Delays in Cervical Cancer Treatment Initiation for Patients Living With or Without HIV in Botswana: An Observational Cohort Analysis (2015-2019).

PURPOSE: To assess delays in treatment initiation of chemoradiation or radiation alone for patients with advanced stage cervical cancer in Botswana. METHODS AND MATERIALS: Females with locally advanced cervical cancer (stages IB2-IVB) were prospectively enrolled in an observational cohort study from 2015 to 2019. We evaluated delays at 30, 60, 90, 120, 150, and 180 or greater days between the date of diagnosis and treatment initiation. Factors associated with overall survival were modeled with multivariable Cox proportional hazards regression (aHR). Associations between delays in cervical cancer treatment initiation were evaluated via univariable logistic regression. RESULTS: Among the 556 patients included (median age = 47.9 years), 386 (69.4%) were females living with HIV with a median CD4 count of 448.0 cells/µL (IQR, 283.0-647.5 cells/µL) at diagnosis. Most patients had stages 2 (38.1%) or 3 (34.5%) cervical cancer. Early-stage patients experienced longer delays in treatment initiation compared to late-stage patients (P = .033). Early-stage patients with delays ≥90 days and pathology diagnosis between 2016 and 2019 (aHR, 0.34; P < .001) versus <90 days had a decreased risk of mortality, and those with delays ≥90 days and pathology diagnosis before 2016 (aHR, 5.67; P = .022) versus <90 days had an increased risk of mortality. Late-stage patients with delays ≥120 days and pathology diagnosis between 2018 and 2019 (aHR, 1.98; P = .025) versus <120 days had an increased risk of mortality. Early-stage patients with pathology diagnosis between 2016 and 2019 (odds ratio, 2.32; P = .043) versus before 2016 were more likely to experience delays ≥90 days, and late-stage patients who traveled >100 km to the treatment facility (odds ratio, 2.83; P < .001) versus <100 km were more likely to experience delays ≥120 days. CONCLUSIONS: Delays in care are common in Botswana, particularly for those living farther from the treatment clinic and at advanced stages. This paper is among the first to show an association between treatment delays and worsened overall survival at advanced stages of cervical cancer, highlighting the need for interventions to help patients receive timely care in global settings.

Oncologic and Functional Outcomes After Stereotactic Body Radiation Therapy for High-Grade Malignant Spinal Cord Compression.

Purpose: Although surgical decompression is the gold standard for metastatic epidural spinal cord compression (MESCC) from solid tumors, not all patients are candidates or undergo successful surgical Bilsky downgrading. We report oncologic and functional outcomes for patients treated with stereotactic body radiation therapy (SBRT) to high-grade MESCC. Methods and Materials: Patients with Bilsky grade 2 to 3 MESCC from solid tumor metastases treated with SBRT at a single institution from 2009 to 2020 were retrospectively reviewed. Patients who received upfront surgery before SBRT were included only if postsurgical Bilsky grade remained ≥2. Neurologic examinations, magnetic resonance imaging, pain assessments, and analgesic usage were assessed every 3 to 4 months post-SBRT. Cumulative incidence of local recurrence was calculated with death as a competing risk, and overall survival was estimated by Kaplan-Meier. Results: One hundred forty-three patients were included. The cumulative incidence of local recurrence was 5.1%, 7.5%, and 14.1% at 6, 12, and 24 months, respectively. At first post-SBRT imaging, 16.2% of patients with initial Bilsky grade 2 improved to grade 1, and 53.8% of patients were stable. Five of 13 patients (38.4%) with initial Bilsky grade 3 improved to grade 1 to 2. Pain response at 3 and 6 months post-SBRT was complete in 45.4% and 55.7%, partial in 26.9% and 13.1%, stable in 24.1% and 27.9%, and worse in 3.7% and 3.3% of patients, respectively. At 3 and 6 months after SBRT, 17.8% and 25.0% of patients had improved ambulatory status and 79.7% and 72.4% had stable status. Conclusions: We report the largest series to date of patients with high-grade MESCC treated with SBRT. The excellent local control and functional outcomes suggest SBRT is a reasonable approach in inoperable patients or cases unable to be successfully surgically downgraded.

