Abstract Background In-silico and in-vitro studies have revealed an appropriate posterior tibial slope (PTS) is critical for normal anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) tension and knee biomechanical behavior of unicompartmental knee arthroplasty (UKA). However, the effects of PTS on in-vivo elongation of ACL and PCL in UKA remains unknown. The study aimed to quantify in-vivo ACL and PCL elongations during lunge and analyze their relations with PTS. Methods Thirteen fixed-bearing (FB) and 11 mobile-bearing (MB) UKA patients were recruited. The postoperative medial PTS was defined as the angle between the tibial transverse plane (perpendicular to mechanical axis) and cut plane. Accurate knee spatial postures of UKA and contralateral native knees during single-leg lunge were measured by the dual fluoroscopic imaging system. The ACL (AM, PL bundles) and PCL (AL, PM bundles) footprints were determined based on anatomical features on femoral and tibial 3D surface model reconstructed from CT. A validated 3D wrapping method was used to measure ligament bundle length. The paired Wilcoxon signed-rank test was used to analyze the ligament elongation difference between bilateral knees. The Spearman correlation between PTS and average ligament elongation difference (ACL during 0–30° early-flexion, PCL during 60–100° deep-flexion) was calculated. Results The elongation of FB UKA PCL double-bundle was larger than contralateral sides in most flexion range of lunge (Max-Difference: AL 7.6 ± 8.7%, PM 8.2 ± 5.1%, p < 0.05). In contrast, ACL double-bundle elongations of MB UKA in mid-flexion were larger than contralateral sides (Max-Difference: AM 8.0 ± 8.1%, PL 7.6 ± 9.8%, p < 0.05). The increased PTS was significantly relevant to the increased ACL double-bundle elongation difference of bilateral knees for both FB and MB UKA patients (R > 0.6, p < 0.05). Conclusion There was abnormal in-vivo elongation of PCL in FB UKA and ACL in MB UKA during lunge and cause over-constraints to the contralateral knee. There was a positive correlation between PTS and ACL elongation difference for both FB and MB UKA, indicating excessive PTS should be avoided to preserve native ACL function in further UKA implantation. Levels of Evidence III.
The aim of this study was to investigate the role of point of care ultrasound (POCUS) as an alternative imaging modality to confirm the location of gastric and post-pyloric feeding tubes in patients admitted to the pediatric intensive care unit (PICU). This was a prospective descriptive study performed at a tertiary care children’s hospital. Patients from birth to 17 years of age in whom the medical team placed a temporary enteral feeding tube were eligible for enrollment. The study physician, who was blinded to the radiographic findings, performed a POCUS study of the abdomen. An abdominal radiograph was obtained to confirm the placement in all patients. A total of 13 patients were enrolled, and 14 abdominal POCUS exams were completed. POCUS accurately identified the location of the enteral feeding tube in 10 of the 14 cases. POCUS had a sensitivity and specificity of 85.7% and 57.1%, respectively, in identifying gastric tubes. It had a sensitivity and specificity of 66.7% and 87.5%, respectively, in identifying post-pyloric tubes. No adverse events were reported. This study showed that POCUS had moderate sensitivity and specificity and was, overall, safe. Further studies can assess the level of training needed for improvement in accuracy, and larger studies can help support the findings of this data that POCUS is a safe and accurate alternative to radiographs for enteral feeding tube placement confirmation.
Jean S. Edward, Amanda Thaxton Wiggins, Louis G. Baser
et al.
Few evidence-based trainings exist on how to equip healthcare providers, particularly nurses, with the skills to engage in cost of care conversations with patients/caregivers to mitigate the impact of cancer-related financial toxicity. This study evaluated a pilot training developed in collaboration with Triage Cancer<sup>®</sup> to prepare oncology nurses to identify and assist patients/caregivers facing financial and/or legal barriers to care. Ten pediatric oncology nurses completed the training and pre/post-surveys on behaviors related to financial and legal need screening, frequency and comfort level of answering questions, knowledge, and behavior changes, along with training evaluation questions. At baseline, six nurses reported never screening for financial needs and nine for legal needs. Following the training, seven nurses stated they were likely to screen for financial/legal needs. At six months post-training, nurses had referred 85 patients/caregivers to financial/legal navigation services. Comfort levels in answering financial/legal questions increased by 6.5 points and knowledge scores increased by 1.7 points post-training. Most nurses recommended this training to other healthcare providers who work with patients with cancer and their caregivers. This study highlights the importance of providing oncology nurses with resources to engage in cost of care conversations and oncology financial legal navigation programs to mitigate the impact of cancer-related financial toxicity.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Laura Izquierdo Sanchez, Julen Matin Robles, Jone Narbaiza
et al.
