Forecasting Hepatitis C Virus Status for Children in the United States: A Modeling Study.

BACKGROUND: Virtually all cases of hepatitis C virus (HCV) infection in children in the United States occur through vertical transmission, but it is unknown how many children are infected. Cases of maternal HCV infection have increased in the United States, which may increase the number of children vertically infected with HCV. Infection has long-term consequences for a child's health, but treatment options are now available for children ≥3 years old. Reducing HCV infections in adults could decrease HCV infections in children. METHODS: Using a stochastic compartmental model, we forecasted incidence of HCV infections in children in the United States from 2022 through 2027. The model considered vertical transmission to children <13 years old and horizontal transmission among individuals 13-49 years old. We obtained model parameters and initial conditions from the literature and the Centers for Disease Control and Prevention's 2021 Viral Hepatitis Surveillance Report. RESULTS: Model simulations assuming direct-acting antiviral treatment for children forecasted that the number of acutely infected children would decrease slightly and the number of chronically infected children would decrease even more. Alone, treatment and early screening in individuals 13-49 years old reduced the number of forecasted cases in children and, together, these policy interventions were even more effective. CONCLUSIONS: Based on our simulations, acute and chronic cases of HCV infection are remaining constant or slightly decreasing in the United States. Improving early screening and increasing access to treatment in adults may be an effective strategy for reducing the number of HCV infected children in the United States.

The Pancreatic Cancer Early Detection (PRECEDE) Study is a Global Effort to Drive Early Detection: Baseline Imaging Findings in High-Risk Individuals.

BACKGROUND: Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. METHODS: PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. RESULTS: A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. CONCLUSIONS: PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.

Pancreatic Cysts Greater Than 1 cm Are Associated With an Increased Risk for Developing Pancreatic Cancer in Individuals From Pancreatic-Cancer Prone Kindreds Undergoing Surveillance.

BACKGROUND: The International Cancer of the Pancreas Screening Consortium recommended annual imaging for individuals at increased risk for developing a pancreatic ductal adenocarcinoma (PDAC) who did not have concerning pancreatic findings or a cyst <3 cm without worrisome features. We aimed to determine if 3-cm cyst size accurately predicted advanced precursor lesions in high-risk individuals undergoing surveillance. METHODS: Imaging for high-risk individuals (HRIs) undergoing PDAC surveillance from 2007 to 2021 was reviewed and pancreatic abnormalities were recorded including dominant cyst size and number of cysts. Subjects were excluded if they had the following: (1) no follow-up imaging after baseline, (2) solid lesion at baseline, or (3) development of solid lesion without having cyst on prior imaging. RESULTS: Five of the 77 HRIs found to have a cystic lesion on surveillance developed a PDAC: 3 with cystic lesion >1 cm as compared with only 2 of 67 HRIs with cystic lesions <1 cm (P < 0.05). None of these cysts developed worrisome findings and 4/5 PDACs did not arise from visualized cystic precursor lesion. CONCLUSIONS: Patients with a cyst ≥1 cm were at increased risk for developing PDAC compared with patients with cyst <1 cm. Pancreatic ductal adenocarcinoma usually did not arise from a recognized cystic lesion.

Trends in Indications and Contraindications for Cervical Disk Arthroplasty from 2009 to 2019.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: Assess trends of indications and contraindications for the use of Cervical Disk Arthroplasty (CDA). SUMMARY OF BACKGROUND DATA: As spine surgeons become more familiar with CDA, there have been expansions in indications. METHODS: The Medicare Provider Analysis and Review Limited Data Sets for 2009, 2014, and 2019 were utilized. Patients undergoing elective CDA were included. Diagnosis for index surgery and "contraindications" as defined by original CDA Investigative Device Exemption (IDE) criteria were assessed. Variables were identified by the International Classification of Diseases (ICD)-9 or ICD-10 diagnosis and procedural codes. RESULTS: A total of 1067 elective CDA patients were included. There were 230 patients in 2009, 300 patients in 2014, and 537 patients in 2019. The proportion of patients aged >65 increased from 35% to 51% (P<0.001). Incidence of CDA for radiculopathy increased from 57% to 69% (P<0.001), myelopathy increased from 23% to 78% (P<0.001), and spondylosis without radiculopathy or myelopathy decreased from 19% to 3% (P<0.001). There were increased incidences of ankylosing spondylitis (0.4% to 2.8%, P=0.007), long-term steroid use (1% to 2%, P=0.039), morbid obesity (2% to 6%, P=0.019), and osteoporosis (1% to 5%, P=0.014). The incidence of hybrid CDA and anterior cervical discectomy and fusion (ACDF) decreased from 28% to 23% (P=0.007). CONCLUSION: From 2009 to 2019, the number of CDA performed in older patients increased. An increase in the use of CDA for the treatment of myelopathy and radiculopathy and a decrease in the treatment of isolated cervical spondylosis was observed. The proportion of CDA performed in patients with original IDE trial "contraindications" increased. Further research into the efficacy of CDA for patients with contraindications is warranted.

