Early Leishmania infectivity depends on miR-372/373/520d family-mediated reprogramming of polyamines metabolism in THP-1-derived macrophages.

Leishmania amazonensis is a protozoan that primarily causes cutaneous leishmaniasis in humans. The parasite relies on the amino acid arginine to survive within macrophages and establish infection, since it is a precursor for producing polyamines. On the other hand, arginine can be metabolized via nitric oxide synthase 2 (NOS2) to produce the microbicidal molecule nitric oxide (NO), although this mechanism does not apply to human macrophages since they lack NOS2 activity. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at posttranscriptional levels. Our previous work showed that mmu-miR-294 targets Nos2 favoring Leishmania survival in murine macrophages. Here, we demonstrate that human macrophages upregulate the hsa-miR-372, hsa-miR-373, and hsa-miR-520d, which present the same seed sequence as the murine mmu-miR-294. Inhibition of the miR-372 impaired Leishmania survival in THP-1 macrophages and the effect was further enhanced with combinatorial inhibition of the miR-372/373/520d family, pointing to a cooperative mechanism. However, this reduction in survival is not caused by miRNA-targeting of NOS2, since the seed-binding motif found in mice is not conserved in the human 3'UTR. Instead, we showed the miR-372/373/520d family targeting the macrophage's main arginine transporter SLC7A2/CAT2 during infection. Arginine-related metabolism was markedly altered in response to infection and miRNA inhibition, as measured by Mass Spectrometry-based metabolomics. We found that Leishmania infection upregulates polyamines production in macrophages, as opposed to simultaneous inhibition of miR-372/373/520d, which decreased putrescine and spermine levels compared to the negative control. Overall, our study demonstrates miRNA-dependent modulation of polyamines production, establishing permissive conditions for intracellular parasite survival. Although the effector mechanisms causing host cell immunometabolic adaptations involve various parasite and host-derived signals, our findings suggest that the miR-372/373/520d family may represent a potential target for the development of new therapeutic strategies against cutaneous leishmaniasis.

Clinical and neurodevelopmental outcomes in premature infants exposed to intravenous fish- and soybean oil-based lipid emulsions.

BACKGROUND: The optimal composition of lipid emulsions in parenteral nutrition (PN) for premature infants remains controversial. This study examined the effects of a combination of soybean oil-based (SoyLE) and fish oil-based (FishLE) lipid emulsions compared to FishLE as monotherapy on the lipid and fatty acid profiles and clinical outcomes of premature infants requiring prolonged PN. METHODS: 42 premature infants received FishLE+SoyLE or FishLE. Serum concentrations of lipoproteins and 29 fatty acids (FA) were measured at baseline, 4, and 8 weeks of PN and growth and neurodevelopmental outcomes were measured at 3, 6, 12, 18, and 24 months of life. RESULTS: Lipid profiles were similar between groups. Plasma concentrations of ω-6 fatty acids tended to decrease over time in both groups. Concentrations of most ω-3 fatty acids, in particular docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid, were significantly increased over time in the FishLE+SoyLE group whereas they did not change in the FishLE alone group. However, serum concentrations of almost all fatty acids were similar between groups at the end of the study period. No differences in growth parameters including weight, height, fronto-occipital circumference (FOC), and body mass index (BMI) were observed up to two years of age. Similarly, there were no differences in neurodevelopmental test scores at 6, 12, 18, and 24 months of age. CONCLUSIONS: No substantial differences in lipid profiles and short clinical outcomes were found in infants exposed to FishLE+SoyLE when compared to FishLE.

Real-world integration of the protocol for responding to and assessing patients' assets, risks, and experiences tool to assess social determinants of health in the electronic medical record at an academic medical center.

Objective: To describe the real-world deployment of a tool, the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE), to assess social determinants of health (SDoH) in an electronic medical record (EMR). Methods: We employed the collection of the PRAPARE tool in the EMR of a large academic health system in the ambulatory clinic and emergency department setting. After integration, we evaluated SDoH prevalence, levels of missingness, and data anomalies to inform ongoing collection. We summarized responses using descriptive statistics and hand-reviewed data text fields and patterns in the data. Data on patients who were administered with the PRAPARE from February to December 2020 were extracted from the EMR. Patients missing ≥ 12 PRAPARE questions were excluded. Social risks were screened using the PRAPARE. Information on demographics, admittance status, and health coverage were extracted from the EMR. Results: Assessments with N = 6531 were completed (mean age 54 years, female (58.6%), 43.8% Black). Missingness ranged from 0.4% (race) to 20.8% (income). Approximately 6% of patients were homeless; 8% reported housing insecurity; 1.4% reported food needs; 14.6% had healthcare needs; 8.4% needed utility assistance; and 5% lacked transportation related to medical care. Emergency department patients reported significantly higher proportions of suboptimal SDoH. Conclusions: Integrating the PRAPARE assessment in the EMR provides valuable information on SDoH amenable to intervention, and strategies are needed to increase accurate data collection and to improve the use of data in the clinical encounter.

