Identification of asymptomatic Leishmania infections: a scoping review

Background Asymptomatic Leishmania infection may play an important role in the transmission of the parasite in endemic areas. At present there is no consensus on the definition of asymptomatic Leishmania infection, nor is there a safe and accessible gold standard test for its identification. Methods This paper presents a scoping review to summarize definitions of asymptomatic Leishmania infection found in the literature, as well as to detail the approach (molecular, serological, cellular, and/or parasitological tests) used by researchers to identify this asymptomatic population. A scoping review of published and gray literature related to asymptomatic Leishmania infection was conducted; retrieved citations were screened based on predefined eligibility criteria, and relevant data items were extracted from eligible articles. The analysis is descriptive and is presented using tables, figures, and thematic narrative synthesis. Results We conducted a screening of 3008 articles, of which 175 were selected for the full review. Of these articles, we selected 106 that met the inclusion criteria. These articles were published between 1991 and 2021, and in the last 5 years, up to 38 articles were reported. Most of the studies were conducted in Brazil (26%), Spain (14%), India (12%), Bangladesh (10%), and Ethiopia (7%). Of the studies, 84.9% were conducted in the immunocompetent population, while 15.1% were conducted in the immunosuppressed population (HIV, immunosuppressive drugs, and organ transplantation population). We report 14 different techniques and 10 strategies employed by researchers to define asymptomatic Leishmania infection in an endemic area. Conclusions The definition of asymptomatic Leishmania infection is not unified across the literature, but often includes the following criteria: residence (or extended stay) in a Leishmania-endemic area, no reported signs/symptoms compatible with leishmaniasis, and positive on a combination of serological, molecular, cellular, and/or parasitological tests. Caution is recommended when comparing results of different studies on the subject of asymptomatic infections, as the reported prevalence cannot be confidently compared between areas due to the wide variety of tests employed by research groups. More research on the importance of asymptomatic immunosuppressed and immunocompetent Leishmania-positive populations in leishmaniasis epidemiology is required. Graphical Abstract

Diagnosis of Primary Ciliary Dyskinesia: Discrepancy according to different algorithms

BackgroundDiagnosis of primary ciliary dyskinesia (PCD) is challenging since there is no gold standard test. The European Respiratory (ERS) and American Thoracic (ATS) Societies developed evidence-based diagnostic guidelines with considerable differences.ObjectiveWe aimed to compare the algorithms published by the ERS and the ATS with each other and with our own PCD-UNIBE algorithm in a clinical setting. Our algorithm is similar to the ERS algorithm with additional immunofluorescence staining. Agreement (Cohen's kappa) and concordance between the three algorithms were assessed in patients with suspicion of PCD referred to our diagnostic centre.ResultsIn 46 out of 54 patients (85%) the final diagnosis was concordant between all three algorithms (30 PCD negative, 16 PCD positive). In eight patients (15%) PCD diagnosis differed between the algorithms. Five patients (9%) were diagnosed as PCD only by the ATS, one (2%) only by the ERS and PCD-UNIBE, one (2%) only by the ATS and PCD-UNIBE, and one (2%) only by the PCD-UNIBE algorithm. Agreement was substantial between the ERS and the ATS (κ=0.72, 95% Confidence Interval (CI) 0.53–0.92) and the ATS and the PCD-UNIBE (κ=0.73, CI 0.53–0.92) and almost perfect between the ERS and the PCD-UNIBE algorithms (κ=0.92, CI 0.80–1.00).ConclusionThe different diagnostic algorithms lead to a contradictory diagnosis in a considerable proportion of patients. Thus, an updated, internationally harmonized and standardised PCD diagnostic algorithm is needed to improve diagnostics for these discordant cases.

Standardization of the psychometric hepatic encephalopathy score in a French population

The Psychometric Hepatic Encephalopathy Score (PHES) has previously been standardized in thirteen countries on three continents, confirming its status of gold standard test to detect minimal hepatic encephalopathy (MHE). In the meantime, performance has also been shown to vary with variables such as age, education, and barely sex. The present study aimed at standardizing the PHES in a French population. One hundred and ninety-six French healthy participants completed a French version of the paper-and-pencil PHES, involving five tests and six measures. Importantly, the balance was perfect between all levels of the three controlled factors, which were sex, age (seven decade-levels from 20–29 to 80–89 years), and education (two levels below or above 12 years of education). Raw measures were transformed to fit the normal distribution. ANOVAs on transformed variables showed no effect of sex, but an effect of age on all measures, and of education on five measures. Multiple or simple regressions were completed to build up normograms. Thorough analysis of variability within each test failed to find outliers that may bias the results. Comparison between French and seminal German data showed that they highly fitted though cultural and cognitive style specificities could be observed. This is the first study to standardize the PHES in a French population and to extensively explore the effects of sex, age and education using perfectly balanced samples. Subtle differences between countries of the same continent emphasize the need to build up normative data in each country to get accurate PHES in patients.

