficult insertion for a specific SAD, the Laryngeal Mask Airway LMA-Supreme™ (LMAS). This was a prospective multicentric observational study on a cohort of Italian adult patients receiving general anaesthesia for elective surgery. The possible causes of difficulty in LMAS placement (difficulty in insertion or unsatisfactory ventilation) were identified based on literature and on the opinion of international airway management experts. A dedicated datasheet was prepared to collect patients' data, including anthropometric parameters and parameters for the prediction of difficult airway management, as well as technical choices for the use of LMAS. Data were analysed to discover the risk factors for difficult LMAS placement and the association between each risk factor and the proportion of incorrect positioning was evaluated through the relative risk and its confidence interval.

Results: Four hundred thirty-two patients were enrolled; seventy required two or more attempts to insert the LMAS; nine required a change of strategy. At multivariate analysis, the following factors were significantly associated with difficult LMAS placement: Mallampati III - IV with either phonation or not; inter-incisor distance < 3 cm; reduced neck mobility; no administration of neuromuscular blocking agents (NMBAs).

Conclusions: The alignment of the laryngeal and pharyngeal axes seems to facilitate the procedure, together with NMBA administration; on the contrary, Mallampati grade III-IV are associated with difficult LMAS placement.
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http://dx.doi.org/10.23736/S0375-9393.20.15001-6DOI Listing
February 2021

ST3GAL1 is a target of the SOX2-GLI1 transcriptional complex and promotes melanoma metastasis through AXL.

Nat Commun 2020 11 17;11(1):5865. Epub 2020 Nov 17.

Core Research Laboratory - Institute for Cancer Research and Prevention (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy.

Understanding the molecular events controlling melanoma progression is of paramount importance for the development of alternative treatment options for this devastating disease. Here we report a mechanism regulated by the oncogenic SOX2-GLI1 transcriptional complex driving melanoma invasion through the induction of the sialyltransferase ST3GAL1. Using in vitro and in vivo studies, we demonstrate that ST3GAL1 drives melanoma metastasis. Silencing of this enzyme suppresses melanoma invasion and significantly reduces the ability of aggressive melanoma cells to enter the blood stream, colonize distal organs, seed and survive in the metastatic environment. Analysis of glycosylated proteins reveals that the receptor tyrosine kinase AXL is a major effector of ST3GAL1 pro-invasive function. ST3GAL1 induces AXL dimerization and activation that, in turn, promotes melanoma invasion. Our data support a key role of the ST3GAL1-AXL axis as driver of melanoma metastasis, and highlight the therapeutic potential of targeting this axis to treat metastatic melanoma.
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http://dx.doi.org/10.1038/s41467-020-19575-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673140PMC
November 2020

The switch from etanercept originator to SB4: data from a real-life experience on tolerability and persistence on treatment in joint inflammatory diseases.

Ther Adv Musculoskelet Dis 2020 13;12:1759720X20964031. Epub 2020 Oct 13.

Department Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy.

Aims: Switching from originator to biosimilar is part of current practice in inflammatory rheumatic musculoskeletal diseases (iRMDs) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA), with evidences derived from both etanercept (ETN) to SB4-switching randomized controlled trials and real-life registries. We investigated the safety and treatment persistence of ETN/SB4 in a multi-iRMD cohort derived from two rheumatology departments in our region.

Methods: Adult patients with iRMDs, treated with ETN for at least 6 months and switched to SB4 in stable clinical condition, were eligible for this retrospective evaluation. Retrospective data on adverse events, loss of efficacy and persistence on treatment were collected until latest available follow-up.

Results: A total of 220 patients (85 RA, 81 PsA, 33 axSpA, 14 juvenile idiopathic arthritis and seven other conditions; 142 females, mean age 58 ± 7 years, disease duration 12 ± 4 years, ETN duration 7 ± 4 years) were enrolled, with median follow-up of 12.1 (9.7-15.8) months. A total of 50 patients (22.7%) presented with at least one adverse event, with 36 (16.4%) disease flares and 30 (13.6%: 11 for safety and 19 loss of efficacy) SB4 withdrawals. Cumulative SB4 treatment persistence was 99.1%, 88.6% and 64.6% at 6, 12 and 18 months respectively. Back-switch to ETN was performed in 17/30 cases, the remaining cases were managed with change of biologic disease modifying or conventional synthetic anti-rheumatic drug. Age was the only significant predictor of SB4 interruption at 6 months.

Conclusion: Our real-life data confirm the safety profile of switching from ETN to SB4, with slightly higher treatment persistence rates compared with other real-life registries.
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http://dx.doi.org/10.1177/1759720X20964031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576915PMC
October 2020

Low bone mass and hypovitaminosis D in haemophilia: A single-centre study in patients with severe and moderate haemophilia A and B.

Haemophilia 2020 Sep 25;26(5):898-906. Epub 2020 Aug 25.

Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Firenze, Italy.

Introduction: Haemophilia (H) is frequently associated with a multifactorial reduction in bone mineral density (BDM), but little is known about possible differences between HA and HB according to their severity.

Aim: To evaluate the association between low bone mineral density (BMD), 25-hydroxyvitamin D [25(OH)D] concentrations and bone turnover markers in patients with HA and HB younger or older than 50 years.

Methods: In 78 patients <50 years and 33 patients >50 years with severe (S) or moderate (M) HA and HB, BMD was measured by dual-energy X-ray absorptiometry at femoral neck (FN) and lumbar spine and then correlated to annual bleeding rate (ABR), World Federation of Haemophilia orthopaedic joint scale (WFH score), 25(OH)D concentrations, parathyroid hormone (PTH), amino-terminal telopeptide of type 1 collagen (NTx), urinary pyridinolines, osteocalcin and bone-specific alkaline phosphatase.

Results: Overall, a high prevalence of hypovitaminosis D was diagnosed. In patients <50 years, low FN-BMD was significantly more frequent in HA than in HB, while PTH, pyridinolines, ABR and WFH score were associated with H type and severity. In patients >50 years, similarly low FN-BMD was observed in HA and HB, while ABR and WFH score were associated with H type and severity, being milder in HB.

Conclusions: Low bone mass is a frequent comorbidity in haemophilic patients of all ages, apart from those with MHB. Clinical and laboratory assessments confirm a higher bone impairment and faster bone resorption in HA compared with HB. Looking at H type and severity, MHB seems to have a normal bone metabolism and a less severe disease.
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http://dx.doi.org/10.1111/hae.14127DOI Listing
September 2020

Use of Guselkumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: A 1 Year Real-Life Study.

