Recipient hepatectomy technique may affect oncological outcomes of liver transplantation for hepatocellular carcinoma.

To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.

Extracellular vesicle features are associated with COVID-19 severity.

COVID-19 is heterogeneous; therefore, it is crucial to identify early biomarkers for adverse outcomes. Extracellular vesicles (EV) are involved in the pathophysiology of COVID-19 and have both negative and positive effects. The objective of this study was to identify the potential role of EV in the prognostic stratification of COVID-19 patients. A total of 146 patients with severe or critical COVID-19 were enrolled. Demographic and comorbidity characteristics were collected, together with routine haematology, blood chemistry and lymphocyte subpopulation data. Flow cytometric characterization of the dimensional and antigenic properties of COVID-19 patients' plasma EVs was conducted. Elastic net logistic regression with cross-validation was employed to identify the best model for classifying critically ill patients. Features of smaller EVs (i.e. the fraction of EVs smaller than 200 nm expressing either cluster of differentiation [CD] 31, CD 140b or CD 42b), albuminemia and the percentage of monocytes expressing human leukocyte antigen DR (HLA-DR) were associated with a better outcome. Conversely, the proportion of larger EVs expressing N-cadherin, CD 34, CD 56, CD31 or CD 45, interleukin 6, red cell width distribution (RDW), N-terminal pro-brain natriuretic peptide (NT-proBNP), age, procalcitonin, Charlson Comorbidity Index and pro-adrenomedullin were associated with disease severity. Therefore, the simultaneous assessment of EV dimensions and their antigenic properties complements laboratory workup and helps in patient stratification.

Rare forms of genetic paediatric adrenal insufficiency: Excluding congenital adrenal hyperplasia.

Adrenal insufficiency (AI) is a severe endocrine disorder characterized by insufficient glucocorticoid (GC) and/or mineralocorticoid (MC) secretion by the adrenal glands, due to impaired adrenal function (primary adrenal insufficiency, PAI) or to insufficient adrenal stimulation by pituitary ACTH (secondary adrenal insufficiency, SAI) or tertiary adrenal insufficiency due to hypothalamic dysfunction. In this review, we describe rare genetic causes of PAI with isolated GC or combined GC and MC deficiencies and we also describe rare syndromes of isolated MC deficiency. In children, the most frequent cause of PAI is congenital adrenal hyperplasia (CAH), a group of adrenal disorders related to steroidogenic enzyme deficiencies, which will not be included in this review. Less frequently, several rare diseases can cause PAI, either affecting exclusively the adrenal glands or with systemic involvement. The diagnosis of these diseases is often challenging, due to the heterogeneity of their clinical presentation and to their rarity. Therefore, the current review aims to provide an overview on these rare genetic forms of paediatric PAI, offering a review of genetic and clinical features and a summary of diagnostic and therapeutic approaches, promoting awareness among practitioners, and favoring early diagnosis and optimal clinical management in suspect cases.

Stem Cells mobilization and collection in allogeneic related and unrelated donors: a single center experience with focus on plerixafor.

INTRODUCTION: Poor CD34 + cells mobilization in allogeneic donors could affect transplant outcome. In a subgroup of patient mobilization with granulocyte colony-stimulating factor (G-CSF) alone is unsatisfactory, and Plerixafor could be used to enhance CD34 + cells release from bone marrow niche. MATERIALS AND METHODS: We conducted a retrospective single-center, cohort study on healthy allogeneic donors both related and unrelated, treated by Udine Transfusion Center over the last 10 years (2012-2022). In the 195 allogeneic donors treated we analyzed age, sex, body weight, BMI, comorbidities, G-CSF dosage and even baseline white blood cell count as possible predictor of insufficient CD34 + cells mobilization on day 5. In the subgroup of related donors we evaluated even baseline CD34 + cells (measured before mobilization start). Processed donor blood volume, collection efficiency and apheresis product were examined. Additionally a comparative analysis was conducted between G-CSF alone treated donors and poor mobilizing ones, in which Plerixafor was administered at a dose of 0.24 mg/kg as a pre-emptive or rescue agent. RESULTS: In 9 donors, due to poor mobilization (defined as CD34 + < 20/µL or estimated yield < 1 ×106 kg/recipient body weight), the use of plerixafor was necessary. PLX at a dose of 0.24 mg/kg was administered 5 h before collection, inducing an average increase of 5.1 (1.7-12.6) in CD34 + circulating cells. In this subgroup of patients, BMI and weight were significantly lower (p = 0.03). Interestingly, baseline CD34 + cells (measured before the onset of mobilization) also seems to predict poor mobilization (p = 0.003). In donors additionally treated with Plerixafor compared to those who received G-CSF alone, collection efficiency was higher (p = 0.02) and CD34 + cells collected were comparable (p = 0.2). Side effects related to the administration of plerixafor, if they occurred, were well tolerated. CONCLUSIONS: Plerixafor is a safe and effective drug in the rescue and prevention of poor mobilization. New prospective studies on allogeneic donors should be performed to increase the treatable population to avoid inadequate collection and mobilization. New laboratory predictors such as baseline CD34 + cells should be investigated in larger cohorts and then used as early screening.

