Association between mechanical power and intensive care unit mortality in Korean patients under pressure-controlled ventilation.

BACKGROUND: Mechanical power (MP) has been reported to be associated with clinical outcomes. Because the original MP equation is derived from paralyzed patients under volume-controlled ventilation, its application in practice could be limited in patients receiving pressure-controlled ventilation (PCV). Recently, a simplified equation for patients under PCV was developed. We investigated the association between MP and intensive care unit (ICU) mortality. METHODS: We conducted a retrospective analysis of Korean data from the Fourth International Study of Mechanical Ventilation. We extracted data of patients under PCV on day 1 and calculated MP using the following simplified equation: MPPCV = 0.098 ∙ respiratory rate ∙ tidal volume ∙ (ΔPinsp + positive end-expiratory pressure), where ΔPinsp is the change in airway pressure during inspiration. Patients were divided into survivors and non-survivors and then compared. Multivariable logistic regression was performed to determine association between MPPCV and ICU mortality. The interaction of MPPCV and use of neuromuscular blocking agent (NMBA) was also analyzed. RESULTS: A total of 125 patients was eligible for final analysis, of whom 38 died in the ICU. MPPCV was higher in non-survivors (17.6 vs. 26.3 J/min, P<0.001). In logistic regression analysis, only MPPCV was significantly associated with ICU mortality (odds ratio, 1.090; 95% confidence interval, 1.029-1.155; P=0.003). There was no significant effect of the interaction between MPPCV and use of NMBA on ICU mortality (P=0.579). CONCLUSIONS: MPPCV is associated with ICU mortality in patients mechanically ventilated with PCV mode, regardless of NMBA use.

Erratum: Correction of Affiliations in the Article "Validity of Outcome Prediction Scoring Systems in Korean Patients with Severe Adult Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation Therapy".

This corrects the article on p. 932 in vol. 31, PMID: 27247503.

Deaths from tuberculosis: differences between tuberculosis-related and non-tuberculosis-related deaths.

Objective: Tuberculosis (TB) is a major cause of ill health and one of the leading causes of death worldwide. The first step in developing strategies to reduce TB mortality is to identify the direct causes of death in patients with TB and the risk factors for each cause. Methods: Data on patients with TB systemically collected from the National Surveillance System of South Korea from January 2019 to December 2020 were included in this study. We analyzed the clinical characteristics associated with TB and non-TB-related deaths, including TB-related symptoms, comorbidities, and radiographic and microbiological findings. Results: Of the total of 12,340 patients with TB, 61% were males with a mean age of 61.3 years. During the follow-up period, the overall mortality rate was 10.6%, with TB-related deaths accounting for 21.3% of all TB deaths. The median survival time in the TB-related death group was 22 days. TB-related death was associated with older age, lower body mass index (BMI), dyspnea, fever, general weakness, bilateral radiographic patterns, and acid-fast bacilli (AFB)-positive smears. Non-TB-related deaths were associated with older age, male sex, lower BMI, comorbidities of heart, liver, kidney, and central nervous system (CNS) diseases, CNS TB involvement, the presence of dyspnea, general weakness, and bilateral radiographic patterns. Conclusion: Patients with high-risk TB must be identified through cause-specific mortality analysis, and the mortality rate must be reduced through intensive monitoring of patients with a high TB burden and comorbidities.

Initial Tumor Necrosis Factor-Alpha and Endothelial Activation Are Associated with Hemorrhagic Complications during Extracorporeal Membrane Oxygenation.

