Assessing the Efficacy of Poly(N-isopropylacrylamide) for Drug Delivery Applications Using Molecular Dynamics Simulations.

All-atom molecular dynamic simulations (AA-MD) are performed for aqueous solutions of hydrophobic drug molecules (phenytoin) with model polymer excipients, namely, (1) N-isopropylacrylamide, (pNIPAAm), (2) pNIPAAm-co-acrylamide (Am), and (3) pNIPAAm-co-dimethylacrylamide (DMA). After validating the force field parameters using the well-known lower critical solution behavior of pNIPAAm, we simulate the polymer-drug complex in water and its behavior at temperatures below (295 K) and above the LCST (310 K). Using radial distribution functions, we find that there is an optimum comonomer molar fraction of around 20-30% DMA at which interaction with phenytoin drug molecules is strongest, consistent with recent experimental findings. The results provide evidence that molecular simulations are able to provide guidance in the optimization of novel polymer excipients for drug release.

Free TcO 4- in 99m Tc-PSMA Scan : A Case Report and Review of an Old Pitfall in the New Era of Modern Imaging.

ABSTRACT: In a recent 99m Tc-HYNIC-PSMA study conducted at our department, we examined 2 patients with prostate cancer referred for initial staging on the same day. The whole-body scans revealed radiotracer uptake in the gastric mucosa and thyroid glands, alluding to high levels of free TcO 4- in the injected vial. The scans were repeated after confirming acceptable radiopharmaceutical purity of 97% (normal range, 95%-100%). Interestingly, 1 patient had liver metastases at presentation, which remained non-PSMA-avid after repeating the scan. We have reviewed this pitfall, which has been reported with many radiotracers, yet not reported with PSMA tracers.

Complete Resolution of Locally Advanced Prostate Cancer After Molecular Endoradiotherapy With 177 Lu-PSMA.

ABSTRACT: A 76-year-old man with castration-resistant prostate cancer underwent 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT for restaging. A large PSMA-avid tumor with invasion to adjacent organs was noted causing gross hematuria and symptomatic anemia. Two cycles of 177 Lu-PSMA were administered, and the patient showed significant reduction of hematuria as well as declining in PSA levels. 177 Lu-PSMA therapy can be a good treatment option in patients with locally invasive tumors.

Estimation of ecological footprint based on tourism development indicators using neural networks and multivariate regression.

The ecological footprint has attracted a lot of attention in the top tourism destination countries, and this issue may be worrying. This study aims to estimate the ecological footprint, using such indicators as economic growth, natural resources, human capital, and the number of tourists in top tourism destination countries. For this purpose, artificial neural network models and multivariate regression were used for a period of 24 years (1995-2019). The results of the study showed a significant positive correlation between economic growth and ecological footprint. Multivariate regression estimation (R = 0.75) is weaker than neural network models (R = 96.3). Regarding predicting the ecological footprint, neural network models have better performance in comparison with the multivariate regression statistical methods. Accordingly, one can say that for planning ecological footprint, deeper look at neural networks can be more effective in predicting top tourism destination countries.

Chronological perspective of substitute materials used for the surgical treatment of Peyronie's disease: A scoping review of literature.

This comprehensive scoping review aimed to identify all up-to-date original publications relating to substitute materials used for the surgical treatment of Peyronie's disease (PD), and characterize what material in which chronological trends were published in the current literature. Using the PCC framework (P: population, C: concept, and C: context), a search strategy was developed and used in four electronic databases, in addition to the Google scholar. All current published, in-press, and pre-print manuscripts with available English full-text were included. Eligible studies were required to be original research articles of any study design, reporting the usage of grafts on surgical treatment of PD. Included studies were reported in a narrative synthesis format. A total of 3379 articles were identified via an electronic search of databases and a total of 171 articles entered this scoping review. Most studies originated from Europe (n = 72) and North America (n = 66). Reports from the other continents increase in number in the 21st century. Highest number of the published papers was seen in 2001 to 2005 pentad. Autologous grafts (53.5%). Allografts (22.7%) and xenografts (15.7%) were the most frequently reported materials. Time flow of the used material and the alterations in trends for them is quite considerable. A global perspective of relevant publications on substitute materials in the surgical management of PD is presented in this review. The information in this summary may assist in establishing future research priorities in this area.