J Clin Med 2020 Jul 9;9(7). Epub 2020 Jul 9.

Dermatology Unit, Fondazione Policlinico, "Tor Vergata", 00133 Rome, Italy.

Little information is available from real-life studies evaluating the efficacy of guselkumab in moderate-to-severe psoriasis. In this real-life study, we retrospectively examined a database of 52 patients with moderate-to-severe psoriasis treated with guselkumab (100 mg, s.c.) and followed for 1 year. Disease severity and treatment response was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 4, 12, 20, 28, 36, 44, and 52 weeks. Predictors of a PASI response were evaluated by univariate and multivariate regression. After 12 months, 84.2% of patients (mean age 51.3 ± 14.1 years) treated with guselkumab achieved a PASI score of <3. Furthermore, PASI score decreased from 20 ± 13.3 at baseline to 4.4 ± 4.7 and 2.7 ± 3.9 at 12 and 20 weeks, and PASI 75, 90, and 100 response was achieved in 84.2%, 78.9%, and 63.2% of patients respectively at 12 months. Stepwise multivariate regression analysis revealed that previous biological treatment and the presence of comorbidities were associated with poorer response between 28-44 weeks, however the presence of obesity was not associated with poorer response. Difficult-to-treat areas were also improved as early as 12 weeks following guselkumab. Guselkumab was observed to be effective and safe in patients with moderate-severe chronic psoriasis in a real world-setting.
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http://dx.doi.org/10.3390/jcm9072170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408922PMC
July 2020

The relationship between intra-parenchymal renal resistive index variation and renal functional reserve in healthy subjects.

J Nephrol 2021 Apr 29;34(2):403-409. Epub 2020 Jun 29.

Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute Vicenza (IRRIV), San Bortolo Hospital, Vicenza, Italy.

Background: Renal functional reserve can be used as a clinical tool for risk stratification of patients undergoing potentially nephrotoxic procedures. Ultrasound assessment of intra-parenchymal renal resistive index variation-IRRIV test-has been recently proposed as a safe, reproducible, inexpensive and easy to perform technique to identify the presence of renal functional reserve. The present study has been designed to externally validate the IRRIV test in a validation cohort of healthy subjects.

Methods: We examined data from a group of 47 healthy subjects undergoing protein loading and IRRIV testing. The correlation between IRRIV and renal functional reserve was tested using Pearson correlation analysis. Concordance between presence of renal functional reserve (i.e. a value of renal functional reserve ≥ 15 ml/min/1.73 m) and IRRIV was evaluated using logistic regression analysis.

Results: We found a significant correlation between IRRIV and renal functional reserve (Pearson correlation coefficient = 0.83 [95% confidence interval (CI) 0.71-0.90; p < 0.01]). Concordance between the presence of renal functional reserve and the IRRIV test was described in 45 (95.7%) subjects. In particular, a negative IRRIV test correctly predicted the absence of renal functional reserve in 5 subjects, while a positive IRRIV test correctly predicted the presence of renal functional reserve in 40 subjects. Only two subjects were incorrectly classified by the IRRIV test. IRRIV predicts renal functional reserve with a ROC-AUC of 0.86 [CI 95% 0.68-1].

Conclusions: The IRRIV test is an ultrasound technique that significantly predicts the presence and the degree of renal functional reserve in healthy subjects.
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http://dx.doi.org/10.1007/s40620-020-00786-1DOI Listing
April 2021

Efficacy and safety of switching from reference adalimumab to SB5 in a real-life cohort of inflammatory rheumatic joint diseases.

Clin Rheumatol 2021 Jan 8;40(1):85-91. Epub 2020 Jun 8.

Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Firenze, Via delle Oblate 4, 50141, Florence, Italy.

Objective: SB5 showed comparable efficacy and safety profile in respect to adalimumab originator (ADA) in randomized clinical trials of rheumatoid arthritis (RA) and psoriasis. We aimed to describe the efficacy and safety of SB5 after switching from ADA in RA, axial spondyloarthritis (axSpA), psoriatic arthritis (PsA) and juvenile idiopathic arthritis (JIA) patients.

Method: Adult RA, PsA, axSpA, JIA patients treated with ADA for at least 6 months, switched to SB5 in stable clinical conditions, were eligible. Data on safety, activity indexes and patient-reported outcomes were collected at baseline, 3 and 6 months after switching.

Results: Eighty-two patients (19 RA, 28 PsA, 32 axSpA and 3 JIA; 45 females, mean age 54 ± 14 years, disease duration 13 ± 7 years, ADA duration 6 ± 3 years) were enrolled. RA patients showed stable conditions, while PsA patients showed an increase in both HAQ, DAS28(CRP) and DAPSA and axSpA patients an increase in VAS pain, VAS patient disease activity and ASDAS, both at 3 months. There were changes in the concomitant medications profile, with regression of activity indexes increases at 6 months. Adverse events were reported by 33.7% patients at 3 months and 16.6% patients at 6 months, mostly disease flares and infectious events. Two patients stopped SB5.

Conclusions: Despite temporary changes in the concomitant medication profile for mild disease flares, our real-life data replicate the safety profile of switching from ADA to SB5 in RA, with additional data for its applicability in PsA and axSpA patients, further supporting switching to biosimilars in treating inflammatory rheumatic conditions. Key Points • Switching from adalimumab originator to SB5 is feasible in real life rheumatic inflammatory joint diseases. • Mild disease flares can present after switching from originator adalimumab to SB5, in particular in axial spondyloarthritis and psoriatic arthritis. • Changes in concomitant medications profile allows the control of minor disease flares presenting after switching from adalimumab originator to SB5.
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http://dx.doi.org/10.1007/s10067-020-05199-wDOI Listing
January 2021

Status of a real-life cohort of patients with moderate-to-severe plaque psoriasis treated with secukinumab and considerations on the use of biological agents in the Covid-19 era.

Expert Opin Biol Ther 2020 08 16;20(8):829-830. Epub 2020 Jun 16.

Dermatology Unit, Fondazione Policlinico Tor Vergata , Rome, Italy.

