Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study.

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00-3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10-2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12-3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. PATIENT SUMMARY: A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment.

Pediatric hemophagocytic lymphohistiocytosis: A rarely diagnosed entity in a developing country.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an exaggerated inflammatory reaction secondary to a host's inadequate immune response causing a self-perpetuating loop of altered regulation. Signs and symptoms of HLH are compatible with other common diseases and are nonspecific. Underdiagnosis makes it difficult to estimate the real incidence of HLH, especially in developing countries. METHODS: Retrospective, descriptive study of pediatric patients admitted to a high-complexity institution in Cali, Colombia between 2012 and 2019 with HLH diagnosis. Medical history review to complete an electronic database and a secondary, descriptive analysis was carried out. The study was approved by the Institutional Ethics Committee. RESULTS: Twenty-one patients were included. 52.4 % of the population was male with a median age of 9.3 years [IQR (3.0-13.7 years)]. More than half of patients (66.6 %) had viral disease at diagnosis, the most frequent being Epstein-Barr Virus (EBV) (52.3 %) and dengue (14.3 %). Three patients had confirmed gene mutations (G6PC3, XIAP, and UNC13D). 95 % of the patients were treated with the HLH 2004 protocol, half of them received incomplete protocol with intravenous immunoglobulin (IVIG) and/or systemic steroids, while the other half received the complete protocol including etoposide and cyclosporine. More than three-fourths (76.2 %) required admission to an ICU with a median stay of 14 days [IQR (11-37 days)] and a median hospital stay of 30 days [IQR (18-93 days)]. 14.3 % (n = 3) of patients died. CONCLUSIONS: HLH is a complex disease that requires multidisciplinary management with secondary HLH due to EBV infection being a common cause. There is increasing awareness of HLH diagnosis in developing countries such as Colombia which can offer earlier treatment options and better outcomes.

Tuberculosis musculoesquelética que imita neoplasia de tejidos blandos: A propósito de dos casos / Musculoskeletal Tuberculosis mimicking soft tissue neoplasms: report of two cases

Resumen La tuberculosis (TB) es una de las enfermedades infecciosas con mayor carga de morbimortalidad a nivel mundial,la presentación pulmonar es la forma más común, sin embargo, las manifestaciones extrapulmonares, especialmente las osteoarticulares, pueden ser difíciles de diagnosticar debido a sus síntomas inespecíficos sugestivos de otras entidades como neoplasias o enfermedades infiltrativas, lo que hace de su diagnóstico un reto clínico. Está enfermedad esta asociada a múltiples factores de riesgo como inmunosupresión, contacto cercano con pacientes con tuberculosis, hacinamiento, residir en zona endémica, entre otros. A continuación, se presentan dos casos de pacientes pediátricos sin compromiso inmune que cursaron con cuadros sugestivos de neoplasias musculoesqueleticas, con hallazgos imagenológicos congruentes, pero con estudios microbiológicos positivos para TB.

Abstract Tuberculosis (TB) is one of the infectious diseases with the highest burden of morbidity and mortality worldwide. Pulmonary presentation is the most common, however, extrapulmonary manifestations, especially osteoarticular, can be difficult to diagnose due to their nonspecific symptoms suggestive of other entities such as neoplasms or infiltrative diseases. Tuberculosis is also associated with multiple risk factors, especially immunosuppression, and among others, household contact with patients with tuberculosis or residing in an endemic area. We present two pediatric patients without immunecompromise, with clinical history suggestive of musculoskeletal neoplasms, with congruent imaging findings, but with positive microbiological studies for TB.

Factors Predicting Metastatic Disease in 68Ga-PSMA-11 PET-Positive Osseous Lesions in Prostate Cancer.

Bone is the most common site of distant metastatic spread in prostate adenocarcinoma. Prostate-specific membrane antigen (PSMA) uptake has been described in both benign and malignant bone lesions, which can lead to false-positive findings on 68Ga-PSMA-11 PET. The purpose of this study was to evaluate the diagnostic accuracy of 68Ga-PSMA-11 PET for osseous prostate cancer metastases and improve bone uptake interpretation using semiquantitative metrics. Methods: Fifty-six prostate cancer patients (18 before prostatectomy and 38 with biochemical recurrence) who underwent 68Ga-PSMA-11 PET/MRI or PET/CT examinations with osseous PSMA-ligand uptake were included in the study. Medical records were reviewed retrospectively by board-certified nuclear radiologists to determine true or false positivity based on a composite endpoint. For each avid osseous lesion, we measured biologic volume; size; PSMA Reporting and Data System (RADS) rating; SUVmax; and ratio of lesion SUVmax to liver, blood pool, and background bone SUVmax Differences between benign and malignant lesions were evaluated for statistical significance, and cutoffs for these parameters were determined to maximize diagnostic accuracy. Results: Among 56 participants, 13 (22.8%) had false-positive osseous 68Ga-PSMA-11 findings and 43 (76.8%) had true-positive osseous 68Ga-PSMA-11 findings. Twenty-two patients (39%) had 1 osseous lesion, 18 (32%) had 2-4 lesions, and 16 (29%) had 5 or more lesions. Cutoffs resulting in statistically significant (P < 0.005) differences between benign and malignant lesions were a PSMA RADS rating of at least 4, an SUVmax of at least 4.1, and SUVmax ratios of at least 2.11 for lesion to blood pool, at least 0.55 for lesion to liver, and at least 4.4 for lesion to bone. These measurements corresponded to a lesion-based 68Ga-PSMA-11 PET lesion detection rate of 80%, 93%, 89%, 21%, and 89%, respectively, for malignancy, and a specificity of 73%, 73%, 73%, 93%, and 60%, respectively. Conclusion: PSMA RADS rating, SUVmax, and SUVmax ratio for lesion to blood pool can help differentiate benign from malignant lesions on 68Ga-PSMA-11 PET. An SUVmax ratio of more than 2.2 for lesion to blood pool is a reasonable parameter to support image interpretation and presented a superior lesion detection rate and specificity when compared with visual interpretation by PSMA RADS. These parameters hold clinical value by improving diagnostic accuracy for metastatic prostate cancer on 68Ga-PSMA-11 PET/MRI and PET/CT.

Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer.

PURPOSE: Systemic androgen-signaling inhibition added to ongoing androgen-deprivation therapy (ADT) improved clinical outcomes in patients with nonmetastatic castration-resistant prostate cancer without detectable metastases by conventional imaging (nmCRPC). Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) detects prostate cancer with superior sensitivity to conventional imaging, but its performance in nmCRPC remains largely unknown. We characterized cancer burden in high-risk patients with nmCRPC using PSMA-PET. EXPERIMENTAL DESIGN: We retrospectively included 200 patients with nmCRPC, prostate-specific antigen (PSA) >2 ng/mL, and high risk for metastatic disease [PSA doubling time (PSADT) of ≤10 months and/or Gleason score of ≥8] from six high-volume PET centers. We centrally reviewed PSMA-PET detection rate for pelvic disease and distant metastases (M1). We further evaluated SPARTAN patients stratified by risk factors for PSMA-PET-detected M1 disease. RESULTS: PSMA-PET was positive in 196 of 200 patients. Overall, 44% had pelvic diseases, including 24% with local prostate bed recurrence, and 55% had M1 disease despite negative conventional imaging. Interobserver agreement was very high (κ: 0.81-0.91). PSA ≥ 5.5 ng/mL, locoregional nodal involvement determined by pathology (pN1), prior primary radiation, and prior salvage radiotherapy independently predicted M1 disease (all P < 0.05). CONCLUSIONS: PSMA-PET detected any disease in nearly all patients and M1 disease in 55% of patients previously diagnosed with nmCRPC, including subgroups with PSADT of ≤10 months and Gleason score of ≥8. The value of PSMA-PET imaging for treatment guidance should be tested in future studies.

Amino Acid-Derived Sensors for Specific Zn2+ Detection Using Hyperpolarized 13 C Magnetic Resonance Spectroscopy.

Alterations in Zn2+ concentration are seen in normal tissues and in disease states, and for this reason imaging of Zn2+ is an area of active investigation. Herein, enriched [1-13 C]cysteine and [1-13 C2 ]iminodiacetic acid were developed as Zn2+ -specific imaging probes using hyperpolarized 13 C magnetic resonance spectroscopy. [1-13 C]cysteine was used to accurately quantify Zn2+ in complex biological mixtures. These sensors can be employed to detect Zn2+ via imaging mechanisms including changes in 13 C chemical shift, resonance linewidth, or T1 .

Heterogeneous Uptake of 18F-FDG and 68Ga-PSMA-11 in Hepatocellular Carcinoma.

We present the case of an 87-year-old man with a history of melanoma metastatic to the lungs found to have an FDG-negative liver lesion that was initially thought to be benign. Follow-up CT revealed growth of the liver lesion despite excellent response to nivolumab therapy of the pulmonary melanoma metastases. Biopsy of the lesion confirmed primary hepatocellular carcinoma. Follow-up F-FDG PET/CT showed minimal FDG uptake, slightly above liver background, and subsequent Ga-PSMA-11 PET/MR showed focal, intense uptake of radiotracer in a different region of the tumor. These imaging findings support intratumor metabolic heterogeneity with radiotracer uptake in different tumor locations.

Intertumoral Heterogeneity of 18F-FDG and 68Ga-PSMA Uptake in Prostate Cancer Pulmonary Metastases.

We present a case of a 61-year-old man with history of prostate cancer and rising PSA levels referred for restaging. Ga-PSMA-11 PET/CT identified 2 lung nodules with low and moderate PSMA uptake. Subsequent F-FDG PET/CT showed high hypermetabolism in the nodule with low PSMA uptake, and low hypermetabolism in the nodule with moderate PSMA uptake. The isolated pulmonary findings and metabolic appearance is an atypical presentation of prostate cancer metastases and raised concern for a second primary malignancy. Fine-needle aspiration of the F-FDG active lung nodule confirmed metastatic prostatic adenocarcinoma that subsequently responded to androgen deprivation therapy and abiraterone acetate.

Effect of ELP Sequence and Fusion Protein Design on Concentrated Solution Self-Assembly.

Fusion proteins provide a facile route for the purification and self-assembly of biofunctional protein block copolymers into complex nanostructures; however, the use of biochemical synthesis techniques introduces unexplored variables into the design of the structures. Using model fusion constructs of the red fluorescent protein mCherry and the coil-like protein elastin-like polypeptide (ELP), it is shown that the molar mass and hydrophobicity of the ELP sequence have a large effect on the propensity of a fusion to form well-ordered nanostructures, even when the ELP is in the low temperature, highly solvated state. In contrast, the presence of a 6xHis purification tag has little effect on self-assembly, and the order of blocks in the construct (N-terminal vs C-terminal) only has a significant effect on the nanostructure when the conjugates are heated above the transition temperature of the ELP block. These results indicate that for a sufficiently hydrophobic and high molar mass ELP block, there is a great deal of design latitude in the construction of fusion protein block copolymers for self-assembling nanomaterials.