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Objective: The gastrointestinal tract (GIT) is the most commonly affected internal organ in systemic sclerosis (SSc). We sought to determine the prevalence and impact of GIT symptoms on survival and patient-reported outcomes., Methods: A total of 907 consecutive patients from the Australian Scleroderma Cohort Study who had prospectively completed the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 Questionnaire (UCLA GIT) between 2015 and 2021 were included. The associations between UCLA GIT scores and physical function (Scleroderma Health Assessment Questionnaire), quality of life (QoL; Short Form 36), mood (Patient-Reported Outcomes Measurement Information System [PROMIS] anxiety and depression domains), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score), and employment were investigated using multivariable population-averaged panel models using generalized estimating equations (GEEs). Kaplan-Meier curves and multivariable Cox proportional hazard regression models were used to evaluate survival according to total UCLA GIT scores., Results: GIT symptoms were reported in 87% of participants, with 46% to 52% reporting moderate to very severe symptoms of reflux, distension, diarrhea, and constipation. Higher total UCLA GIT scores were associated with worse QoL, physical function, fatigue, anxiety, and depression (P < 0.001). In the multivariable GEE analysis, moderate and severe to very severe total scores, reflux scores, and distension scores were associated with worse physical function, QoL, fatigue, anxiety, and depression compared to mild scores (P < 0.05). Patients with severe total scores and diarrhea scores were more likely to be unemployed compared to those with mild scores (P < 0.05). UCLA GIT total scores were not independently associated with death in our cohort., Conclusion: GIT manifestations are common in SSc and negatively impact QoL, physical function, and employment but are not directly associated with increased death., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The aim of this study was to determine the impact of season, temperature and humidity on the severity of Raynaud phenomenon (RP) in systemic sclerosis., Methods: Data from the Australian Scleroderma Cohort Study were used to assess associations of patient-reported worsened RP in the month preceding each study visit. Mean monthly weather data were obtained from the closest weather station to the patient's address. We evaluated the relationship between worsened RP and health-related quality of life (HRQoL) measured using the Short Form 36 instrument., Results: Among 1,972 patients with systemic sclerosis, RP was a near-universal finding, and worsened RP in the preceding month was reported in 26.7% of 9,175 visits. "Worsened RP" showed significant environmental variability. On multivariable analysis, worsened RP was associated with low mean maximum temperatures (odds ratio [OR] 0.91, 95% confidence interval [95% CI] 0.90-0.92, P < 0.001), high relative humidity (OR 1.05, 95% CI 1.04-1.05, P < 0.001) and lower mean daily evaporation (OR 0.77, 95% CI 0.73-0.81, P < 0.001). Worsened RP was strongly associated with telangiectasia, calcinosis, and digital ulceration, as well as demonstrating an association with anticentromere antibody and gastroesophageal reflux disease and a negative correlation with diffuse disease. Worsened RP was also strongly associated with worse HRQoL., Conclusion: Lower environmental temperature and higher relative humidity had significant associations with worsened RP in this systemic sclerosis cohort, suggesting an important role for dry warmth in managing this condition., (© 2024 American College of Rheumatology.)

Objective: Physician global assessments (PhyGAs) are variably applied in systemic sclerosis (SSc) clinical trials. The comparability of different PhyGA results is unknown. We sought to assess the comparability of results from three different PhyGA instruments simultaneously applied in the Australian Scleroderma Cohort Study (ASCS)., Methods: Using data from 1,965 ASCS participants, we assessed the correlation between results of three PhyGA assessments: (1) overall health, (2) activity, and (3) damage. We evaluated the concordance of change in each PhyGA between study visits. Ordered logistic regression analysis was used to evaluate the clinical associations of each PhyGA., Results: The absolute scores of each PhyGA were strongly correlated at individual study visits. Concordant changes of the PhyGA scores occurred between 50% of study visits. Only patient-reported breathlessness was associated with all three PhyGA scores (overall health: odds ratio [OR] 1.67, P < 0.01; activity: OR 1.44, P < 0.01; damage: OR 1.32, P < 0.01). Changes in physician-assessed activity scores were also associated with patient-reported worsening skin disease (OR 1.25, P = 0.03) and fecal incontinence (OR 1.23, P = 0.01), whereas damage scores were associated with respiratory disease (pulmonary arterial hypertension: OR 1.25, P = 0.03; chronic obstructive pulmonary disease: OR 1.37, P = 0.04), as well as skin scores (OR 1.02, P < 0.01) and fecal incontinence (OR 1.21, P = 0.02)., Conclusion: PhyGAs of overall health, activity, and damage are each associated with different SSc features, and changes in different PhyGA scores are discordant 50% of the time. Our findings suggest results of variably worded PhyGAs are not directly interchangeable and support the development of a standardized PhyGA., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Introduction: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that presents with a progressive movement disorder along with cognitive and psychiatric problems. It is caused by a Cytosine-adenin-guanine (CAG) expansion in exon 1 of the huntingtin gene which codes for mutant huntingtin (mHTT) that over time accumulates in cells, causing dysfunction and then death through new toxic gain-of-function mechanisms. Autophagy has been shown to be critical for the degradation of diverse intracytoplasmic aggregate-prone proteins that cause neurodegenerative disease, including mHTT. From a screen of a library enriched in approved drugs, felodipine was selected as the most suitable candidate showing strong autophagy-inducing effects in preclinical models of HD. We are, therefore, conducting a trial to assess the safety and tolerability of felodipine in people with early HD., Methods and Analysis: FELL-HD is a phase II, single-centre, open-label, dose-finding trial in people with early HD. 18 participants with early clinical features of the disease will be treated with felodipine for 58 weeks, with a further 4-week follow-up. The primary outcome measure is the number of adverse events attributable to felodipine. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life scales, as well as peripheral and central disease biomarkers assessed through brain MRI. Analysis of blood and cerebrospinal fluid will also be performed through an associated sample study, FELL HD-s., Ethics and Dissemination: The study was approved by the London-Brent Research Ethics Committee (reference 22/LO/0387) and has been accepted by the Medicines and Healthcare products Regulatory Agency for clinical trials authorisation (reference CTA 12854/0256/001-0001). A lay summary of the results of the trial will be uploaded to our research group website which is publicly accessible. A webinar or in-person open day, to present results of the trial to participants and our wider cohort of patients who attend our centre, will be held once the trial is completed. The results of the trial will also be published in scientific journals and presented at national and international conferences., Trial Registration Numbers: EudraCT-2021-000897-27, ISRCTN56240656., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: The study objective was to determine the event-free survival (EFS) of Australian patients with diffuse cutaneous systemic sclerosis (dcSSc) who met eligibility criteria for autologous stem cell transplant (ASCT) in previously published randomized controlled trials but were not treated with ASCT., Methods: Patients who met inclusion criteria for the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) and Scleroderma: Cyclophosphamide Or Transplantation (SCOT) trials were identified from the multicenter Australian Scleroderma Cohort Study (ASCS). EFS (survival without cardiac, renal, or pulmonary failure or death) at 4 years was assessed. ASCS patients who had already undergone transplantation were excluded from analysis., Results: Of the 492 patients with dcSSc in the ASCS, 56 met ASTIS inclusion criteria for ASCT (56 of 492 [11.4%]) and 30 met SCOT inclusion criteria (30 of 492 [6.1%]). An additional 11 patients met ASTIS or SCOT inclusion criteria, but they were excluded due to severe organ manifestations. EFS at 4 years in ASCS patients meeting ASTIS inclusion criteria was 83.3% and in ASCS patients meeting SCOT inclusion criteria was 81.2%. EFS at 4 years in ASCS patients who met ASTIS and SCOT inclusion but also exclusion criteria was 46.7% and 45.7%, respectively., Conclusion: ASCS patients meeting ASTIS and/or SCOT inclusion criteria who were not treated with ASCT have similar EFS at 4 years as patients receiving ASCT and better EFS than those receiving cyclophosphamide in the ASTIS and SCOT trials. This may reflect confounders unable to be controlled for, including survivor bias, but may also reflect improved standard of care for dcSSc over time., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Patients with pulmonary arterial hypertension (PAH) may be stratified as low, intermediate, or high risk of 1-year mortality. In 2022, the European Society of Cardiology (ESC) updated and simplified its risk stratification tool, based on three variables: World Health Organization functional class, serum N-terminal pro-brain type natriuretic peptide and six-minute walk distance, applied at follow-up visits, intended to guide therapy over time., Methods: We applied the 2022 ESC risk assessment tool at baseline and follow-up (within 2 years) to a multinational incident cohort of systemic sclerosis-associated PAH (SSc-PAH). Kaplan-Meier curves, Cox hazards regression, and accelerated failure time models were used to evaluate survival by risk score., Results: At baseline (n = 260), the majority of SSc-PAH (72.2%) were graded as intermediate risk of death according to the 2022 tool. At follow-up, according to 2022 tool, half (55.5%) of the cohort were classified as low or intermediate-low risk. The 2022 risk model at follow-up was able to differentiate survival between risk strata. All three individual parameters (World Health Organization functional class, N-terminal pro-brain type natriuretic peptide, six-minute walk distance) were significantly associated with mortality at baseline and/or follow-up., Conclusion: The 2022 ESC risk assessment strategy applied at baseline and follow-up predicts survival in SSc-PAH. Treatment decisions for SSc-PAH should include risk assessments, aiming to achieve low-risk status according to the 2022 ESC guidelines., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: To determine the relationship between gastroesophageal reflux disease (GORD) and its treatment and interstitial lung disease in patients with systemic sclerosis (SSc)., Methods: SSc patients from the Australian Scleroderma Cohort Study (ASCS) were included. GORD was defined as self-reported GORD symptoms, therapy with a proton pump inhibitor (PPI) or histamine 2 receptor antagonist (H2RA) and/or the presence of reflux oesophagitis diagnosed endoscopically. The impact of GORD and its treatment on ILD features (including severity and time to ILD development) and survival was evaluated., Results: GORD was a common manifestation affecting 1539/1632 (94%) of SSc patients. GORD affected 450/469 (96%) of those with SSc-ILD cohort. In SSc-ILD, there was no relationship between the presence of GORD or its treatment and time to ILD development or ILD severity. However, GORD treatment was associated with improved survival in those with ILD (p = 0.002). Combination therapy with both a PPI and a H2RA was associated with a greater survival benefit than single agent therapy with PPI alone (HR 0.3 vs 0.5 p < 0.050 respectively)., Conclusion: GORD is a common SSc disease manifestation. While the presence or treatment of GORD does not influence the development or severity of ILD, aggressive GORD treatment, in particular with a combination of PPI and H2RA, is associated with improved survival in those with SSc-ILD., (© 2024. The Author(s).)

