Long-term investigation of methane and carbon dioxide emissions in two Italian landfills.

Landfills play a key role as greenhouse gas (GHGs) emitters, and urgently need assessment and management plans development to swiftly reduce their climate impact. In this context, accurate emission measurements from landfills under different climate and management would reduce the uncertainty in emission accounting. In this study, more than one year of long-term high-frequency data of CO2 and CH4 fluxes were collected in two Italian landfills (Giugliano and Case Passerini) with contrasting management (gas recovery VS no management) using eddy covariance (EC), with the aim to i) investigate the relation between climate drivers and CO2 and CH4 fluxes at different time intervals and ii) to assess the overall GHG balances including the biogas extraction and energy recovery components. Results indicated a higher net atmospheric CO2 source (5.7 ± 5.3 g m2 d-1) at Giugliano compared to Case Passerini (2.4 ± 4.9 g m2 d-1) as well as one order of magnitude higher atmospheric CH4 fluxes (6.0 ± 5.7 g m2 d-1 and 0.7 ± 0.6 g m2 d-1 respectively). Statistical analysis highlighted that fluxes were mainly driven by thermal variables, followed by water availability, with their relative importance changing according to the time-interval considered. The rate of change in barometric pressure (dP/dt) influenced CH4 patterns and magnitude in the classes ranging from -1.25 to +1.25 Pa h-1, with reduction when dP/dt > 0 and increase when dP/dt < 0, whilst a clear pattern was not observed when all dP/dt classes were analyzed. When including management, the total atmospheric GHG balance computed for the two landfills of Giugliano and Case Passerini was 174 g m2 d-1 and 79 g m2 d-1 respectively, of which 168 g m2 d-1 and 20 g m2 d-1 constituted by CH4 fluxes.

Uncertainties in the adaptation of alpine pastures to climate change based on remote sensing products and modelling.

Over the last century, the management of pastoral systems has undergone major changes to meet the livelihood needs of alpine communities. Faced with the changes induced by recent global warming, the ecological status of many pastoral systems has seriously deteriorated in the western alpine region. We assessed changes in pasture dynamics by integrating information from remote-sensing products and two process-based models, i.e. the grassland-specific, biogeochemical growth model PaSim and the generic crop-growth model DayCent. Meteorological observations and satellite-derived Normalised Difference Vegetation Index (NDVI) trajectories of three pasture macro-types (high, medium and low productivity classes) in two study areas - Parc National des Écrins (PNE) in France and Parco Nazionale Gran Paradiso (PNGP) in Italy - were used as a basis for the model calibration work. The performance of the models was satisfactory in reproducing pasture production dynamics (R2 = 0.52 to 0.83). Projected changes in alpine pastures due to climate-change impacts and adaptation strategies indicate that: i) the length of the growing season is expected to increase between 15 and 40 days, resulting in changes in the timing and amount of biomass production, ii) summer water stress could limit pasture productivity; iii) earlier onset of grazing could enhance pasture productivity; iv) higher livestock densities could increase the rate of biomass regrowth, but major uncertainties in modelling processes need to be considered; and v) the carbon sequestration potential of pastures could decrease under limited water availability and warming.

An integrated approach to estimate how much urban afforestation can contribute to move towards carbon neutrality.

Urban afforestation is considered a promising nature-climate solution that may contribute to achieve climate neutrality by 2050, since it can increase C-storage and C-sequestration, whilst providing further multiple ecosystem services for citizens. However, the quantification of the CO2 sequestration capacity that may be provided by an urban forest as well as the capacity to impact the city-level C-balance and offset anthropogenic emissions is a complex issue. Methodological approaches, quantity and quality of information contained in urban tree database, and the level of detail of the planned urban forest can strongly influence the estimation of C-sequestration potential offered by urban forests. In this work, an integrated framework based on emission inventory, tree species/morphology and ecosystem modelling has been proposed for the city of Prato, Italy, a representative medium size European city to: i) evaluate the current C-sequestration capacity of urban trees; ii) upscale such capacity with different afforestation scenarios, iii) compare the sink capacity offered by ecosystems with current and projected anthropogenic emissions. Results indicated that the green areas within the Municipality of Prato can sequester 33.1 ktCO2 yr-1 under actual conditions and 51.0 ktCO2 yr-1 under the afforestation scenario which maximize the CO2 sequestration capacity, offsetting the 7.1 % and 11 % of the total emissions (465.8 ktCO2 yr-1), respectively. This study proves that, in the various afforestation scenarios tested, the contribution of urban afforestation to the municipality carbon balance is negligible and that carbon neutrality can only be reached by the substantial decarbonization of emission sectors.

