Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer were updated and published online in 2023, and adapted, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with early breast cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with breast cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and KSMO. The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with early breast cancer across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling, as well as the age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Principles for management of hip fracture for older adults taking direct oral anticoagulants: an international consensus statement.

Hip fracture is a common serious injury among older adults, yet the management of hip fractures for patients taking direct oral anticoagulants remains inconsistent worldwide. Drawing from a synthesis of available evidence and expert opinion, best practice approaches for managing patients with a hip fracture and who are taking direct oral anticoagulants pre-operatively were considered by a working group of the Fragility Fracture Network Hip Fracture Audit Special Interest Group. The literature and related clinical guidelines were reviewed and a two-round modified Delphi study was conducted with a panel of experts from 16 countries and involved seven clinical specialities. Four consensus statements were achieved: peripheral nerve blocks can reasonably be performed on presentation for patients with hip fracture who are receiving direct oral anticoagulants; hip fracture surgery can reasonably be performed for patients taking direct oral anticoagulants < 36 h from last dose; general anaesthesia could reasonably be administered for patients with hip fracture and who are taking direct oral anticoagulants < 36 h from last dose (assuming eGFR > 60 ml.min-1.1.73 m-2); and it is generally reasonable to consider recommencing direct oral anticoagulants (considering blood loss and haemoglobin) < 48 h after hip fracture surgery. No consensus was achieved regarding timing of spinal anaesthesia. The consensus statements were developed to aid clinicians in their decision-making and to reduce practice variations in the management of patients with hip fracture and who are taking direct oral anticoagulants. Each statement will need to be considered specific to each individual patient's treatment.

Disease burden of bacteraemia with extended-spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales in Korea.

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.

Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study.

INTRODUCTION: Dacomitinib showed superior progression-free survival (PFS) and overall survival compared to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations in the ARCHER1050 study. However, because that study did not include patients with brain metastases, the efficacy of dacomitinib in patients with brain metastases has not been clarified. PATIENTS AND METHODS: This single-arm phase II study enrolled 30 patients with treatment-naïve advanced NSCLC harboring activating EGFR mutations from January 2021 to June 2021 and started them on dacomitinib (45 mg/day). All patients had non-irradiated brain metastases with a diameter of ≥5 mm. The primary endpoint was confirmed intracranial objective response rate (iORR). RESULTS: Patients had exon 19 deletions (46.7%) and L858R mutations in exon 21 (55.3%). The confirmed iORR was 96.7% (29/30), with an intracranial complete response of 63.3%. Median intracranial PFS (iPFS) was not reached, with 12- and 18-month iPFS rates of 78.6% [95% confidence interval (CI) 64.8% to 95.4%] and 70.4% (95% CI 54.9% to 90.1%), respectively. In the competing risk analysis, the 12-month cumulative incidence of intracranial progression was 16.7%. Regarding the overall efficacy for intracranial and extracranial lesions, the overall ORR was 96.7%, and the median PFS was 17.5 months (95% CI 15.2 months-not reached). Grade 3 or higher treatment-related adverse events were reported in 16.7% of patients, and 83.3% required a reduced dacomitinib dose to manage adverse events. However, none permanently discontinued dacomitinib treatment due to treatment-related adverse events. CONCLUSIONS: Dacomitinib has outstanding intracranial efficacy in patients with EGFR-mutant NSCLC with brain metastases.

Association of body mass index and bloodstream infections in patients on extracorporeal membrane oxygenation: a single-centre, retrospective, cohort study.

BACKGROUND: Obesity is associated with poor clinical outcomes in critically ill patients. However, under some clinical conditions, obesity has protective effects. Bloodstream infections (BSI) are among the most common nosocomial infections associated with extracorporeal membrane oxygenation (ECMO). BSI during ECMO is associated with higher mortality rates and poorer clinical outcomes. AIM: To analyse whether body mass index (BMI) is associated with BSI during ECMO or with in-hospital mortality. METHODS: All adult patients who had received ECMO support for >48 h were included in the analysis. The analysis of total duration of ECMO support, in-hospital mortality and BSI was stratified by BMI category. The Cox proportional hazards model was used to compare the risk of BSI among BMI categories. FINDINGS: In total, 473 patients were enrolled in the study. The average age was 56.5 years and 65.3% were men. The total duration of ECMO was approximately 11.8 days, with a mortality rate of 47.1%. The incidence rates of BSI and candidaemia were 20.5% and 5.5%, respectively. The underweight group required ECMO for respiratory support, whereas the overweight and obese groups required ECMO for cardiogenic support (P<0.0001). No significant difference in BSI rate was found (P=0.784). However, after adjusting for clinical factors, patients in Group 4 (BMI 25.0-<30.0 kg/m2) exhibited lower mortality compared with patients in Group 2 (normal BMI) (P=0.004). CONCLUSION: BMI was not associated with risk of BSI, but patients with higher BMI showed lower in-hospital mortality associated with ECMO support.

