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The optimal frequency and timing of laboratory monitoring during isotretinoin treatment remains controversial. We aimed to investigate the frequency, timing, and severity of abnormal results during isotretinoin for acne. We conducted a retrospective cohort study comprising 444 acne patients prescribed isotretinoin at Boston Medical Center from 2004 to 2017; these patients had at least one available baseline laboratory result. We categorized patients into two groups: group A (normal values at baseline and during the first 2 months of isotretinoin therapy) and group B (abnormal values at baseline or during the first 2 months of isotretinoin therapy) and assessed the laboratory values after 2 months. The frequency of abnormal results for triglycerides, cholesterol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) after 2 months for patients in group A was 21.1%, 13.6%, 8.8%, and 6.0%, respectively, with very rare grade 2 (moderate) or higher abnormalities. In contrast, the frequency of abnormal results for patients in group B for triglycerides, cholesterol, AST, and ALT was higher at 67.9%, 88.0%, 40.0%, and 25.0%, respectively (P < 0.05, except for ALT). No patient developed higher than grade 1 (mild) complete blood count (CBC) abnormality. This study proposed that healthy patients with normal results at baseline and during the first 2 months of isotretinoin therapy might not need routine monitoring after month 2 of medication. Routine monitoring of CBC is not necessary.
Subject(s)
Acne Vulgaris , Alanine Transaminase , Aspartate Aminotransferases , Dermatologic Agents , Isotretinoin , Humans , Isotretinoin/therapeutic use , Isotretinoin/adverse effects , Isotretinoin/administration & dosage , Acne Vulgaris/drug therapy , Retrospective Studies , Male , Dermatologic Agents/therapeutic use , Dermatologic Agents/administration & dosage , Dermatologic Agents/adverse effects , Female , Alanine Transaminase/blood , Young Adult , Aspartate Aminotransferases/blood , Adolescent , Adult , Triglycerides/blood , Cholesterol/blood , Time Factors , Drug Monitoring/methodsABSTRACT
BACKGROUND: Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including GBA1 and LRRK2. OBJECTIVES: Our goal was to investigate the effects of genetic variants on risk and time to LID. METHODS: We performed a genome-wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores (PRS) including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1612 PD patients with and 3175 without LID. RESULTS: We found that GBA1 variants were associated with LID risk (odds ratio [OR] = 1.65; 95% confidence interval [CI], 1.21-2.26; P = 0.0017) and LRRK2 variants with reduced time to LID onset (hazard ratio [HR] = 1.42; 95% CI, 1.09-1.84; P = 0.0098). The fourth quartile of the PD PRS was associated with increased LID risk (ORfourth_quartile = 1.27; 95% CI, 1.03-1.56; P = 0.0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HRthird_quartile = 1.38; 95% CI, 1.07-1.79; P = 0.0128; HRfourth_quartile = 1.38; 95% CI = 1.06-1.78; P = 0.0147). CONCLUSIONS: This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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We present a challenging clinical case of a 68-year-old female kidney transplant recipient who had a complicated posttransplant course marked by borderline T-cell-mediated rejection and BK virus nephropathy. The treatment for borderline rejection with steroids resulted in overimmunosuppression, and the patient acquired cytomegalovirus infection manifesting as colitis and SARS-CoV-2 infection. This progressed rapidly to collapsing glomerulopathy and allograft failure. This study also highlights the challenges in surveillance with donor-derived cell-free DNA in the setting of allograft injury by multiple viral infections.
