Citations

AbstractObjectiveTo evaluate the impact of a virtual registered nurse (ViRN) model on safety and care outcomes. ViRN is a telemedicine intervention that enables an experienced virtual nurse to assist the in‐person care team in providing care to patients.Data Sources and Study SettingElectronic health records data were utilized from the Mayo Clinic during the intervention (December 2020–November 2021) and historical periods (December 2018–November 2019). ViRN was implemented on general medical units at the Mayo Clinic Rochester. We used general medical units at the Mayo Clinic Arizona as the comparison group.Study DesignThis study used a difference‐in‐differences design to evaluate the impact of ViRN compared to usual care on transfer to the intensive care unit (ICU), inpatient mortality, and length of stay (LOS). We used logistic regression for transfer to the ICU and inpatient mortality and negative binomial regression for LOS. We controlled for demographics, patient interaction with the health system, clinical characteristics, and admission characteristics. We clustered standard errors to account for patients who have multiple admissions during the study period.Principal FindingsThere were no significant differences for transfer to the ICU (average marginal effect (AME) −0.08 percentage point [95% confidence interval (CI): −1.34, 1.18]), inpatient mortality (AME 0.43 percentage point [95% CI: −0.33, 1.18]), or LOS (AME −0.20 days [95% CI: −0.57, 0.17]). The findings were mostly consistent across the sensitivity analyses.ConclusionsOur results suggest that ViRN led to similar outcomes as usual care in general medical units. These findings support the potential to develop more advanced models of ViRN at the Mayo Clinic and the dissemination of the ViRN model to other systems. In the context of staffing shortages and other disruptions to the delivery of nursing care, it is critical to understand whether new models like ViRN provide nurse staffing alternatives without negatively affecting outcomes.

Background Although online self-triage is easily accessible, little is known about the patients who use self-triage or their subsequent diagnoses. We compared ear/hearing self-triage subsequent diagnoses to ear/hearing visit diagnoses in emergency departments (ED) and ambulatory clinics across the United States. Methods We compared International Classification of Diseases version 10 (ICD10) coded diagnoses following online self-triage for ear/hearing concerns with those from national ED and ambulatory clinic samples. We used data from the Centers for Disease Control (CDC) National Hospital Ambulatory Medical Care Survey (NHAMCS) and National Ambulatory Medical Care Survey (NAMCS) for comparison. Using matched ear/hearing diagnostic categories for those aged 1 and over, we compared self-triage diagnosis frequencies with national ED and ambulatory diagnosis frequencies. Results Following ear/hearing self-triage, there were 1092 subsequent office visits with a primary diagnosis code. For five frequently diagnosed ear/hearing conditions (i.e., suppurative and nonsuppurative otitis media [OM], otalgia, otitis externa, and cerumen impaction), there was a strong correlation between diagnosis counts made following self-triage and estimated counts of national ED visit diagnoses (r = 0.94; CI 95% [0.37 to 0.99]; p = .016, adjusted r2 = 0.85). Seven diagnoses were available to compare with the national ambulatory sample; correlation was r = 0.79; CI 95% [0.08 to 0.97]; p = .037, adjusted r2 = 0.54. For ages 1 and over, estimated hospital admissions from the national ED visits for ear/hearing were 0.76%, CI 95% [0.28-2.1%]; estimated total national ear/hearing ED visits were 7.5 million (for 4 years, 2016 through 2019). Conclusion The strong correlation of ear-related self-triage diagnoses with national ED diagnoses and the low hospitalization risk for these diagnoses suggests that there is an opportunity for self-triage of ear/hearing concerns to decrease ED visits for these symptoms.

ObjectiveTo describe a 41‐year‐old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin‐1 receptor antagonist (IL‐1Ra) protein, anakinra, since the age of 28, who presented with golf‐ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation.MethodsClinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo‐red staining and proteomic evaluation of microdissected Congo red–positive amyloid deposits by liquid chromatography‐tandem mass spectrometry.ResultsThe skin, stomach, and kidney biopsies all showed the presence of Congo red–positive amyloid deposits. Mass spectrometry‐based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL‐1Ra protein)‐type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P‐component) and the amyloidogenic IL‐1Ra protein, which were present in Congo red–positive areas and absent in Congo red–negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL‐1Ra (anakinra) and not endogenous wild‐type IL‐1Ra.ConclusionThis is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra).

