Reimagining critical care:Trends and shifts in 21st century medicine

primarily driven by advancements in technology,changes in healthcare delivery,and a deeper understanding of disease processes.Advancements in technology have revolutionized patient monitoring,diagnosis,and treatment in the critical care setting.From minimally invasive procedures to advances imaging techniques,clinicians now have access to a wide array of tools to assess and manage critically ill patients more effectively.In this editorial we comment on the review article published by Padte S et al wherein they concisely describe the latest developments in critical care medicine.

Explosion of research on psychopathology and social media use after COVID-19:A scientometric study

BACKGROUND Despite advances in research on psychopathology and social media use,no comprehensive review has examined published papers on this type of research and considered how it was affected by the coronavirus disease 2019(COVID-19)outbreak.AIM To explore the status of research on psychopathology and social media use before and after the COVID-19 outbreak.METHODS We used Bibliometrix(an R software package)to conduct a scientometric analysis of 4588 relevant studies drawn from the Web of Science Core Collection,PubMed,and Scopus databases.RESULTS Such research output was scarce before COVID-19,but exploded after the pandemic with the publication of a number of high-impact articles.Key authors and institutions,located primarily in developed countries,maintained their core positions,largely uninfluenced by COVID-19;however,research production and collaboration in developing countries increased significantly after COVID-19.Through the analysis of keywords,we identified commonly used methods in this field,together with specific populations,psychopathological conditions,and clinical treatments.Researchers have devoted increasing attention to gender differences in psychopathological states and linked COVID-19 strongly to depression,with depression detection becoming a new trend.Developments in research on psychopathology and social media use are unbalanced and uncoordinated across countries/regions,and more indepth clinical studies should be conducted in the future.CONCLUSION After COVID-19,there was an increased level of concern about mental health issues and a changing emphasis on social media use and the impact of public health emergencies.

Outcomes of combined mitochondria and mesenchymal stem cellsderived exosome therapy in rat acute respiratory distress syndrome and sepsis

BACKGROUND The treatment of acute respiratory distress syndrome(ARDS)complicated by sepsis syndrome(SS)remains challenging.AIM To investigate whether combined adipose-derived mesenchymal-stem-cells(ADMSCs)-derived exosome(EXAD)and exogenous mitochondria(mitoEx)protect the lung from ARDS complicated by SS.METHODS In vitro study,including L2 cells treated with lipopolysaccharide(LPS)and in vivo study including male-adult-SD rats categorized into groups 1(sham-operated-control),2(ARDS-SS),3(ARDS-SS+EXAD),4(ARDS-SS+mitoEx),and 5(ARDS-SS+EXAD+mitoEx),were included in the present study.RESULTS In vitro study showed an abundance of mitoEx found in recipient-L2 cells,resulting in significantly higher mitochondrial-cytochrome-C,adenosine triphosphate and relative mitochondrial DNA levels(P<0.001).The protein levels of inflammation[interleukin(IL)-1β/tumor necrosis factor(TNF)-α/nuclear factor-κB/toll-like receptor(TLR)-4/matrix-metalloproteinase(MMP)-9/oxidative-stress(NOX-1/NOX-2)/apoptosis(cleaved-caspase3/cleaved-poly(ADP-ribose)polymerase)]were significantly attenuated in lipopolysaccharide(LPS)-treated L2 cells with EXAD treatment than without EXAD treatment,whereas the protein expressions of cellular junctions[occluding/β-catenin/zonula occludens(ZO)-1/E-cadherin]exhibited an opposite pattern of inflam-mation(all P<0.001).Animals were euthanized by 72 h post-48 h-ARDS induction,and lung tissues were harvested.By 72 h,flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflam-matory cells(Ly6G+/CD14+/CD68+/CD11b/c+/myeloperoxidase+)and albumin were lowest in group 1,highest in group 2,and significantly higher in groups 3 and 4 than in group 5(all P<0.0001),whereas arterial oxygen-saturation(SaO2%)displayed an opposite pattern of albumin among the groups.Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers(CD68+/γ-H2AX)displayed an identical pattern of SaO2%among the groups(all P<0.0001).The protein expressions of inflammatory(TLR-4/MMP-9/IL-1β/TNF-α)/oxidative stress(NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged(cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic(beclin-1/Atg-5/ratio of LC3B-II/LC3B-I)biomarkers exhibited a similar manner,whereas antioxidants[nuclear respiratory factor(Nrf)-1/Nrf-2]/cellular junctions(ZO-1/E-cadherin)/mitochondrial electron transport chain(complex I-V)exhibited an opposite manner of albumin among the groups(all P<0.0001).CONCLUSION Combined EXAD-mitoEx therapy was better than merely one for protecting the lung against ARDS-SS induced injury.

