The Bobath concept (NDT) in adult neurorehabilitation: a scoping review of conceptual literature.

PURPOSE: This scoping review aims to describe how Bobath concept is conceptualized, operationalized, and studied in adult neurorehabilitation. METHODS: The Joanna Briggs Institute (JBI) and the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) guidelines were adopted. Non-scientific and research articles were searched in electronic databases PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Web of Science, ScienceDirect, and Physiotherapy Evidence Database (PEDro), with the keywords "Bobath" or "Neurodevelopmental Treatment", published in English, Spanish, and Portuguese, between 2013 and 2023. RESULTS: Of the 78 publications identified, 31 articles addressed the conceptual underpinnings of Bobath concept (seven theoretical papers, seven Delphi/surveys/mixed methods studies, four qualitative studies, one scoping review, 10 letters to the editor, and two editorials), comprising five themes: (a) theoretical principles; (b) clinical principles; (c) clinical reasoning; (d) conceptualizing movement; and, current (e) evidence debate. The revised definition and the Model of Bobath Clinical Practice provide a clarification of the unique aspects of Bobath concept. A new clinical skill was identified beyond facilitation - visuospatial kinesthetic perception - as well as how Bobath experts conceptualize movement, which are all integral to clinical reasoning. CONCLUSIONS: This review provides an updated Bobath clinical framework that gathers the theoretical foundations and clinical practice principles that require careful consideration in the design of future intervention studies.Implications for rehabilitationThis scoping review consolidates the clinical and theoretical principles of contemporary Bobath practice, providing a clear framework for clinicians.The Model of Bobath Clinical Practice (MBCP) framework enables detailed documentation of movement analysis and movement diagnosis, guiding clinical reasoning and interventions.This review identifies fundamental principles and practices to inform future Bobath intervention studies, ensuring their clinical relevance.A framework with specific recommendations has been developed to guide Bobath intervention studies, enhancing the integration of clinical practice, education, and research.

Embracing a New Evidence-Based Thought Paradigm of Sepsis.

ABSTRACT: In 1991, sepsis was first defined by the Society of Critical Care Medicine as the systemic inflammatory response syndrome, in the presence of infection. Systemic inflammatory response syndrome is an adaptive host response to infection, as well as to other insults like trauma and stress. Research pertaining to sepsis was guided by this adaptive definition for 25 years. After established guidelines for sepsis management were challenged in 2014, sepsis was redefined in 2016 as a dysregulated host response to infection. However, there still remains no consensus on which immunologic or metabolic mechanisms have become dysregulated. We sought to examine sepsis literature published after the 2016 consensus definition and compare it to the original systemic inflammatory response syndrome paradigm proposed in 1991. The purpose of this intensive analysis was to recommend a new sepsis archetype, with consideration to dysregulated immunologic and metabolic mechanisms that have recently been identified in sepsis. Nurses and other clinicians must shift their thought paradigm toward an evidence-based dysregulated model, in order to improve on sepsis recognition and management.

The Toxic Stress of Racism and Its Relationship to Frailty.

