Careggi University Hospital Research Articles

Editorial introductions

Current Opinion in Pulmonary Medicine was launched in 1995. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of pulmonary medicine is divided into nine sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Editors in Chief and Section Editors for this issue. EDITORS IN CHIEF Robert BaughmanRobert BaughmanDr Robert Baughman is Professor of Medicine at the University of Cincinnati, USA. After completing undergraduate training at Yale University, USA, he received his medical degree from Case Western Reserve School of Medicine, USA. He joined the Internal Medicine staff at the University of Cincinnati after completing both an internal medicine residency and fellowship training in pulmonary diseases at the University of Cincinnati. His major research interests include the treatment of sarcoidosis and bronchoalveolar lavage. Along with his long-time collaborator Dr Elyse Lower, he has developed several novel treatments for sarcoidosis, including methotrexate, thalidomide, leflunomide, and infliximab. Current studies include treatments for sarcoidosis associated fatigue and pulmonary hypertension due to sarcoidosis. Dr Baughman's publications include over 200 original papers and over 70 review articles and/or book chapters. He is on the editorial board of several journals and co-Editor of the journals Current Opinion in Pulmonary Medicine and Sarcoidosis, Interstitial Lung Disease, and Vasculitis. In addition, Dr Baughman is the editor of books on sarcoidosis, interstitial lung disease, and interstitial lung disease associated pulmonary hypertension. Marjolein DrentMarjolein DrentDr Marjolein Drent is Professor of Interstitial Lung Diseases (ILD) at the Department of Pharmacology and Toxicology of the Faculty of Heath, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands, and Pulmonologist at the ILD Center of Excellence St. Antonius Hospital, Nieuwegein, Netherlands. Her oration was entitled: ‘Breathtaking inspirations’. After she finished her training as a physical therapist, she received her medical degree from the Catholic University of Nijmegen, Netherlands. Her major research interests include sarcoidosis, ILD, drug-induced ILD and quality of life related topics. She is a co-editor, member of the editorial board and guest editor of several international journals, as well as editor of ILD Care Today. She has (co-) authored over 400 papers and book chapters. She is the co-editor of several ILD related e-learning modules. She is president emeritus of WASOG (World Association of Sarcoidosis and other Granulomatous diseases). She is a member of the Foundation for Sarcoidosis Research (FSR) Scientific Advisory Board. She is the founder and chair of the ILD Care (interstitial lung diseases including sarcoidosis and lung diseases related to occupation and environment management and research) Foundation. She is an honorary member of Sarcoidose.nl (Dutch Sarcoidosis Society) and co-founder and a member of the advisory board of the Dutch Pulmonary Fibrosis Society. In 2012, she was nominated for the World Sarcoidosis Person of the Year Award for her tireless research work in defining the psychological burden faced by patients and their families. Dublin, Ireland. She is ambassador for Compassion for Care and the youth smoking prevention foundation. She was appointed as an Officer in the Order of Orange Nassau by Royal Decree. This royal honour was awarded in 2016 by the deputy mayor of Ede, Netherlands. SECTION EDITORS Sadia BenzaquenSadia BenzaquenSadia Benzaquen, MD, FACP, FCCP, ATSF, DAABIP is the Chairman of Pulmonary, Critical Care, Sleep and Allergy at Einstein Medical Center, Philadelphia, USA. He is a Professor of Medicine at the Sidney Kimmel Medical College at Jefferson University, Philadelphia, USA. He is an expert in the interventional pulmonology field with extensive research and publications in lung cancer, pleural disease and ILD. Sara TomassettiSara TomassettiSara Tomassetti is currently Associate Professor of Respiratory Medicine at Florence University, Italy, and Head of Interventional Pulmonology Unit at Careggi University Hospital, Florence, Italy. She has extensive experience in all aspects of interstitial lung diaseses and interventional pulmonology, including cryobiopsy. She is a faculty member of the European Respiratory Society, and BOND National member for Italy of the European Association for Bronchology and Interventional Pulmonology. From a clinical research perspective, she has been the primary investigator (PI) of several sponsored and investigator initiated clinical trials on diagnosis and treatemnt of ineterstiatial lung diseases and idiopathic pulmonary fibrosis. She publishes on clinical research aspects of interstitial lung diseases and interventional pulmonology. She regularly reviews research and clinical manuscripts for international journals.

