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INTRODUCTION: Randomized clinical trials (RCTs) have suggested that BTK inhibitors (BTKis) might increase infectious disease (ID) risk. Systematic analysis on this topic as derived from RCTs and clinical practice is needed. AREAS COVERED: An extensive Medline, Embase and Cochrane search of peer-reviewed sources reporting on ID morbidity in patients on BTKis was performed (1/1/2014-12/31/2023). Contribution of intrinsic immune defects in indolent B-cell lymphomas to this morbidity was carefully considered. EXPERT OPINION: Patients with indolent B-cell lymphomas display a wide range of innate and adaptive immune defects. In addition, BTKi use is linked with an increased signal of upper respiratory tract infections (URTIs) and pneumonias, mainly grade 1-2. These agents also increase the risk of rare invasive fungal infections (IFIs), mainly due to Cryptococcus and Aspergillus spp. with a peak within several months after the start of therapy. More than half of these IFIs are fatal. Research suggests a similar ID risk across 1st, 2nd and 3rd generations of BTKis, all causing B-cell dysfunction due to BTK inhibition, along with off-target functional neutrophil/macrophage alterations. Expanding the knowledge base on ID morbidity in patients on BTKis would facilitate timely diagnosis and treatment, and improve clinical outcomes.
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INTRODUCTION: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR) are linked with side effects involving skin and mucosa. Herein, we present a unique case of oral lichenoid drug eruption (LDE) in a patient treated with osimertinib. CASE REPORT: A 75-year-old woman was diagnosed with metastatic EGFR-mutated lung adenocarcinoma, and started on osimertinib 80â mg PO daily. At 24 months of therapy, the patient developed a painful, red, and white striated oral lesion involving the left buccal mucosa and the adjacent buccal aspect of gingivae. Biopsy showed oral LDE. Causality assessment between osimertinib and the oral LDE via Naranjo Adverse Drug Reaction probability scale revealed a score of 5. MANAGEMENT AND OUTCOME: Osimetinib discontinuation was not felt to be in the best interest of the patient. Therefore, diphenhydramine HCL mouthwash every 6â h PRN (before meals) was started. Spicy and hot foods were discontinued. At a four-week follow-up visit, the patient reported moderate improvement in her symptoms. CONCLUSION: Oral LDEs are considered premalignant lesions as they can transform into squamous cell carcinoma; therefore, regular follow-up is needed. Awareness of this potential side effect of osimertinib would also prevent unnecessary (and potentially costly) work-up and lead to its prompt diagnosis and treatment.
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INTRODUCTION: Careful adverse event assessment and management are important when prescribing immune checkpoint inhibitors (ICIs) to cancer patients. Iatrogenic Sjogren's syndrome is a relatively rare immune-related adverse event (irAEs) that affects the moisture-producing glands. METHODS: We describe a series of four patients who developed Sjogren's syndrome while being treated with ICIs at a community cancer center in Southern California, USA (1/1/2017-12/31/2023). Patient, drug and disease-related data were collected by retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases in the literature (1/1/2016-12/31//2023). RESULTS: Of 224 cancer patients at our center treated with ICIs, four (1.8%) developed iatrogenic Sjogren's syndrome. All of our patients were male; three received PD-1 inhibitors (nivolumab, pembrolizumab) and one received the PD-L1 inhibitor atezolizumab. The median time to development of Sjogren's syndrome was 24 weeks (range, 8-36 weeks); dry mouth symptoms were more prominent than dry eye symptoms. None of the patients had elevated SS-A, SS-B or antinuclear antibodies. One patient developed multiple tooth cavities and had several extractions, due to severe xerostomia. Management of all patients was primarily symptomatic. Two cases were irreversible; one was reversible and the 4th case is undermined as he is still on ICI therapy. Our systematic review of the literature identified 80 cases in five articles. Incidence of xerostomia was twice of that of xerophthalmia. The male/female ratio was 1.5:1. SS-A, SS-B, or antinuclear antibodies were found in only 9% of patients. Steroids were reported to have had only a limited role in management. CONCLUSIONS: The incidence of Sjogren's syndrome due to ICIs in our center was 1.8%. Details of clinical course and management in these patients are presented. Caring for patients with ICI-related Sjogren's syndrome is facilitated by a multidisciplinary effort including oncologists, otolaryngologists, dentists, ophthalmologists and rheumatologists. Expanding the knowledge base pertaining to iatrogenic Sjogren's syndrome in patients on ICIs will be helpful in promoting early detection and treatment, and improving outcomes.