Significant morbidity and mortality from COVID-19-related illnesses have been observed among people of color within the United States. While theories involving healthcare inequity and political division have emerged to explain this observation, the role of chronic stress and inflammation is also being explored. Toxic stress is experienced disproportionately by race, ethnicity, and socioeconomic status and increases frailty and vulnerability to diseases such as COVID-19. C-reactive protein (CRP) is a biomarker associated with the inflammatory response that is typically elevated due to exposure to acute or chronic traumatic stress, as well as COVID-19. This study explored the relationship between CRP and Hispanic/non-Hispanic ethnicity among adults hospitalized with COVID-19 via a secondary analysis of retrospective electronic health record (EHR) data collected from a community healthcare system in Southern California. A total of 1,744 cases representing hospitalized adults with COVID-19 were reviewed. Data were extracted from the EHR to reflect demographics, medical diagnoses, medications, CRP, and comorbidity burden. Frequencies, percentages, and measures of central tendency were assessed to understand the distribution of data. Associations were conducted using Pearson's r and the chi-square test of independence. Differences between groups were examined via independent samples t-tests. The sample was 52% Hispanic, 56% male, and the mean age was 62 years (SD = 16.1). The mean age of Hispanic cases was younger than non-Hispanic cases (p < .001, η = 0.289). Serum CRP was significantly higher in the Hispanic cases, with a high degree of association (p < .001, η = 0.472). In addition, higher CRP levels were significantly associated with the need for mechanical ventilation (p < .001, φc = 0.216). No significant relationships were found between CRP and age, body mass index (BMI), or comorbidity burden. Findings challenge the assumption that the disproportionate morbidity and mortality suffered by the Hispanic population due to COVID-19 was due to age, BMI, or comorbidities such as metabolic syndrome or heart disease. CRP in the Hispanic population should be further investigated to understand its relationship to chronic stress, frailty, and risk for COVID-19 in this population.

Clinical metabolic monitoring to inform metabolic dysregulation in sepsis.

OBJECTIVE: The objective of this study was to offer further evidence of the utility of metabolic monitoring in early recognition of sepsis. Metabolic derangement in sepsis is of increasing interest. Sepsis was redefined as a dysregulated host response to infection, and studies have since emerged advising that disrupted metabolic pathways in sepsis may interfere with the host's ability to convert oxygen to useable energy. Indirect calorimetry (IC) is a metabolic monitoring technology that measures oxygen consumption (V02) and resting energy expenditure (REE). IC offers clinically important, specific information in terms of patient's metabolic state and has been shown to differentiate patients with sepsis from those without. Additionally, IC is more specific than predictive equations used as the established standard for clinical nutrition. RESEARCH METHODS AND PROCEDURES: Data for this retrospective descriptive study were obtained from chart review of records of critically ill patients who received metabolic monitoring while under the care of the nutrition support team. Data were retrieved from January through March of 2020. The cases included were from January 2018 through January 2020. Variables included key demographics, sepsis diagnosis and specific metabolic variables of cellular respiration and energy expenditure. RESULTS: For this all-male sample (N = 56), mean age was 56 years (±17.5). Significant differences were noted in V02 between the two groups of cases (sepsis and non-sepsis); (p = .026, Cohen's d = 0.618); and REE (p = .032, Cohen's d = 0.607). A strong association was found between V02 and sepsis (Eta 0.981). REE as measured by IC was statistically more specific than predictive equation (p < .001, Cohen's d = 0.527). CONCLUSIONS: VO2 and REE were significantly altered in subjects with sepsis in this study, demonstrating that IC may be a useful tool in identifying sepsis. This study was based on an earlier pilot which yielded similar results. Indirect calorimetry can be easily performed clinically, offering specific metabolic information that can be helpful in the determination of a diagnosis of sepsis. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution to this manuscript. The study design, analysis of retrospective data, and manuscript preparation were completed entirely by the authors. IMPLICATIONS FOR CLINICIANS: Sepsis remains one of the number one killers of hospitalized patients globally Current means of identifying sepsis remain overly sensitive and under-specific, making recognition of sepsis challenging for Emergency Clinicians Metabolic monitoring can be done easily in the clinical setting by nurses and respiratory therapists. Metabolic monitoring has the capability of offering further information specific to the identification of sepsis, and to further understanding of the altered metabolic phenotype of patients with sepsis.

Raspberry plant stress detection using hyperspectral imaging.

