Diagnostic Gold Standard Research Articles

Psychiatric management of Patients in intensive care units.

Psychiatric management of Patients in intensive care units.

Läsionen der Trizepssehne

The triceps brachii muscle is the main extender of the elbow joint. Triceps tendon rupture or tearing presents arare injury pattern in general. Distal tendon ruptures occur most commonly in the area of the insertion of the olecranon. Fractures of the radial head are reported as the most common concomitant injury. In many cases, pre-existing degenerative damage predisposes for tendon injury. These include local steroid injections, anabolic steroid abuse, renal insufficiency requiring dialysis, hyperparathyroidism, lupus erythematosus and Marfan's syndrome. However, the most frequent trauma mechanism is adirect fall onto the extended forearm or ablow to the elbow. Beside clinical examination and sonography, magnetic resonance imaging is the diagnostic gold standard. The treatment of triceps tendon injuries includes conservative as well as operative approaches, whereby the indications for surgical treatment must be generously considered depending on the patient's age, functional demands of the patient, involvement of the dominant extremity as well as on the extent of the tendon rupture.

The Obstructive Lung Diseases Program: Integrated obstructive lung disease services within primary care in Pakistan.

Objective:To assess the learning impact of e-curriculums on healthcare professionals (HCPs). The second objective was to report the screening, detection and clinical features of patients with obstructive lung diseases (OLD) through an integrated care program at The Indus Hospital & Health Network (IHHN), Karachi, Pakistan.Methods:A retrospective, observational study was conducted in the Family Medicine outpatient department from January 2019 till July 2021. HCPs were trained on the diagnosis and management of OLD through e-learning. Patients were screened clinically for OLD and had spirometry performed if suspect. Baseline characteristics, patient-reported outcome measures (PROMs), spirometry and treatment modalities were collected. Univariate analysis was done on Excel and paired t-testing was performed on Stata 16.Results:Online training on clinical aspects of OLD was completed by 33 HCPs, amongst whom 77.9% demonstrated improved post-test evaluations of 26.8% (p=0.000). Of 1896 patients screened, 60.8% were diagnosed as OLD. Asthmatics accounted for 66.5% (60.9% females, median age 39 years). In 84.5% of patients who completed PROMs, poor control of symptoms was reported. Inhaler technique was taught in 66.5%. Breathless patients, with a high modified Medical Research Council score (mMRC ≥ 2, n=234), were referred for pulmonary rehabilitation in 92% of cases. Tobacco cessation advice was delivered to 61.1% of all current users (n=229).Conclusion:The OLD program uses capacity building, gold standard diagnostics and updated management strategies in primary care, allowing earlier diagnosis of suspected patients and implementation of evidence-based interventions, aiming to improve their morbidity and mortality.

Noninvasive biomarkers in predicting nonalcoholic steatohepatitis and assessing liver fibrosis: systematic review and meta-analysis.

Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation, ballooned hepatocytes and possible fibrosis, which may progress to liver cirrhosis. Although liver biopsy, remains the diagnostic gold standard of NASH, several noninvasive biomarkers have been studied, to avoid the need for this invasive procedure. We performed a systematic review with meta-analysis to evaluate the accuracy of several noninvasive biomarkers in predicting NASH and assessing liver fibrosis in NASH patients. An electronic search on PubMed and Embase was systematically performed. The principal summary outcome was the area under the curve (AUC), assessing the accuracy of NashTest, BARD (Body Mass Index, AST/ALT ratio, diabetes) score, NAFLD fibrosis score (NFS), APRI (aspartate aminotransferase-to-Platelet Ratio Index), and Fibrosis-4 (FIB-4) Index in predicting NASH and assessing liver fibrosis. Thirteen studies involving 6557 adult patients were included in the qualitative assessment of this review, out of which, six studies were included in the quantitative assessment. Prediction of NASH was evaluated better using NFS (AUC of 0.687) and FIB-4 (AUC of 0.729). Fibrosis stages 0 vs. 1-4 was diagnosed better using NFS (AUC of 0.718) and FIB-4 (AUC of 0.723). Advanced fibrosis was assessed better by BARD (AUC of 0.673), APRI (AUC of 0.762), NFS (AUC of 0.787) and FIB-4 (AUC of 0.821). FIB-4 predicted NASH and quantified liver fibrosis, stages 0 vs. 1-4 more precisely compared to NFS, APRI, and BARD. However, considering that methodological quality of the assessed studies is limited, the results should be considered with caution.

