Abstract
The spectrum of placental pathology in human immunodeficiency virus (HIV) is vast. Features observed are not only limited to the effects of the virus itself but may include that of ...coinfections such as tuberculosis and syphilis. The presence of other comorbidities and changes as a result of antiretroviral therapy may further confound the histologic findings. There is a paucity of unbiased information of the effects of maternal HIV on the placenta and how these changes relate to birth outcomes. Antiretroviral therapy, now in widespread use, has altered the course of maternal HIV disease and it is unknown whether this has altered the pathophysiology of HIV on the placenta. HIV-associated placental findings that have been most well described include acute chorioamnionitis, low placental weight, and maternal vascular malperfusion, with a tendency towards lower rates of chronic villitis.
Tuberculosis lymphadenitis (TBL) is the most common extrapulmonary tuberculosis (EPTB) manifestation. Xpert MTB/RIF Ultra (Ultra) is a World Health Organization-endorsed diagnostic test, but ...performance data for TBL, including on noninvasive specimens, are limited. Fine-needle aspiration biopsy specimens (FNABs) from outpatients (≥18 years) with presumptive TBL (
= 135) underwent (i) routine Xpert MTB/RIF testing (later with Ultra once programmatically available), (ii) MGIT 960 culture (if Xpert or Ultra negative or rifampicin resistant), and (iii) study Ultra testing. Concentrated paired urine specimens underwent Ultra testing. Primary analyses used a microbiological reference standard (MRS). In a head-to-head comparison (
= 92) of an FNAB study Ultra and Xpert, Ultra had increased sensitivity (91% 95% confidence interval: 79, 98 versus 72% 57, 84;
= 0.016) and decreased specificity (76% 61, 87 versus 93% 82, 99;
= 0.020) and diagnosed patients not on treatment. Neither HIV nor alternative reference standards affected sensitivity and specificity. In patients with both routine and study Ultra tests, the latter detected more cases (+20% 0, 42;
= 0.034), and false-negative study Ultra results were more inhibited than true-positive results. Study Ultra false positives had less mycobacterial DNA than true positives (trace-positive proportions, 59% 13/22 versus 12% 5/51;
< 0.001). "Trace" exclusion or recategorization removed potential benefits offered over Xpert. Urine Ultra tests had low sensitivity (18% 7, 35). Ultra testing on FNABs is highly sensitive and detects more TBL than Xpert (Ultra still missed some cases due in part to inhibition). Patients with FNAB Ultra-positive "trace" results, most of whom will be culture negative, may require additional clinical investigation. Urine Ultra testing could reduce the number of patients needing invasive sampling.
•Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virions were identified by transmission electron microscopy in placental tissue.•Mother, neonate and placental tissue tested positive for ...SARS-CoV-2 using molecular testing.•This study provided ultrastructural evidence in support of molecular evidence for vertical transmission.
IMPORTANCE: Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far ...less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify. OBJECTIVE: To characterize the sensitivity of preferably minimally invasive specimen and assay combinations relative to maximum observed yield from all specimens and assays combined. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cross-sectional diagnostic study, the reference standard was a panel of up to 2 samples of each of 6 specimen types tested for Mycobacterium tuberculosis complex by Xpert MTB/RIF assay and mycobacteria growth indicator tube culture. Multiple different combinations of specimens and tests were evaluated as index tests. A consecutive series of children was recruited from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. Participants were children younger than 5 years who had symptoms of tuberculosis (unexplained cough, fever, malnutrition) and parenchymal abnormality on chest radiography or who had cervical lymphadenopathy. Children with 1 or more evaluable specimen for 4 or more primary study specimen types were included in the analysis. Data were analyzed from February 2015 to October 2020. MAIN OUTCOMES AND MEASURES: Cumulative and incremental diagnostic yield of combinations of specimen types and tests relative to the maximum observed yield. RESULTS: Of the 300 enrolled children, the median (interquartile range) age was 2.0 (1.0-3.6) years, and 151 (50.3%) were female. A total of 294 met criteria for analysis. Of 31 participants with confirmed tuberculosis (maximum observed yield), 24 (sensitivity, 77%; interdecile range, 68%-87%) had positive results on up to 2 GA samples and 20 (sensitivity, 64%; interdecile range, 53%-76%) had positive test results on up to 2 induced sputum samples. The yields of 2 nasopharyngeal aspirate (NPA) samples (23 of 31 sensitivity, 74%; interdecile range, 64%-84%), of 1 NPA sample and 1 stool sample (22 of 31 sensitivity, 71%; interdecile range, 60%-81%), or of 1 NPA sample and 1 urine sample (21.5 of 31 sensitivity, 69%; interdecile range, 58%-80%) were similar to reference-standard specimens. Combining up to 2 each of GA and NPA samples had an average yield of 90% (28 of 31). CONCLUSIONS AND RELEVANCE: NPA, in duplicate or in combination with stool or urine specimens, was readily obtainable and had diagnostic yield comparable with reference-standard specimens. This combination could improve tuberculosis diagnosis among children in resource-limited settings. Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings.
