Genetic testing in prostate cancer management: Considerations informing primary care.

Inherited genetic mutations can significantly increase the risk for prostate cancer (PC), may be associated with aggressive disease and poorer outcomes, and can have hereditary cancer implications for men and their families. Germline genetic testing (hereditary cancer genetic testing) is now strongly recommended for patients with advanced/metastatic PC, particularly given the impact on targeted therapy selection or clinical trial options, with expanded National Comprehensive Cancer Network guidelines and endorsement from multiple professional societies. Furthermore, National Comprehensive Cancer Network guidelines recommend genetic testing for men with PC across the stage and risk spectrum and for unaffected men at high risk for PC based on family history to identify hereditary cancer risk. Primary care is a critical field in which providers evaluate men at an elevated risk for PC, men living with PC, and PC survivors for whom germline testing may be indicated. Therefore, there is a critical need to engage and educate primary care providers regarding the role of genetic testing and the impact of results on PC screening, treatment, and cascade testing for family members of affected men. This review highlights key aspects of genetic testing in PC, the role of clinicians, with a focus on primary care, the importance of obtaining a comprehensive family history, current germline testing guidelines, and the impact on precision PC care. With emerging evidence and guidelines, clinical pathways are needed to facilitate integrated genetic education, testing, and counseling services in appropriately selected patients. There is also a need for providers to understand the field of genetic counseling and how best to collaborate to enhance multidisciplinary patient care.

Development and Optimization of a Subtraction-Normalized Immunocyte Profiling Signature for Prostate Cancer Active Surveillance Risk Stratification.

PURPOSE: Less invasive decision support tools are desperately needed to identify occult high-risk disease in men with prostate cancer (PCa) on active surveillance (AS). For a variety of reasons, many men on AS with low- or intermediate-risk disease forgo the necessary repeat surveillance biopsies needed to identify potentially higher-risk PCa. Here, we describe the development of a blood-based immunocyte transcriptomic signature to identify men harboring occult aggressive PCa. We then validate it on a biopsy-positive population with the goal of identifying men who should not be on AS and confirm those men with indolent disease who can safely remain on AS. This model uses subtraction-normalized immunocyte transcriptomic profiles to risk-stratify men with PCa who could be candidates for AS. MATERIALS AND METHODS: Men were eligible for enrollment in the study if they were determined by their physician to have a risk profile that warranted prostate biopsy. Both training (n = 1017) and validation cohort (n = 1198) populations had blood samples drawn coincident to their prostate biopsy. Purified CD2+ and CD14+ immune cells were obtained from peripheral blood mononuclear cells, and RNA was extracted and sequenced. To avoid overfitting and unnecessary complexity, a regularized regression model was built on the training cohort to predict PCa aggressiveness based on the National Comprehensive Cancer Network PCa guidelines. This model was then validated on an independent cohort of biopsy-positive men only, using National Comprehensive Cancer Network unfavorable intermediate risk and worse as an aggressiveness outcome, identifying patients who were not appropriate for AS. RESULTS: The best final model for the AS setting was obtained by combining an immunocyte transcriptomic profile based on 2 cell types with PSA density and age, reaching an AUC of 0.73 (95% CI: 0.69-0.77). The model significantly outperforms (P < .001) PSA density as a biomarker, which has an AUC of 0.69 (95% CI: 0.65-0.73). This model yields an individualized patient risk score with 90% negative predictive value and 50% positive predictive value. CONCLUSIONS: While further validation in an intended-use cohort is needed, the immunocyte transcriptomic model offers a promising tool for risk stratification of individual patients who are being considered for AS.

Emergency-release blood transfusions after postpartum hemorrhage at the Intermountain Healthcare hospitals.

