Endoluminal calprotectin measurement in assessment of pouchitis and a new index of disease activity. A pilot study

Pouchitis is the most common complication following proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis (UC). To provide a standardized definition of pouchitis clinical, endoscopic and histological markers were grouped and weighted in the pouch disease activity index (PDAI). However, the delay in the assessment of the final score due to the time requested for histological analysis remains the main obstacle to the index implementation in clinical practice so that the use of modified-PDAI (mPDAI) with exclusion of histologic subscore has been proposed. We tested the ability of calprotectin measurement in the pouch endoluminal content to mimic the histologic score as defined in the PDAI, the index that we adopted as gold standard for pouchitis diagnosis. Calprotectin was measured by ELISA in the pouch endoluminal content collected during endoscopy in 40 consecutive patients with J-pouch. In each patient PDAI and mPDAI were calculated and 15% of patients were erroneously classified by mPDAI. ROC analysis of calprotectin values vs. acute histological subscore 3 identified different calprotectin cut-off values with corresponding sensitivity and specificity allowing the definition and scoring of different range of calprotectin subscores. We incorporated the calprotectin score in the mPDAI obtaining a new score that shows the same specificity as PDAI for diagnosis of pouchitis and higher sensitivity when compared with mPDAI. The use of the proposed new score, once validated in a larger series of patients, might be useful in the early management of patients with symptoms of pouchitis

New statistical RI index allow to better track the dynamics of COVID-19 outbreak in Italy

COVID-19 pandemic in Italy displayed a spatial distribution that made the tracking of its time course quite difficult. The most relevant anomaly was the marked spatial heterogeneity of COVID-19 diffusion. Lombardia region accounted for around 60% of fatal cases (while hosting 15% of Italian population). Moreover, 86% of fatalities concentrated in four Northern Italy regions. The ‘explosive’ outbreak of COVID-19 in Lombardia at the very beginning of pandemic fatally biased the R-like statistics routinely used to control the disease dynamics. To (at least partially) overcome this bias, we propose a new index RI = dH/dI (daily derivative ratio of H and I, given H = Healed and I = Infected), corresponding to the ratio between healed and infected patients relative daily changes. The proposed index is less flawed than R by the uncertainty related to the estimated number of infected persons and allows to follow (and possibly forecast) epidemic dynamics in a largely model-independent way. To analyze the dynamics of the epidemic, starting from the beginning of the virus spreading—when data are insufficient to make an estimate by adopting SIR model—a "sigmoidal family with delay" logistic model was introduced. That approach allowed in estimating the epidemic peak using the few data gathered even before mid-March. Based on this analysis, the peak was correctly predicted to occur by end of April. Analytical methodology of the dynamics of the epidemic we are proposing herein aims to forecast the time and intensity of the epidemic peak (forward prediction), while allowing identifying the (more likely) beginning of the epidemic (backward prediction). In addition, we established a relationship between hospitalization in intensive care units (ICU) versus deaths daily rates by avoiding the necessity to rely on precise estimates of the infected fraction of the population The joint evolution of the above parameters over time allows for a trustworthy and unbiased estimation of the dynamics of the epidemic, allowing us to clearly detect the qualitatively different character of the ‘so-called’ second wave with respect to the previous epidemic peak

Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas

Background: Low-grade incomplete post-dexamethasone cortisol suppression in patients with adrenal incidentalomas – recently defined as possible autonomous cortisol secretion (pACS) – has been associated with increased cardiovascular events and mortality. However, prospective studies documenting cardiac abnormalities in these patients are lacking. Subjects and methods: Between July 2016 and September 2017, 71 consecutive patients with adrenal lesions were prospectively screened for hypercortisolism by dexamethasone suppression test (NCT 02611258). Complete anthropometric, metabolic and hormonal parameters were recorded along with full cardiac ultrasound assessment and noninvasive measurement of arterial stiffness. All patients underwent chemical-shift magnetic resonance imaging to characterize the lesions. Cardiovascular outcomes were recorded in blind. Results: According to post-dexamethasone suppression cortisol values (post-DST), 34 patients had pACS and 37 nonfunctioning adenomas (NFA). The two groups were similar in sex, BMI, age distribution, cardiovascular risk factors and comorbidities. Left ventricular mass index (LVMIBSA) was increased in pACS compared to NFA (P=0.006) and mildly correlated to the post-DST cortisol level (rho=0.347; P=0.004). The post-DST cortisol levels explained up to 13.7% of LVMIBSAvariance (P=0.002). Compared to NFA, patients with pACS had a higher prevalence of diastolic dysfunction (35.1% vs 82.6%; P=0.001) and worse arterial stiffness assessed by pulse wave velocity (P=0.033). Conclusions: In apparently asymptomatic patients, mild autonomous cortisol secretion can sustain early cardiac and vascular remodeling, independently of other risk factors. The morphological and functional cardiovascular changes observed in pACS underline the need for further studies to correctly define the long-term management of this relatively common condition

Atmospheric deposition of organic matter at a remote site in the central Mediterranean Sea: implications for the marine ecosystem

