Dr. Manuel Martinez-Maldonado: A Pioneer in Renal Therapeutics and Mentor to a Generation of Minority Physician-Scientists.

Dr. Manuel Martinez-Maldonado is a distinguished Puerto Rican internist, nephrologist, physician-scientist, mentor, and prolific writer whose leadership in academic and clinical settings has significantly advanced the fields of nephrology, renal physiology and pharmacology, fluids and electrolyte metabolism, calcium metabolism, hypertension research, and medical education. His research on electrolyte imbalances has led to innovative hypercalcemia treatments, notably furosemide with IV fluid therapy. This is an approach that, combined with pharmacotherapy using calcitonin and bisphosphonates, became the standard practice for managing hypercalcemia until specific therapies became available. His nephrology research team and laboratory in the San Juan VA (Veterans Affairs) Medical Center and the Medical School of the University of Puerto Rico were internationally renowned. Throughout his career, he fostered a culture of mentorship while spearheading superb clinical teaching and research initiatives. His transformative tenures at several institutions, including Baylor College of Medicine; the University of Puerto Rico-Medical Sciences Campus; the VA medical centers in Atlanta, Houston, and San Juan; Emory University; Oregon Health Sciences University; Ponce School of Medicine; and the University of Louisville School of Medicine demonstrate his lasting contributions to medical science and education. His interdisciplinary approach, advocacy for kidney and clinical research, and contributions to understanding the renin-angiotensin system and the role of sodium-potassium-activated adenosine triphosphatase in renal concentration mechanisms illustrate his enduring impact on renal physiology and human health.

Evaluating the added value of concurrent contrast-enhanced diagnostic CT for PSMA-PET/CT Interpretation.

RATIONALE AND OBJECTIVES: To determine whether concurrent contrast-enhanced diagnostic CT (DxCT) confers added diagnostic certainty compared to PSMA-PET/CT alone. MATERIALS AND METHODS: This retrospective multi-reader study analyzed imaging comprising combined F-18-piflufolastat PSMA-PET/CT with diagnostic chest/abdominopelvic CT from prostate cancer patients within the first 6 months of FDA-approval of the PET agent. Six nuclear radiology readers were randomly presented with PSMA-PET/CT studies with or without DxCT and asked to report their diagnostic certainty for PSMA-avid lesions found on PET. Subsequently, readers re-reviewed the same study after an interlude (with the CT if not previously presented and vice-versa) to determine if DxCT altered their diagnostic assessment. Inter-rater concordance was assessed on a subset of images read by all readers. Diagnostic certainties for PSMA-PET/CT with and without DxCT were compared, and the variables for which DxCT may add value were examined. RESULTS: Good inter-rater concordance across readers was noted for both PET/CT (Finn's coefficient of reliability for overall scan certainty: 0.85,p < 0.01) and combined DxCT-PET/CT (0.59,p < 0.01). Overall certainty and concordance between PET/CT and combined DxCT-PET/CT datasets were similar (overall scan certainty: 92% ± 16 vs. 92% ± 17,p = 0.43), with no significant advantage for adding DxCT across different anatomic locations or clinical parameters. A slight predilection for combined DxCT-PET/CT was noted when interpreting images acquired for the initial staging of prostate cancer (89% ± 16 vs. 93% ± 17,p = 0.08). CONCLUSION: Good inter-reader concordance can be achieved across different training levels with PSMA-PET/CT. Furthermore, using DxCT concurrent with PSMA-PET/CT does not significantly improve diagnostic certainty for most indications but may be useful for initial staging.

COVID-19: Findings in nuclear medicine from head to toe.