BACKGROUND: Most low-risk obstetric patients do not have crossmatched blood available to treat unexpected postpartum hemorrhage. An emergency-release blood transfusion (ERBT) program is critical for hospitals with obstetrical services. We performed a retrospective analysis of obstetrical ERBTs administered in our multihospital system. DESIGN AND METHODS: We collected data from the past 8 years at all Intermountain Healthcare hospitals on every ERBT after postpartum hemorrhage; logging circumstances, number and type of transfused products, and outcomes. RESULTS: Eighty-nine women received ERBT following 224,035 live births, for an incidence of 3.97 transfused women/10,000 births. The most common causally-associated conditions were: uterine atony (40%), placental abruption/placenta previa (16%), retained placenta (11%), and uterine rupture (5%). The mean number of total units transfused was 7.9 (range 1-76). The mean number of red blood cells (RBCs) transfused was 4.8, the median 4, and SD was ±4.4. Massive transfusion protocols (MTPs) for trauma recommend using a ratio of 1:1:1 or 2:1:1 of RBC:FFP:Platelets, however the ratios varied widely for postpartum hemorrhage. Only 1.5% received a 1:1:1 ratio and 7.5% received a 2:1:1 ratio. Nineteen percent (17/89) of women underwent hysterectomy, 7% (6/89) had uterine artery embolization, 36% (32/89) had an intensive care unit admission, and 1% (1/89) died. CONCLUSION: Emergency transfusion for postpartum hemorrhage occurred after 1/2500 births. Most women received less FFP and platelets than recommended for traumatic hemorrhage. A potentially better practice for postpartum hemorrhage would be a balanced ratio of blood products, transfusion of low-titer, group O, cold-stored, whole blood, or inclusion in a MTP.

Whole blood for postpartum hemorrhage: early experience at two institutions.

BACKGROUND: Death from postpartum hemorrhage (PPH) remains a significant preventable problem worldwide. Cold-stored, low-titer, type-O whole blood (LTOWB) is increasingly being used for resuscitation of injured patients, but it is uncommon in PPH patients, and it is unclear what its role may be in this population. STUDY DESIGN AND METHODS: Brief report of the early experience of WB use for PPH in two institutions, one university hospital and one private hospital. RESULTS: Different approaches have been implemented at the two institutions, one designed for emergency release, uncrossmatched transfusion of LTOWB as part of a massive transfusion protocol (MTP) and one for high-risk obstetric patients with known placental abnormalities. A total of 7 PPH patients have received a total of 17 units of LTOWB between the two institutions. No severe adverse transfusion reactions were observed clinically in either institution and the clinical outcomes were favorable in all cases. CONCLUSION: In our early experience, LTOWB can be implemented for two different PPH clinical scenarios. Larger studies are needed to compare outcomes between LTOWB and traditional component resuscitation strategies.

First report of using low-titer cold-stored type O whole blood in massive postpartum hemorrhage.

BACKGROUND: In cases of massive hemorrhage in the US military, improved outcomes have been reported with the use of warm, fresh whole blood transfusions. Cold-stored low-titer type O whole blood (LTOWB) has become the preferred product for resuscitation of severe bleeding in deployed surgical units. Reports of LTOWB use in civilian trauma are becoming more frequent. CASE REPORT: We report our experience with emergency transfusion of LTOWB for a woman with massive postpartum hemorrhage. The patient had two previous cesarean section deliveries at term without complications. With her third elective cesarean section at term, blood loss during surgery was not excessive, but 3 to 4 hours later she had an estimated blood loss of 3600 mL. Despite measures to control the hemorrhage, she rapidly became hypotensive and tachycardic, and our massive transfusion protocol (MTP) was activated. The transfusion service had very recently incorporated LTOWB into Trauma Pack 1 of the MTP. She received two LTOWB units, after which her hemorrhaging ceased, blood pressure normalized, and she became alert. One hour later she received one unit of fresh frozen plasma and one unit of red blood cells (RBCs). The following morning she received one unit of crossmatched RBCs, for a hematocrit of 20.7%. She was discharged home on Day 4, and she remains healthy. CONCLUSIONS: This is the first report of which we are aware of massive postpartum hemorrhage treated using LTOWB. Our positive experience leads us to speculate that this approach could have a role in massive obstetric hemorrhage.

Definitive airway management after pre-hospital supraglottic airway insertion: Outcomes and a management algorithm for trauma patients.

