Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study.

PURPOSE: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. METHODS: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. RESULTS: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). CONCLUSIONS: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

Theragnostics before we found its name.

Theragnostics embraces "gnosis" and "prognosis" and concerns a treatment strategy which combines diagnostics with therapeutics. The birth of what we call today theragnostics can be traced in 1936, with the proposal of radioiodine, the first radiopharmaceutical approved in 1951 by FDA, in USA, as 131I sodium iodide. In 1957, 89Sr was also approved as first therapeutic radiotracer for skeletal metastases, followed in the subsequent years by 186Rh, 153Sm and, more recently, 223Ra, the first alpha emitter clinically utilized, allowing curative results and not only a palliative effect. Proposed in first eighties as [131I] Metaiodobenzylguanidine (MIBG), the theragnostic couple 123I/131I MIBG is still used in neural crest tumors, while, starting from partially unsatisfactory results in 70's, models based on antibodies for radioimmunoscintigraphy/radioimmunotherapy have been subsequently upgraded thanks to the introduction of monoclonal antibodies and other significant biological and technical improvements. The "Theragnostics called with this name" can be dated to early 90's with the first proposal of the somatostatin model, actually widely operating in neuroendocrine tumors with radio-chelates usable for diagnosis and therapy. Since then, many investigators are working on new theragnostics agents, also outside of the nuclear medicine, based on peptides, antibodies and other tools to find new models applicable in the clinical practice. The fast growth is stimulated by the interest of big pharma. Theragnostic concepts are the roots of nuclear medicine and new great goals are soon to be achieved in the direction of an increasing precision and tailored medicine.

Association of CSF and PET markers of neurodegeneration with electroclinical progression in Lafora disease.

Purpose: To evaluate the electro-clinical features in association with laboratory and instrumental correlates of neurodegeneration to detect the progression of Lafora disease (LD). Methods: We investigated the electro-clinical longitudinal data and CSF Aß42, p-tau181 and t-tauAg, amyloid, and 18F-FDG PET of five unrelated LD families. Results: Three progressive electro-clinical stages were identified. The early phase was characterized by rare, generalized tonic-clonic and focal visual seizures, followed by the occurrence of myoclonus after a period ranging from 2 to 12 months. The intermediate stage, usually occurring 2 years after the onset of epilepsy, is characterized by a worsening of epilepsy and myoclonus associated with progressive dementia and cerebellar signs. Finally, the late stage, evolving after a mean period of 7 ± 1.41 years from the onset of the disease, was characterized by gait ataxia resulting in bedriddenness, severe dementia, daily/pluri-daily myoclonus, drug-resistant epilepsy, clusters of seizures or status epilepticus, and medical complications. Amyloid (CSF Aß42, amyloid PET) and neurodegenerative (CSF p-tau181 and t-tauAg, FDG-PET) biomarkers indicate a pattern of cognitive impairment of the non-Alzheimer's disease type. A total of 80% of the LD patients showed more severe hypometabolism in the second FDG-PET scan compared to the first scan performed in a lower phase; the lateral temporal lobe and the thalamus hypometabolism were associated with the presence of intermediate or late phase. Conclusions: Three electroclinical and 18F-FDG PET evolutive stages are useful biomarkers for the progression of LD and could help to evaluate the efficacy of new disease-modifying treatments. The combination of traditional CSF biomarkers improves the diagnostic accuracy of cognitive decline in LD patients, indicating a cognitive impairment of the non-Alzheimer's disease type.

Impact of 68Ga-DOTATOC PET/CT in comparison to 111In-Octreotide SPECT/CT in management of neuro-endocrine tumors: A case report.