Impact of Virtual Interviewing on Geographic Placement for Cardiology Fellowship Recruitment.

Background Virtual interviewing for cardiology fellowship was instituted in the 2021 fellowship application cycle because of the COVID-19 pandemic and restricted travel. The impact on geographic patterns of fellow-training program matching is unknown. This study sought to determine if there was a difference in geographic placement of matched fellows for cardiology fellowship match after initiation of virtual interviews compared with in-person interviewing. Methods and Results All US-based accredited cardiovascular disease fellowship programs that participated in the 2019 to 2021 fellowship match cycles and had publicly available data with fellowship and residency training locations and training year were included. Each fellow was categorized based on whether their fellowship and residency programs were in the same institution, same state, same US census region, or different census region. Categories were mutually exclusive. Of 236 eligible programs, 118 (50%) programs were identified, composed of 1787 matched fellows. Compared with the previrtual cohort (n=1178 matched fellows), there was no difference in the geographic placement during the 2021 virtual cycle (n=609 matched fellows) (P=0.19), including the proportion matched at the same program (30.6% versus 31.5%), same state but different program (13% versus 13.8%), same region but different state (24.2% versus 19.7%), or different region (35% versus 33.1%). There was also no difference when stratified by program size or geographic region. Conclusions The use of virtual interviewing in the 2021 cardiology fellowship application cycle showed no significant difference in the geographic placement of matched fellows compared with in-person interviewing. Further study is needed to evaluate the impact of virtual interviewing and optimize its use in fellowship recruitment.

Altered functional connectivity in common resting-state networks in patients with major depressive disorder: A resting-state functional connectivity study.

The neural correlates of major depressive disorder (MDD) remain disputed. In the absence of reliable biological markers, the dysfunction and interaction of neural networks have been proposed as pathophysiological neural mechanisms in depression. Here, we examined the functional connectivity (FC) of brain networks. 51 healthy volunteers (mean age 33.57 ± 7.80) and 55 individuals diagnosed with MDD (mean age 33.89 ± 11.00) participated by performing a resting-state (rs) fMRI scan. Seed to voxel FC analyses were performed. Compared to healthy control (HC), MDD patients showed higher connectivity between the hippocampus and the anterior cingulate cortex (ACC) and lower connectivity between the insula and the ACC. The MDD group displayed lower connectivity between the inferior parietal lobule (IPL) and the superior frontal gyrus (SFG). The current data replicate previous findings regarding the cortico-limbic network (hippocampus - ACC connection) and the salience network (insula - ACC connection) and provide novel insight into altered rsFC in MDD, in particular involving the hippocampus - ACC and the insula - ACC connection. Furthermore, altered connectivity between the IPL and SFG indicates that the processing in higher cognitive processes such as attention and working memory is affected in MDD. These data further support dysfunctional neuronal networks as an interesting pathophysiological marker in depression.

Exploring Match Space: How Medical School and Specialty Characteristics Affect Residency Match Geography in the United States.

PURPOSE: To explore how school and specialty characteristics impact the geographic match location of U.S. senior medical students. METHOD: The authors collected student match data between 2018 and 2020 from U.S. MD-granting medical schools and calculated the distance between students' medical schools and residency training programs. They use the term "match space" to describe this distance. Match space was codified on a 5-point ordinal scale by where the student matched: 1 = home institution, 2 = home state, 3 = an adjacent state, 4 = the same or adjacent U.S. Census division (and not adjacent state), and 5 = skipped at least one U.S. Census division. Ordinal logistic regression correlated school and specialty characteristics with match space. RESULTS: During the study period, 26,102 medical students, representing 66 medical schools from 28 states, matched in 23 specialties. Fifty-nine percent of students were from public institutions, and 27% of schools ranked in the top 40 of National Institutes of Health (NIH) research funding. The match space was higher for students graduating from private institutions (odds ratio [OR] 1.14; 95% confidence interval [CI], 1.06 to 1.22) and matching into more competitive specialties (OR 1.07; 95% CI, 1 to 1.14). The match space was lower for students graduating from top NIH-funded institutions (OR 0.89; 95% CI, 0.85 to 0.94) and from schools with a higher percentage of in-state matriculants (OR 0.75; 95% CI, 0.72 to 0.77). CONCLUSIONS: School characteristics such as region, public/private designation, NIH funding, and percentage of in-state students were associated with residency match geography. Matching into more competitive specialties also showed a marginal increase in match distance. These findings suggest that a student's choice of specialty and medical school may impact subsequent geographic placement for residency training, which should be considered by students and residency programs alike.

