Search

The management of hepatic hemangioendothelioma (HHE) may be challenging. We aimed to review a large cohort of children who presented to our centers with symptomatic HHE in the last 16 years. We collected age at presentation, clinical features, histology, diagnostic process, management and outcome. Twenty seven patients (male/female 5/22), median age 13 days (1–1530) presented with hepatomegaly (24/27), cardiac failure (10/27), cutaneous hemangiomas (8/27), fever and anemia (6/27 each), vomiting (5/27), splenomegaly (4/27). The lesion was focal, multifocal, or diffuse in 9 patients of each group. The management included medical treatment (8/27), embolization (8/27), resection (3/27), observation (6/27), transplantation (2/27). After 16 months’ follow-up (30 days–11 years), 23/27 (85%) were alive. Diffuse lesions (4/4), cardiac failure (4/4), type II histology (4/4), age older than 6 months at diagnosis (3/4) predicted mortality (all p

Objective It is reported that recovery from COVID-19 chemosensory deficit generally occurs in a few weeks, although olfactory dysfunction may persist longer. Here, we provide a detailed follow-up clinical investigation in a very young female patient (17-year-old) with a long-lasting anosmia after a mild infection, with partial recovery 15 months after the onset. Methods Neuroimaging and neurophysiologic assessments as well as olfactory mucosa swabbing for microbiological and immunocytochemical analyses were performed. Olfactory and gustatory evaluations were conducted through validated tests. Results Chemosensory evaluations were consistent with anosmia associated with parosmia phenomena and gustatory impairment, the latter less persistent. Brain MRI (3.0 T) showed no microvascular injury in olfactory bulbs and brain albeit we cannot rule out slight structural abnormalities during the acute phase, and a high-density EEG was negative. Immunocytochemistry of olfactory mucosa swabs showed high expression of ACE2 in sustentacular cells and lower dot-like cytoplasmic positivity in neuronal-shaped cells. Discussion The occurrence of long-term persistent olfactory deficit in spite of the absence of structural brain and olfactory bulb involvement supports the view of a possible persistent dysfunction of both sustentacular cells and olfactory neurons. The gustatory dysfunction even if less persisting for the described features could be related to a primary gustatory system involvement. Future longitudinal studies are needed to investigate the persistence of chemosensory impairment, which could have a relevant impact on the daily life. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05635-y.

Recently, the use of antiretroviral drug tenofovir disoproxil fumarate (TDF) is increased, thanks to the new co-formulation with doravirine, the availability of booster-free regimens, and its advantageous lipid-lowering effect. The aim of our study was to identify genetic markers that contribute to assess the risk of TDF-related renal toxicity. We have retrospectively investigated, in 179 HIV positive patients treated with TDF, the association between the main variants in ABCC2, ABCC4, and ABCC10 genes and four safety endpoints, three clinically relevant as renal outcomes and a higher tenofovir plasma concentration. In patients with an annual eGFR decline >5 mL/min/1.73 m2 a difference in genotype frequencies was observed for ABCC10 c.1875 + 526 G>A (3 subjects AA vs. 44 GG + GA, p = 0.045). In patients with an eGFR decrement >25%, plus a decline in GFR category and TDF discontinuation, a difference was observed for ABCC4 c.*38T>G (35 subjects TG + GG vs. 18 TT, p = 0.052). At univariate analysis OR was 1.39 [(95% CI 1.00-1.96) p = 0.054] and at multivariate analysis OR was 1.49 [(95% CI 1.00-2.22) p = 0.049]. The stronger associations were found between the tenofovir accumulation and ABCC4 c.*38T>G and c.3348G>A: the percentage of these patients was higher in the TG + GG (p = 0.011) and in the AA (p = 0.004) genotype, respectively. The logistic regression analysis confirmed these significant relationships. No significant association was observed in patients with eGFR < 60 mL/min/1.73m2 and with the studied ABCC2 polymorphisms. Our results show a major role for a combined determination of ABCC4/ABCC10 variants as an indicator of tenofovir toxicity in the clinical practice.

This study of real‐world data from the Maccabi database in Israel compared the risk of heart failure hospitalization (HHF) or death in patients with type 2 diabetes (T2D) initiating sodium‐glucose cotransporter‐2 (SGLT2) inhibitors versus other glucose‐lowering drugs (OGLDs) according to baseline left ventricular (LV) ejection fraction (EF). After propensity‐matching patients by baseline EF there were 10 614 episodes of treatment initiation; 57% had diabetes for >10 years, the mean glycated haemoglobin level was 66 mmol/mol (8.2%), ∼43% had cardiovascular disease, ∼7% had heart failure and ∼ 20% had chronic kidney disease. A total of 2876 patients (∼9%) had reduced EF (

Taxanes are used in the treatment of several solid tumours. Adverse events (AEs) might be influenced by single nucleotide polymorphisms (SNPs) in genes encoding proteins responsible for pharmacokinetic and pharmacodynamic. In this prospective, monocentric, observational study we explored the effect of SNPs in the main genes involved in taxanes metabolism and transport, on toxicity and efficacy in 125 patients (pts) treated with paclitaxel, nab-paclitaxel, or docetaxel for neoplasms. There was no statistically significant association between the investigated SNPs and AEs. The heterozygous genotype of CYP3A4*22 showed a trend of association with skin reactions in pts treated with paclitaxel and nab-paclitaxel (RR = 6.92; 95% CI 0.47, 99.8; p = 0.0766). CYP2C8*3/*4 variant carriers showed a trend of association with overall AEs in pts treated with paclitaxel and nab-paclitaxel (RR = 1.28; 95% CI 0.96, 1.67; p = 0.0898). No statistically significant relationship with treatment efficacy was found. ABCB1 3435TT showed a trend of association with a higher treatment response (RR = 0.22; 95% CI 0.03, 1.51; p = 0.0876). Despite the population was heterogeneous, CYP3A4*22 and CYP2C8 SNPs may influence paclitaxel and nab-paclitaxel toxicity and ABCB1 c.3435 may affect taxanes effectiveness, even if any statistically significant was found.