Resource Utilization following Anterior Versus Posterior Cervical Decompression and Fusion for Acute Central Cord Syndrome.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The purpose of this study is to compare the impact of anterior cervical decompression and fusion (ACDF) versus posterior cervical decompression and fusion (PCDF) for the treatment of acute traumatic central cord syndrome (CCS) on hospital episodes of care in terms of (1) cost, (2) length of hospital stay, and (3) discharge destination. SUMMARY OF BACKGROUND DATA: Acute traumatic CCS is the most common form of spinal cord injury in the United States. CCS is commonly treated with surgical decompression and fusion. Hospital resource utilization based on surgical approach remains unclear. METHODS: Patients undergoing ACDF and PCDF for acute traumatic CCS were identified using the 2019 Medicare Provider Analysis and Review Limited Data Set and Centers for Medicare and Medicaid Services 2019 Impact File. Multivariate models for hospital cost of care, length of stay, and discharge destination were performed, controlling for confounders. Subanalysis of accommodation and revenue center cost drivers was performed. RESULTS: There were 1474 cases that met inclusion criteria: 673 ACDF (45.7%) and 801 PCDF (54.3%). ACDF was independently associated with a decreased cost of $9802 (P<0.001) and a 59.2% decreased risk of discharge to nonhome destinations (adjusted odds ratio: 0.408, P<0.001). The difference in length of stay was not statistically significant. On subanalysis of cost drivers, ACDF was associated with decreased charges ($55,736, P<0.001) compared with PCDF, the largest drivers being the intensive care unit ($15,873, 28% of total charges, P<0.001) and medical/surgical supply charges ($19,651, 35% of total charges, P<0.001). CONCLUSIONS: For treatment of acute traumatic CCS, ACDF was associated with almost $10,000 less expensive cost of care and a 60% decreased risk of discharge to nonhome destination compared with PCDF. The largest cost drivers appear to be ICU and medical/surgical-related. These findings may inform value-based decisions regarding the treatment of acute traumatic CCS. However, injury and patient clinical factors should always be prioritized in surgical decision-making, and increased granularity in reimbursement policies is needed to prevent financial disincentives in the treatment of patients with CCS better addressed with posterior approach-surgery.

Fluorine in Complex Alumino-Boro-Silicate Glasses: Insight into Chemical Environment and Structure.

Fluorine incorporation into silicate glasses is important for technical fields as diverse as geophysics, extractive metallurgy, reconstructive dentistry, optical devices, and radioactive waste management. In this study, we explored the structural role of fluorine in alkaline alumino-borosilicate glass, with increasing amounts of fluorine up to 25 mol % F while maintaining the glass composition. Glasses were characterized by X-ray diffraction (XRD), 27Al and 19F magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy, and electron probe microanalysis. Results showed that essentially all F was retained; however, between 12 and 15 mol % F (∼3.6 and 4.5 wt % F), excess fluorine partitions to CaF2 and then NaF and Na-Al-F crystalline phases. Even prior to crystallization, there exist five distinct F sites, three of which evolve into crystalline phases. The two persistent glassy sites likely involve [4]Al-F-Ca/Na local structures. We propose a general understanding of the expected chemical shift of 19F NMR in systems containing Al, Ca, and Na.

Pressure dependent structure of amorphous magnesium aluminosilicates: The effect of replacing magnesia by alumina at the enstatite composition.

The effect of replacing magnesia by alumina on the pressure-dependent structure of amorphous enstatite was investigated by applying in situ high-pressure neutron diffraction with magnesium isotope substitution to glassy (MgO)0.375(Al2O3)0.125(SiO2)0.5. The replacement leads to a factor of 2.4 increase in the rate-of-change of the Mg-O coordination number with pressure, which increases from 4.76(4) at ambient pressure to 6.51(4) at 8.2 GPa, and accompanies a larger probability of magnesium finding bridging oxygen atoms as nearest-neighbors. The Al-O coordination number increases from 4.17(7) to 5.24(8) over the same pressure interval at a rate that increases when the pressure is above ∼3.5 GPa. On recovering the glass to ambient conditions, the Mg-O and Al-O coordination numbers reduce to 5.32(4) and 4.42(6), respectively. The Al-O value is in accordance with the results from solid-state 27Al nuclear magnetic resonance spectroscopy, which show the presence of six-coordinated aluminum species that are absent in the uncompressed material. These findings explain the appearance of distinct pressure-dependent structural transformation regimes in the preparation of permanently densified magnesium aluminosilicate glasses. They also indicate an anomalous minimum in the pressure dependence of the bulk modulus with an onset that suggests a pressure-dependent threshold for transitioning between scratch-resistant and crack-resistant material properties.

