Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era.

ABSTRACT: Progression of myeloproliferative neoplasms (MPNs) to accelerated or blast phase is associated with poor survival outcomes. Since 2017 there have been several therapies approved for use in acute myeloid leukemia (AML); these therapies have been incorporated into the management of accelerated/blast-phase MPNs (MPN-AP/BP). We performed a multicenter analysis to investigate outcomes of patients diagnosed with MPN-AP/BP in 2017 or later. In total, 202 patients were identified; median overall survival (OS) was 0.86 years. We also analyzed patients based on first-line treatment; the 3 most common approaches were intensive chemotherapy (n = 65), DNA methyltransferase inhibitor (DNMTi)-based regimens (n = 65), and DNMTi + venetoclax-based regimens (n = 54). Median OS was not significantly different by treatment type. In addition, we evaluated response by 2017 European LeukemiaNet AML criteria and 2012 MPN-BP criteria in an effort to understand the association of response with survival outcomes. We also analyzed outcomes in 65 patients that received allogeneic hematopoietic stem cell transplant (allo-HSCT); median OS was 2.30 years from time of allo-HSCT. Our study demonstrates that survival among patients with MPN-AP/BP is limited in the absence of allo-HSCT even in the current era of therapeutics and underscores the urgent need for new agents and approaches.

The impact of cancer metastases on COVID-19 outcomes: A COVID-19 and Cancer Consortium registry-based retrospective cohort study.

BACKGROUND: COVID-19 can have a particularly detrimental effect on patients with cancer, but no studies to date have examined if the presence, or site, of metastatic cancer is related to COVID-19 outcomes. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, the authors identified 10,065 patients with COVID-19 and cancer (2325 with and 7740 without metastasis at the time of COVID-19 diagnosis). The primary ordinal outcome was COVID-19 severity: not hospitalized, hospitalized but did not receive supplemental O2, hospitalized and received supplemental O2, admitted to an intensive care unit, received mechanical ventilation, or died from any cause. The authors used ordinal logistic regression models to compare COVID-19 severity by presence and specific site of metastatic cancer. They used logistic regression models to assess 30-day all-cause mortality. RESULTS: Compared to patients without metastasis, patients with metastases have increased hospitalization rates (59% vs. 49%) and higher 30 day mortality (18% vs. 9%). Patients with metastasis to bone, lung, liver, lymph nodes, and brain have significantly higher COVID-19 severity (adjusted odds ratios [ORs], 1.38, 1.59, 1.38, 1.00, and 2.21) compared to patients without metastases at those sites. Patients with metastasis to the lung have significantly higher odds of 30-day mortality (adjusted OR, 1.53; 95% confidence interval, 1.17-2.00) when adjusting for COVID-19 severity. CONCLUSIONS: Patients with metastatic cancer, especially with metastasis to the brain, are more likely to have severe outcomes after COVID-19 whereas patients with metastasis to the lung, compared to patients with cancer metastasis to other sites, have the highest 30-day mortality after COVID-19.

Efficacy and specificity of melanopsin reporters for retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are specialized retinal output neurons that mediate behavioral, neuroendocrine, and developmental responses to environmental light. There are diverse molecular strategies for marking ipRGCs, especially in mice, making them among the best characterized retinal ganglion cells (RGCs). With the development of more sensitive reporters, new subtypes of ipRGCs have emerged. We therefore tested high-sensitivity reporter systems to see whether we could reveal yet more. Substantial confusion remains about which of the available methods, if any, label all and only ipRGCs. Here, we compared many different methods for labeling of ipRGCs, including anti-melanopsin immunofluorescence, Opn4-GFP BAC transgenic mice, and Opn4cre mice crossed with three different Cre-specific reporters (Z/EG, Ai9, and Ai14) or injected with Cre-dependent (DIO) AAV2. We show that Opn4cre mice, when crossed with sensitive Cre-reporter mice, label numerous ganglion cell types that lack intrinsic photosensitivity. Though other methods label ipRGCs specifically, they do not label the entire population of ipRGCs. We conclude that no existing method labels all and only ipRGCs. We assess the appropriateness of each reporter for particular applications and integrate findings across reporters to estimate that the overall abundance of ipRGCs among mouse RGCs may approach 11%.