Scleral Buckle Removal: Long-Term Patient Outcomes.

PURPOSE: Scleral buckling has been a reliable treatment option in the repair of primary rhegmatogenous retinal detachments. Occasionally, patients require scleral buckles (SBs) to be removed for various reasons. While outcomes of SB removal have been investigated in this subset of patients, there has not been any large patient series to reach any conclusions. Long-term sequelae of SB removal are debated in the literature, specifically around the risk of redetachment. DESIGN: We performed a retrospective, observational study to evaluate the clinical indications for, and outcomes of, SB removal. PARTICIPANTS: No control patients in this retrospective, observational study. METHODS: Eighty-six individuals with a history of SB removal from June 1, 2000, to January 1, 2021, were followed from a large academic center and a private, retina-only practice in Chicago. Exclusion criteria were age of < 18 years and unplanned or self-explanted SB removal. MAIN OUTCOME MEASURES: Data extracted included patient symptoms before SB removal, indications for removal, resolution of symptoms following removal, rate of redetachment, and rate of additional ocular surgery. Secondary outcomes included identifying factors associated with poorer outcomes. RESULTS: Eighty-six eyes with history of SB removal were included with an average follow-up of 4 years. Approximately 60% were males and the mean age at the time of SB removal was 59 years. Leading indications for removal were exposure (61.63%), infection (20.93%), and diplopia/strabismus (19.77%). The average time from SB placement to removal was 12.28 ± 11.16 years. Most patients requiring SB removal presented with symptoms, specifically of pain and discomfort (65.12%), diplopia (22.09%), and drainage/discharge (18.60%). Of these patients, 86.59% experienced symptom resolution following SB removal. Notably, 6.56% (4 eyes) of all eyes with at least 1 year of follow-up experienced a redetachment requiring surgery. Within this subset, the average time from SB placement to removal was 2.05 ± 2.01 years and time to redetachment following removal was 15.95 ± 25.71 months. Nine percent of all eyes required additional strabismus or oculoplastic surgery. CONCLUSIONS: Scleral buckle removal provides a high rate of symptomatic relief and low risk of subsequent detachment. Nevertheless, close monitoring is warranted to monitor for recurrent retinal detachments. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Impact of socioeconomic status and chemotherapy on neurocognitive performance in children with brain tumors.

Background: Although the relationship between radiation and neurocognition has been extensively studied in the pediatric brain tumor population, it is increasingly recognized that neurocognitive impairment is multifactorial. Therefore, we quantified the effect of socioeconomic status (SES) and chemotherapy on neurocognitive impairment and decline post-treatment. Methods: Eligible patients included those diagnosed with a brain tumor at < 22 years of age with ≥1 neurocognitive assessment. Neurocognitive impairment was defined as performance 1.5 standard deviations below the normative mean using age-standardized measures of intellectual function. Neurocognitive decline was defined as a negative slope. Neurocognitive outcomes included Wechsler indices of Full-Scale Intelligence Quotient (IQ). Logistic regression identified variables associated with neurocognitive impairment. Longitudinal data was analyzed using linear mixed models. Results: Eligible patients (n = 152, median age at diagnosis = 9.6 years) had a mean neurocognitive follow-up of 50.2 months. After accounting for age and receipt of craniospinal irradiation, patients with public insurance had 8-fold increased odds of impaired IQ compared to private insurance (odds ratio [OR]: 7.59, P < .001). After accounting for age, change in IQ was associated with chemotherapy use (slope: -0.45 points/year with chemotherapy vs. 0.71 points/year without chemotherapy, P = .012). Conclusions: Public insurance, an indicator of low SES, was associated with post-treatment impairment in IQ, highlighting the need to incorporate SES measures into prospective studies. Chemotherapy was associated with change in IQ. Further work is needed to determine whether impairment associated with low SES is secondary to baseline differences in IQ prior to brain tumor diagnosis, brain tumor/therapy itself, or some combination thereof.

