Long-term Clinical Monitoring Research Articles

МЕЖДУНАРОДНЫЙ ПРОФИЛЬ БЕЗОПАСНОСТИ ПРИМЕНЕНИЯ ОМАЛИЗУМАБА В КЛИНИЧЕСКОЙ ПРАКТИКЕ

The article provides an overview of information on cases of adverse reactions with the use of omalizumab, the reports of which are included in the database of the World Health Organization's international drug monitoring program in 6 years (selected period 01.01.2017-01.01.2024). An analysis of the safety indicators of omalizumab, which is the drug of choice in the treatment of a number of severe atopic diseases, was carried out. Despite the long-term use of the drug in medical practice (more than 15 years) and reports on its efficacy, there is insufficient information on adverse reactions during its use, especially in the Russian Federation, since long-term clinical monitoring has not been carried out. The obtained characteristics of the structure of adverse reactions to the use of omalizumab by gender, age of patients, nature of their complaints, severity of outcomes, geography and initiators of reports, constitute a theoretical basis for improving and fine-tuning the domestic system of pharmacovigilance and drug monitoring, and may also be of practical interest to doctors, researchers and health regulators. The first rank places in the structure of adverse reactions to omalizumab are occupied by: general disorders and reactions at the site of administration, disorders of the skin and subcutaneous tissue, disorders of the respiratory system, thoracic and mediastinal organs, injuries, intoxication and complications of procedures, disorders of the nervous system. In the overall structure of NR, serious adverse reactions to omalizumab accounted for 35,1%. The analysis showed that in the assessment of adverse reactions, a significant role is given to patients (their representatives), whose opinion is determined by subjective feelings and the level of awareness, so more attention should be paid to drug informing patients.

Microsurgical management of recurrent intracranial aneurysm after endovascular treatment: a series of 60 consecutive patients

OBJECTIVE The aim of this study was to evaluate the morbidity associated with microsurgical treatment in patients with a recurrent aneurysm to improve their surgical management. METHODS From 2012 to 2022, among the 3128 patients with ruptured or unruptured intracranial aneurysms managed at the authors’ institution, 954 patients were treated by a microsurgical procedure. Of these 3128 patients, 60 consecutive patients (6.3%) who had a recurrent microsurgically treated aneurysm after previous endovascular treatment were included in this study. Additional microsurgical treatment was considered in case of progressive remnant growth or significant aneurysm recurrence. Intraoperative and postoperative complications were noted. Early (< 7 days) and long-term clinical and radiological monitoring were performed. Good functional outcome was considered as a modified Rankin Scale score < 3. RESULTS The mean age at initial treatment was 45 years (range 26–65 years). The mean delay between the first treatment and microsurgical treatment of the recurrence was 64 months (range 2 days–296 months). The mean size of the fundus recurrence was 5 mm, and the mean size of the neck recurrence was 4.6 mm. Five patients (8.3%) presented with subarachnoid hemorrhage associated with rupture of the recurrent aneurysm. Three patients died (6%) of aneurysm rupture and/or intensive care complications. The total morbidity rate associated with the microsurgical procedure was 14.5% (8/55) in patients with unruptured recurrent aneurysms. Among these patients, postoperative definitive complications (ischemic lesions) directly related to the microsurgical procedure were present in 3 patients (5.5%). Intraoperative rupture was recorded in these 3 patients. In the 54 surviving patients with unruptured recurrent aneurysms, good functional outcome was noted in 49 (91%). Poor functional outcome was significantly associated with intraoperative rupture. CONCLUSIONS Microsurgery remains an effective therapeutic option for recurrent intracranial aneurysms. However, in the authors’ experience, postoperative morbidity is higher than in patients with nonrecurrent aneurysms. Therefore, a pretherapeutic multidisciplinary evaluation is mandatory to reduce the potential morbidity associated with the retreatment as much as possible. When endovascular occlusion of the aneurysm requires both stenting and coiling, alternative microsurgical treatment should be carefully evaluated, as microsurgical clipping will become much more challenging in cases of aneurysm recurrence.

