Need For Treatment Research Articles

Caenorhabditis elegans as in vivo model for the screening of natural plants-derived novel anti-aging compounds: a short introduction.

The global aging population highlights the need for effective anti-aging treatments. Natural products show promise, but thorough evaluation requires in vivo models due to the complexity of aging. Ethical concerns are driving a shift from traditional models like rabbits and mice to alternatives such as Caenorhabditis elegans. This microscopic nematode, with its short life cycle, genetic similarities to humans, and cost-effectiveness, is ideal for testing anti-aging compounds. We review studies using C. elegans to assess natural products, suggesting it could serve as a primary model for -evaluating the safety and efficacy of plant-derived anti-aging compounds.

Exploring transferability in psychiatric interventions: a conceptual framework.

The growing significance of generalization in psychiatric interventions stems from the need for effective and applicable treatments across diverse populations and settings. Addressing psychiatric disorders involves navigating the complex interplay of biological, cognitive, and behavioral factors, making it crucial to assess the transferability of interventions beyond controlled environments. To tackle this challenge, we propose a novel conceptual framework, the FIELD model (Function, Implement, Ecology, Level, and Durability). This model offers a comprehensive exploration of generalization by considering the function and tools used in interventions, the ecological contexts of their application, the various levels of impact, and the durability of effects over time. In this study, we explore the dimensions of the FIELD model, emphasizing the role of assessment tools as valuable indicators and the significance of effect sizes in quantifying the transfer of training effects. The FIELD model stands as a tool to enhance our understanding of psychiatric interventions, providing a systematic and nuanced approach to evaluate their generalization across diverse scenarios.

Update on Neoadjuvant and Adjuvant BRAF Inhibitors in Papillary Craniopharyngioma: A Systematic Review

Background/Objectives: The recent discovery of BRAF mutation in papillary craniopharyngiomas opened new avenues for targeted therapies to control tumour growth, decreasing the need for invasive treatments and relative complications. The aim of this systematic review was to summarize the recent scientific data dealing with the use of targeted therapies in papillary craniopharyngiomas, as adjuvant and neoadjuvant treatments. Methods: The PRISMA guidelines were followed with searches performed in Scopus, MEDLINE, and Embase, following a dedicated PICO approach. Results: We included 21 pertinent studies encompassing 53 patients: 26 patients received BRAF inhibitors (BRAFi) as adjuvant treatment, while 25 received them as neoadjuvant treatment. In the adjuvant setting, BRAFi were used to treat recurrent tumours after surgery or adjuvant radiation therapy. The most common regimen combined dabrafenib (BRAFi) with trametinib (MEK1 and 2 inhibitor) in 81% of cases. The mean treatment length was 8.8 months (range 1.6 to 28 months) and 32% were continuing BRAFi. A reduction of tumour volume variable from 24% to 100% was observed at cerebral MRI during treatment and volumetric reduction ≥80% was described in 64% of cases. Once the treatment was stopped, adjuvant treatments were performed to stabilize patients in remission in 11 cases (65%) or when a progression was detected in three cases (12%). In four cases no further therapies were administered (16%). Mean follow-up after the end of targeted therapy was 17.1 months. As neoadjuvant regimen, 36% of patients were treated with dabrafenib and trametinib with a near complete radiological response in all the cases with a mean treatment of 5.7 months. The neoadjuvant use of verumafenib (BRAFi) and cometinib (MEK1 inhibitor) induced a near complete response in 15 patients (94%), with a median volumetric reduction between 85% and 91%. Ten patients did not receive further treatments. Side effects varied among studies. The optimal timing, sequencing, and duration of treatment of these new therapies should be established. Moreover, questions remain about the choice of specific BRAF/MEK inhibitors, the optimal protocol of treatment, and the strategies for managing adverse events. Conclusions: Treatment is shifting to a wider multidisciplinary management, where a key role is played by targeted therapies, to improve outcomes and quality of life for patients with BRAF-mutated craniopharyngiomas. Future, larger comparative trials will optimize their protocol of use and integration into multimodal strategies of treatment.

