Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.

Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.

Intravenous MELAtonin for prevention of Postoperative Agitation and Emergence Delirium in children (MELA-PAED): A protocol and statistical analysis plan for a randomized clinical trial.

BACKGROUND: Emergence agitation and delirium in children remain a common clinical challenge in the post-anesthetic care unit. Preoperative oral melatonin has been suggested as an effective preventive drug with a favorable safety profile. The oral bioavailability of melatonin, however, is low. Therefore, the MELA-PAED trial aims to investigate the efficacy and safety of intraoperative intravenous melatonin for the prevention of emergence agitation in pediatric surgical patients. METHODS: MELA-PAED is a randomized, double-blind, parallel two-arm, multi-center, superiority trial comparing intravenous melatonin with placebo. Four hundred participants aged 1-6 years will be randomized 1:1 to either the intervention or placebo. The intervention consists of intravenous melatonin 0.15 mg/kg administered approximately 30 min before the end of surgery. Participants will be monitored in the post-anesthetic care unit (PACU), and the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) will be performed on days 1, 7, and 14 after the intervention. Serious Adverse Events (SAE) will be assessed up to 30 days after the intervention. RESULTS: The primary outcome is the incidence of emergence agitation, assessed dichotomously as any Watcha score >2 during the participant's stay in the post-anesthetic care unit. Secondary outcomes are opioid consumption in the post-anesthetic care unit and adverse events. Exploratory outcomes include SAEs, postoperative pain, postoperative nausea and vomiting, and time to awakening, to first oral intake, and to discharge readiness. CONCLUSION: The MELA-PAED trial investigates the efficacy of intravenous intraoperative melatonin for the prevention of emergence agitation in pediatric surgical patients. Results may provide further knowledge concerning the use of melatonin in pediatric perioperative care.

Surgical wound assessment tool: Construct validity and inter-rater reliability of a tool designed for nurses.

AIMS AND OBJECTIVES: To validate construct validity and inter-rater reliability of a surgical wound assessment tool. BACKGROUND: Wound assessment is central to appropriate wound management. However, limited standard surgical wound assessment tools are available to assist nurses in assessing and recording progress in the healing of surgical wounds. DESIGN: A prospective observational study was utilised to test the validity and reliability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline was used. METHODS: Convenience sampling was used to recruit 260 patients who underwent elective or emergency surgery at a hospital in Vietnam. Exploratory factor analysis was used to examine the construct validity of the surgical wound assessment tool. Inter-rater reliability was calculated using the intraclass correlation coefficient and Cohen's kappa to determine reliability of the overall scale and identified items. RESULTS: The results of the exploratory factor analysis supported a three-component structure of the surgical wound assessment tool. The intraclass correlation coefficient value of the overall scale was 0.79 (95% CI 0.67-0.89), p < .001, confirming excellent inter-rater reliability. Cohen's kappa value ranged from 0.5 to 1, demonstrating moderate to almost perfect level of agreement for individual items, except for one item on pain. CONCLUSION: The surgical wound assessment tool was deemed to be acceptable, valid and reliable for monitoring the status of surgical wound healing. However, further modification and testing are needed to strengthen the tool and to determine the applicability of the tool in other populations. RELEVANCE TO CLINICAL PRACTICE: The application of the SWAT would improve the assessment of surgical wounds in daily nursing practice which will promote improved postoperative wound management. It is an easy and practical tool for enhancing inter-disciplinary communication and care outcomes for all patients with surgical wounds.

Notes on Culturable Endophytic Microorganisms Isolated from 14 Medicinal Plants in Vietnam: A Diversity Analysis to Predict the Host-Microbe Correlations.