Association between Hashimoto's thyroiditis and melanoma: a retrospective matched cohort study.

An inflammatory microenvironment has been shown to increase risk for malignant melanoma, suggesting that melanoma may be related to a pro-inflammatory state. Though Hashimoto's thyroiditis is one of the most common autoimmune diseases, there are no investigations of its relationship with melanoma. We aim to determine if Hashimoto's increases risk of developing melanoma. A retrospective, validated cohort of patients with a diagnosis of Hashimoto's between 2005 and 2020 were identified using the Olmsted County database. Patients were age and sex matched to controls without a Hashimoto's diagnosis. The primary outcomes were development of melanoma and time to first melanoma diagnosis. 4805 patients were included in the study, with 1726 (36%) having a diagnosis of Hashimoto's. Hashimoto's patients had no significant difference in risk of melanoma (relative risk 0.96, 95% CI 0.78-1.17) or nonmelanoma skin cancer (relative risk 0.95, 95% CI 0.86-1.06) compared with matched controls. This suggests that the local proinflammatory environment present in Hashimoto's does not contribute significantly to melanoma risk. Larger studies may be needed to further characterize the relationship between these diseases.

Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ.

Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.

Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. METHODS: Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. RESULTS: Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. CONCLUSIONS: Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.

First Observation of Λπ

Using the data sample of 980 fb^{-1} collected with the Belle detector operating at the KEKB asymmetric-energy e^{+}e^{-} collider, we present the results of an investigation of the Λπ^{+} and Λπ^{-} invariant mass distributions looking for substructure in the decay Λ_{c}^{+}→Λπ^{+}π^{+}π^{-}. We find a significant signal in each mass distribution. When interpreted as resonances, we find for the Λπ^{+} (Λπ^{-}) combination a mass of 1434.3±0.6(stat)±0.9(syst) MeV/c^{2} [1438.5±0.9(stat)±2.5(syst) MeV/c^{2}], an intrinsic width of 11.5±2.8(stat)±5.3(syst) MeV/c^{2} [33.0±7.5(stat)±23.6(syst) MeV/c^{2}] with a significance of 7.5σ (6.2σ). As these two signals are very close to the K[over ¯]N threshold, we also investigate the possibility of a K[over ¯]N cusp, and find that we cannot discriminate between these two interpretations due to the limited size of the data sample.

Measurement of the Λ_{c}

An absolute measurement of the Λ_{c}^{+} lifetime is reported using Λ_{c}^{+}→pK^{-}π^{+} decays in events reconstructed from data collected by the Belle II experiment at the SuperKEKB asymmetric-energy electron-positron collider. The total integrated luminosity of the data sample, which was collected at center-of-mass energies at or near the ϒ(4S) resonance, is 207.2 fb^{-1}. The result, τ(Λ_{c}^{+})=203.20±0.89±0.77 fs, where the first uncertainty is statistical and the second systematic, is the most precise measurement to date and is consistent with previous determinations.

Search for the Pair Production of Dark Particles X with K_{L}

We present the first search for the pair production of dark particles X via K_{L}^{0}→XX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}→XX)<(1-4)×10^{-7} and B(K_{L}^{0}→XX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.

Impact of tuberculosis on the incidence of osteoporosis and osteoporotic fractures: a nationwide population-based cohort study.