Background: Despite the fact that Kasai portoenterostomy (KPE) is the primary treatment for biliary atresia (BA), liver transplantation (LT) remains the ultimate surgery for two-thirds of these patients. Their true survival rate with the native liver reflects the original KPE and the burden of post-operative complications. We report an original modification of the adhesion-sparing liver eversion (ASLE) technique during KPE that facilitates the total native hepatectomy at time of transplantation. Methods: All consecutive patients with BA who underwent KPE at our department and subsequent LT at Paediatric Liver Transplant Centre at Papa Giovanni XXIII Hospital between 2010–2018 were retrospectively enrolled. All patients underwent ASLE during KPE. Patients’ demographic data, type of KPE, total transplant time (TTT), hepatectomy time (HT), intra-operative packed red blood cells and plasma transfusions, intra- and post-operative complications were noted. Results: 44 patients were enrolled. Median TTT and HT were 337 and 57 min, respectively. The median volume of packed red blood cell transfusion was 95 mL. No patients presented bowel perforation during the procedure or in the short post-operative course. No mortality after LT was recorded. Conclusions: In addition to the well-known advantages of the standard liver eversion technique, ASLE reduces the formation of intra-abdominal adhesions, lowering significantly the risk of bowel perforation and bleeding when liver transplantation is performed for failure of KPE.

Background: To demonstrate an inflammatory process in the central nervous system, the presence of at least two immunoglobulin (Ig) bands in the cerebrospinal fluid (CSF) is required. So far, the presence of a single abnormal Ig band is considered as negative. Objective: The objective was to assess retrospectively the significance of a single CSF Ig band in clinical practice. Methods and results: Out of 10,286 CSF analyses, we retained 214 results with single Ig. An inflammatory neurological disorder was diagnosed in 41% of patients. Conclusion: Despite a modest sensitivity, the presence of a single CSF Ig band may be a biomarker of an inflammatory mechanism and, as such, may prompt the clinician to repeat the analysis when the clinical context remains suggestive.

To pilot-test the effectiveness of a online compassion-focused crisis intervention for persons who were diagnosed with brief psychotic disorder and were still at high risk for a psychotic episode a...

Background: Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. Methods: In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. Findings: Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12·2), 170 335 (44·1%) of 386 248 were women, and 111 933 (30·1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0·69, 95% CI 0·61–0·77; p

Exposure and clinical response to CNS drugs are largely variable. AGNP guidelines suggest therapy individualisation with therapeutic drug monitoring of plasma concentrations and pharmacogenetic testing. We present the retrospective analysis of the last 5 years' data collected in real life settings as indirect evidence of the applications of the AGNP guidelines in the routine clinical management of psychiatric patients requiring pharmacologic treatments.Plasma concentrations were quantified using a liquid chromatography/tandem mass spectrometry method. Genomic DNA was isolated using an automatic DNA extraction system. All genotypes were determined by Real-Time PCR.We collected a total of 4582 requests for TDM and 212 requests for pharmacogenetic analysis. A wide distribution in the trough concentrations was observed for most drugs indicating a high interpatient variability. Nearly 45% of the samples had trough levels below the minimum effective drug concentrations set by the AGNP guidelines; only 8% of the samples had high concentrations. For pharmacogenetics analysis, among antipsychotics, clozapine, haloperidol and aripiprazole were the most requested (78%); while for antidepressants SSRIs were the most frequently prescribed.These data suggest that physicians are becoming more confident with the laboratory pharmacologic tools to optimise treatments and/or that the pharmacological treatment of patients with psychiatric disorders is becoming more challenging. TDM and PGx might significantly contribute to the rational selection of the best drug and best dose in individual cases.

Little is known about the effect of prematurity on later development of celiac disease (CD). We conducted a retrospective analysis of real-world data examining the association between very low birth weight (VLBW) prematurity and later development of CD autoimmunity (CDA) in 3580 infants born between years 2000 and 2012 and their matched controls. At a median of 12 years, VLBW prematurity was negatively associated with later development of CDA with a cumulative prevalence of 5.9 per 1000 versus 10.3 per 1000 (P = 0.02), though more former VLBW premature infants were ever tested for CDA (48.5% vs 37.4%, P < 0.001). The odds ratio for developing CDA among children born preterm at VLBW was 0.57 (95% confidence interval (CI) 0.35-0.92) as compared with matched controls. There was no difference in clinical characteristics of CDA between both groups. In conclusion, VLBW preterm infants present a decreased risk for the development of CDA during childhood and adolescence.

Background: Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. Aims: To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). Methods: From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). Results: In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) μg/g creatinine/12h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3μg/g creatinine/12h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. Discussion: The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. Conclusion: The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

Neuromyelitis optica spectrum disorder (NMOSD) is not defined as a classical paraneoplastic neurological syndrome, however there are growing evidences that NMOSD may be rarely associated with cancer. Older (>45 years old) male patients with longitudinally extensive transverse myelitis (LETM) or patients with “area postrema” syndrome (intractable vomiting and hiccups) at onset are at higher risk for neoplasm-associated NMOSD. We report the case of 79-years old man who developed, a month after radiotherapy for prostatic adenocarcinoma, an area postrema syndrome rapidly followed by a LETM involving the whole spinal cord (from C2 to the conus). Aquaporin-4-IgG antibodies were positive in serum.

In the last three decades, fetal ovarian cysts were diagnosed more frequently, due to technological improvement and the increasing use of prenatal screening ultrasound. Nonetheless, treatment uncertainties are still present, either prenatally or postnatally. Recently, significant innovations on diagnosis and treatment have been proposed and a more conservative, minimally invasive approach may be offered to the Pediatrician or the Surgeon who face with this condition during prenatal or neonatal age. (...)

A comprehensive description of morbidity and mortality as well as risk factors of interventional cardiac catheterization performed in neonatal age was reported in our paper recently published on the International Journal of Cardiology (IJCA28502; PII: S0167-5273(20)30384-3; DOI: 10.1016/j.ijcard.2020.04.013). Eight Italian high-volume centres of Paediatric Cardiology were involved in this observational, retrospective data collection and analysis. In this dataset, clinical and procedural characteristics of 1423 newborns submitted to 1551 interventional cardiac catheterization procedures were analyzed. Primary outcomes were considered procedure and in-hospital mortality as well as major adverse event and procedural failure rates. Secondary outcomes were considered minor adverse events and need for blood transfusion. Targets of this data analysis were: 1) to evaluate the overall major risk factors of interventional cardiac catheterization; 2) to identify the most hazardous interventional procedures; 3) to assess possible trends of individual procedures as well as their outcome over time; 4) to find possible relationships between the volume activity of any centre and the procedure and follow-up outcome. In particular, this Data in Brief companion paper aims to report the specific statistic highlights of the multivariable analysis (binary logistic regression) used to assess the impact of any potential risk factors on the type of procedure over a short-term follow-up.