Studies on inflammatory markers, endothelial activation, and bleeding during extracorporeal membrane oxygenation (ECMO) are lacking. Blood samples were prospectively collected after ECMO initiation from 150 adult patients who underwent ECMO for respiratory failure between 2018 and 2021. After excluding patients who died early (within 48 h), 132 patients were finally included. Their tumor necrosis factor-alpha (TNF-α), tissue factor (TF), soluble thrombomodulin (sTM), and E-selectin levels were measured. A Cox proportional hazards regression model was used to estimate the hazard ratio for hemorrhagic complications during ECMO. The 132 patients were divided into hemorrhagic (n = 23, H group) and non-complication (n = 109, N group) groups. The sequential organ failure assessment score, hemoglobin level, and ECMO type were included as covariates in all Cox models to exclude the effects of clinical factors. After adjusting for these factors, initial TNF-α, TF, sTM, E-selectin, and activated protein C levels were significantly associated with hemorrhagic complications (all p < 0.001). TNF-α, TF, and E-selectin better predicted hemorrhagic complications than the model that included only the aforementioned clinical factors (clinical factors only (area under the curve [AUC]: 0.804), reference; TNF-α (AUC: 0.914); TF (AUC: 0.915); E-selectin (AUC: 0.869)). Conclusions: TNF-α levels were significantly predictive of hemorrhagic complications during ECMO.

Polymorphic display and texture integrated systems controlled by capillarity.

Soft robotics offer unusual bioinspired solutions to challenging engineering problems. Colorful display and morphing appendages are vital signaling modalities used by natural creatures to camouflage, attract mates, or deter predators. Engineering these display capabilities using traditional light emitting devices is energy expensive and bulky and requires rigid substrates. Here, we use capillary-controlled robotic flapping fins to create switchable visual contrast and produce state-persistent, multipixel displays that are 1000- and 10-fold more energy efficient than light emitting devices and electronic paper, respectively. We reveal the bimorphic ability of these fins, whereby they switch between straight or bent stable equilibria. By controlling the droplets temperature across the fins, the multifunctional cells simultaneously exhibit infrared signals decoupled from the optical signals for multispectral display. The ultralow power, scalability, and mechanical compliance make them suitable for curvilinear and soft machines.

Remote control of muscle-driven miniature robots with battery-free wireless optoelectronics.

Bioengineering approaches that combine living cellular components with three-dimensional scaffolds to generate motion can be used to develop a new generation of miniature robots. Integrating on-board electronics and remote control in these biological machines will enable various applications across engineering, biology, and medicine. Here, we present hybrid bioelectronic robots equipped with battery-free and microinorganic light-emitting diodes for wireless control and real-time communication. Centimeter-scale walking robots were computationally designed and optimized to host on-board optoelectronics with independent stimulation of multiple optogenetic skeletal muscles, achieving remote command of walking, turning, plowing, and transport functions both at individual and collective levels. This work paves the way toward a class of biohybrid machines able to combine biological actuation and sensing with on-board computing.

Clinical values of diaphragmatic movement in patients with chronic obstructive pulmonary disease.

BACKGROUND: The limitation of activity due to dyspnea in chronic obstructive pulmonary disease (COPD) patients is affected by diaphragmatic dysfunction and reduced lung function. This study aimed to analyze the association between diaphragm function variables and forced expiratory volume in the first second (FEV1) and to estimate the clinical significance of diaphragm function in the correlation between COPD severity and lung function. METHODS: This prospective, single-center, cross-sectional observational study enrolled 60 COPD patients in a respiratory outpatient clinic. Data for baseline characteristics and the dyspnea scale were collected. Participants underwent a pulmonary function test (PFT), a 6-minute walk test (6MWT), and diaphragm function by ultrasonography. RESULTS: The right excursion at forced breathing showed the most significant correlation with FEV1 (r = 0.370, p = 0.004). The cutoff value was 6.7 cm of the right diaphragmatic excursion at forced breathing to identify the FEV1 above 50% group. In the group with a right diaphragmatic excursion at forced breathing < 6.7 cm, modified Medical Research Council (mMRC), St. George's Respiratory Questionnaire and the total distance of 6MWT showed no difference between groups with FEV1 under and above 50% (p > 0.05). In the group with ≥ 6.7 cm, mMRC and the total distance of 6MWT showed a significant difference between FEV1 under and above 50% (p = 0.014, 456.7 ± 69.7 m vs. 513.9 ± 60.3 m, p = 0.018, respectively). CONCLUSION: The right diaphragmatic forced excursion was closely related to FEV1, and analysis according to the right diaphragmatic forced excursion-based cut-off value showed a significant difference between both groups. When the diaphragm function was maintained, there was a lot of difference in the 6MWT's factors according to the FEV1 value. Our data suggest that diaphragmatic function should be performed when interpreting PFT.

