Placental Heterogeneity in Stillbirth and Its Relations to Maternal Exogenous Characteristics.

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.

HIV, Placental Pathology, and Birth Outcomes-a Brief Overview.

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.

Xpert MTB/RIF Ultra Is Highly Sensitive for the Diagnosis of Tuberculosis Lymphadenitis in a High-HIV Setting.

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 (n = 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 (n = 92) of an FNAB study Ultra and Xpert, Ultra had increased sensitivity (91% [95% confidence interval: 79, 98] versus 72% [57, 84]; P = 0.016) and decreased specificity (76% [61, 87] versus 93% [82, 99]; P = 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]; P = 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]; P < 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.

Placental pathology in HIV infection at term: a comparison with HIV-uninfected women.

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.

Ultrathin bronchoscopy for solitary pulmonary lesions in a region endemic for tuberculosis: a randomised pilot trial.

BACKGROUND: The evaluation of solitary pulmonary lesions (SPL) requires a balance between procedure-related morbidity and diagnostic yield, particularly in areas where tuberculosis (TB) is endemic. Data on ultrathin bronchoscopy (UB) for this purpose is limited. To evaluate feasibility and safety of UB compared to SB for diagnosis of SPL in a TB endemic region. METHODS: In this prospective randomised trial we compared diagnostic yield and adverse events of UB with standard-size bronchoscopy (SB), both combined with fluoroscopy, in a cohort of patients with SPL located beyond the visible range of SB. RESULTS: We included 40 patients (mean age 55.2 years, 45 % male) with malignant SPL (n = 16; 40 %), tuberculous SPL (n = 11; 27.5 %) and other benign SPL (n = 13; 32.5 %). Mean procedure time in UB and SB was 30.6 and 26.0 min, respectively (p = 0.15). By trend, adverse events were recorded more often with UB than with SB (30.0 vs. 5.0 %, p = 0.091), including extensive coughing (n = 2), blocked working channel (n = 2), and arterial hypertension requiring therapeutic intervention (n = 1), all with UB. The overall diagnostic yield of UB compared to SB was 55.0 % vs. 80.0 %, respectively (p = 0.18). Sensitivity for the diagnosis of malignancy of UB and SB was 50.0 % and 62.5 %, respectively (p = 0.95). CONCLUSION: UB is not superior to SB for the evaluation of SPL in a region endemic with tuberculosis, when combined with fluoroscopic guidance only. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02490059 ).

Adjunctive tests for diagnosis of tuberculosis: serology, ELISPOT for site-specific lymphocytes, urinary lipoarabinomannan, string test, and fine needle aspiration.

The diagnostic gold standard for active tuberculosis (TB) is the detection of Mycobacterium tuberculosis (MTB) by culture or molecular methods. However, despite its limited sensitivity, sputum smear microscopy is still the mainstay of TB diagnosis in resource-limited settings. Consequently, diagnosis of smear-negative pulmonary and extrapulmonary TB remains challenging in such settings. A number of novel or alternative techniques could provide adjunctive diagnostic use in the context of difficult-to-diagnose TB. These may be especially useful in certain patient groups such as persons infected with human immunodeficiency virus (HIV) and children, who are disproportionably affected by smear-negative and extrapulmonary disease and who are also most adversely affected by delays in TB diagnosis and treatment. We review a selection of these methods that are independent of nucleic acid amplification techniques and could largely be implemented in resource-limited settings in current or adapted versions. Specifically, we discuss the diagnostic use and potential of serologic tests based on detection of antibodies to MTB antigens; interferon gamma release assays using site-specific lymphocytes; detection of lipoarabinomannan, a glycolipid of MTB, in urine; the string test, a novel technique to retrieve lower respiratory tract samples; and fine needle aspiration biopsy of lymph nodes.

Placental pathology in spontaneous and iatrogenic preterm birth: Different entities with unique pathologic features.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Processing and Analysis of Tissue Samples from Esophageal Cancer Patients in an African Setting.