Monitoring plant responses to stress is an ongoing challenge for crop breeders, growers, and agronomists. The measurement of below-ground stress is particularly challenging as plants do not always show visible signs of stress in the above-ground organs, particularly at early stages. Hyperspectral imaging is a technique that could be used to overcome this challenge if associations between plant spectral data and specific stresses can be determined. In this study, three genotypes of red raspberry plants grown under controlled conditions in a glasshouse were subjected to below-ground biotic stresses (root pathogen Phytophthora rubi and root herbivore Otiorhynchus sulcatus) or abiotic stress (soil water availability) and regularly imaged using hyperspectral cameras over this period. Significant differences were observed in plant biophysical traits (canopy height and leaf dry mass) and canopy reflectance spectrum between the three genotypes and the imposed stress treatments. The ratio of reflectance at 469 and 523 nm showed a significant genotype-by-treatment interaction driven by differential genotypic responses to the P. rubi treatment. This indicates that spectral imaging can be used to identify variable plant stress responses in raspberry plants.

Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer.

This single-arm pilot study (NCT03329937) evaluated neoadjuvant niraparib antitumor activity and safety in patients with localized HER2-negative, BRCA-mutated breast cancer. Twenty-one patients received niraparib 200 mg once daily in 28-day cycles. After 2 cycles, tumor response (≥30% reduction from baseline) by MRI was 90.5% and 40.0% (6 of 15) of patients who received only niraparib (2-6 cycles) had pathological complete response; no new safety signals were identified. High niraparib intratumoral concentration was observed.

Physiotherapy students' perspectives on the use and implementation of exoskeletons as a rehabilitative technology in clinical settings.

PURPOSE: Wearable lower body robotic exoskeletons are an emerging technology used in gait rehabilitation to facilitate task-specific overground walking. Despite their proposed utility as a rehabilitation intervention, exoskeletons have not been widely implemented into clinical practice by physiotherapists. This study aims to inform future development of exoskeleton technology through the exploration of physiotherapy student perspectives on the use of the H2 robotic exoskeleton and the implementation of exoskeletons as a therapeutic technology in neurological gait rehabilitation. METHODS: A qualitative descriptive study, including fifteen physiotherapy students, was conducted using three equally sized focus groups. A collaborative data analysis process was employed using the DEPICT model. RESULTS: Five themes were identified during data analysis: developing evidence-informed practice, clinical considerations for exoskeleton use, resource demands, device-specific challenges for implementation, and future development. The results suggest there are several barriers limiting novel clinicians' future use of exoskeletons. CONCLUSION: This study highlights current challenges surrounding exoskeleton implementation into clinical practice and provides direction for future exoskeleton development.Implications for rehabilitationPhysiotherapy students view exoskeletons as a potentially valuable rehabilitation tool once perceived limitations are addressed.This study encourages collaboration between physiotherapists and biomedical engineers for future exoskeleton development.More research is needed to inform treatment parameters and appropriate client criteria to guide exoskeleton use for gait rehabilitation.

Implementation of an Emergency Department-Embedded Infusion Center for the Administration of Monoclonal Antibody Therapy in Patients With Early COVID-19 Infection.

The coronavirus disease 2019 (COVID-19) pandemic has tested nurse staffing and other resources necessary for lifesaving treatment. The emergency use authorization in November 2020 of bamlanivimab as monotherapy and casirivimab/imdevimab as combination therapy brought hope to many as an option for outpatients at risk for severe illness. However, logistical concerns were soon revealed, because safe administration requires a location where patients can receive specialized care and monitoring for a period of 2 hours. This type of therapy would normally be offered at an outpatient infusion center. These centers often serve persons who are immunocompromised, and introducing COVID-19-positive individuals could threaten the safety of this population. This article describes the deployment of an emergency department-embedded infusion center set up for the purpose of supporting community members and providers electing for this treatment option.

Analyzing the Eye Gaze Behaviour of Students and Experienced Physiotherapists during Observational Movement Analysis.