BACKGROUND: Prehospital airway management increasingly involves supraglottic airway insertion and a paucity of data evaluates outcomes in trauma populations. We aim to describe definitive airway management in traumatically injured patients who necessitated prehospital supraglottic airway insertion. METHODS: We performed a single institution retrospective review of multisystem injured patients (≥15years) that received prehospital supraglottic airway insertion during 2009 to 2016. Baseline demographics, number and type of: supraglottic airway insertion attempts, definitive airway and complications were recorded. Primary outcome was need for tracheostomy. Univariate and multivariable statistics were performed. RESULTS: 56 patients met inclusion criteria and were reviewed, 78% were male. Median age [IQR] was 36 [24-56] years. Injuries comprised blunt (94%), penetrating (4%) and burns (2%). Median ISS was 26 [22-41]. Median number of prehospital endotracheal intubation (PETI) attempts was 2 [1-3]. Definitive airway management included: (n=20, 36%, tracheostomy), (n=10, 18%, direct laryngoscopy), (n=6, 11%, bougie), (n=9, 15%, Glidescope), (n=11, 20%, bronchoscopic assistance). 24-hour mortality was 41%. Increasing number of PETI was associated with increasing facial injury. On regression, increasing cervical and facial injury patterns as well as number of PETI were associated with definitive airway control via surgical tracheostomy. CONCLUSIONS: After supraglottic airway insertion, operative or non-operative approaches can be utilized to obtain a definitive airway. Patients with increased craniofacial injuries have an increased risk for airway complications and need for tracheostomy. We used these factors to generate an evidence based algorithm that requires prospective validation. LEVEL OF EVIDENCE: Level IV - Retrospective study. STUDY TYPE: Retrospective single institution study.

Securing a Chest Tube Properly: A Simple Framework for Teaching Emergency Medicine Residents and Assessing Their Technical Abilities.

BACKGROUND: Quality-improvement efforts at our institution have identified chest tube dislodgement as a preventable complication of tube thoracostomy. Because proper fixation techniques are not well described in the literature and are seldom formally taught, techniques vary among residents. OBJECTIVE: Our aim was to develop and test a framework for teaching and assessing chest tube securement. METHODS: A repeated-measures study design was used. At baseline, 19 emergency medicine residents (program years 1-3) placed and secured a chest tube in a cadaver. After a 45-min proficiency-based teaching session using a low-cost chest tube simulator (approximate cost, $5), each resident again placed and secured a chest tube in a cadaver, followed by 3-month retention testing. All securements were evaluated by two raters using a four-point checklist and a five-point global assessment scale (GAS). The checklist addressed suture selection, tying knots down to the tube, wound approximation, and tube displacement relative to skin. RESULTS: After the initial educational intervention, median scores for the group improved significantly over baseline for the GAS (p < 0.001), checklist (p < 0.001), and amount of displacement (p = 0.01). At 3 months, GAS, checklist, and displacement scores did not differ significantly from the immediate post-test scores. Inter-rater reliability was substantial, with weighted κ values of .77 for the GAS and .70 for the checklist. CONCLUSIONS: Quality of chest tube securement by emergency medicine residents can be significantly improved with an inexpensive chest tube simulator and a brief workshop. The four-point checklist served as a reliable and effective means for teaching and assessing chest tube securement.

Validation of the anatomic severity score developed by the American Association for the Surgery of Trauma in small bowel obstruction.

BACKGROUND: The anatomic severity schema for small bowel obstruction (SBO) has been described by the American Association for the Surgery of Trauma (AAST). Although acknowledging the importance of physiological and comorbid parameters, these factors were not included in the developed system. Thus, we sought to validate the AAST-SBO scoring system and evaluate the effect of adding patient's physiology and comorbidity on the prediction for the proposed system. METHODS: Patients aged ≥18 y who were treated for SBO at our institution between 2009 and 2012 were identified. The physiology and comorbidity as well as the AAST anatomic scores were determined, squared, and added to calculate the score that we termed Acute General Emergency Surgical Severity-Small Bowel Obstruction (AGESS-SBO). The area under the receiver operating characteristic (AUROC) curve analyses were performed for the AAST anatomic score and compared with the AGESS-SBO score as a predictor for inhospital mortality, extended hospital stay, and inhospital complications. RESULTS: A total of 351 patients with mean age of 66 ± 17 years were identified, of whom 145 (41%) underwent operation to treat bowel obstruction. Extended hospital stay (>9 d) occurred in 86 patients (25%), inhospital complications in 73 (21%), and inhospital mortality in eight patients (2%). The median (interquartile range [IQR]) AAST anatomic score was 1 point (IQR: 1-2), physiology score was 0 point (IQR: 0-1), and comorbidity score was 1 point (IQR: 1-3); for overall median AGESS-SBO score of 5 points (IQR: 3-13). The AUROC curve analyses demonstrated that the AGESS-SBO system with measures of presenting physiology, comorbidities in addition to AAST anatomic criteria could be beneficial in predicting key outcomes including inhospital mortality (AUROC curve: 0.80 versus 0.54, P = 0.03). CONCLUSIONS: The AAST anatomic score is a reliable system, which assists care providers to categorize SBO. Adding physiology and comorbidity parameters to the described anatomic criteria can be helpful in predicting the outcomes including mortality. Further studies evaluating its usefulness in research and quality improvement purposes across institutions are still required.

