Faculty Bibliography

PURPOSE/OBJECTIVE:To report the clinical and multimodal imaging (MMI) findings and long-term follow-up of stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) contiguous with midperipheral retinoschisis (MPRS) and to describe a severe SNIFR variant termed CARPET (Central Anomalous Retinoschisis with mid-PEripheral Traction). DESIGN/METHODS:Retrospective case series. SUBJECTS/METHODS:Eleven patients (15 eyes) with SNIFR contiguous with MPRS in at least one eye at baseline or final follow-up. METHODS:MMI features, including cross-sectional and en face macular and peripheral spectral-domain optical coherence tomography (OCT) and OCT angiography, were reviewed in all cases at baseline and at the final follow-up visit. MAIN OUTCOME MEASURES/METHODS:Various courses (including progression, regression, or stability) of MPRS or SNIFR over time were evaluated. RESULTS:MPRS exhibited centripetal progression to SNIFR in 5 eyes of 3 patients with follow up of 67, 60, and 27 months, respectively, with maintenance of excellent visual acuity (range: 20/25-20/20) in 4 of these 5 eyes. In 2 eyes of 2 patients (including 1 eye with initial centripetal progression of MPRS to SNIFR), MPRS contiguous with SNIFR spontaneously resolved with long-term follow-up (77 and 48 months, respectively). SNIFR contiguous with MPRS partially regressed after 48 months in one patient, and was stable after 54 months in another. A distinctive midperipheral microvasculopathy, associated with MPRS that was contiguous with SNIFR, was identified in 7 eyes of 4 patients. Finally, 3 eyes of 3 patients exhibited additional unique features, including central neurosensory detachment and outer lamellar macular hole, which were associated with significant midperipheral traction, representing a severe variant subtype of SNIFR that we refer to as CARPET. Two of these 3 eyes progressed with short-term follow-up of 6 and 2 months, respectively, while the schisis resolved and vision improved after pars plana vitrectomy in the third case. CONCLUSIONS:MPRS can progress to SNIFR over multiple years of follow-up. SNIFR with MPRS can also spontaneously resolve or remain stable. MPRS can additionally be complicated by a midperipheral inner retinal microvasculopathy. Finally, CARPET may represent a unique and severe variant form of SNIFR driven by midperipheral vitreoretinal traction and associated with significant vision loss.

BACKGROUND:Cognitive impairment is linked with increased risk of falls in people with multiple sclerosis (pwMS), but it is not clear whether cognitive performance may help to account for the discordance between fall-risk due to actual physiological functioning and the individual's perception of their fall-risk. This study examined the relationship between cognitive performance and the concordance/discordance of physiological and perceived fall-risk in pwMS. METHODS:) fall-risk. Cognitive performance was evaluated using the NeuroTrax computerized cognitive battery, which generates a global cognitive score (GCS) as well as scores for individual cognitive domains. RESULTS:group. CONCLUSION/CONCLUSIONS:In this study, one in 4 pwMS had a discordance between their physiological and perceived fall-risk. This discordance was not explained by cognitive performance.

BACKGROUND:Incidence estimates of post-acute sequelae of SARS-CoV-2 infection, also known as long-COVID, have varied across studies and changed over time. We estimated long-COVID incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes). METHODS:This EHR-based retrospective cohort study included adult and pediatric patients with documented acute SARS-CoV-2 infection and two control groups-- contemporary COVID-19 negative and historical patients (2019). We examined the proportion of individuals identified as having symptoms or conditions consistent with probable long-COVID within 30-180 days after COVID-19 infection (incidence proportion). Each network (the National COVID Cohort Collaborative (N3C), National Patient-Centered Clinical Research Network (PCORnet), and PEDSnet) implemented its own long-COVID definition. We introduced a harmonized definition for adults in a supplementary analysis. RESULTS:Overall, 4% of children and 10-26% of adults developed long-COVID, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 1.5% in children and ranged from 5-6% among adults, representing a lower-bound incidence estimation based on our control groups. Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants. CONCLUSION/CONCLUSIONS:Our findings indicate that preventing and mitigating long-COVID remains a public health priority. Examining temporal patterns and risk factors of long-COVID incidence informs our understanding of etiology and can improve prevention and management.

Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is the current standard of care. This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was not planned as the initial therapy (transplant deferred). Some 395 patients with transplant-ineligible or transplant-deferred NDMM were randomly assigned to eight cycles of D-VRd or VRd followed by D-Rd or Rd until progression. The primary endpoint was overall minimal residual disease (MRD)-negativity rate at 10^-

Bowel endometriosis is a complex condition predominantly impacting women in their reproductive years, which may lead to chronic pain, gastrointestinal symptoms, and infertility. This review highlights current approaches to the diagnosis and management of bowel endometriosis, emphasizing a multidisciplinary strategy. Diagnostic methods include detailed patient history, physical examination, and imaging techniques like transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI), which aid in preoperative planning. Management options range from hormonal therapies for symptom relief to minimally invasive surgical techniques. Surgical interventions, categorized as shaving excision, disc excision, or segmental resection, depend on factors such as lesion size, location, and depth. Shaving excision is preferred for its minimal invasiveness and lower complication rates, while segmental resection is reserved for severe cases. This review also explores nerve-sparing strategies to reduce surgical morbidity, particularly for deep infiltrative cases close to the rectal bulb, anal verge, and rectosigmoid colon. A structured, evidence-based approach is recommended, prioritizing conservative surgery to avoid complications and preserve fertility as much as possible. Comprehensive management of bowel endometriosis requires expertise from both gynecologic and gastrointestinal specialists, aiming to improve patient outcomes while minimizing long-term morbidity.

While there is agreement on the indications for intracranial pressure monitoring (ICPm) in patients with sTBI, there continues to be controversy concerning the ideal timing of its implementation. It is within this context that we decided to investigate whether a protocolization approach could optimize the timeliness of ICPm implementation. Neurosurgical and SICU providers agreed to a 3-tier protocol to identify patients with sTBI who could benefit from timelier ICPm implementation. The monthly compliance was monitored for a 9-month period. The study included a pre-protocolization group of 11 patients (2022) and a post-protocolization group of 9 patients (2023-2024). There was a trend toward earlier use of ICPm but the difference did not achieve statistical significance; there was no difference in the mortality rates between groups. A protocolization approach to the treatment of patients with sTBI developed with a consensus strategy may lead to earlier implementation of ICPm and possibly improved functional outcome.

Precision medicine approaches to cancer treatment aim to exploit genomic alterations that are specific to individual patients to tailor therapeutic strategies. Yet, some targetable genes and pathways are essential for tumor cell viability even in the absence of direct genomic alterations. In underrepresented populations, the mutational landscape and determinants of response to existing therapies are poorly characterized because of limited inclusion in clinical trials and studies. One way to reveal tumor essential genes is with genetic screens. Most screens are conducted on cell lines that bear little resemblance to patient tumors, after years of culture under nonphysiologic conditions. To address this problem, we aimed to develop a CRISPR screening pipeline in three-dimensionally grown patient-derived tumor organoid (PDTO) models. A breast cancer PDTO biobank that focused on underrepresented populations, including West African patients, was established and used to conduct a negative-selection kinome-focused CRISPR screen to identify kinases essential for organoid growth and potential targets for combination therapy with EGFR or MEK inhibitors. The screen identified several previously unidentified kinase targets, and the combination of FGFR1 and EGFR inhibitors synergized to block organoid proliferation. Together, these data demonstrate the feasibility of CRISPR-based genetic screens in patient-derived tumor models, including PDTOs from underrepresented patients with cancer, and identify targets for cancer therapy. Significance: Generation of a breast cancer patient-derived tumor organoid biobank focused on underrepresented populations enabled kinome-focused CRISPR screening that identified essential kinases and potential targets for combination therapy with EGFR or MEK inhibitors. See related commentary by Trembath and Spanheimer, p. 407.