Building a local climate reference dataset: application to the Abruzzo region (Central Italy), 1930–2019

Reliable secular time series of essential climatic variables are a fundamental element for the assessment of vulnerability, impact and adaptation to climate change. Here, we implement a readily portable procedure for building an upgradable long‐term homogeneous climate dataset using monthly and daily observations of temperature and precipitation over a given area of interest, exemplified here with Abruzzo, a region in Central Italy characterized by complex orography. We process the dataset according to a preliminary ranking of stations based on data quantity and quality, and we exploit the Climatol algorithm for inhomogeneity correction. The corrected time series show trends in broad agreement with external databases (CRU, Berkeley Earth, E‐OBS), and highlight the importance of relying on a local network for a better representation of gradients and variability over the territory. We estimate that maximum (TX) and minimum temperature (TN) increased by ~1.6 and ~2.2°C/century, respectively, over the period 1930–2019, while in the recent decades 1980–2019 we found an accelerated trend of ~5.7 and ~3.9°C/century. Precipitation (RR) decreased by ~10%/century in 1930–2019, while it has been increasing at a rate of ~26%/century in 1980–2019. The Köppen–Geiger climate classification is sensitive to the increase of precipitation in the recent decades, which is attributable to decreased summer precipitation overcompensated by more rain in late spring and early autumn. The cold climate types are retreating upwards along the slopes of the mountain ranges. Over the period 1980–2019, extreme values are also displaying significant trends. Every 2 years, there is one less frost day (TN 25°C) in the Apennines area, while there is one more tropical night (TN >20°C) in the Adriatic coastal area. Precipitation extremes are increasing, especially along the coast, with rain accumulated in the rainiest days increasing at a rate of 1–2%/year

Increased Urinary Albumin Excretion, Insulin Resistance, and Related Cardiovascular Risk Factors in Patients With Type 2 Diabetes

OBJECTIVE—While the relevant role of insulin resistance in the pathogenesis of increased urinary albumin excretion (UAE) is well established in type 1 diabetes, its contribution in type 2 diabetes is controversial. Our aim was to investigate whether insulin resistance was associated with increased UAE in a large cohort of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS— A total of 363 men and 349 women, aged 61 ± 9 years, with a disease duration of 11 ± 9 years and HbA1c levels of 8.6 ± 2.0% were included. Insulin resistance was derived from the homeostasis model assessment of insulin resistance (HOMAIR), and UAE was derived from the albumin-to-creatinine ratio (ACR) defined as increased if the value was ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women. ACR was correlated with HOMAIR (r = 0.15, P = 0.0001), independently of age, disease duration, blood pressure, HbA1c, triglycerides, waist circumference, and smoking. RESULTS—When the two sexes were investigated separately, a significant correlation between ACR and HOMAIR was reached in men (n = 363; r = 0.21, P = 0.0001) but not women (n = 349; r = 0.08, P = 0.14), suggesting that insulin resistance and sex may interact (P for interaction = 0.04) in determining UAE. When men were subgrouped into quartiles of HOMAIR, those of the third and fourth quartile (i.e., the most insulin resistant) were at higher risk to have increased ACR than patients of the first quartile (third quartile: odds ratio 2.2 [95% CI 1.2–4.2], P = 0.01) (fourth quartile: 4.1 [2.2–7.9], P = 0.00002). Finally, ACR was significantly higher in men with two or more insulin resistance–related cardiovascular risk factors (i.e., abdominal obesity, dyslipidemia, and arterial hypertension) than in men with fewer than two insulin resistance–related cardiovascular risk factors (0.90 [0.2–115.1] vs. 1.56 [0.1–1367.6], respectively, P = 0.005). CONCLUSIONS—In type 2 diabetic patients, increased UAE is strongly associated with insulin resistance and related cardiovascular risk factors. This association seems to be stronger in men than in women

