Correlation between serum anti-TSH receptor autoantibodies (TRAbs) and the clinical feature of Graves' orbitopathy.

BACKGROUND: Graves' orbitopathy (GO) is the most common extrathyroidal manifestation of Graves' disease (GD). Several studies support the involvement of TSH receptor autoantibodies (TRAbs) in the pathogenesis of GO, and a correlation between GO features and TRAbs has been reported, but not confirmed by all studies. Thus, we conducted a cross-sectional investigation to determine whether there is a correlation between TRAbs and the clinical features of GO in an initial phase of the eye disease. METHODS: Ninety consecutive patients with untreated GO (67 women and 23 men, age 48.9 ± 12.6 years) were included. Patients who had received treatments other than anti-thyroid drugs for hyperthyroidism or lubricants for GO were excluded. All patients underwent an endocrinological and ophthalmological evaluation, the latter including exophthalmometry, measurement of eyelid width, clinical activity score (CAS), visual acuity, assessment of diplopia, and NOSPECS score. TRAb levels were measured by a third-generation competitive immunoassay. RESULTS: There was a statistically significant, direct correlation between serum TRAb levels and CAS by linear regression analysis (R = 0.278, P = 0.007). The correlation was confirmed by a multiple regression analysis (R = 0.285; P = 0.006) including age and FT3 levels, which also correlated with CAS. There were no relationships between TRAbs and exophthalmometry, eyelid aperture, degree of diplopia, visual acuity, and NOSPECS score. CONCLUSIONS: The levels of TRAb in subjects with a recent-onset, untreated GO are directly correlated with the clinical activity of the disease, confirming a possible role of these antibodies in the pathogenesis of GO.

Putative protective role of autoantibodies against the insulin-like growth factor-1 receptor in Graves' Disease: results of a pilot study.

BACKGROUND: The insulin-like growth factor-1 receptor (IGF-1R) is a key element in the pathogenesis of Graves' Orbitopathy (GO), but the role of IGF-1R autoantibodies (IGF-1RAbs) has not been established. METHODS: We designed a cross-sectional investigation to measure IGF-1RAbs in patients with Graves' disease (GD), with or without GO, who underwent radioiodine therapy followed by glucocorticoids (GC). Twenty-nine patients were included, 15 of which with GO. Patients were evaluated at baseline and three and 6 months after radioiodine. The primary objective was the prevalence of positive tests for IGF-1RAbs. The secondary objectives were: (1) IGF-1RAbs concentrations and their variations; (2) relationship between IGF-1RAbs and the features of GO; (3) relationship between IGF-1RAbs and anti-thyroid autoantibodies. RESULTS: IGF-1RAbs above the cut-off value were found only in one patient with GD without GO. IGF-1RAb levels were greater in patients with GD without GO, at baseline (P < 0.0001), and after three (P < 0.0001) and six (P = 0.0001) months. No correlations were observed between IGF-1RAbs and the features of GO, nor between IGF-1RAbs and anti-thyroglobulin or anti-thyroperoxidase autoantibodies. There was an inverse correlation between anti-TSH receptor autoantibodies (TRAbs) and IGF-1RAb levels in GD patients with GO at 6 months (P = 0.03). CONCLUSIONS: IGF-1RAbs appear to be greater in patients with GD without GO compared with those with GO, suggesting a putative protective role of IGF-1RAbs on the development of GO, in line with the beneficial effects of Teprotumumab on GO. The inverse correlation between IGF-1RAbs and TRAbs 6 months after radioiodine may reflect antigen spreading and/or GC treatment.

Clinical outcomes of stapled transanal rectal resection for obstructed defaecation syndrome at 10-year follow-up.

AIM: The long-term efficacy of stapled transanal rectal resection (STARR) for surgical management of obstructed defaecation syndrome (ODS) has not been evaluated. Therefore, we investigated the long-term efficacy (> 10 years) of STARR for treatment of ODS related to rectocele or rectal intussusception and the factors that predict treatment outcome. METHOD: This study was a retrospective cohort analysis conducted on prospectively collected data. Seventy-four consecutive patients who underwent STARR for ODS between January 2005 and December 2006 in two Italian hospitals were included. RESULTS: Seventy-four patients [66 women; median age 61 (29-77) years] underwent STARR for ODS. No serious postoperative complications were recorded. Ten years postoperatively, 60 (81%) patients completed the expected follow-up. Twenty-three patients (38%) reported persistent perineal pain and 13 (22%) experienced the urge to defaecate. ODS symptoms recurred in 24 (40%) patients after 10 years. At the 10-year follow-up, 35% of patients were very satisfied and 28% would recommend STARR and undergo the same procedure again if necessary. In contrast, 21% of patients would not select STARR again. Previous uro-gynaecological or rectal surgery and high constipation scores were identified as risk factors for recurrence. CONCLUSIONS: Stapled transanal rectal resection significantly improves the symptoms of ODS in the short term. In the long term STARR is less effective, however.

