Diagnostic Trial Research Articles

Diabetic Cardiomyopathy: An Update on Emerging Pathological Mechanisms.

Diabetic Cardiomyopathy (DCM) is a notable consequence of diabetes mellitus, distinguished by cardiac dysfunction that occurs separately from coronary artery disease or hypertension. A recent study has revealed an intricate interaction of pathogenic processes that contribute to DCM. Important aspects involve the dysregulation of glucose metabolism, resulting in heightened oxidative stress and impaired mitochondrial function. In addition, persistent high blood sugar levels stimulate inflammatory pathways, which contribute to the development of heart fibrosis and remodelling. Additionally, changes in the way calcium is managed and the presence of insulin resistance are crucial factors in the formation and advancement of DCM. This may be due to the involvement of many molecular mechanistic pathways such as NLRP3, NF- κB, PKC, and MAPK with their downstream associated signaling pathways. Gaining a comprehensive understanding of these newly identified pathogenic pathways is crucial in order to design precise therapy approaches that can enhance the results for individuals suffering from diabetes. In addition, this review offers an in-depth review of not just pathogenic pathways and molecular mechanistic pathways but also diagnostic methods, treatment options, and clinical trials.

EVALUATING THE LEARNING CURVE OF A NOVICE OPTOMETRY STUDENT IN SCLERAL LENS FITTING: A PROSPECTIVE QUANTITATIVE STUDY USING DELIBERATE PRACTICE AND CUMULATIVE SUMMATION (LC-CUSUM)

Background and Objective: To evaluate the learning curve of a novice optometry student in scleral lens fitting through deliberate practice and to objectively quantify the learning process using the LearningCurve-Cumulative Summation (LC-CUSUM) test, ensuring accurate and unbiased results. Method: The complexity of scleral contact lens fittings was assessed by categorizing subjects into regular and irregular cornea groups. A student enrolled in the Master of Optometry program conducted the fittings using a dedicated scleral lens record form (rubrics) designed to quantify the lens management approach. Prior to performing fittings independently, the student received four weeks of training from a contact lens expert, who also served as her guide for the study. This training period and the subsequent fittings were structured based on the principles of deliberate practice, with the student performing repeated diagnostic trials. A maximum of three diagnostic trials were performed for each subject to achieve the optimal fit. After each trial, the student completed a self-efficacy scale questionnaire to assess her perceived diffi-culty and clinical judgement skills, recording “FIRST trial scores” following the initial trial and ‘LAST trial scores’ after achieving the optimal fit. The guide consistently provided verbal feedback after each case throughout the fitting process as part of the deliberate practice methodology to enhance the student’s understanding of the fitting procedure while keeping the scores confidential to ensure unbiased self-as-sessment. Following the complete supervision of the fitting procedure, the guide evaluated the student’s clinical skills using a specially designed observation scale questionnaire, referred to as the ‘GUIDE scores.’ A seven-point Likert scale was used to rate the judgement for both the self-efficacy scale and observation scale questionnaire. The student’s LAST trial scores were subsequently compared with the GUIDE scores. Results: A total of 80 scleral lens fittings were evaluated. The Intraclass Correlation Coefficient (ICC) demonstrated excellent agreement between student-reported self-efficacy scores and guide-reported observation scores. The difference in self-efficacy scores between the initial and final lens fittings was statistically significant (p < 0.05), as determined by the Wilcoxon signed-rank test. The Learning Curve-Cumulative Summation (LC-CUSUM) chart revealed that learning stabilized after 26 fittings, marking a consolidation phase where minimal further improvement was observed beyond this point, and additional practice primarily helped to maintain proficiency. The average number of trials required per eye was higher in patients with irregular corneas than those with regular corneas. Conclusion: This study evaluated the learning curve of a novice optometry student in scleral lens fitting through deliberate practice, utilizing the LC-CUSUM test to quantify progress and assess skill acquisition objectively. Proficiency was achieved after 26 fittings, with additional trials needed for irregular corneas, underscoring the influence of patient characteristics on learning. These findings emphasize the importance of structured training, personalized feedback, and self-assessment in developing clinical competence. The insights contribute to advancing education and research in contact lens science by providing practical guid-ance for designing effective programs focused on planning, teaching, and learning about scleral lens fittings.