Endophytes can generate a cornucopia of marvelous bioactive secondary metabolites useful for mankind but their biodiversity and associations with host plants are still elusive. In this study, we explored the culturable endophytic microorganisms associated with 14 medicinal plants that are of high socio-economic value and/or reportedly endemic to northern Vietnam. Specifically, we isolated the endophytic microorganisms by applying surface sterilization methods and identified them based on morphological and rDNA sequence analyses. Agglomerative Hierarchical Clustering (AHC) and Principal Component Analysis (PCA) were used to analyze the correlations between the taxonomic affiliations of the culturable endophytes and the characteristics of their hosts. Most of the culturable endophytes obtained were bacteria (80), and few of those were actinomycetes (15) and fungi (8). Many of them are reported to be endophytes of medicinal plants for the first time. A number of plants (5) are also reported for the first time to contain microbial endophytes, while some plants with powerful pharmaceutical potential harbor unique endophytes. Furthermore, our results reveal a strikingly close relation between the compositions of bacterial and fungal isolates from plants having anti-bacterial activity and those from plants having anti-inflammatory activity, or between the compositions of the microbial endophytic isolates from plants having anti-cancer activity and those from plants having antioxidant activity. Altogether, the results provide new findings which can be inspiring for further in-depth studies to explore and exploit the relationships between medicinal plants and their associated endophytes in northern Vietnam and world-wide.

Development of a surgical wound assessment tool to measure healing and risk factors for delayed wound healing in Vietnam: a Delphi process.

OBJECTIVE: To identify items and develop a surgical wound assessment tool (SWAT) to measure progress in healing and early detection of risk factors for delayed healing in surgical wounds in patients in Vietnam. METHOD: The development process included two phases: (i) development of the initial SWAT based on evidence-based guidelines, results of a literature review and consultation with surgeons; and (ii) a Delphi process with wound care nurse experts to refine and provide consensus on a final version of the SWAT. Data collection took place between April-August 2017. RESULTS: In phase one, 22 items were included and were evaluated by ten Vietnamese surgeons, with item-content validity index (I-CVI) scores of 1.00 in 17 out of 22 items. The remaining items had I-CVI ranking of 0.8 to 0.9. The overall scale-content validity index was 0.97. Eight more items were recommended for inclusion, increasing the total to 30 items. In phase two, 21 Vietnamese nurse wound care experts completed all three rounds of the Delphi process. After three rounds, 24 items out of 30 reached full consensus for the final tool. CONCLUSION: This study was the first step to confirm the content validity of the newly developed SWAT. Further development of the tool including the evaluation of validity and reliability was undertaken to strengthen the tool.

Prophylactic acid suppressants in children in the intensive care unit: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Critically ill children are at risk of stress-induced gastrointestinal ulceration. Acid suppressants are frequently used in intensive care units even though there is uncertainty about the benefits and harms. With this systematic review, we aimed to assess patient-important benefits and harms of stress ulcer prophylaxis (SUP) in children in intensive care. METHODS: We conducted the review according to the PRISMA statement, the Cochrane Handbook, and GRADE, using conventional meta-analysis and trial sequential analysis (TSA). We included randomised clinical trials comparing SUP with histamine-2-receptor antagonists or proton pump inhibitors vs placebo/no prophylaxis in children admitted for intensive care. Primary outcomes were all-cause mortality and overt gastrointestinal bleeding. Secondary outcomes were serious adverse events, hospital-acquired pneumonia, Clostridium difficile enteritis, myocardial ischemia, acute kidney injury and quality of life. RESULTS: We included a total of seven trials (n = 504) with eight trial comparisons. We found no statistically significant difference in all-cause mortality (relative risk (RR) 1.43, 95% confidence interval (CI) 0.86-2.37), overt gastrointestinal bleeding (RR 0.75, 95% CI 0.42-1.35) or hospital-acquired pneumonia (RR 1.18, 95% CI 0.77-1.82) between SUP vs placebo/no prophylaxis. No trials reported on remaining secondary outcomes. TSA was unable to draw firm conclusions for all outcomes and certainty of evidence for all outcomes was "very low." CONCLUSIONS: We found no difference in all-cause mortality, overt gastrointestinal bleeding or hospital-acquired pneumonia in children in intensive care receiving acid suppressants compared with placebo/no prophylaxis. However, the quantity and quality of evidence was very low with no firm evidence for benefit or harm.

Postoperative wound assessment documentation and acute care nurses' perception of factors impacting wound documentation: A mixed methods study.

