Thrombolysis and bridging therapy in patients with acute ischaemic stroke and Covid-19.

BACKGROUND AND PURPOSE: Comorbidity of acute ischaemic stroke with Covid-19 is a challenging condition, potentially influencing the decision of whether to administer intravenous thrombolysis (IVT). We aimed to assess the 1-month outcome in ischaemic stroke patients with Covid-19 infection who received IVT alone or before thrombectomy (bridging therapy). METHODS: As a collaboration initiative promoted by the Italian Stroke Organization, all Italian stroke units (n = 190) were contacted and invited to participate in data collection on stroke patients with Covid-19 who received IVT. RESULTS: Seventy-five invited centers agreed to participate. Thirty patients received IVT alone and 17 received bridging therapy between 21 February 2020 and 30 April 2020 in 20 centers (n = 18, Northern Italy; n = 2, Central Italy). At 1 month, 14 (30.4%) patients died and 20 (62.5%) survivors had a modified Rankin Scale (mRS) score of 3 to 5. At 24 to 36 hours, asymptomatic intracerebral hemorrhage (ICH) was reported in eight (17.4%) patients and symptomatic ICH (sICH) in two (4.3%) patients. Causes of death were severe ischaemic stroke (n = 8), a new ischaemic stroke (n = 2), acute respiratory failure (n = 1), acute renal failure (n = 1), acute myocardial infarction (n = 1), and endocarditis (n = 1). In survivors with a 1-month mRS score of 3 to 5, baseline glucose level was higher, whereas endovascular procedure time in cases of bridging therapy was longer. Baseline National Institutes of Health Stroke Scale glucose and creatinine levels were higher in patients who died. CONCLUSIONS: Intravenous thrombolysis for patients with stroke and Covid-19 was not a rare event in the most affected areas by pandemic, and rates of 1-month unfavorable outcomes were high compared to previous data from the pre-Covid-19 literature. However, risk of sICH was not increased.

Strictureplasty for Crohn's disease of the small bowel in the biologic era: long-term outcomes and risk factors for recurrence.

BACKGROUND: The number of indications for strictureplasty for Crohn's disease has been greatly reduced since the widespread use of biologics, although the risk of intestinal failure remains. The aim of the study was to analyze the outcomes of strictureplasty and to identify risk factors for site-specific recurrence in the era of biologics. METHODS: Consecutive patients treated with strictureplasty for Crohn's disease between 2002 and 2018 were retrospectively included. Univariate analysis was carried out. Risk factors for recurrence were identified through a multilevel logistic regression analysis. RESULTS: Two hundred sixty-six patients were included in the study ( 171 males, median age 39.5 years, range 18-76 years). The majority of the 718 strictures requiring surgery in these patients were located in the ileum (61%), treated with conventional strictureplasty (89.6%) and required an additional resection (73.7%). Median follow-up time and time to recurrence were 96 months and 62.5 months respectively. The site-specific recurrence rate was 12.2% at 5 years and 25.7% at 10 years. Smoking was associated with a higher risk of recurrence in patients with milder disease. The 10-year recurrence rate was significantly higher for strictureplasties performed in the terminal ileum (30.9%, p = 0.0019) as compared to the ileum (21.8%) and the jejunum (8.4%). Multilevel logistic regression analysis showed that postoperative exposure to biologics (OR 4.74, p 0.001), nonconventional strictureplasty (OR 3.57, p 0.008) and a strictureplasty performed on a previous anastomosis (OR 13.58, p 0.002) were associated with site-specific recurrence. CONCLUSIONS: Strictureplasty is associated with optimal long-term outcomes in the biologic era and should be performed when feasible, to reduce the risk of intestinal failure in Crohn's disease patients.

Validation of a model-based inverse kinematics approach based on wearable inertial sensors.

Wearable inertial measurement units (IMUs) are a promising solution to human motion estimation. Using IMUs 3D orientations, a model-driven inverse kinematics methodology to estimate joint angles is presented. Estimated joint angles were validated against encoder-measured kinematics (robot) and against marker-based kinematics (passive mechanism). Results are promising, with RMS angular errors respectively lower than 3 and 6 deg over a minimum range of motion of 50 deg (robot) and 160 deg (passive mechanism). Moreover, a noise robustness analysis revealed that the model-driven approach reduces the effects of experimental noises, making the proposed technique particularly suitable for application in human motion analysis.