Analysis of problems and management of in vitro diagnostic reagent clinical trials in medical laboratory

Clinical trials are an important method for evaluating the safety and efficacy of in vitro diagnostic reagents, and are a key basis for product registration review and approval. In order to strengthen the management of clinical trials of in vitro diagnostic reagents, the National Medical Products Administration and relevant departments have formulated a series of regulations at the regulatory level, and require applicants and clinical trial institutions to establish a quality management system for clinical trials of in vitro diagnostic reagents. Medical laboratory is the main department and implementer of in vitro diagnostic reagent clinical trials in medical institutions. In recent years, with the rapid development of the in vitro diagnostic industry, the clinical trial projects of in vitro diagnostic reagents conducted by medical laboratory have been increasing day by day. However, there are currently few discussions on the clinical trial of in vitro diagnostic reagents from the perspective of researchers. Therefore, this article summarizes the characteristics of clinical trials of in vitro diagnostic reagents, analyzes the problems and difficulties in conducting clinical trials of in vitro diagnostic reagents in current medical laboratories, and introduces the laboratory's experience in management; to provide reference for medical testing laboratories that have not yet conducted or have already conducted clinical trials of in vitro diagnostic reagents, in order to improve the quality and efficiency of clinical trials.

Symptoms across the phases of the migraine cycle from the patient's perspective: Results of the MiCOAS qualitative study.

To better understand the breadth and frequency of symptoms across the phases of the migraine cycle using data captured from qualitative patient interviews conducted through the Migraine Clinical Outcome Assessment System (MiCOAS) project. People living with migraine experience a range of symptoms across the pre-headache, headache, post-headache, and interictal phases of the migraine cycle. Although clinical diagnostic criteria and clinical trial endpoints focus largely on cardinal symptoms or monthly migraine days, migraine symptom profiles are far more complex. As a part of the MiCOAS project, semi-structured qualitative interviews were undertaken to better understand the migraine-related symptomology from the patient's viewpoint. This concept elicitation study used iterative purposeful sampling to select 40 people with self-reported medical diagnosis of migraine for interviews that were conducted via audio-only web conferencing. Key topics related to migraine symptoms, including mood/emotion symptoms, were identified using content analysis. Interview transcripts were also coded to reflect the phase of migraine under discussion, so that patient experiences could be compared by phase. Forty participants (50%, n = 20 episodic migraine; 50%, n = 20 chronic migraine), aged from 21 to 70 years old reported a total of 60 unique symptoms, which were categorized into 30 broader symptom categories. Participants reported between 7 and 22 unique symptom categories across all phases. During pre-headache and headache, participants reported a median of 7.5 (interquartile range [IQR] = 5.5) and 8 (IQR = 4.0) different symptom categories compared to 4 (IQR = 3.0) and 1.5 (IQR = 2.5) for the post-headache and interictal periods, respectively. Head pain during the headache phase was the only universally reported symptom (100%, n = 40). Pooling across all phases, the next most reported symptoms were light sensitivity (93%, n = 37), nausea (88%, n = 35), irritability/impatience (83%, n = 24), sound sensitivity (80%, n = 32), and fatigue/exhaustion (80%, n = 32). One or more interictal symptoms were reported by 73% (n = 29) of participants and included mood/emotion symptoms, such as anxiety (30%, n = 12), depression (18%, n = 7), and anger (15%, n = 6), as well as cardinal symptoms, such as light sensitivity (13%, n = 5) and nausea (13%, n = 5). Patients experience a range of symptoms across the phases of the migraine cycle. Results often aligned with clinical expectations, but non-cardinal migraine-related symptoms were reported both inside and outside the headache phase, including between attacks. These discoveries highlight the importance of assessing a range of symptoms and timing when developing patient-reported outcome measures for migraine clinical trials.

