A flowchart for adequate controls in virus-based monosynaptic tracing experiments identified Cre-independent leakage of the TVA receptor in RΦGT mice.

BACKGROUND: A pseudotyped modified rabies virus lacking the rabies glycoprotein (G-protein), which is crucial for transsynaptic spread, can be used for monosynaptic retrograde tracing. By coupling the pseudotyped virus with transgene expression of the G-protein and the avian leukosis and sarcoma virus subgroup A receptor (TVA), which is necessary for cell entry of the virus, researchers can investigate specific neuronal populations. Responder mouse lines, like the RΦGT mouse line, carry the genes encoding the G-protein and TVA under Cre-dependent expression. These mouse lines are valuable tools because they reduce the number of viral injections needed compared to when using helper viruses. Since RΦGT mice do not express Cre themselves, introducing the pseudotyped rabies virus into their brain should not result in viral cell entry or spread. RESULTS: We present a straightforward flowchart for adequate controls in tracing experiments, which we employed to demonstrate Cre-independent expression of TVA in RΦGT mice. CONCLUSIONS: Our observations revealed TVA leakage, indicating that RΦGT mice should be used with caution for transgene expression of TVA. Inaccurate tracing outcomes may occur if TVA is expressed in the absence of Cre since background leakage leads to nonspecific cell entry. Moreover, conducting appropriate control experiments can identify the source of potential caveats in virus-based neuronal tracing experiments.

Imaging Characteristics and Interpretation Strategy for Renal Hyperparathyroidism: A Retrospective 4-Dimensional Computed Tomography Study.

OBJECTIVE: Parathyroidectomy treats uncontrolled renal hyperparathyroidism (RHPT), requiring identification of all glands. Three types of enhancement are proposed. Type A lesions have higher arterial phase attenuation than the thyroid, type B lesions lack higher arterial phase attenuation but have lower venous phase attenuation, and type C lesions have neither higher arterial phase attenuation nor lower venous phase attenuation than the thyroid. We aimed to outline the image features of problematic parathyroid glands in RHPT and propose a 4-dimensional computed tomography (4DCT) interpretation algorithm. METHODS: This retrospective study involved data collection from patients with RHPT who underwent preoperative 4DCT for parathyroidectomy between January and November 2022. Pathologically confirmed parathyroid lesions were retrospectively identified on 4DCT according to the location and size described in the surgical notes. The attenuation of parathyroid lesions and the thyroid glands was assessed in 3 phases, and demographic data of the patients were collected. RESULTS: Ninety-seven pathology-proven parathyroid glands from 27 patients were obtained, with 86 retrospectively detected on 4DCT. In the arterial phase, the attenuation of parathyroid lesions in RHPT did not exceed that of the thyroid gland (P < .001). In the venous phase, parathyroid lesions demonstrated lower attenuation than the thyroid gland (P < .001). A total of 81 parathyroid lesions (94.2%) exhibited type B patterns. CONCLUSION: Unlike primary hyperparathyroidism, lesions in RHPT exhibited more type B enhancement, making them less readily identifiable in the arterial phase. Therefore, we propose a distinct imaging interpretation strategy to locate these problematic glands more efficiently.

Disease spectrum of torticollis in children and diagnostic flowchart: A retrospective, single-centre study.

AIM: To describe the disease spectrum of torticollis in Chinese children and to improve its diagnostic flowchart. METHODS: A retrospective analysis was conducted at the Rehabilitation Department of Beijing Children's Hospital from 2017 to 2021. Patients were diagnosed and referred based on a diagnostic flowchart of torticollis. Detailed patient data were collected from the outpatient electronic medical record system. RESULTS: A total of 2047 patients met the inclusion criteria. The top five conditions were congenital muscular torticollis (CMT) (76.6%), cerebral palsy (5.1%), ocular torticollis (4.7%), brachial plexus injury (1.9%) and atlantoaxial rotary subluxation (1.3%). CMT was most common in 0-2 year olds, cerebral palsy in 3-5 year olds, and atlantoaxial rotary subluxation in 7-12 year olds. The top five referral departments were orthopaedics, ophthalmology, otolaryngology, head and neck surgery, neurology and neurosurgery. CONCLUSIONS: The disease spectrum of torticollis in children and the diagnostic flowchart provide important references for diagnosing torticollis, which necessitates multidisciplinary collaboration.