Elective Single-Level Primary Anterior Cervical Decompression and Fusion for Degenerative Spondylotic Cervical Myelopathy is Associated With Decreased Resource Utilization Versus Posterior Cervical Decompression and Fusion.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare elective single-level anterior cervical discectomy and fusion (ACDF) versus posterior cervical decompression and fusion (PCDF) for degenerative cervical myelopathy (DCM) in terms of (1) cost, (2) length of hospital stay, and (3) discharge destination in Medicare patients. A sub-analysis of potential cost drivers was also performed. BACKGROUND: In the era of value-based medicine, there is substantial interest in reducing the cost of care. Both ACDF and PCDF are used to treat DCM but carry different morbidity and risk profiles that can impact hospital resource utilization. However, this has not been assessed on a national level. METHODS: Patients undergoing single-level elective ACDF and PCDF surgery were identified using the 2019 Medicare Provider Analysis and Review (MedPAR) Limited Data Set (LDS) and Centers for Medicare and Medicaid Services (CMS) 2019 Impact File. Multivariate models of hospital cost of care, length of stay, and discharge destination were performed, controlling for confounders. A univariate sub-analysis of 9 revenue centers was performed. RESULTS: In all, 3942 patients met the inclusion criteria. The mean cost of elective single-level cervical fusion for myelopathy was $18,084±10,783, and the mean length of stay was 2.45±2.95 d. On multivariate analysis, ACDF was independently associated with decreased cost of $5,814 (P<0.001), shorter length of stay by 1.1 days (P<0.001), and decreased risk of nonhome discharge destination by 58% (adjusted odds ratio: 0.422, P<0.001).On sub-analysis of 9 revenue centers, medical/surgical supply ($10,497, 44%), operating room charges ($5401, 23%), and accommodations ($3999, 17%) were the largest drivers of charge differences. CONCLUSIONS: Single-level elective primary ACDF for DCM was independently associated with decreased cost, decreased hospital length of stay, and a lower rate of nonhome discharge compared with PCDF. Medical and surgical supply, operating room, and accommodation differences between ACDF and PCDF are potential areas for intervention. Increased granularity in reimbursement structures is warranted to prevent the creation of disincentives to the treatment of patients with DCM with pathology that is better addressed with PCDF. LEVEL OF EVIDENCE: Level-III Retrospective Cohort Study.

Solvation Structure of Methanol-in-Salt Electrolyte Revealed by Small-Angle X-ray Scattering and Simulations.

The solvation structure of water-in-salt electrolytes was thoroughly studied, and two competing structures─anion solvated structure and anion network─were well-defined in recent publications. To further reveal the solvation structure in those highly concentrated electrolytes, particularly the influence of solvent, methanol was chosen as the solvent for this proposed study. In this work, small-angle X-ray scattering, small-angle neutron scattering, Fourier-transform infrared spectroscopy, and Raman spectroscopy were utilized to obtain the global and local structural information. With the concentration increment, the anion network formed by TFSI- became the dominant structure. Meanwhile, the hydrogen bonds among methanol were interrupted by the TFSI- anion and formed a new connection with them. Molecular dynamic simulations with two different force fields (GAFF and OPLS-AA) are tested, and GAFF agreed with synchrotron small-angle X-ray scattering/wide-angle X-ray scattering (SAXS/WAXS) results well and provided insightful information about molecular/ion scale solvation structure. This article not only deepens the understanding of the solvation structure in highly concentrated solutions, but more importantly, it provides additional strong evidence for utilizing SAXS/WAXS to validate molecular dynamics simulations.

Tryptophan intake and pancreatic cancer: findings from a case-control study.