OBJECTIVES: Despite the high prevalence of tuberculosis (TB) and the disease burden of osteoporosis and osteoporotic fractures, there is still a lack of well-designed, large-scale studies demonstrating associations among them. We aimed to investigate the effect of TB on the incidence of osteoporosis and osteoporotic fractures. STUDY DESIGN: This was a nationwide population-based cohort study. METHODS: This study was conducted using the National Health Insurance Service Database of South Korea. We included patients with newly diagnosed TB aged >40 years from January 2006 to December 2017. An uninfected control for each TB patient was randomly extracted by frequency matching for sex, age, income level, residence, and registration date at a 2:1 ratio. The primary outcome was the incidence of osteoporosis and osteoporotic fractures between the two groups, adjusted for sex, age, income level, residence, comorbidities, body mass index, blood pressure, laboratory tests, alcohol drinking, and smoking. The risk factors associated with osteoporosis or osteoporotic fractures were also investigated. RESULTS: A total of 164,389 patients with TB and 328,778 matched controls were included (71.9% males). The mean duration of follow-up was 7.00 ± 3.49 years. The incidence of osteoporosis in patients with TB was 6.1 cases per 1000 person-years, which was significantly higher than that in matched controls (adjusted hazard ratio [aHR] 1.349, 95% confidence interval [CI] 1.302-1.398, P < 0.001). The incidence of osteoporotic fractures was also higher in patients with TB than in controls (aHR 1.392, 95% CI 1.357-1.428, P < 0.001). Among fractures, the risk of hip fracture was the highest (aHR 1.703, 95% CI 1.612-1.798, P < 0.001). CONCLUSIONS: TB independently contributes to the incidence of osteoporosis and osteoporotic fractures, particularly hip fractures.

Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube.

BACKGROUND: The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonizing MDRO. AIM: To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage. METHODS: This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube. FINDINGS: A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT. CONCLUSION: Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.

Validation study of machine-learning chest radiograph software in primary and emergency medicine.

AIM: To evaluate the performance of a machine learning based algorithm tool for chest radiographs (CXRs), applied to a consecutive cohort of historical clinical cases, in comparison to expert chest radiologists. MATERIALS AND METHODS: The study comprised 1,960 consecutive CXR from primary care referrals and the emergency department (992 and 968 cases respectively), obtained in 2015 at a UK hospital. Two chest radiologists, each with >20 years of experience independently read all studies in consensus to serve as a reference standard. A chest artificial intelligence (AI) algorithm, Lunit INSIGHT CXR, was run on the CXRs, and results were correlated with those by the expert readers. The area under the receiver operating characteristic curve (AUROC) was calculated for the normal and 10 common findings: atelectasis, fibrosis, calcification, consolidation, lung nodules, cardiomegaly, mediastinal widening, pleural effusion, pneumothorax, and pneumoperitoneum. RESULTS: The ground truth annotation identified 398 primary care and 578 emergency department datasets containing pathologies. The AI algorithm showed AUROC of 0.881-0.999 in the emergency department dataset and 0.881-0.998 in the primary care dataset. The AUROC for each of the findings between the primary care and emergency department datasets did not differ, except for pleural effusion (0.954 versus 0.988, p<0.001). CONCLUSIONS: The AI algorithm can accurately and consistently differentiate normal from major thoracic abnormalities in both acute and non-acute settings, and can serve as a triage tool.

Is there a clinical difference in paediatric congenital cholesteatoma according to age?

OBJECTIVE: This study aimed to analyse surgical outcomes of paediatric patients with congenital cholesteatoma according to age. METHOD: This was a retrospective study reviewing the records of 186 children (136 boys and 50 girls) from August 1993 to January 2016. Patients were divided into three age groups (equal to or less than 3 years, over 3 and less than 7 years, and 7 to 15 years). RESULTS: There were significant differences in chief complaints, location of cholesteatoma in the middle ear, computed tomography findings, operation methods, ossicular erosion and type of cholesteatoma sac among the three groups. In addition, older age, open type cholesteatoma, ossicular erosion and mastoid invasion of cholesteatoma increased the recurrence rate after surgery. However, despite higher pre-operative air-bone gap in older children, hearing can be improved enough after proper surgery with ossicular reconstruction. CONCLUSION: Delayed detection of paediatric cholesteatoma can lead to extensive disease and the need for an aggressive operation, which can result in worse hearing outcomes and an increased recurrence risk.

Acute Lower Extremity Fracture Management in Chronic Spinal Cord Injury: 2022 Delphi Consensus Recommendations.

