Lung volume reduction surgery is safe and leads to functional improvement in patients who fail or cannot undergo bronchoscopic lung volume reduction.

Background: Bronchoscopic lung volume reduction (BLVR) has supplanted surgery in the treatment of patients with advanced emphysema, but not all patients qualify for it. Our study aimed to investigate the outcomes of lung volume reduction surgery (LVRS) among patients who either failed BLVR or were not candidates for it. Methods: We conducted a retrospective analysis of patients who underwent LVRS for upper lobe-predominant emphysema at a single tertiary center between March 2018 and December 2022. The main outcomes measures were preoperative and postoperative respiratory parameters, perioperative morbidity, and mortality. Results: A total of 67 LVRS recipients were evaluated, including 10 who had failed prior valve placement. The median patient age was 69 years, and 35 (52%) were male. All procedures were performed thoracoscopically, with 36 patients (53.7%) undergoing bilateral LVRS. The median hospital length of stay was 7 days (interquartile range, 6-11 days). Prolonged air leak (>7 days) occurred in 20 patients. There was one 90-day mortality from a nosocomial pneumonia (non-COVID-related) and no further deaths at 12 months. There were mean improvements of 10.07% in forced expiratory volume in 1 second and 4.74% in diffusing capacity of the lung for carbon monoxide, along with a mean decrease 49.2% in residual volume (P < .001 for all). The modified Medical Research Council dyspnea scale was improved by 1.84 points (P < .001). Conclusions: LVRS can be performed safely in patients who are not candidates for BLVR and those who fail BLVR and leads to significant functional improvement. Long-term follow-up is necessary to ensure the sustainability of LVRS benefits in this patient population.

Lung Transplantation for COVID-19 Pulmonary Sequelae.

BACKGROUND: The role of lung transplantation for coronavirus disease 2019 (COVID-19)-related lung failure is evolving as the pandemic persists. METHODS: From January 2021 to April 2022, 20 patients (median age 62 y; range 31-77) underwent lung transplantation for COVID-related lung failure at our institution. We reviewed their clinical and intraoperative characteristics and early outcomes including postoperative complications. RESULTS: Eleven patients (55%) had chronic lung disease when they contracted COVID-19. All 20 patients required hospitalization for antivirus treatment. Median lung allocation score was 74.7 (33.1-94.0). Thirteen patients (65%) underwent single-lung transplants, and 7 patients (35%) underwent double-lung transplants. Concomitant coronary artery bypass graft surgery was performed in 2 (10%) patients because of severe coronary artery disease. Postoperatively, venovenous extracorporeal membrane oxygenation was needed in 3 patients (15%) because of severe primary graft dysfunction; all were eventually weaned. Ten patients (50%) experienced deep venous thrombosis, and 1 eventually developed a major pulmonary embolus. The median intensive care unit stay and hospital stays were 6.5 d (3-44) and 18 d (7-77), respectively. During a median follow-up of 201 d (47-418), we experienced 1 late mortality due to COVID-19-related myocarditis. Among the 13 patients with single-lung transplant, 5 demonstrated improvement in their native lungs. CONCLUSIONS: Lung transplantation yielded favorable early outcomes in a heterogeneous patient cohort that included older patients, obese patients, and patients with coronary artery disease or preexisting chronic lung disease. Our data also shed light on the transforming role of lung transplantation for the pulmonary sequelae of a complex multisystem COVID-19 disorder.

Single Lung Transplant Remains a Viable Option for Patients With Severe Secondary Pulmonary Hypertension.

