Journal of Clinical Pathology

AimsHistological examination of the rib is of critical value in perinatal pathology and points to the health of the child preceding death. The rib is considered ideal because it is the most rapidly growing long bone in infants and demonstrates growth arrest at onset of the insult. We aimed to identify: 1: changes in the perichondrial ring in the rib of infants and children up to 16 months of age dying suddenly at our institution and 2: any association with presence of histological changes of vitamin D deficiency (VDD) /metabolic bone disease (MBD) in the growth plate. MethodsRetrospective review of the perichondrial rib histology and comparison with the presence or absence of histological features of VDD in the growth plate of 167 cases. The cases were anonymised and divided in six age/sex categories. ResultsPeriphyseal abnormalities were only seen in 38% of the cases; of whom 33% had established and 67% had mild changes. Only 14.5% of cases with established histological appearance of VDD at the growth plate had significant PR abnormality; of whom majority (83%) were [≤]3 months of age and none [≥]9 months old, reflecting a temporal relation with birth and beyond the perinatal period. ConclusionThe histological changes in the perichondrial ring are significantly associated with histological changes of VDD /MBD at the rib growth plate with an Odds Ratio of 3.04.

BackgroundNeonatal sepsis, a significant cause of morbidity and mortality, is a systemic response to infection in the first month of life. Its early diagnosis is challenging due to nonspecific clinical manifestations and the time-intensive nature of blood cultures, the diagnostic gold standard. The Hematological Sepsis Scoring (HSS) system, introduced in 1988, offers a rapid diagnostic alternative using hematological parameters. To enhance diagnostic accuracy, the Modified HSS incorporates additional parameters, such as nucleated RBC, and assigns higher weightage to neutropenia. This study evaluates the utility of the Modified HSS in the early diagnosis of neonatal sepsis, aiming to facilitate prompt treatment and reduce neonatal mortality. MethodsThis descriptive analytical study was conducted over a year at B.P. Koirala Institute of Health Sciences, involving neonates >34 weeks of gestation within four weeks of birth, clinically suspected of sepsis. Blood samples were analyzed using Modified Hematological Sepsis Scoring (HSS) and BacT/ALERT for culture. Purposive sampling selected 147 cases. Ethical clearance was obtained, and informed consent secured. Hematological parameters, including TLC, ANC, IT ratio, and nucleated RBC, were assessed, and cultures were processed for microbial identification and susceptibility. ResultsThe study included 147 neonates with suspected sepsis (male:female ratio 1.33). Blood cultures were positive in 21 cases, with early-onset sepsis predominant (81%). Modified Hematological Sepsis Scoring (HSS) showed high diagnostic accuracy: sensitivity (90.48%), specificity (96.83%), and accuracy (95.91%) for HSS [≥]4. Among hematological parameters, degenerative changes had the highest sensitivity (95.23%), and nucleated RBC showed the highest accuracy (91.15%). Staphylococcus aureus (52.3%) was the most common pathogen. Modified HSS proved effective for early sepsis diagnosis. ConclusionModified HSS is an effective and accurate tool for early neonatal sepsis diagnosis, with high sensitivity, especially when using a score [≥]4 as the cutoff. The inclusion of nucleated RBC enhances sensitivity, while the systems diagnostic accuracy is improved by recalibrating parameters. Modified HSS, utilizing common hematological parameters, shows significant potential for clinical application.