262.6: Absolute dd-cfDNA monitoring reduces time to ABMR diagnosis in kidney transplant recipients with de novo DSA: a diagnostic randomized clinical trial.

262.6: Absolute dd-cfDNA monitoring reduces time to ABMR diagnosis in kidney transplant recipients with de novo DSA: a diagnostic randomized clinical trial.

Temporary Vocal Fold Augmentation Outcomes for Refractory Chronic Cough with Concurrent Nonparalytic Glottic Insufficiency due to Vocal Fold Atrophy

ObjectiveDetermine the effect of temporary vocal fold augmentation on refractory chronic cough in patients with glottic insufficiency due to vocal fold atrophy. MethodsRetrospective electronic chart review was conducted for patients with a diagnosis of bilateral vocal fold atrophy and refractory chronic cough undergoing vocal fold augmentation with carboxymethylcellulose. Patients with vocal fold immobility were excluded, and cough must have been present for at minimum 8 weeks. VHI-10, CSI, and RSI scores along with subjective overall patient report of chronic cough improvement were collected. ResultsA total of 28 patients underwent 30 vocal fold augmentation procedures with carboxymethylcellulose. All had undergone extensive cough work-up and treatment trials prior to their augmentation procedure. From chart review, 13 overall subjectively reported satisfactory improvement in their cough, 5 reported partial improvement, and 7 reported no improvement in their cough. An uncertain effect on cough was documented in 5 (either patient was uncertain or no mention of cough symptom in the interval chart history note). For those subjects with both pre- and post-augmentation data, mean pre-augmentation CSI: 22.08 + 6.8 (n=13); VHI-10: 13.6 + 8.9 (n=18); RSI: 22.4 + 7.5 (n=17). Mean post-augmentation CSI was 20.7 + 9.2 (n=13); VHI-10: 15.2 + 8.2 (n=18); RSI: 21.1 + 5.8 (n=17). Mean pre-post change in CSI was -1.4 + 5.1 (p=0.175, n=13, range -10 – +6). ConclusionsVocal fold augmentation seems to provide subjective cough improvement in some patients with concurrent glottic insufficiency due to vocal fold atrophy and refractory chronic cough. It can be offered as a diagnostic trial, on which further augmentation may be offered, for patients with persistent cough despite prior work-up and treatment trials. Further controlled prospective studies are needed to identify factors that are predictive of successful cough improvement following vocal fold augmentation, as well as the effect of durable augmentation in those patients who had improvement with a diagnostic trial.

Current Advances in Radioactive Iodine-Refractory Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, and certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine (RAI) therapy is a cornerstone in DTC management, but cancer cells can eventually develop resistance to RAI. Radioactive iodine-refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. The RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. 18F-FDG PET/CT has been widely used and has demonstrated prognostic value, but 18F-FDG DTC avidity may remain low. Fibroblast activation protein inhibitors (FA-Pi)s, prostatic-specific membrane antigen (PSMA), and somatostatin receptor (SSTR) tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in the diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse-event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed at re-inducing RAI accumulation in DTC cells. Results appear promising, but not excellent. RAIR-DTC remains a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation, with post-therapy whole-body scan (PT-WBS) the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents obliges physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice.

Potential New Inflammatory Markers in Bronchiectasis: A Literature Review.

Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as "precision medicine". With respect to bronchiectasis, many comorbidities and underlying causes have been identified. Inflammatory endotypes have also been widely studied and reported. Additionally, several genes have been shown to affect disease progression. However, the lack of a clear classification has also hampered our understanding of the disease's natural course. The aim of this review is, thus, to summarize the current knowledge on biomarkers and actionable targets of this complex pathologic condition and to point out unmet needs, which are required in the design of effective diagnostic and therapeutic trials.