Real-time inverse kinematics and inverse dynamics for lower limb applications using OpenSim.

Real-time estimation of joint angles and moments can be used for rapid evaluation in clinical, sport, and rehabilitation contexts. However, real-time calculation of kinematics and kinetics is currently based on approximate solutions or generic anatomical models. We present a real-time system based on OpenSim solving inverse kinematics and dynamics without simplifications at 2000 frame per seconds with less than 31.5 ms of delay. We describe the software architecture, sensitivity analyses to minimise delays and errors, and compare offline and real-time results. This system has the potential to strongly impact current rehabilitation practices enabling the use of personalised musculoskeletal models in real-time.

Predictive outcome indexes in neonatal Congenital Diaphragmatic Hernia.

OBJECTIVE: We examined the reliability of the main prenatal and postnatal prognosis-related indexes that can be used to evaluate congenital diaphragmatic hernia (CDH) outcome. METHODS: Seventy-seven neonates with CDH were analyzed according to CDH prognosis-related factors, divided into prenatal findings, postnatal clinical values and postnatal predictive outcome scores applied at birth and within the first 12-24 h. The data are compared between two groups: survivors and non-survivors. RESULTS: During prenatal age, major associated anomalies, intrathoracic stomach, diagnosis prior to 25 weeks of gestational age and lung-to-head ratio < 0.6 were statistically significant, demonstrating their greater incidence in non-survivors. The majority of postnatal values at PICU admission were found to be reliable in identifying the CDH outcome: paO2/FiO2, oxygenation index, alveolar-arterial-O2 gradient, arterial-alveolar-O2 tension ratio, pH, mean blood pressure, body temperature. All the postnatal predictive outcome scores (Apgar 1' and 5', CDH-Study-Group equation, Score for Neonatal-Acute-Physiology II, SNAP-Perinatal-Extension II, Pediatric Risk of Mortality III and Wilford-Hall/Santa-Rosa formula) were statistically significant with more favorable values for prognosis in the survivors group. CONCLUSION: The chances of predicting CDH outcome are fairly high. During prenatal age, only a few findings may be obtained. Conversely, many postnatal indexes and scores can reliably predict such outcome.

Tumours of the skin adnexa: a case series with focus on multiple segmental forms.

OBJECTIVE: Skin adnexal tumours (SAT) as a whole are rare tumours, and most of our current knowledge on SAT is from single case reports or small series focused on single histotypes. The purpose of this paper is to review a series of benign and malignant SAT diagnosed in a 20-year period. METHODS: All consecutive cases of SAT diagnosed between January 1992 and Dicember 2011 were retrieved. All slides were reviewed and diagnosed according to currently accepted criteria. RESULTS: 281 consecutive cases of SAT were found. The majority of cases (94.3%) were benign, the most frequent histotypes were eccrine spiradenoma, hidrocystoma, eccrine poroma, syringoma, sebaceous adenoma and trichofolliculoma. Benign SAT affected adult males more frequently (M/F = 153/112) (mean age 59 years). Recurrences were rare (2/265). Three cases of multiple segmental spiroadenoma were observed. Malignant SAT consituted only 5.7% of all cases comprising sebaceous carcinoma, extramammary Paget disease and apocrine carcinoma. There was a slight female predilection (M/F = 7/9) (mean age 72 years), although patients were older than those affected by benign SAT. All neoplasms were small and no recurrences were recorded. CONCLUSION: SAT are rare and most frequently benign. Correct diagnosis and complete surgical removal are important.

Neonatal congenital diaphragmatic hernia: respiratory and blood-gas derived indices in choosing surgical timing.

