Multisystem Comorbidities Research Articles

Bacterial Skin Infections in Hospitalized Patients with Bullous Pemphigoid.

To explore the features and risk factors of bacterial skin infections (BSIs) in hospitalized patients with bullous pemphigoid (BP). Records were retrospectively reviewed for 110 hospitalized patients with BP admitted to Peking University First Hospital between 2013 and 2019. Bacterial species and drug resistance were assessed, and then the underlying risk factors for BSIs were evaluated. Infections were present in 40% (44/110) of the patients. Staphylococcus aureus (72.7%, 32/44) was the most common bacterium, and it was highly resistant to penicillin (81.3%, 26/32), erythromycin (62.5%, 20/32), and clindamycin (56.3%, 18/32), but 100.0% sensitive to vancomycin and tigecycline. Coronary heart disease (P = .02; odds ratio [OR], 12.68), multisystem comorbidities (P = .02; OR, 3.67), hypoalbuminemia (P = .04; OR, 3.70), high levels of anti-BP180 antibodies (>112.4 U/mL; P = .003; OR, 6.43), and season (spring: reference; summer: P = .002; OR, 23.58; autumn: P = .02; OR, 12.19; winter: P = .02; OR, 13.19) were significantly associated with BSIs. Hospitalized patients with BP had a high incidence of BSIs, and those patients with underlying risk factors require careful management to prevent and control BSIs.

Rett syndrome: think outside the (skull) box.

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder characterized by neurodevelopmental regression between 6 and 18 months of life and associated with multi-system comorbidities. Caused mainly by pathogenic variants in the MECP2 (methyl CpG binding protein 2) gene, it is the second leading genetic cause of intellectual disability in girls after Down syndrome. RTT affects not only neurological function but also a wide array of non-neurological organs. RTT-related disorders involve abnormalities of the respiratory, cardiovascular, digestive, metabolic, skeletal, endocrine, muscular, and urinary systems and immune response. Here, we review the different aspects of RTT affecting the main peripheral groups of organs and sometimes occurring independently of nervous system defects.

Pediatric Liver Transplantation for Alagille Syndrome: Anesthetic Evaluation and Perioperative Management.

BackgroundAlagille syndrome (AGS) is an autosomal dominant hereditary disorder characterized by identifiable abnormalities in the liver, heart, face, skeleton, and eyes. Recently, liver transplantation (LT) has been proposed as a therapeutic strategy for patients with AGS complicated by end-stage liver disease, but clinical experience in performing anesthesia in LT for AGS is still scarce. We aimed to summarize our preliminary experience in the anesthetic management of LT for AGS in this study.Material/MethodsWe reviewed the cases of 11 patients with AGS who underwent LT from September 2017 to April 2019. Preoperative multi-system comorbidities, intraoperative details, and postoperative outcomes were retrospectively collected and summarized.ResultsCardiopulmonary abnormalities were common (81.8%) in AGS patients before LT, and the most frequent comorbidity was pulmonary artery stenosis. After careful anesthetic evaluation and perioperative management, all patients survived during the perioperative period without significant cardiovascular complications. However, there was an unexpectedly high prevalence of surgical complications and re-operations in AGS patients compared to biliary atresia recipients (54.5% vs. 22.4%, P=0.031; and 45.5% vs. 15.3%, P=0.028, respectively).ConclusionsPerioperative management of LT for AGS patients can be particularly challenging, requiring a full understanding of the pathophysiology, as well as a careful preoperative evaluation of the multi-system comorbidities. The high prevalence of postoperative surgical complications should be a matter of concern.

Consensus guidelines on managing Rett syndrome across the lifespan

BackgroundRett syndrome (RTT) is a severe neurodevelopmental disorder with complex medical comorbidities extending beyond the nervous system requiring the attention of health professionals. There is no peer-reviewed, consensus-based therapeutic guidance...