Price Transparency for Cervical Spinal Fusion Among High-Performing Spine Centers in the United States.

BACKGROUND AND OBJECTIVES: As of January 1, 2021, all US hospitals are required by the Hospital Price Transparency Final Rule (HPTFR) to publish standard charges for all items and services, yet the state of price transparency for cervical spinal fusion is unknown. Here, we assess the nationwide price transparency landscape for cervical spinal fusion among high-performing spine centers in the United States. METHODS: In this cross-sectional economic evaluation, we queried publicly available price transparency websites of 332 "high-performing" spine centers, as defined by the US News and World Report. We extracted variables including gross charges for cervical spinal fusion, payor options, price reporting methodology, and prices relevant to consumers including listed cash prices and minimum and maximum negotiated charges. RESULTS: While nearly all 332 high-performing spine surgery centers (99.4%) had an online cost estimation tool, the HPTFR compliance rate was only 8.4%. Gross charges for cervical spinal fusion were accessible for 68.1% of hospitals, discounted cash prices for 46.4% of hospitals, and minimum and maximum charges for 10.8% of hospitals. There were large IQRs for gross charges ($48 491.98-$99 293.37), discounted cash prices ($26 952.25-$66 806.63), minimum charges ($10 766.11-$21 248.36), and maximum charges ($39 280.49-$89 035.35). There was geographic variability in the gross charges of cervical spinal fusion among high-performing spine centers within and between states. There was a significant association between "excellent" discharge to home status and lower mean gross charges. CONCLUSION: Although online cost reporting has drastically increased since implementation of the HPTFR, data reported for cervical spinal fusion remain inadequate and difficult to interpret by both providers and patients.

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19.

Importance: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking. Objective: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022. Exposure: Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19. Main Outcomes and Measures: Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up. Results: Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13). Conclusions and Relevance: In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer.

A case of Lactobacillus jensenii associated native valve endocarditis.

Lactobacillus jensenii is rarely reported as a cause of endocarditis in immunocompetent patients. We describe a case of Lactobacillus jensenii associated native valve endocarditis that was identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) technology. While most Lactobacillus species are generally resistant to vancomycin, Lactobacillus jensenii is frequently susceptible, but treatment requires accurate susceptibility results followed by timely medical and surgical intervention. Probiotic use in patients can be a risk factor for infection with Lactobacillus species.

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma.

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

Articular Findings on Chest Computed Tomography: An Algorithmic Approach for Radiologists.

ABSTRACT: Chest computed tomography (CT) is one of the most frequently performed imaging studies. Incidental osseous and articular findings are commonly encountered in chest CTs in daily practice. The spectrum of findings is broad, varying from benign to malignant, and interpretation of these incidental musculoskeletal findings could be challenging for radiologists. In this review, we provide a systematic algorithmic approach for the diagnosis of common articular findings seen on chest CT with recommendations for appropriate follow-up evaluation.

Incidental osseous lesions on chest CT: an algorithmic approach for radiologists.

Numerous osseous findings are commonly discovered incidentally at chest CTs in daily practice. A broad spectrum of these findings ranges from benign and do not touch lesions to ominous conditions requiring further imaging evaluation and/or intervention. Interpretation of these incidental musculoskeletal findings may constitute a diagnostic challenge to radiologists. This review provides a systematic, algorithmic approach to common osseous lesions on chest CT based on imaging findings with recommendations for proper next step management.

Gender Differences in Ophthalmic Procedural Volume: A Study of Male vs. Female Glaucoma Specialists.