Purpose: Physiotherapists use observational movement analysis (OMA) to inform clinical reasoning. This study aimed to (1) determine the feasibility of characterizing eye gaze behaviour during OMA with eye-tracking technology, (2) characterize experienced neurological physiotherapists' and physiotherapy students' eye gaze behaviour during OMA, and (3) investigate differences in eye gaze behaviour during OMA between physiotherapy students and experienced physiotherapists. Method: Eight students and eight physiotherapists wore an eye-tracking device while watching a video of a person with a history of stroke and subsequent concussion perform sit to stand. Feasibility criteria were (1) successful calibration of the eye tracker, and successful collection of data, for 80% of the participants and (2) moderate interrater reliability of the investigators, measured by intra-class correlation coefficients (ICCs). Three investigators independently recorded the participants' foveal fixations. Differences between physiotherapists and students in number of fixations, duration per fixation, and total duration of fixations were evaluated using unpaired t-tests, mean differences, and 95% CIs. Results: Data were collected for all participants. ICCs ranged from 0.64 to 0.78. Fixations by physiotherapists were shorter (mean 368.5 [SD 80.8] ms) and greater in number (mean 18.9 [SD 2.2]) than those by students (mean 459.0 [SD 64.2] ms, p = 0.03, and mean 15.9 [SD 2.7], p = 0.03), respectively. Conclusions: Measuring eye gaze behaviour during OMA using eye tracker technology is feasible. Physiotherapists made more fixations of shorter duration than students. Further investigation of how experienced therapists perform OMA and apply it to clinical reasoning may inform the instruction of OMA.

Objectif : les physiothérapeutes font appel à l'analyse observationnelle des mouvements (AOM) pour éclairer leur raisonnement clinique. La présente étude visait à 1) déterminer la faisabilité de caractériser le comportement du regard pendant l'AOM par la technologie de l'oculométrie, 2) caractériser le comportement du regard des physiothérapeutes neurologiques expérimentés et des étudiants en physiothérapie pendant l'AOM et 3) examiner les différences de comportement du regard des élèves physiothérapeutes par rapport aux physiothérapeutes d'expérience pendant l'AOM. Méthodologie : huit étudiants et huit physiothérapeutes ont porté un oculomètre en regardant la vidéo d'une personne ayant des antécédents d'accident vasculaire cérébral (AVC) et de commotion subséquente pour effectuer l'exercice assis-debout. Les critères de faisabilité s'établissaient comme suit : 1) la calibration réussie de l'oculomètre et la collecte réussie des données pour 80 % des participants et 2) une variabilité interévaluateurs modérée des chercheurs, mesurée par les coefficients de corrélation intraclasse (CCI). Trois chercheurs ont enregistré la fixation fovéale des participants. Ils ont évalué les différences entre les physiothérapeutes et les étudiants pour ce qui est du nombre de fixations, de la durée de chaque fixation et de la durée totale des fixations à l'aide des tests de Student non appariés, des différences moyennes et des intervalles de confiance à 95 %. Résultats : les données ont été colligées pour tous les participants. Les CCI se situaient entre 0,64 et 0,78. Les fixations des physiothérapeutes étaient plus courtes (368,5 [ÉT 80,8] ms) et plus fréquentes (18,9 [ÉT 2,2]) que celles des étudiants (459,0 [ÉT 64,2] ms, p = 0,03; 15,9 [ÉT 2,7], p = 0,03), respectivement. Conclusion : il est possible de mesurer le comportement du regard par oculométrie pendant l'AOM. Les physiothérapeutes avaient plus de fixations de courte durée que les étudiants. D'autres recherches sur la manière dont les thérapeutes d'expérience procèdent à l'AOM et l'appliquent à leur raisonnement clinique pourront éclairer les directives sur l'AOM.

Cranial Nerve Noninvasive Neuromodulation in Adults With Neurological Conditions: Protocol for a Scoping Review.