Phenotypical characterization of exteroceptive sensation and pain symptoms on diabetic patients.

Diabetic neuropathy (DN) is one of the most common complications of diabetes, affecting about half of individuals with the disease. Among the various symptoms of DN, the development of chronic pain stands out and manifests as exacerbated responses to sensorial stimuli. The conventional clinical treatments used for general neuropathy and associated painful symptoms, still brings uncomplete and unsatisfactory pain relief. Patients with neuropathic pain syndromes are heterogeneous. They present with a variety of sensory symptoms and pain qualities which difficult the correct diagnosis of sensory comorbidities and consequently, the appropriate chronic pain management. Herein, we aimed to demonstrate the existence of different sensory profiles on diabetic patients by investigating epidemiological and clinical data on the symptomatology of a group of patients with DN. This is a longitudinal and observational study, with a sample of 57 volunteers diagnosed with diabetes from outpatient day clinic of Hospital Universitário of the University of São Paulo-Brazil. After being invited and signed the Informed Consent Form (ICF), patients were submitted to clinical evaluation and filled out pain and quality of life questionnaires. They also performed quantitative sensory test (QST) and underwent skin biopsy for correlation with cutaneous neuropathology. Data demonstrate that 70% of the studied sample presented some type of pain, manifesting in a neuropathic or nociceptive way, what has a negative impact on the life of patients with DM. We also demonstrated a positive association between pain and anxiety and depression, in addition to pain catastrophic thoughts. Three distinct profiles were identified in the sample, separated according to the symptoms of pain: (i) subjects without pain; (ii) with mild or moderate pain; (iii) subjects with severe pain. We also identified through skin biopsy that diabetic patients presented advanced sensory impairment, as a consequence of the degeneration of the myelinated and unmyelinated peripheral fibers. This study characterized the painful symptoms and exteroceptive sensation profile in these diabetic patients, associated to a considerable level of sensory degeneration, indicating, and reinforcing the importance of the long-term clinical monitoring of individuals diagnosed with DM, regarding their symptom profiles and exteroceptive sensitivity.

Long-term Follow-up Results after Prophylactic Antiviral Administration in Patients with Herpes Simplex Keratitis

Purpose: We analyzed the effectiveness of prophylactic oral antivirals in preventing herpes simplex keratitis (HSK) and the clinical manifestations of recurrence.Methods: A retrospective analysis was conducted on 30 eyes of 30 patients diagnosed with HSK who received prophylactic oral antiviral agents for > 6 months. We analyzed the initial and recurrent clinical features of HSK, the recurrence rate, and the relationship between recurrence and the duration of oral antivirals.Results: The mean age of the patients was 64.5 ± 14.0 years, and the mean follow-up duration was 72.4 ± 40.3 months. Of the 30 eyes, 21 (70%) experienced HSK recurrence. The initial clinical features of recurrent cases included herpetic epithelial keratitis (14.3%), stromal keratitis (47.6%), and endotheliitis (38.1%). Notably, no significant associations were observed between the initial clinical features of HSK or the duration of oral antivirals and HSK recurrence. However, male patients exhibited a significantly higher recurrence rate. Epithelial keratitis (47.6%) was the most common HSK type observed during recurrence.Conclusions: A recurrence rate of 70% was observed in patients who received prophylactic oral antiviral treatment for > 6 months. Herpetic epithelial keratitis was the most common clinical phenotype after recurrence. Notably, long-term clinical monitoring could assist in predicting and preventing recurrence.

Propuesta de seguimiento tras cirugía protésica de cadera primaria: Revisión sistemática de la literatura.

Total hip replacement is probably the most successful surgical technique within orthopedic surgery, despite this it is foreseeable that some patients will require revision of their implant over time. These facts make it necessary to adopt a cost-effective model for long-term clinical monitoring and control of patients and their implants. Generally, the clinical reviews carried out tend to have an annual frequency, which seems to constitute an unnecessary action due to its low effectiveness in detecting cases that require an action derived from their visit (around 0.6%) and a significant financial burden. We carried out a systematic review of the last ten years around: "hip arthroplasty follow up recommendations" and "total hip replacement recommendations for follow-up", with a proposal for follow-up planning.