Introduction: In light of the current Covid-19 pandemic and the ongoing, extensive debate about the use of biological agents in psoriatic patients, we felt compelled to relate our experience in the use of secukinumab in the same cohort before and during the lockdown in Italy. : Secukinumab was not discontinued, and there were no cases of confirmed infection with SARS-CoV-2 in this cohort. : In our practice, there is no evidence favoring the discontinuation of secukinumab in these patients. We also present a brief commentary on the use of biological agents in patients with moderate-to-severe plaque psoriasis.
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http://dx.doi.org/10.1080/14712598.2020.1779217DOI Listing
August 2020

Effect of Dysmetabolisms and Comorbidities on the Efficacy and Safety of Biological Therapy in Chronic Inflammatory Joint Diseases.

J Clin Med 2020 May 2;9(5). Epub 2020 May 2.

Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, Via delle Oblate 4, 50141 Florence, Italy.

In the present study we evaluated how systemic arterial hypertension (SAH), dyslipidemia and diabetes mellitus influence the efficacy, safety and retention rate of biological disease-modifying anti-rheumatic drug (bDMARD) treatment in rheumatic musculoskeletal disorders (RMDs). The charts of RMD patients treated with the first-line bDMARD were reviewed, collecting data on safety, efficacy and comorbidities at prescription (baseline, BL), after 6 months (6M) and at last observation on bDMARD (last observation time, LoT). In 383 RMD patients, a higher rate of adverse events at 6M ( = 0.0402) and at LoT ( = 0.0462) was present in dyslipidemic patients. Patients who developed dyslipidemia or SAH during bDMARD treatment had similar results (dyslipidemia = 0.0007; SAH = 0.0319) with a longer bDMARD retention as well (dyslipidemia < 0.0001; SAH < 0.0001). SAH patients on angiotensin converting enzyme inhibitors (ACEis) or angiotensin-II receptor blockers (ARBs) continued bDMARDs for longer than non-exposed patients ( = 0.001), with higher frequency of drug interruption for long-standing remission rather than inefficacy or adverse reactions ( = 0.0258). Similarly, dyslipidemic patients on statins had a better bDMARD retention than not-exposed patients ( = 0.0420). In conclusion, SAH and dyslipidemia may be associated with higher frequency of adverse events but a better drug retention of first-line bDMARD in RMDs, suggesting an additional effect of ACEis/ARBs or statins on the inflammatory process and supporting their use in RMD bDMARD patients with SAH/dyslipidemia.
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http://dx.doi.org/10.3390/jcm9051310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290363PMC
May 2020

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL).

Br J Cancer 2020 07 29;123(1):26-32. Epub 2020 Apr 29.

Medical Oncology Unit, Policlinico Sant'Orsola-Malpighi, Bologna, Italy.

Background: Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC.

Methods: In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).

Results: Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months).

Conclusions: Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met.

Clinical Trial Registration: Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.
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http://dx.doi.org/10.1038/s41416-020-0845-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341887PMC
July 2020

Inappropriate use of carbapenems in an internal medicine ward: Impact of a carbapenem-focused antimicrobial stewardship program.

Eur J Intern Med 2020 08 14;78:50-57. Epub 2020 Apr 14.

Department of Internal Medicine, San Giovanni di Dio Hospital, Via di Torregalli 3, Florence, 50143, Italy.

Purpose: Carbapenem consumption is a major driver for selection and spread of carbapenem-resistant Enterobacterales (CRE). We assessed the impact of a carbapenem-focused multimodal antimicrobial stewardship program (ASP) in the internal medicine unit of a medium-size acute-care hospital.

Methods: We compared the percentage of inappropriate carbapenem prescriptions and the proportion of carbapenem treated patients registered in a 12-month pre-intervention and in a 24-month post-intervention period by using an interrupted time series analysis. The consumption of carbapenems, expressed in defined daily doses (DDD), was also assessed. As a secondary objective, the incidence of infections by carbapenem-resistant Klebsiella pneumoniae (CRKP) and the percentage of CRKP invasive isolates in the same time periods were compared.

Results: After the ASP intervention, the mean monthly percentage of inappropriate carbapenem prescriptions dropped from 59% to 25%, and the mean monthly proportion of carbapenem treated patients decreased from 3% to 1%. The interrupted time series analysis confirmed a significant decrease in the percentage of inappropriate carbapenem prescriptions (-41.6%, p = 0.0262) and in the proportion of carbapenem treated patients (-2.1%, p < 0.0001). Carbapenem consumption decreased from 5.2 to 1.6 DDD x 100 patient-days. The incidence of CRKP infections remained unchanged (29.1 × 100,000 patient-days vs 28.9 × 100,000 patient-days, p = 0.9864) and the percentage of CRKP invasive isolates decreased, though not significantly, from 36.4% to 13.3% (p = 0.3478).

Conclusions: The implementation of a carbapenem-focused ASP was effective at limiting the inappropriate use of carbapenems and was associated with a significant decrease in carbapenem consumption. Such effects were sustained during a 24-month post-intervention period.
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http://dx.doi.org/10.1016/j.ejim.2020.03.017DOI Listing
August 2020

Sleep duration and architecture in non-intubated intensive care unit patients: an observational study.

Sleep Med 2020 06 18;70:79-87. Epub 2019 Dec 18.

Department of Cardiology and Cardiac Surgery, Pediatric Cardiac Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Objective/background: Sleep disturbances are very common and associated with severe complications in patients admitted to intensive care units (ICU). Commonly, sedatives like propofol or benzodiazepines have been demonstrated to increase sleep duration but worsen sleep architecture. Dexmedetomidine seems to positively affect both sleep aspects.

Patients/methods: The present study aimed to investigate sleep characteristics in non-intubated patients admitted to intensive care unit. The subgroups consisted of those without sedation (NO-DEX), and those which received dexmedetomidine infusion (DEX), titrated to a Richmond Agitation-Sedation Scale target of -1/-2, were also explored. An auto-staged electroencephalographer was used to measure sleep duration and architecture. The Richard-Campbell-Sleep questionnaire was administered to all patients.