RATIONALE: In the diagnostics of neuroendocrine tumors (NETs), scintigraphy and Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) with Indium-Octreotide occupy a prominent place.The introduction in clinical practice of Gallium-labelled somatostatin analogues (DOTA-TOC, DOTA-TATE, DOTA-NOC) for Positron Emission Tomography/Computed Tomography (PET/CT), significantly improved NETs diagnostics due to greater sensitivity and improved lesion detection in addition to better patient convenience and decreased radiation dose. PATIENT CONCERNS: We report a case of a patient who was diagnosed with a neuroendocrine tumor of the ileocecal valve. DIAGNOSES: Diagnosis was made by ultrasonography, CT, and colonoscopy. Hystology after surgery was G2 NET of ileo-cecal valve. Restaging was carried out by In-Octreotide SPECT/CT and, 1 month later, by Ga-DOTATOC PET/CT. F-FDG PET/C was also carried out. INTERVENTIONS: Ga-DOTATOC PET/CT showed larger disease that modified disease management from surgery to medical treatment. OUTCOMES: After an initial improvement in the patient clinical condition, the tumor caused a worsening with the appearance of ascites. LESSONS: Ga-DOTA-conjugate PET/CT is appropriate in low and intermediate NET (Ki67 index respectively ≤3% and 3%-20%) characterized by better survival and better response after Peptide Receptor Radionuclide Therapy.F-FDG is mostly useful in high grade (G3) of disease, so that Ga-DOTA-conjugate SUV and F-FDG SUV have an opposite trend in relation to the tumor grade. Ga-DOTATOC PET/CT changes, as in our case, therapeutic management in about 40% of cases.

Radioiodine treatment of Plummer and multinodular toxic and nontoxic goiter disease by the first approximation dosimetry method.

The aim of this study was to assess the efficacy of mean radioiodine activities of 12.6 MBq/mL in order to achieve a successful treatment of hyperthyroidism with a single radioiodine dose and a low incidence of hypothyroidism. We evaluated 51 patients with Plummer disease, 41 patients with multinodular toxic goiter, and 9 patients with compressive toxic and nontoxic goiter, after a short suspension of antithyroid drugs, with the exclusion of patients with critical cardiovascular conditions, an expanded iodine pool, and a nodular volume larger than 120 mL. Target volume was measured by ultrasonography and calculated by the ellipsoid method. All the patients underwent a thyroid uptake test with 1.85 MBq of (131)I and measurements on the neck and thigh at 2, 6, and 24 hours. Target volume was 21.5 +/- 21.4 mL for group 1, 15.4 +/- 10.7 mL for group 2, and 56.4 +/- 12.8 mL for group 3. The 24 hours uptake (mean % +/- standard deviation) was 43.1 +/- 19.9, 48.5 +/- 15.4, 56.4 +/- 12.8, respectively, for groups 1, 2 and 3. Mean follow-up was group 1: 23 +/- 17 months; group 2: 23 +/- 14 months; and group 3: 28 +/- 20 months. First approximation dosimetry took into account thyroid volume and the 24-hour uptake percentage. A euthyroidism condition was reached in 40 of 51 patients (78.4%) of group 1, 35 of 41 patients (85.4%) of group 2, and 6 of 9 patients (66.7%) of group 3. Hypothyroidism was observed in 13 of 101 patients (12.9%). Only 9 of 101 (8.9%) patients were subclinically hyperthyroid at the end of follow-up. The over-all efficacy of treatment was 91.1%. Reduction (%) of nodule volume was 66 +/- 23, 57 +/- 18, and 79 +/- 13, respectively, in groups 1, 2, and 3, with scintigraphic disappearance of hot nodules or persistence of cold nodules with the recovery of extranodular thyroid tissue in 76 patients.

Reinduction of cell differentiation and 131I uptake in a poorly differentiated thyroid tumor in response to the reverse transcriptase (RT) inhibitor nevirapine.