110 Sex-related differences in clinical presentation and outcome of patients with cardiac transthyretin amyloidosis and light chain amyloidosis

Abstract Aims We aimed to ascertain whether sex-related differences are relevant to the pathophysiology, presentation, and outcomes in different types of cardiac amyloidosis—a field still poorly investigated. Medical files from consecutive patients diagnosed with cardiac amyloidosis between 2000 and 2020, at Careggi University Hospital, were retrospectively evaluated. Methods and results Over this period, 259 patients (12% females) were diagnosed with wild type transthyretin amyloidosis (wtATTR), 52 (25% females) with hereditary transthyretin amyloidosis (hATTR) and 143 (47% females) with light chain amyloidosis (AL). Wt-ATTR women, compared to men, were significantly older at the time of diagnosis and showed higher National Amyloidosis Centre score, thicker normalized interventricular septum, higher diastolic dysfunction and worse right ventricular function. Females with hATTR and AL had lower normalized cardiac mass compared to men. Otherwise, bio-humoural parameters, NYHA class, and ECG characteristics were similar. No differences in outcome were observed with regard to sex. Conclusions In conclusion, we did not observe major differences in clinical expression related to sex in different types of cardiac amyloidosis: specifically, outcome was not affected. Nevertheless, women with wtATTR showed a worse profile at diagnosis and evidence suggesting a later recognition of disease compared to men, highlighting the need for a higher index of suspicion in female patients.

Maternal hemodynamic changes in gestational diabetes: a prospective case-control study.

The aim of the study is to compare maternal hemodynamic adaptations in gestational diabetes (GDM) versus healthy pregnancies. A prospective case-control study was conducted, comparing 69 singleton pregnancies with GDM and 128 controls, recruited between September 2018 and April 2019 in Maternal-Fetal Medicine Unit, Careggi University Hospital, Florence, Italy. Hemodynamic assessment by UltraSonic Cardiac Output Monitor (USCOM) was performed in both groups in four gestational age intervals: 17-20weeks (only in early GDM cases), 26-30weeks, 32-35weeks and 36-39weeks. We evaluated six hemodynamic parameters comparing GDM cases versus controls: cardiac output (CO), cardiac index (CI), stroke volume (SV), total vascular resistance (TVR), inotropy index (INO) and potential to kinetic energy ratio (PKR). GDM group had significantly lower values of CO and SV than controls from the early third trimester (26-30weeks) until term (p < 0.001). CI is significantly lower in GDM women already at the first evaluation (p = 0.002), whereas TVR and PKR were significantly higher in GDM (p < 0.001). GDM women showed also lower INO values than controls in all assessments. A hemodynamic maternal maladaptation to pregnancy can be detected in GDM women. The effect of hyperglycemia on vascular system or a poor pre-pregnancy cardiovascular (CV) reserve could explain this hemodynamic maladaptation. The abnormal CV response to pregnancy in GDM women may reveal a predisposition to develop CV disease later in life and might help in identifying patients who need a CV follow-up.

Prevalence and clinical course of SARS-CoV-2 infection in patients with Behçet's syndrome.

We aimed to assess the prevalence of SARS-CoV-2 infection among Behçet's syndrome (BS) patients, evaluating the possible association between demographic and clinical features and the risk of infection. Moreover, we aimed to evaluate the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection. A survey was conducted on BS patients followed at the Behçet's Centre of the Careggi University Hospital, Florence, Italy. We further evaluated the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection. Out of 335 BS patients contacted, fourteen cases of SARS-CoV-2 were identified between April 1st, 2020 and February 9th, 2021, suggesting a prevalence of SARS-CoV-2 infection among BS patients of 4.2%, in line with the data of the general population in Italy (4.4%). When comparing clinical features between SARS-CoV-2 cases and matched SARS-CoV-2 negative BS patients, we found that the presence of different disease manifestations did not significantly differ between the two groups. SARS-CoV-2 cases and controls were also comparable in terms of immunosuppressive therapy, with the only exception of corticosteroids (71.4% vs. 35.7%, p=0.030), whose daily dose was significantly higher in cases than controls [5mg/day (IQR 0-10,) vs. 0 mg/day (IQR 0-5), p=0.005], suggesting that the right timing of usage and the more appropriate dosage of corticosteroid are a key question for the better management of these patients. Based on our results, patients with BS do not seem to be at a greater risk of SARS-CoV-2 infection or severe complications compared with the general population.

