University of New Mexico Hospital

BACKGROUND: In May 1993 an outbreak of severe respiratory illness occurred in the southwestern United States. A previously unknown hantavirus was identified as the cause. In Asia hantaviruses are associated with hemorrhagic fever and renal disease. They have not been known as a cause of human disease in North America. METHODS: We analyzed clinical, laboratory, and autopsy data on the first 17 persons with confirmed infection from this newly recognized strain of hantavirus. RESULTS: The mean age of the patients was 32.2 years (range, 13 to 64); 61 percent were women, 72 percent were Native American, 22 percent white, and 6 percent Hispanic. The most common prodromal symptoms were fever and myalgia (100 percent), cough or dyspnea (76 percent), gastrointestinal symptoms (76 percent), and headache (71 percent). The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). The laboratory findings included leukocytosis (median peak cell count, 26,000 per cubic millimeter), often with myeloid precursors, an increased hematocrit, thrombocytopenia (median lowest platelet count, 64,000 per cubic millimeter), prolonged prothrombin and partial-thromboplastin times, an elevated serum lactate dehydrogenase concentration, decreased serum protein concentrations, and proteinuria. Rapidly progressive acute pulmonary edema developed in 15 of the 17 patients (88 percent), and 13 patients, all of whom had profound hypotension, died (case fatality rate, 76 percent). Increases in the hematocrit and partial-thromboplastin time were predictive of death. CONCLUSIONS: Infection with a newly described hantavirus causes the hantavirus pulmonary syndrome, which is characterized by a brief prodromal illness followed by rapidly progressive, noncardiogenic pulmonary edema.

BACKGROUND: The Injury Severity Score (ISS) has served as the standard summary measure of human trauma for 20 years. Despite its stalwart service, the ISS has two weaknesses: it relies upon the consensus derived severity estimates for each Abbreviated Injury Scale (AIS) injury and considers, at most, only three of an individual patient's injuries, three injuries that often are not even the patient's most severe injuries. Additionally, the ISS requires that all patients have their injuries described in the AIS lexicon, an expensive step that is currently taken only at hospitals with a zealous commitment to trauma care. We hypothesized that a data driven alternative to ISS that used empirically derived injury severities and considered all of an individual patient's injuries would more accurately predict survival. METHODS: Survival risk ratios were derived for every International Classification of Disease 9th Edition (ICD-9) injury category (800-959.9) using the North Carolina State Discharge Database experience with 300,000 trauma patients over 5 years. An ICD-9 Injury Severity Score (ICISS) was then defined as the product of all survival risk ratios for an individual patient's traumatic ICD-9 codes. We compared the performance of ISS and ICISS in a group of 3,142 patients accrued at the University of New Mexico Trauma Center over 4 years. These patients had both AIS and ICD-9 descriptors meticulously assigned prospectively by designated trauma data base personnel. RESULTS: ICISS outperformed ISS at a level that was highly statistically significant (p < 0.0001) and may be clinically important: ISS misclassification rate 7.67%, ISS Receiver Operator Characteristic Curve area = 0.872; ICISS misclassification rate 5.95%, ICISS Receiver Operator Characteristic Curve area = 0.921. Moreover, these improvements are largely preserved when ICISS is used in a probability of survival model that includes age, mechanism, and revised trauma score. About half of ICISS's improvement in predictive power is because of its use of an individual patient's worst three injuries regardless of body region. The remainder is because of better modeling of individual injuries and allowing all injuries to contribute to the final score. CONCLUSIONS: We conclude that ICISS is a much better predictor of survival than ISS in injured patients. The use of the ICD-9 lexicon may avoid the need for AIS coding, and thus may add an economic incentive to the statistical appeal of ICISS. It is possible that a similar data driven revision of ISS using the AIS vocabulary might perform as well or better than ICISS. Indeed, the actual lexicon used to divide up the injury "landscape" into individual injuries may be of little consequence so long as all injuries are considered and empirically derived SRRs are used to calculate the final injury measure.

