One- and 2-year outcomes of lumbar facet arthroplasty versus spinal fusion in young (<65 years) and old (≥65 years) patients for the treatment of degenerative spondylolisthesis and stenosis.

Background: Facet arthroplasty, an alternative to lumbar fusion, offers stabilization and preserves range of motion. This subanalysis of the TOPS IDE trial (FDA #G160168) compared facet arthroplasty, using the TOPS device, with a standard single-level transforaminal lumbar interbody fusion (TLIF) in patients stratified by age (<65 and ≥65 years) with symptomatic grade 1 degenerative spondylolisthesis with moderate to severe spinal stenosis at L2-5. Methods: Patient-reported outcomes (PROMS), including Oswestry disability index (ODI), visual analog pain scales (VAS), and Zurich claudication questionnaires (ZCQ), were assessed at baseline and multiple postoperative timepoints. Radiographic evaluation of flexion/extension range of motion (ROM) occurred at baseline, 12 months, and 24 months. Data were analyzed following an intention-to-treat model. Significance was defined as p<.05. Results: About 299 patients were included (TOPS=206, TLIF=93). The groups were similar at baseline. At 2 years, the TOPS group had a greater proportion of patients report ≥15-point improvement for ODI (93.8% versus 77.1%, p=.011) and ≥20-point improvement for VAS back (84.4% versus 61.8%, p=.014). At 1 year, TOPS group had a greater proportion of patients report clinically significant improvements in all ZCQ categories (91.6% versus 78.5%, p=.012). In patients <65 years, the TOPS group had improved PROMS compared to TLIF at 2 years; however, these differences were less pronounced in patients ≥65 years old. The TOPS groups preserved more ROM at 12 (2.8° 95%CI [1.87; 3.74], p<.0001) and 24 (2.99° 95%CI [1.82; 4.15], p<.0001) months compared to TLIF. ROM was similarly preserved in patients aged <65 and ≥65. The rate of adverse events did not differ significantly between treatment groups. Conclusions: Facet arthroplasty preserves more ROM in all ages and leads to improved PROMS compared to TLIF, particularly in younger patients.

Exploring optimal microscopic keyhole access to the skull base: an anatomical evaluation of transciliary supraorbital and transpalpebral orbitofrontal craniotomy approaches.

PURPOSE: The past two decades have witnessed the rise of keyhole microscopic minimally invasive surgeries, including the transciliary supraorbital approach (TCA) and transpalpebral approach (TPA), commonly known as the transorbital approach. This study aims to elucidate the nuances, specific indications, and advantages of each approach. METHODS: A series of dissections were conducted on five formalin-fixed, alcohol-preserved cadaver heads. The TCA was performed on one side, and the TPA on the other. Virtual measurements of working angles for both approaches were recorded. Additionally, three clinical cases were presented to illustrate the practical application of the techniques. RESULTS: For TCA, the craniotomy dimensions were 1.7 cm x 2.5 cm (Cranial-Caudal (CC) x Lateral-Lateral (LL)), while for TPA, they measured 2.1 cm x 2.9 cm (CC x LL). The measurements of anterior clinoid processes (ACP) were obtained and compared between approaches. In the TCA, the mean ipsilateral ACP measurement was 62 mm (Range: 61 -63 mm), and the mean contralateral ACP measurement was 71.2 mm (Range: 70 -72 mm). In TPA, these measurements were 47.8 mm (Range: 47 -49 mm) and 62.8 mm (Range: 62 -64 mm), respectively. TCA exhibited an average cranial-caudal angle of 14.9°, while TPA demonstrated an average of 8.3°. CONCLUSION: The anterior cranial fossa was better exposed by a TCA, which also featured shorter operative times, enhanced midline visualization, and a quicker learning curve. Conversely, the middle fossa was better exposed by a TPA, making it an excellent option for middle fossa pathologies, including those in the anterior temporal lobe. After sphenoid bone wing drilling, the TPA offers superior visualization from the lateral to the medial aspect and enhances the CC angle. Additionally, the TPA reduces the risk of postoperative frontalis palsy based on anatomic landmarks. However, the TPA requires a greater cranial osteotomy, and due to unfamiliarity with eyelid anatomy, the learning curve for most neurosurgeons is lengthier for this procedure.

Description of the local hemodynamic environment in intracranial aneurysm wall subdivisions.

