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1.
Early Hum Dev ; 192: 106004, 2024 May.
Article En | MEDLINE | ID: mdl-38636257

AIM: To implement a culturally-adapted screening program aimed to determine the ability of infant motor repertoire to predict early neurodevelopment on the Hammersmith Infant Neurological Examination (HINE) and improve Australian First Nations families' engagement with neonatal screening. METHODS: A prospective cohort of 156 infants (55 % male, mean (standard deviation [SD]) gestational age 33.8 (4.6) weeks) with early life risk factors for adverse neurodevelopmental outcomes (ad-NDO) participated in a culturally-adapted screening program. Infant motor repertoire was assessed using Motor Optimality Score-revised (MOS-R), captured over two videos, 11-13+6 weeks (V1; <14 weeks) and 14-18 weeks (V2; ≥14 weeks) corrected age (CA). At 4-9 months CA neurodevelopment was assessed on the HINE and classified according to age-specific cut-off and optimality scores as; developmentally 'on track' or high chance of either adverse neurodevelopmental outcome (ad-NDO) or cerebral palsy (CP). RESULTS: Families were highly engaged, 139/148 (94 %) eligible infants completing MOS-R, 136/150 (91 %), HINE and 123 (83 %) both. Lower MOS-R at V2 was associated with reduced HINE scores (ß = 1.73, 95 % confidence interval [CI] = 1.03-2.42) and high chance of CP (OR = 2.63, 95%CI = 1.21-5.69) or ad-NDO (OR = 1.38, 95%CI = 1.10-1.74). The MOS-R sub-category 'observed movement patterns' best predicted HINE, infants who score '4' had mean HINE 19.4 points higher than score '1' (95%CI = 12.0-26.9). Receiver-operator curve analyses determined a MOS-R cut-off of <23 was best for identifying mild to severely reduced HINE scores, with diagnostic accuracy 0.69 (sensitivity 0.86, 95%CI 0.76-0.94 and specificity 0.40, 95 % CI 0.25-0.57). A trajectory of improvement on MOS-R (≥2 point increase in MOS-R from 1st to 2nd video) significantly increased odds of scoring optimally on HINE (OR = 5.91, 95%CI 1.16-29.89) and may be a key biomarker of 'on track' development. INTERPRETATION: Implementation of a culturally-adapted program using evidence-based assessments demonstrates high retention. Infant motor repertoire is associated with HINE scores and the early neurodevelopmental status of developmentally vulnerable First Nations infants.


Child Development , Neurologic Examination , Humans , Female , Male , Infant, Newborn , Neurologic Examination/methods , Infant , Neonatal Screening/methods , Australia , Motor Skills/physiology , Prospective Studies , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/epidemiology
2.
J Nurs Adm ; 54(4): 235-239, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38501818

OBJECTIVE: The aim of this study was to assess nurse preceptor burnout and examine related factors. BACKGROUND: Nurse preceptors are essential to the provision of optimal hospital-based care. Preceptors guide and support nurses' transition from professional training to practice as well as movement within practice roles. METHODS: As a component of the DevelopYou database, nurse preceptors (N = 210) were surveyed electronically using the BHLex Preceptor Role Questionnaire. Data retrieved from this data set were analyzed. RESULTS: Twenty-eight percent (n = 60) of participants experienced burnout. Most (n = 203, 96.7%) enjoyed their role. Reasons for becoming a preceptor included a love for teaching, a desire to help others, and feelings of responsibility to the profession and the institution. Strategies to enable perceived value of the role focused on activities involving person-to-person interactions. CONCLUSIONS: On the basis of the results of this analysis, it is apparent that nurse preceptors want to feel valued and supported by administration and have opportunities to interact regularly with colleagues.


Burnout, Professional , Preceptorship , Humans , Emotions , Surveys and Questionnaires
3.
Mil Med ; 2023 Nov 23.
Article En | MEDLINE | ID: mdl-37997687