Objectives
To describe and correlate placental characteristics from pregnancies in HIV‐infected and HIV‐negative women with maternal and infant clinical and immunological data.
Methods
Prospective ...descriptive study of placentas from term, uncomplicated vaginal births in a cohort of HIV‐infected (n = 120) and HIV‐negative (n = 103) women in Cape Town, South Africa. Microscopic and macroscopic features were used to determine pathological cluster diagnoses. The majority of HIV‐infected women received some form of drug treatment for the prevention of vertical transmission of HIV. Data were analysed using logistic regression.
Results
HIV‐infected women were older (median IQR 27.4 years 24–31 vs. 25.8 23–30), more likely to be multiparous (81.7% vs. 71.8%) and had lower CD4 counts (median IQR 323.5 cells/ml 235–442 vs. 467 370–656). There were no differences in gestational age at first antenatal visit or at delivery. The proportion of specimens with placental lesions was similar in both groups (39.2% vs. 44.7%). Half of all samples were below the tenth percentile expected‐weight‐for‐gestation regardless of HIV status. This was unaffected by adjustment for confounding variables. Maternal vascular malperfusion (MVM) was more frequent in HIV infection (24.2% vs. 12.6%; P = 0.028), an association which strengthened after adjustment (aOR 2.90 95% confidence interval 1.11–7.57). Otherwise the frequency of individual diagnoses did not differ between the groups on multivariate analysis.
Conclusions
In this cohort of term, uncomplicated pregnant women, few differences were observed between the HIV‐infected and uninfected groups apart from MVM. This lesion may underlie the development of hypertensive disorders of pregnancy, which have been observed at higher rates in some HIV‐infected women on ART.
Objectifs
Décrire et corréler les caractéristiques du placenta des grossesses chez les femmes infectées et non infectées par le VIH avec les données cliniques et immunologiques maternelles et infantiles.
Méthodes
Etude descriptive prospective sur des placentas des naissances vaginales à terme non compliquées dans une cohorte de femmes infectées (n = 120) et non infectées (n = 103) par le VIH à Cape Town, en Afrique du Sud. Des caractéristiques microscopiques et macroscopiques ont été utilisées pour déterminer les diagnostics de groupes pathologiques. La majorité des femmes infectées par le VIH ont reçu une certaine forme de traitement médicamenteux pour la prévention de la transmission verticale du VIH. Les données ont été analysées par la régression logistique.
Résultats
Les femmes infectées par le VIH étaient plus âgées (IQR médian: 27,4 ans 24 à 31 contre 25,8 23 à 30), plus susceptibles d’être multipares (81,7% contre 71,8%) et avaient des taux de CD4 plus faibles (médiane IQR 323,5 cellules/ml 235 à 442 contre 467 370 à 656). Il n'y avait pas de différence d’âge gestationnel à la première visite prénatale ou à l'accouchement. La proportion de spécimens présentant des lésions placentaires était similaire dans les deux groupes (39,2% contre 44,7%). La moitié de tous les échantillons étaient en deçà du dixième percentile de poids attendu pour la gestation quel que soit le statut VIH. Cela n'a pas été affecté par l'ajustement pour les variables confusionnelles. La mauvaise vascularisation maternelle (MVM) était plus fréquente dans l'infection VIH (24,2% contre 12,6%; p = 0,028); association qui s'est renforcée après ajustement (aOR: 2,90 intervalle de confiance à 95% 1,11 à 7,57). Sinon, la fréquence des diagnostics individuels ne différait pas entre les groupes dans l'analyse multivariée.