Fabry-Stroke Italian Registry (FSIR): a nationwide, prospective, observational study about incidence and characteristics of Fabry-related stroke in young-adults. Presentation of the study protocol

BackgroundTIA and stroke, both ischemic and hemorrhagic, may complicate Fabry disease at young-adult age and be the first manifestation that comes to the clinician’s attention. No definite indications have yet been elaborated to guide neurologists in Fabry disease diagnostics. In current practice, it is usually sought in case of cryptogenic strokes (while Fabry-related strokes can also occur by classical pathogenic mechanisms) or through screening programs in young cerebrovascular populations. Data on recurrence and secondary prevention of Fabry’s stroke are scanty.MethodsThe study had a prospective observational design involving 33 Italian neurological Stroke Units. Considering the incidence of TIA/stroke in the European population aged < 60 years and the frequency of Fabry disease in this category (as foreseen by a pilot study held at the Careggi University-Hospital, Florence), we planned to screen for Fabry disease a total of 1740 < 60-year-old individuals hospitalized for TIA, ischemic, or hemorrhagic stroke. We investigated TIA and stroke pathogenesis through internationally validated scales and we gathered information on possible early signs of Fabry disease among all cerebrovascular patients. Every patient was tested for Fabry disease through dried blood spot analysis. Patients who received Fabry disease diagnosis underwent a 12-month follow-up to monitor stroke recurrence and multi-system progression after the cerebrovascular event.DiscussionThe potential implications of this study are as follows: (i) to add information about the yield of systematic screening for Fabry disease in a prospective large cohort of acute cerebrovascular patients; (ii) to deepen knowledge of clinical, pathophysiological, and prognostic characteristics of Fabry-related stroke.

Impact of COVID-19 related lockdown measures on stroke care quality in Careggi University Hospital, Florence

The COVID-19 pandemic and related restrictions has been disruptive for healthcare systems, especially for time-sensitive emergencies. During the viral outbreak, a reduction of stroke patients' volume in hospitals in Italy and worldwide has been extensively reported, as well as a severe delay in all integrated steps of hyperacute treatments and management.

CO2 laser colposcopic guided surgery for the see and treat management of VHSIL: a preliminary experience

The purpose of this study is to evaluate the efficiency of CO2 laser colposcopic guided surgery performed in an outpatient see and treat setting in the management of VHSIL. Women with a suspected diagnosis of VHSIL and no vulvoscopic suspicion of vSCC were enrolled. An electronic register of CO2 laser treatment was created where description of performing parameters (excision or ablation) was specified and personal history was recorded. Statistical analysis was performed by Fisher’s exact test. Relative risks (RR) of risk factor were calculated and expressed in odds. From September 2014 to September 2018, we enrolled a total of 63 patients who underwent CO2 laser procedure and had a minimum follow-up time of 2 years at Careggi University Hospital in Florence. Forty-eight (76.2%) patients underwent laser excision and 15 (23.8%) patients underwent ablative treatment without histological results. Undertreatment was performed in 3 cases (6.3%) with definitive histology of vSCC. Therapeutical appropriateness of CO2 laser excision was reached in 85.4% of the cases (41/48). No volunteer loss to follow-up was registered; thus, fidelity to treatment was assess at 100%. Recurrence rate within 2 years attested in 8/60 followed patients (13.3%). No personal factor was found to influence the VHSIL course. CO2 laser excision may represent an excellent therapeutic option to VHSIL because it provides adequate oncological purpose with good cosmetic and functional results and high patients’ loyalty to treatment. An expert team could allow to undergo patients with VHSIL suspicion to unique diagnostic and therapeutic procedure with significant benefits.