Risk of malignancy in thyroid nodules with indeterminate (THY3f) cytology.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is an integral part of thyroid nodule assessment. Nodules with an indeterminate cytology (THY3a-f) require formal histological assessment to confirm benign or malignant pathology. This study aimed to provide data for an evidence-based approach for management of patients with THY3f nodules. METHODS: Retrospective review of patients who had a thyroid FNAC reported as suspicious of follicular neoplasm (THY3f) or showing atypia (THY3a) were identified, and clinical, operative and outcomes data were analysed. RESULTS: Between 2018 and 2020, 200 patients (167F:33M, median age 51 years (range:18-86 years)) had a THY3f cytology. Most presented with a palpable nodule (n=104; 68.4%). Overall, 152 (76.0%;130F:23M) underwent surgery and 31 (20.4%) were found to have a thyroid carcinoma (22 follicular carcinomas, 7 papillary carcinomas, 1 medullary thyroid carcinoma and 1 metastatic renal carcinoma). An additional incidental carcinoma (size: 0.7-13mm) was found in seven (4.6%). Among those with cancer, a completion thyroidectomy and radioactive iodine treatment was indicated in nine (<6% of the entire cohort). Previously suggested risk factors for malignancy, eg male gender, large tumour size (>4cm) or age, were not found to be associated with increased risk. During the same period, THY3a cytology was reported in 53 patients, of whom 29 underwent diagnostic surgery and 4 patients were found to have a thyroid cancer (follicular, n=3 and medullary, n=1). CONCLUSION: One in five patients with features suspicious of a follicular neoplasm (THY3f) has a thyroid carcinoma. This risk is much lower for THY3a. This study reinforces the current recommendation for thyroid surgery in all patients with a reliable THY3f cytology, as no further stratifying risk factors could be identified.

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

Are We Measuring What Matters? How Student and Clerkship Characteristics Influence Clinical Grading.

PURPOSE: Given the growing emphasis placed on clerkship performance for residency selection, clinical evaluation and its grading implications are critically important; therefore, the authors conducted this study to determine which evaluation components best predict a clinical honors recommendation across 3 core clerkships. METHOD: Student evaluation data were collected during academic years 2015-2017 from the third-year internal medicine (IM), pediatrics, and surgery clerkships at the University of Alabama at Birmingham School of Medicine. The authors used factor analysis to examine 12 evaluation components (12 items), and they applied multilevel logistic regression to correlate evaluation components with a clinical honors recommendation. RESULTS: Of 3,947 completed evaluations, 1,508 (38%) recommended clinical honors. The top item that predicted a clinical honors recommendation was clinical reasoning skills for IM (odds ratio [OR] 2.8; 95% confidence interval [CI], 1.9 to 4.2; P < .001), presentation skills for surgery (OR 2.6; 95% CI, 1.6 to 4.2; P < .001), and knowledge application for pediatrics (OR 4.8; 95% CI, 2.8 to 8.2; P < .001). Students who spent more time with their evaluators were more likely to receive clinical honors (P < .001), and residents were more likely than faculty to recommend clinical honors (P < .001). Of the top 5 evaluation items associated with clinical honors, 4 composed a single factor for all clerkships: clinical reasoning, knowledge application, record keeping, and presentation skills. CONCLUSIONS: The 4 characteristics that best predicted a clinical honors recommendation in all disciplines (clinical reasoning, knowledge application, record keeping, and presentation skills) correspond with traditional definitions of clinical competence. Structural components, such as contact time with evaluators, also correlated with a clinical honors recommendation. These findings provide empiric insight into the determination of clinical honors and the need for heightened attention to structural components of clerkships and increased scrutiny of evaluation rubrics.

