Multicenter Registry of Adenomas of the Pituitary and Related Disorders: Initial Description of Cushing Disease Cohort, Surgical Outcomes, and Surgeon Characteristics.

BACKGROUND AND OBJECTIVES: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies. METHODS: Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission. RESULTS: By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years. CONCLUSION: This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD.

Prognostic value of DNA methylation subclassification, aneuploidy, and CDKN2A/B homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas.

INTRODUCTION: IDH mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System WHO introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma. METHODS: We analyzed 98 IDH mutant astrocytomas diagnosed at NYU Langone Health between 2014 and 2022. We reviewed DNA methylation subclass, CDKN2A/B homozygous deletion, and ploidy and correlated molecular biomarkers with histological grade, progression free (PFS), and overall (OS) survival. Findings were confirmed using two independent validation cohorts. RESULTS: There was no significant difference in OS or PFS when stratified by histologic WHO grade alone, copy number complexity, or extent of resection. OS was significantly different when patients were stratified either by CDKN2A/B homozygous deletion or by DNA methylation subclass (p-value=0.0286 and 0.0016, respectively). None of the molecular biomarkers were associated with significantly better progression free survival (PFS), although DNA methylation classification showed a trend (p-value= 0.0534). CONCLUSIONS: The current WHO recognized grading criteria for IDH mutant astrocytomas show limited prognostic value. Stratification based on DNA methylation shows superior prognostic value for OS.

Percutaneous Juxtapedicular Cement Salvage of Failed Spinal Instrumentation? Institutional Experience and Cadaveric Biomechanical Study.

BACKGROUND AND OBJECTIVES: Instrumented spinal fusion constructs sometimes fail because of fatigue loading, frequently necessitating open revision surgery. Favorable outcomes after percutaneous juxtapedicular cement salvage (perc-cement salvage) of failing instrumentation have been described; however, this approach is not widely known among spine surgeons , and its biomechanical properties have not been evaluated. We report our institutional experience with perc-cement salvage and investigate the relative biomechanical strength of this technique as compared with 3 other common open revision techniques. METHODS: A retrospective chart review of patients who underwent perc-cement salvage was conducted. Biomechanical characterization of revision techniques was performed in a cadaveric model of critical pedicle screw failure. Three revision cohorts involved removal and replacement of hardware: (1) screw upsizing, (2) vertebroplasty, and (3) fenestrated screw with cement augmentation. These were compared with a cohort with perc-cement salvage performed using a juxtapedicular trajectory with the failed primary screw remaining engaged in the vertebral body. RESULTS: Ten patients underwent perc-cement salvage from 2018 to 2022 to address screw haloing and/or endplate fracture threatening construct integrity. Pain palliation was reported by 8/10 patients. Open revision surgery was required in 4/10 patients, an average of 8.9 months after the salvage procedure (range 6.2-14.7 months). Only one revision was due to progressive hardware dislodgement. The remainder avoided open revision surgery through an average of 1.9 years of follow-up. In the cadaveric study, there were no significant differences in pedicle screw pullout strength among any of the revision cohorts. CONCLUSION: Perc-cement salvage of failing instrumentation is reasonably efficacious. The technique is biomechanically noninferior to other revision strategies that require open surgery for removal and replacement of hardware. Open revision surgery may be avoided by perc-cement salvage in select cases.

Development and implementation of an Enhanced Recovery After Cranial Surgery pathway following supratentorial tumor resection at a tertiary care center.