COVID-19 is a multisystemic disease, and hence its potential manifestations on nuclear medicine imaging can extend beyond the lung. Therefore, it is important for the nuclear medicine physician to recognize these manifestations in the clinic. While FDG-PET/CT is not indicated routinely in COVID-19 evaluation, its unique capability to provide a functional and anatomical assessment of the entire body means that it can be a powerful tool to monitor acute, subacute, and long-term effects of COVID-19. Single-photon scintigraphy is routinely used to assess conditions such as pulmonary embolism, cardiac ischemia, and thyroiditis, and COVID-19 may present in these studies. The most common nuclear imaging finding of COVID-19 vaccination to date is hypermetabolic axillary lymphadenopathy. This may pose important diagnostic and management dilemmas in oncologic patients, particularly those with malignancies where the axilla constitutes a lymphatic drainage area. This article aims to summarize the relevant literature published since the beginning of the pandemic on the intersection between COVID-19 and nuclear medicine.

Prevalence and clinical implications of subretinal fluid in retinal diseases: a real-world cohort study.

BACKGROUND/AIMS: To characterise the baseline prevalence of subretinal fluid (SRF) and its effects on anatomical and visual acuity (VA) outcomes in diabetic macular oedema (DME) and retinal vein occlusion (RVO) following anti-vascular endothelial growth factor (VEGF). METHODS: This is a retrospective cohort study of 122 DME and 54 RVO patients who were initiated on anti-VEGF therapy with real-world variable dosing. The DME and RVO cohorts were subclassified based on the presence of SRF at presentation. Snellen VA was measured and converted to logarithm of the minimum angle of resolution (LogMAR). Changes in VA and central subfield thickness (CST) were assessed up to 24 months. RESULTS: SRF was present in 22% and 41% in DME and RVO patients, respectively. In the DME subcohort, eyes with SRF showed an improvement of 0.166 logMAR (1.7 Snellen chart lines) at 12 months and 0.251 logMAR (2.6 Snellen chart lines) at 24 months, which were significantly greater compared with those of the non-SRF group. A significantly greater reduction in CST was noted in the SRF eyes compared with the non-SRF eyes at 3 months and 1 month in the DME and RVO subcohorts, respectively. CONCLUSION: Baseline SRF is a good marker for a greater reduction in CST in both DME and RVO, but an improvement in VA associated with SRF may be only noted in DME.

Key Factors to Attract More U.S. Diagnostic Radiology Residents into the Field of Nuclear Medicine and Molecular Imaging: A National Survey.

RATIONALE AND OBJECTIVES: To understand the current state of radiology residents' exposure to nuclear medicine and molecular imaging (NM/MI), determine key factors that may attract more trainees into the field, and identify differentiating aspects between those specializing in NM/MI and those who are not. MATERIALS AND METHODS: An anonymous web-based survey was sent to contacts at all diagnostic radiology residency programs in the United States for dissemination to their residents, collecting information about trainees' NM/MI exposure during residency and factors that may attract them to NM/MI. RESULTS: A total of 198 trainees responded to the survey, 34 of whom plan on pursuing a career in NM/MI. Most trainees reported early exposure to NM/MI during residency; most (97.4%) reported ample exposure to general NM/MI and oncologic studies. Less than 3% of trainees reported adequate exposure to therapies, neurological applications, molecular imaging/research advances, and physics. Respondents reported a need for better quality education (38.9%) and exposure to mentors (28.8%) as ways to attract trainees to NM/MI. Routinely encountered clinical pathology was the most interesting for those specializing in NM/MI (29.4%), whereas lifestyle was the most attractive aspect of NM/MI for those not pursuing a career in the field (27.4%). NM/MI-associated research was the least attractive for those specializing in NM/MI (35.3%), while job market concerns was the least attractive aspect for those not specializing in NM/MI (37.2%). Trainees planning to specialize in NM/MI reported higher satisfaction with their orientation to NM/MI during their first clinical rotation compared to those who do not plan to specialize in the field (3.03/5.00 and 2.67/5.00, respectively, p = 0.04). CONCLUSION: This survey highlights several factors that training programs and national societies can target to improve interest in NM/MI among radiology residents. We found that optimized education initiatives, including improved orientation to the field, increased mentoring, and career opportunities are essential levers for recruiting radiology trainees into the NM/MI workforce.