BACKGROUND: Wound care documentation is an essential component of best practice wound management in order to enhance inter-disciplinary communication and patient care. However, evidence suggests that wound care documentation is often carried out poorly and sporadically. OBJECTIVES: Determine postoperative wound assessment documentation by acute care nurses and explore their perception of factors constraining adequate nursing documentation. METHODS: A two-phase sequential exploratory mixed methods design was used. Phase one: A retrospective clinical chart audit of nurses' documentation was undertaken. A random selection of 200 medical records were reviewed over 3 months at a provincial hospital in Vietnam. Phase two: semi-structured interviews were conducted with 13 surgical nurses to explore their perceptions of factors influencing appropriate documentation. Inductive qualitative content analysis was applied for qualitative data. This manuscript adheres to COREQ guidelines for reporting the qualitative phase. FINDINGS: Phase one: 200 records were audited. Less than 10% of preoperative factors (such as co-morbidities, smoking and nutrition status) related to the risk of delayed wound healing were documented. During the first 5 days postoperation, there was no documentation about incision location, wound dimension, wound bed (in wounds healing by secondary intention) or odour. In less than 10% colour and type of exudate were recorded. Phase two: Emerging key categories were: unimportance of nursing documentation, difficulty to change existing practice, and personal factors. CONCLUSION: This study indicated that surgical wound assessment documentation was insufficient and inconsistent among nurses. Nurses viewed the wound assessment documentation as unimportant. Therefore, extensive exploration of strategies is required to enhance the quality of wound assessment documentation.

Surgical wound assessment in Vietnam: a think-aloud technique and interview analysis.

OBJECTIVE: To identify the key components of a surgical wound assessment tool that nurses in Vietnam could use when conducting a surgical wound assessment. The study also explored Vietnamese nurses' perceptions of current practices in surgical wound assessment and assessed their requirements for a surgical wound assessment tool. METHOD: Registered nurses from surgical wards in a Vietnamese hospital were invited to participate in this descriptive, qualitative study. A combination of the think-aloud technique and semi-structured interviews was undertaken. Transcribed responses were analysed using inductive content analysis to indicate how Vietnamese nurses undertook wound assessment and the data they collected. RESULTS: A total of 13 nurses took part. Data from both the think-aloud process and interviews indicated that nurses evaluated surgical wounds based on their experience and observation without using standard guidelines. Some components, such as wound edge, periwound skin, exudate volume and signs of infection, were identified by the nurses. Other wound characteristics, such as wound site, wound bed, exudate and pain, and risk factors were less frequently collected. Nurses expressed their need for a tool with comprehensive content, precise terms, user-friendly language and a scoring system to facilitate their wound assessment. CONCLUSION: Hospitals in Vietnam need a standard tool to help nurses improve surgical wound assessment in daily nursing practice, and to enhance multidisciplinary communication and patient care.

Stress ulcer prophylaxis in critically ill children: Protocol for a systematic review.

BACKGROUND: Stress ulcer prophylaxis is the considered standard of care in many critically ill patients in the intensive care unit (ICU). Whether there is overall benefit or harm of stress ulcer prophylaxis in critically ill children is unknown. Accordingly, we aim to assess patient-important benefits and harms of stress ulcer prophylaxis versus placebo or no treatment in critically ill children in the ICU. METHODS/DESIGN: We will conduct a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis and assess the use of proton pump inhibitors (PPIs) or histamine-2-receptor antagonists (H2RAs) versus placebo or no prophylaxis. We will systematically search the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, BIOSIS, and Epistemonikos for relevant literature. We will follow the recommendations by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The risk of systematic errors (bias) and random errors will be assessed, and the overall quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. DISCUSSION: There is a need for an updated systematic review to summarize the benefits and harms of stress ulcer prophylaxis in critically ill children to inform practice and future research.

Coffee consumption and work satisfaction among Scandinavian anaesthesiologists: A survey.