Modern approaches in the treatment of patients with Paget-Schretter syndrome

Goal. Consider the management of patients with effort thrombosis (Paget-Schretter syndrome).The article presents the modern vision of the problem of effort thrombosis. This review is aimed at describing the epidemiology, pathophysiology, diagnosis and treatment of patients with Paget-Schretter syndrome. SPS occurs spontaneously, as a rule, in young, healthy and active patients aged 20-30 years after strenuous physical activity. The ratio of men and women is 2:1, recently there has been a growing trend among women. The main complaints of patients with SPS include swelling of the affected limb, discomfort when moving the affected arm, pain and heaviness when trying to raise the arm up. When examining these patients, attention is paid to hyperemia of the skin or their cyanotic nature, pasty limbs, as well as an enhanced venous pattern on the shoulder, the so-called Arshel sign. The diagnosis is based on the data of anamnesis, physical examination, the “gold standard of diagnostics” – ultrasound examination of veins, the sensitivity and specificity of which is 70-100%. The first step in the diagnosis can be the evaluation of the D-dimer, with its negative values, the SPSH is rejected. With an obvious clinic and controversial results of serial ultrasound examinations, other imaging methods are used, such as computed contrast tomography, magnetic resonance imaging, the diagnostic value of which is especially significant in occlusive venous thrombosis.SPS differs not only from DVT of the lower extremities, but also from secondary DVT of the upper extremities, which determines the peculiarities of management of this category of patients, including surgical treatment aimed at preventing subclavian vein compression in the future. The article summarizes the experience in the management of patients with blood thrombosis.

Cardiovascular magnetic resonance of cardiac tumors and masses.

Cardiac masses diagnosis and treatment are a true challenge, although they are infrequently encountered in clinical practice. They encompass a broad set of lesions that include neoplastic (primary and secondary), non-neoplastic masses and pseudomasses. The clinical presentation of cardiac tumors is highly variable and depends on several factors such as size, location, relation with other structures and mobility. The presumptive diagnosis is made based on a preliminary non-invasive diagnostic work-up due to technical difficulties and risks associated with biopsy, which is still the diagnostic gold standard. The findings should always be interpreted in the clinical context to avoid misdiagnosis, particularly in specific conditions (e.g., infective endocarditis or thrombi). The modern multi-modality imaging techniques has a key role not only for the initial assessment and differential diagnosis but also for management and surveillance of the cardiac masses. Cardiovascular magnetic resonance (CMR) allows an optimal non-invasive localization of the lesion, providing multiplanar information on its relation to surrounding structures. Moreover, with the additional feature of tissue characterization, CMR can be highly effective to distinguish pseudomasses from masses, as well as benign from malignant lesions, with further differential diagnosis of the latter. Although histopathological assessment is important to make a definitive diagnosis, CMR plays a key role in the diagnosis of suspected cardiac masses with a great impact on patient management. This literature review aims to provide a comprehensive overview of cardiac masses, from clinical and imaging protocol to pathological findings.

Abstract 13402: Continuous Rhythm Monitoring in Patients After Embolic Stroke of Undetermined Source Yields High Evaluation Burden