PURPOSE: To investigate whether differences in procedural volume exist between practicing male and female glaucoma specialists. DESIGN: A cross-sectional analysis. SUBJECTS: A total of 213 female and 666 male glaucoma specialists who performed ≥ 11 traditional, incisional glaucoma procedures for Medicare beneficiaries between 2014 and 2018. METHODS: The 2014 to 2018 Medicare Provider Utilization and Payment Data database was queried using Current Procedural Terminology and Evaluation and Management codes to identify clinic visits and cataract, glaucoma drainage implant (GDI), trabeculectomy, minimally invasive glaucoma surgery (MIGS), and office-based glaucoma laser procedures. The number of procedures performed per provider was averaged and compared between genders. The univariate ordinary least squares linear regression analysis was used to investigate the effects of gender on procedural volume. The multivariate ordinary least squares linear regression analysis was used to examine the effects of gender, the number of group practice members, and the number of years after medical school graduation on cataract, GDI, trabeculectomy, MIGS, and glaucoma laser procedural volumes. MAIN OUTCOME MEASURES: Mean difference in the number of procedures by gender and predictors of procedural volume. RESULTS: In the univariate analysis, men performed an estimated 7.8 more MIGSs (95% confidence interval [CI], 2.7-12.9; P = 0.003), 138.9 more cataract procedures (95% CI, 59.6-218.3; P = 0.0006), and 1.99 more GDI procedures (95% CI, 0.03-3.95; P = 0.046) than women. This relationship remained true for MIGS and cataract procedures in the multivariate analysis after controlling for clinical volume, the number of group practice members, and the number of years after medical school graduation (MIGS, ß = 6.1 [95% CI, 0.5-11.8; P = 0.03]; cataract, ß = 110.2 [95% CI, 16.9-203.5; P = 0.02]). Glaucoma drainage implant procedures were no longer associated with the gender of the surgeon in the multivariate analysis (ß = 2.1, 95% CI, -0.1 to 4.2; P = 0.06). The volumes of trabeculectomy and office-based glaucoma laser procedures did not differ between the genders in both the univariate (glaucoma laser, ß = 7.0 [95% CI, -4.4 to 18.5; P = 0.23]; trabeculectomy, ß = 2.7 [95% CI, -0.8 to 6.2; P = 0.13]) and multivariate analyses (glaucoma laser, ß = -7.3 [95% CI, -18.7 to 4.1; P = 0.21]; trabeculectomy, ß = 1.7 [95% CI, -5.6 to 2.1; P = 0.38]). CONCLUSIONS: Women performed fewer MIGS and cataract procedures than men, even after controlling for clinical volume, the number of years after medical school graduation, and the number of group practice members. After controlling for these factors, there was no difference in the incisional glaucoma or glaucoma laser procedural volume between genders. Further research is needed to understand factors contributing to these differences.

Implementation of a Collaborated Antimicrobial Stewardship Program and Outpatient Parenteral Antimicrobial Therapy (OPAT) Unit-driven Monoclonal Antibody Therapy Program for COVID-19 at an NYC Hospital.

OBJECTIVES: This study aimed to assess the processes and clinical outcomes of a joint collaboration between Antimicrobial Stewardship Program (ASP) and the outpatient parenteral antimicrobial therapy (OPAT) unit for delivery of monoclonal antibody therapy for mild-to-moderate COVID-19. METHODS: We carried out a retrospective, interim analysis of our COVID-19 monoclonal antibody therapy program. Outcomes included clinical response, incidence of hospitalization, and adverse events. RESULTS: A total of 175 patients (casirivimab-imdevimab, n = 130; bamlanivimab, n = 45) were treated between December 2020 and March 1, 2021. The median time from symptom onset was 6 (IQR 4, 8) days at time of treatment. Of 135 patients available for follow-up, 71.9% and 85.9% of patients reported symptom improvement within 3 and 7 days of treatment, respectively. A total of 9 (6.7%) patients required COVID-19-related hospitalization for progression of symptoms, all within 14 days of treatment. A total of 7 (4%) patients experienced an infusion-related reaction. CONCLUSIONS: ASP-OPAT collaboration is a novel approach to implement an efficient and safe monoclonal antibody therapy program for the treatment of mild-to-moderate COVID-19.

Fatal case of disseminated cryptococcal infection and meningoencephalitis in the setting of prolonged glucocorticoid use in a Covid-19 positive patient.

Based on the RECOVERY trial, glucocorticoids have become the mainstay of treatment for COVID-19, thus increasing the risk of opportunistic infections. We report a case of disseminated Cryptococcus neoformans with documented meningoencephalitis in a patient with severe COVID-19 in the setting of prolonged glucocorticoid administration with poor outcome likely due to adrenal involvement.

Accuracy of the Veterans Health Administration COVID-19 (VACO) Index for predicting short-term mortality among 1307 US academic medical centre inpatients and 427 224 US Medicare patients.