Subject(s)
BK Virus , COVID-19 , Cytomegalovirus Infections , Graft Rejection , Kidney Transplantation , Polyomavirus Infections , Tumor Virus Infections , Humans , Female , COVID-19/complications , COVID-19/immunology , COVID-19/diagnosis , Aged , Kidney Transplantation/adverse effects , Polyomavirus Infections/immunology , Polyomavirus Infections/virology , Polyomavirus Infections/diagnosis , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/drug therapy , Graft Rejection/immunology , Graft Rejection/virology , BK Virus/pathogenicity , BK Virus/immunology , Tumor Virus Infections/immunology , Tumor Virus Infections/virology , Tumor Virus Infections/diagnosis , Disease Progression , Treatment Outcome , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , CoinfectionABSTRACT
Lichens are remarkable and classic examples of symbiotic organisms that have fascinated scientists for centuries. Yet, it has only been for a couple of decades that significant advances have focused on the diversity of their green algal and/or cyanobacterial photobionts. Cyanolichens, which contain cyanobacteria as their photosynthetic partner, include up to 10% of all known lichens and, as such, studies on their cyanobionts are much rarer compared to their green algal counterparts. For the unicellular cyanobionts, i.e. cyanobacteria that do not form filaments, these studies are even scarcer. Nonetheless, these currently include at least 10 different genera in the cosmopolitan lichen order Lichinales. An international consortium (International Network of CyanoBionts; INCb) will tackle this lack of knowledge. In this article, we discuss the status of current unicellular cyanobiont research, compare the taxonomic resolution of photobionts from cyanolichens with those of green algal lichens (chlorolichens), and give a roadmap of research on how to recondition the underestimated fraction of symbiotic unicellular cyanobacteria in lichens.
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PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but have the greatest potential impact for improving patient care when the surgeon has limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in OPSCC patients. PATIENTS AND METHODS: 12 consecutive patients with OPSCC were enrolled as part of a non-randomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. RESULTS: Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. CONCLUSIONS: Results from this OPSCC patient cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.
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Introduction: Atypical hemolytic uremic syndrome (aHUS) is a complement system (CS)-mediated ultrarare disease that manifests as thrombotic microangiopathy (TMA) with preferential small kidney vessels involvement. Transient CS activation is also observed in secondary TMA or in patients at risk of developing aHUS. There is no gold standard test to monitor disease activity; however, the ex vivo C5b-9 deposition test seems to be a good approach. Methods: We assessed the C5b-9 deposition induced by serum samples of patients with aHUS (n = 8) and with TMA associated with kidney (n = 2), lung (n = 1) or hematopoietic stem cell (HSC) transplantation (HSCT, n = 2) during the acute phase of the disease or in remission. As control for transplant-associated TMA (TA-TMA), we analyzed samples of clinically stable kidney and HSC-transplanted patients without signs of TMA. In addition, we studied 1 child with genetic risk of aHUS during an acute infection. Results: In the acute disease phase or in patients with disease activity despite C5 blockade, a significant increase of C5b-9 deposition was detected. In all patients with clinical response to C5 blockade but one, levels of C5b-9 deposition were within the normal range. Finally, we detected increased C5b-9 deposition levels in an asymptomatic child with genetic risk of aHUS when a concomitant otitis episode was ongoing. Conclusion: The ex vivo C5b-9 deposition test is an auspicious tool to monitor CS activity in aHUS and TA-TMA. In addition, we demonstrate that the test may be useful to detect subclinical increase of CS activity, which expands the spectrum of patients that would benefit from a better CS activity assessment.
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BACKGROUND: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD). OBJECTIVE: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL). PATIENTS AND METHODS: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL. RESULTS: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (ß = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (ß = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ-39SI. CONCLUSION: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.
Subject(s)
Antiparkinson Agents , Dyskinesia, Drug-Induced , Levodopa , Parkinson Disease , Quality of Life , Humans , Levodopa/adverse effects , Parkinson Disease/drug therapy , Male , Female , Middle Aged , Dyskinesia, Drug-Induced/epidemiology , Dyskinesia, Drug-Induced/etiology , Aged , Antiparkinson Agents/adverse effects , Follow-Up Studies , Severity of Illness IndexABSTRACT
INTRODUCTION: As our growing population demonstrates a significant increase in the incidence of thyroid cancer, so does patient access to their medical records. Poor health literacy and understanding of disease severity, underscores the importance of effective and accessible patient-doctor communication. No previous studies on patient understanding of thyroid pathology reports exist; therefore, we sought to characterize health literacy in this population. METHODS: Using a modified Delphi technique, a 12-question multiple-choice survey regarding common pathology terms with possible definitions for each term was synthesized and administered to patients in a high-volume endocrine surgery clinic. Survey results, patient demographics, history of prior thyroid procedure (biopsy or surgery), and self-reported health literacy were collected. Data analysis included t tests, chi-squared, and multivariable linear regression using R. RESULTS: The survey was completed by 54 patients (response rate: 69.8%). On univariate analysis, White race, previous thyroid procedure, and at least a high school level education were all more likely to score higher on the survey than their counterparts (P < 0.05). On multivariable logistic regression for predicting a higher survey score, only race (est: 2.48 [95% confidence interval: 1.01-3.96]) and higher educational attainment (est: 3.98 [95% confidence interval: 2.32-5.64]) remained predictive (P < 0.05). The remaining demographic groups (age, health literacy confidence, and previous thyroid procedure) did not show a statistically significant difference. CONCLUSIONS: Overall, terms on a thyroid pathology report are poorly understood by patients. This is exacerbated by non-White race and low educational attainment. There is a need for patient-facing pathology education.
