Evaluation of ImpENSA technology-enabled behaviour change module delivered to healthcare professionals in South Africa to improve micronutrient nutrition during the first 1000 days.

Healthcare professionals (HCPs) have vital roles in providing evidence-based care to promote healthy micronutrient nutrition in early life. Providing such care requires scalable training to strengthen knowledge and confident application of effective behaviour change skills. Among 33 public and private HCPs (primarily dietitians) in South Africa, we evaluated the behaviour change aspects of a technology-enabled National Qualification Sub-Framework level 6 programme, Improving Early Nutrition and Health in South Africa ('ImpENSA'). This programme comprises two self-directed micronutrient and behaviour change knowledge-based eLearning and one facilitated online practical skills modules to improve maternal and infant micronutrient nutrition. Using assessments, questionnaires and interviews, we collected data at baseline, after module completion and at 3-month follow-up after programme completion. Questionnaire and interview data showed major improvements in understanding of and attitudes towards person-centred behaviour change support immediately following the eLearning module on behaviour change. The assessment pass rate increased from 38% at baseline to 88% postmodule, demonstrating significant knowledge gain in behaviour change support. Intention to change practice towards a person-centred approach was high and many had already started implementing changes. Three months postprogramme, support was centred around patients' needs. Open relationships with patients, improved patient outcomes and increased job satisfaction were among reported outcomes. Many reported becoming better change facilitators and reflective practitioners. Additional improvements in understanding and attitudes to behaviour change support were evident, reinforced by making changes and experiencing positive outcomes. The findings suggest that technology-enabled learning can equip HCPs with knowledge and skills to effectively support behaviour change for healthy micronutrient nutrition during pregnancy and infancy.

Ultrasound-Assisted Lumbar Punctures in Children: An Updated Systematic Review With Meta-Analysis.

CONTEXT: Lumbar puncture (LP) is a common procedure in children, but the rates of unsuccessful and traumatic LPs remain high. Point-of-care ultrasound (POCUS) has been proposed as a tool for improvement. OBJECTIVES: Our aim was to systematically review current evidence on the usefulness of POCUS assisted LP in children. DATA SOURCES: PubMed, Embase, and the CENTRAL were searched up to November 2022. STUDY SELECTION: We searched for randomized control trials assessing the effectiveness of POCUS assisted LP in children. DATA EXTRACTION: Data were extracted by 2 reviewers independently. RESULTS: Seven randomized control trials involving 618 participants were included. Overall, the first attempt POCUS assisted LP was successful in 72% compared with 59.6% in the standard group, regardless of the definition used. The calculated risk difference was 13.0% (95% confidence interval [CI]: 3% to 23%) I2:53%, odds ratio: 2.00 (95% CI: 1.13 to 3.53), I2: 45% and risk ratio:1.21 (95% CI: 1.01 to 1.44) I2:64%. Additionally, fewer traumatic LPs occurred in the US-assisted group, with a risk difference of -12% (95% CI: -0.22 to -0.03), odds ratio: 0.45 (95% CI: 0.26 to 0.78) and risk ratio: 0.53 (95% CI: 0.35 to 0.79). POCUS did not extend the duration of LP procedure with mean difference: -1.11 (95% CI: -2.88 to 0.66). CONCLUSIONS: POCUS improved the first attempt success rate and reduced the incidence of traumatic LPs compared with standard LP procedure in children. Therefore, if it is available, POCUS should be used routinely before every LP, especially when performed by less experienced physicians.

Point-of-care ultrasound to assess degree of dehydration in children: a systematic review with meta-analysis.