Diagnosis and treatment of acute pulmonary inflammation in critically ill patients: The role of inflammatory biomarkers

Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite early antimicrobial therapy and lung protective mechanical ventilation. Both clinical entities are characterized by acute pulmonary inflammation in response to direct or indirect lung injury. Adjunct anti-inflammatory treatment with corticosteroids is increasingly used, although the evidence for benefit is limited. The treatment decisions are based on radiographic, clinical and physiological variables without regards to inflammatory state. Current evidence suggests a role of biomarkers for the assessment of severity, and distinguishing sub-phenotypes (hyperinflammatory versus hypo-inflammatory) with important prognostic and therapeutic implications. Although many inflammatory biomarkers have been studied the most common and of interest are C-reactive protein, procalcitonin, and pro-inflammatory cytokines including interleukin 6. While extensively studied as prognostic tools (prognostic enrichment), limited data are available for the role of biomarkers in determining appropriate initiation, timing and dosing of adjunct anti-inflammatory treatment (predictive enrichment)

A Mindfulness-Based Cognitive Therapy (MBCT) Intervention to Improve Resilience and Mitigate Symptoms of Burnout Syndrome in Critical Care Nurses: Results of a Randomized Trial

Objective: Critical care nurses work in a challenging intensive care (ICU) environment that results in work-related psychological distress. Our objective was to pilot an in-person or virtual mindfulness-based cognitive therapy (MBCT) program enhanced resilience and a similarly designed attention control group. Methods: We randomized ICU nurses with symptoms of burnout syndrome and decreased resilience to an MBCT program or a similarly formatted book club control. Our primary outcome was change in resilience as measured by the Connor-Davidson Resilience Scale (CD-RISC). Results: One-hundred one nurses completed study-related procedures. Overall, 70% had baseline symptoms of anxiety and 26% had symptoms of depression. For the in-person cohorts, there was no statistical difference between intervention and control groups regarding the total number of sessions attended (3.85 days ± 1.4 versus 3.75 days ± 0.15;p = 0.64). Using the Client/Patient Satisfaction Questionnaire-8 (CSQ-8), satisfaction scores were higher in the intervention group for weeks two through four of the program: p = 0.03, 0.0003, 0.007 respectively. There was no difference in the change in CD-RISC scores between the two groups (mean difference: treatment = 5.0, control = 7.0;p = 0.30). The online intervention cohort had greater improvements in the change of their median emotional exhaustion burnout scores when compared to the in-person intervention cohorts (-5 [-8 to -1.5] vs. 2 [-5 to 8], p = 0.049). Conclusions: We developed a feasible and acceptable in-person and online MBCT-ICU intervention that did not increase resilience scores in ICU nurses when compared to an attention control group. These results could help guide the proper design of larger trials to determine the efficacy of other resilience interventions.

Pulmonary sequestration infected with nontuberculous mycobacteria:a report of two cases and literature review

We report two cases of pulmonary sequestration infected with nontuberculous mycobacteria(NTM): Mycobacterium avium and Mycobacterium abscessus.Chest computed tomography showed pneumonic consolidation in the right lower lobe,which received a systemic blood supply from the descending aorta in both patients.Video-assisted thoracoscopic surgeries were successfully performed and pathologica]examinations revealed multiple caseating granulomas.A review of the literature revealed only seven previous case reports of pulmonary sequestration infected with NTM,and no case with Mycobacterium abscessus has been reported.

Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rejection risk

BACKGROUND Gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.AIM To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.METHODS This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant.Patients with pretransplant anti-reflux surgery were excluded.Baseline characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were recorded.Reflux testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH monitoring.Post-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients.The primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria.Statistical analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards modeling.RESULTS After applying inclusion and exclusion criteria,a total of 60 patients were included in the study.Among all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant evaluation.Objective evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subjects,representing 58%of the tested group.CF patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical esophageal reflux symptoms(53.7%vs 26.3%,P=0.06)compared to those without reflux testing.Other patient demographics and baseline cardiopulmonary function did not significantly differ between CF subjects with and without pre-transplant reflux testing.Patients with CF were less likely to undergo pre-transplant reflux testing compared to other pulmonary diagnoses(68%vs 85%,P=0.003).There was a decreased risk of CLAD in patients with CF who underwent reflux testing compared to those who did not,after controlling for confounders(Cox Hazard Ratio 0.26;95%CI:0.08-0.92).CONCLUSION Pre-transplant reflux testing revealed high prevalence of pathologic reflux in CF patients and was associated with decreased risk of CLAD.Systematic reflux testing may enhance outcomes in this patient population.

