[Alterations of thyroid function in cancer patients: a case of hypothyroidism during immunotherapy.] / Alterazioni della funzionalità tiroidea nel paziente oncologico: un caso di ipotiroidismo in corso di immunoterapia.

Endocrinopathies, especially hypothyroidism, are very frequent during immunocheckpoint inhibitors treatment. An early diagnosis, through a correct clinical evaluation and the execution of blood tests, and the use of Levothyroxine therapy, allow you to continue the established tretament in most cases.

A diagnostic circulating miRNA signature as orchestrator of cell invasion via TKS4/TKS5/EFHD2 modulation in human gliomas.

BACKGROUND: Altered microRNA profiles have been observed not only in tumour tissues but also in biofluids, where they circulate in a stable form thus representing interesting biomarker candidates. This study aimed to identify a microRNA signature as a non-invasive biomarker and to investigate its impact on glioma biology. METHODS: MicroRNAs were selected using a global expression profile in preoperative serum samples from 37 glioma patients. Comparison between serum samples from age and gender-matched controls was performed by using the droplet digital PCR. The ROC curve and Kaplan-Meier survival analyses were used to evaluate the diagnostic/prognostic values. The functional role of the identified signature was assessed by gain/loss of function strategies in glioma cells. RESULTS: A three-microRNA signature (miR-1-3p/-26a-1-3p/-487b-3p) was differentially expressed in the serum of patients according to the isocitrate dehydrogenase (IDH) genes mutation status and correlated with both patient Overall and Progression Free Survival. The identified signature was also downregulated in the serum of patients compared to controls. Consistent with these results, the signature expression and release in the conditioned medium of glioma cells was lower in IDH-wild type cells compared to the mutated counterpart. Furthermore, in silico analysis of glioma datasets showed a consistent deregulation of the signature according to the IDH mutation status in glioma tumour tissues. Ectopic expression of the signature negatively affects several glioma functions. Notably, it impacts the glioma invasive phenotype by directly targeting the invadopodia-related proteins TKS4, TKS5 and EFHD2. CONCLUSIONS: We identified a three microRNA signature as a promising complementary or even an independent non-invasive diagnostic/prognostic biomarker. The signature displays oncosuppressive functions in glioma cells and impacts on proteins crucial for migration and invasion, providing potential targets for therapeutic intervention.

Red cell distribution width: A new parameter for predicting the risk of exacerbation in COPD patients.

BACKGROUND: Red cell distribution width (RDW) is a numerical measurement of the size variability of erythrocytes and is routinely reported as a component of complete blood count in the differential diagnosis of anemia. In recent years, researchers have reported high mortality and poor prognosis associated with higher RDW in populations with cardiovascular disease, cancer, pneumonia, and chronic obstructive pulmonary disease (COPD). The aim of the study is to evaluate the role of RDW in predicting the risk of COPD exacerbations and the impact of symptoms. METHODS: We designed an observational retrospective study based on patients hospitalized for acute exacerbation of COPD, between January 2015 and December 2018. RESULTS: We included 169 patients, 120 at GOLD four stage. RDW was significantly higher in COPD patients vs controls (P = .014). We found a positive correlation with c-reactive protein (r  = 0.375, P < .01), COPD assessment test (CAT) Score (R2 = 0.658, sy.x = 2.226; P < .01), number of exacerbations (R2=0.289; sy.x = 0.86; P = .002), and GOLD score (r = 0.30; P = .05). In ROC curve analysis, the area under the curve of RDW for the identification of frequent exacerbator was 1.0 (95% confidence interval, 1.0-1.0; P < .0001). CONCLUSION: Our data show that elevated RDW may be a useful tool in predicting the risk of exacerbation in COPD patients and may be a good indicator of the impact of symptoms.

Coronavirus disease 2019 infection in patients with recent cardiac surgery: does chronic anticoagulant therapy have a protective effect?