Impact of Sociodemographic, Premorbid, and Injury-Related Factors on Patient-Reported Outcome Trajectories after Traumatic Brain Injury (TBI)

Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide. To better understand its impact on various outcome domains, this study pursues the following: (1) longitudinal outcome assessments at three, six, and twelve months post-injury; (2) an evaluation of sociodemographic, premorbid, and injury-related factors, and functional recovery contributing to worsening or improving outcomes after TBI. Using patient-reported outcome measures, recuperation trends after TBI were identified by applying Multivariate Latent Class Mixed Models (MLCMM). Instruments were grouped into TBI-specific and generic health-related quality of life (HRQoL; QOLIBRI-OS, SF-12v2), and psychological and post-concussion symptoms (GAD-7, PHQ-9, PCL-5, RPQ). Multinomial logistic regressions were carried out to identify contributing factors. For both outcome sets, the four-class solution provided the best match between goodness of fit indices and meaningful clinical interpretability. Both models revealed similar trajectory classes: stable good health status (HRQoL: n = 1944; symptoms: n = 1963), persistent health impairments (HRQoL: n = 442; symptoms: n = 179), improving health status (HRQoL: n = 83; symptoms: n = 243), and deteriorating health status (HRQoL: n = 86; symptoms: n = 170). Compared to individuals with stable good health status, the other groups were more likely to have a lower functional recovery status at three months after TBI (i.e., the GOSE), psychological problems, and a lower educational attainment. Outcome trajectories after TBI show clearly distinguishable patterns which are reproducible across different measures. Individuals characterized by persistent health impairments and deterioration require special attention and long-term clinical monitoring and therapy.

Macroprolactinoma and empty sella: Swinging pendulum and lessons for dopamine agonists therapy

Abstract Prolactinomas account for nearly 40% of all pituitary tumors with a remarkable response to dopamine agonist (DA) therapy, rendering surgical intervention unnecessary in most cases. Clinical guidelines recommend discontinuing DA therapy two years after achieving normalized prolactin levels and without tumor visibility on MRI. We report a middle-aged man with a macroprolactinoma who presented with apoplexy and panhypopituitarism. The patient responded remarkably to cabergoline with normalization of prolactin and complete tumor disappearance with radiological empty sella within 18 months, and subsequently, he discontinued cabergoline. The patient presented lately (after 10 years) with a recurrence of macroprolactinoma, for which he was reinitiated on cabergoline therapy. Patients with an empty sella remain susceptible to tumor recurrence, as pituitary adenomas may arise from residual pituitary tissue or microscopic tumor remnants may persist, which is not discernible radiologically. This case is a poignant reminder of the importance of diligent and long-term clinical and biochemical monitoring in patients with prolactinomas.

Safety of omalizumab in the treatment of moderate-to-severe bronchial asthma

This review aimed to analyze national and international literature on the safety of omalizumab in the treatment of moderate-to-severe bronchial asthma. Omalizumab is one of the longest-standing monoclonal antibodies and the first available treatment option for severe allergic asthma in patients aged 6 years. Several randomized controlled studies have established its efficiency and safety, leading to its final registration more than 15 years ago. In most cases, long-term treatment with omalizumab is safe without increasing the risk of adverse reactions. However, over the years, a growing trend has been observed in several registrations of adverse events associated with the use of omalizumab. A review of the literature revealed a lack of long-term clinical monitoring data (over 2 years) in both patients aged 18 years and children. Long-term adverse reactions during omalizumab therapy are insufficiently examined and require more detailed analysis, despite reports of an association between omalizumab and some adverse events. Moreover, extremely few cases of adverse reactions to omalizumab were reported in the Russian Federation. Thus, further investigations of the safety profile of omalizumab and monitoring of its delayed adverse reactions are required.

