Efficacy of clear aligner therapy over conventional fixed appliances in controlling orthodontic movement: A systematic review.

OBJECTIVE: The purpose of the current systematic review was to answer the clinical research question "Is Clear Aligner Therapy (CAT) effective in controlling the orthodontic movement?" by bringing together the most up-to-date information about the available evidence for CAT. METHODOLOGY: On January 1, 2023, a search was conducted in PubMed, ERIC, Embase, and CINHAL for any research papers published in the previous 10 years that provided an overview of the PICO questions. Both the titles and abstracts of the selected studies were evaluated independently by two different authors, and if there was any disagreement between the two review authors, a third reviewer was brought in to settle it. RESULTS: Among included studies, three were retrospective non-randomized and two studies were prospective randomized clinical trials. Various authors reported better outcome for fixed orthodontic appliances than for clear aligner treatment (CAT) in relation to mandibular incisor proclination. The mean objective grading system score was better for braces (17) than for CAT (12) with no clinically significant difference, while staging had a significant impact on treatment efficacy. CONCLUSION: The results of this study suggest that clear aligners may be an effective alternative to traditional braces, but more research is needed to confirm these findings and determine the optimal size of future prospective studies evaluating this treatment.

The academic progress of female general surgery and orthopaedic surgery trainees in South Africa.

BACKGROUND: Globally, medical institutes have seen an increase in female graduates, however surgical disciplines remain male-dominated. An epidemiological shift towards non-communicable diseases and trauma may result in a shortage of surgical specialists. One strategy to improve the surgical workforce is the recruitment of female graduates. METHODS: A non-validated questionnaire was administered to females registered for the Master of Medicine (MMED) degree in General and Orthopaedic Surgery at the University of KwaZulu-Natal (UKZN) between 2000 and 2015. The study evaluated reasons for choice of surgery as a career, challenges faced on the domestic and work front, as well as factors that assisted with successful completion of training. RESULTS: Seventy-two female trainees in General Surgery and Orthopaedics were identified from the UKZN databases. The contact details for 62 of these trainees were available. The overall response rate was 71.0% (44/62). A total of 95.5% (42/44) of participants selected surgery due to a passion for the field. Major challenges identified were a poor home and work-life balance (72.1%, 31/43) and poor working conditions (62.8%, 27/43). Female trainees perceived that they were viewed as inferior by patients (65.9%, 29/44). Successful trainees had a good home support system (89.3%, 25/28) and mentorship during training (60.7%, 17/28), and 85.7% (24/28) did not regret their career choice. CONCLUSION: The recruitment and retention of females in surgery will contribute to maintaining an adequate surgical workforce. Training programmes need to improve work-life balance without compromising on producing competent surgeons. Improved visibility of female surgeons in leadership roles should be encouraged to promote mentorship and recruitment of trainees.

Effectiveness and Safety of Retreatment with 177Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States.

Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of 177Lu-DOTATATE therapy in patients with progressive NETs. Methods: This was a retrospective chart review of adults with advanced NETs. The patients had undergone initial treatment with up to 4 cycles of 177Lu-DOTATATE and, after disease progression and a period of at least 6 mo since the end of the initial treatment, were retreated with at least 1 additional cycle at a single center (2010-2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using criteria from Common Terminology Criteria for Adverse Events, version 5.0. Kaplan-Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177Lu-DOTATATE retreatment, 61% were male and 94% were White. Overall, patients received a median of 6 cycles (4 initial cycles and 2 retreatment cycles), and the mean administered activity was 41.9 GBq. Two patients also went on to receive additional retreatment (1 and 2 cycles, individually) after a second period of at least 6 mo and progression after retreatment. Best responses of partial response and stable disease were observed in 35% and 65% of patients after the initial treatment and 23% and 45% of patients after retreatment, respectively. The median PFS after the initial treatment was 20.2 mo and after retreatment was 9.6 mo. The median OS after the initial treatment was 42.6 mo and after retreatment was 12.6 mo. Hematologic parameters decreased significantly during both the initial treatment and retreatment but recovered such that there was little difference between the values before the initial treatment and before the retreatment. Clinically significant hematotoxicity occurred in 1 and 3 patients after the initial treatment and retreatment, respectively. No grade 3 or 4 nephrotoxicity was observed. Conclusion: Retreatment with 177Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial 177Lu-DOTATATE treatment.