Time of Onset of Necrotizing Enterocolitis and Focal Perforation in Preterm Infants: Impact on Clinical, Surgical, and Histological Features

Objective: There is no gold standard test for diagnosis of necrotizing enterocolitis (NEC). Timing of onset is used in some definitions and studies in an attempt to separate NEC from focal intestinal perforation (FIP) with 14 days used as a cutoff. In a large, detailed data set we aimed to compare NEC and FIP in preterm infants born <32 weeks gestation, presenting before 14 days of life in comparison to cases presenting later.Design: Infants with NEC or FIP when parents had consented to enrollment in an observational and sample collection study were included from 2009 to 2019. Clinical, surgical, histological, and outcome data were extracted and reviewed by each author independently.Patients/Episodes: In 785 infants, 174 episodes of NEC or FIP were identified of which 73 (42%) occurred before 14 days, including 54 laparotomies and 19 episodes of medically managed NEC (“early”). There were 56 laparotomies and 45 episodes of medically managed NEC presenting on or after 14 days age (“late”).Results: In early cases, 41% of laparotomies were for NEC (22 cases) and 59% for FIP (32 cases), and in late cases, 91% of laparotomies (51 cases) were for NEC and 9% (five cases) were for FIP. NEC presenting early was more likely to present with an initial septic presentation rather than discrete abdominal pathology and less likely to have clear pneumatosis. Early cases did not otherwise differ clinically, surgically, or histologically or in outcomes compared with later cases. FIP features did not differ by age at presentation.Conclusions: Although most FIP occurred early, 14% occurred later, whereas almost one third (29%) of NEC cases (surgical and medical) presented early. Infant demographics and surgical and histological findings of early- and late-presenting disease did not differ, suggesting that early and late cases are not necessarily different subtypes of the same disease although a common pathway of different pathogenesis cannot be excluded. Timing of onset does not accurately distinguish NEC from FIP, and caution should be exercised in including timing of onset in diagnostic criteria.

Serological, Molecular and Culture-Based Diagnosis of Lentiviral Infections in Small Ruminants

Small ruminant lentiviruses (SRLVs) infections lead to chronic diseases and remarkable economic losses undermining health and welfare of animals and the sustainability of farms. Early and definite diagnosis of SRLVs infections is the cornerstone for any control and eradication efforts; however, a “gold standard” test and/or diagnostic protocols with extensive applicability have yet to be developed. The main challenges preventing the development of a universally accepted diagnostic tool with sufficient sensitivity, specificity, and accuracy to be integrated in SRLVs control programs are the genetic variability of SRLVs associated with mutations, recombination, and cross-species transmission and the peculiarities of small ruminants’ humoral immune response regarding late seroconversion, as well as intermittent and epitope-specific antibody production. The objectives of this review paper were to summarize the available serological and molecular assays for the diagnosis of SRLVs, to highlight their diagnostic performance emphasizing on advantages and drawbacks of their application, and to discuss current and future perspectives, challenges, limitations and impacts regarding the development of reliable and efficient tools for the diagnosis of SRLVs infections.

Diagnostic Accuracy of tumor marker CA 19-9 in patients with cholangiocarcinoma taking ERCP as gold standard test”

Background: Majority of the cases of Cholangiocarcinoma at presentation are unresectable, it’s diagnosis at an early stage is pivotal but generally difficult due to lack of easy availaibility of confirmatory test at the moment in our country. Endoscopic Retrograde Cholangiopancreatography (ERCP) is not only helpful in reaching the diagnosis Aim: To find out the diagnostic accuracy of tumour marker CA 19-9, in suspected patients of Cholangiocarcinoma taking ERCP as gold standard test Methods: This cross sectional study was conducted in general and private clinics of Department of Gastroenterology of the Fatima Memorial Hospital Lahore from, October 21, 2014 to April 20, 2015. Sampling technique used was probability purposive sampling. Results: A total of 150 suspected patients of cholangiocarcinoma were included in the study in which 61 (40.7%) were male and 89(59.3%) were female with total mean age of 56.32±14.13 years. Among the studied patients, 88(58.7%) were found positive for malignant stricture on ERCP and CBD brushing cytology. Sensitivity, specificity and accuracy of the tumour marker CA 19-9 was 53.4%, 66.1% and 58% respectively. Conclusions: CA 19-9 is a very important tumor marker in making diagnosis of cholangiocarcinoma and in our country due to lack of easy access/availability to invasive diagnostic methods like endoscopic ultrasonography (EUS) and fine needle aspiration (FNA) of the tumor. It should be used as routine early diagnostic modality in suspected cases of Cholangiocarcinoma. Keywords: Cholangiocarcinoma, Cancer antigen (CA) 19-9, ERCP, biliary brushing and cytology

Complications of nasal SARS-CoV-2 testing: a review

Transnasal swab testing for the detection of SARS-CoV-2 is well established. The Centers for Disease Control and Prevention advocates swabbing either of the anterior nares, middle turbinate, or nasopharynx for specimen collection depending on available local resources. The purpose of this review is to investigate complications related to transnasal SARS-CoV-2 testing with specific attention to specimen collection site and swab approach. The literature demonstrates that while nasopharyngeal swabbing is associated with an increased risk of complications, it should remain the gold-standard test due to greater diagnostic accuracy relative to anterior nasal and middle turbinate swabs.