BACKGROUND: Although double lung transplant is recommended in patients with severe secondary pulmonary hypertension (SPH), our institutional experiences suggest a role for single lung transplant in these patients. Here, we review our experience prioritizing single lung transplant in patients with SPH to minimize their surgical burden. METHODS: We conducted a retrospective review of our lung transplant database to identify patients with SPH who underwent single lung transplant. Patients were stratified as either mild SPH (mean pulmonary artery pressure 25-40 mm Hg) or severe SPH (mean pulmonary artery pressure >40 mm Hg). Singe lung recipients without PH transplanted over the same time were also examined. RESULTS: Between January 2017 and December 2019, 318 patients underwent single lung transplantation; 217 had mild SPH (68%), and 59 had severe SPH (18.5%). Forty-two patients without PH underwent single lung transplant. When the groups were compared, significantly higher pulmonary vascular resistance was noted in the severe SPH group, and obesity was noted in both the mild and severe SPH groups. Although the severe SPH group required more intraoperative cardiopulmonary support (37.3% versus 10.3% versus 4.7%, P < 0.05), there were no significant differences in most major postoperative parameters, including the duration of postoperative mechanical ventilation or the incidence of severe primary graft dysfunction. Survival 1 y posttransplant was not significantly different among the groups (93.2% versus 89.4% versus 92.9%, P = 0.58). CONCLUSIONS: Our experience supports the option of single lung transplantation with appropriate intraoperative mechanical circulatory support in patients with SPH. This strategy is worth pursuing, especially with ongoing donor lung shortages.

'A roller coaster of emotions': a phenomenological study on medical students lived experiences of emotions in complex simulation.

BACKGROUND: Simulation-based education can induce intense learner emotions. The interplay between emotions and learning is less well understood. Gaining greater insights into learner emotions has potential to guide how best we manage emotions and optimise learning. This study aimed to understand learners' lived emotional experiences in complex simulation and the perceived impact on learning. METHODS: Eight final-year medical students participated in the study. Wearing video-glasses, participants took part in a ward-based simulation. Video-footage was used to elicitate exploratory interviews and analysed using Template Analysis reflexively. RESULTS: Analysis yielded four main themes: 'nervous anticipation': encapsulating the fear, anxiety and uncertainty experienced by learners prior to simulation; 'shock and awe': feelings of anxiousness and being overwhelmed at the start of a simulation; 'in the moment: flowing or buffeting with the emotions': experiencing fear of being judged as incompetent, but also experiencing positive emotions such as satisfaction; 'safe-landing?': whilst debriefing aimed to encourage more positive emotions, negative emotions about the simulation could persist even with debriefing. CONCLUSIONS: Complex simulation can evoke intense emotions in students. If students experienced a positive progression, they reported positive emotions and felt competent which was perceived to have a positive impact on learning. If students experienced failure, they reported strong negative emotions which made them question about their future performance and was perceived as negative for learning. Bringing to the surface these complex emotional dynamics, could permit educators to be aware of and adapt the emotional climate within simulation in order to optimise learning.

CAG Repeat Size Influences the Progression Rate of Spinocerebellar Ataxia Type 3.

OBJECTIVE: In spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the expanded cytosine adenine guanine (CAG) repeat in ATXN3 is the causal mutation, and its length is the main factor in determining the age at onset (AO) of clinical symptoms. However, the contribution of the expanded CAG repeat length to the rate of disease progression after onset has remained a matter of debate, even though an understanding of this factor is crucial for experimental data on disease modifiers and their translation to clinical trials and their design. METHODS: Eighty-two Dutch patients with SCA3/MJD were evaluated annually for 15 years using the International Cooperative Ataxia Rating Scale (ICARS). Using linear growth curve models, ICARS progression rates were calculated and tested for their relation to the length of the CAG repeat expansion and to the residual age at onset (RAO): The difference between the observed AO and the AO predicted on the basis of the CAG repeat length. RESULTS: On average, ICARS scores increased 2.57 points/year of disease. The length of the CAG repeat was positively correlated with a more rapid ICARS progression, explaining 30% of the differences between patients. Combining both the length of the CAG repeat and RAO as comodifiers explained up to 47% of the interpatient variation in ICARS progression. INTERPRETATION: Our data imply that the length of the expanded CAG repeat in ATXN3 is a major determinant of clinical decline, which suggests that CAG-dependent molecular mechanisms similar to those responsible for disease onset also contribute to the rate of disease progression in SCA3/MJD. ANN NEUROL 2021;89:66-73.