Antimicrobial and antioxidant activities of Bromelin Propolis Spray

The indiscriminate use of antibiotics over the last 60 years has led to the development of resistant strains, leading an urgent need for new treatments, new molecules or combinations of products, safety and effective. In this regard, propolis has been used in traditional medicine due its therapeutic effects, such as antibacterial, antifungal and antiseptic, tested in vitro, in vivo and clinically. The aim of this study is to evaluate the antimicrobial and antioxidant activities of a commercial oral flavoring product against bacterial strains of clinical interest from the upper respiratory tract. Bacteria sensitivity against Bromelin Propolis Sprayâ (BPS) was evaluated using macrodilution in broth and no turbid tubes plated on TSA to confirm the results. Tested bacteria were Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa. BPS showed antimicrobial activity for all tested strains and the MBC was 2.5mg/mL. Moreover, the antioxidant activity was determined by the ability to scavenge the stable radical DPPH. 0.007% of BPS showed the maximum antioxidant effect, of 6.63mM, which demonstrate its high antioxidant effect. Therefore, these results indicate that the commercial product BPS at 0.7% can be a potential candidate as adjuvant in antibiotic therapy for upper respiratory tract disorders, due possible antimicrobial effect and its high antioxidant potential.

Exploring the Factors Associated with Sleep Concerns and Perceived Need for Treatment among Patients with Sleep Disorders

ABSTRACT Objectives This study aimed to investigate the factors affecting patient perceptions of sleep concerns and the need for treatment to understand and enable effective management. Methods This cross-sectional study analyzed data collected between November 2018 and October 2022 at the sleep clinic of a tertiary hospital. Adults aged > 19 years who completed sleep questionnaires and polysomnography (PSG) were included. Logistic regression models were used to assess the associations between demographic, clinical, and social factors, sleep questionnaire responses, and PSG data with self-reported sleep concerns (n = 3,457) and perceived need for treatment(n = 3,135). Results Insomnia-related symptoms affect both sleep concerns and need for treatment, and sleep maintenance is the most influential factor in both sleep concerns (odds ratio[OR] = 19.74, 95% confidence interval[CI] 6.17–63.20) and need for treatment (OR = 3.84, 95% CI 2.19–6.73). Young age (OR = 2.66, 95% CI 1.38–5.12), employment status, and daily life dysfunction were determinants of treatment readiness. None of the PSG parameters showed an independent association with sleep concerns or need for treatment. Conclusions Sleep maintenance problems had the most profound effect on sleep concerns and the need for treatment. Social needs are key factors in seeking treatment. A discrepancy has been noted between the effects of subjective and objective factors on sleep concerns and the need for treatment; therefore, patient management should pay attention to subjective sleep complaints.

Role of Non-Mesh Grafts in Surgical Treatment of Stress Urinary Incontinence

Stress urinary incontinence refers to a multifactorial disease characterized by involuntary urination associated with a sudden increase in intra­abdominal pressure. Millions of females around the world suffer from stress incontinence each year. Conservative methods of treatment and physical rehabilitation are considered to be ineffective, thereby driving the need for surgical treatment. Sling surgeries comprise a widely used surgical technique for the treatment of stress urinary incontinence due to their affordability and minimal time investment. Introduction of synthetic polypropylene mesh prostheses in the treatment of stress incontinence made them the most common material. However, the accumulated experience and complications associated with the use of mesh grafts contribute to the recent decline in the popularity of synthetic slings and give rise to the search for and development of alternative materials for the surgical treatment of stress urinary incontinence. Since the need for treatment of urinary incontinence remains high, fascia autograft surgeries have been proposed, even though they require an additional surgical procedure and expose the patient to complications at the donor site of the graft. In addition, surgeons use allografts and xenografts, and regenerative technology is developing in this field. Considering high social significance of this problem, the present paper is aimed at reviewing the scientific literature concerning grafts for the treatment of stress incontinence.

Classical surgical treatment of acute pleural empyema

Objective. To determine the need for open surgical treatment in patients with acute pleural empyema with and without the use of video thoracoscopic rehabilitation interventions. Materials and methods. We analyzed the results of treatment of 426 patients with acute pleural empyema in the period 2008–2022, of whom 109 (25.6%) required open surgery after pleural cavity rehabilitation. Results. This study allowed us to form an idea of the need for open surgery at different periods from the beginning of complex treatment of acute pleural empyema, the nature and extent of surgical interventions, complications and their consequences. Conclusions. The need for operations such as pneumonectomy and pleuropneumonectomy after the rehabilitation of the pleural cavity in acute pleural empyema remains at the level of 3.6–6.9%.