Our objective was to develop a clinical practice guideline (CPG) for the treatment of acute lower extremity fractures in persons with a chronic spinal cord injury (SCI). Methods: Information from a previous systematic review that addressed lower extremity fracture care in persons with an SCI as well as information from interviews of physical and occupational therapists, searches of the literature, and expert opinion were used to develop this CPG. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to determine the quality of evidence and the strength of the recommendations. An overall GRADE quality rating was applied to the evidence. Conclusions: Individuals with a chronic SCI who sustain an acute lower extremity fracture should be provided with education regarding the risks and benefits of operative and nonoperative management, and shared decision-making for acute fracture management should be used. Nonoperative management historically has been the default preference; however, with the advent of greater patient independence, improved surgical techniques, and advanced therapeutics and rehabilitation, increased use of surgical management should be considered. Physical therapists, kinesiotherapists, and/or occupational therapists should assess equipment needs, skills training, and caregiver assistance due to changes in mobility resulting from a lower extremity fracture. Therapists should be involved in fracture management as soon as possible following fracture identification. Pressure injuries, compartment syndrome, heterotopic ossification, nonunion, malunion, thromboembolism, pain, and autonomic dysreflexia are fracture-related complications that clinicians caring for patients who have an SCI and a lower extremity fracture may encounter. Strategies for their treatment are discussed. The underlying goal is to return the patient as closely as possible to their pre-fracture functional level with operative or nonoperative management.

Clinical and radiological outcome of the locked plate osteosynthesis in distal metadiaphyseal tibial fracture according to the severity of comminution: Varus reduction would not be preferable with lower clinical outcomes.

Background: The optimal treatment for distal tibial fractures remains a matter of debate. Nonetheless, plate osteosynthesis produces favorable results to intramedullary stabilization in aspects of alignment restoration. Aim: The aim of the study was to compare the radiologic and clinical outcomes of distal metadiaphyseal tibial fracture between a simple/wedge fracture (SWF) and a comminuted fracture (CF) using minimally invasive plate osteosynthesis (MIPO). Patients and Methods: This retrospective study analyzed patients with SWF or CF of the distal tibial metadiaphysis that was surgically treated with a locking compression plate. Postoperative radiographic assessments and the time to radiologic union were noted. Clinical assessments were evaluated using both the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the foot function index (FFI). Postoperative complications were documented. Results: Seventy-one cases were analyzed over a mean follow-up period of 20.9 months. Thirty-six patients had SWF and 35 patients presented with CF. The mean time to radiologic union, amounts of postoperative coronal angulation, and incidence of malunion showed no statistical differences. Fibular fixation was more applied in the CF group (P < 0.001). Moreover, the clinical scores revealed no differences. Nonetheless, in the valgus union group, the AOFAS ankle-hindfoot score was 90.9 compared to 84.1 in the varus union group (P = 0.042) and the FFI was 9.2% compared to 20.2% in the varus union group (P = 0.017). Conclusion: Plate osteosynthesis for SWF or CF of the distal tibial metadiaphysis led to high union rates and good clinical outcomes. There was no significant difference in the radiologic and clinical results according to the presence of fracture comminution. Nonetheless, the valgus union group showed better clinical outcomes than the varus union group. Clinically, it would be preferred to avoid intraoperative varus reduction.

The efficacy of immune checkpoint inhibitors in elderly patients: a meta-analysis and meta-regression.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy has improved patient survival in advanced cancers; however, the efficacy of ICIs in elderly patients is still elusive. This study assessed the efficacy of ICIs in elderly patients with advanced cancer in terms of overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: We carried out a systematic review and identified 30 head-to-head phase II/III randomized controlled trials that compared immunotherapy with the standard of care in advanced solid tumor patients. The data on patients younger or over 65 years of age were indexed from PubMed-Medline, Embase, and Scopus and obtained for meta-analysis. The subgroup analyses were stratified by primary tumor type, line of treatment, or type of immunotherapy, and a meta-regression analysis was carried out after adjusting for all other variables. RESULTS: The study included 17 476 patients, comprising 58% (10 119) younger (<65 years old) and 42% (7357) elderly (≥65 years old) patients. The hazard ratio (HR) for OS was 0.77 [95% confidence interval (CI) 0.70-0.85] and 0.77 (95% CI 0.70-0.85) in the younger and elderly groups, respectively, suggesting similar efficacies of ICIs in these two age groups. The subgroup analyses revealed no significant relationship between age and treatment outcomes, except for the PFS benefit in younger patients with melanoma than in elderly patients (HR 0.44 in younger patients versus 0.65 in elderly patients, P = 0.04). These results were further supported by meta-regression analysis, which showed no statistically significant difference in OS (P = 0.954) and PFS (P = 0.555) between the two age groups. CONCLUSIONS: The findings suggest that age-associated impairments of the immune system did not affect the efficacy of ICIs in elderly patients compared to younger patients. Therefore, the choice of ICIs for elderly patients can be considered, regardless of chronological age.