BackgroundBarth syndrome is an inherited disorder that results from pathogenic mutations in TAZ, the gene responsible for encoding tafazzin, an enzyme that remodels the mitochondrial phospholipid cardiolipin. Barth syndrome is characterized by heart and skeletal muscle myopathy, growth delay, and neutropenia among other features. The TAZPOWER clinical trial investigated the effects of the mitochondria-targeting peptide elamipretide in patients with Barth syndrome. Methods and findingsTAZPOWER included a randomized, double-blind, crossover study of 12 weeks treatment with elamipretide or placebo in 12 patients with Barth syndrome. A broad spectrum of plasma and urine metabolites were measured using liquid chromatography-tandem mass spectrometry at baseline and after 12 weeks treatment with elamipretide or placebo. Of 51 "energy-linked" metabolites analyzed, we highlight here the effects of elamipretide on the plasma and urinary concentrations of several metabolites previously observed to be abnormal in patients with Barth syndrome. Elamipretide treatment was associated with significantly lowered medium- and short-chain acylcarnitines in plasma and urine, respectively (p < 0.05). Acetylcarnitine, 3-hydroxybutyrate, and 3-methylglutaconate trended to decrease after 12 weeks of elamipretide, but these trends did not reach statistical significance. After 12 weeks of treatment, elamipretide had no discernible effect on four amino acids previously characterized as having abnormal concentrations in patients with Barth syndrome. Lastly, elamipretide caused a significant rise in plasma taurine concentrations, an amino acid which has been observed to be decreased in patients with Barth syndrome. ConclusionsAs evidenced by reduced plasma and urinary content of acylcarnitines and trends for lowered ketone body 3-hydroxybutyrate, fat metabolism in Barth syndrome appears to be modified after 12 weeks of elamipretide treatment. Overall, these data are consistent with the improved mitochondrial function that may precede functional benefits with a longer duration of therapy with elamipretide in patients with Barth syndrome. Trial registrationClinicalTrials.gov NCT03098797. Summary pointsO_LIExploratory targeted metabolomic analyses of plasma and urine were performed after a double-blind, crossover trial in patients with Barth syndrome receiving elamipretide or placebo for 12 weeks. C_LIO_LIAmong 51 "energy-linked" metabolites analyzed in both plasma and urine, prominent changes were observed in metabolites associated with fat metabolism. C_LIO_LICollectively, plasma medium-chain (C6-C12) acylcarnitines were reduced after 12 weeks of elamipretide treatment in patients with Barth syndrome. C_LIO_LIUrinary acylcarnitine concentrations were also lowered with elamipretide in Barth syndrome patients, most prominently for shorter chain acylcarnitines. C_LIO_LIElamipretide for 12 weeks also trended to lower 3-methylglutaconate and the ketone body 3-hydroxybutyrate, although these decreases did not reach statistical significance. C_LIO_LIElamipretide also caused a significant rise in plasma taurine, which has been previously reported to be low in Barth syndrome patients. C_LIO_LIThese metabolite changes may be consistent with improved mitochondrial function that precedes the functional benefits observed in patients with Barth syndrome after longer-term therapy. C_LI

BackgroundHypercoagulability is becoming widely recognized as a major complication of COVID-19 infection as evidenced by high levels of fibrinogen degradation products and microthrombi identified within the lungs and kidneys of autopsy specimens from these patients. We report thromboelastography (TEG) testing on a cohort of patients with suspected COVID-19 infection at the time of admission to the intensive care unit. MethodsTEG testing was performed using the TEG 6s analyzer near or at the time of ICU admission. We also report the results of other coagulation or inflammatory related indices such as platelet count, prothrombin time, fibrinogen, D-dimer, C-reactive protein, ferritin, and procalcitonin. All laboratory testing was performed at the discretion of the attending physician in the course of normal patient care and retrospectively reviewed. ResultsWe found that maximum clot strength was consistently elevated in COVID-19 patients while normal in all patients found to be negative. We did not encounter significant prolongations of coagulation assays outside of those expectedly prolonged by heparin therapy nor was meeting the criteria for disseminated intravascular coagulation encountered. ConclusionsWe postulate that elevated maximum clot strength by TEG testing is predictive of COVID-19 status as within our cohort this perfectly predicted patients COVID-19 status despite a high level of suspicion in negative patients with normal TEG results. While these results require a larger cohort for confirmation, we feel that TEG testing could improve confidence in COVID-19 testing results in suspected patients possibly allowing for earlier de-escalation of infectious precautions and personal protective equipment utilization.