OBJECTIVE: Controlling length of stay (LOS) reduces rates of nosocomial infections and falls, facilitates earlier return to daily activities, and decreases strain on the healthcare system. Complications following supratentorial tumor resection present early in the postoperative period, thereby enhancing the prospect of safe, early discharge. Here, the authors describe their initial experience with the development and implementation of an Enhanced Recovery After Cranial Surgery (ERACS) pathway following resection of supratentorial tumors in select patients. METHODS: This was a nonrandomized, ambispective quality improvement study of patients undergoing elective craniotomy for supratentorial tumor resection at New York University Langone Health between November 17, 2020, and May 19, 2022. Eligible patients were prospectively enrolled in either the ERACS pathway or the standard pathway. These prospective cohorts were compared to a retrospective cohort of patients who met eligibility criteria for the pathway. Patients in the ERACS pathway cohort were targeted for discharge on postoperative day 2. The primary outcome metric was hospital LOS. Secondary outcome metrics included duration of intensive care unit (ICU) care and rates of 30-day emergency department visits, readmissions, and complications. RESULTS: Over the study period, 188 of 317 patients (59.3%) who underwent supratentorial tumor resection met inclusion criteria for ERACS pathway enrollment. Sixty-three patients were enrolled in the ERACS pathway, and 125 patients completed the standard pathway. The historical cohort consisted of 332 patients who would have been eligible for ERACS enrollment. Patients in the ERACS pathway cohort had a median LOS of 1.93 days compared with 2.92 and 2.88 days for patients in the standard pathway and historical cohort, respectively (p < 0.001). There was a significant reduction in ICU utilization in ERACS pathway patients (16.0 ± 6.53 vs 29.5 ± 53.0 vs 21.8 ± 18.2 hours, p = 0.005). There were no differences in the rates of 30-day emergency department visits (12.7% vs 9.6% vs 10.9%, p = 0.809) and readmissions (4.8% vs 4.0% vs 7.8%, p = 0.279) between groups. CONCLUSIONS: Patients in the ERACS pathway cohort experienced reduced LOS and ICU utilization, with similar rates of adverse outcomes compared to standard pathway patients. The authors' initial experience suggests that an accelerated recovery pathway can be safely implemented following supratentorial tumor resection in select patients.

Health Care Disparities in Transsphenoidal Surgery for Pituitary Tumors: An Experience from Neighboring Urban Public and Private Hospitals.

Objectives Few studies have assessed the role of socioeconomic health care disparities in skull base pathologies. We compared the clinical history and outcomes of pituitary tumors at private and public hospitals to delineate whether health care disparities exist in pituitary tumor surgery. Methods We reviewed the records of patients who underwent transsphenoidal pituitary tumor resection at NYU Langone Health and Bellevue Hospital. Seventy-two consecutive patients were identified from each hospital. The primary outcome was time-to-surgery from initial recommendation. Secondary outcomes included postoperative diabetes insipidus, cerebrospinal fluid (CSF) leak, and gross total resection. Results Of 144 patients, 23 (32%) public hospital patients and 24 (33%) private hospital patients had functional adenomas ( p = 0.29). Mean ages for public and private hospital patients were 46.5 and 51.1 years, respectively ( p = 0.06). Private hospital patients more often identified as white ( p < 0.001), spoke English ( p < 0.001), and had private insurance ( p < 0.001). The average time-to-surgery for public and private hospital patients were 46.2 and 34.8 days, respectively ( p = 0.39). No statistically significant differences were found in symptom duration, tumor size, reoperation, CSF leak, or postoperative length of stay; however, public hospital patients more frequently required emergency surgery ( p = 0.03), developed transient diabetes insipidus ( p = 0.02), and underwent subtotal resection ( p = 0.04). Conclusion Significant socioeconomic differences exist among patients undergoing pituitary surgery at our institution's hospitals. Public hospital patients more often required emergency surgery, developed diabetes insipidus, and underwent subtotal tumor resection. Identifying these differences is an imperative initial step in improving the care of our patients.

Clinical utility of whole-genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors-A prospective study and guidelines for clinical testing.

Background: Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. Methods: We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. Results: Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. Conclusions: DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

Developing an Automated Registry (Autoregistry) of Spine Surgery Using Natural Language Processing and Health System Scale Databases.

BACKGROUND AND OBJECTIVES: Clinical registries are critical for modern surgery and underpin outcomes research, device monitoring, and trial development. However, existing approaches to registry construction are labor-intensive, costly, and prone to manual error. Natural language processing techniques combined with electronic health record (EHR) data sets can theoretically automate the construction and maintenance of registries. Our aim was to automate the generation of a spine surgery registry at an academic medical center using regular expression (regex) classifiers developed by neurosurgeons to combine domain expertise with interpretable algorithms. METHODS: We used a Hadoop data lake consisting of all the information generated by an academic medical center. Using this database and structured query language queries, we retrieved every operative note written in the department of neurosurgery since our transition to EHR. Notes were parsed using regex classifiers and compared with a random subset of 100 manually reviewed notes. RESULTS: A total of 31 502 operative cases were downloaded and processed using regex classifiers. The codebase required 5 days of development, 3 weeks of validation, and less than 1 hour for the software to generate the autoregistry. Regex classifiers had an average accuracy of 98.86% at identifying both spinal procedures and the relevant vertebral levels, and it correctly identified the entire list of defined surgical procedures in 89% of patients. We were able to identify patients who required additional operations within 30 days to monitor outcomes and quality metrics. CONCLUSION: This study demonstrates the feasibility of automatically generating a spine registry using the EHR and an interpretable, customizable natural language processing algorithm which may reduce pitfalls associated with manual registry development and facilitate rapid clinical research.

