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ABSTRACT Background Morphology and morphometric evaluation of lesions beyond conventional parameters can inform the pathophysiology of chronic kidney disease (CKD). We sought to determine whether the occurrence of glomerulotubular neck stenoses associates with progressive CKD. Methods We evaluated the normal parenchyma from radical nephrectomies removed for tumor between 2000 and 2021 and analyzed cortex for stenoses of the glomerulotubular neck. Stenosis of the glomerulotubular neck is defined a focal narrowing for which the draining tubule has a greater diameter than at the neck. Progressive CKD was defined as dialysis, kidney transplantation, sustained estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m2 or sustained 40% decline from the post-nephrectomy eGFR. Each case of progressive CKD was age- and sex-matched to two controls without progressive CKD. Logistic regression models assessed the risk of progressive CKD with stenotic necks adjusting for other histological features, kidney function and CKD risk factors. Results There were 65 cases with a mean of 255 glomeruli and 130 controls with a mean of 329 glomeruli. Among both cases and controls, 5% of glomeruli showed visible glomerulotubular necks. The proportion of necks that were stenotic was higher in cases than controls (35% vs 11%, P < .0001). Stenotic necks associated with progressive CKD independent of other histologic and clinical characteristics. Conclusion Glomerulotubular neck stenosis is associated with development of progressive CKD.

The NCCN Guidelines for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer provide multidisciplinary diagnostic workup, staging, and treatment recommendations for this disease. These NCCN Guidelines Insights detail how the evolution of the use of PARP inhibitors as maintenance and single-agent regimens for the treatment of ovarian cancer informed panel recommendations in the guidelines.

Background: Value is defined as the ratio of patient outcomes to the cost of care. One method to assess value is through patient-level value analysis (PLVA). To our knowledge, this tool has not previously been implemented in the setting of total hip arthroplasty (THA). The purposes of this study were to perform PLVA for a 1-year episode of care among patients undergoing primary THA and to identify characteristics that affect value in a metropolitan health-care system. Methods: The patient-reported outcome (PRO) measure database of the institution was queried for all primary THAs from 2018 to 2019. The PRO measure that was utilized was the Hip disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS-JR). Cost was evaluated with use of time-driven activity-based costing (TDABC) for a 1-year episode of care (consisting of the day of surgery, inpatient stay, discharge facility, postoperative appointments, and physical therapy). The primary outcome was the 1-year value quotient, or the ratio of the 1-year change in HOOS-JR to the cost of the episode of care (V HOOS ). The value quotient was compared among all included patients and evaluated for variables that may affect the overall value of the episode of care. Results: In total, 480 patients were included in the analysis. The mean improvement in the HOOS-JR was +34.9 ± 16.1 (95% confidence interval [CI]: 33.5, 36.3). The mean cost was $13,835 ± $3,471 (95% CI: $13,524, $14,146). The largest contributor to cost was implants (39.0%), followed by post-recovery care (i.e., inpatient stay and specialized nursing facilities; 24.1%). Change in the HOOS-JR was poorly correlated with the cost of care (r = −0.06; p = 0.19). THAs performed at an ambulatory surgery center (ASC) with discharge to home demonstrated higher value (V HOOS = 0.42) than THAs performed at a hospital with discharge to a rehabilitation facility (V HOOS = 0.15; analysis of variance F-test, p < 0.01). Conclusions: Our study found that PROs did not correlate with costs in the setting of primary THA. Implants were the largest cost driver. Surgical setting (an ASC versus a hospital) and discharge destination influenced value as well. PLVA is a value measurement tool that can be utilized to optimize components of the care delivery pathway. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

The mature splenic B‐cell lymphomas are an enigmatic group of lymphoid neoplasms that have long caused significant difficulty for the practicing pathologist due to overlapping diagnostic features among entities and the decreasing availability of splenic tissue for assessment. While some entities have highly characteristic and specific clinicopathological features (e.g. hairy cell leukaemia), others are substantially more difficult to recognise (e.g. splenic diffuse red pulp lymphoma). At the same time, classification systems have been evolving, resulting in multiple changes to the boundaries among these entities and even the existence of some entities in their own right. Moreover, unbiased multi‐omic interrogation (whole genome/transcriptome sequencing, methylome) of the splenic B‐cell lymphomas over the past decade has given us significant insights into the underling biology of these neoplasms. We present a clinicopathological perspective on the historical, current and future state of the diagnosis and classification of splenic B‐cell lymphomas integrating multi‐omic data and highlighting areas of focus for the field in order to continue to strive to improve patient outcomes through accurate diagnosis.