Lessons learnt while designing and conducting a longitudinal study from the first Italian COVID-19 pandemic wave up to 3 years.

BACKGROUND: Several scientific contributions have summarized the "lessons learnt" during the coronavirus disease 2019 (COVID-19) pandemic, but only a few authors have discussed what we have learnt on how to design and conduct research during a pandemic. The main intent of this study was to summarize the lessons learnt by an Italian multidisciplinary research group that developed and conducted a longitudinal study on COVID-19 patients infected during the first wave in March 2020 and followed-up for 3 years. METHODS: A qualitative research approach embedded into the primary CORonavirus MOnitoRing study (CORMOR) study was developed, according to the the consolidated criteria for reporting qualitative research. Multiple data collection strategies were performed: each member was invited to report the main lessons learnt according to his/her perspective and experience from the study design throughout its conduction. The narratives collected were summarized and discussed in face-to-face rounds. The narratives were then thematically analysed according to their main topic in a list that was resent to all members to check the content and their organization. The list of the final "lessons learnt" has been agreed by all members, as described in a detailed fashion. RESULTS: Several lessons were learnt while designing and conducting a longitudinal study during the COVID-19 pandemic and summarised into ten main themes: some are methodological, while others concern how to conduct research in pandemics/epidemics/infectious disease emergencies. CONCLUSIONS: The multidisciplinary approach, which also included patients' perspective, helped us to protect the consistency and quality of the research provided in pandemic times. The lesson learnt suggest that our research approach may benefit from changes in education, clinical practice and policies.

Evaluation of Kinesio Taping for Edema, Ecchymosis, and Pain After Liposuction: A Prospective Pilot Study.

BACKGROUND: Liposuction is a safe, simple, and effective method of body contouring. Pain, ecchymosis, and edema are often local complications at the removal site, especially in the first weeks after surgery. Several studies have shown that kinesiology (kinesio) taping improves blood and lymphatic flow, removing congestions of lymphatic fluid and alleviating hemorrhage. However, there are limited data on the effect of kinesio taping in mitigating local complications at fat grafting donor sites. OBJECTIVES: The aim of this pilot study was to evaluate the impact of kinesio taping in reducing postoperative edema, pain, and ecchymosis in the liposuction area. METHODS: Over a period of 18 months (January 2021-June 2022), 52 patients underwent liposuction of both flanks with subsequent breast fat grafting. Immediately after the surgery, kinesio taping was used on the right abdomen flank in all patients. Degree of edema as well as ecchymosis and pain were quantified at 7, 14, and 21 days after surgery. RESULTS: There were statistically significant differences in the taping area for ecchymosis at 7 days after surgery, edema at 14 and 21 days after surgery, and in pain, rated on a visual analog scale, at 7, 14 and 21 days after surgery. CONCLUSIONS: Kinesio taping, as used in this study, is beneficial in the reduction of edema and pain and the resolution of ecchymosis after liposuction.

Twin-Engine Janus Supramolecular Nanomotors with Counterbalanced Motion.