The Social Support Perceived by Patients with Schizophrenia at Ali-Kamal Center in Sulaimani City, Kurdistan of Iraq

Background: Schizophrenia is a major mental disorder marked by a diverse range of symptoms. Patients’ perception of social support affects the progress of schizophrenia. Aim: This study aimed mainly to assess social support perceived by patients with schizophrenia. Methods: The present study quantitative- descriptive study on a convenience sample of 100 patients experiencing schizophrenia recruited from the outpatient psychiatric clinic of Ali-kamal Center in Sulaiamani City/Iarq. A valid and reliable questionnaire was used which includes sociodemographic and clinical characteristics and a multidimensional of perceived social support scale. The interview method was employed to collect the data. Results: Low social support was perceived by patients with schizophrenia. Gender P = 0.05; economic status,P = 0.04; and educational level P = 0.01 were statistically significantly associated with low social support among the sample. Conclusion and Recommendation: The role of social support emphasized by schizophrenic patients and the essential need for treatment that includes psychological treatment is also addressed to improve prognosis; moreover, additional studies are needed about the effect of social support on schizophrenic patients.

Effect of Complex Decongestive Therapy Program on Volume and Functioning in Breast Cancer-Related Lymphedema: Global Effect and Predicting Factors.

Background: The aim of this prospective study was to investigate the effect of a first and repeated complex decongestive therapy (CDT) program on volume and functioning in patients with unilateral breast cancer-related lymphedema (BCRL) and to identify whether the volume before treatment and/or the number of previous treatment influence outcomes. Methods and Results: In total, 100 and 42 patients with BCRL treated by 499 CDT (6 hours a day during 5 consecutive days) between April 2018 and December 2021 were included. Patients were assessed using volume including percentage of excess volume and percentage reduction in excess volume and lymph-International Classification of Functioning-UL questionnaire. After CDT, a significant reduction in BCRL volume (50%) and improvement in functioning (30%) were observed. The volume reduction was greater when the BCRL volume before treatment was low (10%-20%) and when CDT was performed for the first time. The functioning improvement was identical whatever the volume is before treatment and the number of previous CDT. Conclusion: A greater volume reduction after CDT was obtained in BCRL with low volume before treatment and after the first CDT. Such findings support the need for early intensive BCRL treatment to control volume and improve functioning.

Evaluation of human and ecological health risks associated with the potentially toxic heavy metals in groundwater of Vellore city, Tamil Nadu, India

Groundwater pollution by heavy metals is a significant and alarming threat globally, through its chronic effect on human health and ecosystem. The current study evaluated the identification and risk assessment of heavy metals in groundwater of the Vellore city, Tamilnadu, India. Groundwater samples were collected from 32 locations over a continuous period of 2022–2023 for every three months on seasonal basis. The samples were analysed for pH, Total Dissolved Solids (TDS), Hardness and heavy metals (Al, As, Ba, Cd, Cu, Pb, Al and Zn). The analysed mean concentrations of these heavy metals were found in the order: As > Cd > Pb > Ba >Zn >Al> Cu. Elevated concentrations of heavy metals were observed in 2022, likely influenced by rainfall and land use patterns. Heavy metals such as Al, As, Pb, and Cd exceeded the BIS limits and whereas Ba, Cu, and Zn concentrations remain within desirable limits. Groundwater Quality Index (GWQI) classified 41% as 'unfit for drinking'. Ecological risk indices (ERI) indicate significant contamination in 34% of samples, with Al and Pb being primary contributors. Non-carcinogenic health risk assessments reveal, chronic hazards, where children facing higher risks followed by men and women groups. Carcinogenic risk assessments indices such as Heavy metal pollution Index (HPI) shown 25% of samples in critical quality, Heavy metal Evaluation Index (HEI) evaluated all samples were in low contamination and Contamination Index (CI) shown 72% samples under high contamination posing high risk to humans. Probable Cancer Risk (PCR) values for As, Pb, and Cd exceed acceptable ranges across all demographic groups posing cancer risk to humans particularly children. The present study highlights the need for groundwater treatment and regulatory interventions to mitigate health and ecological risks due to the contamination of heavy metals in Vellore city.