OBJECTIVE Some patients treated surgically for grade 1 spondylolisthesis require revision surgery. Outcomes after revision surgery are not well studied. The objective of this study was to determine how revision surgery impacts patient-reported outcomes (PROs) in patients undergoing decompression only or decompression and fusion (D+F) for grade 1 spondylolisthesis within 5 years of the index surgery. METHODS Patients in the 12 highest Quality Outcomes Database (QOD) enrolling sites with a diagnosis of grade 1 spondylolisthesis were identified and the incidence of revision surgery between the decompression-only and D+F patients were compared. PROs were compared between cohorts requiring revision surgery versus a single index procedure. RESULTS Of 608 patients enrolled, 409 had complete 5-year data available for this study. Eleven (13.3%) of 83 patients underwent revision in the decompression-only group as well as 32 (9.8%) of 326 in the D+F group. For the entire cohort, patients requiring revision had significantly worse PROs at 5 years: Oswestry Disability Index (ODI) 27.4 versus 19.4, p = 0.008; numeric rating scale for back pain (NRS-BP) 4.1 versus 3.0, p = 0.013; and NRS for leg pain (NRS-LP) 3.4 versus 2.1, p = 0.029. In the decompression-only group, the change in 5-year PROs was not impacted by revision status: ODI 31.9 versus 24.2, p = 0.287; NRS-BP 1.9 versus 2.9, p = 0.325; and NRS-LP 6.2 versus 3.7, p = 0.011. In the D+F group, the change in 5-year PROs was diminished if patients required revision: ODI 19.1 versus 29.1, p = 0.001; NRS-BP 3.0 versus 4.0, p = 0.170; and NRS-LP 2.3 versus 4.6, p = 0.001. CONCLUSIONS The most common reasons for reoperation within 5 years in the decompression-only group were repeat decompression and instability, whereas in the D+F group the most common reason was adjacent-segment disease. The need for revision resulted in modestly diminished benefit compared with patients with no revisions. These differences were greater in the fusion cohort compared with the decompression-only cohort. The mean PRO improvement still far exceeded minimal clinically important difference thresholds for all measures for patients who underwent a revision surgery.

Abstract Many patients in the emergency department present with signs and symptoms that arouse concern for sepsis; however, other explanations are also possible. There are currently no rapid tests used in clinical practice that reliably distinguish the presence of a bacterial or viral infection vs. a non-infectious etiology and can predict a patient’s likelihood to decompensate. The diagnostic and prognostic uncertainty in “gray zone” patients complicates the decision to begin therapy as clinicians need to balance the risk of withholding therapy vs. the risk of the therapy itself (e.g., overtreatment with antibiotics and hospitalization, which is costly, potentially harmful, and contributes to antibiotic resistance). The TriVerity™ Test uses isothermal amplification and machine-learning algorithms to quantify and interpret mRNA expression levels to determine both likelihood of bacterial infection, viral infection, or no infection, and whether the patient will likely require one or more critical interventions within 7 days. The three scores each fall into one of five interpretation bands ranging from Very high to Very low. Testing takes approximately 30 minutes using the proprietary Myrna™ Instrument with an operator hands-on-time of under one minute. We enrolled 1,222 patients from 22 emergency departments (ED) to validate the performance of the TriVerity Test. Patients were treated as per local standard of care and were followed for 28 days. Bacterial and viral TriVerity results were validated against clinically adjudicated infection status; the illness severity TriVerity result was validated against the need for at least one critical interventions within 7 days. The bacterial TriVerity result had high AUROC for the diagnosis of bacterial infection (0.83; 80% CI 0.81–0.85) and divided bacterial infection likelihood scores into five interpretation bands with increasing likelihood ratios of infection ranging from Very low (LR- 0.08, 80% CI 0.06–0.11) to Very high (LR + 8.04, 80% CI 5.72–11.78). The AUROC for the bacterial TriVerity result was significantly higher compared to AUROCs for C-reactive protein, procalcitonin or white blood cell count. Similarly, the viral TriVerity score showed high AUROC for the diagnosis of viral infection (0.91; 80% CI 0.90–0.93) and likelihood ratios from Very low (LR- 0.09, 80% CI 0.05–0.14) to Very high (LR + 40.93; 80% CI 29.11–79.23). The TriVerity Illness Severity score showed a high AUROC for the prediction of illness severity (0.77; 80% CI 0.77–0.81) with scores divided into five interpretation bands with increasing likelihood ratios ranging from Very low (LR- 0.22; 80% CI 0.14–0.33) to Very high (LR + 11.33; 80% CI 7.31–17.00). TriVerity illness severity results allowed marked re-classification of the risk for “ICU-level care” as compared to clinical assessment (qSOFA scores) alone. In conclusion, TriVerity provides rapid, highly accurate and actionable results for the diagnosis and prognosis of patients with suspected acute infection and/or sepsis, supporting a major unmet medical need. TriVerity may improve personalized management of patients with suspected acute infections and suspected sepsis for improved overall healthcare outcomes.