The recent increase in the incidence of hepatocellular cancer in the United States is thought to underlie the rising mortality of this malignancy. However, it remains unknown whether survival of patients with hepatocellular carcinoma (HCC) has changed during the same time period. Using the SEER database (Surveillance, Epidemiology, and End Results) of the National Cancer Institute, we examined the temporal changes and determinants of survival among patients with histologically proven HCC over a 20-year period. Between 1977 and 1996, 7,389 patients diagnosed with HCC were followed in the survival database of SEER. The overall 1-year relative survival rate increased from 14% (95% confidence intervals (CI): 12-16) during 1977-1981 to 23% (95% CI: 21-24) during 1992 to 1996. Between the same two time periods, less improvement was seen in the 5-year survival rates, which increased from 2% (95% CI: 1-3) to only 5% (95% CI: 4-7). The median survival increased slightly from 0.57 years during 1977 to 1981 to 0.64 years during 1992 to 1996. In general, there were no significant differences in survival between men and women or between ethnic groups. During 1987 to 1991, a small fraction (0.8%) of patients underwent radical surgery; these patients had 1-year survival of 59% (95% CI: 35-83%), and 5-year survival of 35% (95% CI: 12-58%). Similar rates were seen during 1992-1996. In conclusion, a small improvement in survival of patients with HCC was seen between 1977 and 1996. Most of this apparent benefit is restricted to the first year following cancer diagnosis, raising the possibility of lead-time bias. There were no significant differences related to gender or ethnicity.

Venous thromboembolism (VTE) is a serious medical condition associated with significant morbidity and mortality, and an incidence that is expected to double in the next forty years. The advent of direct oral anticoagulants (DOACs) has catalyzed significant changes in the therapeutic landscape of VTE treatment. As such, it is imperative that clinicians become familiar with and appropriately implement new treatment paradigms. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for VTE treatment with the DOACs. When possible, guidance statements are supported by existing published evidence and guidelines. In instances where evidence or guidelines are lacking, guidance statements represent the consensus opinion of all authors of this manuscript and are endorsed by the Board of Directors of the Anticoagulation Forum.The authors of this manuscript first developed a list of pivotal practical questions related to real-world clinical scenarios involving the use of DOACs for VTE treatment. We then performed a PubMed search for topics and key words including, but not limited to, apixaban, antidote, bridging, cancer, care transitions, dabigatran, direct oral anticoagulant, deep vein thrombosis, edoxaban, interactions, measurement, perioperative, pregnancy, pulmonary embolism, reversal, rivaroxaban, switching, \thrombophilia, venous thromboembolism, and warfarin to answer these questions. Non- English publications and publications > 10 years old were excluded. In an effort to provide practical information about the use of DOACs for VTE treatment, answers to each question are provided in the form of guidance statements, with the intent of high utility and applicability for frontline clinicians across a multitude of care settings.

These cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Cancer Genetic Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Key components include the intake (medical and family histories), psychosocial assessment (assessment of risk perception), cancer risk assessment (determination and communication of risk), molecular testing for hereditary cancer syndromes (regulations, informed consent, and counseling process), and follow-up considerations. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client.

