Effect of Hearing Intervention versus Health Education Control on Fatigue: A Secondary Analysis of the ACHIEVE study.

BACKGROUND: Fatigue is a common complaint among older adults with hearing loss. The impact of addressing hearing loss on fatigue symptoms has not been studied in a randomized controlled trial. In a secondary analysis of the ACHIEVE study, we investigated the effect of hearing intervention versus health education control on 3-year change in fatigue in community-dwelling older adults with hearing loss. METHODS: Participants aged 70-84 years old with untreated hearing loss recruited across 4 study sites in the United States (Forsyth County, NC; Jackson, MS; Minneapolis, MN; Washington County, MD) were randomized (1:1) to hearing intervention or health education control and followed for 3 years. Three-year change in fatigue symptoms was measured by 2 instruments (RAND-36 and PROMIS). We estimated the intervention effect as the difference in the 3-year change in fatigue between intervention and control groups using a linear mixed-effects model under the intention-to-treat principle. RESULTS: Participants (n=977) had a mean age (SD) of 76.8 (4.0) years, were 53.5% female and 87.8% White. Over 3 years, a beneficial effect of the hearing intervention versus health education control on fatigue was observed using the RAND-fatigue score (ß= -0.12 [95% CI -0.22, -0.02]). Estimates also suggested beneficial effect of hearing intervention on fatigue when measured by the PROMIS fatigue score (ß= -0.32 [95% CI -1.15, 0.51]). CONCLUSIONS: Our findings suggest that hearing intervention may reduce fatigue over 3 years among older adults with hearing loss.

Effect of nocturia in patients with different severity of obstructive sleep apnea on polysomnography: A retrospective observational study.

Objective: Obstructive sleep apnea (OSA) is one of the etiologies of nocturia. We analyzed polysomnography (PSG) results to determine correlated factors related to nocturia in OSA patients with different severity. Methods: Patients with suspected OSA were examined using PSG. They were divided into two groups based on the presence of nocturia. Nocturia was defined as a patient who needed to void at least once. Apnea-hypopnea index (AHI) was employed to classify patients according to degrees of severity: AHI<5 events/h, 5 events/h≤AHI<15 events/h, 15 events/h≤AHI<30 events/h, and AHI≥30 events/h, defined as normal, mild OSA, moderate OSA, and severe OSA, respectively. Demographic variables, PSG parameters, International Prostate Symptom Scores (IPSSs), and quality of life scores due to urinary symptoms were analyzed. Results: In total 140 patients, 114 patients had OSA (48 had mild OSA; 34 had moderate OSA; and 32 had severe OSA) and 107 patients had nocturia. The total IPSS was significantly higher in nocturia patients in all groups except the group of severe OSA patients. With the increasing severity of OSA, more correlated factors related to nocturia were determined. In mild OSA patients, nocturia related to increased age (p=0.025), minimum arterial blood oxygenation saturation (p=0.046), and decreased AHI of non-rapid eye movement (p=0.047), AHI of total sleep time (p=0.010), and desaturation index (p=0.012). In moderate OSA patients, nocturia related to increased age (p<0.001), awake time (p=0.025), stage 1 sleep (p=0.033), and sleep latency (p=0.033), and decreased height (p=0.044), weight (p=0.025), and sleep efficiency (p=0.003). In severe OSA patients, nocturia related to increased weight (p=0.011), body mass index (p=0.009), awake time (p=0.008), stage 1 sleep (p=0.040), arousal number (p=0.030), arousal index (p=0.013), periodic limb movement number (p=0.013), and periodic limb movement index (p=0.004), and decreased baseline arterial blood oxygenation saturation (p=0.046). Conclusion: Our study revealed that there were more correlated factors related to nocturia with increasing severity of OSA. This study helps in clinical education and treatment for OSA patients with different severity.

Endometriosis of the Colon and Pericolic Lymph Nodes Presenting as Cecal Volvulus.

Endometriosis, characterized by the ectopic implantation of endometrial tissue, typically involves pelvic structures but infrequently extends to extrapelvic sites such as the gastrointestinal tract. In this report, we present a case of a 44-year-old woman with diffuse abdominal discomfort and constipation. Computed tomography imaging revealed a mass in the cecum, leading to diagnostic colonoscopy and subsequent magnetic resonance imaging. Ultimately, laparoscopy revealed a puckered cecal mass suspected to be invasive malignancy but pathologically confirmed as extensive endometriosis involving the colonic wall and pericolic lymph nodes. Cecal volvulus secondary to endometriosis is exceedingly rare, with surgical intervention being the primary treatment modality. Endometriosis-associated gastrointestinal involvement often masquerades as irritable bowel syndrome, highlighting the importance of considering atypical presentations in young women. This case underscores the need to maintain a high index of suspicion for unusual etiologies in patients with gastrointestinal symptoms and atypical imaging findings to facilitate timely diagnosis and management.