LMIC-10. GLOBAL MAPPING OF CLINICAL TRIALS FOR CHILDREN WITH CNS TUMORS

Abstract BACKGROUND While there has been an international call to increase access to pediatric oncology clinical trials, the current landscape of global clinical trials for pediatric central nervous system (CNS) tumors has not been described. We sought to analyze the availability of clinical trials available for children with CNS tumors worldwide. METHODS Clinical trials were included if they were interventional studies registered in International Clinical Trials Registry Platform (ICTRP) that included pediatric patients (≤17 years old) with a CNS tumor. PubMed and Google Scholar were used to identify peer-reviewed manuscripts describing the results of identified trials. RESULTS From 114,414 oncology trials, 322 studies met inclusion criteria. Geographically, 307 (95%) studies were sponsored by and conducted in high-income countries (HICs), while 15 studies (4.7%) were sponsored by and conducted in middle-income countries (MICs). No studies were registered in or accrued from low-income countries. Studies were mostly sponsored in the United States (244, 76%), United Kingdom (20, 6.2%), or France (13, 4.0%). Trials were mostly sponsored by individual institutions (168, 52%), followed by governmental organizations (100, 31%), collaborative groups (36, 11%) and pharmaceutical companies (18, 5.5%). Study characteristics differed with income status, with HICs registering mostly clinical trials for cancer-directed treatment (261, 85%) and MICs registering later phase supportive care-based or diagnostic trials (9, 60%). Of the studies included, 132 (43%) were published. There were similar rates of publishing results in HIC and MICs. Discussion: Low- and middle-income countries are under-represented in the global clinical research landscape of pediatric CNS tumors. Furthermore, these data describe the urgent needs to invest in clinical research infrastructure in LMICs and to foster collaborations that include LMICs as a critical step in achieving equity in global pediatric cancer care.

Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis.

Previous studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration. To compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF. Thirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8-45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP). MP perfusion score and QDP correlated strongly with the CE perfusion score (both r = 0.81; p < 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 (r = -0.75 and r = -0.83; p < 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated (r = 0.74 and r = 0.78; both p < 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated (r = 0.88 and r = 0.86; both p < 0.01). MP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials.

#1166 ACTION3 pivotal Phase 3 &amp; open-label extension study assessing DMX-200 in adult &amp; paediatric patients with focal segmental glomerulosclerosis (FSGS)

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is a major cause of glomerular disease that affects both adults and children. FSGS can rapidly progress to end-stage kidney disease. Lack of safe and effective treatment represents a significant unmet need for patients with FSGS. Development of treatments has been hampered by complexities including the rare nature of the disease, varying drivers of pathogenesis, and the evolving diagnostic and clinical trial designs, necessitating innovative research approaches. DMX-200 (repagermanium) is a C-C motif chemokine receptor 2 (CCR2) pathway inhibitor. Activation of the angiotensin II type 1 receptor (AT1R) and CCR2 have been independently implicated in the pathogenesis and progression of FSGS. These receptors form a functional complex so inhibition of both receptors may provide an efficient approach to FSGS treatment. In vivo data shows co-administration of DMX-200 and the angiotensin receptor blocker (ARB) irbesartan demonstrated a synergistic reduction in proteinuria, macrophage infiltration, and podocyte loss compared with vehicle or either antagonist alone. A subsequent Phase 2a cross-over study (NCT03649152) in N = 8 patients with biopsy-proven primary FSGS showed that the combination of DMX-200 and irbesartan (compared to placebo) was well tolerated with most patients experiencing a reduction in proteinuria. Based on these data, the global Phase 3 study (ACTION3) was initiated to confirm the proteinuria lowering effects of DMX-200 and assess effects on eGFR decline. ACTION3 is a randomised, placebo-controlled, double-blind, long-duration study of FSGS patients and on completion will provide a resource for the wider nephrology community and advocacy groups on the natural history of FSGS patients and the effects of a CCR2-inhibitor on the background of an ARB. Here we present the baseline data from the first 90 patients enrolled in ACTION3 at 12th January 2024. Method The ACTION3 (NCT05183646) study is a pivotal Phase 3, multicentre study of the efficacy and safety of DMX-200, 120 mg twice daily compared with placebo in adult patients with biopsy-proven FSGS receiving maximal tolerated ARB, with persistent proteinuria &amp;gt;1.5g/ day and eGFR &amp;gt;25 ml/min/1.73 m2. The study plans to enroll approximately 286 patients with primary FSGS, genetic FSGS and FSGS of undetermined cause with the primary objective of evaluating the efficacy of DMX-200 in percent change in 24-hour urine PCR and eGFR slope. The initial 104-week randomized period will be extended in a 2-year open label extension study. A futility analysis by an Independent Data Monitoring Committee following the first 72 patients completing 35 weeks of treatment confirm that continuation of the study is non-futile. Results The study is actively recruiting at 71 sites in 11 countries listed in Table 1. Demographic data of randomised patients is listed in Table 2. Patients are predominantly male (65%), with an average age of 46.6 yrs. and mean eGFR 56.3 ± 27.6 (ml/min/1.73 m2). The study is expanding recruitment into additional countries in the Asia Pacific, Europe, and Latin American regions. Further, the study protocol has sought and received regulatory approval to enroll adolescent patients aged 12-18 in Argentina, Mexico, UK and the US. Conclusion DMX-200 (repagermanium) has shown encouraging signs of safety and efficacy in combination with an ARB for the treatment of FSGS. The contributing countries and baseline characteristics of the patients enrolled in ACTION3 are similar to the populations studied in other recent FSGS trials. No clinically significant safety concerns have been observed in patients enrolled to date in the ACTION3 Phase 3 study.

