While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer, the optimal choice for treatment in the second-line setting and beyond is less well defined. A variety of cytotoxic agents, either alone or in combination, have been evaluated, although primarily in the context of small single-arm or retrospective studies. Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8 mo, highlighting the very poor prognosis of patients who are candidates for such treatment. Targeted therapies studied in this chemotherapy-refractory setting, meanwhile, have produced even worse efficacy results. In the current article, we review the clinical evidence for treatment of refractory disease, primarily in patients who have progressed on front-line gemcitabine-based chemotherapy. In the process, we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting, including how to select an appropriate control arm given the absence of a well-established reference standard, and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.

This study aimed to identify retinal vessel whitening outside the standard Early Treatment Diabetic Retinopathy Study (ETDRS) fields and to correlate the findings with vision and severity of diabetic retinopathy. Patients with diabetes mellitus who were seen in the retinal clinic to assess diabetic retinopathy status were included. Retinal vessel whitening was identified using ultra-widefield imaging. Four hundred and forty-five eyes of 260 patients were included. Thirty-five eyes in 24 patients (7.9%) were noted to have peripheral retinal vessel whitening. Thirty-one eyes with peripheral retinal vessel whitening did not have vessel whitening within the standard 7 ETDRS fields (p < 0.001). The proportion of whitening increased as DR severity increased, from 4.0% for patients with no DR (OR 0.249) to 33.3% for those with severe NPDR and PDR (OR 6.430 and 7.232, respectively). In addition, patients with peripheral retinal vessel whitening had worse visual acuity (logMAR = 0.34) compared to those without (logMAR = 0.15) (p < 0.001). In conclusion, we found an association between peripheral retinal vessel whitening in diabetic patients which correlated with diabetic retinopathy severity. Additionally, we found an association between vessel whitening and reduced vision, suggesting that vessel whitening identified using ultra-widefield imaging may be a prognostic indicator of vision in diabetic retinopathy.

Context

Documenting patients' advance care planning (ACP) wishes is essential to providing value-aligned care, as is having this documentation readily accessible. Little is known about ACP documentation practices in the electronic health record.

Objectives

The objective of this study was to describe ACP documentation practices and the accessibility of documented discussions in the electronic health record.

Methods

Participants were primary care patients at the San Francisco Veterans Affairs Medical Center, were ≥60 years old, and had ≥2 chronic/serious health conditions. In this cross-sectional study, we assessed the prevalence of ACP documentation, including any legal forms/orders and discussions in the prior five years. We also determined accessibility of discussions (i.e., accessible centralized posting vs. inaccessible free text in progress notes).

Results

The mean age of 414 participants was 71 years (SD ± 8), 9% were women, 43% were nonwhite, and 51% had documented ACP including 149 (36%) with forms/orders and 138 (33%) with discussions. Seventy-four participants (50%) with forms/orders lacked accompanying explanatory documentation. Most (55%) discussions were not easily accessible, including 70% of those documenting changes in treatment preferences from prior forms/orders.

Conclusion

Half of chronically ill, older participants had documented ACP, including one-third with documented discussions. However, half of the patients with completed legal forms/orders had no accompanying documented explanatory discussions, and the majority of documented discussions were not easily accessible, even when wishes had changed. Ensuring that patients' preferences are documented and easily accessible is an important patient safety and quality improvement target to ensure patients' wishes are honored.

Background

Statins are cholesterol-lowering medications with pleiotropic effects, including alterations in growth signaling, as well as immunomodulatory and anti-inflammatory effects that may alter cancer risk. Evidence from previous epidemiologic studies is inconsistent about whether statin use is associated with a reduced risk of pancreatic cancer (PC).

Methods

Patients with confirmed diagnoses of PC (cases) were recruited from medical and surgical oncology clinics, with controls (frequency-matched by sex and age) recruited from general medicine clinics, at a high-volume academic medical center over a 6-year period (2006-2011). Direct interviews were conducted with an epidemiological risk factor questionnaire covering topics such as medical history, lifestyle factors, and medication usage. Adjusted multivariable logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the relative risk of PC.

Results

Data were obtained from 536 cases and 869 controls. Ever use of statins was associated with a 34% reduced PC risk (OR, 0.66; 95% CI, 0.47-0.92). In sex-stratified analyses, risk was statistically significantly reduced in men only (OR for men, 0.50; 95% CI, 0.32-0.79; OR for women, 0.86; 95% CI, 0.52-1.43). Duration of use was inversely associated with PC risk (>10-year use: overall OR, 0.51; OR for men, 0.41; 95% CI, 0.21-0.80; P(trend)  = .006).

Conclusions

This is the largest case-control study to demonstrate an inverse association between statin use and PC risk. Risk reduction in statin users appears to be sex-specific and is more pronounced in long-term users. Further research is warranted to better characterize this association and clarify the roles of underlying biologic mechanisms.