Digital Biomarkers and the Evolution of Spine Care Outcomes Measures: Smartphones and Wearables.

Over the past generation, outcome measures in spine care have evolved from a reliance on clinician-reported assessment toward recognizing the importance of the patient's perspective and the wide incorporation of patient-reported outcomes (PROs). While patient-reported outcomes are now considered an integral component of outcomes assessments, they cannot wholly capture the state of a patient's functionality. There is a clear need for quantitative and objective patient-centered outcome measures. The pervasiveness of smartphones and wearable devices in modern society, which passively collect data related to health, has ushered in a new era of spine care outcome measurement. The patterns emerging from these data, so-called "digital biomarkers," can accurately describe characteristics of a patient's health, disease, or recovery state. Broadly, the spine care community has thus far concentrated on digital biomarkers related to mobility, although the researcher's toolkit is anticipated to expand in concert with advancements in technology. In this review of the nascent literature, we describe the evolution of spine care outcome measurements, outline how digital biomarkers can supplement current clinician-driven and patient-driven measures, appraise the present and future of the field in the modern era, as well as discuss present limitations and areas for further study, with a focus on smartphones (see Supplemental Digital Content , http://links.lww.com/NEU/D809 , for a similar appraisal of wearable devices).

Discontinuation of Postoperative Prophylactic Antibiotics for Endoscopic Endonasal Skull Base Surgery.

Background Postoperative prophylactic antibiotic usage for endoscopic skull base surgery varies based on the institution as evidence-based guidelines are lacking. The purpose of this study is to determine whether discontinuing postoperative prophylactic antibiotics in endoscopic endonasal cases led to a difference in central nervous system (CNS) infections, multi-drug resistant organism (MDRO) infections, or other postoperative infections. Methods This quality improvement study compared outcomes between a retrospective cohort (from September 2013 to March 2019) and a prospective cohort (April 2019 to June 2019) after adopting a protocol to discontinue prophylactic postoperative antibiotics in patients who underwent endoscopic endonasal approaches (EEAs). Our primary end points of the study included the presence of postoperative CNS infection, Clostridium difficile ( C. diff ), and MDRO infections. Results A total of 388 patients were analyzed, 313 in the pre-protocol group and 75 in the post-protocol group. There were similar rates of intraoperative cerebrospinal fluid leak (56.9 vs. 61.3%, p = 0.946). There was a statistically significant decrease in the proportion of patients receiving IV antibiotics during their postoperative course ( p = 0.001) and those discharged on antibiotics ( p = 0.001). There was no significant increase in the rate of CNS infections in the post-protocol group despite the discontinuation of postoperative antibiotics (3.5 vs. 2.7%, p = 0.714). There was no statistically significant difference in postoperative C. diff (0 vs. 0%, p = 0.488) or development of MDRO infections (0.3 vs 0%, p = 0.624). Conclusion Discontinuation of postoperative antibiotics after EEA at our institution did not change the frequency of CNS infections. It appears that discontinuation of antibiotics after EEA is safe.

Detection of Cerebrospinal Fluid Leaks Using the Endoscopic Fluorescein Test in the Postoperative Period following Pituitary and Ventral Skull Base Surgery.

Objective Diagnosis of cerebrospinal fluid (CSF) leaks is sometimes challenging in the postoperative period following pituitary and ventral skull base surgery. Intrathecal fluorescein (ITF) may be useful in this setting. Design Retrospective chart review. Setting Tertiary care center. Methods and Participants All patients who underwent pituitary and ventral skull base surgery performed by a single rhinologist between January 2017 and March 2020 were included. There were 103 patients identified. Eighteen patients received 20 ITF injections due to clinical suspicion for CSF leak during the postoperative period without florid CSF rhinorrhea on clinical exam. Computed tomography scans with new or increasing intracranial air and intraoperative findings were used to confirm CSF leaks. Clinical courses were reviewed for at least 6 months after initial concern for leak as the final determinate of CSF leak. Main Outcome Measures Specificity and safety of ITF. Results Eleven (61%) ITF patients were female and 7 (39%) were male. Average patient age was 52.50 ± 11.89. There were six patients with confirmed postoperative CSF leaks, 3 of whom had evaluations with ITF. ITF use resulted in 2 true positives, 1 false negative, 17 true negatives, and 0 false positives. ITF sensitivity was 67%, specificity was 100%, and positive and negative predictive values were 100 and 94.4%, respectively. There were no adverse effects from ITF use. Conclusions Existing modalities for detecting postoperative CSF leaks suffer from suboptimal sensitivity and specificity, delayed result reporting, or limited availability. ITF represents a specific and safe test with potential utility in the postoperative setting.