Results: A multivariate analysis conducted in the overall population showed that dexmedetomidine infusion was the only variable independently associated with N2 increase (p < 0.001). DEX (n = 36) versus NO-DEX (n = 36) group showed longer N2 stage [68.9% (57.5-80.9) versus 49.5% [35.7-61.4]; p < 0.0003]; longer Total Sleep Time [6.5 h (5.7-7.7) versus 3.4 h (1.8-4.9); p < 0.0001, and higher Sleep Efficiency [84.2% (71.3-92.6) versus 47.7% (23.4-60.9); p < 0.0001]; shorter N1 (percentage of Total Sleep Time) [10.5% (7.8-20.0) and 38.8% (25.6-50.3); p < 0.0001]; longer N3 stage [13.6% (1.9-23.3) versus 4.3% (0.4-14.0); p = 0.058]; fewer Cortical Arousals [15 episodes/hour (8.1-24.6) versus 48.7 episodes/hour (29.7-80.4); p < 0.0001]. The questionnaire showed better values in DEX-group in all explored items (p < 0.0001).

Conclusions: Abnormal sleep is common in intensive care unit patients who have not received sedation. Dexmedetomidine, titrated to reach an appropriate sedation level, may optimize sleep duration and architecture.
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http://dx.doi.org/10.1016/j.sleep.2019.11.1265DOI Listing
June 2020

Neuroprotection induced by dexpramipexole delays disease progression in a mouse model of progressive multiple sclerosis.

Br J Pharmacol 2020 07 18;177(14):3342-3356. Epub 2020 Apr 18.

Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.

Background And Purpose: Drugs able to counteract progressive multiple sclerosis (MS) represent a largely unmet therapeutic need. Even though the pathogenesis of disease evolution is still obscure, accumulating evidence indicates that mitochondrial dysfunction plays a causative role in neurodegeneration and axonopathy in progressive MS patients. Here, we investigated the effects of dexpramipexole, a compound with a good safety profile in humans and able to sustain mitochondria functioning and energy production, in a mouse model of progressive MS.

Experimental Approach: Female non-obese diabetic mice were immunized with MOG . Functional, immune and neuropathological parameters were analysed during disease evolution in animals treated or not with dexpramipexole. The compound's effects on bioenergetics and neuroprotection were also evaluated in vitro.

Key Results: We found that oral treatment with dexpramipexole at a dose consistent with that well tolerated in humans delayed disability progression, extended survival, counteracted reduction of spinal cord mitochondrial DNA content and reduced spinal cord axonal loss of mice. Accordingly, the drug sustained in vitro bioenergetics of mouse optic nerve and dorsal root ganglia and counteracted neurodegeneration of organotypic mouse cortical cultures exposed to the adenosine triphosphate-depleting agents oligomycin or veratridine. Dexpramipexole, however, was unable to affect the adaptive and innate immune responses both in vivo and in vitro.

Conclusion And Implication: The present findings corroborate the hypothesis that neuroprotective agents may be of relevance to counteract MS progression and disclose the translational potential of dexpramipexole to treatment of progressive MS patients as a stand-alone or adjunctive therapy.
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http://dx.doi.org/10.1111/bph.15058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312322PMC
July 2020

Validation of END-of-life ScorING-system to identify the dying patient: a prospective analysis.

BMC Anesthesiol 2020 03 9;20(1):63. Epub 2020 Mar 9.

Section of Anesthesiology, Intensive Care and Pain Therapy, Departmnt of Health Sciences, University of Florence, Florence, Italy.

Background: The "END-of-Life ScorING-System" (ENDING-S) was previously developed to identify patients at high-risk of dying in the ICU and to facilitate a practical integration between palliative and intensive care. The aim of this study is to prospectively validate ENDING-S in a cohort of long-term critical care patients.

Materials And Methods: Adult long-term ICU patients (with a length-of-stay> 4 days) were considered for this prospective multicenter observational study. ENDING-S and SOFA score were calculated daily and evaluated against the patient's ICU outcome. The predictive properties were evaluated through a receiver operating characteristic (ROC) analysis.

Results: Two hundred twenty patients were enrolled for this study. Among these, 21.46% died during the ICU stay. ENDING-S correctly predicted the ICU outcome in 71.4% of patients. Sensitivity, specificity, positive and negative predictive values associated with the previously identified ENDING-S cut-off of 11.5 were 68.1, 72.3, 60 and 89.3%, respectively. ROC-AUC for outcome prediction was 0.79 for ENDING-S and 0.88 for SOFA in this cohort.

Conclusions: ENDING-S, while not as accurately as in the pilot study, demonstrated acceptable discrimination properties in identifying long-term ICU patients at very high-risk of dying. ENDING-S may be a useful tool aimed at facilitating a practical integration between palliative, end-of-life and intensive care.

Trial Registration: Clinicaltrials.gov Identifier: NCT02875912; First registration August 4, 2016.
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http://dx.doi.org/10.1186/s12871-020-00979-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068991PMC
March 2020

hERG1 and HIF-2α Behave as Biomarkers of Positive Response to Bevacizumab in Metastatic Colorectal Cancer Patients.

Transl Oncol 2020 Mar 25;13(3):100740. Epub 2020 Feb 25.

Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address:

Background: In search of novel biomarkers of response to bevacizumab in metastatic colorectal cancer (mCRC), we analyzed the expression and prognostic role of several proteins related to angiogenesis.

Methods: A retrospective, multicenter study on 80 surgical samples from mCRC patients treated in first line with bevacizumab plus chemotherapy was accomplished. The following proteins were analyzed by immunohistochemistry: hERG1 potassium channel, β1-integrin, pAKT, NFkB, HIF-1α, HIF-2α, p53, VEGF-A, GLUT-1, and CA-IX. Data were analyzed in conjunction with the clinicopathological characteristics of the patients, KRAS status, response to bevacizumab, and follow-up.

Results: (1) All the proteins were expressed in the samples, with statistically significant associations between HIF-1α and gender, HIF-2α and left colon, hERG1 and VEGF-A, β1-integrin and HIF-2α, GLUT-1 and both HIF-1α and HIF-2α, and CA-IX and VEGF-A. (2) At the univariate analysis, positivity for hERG1, VEGF-A, and the active form of HIF-2α (aHIF-2α), and the G3 histological grade showed a positive impact on progression-free survival (PFS). (3) hERG1 and aHIF-2α maintained their positive impact on PFS at the multivariate analysis. (4) hERG1 behaved as a protective factor for PFS independently on KRAS status.

Conclusions: hERG1 and aHIF-2α might help to identify patients who would benefit from bevacizumab treatment.
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http://dx.doi.org/10.1016/j.tranon.2020.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044526PMC
March 2020

Ultra-rapid brain uptake of subcutaneous sumatriptan in the rat: Implication for cluster headache treatment.