BACKGROUND: The Veterans Health Administration COVID-19 (VACO) Index predicts 30-day all-cause mortality in patients with COVID-19 using age, sex and pre-existing comorbidity diagnoses. The VACO Index was initially developed and validated in a nationwide cohort of US veterans-we now assess its accuracy in an academic medical centre and a nationwide US Medicare cohort. METHODS: With measures and weights previously derived and validated in US national Veterans Health Administration (VA) inpatients and outpatients (n=13 323), we evaluated the accuracy of the VACO Index for estimating 30-day all-cause mortality using area under the receiver operating characteristic curve (AUC) and calibration plots of predicted versus observed mortality in inpatients at a single US academic medical centre (n=1307) and in Medicare inpatients and outpatients aged 65+ (n=427 224). RESULTS: 30-day mortality varied by data source: VA 8.5%, academic medical centre 17.5%, Medicare 16.0%. The VACO Index demonstrated similar discrimination in VA (AUC=0.82) and academic medical centre inpatient population (AUC=0.80), and when restricted to patients aged 65+ in VA (AUC=0.69) and Medicare inpatient and outpatient data (AUC=0.67). The Index modestly overestimated risk in VA and Medicare data and underestimated risk in Yale New Haven Hospital data. CONCLUSIONS: The VACO Index estimates risk of short-term mortality across a wide variety of patients with COVID-19 using data available prior to or at the time of diagnosis. The VACO Index could help inform primary and booster vaccination prioritisation, and indicate who among outpatients testing positive for SARS-CoV-2 should receive greater clinical attention or scarce treatments.

Endovascular therapy versus microsurgical clipping of unruptured wide-neck aneurysms: a prospective multicenter study with propensity score analysis.

OBJECTIVE: Numerous techniques have been developed to treat wide-neck aneurysms (WNAs), each with different safety and efficacy profiles. Few studies have compared endovascular therapy (EVT) with microsurgery (MS). The authors' objective was to perform a prospective multicenter study of a WNA registry using rigorous outcome assessments and to compare EVT and MS using propensity score analysis (PSA). METHODS: Unruptured, saccular, not previously treated WNAs were included. WNA was defined as an aneurysm with a neck width ≥ 4 mm or a dome-to-neck ratio (DTNR) < 2. The primary outcome was modified Rankin Scale (mRS) score at 1 year after treatment (good outcome was defined as mRS score 0-2), as assessed by blinded research nurses and compared with PSA. Angiographic outcome was assessed using the Raymond scale with core laboratory review (adequate occlusion was defined as Raymond scale score 1-2). RESULTS: The analysis included 224 unruptured aneurysms in the EVT cohort (n = 140) and MS cohort (n = 84). There were no differences in baseline demographic characteristics, such as proportion of patients with good baseline mRS score (94.3% of the EVT cohort vs 94.0% of the MS cohort, p = 0.941). WNA inclusion criteria were similar between cohorts, with the most common being both neck width ≥ 4 mm and DTNR < 2 (50.7% of the EVT cohort vs 50.0% of the MS cohort, p = 0.228). More paraclinoid (32.1% vs 9.5%) and basilar tip (7.1% vs 3.6%) aneurysms were treated with EVT, whereas more middle cerebral artery (13.6% vs 42.9%) and pericallosal (1.4% vs 4.8%) aneurysms were treated with MS (p < 0.001). EVT aneurysms were slightly larger (p = 0.040), and MS aneurysms had a slightly lower mean DTNR (1.4 for the EVT cohort vs 1.3 for the MS cohort, p = 0.010). Within the EVT cohort, 9.3% of patients underwent stand-alone coiling, 17.1% balloon-assisted coiling, 34.3% stent-assisted coiling, 37.1% flow diversion, and 2.1% PulseRider-assisted coiling. Neurological morbidity secondary to a procedural complication was more common in the MS cohort (10.3% vs 1.4%, p = 0.003). One-year mRS scores were assessed for 218 patients (97.3%), and no significantly increased risk of poor clinical outcome was found for the MS cohort (OR 2.17, 95% CI 0.84-5.60, p = 0.110). In an unadjusted direct comparison, more patients in the EVT cohort achieved a good clinical outcome at 1 year (93.4% vs 84.1%, p = 0.048). Final adequate angiographic outcome was superior in the MS cohort (97.6% of the MS cohort vs 86.5% of the EVT cohort, p = 0.007). CONCLUSIONS: Although the treatments for unruptured WNA had similar clinical outcomes according to PSA, there were fewer complications and superior clinical outcome in the EVT cohort and superior angiographic outcomes in the MS cohort according to the unadjusted analysis. These results may be considered when selecting treatment modalities for patients with unruptured WNAs.