Subject(s)
Health Literacy , Humans , Health Literacy/statistics & numerical data , Male , Female , Middle Aged , Adult , Aged , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Delphi Technique , Surveys and Questionnaires/statistics & numerical data , Physician-Patient Relations , Thyroid Gland/pathology , Thyroid Gland/surgery , Thyroid Diseases/pathology , Thyroid Diseases/surgeryABSTRACT
BACKGROUND: Several studies have suggested secreted frizzled-related protein 2 (SFRP2) gene as a potential clinical biomarker in colorectal cancer (CRC). However, its diagnostic role remains unclear. In this study, we aimed to investigate the significance of SFRP2 methylation levels in a large cohort of biological specimens (including blood, adipose and colonic tissues) from patients with CRC, thereby potentially identifying new biomarker utility. METHODS: We examined the expression (by qPCR) and methylation status (by 450 K DNA array and DNA pyrosequencing) of the SFRP2 gene in healthy participants (N = 110, aged as 53.7 (14.2), 48/62 males/females) and patients with CRC (N = 85, aged 67.7 (10.5), 61/24 males/females), across different biological tissues, and assessing its potential as a biomarker for CRC. Additionally, we investigated the effect of recombinant human SFRP2 (rhSFRP2) as a therapeutic target, on cell proliferation, migration, and the expression of key genes related to carcinogenesis and the Wnt pathway. RESULTS: Our findings revealed that SFRP2 promoter methylation in whole blood could predict cancer stage (I + II vs. III + IV) (AUC = 0.653), lymph node invasion (AUC = 0.692), and CRC recurrence (AUC = 0.699) in patients with CRC (all with p < 0.05). Furthermore, we observed a global hypomethylation of SFRP2 in tumors compared to the adjacent area (p < 0.001). This observation was validated in the TCGA-COAD and TCGA-READ cohorts, demonstrating overall hypermethylation (both with p < 0.001) and low expression (p < 0.001), as shown in publicly available scRNA-Seq data. Notably, neoadjuvant-treated CRC patients exhibited lower SFRP2 methylation levels compared to untreated patients (p < 0.05) and low promoter SFRP2 methylation in untreated patients was associated with poor overall survival (p < 0.05), when compared to high methylation. Finally, treatment with 5 µg of rhSFRP2 treatment in CRC cells (HCT116 cells) inhibited cell proliferation (p < 0.001) and migration (p < 0.05), and downregulated the expression of AXIN2 (p < 0.01), a gene involved in Wnt signaling pathway. CONCLUSIONS: These findings establish promoter methylation of the SFRP2 gene as a prognostic candidate in CRC when assessed in blood, and as a therapeutic prognostic candidate in tumors, potentially valuable in clinical practice. SFRP2 also emerges as a therapeutic option, providing new clinical and therapeutical avenues.
Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Gene Silencing , Membrane Proteins , Promoter Regions, Genetic , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Male , DNA Methylation/genetics , Membrane Proteins/genetics , Female , Middle Aged , Biomarkers, Tumor/genetics , Aged , Promoter Regions, Genetic/genetics , Cell Proliferation/genetics , Cell Movement/genetics , Wnt Signaling Pathway/genetics , Cell Line, TumorABSTRACT
Leptomeningeal disease (LMD) is a devastating sequela of many cancers, with an extremely poor prognosis. Barriers to improving outcomes are related to the inability of many traditional therapies to effectively reach the cerebrospinal fluid (CSF) space within the central nervous system. Liquorpheresis is an emerging treatment modality specific to CSF diseases, the primary mechanism of action of which is direct targeted filtration of CSF content by neurosurgical access. In this review, we highlight the principles of liquorpheresis and detail how LMD can be amenable to this treatment. Further, we summarize the current in vitro and in vivo evidence supporting liquorpheresis as a feasible method to treat LMD and other central nervous system diseases as well as describe its conceivable limitations.
Subject(s)
Meningeal Neoplasms , Humans , Meningeal Neoplasms/therapy , AnimalsABSTRACT
Area A5 is a noradrenergic cell group in the brain stem characterised by its important role in triggering sympathetic activity, exerting a profound influence on the sympathetic outflow, which is instrumental in the modulation of cardiovascular functions, stress responses and various other physiological processes that are crucial for adaptation and survival mechanisms. Understanding the role of area A5, therefore, not only provides insights into the basic functioning of the sympathetic nervous system but also sheds light on the neuronal basis of a number of autonomic responses. In this review, we look deeper into the specifics of area A5, exploring its anatomical connections, its neurochemical properties and the mechanisms by which it influences sympathetic nervous system activity and cardiorespiratory regulation and, thus, contributes to the overall dynamics of the autonomic function in regulating body homeostasis.
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Background: Foley catheters have been subject to limited development in the last few decades. They fulfil their basic function of draining urine from the bladder but cause other associated problems. T-Control is a new silicone Foley catheter with an integrated fluid control valve whose design aims to reduce the risks associated with bladder catheterization by a multifactorial approach. The general purpose of this study is to determine the effectiveness, comfort, and experience of the patient catheterized with T-Control® compared with patients with a conventional Foley catheter. Study Design: This trial is a mixed-method study comprising a two-arm, pilot comparative study with random allocation to T-Control catheter or traditional Foley catheter in patients with long-term catheterization and a study with qualitative methodology, through discussion groups. Endpoints: The comfort and acceptability of the T-Control® device (qualitative) and the quality of life related to self-perceived health (quantitative) will be analysed as primary endpoints. As secondary endpoints, the following will be analysed: magnitude and rate of infections (symptomatic and asymptomatic); days free of infection; indication of associated antibiotic treatments; determination of biofilm; number of catheter-related adverse events; use of each type of catheterization's healthcare resources; and level of satisfaction and workload of health professionals. Patients and Methods: Eligible patients are male and female adults aged ≥18 years, who require a change of long-term bladder catheter. The estimated sample size is 50 patients. Patient follow-up includes both the time of catheter insertion and its removal or change 4 weeks later, plus the time until the discussion groups take place.
ABSTRACT
Background: Foley catheters have been subject to limited development in the last few decades. They fulfil their basic function of draining urine from the bladder but cause other associated problems. T-Control is a new silicone Foley catheter with an integrated fluid control valve whose design aims to reduce the risks associated with bladder catheterisation by a multifactorial approach. The general purpose of this study is to evaluate the effectiveness and cost-effectiveness of the T-Control catheter versus the Foley-type catheter in patients with Acute Urine Retention (AUR). Study design: This is a pragmatic, open, multicentre, controlled clinical trial with random allocation to the T-Control catheter or a conventional Foley-type catheter in patients with AUR. Endpoints: The magnitude of infections will be analysed as a primary endpoint. While as secondary endpoint, the following will be analysed: rate of symptomatic and asymptomatic infections; days free of infection; quality of life-related to self-perceived health; indication of associated antibiotic treatments; determination of biofilm; number of catheter-related adverse events; use of each type of catheterisation's healthcare resources; level of satisfaction and workload of health professionals and acceptability of the T-Control device as well as the patient experience. Patients and methods: Eligible patients are male adults aged ≥50 years, with AUR and with an indication of bladder catheterisation for at least 2 weeks. The estimated sample size is 50 patients. Patient follow-up includes both the time of catheter insertion and its removal or change 2 weeks later, plus 2 weeks after this time when the patient will be called for an in-depth interview.