Recommendations for Cost-Conscious Treatment of Basal Cell Carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) affects 3.3 million Americans annually. Treatment modalities for BCC include many surgical and nonsurgical options. The cost of BCC treatment can pose a substantial burden to patients and the healthcare system. Cost can be an important consideration in BCC treatment planning. OBJECTIVE: We present an approach to the management of BCC when cost reduction is a priority. METHODS: A PubMed literature search identified studies on effectiveness of current BCC therapies. Treatment prices were obtained from the Medicare National Fee Schedule, GoodRx, and pharmaceutical companies. The American Academy of Dermatology's (AAD) guidelines for treating BCC were used to develop recommendations for cost-reductive treatment. RESULTS: The cost of treating a primary superficial BCC < 0.5 cm arising on Area M (cheeks, forehead, scalp, neck, jawline, pretibial surface) was $143 with curettage and electrodesiccation (C&E), $143 with cryosurgery, $210 with standard excision and simple reconstruction (SE), $1221 with Mohs Micrographic Surgery (MMS) and simple reconstruction, $472 with imiquimod, $186 with 5-fluorouracil (5-FU), and $354-$371 for photodynamic therapy (PDT). The cost of treating a primary nodular BCC 1.1-2 cm arising on Area L (trunk and extremities, excluding pretibial surface, hands, feet, nail units and ankles) was $183 with C&E, $183 with cryosurgery, $251 with SE and simple reconstruction, $1163-1351 with MMS and simple reconstruction, $472 with imiquimod, $186 with 5-FU, and $354-$371 for photodynamic therapy (PDT). The cost of treating a giant BCC (BCC > 10 cm with aggressive behavior) was $465-3311 with radiation, $139,560 with vismodegib, $144,452 with sonidegib, ~ $44.5 with cisplatin (medication cost only), and at least $184,836 with cemiplimab-rwlc. CONCLUSIONS: For a primary superficial BCC < 0.5 cm arising on Area M, the cost-conscious algorithm prioritizes C&E or cryosurgery. For a primary nodular BCC 1.1-2 cm arising on Area L, the cost-conscious algorithm prioritizes C&E, cryosurgery, or 5-FU. For a giant BCC, the cost-conscious algorithm identifies superficial radiation therapy as first line.

The Impact of Social Determinants of Health on Presentation, Treatment, and Outcomes in Branch Retinal Vein Occlusion With Cystoid Macular Edema.

BACKGROUND AND OBJECTIVE: To investigate the impact of social determinants of health on the presentation, treatment, and outcomes of branch retinal vein occlusion (BRVO) with cystoid macular edema (CME). PATIENTS AND METHODS: A retrospective chart review was conducted of patients with BRVO and CME treated with anti-vascular endothelial growth factor (anti-VEGF) injections at Atrium Health Wake Forest Baptist from 2013 to 2021. Patients' baseline characteristics including visual acuity (VA), age, sex, race, Area Deprivation Index (ADI), insurance status, baseline central macular thickness (CMT), treatment details, final VA, and final CMT were recorded. The primary outcome measure was final VA comparing more and less deprived groups, and White and non-White groups. RESULTS: Two hundred forty-four eyes of 240 patients were included. Patients with higher socioeconomic deprivation scores had thicker final CMT (P = 0.05). Non-White patients had worse presenting (P = 0.01) and final VA (P = 0.02). CONCLUSION: This study demonstrated disparities in presentation and outcomes based on socioeconomic status and race in patients with BRVO and CME treated with anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina 2023;54:411-416.].

Artificial Intelligence-Based PTEN Loss Assessment as an Early Predictor of Prostate Cancer Metastasis After Surgery: A Multicenter Retrospective Study.

Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and can be measured via immunohistochemistry. The purpose of the study was to establish the clinical application of an in-house developed artificial intelligence (AI) image analysis workflow for automated detection of PTEN loss on digital images for identifying patients at risk of early recurrence and metastasis. Postsurgical tissue microarray sections from the Canary Foundation (n = 1264) stained with anti-PTEN antibody were evaluated independently by pathologist conventional visual scoring (cPTEN) and an automated AI-based image analysis pipeline (AI-PTEN). The relationship of PTEN evaluation methods with cancer recurrence and metastasis was analyzed using multivariable Cox proportional hazard and decision curve models. Both cPTEN scoring by the pathologist and quantification of PTEN loss by AI (high-risk AI-qPTEN) were significantly associated with shorter metastasis-free survival (MFS) in univariable analysis (cPTEN hazard ratio [HR], 1.54; CI, 1.07-2.21; P = .019; AI-qPTEN HR, 2.55; CI, 1.83-3.56; P < .001). In multivariable analyses, AI-qPTEN showed a statistically significant association with shorter MFS (HR, 2.17; CI, 1.49-3.17; P < .001) and recurrence-free survival (HR, 1.36; CI, 1.06-1.75; P = .016) when adjusting for relevant postsurgical clinical nomogram (Cancer of the Prostate Risk Assessment [CAPRA] postsurgical score [CAPRA-S]), whereas cPTEN does not show a statistically significant association (HR, 1.33; CI, 0.89-2; P = .2 and HR, 1.26; CI, 0.99-1.62; P = .063, respectively) when adjusting for CAPRA-S risk stratification. More importantly, AI-qPTEN was associated with shorter MFS in patients with favorable pathological stage and negative surgical margins (HR, 2.72; CI, 1.46-5.06; P = .002). Workflow also demonstrated enhanced clinical utility in decision curve analysis, more accurately identifying men who might benefit from adjuvant therapy postsurgery. This study demonstrates the clinical value of an affordable and fully automated AI-powered PTEN assessment for evaluating the risk of developing metastasis or disease recurrence after radical prostatectomy. Adding the AI-qPTEN assessment workflow to clinical variables may affect postoperative surveillance or management options, particularly in low-risk patients.

A DNA copy number alteration classifier as a prognostic tool for prostate cancer patients.

BACKGROUND: Distinguishing between true indolent and potentially life-threatening prostate cancer is challenging in tumours displaying clinicopathologic features associated with low or intermediate risk of relapse. Several somatic DNA copy number alterations (CNAs) have been identified as potential prognostic biomarkers, but the standard cytogenetic method to assess them has a limited multiplexing capability. METHODS: Multiplex ligation-dependent probe amplification (MLPA) targeting 14 genes was optimised to survey 448 tumours of patients with low or intermediate risk (Grade Group 1-3, Gleason score ≤7) who underwent radical prostatectomy. A 6-gene CNA classifier was developed using random survival forest and Cox proportional hazard modelling to predict biochemical recurrence. RESULTS: The classifier score was significantly associated with biochemical recurrence after adjusting for standard clinicopathologic variables and the known prognostic index CAPRA-S score with a hazard ratio of 2.17 and 1.80, respectively (n = 406, P < 0.01). The prognostic value of this classifier was externally validated in published CNA data from three radical prostatectomy cohorts and one radiation therapy pre-treatment biopsy cohort. CONCLUSION: The 6-gene CNA classifier generated by a single MLPA assay compatible with the small quantities of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue specimens has the potential to improve the clinical management of patients with low or intermediate risk disease.

Systematic review of economic evaluations in pediatric ophthalmology and strabismus.