BACKGROUND: It is a common prejudice that anaesthetic doctors are believed to have high coffee consumption. In this study, we aimed to assess the association between coffee drinking and work satisfaction among Scandinavian anaesthesiologists. We hypothesised that coffee consumption was positively correlated with work satisfaction. METHODS: We invited anaesthesiologists attending the 34th congress of The Scandinavian Society of Anaesthesiology and Intensive Care Medicine in Malmö, Sweden, September 2017 to participate in a paper-based survey. We collected data on characteristics of the respondents, coffee drinking and work satisfaction, and compared coffee vs non-coffee drinkers with regard to work satisfaction scored on a modified Wong-Baker Faces Pain Rating Scale (Visual Analogue Scale from 0 to 10). RESULTS: A total of 271 anaesthesiologists participated in the survey, of which 265 (97.7%) of the questionnaires contained valid data. Some 143 (54.0%) of the respondents were women, the median (interquartile range, IQR) age was 41.0 (35.0-49.5) years, and 242 (91.3%) were coffee drinkers. Coffee drinkers consumed median 4.0 (IQR: 2.5-5.0) cups of coffee daily. Overall work satisfaction was median 8 (IQR: 8-9), with no difference between respondents drinking coffee and those who did not (median 8 (IQR: 8-9) vs 8 (IQR: 8-9), Wilcoxon rank sum test, P = 0.62). Also, we found no association between work satisfaction and the number of cups of coffee consumed daily (r2  = 0.005, P = 0.24). CONCLUSION: In this survey, we found high work satisfaction among Scandinavian anaesthesiologists, with no difference between coffee and non-coffee drinkers.

Synthesis of Either C2- or C4'-Alkylated Derivatives of Honokiol and Their Biological Evaluation for Anti-inflammatory Activity.

Honokiol, a biphenolic neolignan isolated from Magnolia officinalis, was reported to have a promising anti-inflammatory activity for the treatment of various diseases. There are many efforts on the synthesis and structure-activity relationship of honokiol derivatives. However, regioselective O-alkylation of honokiol remains a challenge and serves as a tool to provide not only some derivatives but also chemical probes for target identification and mode of action. In this study, we examined the reaction condition for regioselective O-alkylation, in which C2 and C4'-alkylated analogs of honokiol were synthesized and evaluated for inhibitory activity on nitric oxide production and cyclooxygenase-2 expression. Furthermore, we successfully synthesized a potential photoaffinity probe consisting of biotin and benzophenone based on a C4'-alkylated derivative.

Identifying relationships between symptom clusters and quality of life in adults with chronic mixed venous and arterial leg ulcers.

The objective of this study was to identify symptom clusters and their effect on quality of life (QOL) of adults with chronic leg ulcers of mixed venous and arterial aetiology. A secondary analysis of data from four existing prospective longitudinal studies conducted by a wound healing research group in Australia was undertaken. A total of 110 patients who met the inclusion criteria were selected for this study. Exploratory factor analysis (EFA) was used to identify symptom clusters and correlational analyses to examine relationships between the identified symptom clusters and QOL. The EFA identified two distinct symptom clusters: a 'systemic symptom cluster' consisting of pain, fatigue and depressive symptoms; and a 'localised-leg symptom cluster' including pain, fatigue, oedema, lower limb inflammation and exudate. Physical QOL correlated significantly with the systemic symptom cluster (r = -0·055, P < 0·0001) and the localised-leg symptom cluster (r = -0·054, P < 0·0001), whereas mental QOL was associated only with the systemic symptom cluster (r = -0·038, P = 0·01). The results suggest that appropriate intervention strategies targeting specific symptom clusters should be developed. Targeting patients with symptom clusters is particularly important because they are at high risk and the most vulnerable for reduced QOL.

Photoinduced, copper-catalyzed alkylation of amides with unactivated secondary alkyl halides at room temperature.

The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for SN2 reactions) is an ongoing challenge in organic synthesis. We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C-N bond formation at room temperature. The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist. A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that includes photoexcitation of a copper-amidate complex, followed by electron transfer to form an alkyl radical.

Is air transport of stroke patients faster than ground transport? A prospective controlled observational study.

BACKGROUND: Helicopters are widely used for interhospital transfers of stroke patients, but the benefit is sparsely documented. We hypothesised that helicopter transport would reduce system delay to thrombolytic treatment at the regional stroke centre. METHODS: In this prospective controlled observational study, we included patients referred to a stroke centre if their ground transport time exceeded 30 min, or they were transported by a secondarily dispatched, physician-staffed helicopter. The primary endpoint was time from telephone contact to triaging neurologist to arrival in the stroke centre. Secondary endpoints included modified Rankin Scale at 3 months, 30-day and 1-year mortality. RESULTS: A total of 330 patients were included; 265 with ground transport and 65 with helicopter, of which 87 (33%) and 22 (34%), received thrombolysis, respectively (p=0.88). Time from contact to triaging neurologist to arrival in the regional stroke centre was significantly shorter in the ground group (55 (34-85) vs 68 (40-85) min, p<0.01). The distance from scene to stroke centre was shorter in the ground group (67 (42-136) km) than in the helicopter group (83 (46-143) km) (p<0.01). We did not detect significant differences in modified Rankin Scale at 3 months, in 30-day (9.4% vs 0%; p=0.20) nor 1-year (18.8% vs 13.6%; p=0.76) mortality between ground and helicopter transport. CONCLUSIONS: We found significantly shorter time from contact to triaging neurologist to arrival in the regional stroke centre if stroke patients were transported by primarily dispatched ground ambulance compared with a secondarily dispatched helicopter.