BACKGROUND: There is no perfect method to assess level of dehydration in children. There are studies with conflicting results, where point-of-care ultrasound (POCUS) measurement of diameter ratio of the inferior vena cava to the aorta (IVC/Ao) was used to predict degree of dehydration. OBJECTIVE: To systematically review the diagnostic accuracy of POCUS measurement of IVC/Ao ratio in predicting dehydration in children. METHODS: MEDLINE, EMBASE and Cochrane databases were searched. The primary outcome was the diagnostic accuracy of IVC/Ao ratio. The pooled sensitivity and specificity were calculated. Quality analysis was conducted using Quality Assessment of Diagnostic Accuracy Studies-2. RESULTS: Eleven studies (2679 patients) were included. The most numerous group (five studies) used percentage weight change as a reference standard; the pooled sensitivity, specificity of POCUS in this group were: 0.7 (95% CI: 0.67 to 0.73), I2: 82%; 0.53 (95% CI: 0.5 to 0.53), I2: 84%. In the remaining studies, different comparator tests were used: Clinical Dehydration Scale (two studies, 0.8 (95% CI: 0.72 to 0.86), I2: 0%; 0.56 (95% CI: 0.48 to 0.65), I2: 0%; clinical judgement (three studies, 0.78 (95% CI: 0.73 to 0.83), I2: 95%; 0.82 (95% CI: 0.77 to 0.86), I2: 93% and one study used the Dehydration: Assessing Kids Accurately score model. CONCLUSION: This systematic review and meta-analysis showed that POCUS has a moderate sensitivity and specificity for identifying dehydration in children. Its use as a complementary diagnostic tool could be promising but needs to be validated in randomised controlled trials. PROSPERO REGISTRATION NUMBER: CRD42022346166.

Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE-A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center.

Neuroendocrine neoplasms (NENs) are a group of neoplasms arising from neuroendocrine cells. The worldwide incidence and prevalence of the NENs are estimated to be 6/100,000 and 35/100,000, respectively. Those numbers are increasing every decade, requiring higher and higher diagnosis and treatment costs. Radioligand therapy (RLT) using beta-emitting radioisotopes is an efficient and relatively safe method of treatment, typically used as a second-line treatment. RLT tolerability is higher than other available pharmacotherapies (chemotherapy or tyrosine kinase inhibitors). Recent studies show an increase in overall survival among patients treated with RLT. The present study aimed to learn the epidemiology of NENs in Poland and assess the effectiveness of RLT in a high-reference center. A prospective analysis of 167 patients treated with RLT in one of Poland's highest-reference NEN centers was performed. The analysis covered 66 months of observation (1 December 2017-30 May 2023), during which 479 RLT single administrations of radioisotope were given. The standard procedure was to give four courses of [177Lu]Lu-DOTA-TATE alone, or tandem therapy-[177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE. Grading analysis showed that most patients had non-functioning G2 NEN with a mean Ki-67 of 6.05% (SD ± 6.41). The most common primary tumor location was the pancreas. Over two-thirds of patients did undergo surgery due to primary tumors or distant metastases. The majority of patients were using lanreotide as a chronically injected somatostatin analog. Median progression-free survival (PFS) on somatostatin analogs was 21.0 (IQR = 29.0) months. Directly after the last course of RLT, disease stabilization was noted in 69.46% of patients, partial regression was noted in 20.36% of patients, complete regression was noted in 0.60% of patients, and progression was noted in 9.58% of patients. In long-term follow-up, the median observation time among patients who underwent four treatment cycles (n = 108) was 29.8 (IQR = 23.9) months. Stabilization of the disease was observed in 55.56% of the patients and progression was observed in 26.85% of the patients, while 17.59% of patients died. Median PFS was 29.3 (IQR 23.9), and the median OS was 34.0 months (IQR 16.0). The mean age of NEN diagnosis is the sixth decade of life. It takes almost three years from NEN diagnosis to the start of RLT. In long-term observation, RLT leads to disease stabilization in over half of the patients with progressive disease. No differences in PFS or OS depend on the radioisotope used for RLT. In Poland, organized coordination of NEN treatment in high-reference centers ensures the continuity of patient care.

Radioligand Therapy with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE in Patients with Neuroendocrine Neoplasms of Unknown Locations, or Locations Other Than the Midgut and Pancreas as Primaries in a G1, G2 and G3 Grade.