BACKGROUND: Congenital diaphragmatic hernia (CDH) still has a high mortality despite advanced assistance techniques. The aim of this study is to verify the validity of five respiratory and blood-gas-derived indices in defining presurgical stabilization: the oxygenation index (OI), the alveolar-arterial O(2) gradient (A-aDO(2)), the arterial-alveolar O(2) tension ratio (a/AO(2)), the arterial pH and the PaCO(2). METHODS: The study involved 73 neonates with CDH where the accuracy of stabilization was assessed through the survival percentage and the contemporary behaviour of mean arterial pressure (MAP), ductal shunting, urine output and lactate levels. The trend of the indices was compared in two groups (stable/fit for surgery vs unstable/unfit for surgery) at five times (PICU admission, 6, 12, 24 hours after admission, assessment of clinical stabilization). RESULTS: Fifty-five neonates were defined stabilized on the basis of the indices and underwent surgery with a 100% survival rate; 18 patients died before surgery, having never achieved clinical stabilization. MAP, ductal shunting, urine output and lactate levels were normal in the stabilized patients and altered in the non stabilized. Of the five parameters considered, all three oxygenation-linked indices (OI, A-aDO(2), a/AO(2)) are very powerful, whereas pH and PaCO(2) appears valid but more tardive. Their progressive improvement (OI<10, A-aDO(2)<250 mmHg, a/AO(2)>0.50, PaCO(2)<55 mmHg, pH>7.35) defined presurgical stabilization, thus allowing CDH surgical correction. CONCLUSION: The study confirms the validity of these indices as a guide to the treatment of neonates with CDH, showing a good reliability in identifying presurgical stabilization.

Densitometric CT evaluation of acute and chronic thromboembolic filling defects of the pulmonary arteries before and after contrast injection.

PURPOSE: The aim of this study was to assess the baseline computed tomography (CT) attenuation of acute and chronic pulmonary thromboemboli, their contrast enhancement (CE), correlation with haematocrit (Ht) levels and the presence of hypertrophic bronchial arteries. MATERIALS AND METHODS: From January 2006 to October 2009, we measured the baseline and postcontrast attenuation values of acute pulmonary thrombi emboli on CT angiograms of 86 patients with acute pulmonary embolism (PE) and those of chronic thrombi in 29 patients with pulmonary hypertension of various origins. The attenuation of acute thrombi was correlated with Ht and CE of chronic thrombi with the presence of hypertrophic bronchial arteries. RESULTS: Acute emboli had a mean baseline attenuation of 54.9 Hounsfield units (HU) and showed no CE. The attenuation of acute thrombi was not dependent on Ht. Chronic thrombi had a mean baseline attenuation of 33.8 HU, and 54% of thrombi showed significant CE. In 57% of cases, a collateral circulation had developed. In 76.5% of cases, CE and hypertrophic bronchial arteries coexisted (p=0.026). Neither thrombotic CE nor bronchial artery hypertrophy predominated in any one of the diseases associated with chronic thrombosis. CONCLUSIONS: Before contrast administration, acute emboli coare prevalently hyperattenuating and therefore more conspicuous. Only chronic thrombi exhibit CE, and CE is significantly associated with the development of collateral circulation, which may be involved in the process of thrombotic recanalisation.

SPARTACUS: underdiagnosis of chronic daily headache in primary care.

Despite the burden of chronic daily headache (CDH), general practitioners' (GPs) ability to recognize it is unknown. This work is a sub-study of a population-based study investigating GPs' knowledge on their CDH patients. Patients diagnosed with CDH through the screening questionnaire were interviewed by their GPs who indicated if subjects were known as patients suffering from CDH with medication overuse (MO), CDH without MO, episodic headache (EH) or non-headache sufferers. Our study showed that 64.37 % of CDH sufferers are misdiagnosed by their GPs. However, overusers are better known to GPs.

Application of a new pulmonary artery obstruction score in the prognostic evaluation of acute pulmonary embolism: comparison with clinical and haemodynamic parameters.

