Informational needs of individuals from families harboring BRCA pathogenic variants: A systematic review and content analysis.

PURPOSE: Personalized information is paramount to patient-centered communication and decision-making regarding risk management in hereditary cancer syndromes. This systematic review identified information needs of individuals from families harboring BRCA pathogenic variants and compared findings based on gender (women vs men) and clinical characteristics (patients with cancer vs previvors and BRCA heterozygotes vs untested relatives). METHODS: We screened 8115 studies identified from databases and citation searching. The quality of selected studies was assessed using the Mixed Methods Appraisal Tool. Narrative synthesis was conducted based on content analysis. RESULTS: From 18 selected studies including 1063 individuals, we identified 9 categories of information needs. Risk of bias in the selected studies was moderate. Men, untested relatives, and racial and ethnic minorities were underrepresented. Frequently required information was personalized cancer risk and risk-reducing strategies, including decision-making, family implications of hereditary cancers, psychological issues, and cascade testing. Subgroup analyses showed that information needs depended on gender, personal cancer history, and cascade testing in relatives. CONCLUSION: We identified comprehensive and detailed informational needs of individuals from families harboring BRCA pathogenic variants and gaps in international guidelines. Needs for personalized information varied based on gender, health, and genetic testing status. Findings of this study have implications for genetic counseling, tailoring educational materials, and personalizing interventions.

Impact of frailty on the outcomes of patients undergoing degenerative spine surgery: a systematic review and meta-analysis.

BACKGROUND: Degenerative spinal diseases are common in older adults with concurrent frailty. Preoperative frailty is a strong predictor of adverse clinical outcomes after surgery. This study aimed to investigate the association between health-related outcomes and frailty in patients undergoing spine surgery for degenerative spine diseases. METHODS: A systematic review and meta-analysis were performed by electronically searching Ovid-MEDLINE, Ovid-Embase, Cochrane Library, and CINAHL for eligible studies until July 16, 2022. We reviewed all studies, excluding spinal tumours, non-surgical procedures, and experimental studies that examined the association between preoperative frailty and related outcomes after spine surgery. A total of 1,075 articles were identified in the initial search and were reviewed by two reviewers, independently. Data were subjected to qualitative and quantitative syntheses by meta-analytic methods. RESULTS: Thirty-eight articles on 474,651 patients who underwent degenerative spine surgeries were included and 17 papers were quantitatively synthesized. The health-related outcomes were divided into clinical outcomes and patient-reported outcomes; clinical outcomes were further divided into postoperative complications and supportive management procedures. Compared to the non-frail group, the frail group was significantly associated with a greater risk of high mortality, major complications, acute renal failure, myocardial infarction, non-home discharge, reintubation, and longer length of hospital stay. Regarding patient-reported outcomes, changes in scores between the preoperative and postoperative Oswestry Disability Index scores were not associated with preoperative frailty. CONCLUSIONS: In degenerative spinal diseases, frailty is a strong predictor of adverse clinical outcomes after spine surgery. The relationship between preoperative frailty and patient-reported outcomes is still inconclusive. Further research is needed to consolidate the evidence from patient-reported outcomes.

Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. METHODS: This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. RESULTS: The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). CONCLUSION: Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

Caring experiences of family caregivers of patients with pancreatic cancer: an integrative literature review.

PURPOSE: This review summarizes and synthesizes the available empirical literature on the experiences concerned with the problems and challenges faced by caregivers of patients with pancreatic cancer. METHODS: An integrative review method was used, and a literature search was conducted using five databases. We searched the terms "pancreatic cancer," "caregiver," and "experience," and used the Boolean operators OR and AND to combine them. The Joanna Briggs Institute critical appraisal tools were used to assess the quality of the included studies. RESULTS: Four qualitative studies, one mixed method, and three quantitative studies met the selection criteria and were included in the review. Informal family caregivers of patients with pancreatic cancer experienced multifaceted roles, lack of information, difficulties in maintaining emotional well-being, and positive coping. The factors associated with their caring experience included the caregivers' demographics, patients' psychological status, and clinical characteristics. CONCLUSION: Caregivers of patients with pancreatic cancer have various experiences while providing care. Health care providers should offer opportunities for caregivers to recognize their feelings, provide sufficient information and psychological support, and foster coping strategies to maintain the physical and psychosocial well-being of caregivers.