Ophthalmic manifestation in neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) is a genetically determined tumor-predisposing syndrome. Ocular manifestations include cataracts, epiretinal membranes, retinal hamartomas, optic disk gliomas, and optic nerve sheath meningiomas. Moreover, optic disk edema, optical atrophy, motility disorders, pupil and lid dysfunction, and neurotrophic keratitis can be observed as indirect signs. An observational study was conducted with the aim to collect clinical data and describe the most frequent NF2 ocular manifestations. Fourteen patients affected by NF2, according to the Manchester criteria, were enrolled. All patients underwent complete ophthalmologic and orthoptic evaluation and a spectral domain optical coherence tomography. Ocular manifestations were present in all patients. The slit lamp evaluation of the anterior segment highlighted cataracts in five patients, keratitis in two patients, corneal leukoma in two patients, and corneal pannus in one patient. Fundus oculi and OCT evaluation identified epiretinal membranes in four patients, vitreoretinal tufts in three patients, optic nerve edema in one patient, and retinal hamartoma in one patient. Moreover, the orthoptic evaluation identified different types of ocular motility disorders in seven patients. This is a descriptive study of a rare disease with poor previous literature. Clinical data are shown, emphasizing the role of NF2-specific ophthalmological and orthoptic findings to help establish an early diagnosis

Prevention, Screening, Treatment and Follow-Up of Gynecological Cancers: State of Art and Future Perspectives

Objective: This study aims to analyze the available data on prevention and early diagnosis in gynecological cancers. Mechanism: A comprehensive search was performed in the PubMed (MEDLINE), EMBASE, SCOPUS and Web of Science databases. Findings in Brief: To date the prevention programmes of all degrees exist exclusively for cervical cancer. Human Papilloma Virus (HPV) vaccination prevents from infection and development of precancerous lesions and contributes significantly to the deflection of the incidence of cervical cancer. Screening for HPV-related lesions is worldwide performed by cervical smear (Pap-test) and HPV test. Finally, tertiary prevention is aimed at the treatment of previously diagnosticated lesions with the aid of surgery, chemotherapy, radiotherapy and immunotherapy. Unfortunately, to date the prevention programmes of other gynecological tumors have not reached a good performance; indeed, the primum movens that leads to the development of such neoplasms has not been identified yet. Actually, no screening programs for the early diagnosis of endometrial cancer are available, however, it is recommended the adoption of a healthy lifestyle and a balanced diet. Diagnostic biomarkers would be helpful for screening asymptomatic high-risk women, but histopatological examinations remain the gold standard for diagnosis of endometrial cancer. Similarly, there are no screening tests for the diagnosis of ovarian cancer. In recent years many steps forward have been made in this field and new perspectives have been presented, however, additional investigation is needed to optimize the duration and timing of treatment, examine its cost-effectiveness, and identify potential tumor or host biologic factors predictive of the efficacy and adverse events. Finally, there are no primary and secondary prevention for vulvar cancer so patients should be invited to self-examination and pay attention to the presence of symptoms. Conclusions: Are the available screening programs for the diagnosis of gynecological carcinomas sufficient? The prevention and the diagnosis of precancerous lesions is the goal to be achieved for all gynecological cancers in order to improve patient outcomes, reduce the costs for managing the disease and prolonged follow up

A challenging surgical approach to locally advanced primary urethral carcinoma: A case report and literature review

Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and "en bloc" removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of the bulbomembranous urethra should be managed with radical surgery including the corporas up to the ischiatic tuberosity attachment, and membranous urethra in continuity with the prostate and bladder. Neo-adjuvant treatment may be advisable with the aim of improving the poor prognosis, even if the efficacy is not certain while it can delay the radical treatment of the disease

The Ubiquitin-Proteasome System and Inflammatory Activity in Diabetic Atherosclerotic Plaques