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In humans, speech is a complex process that requires the coordinated involvement of various components of the phonatory system, which are monitored by the central nervous system. The larynx in particular plays a crucial role, as it enables the vocal folds to meet and converts the exhaled air from our lungs into audible sounds. Voice production requires precise and sustained exhalation, which generates an air pressure/flow that creates the pressure in the glottis required for voice production. Voluntary vocal production begins in the laryngeal motor cortex (LMC), a structure found in all mammals, although the specific location in the cortex varies in humans. The LMC interfaces with various structures of the central autonomic network associated with cardiorespiratory regulation to allow the perfect coordination between breathing and vocalization. The main subcortical structure involved in this relationship is the mesencephalic periaqueductal grey matter (PAG). The PAG is the perfect link to the autonomic pontomedullary structures such as the parabrachial complex (PBc), the Kölliker-Fuse nucleus (KF), the nucleus tractus solitarius (NTS), and the nucleus retroambiguus (nRA), which modulate cardiovascular autonomic function activity in the vasomotor centers and respiratory activity at the level of the generators of the laryngeal-respiratory motor patterns that are essential for vocalization. These cores of autonomic structures are not only involved in the generation and modulation of cardiorespiratory responses to various stressors but also help to shape the cardiorespiratory motor patterns that are important for vocal production. Clinical studies show increased activity in the central circuits responsible for vocalization in certain speech disorders, such as spasmodic dysphonia because of laryngeal dystonia.
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The NF-κB pathway is involved in the pathogenesis of neurological disorders that have inflammation as a hallmark, including Parkinson's disease (PD). Our objective was to determine whether common functional variants in the NFKB1, NFKBIA and NFKBIZ genes were associated with the risk of PD. A total of 532 Spanish PD cases (61% male; 38% early-onset, ≤ 55 years) and 300 population controls (50% ≤55 years) were genotyped for the NFKB1 rs28362491 and rs7667496, NFKBIA rs696, and NFKBIZ rs1398608 polymorphisms. We compared allele and genotype frequencies between early and late-onset, male and female, and patient's vs. controls. We found that the two NFKB1 alleles were significantly associated with PD in our population (p = 0.01; total patients vs. controls), without difference between Early and Late onset patients. The frequencies of the NFKB1 variants significantly differ between male and female patients. Compared to controls, male patients showed a significantly higher frequency of rs28362491 II (p = 0.02, OR = 1.52, 95%CI = 1.10-2.08) and rs28362491 C (p = 0.003, OR = 1.62, 95%CI = 1.18-2.22). The two NFKB1 variants were in strong linkage disequilibrium and the I-C haplotype was significantly associated with the risk of PD among male (p = 0.002). In conclusion, common variants in the NF-kB genes were associated with the risk of developing PD in our population, with significant differences between male and female. These results encourage further studies to determine the involvement of the NF-kB components in the pathogenesis of Parkinson´s disease.
Subject(s)
Genetic Predisposition to Disease , NF-kappa B p50 Subunit , Parkinson Disease , Humans , Male , Parkinson Disease/genetics , Parkinson Disease/epidemiology , Female , NF-kappa B p50 Subunit/genetics , Middle Aged , Genetic Predisposition to Disease/genetics , Aged , Adult , Polymorphism, Single Nucleotide , Sex Factors , Genotype , Spain/epidemiology , Gene Frequency , Genetic Association StudiesABSTRACT
BACKGROUND: Open respiratory secretion suctioning with a catheter causes pain and tracheobronchial mucosal injury in intubated patients. The goal of mechanical insufflation-exsufflation (MI-E) is to move secretions proximally and noninvasively by generating a high peak expiratory air flow. Nebulized hypertonic saline with hyaluronic acid (HS-HA) may facilitate suctioning by hydration. We assessed the safety and tolerance of a single session of airway clearance with MI-E and HS-HA in critically ill intubated patients. METHODS: Adults with a cuffed artificial airway were randomized to (1) open suctioning, (2) open suctioning after HS-HA, (3) MI-E, or (4) MI-E with HS-HA. Adverse events, pain and sedation/agitation scores, and respiratory and hemodynamic variables were collected before, during, and 5-min and 60-min post intervention. RESULTS: One-hundred twenty subjects were enrolled and completed the study. Median (interquartile range [IQR]) Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22 (16-28); median (IQR) age was 69.0 (57.0-75.7) y, and 90 (75%) were male. Baseline respiratory and hemodynamic variables were comparable. Adverse events occurred in 30 subjects (25%), with no between-group differences. Behavioral pain equivalents and Richmond Agitation-Sedation Scale were higher during suctioning in groups 1 (P < .001) and 2 (P < .001). Independent predictive variables for higher pain and agitation/sedation scores were study groups 1 and 2 and simultaneous analgosedation, respectively. Noradrenaline infusion rates were lower at 60 min in groups 2 and 4. PaO2 /FIO2 had decreased at 5 min after open suctioning in group 1 and increased at 60 min in group 3. CONCLUSIONS: We observed no difference in adverse events. MI-E avoids pain and agitation.