Genetic data improves niche model discrimination and alters the direction and magnitude of climate change forecasts.

Ecological niche models (ENMs) have classically operated under the simplifying assumptions that there are no barriers to gene flow, species are genetically homogeneous (i.e., no population-specific local adaptation), and all individuals share the same niche. Yet, these assumptions are violated for most broadly distributed species. Here, we incorporate genetic data from the widespread riparian tree species narrowleaf cottonwood (Populus angustifolia) to examine whether including intraspecific genetic variation can alter model performance and predictions of climate change impacts. We found that (1) P. angustifolia is differentiated into six genetic groups across its range from México to Canada and (2) different populations occupy distinct climate niches representing unique ecotypes. Comparing model discriminatory power, (3) all genetically informed ecological niche models (gENMs) outperformed the standard species-level ENM (3-14% increase in AUC; 1-23% increase in pROC). Furthermore, (4) gENMs predicted large differences among ecotypes in both the direction and magnitude of responses to climate change and (5) revealed evidence of niche divergence, particularly for the Eastern Rocky Mountain ecotype. (6) Models also predicted progressively increasing fragmentation and decreasing overlap between ecotypes. Contact zones are often hotspots of diversity that are critical for supporting species' capacity to respond to present and future climate change, thus predicted reductions in connectivity among ecotypes is of conservation concern. We further examined the generality of our findings by comparing our model developed for a higher elevation Rocky Mountain species with a related desert riparian cottonwood, P. fremontii. Together our results suggest that incorporating intraspecific genetic information can improve model performance by addressing this important source of variance. gENMs bring an evolutionary perspective to niche modeling and provide a truly "adaptive management" approach to support conservation genetic management of species facing global change.

Sleep Duration and Efficiency Associated With Better Functional Exercise Capacity in Black Smokers at Risk for COPD.

BACKGROUND: Black smokers have earlier development of lung disease as well as poorer sleep health than whites. RESEARCH QUESTION: In a sample of black smokers, to what extent does sleep health modify the association between smoking level and functional exercise capacity? DESIGN AND METHODS: Cross-sectional data from 209 black smokers (≥ 1 cigarette in last month), aged 40 to 65 years with no evidence of sleep-disordered breathing (apnea-hypopnea index < 15) or severe COPD (FEV1 > 50%), were used for the current study. Self-reported smoking rate, objectively measured sleep efficiency (SE), total sleep time (TST), and the 6-min walk test (6MWT) for functional exercise capacity were the key assessments. RESULTS: The mean age was 54.8 years (SD, 5.96), and mean cigarettes smoked per day (cpd) was 8.71 (SD, 6.78). Mean SE was 69.9% (SD, 12.3%), and mean TST was 307.99 min (SD 92.2). In adjusted linear regression models of the 6MWT (meters), TST (slope estimate, -0.14; P = .14) and SE (slope estimate, -1.0; P = .19) were negatively associated with 6MWT. The smoking rate × SE interaction was highly significant (slope estimate, 0.18; P = .007) such that in individuals who smoked ≥ 10 cpd, every additional percentage of SE garnered an additional distance of 0.83 to 6.62 m. Similarly, the smoking rate × TST interaction was significant (slope estimate, 0.019; P = .03) such that in smokers who smoked ≥ 10 cpd, every additional minute of TST garnered an additional distance of 0.04 to 0.60 m. INTERPRETATION: Higher SE and, to a lesser extent, longer TST, in black adults who smoke ≥ 10 cpd is associated with better 6MWT performance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03534076; URL: www.clinicaltrials.gov.

Exploring undergraduate students achievement emotions during ward round simulation: a mixed-method study.