Background: During the COVID-19 pandemic, three European countries (Austria, Greece, Italy) announced and/or implemented mandatory COVID-19 vaccination for high-risk groups in the general population. Besides the ethical justification for this policy, it is important to assess and quantify the effectiveness of the mandate in raising vaccination rates., Methods: Controlled interrupted time series analysis of first-dose vaccination rates in the targeted age groups (Greece: ≥60 years; Italy: ≥50 years) relative to a control group (Greece: 50-59 years; Italy: 25-49 years) between week 35/2021 and week 50/2022. For Austria an uncontrolled analysis was performed, as the vaccine mandate targeted all adults ≥18 years., Results: Announcement of mandatory vaccination substantially increased vaccination rates in the targeted age groups compared to control in both Greece (RR = 4.36, 95 % CI: 3.57-5.32) and Italy (RR = 2.90, 95 % CI: 2.37-3.56), an effect which persisted throughout the study period. There were 176,428 (95 % CI: 164,097-187,226) mandate-attributable first-dose vaccinations in Greece and 316,192 (95 % CI: 282,467-346,678) in Italy, most of which occurred before the mandate came into effect. In Austria no discernible increase in vaccination rates was observed after the announcement of mandatory vaccination. At the end of the study period, 9.5 % of ≥60 year-olds in Greece, 4.9 % of ≥50 year-olds in Italy and 13.8 % of ≥18 year-olds in Austria remained unvaccinated., Conclusions: In Greece and Italy - though not in Austria - simple announcement of a vaccine mandate rapidly increased COVID-19 vaccination rates in the targeted age groups, without fully closing the vaccination gap. Mandatory vaccination appears to effectively target complacency but not vaccine hesitancy, and its public health benefits need to be weighted against possible detrimental effects on confidence and trust., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Regular clinical assessment for complications of systemic sclerosis (SSc) such as pulmonary arterial hypertension (PAH) is essential for early institution of therapy and improved outcomes. The objective of this study was to determine the impact of COVID-19 pandemic-related restrictions on health care access of patients with SSc, including screening for PAH., Methods: South Australian and Victorian patients enrolled in the Australian Scleroderma Cohort Study were surveyed about their perceptions of the impact of the pandemic on mental well-being, access to medications, investigations, and management of SSc. Frequency of annual rheumatology assessments, pulmonary function tests (PFT), and transthoracic echocardiography (TTE) to screen for PAH were compared with rates from before the pandemic., Results: A total of 312 of 810 patients with SSc responded (38.5% response); 273 were female (87.5%), the median age was 64.7 years, 77.2% had limited disease, the median illness duration was 15.6 years, 15.7% were immunosuppressed, 32.1% had interstitial lung disease, and 6.4% had PAH. A total of 65.7% of consultations were by telehealth, of which 81.2% were by telephone. Compared with respondents in South Australia (n = 109), Victorian respondents (n = 203) experiencing prolonged lockdown, reported reduced access to their rheumatologist (49.3% vs 27.9%; P = 0.004), greater use of consultation by video (17.3% vs 2.1%; P = 0.008), greater health care disruption (49.0% vs 23.2%; P < 0.001), and worse mental health (P = 0.002). Respondents reported reduced access to PFT and TTE (31.7% and 22.5%, respectively). Annual visits, PFT, TTE, and new diagnoses of PAH were reduced in 2020 to 2022 compared with 2011 to 2019., Conclusion: The COVID-19 pandemic-related disruption to health care for patients with SSc was associated with worse mental health and reduced screening and diagnosis of PAH, which may impact long-term outcomes., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: This prospective, multicenter, open-label, randomized, crossover trial study was to evaluate the diagnostic performance of 18F-PSMA-1007 (PSMA) vs. 18F-Choline PET/CT (FCH) in prostate cancer (PCa) patients (pts) with biochemical recurrence (BCR)., Methods: One hundred eighty-six pts, who have undergone primary definitive treatment for PCa with BCR, were recruited to this prospective study. All pts underwent one PSMA and one FCH PET/CT examination in randomized order within a time frame of 8 days and were followed up for at least 6 months (182 ± 10 days)., Results: Recurrence of PCa was observed in 176 out of 186 pts. The overall correct detection rate (DR) was 84% (95% CI 0.7967-0.8830) for PSMA and 69% (95% CI 0.6191-0.7489) for FCH, yielding a difference in proportion of 16% ( P  < 0.0001). PSMA had a sensitivity of 0.8464 and FCH 0.6857 with an odds ratio of 2.5259 ( P  < 0.0001), with statistically significant greater sensitivity of PSMA (ORs, 2.7877 and 2.1283 respectively) ( P  < 0.0001). PET/CT imaging led to a more accurate diagnosis in 166 (89.2%) pts, of which PSMA had contributed more than FCH in 91 (54.8%) of them. The DR for cutoff point PSA ≤ 1 ng/ml was higher for PSMA compared to FCH (61.8% vs. 39.5%). DR value of 51.6% for PSMA reached at PSA ≤ 0.3 ng/ml, while FCH reached that DR value with PSA ≤ 2.2 ng/ml., Conclusion: 18F-PSMA-1007 is more efficacious than 18F-Choline for the identification metastatic lesions both in patient and in regional level analysis in PCa patients with BCR., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We present a case of severe juvenile dermatomyositis with limited response to steroids in an adolescent who developed symptoms within hours after receiving Pfizer BNT162b2 coronavirus disease 2019 vaccine. The patient presented with severe weakness of proximal muscles, dyspnoea, and tachycardia. His muscle enzymes were raised, and he was diagnosed with severe juvenile dermatomyositis following magnetic resonance imaging and muscle biopsy. His management was challenging, requiring multidisciplinary input, and difficult decisions with regard to the appropriate immunomodulatory treatments. The patient had to undergo escalating immunosuppressive treatments before he began to recover clinically and biochemically. To our knowledge, this is the first case in an adolescent although a few cases of similar presentations following coronavirus disease 2019 vaccination have been reported in adults. Elucidating the potential relationship of the vaccine with this severe myopathy in an adolescent is important for global vaccination policies, but avoiding the conflation of association with causation is also crucial in the context of the pandemic., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Purpose: The purpose of this study was to evaluate renal parenchymal trauma of two-step dilation compared to the conventional Amplatz gradual dilation during percutaneous nephrolithotomy on a porcine model., Materials and Methods: A nonpapillary percutaneous access tract was established under fluoroscopic guidance in both kidneys of four female pigs. On the right kidney of each pig, gradual dilation was performed using an Amplatz dilator set with a gradual dilation to 30 Fr, whereas on the left, a two-step dilation was utilized using only 16 Fr and 30 Fr dilators. Two of the animals were euthanized immediately after the procedure and the remaining two 1 month later. The pigs that were kept alive underwent a contrast-enhanced computed tomography immediately, 15, and 30 days postoperatively. A dimercaptosuccinic acid (DMSA) scintigraphy and single-photon emission computed tomography-computed tomography (CT) were also performed after the last CT and afterward, the pigs were sacrificed. All kidneys were harvested for pathohistological examination., Results: The follow-up radiologic imaging showed similar parenchymal damage caused by the compared dilation techniques and an expected reduction in scar size in the later scans. No scar was identified by DMSA in any kidney. Gross and microscopic examinations conducted both on the kidneys that were harvested immediately after the procedure and the ones from the animals that were left to heal, revealed no significant differences in tissue damage, grade of fibrosis, or inflammation depending on the dilation method., Conclusions: Our study showed no inferior outcomes caused by two-step dilation compared to gradual dilation regarding renal parenchymal damage following a nonpapillary puncture. In fact, postoperative imaging findings suggested a trend toward better healing and less scar tissue when the two-step method was used., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Urology Annals.)