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Previous studies have suggested a relationship between the number of CAG triplet repeats in the HTT gene and neurodegenerative diseases not related to Huntington's disease (HD). This study seeks to investigate whether the number of CAG repeats of HTT is associated with the risk of developing certain tauopathies and its influence as a modulator of the clinical and neuropathological phenotype. Additionally, it aims to evaluate the potential of polyglutamine staining as a neuropathological screening. We genotyped the HTT gene CAG repeat number and APOE-â° isoforms in a cohort of patients with neuropathological diagnoses of tauopathies (n=588), including 34 corticobasal degeneration (CBD), 98 progressive supranuclear palsy (PSP) and 456 Alzheimer's disease (AD). Furthermore, we genotyped a control group of 1070 patients, of whom 44 were neuropathologic controls. We identified significant differences in the number of patients with pathological HTT expansions in the CBD group (2.7%) and PSP group (3.2%) compared to control subjects (0.2%). A significant increase in the size of the HTT CAG repeats was found in the AD compared to the control group, influenced by the presence of the Apoliprotein E (APOE)-â°4 isoform. Post-mortem assessments uncovered tauopathy pathology with positive polyglutamine aggregates, with a slight predominance in the neostriatum for PSP and CBD cases and somewhat greater limbic involvement in the AD case. Our results indicated a link between HTT CAG repeat expansion with other non-HD pathology, suggesting they could share common neurodegenerative pathways. These findings support that genetic or histological screening for HTT repeat expansions should be considered in tauopathies.
Subject(s)
Huntingtin Protein , Tauopathies , Humans , Male , Female , Aged , Tauopathies/genetics , Tauopathies/pathology , Middle Aged , Huntingtin Protein/genetics , Aged, 80 and over , Supranuclear Palsy, Progressive/genetics , Supranuclear Palsy, Progressive/pathology , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Trinucleotide Repeats/genetics , Brain/pathology , Trinucleotide Repeat Expansion/genetics , Genotype , Corticobasal Degeneration/genetics , Corticobasal Degeneration/pathology , PeptidesABSTRACT
Transoral laser microsurgery represents the primary surgical modality for early laryngeal cancers with oncologic outcomes equivalent to radiotherapy. Accurate tumor mapping and margin assessment can be difficult, however, particularly during piecemeal or ablative resections, and for tumors with a wider geographic footprint. Tumor-targeted fluorescence-guided surgery in patients with head and neck cancer has empirically improved tumor and margin identification; this case details, for the first time, a fluorescence-guided surgical resection of a T2N0M0 transglottic tumor using panitumumab-IRDye800, an epidermal growth factor receptor monoclonal antibody covalently linked to near-infrared (NIR) dye. Laryngoscope, 134:1837-1841, 2024.