Supramolecular nanomotors were created with two types of propelling forces that were able to counterbalance each other. The particles were based on bowl-shaped polymer vesicles, or stomatocytes, assembled from the amphiphilic block copolymer poly(ethylene glycol)-block-polystyrene. The first method of propulsion was installed by loading the nanocavity of the stomatocytes with the enzyme catalase, which enabled the decomposition of hydrogen peroxide into water and oxygen, leading to a chemically induced motion. The second method of propulsion was attained by applying a hemispherical gold coating on the stomatocytes, on the opposite side of the opening, making the particles susceptible to near-infrared laser light. By exposing these Janus-type twin engine nanomotors to both hydrogen peroxide (H2O2) and near-infrared light, two competing driving forces were synchronously generated, resulting in a counterbalanced, "seesaw effect" motion. By precisely manipulating the incident laser power and concentration of H2O2, the supramolecular nanomotors could be halted in a standby mode. Furthermore, the fact that these Janus stomatocytes were equipped with opposing motile forces also provided a proof of the direction of motion of the enzyme-activated stomatocytes. Finally, the modulation of the "seesaw effect", by tuning the net outcome of the two coexisting driving forces, was used to attain switchable control of the motile behavior of the twin-engine nanomotors. Supramolecular nanomotors that can be steered by two orthogonal propulsion mechanisms hold considerable potential for being used in complex tasks, including active transportation and environmental remediation.

Performing real time neuropsychological testing during awake craniotomy: are dexmedetomidine or propofol the same? A preliminary report.

PURPOSE: In awake surgery, the patient is sedated, but is also required to be sufficiently alert and collaborative during extensive neurocognitive testing. In the present preliminary report of a retrospective single-center study, a continuous series of 168 patients who underwent awake surgery for brain tumor located near eloquent areas, was investigated to observe the effect of dexmedetomidine (n = 58) compared with propofol (n = 110) on vigilance and collaboration required to perform extensive intra-operatory Real Time Neuropsychological Testing (RTNT). METHODS: We assigned a score to each patient, by using a scale that combines vigilance and collaboration in a 5 levels score (the higher score denoting higher level). RESULTS: The median interquartile range was significantly lower (range 3-5) for the dexmedetomidine group compared to the propofol one (range 4-5, p = .044). Patients with intra-operative seizures (p = .014) and/or electrocorticographic slow/epileptiform activity (p = .042), and patients in the propofol group who showed increased heart rate (p = .032) were those who obtained the lower scores (lower vigilance and collaboration level). CONCLUSION: The study shows that the effect of dexmedetomidine or propofol -based conscious sedation on ability to perform Real Time Neuropsychological Testing during awake surgery for supratentorial tumor resection is different. Although both permit high mean levels of vigilance and collaboration, the patient who received dexmedetomidine was more likely to show lower vigilance and collaboration during RTNT.

Evaluation of qualitative and semi-quantitative cut offs for rapid diagnostic lateral flow test in relation to serology for the detection of SARS-CoV-2 antibodies: findings of a prospective study.

BACKGROUND: There is limited information to compare the qualitative and semi-quantitative performance of rapid diagnostic tests (RDT) and serology for the assessment of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, the objective of the study was (a) to compare the efficacy of SARS-CoV-2 antibody detection between RDT and laboratory serology, trying to identify appropriate semi-quantitative cut-offs for RDT in relation with quantitative serology values and to (b) evaluate diagnostic accuracy of RDT compared to the NAAT gold standard in an unselected adult population. METHODS: SARS-CoV-2 antibodies were simultaneously measured with lateral flow immunochromatographic assays (LFA), the Cellex qSARS-CoV-2 IgG/IgM Rapid Test (by capillary blood), the iFlash-SARS-CoV-2 IgG/IgM chemiluminescent immunoassay (CLIA) (by venous blood) and the nucleic acid amplification test (NAAT) in samples from in- and out-patients with confirmed, suspected and negative diagnosis of coronavirus disease 2019 (COVID-19) attending Udine Hospital (Italy) (March-May 2020). Interpretation of RDT was qualitative (positive/negative) and semi-quantitative based on a chromatographic intensity scale (negative, weak positive, positive). RESULTS: Overall, 720 paired antibody measures were performed on 858 patients. The qualitative and semiquantitative agreement analysis performed in the whole sample between LFA and CLIA provided a Kendall's tau of 0.578 (p < 0.001) and of 0.623 (p < 0.001), respectively, for IgM and IgG. In patients with a diagnosis of COVID-19, accordance between LFA and CLIA was maintained as a function of time from the onset of COVID-19 disease and the severity of disease both for qualitative and semi-quantitative assessments. RDT compared to the NAAT gold standard in 858 patients showed 78.5% sensitivity (95% CI 75.1%-81.7%) and 94.1% specificity (95% CI 90.4%-96.8%), with variable accordance depending on the timing from symptom onset. CONCLUSION: The RDT used in our study can be a non-invasive and reliable alternative to serological tests and facilitate both qualitative and a semi-quantitative antibody detection in COVID-19.