Generalized overview infographic: a customizable library instructional material on the NIH Data Management and Sharing Policy.

The Generalized Overview of the NIH Data Management and Sharing Policy Effective 2023.01.15 (Generalized Overview) is an instructional material that provides a basic, clear, and linear understanding of the NIH policy and its requirements. While not developing or utilizing new technology, the Generalized Overview is innovative and notable for creatively using a freely available graphic design tool to translate government policy language into an accessible and understandable infographic that can disseminate important information about the NIH DMS Policy needed by researchers and by those who support them. Shared via a Creative Commons license, others may fully adapt the infographic or may simply add their own institutional contact information. The Generalized Overview can be used by any who find themselves responsible for publicizing and/or teaching the NIH Data Management and Sharing Policy at their respective libraries and institutions. It is intended for educational purposes only and should not be used as a substitute for official guidance from the NIH.

Standardized reporting of pulmonary transfusion complications: Development of a model reporting form and flowchart.

BACKGROUND: Pulmonary complications of blood transfusion, including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and transfusion-associated dyspnea, are generally underdiagnosed and under-reported. The international TRALI and TACO definitions have recently been updated. Currently, no standardized pulmonary transfusion reaction reporting form exists and most of the hemovigilance forms have not yet incorporated the updated definitions. We developed a harmonized reporting form, aimed at improved data collection on pulmonary transfusion reactions for hemovigilance and research purposes by developing a standardized model reporting form and flowchart. MATERIALS AND METHODS: Using a modified Delphi method among an international, multidisciplinary panel of 24 hemovigilance experts, detailed recommendations were developed for a standardized model reporting form for pulmonary complications of blood transfusion. Two Delphi rounds, including scoring systems, took place and several subsequent meetings were held to discuss issues and obtain consensus. Additionally, a flowchart was developed incorporating recently published redefinitions of pulmonary transfusion reactions. RESULTS: In total, 17 participants completed the first questionnaire (70.8% response rate) and 14 participants completed the second questionnaire (58.3% response rate). According to the results from the questionnaires, the standardized model reporting form was divided into various subcategories: general information, patient history and transfusion characteristics, reaction details, investigations, treatment and supportive care, narrative, and transfused product. CONCLUSION: In this article, we present the recommendations from a global group of experts in the hemovigilance field. The standardized model reporting form and flowchart provide an initiative that may improve data collected to address pulmonary transfusion reactions.

Machine Learning-Based Prediction of Digoxin Toxicity in Heart Failure: A Multicenter Retrospective Study.

Digoxin toxicity (plasma digoxin concentration ≥0.9 ng/mL) is associated with worsening heart failure (HF). Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of adverse drug reactions. The present study aimed to construct a flowchart using DT analysis that can be used by medical staff to predict digoxin toxicity. We conducted a multicenter retrospective study involving 333 adult patients with HF who received oral digoxin treatment. In this study, we employed a chi-squared automatic interaction detection algorithm to construct DT models. The dependent variable was set as the plasma digoxin concentration (≥ 0.9 ng/mL) in the trough during the steady state, and factors with p < 0.2 in the univariate analysis were set as the explanatory variables. Multivariate logistic regression analysis was conducted to validate the DT model. The accuracy and misclassification rates of the model were evaluated. In the DT analysis, patients with creatinine clearance <32 mL/min, daily digoxin dose ≥1.6 µg/kg, and left ventricular ejection fraction ≥50% showed a high incidence of digoxin toxicity (91.8%; 45/49). Multivariate logistic regression analysis revealed that creatinine clearance <32 mL/min and daily digoxin dose ≥1.6 µg/kg were independent risk factors. The accuracy and misclassification rates of the DT model were 88.2 and 46.2 ± 2.7%, respectively. Although the flowchart created in this study needs further validation, it is straightforward and potentially useful for medical staff in determining the initial dose of digoxin in patients with HF.

A comprehensive study of clinicopathological and genetic features of neuronal intranuclear inclusion disease.