One approach to circulation and blood flow in the critical care unit

Evaluating and managing circulatory failure is one of the most challenging tasks for medical practitioners involved in critical care medicine.Understanding the applicability of some of the basic but,at the same time,complex physiological processes occurring during a state of illness is sometimes neglected and/or presented to the practitioners as point-of-care protocols to follow.Furthermore,managing hemodynamic shock has shown us that the human body is designed to fight to sustain life and that the compensatory mechanisms within organ systems are extraordinary.In this review article,we have created a minimalistic guide to the clinical information relevant when assessing critically ill patients with failing circulation.Measures such as organ blood flow,circulating volume,and hemodynamic biomarkers of shock are described.In addition,we will describe historical scientific events that led to some of our current medical practices and its validation for clinical decision making,and we present clinical advice for patient care and medical training.

Anticoagulant use before COVID-19 diagnosis prevent COVID-19 associated acute venous thromboembolism or not:A systematic review and meta-analysis

BACKGROUND Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019(COVID-19)patients.There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease.AIM To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients.METHODS A Literature search was performed on LitCovid PubMed,WHO,and Scopus databases from inception(December 2019)till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19.The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants.Secondary outcomes included COVID-19 disease severity,in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection,and mortality.The random effects models were used to calculate crude and adjusted odds ratios(aORs)with 95%confidence intervals(95%CIs).RESULTS Forty-six observational studies met our inclusion criteria.The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk[n=43851,9 studies,odds ratio(OR)=0.67(0.22,2.07);P=0.49;I2=95%].The association between prior anticoagulation and disease severity was non-significant[n=186782;22 studies,OR=1.08(0.78,1.49);P=0.64;I2=89%].However,pre-hospital anticoagulation significantly increased all-cause mortality risk[n=207292;35 studies,OR=1.72(1.37,2.17);P<0.00001;I2=93%].Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk[aOR=0.87(0.42,1.80);P=0.71],mortality[aOR=0.94(0.84,1.05);P=0.31],and disease severity[aOR=0.96(0.72,1.26);P=0.76].CONCLUSION Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events,improved survival,and lower disease severity in COVID-19 patients.

Computerized decision support in adult and pediatric critical care

Computerized decision support(CDS) is the most advanced form of clinical decision support available and has evolved with innovative technologies to provide meaningful assistance to medical professionals. Critical care clinicians are in unique environments where vast amounts of data are collected on individual patients, and where expedient and accurate decisions are paramount to the delivery of quality healthcare. Many CDS tools are in use today among adult and pediatric intensive care units as diagnostic aides, safety alerts, computerized protocols, and automated recommendations for management. Some CDS use have significantly decreased adverse events and improved costs when carefully implemented and properly operated. CDS tools integrated into electronic health records are also valuable to researchers providing rapid identification of eligible patients, streamlining data-gathering and analysis, and providing cohorts for study of rare and chronic diseases through data-warehousing. Although the need for human judgment in the daily care of critically ill patients has limited the study and realization ofmeaningful improvements in overall patient outcomes, CDS tools continue to evolve and integrate into the daily workflow of clinicians, and will likely provide advancements over time. Through novel technologies, CDS tools have vast potential for progression and will significantly impact the field of critical care and clinical research in the future.

Alectinib-Induced Immune Hemolytic Anemia in a Patient with Lung Adenocarcinoma: Case Report and Literature Review

Alectinib is a selective Anaplastic Lymphoma Kinase (ALK) tyrosine kinase inhibitor used as standard therapy for ALK-rearranged lung adenocarcinoma. Hemolytic anemia is considered a rare but significant adverse event of alectinib. Here, we report the case of a 78-year-old female with advanced ALK rearrangement-positive lung adenocarcinoma who developed grade 4 drug-induced hemolytic anemia after receiving alectinib as first-line therapy. We discontinued alectinib treatment and switched to brigatinib. As a result, anemia improved without recurrence of lung adenocarcinoma over one year.

Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux

AIM： To study the effect of combined omeprazole（Ome） and domperidone（Dom） therapy on asthma symptoms and pulmonary function in asthmatics with gastroesoph- ageal reflux. METHODS： We selected 198 asthmatics with gastro- esophageal reflux diagnosed by 24-h esophageal pH moni- toring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk （1：1 double-blind randomization）. Spirometry was done at baseline and after 16 wk of treatment. The primary outcome measures were： mean daily daytime and nighttime asthma symptom scores. Mean daily reflux symptom scores, albuterol use as rescue medication （number of puffs）, daytime and nighttime peak expiratory flow rate （PEFR）, postbronchodilator forced expiratory volume in 1 second （FEVl） and postbronchodilator forced vital capacity （FVC） were secondary outcome measures. RESULTS： Comparison of mean change from baseline between antireflux therapy and placebo groups revealed significant reduction in daytime asthma symptom score （17.4% vs 8.9 %）, nighttime asthma symptom score （19.6% vs 5.4%）, reflux symptom score （8.7% vs 1.6%） and rescue medication use （23.2% vs 3.1%） after antireflux therapy compared to mean change in placebo group （P 〈 0.001）. There was significant improvement in morning PEFR （7.9% vs 0.2%）, evening PEFR （9.8% vs 0.5%）, FEW （11.1% vs 3.78%） and FVC （9.3%vs 1.52%） in the antireflux therapy group compared to placebo on comparng the mean change from baseline after 16 wk （P 〈 0.01） CONCLUSION： Combined therapy with Ome and Dom in adult asthmatics with gastroesophageal reflux may be beneficial by reducing asthma symptoms, rescuing medi- cation use, and improving pulmonary function.

Glucose control in critical care

Glycemic control among critically-ill patients has been a topic of considerable attention for the past 15 years. An initial focus on the potentially deleterious effects of hyperglycemia led to a series of investigations regarding intensive insulin therapy strategies that targeted tight glycemic control. As knowledge accumulated, the pursuit of tight glycemic control among critically-ill patients came to be seen as counterproductive, and moderate glycemic control came to dominate as the standard practice in intensive care units. In recent years, there has been increased focus on the importance of hypoglycemic episodes, glycemic variability, and premorbid diabetic status as factors that contribute to outcomes among critically-ill patients. This review provides a survey of key studies on glucose control in critical care, and aims to deliver perspective regarding glycemic management among critically-ill patients.

Characteristics of fever and response to antipyretic therapy in military personnel with adenovirus-positive community acquired pneumonia

Background:In 2014,an outbreak of adenoviral pneumonia occurred in the Korean military training center.However,there are limited data on the characteristics of the fever and its response to antipyretic therapy in immunocompetent adults with adenovirus-positive community-acquired pneumonia(CAP).Methods:The medical records of the patients who were admitted to the Armed Forces Chuncheon Hospital for the treatment of CAP between January 2014 and December 2016 were retrospectively analyzed.The patients were divided into three groups,namely,the adenovirus-positive(Adv)group,the adenovirus-negative(Non-Adv)group and the unknown pathogen group,according to the results of a polymerase chain reaction(PCR)test and sputum culture used to measure adenovirus and other bacteria or viruses in respiratory specimens.We evaluated and compared the demographics,clinicolaboratory findings and radiological findings upon admission between the two groups.Results:Out of the 251 military personnel with CAP during the study periods,67 were classified into the Adv group,while 134 were classified into the Non-Adv group and 50 were classified into the unknown pathogen group.The patients in the Adv group had a longer duration of fever after admission((3.2±1.6)d vs.(1.9±1.2)d vs.(2.2±1.5)d,P=0.018)and symptom onset((5.8±2.2)d vs.(3.9±2.5)d vs.(3.7±2.0)d,P=0.006)than patients in the Non-Adv and unknown pathogen groups,respectively.The patients in the Adv group had a higher mean temperature at admission(37.8±0.3 vs.37.3±0.3 vs.37.3±0.3,P=0.005),and more patients were observed over 40 and 39 to 40(14.9%vs.2.2%vs.4.0%,35.8%vs.3.7%vs.6.0%,P<0.001)than those in the Non-Adv and unknown pathogen groups,respectively.The Adv group more commonly had no response or exhibited adverse events after antipyretic treatment compared to the Non-Adv group(17.9%vs.1.5%,35.0%vs.4.3%,P<0.001,P=0.05,respectively).In addition,the time from admission to overall clinical stabilization was significantly longer in the patients in the Adv group than in those in the Non-Adv group((4.3±2.8)d vs.(2.9±1.8)d,P=0.034,respectively).Furthermore,no significant difference in the length of hospital stay was observed between the two groups,and no patient died in either group.Conclusions:In this study,Adv-positive CAP in immunocompetent military personnel patients had distinct fever characteristics and responses to antipyretic treatment.