BACKGROUND: Pancreatic cancer is a leading cause of cancer-related death worldwide. Tryptophan plays a vital role in cell growth and maintenance as a building block of protein and coordination of organismal responses to environmental and dietary cues. Animal model study showed that dietary tryptophan improved treatment response in those who received chemotherapy or immune checkpoint inhibitors. Limited data are available assessing the association between tryptophan intake and risk of pancreatic cancer. We aimed to evaluate this association in a case-control study in Vietnam. METHODS: We analyzed data from a case-control study, including 3759 cancer cases and 2995 control subjects of whom 37 with pancreatic cancer cases. Tryptophan intake was derived from food frequency questionnaire. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for different levels of tryptophan intake with pancreatic cancer risk. RESULTS: Overall, tryptophan intake was inversely associated with pancreatic cancer risk in a dose-dependent manner. The ORs and 95% CIs of pancreatic cancer were 0.51 (0.29-0.92) for continuous scale, 0.27 (0.10-0.73) for tertile 2 and 0.34 (0.11-1.06) for tertile 3, compared with tertile 1 (the lowest intake) (Ptrend = 0.02). In stratified analysis, this inverse association pattern was present among those with BMI < 23 kg/m2 and ever drinkers. CONCLUSION: A diet with a higher intake of tryptophan was significantly associated with a lower incidence of pancreatic cancer among Vietnamese population. These suggest that dietary modification may be an effective strategy for primary prevention of pancreatic cancer development.

CLINICAL FINDINGS OF DENTAL DISEASE AND POTENTIAL CONTRIBUTING FACTORS IN PYGMY SLOW LORISES (NYCTICEBUS PYGMAEUS) UNDER HUMAN CARE.

Dental disease is a common finding in pygmy slow lorises (Nycticebus pygmaeus) under human care, but the etiology is not fully understood. The small oral cavity in this species can make diagnosis of dental disease difficult. This retrospective study evaluated medical records and diet and husbandry protocols from 18 participating institutions with the objective of describing the signalment, clinical signs, physical exam findings, tooth type, tooth location, diagnostics used, and treatments performed to help guide care for dental disease. In addition, the study aimed to identify potential contributing factors to dental disease in this species. Of 59 animals with medical records evaluated, 42 (71.2%) had dental disease: 19 (44.2%) males, 20 (46.5%) females, and 3 (9.3%) without gender documented. Average age at onset of dental disease was 7.6 yr in males and 9 yr in females. Multiple lorises with dental disease (n = 12; 28.6%) had no premonitory clinical signs, and dental disease was found incidentally on examination. On dental examination, 30 lorises (71.4%) had evidence of gingivitis. In 13 cases skull radiographs were taken, but the majority of images (n = 8; 61.5%) were nondiagnostic for pathologic dental changes. A small proportion of cases with dental abnormalities (n = 4; 9.5%) were diagnosed using computed tomography. In total, 175 teeth were extracted from 31 patients; molars were the most frequently extracted tooth (n = 55; 31.4%). No substantial differences in diets were noted among many of the participating institutions, and not all slow lorises evaluated developed dental disease (n = 17; 28.8%). This retrospective study provides clinical findings on slow loris dental disease and guidance for the veterinary care and management of slow lorises under human care.

What Are the Differences in Hospital Cost Associated With the Use of Cemented Versus Cementless Femoral Stems in Hemiarthroplasty and Total Hip Arthroplasty for the Treatment of Femoral Neck Fracture?

BACKGROUND: The purpose of this study was to determine if there is a difference in hospital costs associated with the use of cemented versus cementless femoral stems in hemiarthroplasty (HA) and total hip arthroplasty (THA) for the treatment of femoral neck fracture (FNF). METHODS: This retrospective cohort study utilizes the 2019 Medicare Provider Analysis and Review Limited Data Set. Patients undergoing arthroplasty for the treatment of FNF were identified. Patients were grouped by cemented or cementless femoral stem fixation. There were 16,148 patients who underwent arthroplasty for FNF available: 4,913 THAs (3,705 patients who had cementless femoral stems and 1,208 patients who had cemented femoral stems) and 11,235 HAs (6,099 patients who had cementless femoral stems and 5,136 who had cemented femoral stems). Index hospital costs were estimated by multiplying total charges by cost-to-charge ratios. Costs were analyzed using univariable and multivariable generalized linear models. RESULTS: Cemented femoral stem THA generated 1.080 times (95% confidence interval, 1.06 to 1.10; P < .001), or 8.0%, greater index hospital costs than cementless femoral stem THA, and cemented femoral stem HA generated 1.042 times (95% confidence interval, 1.03 to 1.05; P < .001), or 4.2%, greater index hospital costs than cementless femoral stem HA. CONCLUSIONS: Cemented femoral stems for FNF treated with either THA or HA are associated with only a small portion of increased cost compared to cementless femoral stems. Providers may choose the method of arthroplasty stem fixation for the treatment of FNF based on what they deem most appropriate for the specific patient.