Our recent findings have shown that the reverse transcriptase (RT) inhibitors, nevirapine and efavirenz, used for 10 years in human immunodeficiency virus (HIV) disease, act as cytostatic and differentiating agents by modulating gene expression in several human tumor cell models. In dedifferentiated thyroid cancer, they reestablish thyroid-stimulating hormone (TSH) signaling, Na/I symporter (NIS), thyroglobulin peroxidase (TPO) expression, and even radioiodine uptake (RIU). In this paper, we describe the case of a 76-year-old woman who was affected by thyroid papillary carcinoma and who underwent a total thyroidectomy and a debulking of the right laterocervical region for lymph-node metastases, vessel infiltration, and neoplastic thrombosis of the internal jugular vein, followed by 3 radioiodine treatments. At restaging, a computed tomography scan revealed that distant metastases were mostly not taking up the radioiodine at the 131I whole-body scan (WBS). An analysis of tumor cells obtained by fine-needle aspiration biopsy of a right laterocervical lymph-node revealed cell anisokaryosis, nuclear pleomorphism, and scanty colloid, as well as the undetectable expression of thyroglobulin and NIS proteins. After starting a nevirapine treatment (NT), higher thyroglobulin levels were observed and some metastases exhibited a significant increase in radioiodine uptake, which led us to again treat the patient with 131I. Five (5) months later, the 131I-WBS revealed the disappearance of RIU in some metastases and its significant reduction in other lesions, with a parallel drop in serum thyroglobulin. No new metastatic lesion was revealed by rh-TSH-stimulated 131IWBS and 18F-flourodeoxyglucose positron emission tomography scan. Cells obtained from the right laterocervical lymph-node 2 months after NT exhibited a reduced nuclear pleomorphism, an increase in colloid production, and a significant upregulation of thyroglobulin and NIS protein expression. This first in vivo molecular and morphologic evidence of cell differentiation in human cancer and low toxicity of nevirapine strongly encourage its use in dedifferentiated thyroid cancer treatment.

Evaluation of different beta-counting systems involved in 90Y-Zevalin quality control.

BACKGROUND: 90Y-ibritumomab tiuxetan (90Y-Zevalin) is currently approved for radioimmunotherapy of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. The radioimmunoconjugate may be administered to the patient only if the radiolabelling yield is higher than 95%. AIM: To evaluate different methods of quality control testing for an accurate and rapid determination of radiolabelling yield in the clinical routine. METHODS: Five beta-counting systems, involved in determining the yield of radiolabelled 90Y-Zevalin, were compared: an autoradiography system (AS), a thin-layer chromatography (TLC) scanner system, a dose calibrator (DC), a liquid scintillation analyser (LSA) and high-performance liquid chromatography (HPLC). These instruments were also analysed in terms of efficiency, spatial resolution, analysis time, operating procedure level, cost and availability. RESULTS: Radiolabelling yields were comparable among all instruments except for DC whose values were dubious. Efficiency was 1.5+/-0.11 MDLU.s for the AS (where DLU means digital light unit), 3.5+/-0.2 kcps for the TLC analyser, 0.74+/-0.02 MBq for the DC, 15+/-0.12 kcps for LSA and 180+/-0.07 kcps for HPLC. Spatial resolution was 1 mm for AS and 5 mm for the TLC analyser. The quality control test needed 8 min with AS and DC, 15 min with TLC and LSA, and 50 min with HPLC. CONCLUSIONS: The short analysis time, high sensitivity, simultaneous detection of multiple radioactive strips and low cost offered by AS make it a suitable tool for radioactivity analysis and quantification in a radiopharmacy laboratory.

How the cognitive reserve interacts with ß-amyloid deposition in mitigating FDG metabolism: An observational study.

This observational study had the aim to assess the interaction between cognitive reserve (CR) and cerebrospinal fluid ß-amyloid1-42 (Aß1-42) in modulating brain [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) metabolism in patients with moderate Alzheimer disease (AD).Twenty-seven patients with probable AD and 25 neurological normal subjects (NNS) entered the study. All participants had an FDG-PET scan, and AD patients also received a lumbar puncture to measure Aß1-42, 181p-tau, and Tau concentrations. Based on years of formal education, AD patients were classified as highly educated-AD (years of formal education >5) or less educated-AD (years of formal education <5). By using a voxel-wise approach, we first investigated differences in the cerebral glucose uptake between AD and NNS, then we assessed the interaction between level of education (a proxy of CR) and cerebrospinal fluid biomarkers on FDG-PET metabolism in the patient groups.Significantly lower glucose uptake was observed in the posterior cingulate gyrus, in the precuneus, in the inferior and medial temporal gyrus, and in the inferior parietal lobule of AD patients compared with NNS. A significant interaction was found between CR and Aß1-42 values on brain metabolism in the inferior and medial temporal gyrus bilaterally.The AD patients with higher CR level and marked signs of neuropathology showed glucose hypometabolism in regions typically targeted by AD pathology. This finding supports the hypothesis that CR partially compensates for the effect of Aß plaques on cognitive impairment, helps in patients' clinical staging, and opens new possibilities for the development of nonpharmacological interventions.

