ABSTRACT
BACKGROUND: Despite the significant impact of multi-drug-resistant bacteraemia, especially extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE), the burden of disease has not been investigated thoroughly. AIM: To evaluate the clinical outcomes and socio-economic burden of ESBL-E and CRE bacteraemia nationwide in the Republic of Korea. METHODS: A search was undertaken for all cases of ESBL-E and CRE bacteraemia and matched controls in 10 hospitals in the Republic of Korea over 6 months. Patients with ESBL-E or CRE bacteraemia were classified as the R group, and matched controls with antibiotic-susceptible bacteraemia and without infection were classified as the S and N groups, respectively. Patients' clinical data were collected, and the economic burden was estimated based on medical expenses, loss of productivity and total costs. FINDINGS: In total, 795 patients were identified, including 265 patients with ESBL-E or CRE bacteraemia and their matched controls. The mean total length of stay for patients with ESBL-E and CRE in the R group was 1.53 and 1.90 times that of patients in the S group, respectively. The 90-day mortality rates for ESBL-E in the R and S groups were 12.1% and 5.6%, respectively, and the corresponding figures for CRE were 28.6% and 12.0%. There were significant differences in the total costs between the R, S and N groups for both ESBL-E and CRE (ESBL-E: $11,151 vs $8712 vs $6063, P=0.004; CRE: $40,464 vs $8748 vs $7279, P=0.024). CONCLUSION: The clinical and economic burden imposed by ESBL-E or CRE bacteraemia was extremely high. These findings suggest that efforts to control resistant bacteraemia are necessary to reduce this burden.
Subject(s)
Bacteremia , beta-Lactamases , Humans , Risk Factors , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Republic of Korea/epidemiology , Carbapenems/pharmacology , Bacteremia/drug therapy , Bacteremia/epidemiology , Cost of IllnessABSTRACT
A series of recent experiments have shown that collision of ballistic electrons in semiconductors can be used to probe the indistinguishability of single-electron wavepackets. Perhaps surprisingly, their Coulomb interaction has not been seen due to screening. Here we show Coulomb-dominated collision of high-energy single electrons in counter-propagating ballistic edge states, probed by measuring partition statistics while adjusting the collision timing. Although some experimental data suggest antibunching behaviour, we show that this is not due to quantum statistics but to strong repulsive Coulomb interactions. This prevents the wavepacket overlap needed for fermionic exchange statistics but suggests new ways to utilize Coulomb interactions: microscopically isolated and time-resolved interactions between ballistic electrons can enable the use of the Coulomb interaction for high-speed sensing or gate operations on flying electron qubits.
ABSTRACT
The Southern Ocean greatly contributes to the regulation of the global climate by controlling important heat and carbon exchanges between the atmosphere and the ocean. Rates of climate change on decadal timescales are therefore impacted by oceanic processes taking place in the Southern Ocean, yet too little is known about these processes. Limitations come both from the lack of observations in this extreme environment and its inherent sensitivity to intermittent processes at scales that are not well captured in current Earth system models. The Southern Ocean Carbon and Heat Impact on Climate programme was launched to address this knowledge gap, with the overall objective to understand and quantify variability of heat and carbon budgets in the Southern Ocean through an investigation of the key physical processes controlling exchanges between the atmosphere, ocean and sea ice using a combination of observational and modelling approaches. Here, we provide a brief overview of the programme, as well as a summary of some of the scientific progress achieved during its first half. Advances range from new evidence of the importance of specific processes in Southern Ocean ventilation rate (e.g. storm-induced turbulence, sea-ice meltwater fronts, wind-induced gyre circulation, dense shelf water formation and abyssal mixing) to refined descriptions of the physical changes currently ongoing in the Southern Ocean and of their link with global climate. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.