BACKGROUND & OBJECTIVES: The U.S. Army fell 25% short of its recruitment goal in 2022 and therefore, increasing the eligibility pool for potential recruits is of interest. Raising the body mass index (BMI) standards for eligibility presents a path to increase the recruitable population; however, there may be additional costs incurred due to attendant health risks that may be present in individuals with higher BMI. METHODS: We filtered the 2017-2020 National Health and Nutrition Examination Survey by age (17-25 years) and BMI (up to 30 kg/m2). A k-means cluster analysis was performed on the filtered dataset for the variables used to determine metabolic syndrome. Metabolic syndrome Clusters were characterized through summary statistics and compared over clinical measurements and questionnaire responses. RESULTS: Five distinct clusters were identified and mean BMI in two clusters (Clusters1 and 3) exceeded the current U.S. Army BMI thresholds. Of these two clusters, Cluster 1 members had metabolic syndrome. Cluster 3 members were at higher risk for metabolic syndrome compared to members of Clusters 2, 4, and 5. Mean waist circumference was slightly lower in Cluster 3 compared to Cluster 1. None of the clusters had significant differences in depression scores, poverty index, or frequency of dental visits. CONCLUSIONS: Potential recruits from Cluster 1 have excessive health risk and may incur substantial cost to the U.S. Army if enlisted. However, potential recruits from Cluster 3 appear to add little risk and offer an opportunity to increase the pool for recruiting.

4.
bioRxiv ; 2023 Aug 28.
Article En | MEDLINE | ID: mdl-37693589

Integrins are essential surface receptors that sense extracellular changes to initiate various intracellular signaling cascades. The rapid activation of the epithelial-intrinsic ß6 integrin during influenza A virus (IAV) infection has been linked to innate immune impairments. Yet, how ß6 regulates epithelial immunity remains undefined. Here, we identify the role of ß6 in mediating the Toll-like receptor 7 (TLR7) through the regulation of intracellular trafficking. We demonstrate that deletion of the ß6 integrin in lung epithelial cells significantly enhances the TLR7-mediated activation of the type I interferon (IFN) response during homeostasis and respiratory infection. IAV-induced ß6 facilitates TLR7 trafficking to lysosome-associated membrane protein (LAMP2a) components, leading to a reduction in endosomal compartments and associated TLR7 signaling. Our findings reveal an unappreciated role of ß6-induced autophagy in influencing epithelial immune responses during influenza virus infection.

5.
J Virol ; 97(9): e0102523, 2023 09 28.
Article En | MEDLINE | ID: mdl-37668367

Human astrovirus is a positive-sense, single-stranded RNA virus. Astrovirus infection causes gastrointestinal symptoms and can lead to encephalitis in immunocompromised patients. Positive-strand RNA viruses typically utilize host intracellular membranes to form replication organelles, which are potential antiviral targets. Many of these replication organelles are double-membrane vesicles (DMVs). Here, we show that astrovirus infection leads to an increase in DMV formation through a replication-dependent mechanism that requires some early components of the autophagy machinery. Results indicate that the upstream class III phosphatidylinositol 3-kinase (PI3K) complex, but not LC3 conjugation machinery, is utilized in DMV formation. Both chemical and genetic inhibition of the PI3K complex lead to significant reduction in DMVs, as well as viral replication. Elucidating the role of autophagy machinery in DMV formation during astrovirus infection reveals a potential target for therapeutic intervention for immunocompromised patients. IMPORTANCE These studies provide critical new evidence that astrovirus replication requires formation of double-membrane vesicles, which utilize class III phosphatidylinositol 3-kinase (PI3K), but not LC3 conjugation autophagy machinery, for biogenesis. These results are consistent with replication mechanisms for other positive-sense RNA viruses suggesting that targeting PI3K could be a promising therapeutic option for not only astrovirus, but other positive-sense RNA virus infections.


Mamastrovirus , Phosphatidylinositol 3-Kinase , Virus Replication , Humans , Autophagy , Class III Phosphatidylinositol 3-Kinases/metabolism , Intracellular Membranes/metabolism , Organelles , Phosphatidylinositol 3-Kinase/metabolism , RNA Viruses , Mamastrovirus/physiology , Signal Transduction
6.
Gynecol Oncol ; 175: 20-24, 2023 08.
Article En | MEDLINE | ID: mdl-37290248