Revealing the Effect of Impacted Canines on the Adjacent Teeth. A Three Dimensional Study Using CBCT.

Objective: The current cross-sectional study aimed to assess the relationship between impacted maxillary canines and their effect on root resorption of neighboring teeth using cone-beam computed tomography (CBCT). Materials and Methods: The study evaluated the effect of 24 impacted maxillary canines on the adjacent tooth roots. We used a CBCT to evaluate the position and size of the dental follicle of impacted maxillary canines and the severity of root resorption on adjacent teeth. We used a t-test to compare the significant differences between the width of the dental follicle and the severity of root resorption. The inter- and intra-rater agreements were assessed. Results: A number of 12 impacted canines had resorbed the roots of adjacent teeth. Lateral incisors were most affected (83.3%), followed by central incisors (16.7%). Mild root resorption was found in 10 cases, while severe resorption was found in two cases. We found no relation between the size of the dental follicle and the degree of root resorption. The inter- and intra-rater agreements were high. Conclusion: In cases with maxillary impacted canines, special consideration should be directed to the roots of the maxillary lateral incisors. Our findings could not confirm any relationship between the size of the dental follicle width of the maxillary impacted canines and the degree of root resorption of the adjacent incisors. More studies are needed to assess the proximity and path of eruption of impacted maxillary canines and their effect on the neighboring teeth.

Fundamentals and Applications of Isolated Perfused Lung (IPL) Model in the Development of Pulmonary Drug Delivery.

Estimating parameters such as pulmonary drug disposition and deposited dose, as well as determining the influence of pulmonary pharmacokinetics (PK) on drug efficacy and safety, are critical factors for the development of inhaled drug products and help to achieve a better understanding of the drugs' fate in the lungs. Pulmonary disposition and PK have remained poorly understood due to the difficulty to access pulmonary fluids, compared to other biological fluids, such as plasma, for direct or surrogate measurement of the concentration of the active compounds and their metabolites in the lung. The use of the isolated perfused lung model (IPL) has become more common, and it is considered a useful tool to increase understanding in this area since it offers the possibility of controlling the administration and easier sampling of perfusate and lavage fluid. The model also provides an opportunity to study the relationship between PK and pharmacodynamics. This review describes the fundamentals of the IPL model, such as preparation and setting up the method, species selection, drug administration, and lung viability investigation. Besides, different applications of the IPL model like pharmacodynamic studies, pharmacokinetic parameters studies such as absorption, distribution, and metabolism, and evaluation of inhaled formulation have also been reviewed.

Enterobiasis among Yemeni children: a cross-sectional study.

Enterobiasis is a highly infectious parasitic disease spreading worldwide including Yemen. Therefore, this study aimed to investigate the prevalence and risk factors of enterobiasis among Yemeni children in Dhamar governorate. A total of 402 children (aged 1-12 years) participated in this cross-sectional survey carried out at Thamar University Al-Wahdah Teaching Hospital (TUWTH), between 2018 and 2019. Enterobius vermicularis infection was examined using the adhesive tape technique. Association between risk factors and enterobiasis were measured by prevalence ratio (PR). The overall prevalence of enterobiasis was found to be 29.4% (118/402). Risk factors that showed independent association with the infection were child's care responsibility (PR = 1.90; 95% CI = 1.37-2.63; P = 0.001); irregular washing hands before meals (PR = 2.01; 95% CI = 1.32-3.05; P = 0.003); habit of nail biting or cutting by teeth (PR = 1.61; 95% CI = 1.18-2.21; P = 0.002); habit of putting toys or pen in mouth (PR = 1.58; 95% CI = 1.19-2.10; P = 0.002); frequent anal itching (PR = 1.46; 95% CI = 1.10-1.93; P = 0.016); using anthelmintic during the last six months (PR = 1.68; 95% CI = 1.20-2.36; P = 0.011); and parents have no knowledge on preventive measures (PR = 1.62; 95% CI = 1.04-2.53; P = 0.036). Prevalence of enterobiasis among Yemeni children in Dhamar governorate is high with higher infection rate among those aged 1-6 years. Health education and mass treatment are highly recommended among this poor population.