BACKGROUND: Neuroendocrine neoplasms (NENs) are a rare group of tumors with a different clinical course, prognosis and location. Radioligand therapy (RLT) can be used as a first or second line of treatment. It is registered in gastroenteropancreatic NENs (GEP-NENs) as grades G1 and G2. Tumors with an unknown point of origin, diagnosed outside the gastrointestinal tract and pancreas (non-GEP) or at the G3 grade, remain in the "grey area" of treatment. MATERIALS AND METHODS: Analysis of 51 patients with NENs who underwent RLT in a single highest reference center from 2018 to 2023 was performed. Treatment was administrated to the patients with neoplasms of unknown origin, non-GEP-NENs, and ones with G3 grade. In total, 35 patients received 177-Lutetium (7.4 GBq), while 16 received 177-Lutetium and 90-Yttrium with equal activities (1.85 + 1.85 GBq). RESULTS: The progression-free survival (PFS) before RLT qualification was 34.39 ± 35.88 months for the whole study group. In subgroups of patients with an unknown tumor location (n = 25), the median PFS was 19 months (IQR = 23), with "other" locations (n = 21) at 31 months (IQR = 28), and with NEN G3 (n = 7) at 18 months (IQR = 40). After RLT, disease stabilization or regression was observed in 42 (87.5% of) patients. RLT did not cause statistical changes in creatinine or GFR values. Hematological parameters (RBC, WBC, PLT, HGB) as well as chromogranin A concentration decreased significantly. There were no statistical differences between both subgroups regarding the type of radioisotope (177-Lutetium vs. 177-Lutetium and 90-Yttrium). After RLT in long-term observation, the median observation time (OT) was 14 months (IQR = 18 months). In patients with progression (n = 8), the median PFS was 20 months (IQR = 16 months), while in patients with confirmed death (n = 9), the median overall survival (OS) was 8 months (IQR = 14 months). CONCLUSIONS: Our study showed that 87.5% of NEN patients with unknown origin, non-GEP-NENs, and those with GEP-NEN G3 grade had benefited from the radioligand therapy. There were no significantly negative impacts on renal parameters. The decrease of bone marrow parameters was acceptable in relation to beneficial disease course. The decrease of chromogranin concentration was confirmed as a predictive factor for disease stabilization or regression.

Renal Disturbances during and after Radioligand Therapy of Neuroendocrine Tumors-Extended Analysis of Potential Acute and Chronic Complications.

Neuroendocrine tumors (NEN) are a group of neoplasms that arise from hormonal and neural cells. Despite a common origin, their clinical symptoms and outcomes are varied. They are most commonly localized in the gastrointestinal tract. Targeted radioligand therapy (RLT) is a treatment option which has proven to be successful in recent studies. However, the possible outcomes and true safety profile of the treatment need to be fully determined, especially by new, more sensitive methods. Our study aimed to present an extended analysis of acute and chronic renal complications during and after radioligand therapy using, for the first time in the literature, innovative and complex renal parameters. Forty patients with neuroendocrine tumors underwent four courses of radioligand therapy with [177Lu]Lu-DOTATATE or [177Lu]Lu/[90Y]Y-DOTATATE. Radioisotopes were administrated in intervals of 8-12 weeks, with concurrent intravenous nephroprotection. New detailed and sensitive renal parameters were used to determine the renal safety profile during and after radioisotope therapy for standard treatment of NEN. During the first and fourth courses of RLT, no change in the glomerular filtration rate (GFR) was observed. However, long-term observations one year after the treatment showed a 10% reduction in the GFR. During the first course of treatment, the fractional urea and calcium excretions increased, while the fractional potassium concentration decreased. The fractional calcium excretion remained highly increased in long-term observations. Decreases in urine IL-18, KIM-1 and albumin concentrations were observed during RLT. The concentrations of IL-18 and KIM-1 remained low even a year after therapy. The ultrasound parameters of renal perfusion changed during treatment, before partially returning to the baseline one year after therapy, and were correlated with the biochemical parameters of renal function. A permanent increase in diastolic blood pressure was correlated with the decrease in the GFR observed during the study. In this innovative and complex renal assessment during and after RLT, we found a permanent 10% per year decrease in the GFR and noticeable disturbances in renal tubule function. The diastolic blood pressure also increased.

Strain-Specificity of Probiotics in Pediatrics: A Rapid Review of the Clinical Evidence.