Children with Functional Nausea—Comorbidities outside the Gastrointestinal Tract

To detail common comorbidities and procedures performed to evaluate functional nausea in children. In total, 63 children age 7-18years seen in a tertiary care pediatric clinic who met Rome IV criteria for functional nausea prospectively completed an Intake Questionnaire, the Pediatric and Parent-Proxy PROMIS-25 Profile v 2.0, the Pediatric and Parent-Proxy Pediatric Sleep Disturbance-Short Form 4a, and the COMPASS 31 orthostatic intolerance scale to assess comorbidities. Medical records were reviewed for diagnostic tests performed to evaluate nausea and for additional comorbidities. Summary statistics were used to determine the most common comorbidities and diagnostic yield of the procedures. Intraclass correlation coefficients assessed agreement between parent and child reports on the PROMIS scales. Patients with functional nausea experienced multisystem comorbidities. A majority reported abdominal pain, headache, orthostatic intolerance, fatigue, disturbed sleep, anxiety, constipation, allergies, and vomiting. Agreement between parent-proxy and child report of symptoms on PROMIS scales was good to excellent (intraclass correlation coefficients=.78-.83; all P<.001). Patients underwent extensive diagnostic testing: 96 endoscopic procedures, 199 radiologic tests, and 4 cholecystectomies. Most of the procedures were not diagnostically informative. Children with functional nausea have comorbidities outside the gastrointestinal tract that warrant evaluation. Gastrointestinal diagnostic tests were of low-yield in identifying a cause. Understanding the relationship with comorbidities may provide insight into etiologies for the nausea and define clinical phenotypes to better tailor care.

Extracutaneous manifestations of adult psoriatic patients attending Dermatology Teaching Center in Slemani, Iraq

Background: Psoriasis is debilitating, albeit remained underdiagnosed and undertreated, disease typically known for its cutaneous manifestations. Recent evidence pointed towards multisystemic comorbidities that we aim to elucidate further in this study.Methods: A cross-sectional descriptive study was conducted in Dermatology Teaching Center in Slemani city from April to September 2019. One hundred dermatologist-confirmed psoriasis patients aged 18 years old and above were subjected to structured interview, physical examination and blood investigations to determine the presence of psoriasis extracutaneous manifestations.Results: There were a total of 100 patients with a mean age of 47.2 ± 15. Majority of the patients comprised of middle age group (42.0%), female (67.0%), with 10-20 years disease duration (36.0%). Only a few of them are currently smoking (16.0%) and consume alcohol (6.0%). Patients with extracutaneous involvement primarily had multiple (37.0%) as opposed to singular (24.0%). Metabolic syndrome was the most prevalent (30.0%) extracutaneous manifestation in this study.Conclusions: Extracutaneous manifestations of psoriasis were ubiquitous and often coexisted. Emerging progressive comorbidities prompted greater recognition and integrated multidisciplinary approach.

"The Overactive Pelvic Floor (OPF) and Sexual Dysfunction" Part 1: Pathophysiology of OPF and Its Impact on the Sexual Response.