AIMS: The aim of this study was to evaluate the clinical course of COVID-19 in patients who had recently undergone a cardiac procedure and were inpatients in a cardiac rehabilitation department. METHODS: All patients hospitalized from 1 February to 15 March 2020 were included in the study (n = 35; 16 men; mean age 78 years). The overall population was divided into two groups: group 1 included 10 patients who presented with a clinical picture of COVID-19 infection and were isolated, and group 2 included 25 patients who were COVID-19-negative. In group 1, nine patients were on chronic oral anticoagulant therapy and one patient was on acetylsalicylic acid (ASA) and clopidogrel. A chest computed tomography scan revealed interstitial pneumonia in all 10 patients. RESULTS: During hospitalization, COVID-19 patients received azithromycin and hydroxychloroquine in addition to their ongoing therapy. Only the patient on ASA with clopidogrel therapy was transferred to the ICU for mechanical ventilation because of worsening respiratory failure, and subsequently died from cardiorespiratory arrest. All other patients on chronic anticoagulant therapy recovered and were discharged. CONCLUSION: Our study suggests that COVID-19 patients on chronic anticoagulant therapy may have a more favorable and less complicated clinical course. Further prospective studies are warranted to confirm this preliminary observation.

First report on clinical and radiological features of COVID-19 pneumonitis in a Caucasian population: Factors predicting fibrotic evolution.

BACKGROUND: At the end of February, the Lombardy region (Northern Italy) was involved in the pandemic spread of the new COVID-19. We here summarize the clinical and radiological characteristics of 90 confirmed cases and analyze their role in predicting the evolution of fibrosis. METHODS: We retrospectively analyzed the clinical and radiological data of 90 patients with COVID-19 pneumonitis. All subjects underwent an HRCT study on the day of admission and eight weeks later, and were treated with lopinavir + ritonavir (Kaletra) 400/100 mg two times a day or darunavir + ritonavir two times a day, and Hydroxychloroquine 200 mg two times a day. Pulmonary fibrosis was defined according to the Fleischner Society glossary of terms for thoracic imaging. RESULTS: Twenty-three patients developed pulmonary fibrosis (25.5%): 15 were males, whose mean age was 75 ± 15. The majority were active smokers (60.8%) and had comorbidities (78.2%), above all, hypertension (47.8%), and diabetes (34.7%). Interestingly, in our series of cases, the "reversed halo sign" is frequent (63%) and seems to be a typical COVID-19 pneumonitis pattern. The patients showing fibrosis had a higher grade of systemic inflammation (ESR and PCR) and appeared to have bone marrow inhibition with a significant reduction in platelets, leukocytes, and hemoglobin. CONCLUSIONS: To conclude, our data showed that the reversed halo sign associated with a ground-glass pattern may be a typical HRCT pattern of COVID-19 pneumonitis. The evolution to pulmonary fibrosis is frequent in older males and patients with comorbidities and bone marrow involvement.

Subclinical Nasal and Lung Lymphocytosis in Ulcerative Colitis.

BACKGROUND: Extraintestinal manifestations are common in ulcerative colitis (UC). Data regarding pulmonary and nasal mucosa involvement are sparse. OBJECTIVES: The aim of the study was to evaluate, by using induced sputum (IS) and nasal cytology (NC), the cytological pattern of the lung and nose in patients with UC. MATERIALS AND METHODS: We enrolled 15 consecutive subjects from the outpatient department with a recent diagnosis of UC. On the same day of enrollment, we performed a global spirometry, including a lung diffusing capacity test, IS analysis, and evaluation of NC. RESULTS: IS analysis showed an increase in lymphocytes in UC patients when compared to those of controls (2.8 ± 0.9 vs. 0.2 ± 0.4%; p < 0.01). NC showed a similar increase in lymphocytes (12.5 ± 5.30 vs. 3.5 ± 4.0%; p < 0.01). We found a positive correlation between lymphocyte counts in IS and NC (r = 0.775; p < 0.001) and between lymphocytes in IS and NC and grade of intestinal inflammation (r = 0.603, p = 0.015; r = 0.60, p = 0.013). CONCLUSIONS: Our data demonstrated that UC patients may have a subclinical nasal and lung lymphocytosis.

A "Crazy Paving" Pattern on CT Scan in a Patient Treated with Pembrolizumab.