Intracranial aneurysms (IAs) pose severe health risks influenced by hemodynamics. This study focuses on the intricate characterization of hemodynamic conditions within the IA walls and their influence on bleb development, aiming to enhance understanding of aneurysm stability and the risk of rupture. The methods emphasized utilizing a comprehensive dataset of 359 IAs and 213 IA blebs from 268 patients to reconstruct patient-specific vascular models, analyzing blood flow using finite element methods to solve the unsteady Navier-Stokes equations, the segmentation of aneurysm wall subregions and the hemodynamic metrics wall shear stress (WSS), its metrics, and the critical points in WSS fields were computed and analyzed across different aneurysm subregions defined by saccular, streamwise, and topographical divisions. The results revealed significant variations in these metrics, correlating distinct hemodynamic environments with wall features on the aneurysm walls, such as bleb formation. Critical findings indicated that regions with low WSS and high OSI, particularly in the body and central regions of aneurysms, are prone to conditions that promote bleb formation. Conversely, areas exposed to high WSS and positive divergence, like the aneurysm neck, inflow, and outflow regions, exhibited a different but substantial risk profile for bleb development, influenced by flow impingements and convergences. These insights highlight the complexity of aneurysm behavior, suggesting that both high and low-shear environments can contribute to aneurysm pathology through distinct mechanisms.

Distribution of rupture sites and blebs on intracranial aneurysm walls suggests distinct rupture patterns in ACom and MCA aneurysms.

The mechanisms behind intracranial aneurysm formation and rupture are not fully understood, with factors such as location, patient demographics, and hemodynamics playing a role. Additionally, the significance of anatomical features like blebs in ruptures is debated. This highlights the necessity for comprehensive research that combines patient-specific risk factors with a detailed analysis of local hemodynamic characteristics at bleb and rupture sites. Our study analyzed 359 intracranial aneurysms from 268 patients, reconstructing patient-specific models for hemodynamic simulations based on 3D rotational angiographic images and intraoperative videos. We identified aneurysm subregions and delineated rupture sites, characterizing blebs and their regional overlap, employing statistical comparisons across demographics, and other risk factors. This work identifies patterns in aneurysm rupture sites, predominantly at the dome, with variations across patient demographics. Hypertensive and anterior communicating artery (ACom) aneurysms showed specific rupture patterns and bleb associations, indicating two pathways: high-flow in ACom with thin blebs at impingement sites and low-flow, oscillatory conditions in middle cerebral artery (MCA) aneurysms fostering thick blebs. Bleb characteristics varied with gender, age, and smoking, linking rupture risks to hemodynamic factors and patient profiles. These insights enhance understanding of the hemodynamic mechanisms leading to rupture events. This analysis elucidates the role of localized hemodynamics in intracranial aneurysm rupture, challenging the emphasis on location by revealing how flow variations influence stability and risk. We identify two pathways to wall failure-high-flow and low-flow conditions-highlighting the complexity of aneurysm behavior. Additionally, this research advances our knowledge of how inherent patient-specific characteristics impact these processes, which need further investigation.

The Osteogenic Peptide P-15 for Bone Regeneration: A Narrative Review of the Evidence for a Mechanism of Action.

Bone regeneration is a complex multicellular process involving the recruitment and attachment of osteoprogenitors and their subsequent differentiation into osteoblasts that deposit extracellular matrixes. There is a growing demand for synthetic bone graft materials that can be used to augment these processes to enhance the healing of bone defects resulting from trauma, disease or surgery. P-15 is a small synthetic peptide that is identical in sequence to the cell-binding domain of type I collagen and has been extensively demonstrated in vitro and in vivo to enhance the adhesion, differentiation and proliferation of stem cells involved in bone formation. These events can be categorized into three phases: attachment, activation and amplification. This narrative review summarizes the large body of preclinical research on P-15 in terms of these phases to describe the mechanism of action by which P-15 improves bone formation. Knowledge of this mechanism of action will help to inform the use of P-15 in clinical practice as well as the development of methods of delivering P-15 that optimize clinical outcomes.

c-Src-induced vascular malformations require localised matrix degradation at focal adhesions.