"The Penitent Magdalene": Jusepe de Ribera (1591-1652).

Jusepe or Jòse de Ribera (1591-1652), known as Lo Spagnoletto ("the Little Spaniard"), has been a leading painter of the Spanish Baroque movement. In one of the portraits, de Ribera represented a scene in which the Magdalene shows a swelling at the base of the neck suggestive of a thyroid nodule.

The combination of baseline magnetic resonance perfusion-weighted imaging-derived tissue volume with severely prolonged arterial-tissue delay and diffusion-weighted imaging lesion volume is predictive of MCA-M1 recanalization in patients treated with endovascular thrombectomy.

INTRODUCTION: Indices of collateral flow deficit derived from MR perfusion imaging that are predictive of MCA-M1 recanalization after intravenous thrombolysis have been recently reported. Our objective was to test the performance of such MRI-derived collateral flow indices for prediction of recanalization after endovascular thrombectomy. METHODS: Fifty-seven patients with MCA-M1 occlusion evaluated with multimodal MRI prior to thrombectomy were included. Bayesian processing allowed quantification of collateral perfusion indices like the volume of tissue with severely prolonged arterial-tissue delay (>6 s) (VolATD6). Baseline DWI lesion volume was also measured. Correlations with angiographic collateral flow grading and post-thrombectomy recanalization were assessed. RESULTS: VolATD6 < 27 ml or DWI lesion volume <15 ml provide the most accurate diagnosis of excellent collateral supply (p < 0.0001). The combination of VolATD6 > 27 ml and DWI lesion volume >15 ml significantly discriminates recanalizers versus nonrecanalizers (whole cohort, p = 0.032; MERCI cohort (n = 50), p = 0.024). When both criteria are positive, 76.2 % of the patients treated with the MERCI retriever do not fully recanalize (p = 0.024). In multivariate analysis, the aforementioned combined criterion and the angiographic collateral grade are the only independent predictors of recanalization with the MERCI retriever (p = 0.015 and 0.029, respectively). CONCLUSION: Bayesian arterial-tissue delay maps and DWI maps provide a non-invasive assessment of the degree of collateral flow and a combined index that is predictive of MCA-M1 recanalization after endovascular thrombectomy. Further studies are needed to evaluate the accuracy of this index in patients treated with novel stent retriever devices.

Comparison of Mepivacaine 2% and Isobaric Bupivacaine 0.5% Spinal Anesthetics for Total Knee Arthroplasty.

Spinal anesthesia is an option for patients during total knee arthroplasty (TKA) procedures. Spinal anesthesia can offer advantages and disadvantages to the patient's experience and outcomes. We conducted an evidence-based, quality improvement project comparing mepivacaine 2% and isobaric bupivacaine 0.5% and retrospectively assessed specific intraoperative and postoperative outcomes that were of interest to the staff at the hospital where the project was completed. Primary outcome measures of interest included intraoperative heart rate, blood pressure, vasopressor use, fluid resuscitation, postoperative pain scores, use of opioid analgesic medications, and time to ambulation after administration of the spinal anesthetic. Compared with patients receiving isobaric bupivacaine 0.5% (n = 30), patients receiving mepivacaine 2% (n = 30) had greater intraoperative hemodynamic stability (defined as heart rate and blood pressure maintained within 20% of baseline values) during the first 30 minutes after anesthetic administration (P < .05 for multiple time points). They also required less opioid medication for postoperative pain management (25 vs 50 mcg fentanyl) and were able to ambulate sooner after the procedure (mean [standard deviation], 452.2 [218.5] vs 681.0 [476.6] minutes; P = .006). In conclusion, mepivacaine 2% was the higher-performing local primary spinal anesthetic for patients undergoing TKA.

Circulating lipoprotein-associated phospholipase A2 in high-grade carotid stenosis: a new biomarker for predicting unstable plaque.