Abstract. Atmospheric fluxes of dissolved organic matter (DOM) were studied for the first time on the island of Lampedusa, a remote site in the central Mediterranean Sea (Med Sea), between 19 March 2015 and 1 April 2017. The main goals of this study were to quantify total atmospheric deposition of DOM in this area and to evaluate the impact of Saharan dust deposition on DOM dynamics in the surface waters of the Mediterranean Sea. Our data show high variability in DOM deposition rates without a clear seasonality and a dissolved organic carbon (DOC) input from the atmosphere of 120.7 mmol DOC m−2 yr−1. Over the entire time series, the average dissolved organic phosphorus (DOP) and dissolved organic nitrogen (DON) contributions to the total dissolved pools were 40 % and 26 %, respectively. The data on atmospheric elemental ratios also show that each deposition event is characterized by a specific elemental ratio, suggesting a high variability in DOM composition and the presence of multiple sources. This study indicates that the organic substances transported by Saharan dust on Lampedusa mainly come from a natural sea spray and that Saharan dust can be an important carrier of organic substances even though the load of DOC associated with dust is highly variable. Our estimates suggest that atmospheric input has a larger impact on the Med Sea than on the global ocean. Further, DOC fluxes from the atmosphere to the Med Sea can be up to 6 times larger than total river input. Longer time series combined with modeling would greatly improve our understanding of the response of DOM dynamics in the Med Sea to the change in aerosol deposition pattern due to the effect of climate change

Does the length of uniportal video-assisted thoracoscopic lobectomy affect postoperative pain? Results of a randomized controlled trial

Background: Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy has become a common approach for the treatment of early stage lung cancer. Here, we aimed to establish whether the length of uniportal incision could affect postoperative pain and surgical outcomes in consecutive patients undergoing uniportal VATS lobectomy for early stage lung cancer. Methods: This was a unicenter Randomized Control Trial (NCT 03218098). Consecutive patients undergoing uniportal VATS lobectomy for Stage I lung cancer were randomly assigned to a Small Incision group or Long Incision group in 1:1 ratio based on whether patients received a 4 cm or 8 cm incision. The endpoints were to compare the intergroup difference regarding (i) postoperative pain measured by brief pain inventory (BPI) questionnaire (first endpoint); (ii) operative time; (iii) length of chest drainage; (iv) length of hospital stay; (v) postoperative complications; and (vi) pulmonary functional status (secondary endpoints). Results: A total of 48 patients were eligible for the study. Four patients were excluded; the study population included 44 patients: 23 within the Small Incision group, and 21 within the Long Incision group. The 11 BPI scores between the two groups showed no significant difference. Small Incision group presented higher operative time than Long Incision group (138.69 vs. 112.14 minutes; P = 0.0001) while no significant differences were found regarding length of hospital stay (P = 0.95); respiratory complications (P = 0.92); FEV1% (P = 0.63), and 6-Minute Walking Test (P = 0.77). Conclusions: A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. Key points: A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. To perform a larger incision could be a valuable strategy, particularly in nonexpert hands or when the patient's anatomy or tumor size make exposure of anatomic structures through smaller incisions difficult

Assessing the risk of osteonecrosis of the jaw due to bisphosphonate therapy in the secondary prevention of osteoporotic fractures

here is evidence that the use oral bisphosphonates can lead to osteronecrosis of the jaws (ONJ). Although the occurrence of ONJ appears rare among oral bisphosphonates (BPs) users, it is important to know that it exists and can be opportunely minimized. Introduction: The purpose of this study is to evaluate the association between BPs prescribed for the secondary prevention of osteoporotic fractures and the occurrence of ONJ. Methods: An Italian record linkage claims database with a target population of around 18 million individuals (6 million over 55 years of age) constituted the data source. We conducted a nested case-control study within a cohort of individuals aged 55+ years old, who were discharged from hospitals with a primary diagnosis of incident osteoporotic fracture. The date related to the discharge diagnosis of ONJ was the index date. Conditional logistic regression for matched data was fitted to estimate the odds ratio (OR) along with 95 % confidence intervals (95 % CI) for the likely association between use of BPs and the risk of ONJ. Results: Any one of the 61 ascertained cases of ONJ (incidence rate, 36.6 per 100,000 person-years) was matched to 20 controls for a total of 1120 controls. When the exposure to BPs was modeled according to recency (i.e., exposure time window prior to the index date) of use, the adjusted OR (95 % CI) for current users was 2.8 (1.3-5.9) against never users. The cumulative use of BPs has shown to increase the incidence of ONJ among patients with primary osteoporotic fractures, although not statistically significant risk has been observed. Conclusions: Although the risk of BP-related ONJ appears low in non-oncological indications, it is important to be aware that it exists and to know how it may be predicted and possibly minimized

Starch/Poly(glycerol-adipate) Nanocomposites: A Novel Oral Drug Delivery Device

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Biocompatible and bio-based materials are an appealing resource for the pharmaceutical industry. Poly(glycerol-adipate) (PGA) is a biocompatible and biodegradable polymer that can be used to produce self-assembled nanoparticles (NPs) able to encapsulate active ingredients, with encouraging perspectives for drug delivery purposes. Starch is a versatile, inexpensive, and abundant polysaccharide that can be effectively applied as a bio-scaffold for other molecules in order to enrich it with new appealing properties. In this work, the combination of PGA NPs and starch films proved to be a suitable biopolymeric matrix carrier for the controlled release preparation of hydrophobic drugs. Dynamic Light Scattering (DLS) was used to determine the size of drug-loaded PGA NPs, while the improvement of the apparent drug water solubility was assessed by UV-vis spectroscopy. In vitro biological assays were performed against cancer cell lines and bacteria strains to confirm that drug-loaded PGA NPs maintained the effective activity of the therapeutic agents. Dye-conjugated PGA was then exploited to track the NP release profile during the starch/PGA nanocomposite film digestion, which was assessed using digestion models mimicking physiological conditions. The collected data provide a clear indication of the suitability of our biodegradable carrier system for oral drug delivery.Peer reviewedFinal Published versio