Patient-reported distress and problems among elderly patients with hematological malignancy in Korea.

PURPOSE: Treatment for hematological malignancies (HMs) and functional decline associated with age can cause distress in elderly patients with HMs. However, information about the nature and effects of distress in this population is scarce. Therefore, this study examined the level of distress, its source, and the practical/familial/physical/emotional problems among elderly patients with HMs. METHODS: We conducted a cross-sectional study of patients with HMs aged ≥ 65 years who visited an outpatient clinic at a tertiary medical center in Korea between November 2019 and March 2020. Patient-reported distress and problems were measured using the distress thermometer (DT) and 39-item Problem List by the National Comprehensive Cancer Network. Descriptive statistics, χ2 test or Fisher's exact test, and multivariate logistic regression analyses were conducted (N = 132). RESULTS: In total, 62.1% of patients had moderate to severe distress (DT score ≥ 4), experiencing an average of nine problems. Significant sources of distress on multivariate logistic analysis included problems with transportation, depression, and constipation, accounting for 47% of distress variance. Most patients had physical (97.0%) or emotional problems (79.5%). Among these, fatigue (60.6%), worry (59.8%), tingling (59.8%), difficulty with mobility (47.0%), and memory/concentration (40.2%) were the most frequently reported problems. CONCLUSIONS: Elderly patients with HMs have a high burden of distress, which is affected by different sources, compared with younger patients with solid tumors. Thus, in this population, assessment and management of distress need to be conducted considering the unique features of their source and burden. Further research on distress should consider the cancer type and population age.

Association between inflammatory cytokines and caregiving distress in family caregivers of cancer patients.

PURPOSE: Caregivers of cancer patients experience distress that can manifest as caregiving burden, burnout, depression, and fatigue. Caregiving distress affects physical health in various ways such as causing the dysregulation of inflammatory functions. We examined the relationships between psychological distress experienced by and inflammatory cytokine levels of family caregivers of cancer patients. METHODS: A descriptive, cross-sectional study involving 93 family caregivers of cancer patients was conducted. Self-report questionnaires were used to measure the distress variables, which included the caregiving burden, burnout, depression, and fatigue, and peripheral blood samples were collected to measure the IL-6, IL-10, and TNF-α levels. Multiple linear regression analyses were conducted to evaluate the impact of caregivers' distress on their inflammatory cytokine levels. RESULTS: Inflammatory cytokine levels were negatively correlated with caregiving distress. High fatigue levels (B = - 0.047, p = 0.026) and additional days of care provided per week (B = - 0.048, p = 0.009) was associated with low IL-6 levels. High depression levels (B = - 0.250, p = 0.007), high fatigue levels (B = - 0.054, p = 0.027), and more days of care provided per week (B = - 0.048, p = 0.033) were associated with low TNF-α levels. The age of the caregiver (B = - 0.011, p = 0.020) and days of care provided per week (B = - 0.138, p = 0.031) were associated factors for IL-10 levels. CONCLUSION: The inflammatory responses were associated with the distress in family caregiving for cancer patients. Thus, interventions are needed to support caregivers and manage their caregiving distress.

The coming era of a new auscultation system for analyzing respiratory sounds.