Overactive pelvic floor (OPF) muscles are defined as muscles that do not relax, or may even contract, when relaxation is needed, for example, during micturition or defecation. Conditions associated with OPF are multifactorial and include multiple possible etiologies and symptom complexes. The complex interplay between biological and psychosocial elements can lead to the persistence of OPF symptoms along with psychological and emotional distress. (1) To review and contextualize, from a pathophysiologic perspective, the evidence for OPF, (2) to provide an overview of common clinical presentations and comorbidities of OPF, and (3) to discuss the effect of OPF on sexual function in men and women. Review of the updated literature on the pathophysiology of OPF was carried out. OPF-associated conditions were overviewed, with special emphasis on the impact on sexual function in men and women. Individuals with suspected OPF often present with a combination of gastrointestinal, gynecological, musculoskeletal, sexual, and urological comorbidities, mostly accompanied by psychoemotional distress. In both women and men, sexual function is significantly impaired by OPF and genitopelvic pain penetration disorders are often the primary manifestation of this condition. Women with OPF report less sexual desire, arousal, and satisfaction; more difficulty reaching orgasm; lower frequencies of intercourse; more negative attitudes toward sexuality; and more sexual distress than women without sexual pain. The most frequently reported sexual dysfunctions in men with OPF include erectile dysfunction, premature ejaculation, and ejaculatory pain. The complex pathophysiology of OPF involving multisystemic comorbidities and psychosocial factors emphasize the importance of a biopsychosocial assessment for guiding effective and personalized management. Padoa A, McLean L, Morin M, etal. "The Overactive Pelvic Floor (OPF) and Sexual Dysfunction" Part 1: Pathophysiology of OPF and Its Impact on the Sexual Response. Sex Med 2021;9:64-75.

Mast Cells in Patients with Hereditary α-Tryptasemia Promote HLA-DR Expression and a Th2-Polarizing Microenvironment in the Gastrointestinal Tract

Abstract Hereditary α-tryptasemia (HαT) is a recently identified, genetic disorder characterized by multisystem comorbidities resulting from increased monoallelic α-tryptase copy number (CN) at TPSAB1 (α-TPSAB1). Affected individuals frequently exhibit heterogeneous multisystem symptoms and comorbidities which negatively impact daily functioning and quality of life. In the cohorts examined thus far, functional dyspepsia and irritable bowel syndrome, were most frequently reported. However, the mechanism by which increased α-TPSAB1 CN produces GI disease is unknown. Tryptase is almost exclusively produced by mast cells (MC). In the gut, MC play important roles in immune responses, leukocyte recruitment, neuroimmune inflammation, and tissue repair. MC can also promote T-cell activation and polarization via cytokine secretion, co-stimulatory marker expression and MHC II antigen presentation. MCs also release exosomes, nanosized vesicles secreted by most cell types present in biological fluids such as blood, cerebrospinal fluid, and urine, which have a reported influence on T cell differentiation. In early experiments, we found increased numbers of GI MCs, activated T cells, and urinary exosomes in HαT patients compared to healthy donors. Thus, we evaluated MC surface antigen expression, exosome proteomics, and cytokine expression of exosome-treated T cells. We found increased HLA-DR and FcɛR1α expression in HαT-patient GI MCs, increased Th2 associated signaling proteins in HαT urinary exosomes, and elevated Th2 cytokine expression in HαT-exosome treated T cells. These results suggest that HαT GI morbidity involves aggravated MC hyperplasia and antigen presentation which promotes T cell activation and Th2 polarization.

A Systematic Network of Autism Primary Care Services (SYNAPSE): A Model of Coproduction for the Management of Autism Spectrum Disorder.

The prevalence of Autism Spectrum Disorder (ASD) is growing rapidly, affecting 1 in 59 children in the United States in 2018. Individuals with ASD currently receive fragmented care that threatens their health and well-being. Challenges of autism care include disconnections between the medical system and school supports, poor care coordination between primary care and specialists, and saturation of neuropsychiatry-based centers' capacity to care for the ASD population. ASD treatment also lacks of a coordinated system of care for patients' multi-system comorbidities. Families are calling for an ASD care delivery system to meet their needs and the needs of their children. To serve people with ASD and their medical and other providers, we propose a coordinated approach to care grounded in primary care. We call the model the "Systematic Network of Autism Primary Care Services (SYNAPSE)." We develop the model by applying the frameworks of "coproduction" of care and chronic disease management. In this Commentary we discuss the model's rationale, underpinnings, and the implications for clinical practice. We advance these ideas to align with policy makers' recognition of the importance of primary care for ASD, as reflected by the most recent Interagency Autism Coordinating Committee (IACC) meeting at the National Institute of Mental Health.