BACKGROUND: Economic evaluations in health care quantitatively compare interventions using cost and outcomes data. These evaluations can aid in the adoption of new surgical or medical treatments and inform policy decisions regarding healthcare spending. Several common types of economic analysis exist (cost-benefit, cost-analysis, cost-effectiveness, and cost-utility). We review all English-language economic evaluations in strabismus surgery and pediatric ophthalmology. METHODS: An electronic literature search of the PubMed and Health Economic Evaluations databases was conducted. Two reviewers independently reviewed the search string yield and assessed articles against inclusion and exclusion criteria. Outcome measures included journal of publication, year of publication, domain of ophthalmology, region/country of study, and type of economic evaluation. RESULTS: We identified 62 articles. Cost-utility studies comprised 30% of evaluations. The most studied domain was retinopathy of prematurity (33%), followed by amblyopia and vision screening (24%) and cataracts (14%). The Journal of the American Association for Pediatric Ophthalmology and Strabismus published the most economic evaluations (15%) followed by Ophthalmology and Pediatrics. The number of published economic evaluations did not increase over time. CONCLUSIONS: Economic evaluations in pediatric ophthalmology and strabismus have not increased over time. A minority (30%) of studies used cost utility-analysis, limiting comparisons to other domains of medicine. This suggests the need to alert pediatric ophthalmologists to the benefits of economic analysis, and cost-utility methodology specifically, to better inform and influence policy decisions regarding healthcare spending.

Atypical Immunologic Manifestations of COVID-19: a Case Report and Narrative Review.

COVID-19 usually presents with classic signs and symptoms, but it can involve multiple systems in atypical cases. SARS-CoV-2 has a complex interaction with the host immune system leading to atypical manifestations. In our case, a 32-year-old male patient presented with fatigue, sores on hands and feet, headache, productive cough with blood-tinged mucus, conjunctival hyperemia, purpuric rash on hands and feet, and splinter hemorrhages of fingernails for 2 weeks. The patient's SARS-CoV-2 antigen and PCR test were positive. Chest X-ray showed mixed density perihilar opacities in both lungs. Computed tomography of the chest showed extensive airspace opacities in both lungs, suggesting COVID-19 multifocal, multilobar pneumonitis. A renal biopsy indicated limited thrombotic microangiopathy and tubulointerstitial nephritis, for which he was started on steroids, and his renal functions gradually improved. He tested positive for C-ANCA during an immune workup. He was discharged with a steroid taper for nephritis. Once the taper reached less than 10 mg/day, he developed acute scleritis and a new pulmonary cavitary lesion of 6 cm. The biopsy via bronchoscopy revealed acute inflammatory cells with hemosiderin-laden macrophages. He was restarted on systemic steroids for scleritis after failing topical steroids, which incidentally also reduced the size of the cavitary lesion, indicating an immune component. Our case demonstrates the involvement of kidneys and vasculitis of the skin, sclera, and lungs by COVID-19. The patient's symptoms were not explained by any diseases other than COVID-19. Atypical cases of COVID-19 disease with multifocal systemic symptoms involving the skin, sclera, lungs, and kidneys should be high on differentials. Early recognition and intervention may decrease hospital stays and morbidity.

Antiresorptive Medications Prior to Stereotactic Body Radiotherapy for Spinal Metastasis are Associated with Reduced Incidence of Vertebral Body Compression Fracture.

STUDY DESIGN: Retrospective Cohort. OBJECTIVE: Antiresorptive drugs are often given to minimize fracture risk for bone metastases, but data regarding optimal time or ability to reduce stereotactic body radiotherapy (SBRT)-induced fracture risk is limited. This study examines the association between antiresorptive use surrounding spinal SBRT and vertebral compression fracture (VCF) incidence to provide information regarding effectiveness and optimal timing of use. METHODS: Patients treated with SBRT for spinal metastases at a single institution between 2009-2020 were included. Kaplan-Meier analysis was used to compare cumulative incidence of VCF for those taking antiresorptive drugs pre-SBRT, post-SBRT only, and none at all. Cox proportional hazards and Fine-Gray competing risk models were used to identify additional factors associated with VCF. RESULTS: Of the 234 patients (410 vertebrae) analyzed, 49 (20.9%) were taking bisphosphonates alone, 42 (17.9%) were taking denosumab alone, and 25 (10.7%) were taking both. Kaplan-Meier analysis revealed a statistically significant lower VCF incidence for patients initiating antiresorptive drugs before SBRT compared to those taking none at all (4% vs 12% at 1 year post-SBRT, P = .045; and 4% vs 23% at 2 years, P = .008). On multivariate analysis, denosumab duration (HR: .87, P = .378) or dose (HR: 1.00, P = .644) as well as bisphosphonate duration (HR: .98, P= .739) or dose (HR: .99, P= .741) did not have statistical significance on VCF incidence. CONCLUSION: Initiating antiresorptive agents before SBRT may reduce the risk of treatment-induced VCF. Antiresorptive drugs are underutilized in patients with spine metastases and may represent a useful intervention to minimize toxicity and improve long-term outcomes.