Low-Cost, Compact Quadrupole Mass Filters with Unity Mass Resolution via Ceramic Resin Vat Photopolymerization.

This study reports novel, compact, and additively manufactured quadrupole mass filters (QMFs) with adequate filtering performance for practical mass spectrometry applications. The QMFs are monolithically fabricated via vat photopolymerization of glass-ceramic resin using 57 µm × 57 µm × 100 µm voxels, and selective electroless plating of nickel-boron. Experimental characterization of QMF prototypes at 1.74 MHz using FC-43 yields 131 Da peaks with 0.50 Da full width at half maximum (260 resolution), surpassing the resolution of reported miniaturized counterparts under similar conditions, and being on par with commercial, non-miniaturized, heavier devices. The sensitivity of the 3D-printed devices is estimated at 0.13 mA Torr-1 (comparable to that of optimized, commercial counterparts), while the devices attained up to 250 Da of mass range (limited by the driving electronics). The work is of interest to low-cost, capable mass spectrometry, 3D-printed instruments, and in-space manufacturing of complex instrumentation.

UNSEG: unsupervised segmentation of cells and their nuclei in complex tissue samples.

Multiplexed imaging technologies have made it possible to interrogate complex tumor microenvironments at sub-cellular resolution within their native spatial context. However, proper quantification of this complexity requires the ability to easily and accurately segment cells into their sub-cellular compartments. Within the supervised learning paradigm, deep learning based segmentation methods demonstrating human level performance have emerged. Here we present an unsupervised segmentation (UNSEG) method that achieves deep learning level performance without requiring any training data. UNSEG leverages a Bayesian-like framework and the specificity of nucleus and cell membrane markers to construct an a posteriori probability estimate of each pixel belonging to the nucleus, cell membrane, or background. It uses this estimate to segment each cell into its nuclear and cell-membrane compartments. We show that UNSEG is more internally consistent and better at generalizing to the complexity of tissue samples than current deep learning methods. This allows UNSEG to unambiguously identify the cytoplasmic compartment of a cell, which we employ to demonstrate its use in an example biological scenario. Within the UNSEG framework, we also introduce a new perturbed watershed algorithm capable of stably and accurately segmenting a cell nuclei cluster into individual cell nuclei. Perturbed watershed can also be used as a standalone algorithm that researchers can incorporate within their supervised or unsupervised learning approaches to replace classical watershed. Finally, as part of developing UNSEG, we have generated a high-quality annotated gastrointestinal tissue dataset, which we anticipate will be useful for the broader research community. Segmentation, despite its long antecedents, remains a challenging problem, particularly in the context of tissue samples. UNSEG, an easy-to-use algorithm, provides an unsupervised approach to overcome this bottleneck, and as we discuss, can help improve deep learning based segmentation methods by providing a bridge between unsupervised and supervised learning paradigms.

Elective THA for Indications Other Than Osteoarthritis Is Associated With Increased Cost and Resource Use: A Medicare Database Study of 135,194 Claims.