Helicobacter pylori and Gastric Cancer: Microbiological Insights and Clinical Implications

Helicobacter pylori is a gram-negative bacterium that is a major factor in a number of gastrointestinal diseases including gastritis, peptic ulcer disease, and gastric cancer. We reviewed the biology of H. pylori, including its microbiological characteristics, pathogenic mechanisms and its key role in gastric carcinogenesis. Here, we discuss the bacterium’s mechanisms of survival and virulence factors, such as CagA and VacA, which together induce chronic inflammation and drive malignant transformation. The current status of clinical manifestations and diagnostic approaches are reviewed, emphasizing the need for accurate detection and effective treatment. Future directions stress the need for novel therapeutic strategies as well as vaccine development, host-pathogen understanding, biomarker discovery and personal medicine to improve patient outcome and reduce the global burden of H. pylori associated diseases.

Living with Mental Illness.

Objective: The situation of patient's relatives is still not broadly studied in psychiatry. Their needs are often overlooked. Method: We developed a digital questionnaire concerning the patient's sociodemographic, disease-related, and family-related data and had the patient's therapist fill it out. The patients included (N = 1766) were persons hospitalized on a selected date. Results: One-third of patients had at least one relative with mental illness, prior treatment, or need for treatment. The main diagnoses in relatives were affective, substance use, and somatoform disorders, often in concordance with their index patient. Teenage patients had the most affected relatives. The therapists of the minors included were better informed about their familial situation, whereas the therapists of the 30-59-year-olds knew the least. Conclusions: The comparably lower rate of affected relatives in adults stems most likely from underassessment and needs further investigation.

Lipophilic bisphosphonates reduced cyst burden and ameliorated hyperactivity of mice chronically infected with Toxoplasma gondii.

The current treatments for toxoplasmosis are only active against fast-growing tachyzoites, present in acute infections, with little effect on slow-growing bradyzoites within tissue cysts, present in latent chronic infections. The mitochondrion of Toxoplasma gondii is essential for its survival, and one of the major anti-parasitic drugs, atovaquone, inhibits the mitochondrial electron transport chain at the coenzyme Q:cytochrome c oxidoreductase site. Coenzyme Q (also known as ubiquinone [UQ]) consists of a quinone head and a lipophilic, isoprenoid tail that anchors UQ to membranes. The synthesis of the isoprenoid unit is essential for cell growth and is inhibited by lipophilic bisphosphonates, which inhibit the parasite growth. In this work, we investigated the effect of lipophilic bisphosphonates on the chronic stages of T. gondii. We discovered that three lipophilic bisphosphonates (BPH-1218, BPH-1236, and BPH-1238), effective for the acute infection, were also effective in controlling the development of chronic stages. We showed effectiveness by testing them against in vitro cysts and in vivo derived tissue cysts and, most importantly, these compounds reduced the cyst burden in the brains of chronically infected mice. We monitored the activity of infected mice non-invasively and continuously with a novel device termed the CageDot. A decrease in activity accompanied the acute phase, but mice recovered to normal activity and showed signs of hyperactivity when the chronic infection was established. Moreover, treatment with atovaquone or BPH-1218 ameliorated the hyperactivity observed during the chronic infection.IMPORTANCETreatment for toxoplasmosis is challenged by a lack of effective drugs to eradicate the chronic stages. Most of the drugs currently used are poorly distributed to the central nervous system, and they trigger allergic reactions in a large number of patients. There is a compelling need for safe and effective treatments for toxoplasmosis. Bisphosphonates (BPs) are analogs of inorganic pyrophosphate and are used for the treatment of bone disorders. BPs target the isoprenoid pathway and are effective against several experimental parasitic infections. Some lipophilic BPs can specifically inhibit the mitochondrial activity of Toxoplasma gondii by interfering with the mechanism by which ubiquinone is inserted into the inner mitochondrial membrane. In this work, we present the effect of three lipophilic BPs against T. gondii chronic stages. We also present a new strategy for the monitoring of animal activity during disease and treatment that is non-invasive and continuous.