Apparent Dengue Fever Turned Out to be Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an extremely uncommon hematologic condition that is potentially fatal. It is a disease of histiocyte or lymphocyte hyperactivity, which can be inherited (primary) or acquired (secondary). Dengue fever and HLH both can present with fever, lethargy, and a blood profile of pancytopenia, which makes it difficult to diagnose HLH promptly in a region with dengue endemicity. Clinical and supportive biochemistry findings help clinicians to suspect and diagnose HLH. This article presents a case report of a patient who was diagnosed with dengue fever during initial presentation with subsequent swerves toward HLH. Diagnosing HLH associated with dengue can be difficult. However, it is of utmost importance to diagnose it early, as an early diagnosis and management can lead to significantly improved outcomes. How to cite this article: Gandhi A, Patel P, Shah D. Apparent Dengue Fever Turned Out to be Hemophagocytic Lymphohistiocytosis. J Assoc Physicians India 2023;71(11):96-99.

Rapid Progression of Large B-cell Lymphoma in Behçet's Disease on Immunosuppressive Therapy: A Case Report with Literature Review.

Behçet's disease (BD) is a systemic vasculitis characterized by various symptoms, including orogenital ulcers, uveitis, arthritis, skin lesions, and the involvement of the gastrointestinal tract and central nervous system. BD has been associated with malignancies such as leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma, Hodgkin's disease, and lymphosarcoma. The rarity of association with B-cell lymphoma may also be added to the list, given our findings in this case report. Patients with vasculitides benefit from immunosuppressive therapy that can minimize disease and may prevent disease manifestations and exacerbations. However, there may be an increased risk of cancer development, which calls for consideration while starting and maintaining this population of patients on immunosuppressive therapy.

Correction: Bishayee et al. Lotus (Nelumbo nucifera Gaertn.) and Its Bioactive Phytocompounds: A Tribute to Cancer Prevention and Intervention. Cancers 2022, 14, 529.

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Laparoscopic Versus Open Surgical Repair of Duodenal Atresia: A NSQIP-Pediatric Analysis.

INTRODUCTION: Laparoscopic repair of duodenal atresia in neonates has gained popularity among some pediatric surgeons. Single-center studies suggest comparable short-term outcomes to open surgery. The purpose of this study was to utilize a large, multi-institutional pediatric dataset to examine 30-day post-operative outcomes by operative approach for newborns who underwent duodenal atresia repairs. METHODS: We identified neonates aged ≤1 wk in the 2016-2018 National Surgical Quality Improvement Program-Pediatric -database that underwent a laparoscopic or open repair for duodenal atresia. Preoperative characteristics were compared between operative approaches. Postoperative complications, operative time, postoperative length of stay (LOS), and supplemental nutrition at discharge were assessed using multivariate regressions. RESULTS: There were 267 neonates who met inclusion criteria. There were 233 (87%) infants who underwent open repairs and 34 (13%) who underwent laparoscopic repairs. Ten (29%) children who had laparoscopy were converted to open. After adjusting for confounding, laparoscopy was associated with an increase in operative time by 65 min (95% confidence interval 45-87 min, P < 0.001) but a five-day shorter LOS (95% confidence interval -9 to -2, P = 0.006) when compared to laparotomy. There were no significant differences in postoperative complications or supplemental nutrition at discharge. CONCLUSIONS: Our findings suggest that laparoscopic repairs of duodenal atresia are associated with shorter postoperative LOS but longer operative times when compared to open repairs. Although the conversion rate to laparotomy remained relatively high, the laparoscopic approach was associated with comparable 30-day postoperative outcomes.