BACKGROUND: Cranial nerve noninvasive neuromodulation (CN-NINM) via translingual nerve stimulation (TLNS) is a promising new intervention combined with neurological rehabilitation to improve outcomes for persons with neurological conditions. A portable neuromodulation stimulation (PoNS) device rests on the tongue and stimulates cranial nerves V and VII (trigeminal and facial nerves, respectively). Emerging evidence suggests that CN-NINM using the PoNS device, combined with targeted physical therapy, improves balance and gait outcomes but has not yet been comprehensively reviewed. OBJECTIVE: This review will describe CN-NINM via TLNS and its applications, effects, and implications for rehabilitation science in adult populations with neurological conditions. We will identify how CN-NINM via TLNS is currently being incorporated into neurological rehabilitation and identify gaps in evidence with respect to this novel technology. METHODS: Joanna Briggs Institute methodology will be used to conduct this scoping review. Electronic databases MEDLINE, AMED, CINAHL, Embase, and Web of Science will be searched, as well as gray literature databases ProQuest, DuckDuckGo, and Google. Studies published in English and French between 2000 and 2021 will be included. Two reviewers will independently screen all titles and abstracts and full-text papers that meet the inclusion criteria. Data will be extracted and collated in a table to synthesize the results. Extracted data will be reported in a comprehensive summary. RESULTS: The final manuscript is intended for submission to an indexed journal in September 2021. CONCLUSIONS: This scoping review will be the first, to our knowledge, to address the current evidence on CN-NINM. The results will inform the use of CN-NINM in neurological rehabilitation and the development of recommendations for future research. TRIAL REGISTRATION: Open Science Framework 10.17605/OSF.IO/XZQFM; https://osf.io/xzqfm. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/29965.

Structuring community-based adapted dance programs for persons post-stroke: a qualitative study.

PURPOSE: Dance improves physical, psychosocial, and cognitive function, while increasing community participation among community-dwelling individuals post-stroke. Yet little is known about how to structure community-based dance classes to optimize benefits and participation. This study aims to gain stakeholders' perspectives about how to optimally structure community-based dance classes for individuals with chronic stroke. METHODS: A qualitative descriptive approach utilizing focus group methods was implemented. Two focus groups were undertaken with each of three stakeholder groups: persons post-stroke (n = 9), rehabilitation therapists (n = 6), and dance instructors (n = 8). Focus groups were audio-recorded and transcribed verbatim, providing the raw data. Analysis of the focus group transcripts were completed using the DEPICT model of collaborative qualitative analysis. RESULTS: This study identified three main themes/topics requiring consideration when structuring community-based dance programs: the environment, flow of the class, and qualities of the dance instructor. The study findings highlight that the pedagogical skills and teaching philosophy of the dance instructor are integral for a successful dance program, as the dance instructor directly mediates both the environment and flow of classes. CONCLUSION: Recommendations generated from our study can inform the development of community-based dance programs that are practical, optimize health benefits, and meet the needs and interests of people post-stroke.IMPLICATIONS FOR REHABILITATIONDance is an effective way to improve physical, psychosocial, and cognitive function for persons post-stroke while also promoting meaningful social relationships within the community.A dance instructor who is a skilled communicator and is willing to adapt to the needs of the class, is the most important factor for a successful dance class.Creating a safe and inviting environment for a dance program, includes both the physical and emotional aspects of environment facilitating individuals to create connections with others and feel more confident in themselves.The structure of a dance class, based on the abilities, interests, and goals of dancers, should include elements of predictability and variability to keep dancers progressing and motivated, and be two times a week for 3 months lasting 1-2 h.

Reflective mulch increases fruit yield of highbush blueberry (Vaccinium corymbosum L. cv. Darrow) grown in a northern maritime environment while maintaining key fruit quality traits.

BACKGROUND: In maritime growing environments, blueberry yield often exhibits excessive season-to-season variation, associated with poorly adapted photosynthetic responses to low light conditions. It is therefore necessary to develop methods that stabilise yield while maintaining or improving fruit quality. Here, we placed reflective mulch alongside plants at the early green fruit stage, to test the hypothesis that increasing the available seasonal light integral could enhance blueberry yield. We further determined several quality characteristics to ensure fruit marketability. RESULTS: Placement of mulch alongside plants reflected up to five times more light compared with bare ground, enhancing the amount of light reaching the canopy. This led to an adaptive increase of light saturated maximal photosynthetic rate of mulch-treated plants, resulting in a twofold increase in yield compared with control plants. Analysis of fruit quality characteristics showed that total soluble solids, sugars and organic acids were similar between treatments. Likewise, antioxidant capacity, total anthocyanin content and the content of individual anthocyanins did not change in response to reflective mulch treatment. CONCLUSIONS: The use of reflective mulch should be explored by industry as a cost-effective method for enhancing blueberry yield while maintaining fruit quality in maritime environments. © 2020 Society of Chemical Industry.