Long-term outcomes of trapeziectomy with Gore-Tex® ligament reconstruction for trapezio-metacarpal osteoarthritis

BackgroundTrapezio-metacarpal osteoarthritis is a common condition for which the reference standard treatment after failure of non-operative measures is trapeziectomy. Several techniques have been devised to avoid proximal migration of the first metacarpal bone (M1) with impingement on the scaphoid bone. We have developed a Gore-Tex® ligament reconstruction technique that avoids potential complications of tendon harvesting. The objective of this study was to assess the long-term outcomes of this technique. HypothesisTrapeziectomy with Gore-Tex® ligament reconstruction is a reliable option for providing lasting pain relief in patients with trapezio-metacarpal osteoarthritis. Materials and methodsWe conducted an observational, single-centre, single-surgeon, retrospective cohort study in consecutive patients managed by primary trapeziectomy. We excluded patients with revision trapeziectomy or less than 10 years’ follow-up. The primary outcome was event-free survival, defined as absence of revision surgery and of a numerical rating scale score for pain above 3/10. The secondary criteria were clinical tolerance of the Gore-Tex® implant and radiological changes. The patients were assessed at last follow-up either in person or during a teleconsultation. ResultsOf 78 included joints, 54 were assessed during patient visits and 24 by teleconsultation. At 10 years, the event-free survival rate was 91.3%, and 60.3% of patients were free of pain. Evidence of osteolysis was visible in 24% of patients. No patient experienced clinical intolerance of the Gore-Tex® implant. The mean Disabilities of Arm, Shoulder and Hand score was 25.5. Metacarpo-phalangeal hyperextension was significantly increased, to 30.6°, and the mean trapezial space ratio was significantly decreased, to 39.1% of the baseline value. ConclusionLong-term event-free survival was high. Functional outcomes and pain were similar to previous reports. Trapeziectomy with Gore-Tex® ligament reconstruction obviates the need for tendon harvesting. Osteolysis developed in some patients but did not correlate with clinical intolerance. Long-term clinical and radiological monitoring is in order after Gore-Tex® implantation. Level of evidenceIV, Observational, single-centre, single-surgeon, retrospective cohort study.

Early-life exposure to APP/PS1 mice increases neuroinflammation through gut microbes

ObjectiveThe gut-brain axis has been implicated in the complex pathogenesis of Alzheimer's disease (AD), but the mechanism of action is unclear. This study was performed to clarify the link between the gut microbiota and AD. MethodsGut microbiota structure, long-term potentiation (LTP), inflammation levels, AD biomarkers, and metabolomics were monitored. Moreover, the regulatory action of bacterial metabolites on tau protein phosphorylation was evaluated. ResultsEarly-life exposure to APP/PS1 mice showed that gut bacteria from donated mice altered the gut microbiota structure in newborn mice, LTP in hippocampal slices was significantly shortened, inflammatory marker levels increased, AD biomarkers were upregulated, and tau protein phosphorylation was significantly higher at multiple sites. Special bacteria, such as Akkermansia, Lactobacillus, and Klebsiella, increased in AD patient samples, which might induce and/or accelerate disease processes. ConclusionThese results implied that the gut bacteria in AD could change the gut microbiota structure, induce metabolism disorders, induce inflammation and autophagy dysfunction (thus leading to accelerated tau protein phosphorylation), reduce LTP in AD cohoused mouse hippocampus, and increase neuroinflammation. Long-term clinical monitoring is needed to design dietary and nutritional interventions for AD based on the gut microbiota and mycobiota.

Transdural spinal cord herniation: A rare cause of neurologic impairment: Report of two cases and review of the literature.