Comparative evaluation of recombinant human thyrotropin-stimulated thyroglobulin levels, 131I whole-body scintigraphy, and neck ultrasonography in the follow-up of patients with papillary thyroid microcarcinoma who have not undergone radioiodine therapy.

CONTEXT: Although the prognosis of papillary thyroid microcarcinoma (PTMC) is usually excellent, the optimal follow-up strategy has never been investigated. OBJECTIVE: The objective of the study was to investigate the role of neck ultrasonography (US), whole-body scintigraphy (WBS), and serum thyroglobulin levels (Tg) after recombinant human (rh) TSH in the follow-up of very low-risk PTMC patients. DESIGN: The study was a 5-yr observational study based on a 6- to 12-month follow-up after near total thyroidectomy. SETTING: The study population consisted of ambulatory patients. PATIENTS: Eighty consecutive patients diagnosed with PTMC, who had not undergone postoperative radioiodine treatment because of unifocal tumor without lymph node metastases and who did not have anti-Tg antibodies, were included. MAIN OUTCOME MEASURES: WBS and Tg after both rhTSH and neck US were measured. RESULTS: rhTSH-Tg was 1 ng/ml or less in 45 (Tg-) and more than 1 in 35 (Tg+) patients. WBS showed no pathological uptake in any patient. US identified node metastases in two Tg (+) and one Tg (-) patients. rhTSH-Tg levels positively correlated with thyroid bed iodine uptake (r = 0.40, P < 0.0001). To date (32 +/- 13 months after surgery), all node-negative patients have undetectable Tg levels on LT(4) treatment and negative US. CONCLUSIONS: For the initial follow-up of PTMC patients without risk factors and anti-Tg antibodies and who did not undergo radioiodine treatment: 1) WBS is useless; 2) US is highly sensitive in detecting node metastases; and 3) detectable rhTSH-Tg levels mainly depend on small normal tissue remnants. In this subgroup of PTMC patients, neck US might be regarded as a primary tool for the initial follow-up.

Percutaneous ethanol injection plus radioiodine versus radioiodine alone in the treatment of large toxic thyroid nodules.

UNLABELLED: Therapeutic options for toxic thyroid nodules (TTNs) are surgery, radioiodine (RAI), and percutaneous ethanol injection (PEI). Surgery is generally considered for TTNs larger than 4 cm. However, some patients may be at high surgical risk. The purpose of the study was to evaluate the efficacy of 2 nonsurgical modalities for these TTNs. METHODS: Twenty-two patients with TTNs larger than 4 cm were randomly assigned to 2 different treatments: to 11 (subgroup A), RAI was administered at a dose of 12,580 kBq/mL of nodular volume (NV) and was corrected for 100% 24-h (131)I uptake (RAIU); to 11 (subgroup B), 2-4 PEI sessions (ethanol injected = 30% NV) preceded 2 mo of 24-h RAIU and RAI dosing. Inclusion criteria were clinical and biochemical hyperthyroidism; a single palpable, hot nodule at (99m)Tc scintigraphy; and high surgical risk or refusal to have surgery. Patients gave informed consent. Local symptoms were evaluated by a previously validated score (symptom score, or SYS). RESULTS: Both treatments were well tolerated. Subgroup B showed a significant reduction of NV 2 mo after PEI: 33.6 +/- 18.5 versus 60.8 +/- 29.5 mL. Their 24-h RAIU was similar to that of subgroup A: 53.9 +/- 13.9 versus 61.8% +/- 11.0%. Consequently, the administered RAI dose was significantly lower for subgroup B (730 +/- 245 MBq) than for subgroup A (1,048 +/- 392 MBq). Twelve months after RAI, subgroup B had a higher NV reduction and a lower SYS than did subgroup A. In subgroup A, 1 patient was subclinically hyperthyroid, 2 showed a slight increase of thyroid-stimulating hormone, and 1 was clinically hypothyroid. In subgroup B, 1 patient had a slight increase of thyroid-stimulating hormone. CONCLUSION: We demonstrated that RAI, alone or with PEI, can be considered a valid alternative for TTNs larger than 4 cm when surgery is either refused or contraindicated. PEI plus RAI can be considered when marked shrinkage of a nodule is required or when reduction of the RAI dose can prevent hospitalization.

Serum thyroglobulin and 131I whole body scan after recombinant human TSH stimulation in the follow-up of low-risk patients with differentiated thyroid cancer.