Menstrual Distress Questionnaire (MEDI-Q): a new tool to assess menstruation-related distress

Research questionMenstruation is a physiological event often associated with subjective distress. Is there a tool that assesses and objectively evaluates the global distress experienced by women during their period? DesignAn observational cross-sectional study conducted between June 2019 and May 2020 at Careggi University Hospital, Florence, Italy. A new questionnaire, The Menstrual Distress Questionnaire (MEDI-Q), was developed and administered to a group of healthy women (n = 418) of fertile age (18–50 years), without known uterine, psychiatric disorders, or both. The MEDI-Q investigated 25 items, covering the following areas: pain, discomfort, psychic or cognitive changes, gastrointestinal symptoms and changes in physiological functions. MEDI-Q Total Score and the three sub-scales, Menstrual Symptoms (MS), Menstrual Symptoms Distress (MSD) and Menstrual Specificity Index (MESI) were evaluated. The validation of MEDI-Q was achieved by testing test–retest reliability and internal consistency, convergent and concurrent validity. ResultsThe MEDI-Q produced reliable results with good internal consistency, convergent and concurrent validity. MEDI-Q Total Score, MS and MSD all positively correlated with general psychopathology and premenstrual symptoms. A receiver operating characteristic analysis was used to determine the cut-off value of 20 (inclusive) and to identify the women with clinically relevant menstrual distress (area under the curve 0.90, 95% CI 0.86 to 0.93; P < 0.001). ConclusionMEDI-Q is a new tool for evaluating menstruation-related distress, and provides a representative score of stress perception. MEDI-Q may be added to routine women's healthcare to help identify and adequately monitor menstruation-related disorders, and their effect on wellbeing, promptly.

Safety of Immune Checkpoint Inhibitors in Elderly Patients: An Observational Study.

Background: Immunotherapy has completely changed the treatment of solid tumors. Although immune checkpoint inhibitors (ICIs) seem to be an appealing alternative to chemotherapy, especially in elderly patients, due to a more tolerable toxicity profile, they can lead to a peculiar variety of immune-related adverse events (irAEs). However, data on tolerability and outcome of ICIs in the elderly are lacking due to poor accrual in clinical trials of these patients. Methods: We performed a retro-prospective analysis on patients treated with single agent anti-PD-L1/PD-1 at the Clinical Oncology Unit, Careggi University Hospital, from March 2016 to March 2020. Data on the treatment responses, type and severity of irAEs, as well as the corticosteroids (CCS) dosage used for irAEs and the discontinuation rate, were described per each patient, according to two different age-based cohorts of patients (< or ≥70 years). Results: We reported a lower incidence of all-grade toxicity in elderly compared to younger patients (64.9% vs. 44.9%, p = 0.018). The two age-cohorts showed a different profile of irAEs. Endocrine irAEs were significantly higher in younger patients (39.7% vs. 21.7%, p = 0.002), while dermatologic toxicities were more common in the older group (35.0% vs. 11.3%, p = 0.047). Use of CCS and treatment discontinuation rate do not differ significantly between the two age groups. Conclusion: Our findings suggest that treatment with ICIs in elderly populations is safe and feasible. Patients over 70 years are more prone to develop skin irAEs, while younger patients are more subject to experience endocrine toxicities.

Prevalence of nutritional risk and malnutrition during and after hospitalization for COVID-19 infection: Preliminary results of a single-centre experience.

Background & aimsThe effect of the COVID-19 infection on nutritional status is not well established. Worldwide epidemiological studies have begun to investigate the incidence of malnutrition during hospitalization for COVID-19. The prevalence of malnutrition during follow-up after COVID-19 infection has not been investigated yet. The primary objective of the present study was to estimate the prevalence of the risk of malnutrition in hospitalized adult patients with COVID-19, re-evaluating their nutritional status during follow-up after discharge. The secondary objective was to identify factors that may contribute to the onset of malnutrition during hospitalization and after discharge.MethodsWe enrolled 142 COVID-19 patients admitted to Careggi University Hospital. Nutritional parameters were measured at three different timepoints for each patient: upon admission to hospital, at discharge from hospital and 3 months after discharge during follow-up. The prevalence of both the nutritional risk and malnutrition was assessed. During the follow-up, the presence of nutritional impact symptoms (NIS) was also investigated. An analysis of the association between demographic and clinical features and nutritional status was conducted.ResultsThe mean unintended weight loss during hospitalization was 7.6% (p < 0.001). A positive correlation between age and weight loss during hospitalization was observed (r = 0.146, p = 0.08). Moreover, for elderly patients (>61 years old), a statistically significant correlation between age and weight loss was found (r = 0.288 p = 0.05). Patients admitted to an Intensive Care Unit (ICU) or Intermediate Care Unit (IMCU) had a greater unintended weight loss than patients who stayed in a standard care ward (5.46% vs 1.19%; p < 0.001). At discharge 12 patients were malnourished (8.4%) according to the ESPEN definition. On average, patients gained 4.36 kg (p < 0.001) three months after discharge. Overall, we observed a weight reduction of 2.2% (p < 0.001) from the habitual weight measured upon admission. Patients admitted to an ICU/IMCU showed a higher MUST score three months after discharge (Cramer's V 0.218, p = 0.035). With regard to the NIS score, only 7 patients (4.9%) reported one or more nutritional problems during follow-up.ConclusionsThe identification of groups of patients at a higher nutritional risk could be useful with a view to adopting measures to prevent worsening of nutritional status during hospitalization. Admission to an ICU/IMCU, age and length of the hospital stay seem to have a major impact on nutritional status. Nutritional follow-up should be guaranteed for patients who lose more than 10% of their habitual weight during their stay in hospital, especially after admission to an ICU/IMCU.