BACKGROUND: Programmed cell death protein 1 (PD-1) and its ligand, PD-L1, have shown great promise in clinical practice and have been incorporated into standard management of NSCLC. Pneumonitis is a serious autoimmune toxicity associated with the use of anti-PD-1/PD-L1 antibodies, resulting in significant morbidity and mortality. METHODS: We described the case of a 73-year-old woman with no history of smoking developing exertional dyspnea four months after taking Pembrolizumab. RESULTS: High resolution contrast CT scan (HRCT) presented a unilateral "crazy paving" pattern, and bronchoalveolar lavage (BAL) an important lymphocytosis (20% of total cell count). The patient reached clinical stability after the administration of systemic steroids (2mg\Kg\die) and was discharged with long term oxygen therapy. DISCUSSION: Pulmonary toxicity is frequent when using PD-1 inhibitors, resulting in significant morbidity and mortality, often leading to the discontinuation of therapy. Clinical presentation is usually protean and HRCT pattern is nonspecific. This is the first case presenting a "crazy paving" pattern associated with BAL lymphocytosis. CONCLUSION: Oncologists, pulmonologists, radiologists and general practitioners have to consider PD-1 and PD-L1 inhibitor pneumonitis as a potentially disabling and fatal event.

Lung Manifestations of IgG4-related Disease. A multifaceted disorder. Presentation of two cases and short review of the literature.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a recently described systemic inflammatory disease associated with elevated circulating levels of IgG4. IgG4-RD may affect one or more organs and lesions can present synchronously or metachronously in different organs. Pulmonary involvement of IgG4-related disease includes airway, lung parenchyma, pleura and mediastinum. In this article, we report two cases of IgG4-RD to show the multifaceted manifestations of this disease in the lungs. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 74-80).

Cognitive and motor reaction times in obstructive sleep apnea syndrome: A study based on computerized measures.

Obstructive Sleep Apnea Syndrome (OSAS) is mainly associated with executive dysfunction. Although delayed reaction times (RTs) in patients with OSAS have been reported, sensitivity of processing speed has not been adequately assessed. This study suggests sensitive and reliable measures to clarify whether different components of information processing speed, i.e. cognitive and motor responses, are equally impaired in OSAS. Thirty-three patients with OSAS were compared with thirty healthy controls. The MoCA test was administered to assess participants' global neuropsychological profile. Cognitive and motor reaction times were measured using a detector panel which allows to distinguish between stimulus encoding, decision processing, and selection of the appropriate motor response. Logistic regression models highlighted both MoCA test and motor RTs as the best predictors differentiating patients from healthy participants. Results support the hypothesis of a slight decline in the cognitive profile of patients with OSAS and identify significant slowing down in the motor component of responses. It could be hypothesized that slower motor responsiveness is the cause of the global cognitive profile of these patients. With aging, motor movements and RTs usually become impaired and hypoxia might accelerate the aging process by compromising first of all the motor component of RTs.

Massive perineal defect after radio-chemotherapy.

Herein, we present a rare complication of radio-chemotherapy. A young man presented with loss of urine from the posterior perineum that showed a massive disappearance. He underwent Hartmann procedure for rectal neoplasia, afterwards treated with intensity-modulated radiotherapy (IMRT) (until 67 Gy) and chemotherapy with FOLFOX protocol (Leucoverin calcium, Fluorouracil, Oxaliplatin).

Third-line treatment of colorectal liver metastases using DEBIRI chemoembolization.

To evaluate safety, efficacy of drug-eluting beads with irinotecan (DEBIRI) on local response and survival of patients affected by colorectal liver metastases (CRLM) progressing during or after second line was evaluated. Sixty-two patients, with colorectal liver metastases, not suitable for surgery or thermal ablation treatments, progressing during or within 6 month from the end of second-line chemotherapy, were treated with DEBIRI chemoembolization between February 2009 and July 2014. CRLM were histologically confirmed. Exclusion criteria were considered. The DEBIRI technique consists in intrahepatic embolization of metastases with non-absorbable beads (75-150 µm and 100-300 µm) preloaded with irinotecan, carried near tumour using a selective catheterization of the right or of the left hepatic artery. To control pain associated with treatment, we use a specific schedule. Efficacy of treatment, defined as lack of disease progression and reduction in size of metastasis according to RECIST 1.1 criteria, was evaluated after two treatments with contrast-enhanced computed tomography (CT) at 4 months. If necessary, more treatments are repeated. A total of 191 procedures were performed. No intra-/peri-procedural death occurred. Pain and post-embolization syndrome were generally controlled by medications. Overall, the efficacy of treatment, evaluated in terms of stability and remission of the disease, was 37.1%. In our experience, DEBIRI technique results as a safe and effective procedure, with good intra- and peri-procedural tolerability.

Obstructive sleep apnea and its controversial effects on cognition.