Endovascular Therapy Versus Microsurgical Clipping of Ruptured Wide Neck Aneurysms (EVERRUN Registry): a multicenter, prospective propensity score analysis.

OBJECTIVE: Randomized controlled trials have demonstrated the superiority of endovascular therapy (EVT) compared to microsurgery (MS) for ruptured aneurysms suitable for treatment or when therapy is broadly offered to all presenting aneurysms; however, wide neck aneurysms (WNAs) are a challenging subset that require more advanced techniques and warrant further investigation. Herein, the authors sought to investigate a prospective, multicenter WNA registry using rigorous outcome assessments and compare EVT and MS using propensity score analysis (PSA). METHODS: Untreated, ruptured, saccular WNAs were included in the analysis. A WNA was defined as having a neck ≥ 4 mm or a dome/neck ratio (DNR) < 2. The primary outcome was the modified Rankin Scale (mRS) score at 1 year posttreatment, as assessed by blinded research nurses (good outcome: mRS scores 0-2) and compared using PSA. RESULTS: The analysis included 87 ruptured aneurysms: 55 in the EVT cohort and 32 in the MS cohort. Demographics were similar in the two cohorts, including Hunt and Hess grade (p = 0.144) and modified Fisher grade (p = 0.475). WNA type inclusion criteria were similar in the two cohorts, with the most common type having a DNR < 2 (EVT 60.0% vs MS 62.5%). More anterior communicating artery aneurysms (27.3% vs 18.8%) and posterior circulation aneurysms (18.2% vs 0.0%) were treated with EVT, whereas more middle cerebral artery aneurysms were treated with MS (34.4% vs 18.2%, p = 0.025). Within the EVT cohort, 43.6% underwent stand-alone coiling, 50.9% balloon-assisted coiling, 3.6% stent-assisted coiling, and 1.8% flow diversion. The 1-year mRS score was assessed in 81 patients (93.1%), and the primary outcome demonstrated no increased risk for a poor outcome with MS compared to EVT (OR 0.43, 95% CI 0.13-1.45, p = 0.177). The durability of MS was higher, as evidenced by retreatment rates of 12.7% and 0% for EVT and MS, respectively (p = 0.04). CONCLUSIONS: EVT and MS had similar clinical outcomes at 1 year following ruptured WNA treatment. Because of their challenging anatomy, WNAs may represent a population in which EVT's previously demonstrated superiority for ruptured aneurysm treatment is less relevant. Further investigation into the treatment of ruptured WNAs is warranted.

The Impact of Interhospital Competition on Treatment Strategy and Outcomes for Unruptured Intracranial Aneurysms.

BACKGROUND: Interhospital competition has been shown to affect surgical outcomes and expenditures. However, interhospital competition's impact on neurosurgery is poorly characterized. OBJECTIVE: To assess how interhospital competition is associated with treatment strategy and outcomes for unruptured intracranial aneurysms (UIAs). METHODS: We identified all elective UIA admissions in the National Inpatient Sample from 2002 to 2011. Competitive intensity of each hospital market was quantified using the validated Herfindahl-Hirschman Index (HHI), with lower values denoting higher competition. We then obtained nationwide HHI values for 2012 to 2016 from the Health Care Cost Project. Outcomes included treatment modality (clipping, coiling, or nonoperative management), inpatient mortality, disposition, complications, length of stay (LOS), and costs. Multivariate regression assessed the association between HHI and outcomes, controlling for patient demographics, severity metrics, hospital characteristics, and treatment. RESULTS: We studied 157 979 elective UIA admissions at 1435 hospitals from 2002 to 2011, with an increase in coiling admissions (13.4% to 33.7%) and decrease in clipping admissions (30.9% to 17.6%). Mean hospital HHI was 0.11 (range = 0.001-0.97). Competition decreased for 61.8% of hospitals from 2002 to 2011 and 68.1% of metropolitan localities from 2012 to 2016. Admissions in more competitive hospital markets exhibited increased odds of undergoing surgery (odds ratio [OR] = 1.37, P < .001), with preference toward coiling over clipping (OR = 1.27, P < .001). HHI was not associated with mortality, disposition, or LOS. However, increased interhospital competition was associated with more complications (OR = 1.09, P = .001) and greater hospital costs (ß-coefficient = 1.06, P < .001). CONCLUSION: For UIA patients, admission to hospitals in more competitive geographies was associated with increased rates of surgical intervention, coiling utilization, complications, and hospitalization costs.