Auscultation with stethoscope has been an essential tool for diagnosing the patients with respiratory disease. Although auscultation is non-invasive, rapid, and inexpensive, it has intrinsic limitations such as inter-listener variability and subjectivity, and the examination must be performed face-to-face. Conventional stethoscope could not record the respiratory sounds, so it was impossible to share the sounds. Recent innovative digital stethoscopes have overcome the limitations and enabled clinicians to store and share the sounds for education and discussion. In particular, the recordable stethoscope made it possible to analyze breathing sounds using artificial intelligence, especially based on neural network. Deep learning-based analysis with an automatic feature extractor and convoluted neural network classifier has been applied for the accurate analysis of respiratory sounds. In addition, the current advances in battery technology, embedded processors with low power consumption, and integrated sensors make possible the development of wearable and wireless stethoscopes, which can help to examine patients living in areas of a shortage of doctors or those who need isolation. There are still challenges to overcome, such as the analysis of complex and mixed respiratory sounds and noise filtering, but continuous research and technological development will facilitate the transition to a new era of a wearable and smart stethoscope.

Risk factors for late-onset hyponatremia and its influence on neonatal outcomes in preterm infants.

Late-onset hyponatremia (LOH), hyponatremia occurring after two weeks of age with the achievement of full feeding, is the result of a negative sodium balance caused by inadequate salt intake or excessive salt loss due to immature renal or intestinal function in preterm infants. The aims of our study were to identify the risk factors for LOH and its influence on neonatal outcomes. This was a retrospective cohort analysis of 161 preterm infants born before 34 weeks of gestation between June 2009 and December 2010 at Seoul National University Hospital. LOH was defined as a sodium level ≤ 132 mEq/L or 133-135 mEq/L with oral sodium supplementation. LOH occurred in 49 (30.4%) of the studied infants. A lower gestational age, a shorter duration of parenteral nutrition, the presence of respiratory distress syndrome, the use of furosemide, and feeding with breast milk were significant risk factors for LOH. In terms of neonatal outcomes, the infants with LOH had longer hospital stays and higher risks of bronchopulmonary dysplasia and retinopathy of prematurity requiring surgery. LOH lasting at least 7 days significantly increased moderate to severe bronchopulmonary dysplasia, periventricular leukomalacia, and extra-uterine growth retardation. LOH is commonly observed in preterm infants; it may be a risk factor for bronchopulmonary dysplasia and retinopathy of prematurity or a marker of illness severity.

Validation of Western common recurrent chromosomal aberrations in Korean chronic lymphocytic leukaemia patients with very low incidence.

In Asia, the incidence of chronic lymphocytic leukaemia (CLL) is lower than in Western countries. Only a few studies of CLL have been conducted in Korea, and no long-term clinical outcome data are available. We assessed the frequency of common chromosomal aberrations in Korean CLL patients using interphase fluorescence in situ hybridization (FISH) and investigated their relationship to clinical outcomes. Between 2000 and 2011, conventional cytogenetic studies were performed in 58 patients, and FISH results were available in 48 patients. We used six DNA probes for the detection of del(13q14), trisomy 12, del(11q22), del(17p13), IGH rearrangement and del(6q23). Chromosomal aberrations were identified in 15 of 58 patients (26%) with conventional cytogenetic studies and in 25 of 48 patients (52%) with interphase FISH, including six patients with complex karyotypes. In contrast with the results of Western studies, trisomy 12 was the most common aberration, followed by IGH rearrangement, del(13q14), del(11q22) and del(17p13). Deletion of 6q23 was not observed, and isolated del(13q14) was less frequent than in Western studies. Compared with the other types of chromosomal aberrations, patients with del(11q22) and del(17p13) were more likely to be Rai stage 3-4 and Binet stage C, resulting in poor responses to chemotherapy and worse outcomes. In contrast, patient with trisomy 12 and isolated del(13q14) showed better responses and superior survival outcomes. The incidence of CLL is lower in Korea than in Western countries, and the frequency of chromosomal aberrations differs, perhaps reflecting differences in the pathogenic mechanism between ethnicities. Large prospective studies are needed to further assess the prognostic value of these results in Korean CLL patients.

Diagnostic Value of Transbronchial Lung Cryobiopsy Using an Ultrathin Cryoprobe and Guide Sheath for Peripheral Pulmonary Lesions.