Multiarray Biosensor for Diagnosing Lung Cancer Based on Gap Plasmonic Color Films.

Adaptable and sensitive materials are essential for the development of advanced sensor systems such as bio and chemical sensors. Biomaterials can be used to develop multifunctional biosensor applications using genetic engineering. In particular, a plasmonic sensor system using a coupled film nanostructure with tunable gap sizes is a potential candidate in optical sensors because of its simple fabrication, stability, extensive tuning range, and sensitivity to small changes. Although this system has shown a good ability to eliminate humidity as an interferant, its performance in real-world environments is limited by low selectivity. To overcome these issues, we demonstrated the rapid response of gap plasmonic color sensors by utilizing metal nanostructures combined with genetically engineered M13 bacteriophages to detect volatile organic compounds (VOCs) and diagnose lung cancer from breath samples. The M13 bacteriophage was chosen as a recognition element because the structural protein capsid can readily be modified to target the desired analyte. Consequently, the VOCs from various functional groups were distinguished by using a multiarray biosensor based on a gap plasmonic color film observed by hierarchical cluster analysis. Furthermore, the lung cancer breath samples collected from 70 healthy participants and 50 lung cancer patients were successfully classified with a high rate of over 89% through supporting machine learning analysis.

An Unusual Case of Basal Cell Carcinoma with Lung and Endobronchial Metastasis.

Recently, some cases of basal cell carcinoma (BCC) with lung metastasis have been reported, but those involving simultaneous tracheal, bronchial, and lung metastases have been rarely reported. Here, we have reported a very unusual case of BCC with metastasis, presenting with lung nodules and endobronchial lesions after two metastasectomies. Since BCC is a slow-growing cancer that rarely metastasizes to distant organs, tumor stage workup including radiological imaging has not been routinely performed in clinical practice. This case showed that BCC can metastasize to the lung, although the currently reported metastasis rate of BCC is extremely low.

MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer.

BACKGROUND: The protein kinase A (PKA)/cAMP response element-binding protein (CREB) has been suggested to be related to the inhibition of the proliferation of non-small cell lung cancer (NSCLC) cells. This study aimed to investigate the efficacy of a novel diarylcyclohexanone derivative, MHY4571, in regulating the PKA-CREB pathway and to study its anti-tumor role in squamous NSCLC. METHODS: We designed MHY4571 as a novel PKA inhibitor with acceptable in silico ADME properties and tested it in vitro in lung cancer cell lines and in vivo in xenograft and orthotopic mouse models of squamous cell lung carcinoma. RESULTS: MHY4571 inhibited PKA activity (> 70% inhibition) and suppressed the expression of p-PKA and p-CREB dose-dependently. MHY4571 treatment reduced lung cancer cell viability and promoted caspase 3-dependent apoptotic cell death. Orally administered MHY4571 significantly suppressed lung tumor growth in xenograft and orthotopic mouse models. PKA catalytic subunit alpha-silencing by siRNA (siPKA) strongly attenuated CREB phosphorylation; siCREB did not alter PKA protein levels or its phosphorylation, suggesting that PKA is an upstream regulator of CREB activity. MHY4571 acted synergistically with cisplatin (on co-treatment) to induce apoptotic cell death in lung cancer cells. CONCLUSIONS: Our results imply that MHY4571 may be a potential drug candidate for squamous cell lung cancer treatment.

Prognostic impact of preoperative respiratory colonization on early-onset pneumonia after lung transplantation.