Improving symptom burden and quality of life in patients with myelofibrosis: current strategies and future directions.

INTRODUCTION: Myelofibrosis (MF) is a complex and aggressive hematologic malignancy resulting from JAK/STAT-driven myeloproliferation and abnormal fibrogenesis. The clinical manifestations are heterogeneous and negatively impact quality of life and survival. JAK inhibitors improve symptoms and splenomegaly to a variable degree in a proportion of patients, but the effects for many patients are insufficient or short-lived. AREAS COVERED: This review examines the constellation of symptoms that befall patients with MF, describes methods to quantify and serially monitor these symptoms, and evaluates pharmacologic and non-pharmacologic interventions for disease-related symptoms. The review also includes a discussion of areas of unmet medical need, and proposes future methods for meeting this need. EXPERT OPINION: The treatment landscape for MF is evolving rapidly. The most effective therapies or combinations of therapies will likely simultaneously impact both the malignant hematopoietic stem cell and mechanisms of aberrant fibrogenesis that drive this disease. The goals of treatment for patients with myelofibrosis should be to improve length and quality of life. Clinical trials must be designed with these goals in mind, with endpoints focused on overall survival and symptom reduction, as opposed to surrogate endpoints such as spleen volume reduction.

Conversion factors to derive organ doses for canine subjects undergoing CT examinations.

Although a large number of CT scans are being conducted on small animals, especially in Western countries, little is known of absorbed dose from veterinary CT scans. In the current retrospective analytical study, we estimated the radiation dose delivered to dogs from CT scans with various scan protocols and compared the results with those of human patients. We adopted a total of three computerized canine models with three sizes combined with a computer simulation model of a CT scanner. The eyes of the dog model received the greatest dose, 1.10 mGy/mGy, in the head scan, followed by a brain dose of 0.85 mGy/mGy. In the chest, abdomen-pelvis (AP), chest-abdomen-pelvis, and head-chest-abdomen-pelvis scans, the heart wall (0.93 mGy/mGy), ovaries (0.99 mGy/mGy), lungs (1.12 mGy/mGy), and thyroid (1.23 mGy/mGy) received the greatest organ doses, respectively. The smallest dog model received up to 1.4-fold greater organ doses than the largest dog in both the chest and AP scans. Overall, the medium-size canine model received organ doses comparable to those of the 1-year-old child model in the head scan, the 5-year-old child in chest scan, and the 10-year-old child in AP scan. The organ dose conversion factors derived from this study should help evaluate absorbed dose for canine patients undergoing CT exams.

Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index.