BACKGROUND: The addition of cryobiopsy to conventional biopsy methods improves the diagnostic yield of peripheral pulmonary lesions. Moreover, cryobiopsy with a guide sheath (GS) provides additional diagnostic benefits. Semi-real-time biopsy can be repeatedly performed using conventional biopsy devices and a GS, and subsequent cryobiopsy can be easily performed at the same location. Recently, a disposable 1.1 mm-diameter ultrathin cryoprobe has been developed and can be used with a 1.95 mm GS in a 2.0 mm working channel. In this study, we evaluated the diagnostic performance of transbronchial lung cryobiopsy (TBLC) with the 1.1 mm cryoprobe and a GS in patients with peripheral pulmonary lesions. METHODS: We retrospectively reviewed the medical records of patients who underwent endobronchial ultrasound transbronchial lung biopsy with a guide sheath and TBLC from July 23, 2021 to April 30, 2022 at Chungnam National University Hospital. RESULTS: Of a consecutive series of 229 patients, 199 were included. The diagnostic yields of forceps biopsy and cryobiopsy were 65.3% (130/199) and 84.4% (168/199), respectively, and the total diagnostic yield was 91.5% (182/199) ( P <0.001 vs. forceps biopsy). Multivariate analysis showed that solid lesion morphology [adjusted odds ratio (OR) 3.659, P =0.002] was associated with a significantly greater diagnostic yield of cryobiopsy, whereas a lesion diameter >20 mm ( P =0.026; adjusted OR 3.816) and 'within' orientation ( P =0.004; adjusted OR 6.174) were associated with a significantly greater overall diagnostic yield. CONCLUSION: TBLC using an ultrathin cryoprobe and GS markedly improves the diagnostic yield.

Immune checkpoint inhibitor score (IChIS) predicts survival benefit of immunotherapy in patients with non-small cell lung cancer.

Background: The use of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer is increasing. Despite ongoing studies to predict the efficacy of ICIs, its use in clinical practice remains difficult. Thus, we aimed to discover a predictive marker by analyzing blood cell characteristics and developing a scoring system for patients treated with ICIs. Methods: This was a prospective multicenter study in patients with advanced non-small cell lung cancer (NSCLC) who received ICIs as second-line treatment from June 2021 to November 2022. Blood cell parameters in routine blood samples were evaluated using an automated hematology analyzer. Immune checkpoint inhibitor score (IChIS) was calculated as the sum of neutrophil count score and immature granulocyte score. Results: A total of 143 patients from 4 institutions were included. The treatment response was as follows: partial response, 8.4%; stable disease, 37.1%; and progressive disease, 44.8%. Median progression-free survival and overall survival after ICI treatment was 3.0 and 8.3 months, respectively. Median progression-free survival in patients with an IChIS of 0 was 4.0 months, which was significantly longer than 1.9 months in patients with an IChIS of 1 and 1.0 month in those with an IChIS of 2 (p = 0.001). The median overall survival in patients with an IChIS of 0 was 10.2 months, which was significantly longer than 6.8 and 1.8 months in patients with an IChIS of 1 and 2, respectively (p < 0.001). Conclusions: Baseline IChIS could be a potential biomarker for predicting survival benefit of immunotherapy in NSCLC.

Piperacillin-Tazobactam versus Cefotaxime as Empiric Treatment for Febrile Urinary Tract Infection in Hospitalized Children.