A smartphone-based portable fundus camera for retinal photography in infants with suspected nonaccidental trauma.

We describe a novel, do-it-yourself smartphone-based fundus camera to help with documentation of retinal hemorrhages in infant patients with suspected nonaccidental trauma. This device can be easily assembled from commercially available and inexpensive materials. We discuss the advantages and limitations of our described fundus camera and provide representative images.

Diagnostic Value of Radiolabelled Somatostatin Analogues for Neuroendocrine Tumour Diagnosis: The Benefits and Drawbacks of [64Cu]Cu-DOTA-TOC.

Neuroendocrine tumours (NETs) arise from secondary epithelial cell lines in the gastrointestinal or respiratory system organs. The rate of development of these tumours varies from an indolent to an aggressive course, typically being initially asymptomatic. The identification of these tumours is difficult, particularly because the primary tumour is often small and undetectable by conventional anatomical imaging. Consequently, diagnosis of NETs is complicated and has been a significant challenge until recently. In the last 30 years, the advent of novel nuclear medicine diagnostic procedures has led to a substantial increase in NET detection. Great varieties of exclusive single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals for detecting NETs are being applied successfully in clinical settings, including [111In]In-pentetreotide, [99mTc]Tc-HYNIC-TOC/TATE, [68Ga]Ga-DOTA-TATE, and [64Cu]Cu-DOTA-TOC/TATE. Among these tracers for functional imaging, PET radiopharmaceuticals are clearly and substantially superior to planar or SPECT imaging radiopharmaceuticals. The main advantages include higher resolution, better sensitivity and increased lesion-to-background uptake. An advantage of diagnosis with a radiopharmaceutical is the capacity of theranostics to provide concomitant diagnosis and treatment with particulate radionuclides, such as beta and alpha emitters including Lutetium-177 (177Lu) and Actinium-225 (225Ac). Due to these unique challenges involved with diagnosing NETs, various PET tracers have been developed. This review compares the clinical characteristics of radiolabelled somatostatin analogues for NET diagnosis, focusing on the most recently FDA-approved [64Cu]Cu-DOTA-TATE as a state-of-the art NET-PET/CT radiopharmaceutical.

One-step electrodeposition of a polypyrrole/NiO nanocomposite as a supercapacitor electrode.

An electrochemical deposition technique was used to fabricate polypyrrole (Ppy)/NiO nanocomposite electrodes for supercapacitors. The nanocomposite electrodes were characterized and investigated by Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), scanning electron microscopy (SEM), cyclic voltammetry (CV), galvanostatic charge-discharge (GCD) and electrochemical impedance spectroscopy (EIS). The performance of supercapacitor electrodes of Ppy/NiO nanocomposite was enhanced compared with pristine Ppy electrode. It was found that the Ppy/NiO electrode electrodeposited at 4 A/cm-2 demonstrated the highest specific capacitance of 679 Fg-1 at 1 Ag-1 with an energy density of 94.4 Wh kg-1 and power density of 500.74 W kg-1. Capacitance retention of 83.9% of its initial capacitance after 1000 cycles at 1 Ag-1 was obtained. The high electrochemical performance of Ppy/NiO was due to the synergistic effect of NiO and Ppy, where a rich pores network-like structure made the electrolyte ions more easily accessible for Faradic reactions. This work provided a simple approach for preparing organic-inorganic composite materials as high-performance electrode materials for electrochemical supercapacitors.

Targeted α-Emitter Therapy with 212Pb-DOTAMTATE for the Treatment of Metastatic SSTR-Expressing Neuroendocrine Tumors: First-in-Humans Dose-Escalation Clinical Trial.