Plectin dysfunction in neurons leads to tau accumulation on microtubules affecting neuritogenesis, organelle trafficking, pain sensitivity and memory.

AIMS: Plectin, a universally expressed multi-functional cytolinker protein, is crucial for intermediate filament networking, including crosstalk with actomyosin and microtubules. In addition to its involvement in a number of diseases affecting skin, skeletal muscle, heart, and other stress-exposed tissues, indications for a neuropathological role of plectin have emerged. Having identified P1c as the major isoform expressed in neural tissues in previous studies, our aim for the present work was to investigate whether, and by which mechanism(s), the targeted deletion of this isoform affects neuritogenesis and proper nerve cell functioning. METHODS: For ex vivo phenotyping, we used dorsal root ganglion and hippocampal neurons derived from isoform P1c-deficient and plectin-null mice, complemented by in vitro experiments using purified proteins and cell fractions. To assess the physiological significance of the phenotypic alterations observed in P1c-deficient neurons, P1c-deficient and wild-type littermate mice were subjected to standard behavioural tests. RESULTS: We demonstrate that P1c affects axonal microtubule dynamics by isoform-specific interaction with tubulin. P1c deficiency in neurons leads to altered dynamics of microtubules and excessive association with tau protein, affecting neuritogenesis, neurite branching, growth cone morphology, and translocation and directionality of movement of vesicles and mitochondria. On the organismal level, we found P1c deficiency manifesting as impaired pain sensitivity, diminished learning capabilities and reduced long-term memory of mice. CONCLUSIONS: Revealing a regulatory role of plectin scaffolds in microtubule-dependent nerve cell functions, our results have potential implications for cytoskeleton-related neuropathies.

What Defines an Honors Student? Survey of Pediatric and Internal Medicine Faculty Perspectives.

OBJECTIVE: Although considerable emphasis is placed on the attainment of honors in core medical school clerkships, little is known about what student characteristics are used by attending physicians to earn this designation. The purpose of this study was to evaluate what values and characteristics that attending physicians consider important in the evaluation of Pediatrics and Internal Medicine clerkship students for clinical honors designation. METHODS: This cross-sectional survey study was framed around Accreditation Council for Graduate Medical Education (ACGME) competencies. It was administered at three tertiary care hospitals associated with one large medical school in an urban setting. Teaching ward attendings in Pediatrics and Internal Medicine who evaluated third-year medical students between 2013 and 2016 were surveyed. RESULTS: Overall, Pediatric and Internal Medicine faculty demonstrated close agreement in which competencies were most important in designating clinical honors. Both groups believed that professionalism was the most important factor and that systems-based practice and patient care were among the least important factors. The only competency with a significant difference between the two groups was systems-based practice, with Internal Medicine placing more emphasis on the coordination of patient care and understanding social determinants of health. CONCLUSIONS: Professionalism, communication skills, and medical knowledge are the most important characteristics when determining clinical honors on Pediatrics and Internal Medicine clerkships.

Boot camps in neonatal-perinatal medicine fellowship programs: A national survey.

BACKGROUND: Simulation is widely used in graduate medical education. A prior survey showed that 80% of Neonatal-Perinatal Medicine (NPM) fellowship programs in the U.S. use simulation. There are multiple ways to provide simulation-based education. One such method is through intensive simulation-based education sessions held at the beginning of a training program, common called 'boot camps'. The aim of this study was to describe the use of simulation-based boot camps in NPM fellowship programs. METHODS: Survey study of Accreditation Council for Graduate Medical Education (ACGME) accredited NPM fellowships in the U.S. RESULTS: Fifty-nine of 98 programs (60%) responded. Thirty six (61%) participated in 1st year fellow boot camps, which focused on procedural skills and newborn resuscitation. Nearly half of programs participated in regional boot camps. Most boot camps were one or two days long. Eleven programs (19%) held 2nd or 3rd year fellow boot camps, which focused on advanced resuscitation and communication. Barriers included lack of faculty protected time (57%), funding (39%), and lack of faculty experience (31%). CONCLUSIONS: A majority of ACGME accredited NPM fellowships participate in 1st year fellows' boot camps. Many participate in regional boot camps. A few programs have 2nd or 3rd year fellow boot camps. Lack of time, funding, and faculty experience were common barriers.

Imbalances in protein homeostasis caused by mutant desmin.