BACKGROUND: Project ECHO (Extension for Community Healthcare Outcomes) trains and mentors primary care providers (PCPs) in the care of patients with complex conditions. ECHO is a distance education model that connects specialists with numerous PCPs via simultaneous video link for the purpose of facilitating case-based learning. This article describes a teleECHO clinic based at the University of New Mexico Health Sciences Center that is focused on treatment of substance use disorders (SUDs) and behavioral health disorders. METHODS: Since 2005, specialists in treatment of SUDs and behavioral health disorders at Project ECHO have offered a weekly 2-hour Integrated Addictions and Psychiatry (IAP) TeleECHO Clinic focused on supporting PCP evaluation and treatment of SUDs and behavioral health disorders. We tabulate the number of teleECHO clinic sessions, participants, and CME/CEU (continuing medical education/continuing education unit) credits provided annually. This teleECHO clinic has also been used to recruit physicians to participate in DATA-2000 buprenorphine waiver trainings. Using a database of the practice location of physicians who received the buprenorphine waiver since 2002, the number of waivered physicians per capita in US states was calculated. The increase in waivered physicians practicing in underserved areas in New Mexico was evaluated and compared with the rest of the United States. RESULTS: Since 2008, approximately 950 patient cases have been presented during the teleECHO clinic, and more than 9000 hours of CME/CEU have been awarded. Opioids are the substances discussed most commonly (31%), followed by alcohol (21%) and cannabis (12%). New Mexico is near the top among US states in DATA-2000 buprenorphine-waivered physicians per capita, and it has had much more rapid growth in waivered physicians practicing in traditionally underserved areas compared with the rest of the United States since the initiation of the teleECHO clinic focused on SUDs in 2005. CONCLUSION: The ECHO model provides an opportunity to promote expansion of access to treatment for opioid use disorder and other SUDs, particularly in underserved areas.

We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitude in a decompression chamber [barometric pressure = 429 Torr, approximately 4,800 m (J. B. West, J. Appl. Physiol. 81: 1850-1854, 1996)], seven men exercised (Ex) at 50% of their altitude-specific maximal workload four times for 30 min in the first 6 h of a 10-h exposure. On another day they completed the same protocol but were sedentary (Sed). Measurements included an AMS symptom score, resting minute ventilation (VE), pulmonary function, arterial oxygen saturation (Sa(O(2))), fluid input, and urine volume. Symptoms of AMS were worse in Ex than Sed, with peak AMS scores of 4.4 +/- 1.0 and 1.3 +/- 0.4 in Ex and Sed, respectively (P < 0.01); but resting VE and Sa(O(2)) were not different between trials. However, Sa(O(2)) during the exercise bouts in Ex was at 76.3 +/- 1.7%, lower than during either Sed or at rest in Ex (81.4 +/- 1.8 and 82.2 +/- 2.6%, respectively, P < 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3-6 h (P = 0.06). The mechanism(s) responsible for the rise in severity and incidence of AMS in Ex may be sought in the observed exercise-induced exaggeration of arterial hypoxemia, in the minor fluid shift, or in a combination of these factors.

Data from two 3-month time periods before and after the arrival of a pediatric intensivist were collected prospectively and compared to determine the intensivist's impact on ICU mortality, use of monitoring and therapeutic modalities, and efficiency of ICU bed utilization. Severity of illness and care modalities were determined daily for all patients with the Physiologic Stability Index and the Therapeutic Intervention Scoring System. The only major organizational change in the postintensivist period was the organization and implementation of a daytime ICU team. Case mix variables, including sex; medical/surgical, emergency/elective, and diagnostic distributions; and nursing hours/patient day, were equivalent in the pre-intensivist and postintensivist samples. After the intensivist's arrival, there was a significant decrease in admissions with very low severity of illness (Physiologic Stability Index less than 4; 52% vs. 34%; p less than .05) and a significant decrease in bed utilization by patients who received only monitoring services (27% vs. 17% of bed days; p less than .001). The severity of the illness-adjusted ICU mortality rate was significantly higher in the pre-intensivist period than in the postintensivist period (weighted mean mortality difference 5.3 +/- 2.6%; p less than .05). The incidence of both therapeutic and monitoring modalities increased in the postintensivist period. These results indicate that a pediatric intensivist can improve mortality rates and efficiency of bed utilization in the pediatric ICU.