Introduction: The diagnostic and therapeutic approach to axillary lymph nodes is considered indispensable in the treatment of breast cancer patients., Aim: To investigate the effectiveness of 3D freehand SPECT (fhSPECT) in sentinel lymph node (SLN) mapping in breast cancer, compared with the use of a conventional gamma probe., Material and Methods: We retrospectively compared the fhSPECT lymph node mapping modality, with gamma probe detection in early-stage, clinically node-negative breast cancer patients, with biopsy-confirmed malignancy. The two techniques were compared based on the average number of LNs excised per axilla. The duration of SLN mapping was also compared between the two groups. The performance of the two methods on obese and post-systemic therapy patients was evaluated. FhSPECT was used in 150 cases, while the gamma probe was employed in 50 cases., Results: FhSPECT detected at least 3 nodes in 83.3% of the patients vs. 72.0% with the γ -probe (p = 0.107). The mean number of SLNs excised per axilla was 3.66 using the γ -probe and 4.18 with fhSPECT (p = 0.03). The average surgical time was 39 ±7 min with the γ -probe and 37.54 ±17 min with fhSPECT (p = 0.228). Sentinel lymph node biopsy (SLNB) mean surgical time evolved from 40.2 ±20.77 min to 32.35 ±10.46 min (p = 0.033). In obese patients, a reduction in surgical times was noted from 45.5 ±3.09 min to 44.04 ±20.9 (p = 0.27), in addition to a significant increase in average LN detection in the fhSPECT group (4.26 ±1.44) compared to the γ -probe group (3.2 ±1.65) (p = 0.043)., Conclusions: The use of the fhSPECT modality is effective and safe, and, when compared to the γ -probe, has significant advantages in SLN mapping., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Fundacja Videochirurgii.)

Objective: To evaluate whether reducing tract dilation diameter in PCNL (percutaneous nephrolithotomy) procedures results in minimizing of renal trauma of the percutaneous tract., Methods: A percutaneous renal access tract was established bilaterally to 11 pigs. Two pigs were euthanized immediately after the experiment, while nine pigs were sacrificed 1 month later. The percutaneous accesses were dilated up to 30Fr, 22Fr or 12Fr. The animals underwent a contrast-enhanced computer tomography immediately after the procedure and 30 days later. DMSA-scintigraphy with SPECT-CT was also performed. The kidneys of all animals were harvested for histological evaluation. The volume of scar tissue and the percentage of renal volume replaced by scar tissue were calculated., Results: Immediate post-procedural CT-scans revealed a significant difference in defect diameter among the three modalities. However, the scar volume calculated on CT-images and histopathology showed a significant difference only when 30Fr dilation was compared to 12Fr dilation. The percentage of scar volume was negligible in all cases, but there was still a statistical difference between 30 and 12Fr dilation. Dilation up to 22Fr revealed no statistical differences compared to the other two modalities. DMSA-scintigraphy showed no scar tissue in any case., Conclusion: Dilation up to 30Fr may cause a significantly larger scar tissue on renal parenchyma compared to 12Fr dilation as it was shown on CT-images and microscopic evaluation, but based on the DMSA/SPECT-CT this difference seems to be insignificant to the renal function. The scar tissue caused by 22Fr dilation seemed to have no significant difference from the other modalities., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The impact of a non-dominant right coronary artery (NDRCA), on single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)has not been clarified., Methods and Results: We compared SPECT-MPI results of consecutive patients without significant (diameter stenosis ≥50%)coronary artery disease (CAD) and a NDRCA (Group-1), with those of patients from our database without CAD and a dominant RCA (Group-2). All patients were subjected to SPECT-MPI with I.V. infusion of adenosine, and TC 99 -tetrofosmin. Group-1 included 69 patients (55 men, 79.7%), mean age 66.8 ± 9.8 years. Group-2 consisted of 79 patients (56 men, 70.9%), mean age 62.7 ± 11.5. There was no difference in demographics and CAD risk factors between the two groups. The SPECT-MPI revealed inferior wall ischemia, in 35 patients (50.7%), in Group-1 and 27 patients (34.1%), in Group-2 (P = 0.041)., Conclusions: A relatively high rate of reversible SPECT-MPI perfusion defects may be anticipated in patients with an unobstructed NDRCA compared to patients with a dominant RCA., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to develop a rapid, reliable, and efficient tool for three-dimensional (3D) dosimetry treatment planning and post-treatment evaluation of liver radioembolization with 90 Y microspheres, using tissue-specific dose voxel kernels (DVKs) that can be used in everyday clinical practice. Materials and Methods: Two tissue-specific DVKs for 90 Y were calculated through Monte Carlo (MC) simulations. DVKs for the liver and lungs were generated, and the dose distribution was compared with direct MC simulations. A method was developed to produce a 3D dose map by convolving the calculated DVKs with the activity biodistribution derived from clinical single-photon emission computed tomography (SPECT) or positron emission tomography (PET) images. Image registration for the SPECT or PET images with the corresponding computed tomography scans was performed before dosimetry calculation. The authors first compared the DVK convolution dosimetry with a direct full MC simulation on an XCAT anthropomorphic phantom. They then tested it in 25 individual clinical cases of patients who underwent 90 Y therapy. All MC simulations were carried out using the GATE MC toolkit. Results: Comparison of the measured absorbed dose using tissue-specific DVKs and direct MC simulation on 25 patients revealed a mean difference of 1.07% ± 1.43% for the liver and 1.03% ± 1.21% for the tumor tissue, respectively. The largest difference between DVK convolution and full MC dosimetry was observed for the lung tissue (10.16% ± 1.20%). The DVK statistical uncertainty was <0.75% for both media. Conclusions: This semiautomatic algorithm is capable of performing rapid, accurate, and efficient 3D dosimetry. The proposed method considers tissue and activity heterogeneity using tissue-specific DVKs. Furthermore, this method provides results in <1 min, making it suitable for everyday clinical practice.