IntroductionHerniation of the thoracic spinal cord is a rare pathology related to the genesis of a breach in the anterior dura. Adding to the previously published cases, we report our department's experience with 2 cases of young adults who presented with transdural spinal cord herniation following spinal trauma.Presentation of the casesWe report the cases of 2 men aged 27 and 57, with history of spinal trauma, who presented diverse clinical complaints (motor impairment, genito-sphincteric disorders, etc.). Spinal cord MRI showed an anterior displacement of the spinal cord. Both patients were operated. Peroperative findings and radiological features were concordant with transdural spinal cord herniation.DiscussionSpinal cord herniation is a rare condition which is usually related to a misdiagnosed spinal trauma. Pathogenesis is still being debated. This condition may lead to a myelopathy potentially responsible for severe neurologic impairment, mainly presenting as a Brown-Sequard syndrome. Diagnosis is based on clinical and radiologic features on MRI. Surgical treatment is proposed when neurological signs are found. Long-term clinical and radiological monitoring is necessary for paucisymptomatic, non-operated patients.ConclusionsBased on the described cases, we tried to review the main clinical, radiological and therapeutic features related to this condition.

Radio Frequency Resonator-Based Flexible Wireless Pressure Sensor with MWCNT-PDMS Bilayer Microstructure.

Flexible pressure sensors have been widely applied in wearable devices, e-skin, and the new generation of robots. However, most of the current sensors use connecting wires for energy supply and signal transmission, which presents an obstacle for application scenarios requiring long endurance and large movement, especially. Flexible sensors combined with wireless technology is a promising research field for realizing efficient state sensing in an active state. Here, we designed and fabricated a soft wireless passive pressure sensor, with a fully flexible Ecoflex substrate and a multi-walled carbon nanotube/polydimethylsiloxane (MWCNT/PDMS) bilayer pyramid dielectric structure. Based on the principle of the radio-frequency resonator, the device achieved pressure sensing with a changeable capacitance. Subsequently, the effect of the pyramid density was simulated by the finite element method to improve the sensitivity. With one-step embossing and spin-coating methods, the fabricated sensor had an optimized sensitivity of 14.25 MHz/kPa in the low-pressure range. The sensor exhibited the potential for application in limb bending monitoring, thus demonstrating its value for long-term wireless clinical monitoring. Moreover, the radio frequency coupling field can be affected by approaching objects, which provides a possible route for realizing non-contact sensing in applications such as pre-collision warning.

Classification Framework for COVID-19 Diagnosis Based on Deep CNN Models

Automated diagnosis based on medical images is a very promising trend in modern healthcare services. For the task of automated diagnosis, there should be flexibility to deal with an enormous amount of data represented in the form of medical images. In addition, efficient algorithms that could be adapted according to the nature of images should be used. The importance of automated medical diagnosis has been maximized with the evolution of COVID-19 pandemic. COVID-19 first appeared in China, Wuhan, and then it has exploded in the whole world with a very bad impact on our daily life. The third wave of COVID-19 in the third world is really a disaster in current days, especially with the emergence of the delta variant of COVID-19 that is widespread. Required inspections should be carried out to monitor the COVID-19 spread in daily life and allow primary diagnosis of suspected cases, and long-term clinical laboratory monitoring. Healthcare professionals or radiologists can exploit AI (Artificial Intelligence) tools to quickly and reliably identify the cases of COVID-19. This paper introduces a DCNN (Deep Convolutional Neural Network) framework for chest X-ray and CT image classification based on TL (Transfer Learning). The objective is to perform multi-class and binary classification of the images in order to determine pneumonia and COVID-19 case. The TL is feasible, when using a small dataset by transferring knowledge from natural image classification to medical image classification. Two types of TL are used. The first type is fine-tuning of the DenseNet121, Densenet169, DenseNet201, ResNet50, ResNet152, VGG16, and VGG19 models. The second type is deep tuning of the LeNet-5, AlexNet, Inception naïve v1, and VGG16 models. Extensive tests have been carried out on datasets of chest X-ray and CT images with different training/testing ratios of 80%:20%, 70%:30%, and 60%:40%. Experimental results on 9,270 chest X-ray ray and 2,762 chest CT images acquired from different institutions show that the TL is effective with an average accuracy of 98.49%.

