Applications of artificial intelligence and bioinformatics methodologies in the analysis of ocular biofluid markers: a scoping review.

PURPOSE: This scoping review summarizes the applications of artificial intelligence (AI) and bioinformatics methodologies in analysis of ocular biofluid markers. The secondary objective was to explore supervised and unsupervised AI techniques and their predictive accuracies. We also evaluate the integration of bioinformatics with AI tools. METHODS: This scoping review was conducted across five electronic databases including EMBASE, Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from inception to July 14, 2021. Studies pertaining to biofluid marker analysis using AI or bioinformatics were included. RESULTS: A total of 10,262 articles were retrieved from all databases and 177 studies met the inclusion criteria. The most commonly studied ocular diseases were diabetic eye diseases, with 50 papers (28%), while glaucoma was explored in 25 studies (14%), age-related macular degeneration in 20 (11%), dry eye disease in 10 (6%), and uveitis in 9 (5%). Supervised learning was used in 91 papers (51%), unsupervised AI in 83 (46%), and bioinformatics in 85 (48%). Ninety-eight papers (55%) used more than one class of AI (e.g. > 1 of supervised, unsupervised, bioinformatics, or statistical techniques), while 79 (45%) used only one. Supervised learning techniques were often used to predict disease status or prognosis, and demonstrated strong accuracy. Unsupervised AI algorithms were used to bolster the accuracy of other algorithms, identify molecularly distinct subgroups, or cluster cases into distinct subgroups that are useful for prediction of the disease course. Finally, bioinformatic tools were used to translate complex biomarker profiles or findings into interpretable data. CONCLUSION: AI analysis of biofluid markers displayed diagnostic accuracy, provided insight into mechanisms of molecular etiologies, and had the ability to provide individualized targeted therapeutic treatment for patients. Given the progression of AI towards use in both research and the clinic, ophthalmologists should be broadly aware of the commonly used algorithms and their applications. Future research may be aimed at validating algorithms and integrating them in clinical practice.

Review of Fractional Nonablative Lasers for the Treatment of Dermatologic Conditions in Darker Skin Phototypes.

BACKGROUND: Fractional nonablative lasers (NAFLs) have demonstrated efficacy and safety for treating dermatologic conditions in patients with darker skin phototypes. Nonablative lasers are preferred in darker skin tones due to lower risk of postinflammatory hyperpigmentation. OBJECTIVE: This review aims to identify the ideal laser options and parameters for treating common dermatologic conditions in patients with skin types IV-VI. MATERIALS AND METHODS: A comprehensive literature search was conducted on PubMed in May 2023. Of 1,065 articles were identified, and 40 articles met the inclusion criteria. The studies were classified based on design, dermatologic condition, and skin phototype of patients, and assigned levels of evidence according to the Modified Criteria of the Oxford Center of Evidence Based Medicine. RESULTS: Strong level 1 evidence supports the treatment of melasma and atrophic scars using NAFL. Moderate level 2 evidence was found for using NAFL in acne vulgaris, striae, and skin rejuvenation; 45% of the studies examined skin types III-IV, 20% III-V, 7.5% II-IV, 5% II-V, 5% IV alone, and 2.5% I-IV. CONCLUSION: Further research is needed to determine the optimal treatment modalities and parameters for skin types V and VI. Appropriate device selection and conservative treatment settings are crucial for optimizing outcomes and minimizing adverse events.

Refractory Giant Cell Arteritis Complicated by Vision Loss From Optic Atrophy and Maculopathy Associated With Pachymeningitis.

BACKGROUND: We describe a 75-year-old woman who experienced vision loss in her left eye due to biopsy-proven giant cell arteritis (GCA). She subsequently developed pachymeningitis causing refractory headaches and bilateral optic neuropathy and maculopathy. METHODS: Case report with literature review. RESULTS: Eighteen months after the initial diagnosis of GCA, imaging studies in our patient demonstrated pachymeningeal enhancement, and meningeal biopsy confirmed lymphoplasmacytic tissue infiltrates with low frequencies of IgG4+ plasma cells. Laboratory investigation revealed the presence of 3 antiretinal antibodies and antimyeloperoxidase antibodies, consistent with autoimmune retinopathy. Treatment with B-cell-depleting anti-CD20 antibodies suppressed meningeal inflammation and prevented further vision loss. CONCLUSIONS: This case illustrates that bilateral vision loss and chronic headaches in patients with GCA may result from retina-directed autoimmunity and pachymeningitis.