Background: Radioembolization with 90 Y microspheres is a treatment approach for liver cancer. Currently, employed dosimetric calculations exhibit low accuracy, lacking consideration of individual patient, and tissue characteristics., Purpose: The purpose of the present study was to employ deep learning (DL) algorithms to differentiate patterns of pretreatment distribution of 99m Tc-macroaggregated albumin on SPECT/CT and post-treatment distribution of 90 Y microspheres on PET/CT and to accurately predict how the 90 Y-microspheres will be distributed in the liver tissue by radioembolization therapy., Methods: Data for 19 patients with liver cancer (10 with hepatocellular carcinoma, 5 with intrahepatic cholangiocarcinoma, 4 with liver metastases) who underwent radioembolization with 90 Y microspheres were used for the DL training. We developed a 3D voxel-based variation of the Pix2Pix model, which is a special type of conditional GANs designed to perform image-to-image translation. SPECT and CT scans along with the clinical target volume for each patient were used as inputs, as were their corresponding post-treatment PET scans. The real and predicted absorbed PET doses for the tumor and the whole liver area were compared. Our model was evaluated using the leave-one-out method, and the dose calculations were measured using a tissue-specific dose voxel kernel., Results: The comparison of the real and predicted PET/CT scans showed an average absorbed dose difference of 5.42% ± 19.31% and 0.44% ± 1.64% for the tumor and the liver area, respectively. The average absorbed dose differences were 7.98 ± 31.39 Gy and 0.03 ± 0.25 Gy for the tumor and the non-tumor liver parenchyma, respectively. Our model had a general tendency to underpredict the dosimetric results; the largest differences were noticed in one case, where the model underestimated the dose to the tumor area by 56.75% or 72.82 Gy., Conclusions: The proposed deep-learning-based pretreatment planning method for liver radioembolization accurately predicted 90 Y microsphere biodistribution. Its combination with a rapid and accurate 3D dosimetry method will render it clinically suitable and could improve patient-specific pretreatment planning., (© 2021 American Association of Physicists in Medicine.)

Background: The Coronavirus Disease (COVID-19) pandemic has greatly impacted people's mental health. Youth with disabilities are at particular risk for the psychological implications of the pandemic. Although much attention has been given to pandemic-related mental health challenges that youth have encountered, little is known about the facilitators for coping with the stresses of the pandemic and how this varies for youth with and without disabilities., Objective: The purpose of this study was to understand facilitators for helping youth and young adults with and without disabilities to cope and maintain mental health during the COVID-19 pandemic., Methods: This qualitative study involved in-depth interviews with 34 youth and young adults (17 with a disability; 17 without), aged 16-29 (mean age 23.2). A narrative, thematic analysis of the transcripts was performed., Results: Our findings revealed several similarities and some differences between youth and young adults with and without disabilities regarding facilitators for maintaining mental health during the pandemic. Enablers of coping included: (1) social support; (2) financial support, (3) keeping busy (i.e., having a daily routine, working to keep the mind occupied, volunteering to boost mental health, focusing on school work), and (4) work-life balance (i.e., reduced commute, more time for exercising, going outdoors, cooking, sleeping better, and reflection on life's purpose)., Conclusions: Our findings highlight how having coping strategies could help to youth and young adults deal with pandemic-related stress. Youth with disabilities may need some additional support in accessing resources, exercising and going outdoors to help enhance their coping strategies., Competing Interests: Conflicts of interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To characterise the prevalence and associations of metabolic syndrome (MetS) in a multiethnic cohort of patients with SLE., Methods: Using a standardised protocol, baseline demographics, per visit disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K) and treatment data, and annual recording of organ damage accrual (Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index) were captured on patients with SLE from a single tertiary centre. The presence of MetS, defined using modified updated joint consensus criteria, was assessed at the final visit from patient records. Serum concentrations of adipocytokines were measured by Quantibody., Results: 116 patients, with median (Q1, Q3) age at enrolment of 39.5 (31.4-51.1) years and disease duration of 6.1 (1.4-12) years, were followed for a median of 6.7 (4.1-8.1) years. The prevalence of MetS was 29% (34/116), while the prevalence of MetS components varied: hypertension (59%), low high-density lipoproteins (HDLs) (51%), hypertriglyceridaemia (32%), obesity (16%) and hyperglycaemia (22%). In univariable analysis, MetS was associated with baseline organ damage (OR 4.34; 95% CI 1.80 to 10.48; p<0.01) and organ damage accrual (OR 2.34; 95% CI 1.02 to 5.36; p=0.04) but not with disease activity. In multivariable analysis, baseline organ damage remained significantly associated with MetS (adjusted OR 3.36; 95% CI 1.32 to 8.59; p=0.01). Glucocorticoid use was not associated with MetS or any of its five components. High serum concentrations of resistin were significantly negatively associated with MetS (OR 0.17; 95% CI 0.04 to 0.70; p=0.014)., Conclusion: MetS was common in a multiethnic cohort of patients with SLE, with the most frequent components being hypertension and low HDL. An independent association was found between MetS and organ damage but not glucocorticoid exposure or disease activity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Evaluating the contribution of glucocorticoid use to organ damage in systemic lupus erythematosus is confounded by glucocorticoid use in active disease. We sought to determine the independence of the contribution of glucocorticoid use to damage accrual from associations with disease activity by analysing patients without measurable disease activity., Methods: Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0., Findings: Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5-3·0), damage accrual events were observed in 255 (14·9%) patients. 1405 (82·3%) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9-8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95% CI 1·01-1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02-1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2%) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6%) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0-5·0). Accrual of irreversible organ damage occurred in 21 (13·4%) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95% CI 1·03-1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03-1·23], p=0·0144), and age at enrolment (1·04 [1·01-1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43-2·06], p=0·8675)., Interpretation: Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity., Funding: UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Cognitive impairment is present in up to 65% of Relapsing Remitting Multiple sclerosis (RRMS) patients and can be extremely debilitating. Although deficits in episodic memory and processing speed occur more frequently than executive deficits, executive dysfunction tends to have a significant impact on MS patients' ability to generate strategies, think divergently, solve and estimate problems, and reason in abstract terms with substantial negative impacts on activities of daily living. In the present study we investigated perfusion detection rate and pattern, as well as the association between perfusion rates and cognitive dysfunction in cognitively impaired RRMS patients., Methods: We present findings from 17 cognitively impaired RRMS patients who were evaluated with a comprehensive neuropsychological battery and additionally evaluated by brain perfusion radiopharmaceutical technetium-99m hexamethyl-propylene amine oxime ( 99m Tc HMPAO)., Results: RRMS patients had hypoperfusion in several predefined Brodmann areas and lobes of the brain, relatively to demographically matched healthy controls according to an established normative database NeuroGam™. However, we noted blood flow reduction, mainly in the frontal lobes and other related prefrontal areas, involving both hemispheres, but with asymmetric left hemisphere predominance. Moreover, associations between measures of response inhibition, set shifting (executive functions) and severity of hypoperfusion in the left frontal lobes were also established., Conclusion: Cerebral hypoperfusion is an integral feature of MS pathology. Executive dysfunction is associated with robust cerebral perfusion deficits in the frontal and prefrontal cortex of cognitively impaired RRMS patients.

Background: The aim of the present study was to compare Emory Cardiac Toolbox, Myovation, and Quantitative Gated SPECT software regarding the automatic measurements of perfusion and functional left ventricular (LV) quantitative parameters, summed stress score (SSS), perfusion defect score, LV ejection fraction (LVEF), end-diastolic volume, and end-systolic volume (ESV)., Methods and Results: 99 mTc-tetrofosmin gated SPECT studies were performed in 634 consecutive patients based on the one-day stress/rest protocol. Participants were divided into subgroups according to heart size (ESV cut-off value: 25 mL), perfusion (SSS >/≤3), and other patient/protocol-related factors. LVEF was categorized as normal (≥50%), mildly moderately impaired (35-49%), and severely abnormal (<35%). The concordance between the packages was good to excellent, in overall population, ESV ≤25 mL, ESV >25 mL, and SSS >3 subgroups (intraclass correlation coefficients, ICCs 0.73-0.93). In SSS ≤3 subgroup, the correlation was excellent for LV functional parameters, but suboptimal for perfusion variables (ICCs 0.30-0.83). LVEF categorization revealed similar variability (discordance 18.1 and 11.1% for stress/rest LVEF values, respectively). Pair comparisons demonstrated considerable differences concerning all parameters for all patient subgroups. The statistical significance of our findings by ESV and SSS classifications was evaluated., Conclusions: Despite the significant concordance between software packages, considerable differences in mean values of myocardial perfusion and LV functional parameters were demonstrated.