OBJECTIVE: The dogma of probiotic strain-specificity is widely accepted. However, only the genus- and species-specific effects of probiotics are supported by evidence from clinical trials. The aim of this rapid review was to assess clinical evidence supporting the claim that the efficacy of probiotics in the pediatric population is strain-specific. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched (up to August 2022) for randomized controlled trials (RCTs) conducted in children aged 0-18 years evaluating the effects of prophylactic or therapeutic administration of probiotics (well-characterized at the strain level) for conditions such as antibiotic-associated diarrhea, acute diarrhea, necrotizing enterocolitis, respiratory tract infections, Helicobacter pylori infection, and atopic dermatitis. To allow evaluation of strain-specificity, a trial could only be included in the review if at least one additional RCT assessed the effect of a different strain of the same species against the same comparator. RCTs without proper strain-level data were excluded. In the absence of identifying head-to-head strain versus strain RCTs, indirect comparisons were made between interventions. RESULTS: Twenty-three RCTs were eligible for inclusion. Out of the 11 performed comparisons, with 1 exception (two Lacticaseibacillus paracasei strains in reducing atopic dermatitis symptoms), no significant differences between the clinical effects of different strains of the same probiotic species were found. CONCLUSIONS: Head-to-head comparison is an optimal study design to compare probiotic strains, but such comparisons are lacking. Based on indirect comparisons, this rapid review demonstrates insufficient clinical evidence to support or refute the claim that probiotic effects in children are strain-specific.

Re-treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE of patients with progressive neuroendocrine neoplasm.

BACKGROUND: Neuroendocrine neoplasms (NENs) are heterogeneous groups of tumours derived from neuroendocrine cells of the ectoderm or endoderm. They are considered rare, with an estimated incidence and prevalence of 6/100,000 and 35/100,000 respectively, and a noticeable upward trend. Radioligand therapy (RLT) using beta-radiation-emitters combined with somatostatin analogues is an effective and relatively safe treatment method. It is usually used as a second-line therapy in case of progressive disease. MATERIAL AND METHODS: In retrospective analysis covering eight years of observation (2015-2023) of patients treated in a single highest-reference NEN centre, a subgroup of 13 who received RLT re-treatment (¹77Lu or ¹77Lu/9°Y-mixture) was identified. Epidemiological aspects, renal, hepatic, haematological parameters and chromogranin A serum concentration were analysed. RESULTS: The median PFS after the first cycle of RLT was 53.8 months (IQR = 19.3). Directly after the second cycle of RLT disease stabilization and progression was observed in 11/13 (84.6%) and 2/13 (15.4%) patients respectively. After the second cycle of RLT median observation time for the study group was 16.2 months. Eight out of 13 patients were reachable for long-term observation and stabilization was confirmed in 62.5 % (5/8), progression in 12.5% (1/8) and death in 25% (2/8) patients. Median survival time in patients with confirmed death was 7 months. During observation, an increase in creatinine concentration with a decrease in glomerular filtration rate (GFR) was noticed, however, the values were at a statistical trend level (p = 0.056; p = 0.071). The increase of liver parameters was statistically, but not clinically significant. The decrease in albumin concentration and fasting glucose concentration were not significant. An increase in chromogranin A concentration correlated, although not statistically, with the progression of the disease. A statistically significant decrease in the number of all bone marrow cell lines was observed. The first RLT cycle caused a higher decrease in blood parameters than the second. There were no differences in PFS or laboratory parameters depending on the radioligand ([¹77Lu]Lu-DOTA-TATE vs. [¹77Lu]Lu-DOTA-TATE/[9°Y]Y-DOTA-TATE). CONCLUSIONS: In follow-up after RLT re-treatment stabilization was observed in 62.5%, progression in 12.5% and death in 25% of patients. Decrease of glomerular filtration, and bone marrow parameters resulted from the cumulative adverse effect of RLT, the natural ageing process, and the progression of the disease. Side effects were mainly caused by the first treatment cycle. There was no significant influence on the measured parameters, depending on the radioisotope used. Re-treatment of RLT seems to be a reliable and relatively safe method, thus should be considered in patients who underwent one cycle of RLT and responded to the treatment.

Infant Formulas With Postbiotics: An Updated Systematic Review.

