Publications by authors named "Annalisa de Silvestri"

200 Publications

Global Meta-Analysis on the Association between Behcet Syndrome and Polymorphisms from the HLA Class I (A, B, and C) and Class II (DRB1, DQB1, and DPB1) Genes.

Dis Markers 2021 13;2021:9348697. Epub 2021 Dec 13.

Scientific Direction, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.

Behcet syndrome (BS) is a multisystemic perivasculitis whose genetic susceptibility is linked to HLA region. We first meta-analysed all HLA class I and II genes involved in BS susceptibility in all ethnic groups worldwide. We identified 1141 articles and finally included 31 case-control studies after multiple rounds of selection. We analysed frequencies for 24 HLA-A alleles (3 alleles for HLA-A∗26 at four digits), 50 HLA-B alleles (11 alleles for HLA-B∗51 at four digits), 15 HLA-C alleles, 16 HLA-DRB1 alleles, 6 HLA-DQB1 alleles, and 15 HLA-DPB1 alleles. We meta-analysed only HLA allelic frequencies from at least three studies; therefore, we investigated 21 alleles out of 140. Going from 7.00 to 1.6 OR, we found 11 class I alleles conferring risk for BS: B∗51 : 08, B∗51, B∗51 : 01, B∗51 : 02, DQB1∗03, A∗26 : 01, Cw∗14, Cw∗15, Cw∗16, B∗15, and A∗26. Overall, the studies included populations from Europe (Greece, Spain, Italy, Germany, and Ireland), Asia (Korea, China, China Han, and Thailand), Middle East (Israel, Saudi Arabia, and Iran), and Morocco (as no other North-African population was included). We collected a number of ethnical groups sufficient to conduct an ethnic-specific meta-analysis where Europeans showed 11.25 OR for B∗51:08 and Japan 3.50 OR for A∗26 : 01. A remarkable result was that the most frequent HLA - B∗51 two-digit alleles associated with BS were different among populations: HLA - B∗51 : 08 in Europe, HLA - B∗51 : 01 in Turkey, and HLA - B∗51 : 02 in Japan. Overall, we discussed our real-world results with other imputation studies.
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http://dx.doi.org/10.1155/2021/9348697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687777PMC
December 2021

A propensity score-matched, real-world comparison of ustekinumab vs vedolizumab as a second-line treatment for Crohn's disease. The Cross Pennine study II.

Aliment Pharmacol Ther 2021 Dec 22. Epub 2021 Dec 22.

Leeds, UK.

Background: The optimal choice of biological agents after failure of anti-tumour-necrosis-factor-(TNF)α agent in Crohn's disease (CD) is yet to be defined.

Aims: To assess the effectiveness and safety of ustekinumab compared to vedolizumab as second-line treatment in CD patients who failed anti-TNFα therapy.

Methods: Retrospective analysis of clinical response and remission at 14 and 52 weeks to ustekinumab by physician global assessment (PGA). A propensity score-matched analysis with a cohort treated with vedolizumab was performed.

Results: Of 282 patients (mean age 40 ± 15, F:M ratio 1.7:1) treated with ustekinumab, clinical response or remission was reached by 200/282 patients (70.9%) at 14 weeks, and 162/259 patients (62.5%) at 52 weeks. Overall, 74 adverse events occurred, of which 26 were labelled as serious (8.3 per 100 person-year). After exclusion of patients without prior anti-TNFα exposure and patients previously exposed to vedolizumab or ustekinumab, we analysed 275/282 patients (97.5%) on ustekinumab and 118/135 patients (87.4%) on vedolizumab. Propensity score analysis revealed that at 14 weeks, patients treated with ustekinumab were 38% (95% CI 25%-50%; P < 0.001) more likely to achieve clinical remission, while at 52 weeks, the difference of 9% (95% CI -15% to 33%; P = 0.462) was not significant.

Conclusions: Ustekinumab was effective and well tolerated in this real-world cohort. While ustekinumab proved more effective at 14-weeks, we found no statistically significant differences at 52 weeks compared to vedolizumab.
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http://dx.doi.org/10.1111/apt.16742DOI Listing
December 2021

Treatment of partial rotator cuff lesions is associated with a higher frequency of post-operative shoulder stiffness. A prospective investigation on the role of surgery-related risk factors for this complication.

Arch Orthop Trauma Surg 2021 Dec 14. Epub 2021 Dec 14.

Laboratory of Applied Biomechanics, Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Mangiagalli 31, 20133, Milan, Italy.

Purpose: Post-operative shoulder stiffness (SS) is a common complication after arthroscopic rotator cuff (RC) repair. The aim of this prospective study is to evaluate the role of surgical risk factors in the development of this complication, with special focus on the characteristics of the RC tears.

Methods: Two-hundred and twenty patients who underwent arthroscopic RC repair for degenerative posterosuperior RC tears were included. Surgery-related risk factors for development of post-operative SS belonging to the following five categories were documented and analyzed: previous surgery, RC tear characteristics, hardware and repair type, concomitant procedures, time and duration of surgery. The incidence of post-operative SS was evaluated according to the criteria described by Brislin and colleagues.

Results: The incidence of post-operative SS was 8.64%. The treatment of partial lesions by tear completion and repair technique was significantly associated with development of post-operative SS (p = 0.0083, pc = 0.04). A multivariate analysis revealed that treatment of partial lesions in patients younger than 60 years was associated to a higher risk of developing post-operative SS (p = 0.007). Previously known pre-operative risk factors such as female sex and younger age were confirmed. No other significant associations were documented.

Conclusion: The treatment of partial lesions of the RC may lead to a higher risk of post-operative SS than the treatment of complete lesions, in particular in patients younger than 60 years. Possible explanations of this finding are the increased release of pro-inflammatory cytokines caused by the additional surgical trauma needed to complete the lesion and the different pain perception of the subgroup of patients who require surgical treatment already for partial tears.

Evidence: A higher risk of post-operative SS should be expected after tear completion and repair of partial lesions, especially in young patients. Appropriate pre-operative counseling and post-operative rehabilitation should be considered when approaching this subgroup of RC tears.

Level Of Evidence: Prognostic study, level II.
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http://dx.doi.org/10.1007/s00402-021-04285-1DOI Listing
December 2021

Trends in the Surgical Incidence of Cystic Echinococcosis in Uzbekistan from 2011 to 2018.

Am J Trop Med Hyg 2021 Dec 13. Epub 2021 Dec 13.

Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.