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Goal-directed navigation requires continuously integrating uncertain self-motion and landmark cues into an internal sense of location and direction, concurrently planning future paths, and sequentially executing motor actions. Here, we provide a unified account of these processes with a computational model of probabilistic path planning in the framework of optimal feedback control under uncertainty. This model gives rise to diverse human navigational strategies previously believed to be distinct behaviors and predicts quantitatively both the errors and the variability of navigation across numerous experiments. This furthermore explains how sequential egocentric landmark observations form an uncertain allocentric cognitive map, how this internal map is used both in route planning and during execution of movements, and reconciles seemingly contradictory results about cue-integration behavior in navigation. Taken together, the present work provides a parsimonious explanation of how patterns of human goal-directed navigation behavior arise from the continuous and dynamic interactions of spatial uncertainties in perception, cognition, and action.
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Spatial Navigation , Humans , Spatial Navigation/physiology , Uncertainty , Cues , Space Perception/physiology , Cognition/physiology , Computer Simulation , Orientation/physiology , GoalsABSTRACT
BACKGROUND: Intraoperative parathyroid hormone (PTH) monitoring is a proven and reliable adjunct to parathyroid surgery, able to improve the outcomes and efficiency of the diagnostic and therapeutic pathway for patients with primary hyperparathyroidism. This study evaluated the innovative, compact, fully automated NBCL CONNECT Analyzer, which can measure whole-blood PTH in 5â min. METHODS: A prospective multicentre study was conducted in stages: results reviews, recommendations, and implementation of improvements to the mechanical design, components of cartridges, calibration, and sampling protocols. Patients undergoing parathyroidectomy had PTH levels measured on the Analyzer and main laboratory platforms, either Roche or Abbott. The Miami criterion of a 50% drop in PTH concentration was used to define biochemical cure during surgery, and normal postoperative calcium level as cure of primary hyperparathyroidism. Measurements on the Analyzer were done by laboratory staff in London and nurses in Stuttgart. The Pearson coefficient (R) and Wilcoxon test were used for statistical analysis. RESULTS: Some 234 patients (55 male, 179 female) with a median age of 58.5 (age full range 15-88) years underwent parathyroidectomy (195 minimally invasive, 38 bilateral neck exploration, 1 thoracoscopic; 12 conversions) for primary hyperparathyroidism between November 2021 and July 2022. Primary hyperparathyroidism was cured in 225 patients (96.2%). The sensitivity, specificity, and overall accuracy of the Analyzer assay in predicting biochemical cure were 83.9, 100, and 84.8% in phase 1; 91.2, 100, and 91.3% in phase 2; and 98.6, 100, and 98.6% in phase 3. There were no false-positive results (positive predictive value 100%). Correlations between Analyzer measurements and those obtained using the Roche device were very strong (R = 0.98, P < 0.001 in phase 1; R = 0.92, P < 0.001 in phase 2; R = 0.94, P < 0.001 in phase 3), and correlations for Analyzer readings versus those from the Abbott platform were strong (R = 0.82, P < 0.001; R = 0.89, P < 0.001; R = 0.91, P < 0.001). The Analyzer showed continued good mechanical performance, with stable and repeatable operations (calibrations, quality controls). Introducing a stricter sampling protocol and improvements in the clot-detecting system led to a decrease in the number of clotted samples and false-negative results. Outcomes were not affected by measurements performed either by nurses or laboratory staff. CONCLUSION: Intraoperative PTH monitoring during parathyroid surgery can be done accurately, simply, and quickly in whole blood using the Analyzer.