Objective: To investigate the anatomical relations of the papillary, infundibular, and pelvic approach to percutaneous nephrolithotomy and evaluate the amount of vascularization at the respective sites., Materials and Methods: 99m Tc-dimercaptosuccinic acid single-photon emission computed tomography/computed tomography (SPECT/CT) renal scintigraphies or computed tomography perfusion (CTP) was performed in 40 patients (prone n = 20 or supine position n = 20). The angle of approach (AoA) for access tracts and the respective regions of interest to the mid-calyceal papilla and infundibulum as well as renal pelvis were designed and compared., Results: The design of access tracts aiming to the renal pelvis, papilla, and infundibulum of the renal calyx was impossible for the nondilated collecting systems as all these tracts were in close vicinity. In both SPECT/CT and CTP, there was no statistical difference between the AoA for infundibular or pelvic access in comparison with the papillary puncture in either prone or supine position regardless of the degree of dilation of the system. The comparison of the measurements in the regions of interest showed that there was no difference in blood supply between the infundibular and pelvic access in comparison with the papillary approach in both positions regardless of the degree of collecting system dilation., Conclusion: The use of SPECT/CT and CTP showed that the punctures to the mid-calyceal renal papilla-fornix and infundibulum as well as the renal pelvis at the same level have similar AoA. The sites of the parenchyma involved in the tract dilation of the respective approaches are not related to significant differences in terms of vascularization., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The treatment of SLE remains complex, and management is constrained by a lack of safe, effective, targeted therapies. Physicians, also, are constrained by a lack of evidence-based approaches with existing agents, including glucocorticoids, utilized in the majority of patients. While Cushingoid side effects of glucocorticoids are widely recognized, emerging literature now suggests that glucocorticoid use actually contributes to harmful outcomes in SLE, over and above these effects. These studies provide a compelling case for a re-evaluation of the long-term use of glucocorticoids in SLE, focusing on minimizing glucocorticoid exposure as part of the strategy to improve long-term outcomes. In this article, we review the evidence for the harmful effects of glucocorticoids in SLE, and propose therapeutic options that reduce reliance on glucocorticoids. We propose that it is time for the lupus community to have a louder conversation about glucocorticoid use, and for any residual complacency about their risk-benefit ratio to be banished., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To determine factors associated with damage accrual in a prospective cohort of patients with SLE., Methods: Patients with SLE who attended the Lupus Clinic at Monash Health, Australia, between 2007 and 2013 were studied. Clinical variables included disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K, SLEDAI-2K), time-adjusted mean SLEDAI, cumulative glucocorticoid dose and organ damage (Systemic Lupus International Collaborating Clinics Damage Index (SDI)). Multivariate logistic regression analyses were performed to identify factors associated with damage accrual., Results: A total of 162 patients were observed over a median (IQR) 3.6 (2.0-4.7) years. Seventy-five per cent (n=121) of patients received glucocorticoids. Damage accrual was significantly more frequent in glucocorticoid-exposed patients (42% vs 15%, p<0.01). Higher glucocorticoid exposure was independently associated with overall damage accrual after controlling for factors including ethnicity and disease activity and was significant at time-adjusted mean doses above 4.42 mg prednisolone/day; the OR of damage accrual in patients in the highest quartile of cumulative glucocorticoid exposure was over 10. Glucocorticoid exposure was independently associated with damage accrual in glucocorticoid-related and non-glucocorticoid related domains of the SDI., Conclusions: Glucocorticoid use is independently associated with the accrual of damage in SLE, including in non-glucocorticoid related domains., Competing Interests: Conflicts of Interest: None declared.

Aim: Ga-68 labeled somatostatin analogues such as 68Ga-DOTA0-Phe1-Tyr3-octrotide (DOTATOC) as PET tracers, have significantly improved the imaging of somatostatin receptors (SSTRs) expressing tumors. Due to unspecific parenchymal binding and the expression of SSTRs on leukocytes in the spleen this is the organ with the highest non-tumor uptake of DOTATOC. Therefore, we investigated the potential changes of normal tissue distribution and tumor concentration in patients with neuroendocrine tumors (NETs) with or without spleenectomy., Methods: Out of 420 patients with pancreatic NET undergoing 68GA-DOTATOC PET/CT eleven patients with and eleven patients without spleenectomy were derived and matched in regard to tumor histology, tumor load, age and gender. The SUV(max) of liver metastases as well as of the following normal tissues was determined: pituitary gland, thyroid gland, liver parenchyma, kidneys and suprarenal glands., Results: SUV(max) values with and without spleenectomy were: in the liver metastasis (19.17 ± 6.05 versus 37.67 ± 16.31), in the thyroid gland (2.56 ± 1.33 versus 2.66 ± 0.94), in the pituitary gland (4.08 ± 1.79 versus 4.92 ± 1.93) in suprarenal glands (7.18 ± 3.33 versus 9.73 ± 3.46 on the left side and 7.32 ± 3.03 versus 11.19 ± 5.72 on the right side), in the kidneys (8.1 3 ± 4.26 on the left side and 8.11 ± 4.16 on the right side versus 8.62 ± 2.17 on the left side and 9.79 ± 2.18 on the right side) and in normal liver tissue (5.74 ± 1.55 versus 6.22 ± 1.95). The difference was statistically significant (Wilcoxon test P<0.05) in tumor lesions, adrenal and kidney tissue., Conclusion: Spleenectomy must be considered as a relevant factor when reporting the outcome of SSTR targeted diagnostics and therapies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by multi-system manifestations. It is regarded as the prototypal connective tissue disease, where the key pathogenesis relates to a dysfunctional immune system that results in over-production of various autoantibodies. Most of its pathology is mediated by either direct or indirect effects of these autoantibodies, as well as other components of the innate and adaptive immune systems.

Purpose: To evaluate the effect of vardenafil on renal function after renal ischemia-reperfusion (IR) injury (IRI) in a rat model., Materials and Methods: Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3-6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle. Four hours of reperfusion were allowed after renal ischemia. Studied parameters were serum creatinine, fractional excretion of sodium (FENa), and histological evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2 phosphorylation as well as renal function by renal scintigraphy were also evaluated., Results: Administration of vardenafil before the induction of ischemia resulted in a significant reduction in creatinine and FENa levels as well as in less histological lesions observed in treated kidneys in comparison with the vehicle-treated group. The underlying mechanism of cytoprotection was cGMP depended and involved the phosphorylation of ERK proteins. Renal scintigraphy confirmed that PDE5 inhibition attenuates renal IRI., Conclusions: Vardenafil attenuates renal IRI. Based on similar results from relevant studies on other PDE-5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5 inhibitors share a common mechanism of cytoprotection.

Background: This study evaluates the appropriate use of myocardial perfusion imaging (MPI) and determines patterns and variables associated with inappropriate testing., Methods: Over a 10-month period data were collected prospectively from consecutive patients referred for MPI in four academic departments and an appropriate use grade was assigned (appropriate, uncertain, inappropriate, and unclassifiable scans) according to established criteria., Results: Among 3,032 referrals appropriate MPI had 72.8% of patients and 19.2% of studies were inappropriate, the remaining being uncertain (7.2%) or unclassifiable (0.8%). In multivariate analysis the asymptomatic status (odds ratio 10.7, P < .001), good functional capacity (odds ratio 1.9, P < .001), an interpretable resting electrocardiogram (odds ratio 1.8, P = .004), an age <65 years (odds ratio 1.5, P = .001) and the absence of diabetes (odds ratio 1.7, P < .001) or dyslipidemia (odds ratio 1.3, P = .014) were independent predictors of inappropriate scintigraphy. The most common indication for inappropriate testing was the assessment of asymptomatic patients <2 years after percutaneous coronary intervention (PCI) (38.9%)., Conclusions: The appropriate use of MPI is relatively high, but a considerable proportion of inappropriate scans is noted which is associated with markers of lower risk. The most common source of inappropriate testing is the assessment of asymptomatic patients <2 years after PCI.