Diagnostic Strategies for Restorations Management: A 70-Month RCT

We aimed to evaluate the impact of 2 visual diagnostic strategies for assessing secondary caries and managing permanent posterior restorations on long-term survival. We conducted a diagnostic cluster-randomized clinical trial with 2 parallel groups using different diagnostic strategies: (C+AS) based on caries assessment, marginal adaptation, and marginal staining aspects of the FDI (World Dental Federation) criteria and (C) based on caries assessment using the Caries Associated with Restorations or Sealants (CARS) criteria described by the International Caries Detection and Assessment System (ICDAS). The treatment for the restoration was conducted based on the decision made following the allocated diagnostic strategy. The restorations were then clinically reevaluated for up to 71 mo. The primary outcome was restoration failure (including tooth-level failure: pain, endodontic treatment, and extraction). Cox regression analyses with shared frailty were conducted in the intention-to-treat population, and hazard ratios (HRs) and 95% confidence intervals (95% CIs) were derived. We included 727 restorations from 185 participants and reassessed 502 (69.1%) restorations during follow-up. The evaluations occurred between 6 and 71 mo. At baseline, C led to almost 4 times fewer interventions compared with the C+AS strategy. A total of 371 restorations were assessed in the C group, from which 31 (8.4%) were repaired or replaced. In contrast, the C+AS group had 356 restorations assessed, from which 113 (31.7%) were repaired or replaced. During follow-up, 34 (9.2%) failures were detected in the restorations allocated to the C group and 30 (8.4%) allocated to the C+AS group in the intention-to-treat population, with no significant difference between the groups (HR = 0.83; 95% CI = 0.51 to 1.38; P = 0.435, C+AS as reference). In conclusion, a diagnostic strategy focusing on marginal defects results in more initial interventions but does not improve longevity over the caries-focused strategy, suggesting the need for more conservative approaches.

Accuracy of Repetitive Ocular Vestibular-Evoked Myogenic Potentials to Diagnose Myasthenia Gravis in Patients With Ptosis or Diplopia.

We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia. In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm. Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG. The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG. This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders. ClinicalTrials.gov: NCT03049956.

TIP24-197: R Role of [99m Tc] DTPA-bis (Choline) in Evaluation of Breast Cancer: A Prospective Diagnostic Trial in Progress at AIIMS Rishikesh.