BACKGROUND: According to international pediatric urinary tract infection (UTI) guidelines, selecting ampicillin/sulbactam or amoxicillin/clavulanate is recommended as the first-line treatment for pediatric UTI. In Korea, elevated resistance to ampicillin and ampicillin/sulbactam has resulted in the widespread use of third-generation cephalosporins for treating pediatric UTIs. This study aims to compare the efficacy of piperacillin-tazobactam (TZP) and cefotaxime (CTX) as first-line treatments in hospitalized children with UTIs. MATERIALS AND METHODS: The study, conducted at Jeju National University Hospital, retrospectively analyzed medical records of children hospitalized for febrile UTIs between 2014 and 2017. UTI diagnosis included unexplained fever, abnormal urinalysis, and the presence of significant uropathogens. Treatment responses, recurrence, and antimicrobial susceptibility were assessed. RESULTS: Out of 323 patients, 220 met the inclusion criteria. Demographics and clinical characteristics were similar between TZP and CTX groups. For children aged ≥3 months, no significant differences were found in treatment responses and recurrence. Extended-spectrum beta-lactamase (ESBL)-positive strains were associated with recurrence in those <3 months. CONCLUSION: In Korea, escalating resistance to empirical antibiotics has led to the adoption of broad-spectrum empirical treatment. TZP emerged as a viable alternative to CTX for hospitalized children aged ≥3 months with UTIs. Consideration of ESBL-positive strains and individualized approaches for those <3 months are crucial.

Avulsion fracture of the supinator crest of the proximal ulna in the context of elbow joint injuries.

PURPOSE: While performing CT examinations of the elbow, we frequently observed a previously undescribed fracture fragment of the supinator crest of the ulna. According to the anatomy of the lateral collateral ligament complex, this fracture might be an avulsion fracture of the annular ligament and/or the lateral ulnar collateral ligament. The aim of this study was to further characterize these fragments and document their associated injuries. METHODS: Retrospective evaluation of CT scans of the elbow was performed. Conventional X-ray and CT diagnoses were used to systematically document any associated injuries. RESULTS: A total of 152 CT scans were evaluated. The fragment in question was discovered in 17 patients (11.2%). The average age of the patients was 40 years (±14.9; 9-71 years). The fragment size varied between a few millimetres and 2.4 cm. Multifragmented fractures were observed. In 82.3% of the cases, associated radial head fractures were diagnosed. In 29.4%, a coronoid process fracture was present. Distal humerus fractures were found in 23.5%. Instability in the medial collateral ligament and an Osborne-Cotterill lesion were found in 11.8% of the patients, respectively. CONCLUSIONS: In a significant percentage of the population, a previously undescribed fracture fragment of the supinator crest of the ulna could be detected. The most frequently occurring associated injuries were fractures of the radial head, the coronoid process, and the distal humerus. The aetiology of these lesions is unknown; however, bony avulsion of the annular or the lateral ulnar collateral ligament seems to be the most likely cause. If this fragment is to be diagnosed by CT, the possibility of lateral or posterolateral instability should be considered.

Role of 16S Ribosomal RNA Analysis in Identification of Microorganisms in Febrile Urinary Tract Infection of Infants.

OBJECTIVES: To assess the role of 16S ribosomal RNA analysis in microbial identification in febrile infants under six months of age diagnosed with UTI, and compare it with the conventional culture results. METHODS: Young infants under 6 mo of age who were suspected UTI from May 2018 to April 2019 had been enrolled. Uropathogens were analyzed by the traditional microbiologic culture system and the 16S rRNA analysis. The 16S rRNA analysis included 16S rRNA amplicon band confirmation and bacterial identification through the sequencing analysis. RESULTS: A total of 57 infants with the febrile UTI were enrolled, and the median age was 3 mo. Uropathogens were identified in 43 patients (75.4%) in a conventional culture method: Escherichia coli in 38 patients (88.4%), Klebsiella pneumoniae in 3 (7.0%), Enterobacter cloacae in 1 (2.3%), and Pseudomonas aeruginosa in 1 (2.3%). Fifty urine samples (87.8%) had positive 16S rRNA amplicon band on electrophoresis. Among the 16S rRNA-positive urines, 40 samples were available for the sequence analysis of 16S rRNA, and the identification of bacteria were as follows: E. fergusonii in 36, K. pneumoniae in 3, and Shigella flexneri in 1. The sensitivity of 16S rRNA sequencing was 81.4% [95% confidence interval (CI), 67.4-90.3%] and the specificity was 64.3% (95% CI, 38.8-83.7%). CONCLUSION: Uropathogen identification using 16S rRNA analysis could be applied to manage the febrile UTI in young infants clinically in combination with the conventional culture.