Introduction and Objectives: Cholangiocarcinoma (CCA) incidence and mortality are rising globally. Chronic liver diseases (CLD) are recognized risk factors. This study aimed to compare the clinical presentation and outcomes of CCA in patients with and without CLD, using data from the International CCA Registry. Patients and Methods: The international CCA Registry is a multicenter observational study enrolling cases from 54 centers across Latin America, Europe, and Asia (2010–2024). Results: Among 3,693 patients enrolled, 916 had CLD and 2,777 did not. Common CLD conditions were fatty liver disease, cirrhosis, viral hepatitis, and primary sclerosing cholangitis. Compared to non-CLD patients, those with CLD were more often male (69% vs. 53%), younger at diagnosis (63 vs. 66 years), and had higher rates of metabolic risk factors, alcohol use, and smoking. Intrahepatic CCA was more frequent in CLD patients (64% vs. 43%), whereas distal CCA was more common in non-CLD cases (20% vs. 9%). CLD patients had better performance status (ECOG 0: 53% vs. 35%), lower CA19-9 levels (59.0 vs. 134.5 U/mL), and more localized disease (56% vs. 48%). Curative-intent surgery was more frequent in the CLD group (59% vs. 48%), translating into longer median overall survival (12.3 vs. 11.0 months) and higher 5-year survival (OR = 1.67; p < 0.001). The benefit was especially evident in intrahepatic CCA. Treatment responses were comparable between groups. Conclusions: CCA is diagnosed at earlier stages in individuals with CLD, likely due to certain clinical surveillance, leading to better prognosis. Prospective validation and standardized surveillance protocols are warrant.
Arterial aneurysms remain a significant public health problem because they often result in death when ruptured; therefore, they require immediate medical treatment. Endovascular aneurysm repair (EVAR) has recently become the primary treatment option, owing to the fewer side effects compared to those with open surgery. However, stents used for conventional EVAR often cause side-branch occlusion, which alters the perfusion of vital organs. Recently, multilayer flow modulator (MFM) stents have been used as a new treatment for arterial aneurysms. These stents appear to be feasible owing to their unique design consisting of an uncoated three-dimensionally braided multilayered structure. MFM stents generally remodulate laminar flow and reduce the flow velocity in the aneurysmal sac, leading to thrombosis, which causes the aneurysm to shrink over time. Thus, they reduce the risk of mortality. Moreover, they reduce morbidity by preserving the side-branch blood flow. They can be easily applied to complex aneurysms and are ready to use without customization, which shortens the waiting time for interventions. This study aimed to evaluate the role of MFM stents in the treatment of arterial aneurysms based on available data.
Diseases of the circulatory (Cardiovascular) system
Introduction
Tobacco users are categorized as single, dual, and triple users based
on the number of tobacco products (cigarettes, e-cigarettes, and heated tobacco
products) used. This study addressed a literature gap by examining how adult
Korean tobacco users’ quit attempts/plans differed based on the user type, and
the associated psychosocial and subjective health-related factors.
Methods
We used a questionnaire to examine participants' self-reported health,
stress, health concerns, health behavior, tobacco addiction, intentions/plans to
quit, and demographic characteristics. Data were analyzed using chi-squared tests,
one-way analysis of variance, and multiple linear regression.
Results
Of the 1288 tobacco users, 55.4%, 28.3%, and 16.4% were single, dual, and
triple users, respectively. Self-rated health and stress were lowest among single
users and highest among triple users. Most user types had intentions/plans to
quit, especially triple users. Quit attempts and plans increased with increasing
health behaviors and time elapsed before first tobacco use in the morning, but
decreased with higher stress and self-rated addiction.
Conclusions
Intentions/plans to quit tobacco use varied based on the type of tobacco
user. Multiple users had higher self-rated health, plans to quit, and self-reported
addiction; they considered themselves healthy or engaged in healthy behaviors
to offset problems from tobacco use and used multiple tobacco products to quit
smoking. Highly stressed users had fewer plans to quit and used tobacco for stress
relief. Thus, the provision of accurate information about tobacco products and
stress management is important to promote successful quitting.
Diseases of the respiratory system, Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Nasal bridge is a common site suffering personal protective equipment-induced skin damages over face among first-line health care workers in this coronavirus disease 2019 pandemic. We hereby report folliculitis as a complication following regular use of N95 respirator and goggles, unreported in literature till now.