AIMS: We investigated newly generated immortalized heterozygous and homozygous R349P desmin knock-in myoblasts in conjunction with the corresponding desminopathy mice as models for desminopathies to analyse major protein quality control processes in response to the presence of R349P mutant desmin. METHODS: We used hetero- and homozygous R349P desmin knock-in mice for analyses and for crossbreeding with p53 knock-out mice to generate immortalized R349P desmin knock-in skeletal muscle myoblasts and myotubes. Skeletal muscle sections and cultured muscle cells were investigated by indirect immunofluorescence microscopy, proteasomal activity measurements and immunoblotting addressing autophagy rate, chaperone-assisted selective autophagy and heat shock protein levels. Muscle sections were further analysed by transmission and immunogold electron microscopy. RESULTS: We demonstrate that mutant desmin (i) increases proteasomal activity, (ii) stimulates macroautophagy, (iii) dysregulates the chaperone assisted selective autophagy and (iv) elevates the protein levels of αB-crystallin and Hsp27. Both αB-crystallin and Hsp27 as well as Hsp90 displayed translocation patterns from Z-discs as well as Z-I junctions, respectively, to the level of sarcomeric I-bands in dominant and recessive desminopathies. CONCLUSIONS: Our findings demonstrate that the presence of R349P mutant desmin causes a general imbalance in skeletal muscle protein homeostasis via aberrant activity of all major protein quality control systems. The augmented activity of these systems and the subcellular shift of essential heat shock proteins may deleteriously contribute to the previously observed increased turnover of desmin itself and desmin-binding partners, which triggers progressive dysfunction of the extrasarcomeric cytoskeleton and the myofibrillar apparatus in the course of the development of desminopathies.

AAV-mediated cardiac gene transfer of wild-type desmin in mouse models for recessive desminopathies.

Mutations in the human desmin gene cause autosomal-dominant and recessive cardiomyopathies and myopathies with marked phenotypic variability. Here, we investigated the effects of adeno-associated virus (AAV)-mediated cardiac wild-type desmin expression in homozygous desmin knockout (DKO) and homozygous R349P desmin knockin (DKI) mice. These mice serve as disease models for two subforms of autosomal-recessive desminopathies, the former for the one with a complete lack of desmin protein and the latter for the one with solely mutant desmin protein expression in conjunction with protein aggregation pathology in striated muscle. Two-month-old mice were injected with either a single dose of 5 × 1012 AAV9-hTNT2-mDes (AAV-Des) vector genomes or NaCl as control. One week after injection, mice were subjected to a forced swimming exercise protocol for 4 weeks. Cardiac function was monitored over a period of 15 month after injection and before the mice were sacrificed for biochemical and morphological analysis. AAV-mediated cardiac expression of wild-type desmin in both the homozygous DKO and DKI backgrounds reached levels seen in wild-type mice. Notably, AAV-Des treated DKO mice showed a regular subcellular distribution of desmin as well as a normalization of functional and morphological cardiac parameters. Treated DKI mice, however, showed an aberrant subcellular localization of desmin, unchanged functional cardiac parameters, and a trend toward an increased cardiac fibrosis. In conclusion, the effect of a high-dose AAV9-based desmin gene therapy is highly beneficial for the heart in DKO animals, but not in DKI mice.

Age-related declines in α-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration.

While young muscle is capable of restoring the original architecture of damaged myofibers, aged muscle displays a markedly reduced regeneration. We show that expression of the "anti-aging" protein, α-Klotho, is up-regulated within young injured muscle as a result of transient Klotho promoter demethylation. However, epigenetic control of the Klotho promoter is lost with aging. Genetic inhibition of α-Klotho in vivo disrupted muscle progenitor cell (MPC) lineage progression and impaired myofiber regeneration, revealing a critical role for α-Klotho in the regenerative cascade. Genetic silencing of Klotho in young MPCs drove mitochondrial DNA (mtDNA) damage and decreased cellular bioenergetics. Conversely, supplementation with α-Klotho restored mtDNA integrity and bioenergetics of aged MPCs to youthful levels in vitro and enhanced functional regeneration of aged muscle in vivo in a temporally-dependent manner. These studies identify a role for α-Klotho in the regulation of MPC mitochondrial function and implicate α-Klotho declines as a driver of impaired muscle regeneration with age.

AAV9-mediated gene transfer of desmin ameliorates cardiomyopathy in desmin-deficient mice.