Cytokine associated with severity of depressive symptoms in female nurses in Korea.

Background: Depression has been associated with the risk of developing physical illnesses and diseases. Inflammatory hypotheses of immunoactive and dysregulated cytokine production have been proposed to describe this association; however, data pertaining to the high prevalence of depression among nurses are limited. Objective: This study aimed to use a comprehensive immune-profiling approach to determine whether an abnormal profile of circulating cytokines could be identified in nurses with self-reported depression and whether this profile is associated with the severity of depression. Methods: We investigated a cohort of 157 female nurses in Korea. The self-report Patient Health Questionnaire was used to measure the depression levels of nurses. In addition, peripheral blood samples were collected and used to measure the cytokine profile using the Luminex multiplexing system. Generalized gamma regression analyses were conducted to evaluate the association between cytokine and depressive symptoms. Results: Regarding severity of depressive symptoms, 28.0% of nurses had moderately severe depression while 9.6% had severe depression. Moderately-severe depressive symptoms in nurses were associated with elevated levels of interleukin-6 (B = 0.460, p = 0.003), interleukin-8 (B = 0.273, p = 0.001), and interleukin-18 (B = 0.236, p = 0.023), whereas interferon-gamma levels (B = -0.585, p = 0.003) showed the opposite profile. Participants with severe depressive symptoms presented decreased interferon-gamma levels (B = -1.254, p < 0.001). Conclusion: This study demonstrated that proinflammatory cytokines were associated with depression among nurses. This calls for early detection and intervention, considering the mechanisms linking depression to physical illness and disease.

A patient with a lung adenosquamous carcinoma harboring a de novo T790M mutation and huge nonbacterial vegetative growths successfully treated with osimertinib: A case report.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition; sterile vegetations attach to heart valves. NBTE is typically found in patients with malignancies or autoimmune disorders. Although surgical interventions are sometimes performed, the appropriate indication and timing are still unclear. Here, we describe a 72-year-old woman diagnosed with adenosquamous carcinoma of the lung. She was initially diagnosed as pT2aN0M0 and underwent RUL lobectomy. After nine months, lung cancer recurred, and she underwent treatment with cytotoxic chemotherapy. However, images showed progression after only one month. Rebiopsy revealed she had comutation of de novo EGFR L858R and T790M. Treatment was changed to gefitinib. After one month, she experienced loss of consciousness. Brain magnetic resonance imaging (MRI) showed multiple lesions resembling infarctions or metastases. Chest computed tomography (CT) revealed progression. Osimertinib was prescribed and she underwent echocardiography to rule out the possibility of a cardiogenic embolism. Surprisingly, severe mitral regurgitation and a massive vegetation on the mitral valve were found. Cardiologists recommended surgery due to the severity of the embolic event and valve dysfunction, but it was decided to continue antibiotics, osimertinib, and anticoagulants instead of surgery due to the patient's poor general condition and the possibility of NBTE. Six weeks later, the patient's condition markedly improved and echocardiography revealed a marked reduction in vegetation size. Clinicians should be aware that targeted therapy can be effective in treating severe cancer complications, such as NBTE, as evidenced by the successful treatment of lung cancer with osimertinib. This option should be considered, particularly for elderly lung cancer patients, before resorting to surgery as a first-line treatment for NBTE.

Evolution of the Stethoscope: Advances with the Adoption of Machine Learning and Development of Wearable Devices.