BACKGROUND: The discovery of skin intranuclear inclusions and GGC repeat expansion of NOTCH2NLC has greatly promoted the diagnosis of neuronal intranuclear inclusion disease (NIID). With highly heterogeneous clinical manifestations, NIID patients tend to be underdiagnosed at early stages. METHODS: This study comprehensively studied clinical manifestations, magnetic resonance imaging (MRI), and peripheral nerve conduction in 24 NIID and 166 other neurodegenerative disease (ND) subjects. The nomogram was plotted using the "rms" package, and the t-distributed stochastic neighbor embedding algorithm was performed. Associations between skin intranuclear inclusions and NOTCH2NLC GGC repeats were further analyzed. RESULTS: The clinical, MRI, and peripheral nerve conduction features seriously overlapped in NIID and ND patients; they were assigned variables according to their frequency and specificity in NIID patients. A nomogram that could distinguish NIID from ND was constructed according to the assigned variables and cutoff values of the above features. The occurrence of skin intranuclear inclusions and NOTCH2NLC GGC repeats ≥ 60 showed 100% consistency, and intranuclear inclusion frequency positively correlated with NOTCH2NLC GGC repeats. A hierarchical diagnostic flowchart for definite NIID was further established. CONCLUSION: We provide a novel nomogram with the potential to realize early identification and update the diagnostic flowchart for definitive diagnosis. Moreover, this is the first study to define the association between skin pathology and NOTCH2NLC genetics in NIID.

Risk evaluation of carbapenem-induced liver injury based on machine learning analysis.

INTRODUCTION: Information regarding carbapenem-induced liver injury is limited, and the rate of liver injury caused by meropenem (MEPM) and doripenem (DRPM) remains unknown. Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of liver injury. Thus, we aimed to compare the rate of liver injury between MEPM and DRPM and construct a flowchart that can be used to predict carbapenem-induced liver injury. METHODS: We investigated patients treated with MEPM (n = 310) or DRPM (n = 320) and confirmed liver injury as the primary outcome. We used a chi-square automatic interaction detection algorithm to construct DT models. The dependent variable was set as liver injury from a carbapenem (MEPM or DRPM), and factors including alanine aminotransferase (ALT), albumin-bilirubin (ALBI) score, and concomitant use of acetaminophen were used as explanatory variables. RESULTS: The rates of liver injury were 22.9% (71/310) and 17.5% (56/320) in the MEPM and DRPM groups, respectively; no significant differences in the rate were observed (95% confidence interval: 0.710-1.017). Although the DT model of MEPM could not be constructed, DT analysis showed that the incidence of introducing DRPM in patients with ALT >22 IU/L and ALBI scores > -1.87 might be high-risk. CONCLUSIONS: The risk of developing liver injury did not differ significantly between the MEPM and DRPM groups. Since ALT and ALBI score are evaluated in clinical settings, this DT model is convenient and potentially useful for medical staff in assessing liver injury before DRPM administration.

The development and initial evaluation of referral flowchart for suspected neuroblastoma for pediatricians in nononcology clinics in China.

BACKGROUND: The delayed diagnosis of neuroblastoma (NB) is common in China, which results in the prognosis of NB in China lagging behind that in developed countries. METHODS: A referral flowchart for suspected NB was implemented in nononcology clinics at Beijing Children's Hospital (BCH). Patients with symptoms of suspected NB were referred from nononcology clinics in BCH to oncology clinics and confirmed NB cases were regarded as referral group. The control group comprised patients initially diagnosed with NB who came directly to oncology clinics in BCH from other regions nationwide. The age at NB diagnosis was compared as primary outcome, and the 5-year overall survival (OS) and event-free survival (EFS) were compared via the Kaplan-Meier method and log-rank tests. RESULTS: In total, 3337 children with suspected NB were screened consecutively from 687 070 pediatric patients. Through examination of urine vanillylmandelic acid and homovanillic acid, or B-ultrasound, 102 of 3337 patients were referred to oncologists for comprehensive evaluations. Eventually, 29 referred patients were diagnosed as NB and the hospital-based diagnosis rate of NB was 4.2 per 100 000 visits. The median age at diagnosis in the referral group was 21.0 months, which was 9 months earlier than that of the control group (30.0 months, P = .026). The 5-year OS rate was 72.4% in the referral group, which was higher than that of the control group (66.7%) but without statistical significance (P = .664). CONCLUSION: Delayed NB detection could be avoided by training pediatricians in nononcology clinics to detect suspected NB and refer these patients to oncologists.

The Comparison of Point Prevalence Survey (PPS) and Gyssens Flowchart Approach on Antimicrobial Use Surveillance in Indonesian National Referral Hospital.