Baseline serum TSH levels predict the absence of thyroid dysfunction in cancer patients treated with immunotherapy.

PURPOSE: Immunotherapy against immune checkpoints has significantly improved survival both in metastatic and adjuvant setting in several types of cancers. Thyroid dysfunction is the most common endocrine adverse event reported. Patients who are at risk of developing thyroid dysfunction remain to be defined. We aimed to identify predictive factors for the development of thyroid dysfunction during immunotherapy. METHODS: This is a retrospective study including a total of 68 patients who were treated with immune checkpoint inhibitors (ICIs) for metastatic or unresectable advanced cancers. The majority of patients were treated with anti-PD1 drugs in monotherapy or in combination with anti-CTLA4 inhibitors. Thyroid function and anti-thyroid antibodies, before starting immunotherapy and during treatment, were evaluated. Thyroid ultrasound was also performed in a subgroup of patients at the time of enrolment in the study. RESULTS: Eleven out of 68 patients (16.1%) developed immune-related overt thyroid dysfunction. By ROC curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l, at baseline, had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction (NPV = 100%, p = 0.0029). At multivariate analysis, both TSH and positive anti-thyroid antibodies (ATAbs) levels, before ICIs treatment, were independently associated with the development of overt thyroid dysfunction during immunotherapy (p = 0.0001 and p = 0.009, respectively). CONCLUSIONS: Pre-treatment serum TSH and ATAbs levels may help to identify patients at high risk for primary thyroid dysfunction. Our study suggests guidance for an appropriate timely screening and for a tailored management of thyroid dysfunctions in patients treated with ICIs.

Indication for radioiodine remnant ablation in differentiated thyroid cancer patients: does 2018 Italian consensus change anything?

PURPOSE: We speculated that radioiodine remnant ablation (RRA) could be performed less frequently in differentiated thyroid cancer (DTC) patients, if the recommendations of the 2018 Italian Consensus (ITA) were applied in clinical practice. Therefore, we compared the ITA indications for RRA with the recommendations by the 2015 American Thyroid Association guidelines (ATA). METHODS: We retrospectively evaluated 380 consecutive DTC patients treated with surgery and RRA, followed at the Section of Endocrinology, University of Siena, Italy from January 2006 to December 2019. RESULTS: Using ITA a significant increase of DTC patients classified as low or high risk and a significant decrease of patients defined at intermediate risk were observed (p < 0.0001). Consequently, the percentage of patients without routinary indication for RRA (47.4%, versus 38.2%, p < 0.0001) and those with a definite indication for RRA (8.2 versus 1.8%, p < 0.0001) was significantly higher compared to ATA. Moreover, using ITA the percentage of patients with a selective use of RRA was lower in comparison to ATA (44.7% versus 60%, p < 0.0001). Nevertheless, the prevalence of distant metastases, at post-ablative whole body scan, in patients without indication for RRA, was not different using either ATA or ITA (2.1% and 1.1% respectively, p = 0.37). CONCLUSION: The use of ITA Consensus, in clinical practice, increases significantly the number of patients for whom RRA is not routinely indicated in comparison to ATA guidelines but without differences in delaying the diagnosis of distant metastatic disease.

Should familial disease be considered as a negative prognostic factor in micropapillary thyroid carcinoma?