Surgery, Neurology. Diseases of the nervous system
Katie S. Gatwood, Bhagirathbhai R. Dholaria, Mariana Lucena
et al.
Abstract Adoptive cellular therapy has made a landmark change within the treatment paradigm of several hematologic malignancies, and novel cellular therapy products, such as chimeric antigen receptor T‐cell therapy (CART), have demonstrated impressive efficacy and produced durable responses. However, the CART treatment process is associated with significant toxicities, healthcare resource utilization, and financial burden. Most of these therapies have been administered in the inpatient setting due to their toxicity profile. Improved toxicity management strategies and a better understanding of cellular therapy processes are now established. Therefore, efforts to transition CART to the outpatient setting are warranted with the potential to translate into enhanced patient quality of life and cost savings. A successful launch of outpatient CART requires several components including a multidisciplinary cellular therapy team and an outpatient center with appropriate clinical space and personnel. Telemedicine should be incorporated for closer monitoring. Additionally, clear criteria for admission upon clinical decompensation, a pathway for prompt inpatient transition, and clear toxicity management guidelines should be implemented. Effective education about cellular therapy and toxicity management is imperative, especially for the Emergency Department and Intensive Care Unit teams. Here, we have outlined the various logistical and clinical considerations required for the care of CART patients, which will aid centers to establish an outpatient CART program.
Sofia Antunes-Duarte, Maria Mendonça-Sanches , Rita Pimenta
et al.
Hailey-Hailey disease (HHD) is a rare autosomal dominant acantholytic dermatosis. It is characterized by a recurrent eruption of vesicles, erosions, and scaly erythematous plaques involving intertriginous areas and first occurring after puberty, mostly in the third or fourth decade. In 2000, mutations in the ATP2C1 gene on band 3q22.1, encoding the secretory pathway Ca2+/Mn2+-ATPase protein 1(hSPCA1), have been identified as the cause of HHD. We report the identification of two novel mutations of ATP2C1 gene in two Portuguese patients, which expands the spectrum of ATP2C1 mutations underlying HHD and provides useful information for genetic counseling.
During tumor development and progression, intrinsic and extrinsic factors trigger endoplasmic reticulum (ER) stress and the unfolded protein response, resulting in the increased expression of molecular chaperones to cope with the stress and maintain tumor cell survival. Heat shock protein (HSP) GRP94, also known as GP96, is an ER paralog of HSP90 and has been shown to promote survival signaling during tumor-induced stress and modulate the immune response through its multiple clients, including TLRs, integrins, LRP6, GARP, IGF, and HER2. Clinically, elevated expression of GRP94 correlates with an aggressive phenotype and poor clinical outcome in a variety of cancers. Thus, GRP94 is a potential molecular marker and therapeutic target in malignancies. In this review, we will undergo deep molecular profiling of GRP94 in tumor development and summarize the individual roles of GRP94 in common cancers, including breast cancer, colon cancer, lung cancer, liver cancer, multiple myeloma, and others. Finally, we will briefly review the therapeutic potential of selectively targeting GRP94 for the treatment of cancers.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Background: Whether retinal microglia can maintain or restore immune homeostasis during and after inflammation is unclear. We performed single-eye mRNA-sequencing on microglia at different timepoints following a single inflammatory stimulus to characterise their transcriptome during and after resolution of endotoxin-induced uveitis (EIU).Experimental Approach:Cx3cr1CreER:R26-tdTomato (C57BL/6) male heterozygotes were administered tamoxifen via different regimes at 4–5 weeks of age. Four weeks post-tamoxifen, mice were injected intravitreally with 10 ng lipopolysaccharide (endotoxin induced uveitis, EIU). Six-hundred retinal microglia were obtained by FACS from individual naïve retinas and at 4 h, 18 h, and 2 weeks following EIU induction. Samples were sequenced to a depth of up to 16.7 million reads using the SMART-Seq v4 Ultra Low Input RNA kit. The data was analysed using Partek software and Ingenuity Pathway Analysis. Genes were considered differentially-expressed (DEG) if the FDR step-up p-value was ≤0.05 and the fold-change was ≥±2.Results: Flow cytometric analysis indicates that the Cx3cr1CreER:R26-tdTomato strain is both sensitive (>95% tagging) and specific (>95% specificity) for microglia when tamoxifen is administered topically to the eye for 3 days. During “early” activation, 613 DEGs were identified. In contrast, 537 DEGs were observed during peak cellular infiltrate and none at 2 weeks, compared to baseline controls (1,069 total unique DEGs). Key marker changes were validated by qPCR, flow cytometry, and fluorescence microscopy. C5AR1 was identified and validated as a robust marker of differentiating microglial subsets during an LPS response.Conclusion: Using EIU to provide a single defined inflammatory stimulus, mRNA-Seq identified acute transcriptional changes in retinal microglia which returned to their original transcriptome after 2 weeks. Yolk-sac derived microglia are capable of restoring their homeostatic state after acute inflammation.