Subject(s)
Carcinoma, Squamous Cell , Indoles , Laryngeal Neoplasms , Laser Therapy , Humans , Laryngeal Neoplasms/pathology , Panitumumab , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Microsurgery , Lasers , Glottis/surgery , Retrospective Studies , Neoplasm StagingABSTRACT
OBJECTIVE: To identify if targeted positron emission tomography (PET) imaging with radiolabeled antibodies can predict tumor growth rate and ultimate tumor size in a murine flank schwannoma model. STUDY DESIGN: Animal research study. METHODS: Rat schwannoma cells were cultured and implanted into 40 athymic nude mice. Once tumors reached 5 mm in diameter, 30 mice were injected with zirconium-89 labeled antibodies (HER2/Neu, vascular endothelial growth factor receptor 2 (VEGFR2), or IgG isotype). PET/CT was performed, and standardized uptake values (SUV) were recorded. Tumors were serially measured until mice were sacrificed per IACUC protocol. Statistical analysis was performed to measure correlations between SUV values, tumor size, and growth. RESULTS: Mean tumor sizes in mm3 on Day 0 were 144 ± 162 for anti-HER2/Neu, 212 ± 247 for anti-VEGFR2, and 172 ± 204 for IgG isotype groups respectively. Mean growth rates in mm3 /day were 531 ± 250 for HER2, 584 ± 188 for VEGFR2, and 416 ± 163 for the IgG isotype group. For both initial tumor size and growth rates, there was no significant difference between groups. There were significant correlations between maximum tumor volume and both the SUV max in the HER2 group (p = 0.0218, R2 = 0.5020), and we observed significant correlations between growth rate, and SUV values (p = 0.0156, R2 = 0.5394). Respectively, in the anti-VEGFR2 group, there were no significant correlations. CONCLUSION: In a murine schwannoma model, immunotargeted PET imaging with anti-HER2/Neu antibodies predicted tumor growth rate and final tumor size. Laryngoscope, 134:1372-1380, 2024.
Subject(s)
Neurilemmoma , Positron Emission Tomography Computed Tomography , Animals , Mice , Mice, Nude , Vascular Endothelial Growth Factor A , Positron-Emission Tomography/methods , Neurilemmoma/diagnostic imaging , Immunoglobulin GABSTRACT
BACKGROUND: Of the half a million cases of thyroid cancer diagnosed annually, 95% are differentiated thyroid cancers. Although clinical guidelines recommend surgical resection followed by radioactive iodine ablation, loss of sodium-iodine symporter expression causes up to 20% of differentiated thyroid cancers to become radioactive iodine refractory. For patients with radioactive iodine refractory disease, there is an urgent need for new diagnostic and therapeutic approaches. We evaluated the thyroid-stimulating hormone receptor as a potential target for imaging of differentiated thyroid cancer. METHODS: We immunostained tissue microarrays containing 52 Hurthle cell carcinomas to confirm thyroid-stimulating hormone receptor expression. We radiolabeled chelator deferoxamine conjugated to recombinant human thyroid-stimulating hormone analog superagonist TR1402 with 89Zr (t1/2 = 78.4 h, ß+ =22.7%) to produce [89Zr]Zr-TR1402. We performed in vitro uptake assays in high-thyroid-stimulating hormone receptor and low-thyroid-stimulating hormone receptor-expressing THJ529T and FTC133 thyroid cancer cell lines. We performed in vivo positron emission tomography/computed tomography and biodistribution studies in male athymic nude mice bearing thyroid-stimulating hormone receptor-positive THJ529T tumors. RESULTS: Immunohistochemical analysis revealed 62% of patients (27 primary and 5 recurrent) were thyroid-stimulating hormone receptor membranous immunostain positive. In vitro uptake of 1nM [89Zr]Zr-TR1402 was 38 ± 17% bound/mg in thyroid-stimulating hormone receptor-positive THJ529T thyroid cancer cell lines compared to 3.2 ± 0.5 in the low-expressing cell line (P < .01), with a similar difference seen in FTC133 cell lines (P < .0001). In vivo and biodistribution studies showed uptake of [89Zr]Zr-TR1402 in thyroid-stimulating hormone receptor-expressing tumors, with a mean percentage of injected dose/g of 1.9 ± 0.4 at 3 days post-injection. CONCLUSION: Our observation of thyroid-stimulating hormone receptor expression in tissue microarrays and [89Zr]Zr-TR1402 accumulation in thyroid-stimulating hormone receptor-positive thyroid cancer cells and tumors suggests thyroid-stimulating hormone receptor is a promising target for imaging of differentiated thyroid cancer.