Postoperative Pneumonia and Aspiration Pneumonia Following Elderly Hip Fractures.

OBJECTIVES: The present study aimed to investigate the incidence of and risk factors for postoperative pneumonia and aspiration pneumonia after hip fracture surgery. DESIGN: Retrospective cohort study from 2005 to 2021. SETTING: Asan Medical Center in Seoul, Republic of Korea. PARTICIPANTS: A total 1,208 patients aged ≥ 65 years who underwent hip fracture surgery. MEASUREMENTS: Postoperative pneumonia was defined as cases with new infiltration on chest x-ray or chest computed tomography (CT) after surgery or confirmed by a pulmonologist's consultation and diagnosis. Aspiration pneumonia was defined as: 1) radiologic findings of hospital-acquired pneumonia on chest radiographs or CT, medical record of aspiration pneumonia confirmed by a pulmonologist's consultation, and history of vomiting or aspiration, or 2) gravity-dependent opacity on chest CT when the history of vomiting or aspiration is ambiguous. Patient demographics, past medical history, pre-injury Koval score, Charlson Comorbidity Index (CCI), blood test results, length of hospital stay, and in-hospital mortality were evaluated. A comparison analysis and binary logistic regression were performed to identify the incidence and risk factors for postoperative pneumonia and aspiration pneumonia. RESULTS: Postoperative pneumonia was diagnosed in 47 patients (3.9%), including 20 with aspiration pneumonia (1.7%). In the multivariate analysis, postoperative delirium (odds ratio [OR], 3.42; P < 0.001), American Society of Anesthesiologists (ASA) scores ≥ 3 (OR, 2.11; P = 0.021), and CCI (OR, 1.21; P = 0.013) were significant risk factors for postoperative pneumonia. Male sex (OR, 3.01; P = 0.017), postoperative delirium (OR, 3.16; P = 0.014), and preoperative serum albumin levels < 3.5 g/dL (OR, 7.00; P = 0.010) were significant risk factors for aspiration pneumonia. CONCLUSION: ASA classification ≥ 3, higher CCI, and postoperative delirium were the risk factors for postoperative pneumonia. Male sex, postoperative delirium, and lower preoperative serum albumin level were the risk factors for aspiration pneumonia. Thus, physicians should pay attention to patients with the risk factors.

Facial erythema in patients with atopic dermatitis treated with Dupilumab - a descriptive study of morphology and Aetiology.

BACKGROUND: The development of dermatitis on face and neck, which was not described in phase 3 clinical trials, has been reported in the literature in patients treated with dupilumab. Little is known regarding the causes or defining features of the facial dermatitis. OBJECTIVES: We conducted surveys of consecutive patients with AD on dupilumab to describe its clinical features, morphology and aetiology. METHODS: A multi-centre prospective cohort study was conducted from 1 January 2020, to 31 December 31 2020. A total of 162 patients under dupilumab treatment were asked to complete a questionnaire and patients were evaluated by dermatologists. RESULTS: Of all 162 patients, 137 (84.6%) patients reported pre-existing facial dermatitis prior to dupilumab therapy. One hundred and twenty-one (88.3%) patients with pre-existing facial dermatitis reported improvement of their facial dermatitis with dupilumab therapy, nine (6.6%) patients reported no change after the treatment and seven (4.3%) patients of them got worse after the treatment (exacerbation group). Of 25 patients who reported no pre-existing active facial dermatitis, six (24%) patients reported new-onset facial erythema after the starting dupilumab therapy (new-onset group). A large proportion of the patients in both the exacerbation (86%) and new-onset groups (67%) had a history of facial TCS use. Both groups showed similar clinical manifestations and distribution with few differences. CONCLUSIONS: The vast majority of patients treated with dupilumab in academic institutions from Korea and the United States experienced improvement in their facial dermatitis with dupilumab therapy. A small proportion of patients had new onset and exacerbation. Although the mechanisms of this adverse event remain unclear, steroid withdrawal should be considered as a diagnosis of the erythema in some patients.