OBJECTIVE: To test plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with high-grade carotid stenosis according to plaque histology. METHODS: This cross-sectional single-centre study included patients with ≥70% North American Symptomatic Carotid Endarterectomy Trial (NASCET) carotid stenosis, who were treated surgically. Serum Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) were determined on the day of surgery. Histopathological analysis classified carotid plaque as stable or unstable, according to AHA classification. RESULTS: Of the 42 patients (mean age 70.4 ± 10.5 years; 67% men), neurological symptoms were present in 16 (38%). Unstable plaques were found in 23 (55%). Median plasma level of Lp-PLA2 was significantly higher in patients with unstable plaque compared to those with stable plaque (222.4 (174.9-437.5) interquartile range (IQR) 63.5 vs. 211.1 (174.9-270.6) IQR 37.2 ng ml(-1); p = 0.02). Moreover, median Lp-PLA2 level were higher in asymptomatic patients with unstable plaque (226.8 ng ml(-1) (174.9-437.5) IQR 76.8) vs. stable plaque (206.9 ng ml(-1) (174.9-270.6) IQR 33.7; p = 0.16). Logistic regression showed that only the neurological symptoms (OR = 30.9 (3.7-244.6); p < 0.001) and the plasma Lp-PLA2 level (OR = 1.7 (1.1-12.3); p = 0.03) were independently associated with unstable carotid plaque as defined by histology. CONCLUSIONS: This study showed that circulating Lp-PLA2 was increased in patients with high-grade carotid stenosis and unstable plaque. Lp-PLA2 may be a relevant biomarker to guide for invasive therapy in asymptomatic patients with carotid artery disease.

Treatment of traumatic scars using fat grafts mixed with platelet-rich plasma, and resurfacing of skin with the 1540 nm nonablative laser.

BACKGROUND: Many treatments have been proposed for cosmetic or functional improvement of scars. It is known that fat grafts and laser treatment can have beneficial effects on remodelling of scar tissue, and platelet-rich plasma (PRP) can be effective during the wound-healing process. We hypothesized that these combined treatments would be effective in improving traumatic scars, with minimal recovery time and few side-effects. AIM: The purpose of this study was to compare and evaluate the efficacy of three procedures for the treatment of traumatic scars. METHODS: We treated 60 patients affected by traumatic scars involving different body parts. All patients were randomly allocated to one of three groups (20 patients per group) and underwent one of three different procedures. Group A was treated with fat grafts mixed with PRP, group B was treated with nonablative laser, and group C was treated with both procedures. RESULTS: Comparison of the groups showed that PRP produced a significant difference in these treatments. The most effective scar treatment was the combination of fat grafts mixed with PRP plus nonablative laser resurfacing (group C). This treatment resulted in group C having an increase of 22% in wound healing compared with group A, and an increase of 11% compared with group B. CONCLUSIONS: The data confirm the efficacy of all three treatments, with the most effective scar treatment being the fat grafts mixed with PRP, followed by skin resurfacing with nonablative laser. This combined treatment appeared to be safe and effective for scar treatment. Further studies are needed to explore the potential use of this combined treatment.

A case of psoriasis with secondary amyloidosis, associated symbrachydactyly of the hand and a transverse deficiency of the foot.

Secondary amyloidosis is associated with a variety of chronic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, familial Mediterranean fever, osteomyelitis, inflammatory bowel diseases and infective or neoplastic conditions. Few cases of secondary amyloidosis complicating psoriasis have been reported. We describe a 58-year-old patient with secondary amyloidosis, psoriasis, an associated symbrachydactyly of the hand and a transverse deficiency of the foot. To the best of our knowledge, no case of this association has been previously reported.

Size assessment of breast lesions by means of a computer-aided detection (CAD) system for magnetic resonance mammography.

PURPOSE: The aim of this study was to investigate the efficacy of a dedicated software tool for automated volume measurement of breast lesions in contrast-enhanced (CE) magnetic resonance mammography (MRM). MATERIAL AND METHODS: The size of 52 breast lesions with a known histopathological diagnosis (three benign, 49 malignant) was automatically evaluated using different techniques. The volume of all lesions was measured automatically (AVM) from CE 3D MRM examinations by means of a computer-aided detection (CAD) system and compared with the size estimates based on maximum diameter measurement (MDM) on MRM, ultrasonography (US), mammography and histopathology. RESULTS: Compared with histopathology as the reference method, AVM understimated lesion size by 4% on average. This result was similar to MDM (3% understimation, not significantly different) but significantly better than US and mammographic lesion measurements (24% and 33% size underestimation, respectively). CONCLUSIONS: AVM is as accurate as MDM but faster. Both methods are more accurate for size assessment of breast lesions compared with US and mammography.

Advances in image enhancement for sarcoma surgery.