Hepatitis B in healthcare workers: Transmission events and guidance for management

Hepatitis B virus(HBV) is the most efficiently transmissible of the bloodborne viruses that are important in healthcare settings. Healthcare workers(HCWs)are at risk for exposure to HBV from infected patients and, if infected, are similarly at risk of transmitting HBV to patients. Published cases of HBV transmission from HCW to patient are relatively rare, having decreased in frequency following the introduction of standard(universal) precautions, adoption of enhanced percutaneous injury precautions such as double-gloving in surgery, and routine HBV vaccination of HCWs. Here we review published cases of HCW-to-patient transmission of HBV, details of which have helped to guide the creation of formal guidelines for the management of HBV-infected HCWs. We also compare the published guidelines for the management of HBV-infected HCWs from various governing bodies, focusing on their differences with regard to vaccination requirements, viral load limits, frequency of monitoring, and restrictions on practice. Importantly, while there are differences among the recommendations from governing bodies, no guidelines uniformly restrict HBV-infected HCWs from performing invasive or exposure-prone procedures.

Xiaoqinglong decoction reduces dendritic cell differentiation and regulates the Th1/Th2 balance in a mouse model of allergic asthma

Background:Xiaoqinglong decoction(XQLD)is a classic Chinese medicinal formula that is widely used to treat allergic asthma.Recently,the use of XQLD to treat allergic asthma has inspired research to determine its mechanism of action.Because dendritic cells(DCs)and the T helper 1(Th1)/Th2 cytokine balance play important roles in allergic asthma,the present work aimed to assess how these immune system components are affected by XQLD.Methods:Thirty-six female BALB/C mice were randomly divided into three groups:an ovalbumin-based allergic asthma model group,a XQLD treatment group,and a control group.Histology was performed with haematoxylin and eosin staining and immunohistochemical staining.Bronchoalveolar lavage fluid and blood were collected from the animals and used to analyze the composition of inflammatory cells and expression levels of the cytokines interleukin(IL)-5 and IL-13.The thymic stromal lymphopoietin(TSLP)protein expression was assessed by western blot analysis,and the Gata3 and Tbx21 mRNA levels were assessed by polymerase chain reaction.Results:Compared with the OVA group,the levels of TSLP expression,IL-5,IL-13,and immunoglobulin E in the XQLD group were lower(all P<.01).The level of IL-4-expressing cells(Th2 cells)was lower(P=.0013),and the percentage of IFN-g-expressing cells(Th1 cells)was higher in the XQLD group compared with those in the OVA group(P=.0065).In addition,XQLD increased the expression of Tbx21 mRNA and decreased the expression of Gata3 mRNA in the lungs compared with the OVA group(both P<.01).Conclusion:These findings suggest that XQLD may ameliorate the course of allergic asthma by regulating the Gata3/Tbx21 balance and inhibiting TSLP expression,changes which are indicative of an altered Th1/Th2 balance.Thus,the clinical effectiveness of XQLD in treating allergic asthma may be due to its regulation of Th1/Th2 balance.

Heart failure in COVID-19 patients:Critical care experience

Patients with heart failure(HF)may be at a higher risk of coronavirus disease 2019(COVID-19)infection and may have a worse outcome due to their comorbid conditions and advanced age.In this narrative review,we aim to study the interaction between COVID-19 and HF from a critical care perspective.We performed a systematic search for studies that reported HF and critical carerelated outcomes in COVID-19 patients in the PubMed and Medline databases.From a total of 1050 papers,we identified 26 that satisfied the eligibility criteria for our review.Data such as patient demographics,HF,intensive care unit(ICU)admission,management,and outcome were extracted from these studies and analyzed.We reported outcomes in heart-transplant patients with COVID-19 separately.In hospitalized patients with COVID-19,the prevalence of HF varied between 4%and 21%.The requirement for ICU admission was between 8%and 33%.HF patients with COVID-19 had an overall mortality rate between 20%and 40%.We identified that HF is an independent predictor of mortality in hospitalized COVID-19 patients,and patients with HF were more likely to require ventilation,ICU admission and develop complications.Patients with HF with reduced ejection fraction did worse than those with HF with midrange ejection fraction,and HF with preserved ejection fraction.COVID-19 patients with HF should be identified early and managed aggressively in an attempt to improve outcomes in this cohort of patients.