Introduction: Embolic stroke of undetermined source (ESUS) accounts for up to 20% of ischemic strokes. Undetected atrial fibrillation (AF) represents one important underlying cause. Once diagnosed, initiation of oral anticoagulation is recommended for secondary stroke prevention. Yet, detection of paroxysmal AF is tedious. Implantable loop recorders (ICM) have evolved as the diagnostic gold standard. Prior studies have indicated that ICM implantation and remote monitoring in particular result in a relevant financial and personnel burden in unselected patients. ESUS patients are considered at higher risk of an AF diagnosis. Hypothesis: We hypothesized that AF diagnosis by ICM and remote monitoring puts considerable strain on health care providers, even in patients at high risk for AF after ESUS. Methods: We investigated all patients of our hospital-based, prospective, single-center, observational ESUS cohort that were equipped with an ICM after ESUS between January 2018 and December 2019. Follow-up was performed through July 2020. Results: Overall, 179 patients were eligible for analysis. Of these, 38 patients (22,1%) were diagnosed with AF by ICM and remote monitoring. During the study period a total of 11,975 episodes were transmitted through remote monitoring, of which 3,766 were alarms for AF. Response to alarms resulted in 307 on site visits and 132 telephone calls to inquire about symptoms, to inform about the diagnosis of AF, and to initiate a change in antithrombotic regimen from antiplatelet therapy to oral anticoagulation. On average, a single ESUS patient generated 40.9 episodes per year for review, triggered one additional on-site visit, and every other patient required additional telephonic follow-up. The number needed to diagnose one ESUS patient with AF within one year was 5. Conclusions: ICM and remote monitoring can successfully diagnose AF in a high-risk cohort after ESUS. Yet, the number of alarms other than for AF, and alarms inappropriately suggesting AF by far exceed appropriate AF diagnoses. Even in a cohort at high risk for AF and with an immediate therapeutic consequence upon AF diagnosis, the resulting burden on personnel and health care resources is high. An optimization of diagnostic ICM algorithms is therefore desirable.

The Agreement between Feline Pancreatic Lipase Immunoreactivity and DGGR-Lipase Assay in Cats-Preliminary Results.

Simple SummaryFeline pancreatitis is a common disease with diagnostics requiring a combination of clinical, laboratory and imaging methods. Measuring of pancreatic lipase concentration is the laboratory mainstay of feline pancreatitis diagnostics. It can be done using immunoenzymatic assay (feline pancreatic immunoreactivity, fPLI) or colorimetric assay based on hydrolyzing a special substrate (DGGR) to a color product. A DGGR-lipase assay is manufactured by various companies. Studies carried out in cats on the DGGR-lipase assay of a single manufacturer have shown a high agreement with fPLI, however studies in dogs indicate that the performance of assays of different manufacturers may vary considerably. One of the largest Polish veterinary laboratories working 24/7 in the largest Polish cities offers the DGGR-lipase assay of a large Polish laboratory solutions provider. The values obtained in this assay are higher than those yielded by the traditional DGGR-lipase assay validated in studies carried out so far. Therefore, we decided to evaluate the agreement between the DGGR-lipase assay of the Polish manufacturer and fPLI. The agreement proved to be as high as for the traditional assay.The colorimetric catalytic assay based on the use of 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) (DGGR) ester as a substrate for pancreatic lipase activity is commonly used for the diagnosis of pancreatitis in dogs and cats. Even though the assay has generally been shown to yield consistent results with feline pancreatic lipase immunoreactivity (fPLI) assay, the agreement may vary between assays of different manufacturers. In this study, the chance-corrected agreement between a DGGR-lipase assay offered by one of the biggest providers of diagnostic solutions in Poland and fPLI assay was investigated. The study was carried out on 50 cats in which DGGR-lipase activity and fPLI were tested in the same blood sample. The chance-corrected agreement was determined using Gwet’s AC1 coefficient separately for the fPLI assay’s cut-off values of >3.5 μg/L and >5.3 μg/L. The DGGR-lipase activity significantly positively correlated with fPLI (Rs = 0.665; CI 95%: 0.451, 0.807, p < 0.001). The chance-corrected agreement between the fPLI assay and DGGR-lipase assay differed considerably depending on the cut-off values of the DGGR-lipase assay. When the cut-off value reported in the literature (>26 U/L) was used, it was poor to fair. It was moderate at the cut-off value recommended by the laboratory (>45 U/L), and good at the cut-off value recommended by the assay’s manufacturer (>60 U/L). The highest agreement was obtained between the fPLI assay at the cut-off value of 3.5 μg/L and the DGGR-lipase assay at the cut-off value of 55 U/L (AC1 = 0.725; CI 95%: 0.537, 0.914) and between the fPLI assay at the cut-off value of 5.3 μg/L and the DGGR-lipase assay at the cut-off value of 70 U/L (AC1 = 0.749; CI 95%: 0.577, 0.921). The study confirms that the chance-corrected agreement between the two assays is good. Prospective studies comparing both assays to a diagnostic gold standard are needed to determine which of them is more accurate.