Cystic echinococcosis (CE) is a zoonosis with a cosmopolitan distribution caused by Echinococcus granulosus sensu lato tapeworms. Although Uzbekistan and other countries in Central Asia are considered endemic, estimates of disease burden are lacking. We present data regarding surgically managed cases of CE obtained from Uzbekistan's national disease surveillance registry. These data are from medical centers in Uzbekistan authorized to treat the disease and reported to the Uzbek Center for Sanitation and Epidemiology from the period 2011 to 2018. Information included data regarding the patient age class (children 14 years or younger), but no data regarding the cyst location. Incidence rates were calculated using data from the national population registry, and the Cuzick nonparametric test for trends was used to test for differences in the incidence over time at the country level and regional levels. A total of 7,309 CE cases were reported. Of these, 857 (11.73%) involved pediatric patients. The mean incidence rates were 4.4 per 100,000 population in 2011 and 2.3 per 100,000 population in 2018 (P = 0.016). One region (Republic of Karalpakistan) showed a nonstatistically significant increase (P = 0.824). All other regions except three showed a statistically significant decrease. We present the decrease in the incidence of surgically treated CE in Uzbekistan from 2011 to 2018. However, the presence of cases involving children suggest ongoing parasite transmission. The absence of clinical information (starting with cyst stage and localization) needs to be addressed to improve the national surveillance system. Field studies are also needed to further explore the epidemiology of CE in the country.
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http://dx.doi.org/10.4269/ajtmh.21-0261DOI Listing
December 2021

Bone Marrow Microenvironment in Light-Chain Amyloidosis: In Vitro Expansion and Characterization of Mesenchymal Stromal Cells.

Biomedicines 2021 Oct 22;9(11). Epub 2021 Oct 22.

Pediatric Hematology Oncology, Cell Factory, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, Italy.

Immunoglobulin light-chain amyloidosis (AL) is caused by misfolded light chains produced by a small B cell clone. Mesenchymal stromal cells (MSCs) have been reported to affect plasma cell behavior. We aimed to characterize bone marrow (BM)-MSCs from AL patients, considering functional aspects, such as proliferation, differentiation, and immunomodulatory capacities. MSCs were in vitro expanded from the BM of 57 AL patients and 14 healthy donors (HDs). MSC surface markers were analyzed by flow cytometry, osteogenic and adipogenic differentiation capacities were in vitro evaluated, and co-culture experiments were performed in order to investigate MSC immunomodulatory properties towards the ALMC-2 cell line and HD peripheral blood mononuclear cells (PBMCs). AL-MSCs were comparable to HD-MSCs for morphology, immune-phenotype, and differentiation capacities. AL-MSCs showed a reduced proliferation rate, entering senescence at earlier passages than HD-MSCs. The AL-MSC modulatory effect on the plasma-cell line or circulating plasma cells was comparable to that of HD-MSCs. To our knowledge, this is the first study providing a comprehensive characterization of AL-MSCs. It remains to be defined if the observed abnormalities are the consequence of or are involved in the disease pathogenesis. BM microenvironment components in AL may represent the targets for the prevention/treatment of the disease in personalized therapies.
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http://dx.doi.org/10.3390/biomedicines9111523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8614719PMC
October 2021

Predictive Ability of the Estimate of Fat Mass to Detect Early-Onset Metabolic Syndrome in Prepubertal Children with Obesity.

Children (Basel) 2021 Oct 26;8(11). Epub 2021 Oct 26.

Pediatric Department, "V. Buzzi" Children's Hospital, 20154 Milano, Italy.

Body mass index (BMI), usually used as a body fatness marker, does not accurately discriminate between amounts of lean and fat mass, crucial factors in determining metabolic syndrome (MS) risk. We assessed the predictive ability of the estimate of FM (eFM) calculated using the following formula: FM = weight - exp(0.3073 × height - 10.0155 ×d-growth-standards/standards/body-mass-index-for-age-bmi-for-age weight- 1 + 0.004571 × weight - 0.9180 × ln(age) + 0.6488 × age + 0.04723×male + 2.8055) (exp = exponential function, score 1 if child was of black (BA), south Asian (SA), other Asian (AO), or other (other) ethnic origin and score 0 if not, ln = natural logarithmic transformation, male = 1, female = 0), to detect MS in 185 prepubertal obese children compared to other adiposity parameters. The eFM, BMI, waist circumference (WC), body shape index (ABSI), tri-ponderal mass index, and conicity index (C-Index) were calculated. Patients were classified as having MS if they met ≥ 3/5 of the following criteria: WC ≥ 95th percentile; triglycerides ≥ 95th percentile; HDL-cholesterol ≤ 5th percentile; blood pressure ≥ 95th percentile; fasting blood glucose ≥ 100 mg/dL; and/or HOMA-IR ≥ 97.5th percentile. MS occurred in 18.9% of obese subjects ( < 0.001), with a higher prevalence in females vs. males ( = 0.005). The eFM was correlated with BMI, WC, ABSI, and Con-I ( < 0.001). Higher eFM values were present in the MS vs. non-MS group ( < 0.001); the eFM was higher in patients with hypertension and insulin resistance ( < 0.01). The eFM shows a good predictive ability for MS. Additional to BMI, the identification of new parameters determinable with simple anthropometric measures and with a good ability for the early detection of MS, such as the eFM, may be useful in clinical practice, particularly when instrumentation to estimate the body composition is not available.
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http://dx.doi.org/10.3390/children8110966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626042PMC
October 2021

Proliferation Pattern of Pediatric Tumor-Derived Mesenchymal Stromal Cells and Role in Cancer Dormancy: A Perspective of Study for Surgical Strategy.

Front Pediatr 2021 4;9:766610. Epub 2021 Nov 4.

Pediatric Department, "Vittore 86 Buzzi", Children's Hospital, Milan, Italy.