BACKGROUND: Under Medicare's fee-for-service and bundled payment models, the basic unit of hospital payment for inpatient hospitalizations is determined by the Medicare Severity Diagnosis Related Group (MS-DRG) coding system. Primary total joint arthroplasties (hip and knee) are coded under MS-DRG code 469 for hospitalizations with a major complication or comorbidity and MS-DRG code 470 for those without a major complication or comorbidity. However, these codes do not account for the indication for surgery, which may influence the cost of care.Questions/purposes We sought to (1) quantify the differences in hospital costs associated with six of the most common diagnostic indications for THA (osteoarthritis, rheumatoid arthritis, avascular necrosis, hip dysplasia, posttraumatic arthritis, and conversion arthroplasty), (2) assess the primary drivers of cost variation using comparisons of hospital charge data for the diagnostic indications of interest, and (3) analyze the median length of stay, discharge destination, and intensive care unit use associated with these indications. METHODS: This study used the 2019 Medicare Provider Analysis and Review Limited Data Set. Patients undergoing primary elective THA were identified using MS-DRG codes and International Classification of Diseases, Tenth Revision, Procedure Coding System codes. Exclusion criteria included non-fee-for-service hospitalizations, nonelective procedures, patients with missing data, and THAs performed for indications other than the six indications of interest. A total of 713,535 primary THAs and TKAs were identified in the dataset. After exclusions were applied, a total of 135,194 elective THAs were available for analysis. Hospital costs were estimated using cost-to-charge ratios calculated by the Centers for Medicare and Medicaid Services. The primary benefit of using cost-to-charge ratios was that it allowed us to analyze a large national dataset and to mitigate the random cost variation resulting from unique hospitals' practices and patient populations. As an investigation into matters of health policy, we believe that assessing the surgical cost borne by the "average" hospital was most appropriate. To analyze estimated hospital costs, we performed a multivariable generalized linear model controlling for patient demographics (gender, age, and race), preoperative health status, and hospital characteristics (hospital setting [urban versus rural], geography, size, resident-to-bed ratio, and wage index). We assessed the principal drivers of cost variation by analyzing the median hospital charges arising from 30 different hospital revenue centers using descriptive statistics. Length of stay, intensive care use, and discharge to a nonhome location were analyzed using multivariable binomial logistic regression. RESULTS: The cost of THA for avascular necrosis was 1.050 times (95% confidence interval 1.042 to 1.069; p < 0.001), or 5% greater than, the cost of THA for osteoarthritis; the cost of hip dysplasia was 1.132 times (95% CI 1.113 to 1.152; p < 0.001), or 13% greater; the cost of posttraumatic arthritis was 1.220 times (95% CI 1.193 to 1.246; p < 0.001), or 22% greater; and the cost of conversion arthroplasty was 1.403 times (95% CI 1.386 to 1.419; p < 0.001), or 40% greater. Importantly, none of these CIs overlap, indicating a discernable hierarchy of cost associated with these diagnostic indications for surgery. Rheumatoid arthritis was not associated with an increase in cost. Medical or surgical supplies and operating room charges represented the greatest increase in charges for each of the surgical indications examined, suggesting that increased use of medical and surgical supplies and operating room resources were the primary drivers of increased cost. All of the orthopaedic conditions we investigated demonstrated increased odds that a patient would experience a prolonged length of stay and be discharged to a nonhome location compared with patients undergoing THA for osteoarthritis. Avascular necrosis, posttraumatic arthritis, and conversion arthroplasty were also associated with increased intensive care unit use. Posttraumatic arthritis and conversion arthroplasty demonstrated the largest increase in resource use among all the orthopaedic conditions analyzed. CONCLUSION: Compared with THA for osteoarthritis, THA for avascular necrosis, hip dysplasia, posttraumatic arthritis, and conversion arthroplasty is independently associated with stepwise increases in resource use. These cost increases are predominantly driven by greater requirements for medical and surgical supplies and operating room resources. Posttraumatic arthritis and conversion arthroplasty demonstrated substantially increased costs, which can result in financial losses in the setting of fixed prospective payments. These findings underscore the inability of MS-DRG coding to adequately reflect the wide range of surgical complexity and resource use of primary THAs. Hospitals performing a high volume of THAs for indications other than osteoarthritis should budget for an anticipated increase in costs, and orthopaedic surgeons should advocate for improved MS-DRG coding to appropriately reimburse hospitals for the financial and clinical risk of these surgeries. LEVEL OF EVIDENCE: Level IV, economic and decision analysis.

Conversion THA With Concomitant Removal of Orthopaedic Hardware Should Be Reclassified as a Revision Surgery in the Medicare Severity Diagnosis-Related Group Coding Scheme: An Analysis of Cost and Resource Use.