The antimicrobial resistance (AMR) rate in Indonesia is steadily rising, despite the existing national action plan in 2014. In line with the Global Action Plan on AMR, proper surveillance on antimicrobial usage and resistance are needed. At present, antimicrobial surveillance (AMS) data in Indonesia is heterogeneous, fragmented, and localized. The common method of antimicrobial surveillance (AMS) in referral hospitals is by implementing Gyssens flowchart during Antimicrobial Resistance Control Program Committee clinical rounds. However, the recent method of AMS with Point Prevalence Survey (PPS) offers many advantages include its concise and simple protocol, large data collection, shorter required time, comprehensive data outcomes, real-time data, and standardized parameters. In low-middle income countries such as Indonesia with its restricted resources in AMS, PPS is superior compared to the 'traditional' hospital clinical round in generating representative and homogenous outcomes that can be compared to data from other centers worldwide.

Sodium-glucose cotransporter 2 inhibitors: a practical guide for the Dutch cardiologist based on real-world experience.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors include a relatively new class of glucose-lowering drugs that reduce plasma glucose concentrations by inhibiting proximal tubular reabsorption of glucose in the kidney, while increasing its excretion in urine. Recent large randomised controlled trials have demonstrated that many of these agents reduce the occurrence of major adverse cardiovascular events, hospitalisation for heart failure, cardiovascular death and/or chronic kidney disease progression in patients with and without type 2 diabetes mellitus (DM2). Given their unique insulin-independent mode of action and favourable efficacy and adverse-event profile, SGLT2 inhibitors are promising and they offer an interesting therapeutic approach for the cardiologist to incorporate into routine practice. However, despite accumulating data supporting this class of therapy, cardiologists infrequently prescribe SGLT2 inhibitors, potentially due to a lack of familiarity with their use and the reticence to change DM medication. Here, we provide an up-to-date practical guide highlighting important elements of treatment initiation based on real-world evidence and expert opinion. We describe how to change DM medication, including insulin dosing when appropriate, and how to anticipate any adverse events based on real-world experience in patients with DM2 in the Meander Medical Centre in Amersfoort, the Netherlands. This includes a simple algorithm showing how to initiate SGLT2 inhibitor treatment safely, while considering the consequence of the glucosuric effects of these inhibitors for the individual patient.

A modern epilepsy surgery treatment algorithm: Incorporating traditional and emerging technologies.

Epilepsy surgery has seen numerous technological advances in both diagnostic and therapeutic procedures in recent years. This has increased the number of patients who may be candidates for intervention and potential improvement in quality of life. However, the expansion of the field also necessitates a broader understanding of how to incorporate both traditional and emerging technologies into the care provided at comprehensive epilepsy centers. This review summarizes both old and new surgical procedures in epilepsy using an example algorithm. While treatment algorithms are inherently oversimplified, incomplete, and reflect personal bias, they provide a general framework that can be customized to each center and each patient, incorporating differences in provider opinion, patient preference, and the institutional availability of technologies. For instance, the use of minimally invasive stereotactic electroencephalography (SEEG) has increased dramatically over the past decade, but many cases still benefit from invasive recordings using subdural grids. Furthermore, although surgical resection remains the gold-standard treatment for focal mesial temporal or neocortical epilepsy, ablative procedures such as laser interstitial thermal therapy (LITT) or stereotactic radiosurgery (SRS) may be appropriate and avoid craniotomy in many cases. Furthermore, while palliative surgical procedures were once limited to disconnection surgeries, several neurostimulation treatments are now available to treat eloquent cortical, bitemporal, and even multifocal or generalized epilepsy syndromes. An updated perspective in epilepsy surgery will help guide surgical decision making and lay the groundwork for data collection needed in future studies and trials.

Towards a New Strategy for Diagnosis of Congenital Trypanosoma cruzi Infection.

The immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to areas of nonendemicity, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy common to all laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenital Trypanosoma cruzi infection, (ii) assess the utility of these techniques for diagnosing a congenital transmission, and (iii) propose a strategy for a prompt, efficient, and cost-effective diagnosis of T. cruzi infection. In noninfected newborns, a continuous decreasing trend of passive IgG antibodies was observed, but none of the serological assays seroreverted in any the infants before 12 months. From 12 months onwards, serological tests achieved negative results in all the samples analyzed, with the exception of the highly sensitive chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally infected infants, the antibody decline was detected only after treatment initiation. In order to improve the diagnosis of congenital T. cruzi infection, we propose a new strategy involving fewer tests that allows significant cost savings. The protocol could start 1 month after birth with a parasitological test and/or a PCR. If negative, a serological test would be carried out at 9 months, which if positive, would be followed by another at around 12 months for confirmation.