Searching for Service and Accessibility Excellence in Paroxysmal Nocturnal Hemoglobinuria in Canada: The Epic Program

Introduction:Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease affecting 1-10 per million per year, characterized by uncontrolled complement-mediated intravascular hemolysis, thrombosis, and marrow failure. PNH manifests in a wide variety of symptoms such as fatigue, dyspnea, chest pain, abdominal pain, and hemoglobinuria. Due to its nonspecific presentation, patients may experience a delay in accurate diagnosis of this rare disease, which has been shown to have a significant impact on quality of life (QoL) and survival. At any point in the patient's journey, they may experience delays or poor accessibility to care. Key challenges in PNH remain its initial identification, diagnosis, and subsequent timely treatment.Methods:The Canadian PNH Network (CPNHN) use the “CATCH criteria” to suspect diagnosis of PNH: Cytopenias, Aplastic anemia/myelodysplasia, Thrombosis, Coombs‘-negative hemolysis, and Hemoglobinuria. This screening tool has not been formally validated, however it was hypothesized to be useful for real-world practitioners. In this study, we aimed to: (1) identify opportunities and gaps during the journey of a patient with suspected or confirmed PNH, referred to a CPNHN center (Pilot sites: University Health Network (UHN) & Sunnybrook Health Sciences Centre (SHSC)); (2) characterize time to diagnosis and treatment initiation, specifically considering CATCH criteria; and (3) assess the presentations with the highest frequency of being referred to a CPNHN center to create a process map.Results:A total of 19 participants were identified at UHN, 17 charts were reviewed, and 15 patients were available for 30-minute individual interviews. The timeline was based on the participants’ initial presentation to start of targeted treatment (i.e., eculizumab). Baseline demographic data are presented in Table 1. Mean age at diagnosis was 46.1 years (standard deviation [SD] 16.7), with varied symptoms at presentation (Figure 1). Median number of healthcare providers seen prior to diagnosis and/or referral was 6 (interquartile range [IQR] 4-10; Figure 2), and time from symptom onset to referral was 17 months (IQR 6-67). The most common CATCH criteria at presentation were hemoglobinuria, Coombs'-negative hemolysis, and cytopenias (i.e., anemia and thrombocytopenia) (Table 2). Flow cytometry revealed large granulocyte (85.9% ± 16.9), monocyte (84.7% ± 17.4), and type III RBC (20.8% ± 18.5) populations. From the interviews, we noted that individual participants had diverse experiences and journeys with PNH. Reflecting on the COVID-19 pandemic, participants reported no change in quality of care they had received, and some endorsed the convenience of virtual consultation without being required to travel long distances for in-person visits. Several suggestions included: improving community physician awareness and education on PNH, assistance with finances (transportation/parking), and need for ongoing patient education on available medications and clinical trials.Discussion and Conclusion:PNH is a rare disease that can manifest in many different, non-specific ways, contributing to delays in diagnosis and treatment initiation. We have characterized the patient journeys of a cohort of patients followed at our centers, and have identified gaps and potential areas for improvement. The variability and delay in assessment for PNH may be attributed to the diverse backgrounds of the participants, first presentation abroad, year of symptom presentation, and availability of high-sensitivity flow cytometry, which is the diagnostic gold standard. In addition to characterizing the initial presentations and barriers to diagnosis and treatment, we also evaluated humanistic factors such as QoL. As PNH is rare, the study was limited by the small sample size and some incomplete records, as some patients were diagnosed and managed elsewhere initially.We plan to expand our work across Canada, which will increase our cohort size and better allow an assessment of the impact of geographical differences on access to care. Following this, we plan to provide recommendations for diagnostic and treatment benchmarks to colleagues across the country, introduce the CATCH criteria, and subsequently evaluate the impact of these knowledge translation strategies with comparison to our initial cohort. [Display omitted] DisclosuresChow: Alexion: Other: Site investigator for clinical trial. Patriquin: Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Speakers Bureau; Apellis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Biocryst: Honoraria; Sanofi: Honoraria.