Peptide receptor radiotherapy with somatostatin analogs has been successfully used for years as a treatment for somatostatin-overexpressing tumors. Treatment of neuroendocrine tumors (NETs) with the ß-particle emitter 177Lu-DOTATATE is currently considered the standard of care for subjects with gastroenteropancreatic NETs. Despite the success of 177Lu-DOTATATE, there remains significant room for improvement in terms of both safety and efficacy. Targeted α-emitter therapy with isotopes such as 212Pb has the potential to improve both. Here, we present the preliminary results of the phase 1 first-in-humans dose-escalation trial evaluating 212Pb-DOTAMTATE (a bifunctional metal chelator [DOTAM] and the SSTR-targeting peptide [TATE]) in patients with somatostatin receptor-positive NETs. Methods: Twenty subjects with histologically confirmed NETs, prior positive somatostatin analog scans, and no prior history of 177Lu/90Y/111In peptide receptor radiotherapy, with different primary sites of the disease, were enrolled. Treatment began with single ascending doses of 212Pb-DOTAMTATE, with subsequent cohorts receiving an incremental 30% dose increase, which was continued until a tumor response or a dose-limiting toxicity was observed. This was followed by a multiple ascending dose regimen. The recommended phase 2 dose regimen consisted of 4 cycles of 2.50 MBq/kg (67.6 µCi/kg) of 212Pb-DOTAMTATE administered at 8-wk intervals, intravenously. Results: Ten subjects received the highest dose, 2.50 MBq/kg/cycle (67.6 µCi/kg/cycle). Treatment was well tolerated, with the most common treatment-emergent adverse events being nausea, fatigue, and alopecia. No serious treatment-emergent adverse events were related to the study drug, and no subjects required treatment delay or a dose reduction. An objective radiologic response of 80% was observed for the first 10 subjects treated at the recommended phase 2 dose. Conclusion: Targeted α-therapy with 212Pb-DOTAMTATE has been shown to be well tolerated. Preliminary efficacy results are highly promising. If these results are confirmed in a larger, multicenter clinical trial, 212Pb-DOTAMTATE would provide a substantial benefit over currently Food and Drug Administration-approved therapies for patients with metastatic or inoperable SSTR-expressing NETs regardless of the grade and location of the primary tumor.

Tumor Sink Effect in 68Ga-PSMA-11 PET: Myth or Reality?

We aimed to systematically determine the impact of tumor burden on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent 68Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, ≤25 cm3), low (quintile 2, 25-189 cm3), moderate (quintile 3, 189-532 cm3), high (quintile 4, 532-1,355 cm3), or very high (quintile 5, ≥1,355 cm3) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using 68Ga-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm3 (interquartile range [IQR], 47-1,076 cm3). The median SUVmean of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7-11.8), 26.0 (IQR, 20.0-33.4), 3.7 (IQR, 3.0-4.7), and 5.3 (IQR, 4.0-7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUVmean of the salivary glands (r = -0.44, P < 0.001), kidneys (r = -0.34, P < 0.001), and liver (r = -0.30, P < 0.001) and a weak negative correlation with the spleen SUVmean (r = -0.16, P = 0.002). Patients with a very high PSMA-VOL (quintile 5, ≥1,355 cm3) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of -38.1%, -40.0%, -43.2%, and -34.9%, respectively (P < 0.001). Conclusion: Tumor sequestration affects 68Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of 68Ga-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk.