ABSTRACT
This study aimed to evaluate the efficacy of deep learning (DL) for the identification and classification of various types of dental implant systems (DISs) using a large-scale multicenter data set. We also compared the classification accuracy of DL and dental professionals. The data set, which was collected from 5 college dental hospitals and 10 private dental clinics, contained 37,442 (24.8%) periapical and 113,291 (75.2%) panoramic radiographic images and consisted of a total of 10 manufacturers and 25 different types of DISs. The classification accuracy of DL was evaluated using a pretrained and modified ResNet-50 architecture, and comparison of accuracy performance and reading time between DL and dental professionals was conducted using a self-reported questionnaire. When comparing the accuracy performance for classification of DISs, DL (accuracy: 82.0%; 95% confidence interval [CI], 75.9%-87.0%) outperformed most of the participants (mean accuracy: 23.5% ± 18.5%; 95% CI, 18.5%-32.3%), including dentists specialized (mean accuracy: 43.3% ± 20.4%; 95% CI, 12.7%-56.2%) and not specialized (mean accuracy: 16.8% ± 9.0%; 95% CI, 12.8%-20.9%) in implantology. In addition, DL tends to require lesser reading and classification time (4.5 min) than dentists who specialized (75.6 ± 31.0 min; 95% CI, 13.1-78.4) and did not specialize (91.3 ± 38.3 min; 95% CI, 74.1-108.6) in implantology. DL achieved reliable outcomes in the identification and classification of various types of DISs, and the classification accuracy performance of DL was significantly superior to that of specialized or nonspecialized dental professionals. DL as a decision support aid can be successfully used for the identification and classification of DISs encountered in clinical practice.
Subject(s)
Dental Implants , Humans , Radiography, Panoramic/methodsABSTRACT
BACKGROUND: Isolating patients infected or colonized with vancomycin-resistant enterococci (VRE) in a private room or cohort room to prevent hospital transmission is controversial. AIM: To evaluate the effect of a relaxed isolation policy for VRE-infected or colonized patients on healthcare-associated (HA) VRE bacteraemia in an acute care hospital with a predominantly shared-room setting. METHODS: The incidence of HA VRE bacteraemia was compared during a private isolation era (October 2014-September 2017), a cohort isolation era (October 2017-June 2020), and a no isolation era (July 2020-June 2022). Using Poisson regression modelling, an interrupted time-series analysis was conducted to analyse level changes and trends in incidences of HA VRE bacteraemia for each era. FINDINGS: The proportion of VRE-infected or -colonized patients staying in shared rooms increased from 18.3% in the private isolation era to 82.6% in the no isolation era (P < 0.001). There was no significant difference in the incidences of HA VRE bacteraemia between the private isolation era and the cohort isolation era (relative risk: 1.01; 95% confidence interval: 0.52-1.98; P = 0.977) or between the cohort isolation era and the no isolation era (0.99; 0.77-1.26; P = 0.903). In addition, there was no significant slope increase in the incidence of HA VRE bacteraemia between any of the eras. CONCLUSION: In a hospital with predominantly shared rooms, the relaxation of isolation policy did not result in increased HA VRE bacteraemia, when other infection control measures were maintained.
Subject(s)
Bacteremia , Cross Infection , Gram-Positive Bacterial Infections , Vancomycin-Resistant Enterococci , Humans , Incidence , Cross Infection/epidemiology , Cross Infection/prevention & control , Patients' Rooms , Vancomycin Resistance , Hospitals , Bacteremia/epidemiology , Bacteremia/prevention & control , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/prevention & controlABSTRACT
BACKGROUND: To reduce transmission of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE), screening is recommended for patients sharing rooms with CP-CRE-detected patients and healthcare workers caring for them. AIM: The aim of this study was to investigate the transmission rate of CP-CRE among exposed people in a tertiary hospital using whole-genome sequencing. METHODS: This study was conducted in a 1751-bed tertiary teaching hospital from January 2017 to December 2019. Index patients were defined as those with positive results in CP-CRE tests during hospitalization. When an index patient was detected in a shared room, we performed CRE screening tests for patients whose stay overlapped with an index patient's stay for at least one day. Where a second case was found, healthcare worker contacts were also screened. CP-CRE were confirmed, and the carbapenemase type identified, by PCR. Whole-genome sequencing was used to compare isolates from index and exposed patients. RESULTS: During the study period, 47 index patients were identified, and they had been in contact with 152 patients in shared rooms and 54 healthcare workers. None of the healthcare workers had CRE. Among the 152 exposed patients, four patients had the same type of carbapenemases as their CP-CRE index patients and all of them were KPC. Whole-genome sequencing revealed that three of these four pairs showed genotypic accordance between the index and the exposed. CONCLUSION: The CP-CRE transmission rate among the exposed patients was calculated as 2.0% (= 3/152).
Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Enterobacteriaceae Infections , Gammaproteobacteria , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenems/pharmacology , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Humans , Tertiary Care Centers , beta-Lactamases/geneticsABSTRACT
BACKGROUND: Acinetobacter baumannii is one of the major pathogens responsible for healthcare-associated infections, especially in intensive care units (ICUs). AIM: To evaluate the effect of room privatization in an ICU on the acquisition of carbapenem-resistant A. baumannii (CRAB). METHODS: Between March and August 2017, a medical ICU was renovated from a multi-bed bay room to single rooms. Acquisition of CRAB was compared between patients admitted to the ICU over 18 months pre-renovation (September 2015 to February 2017) and post-renovation (September 2017 to February 2019). A Cox proportional hazard model was used with adjustment for demographics and comorbidities. FINDINGS: Of the 901 patients, who contributed 8276 patient-days, 95 (10.5%) acquired CRAB during their ICU stay. The CRAB acquisition rate was significantly higher during the pre-renovation period (1.87 per 100 patient-days) than during the post-renovation period (0.39 per 100 patient-days) (P<0.001). In the multi-variable Cox regression model, CRAB acquisition was significantly associated with the presence of a feeding tube (adjusted hazard ratio (aHR), 6.08; 95% confidence interval (CI), 2.46-15.06; P<0.001), continuous renal replacement therapy (aHR, 1.66; 95% CI, 1.09-2.53; P=0.019) and admission after renovation of the ICU to single rooms (aHR, 0.23; 95% CI, 0.12-0.41; P<0.001). CONCLUSIONS: Renovation of ICUs to single rooms is an efficient strategy to prevent transmission of multi-drug-resistant organisms and hospital-acquired infections.
Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Cross Infection , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Acinetobacter Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenems/pharmacology , Cross Infection/drug therapy , Cross Infection/epidemiology , Cross Infection/prevention & control , Humans , Intensive Care Units , PrivatizationABSTRACT
BACKGROUND: Modulating the DNA damage response and repair (DDR) pathways is a promising strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3-related protein, which is crucial for DDR. PATIENTS AND METHODS: This phase II trial evaluated ceralasertib plus durvalumab for the treatment of patients with metastatic melanoma who had failed anti-programmed cell death protein 1 therapy. RESULTS: Among the 30 patients, we observed an overall response rate of 31.0% and a disease control rate of 63.3%. Responses were evident across patients with acral, mucosal, and cutaneous melanoma. The median duration of response was 8.8 months (range, 3.8-11.7 months). The median progression-free survival was 7.1 months (95% confidence interval, 3.6-10.6 months), and the median overall survival was 14.2 months (95% confidence interval, 9.3-19.1 months). Common adverse events were largely hematologic and manageable with dose interruptions and reductions. Exploratory biomarker analysis suggested that tumors with an immune-enriched microenvironment or alterations in the DDR pathway were more likely to respond to the study treatment. CONCLUSION: We conclude that ceralasertib in combination with durvalumab has promising antitumor activity among patients with metastatic melanoma who have failed anti-programmed cell death protein 1 therapy, and constitute a population with unmet needs.
Subject(s)
Melanoma , Skin Neoplasms , Antibodies, Monoclonal/adverse effects , Humans , Indoles , Melanoma/drug therapy , Melanoma/genetics , Morpholines , Pyrimidines , Skin Neoplasms/drug therapy , Sulfonamides , Tumor MicroenvironmentABSTRACT
BACKGROUND: Extrapulmonary TB (EPTB) is more difficult to diagnose than pulmonary TB. The delayed management of EPTB can lead to complications and increase the socio-economic burden.METHODS: Patients newly diagnosed with EPTB were retrospectively enrolled from 11 general hospitals in South Korea from January 2017 to December 2018. The basic characteristics of patients were described. Univariable and multivariable analyses were performed between early and delayed diagnosis groups to identify risk factors for delayed diagnosis and treatment in EPTB.RESULTS: In total, 594 patients were enrolled. Lymph node TB (28.3%) was the predominant form, followed by abdominal (18.4%) and disseminated TB (14.5%). Concurrent lung involvement was 17.8%. The positivity of diagnostic tests showed no significant difference between the two groups. Acute clinical manifestations in disseminated, pericardial and meningeal TB, and immunosuppression were associated with early diagnosis. Delayed diagnosis was associated with outpatient clinic visits, delayed sample acquisition and diagnostic departments other than infection or pulmonology.CONCLUSION: The delay in diagnosis and treatment of EPTB was not related to differences in microbiological characteristics of Mycobacterium tuberculosis itself; rather, it was due to the indolent clinical manifestations that cause referral to non-TB-specialised departments in the outpatient clinic and delay the suspicion of TB and diagnostic testing.