Practical Guidelines for Managing Patients With Psoriasis on Biologics: An Update.

The paradigm for treating inflammatory diseases has shifted dramatically in the past 10 to 20 years with the discovery of targeted therapeutics or "biologic" agents. Patients with rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis, and psoriasis, among others, are reaping the benefits of decades of bench to bedside research, allowing them to live more productive lives with less side effects than traditional systemic therapies. Despite these advances, many physicians unfamiliar with biologics are left to care for the basic needs of these patients and may be unaware of the multisystem comorbidities associated with psoriasis and the screening, monitoring, and other special considerations required of biologics patients. This can be overwhelming to primary care physicians and inadvertently expose patients to undue risks. The aim of this review is to provide a practical approach for all health care providers caring for patients with psoriasis being treated with biologics to facilitate communication with their treating dermatologist and ultimately provide patients with more comprehensive care.

The relationship between fear of movement, pain and fatigue severity, dyspnea level and comorbidities in patients with chronic obstructive pulmonary disease

Purpose: Dyspnea, sedentary lifestyle, and comorbid diseases may reduce the desire to engage in physical movement in chronic obstructive pulmonary disease (COPD). The aims of this study were to assess levels of kinesiophobia among stable COPD patients and evaluate the relationship between kinesiophobia and pain and fatigue severity, dyspnea level, and comorbidities in this patient group.Material and Methods: Thirty-one patients with moderate/severe COPD and thirty-one age- and sex-matched healthy controls participated in the study. All participants were assessed using Visual Analog Scale for pain severity, Fatigue Severity Scale, modified Medical Research Council Dyspnea Scale, Charlson Comorbidity Index, and Tampa Scale of Kinesiophobia.Results: Ninety-three percent of the patients with COPD had a high degree of kinesiophobia (Tampa Scale of Kinesiophobia score >37). The modified Medical Research Council Dyspnea Scale, Charlson Comorbidity Index, and Tampa Scale of Kinesiophobia scores of patients with COPD was significantly higher than those of healthy subjects (p < 0.001). Tampa Scale of Kinesiophobia score was significantly associated with modified Medical Research Council Dyspnea Scale score (r = 0.676, p < 0.001), Charlson Comorbidity Index score (r = 0.746, p < 0.001) and fatigue severity level (r = 0.524, p = 0.005).Conclusion: Most moderate/severe COPD patients express fear of movement. Kinesiophobia is strongly associated with dyspnea perception, fatigue severity, multisystemic comorbidities in COPD. Further studies are needed to determine the effects of kinesiophobia on the success of pulmonary rehabilitation.Implications for rehabilitationMost of moderate-to-severe chronic obstructive pulmonary disease patients have fear of movement.Increase fear of movement in moderate–severe chronic obstructive pulmonary disease is associated with increased dyspnea perception and fatigue severity and multisystemic comorbidities.

Profile of children with developmental disabilities attending a complex pain clinic of a children's hospital in Australia.

To document the profile and management of children with developmental disabilities (DD) attending an outpatient complex pain clinic at a Children's Hospital in Sydney, Australia. Children with DD from 2011 to 2014 were identified from a clinic database, and pain relevant data was collected. A total of 107 (19.6%) of 544 children were identified with DD, and accounted for one-third of clinic attendances. The median age was 14 years (interquartile range: 11-16) and females were slightly over-represented (62, 57.9%). About one-third of children had cerebral palsy (CP) from a variety of prenatal, natal and post-neonatal causes. The lower limb was the most common site for pain in children with CP, while back pain was more frequent in children with other disabilities. Comorbid emotional disorders were significantly associated with the non-CP disabilities. Children who required more than four clinic attendances were more likely to have comorbid anxiety/depression and to be reviewed by multiple specialists. Long-term persistent pain in children with DD forms a significant cohort of children requiring tertiary level paediatric pain services. Multisystem comorbidities and emotional disorders predict greater service utilisation. Further research into the effectiveness of multidisciplinary pain teams and interventions in this cohort of children is required.