The clinical and epidemiological use of SARS-CoV-2 antibody assays is under debate with urgent need to validate and verify the performance of SARS-CoV-2 serologic assays. We aim to assess the clinical and analytical performance of three commercial serological assays of SARS-CoV-2, comparing three anti-SARS-CoV-2-IgG ELISA and identifying the seroconversion and seroprevalence in our population. A cross sectional study conducted from April 2020 to July 2020 at National Institute of Blood disease and Bone Marrow Transplantation Karachi, Pakistan with sample size of 404, enrolled consecutively. Participants were categorized into four groups namely convalescent plasmadonors (CPDs n=239), health care professionals (HCPs n=44), healthy blood donors (HBDs n=70) and from community (n=51). We evaluated the performance of Elecsys anti-SARS-CoV-2 electrochemiluminescence (ECLIA) assay on Cobas-e411 by Roche, three qualitative anti-SARS-CoV-2-IgG enzyme linked imunosorbant assay (ELISA) by (Generic assays, Euroimmun & Omega diagnostics), one quantitative ELISA assay by AESKU Diagnostics and two immune chromatography(ICT) kits namely InstaTest by CORTEZ and TEST IT by TURKLAB. From total 404 subjects, 322 (83.5%) were males. Mean age was 36.79{+/-}11.95 years. Among 239 in CPDs group, 202(84.5%) showed positive antibodies by ECLIA. The qualitative anti-SARS-CoV-2 IgG ELISA was positive in 174 (72.8%) and quantitative IgG in 180(75.3%) with mean titer of 56.7 {+/-}39.7 U/ml. Sensitivity and specificity of ECLIA were 97.44& 99%, ELISA by Generic assays were 67.85% and 89.9%; Euroimmun had 90.38% and 94.9%; Omega Diagnostics 96.4% and 95% and the AESKULISA 93.75% and 100% respectively. Seroconversion was found to be 53.8% and 77.77% within 7 -8 days and 12 to 14 days post onset of symptoms respectively. ICT had more specificity but less sensitivity. Seroprevalence was found to be 84.5%, 40.9% and 21.4% in CPDs, HCPs and HBDs respectively. The Roche ECLIA, qualitative ELISA by Omega Diagnostics & Euroimmun showed higher sensitivity as well as higher specificity. Quantitative ELISA has higher specificity and relatively high sensitivity. Significant numbers of COVID patients do not have detectable antibodies by all assays.

BackgroundThis study aims to investigate whether maternal SARS-CoV-2 status affect placental pathology. MethodsA retrospective case-control study was conducted by reviewing charts and slides of placentas between April 1 to July 24, 2020. Clinical history of "COVID-19" were searched in Pathology Database (CoPath). Controls were matched with SARS-CoV-2-negative women with singleton deliveries in the 3rd-trimester. Individual and group, pathological features were extracted from placental pathology reports. ResultsTwenty-one 3rd-trimester, placentas from SARS-CoV-2-positive women were identified and compared to 20 placentas from SARS-CoV-2-negative women. There were no significant differences in individual or group gross or microscopic pathological features between the groups. Within the SARS-CoV-2+ group, there are no differences between symptomatic and asymptomatic women. ConclusionPlacentas from SARS-CoV-2-positive women do not demonstrate a specific pathological pattern. Pregnancy complicated with COVID-19 during the 3rd trimester does not have a demonstrable effect on placental structure and pathology.

The respiratory system is a complex interconnected functionality which consists of a series of branching tubules and the lungs containing many alveoli. The alveoli are highly vascularized to provide a large surface area for gaseous exchange. The investigation was conducted in the Fauji Foundation Hospitals Department of Microbiology from November 2019 to June 2022.. The various bacterial strains that were recovered from a total of 802 mechanically intubated individuals make up the data presented in this study. Acinetobacter spp 270 (34%), Pseudomons spp 165(21%), and Klebsiella spp 95 (12%) were the most frequently isolated bacteria. Main Gram-positive organisms isolated included Methicillin-Resistant Staphylococcus aureus 66 (8%), Enterococcus 48 (6%). MRSA was 100% sensitive to Vancomycin, but only 97% sensitive to the Linezolid. The Acinetobacter spp found in the tracheal tubes was reported to be 77% sensitive to Polymyxin B.

BackgroundThe concept of sigma metrics & lean six sigma is well known in the field of healthcare. However not many labs utilize the six sigma metrics for maintenance of high quality laboratory performance. A minimum value of 3 {sigma} is desired in any clinical laboratory & values of {sigma}[&ge;] 6 are regarded as gold standard for obtaining high quality lab reports. Aims &ObjectivesTo calculate bias, cv & sigma metrics from the IQC & EQC data in order to ascertain extent of quality management in our lab. Materials &MethodsAn extensive study of sample processing and quality practices was carried out in the Central Laboratory of Department of Biochemistry; PGIMER &Dr. RML Hospital, New Delhi; from Feb 2020 to July 2020. The IQC used(both level I & level II) were from Biorad Laboratories India (lyphochek assayed chemistry control) & the EQC used was from Randox Laboratories, UK. All the controls were run on Beckman Coulter clinical chemistry analyser AU 680. Total 14 clinical parameters were analysed & subsequently; Mean, S.D., CV, bias & {sigma} were calculated through their respective formulas. ResultsSigma level was more than 6 for both levels of IQC was observed for Amylase. It indicates world class performance. Total bilirubin, AST, Triglyceride & HDL depicted {sigma} values between 3.1 - 6 for both L1 & L2. Iron showed {sigma} value of 5.5 in L1 whereas it was 3.78 in L2. ConclusionSigma metrics in clinical laboratory is an essential technique to ascertain poor assay performance, along with assessment of the efficiency of existing laboratory process.