Field Cancerization Therapies for the Management of Actinic Keratosis: An Updated Review.

Field cancerization theory highlights that the skin surrounding actinic keratoses (AK) is also at increased risk for possible malignant transformation; thus, field-directed treatments may both reduce the risk of AK recurrence and potentially reduce the risk of development of cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL), as well as topical treatments such as 5-fluorouracil (5-FU), diclofenac gel, piroxicam, imiquimod, and ingenol mebutate, have all shown higher efficacy than vehicle treatments. PDT is widely recognized for its high efficacy; however, concerns for associated pain have driven new studies to begin using alternative illumination and pretreatment techniques, including lasers. Among topical treatments, a combination of 5-FU and salicylic acid (5-FU-SA) has shown to be the most effective but also causes the most adverse reactions. Tirbanibulin, a new topical agent approved for use in 2020, boasts a favorable safety profile in comparison with imiquimod, 5-FU, and diclofenac. Meanwhile, ingenol mebutate is no longer recommended for the treatment of AKs due to concerns for increased risk of cSCC development. Moving forward, an increasing number of studies push for standardization of outcome measures to better predict risk of future cSCC and use of more effective measures of cost to better guide patients. Here, we present an updated and comprehensive narrative review both confirming the efficacy of previously mentioned therapies as well as highlighting new approaches to PDT and discussing the use of lasers and novel topical treatments for treatment of AK.

Brief Report: Real-World Eligibility for Clinical Trials in Patients With Extensive-Stage SCLC at a Tertiary Care Center.

Introduction: The CASPIAN and IMpower133 trials revealed a significant survival benefit of chemotherapy plus immunotherapy in patients with extensive-stage SCLC. The current study characterizes the proportion of real-world patients who would have met eligibility for these trials and highlights factors influencing eligibility in the real-world setting. Methods: A retrospective analysis of patient data was conducted for stage IV patients with SCLC treated at the Cancer Centre of Southeastern Ontario, Canada. Trial eligibility was based on criteria used in the IMpower133 and CASPIAN trials. Data were summarized using descriptive statistics. Overall survival was assessed using the Kaplan-Meier method. Results: Of the 116 patients included, only 12.1% met the overall eligibility criteria for the IMpower133 trial, and 14.7% for the CASPIAN trial. The most common reasons for ineligibility included: Eastern Cooperative Oncology Group (ECOG) 2 or greater (77.5%), inadequate organ function (48%), and the presence of brain metastases at diagnosis (37.3%). Sixty-one patients (59.8%) met two or more major ineligibility criteria. If trial eligibility was expanded to include ECOG 2 patients, an additional 10.3% would have met eligibility. The median overall survival for all-comers was 6.5 months. Conclusions: Only a small minority of real-world patients with extensive-stage SCLC would have met eligibility for the IMpower133 and CASPIAN trials, with ECOG greater than or equal to 2, inadequate organ function, and brain metastases comprising the most common reasons for trial ineligibility. Future clinical trials should expand the inclusion criteria to better represent real-world patient populations.

Demonstrating the importance of interprofessional health education through an interactive case competition at Queen's Faculty of Health Sciences.

On March 4, 2021, OSLER Kingston and KHealth, student-run organizations at Queen's Faculty of Health Sciences, hosted a two-hour-long virtual interprofessional case competition called "OSLER x KHealth IPR Case Competition: Homelessness," focusing on housing insecurity and homelessness. This event demonstrated that integrating interprofessional education (IPE) competencies into educational experiences of health professional students is feasible to organize and implement while also being valuable. Students who participated found IPE to be helpful for their learning. Consequently, we encourage medical school curriculum leaders and student-led groups to prioritize IPE in their preclerkship curricular and extracurricular offerings.