Lung ultrasound score follows the chronic pulmonary insufficiency of prematurity trajectory in early infancy.

Extremely preterm birth is associated with a high risk of chronic pulmonary insufficiency of prematurity (CPIP). Lung ultrasound score (LUS) proved capable to characterise CPIP progression beyond the acute setting, but still, post-discharge data remain lacking. We hypothesised a priori that LUS in both BPD and no-BPD infants declines with postnatal age from birth through early infancy. This observational retrospective cohort study included preterm infants < 32 gestational weeks, who underwent the follow-up for CPIP. LUS was assessed from birth to 8 months postnatal age, over antero-lateral (LUS) and posterior (pLUS) pulmonary areas, placing the transducer longitudinally over the midclavicular and midaxillary lines and medial to the scapular line respectively. Extended LUS (eLUS) including LUS and pLUS was calculated. The primary outcome was LUS time course. Secondary outcomes included the correlation between LUS and pLUS. Sixty-two infants were included: 22 (35.5%) in the BPD group and 40 (64.5%) in the no-BPD group. BPD group infants were smaller (weight 841 g (± 228) vs 1226 (± 328), p < 0.001) and younger (26.8 weeks (± 2.0) vs 28.9 (± 1.9), p < 0.001). LUS declined over time in the entire population (ß = - 1.75, p < 0.001) and in both no-BPD and BPD groups (ß = - 1.64, p < 0.001 and ß = - 1.93, p < 0.001, respectively). eLUS declined correspondingly (p < 0.001). LUS and likewise eLUS were significantly different between BPD and no-BPD groups over time (p < 0.001).  Conclusion: LUS trajectory progressively decreased from birth to early infancy. BPD cohort tracked higher, implying a worse respiratory status. pLUS had a similar timepoint course, adding no further information to LUS. To the best of our knowledge, this is the first study that describes preterm LUS time course after discharge. LUS may help track the CPIP progression. What is Known: • Extremely preterm birth is associated with high risk of chronic pulmonary insufficiency of prematurity (CPIP). • Several studies investigated the ability of lung ultrasound score (LUS) to characterize CPIP progression beyond the acute setting, still post-discharge data remain lacking. What is New: • LUS trajectory progressively decreases from birth to early infancy; BPD cohort tracks higher, implying a worse respiratory status. pLUS has similar timepoint course, adding no further information to LUS. • The use of LUS may contribute to better characterising and monitoring CPIP in BPD and no-BPD infants.

Early 3-day course of remdesivir to prevent progression to severe Covid-19 in high-risk patients with hospital-acquired SARS-CoV-2 infection: preliminary results from two Italian outbreaks.

In multimorbid, unvaccinated and non-hospitalized patients, early administration of remdesivir, nirmatrelvir/ritonavir and molnupiravir was effective in reducing the risk of hospitalization or death from any cause. Similar data are lacking with regard to patients already hospitalized and who acquire in-hospital SARS-CoV-2 infection. We conducted a retrospective study during two outbreaks of SARS-CoV-2 infections involving 90 inpatients already hospitalized for medical or surgical conditions, in order to assess the effectiveness of early administration of remdesivir. Forty-seven cases were treated with a 3-day course of remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) within a median time of 1.4 day from testing positive, and were compared to a matched case-control cohort of 43 untreated patients; matching was based on age, sex, vaccination status, previous symptomatic infections by SARS-CoV-2, reasons for hospitalization (no significant differences). No case presented adverse events to remdesivir or death from COVID-19. No significant difference in overall in-hospital mortality was observed in cases compared to controls (17% vs 16.3%, p=0.925), but progression to severe pneumonia, although the difference was still not significant, showed an evident trend of a better outcome (8.5% vs 16.3%, p=0.261). Moreover, cases had a median discharge delay of 3 days (p=0.008).