The death rates of medical situations like bacterial meningitis are always quite high. Cerebrospinal fluid (CSF) culture is the most common and reliable test to confirm the diagnosis of bacterial meningitis. All CSF samples that were received in the microbiology lab between January 2017 and December 2021 were included in the study. The study removed all duplicate samples and samples from patients who had recently started taking antibiotics. During the course of the trial, 2000 CSF samples were received. Just 157 of these samples successfully tested positive for the presence of infections. The results of the current investigation showed that the typical pathogens associated with meningitis were not isolated from CSF samples in our method. In contrast, in our setups, highly resistant microorganisms were isolated from CSF. primarily from patients with ventriculoperitoneal shunts.

ObjectiveTo investigate the associations of alkaline phosphatase (ALP) variability measures with new onset heart failure, cardiovascular mortality, and all-cause mortality in type 2 diabetes mellitus patients with a populational-cohort study. MethodThis study included patients with type 2 diabetes mellitus who presented to ambulatory, outpatient and inpatient facilities managed by the public sector in Hong Kong between January 1st, 2000 to December 31st, 2019. Comprehensive clinical and medical data including demographics, past comorbidities, medications, and laboratory examinations of complete blood, lipid/glycemic profile and their variability were collected. ALP and its variability measures were extracted. Univariable and multiple multivariable Cox regression were used to identify the associations of alkaline phosphatase variability with new onset heart failure and mortality risks. Patients were stratified into three subgroups based on the tertiles of baseline ALP level. ResultsThe study cohort consisted of 14289 patients (52.52% males, mean age at initial drug exposure: 74.55 years old [standard deviation (SD): 12.7]). Over a mean follow up of 2513 days [interquartile range (IQR): 1151-4173]), 10182 patients suffered from all-cause mortality (incidence rate [IR]: 71.25%), 1966 patients (IR: 13.75%) died from cardiovascular causes, and 1171 patients (IR: 8.19%) developed with new onset heart failure. Higher cumulative incidences of all three outcomes were observed for the highest tertile of ALP compared to medium/low tertiles. ALP baseline and variability level predicted new onset heart failure, cardiovascular and all-cause mortality before adjusting for subclinical biomarkers (p < 0.01). Amongst the measures of ALP variability, the hazard ratio (HR) of coefficient of variation (CV) was markedly raised in particular (new onset heart failure: HR=2.73, 95% confidence interval [CI]= [1.71-4.37], p <0.0001; all-cause mortality: HR= 5.83, 95% CI= [5.01-6.79], p <0.0001; cardiovascular mortality: HR= 4.81, 95% CI= [3.36-6.88], p <0.0001). ConclusionsRaised ALP level and variability are associated with increased risks of all-cause mortality, cardiovascular mortality and new onset heart failure amongst patients with type 2 diabetes mellitus.

IntroductionResearch has shown clear correlation between inflammatory conditions and a prothrombotic state. Cerebral vein thrombosis can be fatal and diagnosis is challenging as symptoms are unspecific. ObjectivesThe main objective of the study is to find the association between headache and inflammatory bowel diseases. Material and methodsThis cross-sectional study was conducted in Foundation University Islamabad and Dow Medical College Karachi during 2021 to 2022. Data was collected from 20 patients presenting in OPD of the hospital. Patients with inflammatory bowel disease unclassified presented to emergency department with a 3-day history of nausea, vomiting, headache and sporadic abdominal pain along with intermittent bloody stools in recent weeks. ResultsData was collected from 20 patients. There were 8 males and 12 females with mean age of 45.67 {+/-} 2.34 years. No differences were found when comparing the distribution of data including IBD and migraine or severe headache. The prevalence of migraine or severe headache and 95% confidence intervals (CIs) and by selected characteristics were calculated. ConclusionIt is concluded that headache is frequent and disabling in IBD patients, highlighting the probable role of the brain-gut axis in this co-occurrence of pathologies.