Key Points Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists were superior to dipeptidyl peptidase-4 inhibitor and sulfonylurea for preventing kidney complications in patients with type 2 diabetes at moderate cardiovascular disease risk. Sodium-glucose cotransporter 2 inhibitor therapy compared favorably with glucagon-like peptide-1 receptor agonists for kidney disease outcomes. Background CKD is a serious diabetes-related complication. While guidelines recommend use of sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapies to mitigate cardiorenal risk in high-risk patients, the benefit of early initiation of these agents relative to other commonly prescribed glucose-lowering agents in patients at lower baseline cardiovascular disease (CVD) risk remains less clear. Methods This retrospective observational study emulated an idealized target trial using claims data from OptumLabs data warehouse to test the comparative association of treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4i), SGLT2i, GLP-1RA, or sulfonylurea (SU) on a primary kidney composite outcome of incident CKD stages 3–5, kidney failure, or need for KRT in patients with type 2 diabetes and moderate CVD risk. A secondary composite outcome included all components of the primary composite outcome plus death. Results A total of 364,714 adults aged 21 years or older initiating treatment with a DPP-4i ( N =78,843), GLP-1RA ( N =42,049), SGLT2i ( N =45,466), or SU ( N =198,356) were identified. Relative to DPP-4i, SGLT2i (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.67 to 0.74; P < 0.001) and GLP-1RA (HR, 0.87; 95% CI, 0.83 to 0.92; P < 0.001) treatment was superior for the primary composite outcome. Similarly, SGLT2i (HR, 0.69; 95% CI, 0.66 to 0.73) and GLP-1RA (HR, 0.86; 95% CI, 0.82 to 0.91) treatment was associated with risk reductions for the primary outcome relative to SU treatment. When comparing SGLT2i with GLP-1RA therapy, SGLT2is were superior for the primary composite outcome (HR, 0.81; 95% CI, 0.75 to 0.86; P < 0.001). Similar findings were observed for the secondary composite outcome across all comparisons. Conclusions SGLT2is and GLP-1RAs were superior to DPP-4is and SUs for preventing kidney complications in a type 2 diabetes population with moderate baseline CVD risk. Clinical Trial registry name and registration number: NCT05214573.

BACKGROUND AND OBJECTIVES: First-line therapy for most intracranial dural arteriovenous fistulas (dAVFs) is endovascular embolization, but some require microsurgical ligation due to limited endovascular accessibility, anticipated lower cure rates, or unacceptable risk profiles. We investigated the most common surgically treated dAVF locations and the approaches and outcomes of each. METHODS: The Consortium for Dural Arteriovenous Fistula Outcomes Research database was retrospectively reviewed. Patients who underwent dAVF microsurgical ligation were included. Patient demographics, angiographic information, surgical details, and postoperative outcomes were collected. The 5 most common surgically treated dAVF locations were analyzed about used surgical approaches and postoperative outcomes. Univariate analyses were performed with statistical significance set at a threshold of P < .05. RESULTS: In total, 248 patients in the Consortium for Dural Arteriovenous Fistula Outcomes Research database met inclusion criteria. The 5 most common surgically treated dAVF locations were tentorial, anterior cranial fossa (ACF), transverse-sigmoid sinus (TSS), convexity/superior sagittal sinus (SSS), and torcular. Most tentorial dAVFs were approached using a suboccipital, lateral supracerebellar infratentorial approach (39.3%); extended retrosigmoid approach (ERS) (25%); or posterior subtemporal approach (19.6%). All ACF dAVFs used a subfrontal approach; 5.3% also included an anterior interhemispheric approach. Most TSS dAVFs were ligated via ERS (31.3%) or subtemporal (31.3%) approaches. All convexity/SSS dAVFs used an interhemispheric approach. All torcular dAVFs used the suboccipital, lateral supracerebellar infratentorial approach, with 10.5% undergoing simultaneous ERS craniotomy. Angiographic occlusion rates after microsurgery were 85.5%, 100%, 75.8%, 79.2%, and 73.7% for tentorial, ACF, TSS, convexity/SSS, and torcular dAVFs, respectively ( P = .02); the permanent neurological complication rates were 1.8%, 2.6%, 9.1%, 0%, and 0% ( P = .31). There were no statistically significant differences in development of complications ( P = .08) or Modified Rankin Scale at the last follow-up ( P = .11) by fistula location. CONCLUSION: Although endovascular embolization is the first-line treatment for most intracranial dAVFs, surgical ligation is an important alternative. ACF and tentorial fistulas particularly demonstrate high rates of postoperative obliteration.