Up-front single-session radiosurgery for large brain metastases-volumetric responses and outcomes.

BACKGROUND: Patients presenting with large brain metastases (LBM) pose a management challenge to the multidisciplinary neuro-oncologic team. Treatment options include surgery, whole-brain or large-field radiation therapy (WBRT), stereotactic radiosurgery (SRS), or a combination of these. OBJECTIVE: To determine if corticosteroid therapy followed by SRS allows for efficient minimally invasive care in patients with LBMs not compromised by mass effect. METHODS: We analyzed the change in tumor volume to determine the efficacy of single-session SRS in the treatment of LBM in comparison to other treatment modalities. Twenty-nine patients with systemic cancer and brain metastasis (≥ 2.7 cm in greatest diameter) who underwent single-session SRS were included. RESULTS: Among 29 patients, 69% of patients had either lung, melanoma, or breast cancer. The median initial tumor size (maximal diameter) was 32 mm (range 28-43), and the median initial tumor volume was 9.56 cm3 (range 1.56-25.31). The median margin dose was 16 Gy (range 12-18). The average percent decrease in tumor volume compared to pre-SRS volume was 55% on imaging at 1-2 months, 58% at 3-5 months, 64% at 6-8 months, and 57% at > 8 months. There were no adverse events immediately following SRS. Median corticosteroid use after SRS was 21 days. Median survival after radiosurgery was 15 months. CONCLUSION: Initial high-dose corticosteroid therapy followed by prompt single-stage SRS is a safe and efficacious method to manage patients with LBMs (defined as ≥ 2.7 cm).

The Cost Effectiveness of Implementation of a Postoperative Endocrinopathy Management Protocol after Resection of Pituitary Adenomas.

Purpose After developing a protocol for evaluating, diagnosing, and treating postoperative endocrinopathy both during the hospitalization and during the immediate discharge period following resection of pituitary adenomas, we sought to assess the impact of this protocol on quality outcomes. Methods An IRB-exempt, quality improvement initiated, Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective comparison of a pre-and-post-protocol cohort of all patients undergoing endoscopic endonasal resection of pituitary adenomas at NYU Langone Medical Center from January 2013 to December 2018. Demographic characteristics of the patients and their tumors with their postoperative outcomes were recorded. Quality outcomes regarding number of laboratory studies sent, rate of diabetes insipidus, length of stay, and readmission rate were also recorded. Statistical analysis was performed between the pre- and post-protocol groups. Results There was a significant reduction in laboratory studies sent per patient (55.66 vs. 18.82, p <0.001). This corresponded with an overall cost reduction in laboratory studies of $255.95 per patient. There was a decrease in the overall number of patients treated with DDAVP (21.4% in the pre-protocol group vs. 8.9% in the post-protocol group, p = 0.04). All post-protocol patients requiring DDAVP at discharge were identified by 48 hours. There was no significant change in length of stay or need for hydrocortisone supplementation postoperatively between the two groups. Length of stay was driven mostly by need for reoperation during initial hospitalization. There was no significant change in the rate of 30-day readmission. Conclusion Implementation of a postoperative management protocol results in a more efficient diagnosis and management of endocrinopathy after pituitary adenoma surgery which translates to decreased cost.

The Value of Intraoperative Magnetic Resonance Imaging in Endoscopic Endonasal Resection of Pituitary Adenoma.