BACKGROUND: Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples. METHODS AND FINDINGS: We reviewed SARS-CoV-2 testing results within the VA between February 8 and August 18, 2020. The sample was split into a development cohort (test positive between March 2 and April 15, 2020), an early validation cohort (test positive between April 16 and May 18, 2020), and a late validation cohort (test positive between May 19 and July 19, 2020). Our logistic regression model in the development cohort considered demographics (age, sex, race/ethnicity), and pre-existing medical conditions and the Charlson Comorbidity Index (CCI) derived from ICD-10 diagnosis codes. Weights were fixed to create the VACO Index that was then validated by comparing area under receiver operating characteristic curves (AUC) in the early and late validation cohorts and among important validation cohort subgroups defined by sex, race/ethnicity, and geographic region. We also evaluated calibration curves and the range of predictions generated within age categories. 13,323 individuals tested positive for SARS-CoV-2 (median age: 63 years; 91% male; 42% non-Hispanic Black). We observed 480/3,681 (13%) deaths in development, 253/2,151 (12%) deaths in the early validation cohort, and 403/7,491 (5%) deaths in the late validation cohort. Age, multimorbidity described with CCI, and a history of myocardial infarction or peripheral vascular disease were independently associated with mortality-no other individual comorbid diagnosis provided additional information. The VACO Index discriminated mortality in development (AUC = 0.79, 95% CI: 0.77-0.81), and in early (AUC = 0.81 95% CI: 0.78-0.83) and late (AUC = 0.84, 95% CI: 0.78-0.86) validation. The VACO Index allows personalized estimates of 30-day mortality after COVID-19 infection. For example, among those aged 60-64 years, overall mortality was estimated at 9% (95% CI: 6-11%). The Index further discriminated risk in this age stratum from 4% (95% CI: 3-7%) to 21% (95% CI: 12-31%), depending on sex and comorbid disease. CONCLUSION: Prior to infection, demographics and comorbid conditions can discriminate COVID-19 mortality risk overall and within age strata. The VACO Index reproducibly identified individuals at substantial risk of COVID-19 mortality who might consider continuing social distancing, despite relaxed state and local guidelines.

Interhospital competition and hospital charges and costs for patients undergoing cranial neurosurgery.

OBJECTIVE: Research has documented significant growth in neurosurgical expenditures and practice consolidation. The authors evaluated the relationship between interhospital competition and inpatient charges or costs in patients undergoing cranial neurosurgery. METHODS: The authors identified all admissions in 2006 and 2009 from the National Inpatient Sample. Admissions were classified into 5 subspecialties: cerebrovascular, tumor, CSF diversion, neurotrauma, or functional. Hospital-specific interhospital competition levels were quantified using the Herfindahl-Hirschman Index (HHI), an economic metric ranging continuously from 0 (significant competition) to 1 (monopoly). Inpatient charges (hospital billing) were multiplied with reported cost-to-charge ratios to calculate costs (actual resource use). Multivariate regressions were used to assess the association between HHI and inpatient charges or costs separately, controlling for 17 patient, hospital, severity, and economic factors. The reported ß-coefficients reflect percentage changes in charges or costs (e.g., ß-coefficient = 1.06 denotes a +6% change). All results correspond to a standardized -0.1 change in HHI (increase in competition). RESULTS: In total, 472,938 nationwide admissions for cranial neurosurgery treated at 896 unique hospitals met inclusion criteria. Hospital HHIs ranged from 0.099 to 0.724 (mean 0.298 ± 0.105). Hospitals in more competitive markets had greater charge/cost markups (ß-coefficient = 1.10, p < 0.001) and area wage indices (ß-coefficient = 1.04, p < 0.001). Between 2006 and 2009, average neurosurgical charges and costs rose significantly ($62,098 to $77,812, p < 0.001; $21,385 to $22,389, p < 0.001, respectively). Increased interhospital competition was associated with greater charges for all admissions (ß-coefficient = 1.07, p < 0.001) as well as cerebrovascular (ß-coefficient = 1.08, p < 0.001), tumor (ß-coefficient = 1.05, p = 0.039), CSF diversion (ß-coefficient = 1.08, p < 0.001), neurotrauma (ß-coefficient = 1.07, p < 0.001), and functional neurosurgery (ß-coefficient = 1.11, p = 0.037) admissions. However, no significant associations were observed between HHI and costs, except for CSF diversion surgery (ß-coefficient = 1.03, p = 0.021). Increased competition was not associated with important clinical outcomes, such as inpatient mortality, favorable discharge disposition, or complication rates, except for lower mortality for brain tumors (OR 0.78, p = 0.026), but was related to greater length of stay for all admissions (ß-coefficient = 1.06, p < 0.001). For a sensitivity analysis adjusting for outcomes, all findings for charges and costs remained the same. CONCLUSIONS: Hospitals in more competitive markets exhibited higher charges for admissions of patients undergoing an in-hospital cranial procedure. Despite this, interhospital competition was not associated with increased inpatient costs except for CSF diversion surgery. There was no corresponding improvement in outcomes with increased competition, with the exception of a potential survival benefit for brain tumor surgery.