International audience; Background: Docetaxel (DOCE) is a standard of care in metastatic castration-resistant prostate cancer (mCRPC). Several retrospective studies suggested a decrease in Prostate Cancer incidence and mortality with metformin (MET). MET has also demonstrated anti-tumor activity in Prostate Cancer preclinical models, with increased apoptosis when added to DOCE. We aimed at exploring the role of MET in combination with DOCE in mCRPC.Patients and methods: Non-diabetic mCRPC patients were randomly assigned to receive DOCE 75 mg/m2 every 21 days + prednisone (5 mg. BID) with either MET 850 mg BID (D+M) or placebo (D+P) up to 10 cycles. Prostate-Specific Antigen (PSA) response ≥50% from baseline was the primary end point. Secondary end points included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), toxicity and quality of life (QoL).Results: Out of 99 patients were randomized (D+M = 50; D+P = 49) in 10 French centers. The median follow-up was 86 (IQR 73-88) months. The PSA-response rate reached 66% in the D+M arm, but was not different from that observed in the D+P arm (63%, P = 0,94). In the D+M and D+P arms, the ORR was 28% and 24%, the median PFS was 7.8 and 6.0 months and the median OS was 27 and 20 months (ns), respectively. Diarrhea grade I to II was more frequent in the MET arm (66% vs. 43%). No impairment of QoL was observed.Conclusion: MET addition failed to improve the standard DOCE regimen in mCRPC. Further research targeting tumor cell metabolism should be performed.

Background Randomized controlled trials showed that sodium/glucose cotransporter-2 inhibitors (SGLT2i) protect the heart and kidney in an array of populations with type 2 diabetes (T2D) and increased cardiorenal risk. However, the extent of these benefits also in lower kidney-risk T2D populations needs further investigation. Methods Members of Maccabi Healthcare Systems listed in their T2D registry who initiated new glucose lowering agents (GLA), were divided into SGLT2i initiators and other GLAs (oGLAs). Groups were propensity score-matched by baseline demographic and medical characteristics. Two composite cardiovascular outcomes were defined: all-cause mortality (ACM) or hospitalization for heart failure (hHF); and ACM, myocardial infraction (MI) or stroke. The cardiorenal outcome was: ACM, new end-stage kidney disease (ESKD) or ≥ 40% reduction from baseline estimated glomerular filtration rate (eGFR). Renal-specific outcome was new ESKD or ≥ 40% eGFR reduction. Single components of cardiovascular and kidney outcomes were also assessed. Three subgroup definitions of low baseline kidney-risk were used: eGFR > 90 ml/min/1.73 m2; urinary albumin below detectable levels; and low risk according to Kidney Disease: Improving Global Outcomes (KDIGO) classification. Analyses were performed utilizing an unadjusted model, and a model adjusted to baseline eGFR and urinary albumin-to-creatinine ratio. Results Between April 1, 2015 and June 30, 2018; 68,187 patients initiated new GLAs — 11,321 SGLT2i initiators and 42,077 oGLAs initiators were eligible. Propensity score-matching yielded two comparable cohorts; each included 9219 participants. Median follow-up was 1.7 years. Compared to oGLAs, SGLT2i initiators had lower incidence of ACM or hHF [HR95%CI = 0.62(0.51–0.75)]; ACM, MI or stroke [0.67(0.57–0.80)]; the cardiorenal outcome [0.65(0.56–0.76)]; and the renal-specific outcome [0.70(0.57–0.85)]. SGLT2i initiators also had lower risk for ACM, hHF and ≥ 30%, ≥ 40%, ≥ 50%, ≥ 57% eGFR reduction. No difference between groups was observed for MI or stroke. In the low baseline kidney-risk subgroups, SGLT2i initiation was generally associated with lower risk of the cardiovascular and cardiorenal outcomes, driven mainly by lower ACM incidence. Conclusions Our findings in the general population of patients with T2D demonstrates lower risk of cardiorenal outcomes associated with initiation of SGLT2i compared with oGLAs, including specifically in patients with low baseline kidney-risk.

Summary Background Cardiovascular and kidney outcome trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors slow progression of chronic kidney disease in patients with type 2 diabetes with or without chronic kidney disease. The aim of this study was to assess whether these benefits extend to patients with type 2 diabetes treated in routine clinical practice. Methods CVD-REAL 3 was a multinational observational cohort study in which new users of SGLT2 inhibitors and other glucose-lowering drugs with measurements of estimated glomerular filtration rate (eGFR) before and after (within 180 days) initiation were identified via claims, medical records, and national registries in Israel, Italy, Japan, Taiwan, and the UK. Propensity scores for SGLT2 inhibitor initiation were developed in each country, with 1:1 matching with initiators of other glucose-lowering drugs. Propensity score included (in addition to other clinical and demographic variables) baseline eGFR and eGFR slope before SGLT2 inhibitor or other glucose-lowering drug initiation. The main outcome measure was rate of eGFR decline (slope) calculated with a linear mixed regression model. Differences in eGFR slope between SGLT2 inhibitors and other glucose-lowering drugs were calculated and pooled. We also assessed a composite outcome of 50% eGFR decline or end-stage kidney disease. Findings After propensity matching, there were 35 561 episodes of treatment initiation in each group, from 65 231 individual patients. Dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, tofogliflozin, and luseogliflozin accounted for 57·9%, 34·1%, 5·7%, 1·4%, 0·5%, and 0·4% of SGLT2 inhibitor initiation episodes, respectively. At baseline, 29 363 (41·3%) of 71 122 initiations were in women, mean age was 61·3 years, mean HbA1c was 72 mmol/mol (8·71%), and mean eGFR was 90·7 mL/min per 1·73 m2. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other glucose-lowering drugs 1·53 mL/min per 1·73 m2 per year, 95% CI 1·34–1·72, p Interpretation In this large, international, real-world study of patients with type 2 diabetes, initiation of SGLT2 inhibitor therapy was associated with a slower rate of kidney function decline and lower risk of major kidney events compared with initiation of other glucose-lowering drugs. These data suggest that the benefits of SGLT2 inhibitors on kidney function identified in clinical trials seem to be largely generalisable to clinical practice. Funding AstraZeneca.