Le 4 mars 2021, OSLER Kingston et KHealth, deux organisations étudiantes de la Faculté des sciences de la santé de l'Université Queen's, ont organisé un concours virtuel de cas interprofessionnels d'une durée de deux heures intitulé « OSLER x KHealth IPR Case Competition : Homelessness ¼, qui portait sur l'insécurité du logement et l'itinérance. Cette activité a montré qu'il est non seulement possible, mais aussi utile d'intégrer les compétences en formation interprofessionnelle (FIP) dans le parcours d'apprentissage des étudiants des professions de la santé. Les étudiants qui y ont participé ont trouvé que la FIP était utile à leur apprentissage. Nous encourageons donc les responsables de programme des facultés de médecine et les organisations étudiantes à donner la priorité à la FIP dans leurs activités de prexternat et hors programme.

Trauma-Induced Phaeohyphomycosis in an Immunocompetent Host on Dupilumab.

Phaeohyphomycosis is a rare infection caused by dematiaceous fungi containing melanin in their cell wall. Patients are often immunocompromised, and cases seen in immunocompromised hosts have increased in recent years. Dupilumab, a monoclonal antibody against interleukin-4 (IL-4) and interleukin-13 (IL-13) used for the treatment of atopic dermatitis, has been linked to hypersensitivity reactions resulting in facial redness, and there is growing evidence that dupilumab may increase susceptibility to yeast infections as well. We present a case of trauma-induced cutaneous phaeohyphomycosis in an immunocompetent host on dupilumab. As dupilumab becomes more commonly encountered in practice, this case is meant to explore the potential relationship between dupilumab and predisposition to opportunistic fungal infections.

Inhibin B Secreting Ovarian Fibroma.

Background: Nearly 90% of all the hormone-producing ovarian tumours are sex cord-stromal tumours (SCSTs). The Ovarian fibroma is a hormonally inactive variant of SCST. It is composed of spindle, oval, round cells producing collagen and accounts for approximately 4% of all ovarian neoplasms. Amongst the other SCSTs, Inhibin B is an important tumour marker. It is a heterodimeric glycoprotein hormone that is secreted primarily by the granulosa cells of the developing follicles. High levels of Inhibin-B can hamper follicular recruitment, leading to amenorrhea in a reproductive age woman. Finding: In this case report, we describe a rare case of a reproductive age female presenting with secondary amenorrhea, having an Ovarian Fibroma, producing massive amounts of Inhibin B. Significance: Although some pathological variants of ovarian fibromas like cyst-adeno-fibroma and ovarian fibro-thecoma are known to secrete inhibin B, benign /pure ovarian fibromas rarely do so.

The effects of physiological adaptations to calorie restriction on global cell proliferation rates.

Calorie restriction (CR) reduces the rate of cell proliferation in mitotic tissues. It has been suggested that this reduction in cell proliferation may mediate CR-induced increases in longevity. However, the mechanisms that lead to CR-induced reductions in cell proliferation rates remain unclear. To evaluate the CR-induced physiological adaptations that may mediate reductions in cell proliferation rates, we altered housing temperature and access to voluntary running wheels to determine the effects of food intake, energy expenditure, percent body fat, and body weight on proliferation rates of keratinocytes, liver cells, mammary epithelial cells, and splenic T-cells in C57BL/6 mice. We found that ∼20% CR led to a reduction in cell proliferation rates in all cell types. However, lower cell proliferation rates were not observed with reductions in 1) food intake and energy expenditure in female mice housed at 27°C, 2) percent body fat in female mice provided running wheels, or 3) body weight in male mice provided running wheels compared with ad libitum-fed controls. In contrast, reductions in insulin-like growth factor I were associated with decreased cell proliferation rates. Taken together, these data suggest that CR-induced reductions in food intake, energy expenditure, percent body fat, and body weight do not account for the reductions in global cell proliferation rates observed in CR. In addition, these data are consistent with the hypothesis that reduced cell proliferation rates could be useful as a biomarker of interventions that increase longevity.

Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates.

Calorie restriction (CR) increases longevity and retards the development of many chronic diseases, but the underlying metabolic signals are poorly understood. Increased fatty acid (FA) oxidation and reduced FA synthesis have been hypothesized to be important metabolic adaptations to CR. However, at metabolic steady state, FA oxidation must match FA intake plus synthesis; moreover, FA intake is low, not high, during CR. Therefore, it is not clear how FA dynamics are altered during CR. Accordingly, we measured food intake patterns, whole body fuel selection, endogenous FA synthesis, and gene expression in mice on CR. Within 2 days of CR being started, a shift to a cyclic, diurnal pattern of whole body FA metabolism occurred, with an initial phase of elevated endogenous FA synthesis [respiratory exchange ratio (RER) >1.10, lasting 4-6 h after food provision], followed by a prolonged phase of FA oxidation (RER = 0.70, lasting 18-20 h). CR mice oxidized four times as much fat per day as ad libitum (AL)-fed controls (367 +/- 19 vs. 97 +/- 14 mg/day, P < 0.001) despite reduced energy intake from fat. This increase in FA oxidation was balanced by a threefold increase in adipose tissue FA synthesis compared with AL. Expression of FA synthase and acetyl-CoA carboxylase mRNA were increased in adipose and liver in a time-dependent manner. We conclude that CR induces a surprising metabolic pattern characterized by periods of elevated FA synthesis alternating with periods of FA oxidation disproportionate to dietary FA intake. This pattern may have implications for oxidative damage and disease risk.

Quality of Care for the Screening, Diagnosis, and Management of Lupus Nephritis Across Multiple Health Care Settings.

OBJECTIVE: We examined quality measures for screening, diagnosis, and treatment of lupus nephritis (LN) among participants of the California Lupus Epidemiology Study across 25 different clinical sites to identify gaps in quality of care. METHODS: Data from 250 participants with lupus were analyzed across 3 sources (medical records, physician examination, and patient interviews). Overall performance on 8 quality measures was calculated separately for participants with and without LN. We used generalized estimating equations in which the outcome was performance on measures, adjusting for participant demographics, lupus disease severity, and practice characteristics. RESULTS: Of 148 patients without LN, 42% underwent screening laboratory tests for nephritis, 38% underwent lupus activity serum studies, and 81% had their blood pressure checked every 6 months. Of 102 LN patients, 67% had a timely kidney biopsy, at least 81% had appropriate treatment, and 78% achieved target blood pressure within 1 year of diagnosis. Overall performance in participants across quality measures was 54% (no LN) and 80% (LN). Significantly higher overall performance for screening measures for LN was seen at academic (63.4-73%) versus community clinics (37.9-38.4%). Similarly, among those with LN, higher performance in academic (84.1-85.2%) versus community clinics (54.8-60.2%) was observed for treatment measures. CONCLUSION: In this quality-of-care analysis across 25 diverse clinical settings, we found relatively high performance on measures for management of LN. However, future work should focus on bridging the gaps in lupus quality of care for patients without nephritis, particularly in community settings.

Gaps in Ambulatory Patient Safety for Immunosuppressive Specialty Medications.

OBJECTIVES: New specialty drugs such as biologics are now available in record numbers, presenting increased safety risks for people with immune-mediated diseases. However, comprehensive assessments of patient safety for these drugs are lacking. We examined performance on key patient safety measures, such as screening for latent tuberculosis (LTBI), hepatitis B virus (HBV), and hepatitis C virus (HCV), for new users of a broad group of specialty medications. METHODS: Data were extracted via electronic health record data warehouses of a large university health system using structured queries, and extensive chart review was performed to confirm measure elements. We included all new users of immunosuppressive specialty drugs between 2013 and 2017. We assessed screening for LTBI, HBV, and HCV from 12 months before through 60 days after medication initiation, and calculated performance on a composite measure that required screening for all three infections. Multivariable logistic regression was used to assess differences in screening across specialties, adjusting for patient race, sex, age, and comorbidities. RESULTS: Among 2027 patients, the most common drugs prescribed were adalimumab (32%), etanercept (24%), infliximab (19%), and ustekinumab (9%). Overall, 62% of patients were screened for LTBI, 42% for HBV, and 33% for HCV. Only 26% of patients were screened appropriately for all three infections. Screening patterns differed significantly according to treating specialty. CONCLUSIONS: We found gaps in ambulatory safety for patients treated with immunosuppressive specialty drugs for diverse inflammatory conditions across all relevant treating specialties. More robust safety protocols are urgently needed to prevent serious patient safety events in this high-risk population.