Risk factors for postoperative hematoma after inguinal hernia repair: an update.

BACKGROUND: We recently sensed an increase in the frequency of groin hematoma after inguinal hernia repair (IHR) at our institution. The aim of this study was to provide a more updated assessment of the risk factors inherent to this complication. METHODS: We performed a case-control study of all adult patients (age ≥ 18 y) who developed a groin hematoma after IHR at our institution between 2003 and 2015. Univariate and multivariable analyses were performed to assess for independent predictors for groin hematoma. RESULTS: A total of 96 patients (among 6608 IHR) developed a groin hematoma, (60 were observed, 36 required intervention). The hematoma frequency increased from our previous study (1.4 % versus 0.9%, P < 0.01). Mean age was 64.6 y (range: 18-92), and 84.3% were men. There was no significant difference in the laterality, type, or technique of IHR between cases and controls. Univariate analysis (odds ratio [95% confidence interval], P) identified warfarin usage (3.5, [1.6-6.4], P < 0.01), valvular heart disease (11.6, [2.6-51.3], P < 0.01), atrial fibrillation (2.6, [1.2-5.5], P = 0.01), hypertension (2.03, [1.1-3.6], P = 0.02), recurrent hernia (3.7, [1.4-9.7], P < 0.01), and coronary artery disease (2.1, [1.0-4.4 ], P = 0.05) as significant preoperative factors. The proportion of patients on warfarin decreased since our prior report (31% versus 42%, P = 0.20). On multivariable regression, warfarin and recurrent hernia were independent predictors of hematoma development. CONCLUSIONS: Independent risk factors for the development of groin hematoma after IHR included warfarin use and recurrent hernia. Careful consideration for anticoagulation and surgical hypervigilance remains prudent in all patients undergoing IHR and especially those with recurrence.

Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer.

The Polycomb group (PcG) protein EZH2 possesses oncogenic properties for which the underlying mechanism is unclear. We integrated in vitro cell line, in vivo tumor profiling, and genome-wide location data to nominate key targets of EZH2. One of the candidates identified was ADRB2 (Adrenergic Receptor, Beta-2), a critical mediator of beta-adrenergic signaling. EZH2 is recruited to the ADRB2 promoter and represses ADRB2 expression. ADRB2 inhibition confers cell invasion and transforms benign prostate epithelial cells, whereas ADRB2 overexpression counteracts EZH2-mediated oncogenesis. ADRB2 is underexpressed in metastatic prostate cancer, and clinically localized tumors that express lower levels of ADRB2 exhibit a poor prognosis. Taken together, we demonstrate the power of integrating multiple diverse genomic data to decipher targets of disease-related genes.

Low-Titer Type O Whole Blood for Transfusing Perinatal Patients after Acute Hemorrhage: A Case Series.

Objective Acute and massive blood loss is fortunately a rare occurrence in perinatal/neonatal practice. When it occurs, typical transfusion paradigms utilize sequential administration of blood components. However, an alternative approach, transfusing type O whole blood with low anti-A and anti-B titers, (LTOWB) has recently been approved and utilized in trauma surgery. Study Design Retrospective analysis of all perinatal patients who have received LTOWB after acute massive hemorrhage at the Intermountain Medical Center. Results LTOWB was the initial transfusion product we used to resuscitate/treat 25 women with acute and massive postpartum hemorrhage and five infants with acute hemorrhage in the first hours/days after birth. We encountered no problems obtaining or transfusing this product and we recognized no adverse effects of this treatment. Conclusion Transfusing LTOWB to perinatal patients after acute blood loss is feasible and appears at least as safe a serial component transfusion. Its use has subsequently been expanded to multiple hospitals in our region as first-line transfusion treatment for acute perinatal hemorrhage. Key Points Low-titer type O whole blood (LTOWB) was our initial transfusion product for 30 perinatal patients with acute hemorrhage. Twenty-five of these were obstetrical patients and five were neonatal patients. We encountered no problems with, or adverse effects from LTOWB in any of these patients. LTOWB transfusions to women were ten days since donor draw (interquartile range, 8-13) and to neonates was six days (5-8).

Interruptions in bladder cancer care during the COVID-19 public health emergency.

BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.

Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer.