In Supracondylar Humerus Fractures With Nerve Injury, Does Time to Surgery Impact Recovery?

Background: Supracondylar humerus (SCH) fractures are common and present with associated nerve injuries in 11% to 42% of cases. Historically, SCH fractures with neurological compromise warranted urgent surgical intervention. A recent study showed that treatment delay is acceptable in patients with isolated anterior interosseous nerve (AIN) injury. Though indications for urgent treatment are relaxing, no studies have evaluated the need for urgent surgical treatment for other nerve injuries associated with SCH fractures. The aim of this study was to determine if the timing of surgical intervention is related to the timing of neurological recovery in SCH fractures associated with any nerve injury. Methods: A retrospective review of 64 patients with surgically managed SCH fractures and concomitant neurological deficit on presentation was conducted at a single level 1 pediatric trauma hospital from 1997 to 2022. The relationship between the time to surgical intervention and the time to partial and complete nerve recovery was analyzed using linear regression. Results: Sixty-four patients with an average age of 6.9±2.0 years and an average time to surgery of 9.8±5.6 hours were analyzed. Sixty-two patients (97%) were followed to partial neurological recovery and 36 (56%) were followed to full neurological recovery. Neurological deficit included median [n=41 (64%)], radial [n=22 (34%)], and ulnar [n=15 (23%)]. Ten patients (16%) had isolated AIN injury. The average time to partial neurological recovery was 20±23 days and the time to full recovery was 93±83 days. There was a statistically significant relationship between time to partial neurological recovery and time to surgical intervention (P=0.02). There was no relationship between time to full neurological recovery and time to surgery (P=0.8). Conclusion: Earlier time to surgical intervention in pediatric SCH fractures with isolated nerve injury was associated with earlier partial recovery but not full neurological recovery. Prioritizing urgent surgery in these patients did not improve their ultimate neurological recovery. Level of Evidence: Therapeutic level III.

DMRG-Tailored Coupled Cluster Method in the 4c-Relativistic Domain: General Implementation and Application to the NUHFI and NUF3 Molecules.

Heavy atom compounds represent a challenge for computational chemistry due to the need for simultaneous treatment of relativistic and correlation effects. Often such systems also exhibit strong correlation, which hampers the application of perturbation theory or single-reference coupled cluster (CC) methods. As a viable alternative, we have proposed externally correcting the CC method using the density matrix renormalization group (DMRG) wave functions, yielding the DMRG-tailored CC method. In a previous paper [J. Chem. Phys. 2020, 152, 174107], we reported a first implementation of this method in the relativistic context, which was restricted to molecules with real double group symmetry. In this work, we present a fully general implementation of the method, covering complex and quaternion double groups as well. The 4c-TCC method thus becomes applicable to polyatomic molecules, including heavy atoms. For the assessment of the method, we performed calculations of the chiral uranium compound NUHFI, which was previously studied in the context of the enhancement of parity violation effects. In particular, we performed calculations of a cut of the potential energy surface of this molecule along the stretching of the N-U bond, where the system exhibits strong multireference character. Since there are no experimental data for NUHFI, we have performed also an analogous study of the (more symmetric) NUF3 molecule, where the vibrational frequency of the N-U bond can be compared with spectroscopic data.

Overall Survival and Treatment Patterns Among Patients With Warm Autoimmune Hemolytic Anemia in Sweden: A Nationwide Population-based Study.

Warm autoimmune hemolytic anemia (wAIHA) is a rare autoantibody-mediated disorder, and first-line treatment primarily relies on corticosteroids. This study assessed overall survival (OS) and treatment patterns of wAIHA in Sweden. Adults with ≥ 1 primary diagnosis code for wAIHA (or AIHA plus oral corticosteroids (OCS)/immunosuppressants as sensitivity analyses) between 2011 and 2022 were identified from five Swedish national registers and linked through each patient's unique identity number. Kaplan-Meier curves with log-rank tests and Cox regressions were performed to assess OS for patients with primary versus secondary wAIHA and patients with wAIHA and long-term versus short-term (≥ 3 vs. < 3 months) OCS users. The main analysis included 292 patients; 1791 patients were included in the sensitivity analysis. At a median 3.7-year follow-up, a median OS in primary wAIHA was not reached versus 6.0 years for secondary wAIHA (log-rank test: p = 0.003). Subgroup analyses showed no significant difference in risk of death between long-term and short-term OCS users; however, in the sensitivity analysis, long-term OCS users showed significantly higher risk of death (adjusted hazard ratio: 1.45; 95% confidence interval: 1.180, 1.781; p < 0.001) versus short-term OCS users. Secondary wAIHA or long-term OCS use was associated with lower OS, underscoring the disease burden and unmet need for efficacious wAIHA treatments.