Artificial intelligence and computer simulation models in critical illness

Widespread implementation of electronic health records has led to the increased use of artificial intelligence(AI)and computer modeling in clinical medicine.The early recognition and treatment of critical illness are central to good outcomes but are made difficult by,among other things,the complexity of the environment and the often non-specific nature of the clinical presentation.Increasingly,AI applications are being proposed as decision supports for busy or distracted clinicians,to address this challenge.Data driven“associative”AI models are built from retrospective data registries with missing data and imprecise timing.Associative AI models lack transparency,often ignore causal mechanisms,and,while potentially useful in improved prognostication,have thus far had limited clinical applicability.To be clinically useful,AI tools need to provide bedside clinicians with actionable knowledge.Explicitly addressing causal mechanisms not only increases validity and replicability of the model,but also adds transparency and helps gain trust from the bedside clinicians for real world use of AI models in teaching and patient care.

Machine learning in data abstraction: A computable phenotype for sepsis and septic shock diagnosis in the intensive care unit

BACKGROUND With the recent change in the definition(Sepsis-3 Definition)of sepsis and septic shock,an electronic search algorithm was required to identify the cases for data automation.This supervised machine learning method would help screen a large amount of electronic medical records(EMR)for efficient research purposes.AIM To develop and validate a computable phenotype via supervised machine learning method for retrospectively identifying sepsis and septic shock in critical care patients.METHODS A supervised machine learning method was developed based on culture orders,Sequential Organ Failure Assessment(SOFA)scores,serum lactate levels and vasopressor use in the intensive care units(ICUs).The computable phenotype was derived from a retrospective analysis of a random cohort of 100 patients admitted to the medical ICU.This was then validated in an independent cohort of 100 patients.We compared the results from computable phenotype to a gold standard by manual review of EMR by 2 blinded reviewers.Disagreement was resolved by a critical care clinician.A SOFA score≥2 during the ICU stay with a culture 72 h before or after the time of admission was identified.Sepsis versions as V1 was defined as blood cultures with SOFA≥2 and Sepsis V2 was defined as any culture with SOFA score≥2.A serum lactate level≥2 mmol/L from 24 h before admission till their stay in the ICU and vasopressor use with Sepsis-1 and-2 were identified as Septic Shock-V1 and-V2 respectively.RESULTS In the derivation subset of 100 random patients,the final machine learning strategy achieved a sensitivity-specificity of 100%and 84%for Sepsis-1,100%and 95%for Sepsis-2,78%and 80%for Septic Shock-1,and 80%and 90%for Septic Shock-2.An overall percent of agreement between two blinded reviewers had a k=0.86 and 0.90 for Sepsis 2 and Septic shock 2 respectively.In validation of the algorithm through a separate 100 random patient subset,the reported sensitivity and specificity for all 4 diagnoses were 100%-100%each.CONCLUSION Supervised machine learning for identification of sepsis and septic shock is reliable and an efficient alternative to manual chart review.

Open-Label, Pilot Study of the Safety and Clinical Effects of Rituximab in Patients with Rheumatoid Arthritis-Associated Interstitial Pneumonia

Objective: To investigate the clinical effect of rituximab (RTX) in the management of progressive rheumatoid arthritis related interstitial lung disease (RA-ILD). Methods: A total of 10 patients with progressive RA-ILD were enrolled into this 48-week, open-label treatment study. Treatment was with RTX at 1000 mg at day 1, day 15, and again at weeks 24 and 26, with concomitant methotrexate therapy. Results: The study included 4 men and 6 women. Of 7 evaluable patients at week 48, the diffusing capacity to carbon monoxide had worsened by at least 15% in 1 patient, was stable in 4 patients, and increased by >15% of baseline value in 2 patients. The forced vital capacity declined by at least 10% in 1 patient, was stable in 4 patients, and increased by at least 10% in 2 patients. High resolution computed tomo-graphy of the chest showed improvement in 1 patient, and was unchanged in 5. Three patients were withdrawn, one who had an infusion reaction at week 0, one at week 5 who was hospitalized for congestive heart failure at week 5 and who later died at week 32 of complications following a traumatic hip fracture, and one died at week 6 of possible pneumonia. Conclusions: In this pilot study of 10 patients with RA-ILD treated with RTX, measures of lung disease remained stable in the majority of study completers. Further research is needed to clarify whether this treatment has a role in management of RA-ILD.