Backgroundto investigate endometrial carcinoma prognostic value of some histopathological and immunohistochemical factors, fairly easily accessible in every routinely pathology lab set. Methodswe considered patients affected by endometrial carcinoma with available clinical and radiological follow-up data after radical hysterectomy (S. Martino Polyclinic Hospital, Genoa, Italy, period 1/1/2013 - 1/7/2016). We analyzed the following histopathological items: histotype, stage (FIGO), type of infiltration (infiltrative/espansive), desmoplasia, intratumoral necrosis, tumor infiltrating lymphocytes and lymph vascular spaces invasion. Moreover, each case has been investigated with a panel of immunohistochemistry including estrogen receptor , progesteron receptor, Ki67, p53, {beta}-catenin, e-cadherin, bcl-2 and cyclin D1. Primary endpoints were disease free survival and overall survival. Resultsout of 99 cases eligible for our purpose, we found 69 low-grade endometrioid, 8 high-grade endometrioid and 22 other high-grade endometrial carcinomas. Disease free survival multivariate analysis showed a strong significant correlation between poor prognosis and advanced stage (p=0.0042). Advanced stage (p=0.0003) and presence of desmoplasia (p=0.04) resulted significantly correlated to a worse prognosis in overall survival multivariate analysis. In univariate model, the non-endometrioid histotype was significantly correlated with an unfavorable prognosis when compared to the endometriod type. Same for progesteron receptor low expression. Conclusionthe multivariate analysis confirmed the central prognostic role of stage in endometrial carcinoma. Moreover, other immunohistochemical markers in univariate analysis, have confirmed their easily reproducible usefulness, well integrating the recent TGCA molecular classification.

IntroductionThe corona virus disease 2019(COVID-19) is caused by the virus SARS-CoV-2 and is declared as a global pandemic by World Health Organization (WHO). Various hematological parameters alteration has been documented in the Chinese literature in SARS-Cov-2 infection. However, there is a need for research to evaluate the pattern of the hematological parameters of COVID-19 patients in the Indian population. Aims & ObjectivesThe objective of the study is to see the Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), and other hematological parameters alteration of COVID-19 patients along with their clinical course in the Indian scenario. MethodsA single-center prospective study of 32 patients with laboratory-confirmed COVID-19 admitted to Super Speciality Pediatric Hospital & Post Graduate Teaching Institute NOIDA, from March to April, were enrolled for the study. The demographic date, the clinical status of the patients during admission and follow up, baseline, and follow up hematological findings were recorded. Statistical analysis of the data was carried out, and relevant findings were presented. ResultsDemographic characterization shows a mean age of 37.7 years, male (41.9%),female (58.1%)with majority patients are mildly symptomatic to asymptomatic(93%). The CBC values and NLR, PLR at baseline between the male and the female patients, are not showing any statistically significant difference as the 95% C.I. A statistically significant increment in the lab parameters is observed in follow-up visits. ConclusionMajority of the patients are younger and have mild clinical presentation with female predominance. Pediatric cases have mild symptomology. Baseline CBC findings show mild neutrophilia, lymphopenia, eosinopenia and normal to mild thrombocytopenia. An increase in CBC parameters, NLR was noted in follow up cases. Anemia was not noted in baseline CBC and in follow up group. A onetime PLR is not indicative of disease progression.

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has caused several hundreds of thousands of deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of comorbidities to death yet is missing. Here, we report autopsy findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as the most immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.

Nasopharyngeal swabs are critical to the diagnosis of respiratory infections including COVID-19, but collection techniques vary. We compared two recommended nasopharyngeal swab collection techniques in adult volunteers and found that swab rotation following nasopharyngeal contact did not recover additional nucleic acid (as measured by human DNA/RNA copy number). Rotation was also less tolerable for participants. Notably, both discomfort and nucleic acid recovery were significantly higher in Asians, consistent with nasal anatomy differences. Our results suggest that it is unnecessary to rotate the swab in place following contact with the nasopharynx, and reveal that procedural discomfort levels can differ by ethnicity. summaryNasopharyngeal swabs are critical to COVID-19 diagnostics, but collection techniques vary. Comparison of two collection techniques revealed that swab rotation did not recover more nucleic acid and was more uncomfortable. Discomfort and biological material recovery also varied by participant ethnicity.