Nickel/bis(oxazoline)-catalyzed asymmetric Negishi arylations of racemic secondary benzylic electrophiles to generate enantioenriched 1,1-diarylalkanes.

A tertiary stereogenic center that bears two different aryl substituents is found in a variety of bioactive compounds, including medicines such as Zoloft and Detrol. We have developed an efficient method for the synthesis of enantioenriched 1,1-diarylalkanes from readily available racemic benzylic alcohols. Formation of a benzylic mesylate (which is not isolated), followed by treatment with an arylzinc reagent, LiI, and a chiral nickel/bis(oxazoline) catalyst, furnishes the Negishi cross-coupling product in high ee and good yield. A wide array of functional groups (e.g., an aryl iodide, a thiophene, and an N-Boc-indole) are compatible with the mild reaction conditions. This method has been applied to a gram-scale synthesis of a precursor to Zoloft.

After action review of the COVID-19 surveillance system in Quang Ninh Province, Vietnam, in 2020.

Surveillance is the backbone of any response to an infectious disease outbreak, and comprehensive evaluation of surveillance systems is crucial. However, structured evaluations of surveillance systems during the COVID-19 pandemic are scarce. We conducted an after action review (AAR) of the performance of the COVID-19 surveillance system in Quang Ninh Province, Vietnam, during 2020 using the COVID-19-specific AAR methodology developed by the World Health Organization in combination with guidance from the US Centers for Disease Control and Prevention (CDC). We conducted a stakeholder survey, document reviews, and key informant interviews with staff from Quang Ninh CDC's COVID-19 surveillance system. The COVID-19 surveillance system was based on the pre-existing surveillance system in the province. The system's strengths were early preparation for emergency response, strong governance and central coordination, and multidisciplinary collaboration. Stakeholders agreed that the system proved useful and adaptive to the fast-evolving COVID-19 situation but was weakened by overly complex systems, redundant administrative processes, unclear communication channels, and lack of resources. Overall, the surveillance systems in Quang Ninh province proved effective in containing COVID-19 and adaptive in a fast-changing epidemiological context. Several recommendations were made based on identified areas of concern that are of relevance for COVID-19 surveillance systems in Vietnam and similar settings.

After action review of the COVID-19 surveillance system in Quang Ninh Province, Vietnam, in 2020.

Surveillance is the backbone of any response to an infectious disease outbreak, and comprehensive evaluation of surveillance systems is crucial. However, structured evaluations of surveillance systems during the COVID-19 pandemic are scarce. We conducted a after action review (AAR) of the performance of the COVID-19 surveillance system in Quang Ninh Province, Vietnam, during 2020 using the COVID-19-specific AAR methodology developed by the World Health Organization in combination with guidance from the US Centers for Disease Control and Prevention (CDC). We conducted a stakeholder survey, document reviews, and key informant interviews with staff from Quang Ninh CDC's COVID-19 surveillance system. The COVID-19 surveillance system was based on the pre-existing surveillance system in the province. The system's strengths were early preparation for emergency response, strong governance and central coordination, and multidisciplinary collaboration. Stakeholders agreed that the system proved useful and adaptive to the fast-evolving COVID-19 situation but was weakened by overly complex systems, redundant administrative processes, unclear communication channels, and lack of resources. Overall, the surveillance systems in Quang Ninh province proved effective in containing COVID-19 and adaptive in a fast-changing epidemiological context. Several recommendations were made based on identified areas of concern that are of relevance for COVID-19 surveillance systems in Vietnam and similar settings.