SPECIES-SPECIFIC PCR FOR THE DIAGNOSIS OF SPOROTRICHOSIS CAUSED BY SPOROTHRIX BRASILIENSIS

Despite thousands of sporotrichosis cases related to the zoonotic transmission of Sporothrix brasiliensis have been described, the diagnostic gold standard is still the classical culturing methods. The mycological culture results are available afterseven to 30 days of incubation. Since an early diagnosis contributes to improving thetreatment and to the spread control of this mycosis, studies evaluating faster diagnosticmethods are needed. Therefore, we aimed to evaluate the species-specific PCR for thesporotrichosis diagnosis caused by S. brasiliensis, using samples collected with a noninvasive technique. Seventy-four swabs from feline (n=64), canine (n=5), and human(n=5) suspect sporotrichosis cases were included. All samples were submitted to classicalmethods for diagnosis and to S. brasiliensis-specific PCR. Using mycological culture asthe gold standard, the diagnosis of S. brasiliensis-caused infection was confirmed in 69%(51/74) of the cases. PCR was positive in 30 out of these 51 cases, showing 59%sensitivity, 100% specificity, 72% accuracy, 100% positive predictive value, and 52%negative predictive value. Consequently, more studies are needed to elucidate theinterference factors that culminated with the high rate of false-negative results and thenoptimize this molecular test for the accurate diagnosis of infections caused by S.brasiliensis.

Characterization of Collagen I Fiber Thickness, Density, and Orientation in the Human Skin In Vivo Using Second-Harmonic Generation Imaging

The assessment of dermal alterations is necessary to monitor skin aging, cancer, and other skin diseases and alterations. The gold standard of morphologic diagnostics is still histopathology. Here, we proposed parameters to distinguish morphologically different collagen I structures in the extracellular matrix and to characterize varying collagen I structures in the skin with similar SAAID (SHG-to-AF Aging Index of Dermis, SHG—second-harmonic generation; AF—autofluorescence) values. Test datasets for the papillary and reticular extracellular matrix from images in 24 female subjects, 36 to 50 years of age, were generated. Parameters for SAAID, edge detection, and fast Fourier transformation directionality were determined. Additionally, textural analyses based on the grey level co-occurrence matrix (GLCM) were conducted. At first, changes in the GLCM parameters were determined in the native greyscale images and, furthermore, in the Hilbert-transformed images. Our results demonstrate a robust set of parameters for noninvasive in vivo classification for morphologically different collagen I structures in the skin, with similar and different SAAID values. We anticipate our method to enable an automated prevention and monitoring system with an age- and gender-specific algorithm.

26138 Clinical utility and reliability of buccal mucosal biopsies for the diagnosis of ocular cicatricial pemphigoid in patients with isolated ocular disease

Ocular cicatricial pemphigoid (OCP) is a subset of the disease mucous membrane pemphigoid, specifically with involvement of the ocular mucosa. OCP is characterized by chronic conjunctivitis, progressive subepithelial fibrosis, ocular keratinization, and if left untreated, blindness. The current diagnostic gold standard is conjunctival biopsy with direct immunofluorescence demonstrating linear deposition of one or more immunoreactants (IgA, IgG, or C3) at the epithelial basement membrane. However, sensitivity of conjunctival biopsy is variable and reported in the range of 50-80%. Buccal mucosal biopsy has been shown to be positive in patients with OCP, but its use has not been studied in patients with isolated ocular disease. This study aims to identify the utility and reliability of buccal mucosal biopsy for OCP diagnosis in a cohort of 38 patients presenting with cicatrizing conjunctivitis where OCP with isolated ocular involvement is suspected. We observed 37% (14/38) positivity on the first buccal biopsy, with an increase to 53% (20/38) when 2 or more were performed, notably at different time points (mean difference = 298 days). In addition, 50% (6/12) of patients with a negative first buccal biopsy had a positive second biopsy. For patients with persistently negative (>2) buccal biopsies, conjunctival biopsies were positive in 75% (3/4). Serologic studies were largely negative, with less than 5 patients demonstrating autoantibodies via indirect immunofluorescence or ELISA. Therefore, multiple buccal mucosal biopsies done at separate points in time may be an effective alternative to conjunctival biopsy, offering a safer route for diagnosis of OCP in patients with isolated ocular involvement.