BackgroundBlood culture contamination is a significant problem in acute care settings. Contamination of a blood sample with pathogens not present in the patients blood leads to increases in length of stay, overuse of antimicrobials, and increases in healthcare cost. Several interventions have been reported in different settings within the literature to decrease the contamination. However, their overall effectiveness is currently unknown. ObjectiveThis systematic review aimed to identify interventions to reduce contamination from peripherally collected blood cultures and to evaluate the effectiveness of these interventions. DesignSystematic review and meta-analysis MethodsIn March 2019 we performed a systematic search of English language literature from academic databases, registers of clinical trials and grey literature for interventions aimed at reducing blood culture contamination in adult acute care settings. Studies meeting inclusion criteria were reviewed and data were extracted by two independent reviewers. ResultsA total of 6,302 articles were retrieved from searches. After removal of duplicates and screening against inclusion criteria 57 studies were included. The majority of the 57 studies had a medium to high risk of bias. These studies identified eight specific interventions (collection packs, dedicated collection teams, education, staff feedback, intervention bundle, sterile procedure, Initial Specimen Diversion Devices, or change of asepsis solution) used in acute care. Thirty-four studies were included in the meta-analysis. There was a wide variation in the definition of contamination which precluded many studies from being included in the meta-analysis. Dedicated collection teams (RR 0.40, 95%CI 0.21 - 0.76, I2 87%, p<0.001) and initial specimen diversion devices (RR 0.43, 95%CI0.31 - 0.58, I2 84%, p<0.001) were the most successful at reducing blood culture contamination. Heterogeneity was high across all studies and interventions. ConclusionsThe use of dedicated collection teams or initial specimen diversion devices showed the most significant reduction in blood culture contamination; however, other interventions such as intervention bundles, education or feedback, may have benefits in terms of ease of implementation, and have still been shown to lower blood culture contamination.

The current gold standard for clinical pathogen identification relies on a combination of culture-based methods, target-specific molecular techniques, and antigen-detection assays1. Known limitations of the first method include the requirement for viable and culturable microorganisms, while the second approach is constrained to a limited number of predefined targets. These constraints reduce their diagnostic success, as not all pathogens are culturable, easily isolated from commensal microbiota, or represented in the selected detection panels. While culture-based methods are widely recognized for their limited sensitivity, updated quantifications of their actual performance in real-world clinical settings are scarce. To address this gap, we conducted a retrospective survey of all lower respiratory tract (LRT) samples processed by either culture or target-based molecular methods over a five-year period at a Portuguese hospital centre, providing a quantitative assessment of current diagnostic performance.

Antisynthetase syndrome is recently recognized as one of the major entities of autoimmune myositis. The prototype of antisynthetase syndrome is anti-Jo-1 antibody associated syndrome while the syndromes associated with non-Jo-1 antisynthetase antibodies are clinically and pathologically less recognized. Identifying a non-Jo-1 antisynthetase syndrome patient could be challenging because the full panel serology test may not be available at the time of diagnosis in addition to technical difficulty especially for anti-OJ antibody detection. This study aimed to characterize the muscle pathology and explore the utility of myofiber HLA-DR expression for the diagnosis of antisynthetase syndrome. We retrospectively compared 212 muscle biopsies from antisynthetase syndrome patients regarding four pathology domains and histology of interests using t test and Fishers exact test as appropriate. We further compared the myofiber HLA-DR expression pattern in antisynthetase syndrome with 602 muscle biopsies with other autoimmune myositis and 140 muscle biopsies with other myopathies potentially containing myositis-like pathology and calculated sensitivity, specificity, positive predictive value, and negative predictive value to identify the most diagnostic pattern for antisynthetase syndrome. The most common myopathological pattern in antisynthetase syndrome was necrotizing myopathy (46.2%). Perifascular necrosis was present in 28.3% of antisynthetase syndrome. Anti-OJ and anti-EJ antisynthetase syndrome were associated with high muscle fiber scores. Anti-OJ also showed high inflammatory domain score. If muscle biopsies suspicious for dermatomyositis by sarcoplasmic myxovirus resistance protein A immunohistochemical expression and those with inclusion body myositis clinicopathology were excluded, myofiber HLA-DR expression was the most diagnostic of antisynthetase syndrome with 95.4% specificity, 61.2% sensitivity, 85.9% positive predictive value, and 84.2% negative predictive value. HLA-DR expression in perifascicular fibers was highly specific to anti-Jo-1 antisynthetase syndrome. Anti-OJ antisynthetase syndrome has more prominent myopathology than the other antisynthetase syndrome subtypes. Presence of myofiber HLA-DR expression in a clinicopathologically approved non-dermatomyositis and non-inclusion body myositis muscle biopsy is highly indicative of antisynthetase syndrome. Presence of HLA-DR expression suggests the involvement of type II interferon in the pathogenesis in antisynthetase syndrome subpopulation although the detailed mechanism and the reason for preferential perifascicular localization are yet to be identified.