We demonstrate Wavelength Division Multiplexed (WDM)-enabled transmission of 480Gb/s aggregate data traffic (12x40Gb/s) as well as high-quality 1x2 thermo-optic tuning in Dielectric-Loaded Surface Plasmon Polariton Waveguides (DLSPPWs). The WDM transmission characteristics have been verified through BER measurements by exploiting the heterointegration of a 60 μm-long straight DLSPPW on a Silicon-on-Insulator waveguide platform, showing error-free performance for six out of the twelve channels. High-quality thermo-optic tuning has been achieved by utilizing Cycloaliphatic-Acrylate-Polymer as an efficient thermo-optic polymer loading employed in a dual-resonator DLSPPW switching structure, yielding a 9 nm wavelength shift and extinction ratio values higher than 10 dB at both output ports when heated to 90°C.

With metal stripes being intrinsic components of plasmonic waveguides, plasmonics provides a "naturally" energy-efficient platform for merging broadband optical links with intelligent electronic processing, instigating a great promise for low-power and small-footprint active functional circuitry. The first active Dielectric-Loaded Surface Plasmon Polariton (DLSPP) thermo-optic (TO) switches with successful performance in single-channel 10 Gb/s data traffic environments have led the inroad towards bringing low-power active plasmonics in practical traffic applications. In this article, we introduce active plasmonics into Wavelength Division Multiplexed (WDM) switching applications, using the smallest TO DLSPP-based Mach-Zehnder interferometric switch reported so far and showing its successful performance in 4×10 Gb/s low-power and fast switching operation. The demonstration of the WDM-enabling characteristics of active plasmonic circuits with an ultra-low power × response time product represents a crucial milestone in the development of active plasmonics towards real telecom and datacom applications, where low-energy and fast TO operation with small-size circuitry is targeted.

Background: Iodine deficiency (ID) is still a major universal health problem. Iodine deficiency disorders (IDDs) affect people of all ages, among whom the most vulnerable are children and adolescents. The aim of the present study was to assess the long-term effects on growth and pubertal development of correcting severe ID in areas of Azerbaijan between 1999 and 2000., Methods: Iodized oil was administered orally to 293,000 children, aged 6-16 years. Among those, 364 children were randomly selected and were examined 1 year before the administration of iodized oil (Group I-neg, iodine negative) and 295 children (Group I-Rx, iodine treated) were examined 4 years (Group I-R x 4, iodine treated 4 years later; n = 173) or 5 years (Group I-R x 5, iodine treated 5 years later; n = 122) after the last dose of iodide., Results: In Group I-neg the median urine iodine concentration (UIC) (mcg/L) was 36 (mean: 36.272 +/- 11.036) and increased significantly (p < 0.001) in Group I-R x 4: 188 (mean: 230.969 +/- 155.818) and in Group I-R x 5: 175 (mean: 201.176 +/- 130.369). The prevalence of goiter was 99% in Group I-neg and 2% in Group I-R x 4. Children in Group I-Rx had a greater standard deviation score (SDS) for height (-0.1364 +/- 1.279, n = 294) than children in Group I-neg (-0.5019 +/- 1.17, n = 363) (p < 0.001, t = -3.817), which was more significant for boys. SDS for weight was similar in both groups (Group I-neg: -0.17 +/- 0.78, n = 363; Group I-Rx: -0.115 +/- 0.917, n = 294). The rate of puberty development as judged by the development of breast and pubic hair was normalized in both sexes after the correction of ID., Conclusions: Our results demonstrate that long-term correction of severe ID leads to sustained improvement of linear growth accompanied by a normalization of the time of onset of pubertal development for both sexes.

We demonstrate an optical clock recovery circuit that extracts the line rate component on a per packet basis from short data packets at 40Gb/s. The circuit comprises a Fabry-Perot filter followed by a novel power limiting configuration, which in turn consists of a 5m highly nonlinear bismuth oxide fiber in cascade with an optical bandpass filter. Both experimental and simulation-based results are in close agreement and reveal that the proposed circuit acquires the timing information within only a small number of bits, yielding a packet clock for every respective data packet. Moreover, we investigate theoretically the scaling laws for the parameters of the circuit for operation beyond 40 Gb/s and present simulation results showing successful packet clock extraction for 160 Gb/s data packets. Finally, the circuit's potential for operation at 320 Gb/s is discussed, indicating that ultrafast packet clock recovery should be in principle feasible by exploiting the passive structure of the device and the fsec-scale nonlinear response of the optical fiber.

We demonstrate an all-optical, self-synchronization scheme for optical packet switched network nodes. It provides both the packet clock signal and the packet beginning, marker pulse. The circuit uses two hybridly integrated MZI switches and has been evaluated with synchronous, asynchronous and variable length, data packets at 10 Gb/s. It is compact and requires relatively low energies to operate.

Unlabelled: Parathyroid scintigraphy and high-resolution ultrasonography are frequently used as preoperative localization procedures in primary hyperparathyroidism. However, when thyroid disease coexists, their diagnostic accuracy is probably abated., Design: 56 patients with primary hyperparathyroidism were prospectively evaluated with parathyroid scintigraphy (with either thallium or technetium-99m agents or both) and 44 of them were also evaluated with ultrasonography., Results: 33 patients (59%) had coexistent thyroid disease. Upon operation, 48 patients were found to have a solitary parathyroid adenoma and were all cured. One patient had a carcinoma and 7 had multiglandular parathyroid disease. Regarding solitary lesions, the sensitivity of parathyroid scintigraphy with Tc-agents was 97% and thallium 78%, while that of ultrasonography was 74%. The false positive rate was 2.6%, 18%, and 22%, respectively. Concomitant thyroid disease had a non-significant effect on the results of parathyroid scintigraphy and ultrasonography. The efficiency of both modalities in diagnosing multiglandular disease was low (only 3/7 patients, 43%)., Conclusions: Parathyroid scintigraphy, in conjunction with Sestamibi or Tetrofosmin, constitutes the most sensitive localizing technique as regards solitary lesions. Ultrasonography is also useful in confirming scintigraphic findings, offers more precise anatomic information, and is valuable in the evaluation of concomitant thyroid disease. The complementary use of parathyroid scintigraphy and ultrasonography is beneficial and efficacious in areas with high prevalence of thyroid disease. The value of these modalities is considerably lower in multiglandular disease.

Diagnosis of septic loosening of hip endoprosthesis with antigranulocyte scintigraphy (AGS) was analysed. Twenty-one hip prostheses were studied using laboratory tests and, in cases of elevated values, three-phase bone scan (BS) and AGS. Elective SPECT/CT scans were performed. Histologic and microbiologic exams verified the diagnosis. The AGS analysis revealed sensitivity, specificity and accuracy of value 1, while positive and negative predictive values were also 1. BS showed sensitivity of 1 and specificity of 0.33. In three cases, SPECT/CT scans corroborated the AGS interpretation. This diagnostic algorithm proved effective in the detection of septic loosening of hip prostheses. AGS can be avoided without risk of infection being overlooked.

Background: This study investigates the clinical performance of routine 201Tl gated single photon emission computed tomographic (201Tl GSPECT) myocardial perfusion imaging. Equilibrium radionuclide angiography (ERNA) was used as the standard for comparison., Methods and Results: One hundred and seventy-two consecutive patients were submitted to both myocardial 201Tl GSPECT imaging, at stress and in redistribution, and ERNA. Left ventricular ejection fractions (LVEF) and regional wall motion were assessed from both stress and redistribution 201Tl GSPECT datasets, and from ERNA. Linear regression analysis showed a good correlation between LVEF calculated by ERNA and 201Tl GSPECT (r=0.73 at stress, r=0.75 in redistribution, P<0.0001). However, the 95% prediction intervals of 201Tl GSPECT LVEF from ERNA LVEF were wide (minimum 35.4% at stress and 33.2% in redistribution). Moreover, a difference in LVEF > or =10% between ERNA and 201Tl GSPECT was found in 26.4% of cases at stress and 28.6% of cases in redistribution. A fair agreement between ERNA and 201Tl GSPECT was found in regional wall motion assessment in segments with normal or mildly reduced tracer uptake (kappa=0.32 at stress and kappa=0.33 in redistribution). In segments with moderately to severely reduced tracer uptake, a moderate agreement was found in regional wall motion assessment between ERNA and 201Tl GSPECT (kappa=0.44 at stress and kappa=0.42 in redistribution)., Conclusions: Left ventricular function may be misinterpreted in a significant proportion of patients if the calculation of LVEF is based on 201Tl GSPECT. Moreover, the evaluation of regional wall motion by 201Tl GSPECT appears unsatisfactory.