OBJECTIVES: Infant formulas (IF) with postbiotics, defined as inanimate microorganisms and/or their components that confer a health benefit on the host, are available. We systematically updated evidence on the safety and health effects of administering iF with postbiotics (with or without other modifications) compared with standard IF. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched to December 2021. RESULTS: Eleven randomized controlled trials were included. Using the Cochrane Risk of Bias Tool 2, for the primary outcomes, 5 trials had an overall high risk of bias, and 6 trials had some concerns of bias. Most data were available on IF fermented with Bifidobacterium breve C50 and Streptococcus thermophilus (BB/ST). These formulas, compared with the standard IF, were safe and well tolerated. Postbiotic formulas with additional modifications (ie, formula fermented with BB/ST & prebiotics, partly fermented formula with BB/ST and prebiotics with or without modified milk fat, partly fermented antiregurgitation formula with BB/ST and prebiotics) were generally safe and well tolerated but did not offer clear benefits replicated in other studies. Only limited data were available on formula fermented with Lactobacillus paracasei CBA L74. CONCLUSIONS: IF with postbiotics evaluated so far are safe and well tolerated by infants who cannot be breastfed. No firm conclusion can, however, be reached regarding the clinical effects and benefit of one formula over another. It seems reasonable to discuss with healthcare providers current evidence regarding specific modifications in infant formulas and let them decide whether the expected benefits meet expectations and are worth the cost.

Hepatic complications of peptide receptor radionuclide therapy with Lutetium-177 and Yttrium-90 in patients with neuroendocrine neoplasm.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors originating from neuroendocrine cells spread throughout the body, forming the so-called diffuse endocrine system. The gold standard in treating unresectable or disseminated, progressive, and well-differentiated NENs is therapy with radiolabeled somatostatin analogs (peptide receptor radionuclide therapy - PRRT). PRRT is a method based on peptides combined with beta-emitting radionuclides. The study aimed to assess the early and long-term liver complications after administration of Lutetium-177 or Lutetium-177 combined with Yttrium-90. We enrolled 27 patients treated with [177Lu]Lu-DOTATATE with an activity of 7.4 GBq (200 mCi) and 9 patients received the tandem treatment [90Y]Y-DOTATATE + [177Lu]Lu-DOTATATE with an activity of 3.7 GBq (50 mCi + 50 mCi). In the assessment of early as well as long-term complications, no significant effect of the applied treatment on the parameters of liver injury was found. Regarding liver function PRRT was a safe treatment for patients with highly or moderately differentiated, unresectable, or diffuse NENs.

Infectious Etiology of Vomiting in Children With Presumed Acute Gastroenteritis in the Absence of Diarrhea: Protocol for a Cohort Study.

NCT05270291, https://clinicaltrials.gov/ct2/show/. Objectives: In children with acute gastroenteritis (AGE), vomiting often precedes diarrhea. To establish the diagnosis of AGE, enteropathogen detection typically relies on diarrheal stool samples. However, testing requires sufficient stool sample, which may not be easily available. Recent studies suggest that in children presenting to emergency departments with presumed AGE with isolated vomiting, an enteropathogen can be identified using rectal swabs and molecular diagnostic tests. The rate of enteropathogen detection in children with isolated vomiting due to AGE may differ in various populations. Using rectal swabs and molecular diagnostic tests, we plan to assess the proportion of children with isolated vomiting with presumed AGE in whom an enteropathogen can be identified. Methods: This will be a cohort study conducted in the emergency department(s) of one or more pediatric hospital(s) in Poland. Children younger than 5 years with the presence of ≥3 episodes of vomiting due to presumed AGE, lasting no longer than 7 days before enrollment, will be recruited. The primary outcome will be the proportion of children with isolated vomiting in whom an enteropathogen is detected. In all eligible participants, rectal swabs will be taken to perform molecular testing for detection of typical viral and bacterial enteropathogens. All children will be followed-up at 14 days after the initial contact to classify them into one of three groups (i.e., vomiting only, vomiting and diarrhea, and diarrhea only).

Usefulness of PET/CT with Carbon-11-Labeled Methionine in the Diagnosis of Tertiary Hyperparathyroidism.