Endothelial cells lining the blood vessel wall communicate intricately with the surrounding extracellular matrix, translating mechanical cues into biochemical signals. Moreover, vessels require the capability to enzymatically degrade the matrix surrounding them, to facilitate vascular expansion. c-Src plays a key role in blood vessel growth, with its loss in the endothelium reducing vessel sprouting and focal adhesion signalling. Here, we show that constitutive activation of c-Src in endothelial cells results in rapid vascular expansion, operating independently of growth factor stimulation or fluid shear stress forces. This is driven by an increase in focal adhesion signalling and size, with enhancement of localised secretion of matrix metalloproteinases responsible for extracellular matrix remodelling. Inhibition of matrix metalloproteinase activity results in a robust rescue of the vascular expansion elicited by heightened c-Src activity. This supports the premise that moderating focal adhesion-related events and matrix degradation can counteract abnormal vascular expansion, with implications for pathologies driven by unusual vascular morphologies.

Outbreak of Invasive Serratia marcescens among Persons Incarcerated in a State Prison, California, USA, March 2020-December 2022.

Serratia marcescens is an environmental gram-negative bacterium that causes invasive disease in rare cases. During 2020-2022, an outbreak of 21 invasive Serratia infections occurred in a prison in California, USA. Most (95%) patients had a history of recent injection drug use (IDU). We performed whole-genome sequencing and found isolates from 8 patients and 2 pieces of IDU equipment were closely related. We also identified social interactions among patients. We recovered S. marcescens from multiple environmental samples throughout the prison, including personal containers storing Cell Block 64 (CB64), a quaternary ammonium disinfectant solution. CB64 preparation and storage conditions were suboptimal for S. marcescens disinfection. The outbreak was likely caused by contaminated CB64 and propagated by shared IDU equipment and social connections. Ensuring appropriate preparation, storage, and availability of disinfectants and enacting interventions to counteract disease spread through IDU can reduce risks for invasive Serratia infections in California prisons.

Cost of Treatment for Brain Metastases Using Data From a National Health Insurance.

Purpose: In the United States, brain metastases (BMs) affect 10% to 20% of patients with cancer, presenting a significant health care challenge and necessitating intricate, high-cost treatments. Few studies have explored the comprehensive care cost for BMs, and none have used real insurance claims data. Partnering with a northeastern health care insurer, we investigated the true costs of various brain-directed radiation methods, aiming to shed light on treatment expenses, modalities, and their efficacy. Methods and Materials: We analyzed medical claims from Highmark Health-insured patients in Pennsylvania, Delware, West Virginia, and New York diagnosed with BMs (ICD-10 code C79.31) and treated with radiation from January 1, 2020 to July 1, 2022. Costs for radiation techniques were grouped by specific current procedural terminology claim codes. We subdivided costs into technical and physician components and separated hospital from freestanding costs for some modalities. Results: From January 1, 2020 to July 1, 2022, 1048 Highmark Health members underwent treatment for BMs. Females (n = 592) significantly outnumbered males (n = 456), with an average age of 64.4 years. Each member had, on average, 5.309 claims costing $2015 per claim. Total cost totaled $10,697,749. Per-treatment analysis showed that hippocampal avoidance intensity modulated radiation therapy was the costliest treatment at $47,748, followed by stereotactic radiation therapy at $37,230, linear accelerator stereotactic radiosurgery (SRS) at $30,737, Gamma Knife SRS at $30,711, and whole-brain radiation therapy at $5225. Conclusions: Whole-brain radiation therapy was the least costly radiation technique. Similar per-treatment prices for Gamma Knife and linear accelerator SRS support their use in treating BMs. Stereotactic radiation therapy in general was costlier on a per-use basis than SRS, prompting further scrutiny on its frequent use. Hippocampal avoidance intensity modulated radiation therapy was the costliest radiation therapy on a per-use basis by a moderate amount, prompting further discussion about its comparative cost effectiveness against other radiation modalities. This study underscores the importance of multiple considerations in treating BMs, such as tumor control, survival, side effects, and costs.

Comapping Cellular Content and Extracellular Matrix with Hemodynamics in Intact Arterial Tissues Using Scanning Immunofluorescent Multiphoton Microscopy.

Deviation of blood flow from an optimal range is known to be associated with the initiation and progression of vascular pathologies. Important open questions remain about how the abnormal flow drives specific wall changes in pathologies such as cerebral aneurysms where the flow is highly heterogeneous and complex. This knowledge gap precludes the clinical use of readily available flow data to predict outcomes and improve treatment of these diseases. As both flow and the pathological wall changes are spatially heterogeneous, a crucial requirement for progress in this area is a methodology for acquiring and comapping local vascular wall biology data with local hemodynamic data. Here, we developed an imaging pipeline to address this pressing need. A protocol that employs scanning multiphoton microscopy was developed to obtain three-dimensional (3D) datasets for smooth muscle actin, collagen, and elastin in intact vascular specimens. A cluster analysis was introduced to objectively categorize the smooth muscle cells (SMC) across the vascular specimen based on SMC actin density. Finally, direct quantitative comparison of local flow and wall biology in 3D intact specimens was achieved by comapping both heterogeneous SMC data and wall thickness to patient-specific hemodynamic results.