PURPOSE: Evaluation of computed tomography (CT) pulmonary angiography parameters revealing pulmonary embolism (PE) severity with particular attention to pulmonary obstruction indexes. Comparison with clinical and hemodynamic data and determination of predictive role in the development of chronic pulmonary heart disease. MATERIALS AND METHODS: This retrospective study analyzes 45 not consecutive patients from November 2007 to December 2008 with CT angiography diagnosis of acute PE. Included in the study are patients at the first documented episode of acute PE, with 6 month follow-up. Patients with severe pre-existent cardiopulmonary pathology or neoplastic diseases were excluded from the study. CT angiography evaluated right ventricular (RV)/left ventricular (LV) ratio, obstruction index according to Qanadli and Total Clot Burden (Ghanima score). PE indexes were compared with Troponin I measurement and echocardiography result; at last hospitalization and intensive care time were reported. RESULTS: A significant association was found between Ghanima and Qanadli score: the two indexes are equivalent in quantification of pulmonary arterial obstruction (p<0.001). Among others CT parameters, the new Ghanima score evidenced the best accuracy to detect patients evolving to chronic pulmonary heart disease (76%). This value is higher than that of echocardiography (71%). Troponins showed highest accuracy (82%). CONCLUSIONS: Ghanima score can be used in emergency CT angiography diagnosis as prognostic marker for a quickly risk stratification of pulmonary heart disease or death in patients with acute PE. This approach allows to obtain, with just one test, both the diagnosis and a rather accurate acute PE risk stratification.

Changes in exercise capacity induced by heart transplantation: prognostic and therapeutic implications.

Survival and exercise performance are key targets of heart transplantation (HT). We designed this study to help in identifying (1) patients with chronic heart failure (CHF) at risk of poor exercise capacity after HT and (2) HT recipients presenting risk factors modifiable with exercise showing a potential impact on outcome. We enrolled 49 HT recipients (age 52 ± 12 years, 84% males) who underwent a cardiopulmonary exercise test before (9 ± 6 months) and after (20 ± 14 months) HT. In the CHF phase, lower peak oxygen consumption (VO(2) ) (odds ratio 0.69, P=0.017) independently predicted peak VO(2) improvement after HT. In the post-HT phase, body mass index (BMI) [adjusted hazard ratio (HR) 1.16, P=0.034] and VE (ventilation)/VCO(2) (carbon dioxide production) slope (adjusted HR 1.07, P=0.031) independently predicted mortality. In conclusion, CHF patients with only a moderate impairment of peak VO(2) are at a risk of failing to achieve a significant improvement of exercise performance after HT. In the post-HT phase, a BMI≥28 and/or a VE/VCO(2) slope ≥47 represent risk factors for death, which are potentially modifiable with exercise. Prospective randomized studies are needed to analyze the effects of training on functional capacity and outcome in the different subsets of HT recipients.

Is there a prognostic role for C-reactive protein in ischemic stroke?

OBJECTIVES: We investigated the relationship between C-reactive protein (CRP)-values in the acute phase of stroke and the risk of further fatal and non-fatal ischemic events. MATERIALS AND METHODS: We analysed 462 consecutive incident ischemic strokes. Patients were divided into two subgroups on the basis of a CRP cut-off level of 9 mg/l. Primary end points were any new vascular fatal and non-fatal event recorded during the follow-up period. RESULTS: During a follow-up of 2.27 years, in 132 patients occurred a primary end point. Patients with CRP values > or = 9 mg/l had more frequently primary end point. The hazard ratio (HR) for cardiovascular events was 3.59; 1.93 for cerebrovascular events; 7.43 for vascular deaths and 5.78 for death from any cause. Cox proportional hazard multivariate analysis identified CRP values > or = 9 (HR = 4.19, 95% CI: 1.85-9.50, P = 0.001), the lack of secondary prevention therapy at discharge (HR = 4.35, 95% CI: 1.87-10.1, P = 0.001), age >70 years (HR = 3.09, 95% CI: 1.04-9.24, P = 0.04) as independent predictors of fatal events. CONCLUSIONS: CRP levels > or = 9 mg/l, evaluated in incident ischemic stroke within 24 h, predict a higher risk of further ischemic events and mortality.

Five-year survival after first-ever ischaemic stroke is worse in total anterior circulation infarcts: the SINPAC cohort.