This study aimed to understand the profile of hydroxychloroquine-treated patients, referral patterns, and dosing and to assess the adherence of eye care providers to the latest 2016 screening guidelines provided by the American Academy of Ophthalmology. Patients were identified using electronic health records (EHR) taking hydroxychloroquine and were seen by optometrists, retinal specialists, and non-retinal ophthalmologists. Review of EHR data includes demographic characteristics, indications, and dosing profile of hydroxychloroquine use, eye care provider managing the patient, and imaging modalities performed. A total of 166 patients were included in the study. The most common indications for screening were systemic lupus erythematosus and discoid lupus (52.4%) followed by rheumatoid arthritis (18.7%) and Sjögren's syndrome (9.6%). Ninety-two (55.4%) patients were on a higher-than-recommended dose of > 5 mg/kg/day. Patients who weighed less (mean 63.9 kg) were taking a higher-than-recommended dose (vs. 81.5 kg, p < 0.001). Although retinal specialists adhered best to the use of all three recommended imaging modalities, visual field testing was done appropriately for only 8.3% of Asian and 71.1% of non-Asian patients. In conclusion, there is substantial variability in screening by ophthalmic providers and prescribing practices compared with the current recommendations. In particular, there is a marked deficiency in correct visual field testing in Asian patients. These findings are important to highlight potential interventions to improve screening for hydroxychloroquine toxicity.

The role of neoadjuvant chemotherapy and/or radiation for localized or potentially resectable cholangiocarcinoma (CCA) has not been well established. We present here the case of a patient with an extrahepatic CCA who achieved a pathologic complete response after undergoing preoperative gemcitabine-based chemotherapy, without sequential or concurrent use of radiation. Further evaluation of neoadjuvant strategies in CCA, including not only combined-modality therapy but also the use of chemotherapy exclusively, is warranted in prospective study design.

A better understanding of the association between diabetes and pancreatic cancer (PC) may inform prevention and/or early detection strategies. Metformin has been associated with reduced risk of certain cancers, including PC, in some observational clinical studies. We assessed whether metformin use was associated with PC risk among those with type 2 diabetes (DM2), and whether metformin use modulated the association between DM2 and risk of PC. In total, 536 PC cases and 869 frequency-matched controls were recruited predominantly from University of California San Francisco medical clinics from 2006 to 2011. Eligible participants completed direct interviews using a structured risk factor questionnaire. The association between metformin use and PC risk was assessed using propensity score-weighted unconditional logistic regression methods in analyses restricted to diabetics and adjusted multivariable logistic models in the total study population. Ever use of metformin was not associated with PC risk in analyses restricted to DM2 (N = 170) participants (adjusted OR: 1.01, 95% CI: 0.61-1.68). In the total study population (N = 1,405) using nondiabetics as the referent group, PC risk was inversely associated with diabetes duration (ptrend  < 0.001). Further, when DM2 participants were grouped by ever/never use of metformin and compared with nondiabetics, metformin use did not affect the association between DM2 and PC risk (never users: OR: 1.44, 95% CI: 0.78-2.67; ever users: OR: 1.19, 95% CI: 0.72-1.99). Results from our clinic-based case-control study suggest that metformin use is not associated with PC risk among those with DM2 and does not alter the association between DM2 and PC risk.

Macular edema (ME), the accumulation of intraretinal fluid in the macula, is a common sight affecting sequelae of retinitis pigmentosa (RP). However, it is unclear why some patients develop ME, and others do not. This study aims to identify associations between clinical-genetic factors in RP with ME. Patients with clinically confirmed RP cases were identified from the inherited retinal disease database at a large tertiary referral academic center. Demographic and genetic testing findings were noted. Additionally, optical coherence tomography volume scans were graded using a validated grading system. One hundred and six patients (73.1%) were found to have ME in at least one eye (OD = 88, mean = 37.9%, OS = 98, mean = 31.7%). Structurally, the presence of epiretinal membrane (ERM) (p < 0.007) and vitreo-macular traction (VMT) (p < 0.003) were significantly associated with ME. Additionally, X-linked (p < 0.032) and autosomal dominant inheritance (p < 0.039) demonstrated a significant association with ME, with RP1 (p < 0.045) and EYS (p < 0.017) pathogenic variants also significantly associated with ME. This study, in a large cohort of RP patients, confirms previous retinal structural associations for ME in RP and identifies potential new genetic associations.

Background

Retinitis pigmentosa (RP) represents a group of progressive, genetically heterogenous blinding diseases. Recently, relationships between measures of retinal function and structure are needed to help identify outcome measures or biomarkers for clinical trials. The ability to align retinal multimodal images, taken on different platforms, will allow better understanding of this relationship. We investigate the efficacy of artificial intelligence (AI) in overlaying different multimodal retinal images in RP patients.

Methods

We overlayed infrared images from microperimetry on near-infra-red images from scanning laser ophthalmoscope and spectral domain optical coherence tomography in RP patients using manual alignment and AI. The AI adopted a two-step framework and was trained on a separate dataset. Manual alignment was performed using in-house software that allowed labelling of six key points located at vessel bifurcations. Manual overlay was considered successful if the distance between same key points on the overlayed images was ≤1/2°.

Results

Fifty-seven eyes of 32 patients were included in the analysis. AI was significantly more accurate and successful in aligning images compared to manual alignment as confirmed by linear mixed-effects modelling (p < 0.001). A receiver operating characteristic analysis, used to compute the area under the curve of the AI (0.991) and manual (0.835) Dice coefficients in relation to their respective 'truth' values, found AI significantly more accurate in the overlay (p < 0.001).

Conclusion

AI was significantly more accurate than manual alignment in overlaying multimodal retinal imaging in RP patients and showed the potential to use AI algorithms for future multimodal clinical and research applications.