Perampanel-Induced Psychosis in a Young Woman: A Case Report

A case of perampanel-induced psychosis in a young woman is reported, a side effect that has only rarely been reported in the literature. We describe a case of a young woman with epilepsy and no psychiatric history with perampanel-associated altered behavior and psychotic symptoms, requiring hospitalization in an acute psychiatry ward. We also provide a literature review on the possible neurobiological pathways implicated. Perampanel is believed to block a small proportion of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor current, retarding epileptiform discharges while sparing most normal synaptic transmission. Most common adverse events are related to central nervous system (including dizziness, drowsiness, blurred vision and imbalance) and psychiatric symptoms have been reported. The biological vulnerability to psychiatric and behavioral adverse reactions of antiepileptic drugs is multifactorial and different mechanisms and clinical predisposing factors may interact. For this reason, patients starting these antiseizure drugs need long-term and comprehensive clinical monitoring.

Preterm Delivery and Long-term Risk of Hypertension in Women

Preterm delivery has been associated with future cardiometabolic disorders in women. However, the long-term risks of chronic hypertension associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment, clinical monitoring, and cardiovascular prevention strategies in women. To examine the long-term risks of chronic hypertension associated with preterm delivery in a large population-based cohort of women. This national cohort study assessed all 2 195 989 women in Sweden with a singleton delivery from January 1, 1973, to December 31, 2015. Data analyses were conducted from March 8, 2021, to August 20, 2021. Pregnancy duration identified from nationwide birth records. New-onset chronic hypertension identified from primary care, specialty outpatient, and inpatient diagnoses using administrative data. Cox proportional hazards regression was used to compute hazard ratios (HRs) while adjusting for preeclampsia, other hypertensive disorders of pregnancy, and other maternal factors. Cosibling analyses were assessed for potential confounding by shared familial (genetic and/or environmental) factors. In 46.1 million person-years of follow-up, 351 189 of 2 195 989 women (16.0%) were diagnosed with hypertension (mean [SD] age, 55.4 [9.9] years). Within 10 years after delivery, the adjusted HR for hypertension associated with preterm delivery (gestational age <37 weeks) was 1.67 (95% CI, 1.61-1.74) and when further stratified was 2.23 (95% CI, 1.98-2.52) for extremely preterm (22-27 weeks of gestation), 1.85 (95% CI, 1.74-1.97) for moderately preterm (28-33 weeks of gestation), 1.55 (95% CI, 1.48-1.63) for late preterm (34-36 weeks of gestation), and 1.26 (95% CI, 1.22-1.30) for early-term (37-38 weeks of gestation) compared with full-term (39-41 weeks of gestation) delivery. These risks decreased but remained significantly elevated at 10 to 19 years (preterm vs full-term delivery: adjusted HR, 1.40; 95% CI, 1.36-1.44), 20 to 29 years (preterm vs full-term delivery: adjusted HR, 1.20; 95% CI, 1.18-1.23), and 30 to 43 years (preterm vs full-term delivery: adjusted HR, 95% CI, 1.12; 1.10-1.14) after delivery. These findings were not explained by shared determinants of preterm delivery and hypertension within families. In this large national cohort study, preterm delivery was associated with significantly higher future risks of chronic hypertension. These associations remained elevated at least 40 years later and were largely independent of other maternal and shared familial factors. Preterm delivery should be recognized as a lifelong risk factor for hypertension in women.

Humeral metastasis as the only recurrence of a 5-year resected gastrointestinal stromal tumor: a case report