Background: The number of lung transplantation procedures is rapidly increasing worldwide. Little is known about the effect of perioperative respiratory microbial colonization on pneumonia during lung transplantation. We evaluated the microbiome composition and incidence of early pneumonia in patients undergoing lung transplantation. We investigated factors related to post-transplant pneumonia (PTP) after lung transplantation. Methods: A retrospective analysis of patients subjected to lung transplantation between May 2013 and December 2019 was performed. Perioperative microbial colonization, and its relationship with early pneumonia, were examined in specimens from bronchial washing, bronchoalveolar lavage, and sputum aspiration before and after surgery. One-year mortality, as the primary outcome, was analyzed using the Kaplan-Meier curve model. Results: Among 76 patients who underwent lung transplantation, 34 donors (44.7%) and 28 recipients (36.8%) showed positive respiratory cultures with respect to preoperative respiratory colonization. A separate analysis of donors and recipients showed that 42 donors and 48 recipients were in respiratory non-colonized state, and 28 (53.8%) donors and 36 (69.2%) recipients survived 1 year after lung transplantation. Acinectobacter baumannii was the most common respiratory multidrug-resistant (MDR) pathogen. PTP was significantly lower in the survivor group (38.5% vs. 70.8%, P=0.009). Out of the recipients with preoperative respiratory colonization, 57.1% survived 1 year after lung transplantation. Patients with PTP had significantly higher 1-year mortality than those without PTP (P=0.009). Preoperative respiratory colonization of the recipients (P=0.010) and PTP patients (P=0.005) was associated with high 1-year mortality rate. Perioperative respiratory colonization of donors was not associated with the incidence of PTP and 1-year survival. Conclusions: Perioperative colonization of recipients was a powerful predictive factor for PTP, which was associated with 1-year mortality in patients subjected to lung transplantation. Our results suggest that donor acceptance criteria may change to better address potential shortages in organ donation.

The feasibility of granzyme B levels using an amperometric immunosensor for lung cancer detection.

Background: Low-dose computed tomography (LDCT) has improved the early detection of lung cancer. However, LDCT scans present several disadvantages, including the abundance of false-positive results, which lead to a high socioeconomic cost, psychological burden, and repeated exposure to radiation. Therefore, the identification of complementary biomarkers is needed to select high-risk individuals for LDCT. Here, we showed that granzyme B testing with the novel immunosensor has diagnostic value for identifying patients with lung cancer. Methods: We enrolled 44 patients with lung cancer and 51 health controls at Pusan National University Yangsan Hospital in Korea between March 2018 and September 2019. The immunosensor analyzed serum granzyme B levels, and their association with lung cancer detection was evaluated with machine learning models. Results: Serum granzyme B levels were assessed in samples from patients with lung cancer and healthy individuals. Granzyme B testing showed 100% sensitivity, 80% specificity, and an area under the curve of 0.938 for lung cancer detection. After combining granzyme B testing with clinical predictors such as age, smoking status, or pack-years, results from the five-fold cross-validation with random forest model improved diagnostic accuracy of 92.1%, with a sensitivity, specificity, and area under the curve of 92.0%, 92.1%, and 0.977, respectively. Conclusions: This feasibility study suggested that granzyme B may be utilized to detect lung cancer.

Neutrophil gelatinase-associated lipocalin as a prognostic biomarker of severe acute respiratory distress syndrome.