OBJECTIVE: The 'standard' postoperative follow-up of patients with differentiated thyroid cancer (DTC) has been based upon serum thyroglobulin (Tg) measurement and (131)I whole body scan ((131)I-WBS) after thyroid hormone (T(4)) treatment withdrawal. However, (131)I-WBS sensitivity has been reported to be low. Thyroid hormone withdrawal, often associated with hypothyroidism-related side effects, may now be replaced by recombinant human thyroid stimulating hormone (rhTSH). The aim of our study was to evaluate the diagnostic accuracy of (131)I-WBS and serum Tg measurement obtained after rhTSH stimulation and of neck ultrasonography in the first follow-up of DTC patients. DESIGN: Ninety-nine consecutive patients previously treated with total thyroidectomy and (131)I ablation, with no uptake outside the thyroid bed on the post-ablative (131)I-WBS (low-risk patients) were enrolled. METHODS: Measurement of serum Tg and (131)I-WBS after rhTSH stimulation, and ultrasound examination (US) of the neck. RESULTS: rhTSH-stimulated Tg was 1 ng/ml (Tg+) in 21 patients, including 6 patients with Tg levels >5 ng/ml. (131)I-WBS was negative for persistent or recurrent disease in all patients (i.e. sensitivity = 0%). US identified lymph-node metastases (confirmed at surgery) in 4/6 (67%) patients with stimulated Tg levels >5 ng/ml, in 2/15 (13%) with Tg >1<5 ng/ml, and in 2/78 (3%) who were Tg-negative. CONCLUSIONS: (i) diagnostic (131)I-WBS performed after rhTSH stimulation is useless in the first follow-up of DTC patients; (ii) US may identify lymph node metastases even in patients with low or undetectable serum Tg levels.

Media Fill Test for validation of autologous leukocytes separation and labelling by (99m)Tc-HmPAO.

OBJECTIVE: Manufacturing of sterile products must be carried out in order to minimize risks of microbiological contamination. White blood cells (WBC) labelled with (99m)Tc-exametazime ((99m)Tc-hexamethylpropyleneamine oxime; (99m)Tc-HMPAO) are being successfully applied in the field of infection/inflammation scintigraphy for many years. In our radiopharmacy lab, separation and labelling of autologous leukocytes with (99m)Tc-HMPAO were performed in a laminar flow cabinet not classified and placed in a controlled area, whereas (99m)Tc-HMPAO radiolabelling procedure was carried out in a hot cell with manipulator gloves. This study was conducted to validate this process using a Media Fill simulation test. METHODS: The study was performed using sterile Tryptic Soy Broth (TSB) in place of active product, reproducing as closely as possible the routine aseptic production process with all the critical steps, as described in the our internal standard operative procedures (SOP). The final vials containing the media of each processed step were then incubated for 14 days and examined for the evidence of microbial growth. RESULTS: No evidence of turbidity was observed in all the steps assayed by the Media Fill. CONCLUSIONS: In the separation and labelling of autologous leukocytes with (99m)Tc-HmPAO, Media-Fill test represents a reliable tool to validate the aseptic process.

Brain SPECT imaging of ictal smile seizure.

"Ictal smile" is defined as a facial expression during a seizure, which usually translates happiness, clearly distinct from a tonic deviation of the mouth or other abnormal tonic-clonic movements involving the face, not associated to any happiness emotion (Epilepsia. 1998;39:1357-1360). It is a rare condition (6%-10% of patients; Epilepsia. 1998;39:1357-1360) and seems to be related to seizures arising from temporal or frontal regions (Brain. 2003;126:2121-2138).Anecdotal reports of brain perfusion SPECT performed during ictal and interictal phases (Epilepsia. 1998;39:1357-1360) do not supply, unfortunately, imaging documentation. Thus, we report the first evidence of brain perfusion abnormalities induced by ictal smile seizure.

Multiple skeletal muscle metastases from colon carcinoma preceded by paraneoplastic dermatomyositis.