Subject(s)
Delayed Diagnosis , Tuberculosis, Extrapulmonary , Humans , Mycobacterium tuberculosis , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Tuberculosis, Extrapulmonary/diagnosisABSTRACT
Malignant tumours arising from the sublingual glands are very rare, and the extent and frequency of local invasion or regional spread in malignant sublingual gland tumour (MSLT) has not been fully studied due to the disease rarity. To provide comprehensive features of local and regional spread of MSLT, we reviewed 20 surgical cases for detailed pathological analyses among 26 cases diagnosed as having primary MSLT. Adenoid cystic carcinoma (ACC) was the most common pathological subtype, followed by mucoepidermoid carcinoma. Disease-free and overall survivals at 5 years were 76.1 % and 77.7 %, respectively. High-grade malignant tumours and grade 2-3 ACC accounted for 41.7 % and 85.7 %. Clinical and pathological extraparenchymal extensions were found in 34.6 % and 80.0 %, respectively. Tumour invasion to the lingual nerve and submandibular gland/ductal system were also detected in 40.0 % and 28.6 %. The incidences of lingual nerve invasion in ACC and ACC ≥4 cm were 30.8 % and 42.9 %. Regional nodal involvement occurred in seven of 26 cases, and all metastatic lymph nodes were found in neck levels Ib and IIa. In summary, a significant portion of MSLT cases consisted of high-grade tumours and grade 2-3 ACC; therefore local invasion into adjacent structures should be cautiously evaluated in cases of MSLT.
Subject(s)
Carcinoma, Adenoid Cystic , Carcinoma, Mucoepidermoid , Salivary Gland Neoplasms , Sublingual Gland Neoplasms , Carcinoma, Adenoid Cystic/epidemiology , Carcinoma, Adenoid Cystic/surgery , Carcinoma, Mucoepidermoid/surgery , Humans , Neck Dissection , Salivary Gland Neoplasms/surgery , Sublingual Gland Neoplasms/epidemiology , Sublingual Gland Neoplasms/surgeryABSTRACT
OBJECTIVES: Recently, rapid phenotypic antimicrobial susceptibility testing (AST) based on microscopic imaging analysis has been developed. The aim of this study was to determine whether implementation of antimicrobial stewardship programmes (ASP) based on rapid phenotypic AST can increase the proportion of patients with haematological malignancies who receive optimal targeted antibiotics during early periods of bacteraemia. METHODS: This randomized controlled trial enrolled patients with haematological malignancies and at least one positive blood culture. Patients were randomly assigned 1:1 to conventional (n = 60) or rapid phenotypic (n = 56) AST. The primary outcome was the proportion of patients receiving optimal targeted antibiotics 72 hr after blood collection for culture. RESULTS: The percentage receiving optimal targeted antibiotics at 72 hr was significantly higher in the rapid phenotypic AST group (45/56, 80.4%) than in conventional AST group (34/60, 56.7%) (relative risk (RR) 1.42, 95% confidence interval (CI) 1.09-1.83). The percentage receiving unnecessary broad-spectrum antibiotics at 72 hr was significantly lower (7/26, 12.5% vs 18/60, 30.0%; RR 0.42, 95% CI 0.19-0.92) and the mean time to optimal targeted antibiotic treatment was significantly shorter (38.1, standard deviation (SD) 38.2 vs 72.8, SD 93.0 hr; p < 0.001) in the rapid phenotypic AST group. The mean time from blood collection to the AST result was significantly shorter in the rapid phenotypic AST group (48.3, SD 17.6 vs 83.1, SD 22.2 hr). DISCUSSION: ASP based on rapid phenotypic AST can rapidly optimize antibiotic treatment for bacteraemia in patients with haematological malignancy. Rapid phenotypic AST can improve antimicrobial stewardship in immunocompromised patients.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship/methods , Bacteremia/drug therapy , Hematologic Neoplasms/drug therapy , Microbial Sensitivity Tests/methods , Adult , Anti-Bacterial Agents/pharmacology , Bacteremia/complications , Female , Hematologic Neoplasms/complications , Humans , Male , Middle Aged , Time-to-Treatment , Treatment OutcomeABSTRACT