OBJECTIVE: The development of a new weight-related measure to assess quality of life in adolescents [Impact of Weight on Quality of Life (IWQOL)-Kids] is described. RESEARCH METHODS AND PROCEDURES: Using a literature search, clinical experience, and consultation with pediatric clinicians, 73 items were developed, pilot tested, and administered to 642 participants, 11 to 19 years old, recruited from weight loss programs/studies and community samples (mean z-BMI, 1.5; range, -1.2 to 3.4; mean age, 14.0; 60% female; 56% white). Participants completed the 73 items and the Pediatric Quality of Life Inventory and were weighed and measured. RESULTS: Four factors (27 items) were identified (physical comfort, body esteem, social life, and family relations), accounting for 71% of the variance. The IWQOL-Kids demonstrated excellent psychometric properties. Internal consistency coefficients ranged from 0.88 to 0.95 for scales and equaled 0.96 for total score. Convergent validity was demonstrated with strong correlations between IWQOL-Kids total score and the Pediatric Quality of Life Inventory (r = 0.76, p < 0.0001). Significant differences were found across BMI groups and between clinical and community samples, supporting the sensitivity of this measure. Participants in a weight loss camp demonstrated improved IWQOL-Kids scores, suggesting responsiveness of the IWQOL-Kids to weight loss/social support intervention. DISCUSSION: The present study provides preliminary evidence regarding the psychometric properties of the IWQOL-Kids, a weight-related quality of life measure for adolescents. Given the rise of obesity in youth, the development of a reliable and valid weight-related measure of quality of life is timely.

OBJECTIVE: To describe the clinical characteristics of a group of patients infected with the newly recognized hantavirus in the Southwestern United States. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: All patients with confirmed hantavirus infection admitted to the University of New Mexico Hospital between May 1, 1993 and January 1, 1994. INTERVENTIONS: Records of patients with hantavirus infection were reviewed to collect all pertinent clinical data. MEASUREMENTS AND MAIN RESULTS: Pulmonary disease in these patients was characterized by hypoxemia covering a wide range of severity. The cause of hypoxemia was an increased permeability (noncardiac) pulmonary edema which could be differentiated from hydrostatic (cardiac) pulmonary edema by its association with low pulmonary artery occlusion pressures and increased protein content of edema fluid. Hemodynamic measurements in severe cases showed a shock state characterized by a low cardiac index (range 1.6 to 3.0 L/min/min2), a low stroke volume index (range 10.5 to 29 mL/m2), and high systemic vascular resistance index (range 1,653 to 2,997 dyne.sec/cm5.m2). Progression to death was associated with worsening cardiac dysfunction unresponsive to treatment and causing oxygen debt and lactic acidosis. CONCLUSIONS: The two major life-threatening pathophysiologic changes in Hantavirus Pulmonary Syndrome are increased permeability pulmonary edema, and an atypical form of septic shock caused by myocardial depression and hypovolemia.

Vascular cognitive impairment and dementia (VCID) include a wide spectrum of chronic manifestations of vascular disease related to large vessel strokes and small vessel disease (SVD). Lacunar strokes and white matter (WM) injury are consequences of SVD. The main vascular risk factor for SVD is brain hypoperfusion from cerebral blood vessel narrowing due to chronic hypertension. The hypoperfusion leads to activation and degeneration of astrocytes with the resulting fibrosis of the extracellular matrix (ECM). Elasticity is lost in fibrotic cerebral vessels, reducing the response of stiffened blood vessels in times of increased metabolic need. Intermittent hypoxia/ischaemia activates a molecular injury cascade, producing an incomplete infarction that is most damaging to the deep WM, which is a watershed region for cerebral blood flow. Neuroinflammation caused by hypoxia activates microglia/macrophages to release proteases and free radicals that perpetuate the damage over time to molecules in the ECM and the neurovascular unit (NVU). Matrix metalloproteinases (MMPs) secreted in an attempt to remodel the blood vessel wall have the undesired consequences of opening the blood-brain barrier (BBB) and attacking myelinated fibres. This dual effect of the MMPs causes vasogenic oedema in WM and vascular demyelination, which are the hallmarks of the subcortical ischaemic vascular disease (SIVD), which is the SVD form of VCID also called Binswanger's disease (BD). Unravelling the complex pathophysiology of the WM injury-related inflammation in the small vessel form of VCID could lead to novel therapeutic strategies to reduce damage to the ECM, preventing the progressive damage to the WM.