The explanation for cancer recurrence still remains to be fully elucidated. Moreover, tumor dormancy, which is a process whereby cells enter reversible G cell cycle arrest, appears to be a critical step in this phenomenon. We evaluated the cell cycle proliferation pattern in pediatric tumor-derived mesenchymal stromal cells (MSCs), in order to provide a better understanding of the complex mechanisms underlying cancer dormancy. Specimens were obtained from 14 pediatric patients diagnosed with solid tumors and submitted to surgery. Morphology, phenotype, differentiation, immunological capacity, and proliferative growth of tumor MSCs were studied. Flow cytometric analysis was performed to evaluate the cell percentage of each cell cycle phase. Healthy donor bone marrow-derived mesenchymal stromal cells (BM-MSCs) were employed as controls. It was noted that the DNA profile of proliferating BM-MSC was different from that of tumor MSCs. All BM-MSCs expressed the typical DNA profile of proliferating cells, while in all tumor MSC samples, ≥70% of the cells were detected in the G0/G1 phase. In particular, seven tumor MSC samples displayed intermediate cell cycle behavior, and the other seven tumor MSC samples exhibited a slow cell cycle. The increased number of tumor MSCs in the G0-G1 phase compared with BM-MSCs supports a role for quiescent MSCs in tumor dormancy regulation. Understanding the mechanisms that promote dormant cell cycle arrest is essential in identifying predictive markers of recurrence and to promote a dedicated surgical planning.
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http://dx.doi.org/10.3389/fped.2021.766610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600142PMC
November 2021

Prothrombin induced by vitamin K absence or antagonist-II and alpha foetoprotein to predict development of hepatocellular carcinoma in Caucasian patients with hepatitis C-related cirrhosis treated with direct-acting antiviral agents.

Aliment Pharmacol Ther 2022 Feb 5;55(3):350-359. Epub 2021 Nov 5.

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha fetoprotein (AFP) are biomarkers for hepatocellular carcinoma (HCC). However, their performance in patients with cirrhosis related to hepatitis C virus (HCV) treated with direct-acting antiviral agents (DAA) is unknown.

Aim: To evaluate PIVKA-II and AFP as HCC predictors in DAA-treated patients with HCV-related cirrhosis METHODS: In this single centre study, patients with cirrhosis from chronic HCV infection and with a sustained virological response (SVR) to DAA were tested for PIVKA-II and AFP (Fujirebio, Japan) at the start of DAA treatment (baseline), end of treatment (EOT) and at HCC diagnosis.

Results: We included 400 patients with mean age 65 (24-92); 56% were men. From baseline to EOT, PIVKA-II did not change (35 vs 35 mAU/mL, P = 0.43) while AFP significantly decreased (12 vs 6 ng/mL, P < 0.0001). After 52 (3-66) months from baseline, 34 (8.5%) patients developed de novo HCC; median AFP 9 (2-12 868) ng/mL and PIVKA-II 80 (22-1813) mAU/mL. EOT-PIVKA-II (HR 3.05, P < 0.0001) and AFP (HR 2.77, P = 0.001) independently predicted HCC together with diabetes (HR 6.12, P < 0.001) and GGT (HR 1.01, P = 0.03). The 4-year cumulative probability of HCC was 24% vs 2% in patients with EOT-PIVKA-II > or ≤41 mAU/mL (P < 0.0001), and 26% vs 9% for EOT-AFP > or ≤15 ng/mL (P = 0.02). By combining EOT-PIVKA-II and AFP, the 4-year probabilities of HCC were 3% in patients testing negative for both markers, 18% in patients positive for both, and 38% in patients positive for at least one (P < 0.0001).

Conclusions: In patients with HCV-related cirrhosis treated with DAA, PIVKA-II and AFP independently predicted HCC, while their combination improved risk stratification.
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http://dx.doi.org/10.1111/apt.16685DOI Listing
February 2022

A Pre-Release Algorithm With a Confidence Map for Estimating the Attenuation Coefficient for Liver Fat Quantification.

J Ultrasound Med 2021 Nov 3. Epub 2021 Nov 3.

Clinical Epidemiology and Biometeric Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Objectives: To compare the estimates of attenuation coefficient (AC) for liver fat quantification between 2 Ultrasound systems and to evaluate the quality measure of a pre-released software.

Methods: AC were obtained in 30 participants in this single-center IRB-approved, HIPAA compliant study. Images were obtained on the Philips Epiq Elite system using experimental software and the Canon Medical Systems Aplio i800 with released software. Five AC measurements were taken and the median and IQR/M were calculated. Region of interest placement was based on a confidence map. ROI was at the same depth and size for each system. The concordance was estimated using the Lin's concordance correlation coefficient (CCC), the r Pearson's correlation coefficient, the bias-correction factor (Cb), and the Bland-Altman method.

Results: The ACs varied from 0.45 to 1.0 dB/cm/MHz for the Philips system and 0.30 to 0.96 dB/cm/MHz for the Canon system. The CCC (95% CI) was 0.792 (0.666-0.918), Pearson's r was 0.839 with Cb of 0.944, and the mean difference was 0.03 (-0.101; 0.162) suggesting the 2 methods are considered to be in agreement. Based on a Philips confidence map to determine the best location for performing the measurements, a depth of 3.5 to 4.0 cm from the liver capsule was determined, which might be significantly different than that of the Canon system.

Conclusions: Estimation of the AC of the 2 systems showed a high agreement, that is, a similar trend. Assessment of the placement of the measurement box based on the quality of the measurement might be different between the 2 systems.
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http://dx.doi.org/10.1002/jum.15870DOI Listing
November 2021

Primary myelofibrosis: rs2010963 VEGFA polymorphism favors a prefibrotic phenotype and is associated with higher risk of thrombosis.

Leuk Res 2021 12 21;111:106730. Epub 2021 Oct 21.

Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.leukres.2021.106730DOI Listing
December 2021

A bibliometric analysis of international publications and citation trends of articles in mental health produced by Chinese institutions in mainland China (1990-2019).

Glob Ment Health (Camb) 2021 28;8:e37. Epub 2021 Sep 28.

Clinical Epidemiology and Biometric Unit, Foundation IRCCS, Policlinico San Matteo, Pavia, Italy.

Background: The recognition of the importance of mental health as a health-target to be pursued at a global level has received additional theoretical legitimacy through its inclusion in the United Nations (UN) 2030 Agenda for Sustainable development. The theoretical axiom - mental health as a development priority - is today expected to drive the focus of research efforts and orient the future policies and funds expenditures, at global and local level. According to these premises, it becomes central to track the international trajectories of mental health research and how the different countries are progressively defining their role in the global mental health effort. In this paper we have focused on China. In light of heavy burden of mental and substance use disorders affecting this country, and considering the impact of this burden at a global level, a basic research was conducted with the main aim of offering a preliminary view on the Chinese scientific activity within the context of global mental health research. This study is not intended to assess the quality of Chinese research, but merely to retrieve and measure a specific output of this research: the articles in mental-health produced by Chinese institutions based in mainland China, published in international journals. Although the publication of articles in internationally indexed journals in not exhaustive of China's scientific activity in global mental health, it is nevertheless informative of the production of new knowledge, it allows an assessment of the impact of this knowledge at the global scientific community level and it could partially reflect the Chinese capacity to benefit from research conducted globally.