Neutrophil gelatinase-associated lipocalin (NGAL) is produced in the bronchial and alveolar cells of inflamed lungs and is regarded as a potential prognostic biomarker in various respiratory diseases. However, there are no studies on patients with acute respiratory distress syndrome (ARDS). NGAL levels in serum and bronchoalveolar lavage (BAL) were measured at baseline and on day 7 in 110 patients with ARDS. Baseline NGAL levels were significantly higher in ARDS patients than in healthy controls (serum 25 [14.5-41] vs. 214 [114.5-250.3] ng/mL; BAL 90 [65-115] vs. 211 [124-244] ng/mL). In ARDS, baseline NGAL levels in serum and BAL were significantly higher in non-survivors than in survivors (p < 0.001 and p = 0.021, respectively). Baseline NGAL levels showed a fair predictive power for intensive care unit (ICU) mortality (serum area under the curve (AUC) 0.747, p < 0.001; BAL AUC 0.768, p < 0.001). In a multivariate Cox regression analysis, the baseline serum NGAL level (> 240 ng/mL) was significantly associated with ICU mortality (hazard ratio [HR] 5.39, 95% confidence interval [CI] 2.67-10.85, p < 0.001). In particular, day 7 NGAL was significantly correlated with day 7 driving pressure (serum r = 0.388, BAL r = 0.702), and 28 ventilator-free days (serum r = - 0.298, BAL r = - 0.297). Baseline NGAL has good prognostic value for ICU mortality in patients with ARDS. NGAL can be a biomarker for ventilator requirement, as it may be indicative of potential alveolar epithelial injury.

Additional Usefulness of Bronchoscopy in Patients with Initial Microbiologically Negative Pulmonary Tuberculosis: A Retrospective Analysis of a Korean Nationwide Prospective Cohort Study.

Purpose: Bronchoscopy is widely used for microbiological diagnosis of patients with minimal sputum production. However, the usefulness of bronchoscopy in patient groups who benefit from subsequent microbiological confirmation has not been established. Patients and Methods: We retrospectively analyzed Korean tuberculosis (TB) cohort data from September 2018 to October 2019 to evaluate the usefulness of bronchoscopy in patients with microbiologically negative pulmonary TB (based on initial sputum polymerase chain reaction and culture results). The primary outcome was the proportion of microbiological diagnoses made after bronchoscopy. Secondary outcomes were the predictors of microbiological confirmation and the percentage of additional resistance detection after bronchoscopy. Results: A total of 5194 patients were diagnosed with pulmonary TB, 937 of whom were microbiologically negative for pulmonary TB based on the initial sputum findings. Of these, 319 patients underwent bronchoscopy, and further microbiological confirmation was achieved in 157 (49.1%) patients. The predictors of microbiological confirmation after bronchoscopy were age >65 years, female sex, and low body mass index (BMI). The rate of additional resistance detection was 10.5% (multidrug resistant/rifampin-resistant 3.8%; isoniazid-resistant 5.7%). Conclusion: Bronchoscopy can be used for the detection of resistant pathogens. Bronchoscopy should be considered for microbiologically negative pulmonary TB in women aged >65 years and with low BMI for subsequent microbiological confirmation.

Granzyme B for predicting the durable clinical benefit of anti-PD-1/PD-L1 immunotherapy in patients with non-small cell lung cancer.

Background: To identify immunotherapy biomarkers, we examined granzyme B levels in peripheral blood PD-1+ CD8+ T cells and their relationship with treatment outcomes in patients with non-small cell lung cancer (NSCLC). Methods: To evaluate the association of granzyme B with response to immunotherapy, we tested blood samples obtained from 16 patients with stage IIIC to IV NSCLC receiving immune-checkpoint inhibitor treatment. We used flow cytometry to measure the change in the percentage of PD1+ CD8+ T cells expressing granzyme B before (t0) and after (t1) immunotherapy, and we evaluated for an association with tumor response to therapy, progression-free survival (PFS) and overall survival (OS). Additionally, we measured immune markers correlated with immunotherapy response by enzyme-linked immunosorbent assay. Results: We found that the sequential change of granzyme B+ T cells after immunotherapy (t1/t0) significantly predicted durable clinical benefit (DCB) compared to no clinical benefit (NCB) (P=0.048), and prolonged PFS (P=0.025). Patients who demonstrated a PD-L1 tumor proportion score (TPS) >50% showed NCB if patients had low granzyme B t1/t0 levels (<0.805). Additionally, all patients with 1% PD-L1 TPS (or higher) and high granzyme B t1/t0 (≥0.805) showed DCB. Therefore, granzyme B t1/t0 may be an adjunctive marker with available PD-L1 TPS. Conclusions: Our findings revealed that sequential change in granzyme B might be utilized as a predictive biomarker of immune checkpoint inhibitor monotherapy.