The aim of this study was to evaluate the clinical and radiographic outcomes of a lateral window approach for removal of benign minor sinus pathologies combined with transcrestal sinus floor elevation. From 2014 to 2018, all patients who received sinus pathology removal via a lateral window approach combined with transcrestal sinus floor elevation were screened. The serous exudate or minor sinus pathology was drained or removed via lateral window approach. Subsequently, transcrestal sinus floor elevation without grafting and simultaneous implant placement were performed. Panoramic radiographs and cone-beam computed tomography were taken preoperatively, immediately after surgery, and after prosthesis delivery. Twelve patients were included in this study. The decrease in Schneiderian membrane thickness was statistically significant (P<0.001). Endo-sinus bone formation was observed on the buccal (1.35±2.31mm) and palatal (1.61±2.65mm) sites of the implant. The implant survival rate was 100%. All implants survived for an average of 21.83±11.11 months. Within the limitations of this study, we suggest that the lateral window approach for minor sinus pathology removal combined with transcrestal sinus floor elevation has several advantages including endo-sinus bone gain without bone graft, minimal patient discomfort, reduced postoperative complications and shorter treatment period.
Subject(s)
Dental Implants , Sinus Floor Augmentation , Dental Implantation, Endosseous , Humans , Maxillary Sinus/diagnostic imaging , Maxillary Sinus/surgery , Retrospective StudiesABSTRACT
The reported incidence rate of venous and arterial thrombotic events in critically ill patients with COVID-19 infections is high, ranging from 20% to 60%. We adopted a patient-tailored thromboprophylaxis protocol based on clinical and laboratory presentations for these patients in our institution. We hypothesised that patients who received high-intensity thromboprophylaxis treatment would experience fewer thrombotic events. The aims of our study were to explore the incidence of thrombotic events in this population; to assess independent factors associated with thrombotic events and to evaluate the incidence of haemorrhagic events. A retrospective review of all adult patients with confirmed SARS-CoV-2 infection admitted to the intensive care unit (ICU) between 1 March and 29 May 2020 was performed. The primary outcome was a composite of venous and arterial thrombotic events diagnosed during the ICU stay. Multivariable logistic regression was used to identify the independent factors associated with thrombotic events. A total of 188 patients met the inclusion criteria. All received some type of thromboprophylaxis treatment except for six patients who did not receive any prophylaxis. Of the 182 patients who received thromboprophylaxis, 75 (40%) received high-intensity thromboprophylaxis and 24 (12.8%) were treated with therapeutic anticoagulation. Twenty-one patients (11.2%) experienced 23 thrombotic events (incidence rate of 12.2% (95%CI 7.9-17.8)), including 12 deep venous thromboses, 9 pulmonary emboli and 2 peripheral arterial thromboses. The multivariable logistic regression analysis showed that only D-dimer (OR 2.80, p = 0.002) and high-intensity thromboprophylaxis regimen (OR 0.20, p = 0.01) were independently associated with thrombotic events. Thirty-one patients (16.5%) experienced haemorrhagic events; among them, 13 were classified as major bleeding according to the International Society on Thrombosis and Haemostasis criteria. Therapeutic anticoagulation, but not the high-intensity thromboprophylaxis regimen, was associated with major bleeding. A proactive approach to the management of thromboembolism in critically ill COVID-19 patients utilising a high-intensity thromboprophylaxis regimen in appropriately selected patients may result in lower thrombotic events without increasing the risk of bleeding.
Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Clinical Protocols , Critical Care/statistics & numerical data , Enoxaparin/therapeutic use , Venous Thromboembolism/complications , Adult , Aged , Aged, 80 and over , Critical Illness , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Venous Thromboembolism/drug therapy , Young AdultABSTRACT
We investigated the relationship between the prognostic importance of anatomic tumour burden and subtypes of breast cancer using data from the Korean Breast Cancer Registry Database. In HR+/HER2+ and HR-/HER2-tumours, an increase in T stage profoundly increased the hazard of death, while the presence of lymph node metastasis was more important in HR+/HER2+ and HR-/HER2+ tumours among 131,178 patients with stage I-III breast cancer. The patterns of increasing mortality risk and tumour growth (per centimetre) and metastatic nodes (per node) were examined in 67,038 patients with a tumour diameter ≤ 7 cm and < 8 metastatic nodes. HR+/HER2- and HR-/HER2- tumours showed a persistent increase in mortality risk with an increase in tumour diameter, while the effect was modest in HER2+ tumours. Conversely, an increased number of metastatic nodes was accompanied by a persistently increased risk in HR-/HER2+ tumours, while the effect was minimal for HR-/HER2- tumours with > 3 or 4 nodes. The interactions between the prognostic significance of anatomic tumour burden and subtypes were significant. The prognostic relevance of the anatomic tumour burden was non-linear and highly dependent on the subtypes of breast cancer.
Subject(s)
Breast Neoplasms/classification , Breast Neoplasms/pathology , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Tumor Burden , Adolescent , Adult , Aged , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Metastasis , Prognosis , Survival Rate , Young AdultABSTRACT
BACKGROUND: Immune checkpoint inhibitors (ICIs) have been shown to be beneficial for some patients with advanced non-small-cell lung cancer (NSCLC). However, the underlying mechanisms mediating the limited response to ICIs remain unclear. PATIENTS AND METHODS: We carried out whole-exome sequencing on 198 advanced NSCLC tumors that had been sampled before anti-programmed cell death 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy. Detailed clinical characteristics were collected on these patients. We designed a new method to estimate human leukocyte antigen (HLA)-corrected tumor mutation burden (TMB), a modification which considers the loss of heterozygosity of HLA from conventional TMB. We carried out external validation of our findings utilizing 89 NSCLC samples and 110 melanoma samples from two independent cohorts of immunotherapy-treated patients. RESULTS: Homology-dependent recombination deficiency was identified in 37 patients (18.7%) and was associated with longer progression-free survival (PFS; P = 0.049). Using the HLA-corrected TMB, non-responders to ICIs were identified, despite having a high TMB (top 25%). Ten patients (21.3% of the high TMB group) were reclassified from the high TMB group into the low TMB group. The objective response rate (ORR), PFS, and overall survival (OS) were all lower in these patients compared with those of the high TMB group (ORR: 20% versus 59%, P = 0.0363; PFS: hazard ratio = 2.91, P = 0.007; OS: hazard ratio = 3.43, P = 0.004). Multivariate analyses showed that high HLA-corrected TMB was associated with a significant survival advantage (hazard ratio = 0.44, P = 0.015), whereas high conventional TMB was not associated with a survival advantage (hazard ratio = 0.63, P = 0.118). Applying this approach to the independent cohorts of 89 NSCLC patients and 110 melanoma patients, TMB-based survival prediction was significantly improved. CONCLUSION: HLA-corrected TMB can reconcile the observed disparity in relationships between TMB and ICI responses, and is of predictive and prognostic value for ICI therapies.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , B7-H1 Antigen/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , HLA Antigens , Homologous Recombination , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Programmed Cell Death 1 Receptor/geneticsABSTRACT
OBJECTIVE: Epidemiological studies on inflammatory myopathies (IMs) show widely variable results, and studies on Asians are lacking. Despite emerging interest in the cardiovascular disease (CVD) risk associated with IMs, the prevalence of CVD in IM patients and its impact on mortality remain unclear. We conducted a nationwide, population-based study on the incidence, mortality, and associated major CVD events of IMs in the Republic of Korea over 11 years. METHOD: Using the nationwide, population-based National Health Insurance claims database and the Rare Intractable Disease registration programme, we estimated incidence, mortality, and CVD occurrence. Survival was examined using the Kaplan-Meier method. Mortality rate in IMs with CVD was analysed by Cox proportional hazards regression. RESULTS: There were 3014 incident cases, 640 of whom died during the study period. The mean annual incidence was 7.16/106. Dermatomyositis (DM) and polymyositis (PM) had 5 year survival rates of 76.8% and 79.3%, respectively. Cardiovascular events occurred in 155 patients and 40.6% of IM patients with CVD died. Acute myocardial infarction in men had the highest risk of any CVD event in both DM [standardized incidence ratio (SIR) 4.2, 95% confidence interval (95% CI) 2.4-7.2] and PM (SIR 3.5, 95% CI 1.8-7.0). Haemorrhagic stroke had the highest hazard ratio (HR) in both DM (HR 2.31, 95% CI 1.13-4.70) and PM patients (HR 2.10, 95% CI 1.03-4.27) compared with the general population with CVD. CONCLUSION: We found persistently low incidence, poor survival, and high major CVD incidence in IMs, and increased mortality in IMs with CVD.