The Burden of Glucocorticoids: Patterns of Use, Adverse Health Conditions, and Health Care Use in Two Cohorts With Systemic Lupus Erythematosus.

Glucocorticoids (GCs) can be beneficial from both clinical and patient perspectives, but side effects are well documented. We examined patterns of GC use over 15 years (2006-2021) and occurrence of adverse health conditions (AHCs) and health care use by GC exposure in two longitudinal cohorts with systemic lupus erythematosus (SLE). Data from the Lupus Outcomes Study (LOS; 2003-2015) and FORWARD cohort (2015-2021) were used. AHCs examined were diabetes, osteoporosis, nontraumatic fractures, cataracts, and infections. Health care use measures examined were the number of rheumatology and other provider visits, hospitalizations, and specific diagnostic tests. Kaplan-Meier analyses examined time to occurrence of each AHC. Cox regression analyses estimated the risk of occurrence of AHCs, controlling for covariates by GC use and by GC dose (0, 1-5, 5-7.5, and ≥7.5 mg). GC use was relatively consistent over time. At baseline, individuals who used GCs in the LOS were more likely to report osteoporosis (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 1.2-2.6) and cataracts (aOR 1.6, 95% CI 1.04-2.6); individuals who used GCs in the FORWARD cohort were more likely to report diabetes (aOR 5.1, 95% CI 2.2-12.0), osteoporosis (aOR 4.5, 95% CI 2.6-8.0), and fractures (aOR 6.5, 95% CI 3.8-11.1). Individuals who used high doses of GCs in the LOS had greater incidence of osteoporosis, fracture, and cataracts. In the FORWARD cohort, a significant difference in incidence was noted only for infections. In both cohorts, individuals who used GCs had more rheumatology and other physician visits, and greater risk of hospitalization. Despite recommendations on steroid sparing, a large portion of people with SLE appear to remain on steroids. These analyses provide additional evidence of the potential health and health care burden of GC use, underscoring the need for other effective treatments for individuals with SLE.

Can systemic antibiotics reduce the need for surgical intervention in treating peri-implantitis?

A retrospective cohort design was used to assess the long-term clinical effectiveness of systemic amoxicillin and metronidazole, used adjunctively with non-surgical peri-implantitis treatment (NST) and whether it prevents the need for further surgical interventions. Of the 57 peri-implantitis patients examined, 45 patients were included in this study. The participants were divided into two subgroups in accordance to who had received NST with or without systemic antibiotics. Selection was based on prior participation in a three-month randomised control trial, ensuring comparability of data regarding peri-implantitis severity and treatment history. Data were extracted pre-treatment, 3-months post-treatment and at a long-term follow-up interval of 36 months. The primary outcome was the need for additional surgical intervention and was analysed via Kaplan-Meier analysis and Cox regression. A multitude of secondary clinical outcomes were evaluated using parametric and non-parametric tests, including peri- implant probing depth, bleeding scores and treatment success. Overall, 62.2% of the 45 NST patients did not need surgical peri-implantitis treatment: 73.9% of the subgroup with antibiotics and 50% of the subgroup without antibiotics respectively. However, the difference between the two groups was not statistically significant (log-rank test, p = 0.110). The Cox regression analysis also displayed no significance over the first three years post-treatment (p = 0.115). Additionally, the study found that deeper peri- implant pockets at baseline significantly predicted the need for future surgical treatment (p = 0.031), highlighting the importance of initial disease severity in treatment outcomes. The study concludes that the adjunctive use of systemic amoxicillin and metronidazole with NST may delay but not statistically reduce or prevent a future surgical need. Although a short-term reduction in clinical inflammatory parameters was evident, the long-term effectiveness in altering the progression of peri-implantitis remains limited.