Peptide Receptor Radionuclide Therapy in Merkel Cell Carcinoma: A Comprehensive Review.

Merkel cell carcinoma is a rare, aggressive skin malignancy, also known as neuroendocrine carcinoma of the skin, with high rates of recurrence and distant metastasis. In refractory metastatic Merkel cell carcinoma (mMCC), besides immunotherapy, chemotherapy, and radiation, peptide receptor radionuclide therapy (PRRT) may be a viable option since this type of tumor can express somatostatin receptors. Methods: We performed a comprehensive review of the literature to evaluate the efficacy of PRRT in mMCC patients. Results: Thirty-seven patients with mMCC received PRRT (1-5 cycles) with 177Lu- or 90Y-labeled somatostatin analogs (cumulative activity, 1.5-30 GBq). Radiographic response was available for 19 of 28 patients who received PRRT alone. Six (31.6%) of 19 patients showed objective responses, from partial to complete, and no severe adverse events were reported. Conclusion: Our analysis supports the use of PRRT in mMCC with sufficient somatostatin receptor uptake, although the quality of the available evidence is low. Prospective clinical trials are already in development and have started accruing in some parts of the world.

Efficacy, safety and prognostic factors affecting overall survival among metastatic prostate cancer patients undergoing treatment with 177Lu-PSMA-617: A single center study.

BACKGROUND: Determining the efficacy, safety, and prognostic factors affecting overall survival (OS) among metastatic prostate cancer patients undergoing PSMA-targeted radioligand therapy (PRLT). METHOD: In this retrospective study, from November 2016 and December 2019, 43 heavily pretreated (90.7% on 1st line androgen deprivation therapy (ADT), 53.5% on 2nd line ADT, 58.1% on docetaxel) metastatic prostate cancer patients with median age of 71 years (range: 51-88 years) were enrolled. Treatment cycles were repeated every 8 weeks (range: 6-12 weeks). To evaluate the biochemical response after each cycle, prostate specific antigen (PSA) levels were measured and analyzed according to the Prostate Cancer Working Group 3 (PCWG3) criteria cutoffs. Possible adverse events after therapy were retrospectively classified according to the Common Toxicity Criteria for Adverse Events (CTCAE) v.5.0. Kaplan-Meier and multivariable Cox proportional hazard regression analyses were used to identify factors associated with OS. RESULTS: A total of 112 cycles of PRLT with a median of 3 cycles (range: 1-6) and median administered activity per cycle of 6.29 GBq (range: 4.45-7.7 GBq) were used. PSA decline was observed in 65.1% of patients, and best PSA decline of ≥50% and ≥90% were achieved in 39.5% and 23.3% of patients, respectively. Major (grade III) anemia and thrombocytopenia occurred in 11.6% and 7% of patients, respectively. Median OS and median PSA progression-free survival were 52 and 20 weeks, respectively. In univariate analysis, baseline hemoglobin <11.2 g/dL, baseline platelets count ≥327,000/µL, PSA decline <20.94% after first cycle of therapy, Eastern Cooperative Oncology Group (ECOG) >2, baseline PSA ≥ 115 ng/mL, cumulative dose of 177Lu-PSMA <12.95 GBq, initial alkaline phosphatase ≥196.5 U/L, initial lactate dehydrogenase ≥380 U/L and superscan pattern in bone scintigraphy were associated with worse OS. In multivariable Cox regression analysis, higher baseline platelet count, lower baseline hemoglobin, superscan pattern, and lower cumulative dose of 177Lu-PSMA remained significant predictors of poor OS. CONCLUSION: PRLT with 177Lu-PSMA is well-tolerated and effective in metastatic prostate cancer patients who have no other treatment options available. The novel prognostic markers found in this study (high platelet count, superscan pattern) were associated with poor overall survival.