Objectives: To estimate the usefulness of serum tumor markers' monitoring, as predictors of gastric cancer in patients with pernicious anemia., Patients and Methods: We investigated serum levels of carcinoembryonic antigen (CEA), alpha-fetal protein, cancer antigen (CA)-19.9, CA-125 and CA-15.3 in 50 patients with pernicious anemia and in 24 healthy controls, matched for age and sex. In 38 patients, the evaluation was repeated 1-6 months after the correction of cobalamin deficiency., Results: All patients and controls had normal serum CEA and alpha-FP, and the levels of these markers as well as those of CA-125 and CA-19.9 did not differ between the two groups. All 50 patients, but only 2 controls exhibited increased serum CA-15.3, and the difference between the two groups was very significant (129.4 +/- 84.9 vs. 19.8 +/- 7.3 IU/ml, p < 0.001), while no difference between males and females was found. A thorough clinical examination of all patients, and mammographic study in 18 females did not reveal any finding suspicious of breast cancer. CA-15.3 levels were positively correlated with serum lactate dehydrogenase, and negatively with B(12) and hemoglobin, but they were substantially decreased after the correction of anemia, in all 38 patients tested, and in 33 of them they were restored to normal. After a median follow-up of 34 months, one patient developed a colon cancer, but none showed any sign suspicious of breast cancer., Conclusions: Serum CA-15.3 shows an aberrant increase in untreated patients with pernicious anemia, which is reversed after the correction of the anemia. The possible origin seems unrelated to mammary tissue, and may be released by the apoptosing bone marrow megaloblastic erythroblasts., (Copyright (c) 2004 S. Karger AG, Basel)

Background: It has been suggested that symptoms from bile reflux gastritis are related to the frequency and degree of enterogastric reflux (EGR)., Methods: Patients with history of upper gastrointestinal surgery or cholecystectomy as well as control patients were studied. Presence of EGR, degree of EGR, and gastric bile emptying time were assessed and quantified via 99mTC scintillation imaging and then compared between symptomatic and asymptomatic patients., Results: Patients with vagotomy and pyloroplasty, Billroth I, Billroth II, and cholecystectomy demonstrated statistically higher degrees of EGR compared with controls. Although asymptomatic and symptomatic patients with a history of upper gastrointestinal or biliary surgery demonstrated no statistically significant differences between incidence of EGR and degree of EGR, there was a statistically significant difference in gastric emptying time., Conclusions: Delayed gastric emptying time, not frequency or extent of EGR, was associated with the symptoms of bile reflux in patients who had previous upper gastrointestinal or biliary operations.

Objectives: This study investigated whether ST-segment elevation and T-wave normalization (TWN) in Q-wave leads on pre-discharge exercise electrocardiogram (ECG) can contribute to patient management after a recent myocardial infarction (MI)., Background: The clinical relevance of these exercise ECG changes remains controversial despite accumulating evidence of their association with myocardial viability. Because discrepancies of previous studies may depend on patient selection, the value of these ST/T abnormalities in the thrombolytic era should be better defined., Methods: One-hundred one patients, age 58 +/- 11 years, with a recent, first Q-wave MI (57% thrombolyzed, ejection fraction 43 +/- 7%) underwent pre-discharge, submaximal treadmill testing followed, in the absence of severe ischemia, by dobutamine stress echocardiography, thallium-201 single photon emission computed tomography, and coronary angiography., Results: ST elevation at peak exercise, but not TWN, was associated with more severe infarctions as indicated by higher peak creatine kinase (p < 0.05) and with a greater number of scarred segments both on echocardiography (p < 0.05) and scintigraphy (p < 0.01). However, the incidence of myocardial viability and ischemia did not differ between groups with or without these ST/T changes. Anterior infarction location and >or=3 echocardiographically scarred segments were among the independent predictors of ST elevation at peak ergometric exercise. During follow-up (31 +/- 13 months), the rate of hard events was low (8%) and similar between the study groups., Conclusions: In patients after acute Q-wave MI without severe ischemia according to clinical and standard ECG criteria, exercise-induced ST elevation, but not TWN, is associated with larger infarctions. The contribution of these ST/T abnormalities toward identifying patients with myocardial viability or ischemia and determining risk stratification is poor. In-hospital management of such patients based on routine clinical practice is sufficient for selection of a population with a relatively low long-term risk.

The risk of transmission of transfusion-associated infections, mainly AIDS, led to the increased use of autologous transfusion by four methods: predeposition of autologous blood, haemodilution, intraoperative and postoperative blood salvage. We started a program of autologous predeposition at blood transfusion centre of Saint Andrews General Hospital of Patras in co-operation with orthopaedic and plastic surgery in 1992. To date, 617 autologous units have been collected from 257 patients undergoing various operations. Our protocol was as follows: the minimum Hb value before each donation was 12 g/dl, body weight over 50 kg, age 18-70 years and 8-10 day intervals between donations. The exclusion criteria were anaemia, evidence of blood loss, renal disease, chronic and acute inflammatory or malignant disorders, pregnancy and lactation. We chose 40 patients with haemoglobin values of 13-15 g/dl and ferritin levels > 50 ng/ml, who gave three autologous units. They were separated in two groups of twenty patients. Those in group 1 received 300 mg of elemental iron in three daily oral doses, while the others in group 2 received no iron medication. We studied haematologic variables, reticulocytes and ferritin levels in both groups before each autologous donation. We also studied the possible complications and their incidence in patients over 60 years old. According to our results, haematologic variables such as Hb, mean corpuscular Hb (MCH), mean corpuscular volume (MCV) and reticulocytes were not influenced by oral iron therapy. We observed a slight increase in MCV in both study groups which means the production of larger red blood cells. We also noticed a higher decrease of ferritin in patients with no iron therapy, but without a fall of ferritin levels under the normal values. We conclude that oral iron therapy in non-iron deficient patients undergoing a moderate program of three autologous units is not necessary. In addition, autologous blood donation is also feasible in patients over 60 years old without severe complications.

Aims: To evaluate right ventricular function in patients with beta-thalassaemia major and congestive heart failure. Background In patients with beta-thalassaemia major a high incidence of cardiac involvement still exists despite improved prognosis with chelation therapy. Development of severe right heart failure is common and has been attributed to pulmonary hypertension secondary to lung haemochromatosis. However, the possibility of direct right ventricular myocardial involvement in the absence of significant pulmonary hypertension has not been adequately investigated., Methods: Twenty-nine consecutively screened patients with beta-thalassaemia major and congestive heart failure were investigated by Doppler echocardiography, right ventricular first-pass radionuclide examination and cardiac catheterization. Haemodynamic data were obtained both before and after volume loading. A control group of 39 patients with beta-thalassaemia major, free from cardiac disease, and matched for age, gender, body surface area and heart rate was used for comparison. A subset of the control thalassaemic group (n=15) underwent both radionuclide and haemodynamic assessment., Results: The majority of patients were on non-optimal chelation therapy. Only two of 29 patients were found to have cor pulmonale. One other patient suffered from constrictive pericarditis. A restrictive filling pattern in both ventricles and left ventricular systolic dysfunction were evident in the other 26 patients. Pulmonary artery pressure (systolic, 33+/-8 vs 27+/-5 mmHg, P<0.05) and pulmonary vascular resistance (114+/-56 vs 65+/-29 dynes. s. cm(-5), P<0.01) were only mildly elevated in the heart failure group. After volume challenge, cardiac output remained unchanged although the increments of ventricular filling pressures were significant (Deltaright atrial: 4.8+/-2.2 mmHg, P<0.05; Deltapulmonary capillary wedge: 5.6+/-2.9 mmHg, P<0.05) and correlated with each other (r=0.69;P<0.001) in heart failure patients, suggesting pericardial constraint and ventricular interaction. In these patients compared with the control thalassaemic group, a lower right ventricular ejection fraction (29%+/-9 vs 59%+/-6, P<0.0001) without correlation with pulmonary artery pressures was found. Haemodynamically significant right ventricular dysfunction defined as mean right atrial pressure >10 mmHg and ratio of mean right atrial-to-capillary wedge pressure >0.8 was evident in 15 of the 26 patients (58%), all with severe symptoms, representing three fourths of the patients in functional class III and IV. Simultaneous pressure recordings in six of these 15 patients showed equalization of ventricular end-diastolic pressures within 5 mmHg., Conclusion: The majority of patients with beta-thalassaemia major and severe congestive heart failure demonstrated a unique haemodynamic pattern similar to that described in predominant right ventricular infarction, indicating severe right ventricular cardiomyopathy in addition to left ventricular dysfunction. The incidence of cor pulmonale as a cause of right heart failure seems to be much lower than previously hypothesized., (Copyright 2001 The European Society of Cardiology.)