Cephalalgia 2020 04 18;40(4):330-336. Epub 2019 Dec 18.

Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.

Background: In spite of the substantial therapeutic efficacy of triptans, their site of action is still debated. Subcutaneous sumatriptan is the most efficacious symptomatic treatment for cluster headache (CH) patients, showing therapeutic onset within a few minutes after injection even in migraine patients. However, whether subcutaneous sumatriptan is able to reach the CNS within this short time frame is currently unknown.

Methods: Here, by means of liquid chromatography/mass spectrometry, we investigated peripheral and brain distribution of subcutaneous sumatriptan soon after injection in rats at a dose equivalent to that used in patients. Tissue sumatriptan contents were compared to those of oxazepam, a prototypical lipophilic, neuroactive drug.

Results: We report that sumatriptan accumulated within brain regions of relevance to migraine and CH pathogenesis such as the hypothalamus and the brainstem as soon as 1 and 5 minutes after injection. Notably, sumatriptan brain distribution was faster than that of oxazepam, reaching concentrations exceeding its reported binding affinity for 5HT1 receptors, and in the range of those able to inhibit neurotransmitter release .

Conclusion: Our findings indicate that sumatriptan distributes within the CNS soon after injection, and are in line with prompt pain relief by parenteral sumatriptan in CH patients.
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http://dx.doi.org/10.1177/0333102419896370DOI Listing
April 2020

Magnetic nanoantioxidants with improved radical-trapping stoichiometry as stabilizers for inhibition of peroxide formation in ethereal solvents.

Sci Rep 2019 11 20;9(1):17219. Epub 2019 Nov 20.

Department of Chemistry "G. Ciamician", University of Bologna, Via S. Giacomo 11, 40126, Bologna, Italy.

Graphite-coated magnetic cobalt nanoparticles (CoNPs) decorated with hindered phenolic antioxidant analogues of 2,6-di-tert-butyl-4-methylphenol (BHT, E321) provided easily removable nanoantioxidants capable of preventing the autoxidation of organic solvents as tetrahydrofuran (THF).
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http://dx.doi.org/10.1038/s41598-019-53531-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868006PMC
November 2019

Intraoperative core temperature monitoring: accuracy and precision of zero-heat flux heated controlled servo sensor compared with esophageal temperature during major surgery; the ESOSPOT study.

J Clin Monit Comput 2020 Oct 31;34(5):1111-1119. Epub 2019 Oct 31.

Department of Anesthesia and Intensive Care, Careggi University Hospital, Florence, Italy.

Monitoring of intraoperative core temperature is strongly recommended to reduce the risk of perioperative thermic imbalance and related complications. The zero-heat-flux sensor (3M Bair Hugger Temperature monitoring system, ZHF), measures core temperature in a non-invasive manner. This study was aimed at comparing accuracy and precision of the ZHF sensor compared to the esophageal thermometer. Patients scheduled for major elective abdominal or urologic surgery were considered eligible for enrollment. Core body temperature was measured using both an esophageal probe (T) and a ZHF sensor (T) every 15 min from induction until the end of general anaesthesia. A Bland-Altman plot for repeated measures was performed. The proportion of measurements within ± 0.5 °C was estimated; from a clinical point of view, a proportion greater than 90% was considered sufficiently accurate. Lin's concordance correlation coefficient (CCC) for repeated measures were calculated. To evaluate association between the two methods, a generalized estimating equation (GEE) simple linear regression model, was elaborated. A GEE multiple regression model was also performed in order to adjust the estimate of the association between measurements from surgical and patient's features. Ninety-nine patients were enrolled. Bland-Altman plot bias was 0.005 °C with upper and lower limits of agreement for repeated measures of 0.50 °C and - 0.49 °C. The percentage of measurements within 0.5 °C of the reference value was 97.98% (95% confidence interval 92.89-99.75%), indicating a clinically sufficient agreement between the two methods. This was also confirmed by a CCC for repeated measures of 0.89 (95% CI 0.80 to 0.94). The GEE simple regression model (slope value of 0.77) was not significantly influenced by any patient or surgical variables. According to GEE multiple regression model results, the explored patient- and surgery-related variables did not influence the association between methods. ZHF sensor has shown a clinically acceptable accuracy and precision for body core temperature monitoring during elective major surgery. CLINICAL TRIALS: Clinical trial number: NCT03820232.
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http://dx.doi.org/10.1007/s10877-019-00410-zDOI Listing
October 2020

Corrigendum to "Evaluation of sexual function in women with deep infiltrating endometriosis" [Sex. Reprod. Healthcare 16 (2018) 6-9].

Sex Reprod Healthc 2019 Oct 17;21:109. Epub 2018 Mar 17.

Department of Biomedical, Experimental and Clinical Sciences - Division of Obstetrics and Gynecology, University of Florence, Italy.

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http://dx.doi.org/10.1016/j.srhc.2018.03.004DOI Listing
October 2019

Comparison of neostigmine vs. sugammadex for recovery of muscle function after neuromuscular block by means of diaphragm ultrasonography in microlaryngeal surgery: A randomised controlled trial.

Eur J Anaesthesiol 2020 Jan;37(1):44-51

From the Department of Health Sciences, Azienda Ospedaliero Universitaria Careggi (IC, DO, BL, ARDG, CA) and Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy (LT).

Background: Postoperative residual curarisation (PORC) is a risk directly related to the use of neuromuscular blocking agents during surgical procedures. Acceleromyography is distressing for conscious patients when assessing PORC. Diaphragm ultrasonography could be a valid alternative.

Objectives: The primary objective was to achieve a 28% lower incidence of PORC in patients who, after rocuronium administration, received neostigmine or sugammadex at 30 min after surgery. To assess PORC, diaphragm ultrasonography was used, and thickening fractioning [the difference of thickness at the end of inspiration (TEI) and at the end of expiration (TEE), normalised for TEE (TEI - TEE/TEE)] was measured. PORC was defined as thickening fractioning of 0.36 or less. The secondary object was the comparison, in the two treatment groups, of the return to baseline thickening fractioning at 30 min after surgery (ΔTF30).

Design: Randomised, double-blind, single-centre study.

Setting: University Hospital Careggi, Florence, Italy.

Patients: Patients of American Society Anesthesiologists' physical status 1 or 2, 18 to 80 years, receiving rocuronium during microlaryngeal surgery.

