Short-Term Outcomes of Faricimab in Patients with Neovascular Age-Related Macular Degeneration on Prior Anti-VEGF Therapy.

PURPOSE: A subset of patients with neovascular age-related macular degeneration (nAMD) experience treatment burden and suboptimal response with anti-VEGF therapy. The aim of this study was to investigate the effect of switching to a novel, bispecific agent, faricimab, in patients with nAMD currently treated with anti-VEGF. DESIGN: Retrospective, noncomparative cohort study. SUBJECTS: Patients with nAMD previously treated with anti-VEGF and switched to intravitreal faricimab injection (IFI) at the Cleveland Clinic's Cole Eye Institute. METHODS: Switching and administration schedule of IFI was at the discretion of the clinician. Visual acuity (VA) and macular OCT parameters, including central subfield thickness (CST), maximum pigment epithelial detachment (PED) height, and presence of subretinal (SRF) or intraretinal fluid (IRF), were assessed at baseline (day of first IFI) and after each IFI. MAIN OUTCOME MEASURES: Central subfield thickness and presence of IRF or SRF after ≥ 3 IFIs. RESULTS: One hundred twenty-six eyes of 106 patients were included in the analysis with a mean follow-up time of 24.3 ± 5.2 weeks. Before switching to IFI, patients received a mean of either aflibercept (20.0 ± 8.4, mean ± standard deviation), bevacizumab (7 ± 8.9), ranibizumab (1.9 ± 8.5), or brolucizumab (0.3 ± 1.6) injections. The most common agent used before switching to IFI was aflibercept (n = 110, 87%), and the mean treatment interval with any anti-VEGF was 5.6 ± 1.6 weeks before switching. Central subfield thickness was reduced from baseline after the first IFI (266.8 ± 64.7 vs. 249.8 ± 58.6 µm, P = 0.02) and persisted over the 3 IFIs (P = 0.01). Pigment epithelial detachment height was reduced after the third IFI (249.6 ± 179.0 vs. 206.9 ± 130.0 µm, P = 0.01). The mean VA (62.9 vs. 62.7 approximate ETDRS letters, P = 0.42) and interval between injections (6.3 vs. 5.7 weeks, P = 0.16) was similar after the third IFI compared with baseline. Eleven (8.7%) eyes were switched back to their previous anti-VEGF, including 2 (1.6%) eyes from 1 patient with intraocular inflammation requiring cessation of IFI. There were no other adverse events from switching. CONCLUSIONS: Switching to faricimab resulted in a reduction in mean CST (-11.6 µm, P = 0.01) and PED height (-44.2 µm, P = 0.01) after 3 injections, with stable VA and at a similar treatment interval to prior anti-VEGF therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

History of abuse is associated with thoughts of harm among patients with pain after accounting for depressive symptoms.

INTRODUCTION: Screening for depressive symptoms is often the first step to understanding risk for thoughts of harm among patients with pain. Pain characteristics and history of abuse are also associated with thoughts of harm; however, little is known about these associations after accounting for depressive symptoms. This study examined the association between pain characteristics and history of abuse with thoughts of harm among pain patients with moderate to severe and low to mild depressive symptoms. METHODS: We conducted a cross-sectional analysis of patients (n=7510) who presented to a tertiary-care, outpatient pain clinic. RESULTS: Abuse history was significantly associated with increased odds of reporting thoughts of harm for both patients with moderate to severe depressive symptoms as well as low to mild depressive symptoms. Abuse did not modify the association between any of the pain characteristics and thoughts of harm. DISCUSSION: Our results highlight the importance of abuse history in assessing thoughts of harm. Although we are unable to infer causality due to the cross-sectional design, this study highlights the importance of screening for abuse history when assessing for suicidal and homicidal ideation.

Sporadic pediatric colorectal carcinoma without known genetic predisposition - Defying the dictum: Learning lesson with review of the literature.

Pediatric colorectal carcinomas are extremely rare with an incidence of nearly 1.3 per million. Diagnosis is usually delayed following a lack of suspicion at this age. Increasing incidence as well as awareness provides an insight into the disease entity. Two cases of childhood colorectal carcinoma, one in an 11 and another in a 19-year-old boy are presented. However, they have been reparted to carry a forarable outcome. Both the cases showed mucin and signet ring cells which indicates an aggressive behavior. The presentation highlights the clinical characteristics and genetic implications in most of the patients. However, both our cases did not show any predisposing or genetic predisposition. These cases are presented to make aware the readers as to how the common dictum can be reversed and adolescents can also be affected by cancer, a disease of the elderly. Early diagnosis can provide a better management and prognosis.