Introduction Insulin degludec/liraglutide (IDegLira) is a fixed-ratio combination (FRC) of basal insulin and glucagon-like protein-1 receptor agonist (GLP-1 RA) that has demonstrated glycemic and metabolic benefits in patients with type 2 diabetes mellitus (T2DM) in both randomized controlled trials and real-world studies. The impact of adherence to this medication and its effect on patients with T2DM who switch from loose-dose combination therapy to a FRC of insulin and GLP-1RA have not yet been reported. We have examined the metabolic effects and adherence to this medication in a real-life setting, in T2DM patients who initiated IDegLira therapy after being treated with other glucose-lowering drugs. Methods This is a retrospective observational study of adult T2DM patients managed by the Maccabi Healthcare Services (Israel) who initiated IDegLira and persisted with therapy for 180 days between July 2017 and August 2018. Mean glycated hemoglobin (HbA1c), body weight change, metabolic parameters, dose and proportion of days covered (PDC) by IDegLira were recorded from initiation to after 180 days of therapy. Results A total of 413 patients who persisted with IDegLira therapy for at least 180 days were evaluated as a per protocol group. A significant mean reduction in HbA1c of 0.65% (95% confidence limits [CL] − 0.78, − 0.52; P

The primary outcomes are the evaluation and quantification of pain relief and improvement in range of motion after OAT in OCD. The secondary outcomes are: resuming of sport activities, evaluation of the ADL recovery rate and subjective evaluation of the quality of life improvement. Nine patients, affected by an unstable and non-acute OCD lesion of the capitulum humeri, have been treated by the same surgeon. The patient mean age was 22.4 (16–45 years). All subjects were treated with the same surgical technique (arthroscopic OAT from the same side knee, a single cylinder of 6.5–9 mm in diameter) and underwent the same rehabilitation. The mean follow-up was 48 months (30–52 months). The authors documented the clinical assessment of each patient and carried out a questionnaire which included the VAS scale, MEPS Score and Quick DASH score. Patients were asked for MRI and radiographs pre- and post-operatively at follow-up. The mean range of motion improvement was 17.9° in extension (range 13°–27°) and 10.6° in flexion (range 0°–20°) The VAS mean improvement was 7.1 (range 6–8) and the mean post-op value 0.6 (range 0–3). The MEPS score mean post-operative value was 98.3 (range 85–100). The Quick-DASH mean post-operative value was 2.5 (range 0–9.1) with a mean improvement of 41.4 points (range 36.4–47.7 points). All patients resumed sports in 6 months post-operatively. The autologous transplant of an osteochondral plug is a safe and promising procedure. Despite being more demanding, the arthroscopic approach is a valuable tool if the surgeon aims to reduce the invasiveness of the procedure, with all the consequent advantages. Retrospective case series, therapeutic study.

Introduction In both randomized controlled trials and real-world studies, liraglutide has demonstrated glycemic and body weight benefits in patients with type 2 diabetes. However, persistence with diabetes medication can be challenging. This study compared glycated hemoglobin (HbA1c) and other outcomes in patients with type 2 diabetes who continued treatment with liraglutide for over 12 months with those who discontinued treatment earlier, in a real-life setting. Methods This is a retrospective study of adult patients with type 2 diabetes from Maccabi Healthcare Services in Israel, who initiated treatment with liraglutide from 2010 to 2015. Mean HbA1c and body weight change from initiation to after 24 months was compared between patients who received liraglutide for at least 12 months (“continuers”) and those who discontinued within the first year (“discontinuers”). Adjustment for HbA1c, body weight, and other potentially confounding factors was performed using 1:1 propensity score matching. Results The 3580 patients comprised 2695 continuers and 885 discontinuers; 882 patients per group were matched. A significant (p

The EMPRISE study evaluates the effectiveness and safety of empagliflozin (EMPA) in a broader population of patients with T2D in routine clinical care across countries. The study included 67,140 pairs of 1:1 propensity score matched (PSM) patients ≥18 years with T2D newly initiating EMPA or any DPP-4i from large databases/registers in Israel, Finland, Germany, Spain, Sweden, South Korea, Taiwan and Japan. Mostly, PSM used 100+ baseline covariates (Table), and pooled HR with 95% CI were computed using random-effects meta-analysis models. EMPA compared to DPP-4i (Table), was associated with 27-47% lower risk of hospitalization for heart failure (HHF), stroke, all-cause mortality (ACM), and two composite outcomes: HHF & ACM; and myocardial infarction, stroke & ACM. Safety analyses associated EMPA with 46% lower risk of acute kidney injury requiring dialysis. EMPRISE study results showed that EMPA is associated with reduced risk of cardiovascular (CV) disease, incl HHF, in patients with T2D in routine clinical care settings in Israel, Europe and East Asia. These results complement the results from clinical trial EMPA-REG OUTCOME®, and are in line with the ADA/EASD 2019 consensus update to prescribe SGLT-2i for patients with T2D and high-risk, vascular or chronic kidney disease or heart failure to reduce HHF and major adverse CV events/deaths. Disclosure A. Karasik: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S. S. Lanzinger: None. E. C. H. Tan: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. D. Yabe: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Corporation. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., MDS Co., Ltd., Novo Nordisk Pharma Ltd. D. Kim: None. W. Sheu: None. C. Melzer Cohen: None. R. W. Holl: None. K. Ha: None. T. Nystrom: Board Member; Self; Abbott, Lilly Diabetes, Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; AstraZeneca. L. K. Niskanen: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Sanofi-Aventis. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. Stock/Shareholder; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Linnemann Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. M. H. Kyaw: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J. Nunez: Advisory Panel; Self; Novo Nordisk Pharma Ltd. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.

Women of childbearing age are largely affected by several autoimmune disorders (the estimates range between 1.5 and 10 per 10,000). The increasing number of effective biological agents has dramatically revolutionized the treatment of these clinical conditions, ameliorating the patient's quality of life. The use of these agents by women during pregnancy is growing to ensure the disease activity control and avoid adverse health outcomes. However, for many newer biological agents, the degree of information concerning their use in pregnancy is often incomplete to perform a conclusive risk assessment on fetal and maternal health given the exclusion of this specific population from pharmacological clinical trials. More recently, the COVID-19 pandemic has confirmed the unacceptable inequities of pharmacological research and medical treatment for pregnant and lactating women, exacerbating the need for filling the gaps of quantitative and qualitative pharmacology data in this sensitive population. ere we summarize (i) what is already known about safety and effectiveness of biological agents in this understudied population (with specific focus on pregnancy-related health outcomes), and what we are going to learn from the on-going studies among pregnant women treated with biological agents; (ii) the methodological and ethical considerations that characterize the pharmacological research in pregnancy, also discussing emerging evidence on the use of therapeutic drug monitoring (TDM) in this clinical setting.

The analysis of circulating tumor DNA (ctDNA) released by tumor cells holds great promise for patients with lymphoma, to refine the diagnostic procedure, clarify the prognosis, monitor the response to treatment, and detect relapses earlier. One of the main challenges of the coming years is to adapt techniques from highly specialized translational teams to routine laboratories as this requires a careful technical and clinical validation, and we have to achieve this as fast as possible to transform a promising biomarker into a routine analysis to have a direct consequence on patient care. Whatever the analytical technology used, the prerequisite is to obtain high yields of ctDNA of optimal quality. In this review, we propose a step-by-step description of the preanalytical process to obtain high-quality ctDNA, emphasizing the technical choices that need to be made and the experimental data that can support these choices.