Conclusions
Dans cette cohorte de femmes enceintes à terme sans complications, peu de différences ont été observées entre les groupes infectés et non infectés par le VIH en dehors de la MVM. Cette lésion pourrait sous‐tendre le développement des troubles hypertensifs dans la grossesse, qui ont été observés à des taux plus élevés chez certaines femmes infectées par le VIH sous ART.
Objetivos
Describir y correlacionar las características placentarias de embarazos en mujeres infectadas con VIH y mujeres VIH negativas con datos clínicos e inmunológicos maternos e infantiles.
Métodos
Estudio descriptivo prospectivo de placentas de partos a término, vaginales y sin complicaciones en una cohorte de mujeres infectadas con VIH (n=120) y VIH negativas (n=103) en Ciudad del Cabo, Sudáfrica. Se utilizaron características microscópicas y macroscópicas para determinar conglomerados de diagnóstico patológico. La mayoría de mujeres infectadas con VIH recibieron algún tipo de tratamiento con medicamentos para la prevención de la transmisión vertical del VIH. Los datos se analizaron mediante regresión logística.
Resultados
Las mujeres infectadas con VIH eran mayores (mediana IQR 27.4 años 24‐31 versus 25.8 23‐30), con una mayor probabilidad de ser multíparas (81.7% versus 71.8%) y tenían menores conteos de CD4 (mediana IQR 323.5 células/ml 235‐442 versus 467 370‐656). No habían diferencias en la edad gestacional en la primera visita prenatal o en el momento del parto. La proporción de muestras con lesiones placentarias era similar en ambos grupos (39.2% versus 44.7%). La mitad de todas las muestras estaban por debajo del décimo percentil de peso esperado por gestación independientemente del estatus del VIH. Esto no se veía afectado por ajustes para variables confusoras. La Mala perfusión Vascular Materna (MVM) era más frecuente con infección por VIH (24.2% versus 12.6%; p = 0.028); una asociación que se fortalecía tras el ajuste (aOR 2.90 intervalo de confianza 95% 1.11‐7.57). Por lo demás, la frecuencia de los diagnósticos individuales no difería entre grupos en un análisis multivariable.
Conclusiones
En esta cohorte de mujeres embarazadas a término, sin complicaciones, se observaron pocas diferencias entre el grupo infectado con VIH y el grupo sin infectar, aparte de la MVM. Esta lesión puede estar detrás del desarrollo de desórdenes hipertensivos del embarazo, que se han observado con tasas más altas en algunas mujeres infectadas con VIH y recibiendo TAR.
Introduction: Heterogeneous patterns of placental lesions in stillbirth signal important variations in placental histopathology that may be diagnostic in stillbirth. We explore placental ...heterogeneity and its associations with maternal characteristics (including HIV) using latent class analysis.
Methods: Placental and maternal data and slides were assessed retrospectively for 122 confirmed stillbirths (gestational age ≥ 28 weeks) delivered at a major South African academic hospital between January 2016–July 2018. The slides were reviewed by 2 pathologists and classified using the Amsterdam Consensus Classification System. Latent class analyses were conducted on raw data.
Results: We identify 5 latent placental classes in stillbirth based on similarity in patterns of observed diagnostic criteria and their associations with maternal characteristics. Three classes bear similarity to generalized patterns of placental injury identified previously. Our study shows that intrauterine infection was the commonest histopathological condition associated with stillbirth in our setting. Novel findings include 2 classes, distinguished by high placental RPH and maternal HIV, respectively, and the non-emergence of a class distinguished by VUE.