Background Intraoperative magnetic resonance images (iMRIs) have been variably adopted by some centers to help increase the rate of gross total resection (GTR) of pituitary adenomas. In this comparative study, we report our institution's experience with using iMRIs for endoscopic endonasal approach (EEA) pituitary adenoma resection to better elucidate its role and potential value for pituitary surgery. Methods All adult patients who underwent EEA for a pituitary adenoma from January 2013 to September 2021 were retrospectively reviewed. GTR was defined as no residual tumor or recurrence on postoperative imaging within 6 months. Univariate analysis followed by multivariate analysis was performed with GTR as the categorical endpoint. To measure the independent effect of iMRI on GTR, propensity score matching was then performed. Results A total of 351 pituitary adenoma patients who underwent EEA were identified. The mean age was 51.2 (range: 18-90) years and 196 (55.8%) patients were female. iMRI was utilized in 87 (24.8%) cases. The overall rate of GTR was 69.2%. On multivariate analysis, low Knosp grade, low tumor volume, and the use of iMRI were predictive of GTR. There was no difference in the need for desmopressin or hydrocortisone at 90 days postoperatively. Conclusion At our institution, we report a significant absolute increase in GTR rates of 16.4% for patients undergoing an iMRI. Among iMRI patients who did not have GTR, the majority of residuals were intentionally left behind after being deemed too risky to pursue. Overall, this study suggests the high value that iMRI adds to endoscopic pituitary adenoma surgery.

Comparing Rates of Postoperative Meningitis After Endoscopic Endonasal Procedures Based on Methicillin-Resistant Staphylococcus aureus/Methicillin-Sensitive Staphylococcus aureus Colonization and Antibiotic Prophylaxis.

BACKGROUND: Endoscopic endonasal approach (EEA) procedures are inherently contaminated due to direct access through the nasopharyngeal mucosa. The reported rate of postoperative meningitis in EEA procedures is 0.7%-3%. A variety of methods exist to minimize the risk of meningitis with antibiotic prophylaxis, although their value is not completely understood. This study investigated whether there is a difference in rates of postoperative meningitis based on Staphylococcus aureus colonization and use of preoperative antibiotic prophylaxis. METHODS: All adult patients who underwent EEA resection at our institution from 2013 to 2021 were retrospectively reviewed. Patients with preoperative cerebrospinal fluid infections were excluded. Data including recent preoperative infections, preoperative colonization status, antibiotic administration, and postoperative outcomes were recorded for each patient. RESULTS: Of 483 patients identified (mean age, 51 years; range, 18-90 years; 274 [56.7%] female), 80 (16.6%) had a positive preoperative methicillin-resistant Staphylococcus aureus (MRSA)/methicillin-sensitive Staphylococcus aureus (MSSA) screening swab. Twenty-one (26.3%) colonized patients were treated with preoperative decolonizing antibiotics. Within 30 days of surgery, 13 (2.7%) patients developed culture-positive meningitis. There was no significant difference in meningitis rates based on MRSA/MSSA colonization status. Among colonized patients, there was no significant difference in rates of MRSA/MSSA meningitis based on preoperative antibiotic decolonization. CONCLUSIONS: Postoperative rates of meningitis after EEA surgery were not significantly changed based on MRSA/MSSA colonization status of the patient or preoperative decolonization. The utility of preoperative testing of MRSA/MSSA status and antibiotics for decolonization to prevent postoperative meningitis should be further investigated.

Sinonasal Undifferentiated Carcinoma with Failed Response to Induction Chemotherapy.

Sinonasal undifferentiated carcinoma (SNUC) is a rapidly growing malignancy with a propensity for extensive local invasion. Multimodal therapy, including surgery, radiotherapy, and chemotherapy, is the standard approach to treatment, but the optimal sequence and combination of these modalities are uncertain. Induction chemotherapy is being increasingly utilized based on recent reports that show better outcomes for patients who respond to chemotherapy and the ability to determine further course of treatment. We present a unique case of a patient with locally advanced SNUC that did not respond to induction chemotherapy and a review of the available literature relating to the management of this rare malignancy.

Skull Base Aerosol Generating Cases Amidst the COVID-19 Pandemic: An Experience from the Epicenter.

Soon after the World Health Organization declared the severe acute respiratory syndrome coronavirus 2 a global health emergency on January 30, 2020, New York City was plagued by the virus and its health system and economy pushed to their limits. The majority of the limited neurosurgical data in relation to COVID-19 is anecdotal and the higher theoretical risk of transmission of the virus among skull base aerosol generating (SBAG) cases has not been investigated or discussed in a neurosurgical population. We discuss a series of 13 patients who underwent 15 SBAG surgical procedures during the peak of COVID-19 in our hospital system and the protocols use perioperatively for their procedures. Our data support that with proper preoperative testing, a well-delineated surgical algorithm, and appropriate personal protective equipment, emergent/urgent cases can be done safely in hospitals that are currently experiencing high volumes of COVID-19 cases as we did in March to May of 2020.