Objective The aim was to characterise the short-term (up to 12 months) direct economic burden of new cardiovascular (CV) events among adults with type 2 diabetes (T2D) in Israel. Methods In this retrospective cohort study utilising the electronic health records of the Maccabi Healthcare Services, adults aged ≥ 21 years with T2D who experienced their first CV event (2013–2016) were identified via adjudicated enrolment in a CV registry. Wilcoxon rank-sum test estimated excess healthcare resource utilisation in three periods after the CV event: immediate (1 month; for all patients), acute (3 months; for survivors of 1 month of follow-up) and short-term (12 months; for survivors of 3 months of follow-up). Direct healthcare expenditure (2018 United States dollars [USD]) was estimated from unit costs from the State of Israel Ministry of Health price list. Results In total, 5133 adults experienced a qualifying CV event, with a mean (standard deviation [SD]) age of 67.4 (11.8) years, diabetes duration of 17.7 (11.1) years and glycated haemoglobin of 7.4% (1.6%); 38.0% were female. In USD per patient, mean (SD) immediate costs were $10,741 ($11,707) compared with $2820 ($5661) at baseline (cost ratio [CR] 3.81), acute costs were $14,586 ($15,410) compared with $5202 ($8971) at baseline (CR 2.80) and short-term costs were $23,847 ($25,227) compared with $11,123 ($15,990) at baseline (CR 2.14). A sensitivity analysis of survivors only was consistent with the main analysis. Conclusions Our results indicate that CV complications of T2D place a substantial excess economic burden on Israel’s healthcare system over the short term (up to 12 months). Supplementary Information The online version contains supplementary material available at 10.1007/s41669-021-00268-5.

N-methyl-d-aspartate receptor (NMDAR) encephalitis is a potentially treatable condition, although a small proportion of patients remains refractory to immunotherapy. Bortezomib is a proteasome inhibitor that has a promising role in autoimmune conditions. We performed an independent PubMed search employing "Anti-N-Methyl‑D-Aspartate encephalitis AND bortezomib", including papers published between January 1st, 2007 to April 15th, 2021. Fourteen articles were included, with 29 patients. 16 patients (55,2%) had a favorable outcome after bortezomib and 11 (37,9%) patients developed side effects. Quality of studies was overall poor and future trials should aim to include more homogeneous and larger cohorts.

We herein report an unusual case of a 40-year-old woman presenting to the emergency department with acute-onset tetraparesis due to inhalation of chemical solvents containing n-hexane. The clinical picture, a mild albumin-cytologic dissociation and the demyelinating features on nerve conduction study initially mimicked the presentation of Guillain-Barré syndrome (GBS), but the patient failed to respond to intravenous immunoglobulin treatment and plasma exchange. Diagnosis of hexane-induced neuropathy was then confirmed by means of sural nerve biopsy, showing axonal enlargement with secondary retraction and thinning of the myelin sheath.

Background The VOLibris Tracking (VOLT) Study was an open-label, prospective, observational, multicenter, post-marketing registry program designed to more fully characterize the safety profile of ambrisentan for the treatment of pulmonary arterial hypertension (PAH). The key outcome was the incidence of aminotransferase elevations >3× the upper limit of normal (ULN). Methods In total, 999 patients from 115 centers in 15 countries, who were prescribed ambrisentan for the treatment of PAH (Functional Class II and III) between 30 June 2008 and 13 May 2011, were enrolled. Of these, 238 had PAH associated with connective tissue disease (PAH-CTD) and 220 had no prior PAH-specific therapy. Routine clinical monitoring data were collected by physicians. Results The incidence of both alanine and aspartate aminotransferase events (>3× ULN) was 0.02 per patient-year (95% confidence interval 0.015 to 0.027). Similar results were reported for the PAH-CTD and PAH-specific-therapy-naive subgroups. Overall, 514 (52%) patients reported treatment-emergent adverse events of special interest, most commonly edema/fluid retention (249, or 25%) and anemia (143, or 14%). Conclusions Data from the VOLT study indicate no new ambrisentan-related safety signals. Ambrisentan was not associated with increases in liver function test abnormalities above the assumed background incidence of 1.5% per year, and the observed safety profile of ambrisentan was consistent with previously published data.

Background: Despite recent technical advances, interventional cardiac catheterization is still challenging in neonatal age and no specific data concerning early outcome are so far published in literature. Methods: Neonatal trans-catheter cardiac interventions performed in high-volume Italian referral centers were retrospectively analyzed. Primary outcomes were procedural major adverse events, in-hospital mortality and procedural failure. Secondary outcomes were minor adverse events and need for blood transfusion. Results: From January 2000 to December 2017, 1423 newborns (mean weight 3.0 ± 0.6 kg, range 1.0–5.8; median age 2.0 days) underwent interventional cardiac catheterization. Overall, global procedure adverse event rate and in-hospital mortality were 10.2% and 5.2%, respectively. At multi-variable analysis, primary composite outcome was significantly related to low-weight (

LGI1 encephalitis is an autoimmune disorder characterized by cognitive symptoms and seizures, which rarely respond to common antiepileptic drugs (AEDs). Rituximab (RTX) is a CD-20-depleting monoclonal antibody which has been used for the treatment of LGI1 encephalitis, however, its efficacy remains controversial. A 54-year-old woman came to our attention due to memory loss and gambling. Brain MRI revealed areas of bilateral hippocampal hyperintensity and LGI1 antibodies were found in both serum and cerebrospinal fluid. Immunotherapy with steroids was started, followed by intravenous immunoglobulins with partial improvement. The patient developed multiple generalized tonic-clonic seizures. She was then administered intravenous rituximab with significant improvement for both cognitive symptoms and seizure control. High-density EEG was recorded before treatment, seven days after the first dose and seven days after the second dose. Topoplot and power spectrum analysis were performed for each recording. Interictal epileptiform discharges, as well as theta power bands, were significantly reduced after each dose, while topoplot analysis showed reduced spreading over posterior and frontal electrodes for interictal epileptiform discharges of temporal origin. Our experience indicates that rituximab is a valid treatment for LGI1 encephalitis, demonstrating efficacy for both cognitive symptoms and seizure control. High-density EEG could represent a novel, safe and reproducible method to study epileptogenesis in autoimmune limbic encephalitis.

The most appropriate treatment for the infantile Hypertrophic Pyloric Stenosis (HPS) is still debated. The non-surgical conservative treatment with oral or intravenous administration of atropine does not enjoy a widespread appreciation for several factors (...)