Introduction: Tertiary hyperparathyroidism (tHP) may develop in patients treated with hemodialysis or peritoneal dialysis. Parathyroidectomy may result in a significant reduction in the severity of symptoms. For the effective surgical treatment of hyperparathyroidism, proper localization of the parathyroid glands prior to surgery is essential. The sensitivity of scintigraphy in the diagnosis of tHP is lower than in the diagnosis of primary hyperparathyroidism. In recent years, positron emission tomography (PET/CT) has been gaining importance, usually as a complementary technique. Aim: The aim of this study was to determine the usefulness of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tertiary hyperparathyroidism caused by chronic kidney disease, in whom first-line diagnostic methods did not allow the localization of pathologically parathyroid glands. Material and methods: The study was conducted in a group of 19 adult patients with severe tHP who were resistant or intolerant to non-invasive treatment, with negative results of scintigraphy and ultrasonography of the neck. The study protocol included measurement of the concentration of calcium, phosphorus, and PTH in the blood serum and performing PET/CT with [11C]MET. Results: A positive result of PET/CT was obtained in 89.5% of the patients (17/19). Parathyroidectomy was performed in 52.9% of the patients (9/17) with positive results of PET/CT with [11C]MET, which were fully consistent with the results of the histopathological examinations of the removed parathyroid glands. On this basis, the sensitivity of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tHP was found to be 100%. Multiple lesions were visualized in 57.9% of the patients (11/19). Ectopic lesions were visualized in 21.1% of the patients (4/19). Conclusions: PET/CT with [11C]MET is a sensitive technique for the second-line preoperative imaging of parathyroid glands in patients with tertiary hyperparathyroidism in whom first-line examinations, such as ultrasound and scintigraphy, has failed.

Long-Term Complications of Radioligand Therapy with Lutetium-177 and Yttrium-90 in Patients with Neuroendocrine Neoplasms.

BACKGROUND: Neuroendocrine neoplasms are a group of tumors deriving from neural crest. They can be located in every tissue, but most commonly in gastrointestinal tract. Targeted therapy with use of radionuclides is an available and acceptable way of treatment, but its long-term safety is still to be determined, especially with sensitive methods. METHODS: Study was performed on a group of 42 patients. They underwent full cycle (4 courses; 8-12 weekly intervals) of radioligand therapy with [177Lu]Lu-DOTATATE alone or tandem therapy with [177Lu]Lu-DOTATATE+[90Y]Y-DOTATATE. Late and long-term marrow and renal complications were assessed. Analysis focused on comparing data before first, fourth, and one year after the last course of RLT. RESULTS: Study showed decreasing of all blood parameters in long-term observation, especially in lymphocytes line. Type of radioisotope, other diseases, primary tumor location, BMI, gender or age did not affect results. The only factor that had influence on hemoglobin and erythrocytes was decreased renal filtration. In long-term observation almost 10% decrease of renal filtration was observed. Type of isotope, gender, age, BMI did not affect these results. Moreover, reduction of urine IL-18, KIM-1, and albumin concentration has been observed. CONCLUSIONS: Though low-grade complications of radioligand therapy are possible, it stay a safe method of NEN treatment where benefits outweigh the risk.

Evaluation of the usefulness of positron emission tomography with [18F]fluorodeoxylglucose performed to detect non-radioiodine avid recurrence and/or metastasis of differentiated thyroid cancer - a preliminary study.