Postanesthetic Cold Sensibility Test as an Indicator for the Efficacy of Inferior Alveolar Nerve Block in Patients with Symptomatic Irreversible Pulpitis of Mandibular Molars

Aim of the Work. The goal of the current study was to investigate the capability of the cold test to predict the profound pulpal anesthesia before starting the endodontic treatment of mandibular first molars with symptomatic irreversible pulpitis (SIP). Materials and Methods. This study was conducted on the mandibular first molars of 54 patients (35 males and 19 females) with signs and symptoms of SIP. To anesthetize the affected molars, all patients received a single carpule of 2% lidocaine with 1 : 100000 epinephrine using a standardized inferior alveolar nerve block (IANB) technique. The cold test was conducted before beginning the endodontic procedures and after gaining lip numbness, and the results were reported as either positive or negative response. The root canal preparation (RCP) was then initiated and the patients’ responses were documented (Gold standard test). True pulpal anesthetic failure was described as a pain perception during the access cavity and pulp tissue removal. True pulpal anesthesia was defined as no pain or discomfort during the access cavity and pulp extirpation. The qualitative variables frequencies and percentages of patients with true/false positive and negative responses were determined and then compared using the Chi-square test. The pain perception of male and female patients during the cold test and gold standard was compared using the Fisher exact test. The following diagnostic parameters were calculated using an online statistical calculator: sensitivity, specificity, predictive values, accuracy, and Youden index. In addition, a receiver operating characteristic curve (ROC) was constructed and the area under the curve (AUC) was calculated. Results. The overall percentage of actual failure of pupal anesthesia was 57%. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and Youden index for the cold test were 0.87, 0.91, 0.93, 0.84, 0.89, and 0.78, respectively. There was no statistically significant difference between male and female patients regarding their responses to cold testing and the gold standard test ( P > 0.05 ). Besides, the patients’ reactions to the cold test were significantly matched with their reactions to the gold standard test ( P < 0.05 ). The area under the ROC was mostly 0.9. Conclusion. The cold test could be a valuable and accurate method for predicting the potential pupal anesthesia before beginning the endodontic treatment of mandibular molars with symptomatic irreversible pulpitis, particularly after obtaining postanesthetic soft tissue numbness.

Neutralizing Antibody Response of Vaccinees to SARS-CoV-2 Variants

Due to their increased transmissibility, three variants of high concern have emerged in the United Kingdom (also known as B.1.1.7 lineage or VOC-202012/01), South Africa (B.1.351 lineage), and Brazil (P1 lineage) with multiple substitutions in the spike protein. Since neutralizing antibodies elicited by vaccination are likely considered as correlates of protection for SARS-CoV-2 infection, it is important to analyze whether vaccinees with mRNA BNT162b2 are equally protected against these emerging SARS-CoV-2 variants. To this aim, we enrolled healthy subjects one month after complete vaccination with Comirnaty and evaluated the neutralizing response against the native Wuhan strain and the emerging B.1.1.7, B.1.351 and P1 lineages, by using the microneutralization assay, currently considered the gold standard test for the evaluation and detection of functional neutralizing antibodies. The most remarkable finding of this study was the significantly lower neutralizing antibody titer against B.1.351 lineage, compared to the wild-type virus. No significant differences were observed with the other two lineages. These findings provide evidence that vaccinated subjects may not be equally protected against all SARS-CoV-2 lineages.

The Effects of Sampling Lateralization on Bilateral Inferior Petrosal Sinus Sampling for Pediatric Cushing’s Disease—A Single Endocrinology Centre Experience and Review of the Literature

BackgroundThis study aims to analyze the diagnostic accuracy of bilateral inferior petrosal sinus sampling (BIPSS), the gold standard test for the differential diagnosis of ACTH-dependent Cushing’s syndrome (CS) in a group of pediatric patients with Cushing’s disease (CD).MethodsThis is a retrospective analysis which include 12 patients with hypercortisolemia and inconclusive pituitary MRI, who underwent bilateral inferior petrosal sinus sampling (BIPSS) and transsphenoidal surgery (TSS) from 2004 to 2020 in the Children’s Memorial Health Institute (CMHI) Warsaw, Poland. Pituitary origin of ACTH secretion was considered if baseline central to peripheral (C/P) ACTH level ratio was ≥ 2 or C/P ratio was ≥ 3 after human corticotropin-releasing hormone (hCRH) stimulation. The diagnosis was histologically confirmed in almost all cases after TSS.ResultsThe diagnostic accuracy of BIPSS reached 75% at baseline and 83.3% after CRH stimulation. The compatibility of localization of a microadenoma by BIPSS with the surgical location was 66.7%.ConclusionsOwing to its high diagnostic effectiveness, BIPSS remains the best test to differentiate CD from EAS. The indications for the procedure should be carefully considered, because EAS in the pediatric population, unlike in adults, is extremely rare. Moreover BIPSS has only limited value for indicating tumor localization.