Introduction The risk of acquiring SARS-CoV-2 in a hospital setting and the need of reorganizing the Emergency Departments (EDs) to cope with infected patients have led to a reduction of ED attendances for non-infectious acute conditions and to a different management of chronic disorders. Methods We performed a retrospective study evaluating the frequency and features of ED attendances for seizures during the lockdown period (March 10th–April 30th 2020) in the University Hospital of Trieste, Italy. We studied the possible pandemic impact on the way patients with seizures sought for medical assistance by comparing the lockdown period to a matched period in 2019 and to a period of identical length preceding the lockdown (January 18th–March 9th 2020). Results A striking decrease in total ED attendances was observed during lockdown (4664) compared to the matched control (10424) and to the pre-lockdown (9522) periods. A similar reduction, although to a lesser extent, was detected for seizure attendances to the ED: there were 37 during lockdown and 63 and 44 respectively during the two other periods. Intriguingly, during the lockdown a higher number of patients attended the ED with first seizures (p = 0.013), and more EEGs (p = 0.008) and CT brain scans (p = 0.018) were performed; there was a trend towards more frequent transport to the ED by ambulance (p = 0.061) in the lockdown period. Conclusions Our data suggest that the pandemic has affected the way patients with seizures access the Health Care System.

Epilepsia partialis continua (EPC) is a rare entity, first described in 1894 by Koževnikov, as a variant of simple focal motor status epilepticus. EPC is most frequently characterized by motor symptoms, but as recently described, non-motor manifestations may occur, such as somatosensory symptoms or aura continua. EPC in adults has been attributed to various etiologies: infectious, vascular, neoplastic, and metabolic. According to the recent definition, we reported a case of EPC with behavioral symptoms, following a tick-borne encephalitis (TBE) contracted in an endemic area (North Eastern Italy). Patient's symptom was a poorly localized "whole body sensation", which is reported as a condition occurring only in frontal lobe epilepsy. Patient's EEG showed a left frontal predominance of epileptiform discharges. Literature highlighted the importance of the Far-eastern TBE variant as a cause of EPC, since no Western variant TBE cases are reported. In contrast to what was claimed so far, our case demonstrates that not only the Far-eastern TBE variant, but also Western variant TBE is a cause of EPC. Prognosis of EPC depends largely on the underlying etiology, and it is frequently drug-resistant. Our patient was treated with intravenous levetiracetam, with a subsequent clinical recovery and a disappearance of epileptiform discharges. The rapid clinic and electroencephalographic response to levetiracetam confirm that it can be a promising therapeutic option for treatment of EPC.

Linee guida della Società Italiana di Videochirurgia Infantile Le Linee Guida della Società Italiana di Videochirurgia Infantile (SIVI) sono uno strumento semplice e pratico redatto ed approvato dal Consiglio Direttivo della Società. Esse sono frutto di un lungo lavoro di revisione sistematica della letteratura integrato dal parere di esperti nel campo della Chirurgia Mininvasiva Pediatrica. Queste linee guida sono intese ad aiutare il chirurgo pediatra che si avvicina, o già pratica, la Chirurgia Mininvasiva, ed hanno lo scopo di facilitare la scelta dell’indicazione e del trattamento chirurgico ottimale per le principali patologie chirurgiche pediatriche. Tuttavia, data la complessità delle malformazioni congenite, delle patologie chirurgiche pediatriche e l’estrema varietà dell’ambiente sanitario, è importante sottolineare come l’approccio suggerito potrebbe non essere necessariamente l’unico approccio accettabile e/o percorribile. Le linee guida devono essere considerate uno strumento flessibile in quanto poi è il medico che, con il consenso dei genitori/tutori, avrà il compito di scegliere l’approccio più adatto al singolo paziente. Tale approccio sarà attuato in scienza e coscienza ed in base alla patologia ed alle eventuali variabili esistenti al momento della decisione. La massima accessibilità possibile alle Linee Guida è garantita dalla loro pubblicazione sulla rivista ufficiale della SIVI: La Pediatria Medica e Chirurgica. Il progetto Linee Guida è stato approvato dall’assemblea generale del Congresso SIVI 2016 di Madrid.

Autoimmune limbic encephalitis (LE) is a neurological condition characterized by seizures and cognitive dysfunction. Fluorine-18 fluorodeoxyglucose (18F-FDG-PET) has recently proved to be an important diagnostic tool in this condition since it may highlight brain metabolism abnormalities in a very early stage of the disease. Two main 18F-FDG-PET patterns have been described: the mixed hypermetabolic/hypometabolic and the neurodegenerative one. Arterial spin labeling (ASL) is an MRI technique showing brain perfusion, rarely used in autoimmune neurological conditions. The aim of the present study was to study patients with LE with both techniques, in order to compare their results. Two patients with LE underwent to 18F-FDG-PET and ASL MRI scans using the pseudo-continuous arterial spin labeling (PCASL) technique. Areas of altered perfusion and metabolism were analyzed by visual inspection, and findings were compared between the two techniques. In the first patient, a relapsing LGI-1 LE, right hippocampal hypermetabolism was detected by 18F-FDG-PET (mixed hypermetabolic/hypometabolic pattern), while ASL MRI showed right hippocampal increased perfusion. In the second patient, a seronegative LE, 18F-FDG-PET scan detected a left hemispheric hypoperfusion (neurodegenerative pattern) and ASL MRI yielded similar results. The two 18F-FDG-PET patterns of altered metabolism were similarly detected by ASL imaging. ASL and 18F-FDG-PET findings are strongly concordant in LE. ASL imaging was able to detect the two main 18F-FDG-PET patterns previously described in patients with LE.

Triceps tendon injuries are probably among the rarest tendon injuries in the human body. Evidence shows male predominance (3:1, male to female) with wide age variance at occurrence. The most common rupture site is at tendon insertion into the olecranon and more rarely at the myotendinous junction or intramuscularly. Several triceps tendon injuries risk factors have been reported. The main injury mechanism is falling on an outstretched hand. Other conditions that can increase risk of triceps ruptures are: sport activities, use of anabolic steroid drugs or local steroid injection, olecranon bursitis. Alternatively, risk of triceps ruptures can arise secondary to surgical exposure (such as following total elbow replacement) or secondary to release for stiff elbow. Conservative management plays a role in partial triceps injuries involving the muscle belly or musculotendinous junction, or in partial ruptures of the distal tendon insertion when there is no significant extension power loss against gravity and no resistance according to the patient’s age and lifestyle. Several surgical techniques and different approaches offer variable options for the surgical management of acute complete or chronic tears as direct olecranon repair, augmentation with auto- or allograft, anconeus rotation flap, Achilles tendon allograft with or without calcaneus bone.