Endometrial cancer is an emerging disease with an increase in prevalence of aggressive histotypes in recent years. In the present study potential histopathological and immunohistochemical prognostic markers are investigated Consecutive cases of high grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered. Each surgical specimen has been routinely processed, the most representative block has been selected for immunohistochemistry and tested for ER, PR, ki67, p53, E-cadherin, {beta}-catenin, Bcl-2 and cyclin D1. For each immunomarker the percentage of positive tumor cells were evaluated (%) and dichotomized as low and high according to the distribution in the study population. Follow-up was collected for disease-free survival (DFS) and overall survival (OS). 33 cases were eligible: 19 resulted FIGO I-II, 14 resulted FIGO III-IV. 12 patients suffered a recurrent disease (mean follow-up 24.6 months); 8 patients died of the disease (mean follow-up 26.6 months). Women with recurrent disease demonstrated a significant higher bcl2% (35.84{+/-}30.96% vs 8.09{+/-}11.56% p=0.0032) while DOD patients had higher ki67% (75{+/-}13.09% vs 58.6{+/-}19.97% p=0.033) and bcl2% of border significance (34.37{+/-}34.99% vs 13{+/-}17.97% p=0.078). As expected FIGO III-IV had a worse DFS (HR=3.34; 95%CI:1.1-10.99; p=0.034) and OS (HR=5.19; 95%CI: 1.27-21.14 p= 0.0217). Bcl2-high patients (bcl2>10%) demonstrated a significant worse DFS (HR=9.11; 95%CI: 2.6-32.4; p=0.0006) and OS (HR=7.63; 95%CI:1.7-34; p=0.0084); also PR low patients (PR[&le;]10%) had a significant worse DFS (HR=3.74; 95%CI:1.2-11.9; p=0,02). HG-NEC represent an heterogeneous group of endometrial aggressive neoplasms with a worrisome prognosis often at an advanced stage at presentation. Bcl2 and PR may represent promising markers to identify a sub-group of patients having an even worse prognosis requiring a careful and close follow-up.

BackgroundMortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries. The placenta is central to the etiology of PE. However, how and to what extent the placenta contributes to worse PE outcomes in persons of African ancestry is yet to be fully elucidated. ObjectiveWe aimed to identify molecular pathways that are unique or enriched in placentas of parturient persons of African ancestry with PE with severe features (sPE) compared to those of Asian and European ancestry with sPE. Study designBulk RNA sequencing was performed on 50 placentas from parturient persons with sPE of African (n=9), Asian (n=18) and European (n=23) ancestries and 73 normotensive controls of African (n=9), Asian (n=15) and European (n=49) ancestries. ResultsMetabolism, hormone regulation and hypoxia/angiogenesis genes, previously described to be upregulated in PE, including: LEP, PAPPA2, INHA, FSTL3, FLT1, PHYHIP and ENG, were upregulated in sPE across ancestries, with high expression of FSTL3 being additionally associated with intrauterine growth restriction (p = .0047). Notably, the upregulation of, FLT1, LEP and PHYHIP was significantly higher in sPE placentas from parturient persons of African versus Asian ancestry (p = .0.35, .020 and .012 respectively). Genes associated with allograft rejection and adaptive immune response were upregulated in placentas from parturients of African ancestry but not in those of Asian and European ancestries. Among the allograft rejection/adaptive immune response genes, IL3RA was of particular interest because the patient with the highest placental IL3RA level, a woman of African ancestry with IL3RA levels 4.5-fold above the average for African ancestry parturients with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients with the highest IL3RA levels among parturients of Asian and European ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p = .0005). ConclusionsPlacentas from parturients of African ancestry express higher levels of metabolism (LEP) and hypoxia/angiogenesis (FLT1) genes, as well as allograft rejection/adaptive immune response genes, including IL3RA. High placental expression of IL3RA may predict worse maternal cardiovascular outcomes, including peripartum cardiomyopathy. Studies evaluating placental IL3RA levels in peripartum cardiomyopathy cohorts are therefore warranted, as are broader studies evaluating placental factors in maternal cardiovascular outcomes postpartum.