Skeletal muscle metastases are very rare events in colorectal carcinoma. By contrast, dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations and a well-recognized association with several human malignancies and, among others, colorectal cancer. Here, we report the case of a 71-year-old woman with paraneoplastic dermatomyositis followed by the development of a metastatic colon cancer. Interestingly, this patient developed multiple skeletal metastases which were preceded by the worsening of systemic symptoms of dermatomyositis. This observation suggests that, while muscle tissue is usually resistant to the development of tumor metastases, the inflammatory and immune response which characterizes and boosts paraneoplastic myopathy may represent a favorable soil for tumor cell invasion and metastasization to skeletal muscles.

A proposal for phosphor imager acceptance testing procedure and routine quality controls in nuclear pharmacy practice.

OBJECTIVE: The digital autoradiography system is currently used in nuclear medicine for quantitative imaging of radioactivity distribution (thin layer chromatography samples, tissue sections, and cell cultures). The aim of this study was to define a set of tests for setting up a specific acceptance testing procedure and routine quality controls for this instrument. MATERIALS AND METHODS: Over a 3-month period, we analyzed the active components of the instrument (phosphor screen and photometer) by using suitable self-manufactured equipment (phantoms, lead plate, lead cylinder, and photographic paper) required to realize, in a routine quality program, the following tests: integral uniformity (IU) and differential uniformity (DU) in a useful field of view (UFOV) and a central field of view (CFOV), resolution, geometric linearity, and sensitivity. RESULTS: Screen IU was 19.7 ± 2.3% (UFOV) and 11.1 ± 3.7% (CFOV). Screen DU ranged between 1.6 ± 1.1 and 1.8 ± 0.9% for UFOV and between 1.2 ± 0.4 and 1.4 ± 0.6% for CFOV. Screen resolution measured as full-width at half-maximum was 1.94 ± 0.08 mm. Screen sensitivity was 505.1 ± 10.4 digital light units and ranged between -3.15 and +3.49% with reference to the mean of measured values. Photometer IU was 17.4 ± 0.2% (UFOV) and 13.7 ± 1.1% (CFOV). Photometer DU ranged between 1.9 ± 0.9 and 2.3 ± 1.2% for UFOV and between 1.9 ± 0.8 and 2.1 ± 1.1% for CFOV. Photometer resolution was good (full-width at half-maximum =0.5 ± 0.076 mm). CONCLUSION: Our results suggest that the methodology we propose could be an easy, accurate, quick, and low-cost tool to guarantee the correct instrument basic function.

Effects of ethylene oxide and steam sterilization on dialysis-induced cytokine release by cuprophan membrane.

The effects of sterilization modalities on dialysis-induced cytokine release are still unknown. To investigate these effects, 8 patients on chronic hemodialysis were enrolled for evaluating at different intervals interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) production (pg/ml/106). They were using a 1.3 m2 ethylene oxide (E3) or steam (E3S) sterilized Cuprophan membrane. The patients underwent a basal test with E3 (A1) and 2 following tests after 1 (B1) and 2 (B2) months of E3S treatment, respectively. Finally, the last test was performed 1 month after the switch to E3 (A2). Il-1beta predialysis release by mononuclear cells was 162 +/- 114 pg/ml/106 in A1, 185 +/- 129 pg/ml/106 in B1, and 226 +/- 138 pg/ml/106 in B2, then decreased to 123 +/- 134 in A2 (p < 0.07). Il-1beta postdialysis levels were 234 +/- 238 pg/ml/106 in A1, 429 +/- 285 pg/ml/106 (B1), and 438 +/- 473 pg/ml/106 (B2) with the steam membrane, decreasing to 204 +/- 134 pg/ml/106 in A2 (p < 0.01). TNF-alpha predialysis basal release (A1) was 826 +/- 817 pg/ml/106, 720 +/- 496 in B1, and 1079 +/- 515 pg/ml/106 in B2, and finally 680 +/- 588 pg/ml/106 in A2 (p < 0.03). In postdialysis TNF-alpha levels were 963 +/- 542 pg/ml/106 in A1, 1,226 +/- 541 pg/ml/106, and 1,183 +/- 776 in B1 and B2 respectively, and 388 +/- 297 pg/ml/106 in A2 (p < 0.003). Steam sterilization seems to induce a higher cytokine release by mononuclear cells when a Cuprophan membrane is used. This finding may be related to a less physiologic action of the steam in the case of Cuprophan membranes. Further studies are needed to clarify this hypothesis.