Subject(s)
Cardiovascular Diseases/mortality , Myositis/complications , Registries , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/etiology , Female , Humans , Incidence , Male , Middle Aged , Republic of Korea/epidemiology , Young AdultABSTRACT
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
ABSTRACT
Ethiopia is an ecologically diverse country; the low altitude regions are hot and humid whereas the high altitude regions are cooler. In this study we analyzed the transcriptome response of high altitude (Addis Ababa) and low altitude (Awash) chickens to heat stress conditions that are prevalent in the low altitude regions. The chickens were free ranged for 20 h in an enclosure in Awash, and then the heart, breast muscle and spleen tissues were collected at 6:00 am, 12:00 noon and 6:00 pm to follow a daily circadian cycle. Through RNA-sequencing analysis, we identified differentially expressed genes (DEGs) that were significant (q < 0.05). These DEGs were subjected to protein-protein interaction (PPI) network and gene co-expression network (GCN) analyses to understand their role. KEGG pathway analysis and Gene Ontology analysis of all the identified DEGs and the genes identified from the PPI network and GCN analyses revealed that several immune-related pathways, such as proteasome, focal adhesion, influenza A, the ErbB signaling pathway and glycerophospholipid metabolism, were enriched in response to heat stress. These results suggest that the high altitude chickens were under heat stress and might be immunologically susceptible. Our findings will help in developing a genetic approach to mitigate production loss due to heat stress.
Subject(s)
Altitude , Chickens/immunology , Heat-Shock Response/immunology , Transcriptome , Animals , Chickens/genetics , Cluster Analysis , Ethiopia , Gene Expression Profiling , MaleABSTRACT
BACKGROUND: Although the hospitalization rate at early period of kidney transplantation (KT) is still high, the association between the hospitalization within 1 year after KT and graft survival is unclear. We investigated the incidence and causes of hospitalization and clinical outcome of the patients hospitalized within 1 year after KT. METHODS: We retrospectively analyzed 174 KT recipients (KTRs) hospitalized within 1 year after KT between 2013 and 2015. RESULTS: Among them, 84 (48%) KTRs were admitted within 1 year after KT, and the number of hospitalizations was 116. The mean time from KT to first hospitalization was 4.2 months. Seventy-eight percent of the patients were hospitalized for medical causes and 22% for surgical causes. The most common cause was cytomegalovirus infection (CMV) (23.3%), followed by acute rejection (11.2%) and urinary tract infection (10.3%). Recipients and donors in the hospitalized group were significantly older than the nonhospitalized group. The proportions of deceased donor KT, acute rejection, more than 50% panel-reactive antibody, and positive donor-specific antibody were significantly higher in the hospitalized group than in the nonhospitalized group. Graft and patient survivals were lower in the hospitalized group than in the nonhospitalized group. Deceased donor KT and acute rejection were independent risk factors for hospitalization. CONCLUSION: The incidence of KTRs hospitalized within 1 year after KT was high. Most causes of hospitalization were CMV infection, acute rejection, and urinary tract infection. Therefore, the immunosuppression status of these patients should be closely monitored to reduce the hospitalization rate.