A fine balance and a shared learning journey: Exploring healthcare engagement through the experiences of youth with Neuromuscular Disorders.

Youth with Neuromuscular Disorders (NMD) who are wheelchair users can now survive well into adulthood if their multisystem comorbidities are prudently managed. Uptake of health behaviors may optimize their health outcomes. To explore youths' perceptions of health, health behaviors and healthcare engagement. This qualitative study purposefully recruited 11 youth with NMD from a concurrent, population-based study for variability of age, gender, type of NMD and their ratings of motivation and engagement. Interview data were analyzed and synthesized by thematic content. Participants perceived healthcare engagement as being given tools (knowledge and responsibility) and using them to maintain their finely balanced health. Nested in adequate social, emotional and physical support, they took responsibility for creatively integrating health behaviors they felt were informed by credible knowledge, gained primarily through personal experience. Cognizant of their compromised health, youth with NMD in this study were motivated to maintain their physical health. Limited NMD condition specific knowledge challenged youths' uptake of health behaviors. They valued a learning partnership with their healthcare professionals. By embracing the youth's experience based knowledge and through facilitating supportive relationships, healthcare professionals co-construct youth's healthcare engagement that may optimize health behaviors and outcomes.

Gastrointestinal disorders associated with migraine: A comprehensive review.

Migraine is a recurrent and commonly disabling primary headache disorder that affects over 17% of women and 5%-8% of men. Migraine susceptibility is multifactorial with genetic, hormonal and environmental factors all playing an important role. The physiopathology of migraine is complex and still not fully understood. Many different neuropeptides, neurotransmitters and brain pathways have been implicated. In connection with the myriad mechanisms and pathways implicated in migraine, a variety of multisystemic comorbidities (e.g., cardiovascular, psychiatric and other neurological conditions) have been found to be closely associated with migraine. Recent reports demonstrate an increased frequency of gastrointestinal (GI) disorders in patients with migraine compared with the general population. Helicobacter pylori infection, irritable bowel syndrome, gastroparesis, hepatobiliary disorders, celiac disease and alterations in the microbiota have been linked to the occurrence of migraine. Several mechanisms involving the gut-brain axis, such as a chronic inflammatory response with inflammatory and vasoactive mediators passing to the circulatory system, intestinal microbiota modulation of the enteric immunological milieu and dysfunction of the autonomic and enteric nervous system, have been postulated to explain these associations. However, the precise mechanisms and pathways related to the gut-brain axis in migraine need to be fully elucidated. In this review, we survey the available literature linking migraine with GI disorders. We discuss the possible physiopathological mechanisms, and clinical implications as well as several future areas of interest for research.

The patient experience of osteopathic healthcare

BackgroundOsteopathy in Australia is a primary care limited scope practice. Practitioner surveys suggest that patients present with chronic pain and receive manual therapies, exercise and lifestyle advice. Further research is required to deepen the understanding of this intervention from the perspective of patients. ObjectiveTo explore the experience of patients receiving osteopathic healthcare. DesignMixed methodology. MethodA quantitative survey of a convenience sample of patients was followed by qualitative semi-structured interviews in a purposive sample of respondents with chronic non-specific low back pain. The transcripts were analysed using a phenomenological approach. ResultsThe survey results suggested directions of enquiry for the interviews. Eleven subjects were interviewed and reported commonalities in their clinical histories with multisystem co-morbidities. Four themes became apparent: patient decision-making, patient shared experiences of the osteopathic healthcare consultation, tailored patient-centred care, and therapeutic relationship in healthcare. ConclusionThis data suggests that patients experience osteopathic healthcare after trying other disciplines; that there are shared aspects of the consultations, with a thorough assessment, education about their condition, multiple manual therapies and lifestyle advice; that the experience is patient-centred and tailored to their context; and that the therapeutic relationship is a key aspect of the experience. These results reflect a number of aspects of osteopathic healthcare from workplace surveys.