Management and outcome of metastatic pheochromocytomas/paragangliomas: a monocentric experience

BackgroundPheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors releasing catecholamines. Metastatic pheochromocytomas/paragangliomas (PPGLs) occur in about 5–26% of cases. To date, the management of patients affected by metastatic disease is a challenge in the absence of guidelines.AimThe aim of this study was to evaluate the overall survival (OS) and the progression-free survival (PFS) in metastatic PPGLs.MethodsClinical data of 20 patients referred to the Careggi University Hospital (Florence, Italy) were retrospectively collected. Follow-up ranged from 1989 to 2019. Site and size of primary tumor, biochemical activity, genetic analysis and employed therapies were considered. Data were analyzed with SPSS version 27.ResultsNine PHEOs (45%) and 11 PGLs (55%) were enrolled. Median age at diagnosis was 43.5 years [30–55]. Mean follow-up was 104.6 ± 89.3 months. Catecholamines were released in 70% of cases. An inherited disease was reported in 50% of patients. OS from the initial diagnosis (OSpt) and from the metastatic appearance (OSmtx) were lower in older patients (OSpt p = 0.028; OSmtx p < 0.001), abdominal PGLs (OSpt p = 0.007; OSmtx p = 0.041), larger tumors (OSpt p = 0.008; OSmtx p = 0.025) and sporadic disease (OSpt p = 0.013; OSmtx p = 0.008).ConclusionOur data showed that older age at the initial diagnosis, sympathetic extra-adrenal localization, larger tumors and wild-type neoplasms are related to worse prognosis. Notably, the employed therapies do not seem to influence the survival of our patients. At present, effective treatments for metastatic PPGLs are missing and a multidisciplinary approach is indispensably required.

Adherence to Mediterranean Diet Measured through Medi-Lite Score and Obesity: A Retrospective Study.

We recently developed and validated a questionnaire to measure adherence to the Mediterranean diet, called Medi-Lite. The aim of this study was to assess the accuracy of the Medi-Lite adherence score in relation to obesity status. A total of 208 patients who attended the Clinical Nutrition Unit of Careggi University Hospital, Florence, were included in this retrospective analysis. Of them, 126 (45%) had abdominal obesity (110 F; 16 M). The mean adherence score, calculated through the Medi-Lite questionnaire, was 9.5 ± 2.2, with significantly (p < 0.001) lower values in patients with abdominal obesity (8.9 ± 1.9) than those without abdominal obesity (10 ± 2.2). Logistic regression analysis adjusted for age and sex showed that the Medi-Lite score determined significant protection (−28%) against the risk of abdominal obesity for every one-unit increase in the total score (OR 0.72, 95% CI 0.63–0.82; p < 0.001). Looking for cut-off values that denote increased risk of having abdominal obesity, we observed that patients who scored ≤9 had a significantly increased risk (OR 3.21, 95% CI 1.91–5.39; p < 0.001). Adherence to the Mediterranean diet assessed through the Medi-Lite score was found to be associated with abdominal obesity. In particular, patients who reported a score of ≤9 had a 3.5-fold times higher risk of having abdominal obesity than those who scored >9.