Interventions: At the end of surgery participants were randomised to receive neostigmine (NEO group) or sugammadex (SUG group) as the reversal drug. Thickening fractioning and ΔTF30 were evaluated at baseline and at 0, 10 and 30 min after surgery.

Main Outcome Measures: TEE and TEI at each time point.

Results: A total of 59 patients with similar demographic characteristics were enrolled. An association between lack of recovery (thickening fractioning ≤0.36) and drug treatment was only observed at 0 min (SUG vs. NEO, P < 0.05). Concerning ΔTF, at 30 min more patients in the SUG group returned to baseline than those in the NEO group (P < 0.001), after adjusting for side (P = 0.52), baseline thickening fractioning (P < 0.0001) and time of measurement (P < 0.01).

Conclusion: We found an early (0 min) but not long-lasting (30 min) association between diaphragm failure and treatment allocation; a full recovery in baseline diaphragm function was observed only in patients receiving sugammadex. We cannot exclude that further differences have not been found due to interpatients variability in assessing diaphragm contractility by ultrasonography.

Trial Registration: EudraCT Identifier: 2013-004787-62, Clinicaltrials.gov Identifier: NCT02698969.
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http://dx.doi.org/10.1097/EJA.0000000000001055DOI Listing
January 2020

In-line filtration reduced phlebitis associated with peripheral venous cannulation: Focus on cost-effectiveness and patients' perspectives.

J Vasc Access 2020 Mar 26;21(2):154-160. Epub 2019 Jul 26.

Department of Health Sciences, Section of Anesthesia, Intensive Care and Pain Medicine, University of Florence, Florence, Italy.

Background: In a previous trial, in-line filtration significantly prevented postoperative phlebitis associated with short peripheral venous cannulation. This study aims to describe the cost-effectiveness of in-line filtration in reducing phlebitis and examine patients' perception of in-hospital vascular access management with and without in-line filtration.

Methods: We analysed costs associated with in-line filtration: these data were prospectively recorded during the previous trial. Furthermore, we performed a follow-up for all the 268 patients enrolled in this trial. Among these, 213 patients responded and completed 6 months after hospital discharge questionnaires evaluating the perception of and satisfaction with the management of their vascular access.

Results: In-line filtration group required 95.60€ more than the no-filtration group (a mean of € 0.71/patient). In terms of satisfaction with the perioperative management of their short peripheral venous cannulation, 110 (82%) and 103 (76.9%) patients, respectively, for in-line filtration and control group, completed this survey. Within in-line filtration group, 97.3% of patients were satisfied/strongly satisfied; if compared with previous experiences on short peripheral venous cannulation, 11% of them recognised in-line filtration as a relevant causative factor in determining their satisfaction. Among patients within the control group, 93.2% were satisfied/strongly satisfied, although up to 30% of them had experienced postoperative phlebitis. At the qualitative interview, they recognised no difference than previous experiences on short peripheral venous cannulation, and mentioned postoperative phlebitis as a common event that 'normally occurs' during a hospital stay.

Conclusion: In-line filtration is cost-effective in preventing postoperative phlebitis, and it seems to contribute to increasing patient satisfaction and reducing short peripheral venous cannulation-related discomfort.
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http://dx.doi.org/10.1177/1129729819861187DOI Listing
March 2020

A Cross-Sectional Study on 3-(2-Deoxy-β-D-Erythro-Pentafuranosyl)Pyrimido[1,2-α]Purin-10(3H)-One Deoxyguanosine Adducts among Woodworkers in Tuscany, Italy.

Int J Mol Sci 2019 Jun 5;20(11). Epub 2019 Jun 5.

Cancer Factor Risk Branch, Regional Cancer Prevention Laboratory, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy.

Occupational exposure to wood dust has been estimated to affect 3.6 million workers within the European Union (EU). The most serious health effect caused by wood dust is the nasal and sinonasal cancer (SNC), which has been observed predominantly among woodworkers. Free radicals produced by inflammatory reactions as a consequence of wood dust could play a major role in SNC development. Therefore, we investigated the association between wood dust and oxidative DNA damage in the cells of nasal epithelia, the target site of SNC. We have analyzed oxidative DNA damage by determining the levels of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (MdG), a major-peroxidation-derived DNA adduct and a biomarker of cancer risk in 136 woodworkers compared to 87 controls in Tuscany, Italy. We then examined the association of MdG with co-exposure to volatile organic compounds (VOCs), exposure length, and urinary 15-F isoprostane (15-F-IsoP), a biomarker of oxidant status. Wood dust at the workplace was estimated by the Information System for Recording Occupational Exposures to Carcinogens. MdG was measured using P-postlabeling and mass spectrometry. 15-F-IsoP was analyzed using ELISA. Results show a significant excess of MdG in the woodworkers exposed to average levels of 1.48 mg/m relative to the controls. The overall mean ratio (MR) between the woodworkers and the controls was 1.28 (95% C.I. 1.03-1.58). After stratification for smoking habits and occupational status (exposure to wood dust alone and co-exposure to VOCs), the association of MdG with wood dust (alone) was even greater in non-smokers workers, MR of 1.43 (95% C.I. 1.09-1.87). Conversely, not consistent results were found in ex-smokers and current smokers. MdG was significantly associated with co-exposure to VOCs, MR of 1.95 (95% C.I. 1.46-2.61), and occupational history, MR of 2.47 (95% C.I. 1.67-3.62). Next, the frequency of MdG was significantly correlated to the urinary excretion of 15-F-IsoP, regression coefficient (β) = 0.442 ± 0.172 (SE). Consistent with the hypothesis of a genotoxic mechanism, we observed an enhanced frequency of MdG adducts in woodworkers, even at the external levels below the regulatory limit. Our data implement the understanding of SNC and could be useful for the management of the adverse effects caused by this carcinogen.
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http://dx.doi.org/10.3390/ijms20112763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600535PMC
June 2019

Wood dust and urinary 15-F isoprostane in Italian industry workers.

Environ Res 2019 06 27;173:300-305. Epub 2019 Mar 27.