Objective: The aim of this study was to characterize nutritional status, body composition, oxidative stress, and inflammatory activity and to determine the possible associations between nutritional...

Sports that entail repeated throwing movements expose the elbow joint to significant forces which, over time, can cause the onset of pathological alterations and injuries. In this context, upper limbs bony joints, ligaments, and muscles act as stabilizers supporting elbow resistance to the valgus stress of throwing. Accurate knowledge of elbow anatomy and biomechanics is required to understand the mechanism of development of throwers’ diseases, make the right diagnosis, and choose the proper treatment.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed the routine activities of pediatric surgical centers, and it determined the reduction of admissions in the pediatric emergency departments (PED). We reviewed the records of patients affected by acute appendicitis (AA) during the COVID-19 pandemic period in a large Italian COVID-19 pandemic area.Methods: Data regarding demographics, age, macroscopic and microscopic findings, and time between symptom onset and PED admission of patients affected by confirmed AA in the period between March and April 2020 were considered. The data were compared with those obtained during the same period of 2019, 2018, and 2017 in the included centers. Data were quoted as median (range) or absolute number. Non-parametric statistical tests were used to compare groups. A p ≤ 0.05 was regarded as significant. Since only anonymous data have been used and the data storage meets current data protection regulations, ethical committee approval was not required for this study.Results: Eighty-six patients underwent surgical appendectomy for AA between February 20th, 2020 and April 20th, 2020; 32.5% were complicated appendicitis and 67.5% were uncomplicated. Fifty-three patients were males and 33 were females. Patients' age ranged from 3 to 17 years and the median age was 10 years. The median time between the onset of symptoms and the admission in PED was 1.85 days. The average time between the symptom onset and PED admission was 1.8 days.Conclusions: Although fear from the COVID-19 pandemic determined a delayed diagnosis of serious pediatric diseases, the increasing prevalence and severity of AA were not demonstrated in the most COVID-19-affected areas of Italy.

BACKGROUND Although nonoptimal vaginal bacteria and inflammation have been associated with increased HIV risk, the upstream drivers of these phenotypes are poorly defined in young African women. SETTING Mombasa, Kenya. METHODS We characterized vaginal microbiome and cytokine profiles of sexually active young women aged 14-24 years (n = 168) in 3 study groups: those engaging in formal sex work, in transactional sex, and nonsex workers. Vaginal secretions were collected using self-inserted SoftCup, and assayed for cytokines and vaginal microbiome through multiplex ELISA and 16S rRNA sequencing, respectively. Epidemiological data were captured using a validated questionnaire. RESULTS The median age of participants was 20 years (interquartile range: 18-22 years). Approximately two-thirds of young women (105/168) had vaginal microbial communities characterized by Gardnerella and/or Prevotella spp. dominance; a further 29% (49/168) were predominantly Lactobacillus iners. Microbiome clustering explained a large proportion of cytokine variation (>50% by the first 2 principal components). Age was not associated with vaginal microbial profiles in bivariable or multivariable analyses. Women self-identifying as sex workers had increased alpha (intraindividual) diversity, independent of age, recent sexual activity, HIV, and other sexually transmitted infections (beta = 0.47, 95% confidence interval: 0.05 to 0.90, P = 0.03). Recent sex (number of partners or sex acts last week, time since last vaginal sex) correlated with increased alpha diversity, particularly in participants who were not involved in sex work. CONCLUSION Nonoptimal vaginal microbiomes were common in young Kenyan women and associated with sex work and recent sexual activity, but independent of age. Restoring optimal vaginal microflora may represent a useful HIV prevention strategy.

Aims Randomized controlled trials have shown that insulin glargine 300 U/mL (Gla‐300) has a more stable and prolonged glucose lowering effect among patients with type 2 diabetes (T2DM) compared to insulin glargine 100 U/mL (Gla‐100), resulting in a reduced risk of hypoglycaemia while maintaining a similar efficacy of lowering HbA1c. We aimed to investigate if the effectiveness of Gla‐300 is reproducible in real‐world settings. Material and methods In this retrospective cohort study, data from a large state‐mandated health organization were used to identify adult T2DM patients who were previously on insulin and initiated Gla‐300 therapy between 6/ 2016 and 12/2017. Changes in HbA1c levels, body weight and insulin dose were calculated from baseline period and over a follow‐up period of 180 days. Documented hypoglycaemia events were also explored. Results A total of 1797 patients were included in this study with a mean age of 64.2 (SD = ±11.0y), baseline HbA1c was 8.7 ± 1.6% and 42.5% were females. Among all patients with HbA1c measurement during follow‐up (n = 1508), HbA1c was significantly reduced by −0.6% (95% CI −0.6,−0.5; P, In this real‐world study, the effectiveness and safety among 1797 type 2 diabetes patients were investigated. The article provides evidence that insulin glargine 300 is effective in reducing blood glucose levels without increasing body weight or hypoglycaemic events.

Background: Efficacy and safety of vitamin K antagonists (VKAs) is optimised in atrial fibrillation (AF) patients when the International Normalised Ratio (INR) is 2.0–3.0. Anticoagulation control comparing different ethnic groups is limited, although epidemiological studies suggest poorer INR control in non-white cohorts. Methods: VKA control was assessed retrospectively by time-in-the-therapeutic range (TTR) (Rosendaal method) and percentage INR-in-range (PINRR) in 991 White, Afro-Caribbean and South-Asian AF patients [overall mean (SD) age 71.6 (9.4) years; 55% male; mean (SD) CHA2DS2-VASc score 3.4 (1.6)] over a median (IQR) follow-up of 5.2 (3.2–7.0) years. Results: Compared to Whites, mean (SD) TTR and PINRR were significantly lower in South-Asians [TTR 67.9% vs. 60.5%; PINRR 58.8% vs. 51.6%, respectively] and Afro-Caribbeans [TTR 67.9% vs. 61.3%; PINRR 58.8% vs. 53.1%, respectively], despite similar INR monitoring intensity. Logistic regression revealed non-white ethnicity [OR 2.62; 95% Confidence Interval [CI] (1.67–4.10) and OR 3.47 (1.44–8.34)] and anaemia [OR 1.65 (1.00–2.70) and OR 6.27 (1.89–20.94)] as independent predictors of both TTR and PINRR < 70%, respectively. At follow-up, 329 (33.2%) patients experienced ≥1 major adverse clinical event. Cardiovascular hospitalisation was significantly higher among South-Asians (32.3%) compared to the Whites and Afro-Caribbeans (21.3% vs 25.6% respectively). Conclusions: Ethnic disparities in quality of anticoagulation control are evident, with South-Asians and Afro-Caribbeans having poorer control compared to Whites, despite similar intensity INR monitoring. Non-white ethnicity remained the strongest independent predictor of poor TTR and PINRR. Interventions to improve anticoagulation control need to be implemented, particularly targeting ethnic minority patients.