#26: Investigating CMV Pathogenesis and Breast Milk Transmission In Premature Infants Who Acquire Symptomatic CMV Viremia

Abstract Background CMV can be transmitted to babies after birth through breast milk and such infections may lead to a “sepsis-like syndrome” with neutropenia, hepatitis, and viremia. CMV infections can be epidemiologically characterized by envelope glycoprotein (gB) genotypes - gB1, gB2, gB3 and gB4. The role of specific genotypes in pathogenesis and immune control of infection is incompletely characterized. These studies aimed to characterize viral and host correlates of breast-milk transmission of CMV in a neonatal intensive care unit (NICU) setting. Methods 200 infants were enrolled in a prospective study of infants &amp;lt;1500 grams at birth in the NICU at the University of MN Masonic Children’s Hospital. Breast milk samples were available from 164 mothers, representing 184 infants (including twin pairs). We compared CMV IgM titer (Gold Standard Diagnostics Corp, CA) and CMV IgG titer (Diamedix, FL) in non-viremic infants of seropositive mothers for whom we had available serum (n=48 infants), and in eight infants with DNAemia. Positive CMV Breast milk samples from 65 mothers were further characterized by a multiplex real-time PCR assay, to characterize and compare gB genotypes. Results The prevalence of DNAlactia in the breast milk was 65/150 (43%). There were 49 mothers for whom CMV was present in breast milk, for which we also had infant whole blood samples (58 infants; 40 singletons and 9 twin pairs). Eight infants, exposed to CMV in the breast milk, developed CMV viremia (8/58=13%). Clinicians had not tested for CMV in 5/8 cases. Anti-CMV IgM antibodies were detected in 6/8 (75%) viremic infants. One non-viremic infant with CMV infection was identified solely by the IgM assay. There was no difference in ELISA IgG titers between infants with CMV viremia, and nonviremic infants. The subset of 65 CMV positive breast milk samples, 25 were positive for gB1 (39%), 13 were positive for gB2 (20%), 23 were positive for gB3 (35%) and 11 were positive for gB4 (17%); 11 samples were positive for multiple gB genotypes. For six samples, the gB genotype was unable to be determined. The gB genotype was determined for 5 of eight breast milk samples from mothers of the viremic babies with gB1 being the most common. In 3 of the 8 viremic samples, genotype was unable to be determined. Conclusion Breast milk from CMV-seropositive lactating mothers in a NICU setting can lead to transmission of infection and development of symptomatic CMV disease, which may not be recognized by clinicians. The distribution of gB genotypes in breast milk is similar to that observed in other CMV epidemiological analyses, and multiple genotypes may be identified in lactating seropositive women. Since gB is a critical target in CMV vaccine design, understanding strain-specific transmission may have implications for understanding the impact of pre-pregnancy vaccination on breast milk transmission. Purified recombinant gB vaccines studied in clinical trials are based on based on the Towne strain of CMV, gB1 genotype (DOI: 10.1128/JVI.01695-18). Future studies should examine the impact of strain-specificity of vaccination on circulation of CMV strains in infants with CMV disease.

