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.

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.

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.

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.

Tandem peptide receptor radionuclide therapy using 90Y/177Lu-DOTATATE for neuroendocrine tumors efficacy and side-effects - polish multicenter experience.

INTRODUCTION: One of the concepts of theranostics in nuclear medicine is peptide receptor radionuclide therapy (PRRT), whereby labeled somatostatin analogs are used for imaging and treating inoperable or disseminated neuroendocrine tumors (NET). AIM: The aim of the study was to determine the therapeutic efficacy and toxicity of tandem 90Y /177Lu-DOTATATE in patients with disseminated NET in a multicenter trial. MATERIALS AND METHODS: 103 patients with NET G1/G2 treated with 90Y/177Lu-DOTATATE (1:1) with amino-acid infusion for nephroprotection were included in the study. RESULTS: Overall survival from the disease diagnosis (OS-D) was 127.4 months and from the time of PRRT (OS-T) was 89.5 months. Progression-free survival (PFS) was 29.9 months. An analysis based on the proliferation index revealed a statistically significant impact on PFS and OS-T (PFS G1 vs G2, 59.3 vs 24.3 months; OS-T G1 vs G2, not reached vs 79.9 months). The effect of the primary disease site was also analyzed. For pancreatic vs small bowel vs large bowel, the PFS was 30.8 vs 30.3 vs 40.6 months, the OS-T was 94 vs 61.9 vs 131.2 months and OS-D was 130.4 vs 89.2 vs not reached months, respectively. The 2-year risk of progression was 42%. The probability of 2-year and 5-year overall survival was 89% and 62%, respectively. PRRT was well tolerated by all patients. One patient (1%) developed myelodysplastic syndrome. No other grade 3 and 4 hematological or renal toxicity was observed. CONCLUSIONS: This multicenter trial showed that tandem 90Y/177Lu-DOTATATE is highly effective and safe therapy for patients with disseminated NET.

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.

Infant formulae supplemented with prebiotics: Are they better than unsupplemented formulae? An updated systematic review.

In 2011, the Committee on Nutrition of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition systematically reviewed published evidence related to the safety and health effects of the administration of formulae supplemented with pro- and/or prebiotics compared with unsupplemented formulae. We updated evidence on the effects of the administration of prebiotic-supplemented infant formulae (IF) compared with unsupplemented IF. Five databases were searched up to March 2017 for randomised controlled trials. In all, forty-one publications were identified, including twenty-five new publications. The administration of currently evaluated prebiotic-supplemented formulae to healthy infants does not raise safety concerns with regard to growth and adverse effects. Some favourable clinical effects are possible, primarily stool softening, which may be beneficial in some infants. Currently, there is no existing robust evidence to recommend the routine use of prebiotic-supplemented formulae. The latter conclusion may reflect the small amount of data on specific prebiotics and outcomes, rather than a genuine lack of an effect. The efficacy and safety should be considered for each prebiotic(s)-supplemented formula.

[Current treatment of neuroendocrine tumors].

Neuroendocrine neoplasms (NEN) are group of rare neoplasms, which frequency is estimated on about 35 cases/100000. Though, during last 30 years the number of NEN new cases increased five-times. Nowadays the only method which allows to cure NEN is surgical treatment. Laparoscopic surgery and endoscopic treatment are also used. These neoplasms are usually diagnosed in advanced stadium, with distant metastases, when surgery is not an option. In this group of patients systemic and local therapies are used, such as somatostatin analogues, chemotherapy or targeted therapy. The choice of proper method is determined not only by neoplasm's localization or its size, but also clinical symptoms caused by tumor itself or by substations released by it. One place hopes in novel molecular-based therapies and currently investigated therapies using i.a. oncolytic viruses.

[Treatment of neuroendocrine tumors with radio-labeled somatostatin analogues].

There is a steady increase in the number of neuroendocrine tumors. Although the knowledge about this tumors' biology is increasing, they are still diagnosed in advanced stadium, when surgical treatment is not an option. One of the treatment methods which are available in this group of patients is peptide receptor radionuclide therapy, which should be considered in selected patients. This treatment is usually well tolerated by patients, though severe adverse events may occur, such as myelosuppression or renal failure.

Probiotic Bacterial and Fungal Strains: Claims with Evidence.

BACKGROUND: Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit for the host. This review summarizes current (i.e. published in the last 5 years) key evidence on probiotic efficacy and its safety in adults and children. To identify relevant data, searches of MEDLINE and the Cochrane Library databases were performed in August 2015 to locate randomized controlled trials (RCTs) or their meta-analyses. The focus was on commonly used, well-specified, bacterial and yeast probiotics for the treatment of gastrointestinal disorders. The MEDLINE database was also searched for evidence-based clinical practice guidelines, developed by scientific societies in the same timeframe. Data on safety of probiotics were obtained from a document developed by the US Agency for Healthcare Research and Quality. KEY MESSAGES: A number of relevant RCTs and meta-analyses are available. Saccharomyces boulardii is the most studied yeast probiotic, and Lactobacillus rhamnosus GG is the most studied bacterial probiotic. For both, the best documented fact is their efficacy for the treatment of acute gastroenteritis, especially in children, and for the prevention of antibiotic-associated diarrhea, both in adults and children. There is some evidence to support the use of probiotics to prevent or treat other diseases, such as necrotizing enterocolitis, infantile colic, Helicobacter pylori infection, and irritable bowel syndrome, but further studies are needed to identify which strain(s) is/are the most effective. Data on safety, particularly long-term safety, are limited. The risk of side effects is greater in people who have severe underlying health conditions. CONCLUSIONS: The evidence on bacterial and yeast probiotics has considerably expanded during recent years. Accumulated data allow one to make informed decisions about the effectiveness of probiotics and about how to reduce the use of those without proven efficacy.

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.

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).

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.

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.

Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs).

PURPOSE: Neuroendocrine tumours (NET) are a heterogeneous group of neoplasms of diffuse neuroendocrine cells. Surgery is the main aim in the treatment of NETs, which becomes impossible in the case of large tumours or infiltration into other tissues and/or important blood vessels. Neoadjuvant therapy might be helpful in decreasing NET size also, leading us to the point where a tumour, previously considered inoperable, becomes operable. The aim of the study was to assess the usage of peptide receptor radionuclide therapy (PRRT) as a neoadjuvant treatment, enabling surgical intervention in primary inoperable NET. METHODS: Among 47 patients treated with PRRT, 6 patients were chosen with large, inoperable tumours, for whom enabling of complete surgical excision of the lesions might offer the prospect for a cure. Response to the therapy was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST). RESULTS: The mean tumour size decreased from 6.9 (min. 3.1 cm, max. 9.6 cm) before therapy to 5.4 cm (min. 3.1 cm, max. 9.5 cm) after the treatment. According to RECIST, stabilization of the disease was observed in four and partial responses in two patients. In two patients, reduction of the tumour size enabled surgical intervention. CONCLUSION: (1) PRRT might be considered a neoadjuvant therapy in primary inoperable NETs. (2) According to RECIST, stabilization of the disease was observed in the majority of patients. (3) We suggest that not only tumour diameter changes, but also tumour volume and contrast enhancement changes in computed tomography should be taken into consideration in assessment of the response to the therapy. (4) Somatostatin receptor scintigraphy is an important tool for qualification of the radioisotope therapy and also for the assessment of the response to PRRT.