Abstract Herpes simplex virus encephalitis tends to localize to the temporal and orbitofrontal lobes, giving characteristic clinical and pathological findings. Since the virus remains latent in the trigeminal ganglia, we postulate that this localization may be explained by reactivated virus spreading along the fifth nerve fibers, which innervate basal meninges of the anterior and middle fossae.

Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE.

IMPORTANCE: General surgical residency continues to experience attrition. To date, work hour amendments have not changed the annual rate of attrition. OBJECTIVE: To determine how often categorical general surgery residents seriously consider leaving residency. DESIGN, SETTING, AND PARTICIPANTS: At 13 residency programs, an anonymous survey of 371 categorical general surgery residents and 10-year attrition rates for each program. Responses from those who seriously considered leaving surgical residency were compared with those who did not. MAIN OUTCOMES AND MEASURES: Factors associated with the desire to leave residency. RESULTS: The survey response rate was 77.6%. Overall, 58.0% seriously considered leaving training. The most frequent reasons for wanting to leave were sleep deprivation on a specific rotation (50.0%), an undesirable future lifestyle (47.0%), and excessive work hours on a specific rotation (41.4%). Factors most often cited that kept residents from leaving were support from family or significant others (65.0%), support from other residents (63.5%), and perception of being better rested (58.9%). On univariate analysis, older age, female sex, postgraduate year, training in a university program, the presence of a faculty mentor, and lack of Alpha Omega Alpha status were associated with serious thoughts of leaving surgical residency. On multivariate analysis, only female sex was significantly associated with serious thoughts of leaving residency (odds ratio, 1.2; 95% CI, 1.1-1.3; P = .003). Eighty-six respondents were from historically high-attrition programs, and 202 respondents were from historically low-attrition programs (27.8% vs 8.4% 10-year attrition rate, P = .04). Residents from high-attrition programs were more likely to seriously consider leaving residency (odds ratio, 1.8; 95% CI, 1.0-3.0; P = .03). CONCLUSIONS AND RELEVANCE: A majority of categorical general surgery residents seriously consider leaving residency. Female residents are more likely to consider leaving. Thoughts of leaving seem to be associated with work conditions on specific rotations rather than with overall work hours and are more prevalent among programs with historically high attrition rates.

Using American Academy of Sleep Medicine research criteria, sleep-disordered breathing (SDB) was assessed in a pilot study of 187 sexual assault survivors with posttraumatic stress symptoms. Nightmares, sleep quality, distress, and quality of life were also assessed along with historical accounts of prior treatments for sleep complaints. Presumptive SDB diagnoses were established for 168 patients. Twenty-one of 168 underwent sleep testing, and all met objective SDB diagnostic criteria. There were no clinically meaningful differences in age, body-mass index, sleep quality, distress, or quality of life measures between 21 confirmed SDB cases and 147 suspected cases not tested. Compared with 19 women without SDB, 168 women with diagnosed or suspected SDB reported significantly worse nightmares, sleep quality, anxiety, depression, posttraumatic stress, and impaired quality of life. Despite suffering from sleep problems for an average of 20 years, which had not responded to repeated use of psychotropic medications or psychotherapy, few of these women had been referred to sleep specialists. SDB appears widespread among sexual assault survivors seeking help for nightmares. Research is needed to clarify the associations among SDB, distress, and physical and mental health impairment in trauma patients.