Diagnostic strategy for inherited hypomagnesemia.

BACKGROUND: Hereditary hypomagnesemia is difficult to diagnose accurately because of its rarity and the variety of causative genes. We established a flowchart for identifying responsible genes for hypomagnesemia, and we confirmed its diagnostic efficacy in patients with suspected inherited hypomagnesemia. METHODS: We established a flowchart and applied it to five index cases with suspected inherited hypomagnesemia. Direct sequence analysis was used to detect the causative gene variants in four cases, and targeted sequencing analysis using next-generation sequencing (NGS) of all causative genes for hypomagnesemia was used in one. RESULTS: Expected pathogenic variants were detected in the HNF1B, TRPM6, CLDN16, CASR, or SLC12A3 gene in all five cases. The results of all genetic analyses were consistent with the clinical diagnostic results using the flowchart. CONCLUSIONS: Accurate genetic diagnosis is crucial for estimating the prognosis, detecting complications in organs other than the kidneys, and for directing genetic counseling. The developed flowchart for identifying responsible genes for hypomagnesemia was useful for diagnosing inherited hypomagnesemia. In addition, NGS analysis will help to resolve clinical difficulties in making an accurate diagnosis and thus improve the diagnostic strategy for inherited hypomagnesemia.

Umbilical venous catheters placement evaluation on frontal radiogram: application of a simplified flow-chart for radiology residents.

BACKGROUND: Umbilical Venous Catheter (UVC) are commonly used in neonatal period; they can be not correctly positioned and could be associated with complications. The purpose of this article is to suggest a flow-chart to evaluate the placement of UVC, testing it in young radiologists-in-training. METHOD: We developed a simple flow-chart to asses, steps by step, UVC placement considering its course and tip location (ideally placed in the atriocaval junction). We tested the flow-chart impact asking to 20 residents to evaluate the placement of 10 UVC before and after they familiarized with the flow-chart and the anatomical findings of a newborn. The agreement among the 20 students was evaluated too. RESULTS: The number of correct characterizations was different due to the administration of the flow-chart. One hundred and six correct UVC assessments at the beginning switched to 196 after the administration of the flow-chart (p = 0.0001). The observed agreement among the twenty radiology residents was statistically significant, both before (kappa = 0.41, p < 0.001) and after (kappa = 0.37, p < 0.001) the flow-chart administration. CONCLUSION: The developed flow-chart demonstrated to be useful in increasing residents performance in UVC placement assessment.

Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial.

BACKGROUND: Even with optimal dopaminergic treatments, many patients with Parkinson's disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmine's ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with advanced PD. METHODS: We performed a multicentre, parallel, double-blind, placebo-controlled, randomised clinical trial (Protocol ID: 2008-002578-36; clinicaltrials.gov reference: NCT00767091) in patients with PD with moderate to severe apathy (despite optimised dopaminergic treatment) and without dementia. Patients from five French university hospitals were randomly assigned 1:1 to rivastigmine (transdermal patch of 9.5 mg/day) or placebo for 6 months. The primary efficacy criterion was the change over time in the Lille Apathy Rating Scale (LARS) score. FINDING: 101 consecutive patients were screened, 31 were eligible and 16 and 14 participants were randomised into the rivastigmine and placebo groups, respectively. Compared with placebo, rivastigmine improved the LARS score (from -11.5 (-15/-7) at baseline to -20 (-25/-12) after treatment; F(1, 25)=5.2; p=0.031; adjusted size effect: -0.9). Rivastigmine also improved the caregiver burden and instrumental activities of daily living but failed to improve quality of life. No severe adverse events occurred in the rivastigmine group. INTERPRETATION: Rivastigmine may represent a new therapeutic option for moderate to severe apathy in advanced PD patients with optimised dopaminergic treatment and without depression dementia. These findings require confirmation in a larger clinical trial. Our results also confirmed that the presence of apathy can herald a pre-dementia state in PD. REGISTRATION: Clinicaltrials.gov reference: NCT00767091.

Endovascular tools for vascular access stenosis: Flow-chart proposal.