IntroductionGastrointestinal stromal tumors represent the most frequently encountered primary mesenchymal tumors. Whereas the liver and the peritoneum are known to be the preferential metastasis sites, no therapeutic standard has yet been established for the management of bone metastases because of their very low incidence. We report a unique example of a single humerus metastasis of a jejunal gastrointestinal stromal tumor.Case presentationWe report the case of a 72-year-old European woman whose jejunal gastrointestinal stromal tumor was resected in 2013 and treated during the following 3 years with imatinib (400 mg daily). In 2018, she developed a single humeral bone lesion that was identified as a gastrointestinal stromal tumor metastasis. After 7 months of imatinib intake, reconstructive surgery was performed. Pathologists confirmed the satisfactory histological regression and assessed the complete tumor resection. The patient is still on imatinib maintenance therapy, with no recurrence reported so far. She fully recovered the upper limb function after following an appropriate rehabilitation program.DiscussionCurrent literature and published case reports indicate that bones are one of the rarest locations of gastrointestinal stromal tumor metastasis (about 1%), with occurrence mainly in the spine. Patients initially diagnosed with gastrointestinal stromal tumor of the small intestine and stomach are more likely to suffer from bone metastasis, compared with other gastrointestinal stromal tumor locations. The median overall survival rate is higher for patients with isolated bone metastasis compared with those having liver metastasis. Metastasis occurs on average 4 years after the primary, but it may take up to 20 years, emphasizing the need for long-term clinical and radiological monitoring. Although specific guidelines for such cases have not yet been established, we suggest that a multimodal concerted approach involving surgery or radiotherapy associated with tyrosine kinase inhibitor intake should be considered.ConclusionBones are one of the rarest locations of gastrointestinal stromal tumor metastasis. A multidisciplinary collaboration was set up to allow conservative surgery of our patient after several months of imatinib treatment. A year and a half later, the patient is still in complete remission. This specific case supports the concept of an intermediate stage between local and oligometastatic disease that should be managed with a curative aim, as much as possible.

Characteristics, incidence, and risk factors for death from fatal pneumonia among patients with primary malignant bone tumors: a SEER-based observational study.

Background(I) To determine whether patients with malignant bone tumors had a higher risk of dying from pneumonia compared with the general US population; (II) to identify the independent risk factor associated with fatal pneumonia among these patients.MethodsWe identified 18,583 patients diagnosed with primary malignant bone tumors between 1973 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios (SMRs) were calculated based on the mortality data of the general population gathered by the National Center for Health Statistics, which provided the risk of death from pneumonia among cancer patients relative to that of the general population. Given that other causes of death were considered as competing events, we also designed the Fine-Gray model to identify demographic and tumor-related characteristics associated with a higher risk of dying from pneumonia among these patients.ResultsPatients with primary malignant bone tumors had a higher risk of dying from pneumonia than the general population after adjusting the distribution difference of age, sex, and race among them (SMR =2.79; 95% CI: 2.17–3.59). The older age, Black and earlier period of diagnosis were found to be the independent prognostic factor for a higher risk of death from pneumonia for these patients. Additionally, amputation due to malignant bone tumors significantly increased the risk of death from pneumonia compared with non-surgery. The highest mortality rate of pneumonia was observed among patients with chordoma. Interaction tests demonstrated that amputation only increased the relative risk of fatal pneumonia among patients with osteosarcoma. Throughout the follow-up period, the mortality rate of fatal pneumonia was the highest within the first year after diagnosis, and the highest relative suicide risks persisted over time in patients with osteosarcoma.ConclusionsTo mitigate the risk of fatal pneumonia among patients with bone tumors, we call for long-term clinical monitoring of the lung condition among these patients, especially for those after amputation for bone tumors.

Target Adaptive Differential Iterative Reconstruction (TADI): A Robust Algorithm for Real-Time Electrical Impedance Tomography