Cancer Factor Risk Branch, Regional Cancer Prevention Laboratory, ISPRO-Study, Prevention and Oncology Network Institute, 50139, Florence, Italy. Electronic address:

Wood dust is one of the most common occupational exposures, with about 3.6 million of workers in the wood industry in Europe. Wood particles can deposit in the nose and the respiratory tract and cause adverse health effects. Occupational exposure to wood dust has been associated with malignant tumors of the nasal cavity and paranasal sinuses. The induction of oxidative stress and the generation of reactive oxygen species through activation of inflammatory cells could have a role in the carcinogenicity of respirable wood dust. Therefore, we conducted a cross-sectional study to evaluate the prevalence of urinary 15-F isoprostane (15-F-IsoP), a biomarker of oxidative stress and peroxidation of lipids, in 123 wood workers compared to 57 unexposed controls living in Tuscany region, Italy. 15-F-IsoP generation was measured by ELISA. The main result of the present study showed that a statistically significant excess of this biomarker occurred in the workers exposed to 1.48 mg/m of airborne wood dust with respect to the unexposed controls. The overall mean ratio (MR) between the workers exposed to wood dust and the controls was 1.36, 95% Confidence Interval (C.I.) 1.18-1.57, after correction for age and smoking habits. A significant increment of 15-F-IsoP (43%) was observed in the smokers as compared to the non-smokers. The urinary excretion of 15-F-IsoP was significantly associated with co-exposure to organic solvents, i.e., MR of 1.41, 95% C.I. 1.17-1.70, after adjustment for age and smoking habits. A 41% excess was observed in long-term wood workers, 95% C.I. 1.14-1.75. Multivariate regression analysis showed that the level of 15-F-IsoP was linearly correlated to the length of exposure, regression coefficient (β) = 0.244 ± 0.002 (SE). The overall increment by exposure group persisted after stratification for smoking habits. For instance, in smokers, a 53% excess was detected in the wood workers as compared to the controls, 95% C.I. 1.23-1.91. Our data support the hypothesis that oxidative stress and lipid peroxidation can have a role in the toxicity of wood dust F-IsoP measure can be a tool for the evaluation of the effectiveness of targeted interventions aimed to reduce exposures to environmental carcinogens.
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http://dx.doi.org/10.1016/j.envres.2019.03.058DOI Listing
June 2019

The clinical relevance of multiple DPYD polymorphisms on patients candidate for fluoropyrimidine based-chemotherapy. An Italian case-control study.

Br J Cancer 2019 04 12;120(8):834-839. Epub 2019 Mar 12.

Medical Oncology Unit, Clinical Cancer Centre, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Background: Deleterious polymorphisms in the gene encoding DPD (DPYD) may result in severe reduction of DPD enzymatic activity that causes life-threatening toxicities when the standard dose of fluorouracil is used. The best panel of single-nucleotide polymorphism (SNPs) of DPYD is not well defined.

Methods: In 2011, we began screening DPYD*2A in patients candidate for fluoropyrimidine-based chemotherapy. We planned a case-control study with all cases of DPYD*2A wild type who developed toxicity ≥G3 and with a cohort of patients who did not present severe toxicities. Then, we tested the additional SNPs: c.2846A>T, c.1679T>G, c.2194G>A.

Results: From 2011 to 2016, we screened 1827 patients for DPD deficiency; of those, 31 subjects (1.7%) showed DPYD*2A SNP. We selected 146 subjects who developed severe toxicities (Cases) and 220 patients who experienced no or mild toxicities (Controls); 53 patients carried one of the additional SNPs: 35 subjects (66%) fell into the Cases and 18 (34%) into the Controls (p < 0.0001). c.2194G>A was the most frequent SNP (12.5%) and showed a correlation with neutropenia. We confirmed that c.2846A>T and c.1679T>G were related to various toxicities.

Conclusions: The additional DPYD polymorphisms could enhance the prevention of fluoropyrimidine toxicity. c.2194G>A is the most frequent polymorphism and it was found to be associated with neutropenia.
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http://dx.doi.org/10.1038/s41416-019-0423-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474277PMC
April 2019

Placental Circulation Intact Trial (PCI-T)-Resuscitation With the Placental Circulation Intact vs. Cord Milking for Very Preterm Infants: A Feasibility Study.

Front Pediatr 2018 27;6:364. Epub 2018 Nov 27.

Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital of Florence, Florence, Italy.

Preterm newborns receiving briefly delayed cord clamping or cord milking at birth have better neonatal outcomes. However, the time frame in which both these procedures are performed (< 60 s of life) is too short to explore the possible beneficial effects on early infant postnatal adaptation and outcomes of a prolonged transfusion strategy associated with neonatal respiration. We have designed a randomized, multicenter, controlled two-phase study: phase 1 to assess the feasibility of carrying out the protocol in a large randomized trial, and phase 2 to assess the efficacy of bedside assistance with intact placental circulation for 3 min in comparison to cord milking to improve outcome in the neonatal period; we present here the feasibility and safety phase of the study. Outcomes included feasibility (recruitment rate of two patients per month, compliance with the trial interventions, completeness of data collection, >90% of infants receiving echographic assessments in the first 24 h) and safety variables (5 min Apgar score, delivery room intubation rate, CRIB II score, admission temperature, maximum hemoglobin concentration and hematocrit in the first 24 h and maximum serum bilirubin value) in the two study groups. We also evaluated the same safety variables in infants delivered during the study period but not recruited. A total of 40 infants were enrolled. In all cases the protocol was completed and all feasibility outcomes were reached. Infants assisted with an intact placental circulation have a higher 5 min Apgar score but their admission temperature was lower than milked infants. Delivery room intubation rate, CRIB II score and peak serum bilirubin value were comparable in both groups. Infants who were not subjected to a placental transfusion strategy (excluded patients) had a higher delivery room intubation rate with respect to both study groups. Delaying cord clamping until 3 min of life was challenging but feasible and appeared to be safe. However, admission temperature must be strictly monitored and a more efficacious warming system could be implemented to prevent hypothermia during the procedure. Clinicaltrials,gov NCT02671305 (date of registration: 26 JAN 2016). https://clinicaltrials.gov/ct2/show/NCT02671305.
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http://dx.doi.org/10.3389/fped.2018.00364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277460PMC
November 2018

Postoperative pain after vitreo-retinal surgery is influenced by surgery duration and anesthesia conduction.

Minerva Anestesiol 2019 Jul 9;85(7):731-737. Epub 2018 Nov 9.

Section of Anesthesiology and Intensive Care, Department of Health Sciences, Careggi University Hospital, University of Florence, Florence, Italy.