PURPOSE Uterine leiomyosarcoma (uLMS) is an aggressive subtype of soft-tissue sarcoma with frequent metastatic relapse after curative surgery. Chemotherapy provides limited benefit for advanced disease. Multiomics profiling studies have identified homologous recombination deficiency in uLMS. In preclinical studies where olaparib and temozolomide provided modest activity, the combination was highly effective for inhibiting uLMS tumor growth. PATIENTS AND METHODS NCI Protocol 10250 is a single-arm, open-label, multicenter, phase II study evaluating olaparib and temozolomide in advanced uLMS. Patients with progression on ≥1 prior line received temozolomide 75 mg/m2 orally once daily with olaparib 200 mg orally twice a day both on days 1-7 in 21-day cycles. The primary end point was the best objective response rate (ORR) within 6 months. A one-stage binomial design was used. If ≥5 of 22 responded, the treatment would be considered promising (93% power; α = .06). All patients underwent paired biopsies that were evaluated with whole-exome sequencing (WES)/RNAseq and a RAD51 foci formation assay. RESULTS Twenty-two patients were evaluable. The median age was 55 years, and 59% had received three or more prior lines. Best ORR within 6 months was 23% (5 of 22). The overall ORR was 27% (6 of 22). The median progression-free survival (mPFS) was 6.9 months (95% CI, 5.4 months to not estimable). Hematologic toxicity was common (grade 3/4 neutropenia: 75%; thrombocytopenia: 32%) but manageable with dose modification. Five of 16 (31%) of tumors contained a deleterious homologous recombination gene alteration by WES, and 9 of 18 (50%) were homologous recombination-deficient by the RAD51 assay. In an exploratory analysis, mPFS was prolonged for patients with homologous recombination-deficient versus homologous recombination-proficient tumors (11.2 v 5.4 months, P = .05) by RAD51. CONCLUSION Olaparib and temozolomide met the prespecified primary end point and provided meaningful clinical benefit in patients with advanced, pretreated uLMS.

Introduction The superficial and deep parasternal intercostal plane (DPIP) blocks are two new blocks for thoracic pain. There are limited cadaveric studies evaluating the dye spread with these blocks. In this study, we examined the dye spread of an ultrasound-guided DPIP block in a human cadaveric model. Methods Five ultrasound-guided DPIP blocks were performed in four unembalmed human cadavers using an in-plane approach with a linear transducer oriented in a transverse plane adjacent to the sternum. Twenty milliliters of 0.1% methylene blue were injected between ribs 3 and 4 into the plane deep to the internal intercostal muscles and superficial to the transversus thoracis muscle layer. The chest muscles were dissected, and the extent of dye spread was documented in both cephalocaudal and mediolateral directions. Results The transversus thoracis muscle slips were stained in all cadavers from 4 to 6 levels. Intercostal nerves were dyed in all specimens. Four levels of intercostal nerves were dyed in each specimen with variability in number of levels stained above and below the level of the injection. Conclusions The DPIP block spreads along the tissue plane above the transversus thoracis muscles to multiple levels to dye the intercostal nerves in this cadaver study. This block may be of clinical value for analgesia in anterior thoracic surgical procedures.

Abstract Background Although a shared experience throughout the world, menstrual symptomatology is underreported and often misunderstood, by both individuals who menstruate and their providers. This study aimed to investigate symptomatology throughout the menstrual cycle, including the frequency of symptoms reported for each phase of the cycle and the relationship between symptoms. Methods This study included self-reported cycle information and symptoms during ovulatory menstrual cycles in mobile application users. Symptom frequency was described overall, by phase, and by day. Relationships between symptoms were examined through correlation coefficients and term frequency-inverse document frequency analysis. Results 437,577 unique users and 896,051 unique cycles were included in the analysis. Somatic symptoms were most frequently reported, logged in 88.3% of cycles. Of the total symptoms logged, somatic, gastrointestinal, and negative mood symptoms were most prevalent in the late luteal and bleeding days. In contrast, positive mood and discharge were most reported in the fertile window. Mood symptoms were highly correlated with each other (energetic mood and happy mood r = 0.62, anxious mood and obsessive thoughts r = 0.60). Fatigue was highly correlated with somatic and gastrointestinal symptoms such as bloating (r = 0.62), headache (r = 0.60), backache (r = 0.58), and nausea (r = 0.55). Conclusions Menstrual cycle-related symptoms are very common and vary throughout the menstrual cycle. While negative symptoms, including pain, bloating, and negative mood, are most commonly reported, women also report positive symptoms, such as energetic and happy mood. Self-reported data from cycle tracking and health apps can improve our understanding of the prevalence and variability of menstrual-related symptoms. Trial Registration Not applicable.