Student perceptions of an online surgical teaching programme during the COVID-19 pandemic at the University of KwaZulu-Natal: A short report

Background. The COVID-19 pandemic has led to an unprecedented global health crisis, with impacts on many facets of the health system, including lack of access to regular training wards and the need for social distancing, which posed particular challenges to undergraduate teaching. Objectives. To explore the perceptions of students of the online surgical programme at the University of KwaZulu-Natal (UKZN). Methods. An online survey was administered to 258 final-year students. Data were collected on student demographics, the impact of COVID-19 restrictions on the teaching programme, engagement and learning from live Zoom sessions, overall perceptions about the module and general feedback on students' experience of the programme. Results. Most students (84%, 77/91) supported the need to change to the virtual programme. The module was perceived as well-structured (89%, 81/91). Most students (87%, 79/91) regarded the online resource materials as beneficial. Analysis of open-ended responses showed that asynchronous delivery allowed students to review and revisit resources in their own time. Student challenges included poor internet connectivity, difficulty in concentrating where live sessions exceeded an hour, and lack of clinical exposure. Conclusion. Online teaching in medical education is a feasible option for remote learning. However, it cannot replace the benefits gained during clinical exposure. Findings from this study will help to set a benchmark for online surgical training at UKZN and develop best practices for blended teaching models. As we adapt to a new normal in the era of COVID-19, the disruptions and results of innovative teaching methods have the potential to change the future of medical education

Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study.

BACKGROUND: Lutetium-177 (177Lu) prostate-specific membrane antigen (177Lu-PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Predictors of outcomes after 177Lu-PSMA to enhance its clinical implementation are yet to be identified. We aimed to develop nomograms to predict outcomes after 177Lu-PSMA in patients with mCRPC. METHODS: In this multicentre, retrospective study, we screened patients with mCRPC who had received 177Lu-PSMA between Dec 10, 2014, and July 19, 2019, as part of the previous phase 2 trials (NCT03042312, ACTRN12615000912583) or compassionate access programmes at six hospitals and academic centres in Germany, the USA, and Australia. Eligible patients had received intravenous 6·0-8·5 GBq 177Lu-PSMA once every 6-8 weeks, for a maximum of four to six cycles, and had available baseline [68Ga]Ga-PSMA-11 PET/CT scan, clinical data, and survival outcomes. Putative predictors included 18 pretherapeutic clinicopathological and [68Ga]Ga-PSMA-11 PET/CT variables. Data were collected locally and centralised. Primary outcomes for the nomograms were overall survival and prostate-specific antigen (PSA)-progression-free survival. Nomograms for each outcome were computed from Cox regression models with LASSO penalty for variable selection. Model performance was measured by examining discrimination (Harrell's C-index), calibration (calibration plots), and utility (patient stratification into low-risk vs high-risk groups). Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort. FINDINGS: Between April 23, 2019, and Jan 13, 2020, 414 patients were screened; 270 (65%) of whom were eligible and were divided into development (n=196) and validation (n=74) cohorts. The median duration of follow-up was 21·5 months (IQR 13·3-30·7). Predictors included in the nomograms were time since initial diagnosis of prostate cancer, chemotherapy status, baseline haemoglobin concentration, and [68Ga]Ga-PSMA-11 PET/CT parameters (molecular imaging TNM classification and tumour burden). The C-index of the overall survival model was 0·71 (95% CI 0·69-0·73). Similar C-indices were achieved at internal validation (0·71 [0·69-0·73]) and external validation (0·72 [0·68-0·76]). The C-index of the PSA-progression-free survival model was 0·70 (95% CI 0·68-0·72). Similar C-indices were achieved at internal validation (0·70 [0·68-0·72]) and external validation (0·71 [0·68-0·74]). Both models were adequately calibrated and their predictions correlated with the observed outcome. Compared with high-risk patients, low-risk patients had significantly longer overall survival in the validation cohort (24·9 months [95% CI 16·8-27·3] vs 7·4 months [4·0-10·8]; p<0·0001) and PSA-progression-free survival (6·6 months [6·0-7·1] vs 2·5 months [1·2-3·8]; p=0·022). INTERPRETATION: These externally validated nomograms that are predictive of outcomes after 177Lu-PSMA in patients with mCRPC might help in clinical trial design and individual clinical decision making, particularly at institutions where 177Lu-PSMA is introduced as a novel therapeutic option. FUNDING: Prostate Cancer Foundation.

Peptide receptor radionuclide therapy for treatment of metastatic neuroendocrine tumors in children.