Amino acid extravasation: a rare red flag to keep in mind during peptide receptor radioligand therapy (PRRT) with [177Lu]Lu-DOTATATE.

A 64 years-old woman with intestinal neuroendocrine tumor (NET) and multiple liver metastases was referred for peptide receptor radioligand therapy (PRRT) with [177Lu]Lu-DOTATATE. A few days after the third cycle of PRRT, erythema and swelling in the injection site is occurred which progressed up to one-month post-therapy. The cutaneous lesion was managed by a plastic surgeon with topical treatment. Amino acid extravasation could have devastating effects and should always be considered in patients who underwent PRRT and who receive amino acids for nephroprotection.

68 Ga-FAPI-46 PET/CT in a Metastatic Castration-Resistant Prostate Cancer Patient With Low PSMA Expression.

ABSTRACT: A 70-year-old man with mCRPC (metastatic castration-resistant prostate cancer) was referred for 68 Ga-PSMA PET/CT for restaging and the possibility of targeted molecular radioligand therapy with 177 Lu-PSMA. Numerous 68 Ga-PSMA-avid skeletal metastases with low SUVs were noted. Because of low PSMA expression, a 68 Ga-FAPI-46 PET/CT was performed to evaluate the eligibility for FAPI-based radioligand therapy. There were some discordant findings between 68 Ga-PSMA and 68 Ga-FAPI PET/CT scans regarding the detectability of lesions and SUVs. Our case signifies that 68 Ga-FAPI theragnostic may have a potential role in the treatment of mCRPC patients with insignificant PSMA expression or in cases after the failure of 177 Lu-PSMA therapy.

Whole-Body 177Lu-Prostate-Specific Membrane Antigen Scan Pattern With Excess Free 177Lu-Chloride in a Metastatic Castration-Resistant Prostate Cancer Patient.

A 56-year-old man with metastatic castration-resistant prostate cancer was referred for radioligand therapy with Lu-prostate-specific membrane antigen. In the third cycle, a posttherapy whole-body scan showed unexpected skeletal and joint uptake apart from his known metastatic lesions. This observation raised suspicion for possible impurity (mainly free lutetium) in the applied radiopharmaceutical product. After contacting the radiopharmaceutical company, we were informed that the radiochemical purity of the used batch of Lu-prostate-specific membrane antigen had been 95%. This is the first report of excess free lutetium scan pattern and its complications in a patient undergoing radioligand therapy.

Medical Event: Accidental Oral Administration of 177Lu-PSMA to a Patient With Hyperthyroidism.

A 74-year-old woman with hyperthyroidism was referred for radioiodine therapy. The patient was accidentally given 60 mCi of Lu-PSMA orally instead of I. Upon discovery of this medical event, we immediately started radiation protective actions including hydration, antiemetics, and laxatives. The patients did not have any symptoms. Static acquisition was performed from the abdominal-pelvic and head and neck regions at 20 and 90 hours after ingestion, which showed prominent intestinal activity and mild systemic activity in the kidneys, bladder, salivary, and lacrimal glands.

Favorable Response After Only One Cycle of Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE in a Patient With Metastatic Merkel Cell Carcinoma.

A 77-year-old man with a history of metastatic Merkel cell carcinoma and debilitating painful cutaneous lesions was referred to our nuclear medicine department for peptide receptor radionuclide therapy with Lu-DOTATATE as ultimate therapeutic option. Post-treatment whole body scan showed multiple zones of Lu-DOTATATE uptake in the metastatic regions, which revealed significant improvement within the next 10 days of therapy. Peptide receptor radionuclide therapy in metastatic Merkel cell carcinoma is an effective therapeutic option that should be considered in earlier stages of the disease.

Slip-Spring and Kink Dynamics Models for Fast Extensional Flow of Entangled Polymeric Fluids.