Change in management and outcome of mechanical ventilation in Korea: a prospective observational study.

BACKGROUND/AIMS: There are few studies describing contemporary status of mechanical ventilation in Korea. We investigated changes in management and outcome of mechanical ventilation in Korea. METHODS: International, prospective observational cohort studies have been conducted every 6 years since 1998. Korean intensive care units (ICUs) participated in 2010 and 2016 cohorts. We compared 2016 and 2010 Korean data. RESULTS: Two hundred and twenty-six patients from 18 ICUs and 275 patients from 12 ICUs enrolled in 2016 and 2010, respectively. In 2016 compared to 2010, use of non-invasive ventilation outside ICU increased (10.2% vs. 2.5%, p = 0.001). Pressure-control ventilation was the most common mode in both groups. Initial tidal volume (7.1 mL/kg vs. 7.4 mL/kg, p = 0.372) and positive end-expiratory pressure (6 cmH2O vs. 6 cmH2O, p = 0.141) were similar, but peak pressure (22 cmH2O vs. 24 cmH2O, p = 0.011) was lower in 2016. More patients received sedatives (70.7% vs. 57.0%, p = 0.002) and analgesics (86.5% vs. 51.1%, p < 0.001) in 2016. The awakening (48.4% vs. 31.0%, p = 0.002) was more frequently attempted in 2016. The accidental extubation rate decreased to one tenth of what it was in 2010 (1.1% vs. 10.2%, p < 0.001). The ICU mortality did not change (31.4% 35.6%, p = 0.343) but ICU length of stay showed a decreasing trend (9 days vs. 10 days, p = 0.054) in 2016. CONCLUSION: There were temporal changes in care of patients on mechanical ventilation including better control of pain and agitation, and active attempt of awakening.

Head-to-Head Comparison between Xpert MTB/RIF Assay and Real-Time Polymerase Chain Reaction Assay Using Bronchial Washing Specimens for Tuberculosis Diagnosis.

BACKGROUND: With the introduction of Xpert MTB/RIF assay (Xpert), its incorporation into tuberculosis (TB) diagnostic algorithm has become an important issue. The aim of this study was to evaluate the performance of the Xpert assay in comparison with a commercial polymerase chain reaction (PCR) assay. METHODS: Medical records of patients having results of both Xpert and AdvanSure TB/NTM real-time PCR (AdvanSure) assays using the same bronchial washing specimens were retrospectively reviewed. RESULTS: Of the 1,297 patients included in this study, 205 (15.8%) were diagnosed with pulmonary TB. Using mycobacterial culture as the reference method, sensitivity of the Xpert assay using smear-positive specimens was 97.5%, which was comparable to that of the AdvanSure assay (96.3%, p=0.193). However, the sensitivity of the Xpert assay using smear-negative specimens was 70.6%, which was significantly higher than that of the AdvanSure assay (52.9%, p=0.018). Usng phenotypic drug susceptibility testing as the reference method, sensitivity and specificity for detecting rifampicin resistance were 100% and 99.1%, respectively. Moreover, a median turnaround time of the Xpert assay was 1 day, which was significantly shorter than 3 days of the AdvanSure assay (p<0.001). CONCLUSION: In comparison with the AdvanSure assay, the Xpert assay had a higher sensitivity using smear-negative specimens, a shorter turnaround time, and could reliably predict rifampin resistance. Therefore, the Xpert assay might be preferentially recommended over TB-PCR in Korean TB diagnostic algorithm.

Dynamic pattern selection in polymorphic elastocapillarity.