Pneumocystis jirovecii pneumonia (PJP) prophylaxis patterns among patients with rheumatic diseases receiving high-risk immunosuppressant drugs.

INTRODUCTION/OBJECTIVES: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal opportunistic infection; however, consensus varies around which conditions or medications confer a level of risk sufficient to justify antibiotic prophylaxis for PJP. We used electronic health record (EHR) data to assess the current patterns of PJP prophylaxis, PJP outcomes, and prophylaxis-related adverse events among patients with rheumatic diseases who were receiving high-risk immunosuppressant drugs. METHODS: Data derive from the EHR of a large health system. We included new immunosuppressant users with diagnoses of vasculitis, myositis, or systemic lupus erythematosus. We calculated the proportion of patients who received PJP prophylaxis for each diagnosis and drug combination. We also calculated the number of PJP infections and the number of antibiotic adverse drug events (ADEs) per patient-year of exposure. RESULTS: We followed 316 patients for 23.2 + /- 14.2 months. Overall, 124 (39%) of patients received prophylactic antibiotics for PJP. At least 25% of patients with the highest risk conditions (e.g. vasculitis) or highest risk immunosuppressants (e.g. cyclophosphamide) did not receive PJP prophylaxis. We found no cases of PJP infection over 640 patient-years of follow up, including among those not receiving prophylaxis, and an overall incidence rate of ADEs of 2.2% per patient-year. CONCLUSIONS: PJP prophylaxis for patients with rheumatic conditions is inconsistent, with one quarter of patients who have high risk conditions or high risk immunosuppressants not receiving prophylaxis. However, given extremely low rates of PJP infection, but detectable ADEs to prophylactic antibiotics, our findings suggest that evidence to guide more personalized risk assessments are needed to inform PJP prophylaxis.

Relationship of predictive modeling to receiver operating characteristics.

BACKGROUND: Discriminatory capabilities of a measurement technique can be assessed by a receiver operating characteristic (ROC) curve analysis (specifically, area under the curve [AUC]) and predictive modeling (predictive accuracy and positive predictive value). Theoretically, predictive accuracy is dependent on disease prevalence while AUC assessments are not. OBJECTIVE: To compare the effect of changes in disease prevalence on ROC AUC analysis and predictive modeling. METHODS: For this comparison, a data set with 72 individuals with coronary artery disease (CAD) and 1,857 individuals without CAD was used. A validated CAD score with a demonstrated AUC of 0.80 was applied. Disease prevalence within the study sample was altered by randomly removing non-CAD patients from the original sample. Predictive accuracy and positive predictive value of the CAD score were calculated using 2 x 2 contingency tables. Three threshold values of the CAD score were applied centering on a value for which sensitivity and specificity were equal. RESULTS: For a chosen CAD score threshold value (eg, 60), sensitivity (0.74), specificity (0.75), and AUC (0.81) did not change significantly while positive predictive value increased (10%-70%) as disease prevalence increased from 4% to 44%. Changes in predictive accuracy were dependent on the selected test threshold value. Predictive accuracy increased (54%-68%), did not change (74%-75%), or decreased (88%-70%) with the same increase in disease prevalence for threshold values of 50, 60, and 70, respectively. CONCLUSIONS: The ROC AUC and predictive accuracy are stable diagnostic characteristics, whereas positive predictive value is greatly influenced by disease prevalence.