Combining Deep Phenotyping of Serum Proteomics and Clinical Data via Machine Learning for COVID-19 Biomarker Discovery.

The persistence of long-term coronavirus-induced disease 2019 (COVID-19) sequelae demands better insights into its natural history. Therefore, it is crucial to discover the biomarkers of disease outcome to improve clinical practice. In this study, 160 COVID-19 patients were enrolled, of whom 80 had a "non-severe" and 80 had a "severe" outcome. Sera were analyzed by proximity extension assay (PEA) to assess 274 unique proteins associated with inflammation, cardiometabolic, and neurologic diseases. The main clinical and hematochemical data associated with disease outcome were grouped with serological data to form a dataset for the supervised machine learning techniques. We identified nine proteins (i.e., CD200R1, MCP1, MCP3, IL6, LTBP2, MATN3, TRANCE, α2-MRAP, and KIT) that contributed to the correct classification of COVID-19 disease severity when combined with relative neutrophil and lymphocyte counts. By analyzing PEA, clinical and hematochemical data with statistical methods that were able to handle many variables in the presence of a relatively small sample size, we identified nine potential serum biomarkers of a "severe" outcome. Most of these were confirmed by literature data. Importantly, we found three biomarkers associated with central nervous system pathologies and protective factors, which were downregulated in the most severe cases.

The Fall in Antibody Response to SARS-CoV-2: a Longitudinal Study of Asymptomatic to Critically Ill Patients Up to 10 Months after Recovery.

The aim of this study was to assess the long-term dynamics and factors associated with the serological response against the severe acute respiratory syndrome coronavirus 2 after primary infection. A prospective longitudinal study was conducted with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with coronavirus disease 2019 (COVID-19) attending Udine Hospital (Italy) during the first wave (from March to May 2020). A total of 546 individuals were included (289 female, mean age 53.1 years), mostly with mild COVID-19 (370, 68.3%). Patients were followed for a median of 302 days (interquartile range, 186 to 311). The overall seroconversion rate within 2 months was 32% for IgM and 90% for IgG. Seroreversion was observed in 90% of patients for IgM at 4 months and in 47% for IgG at 10 months. Older age, number of symptoms at acute onset, and severity of acute COVID-19 were all independent predictors of long-term immunity both for IgM (ß, linear regression coefficient, 1.10, P = 0.001; ß 5.15 P = 0.014; ß 43.84 P = 0.021, respectively) and for IgG (ß 1.43 P < 0.001; ß 10.46 P < 0.001; ß 46.79 P < 0.001, respectively), whereas the initial IgG peak was associated only with IgG duration (ß 1.12, P < 0.001). IgM antibodies disappeared at 4 months, and IgG antibodies declined in about half of patients 10 months after acute COVID-19. These effects varied depending on the intensity of the initial antibody response, age, and burden of acute COVID-19.

Paediatric Cushing's disease: Epidemiology, pathogenesis, clinical management and outcome.