OBJECTIVES: Although universal mismatch repair (MMR) immunohistochemistry (IHC) in endometrial cancer began at our institution in July 2015, not all eligible patients were referred for genetic testing (GT). In April 2017, genetic counselors obtained IHC data and contacted physicians to approve genetic counseling referrals (GCRs) for Lynch Syndrome (LS) in eligible patients. We assessed if this protocol increased frequency of GCRs and GT in patients with abnormal MMR IHC. METHODS: We retrospectively (7/2015-5/2022) identified patients with abnormal MMR IHC at a large urban hospital. GCRs and GT were compared between cases from 7/2015-4/2017 (pre-protocol) and 5/2017-5/2022 (post-protocol) with chi-square and Fisher's exact tests. RESULTS: Of 794 patients with IHC testing, 177 (22.3%) had abnormal MMR results with 46 (26.0%) meeting criteria for LS screening with GT. Of 46 patients, 16 (34.8%) were identified prior to and 30 (65.2%) after the protocol initiation. GCRs significantly increased from 11/16 (68.8%) to 29/30 (96.7%) in the pre-protocol versus post-protocol groups, p = 0.02. There was no statistically significant difference in GT between groups (10/16, 62.5% vs 26/30, 86.7%, p = 0.07). Of 36 patients who underwent GT, 16 (44.4%) had LS: MSH6, 9; MSH2, 4; PMS2, 2; MLH1, 1. CONCLUSIONS: Increased frequency of GCRs was observed following the change in protocol, which is important as LS screening has clinical implications for patients and their families. Despite this additional effort, approximately 15% who met criteria did not undergo GT; further efforts such as universal germline testing in patients with endometrial cancer should be considered.


Colorectal Neoplasms, Hereditary Nonpolyposis , Endometrial Neoplasms , Female , Humans , Retrospective Studies , DNA Mismatch Repair , Immunohistochemistry , Mismatch Repair Endonuclease PMS2/genetics , Mismatch Repair Endonuclease PMS2/metabolism , MutL Protein Homolog 1/genetics , MutL Protein Homolog 1/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Genetic Testing/methods , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
7.
Am J Perinatol ; 2023 Jun 29.
Article En | MEDLINE | ID: mdl-37385293

OBJECTIVE: This study aimed to evaluate the relationship between peripartum mean arterial pressure (MAP) and postpartum readmission for preeclampsia with severe features. STUDY DESIGN: This is a retrospective case-control study comparing adult parturients readmitted for preeclampsia with severe features to matched nonreadmitted controls. Our primary objective was to evaluate the association between MAP at three time points during the index hospitalization (admission, 24-hour postpartum, and discharge) and readmission risk. We also evaluated readmission risk by age, race, body mass index, and comorbidities. Our secondary aim was to establish MAP thresholds to identify the population at highest risk of readmission. Multivariate logistic regression and chi-squared tests were used to determine the adjusted odds of readmission based on MAP. Receiver operating characteristic analyses were performed to evaluate risk of readmission relative to MAP; optimal MAP thresholds were established to identify those at highest risk of readmission. Pairwise comparisons were made between subgroups after stratifying for history of hypertension, with a focus on readmitted patients with new-onset postpartum preeclampsia. RESULTS: A total of 348 subjects met inclusion criteria, including 174 controls and 174 cases. We found that elevated MAP at both admission (adjusted odds ratio [OR]: 1.37 per 10 mm Hg, p < 0.0001) and 24-hour postpartum (adjusted OR: 1.61 per 10 mm Hg, p = 0.0018) were associated with increased risk of readmission. African American race and hypertensive disorder of pregnancy were independently associated with increased risk of readmission. Subjects with MAP > 99.5 mm Hg at admission or >91.5 mm Hg at 24-hour postpartum had a risk of at least 46% of requiring postpartum readmission for preeclampsia with severe features. CONCLUSION: Admission and 24-hour postpartum MAP correlate with risk of postpartum readmission for preeclampsia with severe features. Evaluating MAP at these time points may be useful for identifying women at higher risk for postpartum readmission. These women may otherwise be missed based on standard clinical approaches and may benefit from heightened surveillance. KEY POINTS: · Existing literature focuses on management of antenatal hypertensive disorders of pregnancy.. · Elevated peripartum MAP is associated with increased odds of readmission for preeclampsia.. · Peripartum MAP may predict readmission risk for de novo postpartum preeclampsia..