Atopic diseases and systemic lupus erythematosus: an epidemiological study of the risks and correlations.

Both atopic diseases and systemic lupus erythematosus (SLE) are immune disorders that may lead to physical complications or multi-system comorbidities. This population-based case-control study was designed to evaluate the risk of SLE associated with atopic diseases. Using a national insurance claims dataset in Taiwan, we identified 1673 patients newly diagnosed with SLE and 6692 randomly selected controls frequency matched for gender, age and index date. The odds ratios (OR) for SLE were calculated for associations with allergic rhinitis, allergic conjunctivitis, atopic dermatitis and asthma. The SLE patients were predominantly female (82.5%) with a mean age of 40.1 (SD = 18.2). The patients with SLE had a higher rate of atopic dermatitis (6.81% vs. 3.06%), and asthma (10.6% vs. 7.64%) was approximately 2 times more common in the patients with lupus than in those without. The patients with atopic disease (atopic dermatitis, allergic rhinitis, allergic conjunctivitis and asthma) were at a significant risk for SLE. The overall risk for SLE increased as the number of atopic diseases increased from 1.46 to 2.29, compared with—individuals without the diseases (p < 0.0001). In conclusion, this population-based case-control study demonstrates a significant relationship between atopic diseases and the risk of SLE, especially for females. Atopic dermatitis plays a stronger role than other types of atopic disease in association with SLE.

Rates and Risks of Gastrostomy Tubes in Infants With Cleft Palate

To review data on a cohort of infants with cleft palate to (1) determine rates of gastrostomy (G)-tube placement, (2) identify contributing comorbidities, and (3) use relative risk analyses to improve management of cleft palate in infants with feeding difficulty. Retrospective medical record review. Tertiary care children's hospital. Infants with cleft palate born between January 1, 2000, and December 31, 2008, without G-tubes prior to referral were included. Comorbidities were analyzed, including syndromes and chromosomopathies (syn/chrom) and cardiac, respiratory, neurologic, and gastrointestinal diagnoses. These comorbidities were analyzed independently. Gastrostomy-tube placement. Of 214 infants with cleft palate, 34 required G-tubes. Of these, 19 had syn/chrom. Independent of these diagnoses, 17 infants had 1 system comorbidity and 12 had multisystem comorbidities. Of the 180 patients without G-tubes, 20 had syn/chrom. Independent of these diagnoses, 10 infants had 1 system comorbidity and 2 had multisystem comorbidities. Rates of G-tube placement ranged from 3% in infants without any comorbidity to 94% in infants with respiratory comorbidity. Relative risks of G-tube placement with syn/chrom, 1 system comorbidity, and multisystem comorbidities were 5.68 (95% confidence interval, 3.18-10.16), 21.79 (8.76-54.17), and 29.66 (12.18-72.21), respectively. Diagnosis of syn/chrom or major comorbidity significantly increases risk of G-tube placement. Regardless of syn/chrom association, problems affecting the heart, respiratory system, central nervous system, and lower esophageal sphincter are the most significant risk factors, implying that particular comorbidities are more influential than a simple diagnosis of syn/chrom. These data should help identify children at greatest risk for G-tubes and those expected to overcome feeding difficulties, leading to more persistent use of nonsurgical therapy before resorting to G-tubes.