Electrical impedance tomography (EIT) is a noninvasive functional diagnostic technique that has been successfully applied to human lung and brain. EIT reconstruction is an ill-conditioned problem: the regularization parameters establish a trade-off between acceptable data fitting and acceptable solution stability. This trade-off is necessary to select the optimal regularization parameters for each data frame to continuously obtain high-quality images in real-time monitoring. However, using the objective regularization parameter selection method before each image reconstruction may reduce the reconstruction efficiency, and using heuristic selection for all images may cause significant quality degradation, thereby creating challenges in long-term clinical EIT monitoring. This study explores a robust EIT target adaptive differential iterative reconstruction algorithm that does not require the advance selection of the optimal regularization parameter to facilitate the clinical application of EIT long-term bedside monitoring. Specifically, second-order Taylor approximation expansion and Euler–Lagrange theorem were used to derive the conductivity differential iteration relationship. Furthermore, the reconstruction quality and generalization ability of the proposed algorithm were validated based on comparisons with the L-curve and the generalized cross-validation parameter selection methods through simulations, phantom experiments, and human lung recruitment data. Compared with the L-curve and generalized cross-validation methods, the TADI algorithm reduces the position error by 33.07% and 47.17%, the ringing by 26.49% and 32.69%, and the shape deformation by 18.34% and 19.40% on average, respectively. The results revealed that the TADI algorithm could achieve a significant improvement over the existing state-of-the-art methods in terms of stability, consistency, and efficiency.

Dynamics of immunological reactivity indices in patients with laryngal papillomatosis at different periods after complex treatment with antivirus qudrivalent vaccine "Gardasil"

The aim of the study is to determine di­sorders of immune homeostasis in patients with laryngeal papillomatosis at different periods after complex treatment with the inclusion of the “Gardasil” quadrivalent vaccine in the adjuvant therapy. Studies of the immunity state were conducted in 26 patients with laryngeal papillomatosis (LP) before, 2-12 and 13-29 months after complex treatment, consisting of surgical removal of papillomas and anti-relapse therapy, including inhalation of Laferobion, taking a vitamin-mineral complex and a course of vaccination with antiviral “Gardasil” quadrivalent vaccine according to which the second and third injections were administered in 2 and 6 months after the first. Significant disorders of cellular and humoral immunity indices in patients with LP were revealed in the form of multidirectional changes in the functional activity of natural killer cells, a decrease in the total number of T lymphocytes, mainly due to CD4 + subpopulation, increase in circulating immune complexes level in blood serum and concentration of secretory IgA in the secretion of the oropharynx. Disbalance in the patient’s cytokine system resulted in increased γ-IFN and TNF-α serum levels, an increase in spontaneous production of interferon and inhibition of stimulated production of λ - and γ-interferon by blood cells in vitro. Complex treatment with the use of the “Gardasil” quadrivalent antiviral vaccine in the postoperative period contributed to the normalization of most immunological reactivity indices that were altered in patients. The results indicate the prospects of using the antiviral vaccine as part of adjuvant antirelapse therapy after surgical treatment of LP patients and indicate the advisability of long-term clinical and immunological monitoring at different periods after vaccination.

Physical activity is associated with reduced prevalence of self-reported obstructive sleep apnea in a large, general population cohort study.

Obstructive sleep apnea (OSA) is a common condition with significant symptoms and long-term adverse cognitive, mental health, vascular, and respiratory sequelae. Physical activity has been recognized as a key determinant for good health and has been associated with lower risk of these sequelae. We hypothesized that increased physical activity may be associated with a decreased prevalence of OSA. This cross-sectional study used baseline questionnaire data from the Ontario Health Study, a population-based cohort of residents of Ontario, Canada. Participants were adults who provided lifestyle, medical, socio-demographic, and sleep health information. The study sample consisted of 155,448 men (39.8%) and women (60.2%). The prevalence of physician-diagnosed OSA in this cohort was 6.9%. Logistic regression models were used to investigate the association of OSA with physical activity. Missing data were imputed using a multiple imputation by chained equation approach. In multivariable analyses adjusted for potential confounding factors, increased total physical activity (metabolic equivalent [h/wk]) (odds ratio [OR] = .98, 95% confidence interval [CI] = .96 to 1.00), vigorous-intensity activity (OR = .98, 95% CI = .97 to 1.00), and walking (OR = .98, 95% CI = .96 to 1.00) were all associated (all P ≤ .045) with decreased prevalence of OSA. Moderate-intensity activity was not associated with risk of OSA (P = .826). Independent of known risk factors for OSA, including body mass index, increased levels of physical activity, including walking, were associated with a prevalence of OSA. Our results highlight the importance of physical activity as a preventive measure for sleep apnea.