Objective: In consideration of the very limited number of studies assessing the collective evidence of Chinese research in mental health, we developed our analysis with the purpose of providing a preliminary picture of the Chinese contribution, in terms of scientific publications, in this field of knowledge. Our research performs a bibliometric analysis on the articles in mental-health produced by Chinese institutions based in mainland China and published in English-language SCI-E and SSCI journals from 1990 to 2019, providing a measure of the impact of this research at the global scientific community level.

Methods: We performed a search on the Web of Science (WoS) using seven mental and substance use disorders according to their global prevalence, as per estimates of the Global Burden of Disease 2019. A dataset including the overall number of publications for seven diseases was created and exported in InCites. The dataset was analysed on the basis of 11 research areas (WoS categories) to which mental health topic is associated in SCI-E and SSCI journals in WoS. We further extracted publications that originated in mainland China. The citational trends over time are calculated with nonparametric test for trends across ordered groups. An evaluation of the impact of the Chinese scientific production is provided by the number of citations received at the global scientific community level, both as average and percentile.

Results: From 1990 to 2020 the overall Chinese scientific production in mental health has been generally increasing, reaching the highest growth in the last decade. A statistically significant increase ( < 0.001) is reported for articles produced by Chinese institutions in mainland China regarding 'depression*', 'bipolar disorders*' and 'schizophrenia*'. Published Chinese research is mostly included in SCI-E journals. There is a substantial overlap regarding the average number of citations for articles in mental-health produced by Chinese institutions and the rest of the world. Despite the increasing trend, the percentage of articles in mental health produced by Chinese institutions in mainland China on the overall scientific production worldwide is below 10%.

Conclusion: Notwithstanding a substantial increase in the last decade, the volume of Chinese publications appears to be very limited, thus resulting in a relatively low impact at a global level. These results are affecting the potential contribution of Chinese research in the global mental health effort.
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http://dx.doi.org/10.1017/gmh.2021.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482443PMC
September 2021

Functional assessment and rehabilitation protocol in acute patients affected by SARS-CoV-2 infection hospitalized in the Intensive Care Unit and in the Medical Care Unit.

Eur J Phys Rehabil Med 2021 Oct 4. Epub 2021 Oct 4.

Unit of Rehabilitation, Department of Medical Sciences and Infectious Disease, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.

Background: Coronavirus disease (COVID-19) is characterized by different clinical pictures that may require prolonged hospitalization and produce disabilities challenging the recovery of previous independence.

Aim: The aim is to evaluate the impact of an early assisted rehabilitation program on the functional status of an acutely hospitalized population affected by COVID-19.

Design: Single-institution retrospective longitudinal study.

Setting: Inpatient Intensive Care Units (ICU) and Medical Care Units (MCU).

Population: Acute COVID-19 Patients.

Methods: General information was collected; age-adjusted Charlson Comorbidity Index was used for comorbidities. Duration of hospital stay, the length of stay in ICU and/or MCU, the length of the rehabilitative treatment, and the destination at the discharge were collected. Evaluation was performed when patients were clinically stable (T0), and at hospital discharge (T1); for subjects enrolled in ICU functional status was assessed at the time of transfer to the MCU. Muscle strength of the four limbs was measured with the Medical Research Council (MRC) sum-score. Functional status was assessed using the 3-item Barthel index (BI-3) and the General physical mobility score (GPMS). Early assisted-tailored rehabilitation protocol was applied in ICU and in MCU: the aims were the maintenance (or recovery) of the range of motion and of the strength and the recovery of sitting/standing position and gait.

Results: we evaluated 116 patients (mean age 65, SD 11) (65% male) , 68 in ICU (mean age 60,SD 10), 48 in MCU (mean age 73,SD 9). At discharge, BI-3 and GPMS significantly improved in both ICU (p<0,001) and MCU (p<0,001) subgroups of patients. MRC sum-score significantly improved in ICU patients (p<0.001). Patients hospitalized in ICU had a significantly longer hospital stay. At discharge, patients admitted to the ICU reach a functional state that is close to that of patients admitted to the MCU.

Conclusions: The results suggest that an early assisted rehabilitation program may be helpful in improving the short-term functional status of an acutely hospitalized population affected by COVID-19, with discharge at home of 48%.

Clinical Rehabilitation Impact: this study focuses on a functional assessment method to be used to identify the rehabilitation needs and verify the results of an early rehabilitation protocol applied to the acute COVID-19 patient admitted to ICU and MCU.
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http://dx.doi.org/10.23736/S1973-9087.21.06897-0DOI Listing
October 2021

"Fitness and Fatness" in Children and Adolescents: An Italian Cross-Sectional Study.

Children (Basel) 2021 Aug 31;8(9). Epub 2021 Aug 31.

Department of Human and Social Science, University of Bergamo, 24127 Bergamo, Italy.

Children with obesity tend to have lower level of physical activity compared to non-obese peers. In fact, sedentary behaviors are prevalent in obese children causing difficulties to perform motor tasks and engaging in sport activities. This, in turn, has direct repercussions on adiposity and related comorbidities. The aim of the study was to investigate several components of fitness and their relationship with the degree of fatness in children. We considered 485 Italian schoolchildren (9.5 ± 1.12 years). BMI and prediction modelling outputs of fat mass were employed as markers of body fatness. Physical fitness (PF) was assessed by the 9-item test battery (explosive power, leg muscle power, arm muscle power, upper body power, coordination, agility, speed and endurance). Differences between groups in the PF tests ( < 0.05) were noted. A similar pattern was reflected in both genders. The relationship between anthropometrics' characteristics and PF tests showed that weight and fat mass had a high level of correlation with different PF tests. Our findings highlight the importance of investigating the degree of fatness in relation with different components of fitness, in children and adolescents. This combination of proxies may cover an unexpectedly helpful screening of the youth population, for both health and performance.
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http://dx.doi.org/10.3390/children8090762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470229PMC
August 2021

Ultrasound-based evaluation of the prevalence of abdominal cystic echinococcosis in the Turkestan region of Kazakhstan.

Trans R Soc Trop Med Hyg 2021 Sep 9. Epub 2021 Sep 9.

Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Viale Brambilla 54, 27100 Pavia, Italy.