BACKGROUND: About 30% of patients with disseminated differentiated thyroid cancer (DTC) may experience a loss of iodine uptake. It is associated with higher aggressiveness of the tumour and a reduced 10-year survival rate. The diagnosis of non-radioiodine avid DTC metastases remains a diagnostic challenge. A helpful technique for this diagnosis is positron emission tomography with 2-[¹8F]fluoro-2-deoxy-D-glucose (PET/CT with [¹8F]FDG). On the other hand, there are still discussions about the clinical value of using exogenous thyroid-stimulating hormone (TSH) stimulation before PET/CT with [¹8F]FDG. The aim of the study was the assessment of the usefulness of PET/CT with [¹8F]FDG under TSH suppression and stimulation of TSH performed in the detection of non-radioiodine avid DTC metastases, as well as determination of the thyroglobulin concentration under suppression and stimulation of TSH, which influences the result of PET/CT with [¹8F]FDG in patients with non-radioiodine avid DTC. MATERIAL AND METHODS: Retrospective analysis of 37 PET/CT with [¹8F]FDG performed in patients with DTC diagnosed and treated at the Department of Endocrinology and Isotope Therapy of the Military Institute of Medicine from January 2018 to July 2020. Of these, PET/CT with [¹8F]FDG under exogenous rhTSH stimulation was performed in 22 patients and PET/CT with [¹8F]FDG under TSH suppression in 15 was performed. In all analyzed patients, the result of diagnostic whole-body scintigraphy (WBS) using 80 MBq ¹³¹I under rhTSH stimulation was negative, and the concentration of thyroglobulin after stimulation (sTg) was greater than 1.0 ng/mL. RESULTS: In the group of patients examined under TSH suppression, non-radioiodine avid in PET/CT with [¹8F]FDG were found in 6 out of 15 patients (40%) and in the group of patients examined under rhTSH stimulation in 10 out of 22 patients (45%). The differences between the groups were not statistically significant. The analysis of the receiver operating characteristic (ROC) curves allowed to determine the cut-off point for the positive result of PET/CT performed under TSH suppression with sTg concentration of 11.03 ng/mL. In the group of studies performed under rhTSH stimulation, the cut-off point for sTg was 6.3 ng/mL. There was no statistically significant difference between the baseline thyroglobulin (natTg) and sTg levels and the positive PET/CT result. The administration of rhTSH before the PET/CT examination also had no statistically significant effect on the maximum standard uptake value (SUVmax) of the dominant lesion identified in the PET/CT. CONCLUSIONS: 1) PET/CT with [¹8F]FDG is a useful tool for detection of non-radioiodine avid recurrence and/or metastases of DTC. 2) The concentration of natTg and sTg is highly correlated with a positive result of PET/CT with [¹8F]FDG. 3) The concentration of natTg is comparable with sTg in predicting a positive result of PET/CT with [¹8F]FDG. 4) The cut-off point for a positive result of PET/CT for natTg was 1.36 ng/mL and for sTg was 7.05 ng/mL.

The Safety and Efficacy of the Repeated PRRT with [90Y]Y/[177Lu]Lu-DOTATATE in Patients with NET.

PURPOSE: The peptide receptor radionuclide therapy (PRRT) is a treatment option for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours (NETs). The study aims to evaluate the safety, efficacy, and progression-free survival (PFS) of patients after retreatment (R-PRRT) and re-retreatment (RR-PRRT) with tandem isotopes [90Y]Y/[177Lu]Lu-DOTATATE. Material and Methods. Out of 99 treated patients with G1 and G2 NETs, 26 were included in the study and treated with the repeated PRRT (with 5 undergoing the re-repeated PRRT treatment) after an initial positive response to four PRRT cycles and later progression of the disease. [68Ga]Ga-DOTATATE PET/CT and CT/MRI procedures were performed before and after the treatment. Patients were treated with [90Y]Y/[177Lu]Lu-DOTATATE (1 : 1) with mixed amino acid infusion for kidney protection. Toxicity was evaluated using the CTCAE 3.0 criteria. RESULTS: The median follow-up was 88 months (the range: 42-164). The median cumulative administered activity was 22.2 GBq (the range: 17.8-30.7 GBq). Myelodysplastic syndrome occurred in one patient (3.8%), and grade 4 renal toxicity was also detected in one patient (3.8%). No other cases of grade 3 or 4 bone marrow and renal toxicity were observed. The median PFS rate was 31 months after the PRRT and 23 months following the R-PRRT. The OS rate from the diagnosis (OS-d) was 109 months and from the start of the PRRT (OS-t)-92.4 months. During the restaging, 3-6 months after the PRRT, PR, SD, and PD were observed in 19.2%, 80.8%, and 0% of the patients, respectively. After the R-PRRT, PR, SD, and PD were observed in 50%, 42.3%, and 7.7% of the patients, respectively. CONCLUSIONS: The repeated therapy with [90Y]Y/[177Lu]Lu-DOTATATE is safe and effective for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours.

Carcinoid Heart Disease: How to Diagnose and Treat in 2020?