Medically Complex Children: An Increasing Inpatient Population

Dr Olasin has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device Source: Burns KH, Casey PH, Lyle RE, et al. Increasing prevalence of medically complex children in US hospitals. Pediatrics. 2010; 126( 4): 638– 645; doi: 1031542/peds.2009-1658[OpenUrl][1][Abstract/FREE Full Text][2] Investigators from Arkansas used national data to evaluate changes in hospitalization rates for children aged 8 days to 4 years with complex chronic conditions (CCC) from 1991 through 2005. Medically complex children were defined as individuals in a designated chronic condition category involving more than one organ system, such as children with a specific condition (eg, cerebral palsy [CP] or bronchopulmonary dysplasia [BPD]) and an additional chronic condition. The CCC included multisystem specific comorbidities: neuromuscular, … [1]: {openurl}?query=rft.jtitle%253DPediatrics%26rft_id%253Dinfo%253Adoi%252F10.1542%252Fpeds.2009-1658%26rft_id%253Dinfo%253Apmid%252F20855383%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=pediatrics&resid=126/4/638&atom=%2Faapgrand%2F25%2F2%2F24.atom

Approach to the Patient with Persistent Acromegaly after Pituitary Surgery

The approach to a patient with acromegaly and persistent disease after surgery requires a complex diagnostic assessment. Acromegaly is a chronic and insidious disease that is associated with multisystem comorbidities, including cardiovascular disease, hypertension, sleep apnea syndrome, colon polyposis, arthropathy, and metabolic complications including glucose intolerance and type 2 diabetes mellitus. Patients also have a variety of signs and symptoms, including headache, arthralgias, carpal tunnel syndrome, sweating, fatigue, and psychological issues that impact significantly on quality of life. The recommended approach to the evaluation of the postoperative patient includes a biochemical assessment, with measurement of serum IGF-I along with a glucose-suppressed GH value, radiological assessment to determine location of residual tumor and presence of mass effects, a physical examination for evidence of skeletal and soft tissue overgrowth and related signs of acromegaly, and a thorough clinical assessment for the presence of comorbidities. Repeat surgery is indicated if there is residual tumor that is surgically accessible and there may be a chance for surgical cure, or if there are persistent mass effects upon the optic chiasm. Otherwise, medical therapy is indicated, utilizing somatostatin analogs, dopamine agonists, and pegvisomant, a GH receptor antagonist. Radiation therapy is usually relegated to situations where medical therapy is ineffective or poorly tolerated or where patients would prefer not to sustain the cost of long-term medical therapy. The choice of therapy requires close dialog among endocrinologists, neurosurgeons, radiation therapists, and neuroophthalmologists for optimal care of patients.

Application of Fluorescence Polarization Immunoassay for Determination of Methotrexate-Polyglutamates in Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is a chronic disease characterized by the painful joints, inflammation, uncontrolled proliferation of synovial tissue and multisystem comorbidities. Weekly low-dose methotrexate (MTX) has been established as effective treatment in RA patients. MTX is converted to gamma-glutamyl polyglutamates, an active form of MTX, through the action of folylpolyglutamate synthetase in the cells. MTX-polyglutamates (MTX-PGs) in red blood cells (RBCs) may be useful as a therapeutic marker of RA. However, the previously reported methods for the quantification of MTX and MTX-PGs in RBCs are impractical for clinical use due to time-consuming, laborious and high cost. We attempted to apply a method with the commercially available fluorescence polarization immunoassay (FPIA) kit. We found that anti-MTX monoclonal antibody showed the reactivity to 4-amino-10-methylpteroylheptaglutamic acid (MTX-PG(7)) as equal to MTX. Good agreement was observed in the concentration-response curves between MTX and MTX-PG(7) spiked samples. Accordingly, the anti-MTX monoclonal antibody for FPIA appeared to show the equal reactivity to MTX and MTX-PGs. The recoveries of MTX and MTX-PG(7) from RBCs were 99.0% and 94.1%, respectively. Furthermore, we determined total MTX-PGs concentrations in RBCs of 71 patients with RA treated with weekly pulse MTX. Total MTX-PGs concentrations in 70% of the patients were found to be more than 50 nM that is the lower limit of MTX-PGs concentration in RBCs for expected therapeutic outcome. The routine measurement of total MTX-PGs concentration in RBCs might be useful for prediction about therapeutic outcome of MTX in RA patients.