Conclusion: The size and content of the latent classes and their similarity/dissimilarity to the more generalized patterns identified previously suggest potential new avenues for investigation and theory development concerning the role of the placenta in stillbirth and the impact of HIV.
Placental pathology is an important contributor to the understanding of preterm birth and reveals major differences between spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB). The ...aim of this study was to investigate these relationships.
Research midwives collected placentas from 1101 women with singleton pregnancies who were enrolled in the Safe Passage Study. Trained pathology technologists prepared and processed placenta specimens for macroscopic and microscopic examination by designated pathologists. Statistical analyses were done with STATISTICA version 13.
In SPTB we found more cases of accelerated villous maturation; however, the other features of maternal vascular malperfusion (MVM) were not present. The prevalence rate of funisitis was also increased. In IPTB, multiple features of MVM - accelerated villous maturation, distal villous hypoplasia, decidual arteriopathy, increased syncytial knots, increased perivillous fibrin, and prominent extravillous trophoblast were increased, as were features of fetal vascular malperfusion (FVM) - umbilical cord vessel thrombosis, avascular villi, and fetal vascular thrombosis. Increased syncytial knots were found in 26% of preterm stillbirths and in 29% of preterm infant demises as compared to 81% of IPTB infants alive at one year.
SPTB and IPTB differ. The detected “abnormal” accelerated villous maturation pattern in SPTB and preterm demises, suggests an inability of the placenta to adapt and may be a trigger for SPTB. Funisitis was the only inflammatory response significant for SPTB. MVM and FVM are implicated in IPTB, but not an inflammatory process.
•Abnormally accelerated villous maturation was observed in spontaneous preterm birth.•Possible inability to adapt to injury was identified in preterm demises.•Funisitis, a fetal inflammatory response, significant in spontaneous preterm birth.•Maternal and fetal vascular malperfusion associated with iatrogenic preterm birth.
Immunohistochemistry (IHC) is routinely used to approximate breast cancer intrinsic subtypes, which were initially discovered by microarray analysis. However, IHC assessment of oestrogen receptor ...(ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status, is a poor surrogate of molecular subtype. Therefore, MammaPrint/BluePrint (MP/BP) microarray gene expression profiling is increasingly used to stratify breast cancer patients into different treatment groups. In this study, ER/PR status, as reported by standard IHC and single-gene mRNA analysis using TargetPrint, was compared with molecular subtyping to evaluate the combined use of MP/BP in South African breast cancer patients. Pathological information of 74 ER/PR positive, HER2 negative tumours from 73 patients who underwent microarray testing, were extracted from a central breast cancer genomics database. The IHC level was standardised by multiplying the intensity score (0–3) by the reported proportion of positively stained nuclei, giving a score of 0–300. Comparison between mRNA levels and IHC determination of ER/PR status demonstrated a significant correlation (pSignificance:• Single-gene genomic oestrogen and progesterone receptor reporting adds limited additional information to the molecular stratification of breast cancer tumours and does not supersede the immunohistochemistry results.• Neither single-gene genomic mRNA nor immunohistochemistry reporting of oestrogen and progesterone receptor status can replace the combined use of MammaPrint/BluePrint genomic molecular subtyping.• Reliable distinction between Luminal A and B type tumours is not possible using immunohistochemistry or single-gene genomic mRNA assessment of oestrogen/progesterone and HER2 receptor status.• Combining immunohistochemistry and microarray gene profiling enables the identification of endocrine treatment resistant hormone-positive tumours lacking ERα function (Basal-like), despite positive expression at the protein and single-gene RNA level.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accurate and rapid diagnosis of extrapulmonary nodal tuberculosis in children is of paramount importance. This retrospective study performed at Tygerberg Hospital using data from the laboratory ...records between January 1, 2004 and June 30, 2014 demonstrates how since the introduction laboratory-run FNAB service; fine needle aspiration biopsy has become an acceptable and routine diagnostic procedure for triage of pediatric lymphadenopathy.
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