Background: Human cystic echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus sensu lato. CE is known to be endemic in some parts of Central Asia. We present findings from an ultrasound-based survey to estimate the prevalence of CE in the Turkestan oblast of Kazakhstan.

Methods: In October 2019, six villages were chosen based on records from a national surveillance dataset. Inhabitants aged 5-90 y were invited to undergo a free abdominal ultrasound to screen for CE cysts. All identified cysts were staged according to the WHO-endorsed classification for CE cysts.

Results: A total of 2252 individuals underwent ultrasound screening. Twenty-two (0.98%) individuals had CE, with a combined total of 33 cysts: 25 (75.7%) inactive (14 CE4, 11 CE5) and 8 (24.3%) active/transitional (2 CE1, 1 CE2, 3 CE3a, 2 CE3b). One patient had a postsurgical cavity. Sixty-eight patients (3.0%) reported CE prior to surgical treatment. In 25 (36.8%) previously diagnosed patients, albendazole prophylaxis was not used.

Conclusions: CE is endemic in the study region, with ongoing transmission. The number of surgically treated CE patients suggests an underestimation of the disease burden by the current surveillance system. Further studies on local CE epidemiology and the implementation of expert treatment recommendations are needed.
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http://dx.doi.org/10.1093/trstmh/trab105DOI Listing
September 2021

Characterization of epidemiological distribution and outcome of COVID-19 in patients with hereditary hemorrhagic telangiectasia: a nationwide retrospective multi-centre study during first wave in Italy.

Orphanet J Rare Dis 2021 09 8;16(1):378. Epub 2021 Sep 8.

DIM-Interdisciplinary Department of Medicine, "Frugoni" Internal Medicine and Geriatrics Unit, HHT Interdepartmental Center, VascERN HHT Reference Center, Policlinico Hospital, University of Bari, P.zza Giulio Cesare, 70124, Bari, Italy.

Background: Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue.

Objectives: The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency.

Methods: The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period.

Results: The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population.

Conclusions: COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population.
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http://dx.doi.org/10.1186/s13023-021-02000-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424156PMC
September 2021

Acanthosis Nigricans in Children and Adolescents with Type 1 Diabetes or Obesity: The Potential Interplay Role between Insulin Resistance and Excess Weight.

Children (Basel) 2021 Aug 18;8(8). Epub 2021 Aug 18.

Department of Pediatrics, Children's Hospital "Vittore Buzzi", 20154 Milan, Italy.

Acanthosis nigricans (AN) is associated with obesity and type 2 diabetes, where insulin resistance (IR) is considered a predisposing factor. IR can also affect patients with type 1 diabetes (T1D). We evaluated the prevalence of AN in patients with T1D compared to subjects with obesity in order to define the interplay between IR and excess weight. We considered 138 pediatric patients who presented with T1D and 162 with obesity. As controls, 100 healthy normal-weight subjects were included. A physical examination with the detection of AN and biochemical assessments was performed. IR was calculated by using the homeostasis model assessment for IR in patients with obesity and the estimated glucose disposal rate in T1D. The AN prevalence was higher in T1D and obese subjects compared with controls in whom AN was not detected ( = 0.02 and < 0.001, respectively). A greater number of AN cases were observed in subjects with obesity compared with T1D ( < 0.001). Patients with AN were older than subjects without AN ( = 0.005), and they had higher body mass index (BMI) values, waist circumference (WC), fasting triglycerides and blood pressure (all < 0.001). Thirty-five patients with AN exhibited IR with an association between AN presence and IR in patients with obesity ( < 0.001). In T1D, there was an association between AN and being overweight/obese ( = 0.02), independently of IR. AN is a dermatological condition associated with obesity. In T1D, the presence of AN was significantly associated with overweight status or obesity but not IR. The presence of AN in the absence of IR supports the interplay role between impaired insulin signaling, IR and excess weight in the pathogenic mechanism.
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http://dx.doi.org/10.3390/children8080710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391689PMC
August 2021

Spezifisches IgE gegen Staphylococcus-aureus-Superantigene bei Patienten mit bullösem Pemphigoid.

J Dtsch Dermatol Ges 2021 Aug;19(8):1214-1216

Dermatology Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

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http://dx.doi.org/10.1111/ddg.14518_gDOI Listing
August 2021

Airway Malacia: Clinical Features and Surgical Related Issues, a Ten-Year Experience from a Tertiary Pediatric Hospital.

Children (Basel) 2021 Jul 20;8(7). Epub 2021 Jul 20.

Department of Pediatrics, V. Buzzi Children's Hospital, 20154 Milan, Italy.

Background: Few studies have been carried out with the aim of describing the clinical course and follow-up of patients with tracheomalacia. We aim to describe the symptoms at diagnosis and the post-treatment clinical course of patients affected by airway malacia.

Methods: We retrospectively analyzed characteristics of pediatric patients with a diagnosis of airway malacia. Patients were classified into three groups: bronchomalacia (BM), tracheomalacia (TM) and tracheo-bronchomalacia (TBM). Demographic and clinical data, diagnostic work-up and surgical treatment were recorded.

Results: 13/42 patients were affected by congenital syndromes (30.9%). Esophageal atresia with or without tracheal-esophageal fistula (EA/TEF) was detected in 7/42 patients (16.7%). Cardiovascular anomalies were found in 9/42 (21.4%) and idiopathic forms in 13/42 (30.9%). BM occurred in 7/42 (16.6%), TM in 23/42 (54.7%) and TBM in 12/42 (28.6%). At the diagnosis stage, a chronic cough was reported in 50% of cases with a higher prevalence in EA/TEF ( = 0.005). Surgery was performed in 16/42 (40%) of children. A chronic cough and acute respiratory failure were correlated to the need for surgery. During follow-up, there was no difference in persistence of symptoms between conservative vs surgical treatment ( = 0.47).

Conclusion: the management of tracheomalacia remains a challenge for pediatricians. Clinical manifestations, such as a barking cough and acute respiratory failure may suggest the need for surgery. Follow-up is crucial, especially in those patients affected by comorbidities, so as to be able to manage effectively the possible persistence of symptoms, including those that may continue after surgical treatment.
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http://dx.doi.org/10.3390/children8070613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307910PMC
July 2021

Phototherapy with UVB-NB as a new adjuvant therapy for bullous pemphigoid: A pilot study.

Photodermatol Photoimmunol Photomed 2021 Aug 5. Epub 2021 Aug 5.