ASSURED‐compliant point‐of‐care diagnostics for the detection of human viral infections

AbstractViral disease outbreaks have been always a threat to global public health making affordable, rapid and accurate diagnostics highly important tools to slow down the spread of viruses and decrease the mortality rate. Point‐of‐care (POC) diagnostics have emerged as a strong tool for the diagnosis of viral infections, especially in countries where health‐care systems are inadequate to provide proper services to all citizens. According to the World Health Organization, an ideal POC diagnostic must be Affordable, Sensitive, Specific, User‐friendly, Rapid/Robust, Equipment‐free and Deliverable (ASSURED). This review surveys carefully each ASSURED criterion and identifies where existing viral POC diagnostics fail to meet these criteria. Given the widespread concern with plastic pollution, we also propose the addition of 'disposability' to the existing ASSURED criteria and consider the letter “D” as the representative of both Deliverable and Disposable. Next, the POC tests used for the diagnosis of several common human viral infections which met all the ASSURED criteria (ASSURED‐compliant) are described in detail. Finally, the future of ASSURED‐compliant POC diagnostics, capable of generating comparable results to the viral diagnostic gold standards, is discussed.

Spindle cell neoplasms of the upper gastrointestinal tract, hepatobiliary tract, and pancreas by fine needle aspiration: A single institutional experience of 15 years with follow-up data.

The diagnosis of spindle cell neoplasms (SCN) of the upper gastrointestinal (GI) tract, hepatobiliary tract, and pancreas detected by fine needle aspiration (FNA) is challenging. We describe a single-center experience of these samples with follow-up data and characterization of the morphologic findings. We retrospectively reviewed pathology records for all FNAs diagnostic for or suggestive of SCN on esophagus, stomach, small bowel, liver, and pancreas in a 15 year period. All cases with at least 6 month follow-up were included. Surgical material (biopsy or resection) was the diagnostic gold standard. All FNAs with subsequent surgical specimens were reviewed and assessed for cellularity, architectural features, and nuclear features. In 15 years, 5101 FNAs of the upper GI tract, hepatobiliary tract, and pancreas were performed. SCN was diagnosed in 98 (2%) patients. Seventy-two patients had definitive pathologic diagnoses: 68 were neoplastic and four were non-neoplastic. Cytomorphologic review in relationship to final diagnosis revealed three statistically significant features: low cellularity favors a benign process (P=.00544), epithelioid nuclear morphology favors malignancy (P=.00278), and identification of perinuclear vacuoles favors a diagnosis of GIST over non-GIST SCN (P=.04236). Among cases with follow-up, final pathologic diagnoses were SCN in 94% of cases diagnosed as SCN on FNA of upper GI, hepatobiliary tract, and pancreas. Although some cytomorphologic criteria are more suggestive of malignancy, arriving at a specific diagnosis relies on collaboration of clinical, radiologic, cytomorphologic, and immunohistochemical data.

SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection.

Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS‐CoV‐2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)‐confirmed coronavirus disease 2019 (COVID‐19). Serum samples were collected 1–59 days post‐onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR‐confirmed COVID‐19 and samples collected during convalescence, 35–57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS‐CoV‐2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (p = .05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection.

Grey matter abnormality in progressive multifocal leucoencephalopathy

Progressive multifocal leucoencephalopathy (PML) is a demyelinating white matter disease that most often affects immunocompromised people infected by JC virus. The diagnostic gold standard is demonstrable viral DNA or protein...

Identifying early surrogate markers for blood culture positive sepsis in an urban NICU-A retrospective observational study