Cushing's disease (CD) is rare in paediatric practice but requires prompt investigation, diagnosis and therapy to prevent long-term complications. Key presenting features are a change in facial appearance, weight gain, growth failure, virilization, disturbed puberty and psychological disturbance. Close consultation with an adult endocrinology department is recommended regarding diagnosis and therapy. The incidence of CD, a form of ACTH-dependent Cushing's syndrome (CS), is equal to approximately 5% of that seen in adults. The majority of ACTH-secreting adenomas are monoclonal and sporadic, although recent studies of pituitary tumours have shown links to several deubiquitination gene defects. Diagnosis requires confirmation of hypercortisolism followed by demonstration of ACTH-dependence. Identification of the corticotroph adenoma by pituitary MRI and/or bilateral inferior petrosal sampling for ACTH may contribute to localisation before pituitary surgery. Transsphenoidal surgery (TSS) with selective microadenomectomy is first-line therapy, followed by external pituitary irradiation if surgery is not curative. Medical therapy to suppress adrenal steroid synthesis is effective in the short-term and bilateral adrenalectomy should be considered in cases unfit for TSS or radiotherapy or when urgent remission is needed after unsuccessful surgery. TSS induces remission of hypercortisolism and improvement of symptoms in 70-100% of cases, particularly when performed by a surgeon with experience in children. Post-TSS complications include pituitary hormone deficiencies, sub-optimal catch-up growth, and persisting excess of BMI. Recurrence of hypercortisolism following remission is recognised but infrequent, being less common than in adult CD patients. With experienced specialist medical and surgical care, the overall prognosis is good. Early referral to an experienced endocrine centre is advised.

Cortisol Circadian Rhythm and Insulin Resistance in Muscle: Effect of Dosing and Timing of Hydrocortisone Exposure on Insulin Sensitivity in Synchronized Muscle Cells.

INTRODUCTION/AIM: Circadian clock disruption is emerging as a risk factor for metabolic disorders, and particularly, alterations in clock genes circadian expression have been shown to influence insulin sensitivity. Recently, the reciprocal interplay between the circadian clock machinery and hypothal-amus-pituitary-adrenal axis has been largely demonstrated: the circadian clock may control the physiological circadian endogenous glucocorticoid (GC) secretion and action; GCs, in turn, are potent regulators of the circadian clock and their inappropriate replacement has been associated with metabolic impairment. The aim of the current study was to investigate in vitro the interaction between the timing-of-the-day exposure to different hydrocortisone (HC) concentrations and muscle insulin sensitivity. METHODS: Serum-shock synchronized mouse skeletal muscle C2C12 cells were exposed to different HC concentrations resembling the circulating daily physiological cortisol profile (standard cortisol profile) and the circulating daily cortisol profile that reached in adrenal insufficient (AI) patients treated with once-daily modified-release HC (flat cortisol profile) and treated with thrice-daily conventional immediate-release HC (steep cortisol profile). The 24 h spontaneous oscillation of the clock genes in synchronized C2C12 cells was used to align the timing for in vitro HC exposure (Bmal1 acrophase, midphase, and bathyphase) with the reference times of cortisol peaks in AI patients treated with IR-HC (8 a.m., 1 p.m., and 6 p.m.). A panel of 84 insulin sensitivity-related genes and intracellular insulin signaling proteins were analyzed by RT-qPCR and Western blot, respectively. RESULTS: The steep profile, characterized by a higher HC exposure during Bmal1bathyphase, produced significant downregulation in 21 insulin sensitivity-related genes including Insr, Irs1, Irs2, Pi3kca, and Adipor2, compared to the flat and standard profile. Reduced intracellular IRS1 Tyr608, AKT Ser473, AMPK Thr172, and ACC Ser79 phosphorylations were also observed. CONCLUSIONS: The current study demonstrated that late-in-the-day cortisol exposure modulates insulin sensitivity-related gene expression and intracellular insulin signaling in skeletal muscle cells.

Low risk of reinfections and relation with serological response after recovery from the first wave of COVID-19.

The aim of the study was to assess reinfection rates in relation to long-term antibody dynamics against SARS-CoV-2 after the first wave. A prospective longitudinal study with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with COVID-19 attending Udine Hospital (Italy) from March to May 2020. During the follow-up, reinfections were collected. A total of 546 unselected individuals with COVID-19 acquired from March to May 2020 were included (292 female, mean age 53 years). After a median follow-up of 10 months (IQR 6.2-10.4), reinfection occurred in 6 (1.1%) patients, median age of 44.5 years (IQR 33‒49). All had a previous history of mild COVID-19 (all were healthcare workers) and reinfection occurred a median of 9 months (IQR 8.2‒10.2) after the onset of the first episode. Patients with reinfection were either seronegative (2/56, n = 3.6%), seroreverted (2/137, 1.5%), or seropositive (2/353, 0.6%) (p = 0.085). All reinfections were mild (n = 5) or asymptomatic (n = 1). After reinfection, none of patients developed IgM response and only two had a transitory boosted IgG immunization response. In an unselected population after the first wave of COVID-19, after a prolonged observation period (mean 10 months), reinfection was very uncommon; occurred in patients with a previous history of mild infection, mostly with weak or absent serological response; and manifested with mild or asymptomatic clinical presentation.