Can endogenous ethylene glycol production occur in humans? A detailed investigation of adult monozygotic twin sisters

Introduction To the best of our knowledge, clinically significant endogenous ethylene glycol production has never been reported in humans, very seldom reported in other animals or microorganisms, and then only under rare and specific conditions. We describe the detailed investigations we undertook in two adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol. Methods Two previously healthy monozygotic adult twin sisters presented with recurrent episodes of apparent ethylene glycol poisoning beginning at age 35, requiring chronic hemodialysis to remove ethylene glycol and its metabolites as well as to restore metabolic homeostasis. The sisters denied ingestion or exposure to ethylene glycol. At their request, they were admitted to hospital under strict supervision to exclude surreptitious ingestion of ethylene glycol and to evaluate the need for treatment. Hemodialysis was withheld during this prospective study. Twin A was admitted for 14 days and twin B for 11 days. Serial biochemical analyses were performed in blood and urine. Clinical exome sequencing and mitochondrial deoxyribonucleic acid sequencing were also completed. Results In both twins, ethylene glycol was detected in urine, along with intermittent increases in concentrations of lactate, glycolate, and glycine in blood and/or urine. Blood ethylene glycol concentrations, however, remained <62 mg/L (<1 mmol/L) but became positive soon after discharge. The oxalate concentration remained normal in blood and urine. Plasma and urine amino acid profiles showed intermittent small increases in glycine, serine, taurine, proline, and/or alanine concentrations. Exome sequencing and mitochondrial deoxyribonucleic acid sequencing were non-diagnostic. Neither twin has been admitted with metabolic acidosis nor ethylene glycol poisoning since chronic hemodialysis was started. Twin A developed a calcium oxalate dihydrate lithiasis. Discussion Mitochondrial disease, methylmalonic/propionic/isovaleric aciduria, primary hyperoxaluria, and analyte error were all excluded in these twins, as were obvious common environmental exposures. Conclusion Detailed investigations were performed in adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol. Alternative explanations were excluded to the very best of our efforts and knowledge. Global metabolomics, gut microbiome analyses, and whole genome sequencing are pending.

Does the Combined Arteritis Damage Score (CARDS) in the Diagnosis of Takayasu Arteritis Predict Prognosis and Need for Biologic Therapy?

We aimed to investigate the prognostic value of the combined arteritis damage score (CARDS) in Takayasu arteritis (TAK) patients to predict the need for biologic treatment at diagnosis and the possible contribution of wall thickness (WT). Blind evaluation of MRA/CTA at the time of diagnosis was performed by a reader rheumatologist (RR) and an interventional radiologist (RIR). The CARDS damage score for 21 arterial regions was assessed as normal, mild or moderate/severe stenosis, occclusion or aneursym/dilatation. Additionally, WT was scored for all regions as present or absent. A modified CARDS (mCARDS) was calculated as the sum of CARDS and the number of WT areas. According to follow-up treatment, 10 patients with non-biologic treatment (non-BT) (F/M:8/2, median age 37.5years) and 15 patients with biologic treatment (BT) (F/M:13/2, median age 30years) were included. Indian Takatasu Arteritis Score (ITAS), CRP, and ESR levels were similar in both groups. CARDS (1.4 (0-7.2) vs 4.5 (.6-19), P: .003), WT (1.5 (0-8) vs 7 (1-21), P < .001), and mCARDS (4 (0-14.2) vs 11.4 (1.6-40), P < .001) scores were significantly higher in the BT group compared to nonBT group. Cohen's kappa coefficient between RR and RIR for WT was .99 with 99.6% aggrement, and CARDS was .98 with 99.6% agreement. The AUC values for CARDS, WT, and mCARDS scores were .748 (.605-.892), .837 (.723-.950), and .847 (.735-.958), respectively, and P value was <.0001. The prediction of prognosis and biologic treatment need at TAK diagnosis using non-invasive angiographic images can improve outcomes and prompt closer follow-up. The combination of CARDS and WT as mCARDS achieved the highest sensitivity and specificity, and all scores appear useful for predicting prognosis.