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Hyperparathyroidism, Primary , Monitoring, Intraoperative , Parathyroid Hormone , Parathyroidectomy , Humans , Middle Aged , Female , Parathyroid Hormone/blood , Male , Prospective Studies , Adult , Aged , Monitoring, Intraoperative/methods , Adolescent , Aged, 80 and over , Hyperparathyroidism, Primary/surgery , Hyperparathyroidism, Primary/blood , Hyperparathyroidism, Primary/diagnosis , Young AdultABSTRACT
What is the link between eye movements and sensory learning? Although some theories have argued for an automatic interaction between what we know and where we look that continuously modulates human information gathering behavior during both implicit and explicit learning, there exists limited experimental evidence supporting such an ongoing interplay. To address this issue, we used a visual statistical learning paradigm combined with a gaze-contingent stimulus presentation and manipulated the explicitness of the task to explore how learning and eye movements interact. During both implicit exploration and explicit visual learning of unknown composite visual scenes, spatial eye movement patterns systematically and gradually changed in accordance with the underlying statistical structure of the scenes. Moreover, the degree of change was directly correlated with the amount and type of knowledge the observers acquired. This suggests that eye movements are potential indicators of active learning, a process where long-term knowledge, current visual stimuli and an inherent tendency to reduce uncertainty about the visual environment jointly determine where we look.
Subject(s)
Eye Movements , Learning , Photic Stimulation , Humans , Eye Movements/physiology , Learning/physiology , Male , Young Adult , Female , Adult , Photic Stimulation/methods , Visual Perception/physiology , Fixation, Ocular/physiologyABSTRACT
INTRODUCTION: Immune checkpoint inhibitors (ICIs) are linked with various cutaneous side effects ranging from mild to life-threatening. Herein, we present a unique case of palmar-plantar erythrodysesthesia (PPE) in a patient treated with atezolizumab. CASE REPORT: A 72-year-old white man was diagnosed with Tumor, node, metastasis (TNM) stage IIIA lung adenocarcinoma in November 2022. He underwent right lower lobectomy and mediastinal lymphadenectomy followed by adjuvant cisplatin-pemetrexed. As of May 2023, he did not have any evidence of relapse. He then started switch maintenance therapy with atezolizumab. At 24 weeks, the patient developed erythematous palmar skin lesions, followed by blisters and peeling of both palms, which were associated with swelling and pain, consistent with grade 2 PPE. MANAGEMENT AND OUTCOME: Causality assessment between nivolumab and PPE via adverse drug reaction probability scale revealed a score of 5. Atezolizumab was continued, and he started on a cream consisting of trolamine and 75% water to palms twice daily. A follow-up visit 6 weeks later showed significant improvement in symptoms and appearance of palmar lesions. DISCUSSION: Cutaneous side effects are commonly seen with ICIs. PPE is a common dermatologic toxicity of certain tyrosine kinase inhibitors (TKIs). This effect has been previously reported with combination therapies consisting of an ICI plus a TKIs, but not with ICI monotherapy. Awareness of this potential side effect of ICIs would prevent unnecessary work-up, and lead to its prompt diagnosis and treatment.
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Airway hillocks are stratified epithelial structures of unknown function1. Hillocks persist for months and have a unique population of basal stem cells that express genes associated with barrier function and cell adhesion. Hillock basal stem cells continually replenish overlying squamous barrier cells. They exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium. Hillocks resist a remarkably broad spectrum of injuries, including toxins, infection, acid and physical injury because hillock squamous cells shield underlying hillock basal stem cells from injury. Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway, and eventually regenerate normal airway epithelium with each of its six component cell types. Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia2,3. Here we show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia. Finally, we identify human hillocks whose basal stem cells generate functional squamous barrier structures in culture. The existence of hillocks reframes our understanding of airway epithelial regeneration. Furthermore, we show that hillocks are one origin of 'squamous metaplasia', which is long thought to be a precursor of lung cancer.