Effects of Sleep Deprivation, Non-Dominant Hand Employment, Caffeine and Alcohol Intake During Surgical Performance: Lessons Learned From the Retina Eyesi Virtual Reality Surgical Simulator.

Purpose: Determine whether real-life surgical experience correlates with scores on a retina virtual simulator and the effects of various challenges on surgical performance. Methods: The study was performed using the Eyesi Surgical Simulator, a virtual reality retina surgical simulator. Residents, fellows, and retina staff were assessed on surgical simulations to determine surgical skills. Participants were assigned baseline scores on speed, efficiency of movement, and ability to avoid retinal damage. After receiving their baseline scores, participants were challenged to use their non-dominant hand or to use the simulator after sleep deprivation or the intake of caffeine or alcohol. Results: At baseline, junior residents had an average score of 943; senior residents, 1045; retina fellows, 1153; and surgical retina staff, 1161. A 12.5% overall improvement in scores was achieved when comparing baseline 1 to baseline 2; a major improvement was recorded in residents (14.5%) compared with fellows and retina staff (9.97%). A statistically significant difference was observed between residents and fellows (P = 0.027), as well as between residents and retina staff (P = 0.04). A significant decrease in performance (15.7%) was observed when the non-dominant hand was used (P = 0.043). Performance after sleep deprivation and alcohol intake decreased, but not with a statistically significant difference (P = 0.6 and P = 0.5, respectively). A trend toward increasing performance was observed after caffeine intake (6.1%; P = 0.06). Conclusions: The retina virtual simulator is a novel teaching tool for retinal surgery. A significant association was observed between real surgical experience and the retina surgery virtual simulator results based on surgical experience. Translational Relevance: An association between real surgical experience and retina surgery virtual simulator results was demonstrated. A complete training program with a cut-off threshold score should be validated for retina training programs.

Thoracic Imaging Manifestations of Treated Lymphomas: Response Evaluation, Posttherapeutic Sequelae, and Complications.

Lymphoma is the most common hematologic malignancy comprising a diverse group of neoplasms arising from multiple blood cell lineages. Any structure of the thorax may be involved at any stage of disease. Imaging has a central role in the initial staging, response assessment, and surveillance of lymphoma, and updated standardized assessment criteria are available to assist with imaging interpretation and reporting. Radiologists should be aware of the modern approaches to lymphoma treatment, the role of imaging in posttherapeutic surveillance, and manifestations of therapy-related complications.

Identification and Mitigation of Defensins in the Immunopurification of Peptide MHC-I Antigens from Lung Tissue.

The class I major histocompatibility (MHC-I) complex is a set of diverse cell surface receptors encoded by the human leukocyte antigen gene complex. These receptors present intracellular antigens to cytotoxic T cells providing information on the state and health of cells. Changes in the immunopeptidome during cancer may provide novel targets for therapeutic intervention. To understand how the tumor immunopeptidome is altered, we developed a mass spectrometry (MS) based platform for isolating and identifying MHC-I peptide antigens in lung tumors. In the course of our work, we encountered several large unknown peptide contaminants which had not been previously reported. To understand the source of these major contaminants, we isolated them using offline fractionation and identified them by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as members of the host defense protein family known as the defensins. To mitigate their detrimental effects, we modified our "Original" data-dependent acquisition (DDA) MS method to narrowly target the MHC-I peptides based on their physical properties including charge state and molecular weight ("z state" DDA), evaluated field asymmetric ion mobility spectrometry to attempt gas-phase separation prior to MS analysis, and developed an immunodepletion approach using defensin specific antibodies. This modified approach improves peptide identification and reduces the impact of defensin contamination in lung tissue samples.

The effect of latency on surgical performance and usability in a three-dimensional heads-up display visualization system for vitreoretinal surgery.

PURPOSE: Although latency has been cited as a disadvantage of the three-dimensional heads-up display (3D HUD) visualization system for vitreoretinal surgery, there have been no publications evaluating the effect of latency on surgical performance. METHODS: Thirty participants conducted two tasks (external suturing and inner limiting membrane peeling) on a 3D HUD at 4 levels of latency: 50 ms (ms), 68 ms, 92 ms, and 122 ms. The task completion time was measured and patients answered a subjective questionnaire on usability. RESULTS: No difference in completion times was found between different levels of latencies in either task. Regarding usability, significant decreases were found at 122 ms for both the suturing and peeling task overall, but for experienced HUD users, there was less of a decrease. CONCLUSION: This study is the first to evaluate the effect of latency on 3D HUD for vitreoretinal surgery. The levels of latency in the current models of 3D HUD are unlikely to contribute to a decrease in surgical performance and usability with current technologies which have a latency of 70 ms.

Optimizing Color Performance of the Ngenuity 3-Dimensional Visualization System.

Purpose: To evaluate the effect of surgeon-controlled parameters on the color performance of the Ngenuity 3-dimensional (3D) visualization system. Design: A calibrated reference target was placed inside a model eye to assess the Ngenuity 3D camera under different settings. The Ngenuity 3D display was assessed with a commercial colorimeter. Methods: Manufacturer-recommended methodology for white balancing was compared against all common deviations in technique. Following white balance, images of a calibrated reference target were extracted and tested using Imatest Master software to calculate quantitative color differences (delta E and delta C). The Ngenuity monitor was assessed using a SpyderX Elite commercial colorimeter to assess for image burn-in by quantifying color uniformity and maximum luminescence. Main Outcome Measures: Delta E and delta C were calculated for all variables. Color uniformity and luminance were assessed in candelas per square meter (nits). Results: Color performance using the manufacturer-recommended specifications yielded a delta E of 12.81 ± 1.67. Changing the white balance target to a videography grey card (P = 0.07) and 4 × 4 gauze (P = 0.37) provided similar performance, whereas using white computer paper or the operator's palm significantly increased the delta E from 12.81 ± 1.67 to 15.28 ± 1.22 (P = 0.01) and 17.71 ± 2.03 (P < 0.01), respectively. Changes to card position, magnification, stability, or ambient lighting did not significantly impact white balance results, whereas having the card in crisp focus did decrease color accuracy (15.78 ± 1.63; P = 0.03). Minor improvement in performance occurred when the laser filter was off for white balance and image acquisition (9.28 ± 0.25; P < 0.01), but deterioration occurred if the laser filter was placed after balancing (16.59 ± 1.17; P < 0.01). Both light sources of 23-gauge light pipe at 34% intensity and 25-gauge chandelier at 50% intensity gave similar color accuracy (P = 0.37). When comparing different Ngenuity machines, color uniformity and maximum luminescence decreased with increased device use. Conclusions: Overall, the Ngenuity 3D has robust color performance. A few limitations of both the camera and monitor were identified, and surgeons should be aware of these pitfalls as well as solutions examined herein to mitigate their effects during surgery.

Repeat Evaluation of Lung Shunt Fraction is Unnecessary: A Retrospective Observational Study of Successive Lung Shunt Fractions from Variable Arterial Distributions in Patients Undergoing Radioembolization of Primary and Secondary Liver Tumors.

PURPOSE: To evaluate whether the recalculation of lung shunt fraction (LSF) is necessary prior to next-stage or same lobe repeat radioembolization. MATERIALS AND METHODS: Retrospective chart review was performed for patients who underwent radioembolization between February 2008 and December 2018. Eighty of 312 patients had repeat mapping angiograms and LSF calculations. A total of 160 LSF calculations were made using planar imaging (155, [97%]) and single-photon emission computed tomography (5 [3%]) technetium-99m macroaggregated albumin hepatic arterial injection imaging. The mean patient age was 61.8 years ± 12.7; 69 (86%) patients had metastatic disease and 11 (14%) had hepatocellular carcinoma. RESULTS: Patients had a median LSF of 5% (interquartile range [IQR] 3%-9%) with a median absolute difference of 1.25 (IQR 0.65-3.4) and a median of 76 days (IQR 42.5-120 days) between repeat LSF calculations. There was a median change in LSF of 0.2% between mapping studies (P = .11). There was no statistical significance between the repeat LSFs regardless of the arterial distribution (P = .79) or between tumor types (P = .75). No patients exceeded lung dose limits using actual or predicted prescribed dose amounts. The actual median lung dose was 2.6 Gy (IQR 1.8-4.4 Gy, maximum = 20.5) for the first radioembolization and 2.0 Gy (IQR 1.3-3.7 Gy, maximum = 10.1) for the second radioembolization. CONCLUSIONS: No significant difference in LSF was identified between different time points and arterial distributions within the same patient undergoing repeat radioembolization. In patients who receive well under 30-Gy lung dose for the initial treatment and a 50-Gy cumulative lung dose, repeat radioembolization treatments in the same patient may not require a repeat LSF calculation.

18F-fluorodeoxyglucose positron emission tomography/ computed tomography in the diagnosis of suspected paraneoplastic syndromes: A retrospective analysis.

Paraneoplastic syndromes are a rare clinical presentation of tumor thought to affect 0.01% of patients with cancer. Paraneoplastic syndromes present a diagnostic challenge as a wide variety of signs and symptoms may appear. This study examines the use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) as a diagnostic imaging tool for detecting tumor in suspected paraneoplastic syndrome cases. This single-center retrospective study included patients with suspected paraneoplastic syndrome who underwent whole-body 18F-FDG PET/CT scan between December 2005 and December 2016. Associated clinical data were gathered via electronic chart review. Patient records were reviewed for age, sex, clinical signs and symptoms, ancillary diagnostic procedures, date of diagnosis, and follow-up time. Ninety-nine patients met inclusion criteria for this study. Mean follow-up period was 1.8 years. Cancer prevalence was 12.1%. The 18F-FDG PET/CT results are as follows: 10 true positives, 5 false positives, 82 true negatives, and 2 false negatives. The diagnostic values are as follows: sensitivity 83.3%, specificity 94.3%, positive predictive value 66.7%, and negative predictive value (NPV) 97.6%. The high NPV in our study supports the effectiveness of 18F-FDG PET/CT to rule out tumor in suspected paraneoplastic syndrome. Future research aims to analyze which patients with suspected paraneoplastic syndrome would benefit most from 18F-FDG PET/CT.

Utility of 18F-Fluciclovine PET/CT for Detecting Prostate Cancer Recurrence in Patients With Low (< 1 ng/mL) or Very Low (< 0.3 ng/mL) Prostate-Specific Antigen Levels.

OBJECTIVE. We reviewed a retrospective series of 126 18F-fluciclovine PET/CT studies of patients with biochemically recurrent prostate cancer at low (< 1 ng/mL) and very low (< 0.3 ng/mL) prostate-specific antigen (PSA) levels. CONCLUSION. The rate of PET/CT positivity was 33% (15/46) in patients with low PSA levels and 0% (0/17) in patients with very low PSA levels. Our results suggest that 18F-fluciclovine PET/CT can be helpful for localizing recurrence in patients with PSA levels between 0.3 and 1 ng/mL and that 18F-fluciclovine PET/CT is not recommended in patients with PSA levels less than 0.3 ng/mL.

Therapeutic anticoagulation in patients with traumatic brain injuries and pulmonary emboli.

BACKGROUND: Patients with traumatic intracranial hemorrhage (ICH) and concomitant pulmonary embolus (PE) have competing care needs and demand a careful balance of anticoagulation (AC) versus potential worsening of their ICH. The goal of this study is to determine the safety of therapeutic AC for PE in patients with ICH. METHODS: This is a retrospective single-center study of patients older than 16 years with concomitant ICH and PE occurring between June 2013 and December 2017. Early AC was defined as within 7 days of injury or less; late was defined as after 7 days. Primary outcomes included death, interventions for worsening ICH following AC, and pulmonary complications. Multivariate logistic regression was used to evaluate for clinical and demographic factors associated with worsening traumatic brain injury (TBI), and recursive partitioning was used to differentiate risk in groups. RESULTS: Fifty patients met criteria. Four did not receive any AC and were excluded. Nineteen (41.3%) received AC early (median, 4.1; interquartile range, 3.1-6) and 27 (58.7%) received AC late (median, 14; interquartile range, 9.7-19.5). There were four deaths in the early group, and none in the late cohort (21.1% vs. 0%, p = 0.01). Two deaths were due to PE and the others were from multi-system organ failure or unrecoverable underlying TBI. Three patients in the early group, and two in the late, had increased ICH on computed tomography (17.6% vs. 7.4%, p = 0.3). None required intervention. CONCLUSION: This retrospective study failed to find instances of clinically significant progression of TBI in 46 patients with computed tomography-proven ICH after undergoing AC for PE. Therapeutic AC is not associated with worse outcomes in patients with TBI, even if initiated early. However, two patients died from PE despite AC, underlining the severity of the disease. Intracranial hemorrhage should not preclude AC treatment for PE, even early after injury. LEVEL OF EVIDENCE: Care management, Level IV.

Optimizing Visual Performance With Digitally Assisted Vitreoretinal Surgery.

BACKGROUND AND OBJECTIVE: Evaluate depth of field (DOF) and lateral resolution (LR) on digitally assisted vitreoretinal surgery (DAVS) with different camera aperture values and TV viewing distances to determine maximal optical performance. PATIENTS AND METHODS: Five retinal surgeons objectively evaluated DOF and LR at low (10×), medium (15×), and high (20×) magnification on a conventional microscope (CM) and DAVS. DAVS was evaluated at different camera apertures (30%, 50%, and 75%) and TV viewing distances (1.2 meters [m], 1.5 m, and 2.0 m). A comparison between CM and optimized DAVS values was carried out. RESULTS: On DAVS, DOF significantly increased as camera aperture size was reduced (75% to 50%, P = .022; 75% to 30%, P ≤ .001; and 50% to 30%, P = .001) and as microscope magnification was reduced (high to medium, P = .009; high to low, P ≤ .001; and medium to low, P = .002). LR significantly increased as microscope magnification was increased (low to medium, P = .010; low to high, P ≤ .001; and medium to high, P = .015) and as TV display distance decreased (2.0 m to 1.5 m, P = .019; 2.0 m to 1.2 m, P = .009; and 1.5 m to1.2 m, P = .185). When comparing optimized DAVS against CM, DOF was significantly larger on DAVS (P = .019). LR on DAVS outperformed the CM, but statistical significant was not reached (P = .185). CONCLUSIONS: The authors' study is the first to evaluate different aperture, magnification, and TV distance settings, and when optimized, DAVS can significantly outperform a CM with respect to DOF and LR. Optimized visual performance for DAVS is obtained with a 30% camera aperture and a TV viewing distance no further than 1.5 m. Maximal microscope magnification to exploit LR during macular surgery and low-to-medium magnification to increase DOF for overall vitrectomy surgery is recommended. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S15-S21.].

Biocompatible Chemotherapy for Leukemia by Acid-Cleavable, PEGylated FTY720.

Targeting the inability of cancerous cells to adapt to metabolic stress is a promising alternative to conventional cancer chemotherapy. FTY720 (Gilenya), an FDA-approved drug for the treatment of multiple sclerosis, has recently been shown to inhibit cancer progression through the down-regulation of essential nutrient transport proteins, selectively starving cancer cells to death. However, the clinical use of FTY720 for cancer therapy is prohibited because of its capability of inducing immunosuppression (lymphopenia) and bradycardia when phosphorylated upon administration. A prodrug to specifically prevent phosphorylation during circulation, hence avoiding bradycardia and lymphopenia, was synthesized by capping its hydroxyl groups with polyethylene glycol (PEG) via an acid-cleavable ketal linkage. Improved aqueous solubility was also accomplished by PEGylation. The prodrug reduces to fully potent FTY720 upon cellular uptake and induces metabolic stress in cancer cells. Enhanced release of FTY720 at a mildly acidic endosomal pH and the ability to substantially down-regulate cell-surface nutrient transporter proteins in leukemia cells only by an acid-cleaved drug were confirmed. Importantly, the prodrug demonstrated nearly identical efficacy to FTY720 in an animal model of BCR-Abl-driven leukemia without inducing bradycardia or lymphopenia in vivo, highlighting its potential clinical value. The prodrug formulation of FTY720 demonstrates the utility of precisely engineering a drug to avoid undesirable effects by tackling specific molecular mechanisms as well as a financially favorable alternative to new drug development. A multitude of existing cancer therapeutics may be explored for prodrug formulation to avoid specific side effects and preserve or enhance therapeutic efficacy.

ECTOPIC INNER FOVEAL LAYER CLASSIFICATION SCHEME PREDICTS VISUAL OUTCOMES AFTER EPIRETINAL MEMBRANE SURGERY.

PURPOSE: To evaluate the ectopic inner foveal layer (EIFL) staging scheme as a visual prognostic factor for patients undergoing epiretinal membrane (ERM) surgery. METHODS: Retrospective study of 88 pseudophakic patients with diagnosis of idiopathic ERM who underwent ERM surgery with a minimum follow-up of 12 months. Preoperative and postoperative EIFL staging was correlated with the final best-corrected visual acuity (BCVA). As a secondary outcome, evaluation of the proportion of patients achieving final best-corrected visual acuity ≥20/40 in each stage was assessed. RESULTS: Based on the EIFL staging scheme, of 88 pseudophakic eyes analyzed, 24 (27.4%) were diagnosed as Stage 2 ERM, 45 (51.1%) as Stage 3 ERM, and 19 (21.5%) as Stage 4 ERM preoperatively. At the final follow-up visit, 70.8% of eyes with Stage 2 showed an improvement in EIFL staging scheme, while 68% of eyes in Stage 3 and 4 remained the same. The final best-corrected visual acuity significantly improved with all EIFL stages (P = <0.05). However, earlier stages were associated with better visual outcomes both preoperatively and postoperatively (Stage 2 > Stage 3 > Stage 4 P < 0.001). Final best-corrected visual acuity ≥20/40 was reached in 91.7% of eyes with Stage 2, 42.3% with Stage 3, and 5.2% with Stage 4. CONCLUSION: The EIFL staging scheme is an easy, fast, and reproducible method to evaluate visual prognosis with ERM surgery. Surgery on Stage 2 ERM results in significantly better visual outcomes and a greater chance of reversibility in anatomical changes.

Discovery and in Vivo Evaluation of Macrocyclic Mcl-1 Inhibitors Featuring an α-Hydroxy Phenylacetic Acid Pharmacophore or Bioisostere.

Overexpression of the antiapoptotic protein Mcl-1 provides a survival advantage to some cancer cells, making inhibition of this protein an attractive therapeutic target for the treatment of certain types of tumors. Herein, we report our efforts toward the identification of a novel series of macrocyclic Mcl-1 inhibitors featuring an α-hydroxy phenylacetic acid pharmacophore or bioisostere. This work led to the discovery of 1, a potent Mcl-1 inhibitor (IC50 = 19 nM in an OPM-2 cell viability assay) with good pharmacokinetic properties and excellent in vivo efficacy in an OPM-2 multiple myeloma xenograft model.

FDG-PET for Assessment of Endometrial and Vulvar Cancer.

Fluorodeoxyglucose positron emission tomography computed tomography (FDG-PET/CT) provides a comprehensive whole body evaluation in patients with endometrial and vulvar cancer. Here, we discuss the role of FDG-PET/CT in defining the disease extent in patients presenting with these cancers. Detection of lymph node and distant metastases has implications for staging, treatment planning, and patient prognosis. Procedures for image acquisition and interpretation for optimum accuracy and essential elements that should be included in the PET-CT report are described. Common imaging pitfalls are presented and illustrated with examples.