Two models were developed to estimate Lyme borreliosis (LB) cases. One was based on the seroprevalence of Borrelia infections in human samples. This model used corrections for false negative and false positive results from published test sensitivity and specificity measures. A second model based on Borrelia infections in sentinel dogs was used to quantify the prevalence of Lyme disease Borrelia infections in humans; the reference baseline for this model was human and canine infections in Germany. A comparison of the two models is shown and differences discussed. The relationships between incidence, prevalence and total infection burden for LB were derived from published data and these were used in both models to calculate annual incidence, prevalence and total LB infections. The modelling was conservative and based on medical insurance records coded for erythema migrans. Linear model growth rates were used in place of the commonly adopted exponential growth. The mean of the two models was used to create estimates for various countries and continents. Examples from the analyses for LB estimated for 2018 include: incidence – USA 473,000/year, Germany 471,000/year, France 434,000/year and UK 132,000/year; prevalence – USA 2.4 million, Germany 2.4 million, France 2.2 million and UK 667,000; total infections – USA 10.1 million, Germany 10.0 million, France 9.3 million and UK 2.8 million. Estimates for the world for 2018 are: incidence 12.3 million/year; prevalence 62.1 million; and total infection burden 262.0 million. These figures are far higher than officially published data and reflect not only the underestimation of diagnosed cases, which is acknowledged by health agencies, but also undiagnosed and misdiagnosed cases.
Jonathan D. Cherry, Jesse Mez, John F. Crary
et al.
Abstract The genetic basis of chronic traumatic encephalopathy (CTE) is poorly understood. Variation in transmembrane protein 106B (TMEM106B) has been associated with enhanced neuroinflammation during aging and with TDP-43-related neurodegenerative disease, and rs3173615, a missense coding SNP in TMEM106B, has been implicated as a functional variant in these processes. Neuroinflammation and TDP-43 pathology are prominent features in CTE. The purpose of this study was to determine whether genetic variation in TMEM106B is associated with CTE risk, pathological features, and ante-mortem dementia. Eighty-six deceased male athletes with a history of participation in American football, informant-reported Caucasian, and a positive postmortem diagnosis of CTE without comorbid neurodegenerative disease were genotyped for rs3173615. The minor allele frequency (MAF = 0.42) in participants with CTE did not differ from previously reported neurologically normal controls (MAF = 0.43). However, in a case-only analysis among CTE cases, the minor allele was associated with reduced phosphorylated tau (ptau) pathology in the dorsolateral frontal cortex (DLFC) (AT8 density, odds ratio [OR] of increasing one quartile = 0.42, 95% confidence interval [CI] 0.22–0.79, p = 0.008), reduced neuroinflammation in the DLFC (CD68 density, OR of increasing one quartile = 0.53, 95% CI 0.29–0.98, p = 0.043), and increased synaptic protein density (β = 0.306, 95% CI 0.065–0.546, p = 0.014). Among CTE cases, TMEM106B minor allele was also associated with reduced ante-mortem dementia (OR = 0.40, 95% CI 0.16–0.99, p = 0.048), but was not associated with TDP-43 pathology. All case-only models were adjusted for age at death and duration of football play. Taken together, variation in TMEM106B may have a protective effect on CTE-related outcomes.
David A. Clark, David A. Clark, Seth R. Odell
et al.