BACKGROUND: Simulation based learning (SBL) has increased in its use to best equip students for clinical practice. Simulations that mirror the complex realities of clinical practice have the potential to induce a range of emotions, without a clear understanding of their impact on learning and the learner. Students' emotional states have important effects on their learning process that can be either positive or negative, and are often difficult to predict. We aimed to determine: (1) To what extent achievement emotions are experienced by medical students during a complex simulation based learning activity, i.e. a ward round simulation (WRS). (2) What their performance scores are and too which extent performance scores do correlate with emotions and 3) how these emotions are perceived to impact learning. METHODS: A mixed methods approach was used in this study. Using an Achievement Emotion Questionnaire, we explored undergraduate medical student's emotions as they participated in a complex ward round-based simulation. Their performance was rated using an observational ward round assessment tool and correlated with emotions scores. Six focus groups were conducted to provide a deeper understanding of their emotional and learning experiences. RESULTS: Students experienced a range of emotions during the simulation, they felt proud, enjoyed the simulation and performed well. Students felt proud because they could show in the complex simulation what they had learned so far. Students reported moderate levels of anxiety and low levels of frustration and shame. We found non-significant correlations between achievement emotions and performance during ward round simulation. CONCLUSIONS: Placing undergraduate students in high complex simulations that they can handle raises positive academic achievement emotions which seem to support students' learning and motivation.

Clinical Course of Motor Deficits from Lumbosacral Radiculopathy Due to Disk Herniation.

BACKGROUND: The clinical course of motor deficits from lumbosacral radiculopathy appears to improve with or without surgery. Strength measurements have been confined to manual muscle testing (MMT) and have not been extensively followed and quantified in prior studies. OBJECTIVE: To determine if motor weakness and patient-reported outcomes related to lumbosacral radiculopathy improve without surgical intervention over the course of 12 months. DESIGN: Prospective observational cohort. SETTING: Outpatient academic spine practice. PARTICIPANTS: Adults with acute radicular weakness due to disk herniation. METHODS: Forty patients with radiculopathy and strength deficit were followed over a 12-month period. Objective strength and performance tests as well as survey-based measurements were collected at baseline and then every 3 months. Patients underwent comprehensive pain management and rehabilitation and/or surgical approaches as determined in coordination with the treating specialist. This study was approved by the institutional review board of Colorado. MAIN OUTCOME MEASUREMENTS: Testing of strength was through MMT, handheld dynamometer, and performance-based testing. Furthermore, visual analog scale, modified Oswestry Disability Index, and 36-Item Short Form Health Survey (SF-36) were used to measure pain and disability outcomes. RESULTS: Of the 40 patients, 33 (82.5%) did not have surgery; 7 (17.5%) had surgery. Twenty-four of the 33 patients (60%) did not undergo surgery and were followed for 12 months (Comprehensive Pain Management and Rehabilitation, Complete [CPM&R-C]), and 9 (22%) did not have surgery and lacked at least one follow-up evaluation (Comprehensive Pain Management and Rehabilitation, Incomplete [CPM&R-I]). No statistically significant differences were found on baseline measures of strength deficits and SF-36 domains between the CPM&R-C, Surgery, and CPM&R-I groups. Pain and disability scores in the Surgery group were significantly higher than in the CPM&R-C at baseline. There were statistically significant improvements in all areas of strength, pain, and function when comparing measurements at the 12-month follow-up to baseline in the CPM&R-C group. CONCLUSIONS: Individuals with motor deficits due to lumbosacral radiculopathy improve over time regardless of treatment choice. Most did not choose surgery, and almost all of these patients regained full strength at 1 year. Strength recovery typically occurred in the first 3 months, but there was ongoing recovery over the course of a year. LEVEL OF EVIDENCE: II.

Integrin α6 (CD49f), The Microenvironment and Cancer Stem Cells.

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin α6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.

The distribution of novel biomarkers in carcinoma-in-situ, microinvasive, and squamous cell carcinoma of the uterine cervix.