AbstractBackgroundWomen have higher rates of hypertension at the time of menopausal transition than men. Although elevated systolic and diastolic blood pressures (SBP and DBP) are risk factors for white matter (WM) injury both in women and men, WM hyperintensities (WMH), a marker of WM injury, are more common in women than in men after the age of 60. Thus, women may be vulnerable to the effects of elevated BP on WM integrity during menopausal transition. We investigated the association of BP in recently postmenopausal women with good cardiovascular health with WMH volume assessed 13 years later.MethodWomen (n = 212; median age = 67; range 58‐72), who were previously enrolled in a multi‐site randomized menopausal hormone therapy trial, Kronos Early Estrogen Prevention Study (KEEPS), participated in the present observational KEEPS Continuation Study. SBP and DBP were measured at KEEPS baseline (median age = 54 years; range 44‐59). Participants who were on antihypertensive medications at KEEPS baseline were excluded from the analysis (n = 34). Approximately 9 years after the end of KEEPS menopausal hormones versus placebo 4‐year interventions, WM integrity was assessed with automated WMH volume measurements from 3D‐FLAIR MRI. Associations of baseline SBP and DBP with logWMH volume measured 13 years later were tested by linear regression analyses. Model 1 was adjusted for age, study site, and total intracranial volume. Model 2 was adjusted for covariates of model 1, triglycerides, low density lipoproteins, and waist/hip ratio.ResultThe median SBP was 116 (range 83‐158) and DBP was 74 (range 56‐98). Higher SBP was associated with greater WMH volume (model 1:p = 0.005; model 2:p = 0.005). Similarly, higher DBP was associated with greater WMH volume (model 1:p = 0.008; model 2:p = 0.006) (Figure 1). Neither menopausal hormone therapies versus placebo, nor having high/low SBP (≥120/<120) modified these associations. Voxel‐based analyses demonstrate the association of BPs with the spatial distribution of WMHs (Figure 2).ConclusionHigher BPs in recently menopausal women were associated with greater WM injury more than a decade later after adjusting for CVD risk factors. Early postmenopausal stage is a critical time for BP control in women, which may reduce the risk of WM injury later in life.

Background Hematologic toxicities, including coagulopathy, endothelial activation, and cytopenias, with CD19-targeted chimeric antigen receptor (CAR) T-cell therapies correlate with cytokine release syndrome (CRS) and neurotoxicity severity, but little is known about the extended toxicity profiles of CAR T-cells targeting alternative antigens. This report characterizes hematologic toxicities seen following CD22 CAR T-cells and their relationship to CRS and neurotoxicity. Methods We retrospectively characterized hematologic toxicities associated with CRS seen on a phase 1 study of anti-CD22 CAR T-cells for children and young adults with relapsed/refractory CD22+ hematologic malignancies. Additional analyses included correlation of hematologic toxicities with neurotoxicity and exploring effects of hemophagocytic lymphohistiocytosis-like toxicities (HLH) on bone marrow recovery and cytopenias. Coagulopathy was defined as evidence of bleeding or abnormal coagulation parameters. Hematologic toxicities were graded by Common Terminology Criteria for Adverse Events V.4.0. Results Across 53 patients receiving CD22 CAR T-cells who experienced CRS, 43 (81.1%) patients achieved complete remission. Eighteen (34.0%) patients experienced coagulopathy, of whom 16 had clinical manifestations of mild bleeding (typically mucosal bleeding) which generally subsided following CRS resolution. Three had manifestations of thrombotic microangiopathy. Patients with coagulopathy had higher peak ferritin, D-dimer, prothrombin time, international normalized ratio (INR), lactate dehydrogenase (LDH), tissue factor, prothrombin fragment F1+2 and soluble vascular cell adhesion molecule-1 (s-VCAM-1). Despite a relatively higher incidence of HLH-like toxicities and endothelial activation, overall neurotoxicity was generally less severe than reported with CD19 CAR T-cells, prompting additional analysis to explore CD22 expression in the central nervous system (CNS). Single-cell analysis revealed that in contrast to CD19 expression, CD22 is not on oligodendrocyte precursor cells or on neurovascular cells but is seen on mature oligodendrocytes. Lastly, among those attaining CR, grade 3–4 neutropenia and thrombocytopenia were seen in 65% of patients at D28. Conclusion With rising incidence of CD19 negative relapse, CD22 CAR T-cells are increasingly important for the treatment of B-cell malignancies. In characterizing hematologic toxicities on CD22 CAR T-cells, we demonstrate that despite endothelial activation, coagulopathy, and cytopenias, neurotoxicity was relatively mild and that CD22 and CD19 expression in the CNS differed, providing one potential hypothesis for divergent neurotoxicity profiles. Systematic characterization of on-target off-tumor toxicities of novel CAR T-cell constructs will be vital as new antigens are targeted. Trial registration number NCT02315612 .