TIP24-197: R Role of [99m Tc] DTPA-bis (Choline) in Evaluation of Breast Cancer: A Prospective Diagnostic Trial in Progress at AIIMS Rishikesh.

A Commentary on "Evaluation of transrectal ultrasound-guided tru-cut biopsy as a complementary method for predicting pathological complete response in rectal cancer after neoadjuvant treatment: a phase II prospective and diagnostic trial".

A Commentary on "Evaluation of transrectal ultrasound-guided tru-cut biopsy as a complementary method for predicting pathological complete response in rectal cancer after neoadjuvant treatment: a phase II prospective and diagnostic trial".

A Mini-review on Helicobacter pylori with Gastric Cancer and Available Treatments.

Helicobacter pylori (H. pylori) is the most thoroughly researched etiological component for stomach inflammation and malignancies. Even though there are conventional recommendations and treatment regimens for eradicating H. pylori, failure rates continue to climb. Antibiotic resistance contributes significantly to misdiagnoses, false positive results, and clinical failures, all of which raise the chance of infection recurrence. This review aims to explore the molecular mechanisms underlying drug resistance in H. pylori and discuss novel approaches for detecting genotypic resistance. Modulation of drug uptake/ efflux, biofilm, and coccoid development. Newer genome sequencing approaches capable of detecting H. pylori genotypic resistance are presented. Prolonged infection in the stomach causes major problems such as gastric cancer. The review discusses how H. pylori causes stomach cancer, recent biomarkers such as miRNAs, molecular pathways in the development of gastric cancer, and diagnostic methods and clinical trials for the disease. Efforts have been made to summarize the recent advancements made toward early diagnosis and novel therapeutic approaches for H. pylori-induced gastric cancer.

Degree of Uncertainty in Reporting Imaging Findings for Necrotizing Enterocolitis: A Secondary Analysis from a Pilot Randomized Diagnostic Trial.

Diagnosis of necrotizing enterocolitis (NEC) relies heavily on imaging, but uncertainty in the language used in imaging reports can result in ambiguity, miscommunication, and potential diagnostic errors. To determine the degree of uncertainty in reporting imaging findings for NEC, we conducted a secondary analysis of the data from a previously completed pilot diagnostic randomized controlled trial (2019-2020). The study population comprised sixteen preterm infants with suspected NEC randomized to abdominal radiographs (AXRs) or AXR + bowel ultrasound (BUS). The level of uncertainty was determined using a four-point Likert scale. Overall, we reviewed radiology reports of 113 AXR and 24 BUS from sixteen preterm infants with NEC concern. The BUS reports showed less uncertainty for reporting pneumatosis, portal venous gas, and free air compared to AXR reports (pneumatosis: 1 [1-1.75) vs. 3 [2-3], p < 0.0001; portal venous gas: 1 [1-1] vs. 1 [1-1], p = 0.02; free air: 1 [1-1] vs. 2 [1-3], p < 0.0001). In conclusion, we found that BUS reports have a lower degree of uncertainty in reporting imaging findings of NEC compared to AXR reports. Whether the lower degree of uncertainty of BUS reports positively impacts clinical decision making in infants with possible NEC remains unknown.

Core ion measurements with collective Thomson scattering for DEMO burn control

DEMO burn control will require measurements of a range of plasma parameters, but the suite of feasible diagnostics for this purpose is limited. Here we assess the accuracy with which a collective Thomson scattering (CTS) diagnostic can provide key measurements for burn control in the planned European DEMO (EU-DEMO). This is based on estimated signal-to-noise ratios for a conceptual diagnostic design and trial fits to synthetic DEMO CTS spectra. We show that a diagnostic with a single probe- and receiver beam setup will be able to provide simultaneous measurements of core fusion alpha density and ion temperature to mean accuracies better than 5% and 10%, respectively, along with detecting intrinsic toroidal rotation velocities down to within ∼5 km s−1. Adding a second CTS receiver view furthermore enables inference of the core fuel-ion ratio, allowing discrimination between, e.g. a 50%/50% and 55%/45% D/T mixture, while also providing useful information on the thermalized He content. A DEMO CTS diagnostic would thus be able to monitor fusion alpha densities as well as anomalous transport of fast alphas and heat from the plasma core, quantify plasma rotation for confinement enhancement, and track the core isotope mix for optimum fusion performance. This versatility makes such a diagnostic a potentially valuable tool for real-time burn control on DEMO.