Obstructive sleep apnea syndrome is a sleep disorder that may affect many brain functions. We are interested in the cognitive consequences of the condition with regard to the quality of life of individuals with this disorder. A debate is still underway as to whether cognitive difficulties caused by obstructive sleep apnea actually induce a "pseudodementia" pattern. This work provides a brief overview of the main controversies currently surrounding this issue. We report findings and opinions on structural and cognitive brain changes in individuals affected by obstructive sleep apnea by highlighting the involvement of executive functions and the possible reversibility of signs following-treatment with continuous positive airway pressure. Much research has been done on this issue but, to the best of our knowledge, a review of the present state of the literature evaluating different points of view has not yet been carried out.

Maximal exercise in obese patients with COPD: the role of fat free mass.

BACKGROUND: Obese patients (OB) with COPD may better tolerate exercise as compared to normal weight (NW) COPD patients, even if the reason for this is not yet fully understood. We investigated the interactions between obesity, lung hyperinflation, fat-free mass (FFM) and exercise capacity in COPD. METHODS: Forty-four patients (16 females; age 65 ± 8 yrs) were assessed by resting lung function and body composition and exercised on a cycle-ergometer to exhaustion. RESULTS: Twenty-two OB and 22 NW patients did not differ in age, gender and airflow obstruction degree, but in FFM (p < 0.05). OB had significantly higher values in inspiratory capacity/total lung capacity ratio (IC/TLC) at rest (p < 0.01), but not at peak of exercise and showed significantly higher values in peak workload (p < 0.05) and in peak oxygen uptake (VO2), when expressed as absolute value (p < 0.05), but not when corrected by FFM. OB compared to NW experienced lower leg fatigue (p < 0.05), but similar dyspnea on exertion. In all patients, the regression equation by stepwise multiple regression analysis for peak workload and VO2, as dependent variables included both FFM and IC/TLC at rest, as independent variables (r(2) = 0.43 and 0.37, respectively). CONCLUSIONS: OB with COPD, as compared to NW patients matched for age, gender and airflow obstruction, had greater FFM and less resting lung hyperinflation and showed greater maximal exercise capacity. Pulmonary and non-pulmonary factors may explain the preservation of exercise tolerance in patients with COPD associated with obesity.

Ventilatory response to carbon dioxide output in subjects with congestive heart failure and in patients with COPD with comparable exercise capacity.

BACKGROUND: Patients with congestive heart failure or COPD may share an increased response in minute ventilation (V̇E) to carbon dioxide output (V̇CO2 ) during exercise. The goal of this study was to ascertain whether the V̇E/V̇CO2 slope and V̇E/V̇CO2 intercept can discriminate between subjects with congestive heart failure and those with COPD at equal peak oxygen uptake (V̇O2 ). METHODS: We studied 46 subjects with congestive heart failure (mean age 61 ± 9 y) and 46 subjects with COPD (mean age 64 ± 8 y) who performed a cardiopulmonary exercise test. RESULTS: The V̇E/V̇CO2 slope was significantly higher in subjects with congestive heart failure compared with those with COPD (39.5 ± 9.5 vs 31.8 ± 7.4, P < .01) at peak V̇O2 < 16 mL/kg/min, but not ≥ 16 mL/kg/min (28.3 ± 5.3 vs 28.9 ± 6.6). The V̇E/V̇CO2 intercept was significantly higher in both subgroups of subjects with COPD compared with the corresponding values in the subjects with congestive heart failure (3.60 ± 1.7 vs -0.16 ± 1.7 L/min, P < .01; 3.63 ± 2.7 vs 0.87 ± 1.5 L/min, P < .01). According to receiver operating characteristic curve analysis, when all subjects with peak V̇O2 < 16 mL/kg/min were considered, subjects with COPD had a higher likelihood to have the V̇E/V̇CO2 intercept > 2.14 L/min (0.92 sensitivity, 0.96 specificity). Regardless of peak V̇O2 , the end-tidal pressure of CO2 (PETCO2 ) at peak exercise was not different in subjects with congestive heart failure (P = .42) and was significantly higher in subjects with COPD (P < .01) compared with the corresponding unloaded PETCO2 . CONCLUSIONS: The ventilatory response to V̇CO2 during exercise was significantly different between subjects with congestive heart failure and those with COPD in terms of the V̇E/V̇CO2 slope with moderate-to-severe reduction in exercise capacity and in terms of the V̇E/V̇CO2 intercept regardless of exercise capacity.