8.
PLoS One ; 18(5): e0283566, 2023.
Article En | MEDLINE | ID: mdl-37134066

OBJECTIVE: To identify relationships between body shape, body composition, sex and performance on the new US Army Combat Fitness Test (ACFT). METHODS: Two hundred and thirty-nine United States Military Academy cadets took the ACFT between February and April of 2021. The cadets were imaged with a Styku 3D scanner that measured circumferences at 20 locations on the body. A correlation analysis was conducted between body site measurements and ACFT event performance and evaluated using Pearson correlation coefficients and p-values. A k-means cluster analysis was performed over the circumference data and ACFT performance were evaluated between clusters using t-tests with a Holm-Bonferroni correction. RESULTS: The cluster analysis resulted in 5 groups: 1. "V" shaped males, 2. larger males, 3. inverted "V" shaped males and females, 4. "V" shaped smaller males and females, and 5. smallest males and females. ACFT performance was the highest in Clusters 1 and 2 on all events except the 2-mile run. Clusters 3 and 4 had no statistically significant differences in performance but both clusters performed better than Cluster 5. CONCLUSIONS: The association between ACFT performance and body shape is more detailed and informative than considering performance solely by sex (males and females). These associations may provide novel ways to design training programs from baseline shape measurements.


Military Personnel , Physical Fitness , Male , Female , Humans , United States , Exercise Test/methods , Somatotypes , Body Image , Body Composition
9.
Proc Natl Acad Sci U S A ; 120(19): e2222008120, 2023 05 09.
Article En | MEDLINE | ID: mdl-37126672

Referential signaling, a complex form of communication in which specific signals are associated with external referents, was once thought to be limited to primates. Recent research has documented referential signaling in several other cooperative taxa, predominantly in kin-based societies. Here, we show that greater anis, communally nesting birds that breed in nonkin groups, give one type of alarm call in response to aerial threats (flying raptors) and another to more general threats (nonaerial predators). Observational data show that anis give these calls in response to different classes of threats, and playback experiments in the field confirmed that the alarm calls alone are sufficient to elicit appropriate behavioral responses even in the absence of an actual threat. Genetic data on a subset of groups confirmed that breeding groups are composed of nonkin, suggesting that referential alarm calls are often given in situations when no genetic relatives are present. These results suggest that complex referential communication can occur in social groups composed of nonrelatives, despite the absence of kin-selected fitness benefits.


Raptors , Vocalization, Animal , Animals , Vocalization, Animal/physiology , Birds/physiology
10.
bioRxiv ; 2023 Apr 12.
Article En | MEDLINE | ID: mdl-37090568

Human astrovirus is a positive sense, single stranded RNA virus. Astrovirus infection causes gastrointestinal symptoms and can lead to encephalitis in immunocompromised patients. Positive strand RNA viruses typically utilize host intracellular membranes to form replication organelles, which are potential antiviral targets. Many of these replication organelles are double membrane vesicles (DMVs). Here we show that astrovirus infection leads to an increase in DMV formation, and this process is replication-dependent. Our data suggest that astrovirus infection induces rearrangement of endoplasmic reticulum fragments, which may become the origin for DMV formation. Transcriptional data suggested that formation of DMVs during astrovirus infection requires some early components of the autophagy machinery. Results indicate that the upstream class III phosphatidylinositol 3-kinase (PI3K) complex, but not LC3 conjugation machinery, is utilized in DMV formation. Inhibition of the PI3K complex leads to significant reduction in viral replication and release from cells. Elucidating the role of autophagy machinery in DMV formation during astrovirus infection reveals a potential target for therapeutic intervention for immunocompromised patients. Importance: These studies provide critical new evidence that astrovirus replication requires formation of double membrane vesicles, which utilize class III PI3K, but not LC3 conjugation autophagy machinery for biogenesis. These results are consistent with replication mechanisms for other positive sense RNA viruses. This suggests that targeting PI3K could be a promising therapeutic option for not only astrovirus, but other positive sense RNA virus infections.

