Utility of Angle Correction for Hemodynamic Measurements with Doppler Echocardiography.

OBJECTIVES: The routine application angle correction (AnC) in hemodynamic measurements with transesophageal echocardiography currently is not recommended but potentially could be beneficial. The authors hypothesized that AnC can be applied reliably and may change grading of aortic stenosis (AS). DESIGN: Retrospective analysis. SETTING: Single institution, university hospital. PARTICIPANTS: During phase I, use of AnC was assessed in 60 consecutive patients with intraoperative transesophageal echocardiography. During phase II, 129 images from a retrospective cohort of 117 cases were used to quantify AS by mean pressure gradient. INTERVENTIONS: A panel of observers used custom-written software in Java to measure intra-individual and inter-individual correlation in AnC application, correlation with preoperative transthoracic echocardiography gradients, and regrading of AS after AnC. MEASUREMENTS AND MAIN RESULTS: For phase I, the median AnC was 21 (16-35) degrees, and 17% of patients required no AnC. For phase II, the median AnC was 7 (0-15) degrees, and 37% of assessed images required no AnC. The mean inter-individual and intra-individual correlation for AnC was 0.50 (95% confidence interval [CI] 0.49-0.52) and 0.87 (95% CI 0.82-0.92), respectively. AnC did not improve agreement with the transthoracic echocardiography mean pressure gradient. The mean inter-rater and intra-rater agreement for grading AS severity was 0.82 (95% CI 0.81-0.83) and 0.95 (95% CI 0.91-0.95), respectively. A total of 241 (7%) AS gradings were reclassified after AnC was applied, mostly when the uncorrected mean gradient was within 5 mmHg of the severity classification cutoff. CONCLUSIONS: AnC can be performed with a modest inter-rater and intra-rater correlation and high degree of inter-rater and intra-rater agreement for AS severity grading.

Electronic Care Coordination From the Preoperative Clinic.

Fragmented and variable perioperative care exposes patients to unnecessary risks and handoff errors. The perioperative surgical home aims to optimize quality, value-based care. We performed a retrospective evaluation of how a preoperative assessment center could coordinate care through e-mails sent to a patient's healthcare team that initiate discussion on critical clinical information. During 100 clinic days on which 8122 patients were evaluated, 606 triggered e-mails, with a potential impact on 19 elements across the perioperative care spectrum. Four cases were canceled, and 42 cases were rescheduled. By fostering information exchange, these communications could advance patient-centered, value-enhanced quality and safety outcomes.

A nurse-driven penicillin allergy risk score in the preoperative setting was associated with increased cefazolin use perioperatively.

STUDY OBJECTIVE: To characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use. DESIGN: Quasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated. SETTING: Outpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center. PATIENTS: 670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively. INTERVENTION: A paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use. MEASUREMENTS: Antibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 - April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants. MAIN RESULTS: Of 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09-2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42-0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35-0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention. CONCLUSIONS: A simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation.

Point-Of-Care Ultrasound Screening for Proximal Lower Extremity Deep Venous Thrombosis.

Acute lower extremity deep venous thrombosis (DVT) is a serious vascular disorder that requires accurate and early diagnosis to prevent life-threatening sequelae. While whole leg compression ultrasound with color and spectral Doppler is commonly performed in radiology and vascular labs, point-of-care ultrasound (POCUS) is becoming more common in the acute care setting. Providers appropriately trained in focused POCUS can perform a rapid bedside examination with high sensitivity and specificity in critically ill patients. This paper describes a simplified yet validated approach to POCUS by describing a three-zone protocol for lower extremity DVT POCUS image acquisition. The protocol explains the steps in obtaining vascular images at six compression points in the lower extremity. Beginning at the level of the proximal thigh and moving distally to the popliteal space, the protocol guides the user through each of the compression points in a stepwise manner: from the common femoral vein to the femoral and deep femoral vein bifurcation, and, finally, to the popliteal vein. Further, a visual aid is provided that may assist providers during real-time image acquisition. The goal in presenting this protocol is to help make proximal lower extremity DVT exams more accessible and efficient for POCUS users at the patient's bedside.

Association of neurocognitive disorders with morbidity and mortality in older adults undergoing major surgery in the USA: a retrospective, population-based, cohort study.