Background: The control of postoperative pain (POP) is a key component of perioperative care. POP after vitreo-retinal surgery (VRS) has been under-investigated, and its incidence remains elusive.

Methods: In order to assess POP after VRS, the associated risk factors and efficacy of the analgesic protocol in use at our institution, we made a one-year retrospective study on patients undergoing VRS. Patients aged >18 years, ASA Class I-III undergoing VRS entered the study. POP was evaluated by measuring a Numerical Rating Scale (NRS), and analgesic consumption.

Results: A total of 782 patients entered the study. Patients received locoregional (LRA) or general anesthesia (GA) with supplemental block. Twenty-two percent of patients needed analgesics (acetaminophen in 97% of cases), mostly between two and six hours after surgery. The univariate analysis showed a positive association between POP and duration of surgery (P<0.0001) and glaucoma (P=0.04), and a negative association with age (P=0.008), analgesic administration at the end of surgery (P=0.005) and the intraoperative administration of remifentanil for surgery under LRA (P=0.02); sedation to execute the block for LRA did not reduce POP. Patients treated with GA with supplemental block had less pain compared to those treated with LRA with/without remifentanil (P=0.03, P=0.002, respectively). The multivariate analysis confirmed a positive correlation between POP and duration of surgery (P=0.0007) and a negative correlation with the intraoperative remifentanil administration during LRA (P=0.04), and with GA with supplemental block (P=0.01).

Conclusions: The incidence of POP after VRS is low but not absent, especially for long procedures, it does not require postoperative opioids and can be modified by anesthesiologic choices.
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http://dx.doi.org/10.23736/S0375-9393.18.13078-1DOI Listing
July 2019

Lung Ultrasound for the Differential Diagnosis of Respiratory Distress in Neonates.

Neonatology 2019 10;115(1):77-84. Epub 2018 Oct 10.

Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.

Background: Respiratory distress (RD) is the most common neonatal illness. Lung ultrasound (LUS) is a technique previously tested in neonatal studies on RD, but literature regarding its routine clinical applicability is still lacking.

Objective: To assess the concordance between LUS performed by neonatologists with different training levels and chest X-ray (CXR) for the diagnosis of RD in newborns during the first 24 h of life.

Methods: We enrolled newborns with RD during the first 24 h of life. Patients underwent LUS and CXR. LUS and CXR diagnosis were compared to evaluate concordance. Twenty percent of patients received two LUS (one from an experienced and one from a novice sonographer) to calculate the interobserver agreement. The difference in time needed to reach a diagnosis with LUS and CXR, and from novice and expert operators, was measured.

Results: We studied 124 patients; 134 diagnoses were reported. The concordance between LUS and CXR diagnosis was 91% (95% CI 86-96%) with a κ statistic of 0.88 (95% CI 0.81-0.94). The median time to diagnosis was shorter for LUS (9.5 min, IQR 5-15) than for CXR (50 min, IQR 33-64) (p < 0.0001). In 25/124 patients, LUS was performed by both novice and experienced sonographers with complete concordance. The median time to diagnosis was shorter for expert (9 min, IQR 5-15) than novice operators (15 min, IQR 10-20) (p < 0.0002).

Conclusion: LUS and CXR have a high concordance in the differential diagnosis of neonatal RD in the first 24 h of life. LUS has a shorter operation time than CXR.
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http://dx.doi.org/10.1159/000493001DOI Listing
December 2019

Repurposing of dexpramipexole to treatment of neonatal hypoxic/ischemic encephalopathy.

Neurosci Lett 2018 11 1;687:234-240. Epub 2018 Oct 1.

Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.

Dexpramipexole (DEX) is a drug with a good safety profile in humans, known for its ability to increase mitochondrial ATP production and prompt neuroprotection in adult rodents subjected to cerebral ischemia. In the present study we evaluated the effect of DEX in rat pups subjected to common carotid artery occlusion plus hypoxia (CCAoH, the classic Rice-Vannucci model). Because of the wide range of infarct size distribution in the CCAoH model, a priori subanalysis based on the effect of DEX on mild/moderate or severe brain injuries was conducted. The subanalysis showed that the drug (3 mg/kg bid i.p, after the hypoxic insult) decreased the infarction size in pups with mild/moderate injuries. Next, we developed a distal middle cerebral artery occlusion plus hypoxia (dMCAoH) model, characterized by an intra-experimental infarct size variability lower than that of the CCAoH model. Post-ischemic treatment with DEX (3 mg/kg bid i.p, after the hypoxic insult) reduced brain infarcts in pups exposed to dMCAoH. For the first time, we show that DEX reduces brain injury in different models of neonatal HIE. In light of the favorable safety profile of DEX in humans, the drug might have a realistic translational potential to treatment of perinatal cerebrovascular disorders.
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http://dx.doi.org/10.1016/j.neulet.2018.09.064DOI Listing
November 2018

Evaluation of sexual function in women with deep infiltrating endometriosis.

Sex Reprod Healthc 2018 Jun 3;16:6-9. Epub 2018 Jan 3.

Department of Biomedical, Experimental and Clinical Sciences - Division of Obstetrics and Gynecology, University of Florence, Italy.

Introduction: The influence of deep infiltrating endometriosis (DIE) on sexual function has been poorly studied. The aim of this study was to evaluate the impact of DIE on sexual function by administering questionnaires to women.

Methods: Women with a clinical and ultrasound diagnosis of DIE and histological confirmation of endometriosis were included in the study. In interview, women were asked to rate five pain symptoms, dysmenorrhea, dyspareunia, dyschezia, dysuria and Cronic Pelvic Pain (CPP), on a visual analogue scale (VAS), and sexual function was assessed using the Female Sexual Function Index (FSFI).

Results: A total of 170 women with DIE were identified. A VAS score of 7 or more was taken to indicate that a symptom was 'severe'. Dysmenorrhea was reported to be severe by 66.5% of the sample, dyspareunia by 41.8%, dyschezia by 32.4% and dysuria by 6.5%. Mean FSFI scores did not differ significantly between women with and without endometriosis lesions at particular sites, except for rectovaginal nodules, which were found to be associated with more impaired sexual activity and sexual function.

Conclusions: Women with DIE had significant impairment of sexual activity when a partial or total infiltration of the rectovaginal septum occurred. Particular attention should be given to women with this kind of lesion.
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http://dx.doi.org/10.1016/j.srhc.2017.12.005DOI Listing
June 2018