Importin-ß, exportin-5, p16, Ki-67, Mcl1, PDL1, and cFLIP are each over-expressed in the majority of CIN 1 lesions. These biomarkers, plus HPV E6/E7 RNA, were analyzed in carcinoma-in-situ (CIS), microinvasive, and squamous cell carcinoma (SCC) of the uterine cervix and cervical carcinoma cell lines. Only p16 and Ki-67 continued to be over-expressed in CIS, with a concomitant marked increase in E6/E7 RNA. There was a highly significant increase in PDL1 expression and decrease in Ki-67 (each p < 0.001) in microinvasive cancer compared to CIS whereas p16 and E6/E7 remained stable. As the lesion progressed to SCC, p16 and E6/E7 RNA remained strongly overexpressed with a concomitant over expression of importin-ß and Ki67. HPV positive Caski cells showed significant elevations of p16, importin-ß, exportin-5 and PDL1 compared to the HPV negative cervical cancer cell line C33A, consistent with viral induction of these biomarkers. The data suggest that PDL1 may be a useful biomarker to differentiate CIS from microinvasive cancer and, thus, anti-PDL1 therapy may inhibit the progression of CIS to the invasive stage.

The Atypical Chemokine Receptor ACKR2 is Protective Against Sepsis.

Sepsis is a systemic inflammatory response as a result of uncontrolled infections. Neutrophils are the first cells to reach the primary sites of infection, and chemokines play a key role in recruiting neutrophils. However, in sepsis chemokines could also contribute to neutrophil infiltration to vital organs leading to multiple organ failure. ACKR2 is an atypical chemokine receptor, which can remove and degrade inflammatory CC chemokines. The role of ACK2 in sepsis is unknown. Using a model of cecal ligation and puncture (CLP), we demonstrate here that ACKR2 deficient () mice exhibited a significant reduction in the survival rate compared with similarly treated wild-type (WT) mice. However, neutrophil migration to the peritoneal cavity and bacterial load were similar between WT and ACKR2 mice during CLP. In contrast, ACKR2 mice showed increased neutrophil infiltration and elevated CC chemokine levels in the lung, kidney, and heart compared with the WT mice. In addition, ACKR2 mice also showed more severe lesions in the lung and kidney than those in the WT mice. Consistent with these results, WT mice under nonsevere sepsis (90% survival) had higher expression of ACKR2 in these organs than mice under severe sepsis (no survival). Finally, the lungs from septic patients showed increased number of ACKR2 cells compared with those of nonseptic patients. Our data indicate that ACKR2 may have a protective role during sepsis, and the absence of ACKR2 leads to exacerbated chemokine accumulation, neutrophil infiltration, and damage to vital organs.

Idiopathic pulmonary fibrosis: A guide for nurse practitioners.

Idiopathic pulmonary fibrosis (IPF) is a rare disease characterized by decline in lung function, dyspnea, and cough. The clinical course of IPF is variable and unpredictable. Early referral to specialists is key to ensure timely and accurate diagnosis. Two antifibrotic drugs (nintedanib and pirfenidone) have been approved for the treatment of IPF.

Ward round simulation in final year medical students: Does it promote students learning?

INTRODUCTION: Ward round skills are essential for doctors in hospital settings. Literature shows medical students' deficiencies in these skills. Simulation has been used to train these skills. However, exposing learners to simulation at an early stage may be associated with a high cognitive load and limited learning. This study aims to determine how students experience this load and its interplay with performance and which factors promote and impair learning. METHODS: Fifty-six final year medical students participated in a simulated ward round training exercise. Both students' performance and cognitive load were measured to determine if there was any correlation and interviews were carried out to understand which factors support and impair learning. RESULTS: Performance scores revealed deficiencies in ward round skills. Students experienced a cognitive load that weakly correlated with performance. Qualitative findings provided important insights into simulated ward-based learning. It is clear that well-designed clinical scenarios, prioritization tasks, teamwork and feedback support students' learning process whereas distractions impair learning. CONCLUSIONS: WRS proved to be a good teaching method to improve clinical skills at this stage as the cognitive load is not too high to impair learning. Hence, including tasks in the simulation design can enhance the learning process.