Semantics-weighted lexical surprisal modeling of naturalistic functional MRI time-series during spoken narrative listening.

Probabilistic language models are increasingly used to provide neural representations of linguistic features under naturalistic settings. Word surprisal models can be applied to continuous fMRI recordings during task-free listening of narratives, to detect regions linked to language prediction and comprehension. Here, to this purpose, a novel semantics-weighted lexical surprisal is applied to naturalistic fMRI data. FMRI was performed at 3 Tesla in 31 subjects during task-free listening to a 12-minute audiobook played in both original and word-reversed (control) version. Lexical-only and semantics-weighted lexical surprisal models were estimated for the original and control word series. The two series were alternatively chosen to build the predictor of interest in the first-level general linear model and were compared in the second-level (group) analysis. The addition of the surprisal predictor to the stimulus-related predictors significantly improved the fitting of the neural signal. In average, the semantics-weighted model yielded lower surprisal values and, in some areas, better fitting of the fMRI data compared to the lexical-only model. The two models produced both overlapping and distinct activations: while lexical-only surprisal activated secondary auditory areas in the superior temporal gyri and the cerebellum, semantics-weighted surprisal additionally activated the left inferior frontal gyrus. These results confirm the usefulness of surprisal models in the naturalistic fMRI analysis of linguistic processes and suggest that the use of semantic information may increase the sensitivity of a probabilistic language model in higher-order language-related areas, with possible implications for future naturalistic fMRI studies of language under normal and (clinically or pharmacologically) modified conditions.

Abnormal linear growth in paediatric adrenal diseases: Pathogenesis, prevalence and management.

Abnormal adrenal function can interfere with linear growth, potentially causing either acceleration or impairment of growth in paediatric patients. These abnormalities can be caused by direct effects of adrenal hormones, particularly glucocorticoids and sex steroids, or be mediated by indirect mechanisms such as the disturbance of the growth hormone-insulin-like growth factor-1 axis and aromatization of androgens to oestrogens. The early diagnosis and optimal treatment of adrenal disorders can prevent or minimize growth disturbance and facilitate improved height gain. Mechanisms of growth disturbance in the following abnormal states will be discussed; hypercortisolaemia, hyperandrogenaemia and obesity. Prevalence and features of growth disturbance will be discussed in ACTH-dependent and ACTH-independent Cushing's syndrome, adrenocortical tumours, premature adrenarche, congenital adrenal hyperplasia and adrenal insufficiency disorders. Recommendations for management have been included.

The quality of measurement properties of neurocognitive assessment in brain tumor clinical trials over the last 30 years: a COSMIN checklist-based approach.

PURPOSE: To provide an exhaustive review of the neuropsychological examination as conducted in brain tumor clinical trials over the last 30 years and to provide objective ratings about the reliability and suitability of such tests in neurooncological research and clinical practice. METHODS: Methodologies and tools provided by the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) were exploited in order to assess the measurement properties of questionnaires and performance-based instruments used to evaluate cognitive functioning in brain tumor clinical trials from 1997 to 2017. RESULTS: Twenty-six brain tumor clinical trials were analyzed and an overall set of 10 neuropsychological tests was identified. A list of 24 studies concerning the reliability of such tests was analyzed. Reliability and level of evidence scores for each study and for each test were obtained. The results revealed relevant faults about the quality of measurements and the suitability of the neurocognitive assessment batteries most commonly used in brain tumor clinical trials. CONCLUSION: Our findings suggest that the cognitive assessment in brain tumor clinical trials should be implemented according to specific endpoints and should be addressed to investigate all the cognitive domains known to be affected by brain tumor and treatment.