Background: Neonatal sepsis is a major problem worldwide. Positive blood culture, the diagnostic gold standard is expensive, time consuming and yields result in limited cases. Hence reliable surrogate markers are needed. Aims and Objective: To ascertain haematological parameters which are reliable adjuvants to blood culture for diagnosing Neonatal Sepsis. Materials and Methods: A retrospective observational study was carried over two years in alevel3 NICU among neonates admitted with suspected sepsis. Data on demographics, clinical background, blood laboratory results were extracted from medical records and statistically analysed by multivariate regression analysis to identify surrogate markers for sepsis. Results: Over two years, 182 neonates admitted with Suspected Sepsis were enrolled in the study. In all clinical examination followed by laboratory investigations viz CBP (TLC, ANC, ITR, degenerative changes, platelet count), CRP and blood culture was carried out prior to treatment. A total of 64 (35.2%) were blood culture positive. On multivariable regression analysis, ITR >0.2 [OR 16.3; 95% CI (1.5-176.8), platelet count < 150> Conclusions: The study revealed that Immature to total neutrophil ratio >0.2, platelet count< 150> Key Messages: 1. Blood culture, the gold standard for diagnosing neonatal sepsis is expensive, time consuming and yields positive results in limited cases. 2. Effective surrogate markers are Immature to total neutrophil ratio (ITR), thrombocytopenia and cytotoxic degenerative changes in neutrophils. 3. These surrogate markers would identify the neonate at risk requiring early antibiotic therapy. Keywords: ANC, Blood Culture, ITR, Neonatal Sepsis, Surrogate Markers.

Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management.

Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the course of their disease, which is accompanied by neuropathic pain in 30-40% of cases. Peripheral nerve injury in diabetes can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, and mononeuropathies. The most common diabetic neuropathy is distal symmetric polyneuropathy, which we will refer to as DN, with its characteristic glove and stocking like presentation of distal sensory or motor function loss. DN or its painful counterpart, painful DN, are associated with increased mortality and morbidity; thus, early recognition and preventive measures are essential. Nevertheless, it is not easy to diagnose DN or painful DN, particularly in patients with early and mild neuropathy, and there is currently no single established diagnostic gold standard. The most common diagnostic approach in research is a hierarchical system, which combines symptoms, signs, and a series of confirmatory tests. The general lack of long-term prospective studies has limited the evaluation of the sensitivity and specificity of new morphometric and neurophysiological techniques. Thus, the best paradigm for screening DN and painful DN both in research and in clinical practice remains uncertain. Herein, we review the diagnostic challenges from both clinical and research perspectives and their implications for managing patients with DN. There is no established DN treatment, apart from improved glycaemic control, which is more effective in type 1 than in type 2 diabetes, and only symptomatic management is available for painful DN. Currently, less than one-third of patients with painful DN derive sufficient pain relief with existing pharmacotherapies. A more precise and distinct sensory profile from patients with DN and painful DN may help identify responsive patients to one treatment versus another. Detailed sensory profiles will lead to tailored treatment for patient subgroups with painful DN by matching to novel or established DN pathomechanisms and also for improved clinical trials stratification. Large randomized clinical trials are needed to identify the interventions, i.e. pharmacological, physical, cognitive, educational, etc., which lead to the best therapeutic outcomes.

COVID-19 Seroprevalence among Healthcare Workers of a Large COVID-19 Hospital in Rome Reveals Strengths and Limits of Two Different Serological Tests.

Healthcare workers are at the forefront against COVID-19, worldwide. Since Fondazione Policlinico Universitario A. Gemelli (FPG) IRCCS was enlisted as a COVID-19 hospital, the healthcare workers deployed to COVID-19 wards were separated from those with limited/no exposure, whereas the administrative staff were designated to work from home. Between 4 June and 3 July 2020, an investigation was conducted to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (IgG) antibodies among the employees of the FPG using point-of-care (POC) and venous blood tests. Sensitivity, specificity, and predictive values were determined with reverse-transcription polymerase chain reaction on nasal/oropharyngeal swabs as the diagnostic gold standard. The participants enrolled amounted to 4777. Seroprevalence was 3.66% using the POC test and 1.19% using the venous blood test, with a significant difference (p < 0.05). The POC test sensitivity and specificity were, respectively, 63.64% (95% confidence interval (CI): 62.20% to 65.04%) and 96.64% (95% CI: 96.05% to 97.13%), while those of the venous blood test were, respectively, 78.79% (95% CI: 77.58% to 79.94%) and 99.36% (95% CI: 99.07% to 99.55%). Among the low-risk populations, the POC test’s predictive values were 58.33% (positive) and 98.23% (negative), whereas those of the venous blood test were 92.86% (positive) and 98.53% (negative). According to our study, these serological tests cannot be a valid alternative to diagnose COVID-19 infection in progress.