Department of Clinical-Surgical, Diagnostic, and Pediatric Sciences, Institute of Dermatology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

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http://dx.doi.org/10.1111/phpp.12722DOI Listing
August 2021

Renal Outcomes of Dialysis-Dependent Acute Kidney Injury in Noncritically Ill Patients: A Retrospective Study.

Blood Purif 2021 Jul 28:1-7. Epub 2021 Jul 28.

Unit of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

Introduction: Acute kidney injury (AKI) is a common complication among hospitalized patients, potentially affecting short- and long-term clinical outcomes. In this retrospective study, we evaluated renal outcomes in noncritically ill patients who required acute hemodialysis (HD) because of an AKI episode occurring during hospitalization.

Methods: Sixty-three hemodynamically stable patients with AKI undergoing acute intermittent HD were included. Kidney function was evaluated at baseline control (pre-AKI), at AKI diagnosis and during the follow-up. According to serum creatinine and the estimated glomerular filtration rate (eGFR), we defined three clinical conditions: renal recovery, different stages of acute kidney disease (AKD), and chronic kidney disease (CKD).

Results: Among the 63 patients evaluated, 34 patients (54%) had a history of CKD. Six patients (10%) presented early full renal recovery. HD treatment was stopped in 38 patients (60%), while 25 patients (40%) required maintenance HD. Dialysis-independent patients presented lower comorbidity and higher baseline eGFR and delta creatinine, compared to dialysis-dependent patients. Baseline CKD, previous AKI episodes, and parenchymal causes of AKI were associated with a significant risk of dialysis dependence. At 1-month control, 15 patients (39%) presented AKD stage 0, 6 patients (16%) AKD stage 1, and 17 patients (44%) AKD stage 2-3. At 3-month control, 29 out of 38 patients recovering from AKI (76%) presented CKD. AKD stage was significantly correlated with the risk of CKD development, which, resulted higher in patients with lower baseline eGFR.

Conclusions: AKI might represent a risk factor for the development of chronic kidney damage, even in noncritically ill patients.
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http://dx.doi.org/10.1159/000517707DOI Listing
July 2021

Assessment of chronic liver disease by multiparametric ultrasound: results from a private practice outpatient facility.

Abdom Radiol (NY) 2021 11 25;46(11):5152-5161. Epub 2021 Jul 25.

Department of Radiology, Northeastern Ohio Medical University, Rootstown, OH, USA.

Purpose: To assess chronic liver disease (CLD) using multiparametric US in a private practice setting in a cohort of patients with increased skin-to-liver distance.

Methods: 110 consecutive patients with increased skin-to-liver distance scheduled for US assessment of CLD were reviewed for study completion time, liver stiffness values (LS), attenuation imaging, and shear wave dispersion slope. The ROI was placed 2 cm below the liver capsule. The study included patients with NAFLD/NASH (68), hepatitis C (30), prior Fontan surgery (1), elevated liver function tests (5), alcohol abuse (3), hepatitis B (2), and primary biliary cirrhosis (1). IQR/M values were obtained. Comparison of less experienced sonographers (LES) and more experienced sonographers (MES) were evaluated through Student's t test for independent data. Pearson coefficient r of correlation among quantitative variables was calculated.

Results: The mean time to perform the exam was 129.7 ± 62.1 s. There was a statistically significant difference between LES and MES. The mean IQR/M for LS was 12.3 ± 5.5% m/s. Overall, in a cohort of difficult patients, 4.5% of LS values were not reliable. Fat quantification using attenuation imaging had a mean value of 0.60 ± 0.15 dB/cm/MHz (range 0.35-0.98 cm/dB/MHz) with an IQR/M of 14.7 ± 9.2%. Less reliable measurements of steatosis were obtained in 4.5% of patients. The mean shear wave dispersion slope was 12.74 ± 4.05 (m/s)/kHz (range 7.7-27.5 (m/s)/kHz) with an IQR/M of 38.7 ± 20.2% (range 3-131%). 20.9% of patients had values suggestive of compensated advanced chronic liver disease (cACLD).

Conclusion: Multiparametric US can provide assessment of CLD in less than 3 min in most patients and identify patients at risk for cACLD.
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http://dx.doi.org/10.1007/s00261-021-03225-2DOI Listing
November 2021

Metabolically Unhealthy Phenotype: A Key Factor in Determining "Pediatric" Frailty.

Pediatr Rep 2021 Jul 1;13(3):340-346. Epub 2021 Jul 1.

Clinical Epidemiology & Biometry, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy.

Frailty (FI) and metabolic syndrome (MS) are each associated with adverse health outcomes. A relationship between FI and MS has previously been described in adults. We considered the prevalence of a metabolically unhealthy phenotype (MUP) in malnourished children with neurological impairment and in subjects with obesity in comparison to a group of elderly individuals at risk of FI, and we did so in order to define the potential similarities that may underline the risk of FI in specific children. We considered 50 undernourished (defined as having a body mass index of BMI ≤ 2, standard deviation score, SDS, according to World Health Organization) disabled children; 50 children with obesity (BMI ≥ 2 SDS); 50 children who were a normal weight (-1 SDS ≤ BMI ≤ +1 SDS); 21 patients who were >75 years old. MUP was defined as the presence of at least one of the following risk factors: hypertension, hyperglycemia or diabetes, hypercholesterolemia, and hypertriglyceridemia. In children with a disability and obesity, a higher prevalence ( < 0.001) and risk (disability OR 54.88, obesity OR 13.37) of MUP was noted compared to children of a normal weight. Compared to elderly patients, the prevalence of MUP did not differ in disabled children. On the contrary, MUP was lower in children with obesity ( < 0.001) and in pediatric subjects of a normal weight ( < 0.01). MS might play a key role in "pediatric" frailty. The extremities of the aging process and malnutrition are likely key factors in the development of FI. A multidisciplinary approach to FI may represent an important milestone for pediatric care.
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http://dx.doi.org/10.3390/pediatric13030042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293425PMC
July 2021

Nasal Endoscopy in the Clinical Diagnosis of Hereditary Hemorrhagic Telangiectasia.

J Pediatr 2021 Nov 13;238:74-79.e2. Epub 2021 Jul 13.

Department of Otorhinolaryngology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Objectives: To evaluate the role of nasal endoscopy for early clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and to investigate the characteristics of epistaxis and mucocutaneous telangiectases in our pediatric population.