Drying of fine hair and fibers induces dramatic capillary-driven deformation, with important implications on natural phenomena and industrial processes. We recently observed peculiar self-assembly of hair bundles into various distinct patterns depending on the interplay between the bundle length and the liquid drain rate. Here, we propose a mechanism for this pattern selection, and derive and validate theoretical scaling laws for the polymorphic self-assembly of polygonal hair bundles. Experiments are performed by submerging the bundles into a liquid bath, then draining down the liquid. Depending on the interplay between the drain rates and the length of the fibers, we observe the bundles morphing into stars (having concave sides), polygons (having straight edges and rounded corners), or circles. The mechanism of self-assembly at the high drain regime is governed by two sequential stages. In the first stage of the high drain rate regime, the liquid covers the outside of the bundles, and drainage from inside the bundle does not play a role in the self-assembly due to the high viscous stress. The local pressure at the corners of the wet bundles compresses the fibers inward blunting the corners, and the internal lubrication facilitates fiber rearrangement. In the second stage, the liquid is slowly draining from within the fiber spacing, and the negative capillary pressure at the perimeter causes the fibers to tightly pack. In the slow drainage regime, the first stage is absent, and the fibers slowly aggregate without initial dynamic rearrangement. Understanding the mechanism of dynamic elastocapillarity offers insights for studying the complicated physics of wet granular drying.

Clinical outcomes of dose modification during pirfenidone treatment for IPF: A nationwide post-marketing surveillance study.

Background: Pirfenidone, an antifibrotic medication approved for the treatment of idiopathic pulmonary fibrosis (IPF), often requires dose reduction owing to adverse events. In this study, we evaluated if pirfenidone's reduced dose has any impact on clinical outcomes in patients with IPF. Methods: We used the data of a prospective post-marketing study of pirfenidone conducted at 10 hospitals in South Korea from 2014 to 2017. Dose reduction was defined when the pirfenidone dose was temporarily or permanently reduced to manage adverse events or when the treatment dose failed to reach the standard dose. Study patients were classified based on the most frequently administered dose during 48-week follow-up-1800 mg, 1,200 mg, and <1,200 mg/days. The following clinical outcomes were compared between the groups: death, hospitalization, acute exacerbation, pulmonary function decline, and changes in severity of dyspnea and cough. Results: The median follow-up duration in all 143 patients was 11 months. During the study period, 70.6% experienced at least one dose reduction. Patients treated with standard-dose pirfenidone tended to be young and had the lowest diffusing capacity. Pulmonary function changes did not differ depending on the pirfenidone dose. The three groups were not significantly different in terms of the proportion of death, hospitalization, and acute exacerbation. The symptom changes were also similar between the groups. Conclusion: Reduced doses did not negatively impact clinical outcomes compared with the standard-dose pirfenidone in patients with IPF. Dose reduction may be a useful method to manage adverse events while maintaining therapeutic efficacy.

A DNA-derived phage nose using machine learning and artificial neural processing for diagnosing lung cancer.

There is a growing interest in electronic nose-based diagnostic systems that are fast and portable. However, existing technologies are suitable only for operation in the laboratory, making them difficult to apply in a rapid, non-face-to-face, and field-suitable manner. Here, we demonstrate a DNA-derived phage nose (D2pNose) as a portable respiratory disease diagnosis system requiring no pretreatment. D2pNose was produced based on phage colour films implanted with DNA sequences from mammalian olfactory receptor cells, and as a result, it possesses the comprehensive reactivity of these cells. The manipulated surface chemistry of the genetically engineered phages was verified through a correlation analysis between the calculated and the experimentally measured reactivity. Breaths from 31 healthy subjects and 31 lung cancer patients were collected and exposed to D2pNose without pretreatment. With the help of deep learning and neural pattern separation, D2pNose has achieved a diagnostic success rate of over 75% and a classification success rate of over 86% for lung cancer based on raw human breath. Based on these results, D2pNose can be expected to be directly applicable to other respiratory diseases.