Exposures and suspected intoxications during SARS-CoV-2 pandemic: preliminary results from an Italian poison control centre

Data on cleaner and disinfectant exposure and misuse-related acute intoxications in Italy during SARS-CoV-2 pandemic are still lacking. The aim of the present study was to analyse and describe cleaner and disinfectant-related intoxications during SARS-CoV-2 pandemic in an Italian poison control centre. Data were obtained from the toxicological consultations requested to the Toxicology Unit and Poison Centre, Careggi University Hospital, Florence (Italy). We compared data from January 1st to April 30th of 2019 and 2020. Data concerning probable or acute intoxication from any causative agent in the general population (all age groups), from private individuals or from Regional and National health structures, were included in the analysis. A toxicological evaluation was also performed to calculate the Poisoning Severity Score.In 2019, 451 phone counselling sessions were performed and compared to a total of 410 calls received during the same period of 2020. In both periods, the majority of events occurred in paediatric (0–17 years) and adult (18–65 years) patients, who were mainly exposed to one toxic agent, and intoxications took place principally at home due to domestic accidents. The oral route of intoxication was the most frequently observed one, followed by inhalation of toxic agents, which increased by 4.7% in 2020. In 2020, sanitizers and cleaners were reported in 21.6% of cases compared to 12.5% in 2019. This is the first study describing cleaner and disinfectant-related intoxications in Italy. Our results suggested a possible misuse of these products during the SARS-CoV-2 pandemic, underling the effects of home isolation on mental health and unintentional toxic exposures.

Cigarette Smoking as a Predictor of Sodium–Glucose Cotransporter 2 Inhibitor–Associated Genital Infections: A Retrospective Cohort Study

The most frequent adverse events associated with sodium–glucose cotransporter 2 (SGLT2) inhibitors are genital infections, with an incidence ranging from 3.7% to 11.4% in clinical trials (1,2). Treatment with SGLT2 inhibitors has also been associated with a modest increase in the risk of urinary tract infections (3). Genito-urinary infections are more frequent in women, particularly those reporting previous recurrent episodes of such events (4). To identify further predictors of genital infections, a retrospective cohort study was performed. We enrolled all patients with type 2 diabetes aged ≥18 years and referred to the Diabetes Outpatient Clinic of Careggi University Hospital, Florence, between 1 October and 30 November 2020 who had received a prescription of an SGLT2 inhibitor before 1 October 2018 and who provided their informed consent, with no other exclusion criteria. Demographic and clinical characteristics of patients at the date of prescription were retrieved from patients’ clinical records. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration algorithm and used for categorization of renal function (for eGFR below or above the median value). Information on treatment discontinuation and on genital …

Changes in the perceived epidemiology of amyloidosis: 20 year-experience from a Tertiary Referral Centre in Tuscany

BackgroundAmyloidosis is considered a rare heterogeneous condition comprising different entities. Epidemiological data are limited and often controversial. We aimed to examine epidemiological changes in amyloidosis diagnosed over a 20-year period at a tertiary referral centre for amyloidosis. MethodsWe retrospectively reviewed medical files from all patients diagnosed with amyloidosis between January 2000 and December 2019, at Careggi University Hospital, Florence, Italy.Diagnosis of amyloidosis was performed as per current clinical practice and scientific evidence at the time of patient evaluation. ResultsWe reported data on 654 consecutive patients: 274 (42%) wild type transthyretin amyloidosis (wtATTR), 68 (10%) genetic variant amyloidosis (vATTR), 281 (43%) light-chain amyloidosis (AL) and 31 (5%) serum amyloid A amyloidosis (AA). With limited fluctuations, the absolute number of new AL diagnosis increased during the 20-year period. wtATTR was unrecognized before 2009 but represented by far the most common aetiology at the end of the observation period. AA represented a residual diagnosis throughout the entire examined period. ConclusionsFollowing a rapid and marked increase in the number of new diagnoses over the last decade, ATTR represents by far the most common type of amyloidosis in our regional centre. These data contrasts with recent reports from national referral institutions and may help shed light on the epidemiology of the disease at the community level.

Different Gestational Diabetes Phenotypes: Which Insulin Regimen Fits Better?