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Cell Plasticity , Epithelial Cells , Regeneration , Respiratory Mucosa , Stem Cells , Animals , Female , Humans , Male , Mice , Epithelial Cells/cytology , Epithelial Cells/pathology , Metaplasia/etiology , Metaplasia/pathology , Respiratory Mucosa/cytology , Respiratory Mucosa/injuries , Respiratory Mucosa/pathology , Stem Cells/cytology , Tretinoin/metabolism , Tretinoin/pharmacology , Vitamin A/metabolism , Vitamin A/pharmacology , Lung Neoplasms/etiology , Lung Neoplasms/pathology , Mice, Inbred C57BLABSTRACT
Horizontal basal cells (HBCs) mediate olfactory epithelium (OE) regeneration following severe tissue injury. The dynamism of the post-injury environment is well illustrated by in silico modeling of RNA sequencing data that demonstrate an evolving HBC transcriptome. Unfortunately, spatiotemporally dynamic processes occurring within HBCs in situ remain poorly understood. Here, we show that HBCs at 24 h post-OE injury spatially redistribute a constellation of proteins, which, in turn, helped to nominate Rac1 as a regulator of HBC differentiation during OE regeneration. Using our primary culture model to activate HBCs pharmacologically, we demonstrate that concurrent Rac1 inhibition attenuates HBC differentiation potential. This in vitro functional impairment manifested in vivo as decreased HBC differentiation into olfactory sensory neurons following HBC-specific Rac1 conditional knockout. Taken together, our data potentiate the design of hyposmia-alleviating therapies and highlight aspects of in situ HBC spatiotemporal dynamics that deserve further investigation.
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Schizophrenia is a severe, chronic neuropsychiatric disorder characterized by symptoms that profoundly impact behavior, cognition, perception, and emotions, leading to a reduced quality of life and physical impairment. Given the complexity of schizophrenia, there is a pressing need for clinical markers and tools to predict its course, enhance disease staging, facilitate early intervention, improve differential diagnosis, and tailor individualized treatment approaches. Previous studies focused on the relationship between neurological soft signs (NSS) and factors such as age, illness duration, and symptomatology, indicating NSS as state markers improving in parallel with psychotic symptom remission or predicting treatment resistance. However, there is a lack of consensus on NSS assessment tools, hindering routine clinical monitoring despite diagnostic and prognostic potential. The present longitudinal study involved 81 psychiatric inpatients diagnosed with schizophrenia. Patients were assessed at three time points: baseline, 1 month, and 6 months. The examination included the use of scales to evaluate psychotic and neurological symptoms, as well as the identification of adverse extrapyramidal reactions caused by neuroleptic treatment. The progression of NSS was correlated to both the symptomatology and the sociodemographic data of the patients. The main findings from the present investigation revealed a statistical correlation between NSS and psychopathological symptoms, especially with negative symptoms of schizophrenia. However, it is important to note that neuroleptic side effects only had a limited impact on NSS. Therefore, instead of being linked to extrapyramidal symptoms caused by neuroleptics, NSS appears to be more frequently related with symptoms of schizophrenia. Our findings provide further support for their strong association with the course of schizophrenia, independent of treatment side effects, thus emphasizing their potential as reliable assessment tools in both research and clinical settings.
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OBJECTIVES: Olfactory habituation is a transient decrease in olfactory sensitivity caused by prolonged odor exposure, aiding in the discernment of new olfactory stimuli against the background. We explored the impact of subclinical olfactory impairment on odor habituation using age as a proxy. METHODS: Before the actual experiment, the individual olfactory threshold for the rose-like odorant phenylethyl alcohol (PEA) was assessed separately for the left and right nostril using the "Sniffin' Sticks" test, and ratings for odor intensity and pleasantness were collected. After applying a nasal clip continuously delivering PEA odor to one nostril for 10 min and 2 h, respectively, threshold, intensity, and pleasantness were reassessed immediately after clip removal. RESULTS: In the group of 80 participants (younger adults-mean age 27.7 ± 4.5 years; older adults-mean age 61.5 ± 4.7 years), olfactory thresholds were already significantly elevated after just 10 min, and this habituation was even more pronounced after 2 h. This effect could be observed bilaterally even though significantly more distinct on the exposed side. Older participants generally exhibited a more pronounced habituation on the exposed side after 2 h compared to the younger participants. CONCLUSION: The results indicate that older people experience more notable habituation after extended exposure to odors. This is most likely due to the compromised olfactory function in age. Although older and younger subjects scored in the normosmic range when tested with standardized olfactory tests, the stress on the system after exposure to an odor clearly revealed the lower functionality of the aging sense of smell. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3765-3768, 2024.