Aim To assess the possible risk of acute kidney injury (AKI) with the use of sodium-glucose co-transporter-2 inhibitors (SGLT2-i) as well as changes in estimated glomerular filtration rate (eGFR), hospitalizations and mortality in a real-world setting. Materials and methods Included in this historical cohort study were patients with type 2 diabetes in a large health organization in Israel who initiated therapy with SGLT2-i or dipeptidyl peptidase-4 inhibitors (DPP-4i) during 1 April 2015 to 30 June 2017. We collected data on serum creatinine measurements taken between 180 days prior to and 24 weeks after therapy initiation. Study endpoints included ≥30% reduction in eGFR, hospitalization with AKI, any hospitalization and all-cause mortality. Results Overall 6418 and 5604 patients initiated SGLT2-i and DPP-4i, respectively. Baseline mean (SD) eGFR was higher among the SGLT2-i group compared with the DPP-4i group (88.3 [17.4] and 82.8 [23.7], respectively) but were similar when stratifying by chronic kidney disease (CKD) stages. The adjusted odds ratio (OR) (95% confidence interval [CI]) for ≥30% reduction in eGFR with SGLT2-i versus DPP4-i was 0.70 (0.49-1.00) and ORs ranged from 1.97 (0.62-6.26) to 0.45 (0.21-0.99) in patients with baseline eGFR 30 to 45 and ≥90 mL/min/1.73 m2 , respectively. Risks of AKI (OR = 0.47, 95% CI 0.27-0.80), hospitalization (OR = 0.66, 95% CI 0.56-0.78) or all-cause mortality (OR = 0.43, 95% CI 0.20-0.95) were lower in patients initiating SGLT2-i versus DPP-4i. Conclusions This real-world data analysis supports reassuring findings from previous randomized clinical trials showing no increased AKI risk among SGLT2-i users. Nevertheless, because of the more prominent decrease in eGFR in patients with moderate CKD, cautious use of SGLT2-i in patients with reduced eGFR is advised.

Cornelia de Lange syndrome (CdLS) is a genetic condition characterized by intellectual disability, peculiar facial dysmorphisms, multiorgan malformations, and growth problems. Majority cases of CdLS are caused by mutations in genes of Cohesin pathway. Although feeding problems are a well-known feature, no specific data have been published about the use of nutritional devices. We analyzed use, type, time of introduction, and duration of nutritional devices in 73 CdLS patients. In total, 29/73 (40%) used a device; nasogastric tube (NGT) in 28/73 (38%) and percutaneous endoscopic gastrostomy (PEG) in 7/73 (10%). NGT was placed during the first days/weeks of life. 19/28 (68%) maintained it for less than 3 months, 7/28 (25%) for a period between 3 and 12 months, while 2/28 (7%) for more than 1 year. PEG was placed within the first year in 4/7 (57%) and removed in two patients after 4 years These data have been matched with a wide number of genetic and clinical variables. Presence of upper limb malformations is positively correlated with the need of a device. From the opposite side, the use of a device positively correlates with a more severe prognosis as regard growth, intellectual development and disease severity. Our data show that nutritional devices are frequently used by CdLS patients, also if the majority of them (93.1%) succeed with time in achieving a normal oral nutrition. Finally, the need, the type of device used and the duration of NGT or/plus PEG can be considered a further sign of worse prognosis of the disease itself.

Background Randomized trials demonstrated a lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high...

Objectives Ulnar coronoid apophysis is a primary stabiliser of the elbow; a relatively small amount of bone loss, quantifiable in 40%, could be sufficient to make an elbow incongruent. If coronoid fixation is not possible, the only way of achieving a stable elbow is to reconstruct it. This case series describes the senior author’s original surgical technique in reconstructing the coronoid with a fresh-frozen osteochondral coronoid allograft, reporting a mid-term follow-up (average of 55.5 months, minimum of 26 months) of four patients (described one by one) with subjective and objective outcomes. Methods The senior author operated on four patients with his original surgical technique, fully explained in the text. The mean follow-up at the time is 55.5 months (up to 10 years in one case). Preoperatively and postoperatively, the patients were asked to answer three types of validated scales: Visual Analogue Scale (VAS), Quick-Disabilities of the Arm Shoulder and Hand (Quick-DASH) and Mayo Elbow Performance Index (MEPI). All patients underwent preoperative X-rays and CT scans. Afterwards, they were asked to have further X-rays and a dual- energy CT scan in the last-follow up. Results Three patients achieved 100 points on the MEPI scale. Three patients achieved full range of motion (ROM), while the fourth one easily achieved functional ROM. The VAS score mean improvement was 50%, and two patients were completely pain-free; the Quick-DASH average improvement score was 56.82 points. Conclusions This case series presents an original technique using a coronoid allograft. Three of four patients achieved full ROM, and two were pain-free at follow up. Everyone resumed previous levels at work and in sports. The good outcomes suggest that this procedure seems to be safe and does not necessarily require autologous structures. The lack of registered cases of graft reabsorption may encourage the use of an osteochondral coronoid allograft. Level of evidence Level IV.

Aims To externally validate the United Kingdom Prospective Diabetes Study (UKPDS) Outcome Model 2 (OM2) in contemporary Israeli patient populations. Methods De-identified patient data on demographics, time-varying risk factors, and clinical events of newly diagnosed type 2 diabetes patients were extracted from the Maccabi Healthcare Services (MHS) diabetes registry over years 2000–2013. Depending on the baseline risk, patients were categorized into low-risk and intermediate-risk groups. In addition to assessing discriminatory performance, the predicted and observed 15-year cumulative incidences of diabetes complications and death were compared among all patients and for the two risk-groups. Results The discriminatory capability of OM2 was moderate to good, C-statistic ranging 0.71–0.95. The model overpredicted the risk for MI, blindness and death (Predicted/Observed events (P/O: 1.32–2.31)), and underpredicted the risk of IHD (P/O: 0.5). In patients with a low baseline risk, overpredictions were even more pronounced. OM2 performed well in predicting renal failure and ulcer risk in patients with a low risk but predicted well the risk of death, stroke, CHF, and amputation in patients with an intermediate risk. Conclusion OM2 demonstrated good to moderate discrimination capability for predicting diabetes complications and mortality risks in Israeli diabetes population. The prediction performance differed between patients with different baseline risks.