Evaluation of transrectal ultrasound-guided tru-cut biopsy as a complementary method for predicting pathological complete response in rectal cancer after neoadjuvant treatment: a phase II prospective and diagnostic trial.

Patients with pathological complete response (pCR) of rectal cancer following neoadjuvant treatment had better oncological outcomes. However, reliable methods for accurately predicting pCR remain limited. To evaluate whether transrectal ultrasound-guided tru-cut biopsy (TRUS-TCB) adds diagnostic value to conventional modalities for predicting pathological complete response in patients with rectal cancer after neoadjuvant treatment. This study evaluated data of patients with rectal cancer who were treated with neoadjuvant treatment and reassessed using TRUS-TCB and conventional modalities before surgery. This study is registered with ClinicalTrials.gov. The primary outcome was accuracy, along with secondary outcomes including sensitivity, specificity, negative predictive value, and positive predictive value in predicting tumour residues. Final surgical pathology was used as reference standard. Between June 2021 and June 2022, a total of 74 patients were enroled, with 63 patients ultimately evaluated. Among them, 17 patients (28%) exhibited a complete pathological response. TRUS-TCB demonstrated an accuracy of 0.71 (95% CI, 0.58-0.82) in predicting tumour residues. The combined use of TRUS-TCB and conventional modalities significantly improved diagnostic accuracy compared to conventional modalities alone (0.75 vs. 0.59, P =0.02). Furthermore, TRUS-TCB correctly reclassified 52% of patients erroneously classified as having a complete clinical response by conventional methods. The occurrence of only one mild adverse event was observed. TRUS-TCB proves to be a safe and accessible tool for reevaluation with minimal complications. The incorporation of TRUS-TCB alongside conventional methods leads to enhanced diagnostic performance.

Diagnostic values of ten methods in patients with onychomycosis: A network meta‐analysis

AbstractBackgroundOnychomycosis, a disease was with a high global prevalence, has been the focal point of this study. The research aims to compare diagnostic efficacy among various methods, including potassium hydroxide (KOH), Dimethyl sulfoxide (DMSO), specific colour staining (Chlorazol, lactophenol cotton blue and Chicago sky blue stain), fluorescent staining (calcofluor white stain, acridine orange fluorescent dye), culture on dermatophyte test medium (DTM), conventional PCR, dermoscopy, histopathological examination using PAS stain (HEP‐PAS), real‐time PCR and multiple PCR. This comparison was achieved through a network meta‐analysis involving patients with onychomycosis.MethodsA comprehensive literature search was conducted across eight databases. Subsequently, both direct and indirect evidence were amalgamated to assess sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. This combination analysis helped to estimate the odds ratios (ORs) and surface under the cumulative ranking curve (SUCRA) values of the nine different methods, providing an in‐depth perspective on diagnosing onychomycosis.ResultsThe network meta‐analysis integrated 20 eligible diagnostic trials. The results exhibited that DTM provided higher sensitivity, NPV and accuracy, as indicated by SUCRA values. Meanwhile, DMSO demonstrated higher specificity and positive predictive value in terms of SUCRA values. Among the nine methods, fluorescent staining showcased comparatively superior sensitivity, specificity, NPV, PPV and accuracy. Furthermore, a cluster analysis indicated that DTM held the highest diagnostic value for sensitivity and accuracy among the nine techniques, with fluorescence staining ranking second.ConclusionThis network meta‐analysis strengthens the evidence suggesting that fluorescence staining exhibits strong diagnostic value in onychomycosis. This finding bears diagnostic implications for onychomycosis.