Study Design: From May 2016 to December 2019, a cross-sectional observational study was conducted, recruiting children aged 2-18 years with a parent affected by HHT. To identify the Curaçao criteria, all children underwent collection of clinical history, mucocutaneous examination, and nasal endoscopy. The clinical data were then compared with the genetic data acquired subsequently.

Results: Seventy children (median age, 10.8 years) were included. All underwent nasal endoscopy without complications. Forty-six children were positive by genetic testing; of these, 26 % had skin and oral telangiectases and 91 % had nasal telangiectases. The diagnostic sensitivity of the Curaçao criteria increased from 28 % (95 % CI, 16%-43 %) to 85 % (95 % CI, 71%-94 %; P < .0001) when the nasal telangiectases were included.

Conclusions: The magnified and complete endoscopic view of the nasal cavities proved useful in increasing the diagnostic sensitivity of the Curaçao criteria. Such an examination turned out to be feasible and safe. For this reason, we believe that nasal endoscopy should be included in the diagnostic assessment of pediatric patients with suspected HHT.
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http://dx.doi.org/10.1016/j.jpeds.2021.07.007DOI Listing
November 2021

Daptomycin Pharmacokinetics and Pharmacodynamics in Patients on Methadone Substitution Therapy.

Eur J Drug Metab Pharmacokinet 2021 Jul 6;46(4):547-554. Epub 2021 Jul 6.

Clinica di Malattie Infettive, IRCCS Policlinico San Matteo, Piazzale Golgi 2, 27100, Pavia, Italy.

Background And Objective: When administered for severe infections in intravenous drug users (IDUs) at a daily dose of 6 mg/kg, daptomycin displayed abnormal pharmacokinetic parameters compared with those seen in healthy volunteers; specifically, decreased trough and maximum concentrations (C; C) and increased clearance (CL). The objective of this study was to evaluate the pharmacokinetics and pharmacodynamics of daptomycin administered at a daily dosage of 12 mg/kg for Staphylococcus aureus infective endocarditis (IE) in patients concomitantly treated with methadone, and to compare the results with those published in the literature for healthy controls treated with the same daily dose.

Methods: Antibiotic treatment included daptomycin (12 mg/kg daily) in combination with an antistaphylococcal β-lactam (cefazolin 2 g three times a day). The minimum inhibitory concentration (MIC) of Staphylococcus aureus isolated through blood cultures was used to calculate pharmacokinetic and pharmacodynamic parameters such as the ratio of the area under the concentration-time curve over 24 h to the MIC (AUC/MIC) and C/MIC.

Results: Five IDUs hospitalized for IE were enrolled. The mean measured daptomycin C and C were 54.1 μg/mL (CV: 0.32) and 8.7 μg/mL (CV: 0.59), respectively; the mean calculated AUC was 742.7 μg × h/mL (CV: 0.31). The estimated average volume of distribution at the steady state (V) and the half-life (t) were 316.5 mL/kg (CV: 0.53) and 14.4 h (CV: 0.30), respectively. The mean daptomycin clearance from plasma normalized for body weight (CL) was 17.3 mL/(h × kg) (CV: 0.33). The calculated average C and AUC (183.7 µg/mL and 1277.4 µg × h/mL, respectively) were lower than and statistically significantly different from (p < 0.001 and p = 0.001, respectively) those expected for healthy volunteers.

Conclusions: Treatment of Staphylococcus aureus IE in IDUs on methadone treatment requires the use of high daptomycin daily doses in order to achieve satisfactory pharmacodynamic parameters. Close monitoring of the daptomycin plasma concentration is suggested.
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http://dx.doi.org/10.1007/s13318-021-00690-4DOI Listing
July 2021

A new algorithm shows superior ability to discriminate liver fibrosis stages in chronic hepatitis C.

J Viral Hepat 2021 10 14;28(10):1443-1451. Epub 2021 Jul 14.

Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Previous evidence suggests that sialic acid-binding Ig-like lectin 7 (Siglec-7) protein is significantly increased in patients with chronic hepatitis C virus (HCV) infection and directly correlates with clinical parameters of liver inflammation and fibrosis. The aim of this study was to determine the diagnostic value of Siglec-7 as a non-invasive tool to assess liver fibrosis in patients with chronic hepatitis C in a cross-sectional study. Serum levels of Siglec-7 were retrospectively tested in 1007 consecutive patients with chronic HCV infection recruited at three different European sites and data examined by the 'imperfect gold-standard' statistical analysis. Liver stiffness obtained by transient elastography (TE) was considered the standard reference. Liver fibrosis was staged according to published cut-offs of liver stiffness measurement by TE. Accuracy of detection of liver fibrosis stage was not increased by Siglec-7 alone. However, we developed a new index (SiGAP) including Siglec-7, γ-glutamyl transferase, age and platelet count which showed increased sensitivity and specificity in predicting fibrosis compared with APRI or FIB4 indices. The AUROC of SiGAP for the diagnosis of significant (≥F2) and advanced liver fibrosis (≥F3) showed significantly higher values than those of APRI and FIB-4. Siglec-7 may be useful as a complementary tool to assess liver fibrosis stage in patients with chronic hepatitis C when included in a specifically designed algorithm, which showed high level of accuracy in the detection of F2 and F3 fibrosis stage.
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http://dx.doi.org/10.1111/jvh.13570DOI Listing
October 2021

Specific IgE to Staphylococcus aureus superantigens in patients affected by bullous pemphigoid.

J Dtsch Dermatol Ges 2021 Aug 29;19(8):1214-1216. Epub 2021 Jun 29.

Dermatology Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

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http://dx.doi.org/10.1111/ddg.14518DOI Listing
August 2021

Insulin resistance and potential modulators of ovarian reserve in young reproductive-aged women with obesity and type 1 diabetes.

Gynecol Endocrinol 2021 Sep 17;37(9):823-830. Epub 2021 Jun 17.

Department of Pediatrics, "Vittore Buzzi" Children's Hospital, Milano, Italy.

Introduction: Both obesity and diabetes play a significant role in reproductive disorders in women and insulin resistance (IR) is a confirmed . We evaluated the relationship between IR and an established ovarian reserve biomarker such as anti-mullerian hormone (AMH) together with other potential modulators of ovarian physiology (adiponectin and kisspeptin) in young reproductive-aged group women with obesity and type 1 diabetes (T1D).