The stethoscope has long been used for the examination of patients, but the importance of auscultation has declined due to its several limitations and the development of other diagnostic tools. However, auscultation is still recognized as a primary diagnostic device because it is non-invasive and provides valuable information in real-time. To supplement the limitations of existing stethoscopes, digital stethoscopes with machine learning (ML) algorithms have been developed. Thus, now we can record and share respiratory sounds and artificial intelligence (AI)-assisted auscultation using ML algorithms distinguishes the type of sounds. Recently, the demands for remote care and non-face-to-face treatment diseases requiring isolation such as coronavirus disease 2019 (COVID-19) infection increased. To address these problems, wireless and wearable stethoscopes are being developed with the advances in battery technology and integrated sensors. This review provides the history of the stethoscope and classification of respiratory sounds, describes ML algorithms, and introduces new auscultation methods based on AI-assisted analysis and wireless or wearable stethoscopes.

A Personalized Cancer Vaccine that Induces Synergistic Innate and Adaptive Immune Responses.

To demonstrate potent efficacy, a cancer vaccine needs to activate both innate and adaptive immune cells. Personalized cancer vaccine strategies often require the identification of patient-specific neoantigens; however, the clonal and mutational heterogeneity of cancer cells presents inherent challenges. Here, extracellular nanovesicles derived from alpha-galactosylceramide-conjugated autologous acute myeloid leukemia (AML) cells (ECNV-αGC) are presented as a personalized therapeutic vaccine that activates both innate and adaptive immune responses, bypassing the need to identify patient-specific neoantigens. ECNV-αGC vaccination directly engages with and activates both invariant natural killer T (iNKT) cells and leukemia-specific CD8+ T cells in mice with AML, thereby promoting long-term anti-leukemic immune memory. ECNV-αGC sufficiently serves as an antigen-presenting platform that can directly activate antigen-specific CD8+ T cells even in the absence of dendritic cells, thereby demonstrating a multifaceted cellular mechanism of immune activation. Moreover, ECNV-αGC vaccination results in a significantly lower AML burden and higher percentage of leukemia-free survivors among cytarabine-treated hosts with AML. Human AML-derived ECNV-αGCs activate iNKT cells in both healthy individuals and patients with AML regardless of responsiveness to conventional therapies. Together, autologous AML-derived ECNV-αGCs may be a promising personalized therapeutic vaccine that efficiently establishes AML-specific long-term immunity without requiring the identification of neoantigens.

Clinicians' Prediction of Survival and Prognostic Confidence in Patients with Advanced Cancer in Three East Asian Countries.

Background: Little is known about accuracy and confidence of clinicians' prediction of survival (CPS) in East-Asian countries. Objective: We aimed to examine accuracy of CPS for 7-, 21-, and 42-day survival in palliative inpatients and its association with prognostic confidence. Design: An international prospective cohort study in Japan (JP), Korea (KR), and Taiwan (TW). Setting/Subjects: Subjects were inpatients with advanced cancer admitted to 37 palliative care units in three countries. Measurements: Discrimination of CPS was investigated through sensitivity, specificity, overall accuracy, and area under the receiver operating characteristics curves (AUROCs) according to 7-, 21-, and 42-day survival. The accuracies of CPS were compared with those of Performance Status-based Palliative Prognostic Index (PS-PPI). Clinicians were instructed to rate confidence level on a 0-10-point scale. Results: A total of 2571 patients were analyzed. The specificity was highest at 93.2-100.0% for the 7-day CPS, and sensitivity was highest at 71.5-86.8% for the 42-day CPS. The AUROCs of the seven-day CPS were 0.88, 0.94, and 0.89, while those of PS-PPI were 0.77, 0.69, and 0.69 for JP, KR, and TW, respectively. As for 42-day prediction, sensitivities of PS-PPI were higher than those of CPS. Clinicians' confidence was strongly associated with the accuracy of prediction in all three countries (all p-values <0.01). Conclusions: CPS accuracies were highest (0.88-0.94) for the seven-day survival prediction. CPS was more accurate than PS-PPI in all timeframe prediction except 42-day prediction in KR. Prognostic confidence was significantly associated with the accuracy of CPS.

Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids.

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.