BACKGROUND: Conversion THA, which we defined for this study as THA with concomitant removal of preexisting orthopaedic hardware, has been associated with increased hospital costs and perioperative complications compared with primary THA. Yet, conversion THA is classified as a primary procedure under the Medicare Severity Diagnosis-Related Group coding scheme, and hospitals are reimbursed based on the resource use expected for a routine primary surgery. Prior authors have argued for conversion THA to be reclassified as a revision procedure. Although prior research has focused on comparisons between conversion THAs and primary arthroplasties, little is known about the resource use of conversion THA compared with that of revision THA. QUESTIONS/PURPOSES: (1) Do inpatient hospital costs, estimated using cost-to-charge ratios, differ between conversion THA and revision THA? (2) Do the median length of stay, intensive care unit use, and likelihood of discharge to home differ between conversion and revision THA? METHODS: This was a retrospective study of the Medicare Provider Analysis and Review Limited Data Set for 2019. A total of 713,535 primary and 74,791 revision THAs and TKAs were identified initially. Exclusion criteria then were applied; these included non-fee-for-service hospitalizations, nonelective admissions, and patients with missing data. Approximately 37% (263,545 of 713,535) of primary and 34% (25,530 of 74,791) of revision arthroplasties were excluded as non-fee-for-service hospitalizations. Two percent (13,159 of 713,535) of primaries and 11% (8159 of 74,791) of revisions were excluded because they were nonelective procedures. Among the remaining 436,831 primary and 41,102 revision procedures, 31% (136,748 of 436,831) were primary THAs and 36% (14,774 of 41,102) were revision THAs. Two percent (2761 of 136,748) of primary THAs involved intraoperative removal of hardware and were classified as conversion THAs. After claims with missing data were excluded, there were 2759 conversion THAs and 14,764 revision THAs available for analysis. Propensity scores were generated using a multivariate logistic regression model using the following variables as covariates: gender, age, race, van Walraven index, hospital setting, geography, hospital size, resident-to-bed ratio, and wage index. After matching, 2734 conversion THAs and 5294 revision THAs were available for analysis. The van Walraven index, which is a weighted score of patient preoperative comorbidities, was used to measure patient health status. Hospital costs were estimated by multiplying cost-to-charge ratios obtained from the 2019 Impact File by total hospital charges. This methodology enabled the use of a large national database to mitigate the random effects of individual hospitals' unique practices and patient populations. Multivariable regression was performed after matching to determine the independent effects of surgery type (that is, conversion versus revision THA) on hospital cost, length of stay greater than 2 days, intensive care unit use, and discharge to home. RESULTS: There was no difference in the estimated hospital cost between conversion THA and revision THA (ß = 0.96 [95% confidence interval 0.90 to 1.01]; p = 0.13). Patients undergoing conversion THA had increased odds of staying in the hospital for more than 2 days (odds ratio 1.12 [95% CI 1.03 to 1.23]; p = 0.01), increased odds of using the intensive care unit (OR 1.24 [95% CI 1.03 to 1.48]; p = 0.02), and decreased odds of being discharged to home (OR 0.74 [95% CI 0.67 to 0.80]; p < 0.001). CONCLUSION: The inpatient hospital cost of conversion THA is no different from that of revision THA, although patients undergoing conversion surgery have modestly increased odds of prolonged length of stay, intensive care unit use, and discharge to a nonhome location. These findings support the conclusion that reclassification of conversion THA is warranted. Orthopaedic surgeons must advocate for the reclassification of conversion THA using data-backed evidence or run the risk that orthopaedic procedures will be given decreased reimbursement. LEVEL OF EVIDENCE: Level III, economic and decision analysis.

Maternal hepatitis C virus infection and three adverse maternal outcomes in the United States.

BACKGROUND: Hepatitis Virus C (HCV) infection rates have trended upwards among pregnant people in the USA since 2009. Existing evidence about HCV infections and maternal outcomes is limited; therefore, we used birth certificate data to investigate the association between HCV infection and maternal health outcomes. METHODS: We used the 2017 US birth certificate dataset (a cross-section of 1.4 million birth records) to assess the association between prevalent HCV infection and gestational diabetes, gestational hypertension, and eclampsia. Potential confounding variables included prenatal care, age, education, smoking, presence of sexually transmitted infections (STIs), body mass index (BMI), and weight gain during pregnancy. We restricted our analysis to only women with a first singleton pregnancy. Odds ratios were estimated by logistic regression models and separate models were tested for white and Black women. RESULTS: Only 0.31% of the women in our sample were infected with HCV (n = 4412). In an unadjusted model, we observed a modest significant protective association between HCV infection and gestational diabetes (Odds ratio [OR]: 0.83; 95% CI: 0.76-0.96); but this was attenuated with adjustment for confounding variables (Adjusted odds ratio [AOR]: 0.88; 95% CI: 0.76, 1.02). There was no association between HCV and gestational hypertension (AOR: 1.03; 95% CI: 0.91, 1.16) or eclampsia (AOR: 1.15; 95% CI: 0.69, 1.93). Results from the race stratified models were similar to the non-stratified summary models. CONCLUSION: We observed no statistically significant associations between maternal HCV infection with maternal health outcomes. Although, our analysis did indicate that HCV may lower the risk of gestational diabetes, this may be attributable to confounding. Studies utilizing more accurately measured HCV infection including those collecting type and timing of testing, and timing of infection are warranted to ensure HCV does not adversely impact maternal and/or fetal health. Particularly in the absence of recommended therapy for HCV during pregnancy.

Outcomes of the IMMray PanCan-d Test in High-Risk Individuals Undergoing Pancreatic Surveillance: Pragmatic Data and Lessons Learned.