Stenosis represents the most relevant arteriovenous fistula (AVF) pathology and can affects the entire conduit forming the fistula, from afferent artery to central venous vessels. Correction of vascular access stenosis significantly affects the survival and quality of life for end stage renal disease patients (ESRD) dependent on hemodialysis. Guidelines consider the procedure of percutaneous transluminal angioplasty (PTA) relevant for the primary treatment of these lesions with excellent results in restoring AVF immediately at the end of the procedure. From first AVF angioplasty in 1981 to now, wide scientific innovation has led to development of new devices, composed by different materials and technologies, specific for the site and the type of stenosis to be treated, able to manage resistant stenotic lesion and to reduce stenosis recurrences. International guidelines do not clearly specify all treatment possibilities in the individual case. In this review the authors want to provide specific information on most used devices for stenosis treatment based on literature evidence, showing when and where to use the various tools available with flow-chart treatment proposal.

Comprehensive treatment protocol for peri-implantitis: an up-to date narrative review of the literature.

This narrative review describes up-to-date treatment options for peri-implantitis and proposes a treatment protocol and flowchart based on the current scientific evidence. Peri-implantitis treatment should be based on the phased treatment protocol for periodontitis, which is a continuous flow of decisions for extraction, nonsurgical and surgical treatments with step-by-step re-evaluation. The protocol's goals are to fulfill the success criteria for peri-implantitis treatment (probing depth of ≤5 mm, and absence of bleeding on probing, suppuration, and progressive bone loss) and to halt disease progression. Fixtures with peri-implantitis can initially be classified as failed or failing. A failed implant needs to be removed. In contrast, nonsurgical and surgical treatments can be applied to a failing implant. Nonsurgical treatment should be the initial treatment for failing implants; however, sole nonsurgical treatment was regarded as inefficient for peri-implantitis. Recent studies have found that the adjunctive use of antibiotics to nonsurgical debridement increased the success of nonsurgical treatment for peri-implantitis. Surgical treatments can be classified into resective, access, and reconstructive surgeries. The technique should be selected according to the patient's bone defect configuration, which relate to regenerative potential. Various combinations of decontamination methods (e.g., mechanical, chemical, and pharmacological approaches) are required to achieve absolute surface decontamination. Clinicians should select an appropriate surface decontamination strategy according to the purpose of surgery. After signs of disease disappear and its progression is halted through active peri-implantitis treatment, it is necessary to enroll patients into maintenance programs. Compliance of patients with the maintenance program reduces the recurrence of peri-implantitis and sustains clinical success after treatment. Maintenance visits should include professional plaque control and hygiene care reinforcement for patients, and their interval should be set according to individual peri-implantitis risk. Clinicians should remind that peri-implantitis treatment is not a single procedure, but rather a continuing cycle of treatment and re-evaluation.

Validation of a diagnostic flowchart for tuberculous pleurisy in pleural fluid with high levels of adenosine deaminase.

INTRODUCTION: Adenosine deaminase (ADA) in pleural fluid is a useful marker for diagnosing tuberculous pleurisy. However, recent studies have reported a lower specificity of pleural fluid ADA levels. We previously developed a diagnostic flowchart for patients with pleural fluid ADA ≥40 U/L, incorporating variables such as pleural fluid lactate dehydrogenase <825 U/L, predominant pleural fluid neutrophils or cell degeneration, and a pleural fluid ADA/total protein ratio <14. This flowchart was effective in distinguishing between tuberculous pleurisy and other diseases. Here, we conducted a validation analysis of this flowchart. MATERIALS AND METHODS: We retrospectively collected data from 458 patients with pleural fluid ADA concentrations ≥40 U/L across eight institutions from January 2019 to December 2023. The diagnostic accuracy rate, sensitivity, and specificity of the diagnostic flowchart were analysed and compared to those in the original study. RESULTS: Eighty-seven patients were diagnosed with tuberculous pleurisy, and 371 patients were diagnosed with other diseases. The diagnostic accuracy, sensitivity, and specificity for diagnosing tuberculous pleurisy were 77.7%, 86.2%, and 75.7%, respectively. Compared with that in the original study, the rate of tuberculous pleurisy was lower (19.0% vs. 44.5%, p < 0.001), but the diagnostic accuracy rates were not significantly different (p = 0.253). On the basis of the findings from this validation study, we have revised the flowchart to enhance its utility. CONCLUSION: The diagnostic flowchart exhibited high diagnostic accuracy in this validation study, comparable to that in the original study. This validation confirms the effectiveness of the flowchart, even in settings with a low incidence of tuberculosis.