Subject(s)
Habituation, Psychophysiologic , Odorants , Sensory Thresholds , Smell , Humans , Adult , Habituation, Psychophysiologic/physiology , Male , Female , Middle Aged , Sensory Thresholds/physiology , Aged , Smell/physiology , Age Factors , Young Adult , Olfaction Disorders/physiopathology , Olfaction Disorders/etiology , Aging/physiologyABSTRACT
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL-5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries, and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals, and possible therapy breaks as well as discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.
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We show that a recently-derived model for the propagation of nonlinear waves in the atmosphere admits undular bores as travelling-wave solutions. These solutions represent waves consisting of a damped oscillation behind a front that is preceded by a uniform breeze-type flow. The generation of such wave profiles requires a jump in the heat source across the leading front of the wave, a feature that is consistent with observations.
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STUDY OBJECTIVES: Hypoglossal nerve stimulation is an established therapy for sleep apnea syndrome. Whether or not this therapy on snoring and nighttime noise exposure is effective and how strong this effect may be has not been objectively investigated thus far and was the aim of this study. METHODS: In 15 participants (14 males; age: 30-72 years; mean: 51.7 years), polysomnography and acoustic measurements were performed before and after hypoglossal nerve stimulation. RESULTS: The therapy led to a significant improvement in sleep apnea (apnea-hypopnea index from 35.8 events/h to 11.2 events/h, P < .001). Acoustic parameters showed a highly significant reduction in the average sound pressure level (42.9 db[A] to 36.4 db[A], P < .001), averaged sound energy, A-weighted (LAeq; 33.1 db[A] to 28.7 db[A], P < .001), snoring index (1,068 to 506, P < .001), percentage snoring time (29.7-14.1%, P < .001), and psychoacoustic snore score, the latter being a measure of annoyance due to snoring (47.9 to 24.5, P < .001). CONCLUSIONS: This study was able to show for the first time by means of objective acoustic and psychoacoustic parameters that hypoglossal nerve stimulation can not only cause a significant improvement in sleep apnea but also has a positive effect on snoring and thus noise annoyance experienced by the bed partner. CLINICAL TRIAL REGISTRATION: Registry: German Clinical Trials Register; Name: Effect of Hypoglossal Nerve Stimulation on Snoring: An Evaluation Using Objective Acoustic Parameters; URL: https://drks.de/search/de/trial/DRKS00032354; Identifier: DRKS00032354. CITATION: Fischer R, Vielsmeier V, Kuehnel TS, et al. Effect of hypoglossal nerve stimulation on snoring: an evaluation using objective acoustic parameters. J Clin Sleep Med. 2024;20(3):363-370.
Subject(s)
Sleep Apnea Syndromes , Snoring , Adult , Aged , Humans , Male , Middle Aged , Acoustics , Hypoglossal Nerve/physiology , Polysomnography , Snoring/therapy , FemaleABSTRACT
Normative and descriptive models have long vied to explain and predict human risky choices, such as those between goods or gambles. A recent study reported the discovery of a new, more accurate model of human decision-making by training neural networks on a new online large-scale dataset, choices13k. Here we systematically analyse the relationships between several models and datasets using machine-learning methods and find evidence for dataset bias. Because participants' choices in stochastically dominated gambles were consistently skewed towards equipreference in the choices13k dataset, we hypothesized that this reflected increased decision noise. Indeed, a probabilistic generative model adding structured decision noise to a neural network trained on data from a laboratory study transferred best, that is, outperformed all models apart from those trained on choices13k. We conclude that a careful combination of theory and data analysis is still required to understand the complex interactions of machine-learning models and data of human risky choices.