Neuroendocrine tumors (NETs) of the pancreas and midgut are extremely rare in children, and patients presenting with metastatic disease have poor survival. Given this rarity, treatments are extrapolated from guidelines for adults with NET. Recent clinical trials in adults with NETs have shown that the addition of peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE resulted in a disease control rate of nearly 80%, with minimal side effects. We report our experience using 177 Lu-DOTATATE to treat two pediatric patients with metastatic NET.

Laser-Assisted Adjustable Suture Technique in Strabismus Surgery.

PURPOSE: The aim of this study was to assess the efficacy and safety of a new technique (argon laser-assisted lysis of the adjustable suture) in strabismus surgery. PATIENTS AND METHODS: Recession of lateral rectus muscle was done and was secured to the sclera at the predetermined recession position after suspending it 1.5-2.5 mm farther. A 10-0 nylon suture was placed at the original insertion site, passed under the previously tied muscle suture knot, and tied, advancing the muscle to the new scleral insertion. Postoperatively in the same day of surgery, if the targeted slight overcorrection was not achieved, a topical anesthetic was given, and argon laser was used to cut the nylon suture providing additional muscle recession. RESULTS: Forty-two patients with exotropia were included: 11 children and 31 adults. Eleven (26.2%) patients became orthophoric immediately following muscle recession. Thirty-one (73.8%) patients were undercorrected with a mean residual angle of 8.2±3.3 pd. After laser-assisted release of the suture, 12 (28.6%) patients were orthophoric, with 4 (9.5%) patients still undercorrected and 26 (61.9%) patients overcorrected. By the end of 6 months postoperatively, the overall success rate of the procedure was 88.1%, with only 5 (11.9%) patients with exotropia. CONCLUSION: The laser-assisted adjustable suture technique had an overall success rate of 88.1% with only 11.9% of the patients showing exotropia. The technique can help achieve successful alignment.

Efficacy and Safety of 177Lu-labeled Prostate-specific Membrane Antigen Radionuclide Treatment in Patients with Diffuse Bone Marrow Involvement: A Multicenter Retrospective Study.

The 177Lu-labeled prostate-specific membrane antigen (LuPSMA) radionuclide therapy for metastatic castration-resistant prostate cancer is under investigation in a phase III trial (VISION: NCT03511664). However, patients with diffuse bone involvement, diagnosed with a "superscan" by bone scintigraphy at baseline, were excluded due to a lack of efficacy and safety data. We therefore aimed to investigate the feasibility of LuPSMA in patients with diffuse bone marrow involvement on baseline PSMA-targeted positron emission tomography. The primary end points were prostate-specific antigen (PSA) response (Prostate Cancer Working Group 3 [PCWG3]), hematologic safety profile (Common Terminology Criteria for Common Adverse Events [CTCAE]), and overall survival. Secondary end points of quality of life (assessed with Brief Pain Inventory-Short Form questionnaires) and radiologic response (Response Evaluation Criteria in Solid Tumors [RECIST]) were assessed. Through retrospective screening of databases, we identified 43 eligible patients across four centers worldwide who received 154 cycles of LuPSMA under clinical trials or compassionate access programs. Median baseline PSA was 1000 (interquartile range 431-2151) ng/ml. PSA decline of at least 50% at 12 wk was achieved in 22 (58%) patients, while median time to pain progression was 8.3 (95% confidence interval [CI] 4.1-12.6) mo. Median overall survival was 11.6 (95% CI 8.8-14.3) mo. Objective response in nodal or visceral disease was reported in seven (39%) of 18 patients with RECIST measurable disease. Grade 3 anemia, thrombocytopenia, and neutropenia occurred in nine (22%), seven (17%), and three (8%) patients, respectively. Grade 4 thrombocytopenia was noticed in three (8%) patients. In conclusion, patients with diffuse bone marrow involvement demonstrated similar LuPSMA efficacy and safety to phase II evidence. Acceptable safety outcomes do not support exclusion of patients with a superscan from future LuPSMA treatment protocols. PATIENT SUMMARY: In this report, we investigated the feasibility of prostate-specific membrane antigen (PSMA)-directed radionuclide treatment in patients with metastatic castration-resistant prostate cancer and diffuse bone involvement. We found that, despite a high load of bone metastases, PSMA-targeted therapy remains efficacious and safe when compared with the current phase II trial results.