We combine a slip-spring model with an 'entangled kink dynamics' (EKD) model for strong uniaxial extensional flows (with Rouse Weissenberg number W i R ≫ 1 ) of long ( M w > 1   Mkg / mol for polystyrene) entangled polymers in solutions and melts. The slip-spring model captures the dynamics up to the formation of a 'kinked' or folded state, while the kink dynamics simulation tracks the dynamics from that point forward to complete extension. We show that a single-chain slip-spring model using affine motion of the slip-spring anchor points produces unrealistically high tension near the center of the chain once the Hencky strain exceeds around unity or so, exceeding the maximum tension that a chain entangled with a second chain is able to support. This unrealistic tension is alleviated by pairing the slip links on one chain with those on a second chain, and allowing some of the large tension on one of the two to be transferred to the second chain, producing non-affine motion of each. This explicit pairing of entanglements mimics the entanglement pairing also used in the EKD model, and allows the slip spring simulations to be carried out to strains high enough for the EKD model to become valid. We show that results nearly equivalent to those from paired chains are obtained in a single-chain slip-spring simulation by simply specifying that the tension in a slip spring cannot exceed the theoretical maximum value of ζ ' ϵ ˙ L 2 / 8 where ζ ' , ϵ ˙ and L are the friction per unit length, strain rate and contour length of the chain, respectively. The effects of constraint release (CR) and regeneration of entanglements is also studied and found to have little effect on the chain statistics up to the formation of the kinked state. The resulting hybrid model provides a fast, simple, simulation method to study the response of high molecular weight ( M w > 1   Mkg / mol ) polymers in fast flows ( W i R ≫ 1 ), where conventional simulation techniques are less applicable due to computational cost.

Benign High-Flow Priapism With a Diffuse and Intense 18F-FDG Uptake on 18F-FDG PET/CT Scanning.

We present benign high-flow priapism with intensive F-FDG uptake as an unusual finding in a case of testicular teratocarcinoma with a history of left orchiectomy and chemotherapy. F-FDG PET/CT scan showed pulmonary metastases, left obturator node involvement, and intense F-FDG uptake in the penis. Upon examination, the patient had a painless erection that lasted for couple of days. Because of pulmonary metastases, second-line chemotherapy regimen was started by his physician. The patient's priapism resolved spontaneously, with no episode of recurrence at 2 years' follow-up.

Sagliker Syndrome in a Patient with Secondary Hyperparathyroidism and Chronic Renal Insufficiency: A Case Report.

Sagliker syndrome is a rare form of renal osteodystrophy resulted from untreated secondary hyperparathyroidism. It is described by severe skeletal deformities, high level of PTH in patients with chronic renal failure, and deformed face. This paper reports a 44-year-old male patient with the mentioned characteristics. In addition to the unique clinical features, high levels of ALP and PTH hormones encouraged us to search for syndrome-like a disease, which clinically and paraclinically matched the Sagliker syndrome. This case highlights the importance of clinicians' attention for early monitoring and appropriate treatment as it is shown to be effective in preventing irreversible complications such as soft tissue and bone abnormalities and cardiovascular impairment in patients with Sagliker syndrome. Therefore, considering the syndrome is recommended as one of the diagnostic hypothesis in young patients with renal insufficiency, secondary hyperparathyroidism, and skeletal deformities.

177Lu-Prostate-Specific Membrane Antigen Super Scan and Good Response Even After 1 Cycle of Radioligand Therapy.

A 76-year-old man with castration-resistant prostate cancer and widespread skeletal metastases underwent 2 cycles of Lu-prostate-specific membrane antigen (PSMA) 617 therapy in our department. Whole-body Lu-PSMA scan after the first cycle showed diffuse skeletal PSMA-avid lesions, whereas no PSMA uptake was evident in the kidneys with minimal PSMA uptake by salivary glands (super scan). After 6 weeks, he received the second dose of Lu-PSMA and whole-body scan after the treatment showed remarkable resolution of skeletal metastases and normal PSMA uptake by the kidneys and salivary glands. To our best knowledge, this is the first case report of Lu-PSMA super scan.