11.
Am J Perinatol ; 40(16): 1798-1802, 2023 12.
Article En | MEDLINE | ID: mdl-34808683

OBJECTIVE: Postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality. At present, there are no reliable clinical or laboratory indicators to identify which patients might require blood transfusions during a PPH. Serum lactate has long been used as an early biomarker of tissue hypoperfusion in trauma settings. The aim of this study is to understand serum lactate's role in the management of obstetric hemorrhage. STUDY DESIGN: A retrospective chart review was performed of women who delivered between 2016 and 2019 at our institution and experienced a PPH. The patients were divided into two groups: those with a normal serum lactate level, defined as ≤2 mmol/L, and those with an abnormal serum lactate level, defined as >2 mmol/L. Need for packed red blood cell transfusion, as part of the resuscitation, was assessed for both groups. RESULTS: During the study period, 938 women experienced PPH. Of these, 108 (11.5%) had a normal serum lactate, ≤2 mmol/L, and 830 (88.5%) had an abnormal lactate, >2 mmol/L. Women with elevated lactate levels were more likely to receive a blood transfusion versus those with a normal lactate level (57.0 vs. 46.3%, p = 0.035, respectively). Additionally, the average number of blood transfusions administered was significantly higher in the abnormal lactate group versus in the normal lactate group (1.34 vs. 0.97, respectively, p = 0.004). In a multivariable linear regression model, increasing serum lactate levels were found to be predictive of requiring more than 1 unit of blood (p < 0.001). CONCLUSION: Women with elevated serum lactate levels were more likely to require blood transfusions during a PPH versus those with a normal serum lactate level. Thus, serum lactate levels are useful as an early indicator of requirement for blood transfusion in the management of obstetric hemorrhage. KEY POINTS: · Lactate is a biomarker for blood transfusion in trauma.. · Lactate's role in PPH is unknown.. · Elevated lactate predicts receiving more blood transfusions..


Postpartum Hemorrhage , Pregnancy , Humans , Female , Postpartum Hemorrhage/therapy , Retrospective Studies , Blood Transfusion , Biomarkers , Lactates
12.
Front Genet ; 14: 1331169, 2023.
Article En | MEDLINE | ID: mdl-38169613

The Histocompatibility and Identity Testing Committee offers an overview of the College of American Pathologists' (CAP) Proficiency Testing (PT) program, commemorating its significant 75th anniversary in 2024. The CAP PT program has undergone significant growth and evolution over the years, ultimately achieving Centers for Medicare and Medicaid Services approval. In 1979, CAP's partnership with the American Association for Clinical Histocompatibility Testing marked a pivotal moment, leading to the creation of the first proficiency testing survey in 1980. This laid the foundation for various PT programs managed by the CAP Histocompatibility and Identity Testing Committee, including HLA antibody testing, HLA molecular typing, engraftment monitoring, parentage/relationship testing, HLA disease associations and drug risk, and HLA-B27 typing. Each program's distinctive considerations, grading methodologies, and future prospects are detailed here, highlighting the continual evolution of histocompatibility and identity testing PT to support emerging technologies and evolving laboratory practices in the field.

13.
Article En | MEDLINE | ID: mdl-35915042

Pleomorphic adenoma (PA) is the most common neoplasm of the salivary glands. Although several carcinomas have been reported to arise from PA, only 1 case of salivary gland secretory carcinoma (SC) ex pleomorphic adenoma has been previously reported. SC is a newly described salivary gland tumor harboring an ETV6-NTRK3 translocation, which is classically observed in secretory carcinoma of the breast, although other translocations have recently been observed. We report the first case of the molecular identification of a rare ETV6-RET translocation in an SC arising from a PA in the submandibular salivary gland (SC ex PA). Our results add to the diversity of tumors that are associated with PA and contribute to the molecular characterization of SC, which will have implications on its diagnosis, prognosis, and treatment.


Adenoma, Pleomorphic , Carcinoma , Humans , Adenoma, Pleomorphic/genetics , Adenoma, Pleomorphic/surgery , Proto-Oncogene Proteins c-ret
14.
Int J Palliat Nurs ; 28(7): 333-341, 2022 Jul 02.
Article En | MEDLINE | ID: mdl-35861441

Each year, there are 11 900 new diagnoses of head and neck cancers in the UK, with around 4000 deaths. Survival rates are higher for those diagnosed earlier, however, patients are often diagnosed later, with 20% palliative at the time of diagnosis. There is a scarcity of head and neck cancer palliative care literature available. This review article aims to discuss the unique challenges of head and neck cancer palliation. It specifically focusses on the challenges of pain management, airway obstruction, dysphagia, haemorrhage and the psychology of palliative head and neck cancer management. This article explores the advantages and disadvantages of many of the different treatment options available. It is hoped that this article will highlight the unique difficulties encountered by patients with head and neck cancer towards the end of their life and offer insights and suggestions to improve patients' quality of life in their final weeks and months.