We evaluated the effectiveness of Re-186-HEDP in 25 patients with painful metastatic bone disease. Twenty-five patients with known prostatic (n = 19), non-small-cell lung cancer (n = 1) and breast cancer (n = 5) and multiple confirmed skeletal metastases were studied. All were taking analgesics daily (nonsteroidal antiinflammatory drugs/opiates). Re-186-HEDP (mean 35.2 mCi) was administered and patients were monitored for at least 50 days. In five patients, a repeat dose was administered 9 to 10 weeks later. The evaluation of the analgesic effect was based on a "pain diary" and by recording the use of analgesics. In 80% (20 of 25) of the patients, the effect was significant palliation, moderate in 3 patients (12%), and insignificant in 2 (8%). No significant myelotoxicity was observed. Transient pain flare was recorded in 8 of 25 patients. These results indicate that Re-186-HEDP can offer pain palliation in patients with painful bone metastases without being complicated by significant myelotoxicity.

The objective of the present study was to investigate the efficacy of (111)In-DTPA-octreotide (OC) for in vivo scintigraphic imaging of these relatively uncommon tumors. Thirteen patients (9 males, 4 females, mean age 59 years) with known sarcomatous lesions were studied. All patients had known lesions as demonstrated by previous investigation with other modalities, e.g. CAT, MRI. Following intravenous injection of 10 microg of OC labeled with 2.8-4.2 mCi (111)In, planar imaging was done at 6 +/- 1 and 22 +/- 2 h, respectively. Histologic verification was obtained in all cases, either from fine needle aspiration or from surgically removed tissue. Positive imaging was observed in 12/13 cases (92.3%). One scan was false-negative (7.7%). Occult lesions were demonstrated in two patients. The histologic typing and the scintigraphy results were: fibrosarcoma (1+/1), embryonic rhabdomyosarcoma (1+/1), leiomyosarcomas (3+/3), liposarcomas (2+/2), uterine sarcomas (2+/2), HIV (-) Kaposi sarcoma (1+/1), osteosarcoma (1+/1), chondrosarcoma (1-/1) and neurogenous sarcoma (1+/1). OC appears to have properties that lead to a new indication for its use. Other possible applications relate to the therapeutic use of octreotide either unlabeled or labeled with a beta-emitting radionuclide, as well as its use in radioimmunoguided surgery. Regarding the latter, our preliminary results are encouraging., (Copyright 2000 S. Karger AG, Basel)

The targeting potential of three different monoclonal antibodies (MAbs) was assessed in patients with ovarian cancer. HMFG1, OC-125 and H17E2 labelled with 111In or 123I were evaluated prospectively for their ability to localize ovarian tumour. Forty two patients with ovarian cancer, aged 40-78 years (median = 58 years) were studied using OC-125 (n = 9), HMFG1 (n = 11) and H17E2 (n = 22). Imaging data were compared with the CT and the surgical findings. Presence of tumour was confirmed in 35/42 (83%) patients (8/9 OC-125, 10/11 HMFG1 and 17/22 H17E2) and correlated well with the conventional radiology diagnostic methods. One patient with a negative H17E2 scan and a large abdominal mass detected at laparotomy revealed a PLAP-negative tumour on immunohistochemistry. Scintigraphy revealed the presence of active disease, confirmed by laparotomy/laparoscopy in 6/8 patients considered to be in clinical remission. The sensitivity of the method was high enough and the diagnostic contribution of this approach should be further evaluated.

Unlabelled: The efficacy of 99mTc-tetrofosmin for the detection of parathyroid lesions was investigated prospectively in patients with hyperparathyroidism referred for surgical treatment., Methods: Twenty-seven patients with primary and 18 with tertiary hyperparathyroidism were studied. Twelve patients had undergone one or more previous neck explorations. Static imaging with 201Tl was performed first, immediately followed by a 30-min 99mTc-tetrofosmin dynamic study. Delayed views of up to 3 hr postinjection were also obtained. Technetium-99m-pertechnetate was used for thyroid delineation. The tetrofosmin/99mTc-pertechnetate subtraction scan (TF/TC), the single-tracer washout technique and the thallium/technetium subtraction (TL/TC) were compared. Quantification of relative uptakes of tracers in the thyroid and abnormal parathyroids was accomplished by measuring activity within regions of interest. Kinetics of tetrofosmin in the thyroid and abnormal parathyroids were studied by evaluating the plots of the parathyroid to thyroid ratios against time as well as by calculation of the half-clearance times from the slow component of the time-activity curves., Results: The overall sensitivity, specificity and accuracy of TF/TC and TL/TC were 76%, 92% and 83% and 52%, 85% and 65%, respectively. The respective sensitivities were 87% and 70% for adenomas and 72% and 46% for hyperplasia. The parathyroid-to-thyroid activity ratios of tetrofosmin were significantly higher than those of thallium (p < 0.001). The tetrofosmin single-tracer washout study was less accurate than the subtraction technique (overall sensitivity and specificity, 70% and 69%, respectively). The washout properties of tetrofosmin in abnormal parathyroids were not substantially different from those in the thyroid, with a few exceptions (p = 0.4). No correlation of half-clearance times with parathyroid size, degree of early uptake, parathyroid hormone levels or histology could be established. Comparing adenomas to hyperplasia in respect to tetrofosmin retention, a statistically significant difference was observed (p = 0.005)., Conclusion: Technetium-99m-tetrofosmin is suitable for parathyroid imaging. The kinetic properties of this agent in parathyroid and thyroid tissues do not warrant differential washout protocols. The diagnostic impact of the observed difference in tetrofosmin kinetics between parathyroid adenomas and hyperplasia requires further investigation.

Adsorption of water and ethanol on four starches has been studied in the temperature range of 50-90 degrees C. The results show that adsorption of water on starch-based materials is enhanced when the amount of amylopectin is highest. Adsorption of ethanol is not significantly affected by the kind of starch used. Heats of adsorption calculated from retention data are in the range from -9.3 to -13.7 kcal/g mol for water and -5.6 to -6.76 kcal/g mol for ethanol. Calculated free energies of adsorption suggest that adsorption is most spontaneous at lower temperatures as expected.

Sixty-four selected hypertensive patients, aged 17-45 years, were evaluated for renovascular hypertension. They were studied with 99mTC-DTPA Dynamic Renal Scanning (DRS) and Intravenous Digital Subtraction Angiography (IV-DSA). Intra-arterial DSA was further performed to demonstrate renal vascular anatomy in all disputable cases. Agreement of diagnosis occurred in 58 patients (32 with renal artery stenosis). There was one false positive with DRS and one false positive with IV-DSA. In another four patients with proven renovascular disease, IV-DSA was positive while DRS negative, but in two of them the stenotic lesion was considered insignificant, as they failed to respond to percutaneous transluminal dilatation (PTA). In contrast, nearly all patients whose hypertension improved after PTA or surgery had positive DRS and greater than 40% reduction of relative function of the affected kidney. IV-DSA yielded better results than DRS in the detection of renal arterial stenosis (especially whenever bilateral stenosis or rich collateral circulation was present), but DRS showed better correlation with the functional significance of a certain vascular abnormality. Thus the combination of the two methods seems to be a reasonable diagnostic approach to hypertensive patients with the aim of selecting those with curable hypertension due to renal vascular disease.