Exoskeleton use in post-stroke gait rehabilitation: a qualitative study of the perspectives of persons post-stroke and physiotherapists.

BACKGROUND: Wearable powered exoskeletons are a new and emerging technology developed to provide sensory-guided motorized lower limb assistance enabling intensive task specific locomotor training utilizing typical lower limb movement patterns for persons with gait impairments. To ensure that devices meet end-user needs it is important to understand and incorporate end-users perspectives, however research in this area is extremely limited in the post-stroke population. The purpose of this study was to explore in-depth, end-users perspectives, persons with stroke and physiotherapists, following a single-use session with a H2 exoskeleton. METHODS: We used a qualitative interpretive description approach utilizing semi-structured face to face interviews, with persons post-stroke and physiotherapists, following a 1.5 h session with a H2 exoskeleton. RESULTS: Five persons post-stroke and 6 physiotherapists volunteered to participate in the study. Both participant groups provided insightful comments on their experience with the exoskeleton. Four themes were developed from the persons with stroke participant data: (1) Adopting technology; (2) Device concerns; (3) Developing walking ability; and, (4) Integrating exoskeleton use. Five themes were developed from the physiotherapist participant data: (1) Developer-user collaboration; (2) Device specific concerns; (3) Device programming; (4) Patient characteristics requiring consideration; and, (5) Indications for use. CONCLUSIONS: This study provides an interpretive understanding of end-users perspectives, persons with stroke and neurological physiotherapists, following a single-use experience with a H2 exoskeleton. The findings from both stakeholder groups overlap such that four over-arching concepts were identified including: (i) Stakeholder participation; (ii) Augmentation vs. autonomous robot; (iii) Exoskeleton usability; and (iv) Device specific concerns. The end users provided valuable perspectives on the use and design of the H2 exoskeleton, identifying needs specific to post-stroke gait rehabilitation, the need for a robust evidence base, whilst also highlighting that there is significant interest in this technology throughout the continuum of stroke rehabilitation.

Investigating Visual-Spatial Abilities in Students and Expert Physical Therapists.

Purpose: Visual-spatial abilities (VSAs) - the aptitude for mentally processing, retaining, and manipulating visual input - are used by physical therapists in movement analysis. Superior VSAs have been demonstrated in experts compared with novices in other fields, including surgery, anatomy, and aviation, but no literature has investigated VSAs in physical therapy. The purpose of this study was to quantify VSAs in expert and student physical therapists and investigate the differences between the two groups. Our results could assist future researchers in identifying areas for skill development and improved clinical competency in students and novice therapists. Method: Expert physical therapists and first-year PT students completed four computerized VSA tests in the Psychology Experiment Building Language programme: Four-Choice Response, Sequential Pattern Comparison, Mental Rotation, and Situation Awareness. Results: A total of 16 participants were recruited for each group. Expert physical therapists responded more accurately to the Four-Choice Response test, but not significantly so (p = 0.06), and with a significantly slower response time than student physical therapists (p = 0.03). No other differences were found. Conclusions: These findings suggest that expert physical therapists use selective attention more effectively and may value accuracy over speed. No differences were found in other measures of VSAs. Further studies are required to confirm and expand our findings.