ObjectiveMaternal characteristics and OGTT values of pregnancies complicated by gestational diabetes mellitus (GDM) were evaluated according to treatment strategies. The goal was to identify different maternal phenotypes in order to predict the appropriate treatment strategy.MethodsWe conducted a retrospective study among 1,974 pregnant women followed up for GDM in a tertiary referral hospital for high-risk pregnancies (Careggi University Hospital, Florence, Italy) from 2013 to 2018. We compared nutritional therapy (NT) alone (n = 962) versus NT and insulin analogues (n = 1,012) group. Then, we focused on different insulin analogues groups: long acting (D), rapid acting (R), both D and R. We compared maternal characteristics of the three groups, detecting which factors may predict the use of rapid or long-acting insulin analogue alone versus combined therapy.ResultsAmong women included in the analysis, 51.3% of them needed insulin therapy for glycemic control: 61.8% D, 28.3% combined D and R, and 9.9% R alone. Age >35 years, pre-pregnancy BMI >30, family history of diabetes, previous GDM, altered fasting plasma glucose (FPG), hypothyroidism, and assisted reproductive technologies (ART) were identified as maternal variables significantly associated with the need of insulin therapy. Altered 1-h and 2-h glucose plasma glucose level at OGTT, age >35 years, and previous GDM were found as independent predicting factors for the use of combined therapy with rapid and long acting analogues for glycemic control. On the contrary, pre-pregnancy BMI <25 and normal fasting plasma glucose values at OGTT were found to be significantly associated to the use of rapid insulin analogue only.ConclusionA number of maternal and metabolic variables may be identified at the diagnosis of GDM, in order to identify different GDM phenotypes requiring a personalized treatment for glycemic control.

Absolute eosinophil count as predictive biomarker of irAEs in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs).

345 Background: Nivolumab and ipilimumab are associated with immune-related adverse events (irAEs) and, to date, few biomarkers predictive of ICIs toxicity are reported in mRCC. Methods: We conducted a single-center, observational, retrospective study at Clinical Oncology Unit, Careggi University Hospital, Florence, Italy. We evaluated 43 patients (pts) with mRCC treated with ICIs from April 2013 to May 2020. Absolute Eosinophil Counts (AEC, N°/μL) were registered at baseline and at time of occurrence of irAEs. This study aims to evaluate whether the AEC could be a predictive biomarker of irAEs in patients with mRCC treated with ICIs. Results: Median age was 65 years and males were 81.4%. 10 pts received Nivolumab+Ipilimumab, while 33 pts received Nivolumab single agent. 74.4% pts (32/43) developed at least 1 irAE, 11.6% with G3-G4 irAEs. The most frequent first irAE was endocrine event (40.6% pts; 37.5% with hypo-/hyper-thyroidism). The baseline mean AEC was 163.1/μL in our cohort, in particular 132.2/μL in pts who did not develop irAEs and 176.7/μL in pts who developed irAEs (p=0.134). Among the pts who developed irAEs, the mean AEC was lower in pts with G1-G2 (153.1/μL) than in those with G3-G4 (330/μL; p=0.0013) irAEs. At the time of onset of the first irAE, the mean AEC increased to 247/μL (Δ 140.1%). Analyzing the trend of AEC from baseline to time of occurrence of irAE for the 32 pts who had developed at least one irAE, 53.1% (17 pts) showed an increasing trend; among these pts, the most frequent irAEs were endocrine occurring in 4/17 pts (23.6%). An increasing trend was also observed in the majority of pts who developed G1-2 (14/27, 51.9%) and G3-4 (3/5, 60.0%) irAEs. Additional analyzes are ongoing to identify appropriate cut-offs of AEC to better stratify patients. Conclusions: There is little evidence in the literature about the potential role of absolute eosinophil counts as a predictive biomarker of irAEs in patients with solid tumors treated with ICIs, and most refer to patients with melanoma. In this study we observed that the baseline AEC values in patients that will develop irAEs are higher than in those without irAEs and, among the former, the values are lower for patients with toxicity G1-G2 vs G3-G4. We also found an increase of the mean AEC from baseline to the onset of the first irAE. Of the patients who experience toxicity, most have an upward trend in AEC at the onset of the first irAE. Compatibly with all the limitations of a retrospective analysis, our is the first experience exploring the role of the eosinophil count in the development of irAEs in mRCC patients treated with ICIs, and a prospective study is ongoing in our Unit to confirm the role of the eosinophil count in patients treated with ICIs.