PURPOSE: An increased aggressiveness of familial papillary thyroid carcinoma (FPTC) compared with sporadic form has been reported. On the contrary, the biological behavior of familial microPTC (FmPTC) is still debated. To assess if familial diseases should be considered as a negative prognostic factor in mPTC, the clinical presentation and outcome of FmPTC and sporadic mPTC (SmPTC) were compared. METHODS: We retrospectively analyzed 291 mPTC (SmPTC n = 248, FmPTC n = 43) patients followed for a median follow-up of 8.3 years. FmPTC was defined as the presence of PTC in two or more first-degree relatives, after excluding hereditary syndromes associated with PTC. RESULTS: FmPTC patients had more frequently bilateral tumor (32.6% versus 16.5%, p = 0.01) and lymph node metastases at diagnosis (30.2% versus 14.9%, p = 0.02). At the first follow-up, FmPTC patients had a higher rate of structural disease and a lower rate of remission compared to SmPTC (p = 0.01). Also in a multivariate model, using a "CHAID tree-building algorithm", familial disease correlated with a worse clinical presentation and outcome of mPTC patients. Familial disease was associated with a higher rate of intermediate risk patients in non incidental mPTC and with a higher rate of structural incomplete response in mPTC without lymph node metastases (p = 0.01). CONCLUSIONS: Like in macroPTC, the familial form of the diseases has been shown to be a negative prognostic factor also in mPTC, therefore, it should be highly regarded in the management of mPTC patients.

Small papillary thyroid carcinoma with minimal extrathyroidal extension should be managed as ATA low-risk tumor.

PURPOSE: According to American Thyroid Association (ATA) guideline, papillary thyroid cancer (PTC) with minimal extrathyroidal extension (mETE) is classified at "intermediate risk" of persistent/recurrent disease. However, the impact of mETE per se on patients' outcome is not fully understood. The aim of our study was to evaluate the prognostic significance of mETE in patients with PTC not submitted to therapeutic or prophylactic lymph node dissection, according to tumor size and other prognostic factors. PATIENTS AND METHODS: We retrospectively evaluated a total of 514 PTC patients: 127 (24.7%) had mETE (pT3Nx) and 387 (75.3%) had negative margins (pT1-2Nx). At a median follow-up of 9.1 years, patients were divided in two groups: patients with "good outcome" (no evidence of disease) and patients with "poor outcome" (persistent structural disease or recurrent disease or tumor-related death). RESULTS: The rate of patients with "poor outcome" was significantly higher in patients with mETE compared with patients with negative margins (11.8 versus 5.1%; OR 2.4576, 95% CI 1.2178-4.9594, p = 0.01). However, mETE was significantly associated with poor outcome only in patients with tumors larger than 1.5 cm. CONCLUSIONS: mETE is an unfavorable prognostic factor in tumors larger than 1.5 cm, suggesting that, in the absence of other unfavorable characteristics, smaller tumors with mETE should be classified and managed as "low risk" tumors.

Targeted therapy in radioiodine refractory thyroid cancer.

The majority of differentiated thyroid carcinomas (DTCs) of follicular cell origin are cured with adequate surgical management and radioiodine therapy. Other thyroid malignancies such as medullary thyroid carcinoma (MTC) or poorly differentiated thyroid carcinomas frequently metastasize, precluding patients from a curative resection. Therapeutic options for these patients include additional surgery for resectable lesions, external radiotherapy and chemotherapy. The results of this approach is usually disappointing and the use of novel therapeutic approaches is needed. The outstanding progress in the molecular basis of thyroid carcinoma offered the tool for the development of new drugs, mainly tyrosine-kinase inhibitor and inhibitors of proangiogenic factors, which are currently in phase II or III clinical trials with promising results (the so called targeted therapy). This review will summarize the most relevant achievements in the field and will discuss the limit and perspective of the new compounds.

Familial non-medullary thyroid carcinoma displays the features of clinical anticipation suggestive of a distinct biological entity.

