ZCCHC17 knockdown phenocopies Alzheimer's disease-related loss of synaptic proteins and hyperexcitability.

ZCCHC17 is a master regulator of synaptic gene expression and has recently been shown to play a role in splicing of neuronal mRNA. We previously showed that ZCCHC17 protein declines in Alzheimer's disease (AD) brain tissue before there is significant gliosis and neuronal loss, that ZCCHC17 loss partially replicates observed splicing abnormalities in AD brain tissue, and that maintenance of ZCCHC17 levels is predicted to support cognitive resilience in AD. Here, we assessed the functional consequences of reduced ZCCHC17 expression in primary cortical neuronal cultures using siRNA knockdown. Consistent with its previously identified role in synaptic gene expression, loss of ZCCHC17 led to loss of synaptic protein expression. Patch recording of neurons shows that ZCCHC17 loss significantly disrupted the excitation/inhibition balance of neurotransmission, and favored excitatory-dominant synaptic activity as measured by an increase in spontaneous excitatory post synaptic currents and action potential firing rate, and a decrease in spontaneous inhibitory post synaptic currents. These findings are consistent with the hyperexcitable phenotype seen in AD animal models and in patients. We are the first to assess the functional consequences of ZCCHC17 knockdown in neurons and conclude that ZCCHC17 loss partially phenocopies AD-related loss of synaptic proteins and hyperexcitability.

Does Hospital Operative Volume Influence the Outcomes of Patients After Heated Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis?

BACKGROUND: For some cancer operations, center volume is associated with improved patient outcomes. Whether this association is true for cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC) is unclear. Given the rapidly expanding use of CRS/HIPEC, the aim of this analysis was to determine whether a volume-outcome relationship exists for this strategy. METHODS: The Vizient Clinical Database® was queried for CRS/HIPEC cases from January 2020 through December 2022. Low-, medium-, and high-volume designations were made by sorting hospitals by case volume and creating equal tertiles based on total number of cases. Analysis was performed via one-way ANOVA with post-hoc Tukey test, as indicated. RESULTS: In the 36-month study period, 5165 cases were identified across 149 hospitals. Low- (n = 113), medium- (n = 25), and high-volume (n = 11) centers performed a median of 4, 21, and 47 cases per annum, respectively. Most cases were performed for appendiceal (39.3%) followed by gynecologic neoplasms (20.4%). Groups were similar with respect to age, gender, race, comorbidities, and histology. Low-volume centers were more likely to utilize the ICU post-operatively (59.6% vs. 40.5% vs. 36.3%; p = 0.02). No differences were observed in morbidity (9.4% vs. 7.1% vs. 9.0%, p = 0.71), mortality (0.9% vs. 0.6% vs. 0.7%, p = 0.93), length of stay (9.3 vs. 9.4 vs. 10 days, p = 0.83), 30-day readmissions (5.6% vs. 5.6% vs. 5.6%, p = 1.0), or total cost among groups. CONCLUSIONS: No association was found between CRS/HIPEC hospital volume and post-operative outcomes. These data suggest that in academic medical centers with HIPEC programs, outcomes for commonly treated cancers are not associated with hospital volume.

The Use of Intraoperative Ultrasound During Breast Conserving Surgery.

OBJECTIVES: The purpose of this study is to evaluate the utilization of intraoperative ultrasound (IOUS) for tumor localization in breast-conserving surgery and to examine its impact on margin positivity and re-excision rates. Additionally, the study seeks to identify factors contributing to surgeon utilization of IOUS. METHODS: A retrospective chart review was conducted of patients with preoperative diagnosis of breast cancer undergoing breast-conserving surgery by breast surgeons at multiple centers within a single healthcare system. Characteristics such as lesion size, palpability, histology, receptor status, and use of neoadjuvant chemotherapy were recorded. Re-excision rates were determined based on localization technique and surgeons' status of breast ultrasound certification. RESULTS: A total of 671 cases were performed, with 322 meeting study inclusion. 57 cases utilized IOUS, 250 utilized preoperative wire-guided localization (WGL), 10 used both methods and 5 cases used neither method. There was no significant difference in re-excision rates between IOUS and WGL or among the four surgeons. Ultrasound-certified surgeons were more likely to utilize IOUS, and re-excision rates trended higher for WGL, which may be clinically significant. CONCLUSION: Increasing familiarity with and utilization of IOUS during breast-conserving surgery may be clinically advantageous over traditional localization techniques. Ultrasound certification may lead to increased use of IOUS among surgeons.

Effect of the COVID-19 pandemic on surgical oncology practice-Results of an SSO survey.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic significantly affected healthcare delivery, shifting focus away from nonurgent care. The aim of this study was to examine the impact of the pandemic on the practice of surgical oncology. METHODS: A web-based survey of questions about changes in practice during the COVID-19 pandemic was approved by the Society of Surgical Oncology (SSO) Research and Executive Committees and sent by SSO to its members. RESULTS: A total of 121 SSO members completed the survey, 77.7% (94/121) of whom were based in the United States. Breast surgeons were more likely than their peers to refer patients to neoadjuvant therapy (p = 0.000171). Head and neck surgeons were more likely to refer patients to definitive nonoperative treatment (p = 0.044), while melanoma surgeons were less likely to do so (p = 0.029). In all, 79.2% (95/120) of respondents are currently using telemedicine. US surgeons were more likely to use telemedicine (p = 0.004). Surgeons believed telemedicine is useful for long-term/surveillance visits (70.2%, 80/114) but inappropriate (50.4%, 57/113) for new patient visits. CONCLUSION: COVID-19 pandemic resulted in increased use of neoadjuvant therapy, delays in operative procedures, and increased use of telemedicine. Telemedicine is perceived to be most efficacious for long-term/surveillance visits or postoperative visits.