The role of p16 as putative biomarker for cervical neoplasia: A controversial issue? / O Papel da Proteina p16 como marcador putativo para neoplasia cervical: um tema controverso?

INTRODUCTION: Protein p16 has been extensively studied as a potential biomarker for precursor lesions to distinguish cervical Intraepithelial neoplasia (CIN) from their mimics. However, the use of p16 as prognostic biomarker for diagnosis of cervical cancer and precancer is controversial. This study focuses on the assessment of peer-reviewed scientific data related to the use of p16 to predict disease severity and its controversies. METHODS: We reviewed publications in MEDLINE/PubMed assessing the clinical, diagnostic and prognostic significance of p16 in CIN and cervical cancer; we included publications from 2009 to June 2017. RESULTS: The use of p16 as a prognostic marker is still unreliable, although it could be a useful tool for diagnosis of Cervical Intraepithelial Neoplasia lesions with undetermined morphology. Moreover, p16 appears to be a specific marker of high-risk oncogenic HPV infection. CONCLUSION: This review shows the potential utility and drawbacks of p16 for clinical practice and the diagnosis of cervical cancer. Further studies are required to substantiate the role of p16 in conjunction with other more sensitive and specific biomarkers for diagnosing CIN and predicting its progression.

INTRODUÇÃO: A proteína p16 tem sido estudada como um biomarcador potencialmente específico de lesões cervicais precursoras e como uma forma de diferenciar as lesões parecidas com Neoplasia intra-epitelial cervical (NIC). Contudo existem várias controvérsias sobre a utilização de p16 como um biomarcador prognóstico e como uma ferramenta para o diagnóstico de câncer cervical e de lesões pré-câncer. O objetivo deste estudo foi a revisão de dados científicos por pares de bases, relacionados com a utilização da p16 e suas controvérsias. MÉTODOS: O estudo foi projetado como uma revisão da literatura das publicações do Medline/PubMed que avaliam o significado clínico, diagnóstico ou prognóstico do p16 em lesões de NIC e no câncer cervical no período de janeiro de 2009 a junho de 2017. RESULTADOS: o uso do p16 como um marcador prognóstico ainda não é confiável, apesar de que a p16 poderia ser uma ferramenta útil para o diagnóstico em lesões de NIC com morfologia indeterminada. Além disso, a p16 parece ser um marcador específico de infecção por HPV de alto risco oncogênico. CONCLUSÃO: A presente revisão mostra a potencial utilidade da proteína p16, bem como os inconvenientes para uso clínico-patológico e diagnóstico no câncer cervical. Contudo são necessários mais estudos para fundamentar o papel da p16 em conjunto com os outros biomarcadores mais sensíveis e específicos para diagnosticar NIC e prever a sua progressão.

Dengue fatal cases present virus-specific HMGB1 response in peripheral organs.

Dengue is an important infectious disease that presents high incidence and yields a relevant number of fatal cases (about 20,000) every year worldwide. Despite its epidemiological relevance, there are many knowledge gaps concerning dengue pathogenesis, especially with regards to the circumstances that drive a mild clinical course to a severe disease. In this work, we investigated the participation of high mobility group box 1 (HMGB1), an important modulator of inflammation, in dengue fatal cases. Histopathological and ultrastructural analyses revealed that liver, lung and heart post-mortem samples were marked by tissue abnormalities, such as necrosis and apoptotic cell death. These observations go in line with an HMGB1-mediated response and raised concerns regarding the participation of this cytokine in promoting/perpetuating inflammation in severe dengue. Further experiments of immunohistochemistry (IHC) showed increased expression of cytoplasmic HMGB1 in dengue-extracted tissues when compared to non-dengue controls. Co-staining of DENV RNA and HMGB1 in the host cell cytoplasm, as found by in situ hybridization and IHC, confirmed the virus specific induction of the HMGB1-mediated response in these peripheral tissues. This report brings the first in-situ evidence of the participation of HMGB1 in severe dengue and highlights novel considerations in the development of dengue immunopathogenesis.