Detection of Salmonella Typhi bacteriophages in surface waters as a scalable approach to environmental surveillance.

BACKGROUND: Environmental surveillance, using detection of Salmonella Typhi DNA, has emerged as a potentially useful tool to identify typhoid-endemic settings; however, it is relatively costly and requires molecular diagnostic capacity. We sought to determine whether S. Typhi bacteriophages are abundant in water sources in a typhoid-endemic setting, using low-cost assays. METHODOLOGY: We collected drinking and surface water samples from urban, peri-urban and rural areas in 4 regions of Nepal. We performed a double agar overlay with S. Typhi to assess the presence of bacteriophages. We isolated and tested phages against multiple strains to assess their host range. We performed whole genome sequencing of isolated phages, and generated phylogenies using conserved genes. FINDINGS: S. Typhi-specific bacteriophages were detected in 54.9% (198/361) of river and 6.3% (1/16) drinking water samples from the Kathmandu Valley and Kavrepalanchok. Water samples collected within or downstream of population-dense areas were more likely to be positive (72.6%, 193/266) than those collected upstream from population centers (5.3%, 5/95) (p=0.005). In urban Biratnagar and rural Dolakha, where typhoid incidence is low, only 6.7% (1/15, Biratnagar) and 0% (0/16, Dolakha) river water samples contained phages. All S. Typhi phages were unable to infect other Salmonella and non-Salmonella strains, nor a Vi-knockout S. Typhi strain. Representative strains from S. Typhi lineages were variably susceptible to the isolated phages. Phylogenetic analysis showed that S. Typhi phages belonged to the class Caudoviricetes and clustered in three distinct groups. CONCLUSIONS: S. Typhi bacteriophages were highly abundant in surface waters of typhoid-endemic communities but rarely detected in low typhoid burden communities. Bacteriophages recovered were specific for S. Typhi and required Vi polysaccharide for infection. Screening small volumes of water with simple, low-cost (~$2) plaque assays enables detection of S. Typhi phages and should be further evaluated as a scalable tool for typhoid environmental surveillance.

Occipital-interhemispheric transtentorial pineal mass resection.

The occipital approach for pineal tumors was first described by James Poppen in 1966. Since then, it has been widely used for accessing deep-seated tumors as it offers a wider surgical view than the supracerebellar transtentorial approach. This video demonstrates the technical nuances of the occipital transtentorial approach and the exoscopic dissection of a pineal gland tumor in a 66-year-old male. Use of the exoscope over the microscope provides certain ergonomic advantages and improves surgical workflow, as demonstrated here. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23161.

Frontotemporal craniotomy with orbital osteotomy for superior hypophyseal artery aneurysm clipping.

Superior hypophyseal artery (SHA) aneurysms are rare paraclinoid aneurysms with a mortality rate as high as 3%-6%. Surgical clipping of these aneurysms is technically challenging due to the surrounding anatomy. The large size and complicated surrounding anatomy make endovascular coiling very difficult. Here we present the case of a ruptured right SHA aneurysm. The authors present technical nuances of the clipping using an exoscope rather than a traditional microscope. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23157.

Surgical Posture with Microscopic Versus Exoscopic Visualization in Anterior Cervical Procedures.

BACKGROUND: Surgeons sustain deviated postures during procedures even with the use of loupes or an operative microscope. The surgical exoscope is a new intraoperative visualization technology designed to improve surgical ergonomics; however, no objective data exist to say that surgeon posture is significantly improved. This study aimed to quantify the difference in posture during standard anterior cervical spine procedures performed with the aid of an operative microscope versus an exoscope. METHODS: This was a prospective cohort study utilizing a posture-sensing device at the surgeon's cervicothoracic junction. The primary outcome was the proportion of time under scope spent in a deviated posture, defined as greater than 10 degrees of deviation from neutral in the x- and y-axes (flexion/extension and lateral bending) of the surgeon's upper torso. Average deviation from baseline for the x-, y-, and z-axes (flexion/extension, lateral bending, and axial rotation, respectively), as well as the percentage of operative time spent with the visualization aid was also analyzed. RESULTS: Overall, 37 anterior cervical procedures were recorded: 18 were performed with an exoscope and 19 with a microscope. Surgeons spent significantly more time in the deviated posture with the operative microscope than with the exoscope (32% vs. 8% with x-axis >10 deg, P <0.005; 20% vs. 6% with y-axis >10 deg, P <0.05). This is also reflected by the significant differences in the average deviation in the x- and y-axes, while under scope. CONCLUSIONS: Utilizing the exoscope for anterior cervical spine procedures allows surgeons to spend less time in a deviated posture.