Symmetric neural progenitor divisions require chromatin-mediated homologous recombination DNA repair by Ino80.

Chromatin regulates spatiotemporal gene expression during neurodevelopment, but it also mediates DNA damage repair essential to proliferating neural progenitor cells (NPCs). Here, we uncover molecularly dissociable roles for nucleosome remodeler Ino80 in chromatin-mediated transcriptional regulation and genome maintenance in corticogenesis. We find that conditional Ino80 deletion from cortical NPCs impairs DNA double-strand break (DSB) repair, triggering p53-dependent apoptosis and microcephaly. Using an in vivo DSB repair pathway assay, we find that Ino80 is selectively required for homologous recombination (HR) DNA repair, which is mechanistically distinct from Ino80 function in YY1-associated transcription. Unexpectedly, sensitivity to loss of Ino80-mediated HR is dependent on NPC division mode: Ino80 deletion leads to unrepaired DNA breaks and apoptosis in symmetric NPC-NPC divisions, but not in asymmetric neurogenic divisions. This division mode dependence is phenocopied following conditional deletion of HR gene Brca2. Thus, distinct modes of NPC division have divergent requirements for Ino80-dependent HR DNA repair.

Breast ductal carcinoma with coexistent microfilaria: Diagnosed on cytology.

Filariasis is a major health problem of the tropical and subtropical regions, but filariae are also found in temperate climates. The disease is endemic all over India and microfilariae have been observed as coincidental findings with inflammatory conditions and neoplastic lesions. We report a rare case of a 40-year-old female from a nonendemic area presenting with lump in the left breast. The skin overlying the mass was fungating and ulcerated. Ipsilateral axillary lymph nodes were palpable. Fine-needle aspiration cytology revealed highly cellular smears having ductal epithelial cells arranged in groups, tight clusters, and scattered singly. Cells were large, having pleomorphic round to oval nuclei with prominent nucleoli. Along with these tumor cells, sheathed microfilariae of Wuchureria bancrofti were seen, suggesting a diagnosis of ductal carcinoma with coexistent microfilaria of W. bancrofti. Findings were confirmed on histopathology of the resected specimen following modified radical mastectomy. Coexistent pathologies should always be considered while reporting.

Cytodiagnosis of papillary carcinoma of the male breast: Report of a case with histological correlation.

Papillary lesions of the breast pose great diagnostic challenges on fine needle aspiration cytology (FNAC) due to overlapping features between benign and malignant entities. Preoperative cytodiagnosis is difficult. We present a case of a 52-year-old male who presented with a progressively increasing firm swelling in the left breast for 3 years. The nipple was eroded with ulceration and bleeding. Ultrasonography (USG) revealed a mass measuring 2.9 cm × 1.5 cm in the left breast. FNAC smears were hypercellular with ductal cells arranged in papillae and glandular clusters. At places, the cells had irregular nuclear membrane, prominent nucleoli, fine chromatin, scanty-to-moderate cytoplasm, and high nuclear-cytoplasmic ratio with pleomorphism. Histopathology of the excised swelling was consistent with intracystic papillary carcinoma (IPC) supported with immunohistochemistry markers. The case is being presented due to its rarity.

Recurrent leiomyosarcoma scrotum: An important differential in scrotal masses.

Soft tissue sarcomas of the genitourinary tract are rare. Paratesticular sarcomas are extremely rare with majority of scrotal masses localizing to the testis and being neoplastic in nature. Paratesticular leiomyosarcomas (LMSs) are located in the spermatic cord, epididymis, or scrotum. However, their location in the scrotal skin or subcutaneous tissue is extremely rare. Only 10 cases have been reported from India previously. Ours is the 11th case. A 50-year-old male presented with a recurrent scrotal mass which was painless and gradually increasing in size. Histopathology and immunohistochemistry confirmed it to be paratesticular LMS. A rare case report with the review of literature is presented.

Rhabdomyosarcoma mimicking as pleural effusion.

Rhabdomyosarcoma (RMS), a malignant neoplasm of skeletal muscle origin, is the most common soft tissue sarcoma caused by infectious disease etiology, especially in nondeveloped countries. Despite being a relatively rare cancer, it accounts for approximately 40% of all recorded soft tissue sarcomas. Alveolar RMSs are seen to occur in children, while around 80% cases occur in the first three decades of life. We present here, a case of a 12-year-old child having alveolar RMS, presenting clinically and radiologically with pleural effusion.