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Decision Making , Machine Learning , Humans , Neural Networks, Computer , Risk-Taking , Datasets as Topic , Models, Psychological , Choice Behavior , Adult , BiasABSTRACT
People can use the constant target-heading (CTH) strategy or the constant bearing (CB) strategy to guide their locomotor interception. But it is still unclear whether people can learn new interception behavior. Here, we investigated how people learn to adjust their steering to intercept targets faster. Participants steered a car to intercept a moving target in a virtual environment similar to a natural open field. Their baseline interceptions were better accounted for by the CTH strategy. After five learning sessions across multiple days, in which participants received feedback about their interception durations, they adopted a two-stage control: a quick initial burst of turning accompanied by an increase of the target-heading angle during early interception was followed by significantly less turning with small changes in target-heading angle during late interception. The target's bearing angle did not only show this two-stage pattern but also changed comparatively little during late interception, leaving it unclear which strategy participants had adopted. In a following test session, the two-stage pattern of participants' turning adjustment and the target-heading angle transferred to new target conditions and a new environment without visual information about an allocentric reference frame, which should preclude participants from using the CB strategy. Indeed, the pattern of the target's bearing angle did not transfer to all the new conditions. These results suggest that participants learned a two-stage control for faster interception: they learned to quickly increase the target-heading angle during early interception and subsequently follow the CTH strategy during late interception.
Subject(s)
Motion Perception , Psychomotor Performance , Humans , Learning , NonoxynolABSTRACT
Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent the formation of circular networks and proliferation of CD31+ endothelial AVM cells. Furthermore, the effect of thalidomide and bevacizumab on stretched endothelial AVM cells was evaluated. In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. Thalidomide and bevacizumab reduced endothelial AVM cell proliferation. Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. With promising in vitro results, bevacizumab was used to treat three patients with unresectable AVMs or to prevent regrowth after incomplete resection. Bevacizumab controlled bleeding, pulsation, and pain over the follow up of eight months with no patient-reported side effects. Overall, mechanical stress increases VEGF expression in the microenvironment of AVM cells. The monoclonal VEGF antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. The clinical application of bevacizumab in AVM treatment demonstrates effective symptom control with no side effects.
Subject(s)
Arteriovenous Malformations , Endothelial Cells , Humans , Endothelial Cells/metabolism , Vascular Endothelial Growth Factor A/metabolism , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Bevacizumab/metabolism , Thalidomide/metabolism , Arteriovenous Malformations/genetics , Pain/metabolismABSTRACT
INTRODUCTION: Autoimmune encephalitis is a rare immune-related adverse event of PD-1 inhibitors, nivolumab and pembrolizumab. Autoimmune hypophysitis can also be seen with the use of these agents. The relationship between these two phenomena is currently unknown. CASE REPORT: We describe a 79-year-old man with anterior scalp melanoma who received adjuvant nivolumab therapy. Sixteen weeks after the completion of nivolumab therapy, the patient presented to the hospital with altered mental status, anterograde amnesia, and symptoms of nausea and vomiting. The patient's encephalopathy was associated with confabulations. Workup identified increased CSF protein without increased cellularity, along with decreased serum cortisol and ACTH levels. This was consistent with encephalitis and central adrenal insufficiency. MANAGEMENT AND OUTCOME: The patient had a robust clinical response to steroids, with resolution of mental status changes and normalization of blood pressure. He continues to receive maintenance steroid therapy without any further symptoms six months later. CONCLUSIONS: We report herein a unique case of encephalopathy in the setting of nivolumab use for the treatment of melanoma. The condition resembled Korsakoff psychosis seen in the setting of alcoholism and was associated with central adrenal insufficiency. A prompt response to steroids was both diagnostic and therapeutic in our case, suggesting the resolution of autoimmune phenomena related to nivolumab.