BACKGROUND: Neurocognitive disorders become increasingly common as patients age, and increasing numbers of surgical interventions are done on older patients. The aim of this study was to understand the clinical characteristics and outcomes of surgical patients with neurocognitive disorders in the USA in order to guide future targeted interventions for better care. METHODS: This retrospective cohort study used claims data for US Medicare beneficiaries aged 65 years and older with a record of inpatient admission for a major diagnostic or therapeutic surgical procedure between Jan 1, 2017, and Dec 31, 2018. Data were retrieved through a data use agreement between Dartmouth Hitchcock Medical Center and US Centers for Medicare and Medicaid Services via the Research Data Assistance Center. The exposure of interest was the presence of a pre-existing neurocognitive disorder as defined by diagnostic code within 3 years of index hospital admission. The primary outcome was mortality at 30 days, 90 days, and 365 days from date of surgery among all patients with available data. FINDINGS: Among 5 263 264 Medicare patients who underwent a major surgical procedure, 767 830 (14·59%) had a pre-existing neurocognitive disorder and 4 495 434 (85·41%) had no pre-existing neurocognitive disorder. Adjusting for demographic factors and comorbidities, patients with a neurocognitive disorder had higher 30-day (hazard ratio 1·24 [95% CI 1·23-1·25]; p<0·0001), 90-day (1·25 [1·24-1·26]; p<0·0001), and 365-day mortality (1·25 [1·25-1·26]; p<0·0001) compared with patients without a neurocognitive disorder. INTERPRETATION: Our findings suggest that the presence of a neurocognitive disorder is independently associated with an increased risk of mortality. Identification of a neurocognitive disorder before surgery can help clinicians to better disclose risks and plan for patient care after hospital discharge. FUNDING: Department of Anesthesiology and Perioperative Medicine at Dartmouth Hitchcock Medical Center.

Heparin-induced thrombocytopenia after total knee arthroplasty, with subsequent adrenal hemorrhage.

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune-mediated adverse effect of chemoprophylaxis for venous thromboembolic events. We present the case of a 44-year-old man who developed bilateral adrenal hemorrhage (BAH) as a sequela of HIT after bilateral total knee arthroplasty. In our review of clinical management of HIT-induced BAH, we discuss the 21 published cases of this phenomenon, 14 of which occurred after orthopedic surgery. Given the potentially fatal consequences and the importance of early intervention, physicians should be on the alert for recognizing HIT-induced BAH in patients experiencing shock unresponsive to fluid resuscitation. In addition, chemoprophylaxis with alternative agents such as a synthetic pentasaccharide factor Xa inhibitor and oral direct thrombin inhibitors that are associated with lower risks of HIT in orthopedic patients merits exploration.

VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail.

The product of the von Hippel-Lindau gene (VHL) acts as the substrate-recognition component of an E3 ubiquitin ligase complex that ubiquitylates the catalytic alpha subunit of hypoxia-inducible factor (HIF) for oxygen-dependent destruction. Although emerging evidence supports the notion that deregulated accumulation of HIF upon the loss of VHL is crucial for the development of clear-cell renal cell carcinoma (CC-RCC), the molecular events downstream of HIF governing renal oncogenesis remain unclear. Here, we show that the expression of a homophilic adhesion molecule, E-cadherin, a major constituent of epithelial cell junctions whose loss is associated with the progression of epithelial cancers, is significantly down-regulated in primary CC-RCC and CC-RCC cell lines devoid of VHL. Reintroduction of wild-type VHL in CC-RCC (VHL(-/-)) cells markedly reduced the expression of E2 box-dependent E-cadherin-specific transcriptional repressors Snail and SIP1 and concomitantly restored E-cadherin expression. RNA interference-mediated knockdown of HIFalpha in CC-RCC (VHL(-/-)) cells likewise increased E-cadherin expression, while functional hypoxia or expression of VHL mutants incapable of promoting HIFalpha degradation attenuated E-cadherin expression, correlating with the disengagement of RNA polymerase II from the endogenous E-cadherin promoter/gene. These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin.

Loss of JAK2 regulation via a heterodimeric VHL-SOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia.

Chuvash polycythemia is a rare congenital form of polycythemia caused by homozygous R200W and H191D mutations in the VHL (von Hippel-Lindau) gene, whose gene product is the principal negative regulator of hypoxia-inducible factor. However, the molecular mechanisms underlying some of the hallmark abnormalities of Chuvash polycythemia, such as hypersensitivity to erythropoietin, are unclear. Here we show that VHL directly binds suppressor of cytokine signaling 1 (SOCS1) to form a heterodimeric E3 ligase that targets phosphorylated JAK2 (pJAK2) for ubiquitin-mediated destruction. In contrast, Chuvash polycythemia-associated VHL mutants have altered affinity for SOCS1 and do not engage with and degrade pJAK2. Systemic administration of a highly selective JAK2 inhibitor, TG101209, reversed the disease phenotype in Vhl(R200W/R200W) knock-in mice, an experimental model that recapitulates human Chuvash polycythemia. These results show that VHL is a SOCS1-cooperative negative regulator of JAK2 and provide biochemical and preclinical support for JAK2-targeted therapy in individuals with Chuvash polycythemia.