PURPOSE: An effective blood-based test for pancreatic cancer (PC) screening has remained elusive. The IMMray PanCan-d is the first commercially available blood-based test specifically designed for early detection of PC; however, outcomes from its use in clinical practice have not been reported. METHODS: We performed a blinded spike-in study of 100 individuals who had an IMMray PanCan-d test, including 94 high-risk individuals (HRIs) undergoing PC surveillance and six individuals with known PC. Specimens were processed blindly following the commercial laboratory's standardized operating procedure. Positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Cohort characteristics included a median age of 63 (IQR, 55-70) years, 57% female, 96% non-Hispanic White, 57% with a pathogenic variant in a PC risk gene (BRCA2 most commonly-18%), and 83% with a family history of PC. Among IMMray PanCan-d results from 94 HRIs undergoing PC surveillance, there was one positive (1%), seven borderlines (7%), 73 negatives (78%), and 13 tests not performed because of low CA19-9 expression (14%). No PC was diagnosed among these HRIs; however, there were two sub-cm pancreatic neuroendocrine tumors, seven clinically diagnosed side branch intraductal papillary mucinous neoplasms ≥1 cm, and a sub-cm solid mass with indeterminate cytology requiring close follow-up; all these individuals had negative IMMray PanCan-d tests. Of the six spiked-in PCs, four (67%) yielded a positive and two (33%) yielded a negative. With an estimated disease prevalence of 2%, the PPV and NPV are 52% and 99%, respectively, if borderline results are considered negative and 12% and 99%, respectively, if borderline tests are considered positive. CONCLUSION: In clinical practice, IMMray PanCan-d has a robust NPV; however, PPV is dramatically influenced by whether borderline results are characterized as a positive or negative result.

AN OUTBREAK OF FELINE INFECTIOUS PERITONITIS IN THREE RELATED SAND CATS (FELIS MARGARITA) IN HUMAN CARE.

Feline infectious peritonitis (FIP) is a systemic disease in felid species caused by infection with mutated forms of feline coronavirus (FCoV), and outbreaks can devastate exotic felid populations in human care. Feline infectious peritonitis was diagnosed in three of four related juvenile sand cats (Felis margarita) from a single institution over a 6-wk period. Case 1 was a 7-mon-old male found deceased with no premonitory signs. Case 2, an 8-mon-old male (littermate to Case 1), and Case 3, a 6-mon-old male (from a different litter with identical parentage), were evaluated for lethargy and anorexia 1 mon after Case 1. Both exhibited transient anisocoria and progressive lethargy, anorexia, and dehydration despite antibiotic and supportive treatment. Approximately 1 wk after initial presentation, Case 2 was humanely euthanized, and Case 3 was found deceased. Necropsy findings included intrathoracic and/or intra-abdominal lymphadenopathy (3/3 cases), bicavitary effusion (2/3), multifocal tan hepatic and intestinal nodules (1/3), and multifocal yellow renal nodules (1/3). Histologically, all cats had severe pyogranulomatous vasculitis in multiple organs, and the presence of FCoV antigen was confirmed using immunohistochemical staining. Next-generation sequencing of the virus from Case 3's affected kidney demonstrated ∼93% homology to the UG-FH8 virus, a serotype 1 feline alphacoronavirus isolated from Denmark. Future research will focus on comparative viral genomic sequencing with the goals of identifying potential sources of FCoV infection and identifying features that may have contributed to the development of FIP in this species.

Computational modeling of ventricular-ventricular interactions suggest a role in clinical conditions involving heart failure.

Introduction: The left (LV) and right (RV) ventricles are linked biologically, hemodynamically, and mechanically, a phenomenon known as ventricular interdependence. While LV function has long been known to impact RV function, the reverse is increasingly being realized to have clinical importance. Investigating ventricular interdependence clinically is challenging given the invasive measurements required, including biventricular catheterization, and confounding factors such as comorbidities, volume status, and other aspects of subject variability. Methods: Computational modeling allows investigation of mechanical and hemodynamic interactions in the absence of these confounding factors. Here, we use a threesegment biventricular heart model and simple circulatory system to investigate ventricular interdependence under conditions of systolic and diastolic dysfunction of the LV and RV in the presence of compensatory volume loading. We use the end-diastolic pressure-volume relationship, end-systolic pressure-volume relationship, Frank Starling curves, and cardiac power output as metrics. Results: The results demonstrate that LV systolic and diastolic dysfunction lead to RV compensation as indicated by increases in RV power. Additionally, RV systolic and diastolic dysfunction lead to impaired LV filling, interpretable as LV stiffening especially with volume loading to maintain systemic pressure. Discussion: These results suggest that a subset of patients with intact LV systolic function and diagnosed to have impaired LV diastolic function, categorized as heart failure with preserved ejection fraction (HFpEF), may in fact have primary RV failure. Application of this computational approach to clinical data sets, especially for HFpEF, may lead to improved diagnosis and treatment strategies and consequently improved outcomes.