Patients And Methods: We recruited 32 female youths: 14 of them presented with T1D (14.6 ± 2.6 years) and 18 with obesity (15.1 ± 2.6 years). The control group included 20 age-matched normal weight females. Each patient underwent physical examination and hormonal assessment. AMH, kisspeptin and adiponectin levels were also measured. IR was calculated as the homeostasis model assessment for insulin resistance (HOMA-IR) and the glucose disposal rate (eGDR) in patients with obesity and with T1D, respectively.

Results: adiponectin and kisspeptin levels were significantly different into groups ( ≤ .001), whereas AMH levels were not. Adiponectin values were higher in controls compared to patients with obesity ( < .001) and T1D ( = .02). Kisspeptin levels were lower in controls compared to patients with obesity ( = .001), without reaching statistical significance when compared to T1D ( = .06). IR was associated with lower adiponectin and higher kisspeptin levels ( < .001 and  = .02, respectively), but not with AMH.

Conclusions: IR displays a relationship with adiponectin and kisspeptin in young reproductive-aged women with obesity and T1D. Interventions to correct IR in adolescents could be part of an early approach to prevent reproductive disorders and to promote factors associated with longevity in adult women.
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http://dx.doi.org/10.1080/09513590.2021.1940127DOI Listing
September 2021

Sex-Specific Differences in the Relationship between Insulin Resistance and Adiposity Indexes in Children and Adolescents with Obesity.

Children (Basel) 2021 May 26;8(6). Epub 2021 May 26.

Department of Pediatrics, "Vittore Buzzi" Children's Hospital, 20154 Milan, Italy.

New indexes of adiposity have been introduced to evaluate body-fat distribution and cardiometabolic risk. However, data on the correlation between Insulin Resistance (IR) and these new indexes are limited. We therefore evaluated the relationship between IR and adiposity indexes in children and adolescents with obesity, focusing on gender differences. We retrospectively enrolled 586 patients with obesity (10.80 ± 2.63; 306F/279M). As adiposity indexes we considered body mass index (BMI), BMI-z score, WC, waist-to-height ratio (WHtR), a body shape index (ABSI), triponderal mass index (TMI), visceral adiposity index (VAI) and conicity index (ConI). The homeostasis model assessment for insulin resistance (HOMA-IR), HOMA of percentage β-cell function (HOMA-β), quantitative insulin sensitivity check index (QUICKI), and triglyceride and glucose index (TyG-index) were measured and recorded as IR surrogates. In both sexes, WC and VAI significantly correlated with all IR measurements ( < 0.001). BMI significantly correlated ( < 0.001) with all IR parameters except for the TyG-index in females. Fat mass and TMI correlated with IR parameters only in females, BMI-z score with IR markers except for HOMA-β in males, WHtR with HOMA-β in both sexes ( < 0.05), free fat mass with HOMA-IR and QUICKI only in females ( < 0.01), ConI correlated with the TyG index in females ( = 0.01). Tryglicerides and SBP were correlated with all IR measurements ( < 0.001), in both sexes. Correlations between different sex parameters were significantly more evident in middle puberty. The relationship between IR surrogates and obesity indexes is influenced by gender in pediatrics. Sex-specific differences in obesity-related complications should be considered in preventive intervention decision-making.
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http://dx.doi.org/10.3390/children8060449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226600PMC
May 2021

Field Performance of a Rapid Diagnostic Test for the Serodiagnosis of Abdominal Cystic Echinococcosis in the Peruvian Highlands.

Am J Trop Med Hyg 2021 05 24;105(1):181-187. Epub 2021 May 24.

2Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.

We evaluated the performance of a commercial rapid diagnostic test (RDT) in a field setting for the diagnosis of abdominal cystic echinococcosis (CE) using sera collected during an ultrasound population screening in a highly endemic region of the Peruvian Andes. Abdominal CE was investigated by ultrasonography. Sera collected from individuals with abdominal CE (cases) and age- and gender-matched volunteers with no abdominal CE (controls) were tested independently in two laboratories (Peru and Italy) using the VIRapid® HYDATIDOSIS RDT and RIDASCREEN® Echinococcus IgG enzyme-linked immunosorbent assay. Performance indexes of single and serially combined tests were calculated and applied to hypothetical screening and clinical scenarios. Test concordance was also evaluated. Prevalence of abdominal CE was 6.00% (33 of 546) by ultrasound. Serum was obtained from 33 cases and 81 controls. The VIRapid test showed similar sensitivity (76% versus 74%) and lower specificity (79% versus 96%) than results obtained in a hospital setting. RDTs showed better performance when excluding subjects reporting surgery for CE and if weak bands were considered negative. Concordance between tests was moderate to very good. In hypothetical screening scenarios, ultrasound alone or confirmed by RDTs provided more reliable prevalence figures than serology alone, which overestimated it by 5 to 20 times. In a simulation of case diagnosis with pre-test probability of CE of 50%, positive and negative post-test probabilities of the VIRapid test were 78% and 22%, respectively. The application of the VIRapid test alone would not be reliable for the assessment of population prevalence of CE, but could help clinical decision making in resource-limited settings.
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http://dx.doi.org/10.4269/ajtmh.21-0045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274789PMC
May 2021

In linezolid underexposure, pharmacogenetics matters: The role of CYP3A5.

Biomed Pharmacother 2021 Jul 30;139:111631. Epub 2021 Apr 30.

Unit of Clinical Pharmacology, L. Sacco University Hospital, Milano, Italy. Electronic address:

The exposure to linezolid is characterized by a large inter-individual variability; age, renal dysfunction and body weight explain this variability only to a limited extent and a considerable portion of it remains unexplained; therefore, we decided to investigate the role of individual genetic background focusing in particular on the risk of linezolid underexposure. 191 patients in therapy with linezolid at the standard dose of 600 mg twice daily were considered. Linezolid plasma concentration was determined at the steady state and classified as "below", "within" or "above" reference range. Genetic polymorphisms for ATP Binding Cassette Subfamily B Member 1 (ABCB1), Cytochrome P450 (CYP) enzymes CYP3A4 and CYP3A5, and Cytochrome P450 Oxidoreductase (POR) were investigated. Age significantly correlated with drug exposure, and patients CYP3A5 expressers (GA and AA) were found at high risk to be underexposed to the drug when treated at standard dose. This association was confirmed even after correction with age. No association was found with ABCB1 polymorphism. Our data suggest that CYP3A5 polymorphisms might significantly affect linezolid disposition, putting patients at higher risk to be underexposed, while P-glycoprotein polymorphism seem not to play any role.
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http://dx.doi.org/10.1016/j.biopha.2021.111631DOI Listing
July 2021
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