Prevalence and outcomes of gastrointestinal manifestations in an Australian Scleroderma cohort.

OBJECTIVES: 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: 907 consecutive patients from the Australian Scleroderma Cohort Study (ASCS) 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 association between UCLA GIT scores and physical function (SHAQ), QoL (SF-36), mood (PROMIS anxiety and depression domains), fatigue (FACIT-fatigue score) and employment was investigated using multivariable population-averaged panel models using Generalized Estimating Equations (GEE). Kaplan-Meier curves and multivariable Cox proportional hazard regression model were used to evaluate survival according to total UCLA GIT scores. RESULTS: GIT symptoms were reported in 87% of participants with 46-52% reporting moderate to very severe symptoms of reflux, distension, diarrhoea and constipation. Higher total UCLA GIT scores were associated with worse QoL, physical function, fatigue, anxiety and depression (p<0.001). In multivariable GEE analysis, moderate and severe to very severe total scores, reflux and distension scores were associated with worse physical function, QoL, fatigue, anxiety and depression compared to those with mild scores (p<0.05). Patients with severe total scores and diarrhoea 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 mortality 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 mortality.

The impact of gastroesophageal reflux disease and its treatment on interstitial lung disease outcomes.

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.

Comparison of 68Ga-DOTATOC biodistribution in patients with and without spleenectomy.

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.

0.48Tb/s (12x40Gb/s) WDM transmission and high-quality thermo-optic switching in dielectric loaded plasmonics.

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.

Packet clock recovery using a bismuth oxide fiber-based optical power limiter.

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.

Packet-level synchronization scheme for optical packet switched network nodes.

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.

[Diagnosis of septic loosening of hip prosthesis with LeukoScan. SPECT scan with 99mTc-labeled monoclonal antibodies]. / Diagnose septischer Hüftprothesenlockerung via LeukoScan. SPECT-Scan mit 99mTc-markierten monoklonalen Antikörpern.

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.

Right ventricular cardiomyopathy in beta-thalassaemia major.

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.

Experience with predeposition of autologous blood in elective orthopaedic and plastic surgery: the role of oral iron medication.

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.

Preliminary results of the use of Re-186-HEDP for palliation of pain in patients with metastatic bone disease.

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.

Scintigraphic imaging of sarcomatous tumors with [(111)In-DTPA-phe-1]-octreotide.

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.

Radioimmunoscintigraphy in patients with ovarian cancer.

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.

Technetium-99m-tetrofosmin for parathyroid scintigraphy: comparison to thallium-technetium scanning.

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.

Investigation of renovascular hypertension with 99mTC-DTPA dynamic renal scanning and digital subtraction angiography.

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.

Thermodynamics of water and ethanol adsorption on four starches as model biomass separation systems.

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.