A cavus deformity of the foot is easily recognizable, but appropriate neurologic assessment can help to determine the etiology. Cavovarus, the most frequent type of cavus foot, presents with an elevated medial longitudinal arch, first ray plantarflexion, and, if rigid, a fixed heel varus. Common causes include progressive motor sensory conditions, typically Charcot-Marie-Tooth disease, and nonprogressive conditions such as cerebral palsy and poliomyelitis. A calcaneocavus foot may be seen in poliomyelitis, spinal dysraphism, and peripheral neuropathy. Initially, the cavus deformity is flexible, but if left untreated, it becomes a fixed bony deformity. Physical examination should include the cavovarus block test, which assesses flexibility of the hindfoot deformity and can direct surgical treatment. Standing radiographs of the feet and spine, magnetic resonance imaging, and electrodiagnostic studies may be useful. Management goals are to obtain a plantigrade, mobile, pain-free, stable, motor-balanced foot. Surgical options include soft-tissue and plantar fascia releases for a flexible deformity, osteotomy for a fixed deformity, and tendon transfers to restore muscle balance. Triple arthrodesis has poor long-term results in patients with progressive deformity and sensory impairment.

Importance: Hospital antimicrobial consumption data are widely available; however, large-scale assessments of the quality of antimicrobial use in US hospitals are limited. Objective: To evaluate the appropriateness of antimicrobial use for hospitalized patients treated for community-acquired pneumonia (CAP) or urinary tract infection (UTI) present at admission or for patients who had received fluoroquinolone or intravenous vancomycin treatment. Design, Setting, and Participants: This cross-sectional study included data from a prevalence survey of hospitalized patients in 10 Emerging Infections Program sites. Random samples of inpatients on hospital survey dates from May 1 to September 30, 2015, were identified. Medical record data were collected for eligible patients with 1 or more of 4 treatment events (CAP, UTI, fluoroquinolone treatment, or vancomycin treatment), which were selected on the basis of common infection types reported and antimicrobials given to patients in the prevalence survey. Data were analyzed from August 1, 2017, to May 31, 2020. Exposure: Antimicrobial treatment for CAP or UTI or with fluoroquinolones or vancomycin. Main Outcomes and Measures: The percentage of antimicrobial use that was supported by medical record data (including infection signs and symptoms, microbiology test results, and antimicrobial treatment duration) or for which some aspect of use was unsupported. Unsupported antimicrobial use was defined as (1) use of antimicrobials to which the pathogen was not susceptible, use in the absence of documented infection signs or symptoms, or use without supporting microbiologic data; (2) use of antimicrobials that deviated from recommended guidelines; or (3) use that exceeded the recommended duration. Results: Of 12 299 patients, 1566 patients (12.7%) in 192 hospitals were included; the median age was 67 years (interquartile range, 53-79 years), and 864 (55.2%) were female. A total of 219 patients (14.0%) were included in the CAP analysis, 452 (28.9%) in the UTI analysis, 550 (35.1%) in the fluoroquinolone analysis, and 403 (25.7%) in the vancomycin analysis; 58 patients (3.7%) were included in both fluoroquinolone and vancomycin analyses. Overall, treatment was unsupported for 876 of 1566 patients (55.9%; 95% CI, 53.5%-58.4%): 110 of 403 (27.3%) who received vancomycin, 256 of 550 (46.6%) who received fluoroquinolones, 347 of 452 (76.8%) with a diagnosis of UTI, and 174 of 219 (79.5%) with a diagnosis of CAP. Among patients with unsupported treatment, common reasons included excessive duration (103 of 174 patients with CAP [59.2%]) and lack of documented infection signs or symptoms (174 of 347 patients with UTI [50.1%]). Conclusions and Relevance: The findings suggest that standardized assessments of hospital antimicrobial prescribing quality can be used to estimate the appropriateness of antimicrobial use in large groups of hospitals. These assessments, performed over time, may inform evaluations of the effects of antimicrobial stewardship initiatives nationally.