BACKGROUND: Few studies have addressed predictors of long-term mortality after first-ever ischaemic stroke. METHODS: We prospectively collected data on 361 consecutive patients admitted to 18 neurology departments in Italy for a first-ever ischaemic stroke in 1999, categorized according to the Oxfordshire Community Stroke Project (OCSP) classification. Age, gender, risk factors, previous vascular disease, in-hospital complications, stroke severity, functional status, therapy and living place at admission, discharge and after 6 months were recorded. Follow-up was available for 97% patients at 5 years. RESULTS: Survival probability was 91% (95% CI = 88-94) at 1 month, 84% (80-88) at 6 months and 64% (58-69) at 5 years. Mortality was higher for the TACI (total anterior circulation infarct) group compared to the other categories (p < 0.0001). Hazard ratios for 5-year mortality in the final model were: 5.4 for age >or=65 years (p < 0.0001), 2.8 for TACI (p < 0.0001), 2.7 for previous vascular disease (p < 0.01) and 1.9 for cardio-embolic risk according to the TOAST risk stratification (p < 0.05). CONCLUSIONS: Our study extends the prognostic value of the OCSP classification to 5-year survival.

Melanoma epidemic across the millennium: time trends of cutaneous melanoma in Emilia-Romagna (Italy) from 1997 to 2004.

BACKGROUND: After a rapid increase in malignant melanoma (MM) incidence in the last decades, trends of the melanoma epidemic in the recent years seemed not homogeneous. OBJECTIVE: This study aimed at the monitoring of some epidemiological data referring to melanoma in a region of the Northern Italy during the past 8-year period. METHODS: All cases of melanoma, including also in situ lesions, diagnosed in Emilia-Romagna and San Marino State, with the exclusion of Cesena province, from 1997 to 2004 were recorded and the incidence of melanoma, adjusted for the European standard population by the direct method, was calculated. RESULTS: Mean standardized incidence was 9.7 for invasive MMs and 11.9, considering also in situ ones, showing an ascending trend with an increment of 3.3 new incident cases in 2004 compared with 1997. No differences in age distribution, gender and site were reported. Concerning tumour thickness, although a general ascending trend in all subtypes, only thin melanoma incidence significantly increased over the study period. CONCLUSIONS: Contrary to data from Northern European countries, melanoma incidence still showed an ascending trend in the Italian population of Emilia Romagna.

Ursodeoxycholic acid improves gastrointestinal motility defects in gallstone patients.

AIM: To simultaneously evaluate the presence of defects in gallbladder and gastric emptying, as well as in intestinal transit in gallstone patients (GS) and the effect of chronic ursodeoxycholic acid (UDCA) administration on these parameters and on serum bile acids and clinical outcome in GS and controls (CTR). METHODS: After a standard liquid test meal, gallbla-dder and gastric emptying (by ultrasound), oroileal transit time (OITT) (by an immunoenzymatic technique) and serum bile acids (by HPLC) were evaluated before and after 3 mo of UDCA (12 mg/kg bw/d) or placebo administration in 10 symptomatic GS and 10 matched healthy CTR. RESULTS: OITT was longer in GS than in CTR (P < 0.0001); UDCA significantly reduced OITT in GS (P < 0.0001), but not in CTR. GS had longer gastric half-emptying time (t(1/2)) than CTR (P < 0.0044) at baseline; after UDCA, t(1/2) significantly decreased (P < 0.006) in GS but not in CTR. Placebo administration had no effect on gastric emptying and intestinal transit in both GS and CTR. CONCLUSION: The gallstone patient has simultaneous multiple impairments of gallbladder and gastric emptying, as well as of intestinal transit. UDCA administration restores these defects in GS, without any effect in CTR. These results confirm the pathogenetic role of gastrointestinal motility in gallstone disease and suggest an additional mechanism of action for UDCA in reducing bile cholesterol supersaturation.