Objectif : les physiothérapeutes font appel à leurs aptitudes visuospatiales (AVS), c'est-à-dire les aptitudes mentales à traiter, à retenir et à manipuler les données visuelles, lors de l'analyse des mouvements. Dans d'autres domaines, les spécialistes ont des AVS supérieures à celles des novices, y compris en chirurgie, en anatomie et en aviation, mais aucune publication ne traite des AVS en physiothérapie. La présente étude visait à quantifier les AVS des physiothérapeutes spécialisés et des étudiants en physiothérapie et à explorer les différences entre les deux groupes. Les résultats pourraient aider les futurs chercheurs à déterminer les secteurs où il est nécessaire d'acquérir des aptitudes et d'améliorer les compétences cliniques chez les étudiants en physiothérapie et les thérapeutes novices. Méthodologie : des physiothérapeutes spécialisés et des étudiants en première année de physiothérapie ont effectué quatre tests d'AVS informatisés du programme d'acquisition du langage de psychologie expérimentale : quatre choix de réponses, comparaison de configurations séquentielles, rotation mentale et conscience situationnelle. Résultats : au total, les chercheurs ont recruté 16 participants dans chaque groupe. Les physiothérapeutes spécialisés ont répondu avec plus de précision au test des quatre choix de réponses, mais pas de manière significative (p = 0,06), et leur temps de réponse était significativement plus long que celui des étudiants en physiothérapie (p = 0,03). Aucune autre différence n'a été observée. Conclusions : selon ces résultats, les physiothérapeutes spécialisés utilisent l'attention sélective avec plus d'efficacité et privilégieraient la précision plutôt que la vitesse. Les chercheurs n'ont pas remarqué de différences dans les autres mesures d'AVS. D'autres mesures s'imposent pour confirmer et élargir les observations.

Mitochondrial Dysregulation in Sepsis: A Literature Review.

BACKGROUND: Until 2016, the condition Sepsis was widely understood to be the systemic immune response syndrome in the presence or suspicion of an infectious source. Systemic immune response syndrome, an adaptive response, has been repeatedly demonstrated to lack specificity for sepsis. The current definition of sepsis describes a dysregulated host response to infection, yet the dysregulated nature of the response has yet to be defined. Successful recognition and management of sepsis are critically dependent on understanding and operationalizing the definition of sepsis. OBJECTIVE: The authors sought to review the current literature on sepsis and its relationship to oxygen downregulation within the mitochondria along the electron transport chain. METHODS: Articles retrieved from databases PubMed and CINAHL, pertaining to human cells, post 2001, in English, original experimental, quasi-experimental, or cohort design. Articles were selected and retrieved by the first author and synthesized by both authors. RESULTS: The 10 articles included in the review were all bench science cellular studies. They demonstrated consistent, statistically significant differences when investigating mitochondrial oxygen downregulation in sepsis versus control, offering strong, statistically significant support for the hypothesis of mitochondrial dysregulation in the septic host. CONCLUSIONS: The evidence makes a compelling case for mitochondrial dysregulation to inform the current definition of sepsis as a dysregulated host response. As the evidence points to a linear, progressive time/exposure-dependent disruption in oxygen downregulation in sepsis at the cellular level, it lends credence to the recommendations for early intervention and its relationship with survivability. Time is not on the side of the individual with sepsis.

Author Correction: Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer.

Combined PARP and immune checkpoint inhibition has yielded encouraging results in ovarian cancer, but predictive biomarkers are lacking. We performed immunogenomic profiling and highly multiplexed single-cell imaging on tumor samples from patients enrolled in a Phase I/II trial of niraparib and pembrolizumab in ovarian cancer (NCT02657889). We identify two determinants of response; mutational signature 3 reflecting defective homologous recombination DNA repair, and positive immune score as a surrogate of interferon-primed exhausted CD8 + T-cells in the tumor microenvironment. Presence of one or both features associates with an improved outcome while concurrent absence yields no responses. Single-cell spatial analysis reveals prominent interactions of exhausted CD8 + T-cells and PD-L1 + macrophages and PD-L1 + tumor cells as mechanistic determinants of response. Furthermore, spatial analysis of two extreme responders shows differential clustering of exhausted CD8 + T-cells with PD-L1 + macrophages in the first, and exhausted CD8 + T-cells with cancer cells harboring genomic PD-L1 and PD-L2 amplification in the second.