Deglutition Disorders , Head and Neck Neoplasms , Deglutition Disorders/etiology , Head and Neck Neoplasms/therapy , Humans , Pain Management , Palliative Care , Quality of Life/psychology
15.
Stud Health Technol Inform ; 294: 815-816, 2022 May 25.
Article En | MEDLINE | ID: mdl-35612214

Errors in medication administration involve risks to patient safety. "Bar-Coding Medication Administration" is implemented to prevent these errors. Adoption by nurses is one of the main determinants of their effectiveness. The Hospital Italiano de Buenos Aires implemented BCMA 6 years ago, but its adoption rate still finds resistance in certain sectors. We conducted semi-structured interviews with nursing staff to explore the barriers to the use in low-usage wards and explore the current perceptions of nurses. While nurses recognised the safety and usefulness of the BCMA system, they reported many difficulties. The feedback obtained through this process was useful for the implementation team to plan future interventions, priorities and improvements on the system. The semi-structured interview methodology proved useful as a continuous monitoring strategy.


Medication Errors , Electronic Data Processing , Humans , Medication Errors/prevention & control , Medication Systems, Hospital , Patient Safety , Pharmaceutical Preparations
16.
Stud Health Technol Inform ; 294: 189-193, 2022 May 25.
Article En | MEDLINE | ID: mdl-35612054

The majority of preventable medication errors occur at the administration stage. BCMA systems are used to improve safety and prevent errors in this stage. A variety of devices can be used for this purpose. Hospital Italiano de Buenos Aires is a high complexity medical center implementing a BCMA project since 2015. It is currently migrating to PDA devices for nurses. The objective of this work is to evaluate the implementation of these new devices in selected wards at HIBA using a self-reported questionnaire. From 318 contacted nurses, 58 answered the questionnaire (18.2% response rate). Overall, agreement was high among all statements regarding the new devices. Nurses valued especially the increased safety to reduce errors, improvements in previous hospital processes and achieving improvements in the flow and quality of patient care. Nurses recommended the use of the device in their sector, with a mean score of 4.6/5 and 91.3% agreement, highest in total. This proved to be a cost-effective method of evaluation of the newly implemented devices and acceptance by nurses. Measures to incorporate the remaining nurses' feedback should be considered.


Electronic Data Processing , Medication Errors , Computers, Handheld , Humans , Medication Errors/prevention & control , Medication Systems, Hospital , Pharmaceutical Preparations , Surveys and Questionnaires
17.
Curr Treat Options Oncol ; 23(6): 887-903, 2022 06.
Article En | MEDLINE | ID: mdl-35412195

OPINION STATEMENT: Poly-ADP-ribose polymerase inhibitors (PARPi) are a class of anti-cancer drugs that target DNA repair pathways and have shown promising efficacy in patients with ovarian cancer in recent clinical trials. To date, there have been 9 FDA PARPi approvals/indications in ovarian cancer since 2014, highlighting the importance of this class of agents in the treatment of ovarian cancer. BRCA1/2-mutated tumors or other forms of homologous recombination deficient (HRD) tumors are particularly susceptible to PARP inhibition and have seen the greatest benefits of improvement in response rate and progression-free survival (PFS) in clinical trials. Patients with homologous recombination-proficient tumors also receive benefit, especially when a nice response to paltinum is noted, but to a lesser extent. PARP inhibitors now have FDA approval and indications in first-line and recurrent maintenance, and treatment. PARP inhibitor use as maintenance therapy in the front-line setting is now considered the standard of care in patients with BRCA1/2 mutations based on the SOLO-1/GOG-3004/ENGOT study. PARP inhibitors are also recommended per ASCO guidelines in all patients with ovarian cancer as front-line maintenance therapy based on the PRIMA/ENGOT-OV26/GOG-3012 trial. The combination of PARP inhibitor, olaparib, and the anti-angiogenesis inhibitor bevacizumab is also approved as maintenance therapy after front-line chemotherapy treatment in patients with HRD tumors and is an option for patients who have initiated bevacizumab with their chemotherapy treatment. PARPi are also FDA approved and can be utilized as a treatment in third-line and beyond in recurrent ovarian cancer patients with BRCA1/2 mutations and HRD tumors. In this review, we will cover in detail when PARP inhibitor use is appropriate in ovarian cancer, as well as the various clinical factors to take into consideration when selecting a PARP inhibitor regimen.