Clinical and Laboratory Follow-up After Hospitalization for COVID-19 at an Italian Tertiary Care Center.

We evaluated 100 postacute coronavirus disease 2019 (COVID-19) patients a median (interquartile range) of 60 (48–67) days after discharge from the Careggi University Hospital, Italy. Eighty-four (84%) had at least 1 persistent symptom, irrespective of COVID-19 severity. A considerable number of hospital readmissions (10%) and/or infectious diseases (14%) during the postdischarge period were reported.

Significant and Conflicting Correlation of IL-9 With Prevotella and Bacteroides in Human Colorectal Cancer.

Background and aimGut microbiota (GM) can support colorectal cancer (CRC) progression by modulating immune responses through the production of both immunostimulatory and/or immunosuppressive cytokines. The role of IL-9 is paradigmatic because it can either promote tumor progression in hematological malignancies or inhibit tumorigenesis in solid cancers. Therefore, we investigate the microbiota–immunity axis in healthy and tumor mucosa, focusing on the correlation between cytokine profile and GM signature.MethodsIn this observational study, we collected tumor (CRC) and healthy (CRC-S) mucosa samples from 45 CRC patients, who were undergoing surgery in 2018 at the Careggi University Hospital (Florence, Italy). First, we characterized the tissue infiltrating lymphocyte subset profile and the GM composition. Subsequently, we evaluated the CRC and CRC-S molecular inflammatory response and correlated this profile with GM composition, using Dirichlet multinomial regression.ResultsCRC samples displayed higher percentages of Th17, Th2, and Tregs. Moreover, CRC tissues showed significantly higher levels of MIP-1α, IL-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, P-selectin, and IL-9. Compared to CRC-S, CRC samples also showed significantly higher levels of the following genera: Fusobacteria, Proteobacteria, Fusobacterium, Ruminococcus2, and Ruminococcus. Finally, the abundance of Prevotella spp. in CRC samples negatively correlated with IL-17A and positively with IL-9. On the contrary, Bacteroides spp. presence negatively correlated with IL-9.ConclusionsOur data consolidate antitumor immunity impairment and the presence of a distinct microbiota profile in the tumor microenvironment compared with the healthy mucosa counterpart. Relating the CRC cytokine profile with GM composition, we confirm the presence of bidirectional crosstalk between the immune response and the host’s commensal microorganisms. Indeed, we document, for the first time, that Prevotella spp. and Bacteroides spp. are, respectively, positively and negatively correlated with IL-9, whose role in CRC development is still under debate.

Adverse drug reactions in SARS-CoV-2 hospitalised patients: a case-series with a focus on drug\u2013drug interactions

Due to the need of early and emergency effective treatments for COVID-19, less attention may have been paid to their safety during the global emergency. In addition, characteristics of drug–drug interaction (DDI)-related adverse drug reactions (ADRs) in COVID-19 patients have not yet been studied in depth. The aim of the present case-series study is to describe clinical and pharmacological characteristics of SARS-CoV-2 hospitalised patients, focusing on ADRs, particularly those related to DDIs. We evaluated all reports of COVID-19 medication-related ADRs collected within the COVID-19 Units of Careggi University Hospital, Florence (Italy), between January 1st and 31st May 2020. Information regarding COVID-19 medications, patients’ demographic and clinical characteristics, concomitant drugs, ADRs description and outcome, were collected. Each case was evaluated for the causality assessment and to identify the presence of DDIs. During the study period, 23 Caucasian patients (56.5% males, mean age 76.1 years) experienced one or more ADRs. The majority of them were exposed to polypharmacy and 17.4% presented comorbidities. ADRs were referred to cardiovascular, psychiatric and gastrointestinal disorders. The most frequently reported preferred term was QT prolongation (mean QT interval 496.1 ms). ADRs improved or resolved completely in 60.8% of cases. For all patients, a case-by-case evaluation revealed the presence of one or more DDIs, especially those related to pharmacokinetic interactions. Despite the small number of patients, our evidence underline the clinical burden of DDIs in SARS-CoV-2 hospitalised patients and the risk of unexpected and uncommon psychiatric ADRs.