The 5-factor modified frailty index as a prognostic factor of stereotactic radiosurgery for metastatic disease to the brain.

OBJECTIVE: Frailty, a state of increased vulnerability to adverse health outcomes, is associated with poor neurosurgical outcomes. The relationship between frailty and stereotactic radiosurgery (SRS) for brain metastases (BMs), however, has not been adequately described. In this study, the authors attempted to examine the connection between frailty and outcomes for patients receiving SRS for BMs. METHODS: A single-center retrospective cohort study was performed. The 5-factor modified frailty index (mFI-5) was used to stratify patients into pre-frail (mFI-5 score 0-1), frail (mFI-5 score 2), and severely frail (mFI-5 score ≥ 3) cohorts at the time of SRS treatment. Both overall survival (OS) and progression-free survival (PFS) were evaluated. Factors associated with OS/PFS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model. RESULTS: Two hundred three patients met the inclusion criteria and received SRS to one or more BMs. Fifty-six patients (27.6%) received SRS as an adjuvant treatment. The 12-month OS and PFS rates were 58.6% and 45.5%, respectively. One hundred twenty-six patients (62.1%) were classified as pre-frail, 58 (28.6%) as frail, and 19 (9.4%) as severely frail. Significantly less OS was demonstrated in frailer groups (frail hazard ratio [HR] 3.14, p < 0.005; severely frail HR 3.13, p < 0.005). Compared with pre-frail patients, frail patients had shorter intervals of PFS (frail HR 2.05, p < 0.005). Five patients (2.5%) had symptomatic radiation necrosis (RN) and 60 (29.6%) required repeat radiation. CONCLUSIONS: Higher frailty scores at the time of SRS treatment were predictive of shorter OS and PFS intervals.

Co-mapping Cellular Content and Extracellular Matrix with Hemodynamics in Intact Arterial Tissues Using Scanning Immunofluorescent Multiphoton Microscopy.

Deviation of blood flow from an optimal range is known to be associated with the initiation and progression of vascular pathologies. Important open questions remain about how the abnormal flow drives specific wall changes in pathologies such as cerebral aneurysms where the flow is highly heterogeneous and complex. This knowledge gap precludes the clinical use of readily available flow data to predict outcomes and improve treatment of these diseases. As both flow and the pathological wall changes are spatially heterogeneous, a crucial requirement for progress in this area is a methodology for co-mapping local data from vascular wall biology with local hemodynamic data. In this study, we developed an imaging pipeline to address this pressing need. A protocol that employs scanning multiphoton microscopy was designed to obtain 3D data sets for smooth muscle actin, collagen and elastin in intact vascular specimens. A cluster analysis was developed to objectively categorize the smooth muscle cells (SMC) across the vascular specimen based on SMC density. In the final step in this pipeline, the location specific categorization of SMC, along with wall thickness was co-mapped with patient specific hemodynamic results, enabling direct quantitative comparison of local flow and wall biology in 3D intact specimens.

Artificially Intelligent Billing in Spine Surgery: An Analysis of a Large Language Model.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study assessed the effectiveness of a popular large language model, ChatGPT-4, in predicting Current Procedural Terminology (CPT) codes from surgical operative notes. By employing a combination of prompt engineering, natural language processing (NLP), and machine learning techniques on standard operative notes, the study sought to enhance billing efficiency, optimize revenue collection, and reduce coding errors. METHODS: The model was given 3 different types of prompts for 50 surgical operative notes from 2 spine surgeons. The first trial was simply asking the model to generate CPT codes for a given OP note. The second trial included 3 OP notes and associated CPT codes to, and the third trial included a list of every possible CPT code in the dataset to prime the model. CPT codes generated by the model were compared to those generated by the billing department. Model evaluation was performed in the form of calculating the area under the ROC (AUROC), and area under precision-recall curves (AUPRC). RESULTS: The trial that involved priming ChatGPT with a list of every possible CPT code performed the best, with an AUROC of .87 and an AUPRC of .67, and an AUROC of .81 and AUPRC of .76 when examining only the most common CPT codes. CONCLUSIONS: ChatGPT-4 can aid in automating CPT billing from orthopedic surgery operative notes, driving down healthcare expenditures and enhancing billing code precision as the model evolves and fine-tuning becomes available.