Subject(s)
Adrenal Insufficiency , Encephalitis , Korsakoff Syndrome , Melanoma , Male , Humans , Aged , Nivolumab/adverse effects , Melanoma/drug therapy , Encephalitis/chemically induced , Adrenal Insufficiency/chemically induced , Korsakoff Syndrome/chemically induced , Steroids/therapeutic useABSTRACT
Purpose: To compare combined cardiac fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/MRI with standard-of-care evaluation using cardiac MRI, 18F-FDG PET/CT, and SPECT perfusion imaging in suspected cardiac sarcoidosis (CS) with respect to radiation dose, imaging duration, and diagnostic test performance. Materials and Methods: Consecutive patients with suspected CS undergoing clinical evaluation with cardiac 18F-FDG PET/CT and gated rest technetium 99m sestamibi SPECT perfusion imaging were prospectively recruited between November 2017 and May 2021 for parallel assessment with combined cardiac 18F-FDG PET/MRI on the same day (ClinicalTrials.gov identifier, NCT03356756). Total effective radiation dose and imaging duration were compared between approaches (combined cardiac PET/MRI vs separate cardiac MRI, PET/CT, and SPECT). MRI findings were initially interpreted without PET data, and then PET and late gadolinium enhancement images were fused and interpreted together. Final diagnosis of CS was established using Japanese Ministry of Health and Welfare guidelines. Results: Forty participants (mean age, 54 years ± 14 [SD]; 26 [65%] male participants) were included, 14 (35%) with a final diagnosis of CS. Compared with separate cardiac MRI, PET/CT, and SPECT perfusion imaging, combined cardiac PET/MRI had 52% lower total radiation dose (8.0 mSv ± 1.2 vs 16.8 mSv ± 1.6, P < .001) and 43% lower total imaging duration (122 minutes ± 15 vs 214 minutes ± 26, P < .001). Combined PET/MRI had the highest area under the curve for diagnosis of CS (0.84) with 96% specificity and 71% sensitivity for colocalized FDG uptake and late gadolinium enhancement in a pattern typical for CS. Conclusion: In the evaluation of suspected CS, combined cardiac 18F-FDG PET/MRI had a lower radiation dose, shorter imaging duration, and higher diagnostic performance compared with standard-of-care imaging.Clinical trial registration no. NCT03356756Keywords: Cardiac Sarcoidosis, 18F-FDG PET/MRI, 18F-FDG PET/CT, SPECT Perfusion Imaging, Cardiac MRI, Standard-of-Care Imaging Supplemental material is available for this article. © RSNA, 2023.
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Background: Endometriosis is a chronic inflammatory oestrogen-dependent disease. It is characterised by elevated inflammatory markers in the peritoneal milieu with subsequent adhesiogenesis. Nowadays, excisional, and ablative surgeries are considered the main treatment of endometriosis, and adhesiolysis is being performed almost routinely during these procedures. Postoperative adhesion formation is a significant concern for many surgeons, especially as endometriosis patients are assumed to be predisposed to adhesiogenesis. In order to minimise adhesiogenesis after endometriosis surgery, the usage of different barrier methods have been discussed in the literature. Recent studies aim to investigate the effect of potato starch preparations on adhesion formation in endometriosis patients. Objectives: We aim to describe the findings of a second-look laparoscopy on patients who received a starch-based anti-adhesive agent. Materials and Methods: We present a retrospective case series that included the medical, surgical, and histopathologic data of three patients. Main outcome measures: Intraperitoneal adhesion formation and peritoneal inflammation. Results: All three patients had de-novo adhesions during the second-look laparoscopy. Pathological examination revealed noncaseating granulomatosis of the peritoneum in all patients. Conclusion: The use of potato starch-based agents as a peritoneal adhesion prophylaxis in laparoscopic endometriosis surgery could lead to granulomatous peritoneal inflammation. Correct application by avoiding powder remnants through complete rinsing and transformation to gel seems to be an important factor to avoid this adverse effect. What is new?: We aim to highlight that potato starch-based anti-adhesive agents similar to the one used in this study could be a cause of adhesiogenesis and peritoneal inflammation.