PURPOSE To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline. METHODS An Expert Panel conducted a systematic review to identify randomized clinical trials and prospective-retrospective studies from January 2015 to January 2022. RESULTS The search identified 19 studies informing the evidence base. RECOMMENDATIONS Candidates for a regimen with a phosphatidylinositol 3-kinase inhibitor and hormonal therapy should undergo testing for PIK3CA mutations using next-generation sequencing of tumor tissue or circulating tumor DNA (ctDNA) in plasma to determine eligibility for alpelisib plus fulvestrant. If no mutation is found in ctDNA, testing in tumor tissue, if available, should be used. Patients who are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy should undergo testing for germline BRCA1 and BRCA2 pathogenic or likely pathogenic mutations to determine eligibility for a PARP inhibitor. There is insufficient evidence for or against testing for a germline PALB2 pathogenic variant to determine eligibility for PARP inhibitor therapy in the metastatic setting. Candidates for immune checkpoint inhibitor therapy should undergo testing for expression of programmed cell death ligand-1 in the tumor and immune cells to determine eligibility for treatment with pembrolizumab plus chemotherapy. Candidates for an immune checkpoint inhibitor should also undergo testing for deficient mismatch repair/microsatellite instability-high to determine eligibility for dostarlimab-gxly or pembrolizumab, as well as testing for tumor mutational burden. Clinicians may test for NTRK fusions to determine eligibility for TRK inhibitors. There are insufficient data to recommend routine testing of tumors for ESR1 mutations, for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection. There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Timely and accurate diagnosis of Alzheimer's disease (AD) in clinical practice remains challenging. PET and CSF biomarkers are the most widely used biomarkers to aid diagnosis in clinical research but present limitations for clinical practice (i.e., cost, accessibility). Emerging blood-based markers have the potential to be accurate, cost-effective, and easily accessible for widespread clinical use, and could facilitate timely diagnosis. The EU/US CTAD Task Force met in May 2022 in a virtual meeting to discuss pathways to implementation of blood-based markers in clinical practice. Specifically, the CTAD Task Force assessed: the state-of-art for blood-based markers, the current use of blood-based markers in clinical trials, the potential use of blood-based markers in clinical practice, the current challenges with blood-based markers, and the next steps needed for broader adoption in clinical practice.

RATIONALE: Controversies and practice variations exist related to the pharmacologic and nonpharmacologic management of the airway during rapid sequence intubation (RSI). OBJECTIVES: To develop evidence-based recommendations on pharmacologic and nonpharmacologic topics related to RSI. DESIGN: A guideline panel of 20 Society of Critical Care Medicine members with experience with RSI and emergency airway management met virtually at least monthly from the panel's inception in 2018 through 2020 and face-to-face at the 2020 Critical Care Congress. The guideline panel included pharmacists, physicians, a nurse practitioner, and a respiratory therapist with experience in emergency medicine, critical care medicine, anesthesiology, and prehospital medicine; consultation with a methodologist and librarian was available. A formal conflict of interest policy was followed and enforced throughout the guidelines-development process. METHODS: Panelists created Population, Intervention, Comparison, and Outcome (PICO) questions and voted to select the most clinically relevant questions for inclusion in the guideline. Each question was assigned to a pair of panelists, who refined the PICO wording and reviewed the best available evidence using predetermined search terms. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used throughout and recommendations of "strong" or "conditional" were made for each PICO question based on quality of evidence and panel consensus. Recommendations were provided when evidence was actionable; suggestions, when evidence was equivocal; and best practice statements, when the benefits of the intervention outweighed the risks, but direct evidence to support the intervention did not exist. RESULTS: From the original 35 proposed PICO questions, 10 were selected. The RSI guideline panel issued one recommendation (strong, low-quality evidence), seven suggestions (all conditional recommendations with moderate-, low-, or very low-quality evidence), and two best practice statements. The panel made two suggestions for a single PICO question and did not make any suggestions for one PICO question due to lack of evidence. CONCLUSIONS: Using GRADE principles, the interdisciplinary panel found substantial agreement with respect to the evidence supporting recommendations for RSI. The panel also identified literature gaps that might be addressed by future research.