Antineoplastic Agents , Ovarian Neoplasms , Antineoplastic Agents/therapeutic use , Bevacizumab/therapeutic use , Carcinoma, Ovarian Epithelial/drug therapy , Female , Humans , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
18.
Ecol Lett ; 25(4): 900-912, 2022 Apr.
Article En | MEDLINE | ID: mdl-35098634

Successful control and prevention of biological invasions depend on identifying traits of non-native species that promote fitness advantages in competition with native species. Here, we show that, among 76 native and non-native woody plants of deciduous forests of North America, invaders express a unique functional syndrome that combines high metabolic rate with robust leaves of longer lifespan and a greater duration of annual carbon gain, behaviours enabled by seasonally plastic xylem structure and rapid production of thin roots. This trait combination was absent in all native species examined and suggests the success of forest invaders is driven by a novel resource-use strategy. Furthermore, two traits alone-annual leaf duration and nuclear DNA content-separated native and invasive species with 93% accuracy, supporting the use of functional traits in invader risk assessments. A trait syndrome reflecting both fast growth capacity and understorey persistence may be a key driver of forest invasions.


Forests , Trees , Carbon/metabolism , Introduced Species , Plant Leaves , Trees/genetics
19.
Gynecol Oncol ; 164(2): 304-310, 2022 02.
Article En | MEDLINE | ID: mdl-34922769

BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.


COVID-19/complications , COVID-19/mortality , Carcinoma/complications , Carcinoma/mortality , Genital Neoplasms, Female/complications , Genital Neoplasms, Female/mortality , Hospitalization/statistics & numerical data , Adult , Aged , Aged, 80 and over , COVID-19/therapy , Carcinoma/therapy , Female , Genital Neoplasms, Female/therapy , Humans , Logistic Models , Middle Aged , New York City/epidemiology , Patient Acuity , Retrospective Studies , Risk Factors , Treatment Outcome
20.
Cureus ; 13(10): e18862, 2021 Oct.
Article En | MEDLINE | ID: mdl-34804715

Introduction Stereotactic body radiation therapy (SBRT) is an effective treatment for early-stage non-small cell lung cancer (NSCLC) patients who are either medically inoperable or who decline surgery. SBRT improves tumor control and overall survival (OS) in medically inoperable, early-stage, NSCLC patients. In this study, we investigated the effectiveness of two different SBRT doses commonly used and present our institutional experience. Purpose To determine the clinical outcomes between two treatment regiments (50 Gray [Gy] vs. 55 Gy in five fractions) among Stage I NSCLC patients treated with SBRT at a state academic medical center. Methods We performed a retrospective analysis of 114 patients with Stage I (T1-2 N0 M0) NSCLC treated at a state academic medical center between October 2009 and April 2019. Survival analyses with treatment regimens of 50 Gy and 55 Gy in five fractions were conducted to detect any improvement in outcomes associated with the higher dose. The primary endpoints of this study included OS, local control (LC), and disease-free survival (DFS). Log-rank test and the Kaplan-Meier method were used to analyze the survival curves of the two treatment doses. The SPSS v.24.0 (IBM Corp., Armonk, NY, USA) was used for statistical analyses. Results The 114 early-stage NSCLC patients (median age, 68 years; range 12 to 87 years) had a median follow-up of 25 months (range two to 86 months). The number of males (n = 72; 63.2 %) exceeded the number of females (n = 42; 36.8 %). The majority of patients in this study were Caucasians (n = 68; 59.6 %) and 46 patients were African Americans (40.4 %). Two-thirds of the patients (n = 76; 66.7 %) were treated with 50 Gy in five fractions, and 38 patients (33.3 %) with 55 Gy in five fractions. The one-, two-, and three-year OS and DFS rates were improved in the patients treated with 55 Gy [OS, 81.7 % vs. 72.8 %; 81.7 % vs. 58.9 %; 81.7 % vs. 46.7 % (p = 0.049)], [DFS, 69.7 % vs. 69.7 %; 61.9 % vs. 55.7 %; 61.9 % vs. 52.0 % (p = 0.842)], compared to those treated with 50 Gy. Adenocarcinoma was the most common histology in both groups (51.3 % and 68.4 %). Failure rates were elevated for the 50 Gy regimen [39 (34.2 %) vs. 12 (8.5 %)]. Three year control rates were (66.3 % vs. 96.6 %; p = 0.002) local control; (63.3 % vs. 94.4 %; p = 0.000) regional control; and (65.7 % vs. 97.1 %; p = 0.000) distant control, compared to those treated with 55 Gy. Conclusion Early-stage NSCLC patients treated with SBRT 55 Gy in five fractions did better in terms of local control, overall survival, and disease-free survival rates compared to the 50 Gy in five fractions group.

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