Recently, we identified recurrent gene fusions involving the 5' untranslated region of the androgen-regulated gene TMPRSS2 and the ETS (E26 transformation-specific) family genes ERG, ETV1 or ETV4 in most prostate cancers. Whereas TMPRSS2-ERG fusions are predominant, fewer TMPRSS2-ETV1 cases have been identified than expected on the basis of the frequency of high (outlier) expression of ETV1 (refs 3-13). Here we explore the mechanism of ETV1 outlier expression in human prostate tumours and prostate cancer cell lines. We identified previously unknown 5' fusion partners in prostate tumours with ETV1 outlier expression, including untranslated regions from a prostate-specific androgen-induced gene (SLC45A3) and an endogenous retroviral element (HERV-K_22q11.23), a prostate-specific androgen-repressed gene (C15orf21), and a strongly expressed housekeeping gene (HNRPA2B1). To study aberrant activation of ETV1, we identified two prostate cancer cell lines, LNCaP and MDA-PCa 2B, that had ETV1 outlier expression. Through distinct mechanisms, the entire ETV1 locus (7p21) is rearranged to a 1.5-megabase prostate-specific region at 14q13.3-14q21.1 in both LNCaP cells (cryptic insertion) and MDA-PCa 2B cells (balanced translocation). Because the common factor of these rearrangements is aberrant ETV1 overexpression, we recapitulated this event in vitro and in vivo, demonstrating that ETV1 overexpression in benign prostate cells and in the mouse prostate confers neoplastic phenotypes. Identification of distinct classes of ETS gene rearrangements demonstrates that dormant oncogenes can be activated in prostate cancer by juxtaposition to tissue-specific or ubiquitously active genomic loci. Subversion of active genomic regulatory elements may serve as a more generalized mechanism for carcinoma development. Furthermore, the identification of androgen-repressed and insensitive 5' fusion partners may have implications for the anti-androgen treatment of advanced prostate cancer.

First steps toward a BIG change: A pilot study to implement the Brain Injury Guidelines across a 24-hospital system.

INTRODUCTION: The modified Brain Injury Guidelines (mBIG) support a subset of low-risk patients to be managed without repeat head computed tomography (RHCT), neurosurgical consult (NSC), or hospital transfer/admission. This pilot aimed to assess mBIG implementation at a single facility to inform future systemwide implementation. METHODS: Single cohort pilot trial at a level I trauma center, December 2021-August 2022. Adult patients included if tICH meeting BIG 1 or 2 criteria. BIG 3 patients excluded. RESULTS: No patients required neurosurgical intervention. 72 RHCT and 83 NSC were prevented. 21 isolated BIG 1 were safely discharged home from the ED. No hospital readmissions for tICH. Protocol adherence rate was 92%. CONCLUSION: Implementation of the mBIG at a single trauma center is feasible and optimizes resource utilization. This pilot study will inform an implementation trial of the mBIG across a 24-hospital integrated health system.

Below the knee, let it be: Management of calf DVT in hospitalized trauma patients.

INTRODUCTION: Management of below-knee DVT (BKDVT) in trauma patients is uncertain. We hypothesized that BKDVT can be managed with observation only. METHODS: Secondary analysis on trauma inpatients March 2017-September 2019 with risk assessment profile ≥5. Management of BKDVT included observation with ultrasound. BKDVT was compared to above-knee DVT (AKDVT), and BKDVT with progression to AKDVT/PE compared to no progression. RESULTS: Of 1988 patients, 136 (6.8%) BKDVT and 23 (1.2%) AKDVT. 7 (6.9%) BKDVT progressed to AKDVT/PE. 6.9% had BKDVT progression, associated with higher ISS (36.7 vs 21.6, p â€‹= â€‹0.005), longer prophylaxis delay (121 vs 45 â€‹h, p â€‹= â€‹0.02) and longer hospital LOS (25.6 vs 7.8, p â€‹= â€‹0.01). None experienced post-thrombotic syndrome. CONCLUSION: Majority of BKDVT in hospitalized trauma patients did not progress to AKDVT. Observation for progression, rather than treatment, was not associated with increased PE risk or thrombotic sequelae. Observation with serial ultrasound may serve as a practical alternative to anticoagulation in trauma patients with BKDVT.

Site-directed coordination chemistry with P22 virus-like particles.