Mutations of the human desmin (DES) gene cause autosomal dominant and recessive myopathies affecting skeletal and cardiac muscle tissue. Desmin knockout mice (DES-KO), which develop progressive myopathy and cardiomyopathy, mirror rare human recessive desminopathies in which mutations on both DES alleles lead to a complete ablation of desmin protein expression. Here, we investigated whether an adeno-associated virus-mediated gene transfer of wild-type desmin cDNA (AAV-DES) attenuates cardiomyopathy in these mice. Our approach leads to a partial reconstitution of desmin protein expression and the de novo formation of the extrasarcomeric desmin-syncoilin network in cardiomyocytes of treated animals. This finding was accompanied by reduced fibrosis and heart weights and improved systolic left-ventricular function when compared with control vector-treated DES-KO mice. Since the re-expression of desmin protein in cardiomyocytes of DES-KO mice restores the extrasarcomeric desmin-syncoilin cytoskeleton, attenuates the degree of cardiac hypertrophy and fibrosis, and improves contractile function, AAV-mediated desmin gene transfer may be a novel and promising therapeutic approach for patients with cardiomyopathy due to the complete lack of desmin protein expression.

Uncovering heart failure with preserved ejection fraction in patients with type 2 diabetes in primary care: time for a change.

Undetected heart failure appears to be an important health problem in patients with type 2 diabetes and aged ≥ 60 years. The prevalence of previously unknown heart failure in these patients is high, steeply rises with age, and is overall higher in women than in men. The majority of the patients with newly detected heart failure have a preserved ejection fraction. A diagnostic algorithm to detect or exclude heart failure in these patients with variables from the medical files combined with items from history taking and physical examination provides a good to excellent accuracy. Annual screening appears to be cost-effective. Both unrecognised heart failure with reduced and with preserved ejection fraction were associated with a clinically relevant lower health status in patients with type 2 diabetes. Also the prognosis of these patients was worse than of those without heart failure. Existing disease-management programs for type 2 diabetes pay insufficient attention to early detection of cardiovascular diseases, including heart failure. We conclude that more attention is needed for detection of heart failure in older patients with type 2 diabetes.

Peptide receptor radionuclide therapy of neuroendocrine tumors with (90)Y-DOTATOC: is treatment response predictable by pre-therapeutic uptake of (68)Ga-DOTATOC?

PURPOSE: PET with (68)Ga-DOTATOC allows for imaging and quantitative assessment of somatostatin receptor expression in neuroendocrine tumors (NET). The aim of this retrospective study was to analyze whether pre-therapeutic (68)Ga-DOTATOC PET/CT is able to predict response to Peptide Receptor Radionuclide Therapy (PRRT). PATIENTS AND METHODS: Forty patients with advanced stage NET were treated with a fixed dose of (90)Y-DOTATOC (5550 or 3700MBq). Prior to PRRT, each patient received (68)Ga-DOTATOC PET/CT. Treatment results were evaluated after 3months by CT, tumor marker levels and clinical course and correlated with (68)Ga-DOTATOC uptake (SUVmax) and the assumed uptake of (90)Y-DOTATOC in tumor manifestations (MBq/g). ROC analysis and pairwise comparison of area under the curve (AUC) were performed with pre-treatment uptake of (68)Ga-DOTATOC, assumed uptake of (90)Y-DOTATOC and treatment activity alone and in relation to body weight as continuous variables, and response/no response as classification variable. RESULTS: According to conventional criteria (tumor shrinkage, decrease of tumor markers, improved or stable clinical condition), 20 patients were classified as responders, 16 as non-responders and in four patients findings were equivocal. Using a SUV more than 17.9 as cut-off for favorable outcome, PET was able to predict treatment response of all responders and 15 out of 16 non-responders. All four patients with equivocal findings showed SUV less than or equal to 17.9 and soon experienced tumor progression. The assumed uptake of (90)Y-DOTATOC in tumor manifestations using a cut-off more than 1.26MBq/g as predictor of response was able to correctly classify 19 out of 20 responders, and 14 out of 16 non-responders. In all patients with equivocal findings, the assumed uptake of (90)Y-DOTATOC was below 1.26MBq/g. CONCLUSION: Pre-therapeutic (68)Ga-DOTATOC tumor uptake as well as assumed uptake of (90)Y-DOTATOC are strongly associated with the results of subsequent PRRT. The defined cut-off values should be confirmed by prospective studies and may then provide the rationale for individual dosing and selecting patients with high likelihood of favorable treatment outcome.