Neuroendocrine tumors (NETs, originally termed "carcinoids") create a relatively rare group of neoplasms with an approximate incidence rate of 2.5 to 5 cases per 100 000 persons. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome (CS), and 20% to 50% of subjects with CS are diagnosed with carcinoid heart disease (CaHD). The long-standing exposure to high serum serotonin concentration is one of the crucial factors in CaHD development. White plaque-like deposits on the endocardial surface of heart structures with valve leaflets and subvalvular apparatus thickening (fused and shortened chordae; thickened papillary muscles) are characteristic for CaHD. NT pro-BNP and 5-hydroxyindoleacetic acid are the 2 most useful screening markers. Long-acting somatostatin analogs are the standard of care in symptoms control. They are also the first-line treatment for tumor control in subjects with a metastatic somatostatin receptor avid disease. In cases refractory to somatostatin analogs, several options are available. We can increase a somatostatin analog to off-label doses, add telotristat ethyl or administer peptide receptor radionuclide therapy. Cardiac surgery, which mainly involves valve replacement, is presently the most efficient strategy in subjects with advanced CaHD and can relieve unmanageable symptoms or be partly responsible for better prognosis.

THE ROLE OF PET/CT WITH 11C-METHIONINE IN CONTEMPORARY NUCLEAR MEDICINE.

OBJECTIVE: Positron emission tomography (PET/CT) is a non-invasive molecular imaging technique using isotopes with a short half-life usually in combination with chemical compounds. The most commonly used PET/CT tracer is 2-fluoro-2-deoxy-D-glucose labeled with fluorine (18-FDG). It is used mainly in oncological diagnostics as well as myocardial viability, epilepsy and inflammatory diagnostics. The tracer less commonly used in PET/CT could be carbon-labeled methionine (11C-MET). It is mainly used in the diagnosis of focal lesions in the central nervous system. There are also reports of the use of this tracer in diagnostics of the primary, secondary and tertiary hyperparathyroidism as well as multiple myeloma. This tracer may also be used in the diagnosis of lymphoproliferative diseases and solid tumors, although there is no clear evidence of its advantage over 18-FDG. CONCLUSION: Conclusion: Significant difficulties in the production and transport of this tracer and lack of reimbursement of this type of procedure in Poland limits the use of this tracer for scientific research.

Effect of peptide receptor radionuclide therapy (PRRT) with tandem isotopes - [90Y]Y/[177Lu]Lu-DOTATATE in patients with disseminated neuroendocrine tumours depending on [18F]FDG PET/CT qualification in Polish multicentre experience - do we need [18F]FDG PET/CT for qualification to PRRT?

INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). The aim of the study was the evaluation of the role of [¹8F]FDG PET/CT in predicting response, progression-free survival (PFS) and overall survival (OS) after tandem therapy [9°Y]Y/[¹77Lu]Lu-DOTATATE. MATERIAL AND METHODS: Seventy-five patients with histopathologically proven NET G1 and G2 were included in the study. Before treatment [68Ga]Ga-DOTATATE PET/CT and [¹8F]FDG PET/CT was performed. Patients were treated with [9°Y]Y/[¹77Lu]Lu-DOTATATE (1:1) with mixed amino-acid infusion for kidney protection. RESULTS: Progression-free survival was 22.2 months for [¹8F]FDG-positive patients and 59.3 months for [¹8F]FDG-negative patients (p = 0.003). The OS from diagnosis (OS-D) and from the start of PRRT (OS-T) was not reached in [¹8F]FDG-negative patients, and in [¹8F]FDG-positive patients it was 71.8 months and 55.8 months, respectively. The observed overall one-year survival in [¹8F]FDG-positive vs. [¹8F]FDG-negative patients was 96.8% vs. 99.1%, two-year survival was 88.9% vs. 96%, and five-year survival was 58.8% vs. 88%, respectively. The one-year and two-year risk of progression was 15%vs. 58.9% in [¹8F]FDG-positive patients and 11% vs. 32% in [18F]FDG-negative patients. The objective response rate (ORR) [¹8F]FDG-positive vs. [¹8F]FDG-negative patients was 41.7% vs. 17%. CONCLUSIONS: [¹8F]FDG-positive patients have statistically significant shorter survival parameters than [¹8F]FDG-negative patients. The risk of progression in [¹8F]FDG-positive vs. [¹8F]FDG-negative patients in one-year follow-up is comparable, whereas in two-year follow-up it is nearly two times higher for [¹8F]FDG PET/CT-positive patients.