Trends of Enterovirus D68 Concentrations in Wastewater, California, USA, February 2021-April 2023.

In this retrospective study, we measured enterovirus D68 (EV-D68) genomic RNA in wastewater solids longitudinally at 2 California, USA, wastewater treatment plants twice per week for 26 months. EV-D68 RNA was undetectable except when concentrations increased from mid-July to mid-December 2022, which coincided with a peak in confirmed EV-D68 cases.

Environmental sampling for typhoidal Salmonellas in household and surface waters in Nepal identifies potential transmission pathways.

INTRODUCTION: Salmonella Typhi and Salmonella Paratyphi, fecal-oral transmitted bacterium, have temporally and geographically heterogeneous pathways of transmission. Previous work in Kathmandu, Nepal implicated stone waterspouts as a dominant transmission pathway after 77% of samples tested positive for Salmonella Typhi and 70% for Salmonella Paratyphi. Due to a falling water table, these spouts no longer provide drinking water, but typhoid fever persists, and the question of the disease's dominant pathway of transmission remains unanswered. METHODS: We used environmental surveillance to detect Salmonella Typhi and Salmonella Paratyphi A DNA from potential sources of transmission. We collected 370, 1L drinking water samples from a population-based random sample of households in the Kathmandu and Kavre Districts of Nepal between February and October 2019. Between November 2019 and July 2021, we collected 380, 50mL river water samples from 19 sentinel sites on a monthly interval along the rivers leading through the Kathmandu and Kavre Districts. We processed drinking water samples using a single qPCR and processed river water samples using differential centrifugation and qPCR at 0 and after 16 hours of liquid culture enrichment. A 3-cycle threshold (Ct) decrease of Salmonella Typhi or Salmonella Paratyphi, pre- and post-enrichment, was used as evidence of growth. We also performed structured observations of human-environment interactions to understand pathways of potential exposure. RESULTS: Among 370 drinking water samples, Salmonella Typhi was detected in 7 samples (1.8%) and Salmonella Paratyphi A was detected in 4 (1.0%) samples. Among 380 river water samples, Salmonella Typhi was detected in 171 (45%) and Salmonella Paratyphi A was detected in 152 (42%) samples. Samples located upstream of the Kathmandu city center were positive for Salmonella Typhi 12% of the time while samples from locations in and downstream were positive 58% and 67% of the time respectively. Individuals were observed bathing, washing clothes, and washing vegetables in the rivers. IMPLICATIONS: These results suggest that drinking water was not the dominant pathway of transmission of Salmonella Typhi and Salmonella Paratyphi A in the Kathmandu Valley in 2019. The high degree of river water contamination and its use for washing vegetables raises the possibility that river systems represent an important source of typhoid exposure in Kathmandu.

Correlation between wastewater and COVID-19 case incidence rates in major California sewersheds across three variant periods.

Monitoring for COVID-19 through wastewater has been used for adjunctive public health surveillance, with SARS-CoV-2 viral concentrations in wastewater correlating with incident cases in the same sewershed. However, the generalizability of these findings across sewersheds, laboratory methods, and time periods with changing variants and underlying population immunity has not been well described. The California Department of Public Health partnered with six wastewater treatment plants starting in January 2021 to monitor wastewater for SARS-CoV-2, with analyses performed at four laboratories. Using reported PCR-confirmed COVID-19 cases within each sewershed, the relationship between case incidence rates and wastewater concentrations collected over 14 months was evaluated using Spearman's correlation and linear regression. Strong correlations were observed when wastewater concentrations and incidence rates were averaged (10- and 7-day moving window for wastewater and cases, respectively, ρ = 0.73-0.98 for N1 gene target). Correlations remained strong across three time periods with distinct circulating variants and vaccination rates (winter 2020-2021/Alpha, summer 2021/Delta, and winter 2021-2022/Omicron). Linear regression revealed that slopes of associations varied by the dominant variant of concern, sewershed, and laboratory (ß = 0.45-1.94). These findings support wastewater surveillance as an adjunctive public health tool to monitor SARS-CoV-2 community trends.