Fat-free mass depletion is associated with poor exercise capacity irrespective of dynamic hyperinflation in COPD patients.

BACKGROUND: In patients with COPD, we investigated the effect of the fat-free mass (FFM) on maximal exercise capacity and the relationship with changes in operational lung volumes during exercise. METHODS: In a cross-sectional study 57 patients (16 females; age 65 ± 8 y) were consecutively assessed by resting lung function, symptom-limited cardiopulmonary exercise test, and body composition by means of bioelectrical impedance analysis to measure the FFM index (FFMI; in kilograms per square meter). RESULTS: Patients were categorized as depleted (n = 14) or nondepleted (n = 43) according to FFMI. No significant difference in gender, age, and resting lung function was found between depleted and nondepleted patients. When compared with nondepleted COPD patients, the depleted COPD patients had a significantly lower O2 uptake at the peak of exercise and at anaerobic threshold as well as at peak oxygen pulse, oxygen uptake efficiency slope (OUES), and heart rate recovery (HRR) (P < .05 for all comparisons), but similar inspiratory capacity/total lung capacity at the peak of exercise. Moreover, they also reported significantly higher leg fatigue (P < .05), but not dyspnea on exertion. In all patients, significant correlations (P < .01) were found between FFMI and peak oxygen pulse, OUES, HRR, and leg fatigue. CONCLUSIONS: This study shows that FFM depletion plays a part in the reduction of exercise capacity in COPD patients, regardless of dynamic hyperinflation, and is strictly associated with poor cardiovascular response to exercise and to leg fatigue, but not with dyspnea.

Disease control in patients with asthma is associated with alexithymia but not with depression or anxiety.

This observational cohort study investigated the relationship between alexithymia, coping strategies, anxiety, depression, pulmonary function, and disease control in bronchial asthma (BA) patients who attended a tertiary care center between December 2010 and November 2011. Participants (N = 117) were administered self-report scales measuring anxiety, depression, alexithymia, and coping strategies. Pulmonary function expressed as forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory flow rate over the middle 50% of the FVC (FEF25-75) as% predicted and FEV1/FVC as%, fractional exhaled nitric oxide (FeNO) in ppb and the Asthma Control Test (ACT) were recorded. A hierarchical cluster analysis revealed two clusters of patients with different FEV1 values (p < .001) and alexithymia scores (p < .001). The cluster with lower FEV1 and higher alexithymia used more maladaptive coping strategies (p < .05), and had lower ACT scores (p < .05). Alexithymia was significantly associated with the severity of depression and anxiety symptoms (p < .001 for each comparison). In BA patients, alexithymia was associated with worse pulmonary function and disease control and a more frequent use of maladaptive coping strategies. These results support a multidimensional approach to asthmatic patients, including psychoeducational and behavioral interventions aimed at reducing maladaptive coping strategies.

Erlotinib and concurrent chemoradiation in pretreated NSCLC patients: radiobiological basis and clinical results.

AIMS: To establish feasibility of the combination of Erlotinib and concurrent chemoradiation in pre-treated patients with locally advanced or metastatic NSCLC. MATERIALS AND METHODS: Data regarding 60 consecutive patients with NSCLC previously treated with chemotherapy alone were prospectically collected. All patients started Erlotinib concurrently with chemotherapy and radiation delivered to primary tumor. These data were retrospectively analyzed (observational study). Feasibility and toxicity were the primary endpoints, with response rate and progression being the secondary ones, while survival data are reported just as exploratory analysis. The EGFR mutational status was recorded in 32% of cases and it was always wild type. RESULTS: Compliance to the combination protocol was good. Grade 3-4 esophagitis and acute lung toxicity occurred in 2% and 8% of patients, respectively. No progressive disease was recorded in the majority of cases (65%). Median OS and PFS were 23.3 and 4.7 months, respectively. Patients not responding to chemotherapy administered prior to chemoradiation achieved an objective response rate of 53.3% and complete response in 13.3% of cases. CONCLUSIONS: The addition of Erlotinib to chemoradiation in inoperable NSCLCs is feasible with interesting efficacy profile. These preliminary results warrant further investigation in patients with locally advanced nonmetastatic NSCLC with EGFR mutations.