The recurrence rate of soft tissue and bone sarcomas strongly correlates to the status of the surgical margin after excision, yet excessive removal of tissue may lead to distinct, otherwise avoidable morbidity. Therefore, adequate margination of sarcomas both pre- and intra-operatively is a clinical necessity that has not yet fully been met. Current guidance for soft-tissue sarcomas recommends an ultrasound scan followed by magnetic resonance imaging (MRI). For bone sarcomas, two plane radiographs are required, followed similarly by an MRI scan. The introduction of more precise imaging modalities may reduce the morbidity associated with sarcoma surgery; the PET-CT and PET-MRI approaches in particular demonstrating high clinical efficacy. Despite advancements in the accuracy in pre-operative imaging, translation of an image to surgical margins is difficult, regularly resulting in wider resection margins than required. For soft tissue sarcomas there is currently no standard technique for image guided resections, while for bone sarcomas fluoroscopy may be used, however margins are not easily discernible during the surgical procedure. Near infra-red (NIR) fluorescence guided surgery offers an intra-operative modality through which complete tumour resection with adequate tumour-free margins may be achieved, while simultaneously minimising surgical morbidity. NIR imaging presents a potentially valuable adjunct to sarcoma surgery. Early reports indicate that it may be able to provide the surgeon with helpful information on anatomy, perfusion, lymphatic drainage, tumour margins and metastases. The use of NIR fluorochromes have also been demonstrated to be well tolerated by patients. However, prior to widespread implementation, studies related to cost-effectiveness and the development of protocols are essential. Nevertheless, NIR imaging may become ubiquitous in the future, carrying the potential to transform the surgical management of sarcoma.

Early carotid endarterectomy after intravenous thrombolysis for acute ischaemic stroke.

UNLABELLED: After intravenous thrombolysis (IVT) for acute ischaemic stroke (AIS), a severe cervical internal carotid artery (ICA) stenosis may remain and increase the risk of recurrent stroke. Carotid endarterectomy (CEA) has been shown to be effective in reducing the risk of stroke. However, it is not well known whether CEA can be performed safely after thrombolysis, and, if so, when. We report a prospective study of CEA for residual high-grade cervical ICA stenosis performed within 15 days after IVT for AIS. METHODS: All the patients had a brain magnetic resonance imaging (MRI) within 3h of the stroke onset. One day after IVT in neurovascular unit, computed tomography (CT) angiography was performed to assess the brain and the patency of cervical arteries. CEA was performed on neurologically stable patients after full cerebral artery re-canalisation. Blood pressure was controlled with particular caution before and after CEA. RESULTS: Between January 2005 and January 2008, we operated consecutively on 12 patients. Their median National Institutes of Health Stroke Scale (NIHSS) score was 12 (range: 5-21). Combined intracranial (ICA)-middle cerebral artery (MCA) occlusion was present in 58.3% of the patients. The median time between onset of symptoms until CEA was 8 days (range: 1-16 days). Stroke and death rate at 30 days was 8.3% (one nonfatal haemorrhagic stroke). At 90 days, nine patients had a Rankin score of 0-1, one had a score of 2 and two had a score of 3. CONCLUSION: In patients with residual cervical ICA stenosis after IVT, we achieved full patency of the occluded artery and good functional prognosis at 3 months in all cases. We advocate for an extremely close monitoring of the blood pressure in the pre-, peri- and post-operative course and a close collaboration between neurologist and surgeon to determine the best timing for CEA.

The criterion of proportionality in the activation of Left Ventricular Assist Device implants: the method of "four boxes" to analyze the pre-implant phase.

BACKGROUND: Life-saving technologies have completely changed the normal conception of medical treatments. Left Ventricular Assist Devices (LVAD) can prolong survival for patients who are not candidates for heart transplantation. In order to analyze the pre-implantation phase, which involves a shared-decision making process before activation of the device, attention should be paid to the criterion of "proportionality" in order to properly assess the risks and benefits of implantation. AIM: The aim of our analysis is to provide an useful tool for the assessment of LVAD proportionality during the physicians' decision making. METHODS: The method of the "four boxes", developed by Jonsen et al, was chosen to analyze the notion of proportionality and the other main ethical issues regarding LVAD activation in adult patients. RESULTS: Medical issues are not the sole factors, which influence the choice of implantation by patients. Indeed, patient preferences, his/her quality of life, and contextual features should be taken into consideration when proposing LVADs: these factors are as important as clinical issues where outcomes are concerned. CONCLUSIONS: In order to assess the proportionality of such a device, we present, discuss and examine, in the framework of the pre-implant phase, the content of each topic treated by the "four boxes method", that is, an essential tool for the assessment of the proportionality of the treatment for LVAD candidates.

Donation After Circulatory Death: When Withdrawing Life-Sustaining Treatments Is Ethically Acceptable.

The possibility to determine death based on cardiocirculatory criteria in controlled cases, namely when there is a request to withhold treatment-or, more frequently, withdraw it-specifically recalls the recent Italian law on advance treatment directives and leaves the following question unanswered: Under what conditions is the patient's request legally and ethically acceptable? We present three ethical proportionality criteria for supporting physicians' decision-making facing patients' requests of treatment withdrawal, namely: 1. irreversible pathology with an ominous and worsening prognosis; 2. within an evaluation considering both clinical data and the patient's history; and 3. facing burdens that are no longer bearable. We finally argue that reflection over controlled donor may be a model for giving medicine the chance to responsibly deal with broader end-of-life issues.