NO FACE-DOWN POSITIONING SURGERY FOR THE REPAIR OF CHRONIC IDIOPATHIC MACULAR HOLES.

PURPOSE: To report visual and anatomical outcomes after the repair of chronic idiopathic macular holes (MHs) with no face-down positioning. METHODS: We conducted a retrospective review of chronic MH cases of greater than 1-year duration that were repaired through pars plana vitrectomy with broad internal limiting membrane peeling and no face-down positioning between March 2009 and December 2017. There were 18 eyes of 18 patients that met inclusion criteria. Patients with MH duration of less than 1 year and without at least 1 month of follow-up were excluded. Macular hole staging and measurements were performed with spectral domain optical coherence tomography. RESULTS: Mean MH duration was 5.0 ± 6.9 years. Two-thirds of MHs had a basal diameter of more than 1,000 µm. Mean preoperative Snellen visual acuity was 20/302 and improved to a mean postoperative visual acuity of 20/112 (P ≤ 0.0001). Visual acuity improved in all patients who achieved successful anatomical closure, 94.4% (17/18) of eyes. CONCLUSION AND RELEVANCE: Patients in this series with chronic MH who underwent no-face-down MH repair demonstrated a high single-surgery anatomical closure rate with a significant improvement in visual acuity.

64Cu-DOTATATE PET/CT for Imaging Patients with Known or Suspected Somatostatin Receptor-Positive Neuroendocrine Tumors: Results of the First U.S. Prospective, Reader-Masked Clinical Trial.

Studies demonstrate that the investigational 64Cu-DOTATATE radiopharmaceutical may provide diagnostic and logistical benefits over available imaging agents for patients with somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs). Accordingly, we aimed to prospectively determine the lowest dose of 64Cu-DOTATATE that facilitates diagnostic-quality scans and evaluated the diagnostic performance and safety in a phase III study of patients with SSTR-expressing NETs. Methods: A dose-ranging study was conducted on 12 patients divided into 3 dose groups (111 MBq [3.0 mCi], 148 MBq [4.0 mCi], and 185 MBq [5.0 mCi] ± 10%) to determine the lowest dose of 64Cu-DOTATATE that produced diagnostic-quality PET/CT images. Using the 64Cu-DOTATATE dose identified in the dose-ranging study, 3 independent nuclear medicine physicians who were masked to all clinical information read PET/CT scans from 21 healthy volunteers and 42 NET-positive patients to determine those with disease or no disease, as well as those with localized versus metastatic status. Masked-reader evaluations were compared with a patient-specific standard of truth, which was established by an independent oncologist who used all previously available pathology, clinical, and conventional imaging data. Diagnostic performance calculated for 64Cu-DOTATATE included sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. Inter- and intrareader reliability, as well as ability to differentiate between localized and metastatic disease, was also determined. Adverse events were recorded from 64Cu-DOTATATE injection through 48 h after injection. Results: The dose-ranging study identified 148 MBq (4.0 mCi) as the optimal dose to obtain diagnostic-quality PET/CT images. After database lock, diagnostic performance from an initial majority read of the 3 independent readers showed a significant 90.9% sensitivity (P = 0.0042) and 96.6% specificity (P < 0.0001) for detecting NETs, which translated to a 100.0% sensitivity and 96.8% specificity after correcting for an initial standard-of-truth misread. Excellent inter- and intrareader reliability, as well as ability to distinguish between localized and metastatic disease, was also noted. No adverse events were related to 64Cu-DOTATATE, and no serious adverse events were observed. Conclusion:64Cu-DOTATATE PET/CT is a safe imaging technique that provides high-quality and accurate images at a dose of 148 MBq (4.0 mCi) for the detection of somatostatin-expressing NETs.