Non-medullary thyroid carcinoma (NMTC) is mostly sporadic, but familial clustering is described. We aimed to compare the features of patients with sporadic and familial NMTC (FNMTC) patients and to assess whether FNMTC patients with parent-child relationship exhibit the 'anticipation' phenomenon (earlier age at disease onset and increased severity in successive generations). Among 300 NMTCs followed in the Section of Endocrinology (University of Siena, Italy), 34 (11.3%) patients, all with the papillary histotype, (16 kindred), met the criteria of FNMTC. Twenty-seven of them (79.4%) exhibited a parent-child relationship and seven (20.6%) a sibling relationship. These patients were compared with 235 patients with sporadic papillary thyroid cancer (PTCs). To analyze the features of FNMTC of the first and second generations, we cumulated the series of Siena with 32 additional FNMTC patients (15 kindred) from the Department of Endocrinology-Endocrine Oncology, Thessaloniki, Greece. Significant difference between sporadic PTC and FNMTC patients included more frequent tumor multifocality (P=0.001) and worse final outcome in FNMTC patients (P=0.001). Among 47 FNMTC with parent-child relationship, we found an earlier age at disease presentation (P<0.0001), diagnosis (P<0.0001), and disease onset (P=0.04) in the second generation when compared with the first generation. Patients in the second generation were more frequently males (P=0.02); their tumors were more frequently multifocal (P=0.003) and bilateral (P=0.01), had higher rate of lymph node metastases at surgery (P=0.02) and worse outcome (P=0.04) when compared with the first generation. In conclusion, FNMTC displays the features of clinical 'anticipation' with the second generation acquiring the disease at an earlier age and having more advanced disease at presentation.

Limited value of repeat recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin testing in differentiated thyroid carcinoma patients with previous negative rhTSH-stimulated thyroglobulin and undetectable basal serum thyroglobulin levels.

CONTEXT: One year after initial treatment, low-risk differentiated thyroid cancer (DTC) patients undergo recombinant human (rh)TSH-stimulated serum thyroglobulin (Tg) (rhTSH-Tg) and neck ultrasound (US). OBJECTIVE: The need for more rhTSH-Tg in these patients is controversial. We evaluated the utility of a second rhTSH-Tg in DTC patients 2-3 yr after their first evaluation. RESULTS: At the first rhTSH-Tg, basal and stimulated serum Tg was undetectable in 68 of 85 patients. Neck US was unremarkable in all but one, who had evidence of lymph node disease. Seventeen of 85 patients had undetectable serum Tg that became positive after rhTSH, with negative imaging in 10 and evidence of disease in seven. Patients with no evidence of disease were reevaluated 2-3 yr later (second rhTSH-Tg). In patients in which the first stimulated Tg was undetectable, all had undetectable basal serum Tg, which remained undetectable after rhTSH in 66 of 67 patients (98.5%) and became detectable in one (1.5%) (positive neck US). In the 10 patients with detectable stimulated Tg in the first test, basal serum Tg and US were negative at the second test, but rhTSH-Tg became detectable in six. Compared with the first rhTSH-Tg, the second stimulated Tg in these six patients decreased in one, increased in three, and stabilized in two patients. CONCLUSIONS: The second rhTSH-Tg was informative in patients who had first stimulated Tg detectable but not in those who had undetectable Tg at the first test, in which the only patient with recurrence was diagnosed by neck US. Thus, rhTSH-Tg should be repeated only in patients who have had a positive first rhTSH-Tg and negative imaging.

Cyclic Cushing's disease with paradoxical response to dexamethasone.

Cyclic Cushing's disease is an unusual disorder characterised by ACTH-dependent periodical increase of serum cortisol levels, clinically accompanied by peripheral edema, abnormalities of cardiac rhythm and hypokalemia. The condition may be unrecognised for years, since the typical features of Cushing's disease are usually absent due to the intermittent and brief duration of cortisol hypersecretion. We describe the case of a 42-yr-old man with Cyclic Cushing's disease due to an ACTH-producing pituitary macroadenoma, who presented two episodes of hypercortisolism in a 3-yr-period, clinically characterised by peripheral edema, hypokalemia and arrhythmia. The diagnosis was suspected because of a paradoxical increase of plasma ACTH and cortisol after dexamethasone administration during an asymptomatic period and was confirmed by pituitary imaging and by final histology after transphenoidal resection of the pituitary adenoma. After surgery, the patient resumed a normal pituitary-adrenal function with restoration of the normal ACTH and cortisol suppression after dexamethasone. Cyclic Cushing's disease should be considered in the differential diagnosis of several conditions characterised by recurrent episodes of idiopathic edema, hypokalemia or unexplained cardiac arrhythmia. In such patients, the pituitary-adrenal axis should be tested possibly during the acute phase of their disease or using the dexamethasone suppression test during asymptomatic intervals.