Developing an explainable diagnosis system utilizing deep learning model: a case study of spontaneous pneumothorax.

Objective.The trend in the medical field is towards intelligent detection-based medical diagnostic systems. However, these methods are often seen as 'black boxes' due to their lack of interpretability. This situation presents challenges in identifying reasons for misdiagnoses and improving accuracy, which leads to potential risks of misdiagnosis and delayed treatment. Therefore, how to enhance the interpretability of diagnostic models is crucial for improving patient outcomes and reducing treatment delays. So far, only limited researches exist on deep learning-based prediction of spontaneous pneumothorax, a pulmonary disease that affects lung ventilation and venous return.Approach.This study develops an integrated medical image analysis system using explainable deep learning model for image recognition and visualization to achieve an interpretable automatic diagnosis process.Main results.The system achieves an impressive 95.56% accuracy in pneumothorax classification, which emphasizes the significance of the blood vessel penetration defect in clinical judgment.Significance.This would lead to improve model trustworthiness, reduce uncertainty, and accurate diagnosis of various lung diseases, which results in better medical outcomes for patients and better utilization of medical resources. Future research can focus on implementing new deep learning models to detect and diagnose other lung diseases that can enhance the generalizability of this system.

Primary cilia formation requires the Leigh syndrome-associated mitochondrial protein NDUFAF2.

Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD+ supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.

A Fork in the Road: An Unusual Case of Duodenal-Cecal Fistula Due to a Chronic Foreign Body.

A duodenal-cecal fistula is characterized as an unnatural connection between the duodenum and cecum. Here, we present the case of a 40-year-old male with unintentional weight loss and a history of foreign body ingestion a few years prior. Computerized tomography (CT) small bowel enterography showed a linear soft tissue tract extending from the inferior aspect of the distal duodenum to the cecum. Ultimately, a diagnosis of duodenal-cecal fistula was made following esophagogastroduodenoscopy (EGD) revealing a fistula in the third part of the duodenum. A duodenal-cecal fistula secondary to foreign body ingestion is rare, with surgical intervention or endoscopic fibrin glue closure being potential treatment modalities if the fistula fails to close spontaneously. Duodenal-cecal fistulas are generally seen secondary to malignancies of the duodenum or colon, peptic ulcers, or inflammatory bowel disease. However, a duodenal-cecal fistula due to a foreign body is rare, thus highlighting the importance of keeping a broad differential, as appropriate in the clinical context.

Tacrolimus-Induced Recurrent Acute Coronary Syndrome Due to an Unknown Mechanism.

Tacrolimus, a potent immunosuppressive agent widely used in solid organ transplantation, has been associated with numerous harmful side effects. We report an interesting case of a patient who is status post liver transplantation and who has been maintained on tacrolimus for the past 10 years. She presented in the hospital with a ST-segment elevation myocardial infarction (STEMI), with normal coronary angiography. The patient was found to have a markedly elevated tacrolimus level. After decreasing the dose of tacrolimus and starting isosorbide mononitrate, the patient's symptoms resolved, and the patient had no recurrence of symptoms.

Bronchoscopic management of bronchopleural fistula using free fat pad transplant with platelet-rich plasma: a case study.

BACKGROUND: A bronchopleural fistula (BPF) occurs when an abnormal connection forms between the bronchial tubes and pleural cavity, often due to surgery, infection, trauma, radiation, or chemotherapy. The outcomes of both surgical and bronchoscopic treatments frequently prove to be unsatisfactory. CASE PRESENTATION: Here, we report a case of successful bronchoscopic free fat pad transplantation combined with platelet-rich plasma, effectively addressing a post-lobectomy BPF. Contrast-enhanced chest tomography revealed pleural thickening with heterogeneous consolidations over the right upper and middle lobes, indicative of destructive lung damage and bronchiectasis. The patient underwent thoracoscopic bilobectomy of the lungs. During surgery, severe adhesions and calcification of the chest wall and lung parenchyma were observed. The entire hilar structure was calcified, presenting challenges for dissection, despite the assistance of energy devices. Bronchoscopic intervention was required, during which two abdominal subcutaneous fat pads were retrieved. CONCLUSION: This innovative approach offers promise in the management of BPF and signals potential advancements in enhancing treatment efficacy and patient recovery.

Synergistic Effect of Human Papillomavirus and Environmental Factors on Skin Squamous Cell Carcinoma, Basal Cell Carcinoma, and Melanoma: Insights from a Taiwanese Cohort.

Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96-7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70-5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14-5.74), and melanoma (aHR = 4.36, 95% CI: 2.76-6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health.

2024 multidisciplinary consensus on image-guided lung tumor ablation from the Taiwan Academy of Tumor Ablation.

In this article, the multidisciplinary team of the Taiwan Academy of Tumor Ablation, who have expertise in treating lung cancer, present their perspectives on percutaneous image-guided thermal ablation (IGTA) of lung tumors. The modified Delphi technique was applied to reach a consensus on clinical practice guidelines concerning ablation procedures, including a comprehensive literature review, selection of panelists, creation of a rating form and survey, and arrangement of an in-person meeting where panelists agreed or disagreed on various points. The conclusion was a final rating and written summary of the agreement. The multidisciplinary expert team agreed on 10 recommendations for the use of IGTA in the lungs. These recommendations include terms and definitions, line of treatment planning, modality, facility rooms, patient anesthesia settings, indications, margin determination, post-ablation image surveillance, qualified centers, and complication ranges. In summary, IGTA is a safe and feasible approach for treating primary and metastatic lung tumors, with a relatively low complication rate. However, decisions regarding the ablation technique should consider each patient's specific tumor characteristics.

Recent Advancements and Innovations in Pediatric Precision Oncology.

Precision oncology incorporates comprehensive genomic profiling into the individualized clinical care of pediatric cancer patients. In recent years, comprehensive pan-cancer analyses have led to the successful implementation of genomics-based pediatric trials and accelerated approval of novel targeted agents. In addition, disease-specific studies have resulted in molecular subclassification of myriad cancer types with subsequent tailoring of treatment intensity based on the patient's prognostic factors. This review discusses the progress of the field and highlights developments that are leading to more personalized cancer care and improved patient outcomes. Increased understanding of the evolution of precision oncology over recent decades emphasizes the tremendous impact of improved genomic applications. New technologies and improved diagnostic modalities offer further promise for future advancements within the field.

Precision and Robust Models on Healthcare Institution Federated Learning for Predicting HCC on Portal Venous CT Images.

Hepatocellular carcinoma (HCC), the most common type of liver cancer, poses significant challenges in detection and diagnosis. Medical imaging, especially computed tomography (CT), is pivotal in non-invasively identifying this disease, requiring substantial expertise for interpretation. This research introduces an innovative strategy that integrates two-dimensional (2D) and three-dimensional (3D) deep learning models within a federated learning (FL) framework for precise segmentation of liver and tumor regions in medical images. The study utilized 131 CT scans from the Liver Tumor Segmentation (LiTS) challenge and demonstrated the superior efficiency and accuracy of the proposed Hybrid-ResUNet model with a Dice score of 0.9433 and an AUC of 0.9965 compared to ResNet and EfficientNet models. This FL approach is beneficial for conducting large-scale clinical trials while safeguarding patient privacy across healthcare settings. It facilitates active engagement in problem-solving, data collection, model development, and refinement. The study also addresses data imbalances in the FL context, showing resilience and highlighting local models' robust performance. Future research will concentrate on refining federated learning algorithms and their incorporation into the continuous implementation and deployment (CI/CD) processes in AI system operations, emphasizing the dynamic involvement of clients. We recommend a collaborative human-AI endeavor to enhance feature extraction and knowledge transfer. These improvements are intended to boost equitable and efficient data collaboration across various sectors in practical scenarios, offering a crucial guide for forthcoming research in medical AI.

Radiographic chest wall abnormalities in primary spontaneous pneumothorax identified by artificial intelligence.

Primary spontaneous pneumothorax (PSP) primarily affects slim and tall young males. Exploring the etiological link between chest wall structural characteristics and PSP is crucial for advancing treatment methods. In this case-control study, chest computed tomography (CT) images from patients undergoing thoracic surgery, with or without PSP, were analyzed using Artificial Intelligence. Convolutional Neural Network (CNN) model of EfficientNetB3 and InceptionV3 were used with transfer learning on the Imagenet to compare the images of both groups. A heatmap was created on the chest CT scans to enhance interoperability, and the scale-invariant feature transform (SIFT) was adopted to further compare the image level. A total of 2,312 CT images of 26 non-PSP patients and 1,122 CT images of 26 PSP patients were selected. Chest-wall apex pit (CAP) was found in 25 PSP and three non-PSP patients (p < 0.001). The CNN achieved a testing accuracy of 93.47 % in distinguishing PSP from non-PSP based on chest wall features by identifying the existence of CAP. Heatmap analysis demonstrated CNN's precision in targeting the upper chest wall, accurately identifying CAP without undue influence from similar structures, or inappropriately expanding or minimizing the test area. SIFT results indicated a 10.55 % higher mean similarity within the groups compared to between PSP and non-PSP (p < 0.001). In conclusion, distinctive radiographic chest wall configurations were observed in PSP patients, with CAP potentially serving as an etiological factor linked to PSP. This study accentuates the potential of AI-assisted analysis in refining diagnostic approaches and treatment strategies for PSP.

Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial.

OBJECTIVE: Hearing loss has been identified as a major modifiable risk factor for cognitive decline. The Early Age-Related Hearing Loss Investigation (EARHLI) study will assess the mechanisms linking early age-related hearing loss (ARHL) and cognitive impairment. STUDY DESIGN: Randomized, controlled, single-site, early phase II, superiority trial. SETTING: Tertiary academic medical center. PARTICIPANTS: One hundred fifty participants aged 55 to 75 years with early ARHL (severity defined as borderline to moderate) and amnestic mild cognitive impairment will be included. INTERVENTIONS: Participants will be randomized 1:1 to a best practice hearing intervention or a health education control. MAIN OUTCOME MEASURES: The primary study outcome is cognition measured by the Alzheimer Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite. Secondary outcomes include additional measures of cognition, social engagement, and brain organization/connectivity. RESULTS: Trial enrollment will begin in early 2024. CONCLUSIONS: After its completion in 2028, the EARHLI trial should offer evidence on the effect of hearing treatment versus a health education control on cognitive performance, social engagement, and brain organization/connectivity in 55- to 75-year-old community-dwelling adults with early ARHL and amnestic mild cognitive impairment.

Engineered CD47 protects T cells for enhanced antitumour immunity.

Adoptively transferred T cells and agents designed to block the CD47-SIRPα axis are promising cancer therapeutics that activate distinct arms of the immune system1,2. Here we administered anti-CD47 antibodies in combination with adoptively transferred T cells with the goal of enhancing antitumour efficacy but observed abrogated therapeutic benefit due to rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors. Anti-CD47-antibody-mediated CAR T cell clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered the CD47 variant CD47(Q31P) (47E), which engages SIRPα and provides a 'don't eat me' signal that is not blocked by anti-CD47 antibodies. TCR or CAR T cells expressing 47E are resistant to clearance by macrophages after treatment with anti-CD47 antibodies, and mediate substantial, sustained macrophage recruitment to the tumour microenvironment. Although many of the recruited macrophages manifested an M2-like profile3, the combined therapy synergistically enhanced antitumour efficacy. Our study identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T-cell-directed therapeutics with those designed to activate macrophages. It delivers a therapeutic approach that is capable of simultaneously harnessing the antitumour effects of T cells and macrophages, offering enhanced potency against solid tumours.

Adult-onset hearing loss and incident cognitive impairment and dementia - A systematic review and meta-analysis of cohort studies.

BACKGROUND: We comprehensively summarized the cohort evidence to date on adult-onset hearing loss as risk factor for incident cognitive impairment and dementia, and examined the evidence for dose-response, risk for various dementia subtypes, and other moderators. Previous meta-analyses were less comprehensive. METHODS: We included cohort studies with participants without dementia and with hearing assessments at baseline, minimum 2 years follow-up and incident cognitive outcomes. We used random-effect models and subgroup and meta-regression on moderator analyses. RESULTS: We identified fifty studies (N=1,548,754). Hearing loss (yes/no) was associated with incident dementia risk (HR=1.35 [95% CI = 1.26 - 1.45), mild cognitive impairment (MCI HR=1.29 [95% CI = 1.11 - 1.50]), cognitive decline not specified as MCI or dementia (HR=1.29 [95% CI = 1.17 - 1.42]), and Alzheimer's disease dementia (ADD, HR=1.56 [95% CI = 1.30 - 1.87]), but not with vascular dementia (HR, 1.30 [95% CI = 0.83 - 2.05]). Each 10-decibel worsening of hearing was associated with a 16% increase in dementia risk (95% CI = 1.07 - 1.27). The effect of hearing loss did not vary across potential moderators. CONCLUSIONS: Cohort studies consistently support that adult-onset hearing loss increases the risk of incident cognitive decline, dementia, MCI, and ADD.

Hearing Impairment and Physical Activity and Physical Functioning in Older Adults: Baseline Results From the ACHIEVE Trial.

BACKGROUND: Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood. METHODS: Analyses included 845 participants aged ≥70 years (mean = 76.6 years) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA ≥ 40 dB] vs mild [PTA < 40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day. RESULTS: Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR = 2.17, 95% CI = 1.29-3.67), versus those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00 pm -05:59 pm). CONCLUSIONS: Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control.