The role of ubiquitin-proteasome system in the accelerated atherosclerotic progression of diabetic patients is unclear. We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic diabetic and nondiabetic patients, as well as the effect of rosiglitazone, a peroxisome proliferator–activated receptor (PPAR)-γ activator, in diabetic plaques. Plaques were obtained from 46 type 2 diabetic and 30 nondiabetic patients undergoing carotid endarterectomy. Diabetic patients received 8 mg rosiglitazone (n = 23) or placebo (n = 23) for 4 months before scheduled endarterectomy. Plaques were analyzed for macrophages (CD68), T-cells (CD3), inflammatory cells (HLA-DR), ubiquitin, proteasome 20S activity, nuclear factor (NF)-κB, inhibitor of κB (IκB)-β, tumor necrosis factor (TNF)-α, nitrotyrosine, matrix metalloproteinase (MMP)-9, and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay). Compared with nondiabetic plaques, diabetic plaques had more macrophages, T-cells, and HLA-DR+ cells (P < 0.001); more ubiquitin, proteasome 20S activity (TNF-α), and NF-κB (P < 0.001); and more markers of oxidative stress (nitrotyrosine and O2− production) and MMP-9 (P < 0.01), along with a lesser collagen content and IκB-β levels (P < 0.001). Compared with placebo-treated plaques, rosiglitazone-treated diabetic plaques presented less inflammatory cells (P < 0.01); less ubiquitin, proteasome 20S, TNF-α, and NF-κB (P < 0.01); less nitrotyrosine and superoxide anion production (P < 0.01); and greater collagen content (P < 0.01), indicating a more stable plaque phenotype. Similar findings were obtained in circulating monocytes obtained from the two groups of diabetic patients and cultured in the presence or absence of rosiglitazone (7.0 μmol/l). Ubiquitin-proteasome over-activity is associated with enhanced inflammatory reaction and NF-κB expression in diabetic plaques. The inhibition of ubiquitin-proteasome activity in atherosclerotic lesions of diabetic patients by rosiglitazone is associated with morphological and compositional characteristics of a potential stable plaque phenotype, possibly by downregulating NF-κB-mediated inflammatory pathways

Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment

BACKGROUND: Transarterial chemoembolization (TACE) is one of the most frequently applied treatments for hepatocellular carcinoma (HCC) worldwide. In this study, we aimed at evaluating whether and how TACE application and repetition, as well as the related outcome, have changed over the last three decades in Italy. METHODS: Data of 7,184 patients with HCC were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. Patients were divided according to the period of diagnosis in six cohorts: P1 (1988–1993), P2 (1994–1998), P3 (1999–2004), P4 (2005–2009), P5 (2010–2014), and P6 (2015–2019). All the analyses were repeated in the overall patient population and in Barcelona Clinic Liver Cancer (BCLC) B patients, who are the subgroup of HCC patients originally supposed to receive TACE according to guidelines. TACE was defined as either the first or the main (more effective) treatment. RESULTS: The proportion of patients receiving TACE as first or main therapy declined over time, and less than 50% of BCLC B patients were treated with chemoembolization from P3 onward. Conversely, TACE was widely used even outside the intermediate stage. Survival of TACE-treated patients progressively increased from P1 to P6. Although TACE was performed only once in the majority of patients, there was an increasing proportion of those receiving 2 or ≥3 treatments sessions over time. The overall survival (OS) of patients undergoing repeated treatments was significantly higher compared to those managed with a single TACE (median OS 40.0 vs. 65.0 vs. 71.8 months in 1, 2, and ≥3 TACE groups, respectively; p < 0.0001). However, after a first-line TACE, the adoption of curative therapies provided longer survival than repeating TACE (83.0 vs. 42.0 months; p < 0.0001), which in turn was associated with better outcomes compared to systemic therapies or best supportive care (BSC). CONCLUSIONS: Despite a decline in the percentage of treated patients over time, TACE has still an important role in the management of HCC patients. The survival of TACE-treated patients gradually improved over time, probably due to a better patient selection. Iterative TACE is effective, but an upward shift to curative therapies provides better outcomes while transition to systemic therapies and BSC leads to a worse prognosis

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin