PARP Inhibitors for Cancer Therapy.

Rucaparib is an inhibitor of nuclear poly (ADP-ribose) polymerases (inhibition of PARP-1 > PARP-2 > PARP-3), following a similar drug, Olaparib. It disrupts DNA repair and replication pathways (and possibly transcription), leading to selective killing of cancer cells with BRCA1/2 mutations. Rucaparib is approved for recurrent ovarian cancers with germline or somatic mutations in BRCA1/2.

Reduced healthcare access contributes to delay of care in endometrial cancer.

OBJECTIVE: We aimed to characterize delays to care in patients with endometrioid endometrial cancer and the role healthcare access plays in these delays. METHODS: A chart review was performed of patients with endometrioid endometrial cancer who presented with postmenopausal bleeding at a diverse, urban medical center between 2006 and 2018. The time from symptom onset to treatment was abstracted from the medical record. This interval was subdivided to assess for delay to presentation, delay to diagnosis, and delay to treatment. RESULTS: We identified 484 patients who met the inclusion criteria. The median time from symptom onset to treatment was 4 months with an interquartile range of 2 to 8 months. Most patients had stage I disease at diagnosis (88.6%). There was no significant difference in race/ethnicity or disease stage at time of diagnosis between different groups. Patients who had not seen a primary care physician or general obstetrician-gynecologist in the year before symptom onset were more likely to have significantly delayed care (27.7% vs 14.3%, p = 0.02) and extrauterine disease (20.2% vs 4.9%, p < 0.01) compared to those with established care. Black and Hispanic patients were more likely to experience significant delays from initial biopsy to diagnosis. CONCLUSIONS: Delays exist in the evaluation of endometrial cancer. This delay is most pronounced in patients without an established outpatient primary care provider or obstetrician-gynecologist.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study.

OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.

Ultrasound-assisted ocular drug delivery: A review of current evidence.

Efficient ocular drug delivery is a challenging clinical problem with various therapeutic options but no clearly preferred methodology. Given the ubiquity of ultrasound as a diagnostic technique, the safety profile of ultrasound in an ocular context, and the prospect of custom-made ultrasound-sensitive contrast agents, ultrasound presents an attractive ocular drug delivery modality. In this review, we evaluate our present understanding of ultrasound as it relates to ocular drug delivery and significant knowledge gaps in the field. In doing so, we hope to call attention to a potentially novel drug delivery pathway that could be manipulated to treat or cure ocular diseases.

Ovarian involvement in endometrioid adenocarcinoma of uterus.

OBJECTIVE: Ovarian preservation is an option for some premenopausal patients with early stage endometrial cancer. Studies have shown that ovarian preservation in selected patients does not negatively impact survival outcomes. The objective of this study is to determine the frequency and characteristics of ovarian involvement when endometrial cancer is clinically confined to the uterus. METHODS: Patients with endometrioid adenocarcinoma of uterus treated at our institution between 2000 and 2013 were identified. Patients with ovarian metastasis or synchronous primary ovarian cancer were included. Patients were excluded if there was gross extrapelvic disease on examination or imaging. RESULTS: Seven hundred and fifty-nine patients were found to have endometrial cancer with the disease confined to the pelvis (stages I, II, and III). Fifteen patients (2%) had ovarian metastasis. Twenty-three patients (3%) had synchronous uterine and ovarian cancer. Most ovarian lesions (32 out of 38) were either enlarged or had abnormal appearing surface involvement. Six patients had microscopic ovarian involvement, accounting for 0.8% of the endometrial cancer patients with pelvis-confined disease. All of the patients were greater than 50 years of age. For those patients with microscopic ovarian metastasis, all had FIGO grade 3 disease, deep myometrial invasion, and extrauterine involvement of either cervix or lymph nodes. CONCLUSIONS: Microscopic ovarian involvement occurred in 0.8% of patients with endometrial cancer. For premenopausal patients with endometrial cancer, normal appearing ovaries may be considered for preservation in the absence of extrauterine spread, grade 3 disease and deep myometrial invasion.

Malignant ovarian germ cell tumor - role of surgical staging and gonadal dysgenesis.

OBJECTIVE: To evaluate the effect of comprehensive surgical staging and gonadal dysgenesis on the outcomes of patients with malignant ovarian germ cell tumor. METHODS: We performed a retrospective review of patients with ovarian germ cell tumors who were treated at our institution between 1976 and 2012. RESULTS: Malignant ovarian germ cell tumors (MOGCTs) were identified in 50 females. The median age was 24 years (range 13 to 49). Of all MOGCT patients, 42% had dysgerminoma, 20% immature teratoma, 16% endodermal sinus tumor, and 22% mixed germ cell tumor. Univariate analyses revealed that the lack of surgical staging (p=0.048) and endodermal sinus tumor (p=0.0085) were associated with disease recurrence, while age at diagnosis, ethnicity, and stage of the disease were not. Multivariate analyses revealed that the lack of surgical staging (p=0.029) and endodermal sinus tumor (p=0.016) were independently associated with disease recurrence. In addition, 7 patients (14%) had 46 XY karyotype, including 6 with pure dysgerminoma and 1 with mixed germ cell tumor. Five had Swyer syndrome and 2 had complete androgen insensitivity syndrome. Concurrent gonadoblastoma was found in 5 of the patients. No difference was found in the mean age at presentation, stage distribution, or recurrence rate for MOGCT patients with or without XY phenotype. CONCLUSIONS: Comprehensive surgical staging was associated with a lower rate of recurrence. Fourteen percent of phenotypic females with MOGCT and 29% of those with dysgerminoma had XY karyotype. The clinical outcome of these patients is similar to that of MOGCT patients with XX karyotype.

Prospective Study of Canaloplasty and Trabeculotomy Performed by Trainees.

Purpose: To evaluate outcomes of new adopters of the OMNI® Surgical System (Sight Sciences, Inc.) by prospectively evaluating intermediate-term outcomes of patients operated by trainees. Patients and Methods: This was a prospective study of surgeries performed by trainees on patients with open angle glaucoma undergoing simultaneous cataract surgery and ab interno canaloplasty and trabeculotomy using the OMNI Surgical System. Pre-operative intraocular pressure (IOP) and number of glaucoma medications were recorded. Only patients with a minimum of 6-month follow up were included. Baseline IOP was used to separate subjects into two groups: Group 1 (IOP ≥18 mmHg) and Group 2 (IOP <18 mmHg). Mean decrease in IOP and medications was calculated and compared with paired t-tests for the overall sample as well as the subgroups. Success was defined as those with a ≥20% reduction from pre-operative IOP or with an IOP ≤18 mmHg and ≥6 mmHg and on the same or fewer number of medications while not requiring additional surgery. Adverse events were also recorded. Results: Forty-two eyes of 31 patients were included. Mean pre-operative IOP was 17.2 ± 4.8 mmHg and mean number of medications was 2.4 ± 1.2. The primary endpoint was reached in 83.3% of patients at 12 months. IOP was reduced by 22.3% to 13.4 ± 2.4 (p<0.001). Mean number of medications decreased to 1.7 ± 1.6 (p<0.001). Group 1 mean IOP decreased 35.4% from 22.2 ± 4.6 mmHg to 14.3 ± 2.8 mmHg (p<0.001). Group 2 mean number of medications decreased from 2.3 ± 1.1 to 1.6 ± 1.5 (p<0.001). Conclusion: When operated on by the novice MIGS surgeon, the OMNI device provides effective IOP and glaucoma medication reduction with minimal adverse events. Efficacy and safety of the device in the hands of trainees was comparable to experienced glaucoma surgeons suggesting its ease of adoption.

Durable partial response to pembrolizumab, lenvatinib, and letrozole in a case of recurrent uterine carcinosarcoma with ESR1 gene amplification.

•ESR1 gene amplification occurs in 7% of uterine carcinosarcoma.•The presence of ESR1 gene amplification in recurrent uterine carcinosarcoma may be targeted by aromatase inhibitors.•ESR1 gene amplification may be identified through immunohistochemical staining for estrogen receptor followed by fluorescence in situ hybridization or tumor targeted gene sequencing.

Comparison of Superior versus Inferior Canaloplasty and Trabeculotomy Using the OMNI Surgical System.

Purpose: To compare outcomes of ab-interno canaloplasty and trabeculotomy of the superior versus inferior angle. Patients and methods: This was a prospective, non-randomized, interventional comparison study done at the Veteran Affairs Hospital in Long Beach, California. All patients underwent cataract surgery with intraocular lens implantation combined with ab-interno canaloplasty and trabeculotomy with the OMNI Surgical System (SightSciences, Menlo Park, CA, USA), either superiorly or inferiorly. Pre- and post-operative intraocular pressure using Goldmann applanation tonometry and best corrected visual acuity were obtained and compared using paired t-tests. Patients were excluded if they had any prior intraocular surgery or prior laser trabeculoplasty procedures. Results: 38 eyes from 29 patients were analyzed. 19 eyes were included in the superior group and 19 eyes in the inferior group. Mean pre-operative IOP in the superior group was 17.6 ± 5.2 mmHg and in the inferior group was 17.6 ± 4.6 mmHg (p > 0.99). At 12 months, mean postoperative IOP for the superior group decreased 24% to 13.3 ± 2.8 mmHg while the inferior group decreased 26% to 13.1 ± 2.2 mmHg (p = 0.92). Mean preoperative medications in the superior group were 2.2 ± 1.3 and in the inferior group was 2.4 ± 1.3 (p = 0.88). At 12 months, this decreased to 1.3 ± 1.5 post-operatively in the superior group and 2.2 ± 1.6 post-operatively in the inferior group (p = 0.64). Conclusion: There was no statistical difference in efficacy between superior versus inferior canaloplasty/trabeculotomy with OMNI. Therefore, surgeons can perform the procedure in the direction that is most comfortable for them without affecting outcomes.

Race and Gender Shift among Academic Glaucoma Specialists in the Last 5 Decades.

Purpose: To evaluate the demographic composition of academic glaucoma specialists currently practicing in the United States. Design: Retrospective and observational study. Subjects: Academic glaucoma specialists identified from ophthalmology residency programs listed on the Doximity database. Methods: The American Board of Ophthalmology (ABO) membership directory, Doximity database, publicly available data, and direct communications were used to identify academic glaucoma specialists and their demographics. Information collected included-name, gender, race/ethnicity, geographic location, board certification date, academic affiliation, and academic rank. Ophthalmic age was defined as the number of years since ophthalmology board certification. Underrepresented minority (URM) groups were defined as Hispanics, Black or African Americans, Latinos, American Indians, or Alaskan Natives as defined by San Francisco match. In addition, the temporal, geographic, and academic rank distributions among females and URMs were explored. Main outcome measures: Women and URMs representations among academic glaucoma specialists across academic ranks, geographic regions, as well as ophthalmic age. Results: There were 457 active academic glaucoma specialists identified from 110 institutions in 38 states. Among them, 185 (40.5%) were women and 42 (9.2%) were URM. The proportion of women glaucoma specialists in academia had increased significantly with a rate of 1.049 in odds ratio (OR) per year (p < 0.001). However, there were no significant changes in the proportion of URMs over time. The earliest year of certification was 1,964 for males and 1,974 for females. When controlled for ophthalmic age, there were no significant differences in the distribution of women or URMs between the different academic ranks (p = 0.572 and p = 0.762, respectively). Among assistant professors, women had a significantly higher ophthalmic age compared to men (p < 0.001), but there was no significant difference in ophthalmic age in both the associate and full professor groups. There were no significant differences in the geographic distribution of gender (p = 0.516) and URM across United States regions (p = 0.238). Conclusion: The proportion of women among academic glaucoma specialists has significantly increased over the past 5 decades; however, the proportion of URMs has been stagnant in the same period. Enhancing URM representation among academic glaucoma specialists deserves to be a future priority. How to cite this article: Afzali K, Fujimoto DK, Mohammadi SO, et al. Race and Gender Shift among Academic Glaucoma Specialists in the Last 5 Decades. J Curr Glaucoma Pract 2023;17(2):98-103.

The Incidence of Urgent Tube Shunt Surgery for Diabetic Neovascular Glaucoma at a Tertiary Academic Medical Center.

Background: Diabetic neovascular glaucoma is a secondary glaucoma that may require immediate correction of elevated intraocular pressure to control pain and protect the optic nerve. While there is a seasonal trend to glucose levels, it is unknown if a seasonal trend exists for diabetic neovascular glaucoma. Objective: This study evaluates the incidence of urgent glaucoma tube shunt implantation in diabetic neovascular glaucoma in a tertiary academic referral center in Southern California. Methods: Electronic medical records were queried for urgent glaucoma tube shunt surgery from 2014 to 2021. The number of cases were separated by month of occurrence, and average hemoglobin A1c values were calculated per month. Data were analyzed via ANOVA tests and one-tailed t-tests. Results: A total of 127 cases were identified. The months of March and April contained the most cases averaging 3 and 2.75 cases, respectively. April had statistically significant higher case numbers than that of other months (P = .041). ANOVA tests excluding April showed no statistically significant difference between the remaining months (P = .901). Average hemoglobin A1c values were highest in the months of April and March at 9.8 and 9.6%, respectively. Conclusion: Emergency glaucoma tube shunt surgery for diabetic neovascular glaucoma occurs most frequently in April. This observation may provide insight into disease prevention through diabetes management and help improve surgical operations such that staffing and resources are allocated accordingly.

Anterior Chamber Washout During Ahmed Valve Glaucoma Surgery Reduces the Incidence of Hypertensive Phase.

PRCIS: Intraoperative anterior chamber (AC) washout reduces the odds of hypertensive phase (HP) by 95% compared with those not receiving washout during Ahmed glaucoma implant (AGI), suggesting AC washout is an effective prophylaxis for postoperative HP. PURPOSE: To characterize the incidence of postoperative HP in patients receiving AC washout at the time of AGI. PATIENTS AND METHODS: A total of 24 patients with medically refractory glaucoma who underwent AGI surgery at a tertiary academic medical center in Southern California from December 2018 through March 2021 were included in this retrospective comparative case series. Patients who received a pediatric implant and underwent concurrent intraocular surgery or did not complete a minimum of 6 months of follow-up were excluded. Nine patient's eyes received AC washout and 15 controls that were analyzed through 6 months postprocedure. HP was defined as intraocular pressure (IOP) above 21 mm Hg within 6 months postprocedure with maximum tolerated medical therapy. AC washout was performed by irrigating the AC with a 5 mL balanced salt solution before placing the tube of the AGI into the AC. The rate of postoperative HP, defined as peak IOP >21 mm Hg, at 6 months follow-up, was observed as the primary outcome measure. RESULTS: Patients included in the study had a high mean preoperative IOP ( X̅ = 44.11, SD = 13.85). There were no baseline differences between the washout and control groups. The odds of HP were significantly reduced (odds ratio: 0.050; 95% CI: 0.004, 0.706; P = 0.027) for patients who underwent intraoperative AC washout compared with those who did not. Bivariate analysis of subject baseline characteristics revealed that only washout status was significantly different in subjects with HP compared with subjects without HP ( P = 0.015). A multivariate logistic regression model using washout status and autoimmune conditions as covariates was significant in predicting HP ( X2 (2) = 12.337, P = 0.002), with washout as a significant predictor when controlling for autoimmune comorbidities ( P = 0.027). CONCLUSIONS: AC washout significantly decreases the odds of HP after AGI surgery. AC washout with balanced salt solution adds minimal time and risks to surgery and therefore may be an effective adjunct during AGI placement.

A Case of Refractory Open-angle Glaucoma with Failed Baerveldt Glaucoma Implant and Trabeculectomy Treated with Ab Externo XEN Gel Stent Placement.

Aim: We report a case of successful intraocular pressure (IOP) management in a patient with refractory primary open-angle glaucoma (POAG) following implantation of XEN gel implant in the same hemisphere as prior failed filtering surgeries [i.e., Baerveldt glaucoma implant (BGI) and trabeculectomy bleb)]. Background: Glaucoma is a major cause of blindness worldwide and is typically associated with elevated IOP and retinal ganglion cell loss. Treatment centers around decreasing IOP with eye drops and surgical interventions. The advent of minimally invasive glaucoma surgeries (MIGS) has expanded therapeutic options for patients who have failed traditional treatments. The XEN gel implant creates a shunt between the anterior chamber and the subconjunctival or sub-tenon's space, allowing for drainage of aqueous humor without significant tissue disruption. Given that the XEN gel implant also results in bleb formation, it is generally recommended to avoid placement in the same quadrant of prior filtering surgeries. Case description: A 77-year-old man with a 15-year history of severe POAG of OU presents with persistently elevated IOP despite multiple filtering surgeries and maximal eye drop regimen. The patient had a superotemporal BGI in OU and a scarred trabeculectomy bleb superiorly in the right eye (OD). He underwent an open conjunctiva ab externo XEN gel implant placement in the OD in the same hemisphere as previous filtering surgeries. At 12 months postoperatively, the IOP range continues to be maintained within goal without complications. Conclusion: The XEN gel implant can be successfully placed in the same hemisphere as prior filtering surgeries and can achieve goal IOP without any surgical complications at 12 months postoperatively. Clinical significance: A XEN gel implant can effectively lower patients' IOP and can be a unique surgical option in refractory cases of POAG with multiple failed filtering surgeries, even when inserted in close proximity to prior filtering surgeries. How to cite this article: Amoozadeh SA, Yang MC, Lin KY. A Case of Refractory Open-angle Glaucoma with Failed Baerveldt Glaucoma Implant and Trabeculectomy Treated with Ab Externo XEN Gel Stent Placement. J Curr Glaucoma Pract 2022;16(3):192-194.

Seeing invisible light: 2-photon microperimetry to measure visual function.

Purpose: The accuracy of conventional visual function tests, which emit visible light, decreases in patients with corneal scars, cataracts, and vitreous hemorrhages. In contrast, infrared (IR) light exhibits greater tissue penetrance than visible light and is less susceptible to optical opacities. We therefore compared conventional visual function tests against infrared 2-phton microperimetry (2PM-IR) in a subject with a brunescent nuclear sclerotic and posterior subcapsular cataract before and after cataract surgery. Methods: Testing using infrared light microperimetry from a novel device (2PM-IR), visible light microperimetry from a novel device (2PM-Vis), conventional microperimetry, and the cone contrast threshold (CCT) test were performed before and after cataract surgery. Results: Retinal sensitivity assessed using 2PM-IR, 2PM-Vis, and cMP improved by 3.4 dB, 17.4 dB, and 18 dB, respectively. Cone contrast threshold testing improved for the S-cone, M-cone, and l-cone by 111, 14, and 30. Conclusions and Importance: 2PM-IR, unlike conventional visual function tests, showed minimal variability in retinal sensitivity before and after surgery. Thus, IR visual stimulation may provide a more accurate means of measuring neurosensory retinal function by circumventing optical media opacities, aiding in the diagnosis of early macular disease.

Combinatorial Treatment with PARP-1 Inhibitors and Cisplatin Attenuates Cervical Cancer Growth through Fos-Driven Changes in Gene Expression.

Cervical cancer continues to be a significant cause of cancer-related deaths in women. The most common treatment for cervical cancer involves the use of the drug cisplatin in conjunction with other therapeutics. However, the development of cisplatin resistance in patients can hinder the efficacy of these treatments, so alternatives are needed. In this study, we found that PARP inhibitors (PARPi) could attenuate the growth of cells representing cervical adenocarcinoma and cervical squamous cell carcinoma. Moreover, a combination of PARPi with cisplatin increased cisplatin-mediated cytotoxicity in cervical cancer cells. This was accompanied by a dramatic alteration of the transcriptome. The FOS gene, which encodes the transcription factor Fos, was one of the most highly upregulated genes in the dual treatment condition, leading to increased Fos protein levels, greater Fos binding to chromatin, and the subsequent induction of Fos target genes. Increased expression of Fos was sufficient to hinder cervical cancer growth, as shown by ectopic expression of Fos in cervical cancer cells. Conversely, Fos knockdown enhanced cell growth. Collectively, these results indicate that by inducing FOS expression, PARPi treatment in combination with cisplatin leads to inhibition of cervical cancer proliferation, likely through a Fos-specific gene expression program. IMPLICATIONS: Our observations, which link the gene regulatory effects of PARPi + cisplatin to the growth inhibitory effects of FOS expression in cervical cancer cells, strengthen the rationale for using PARPi with cisplatin as a therapy for cervical cancer.

Fast and Accurate Ophthalmic Medication Bottle Identification Using Deep Learning on a Smartphone Device.

PURPOSE: To assess the accuracy and efficacy of deep learning models, specifically convolutional neural networks (CNNs), to identify glaucoma medication bottles. DESIGN: Algorithm development for predicting ophthalmic medication bottles using a large mobile image-based dataset. PARTICIPANTS: A total of 3750 mobile images of 5 ophthalmic medication bottles were included: brimonidine tartrate, dorzolamide-timolol, latanoprost, prednisolone acetate, and moxifloxacin. METHODS: Seven CNN models were initially pretrained on a large-scale image database and subsequently retrained to classify 5 commonly prescribed topical ophthalmic medications using a training dataset of 2250 mobile-phone captured images. The retrained CNN models' accuracies were compared using k-fold cross-validation (k = 10). The top 2 performing CNN models were then embedded into separate iOS apps and evaluated using 1500 mobile images not included in the training dataset. MAIN OUTCOME MEASURES: Prediction accuracy, image processing time. RESULTS: Of the 7 CNN architectures, MobileNet v2 yielded the highest k-fold cross-validation accuracy of 0.974 (95% confidence interval [CI], 0.966-0.980) and the shortest average image processing time at 3.45 (95% CI, 3.13-3.77) sec/image. ResNet V2 had the second highest accuracy of 0.961 (95% CI, 0.952-0.969). When the 2 app-embedded CNNs were compared, in terms of accuracy, MobileNet V2, with an image prediction accuracy of 0.86 (95% CI, 0.84-0.88), was significantly greater than ResNet V2, 0.68 (95% CI, 0.66-0.71) (Table 1). Sensitivities and specificities varied between medications (Table 1). There was no significant difference in average imaging processing time, 0.32 (95% CI, 0.28-0.36) sec/image and 0.31 (95% CI, 0.29-0.33) sec/image for MobileNet V2 and ResNet V2, respectively. Information on beta-testing of the iOS app can be found here: https://lin.hs.uci.edu/research/. CONCLUSIONS: We have retrained MobileNet V2 to accurately identify ophthalmic medication bottles and demonstrated that this neural network can operate in a smartphone environment. This work serves as a proof-of-concept for the production of a CNN-based smartphone application to empower patients by decreasing risk for error.

Accurate Identification of the Trabecular Meshwork under Gonioscopic View in Real Time Using Deep Learning.

PURPOSE: Accurate identification of iridocorneal structures on gonioscopy is difficult to master, and errors can lead to grave surgical complications. This study aimed to develop and train convolutional neural networks (CNNs) to accurately identify the trabecular meshwork (TM) in gonioscopic videos in real time for eventual clinical integrations. DESIGN: Cross-sectional study. PARTICIPANTS: Adult patients with open angle were identified in academic glaucoma clinics in both Taipei, Taiwan, and Irvine, California. METHODS: Neural Encoder-Decoder CNNs (U-nets) were trained to predict a curve marking the TM using an expert-annotated data set of 378 gonioscopy images. The model was trained and evaluated with stratified cross-validation grouped by patients to ensure uncorrelated training and testing sets, as well as on a separate test set and 3 intraoperative gonioscopic videos of ab interno trabeculotomy with Trabectome (totaling 90 seconds long, 30 frames per second). We also evaluated our model's performance by comparing its accuracy against ophthalmologists. MAIN OUTCOME MEASURES: Successful development of real-time-capable CNNs that are accurate in predicting and marking the TM's position in video frames of gonioscopic views. Models were evaluated in comparison with human expert annotations of static images and video data. RESULTS: The best CNN model produced test set predictions with a median deviation of 0.8% of the video frame's height (15.25 µm) from the human experts' annotations. This error is less than the average vertical height of the TM. The worst test frame prediction of this model had an average deviation of 4% of the frame height (76.28 µm), which is still considered a successful prediction. When challenged with unseen images, the CNN model scored greater than 2 standard deviations above the mean performance of the surveyed general ophthalmologists. CONCLUSIONS: Our CNN model can identify the TM in gonioscopy videos in real time with remarkable accuracy, allowing it to be used in connection with a video camera intraoperatively. This model can have applications in surgical training, automated screenings, and intraoperative guidance. The dataset developed in this study is one of the first publicly available gonioscopy image banks (https://lin.hs.uci.edu/research), which may encourage future investigations in this topic.

Use of endoluminal vacuum therapy after anastomotic leak in a gynecologic oncology patient with rectosigmoid resection: A case report.

•Anastomotic leak is an infrequent complication after colon resection and is associated with high morbidity and mortality.•Endoluminal vacuum therapy (EVAT) promotes wound closure by covering anastomotic leaks intraluminally and applying vacuum.•EVAT has been shown to be safe with mild adverse events.•EVAT should be considered in hemodynamically stable gynecologic oncology patients with a confined anastomotic leak.

Cervical Cancer Immunotherapy: Facts and Hopes.

It is a sad fact that despite being almost completely preventable through human papillomavirus (HPV) vaccination and screening, cervical cancer remains the fourth most common cancer to affect women worldwide. Persistent high-risk HPV (hrHPV) infection is the primary etiologic factor for cervical cancer. Upward of 70% of cases are driven by HPV types 16 and 18, with a dozen other hrHPVs associated with the remainder of cases. Current standard-of-care treatments include radiotherapy, chemotherapy, and/or surgical resection. However, they have significant side effects and limited efficacy against advanced disease. There are a few treatment options for recurrent or metastatic cases. Immunotherapy offers new hope, as demonstrated by the recent approval of programmed cell death protein 1-blocking antibody for recurrent or metastatic disease. This might be augmented by combination with antigen-specific immunotherapy approaches, such as vaccines or adoptive cell transfer, to enhance the host cellular immune response targeting HPV-positive cancer cells. As cervical cancer progresses, it can foster an immunosuppressive microenvironment and counteract host anticancer immunity. Thus, approaches to reverse suppressive immune environments and bolster effector T-cell functioning are likely to enhance the success of such cervical cancer immunotherapy. The success of nonspecific immunostimulants like imiquimod against genital warts also suggest the possibility of utilizing these immunotherapeutic strategies in cervical cancer prevention to treat precursor lesions (cervical intraepithelial neoplasia) and persistent hrHPV infections against which the licensed prophylactic HPV vaccines have no efficacy. Here, we review the progress and challenges in the development of immunotherapeutic approaches for the prevention and treatment of cervical cancer.

Characterization of the Testis-specific LINC01016 Gene Reveals Isoform-specific Roles in Controlling Biological Processes.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of biological processes. However, the aberrant expression of an isoform from the same lncRNA gene could lead to RNA with altered functions due to changes in their conformations, leading to diseases. Here, we describe a detailed characterization of the gene that encodes long intergenic non-protein-coding RNA 01016 (LINC01016, also known as LncRNA1195) with a focus on its structure, exon usage, and expression in human and macaque tissues. In this study we show that it is among the highly expressed lncRNAs in the testis, exclusively conserved among nonhuman primates, suggesting its recent evolution and is processed into 12 distinct RNAs in testis, cervix, and uterus tissues. Further, we integrate de novo annotation of expressed LINC01016 transcripts and isoform-dependent gene expression analyses to show that human LINC01016 is a multiexon gene, processed through differential exon usage with isoform-specific roles. Furthermore, in cervical, testicular, and uterine cancers, LINC01016 isoforms are differentially expressed, and their expression is predictive of survival in these cancers. This study has revealed an essential aspect of lncRNA biology, rarely associated with coding RNAs, that lncRNA genes are precisely processed to generate isoforms with distinct biological roles in specific tissues.