Protein cage nanoparticles (PCNs) are attractive platforms for developing functional nanomaterials using biomimetic approaches for functionalization and cargo encapsulation. Many strategies have been employed to direct the loading of molecular cargos inside a wide range of PCN architectures. Here we demonstrate the exploitation of a metal-ligand coordination bond with respect to the direct packing of guest molecules on the interior interface of a virus-like PCN derived from Salmonella typhimurium bacteriophage P22. The incorporation of these guest species was assessed using mass spectrometry, multiangle laser light scattering, and analytical ultracentrifugation. In addition to small-molecule encapsulation, this approach was also effective for the directed synthesis of a large macromolecular coordination polymer packed inside of the P22 capsid and initiated on the interior surface. A wide range of metals and ligands with different thermodynamic affinities and kinetic stabilities are potentially available for this approach, highlighting the potential for metal-ligand coordination chemistry to direct the site-specific incorporation of cargo molecules for a variety of applications.

Moral values, social ideologies and threat-based cognition: Implications for intergroup relations.

Moral foundations theory (MFT) has provided an account of the moral values that underscore different cultural and political ideologies, and these moral values of harm, fairness, loyalty, authority, and purity can help to explain differences in political and cultural ideologies; however, the extent to which moral foundations relate to strong social ideologies, intergroup processes and threat perceptions is still underdeveloped. To explore this relationship, we conducted two studies. In Study 1 (N = 157), we considered how the moral foundations predicted strong social ideologies such as authoritarianism (RWA) and social dominance orientation (SDO) as well as attitudes toward immigrants. Here, we demonstrated that more endorsement of individualizing moral foundations (average of harm and fairness) was related to less negative intergroup attitudes, which was mediated by SDO, and that more endorsement of binding moral foundations (the average of loyalty, authority, and purity) was related to more negative attitudes, which was mediated by RWA. Crucially, further analyses also suggested the importance of threat perceptions as an underlying explanatory variable. Study 2 (N = 388) replicated these findings and extended them by measuring attitudes toward a different group reflecting an ethnic minority in the United States, and by testing the ordering of variables while also replicating and confirming the threat effects. These studies have important implications for using MFT to understand strong ideologies, intergroup relations, and threat perceptions.

Prehospital decompression of tension pneumothorax: Have we moved the needle?

BACKGROUND: Needle thoracostomy (NT) is the first-line intervention for tension pneumothorax in the prehospital setting. This study examined the effect of ATLS curriculum and EMS protocol changes on patient selection and successful performance of the procedure. METHODS: This is a retrospective chart review of all patients presenting to a Level One Trauma Center from 2015 to 2020 after undergoing prehospital NT. RESULTS: Lateral NT placement increased significantly from 5.1% to 38.9%. Proper patient selection, defined as presence decompensated shock, respiratory distress, and diminished breath sounds increased from 23.1% to 27.8%. There was no difference in radiographic confirmation of the catheter in the pleural space. Iatrogenic injury rates decreased slightly from 28.2% to 16.7%. CONCLUSIONS: Protocol and curriculum changes have fallen short in yielding improved NT success rates or patient selection. Continued development of EMS education on the performance of NT is indicated.

Guidelines for Management of Treatment-Emergent Adverse Events During Rucaparib Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: The US Food and Drug Administration has recently granted accelerated approval of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib as treatment for men with metastatic castration-resistant prostate cancer (mCRPC) associated with a deleterious germline or somatic BRCA1 or BRCA2 (BRCA) alteration. As the safety profile of this new addition to the mCRPC treatment landscape may be unfamiliar to clinicians and patients, we summarize the data from the literature and provide practical guidelines for the management of treatment-emergent adverse events (TEAEs) that may occur during rucaparib treatment. MATERIALS AND METHODS: Safety data were identified from PubMed and congress publications of trials involving men with mCRPC treated with oral rucaparib monotherapy (600 mg twice daily). Management guidelines for TEAEs were developed based on trial protocols, prescribing information, oncology association guidance, and the authors' clinical experience. RESULTS: In clinical trials of men with mCRPC who received rucaparib (n = 193), TEAEs observed were consistent with that of other PARP inhibitors. The most frequent any-grade TEAEs included gastrointestinal events, asthenia/fatigue, anemia, increased alanine/aspartate aminotransferase, rash, and thrombocytopenia; the most frequent grade ≥3 TEAE was anemia. The majority of TEAEs were self-limiting and did not require treatment modification or interruption. Here, we provide recommendations on management of the most common TEAEs reported with rucaparib as well as other TEAEs of interest. CONCLUSION: Rucaparib's recent approval for treatment of BRCA-mutant mCRPC is practice changing. Proper management of TEAEs will allow maximum treatment benefit for patients receiving rucaparib.