A statistical model predicting high hepatocyte proliferation index and the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

BACKGROUND: Incidence of hepatocellular carcinoma in hepatitis C virus-related cirrhosis is 4% per year. Although cost-effective, current screening could be improved. AIM: To develop a statistical model including non-invasive parameters able to identify patients at high risk of developing hepatocellular carcinoma. METHODS: One hundred and fifty-eight patients (73F:85M) with compensated chronic hepatitis C virus liver disease underwent evaluation, including argyrophilic nucleolar organizer regions proliferation index, and were followed up for 56.18 +/- 1.44 months. RESULTS: Fifty-six patients had chronic hepatitis without cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (< or =25%), 65 had hepatitis C virus-related cirrhosis and low argyrophilic nucleolar organizer regions proliferation index and 37 had hepatitis C virus-related cirrhosis and high argyrophilic nucleolar organizer regions proliferation index (>25%). Groups were similar for gender and viral genotype distribution. None of the patients with chronic hepatitis without cirrhosis developed hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar organizer regions proliferation index and 30.6% of high argyrophilic nucleolar organizer regions proliferation index (P = 0.002). By multivariable logistic regression analysis, the following parameters were independently associated with hepatocellular carcinoma development and used for the development of the statistical model: platelets (OR 0.98), gamma-globulins (OR 0.111), alanine aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR 1.0) and ultrasonographic pattern (coarse OR 2.9, coarse nodular OR 10.12). The statistical model properly allocated 95.9% of patients with low argyrophilic nucleolar organizer regions proliferation index and 72.2% of patients with high argyrophilic nucleolar organizer regions proliferation index. CONCLUSIONS: The model, to be validated in large prospective studies, may help tailoring screening according to the risk of hepatocellular carcinoma development.

Determination of crystallinity and crystal structure of Hylamer polyethylene after in vivo wear.

Hylamer polyethylene is a crystalline form of polyethylene of 70% crystallinity whereas conventional polyethylene (PE) has 50% crystallinity. Crystallinity is the percentage by weight of the crystalline phase present in the whole polymer, which comprises both amorphous and crystalline phases. Clinical experience has shown that Hylamer components used in joint prostheses, if sterilized by gamma rays in the presence of oxygen, are easily affected by wear, which leads to osteolysis. The authors have analyzed the crystallinity of polyethylene liners removed from seven patients who had received Hylamer polyethylene implants sterilized by gamma rays in air and had suffered prosthetic loosening, using Raman spectroscopy coupled with partial least squares (PLS) analysis. The results have been compared to those of two controls who had received Hylamer polyethylene implants sterilized by gamma irradiation in a nitrogen atmosphere. The crystal structure of wear particles released into the tissues from the Hylamer liners sterilized by gamma rays in air is also studied. The materials undergoing two different types of sterilization methods show different crystallinity values (71.50 vs. 69.43), but the crystallinity do not change according to wear (worn and unworn liner region). Both monoclinic and orthorhombic phases are present in the liner, while in wear debris prevalently monoclinic crystals are found in both types of sterilized liners. Different crystallinity rates can explain different wear rates observed in vivo.

Isolation and characterization of wear debris generated in patients wearing polyethylene Hylamer inserts, gamma irradiated in air.

Hylamer polyethylene was used in the early 1990s to make hip-joint components. Clinical experience has shown that these components, if sterilized by gamma rays in the presence of oxygen, are easily affected by wear, which then leads to osteolysis. The authors analyzed polyethylene wear particles in seven patients who had received Hylamer polyethylene implants sterilized by gamma rays in air and had suffered prosthetic loosening. The results were compared to those of six controls, who had received traditional polyethylene implants, sterilized by the same method. The frequency distribution of globular and fibrillar particles was similar in both groups (38.5% in Hylamer, 45.2% in controls). The globular particles in the Hylamer samples had a mean area of 0.12 microm2, which was significantly lesser than that of the controls (0.30 microm2). The width of fibrillar particles in the Hylamer samples was significantly lesser than that of the controls. Therefore, the two materials, despite undergoing the same type of sterilization, produced different types of wear, due to their different properties. In conclusion, the difference in the morphology of Hylamer polyethylene wear particles in comparison with PCA might have caused a more intensive biological response, early and massive osteolysis, and therefore, early loosening.