Citations

Abstract Background: In breast cancer, the spatial relationship between immune and tumor cells is increasingly recognized as critical in determining the efficacy of neoadjuvant therapy (NAT). This study investigated how the distribution of immune cells, particularly CD8+ T cells, relative to tumor cells affects treatment outcomes. Methods: Biopsies from 104 breast cancer patients were examined, both pre- and post-NAT, using multiplex immunohistochemistry (mIHC). This study focused on the density and distribution of CD8+ T cells, CD68+ macrophages, FoxP3+ regulatory T cells, and other immune markers. Results: The spatial proximity of CD8+ T cells within 20 µm of cancer cells (N20-CD8+T) was strongly correlated with improved clinical outcomes across diverse tumor subtypes and NAT regimens. A significant post-NAT decrease in CD4+, CD68+, and FoxP3+ cells highlights notable shifts in the tumor immune landscape. A noteworthy finding was the positive correlation between CXCL9 expression and N20-CD8+T cells, suggesting a mechanism for immune cell recruitment and interaction within the tumor microenvironment. These results highlight the complex interplay among NAT, immune cell modifications, and patient outcomes. Conclusions: This study revealed that the proximity of N20-CD8+ T cells to tumor cells is consistently associated with favorable NAT outcomes, transcending tumor subtypes, and treatment differences. This highlights the potential of immune cell dynamics, especially CD8+ T cells, as predictive biomarkers for therapeutic responses in breast cancer, underscoring their vital role in tumor immunity.

Abstract Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) has not been adequately addressed. This study sought to test the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 year). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) of maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after the cessation of exercise and central and peripheral hemodynamics were assessed. MSNA was directly recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+ 15 ± 5 burst/100 bpm) and ExPECO 40% (+ 22 ± 4 burst/100 bpm) and returned to pre-HG levels during ExCON trials. Vasodilation, assessed by the change in leg vascular conductance during PLM, was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate that elevated MSNA attenuates the vasodilatory response to PLM and that the magnitude of reduction in vasodilation during PLM is graded in relation to the degree of sympathoexcitation.

Objective To describe the rare process of osteolytic labyrinthitis, previously referred to as labyrinthine sequestrum, which involves progressive obliteration of the bony and membranous labyrinth with eventual supplantation with soft tissue and, in some cases, bony sequestrum. Patients Three patients with diverse presentations of osteolytic labyrinthitis from two tertiary care academic medical centers. Intervention(s) Case series report analyzing the relevant clinical, radiologic, pathologic, and surgical data on our patients with osteolytic labyrinthitis and comparing these index cases to the existing literature. Main Outcome Measure(s) We describe the varying image findings seen in osteolytic labyrinthitis on computed tomography and magnetic resonance imaging. Also, we report successful surgical intervention and hearing rehabilitation with cochlear implantation in patients with osteolytic labyrinthitis. Results Our three patients presented with profound sudden sensorineural hearing loss and vertigo consistent with labyrinthitis. None of the three patients had a history of chronic otitis media. Imaging workup revealed varying degrees of erosion to the otic capsule bone demonstrating the spectrum of disease seen in osteolytic labyrinthitis. Although two cases showed osteolytic changes to the semicircular canals and vestibule, the first case revealed frank bony sequestrum within the obliterated labyrinth. The three cases were taken for surgical debridement and cochlear implantation. Conclusions We propose the new term, osteolytic labyrinthitis—previously referred to as labyrinthine sequestrum—to describe the rare spectrum of disease characterized by destruction of the osseous and membranous labyrinth and potential supplantation with bony sequestrum. Cochlear implantation is a viable option in selected patients with osteolytic labyrinthitis.

Objective To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure. Study Design Multi-institutional historical cohort study. Setting Five tertiary care referral centers. Patients Adults ≥18 years old with sporadic VS. Intervention Primary and repeat treatment with SRS. Main Outcome Measure Microsurgery-free survival after repeat SRS. Results Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5–18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2–5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90–100%, 24), 84% (71–100%, 13), and 68% (48–96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery. Conclusion Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.

Objective To examine patient preference after stapedotomy versus cochlear implantation in a unique case of a patient with symmetrical profound mixed hearing loss and similar postoperative speech perception improvement. Patients An adult patient with bilateral symmetrical far advanced otosclerosis, with profound mixed hearing loss. Intervention Stapedotomy in the left ear, cochlear implantation in the right ear. Main Outcome Measure Performance on behavioral audiometry, and subjective report of hearing and intervention preference. Results A patient successfully underwent left stapedotomy and subsequent cochlear implantation on the right side, per patient preference. Preoperative audiometric characteristics were similar between ears (pure-tone average [PTA] [R: 114; L: 113 dB]; word recognition score [WRS]: 22%). Postprocedural audiometry demonstrated significant improvement after stapedotomy (PTA: 59 dB, WRS: 75%) and from cochlear implant (PTA: 20 dB, WRS: 60%). The patient subjectively reported a preference for the cochlear implant ear despite having substantial gains from stapedotomy. A nuanced discussion highlighting potentially overlooked benefits of cochlear implants in far advanced otosclerosis is conducted. Conclusion In comparison with stapedotomy and hearing aids, cochlear implantation generally permits greater access to sound among patients with far advanced otosclerosis. Though the cochlear implant literature mainly focuses on speech perception outcomes, an underappreciated benefit of cochlear implantation is the high likelihood of achieving “normal” sound levels across the audiogram.