An animal’s ability to navigate an olfactory environment is critically dependent on the activities of its first-order olfactory receptor neurons (ORNs). While considerable research has focused on ORN responses to odorants, the mechanisms by which olfactory information is encoded in the activities of ORNs and translated into navigational behavior remain poorly understood. We sought to determine the contributions of most Drosophila melanogaster larval ORNs to navigational behavior. Using odorants to activate ORNs and a larval tracking assay to measure the corresponding behavioral response, we observed that larval ORN activators cluster into four groups based on the behavior responses elicited from larvae. This is significant because it provides new insights into the functional relationship between ORN activity and behavioral response. Subsequent optogenetic analyses of a subset of ORNs revealed previously undescribed properties of larval ORNs. Furthermore, our results indicated that different temporal patterns of ORN activation elicit different behavioral outputs: some ORNs respond to stimulus increments while others respond to stimulus decrements. These results suggest that the ability of ORNs to encode temporal patterns of stimulation increases the coding capacity of the olfactory circuit. Moreover, the ability of ORNs to sense stimulus increments and decrements facilitates instantaneous evaluations of concentration changes in the environment. Together, these ORN properties enable larvae to efficiently navigate a complex olfactory environment. Ultimately, knowledge of how ORN activity patterns and their weighted contributions influence odor coding may eventually reveal how peripheral information is organized and transmitted to subsequent layers of a neural circuit.
Abstract Background A cornerstone of conventional dietary advice is the recommendation to replace saturated fatty acids (SFA) with mostly n-6 polyunsaturated fatty acids (PUFA) to reduce the risk of coronary heart disease (CHD). Many clinical trials aimed to test this advice and have had their results pooled in several meta-analyses. However, earlier meta-analyses did not sufficiently account for major confounding variables that were present in some of those trials. Therefore, the aim of the study was to account for the major confounding variables in the diet heart trials, and emphasise the results from those trials that most accurately test the effect of replacing SFA with mostly n-6 PUFA. Design Clinical trials were identified from earlier meta-analyses. Relevant trials were categorised as ‘adequately controlled’ or ‘inadequately controlled’ depending on whether there were substantial dietary or non-dietary differences between the experimental and control groups that were not related to SFA or mostly n-6 PUFA intake, then were subject to different subgroup analyses. Results When pooling results from only the adequately controlled trials there was no effect for major CHD events (RR = 1.06, CI = 0.86–1.31), total CHD events (RR = 1.02, CI = 0.84–1.23), CHD mortality (RR = 1.13, CI = 0.91–1.40) and total mortality (RR = 1.07, CI = 0.90–1.26). Whereas, the pooled results from all trials, including the inadequately controlled trials, suggested that replacing SFA with mostly n-6 PUFA would significantly reduce the risk of total CHD events (RR = 0.80, CI = 0.65–0.98, P = 0.03), but not major CHD events (RR = 0.87, CI = 0.70–1.07), CHD mortality (RR = 0.90, CI = 0.70–1.17) and total mortality (RR = 1.00, CI = 0.90–1.10). Conclusion Available evidence from adequately controlled randomised controlled trials suggest replacing SFA with mostly n-6 PUFA is unlikely to reduce CHD events, CHD mortality or total mortality. The suggestion of benefits reported in earlier meta-analyses is due to the inclusion of inadequately controlled trials. These findings have implications for current dietary recommendations.
Nutrition. Foods and food supply, Nutritional diseases. Deficiency diseases
Ashraf MikhailRenal Unit, Morriston Hospital, Swansea University, Wales, UKAbstract: Peginesatide is a synthetic, dimeric peptide that is covalently linked to polyethylene glycol (PEG). The amino acid sequence of peginesatide is unrelated to that of erythropoietin (EPO) and is not immunologically cross-reactive with EPO. Peginesatide binds to and activates the human EPO receptor, stimulating the proliferation and differentiation of human red cell precursors in vitro in a manner similar to other EPO-stimulating agents (ESAs). In Phase II and III studies in dialysis and predialysis patients, peginesatide administered once monthly was as effective as epoetin alfa given thrice weekly (dialysis patients) or darbepoetin given once weekly (nondialysis patients), in correcting anemia of chronic kidney disease as well as maintaining hemoglobin within the desired target range. In the dialysis population, the reported side-effect profile of peginesatide was comparable to that known with other marketed ESAs. In the nondialysis studies, compared with those treated with darbepoetin, patients treated with peginesatide experienced a higher adverse-effect profile. Peginesatide is likely to be licensed for treatment of renal anemia in dialysis patients and not in nondialysis patients. Despite this limitation, peginesatide is likely to prove valuable in treating dialysis patients because of its infrequent mode of administration, thereby allowing for a reduced number of injections, with associated better compliance, reduced cold storage requirement, and improved stock accountability. PEGylated therapeutic proteins can elicit immunological response to the PEG moiety of the therapeutic complex. Only long-term experience and post-marketing surveillance will address whether this immunological response will have any impact on the clinical efficacy or safety of peginesatide in clinical practice.Keywords: peginesatide, dialysis, chronic kidney disease