Although infectious diseases continue to present a major health care problem in Africa, the incidence of cancer is increasing rapidly on the African continent and this merits an increased investment in cancer research in low to medium resource settings. Esophageal squamous cell carcinoma (ESCC) has a high incidence in Eastern and Southern Africa, with late clinical presentation and a very poor prognosis. There is limited research on the molecular pathology of this cancer in Africa, partly as a result of a lack of infrastructure for biobanking and sample processing in many African countries. The aim of this study was to establish a practical and robust workflow to collect, store, and process esophageal cancer samples such that both the tissue architecture and quality of the samples would be preserved and suitable for future genomic research. We developed a workflow that allows storage of fresh biopsy tissue in sterile Eppendorf tubes containing RNAlater, an efficient RNAse inhibitor. We collected 142 ESCC biopsy samples and showed that storage in RNAlater for up to 18 months did not alter tissue morphology, thus allowing histologic assessment by experienced pathologists and determination of tumor content in each biopsied sample. DNA and RNA extracted from tissue samples was assessed for purity, molecular size, and yield. The quantity and quality of nucleic acids obtained were suitable for genomic applications, and whole-exome sequencing of DNA from tumor tissues produced sequence data with a high proportion of both usable reads and correct base calling. We conclude that this workflow may be applicable to a wide range of malignancies for future genomic research in low-resource settings.

Performance of Xpert MTB/RIF and Mycobacterial Culture on Multiple Specimen Types for Diagnosis of Tuberculosis Disease in Young Children and Clinical Characterization According to Standardized Research Case Definitions.

BACKGROUND: Tuberculosis (TB) is a leading cause of illness and death in children globally. Improved bacteriologic and clinical diagnostic approaches in children are urgently needed. METHODS: In a prospective cohort study, a consecutive series of young (<5 years) children presenting with symptoms suggestive of TB and parenchymal abnormality on chest radiograph in inpatient and outpatient settings in Kisumu County, Kenya from October 2013 to August 2015 were evaluated at baseline and over 6 months. Up to 14 specimens per child were tested for the Mycobacterium tuberculosis complex by fluorescence microscopy, Xpert MTB/RIF and mycobacterial culture. Using detailed clinical characterization, cases were retrospectively classified according to standardized research case definitions and the sensitivity and specificity of microbiological tests on different specimen types were determined. RESULTS: Among 300 young children enrolled, 266 had sufficient information to be classified according to the research clinical case definition. Of these, 36% (96/266) had TB disease; 32% (31/96) with bacteriologically confirmed intrathoracic TB. Compared to culture, the sensitivity of a single Xpert test ranged from 60 to 67% and specificity from 97.5 to 100% for different specimen types. CONCLUSIONS: Despite extensive specimen collection and laboratory testing, TB could not be bacteriologically confirmed in almost two-thirds of children with intrathoracic TB classified by research clinical case definitions. Improved diagnostic tests are needed to identify children with TB and to exclude other potential causes of illness.

Xpert MTB/RIF for rapid diagnosis of tuberculous lymphadenitis from fine-needle-aspiration biopsy specimens.

This study demonstrates the excellent diagnostic accuracy of the Xpert MTB/RIF test in patients with tuberculous lymphadenitis. The test sensitivity and specificity were 96.7% (95% confidence interval [CI], 86.6 to 100%) and 88.9% (95% CI, 69.6 to 100%), respectively, and it correctly identified 6/6 (100%) of the cytology smear-negative/culture-positive cases and 1 of 2 (50%) rifampin-resistant cases.

The diagnostic yield and safety of ultrasound-assisted transthoracic fine-needle aspiration of drowned lung.

BACKGROUND: Proximal lung tumors, though not discernable by means of transthoracic ultrasound (US), may cause varying degrees of pulmonary collapse and postobstructive pneumonitis which may give rise to a 'drowned lung' appearance on chest computed tomography (CT) and US. The diagnostic yield for malignancy of US-assisted transthoracic fine-needle aspiration (FNA) of these areas of drowned lung is unknown. OBJECTIVES: We aimed to explore the feasibility of US-assisted FNA in this setting by prospectively investigating its diagnostic yield and safety. METHODS: We enrolled 31 patients (aged 59.4 ± 9.7 years, 17 males) with central tumors and secondary drowned lung on CT scan. A respiratory physician performed transthoracic US to identify the target drowned lung tissue. Three US-assisted superficial FNA passes (≤20 mm from the pleura) were followed by 3 deeper FNA passes (>20 mm) aimed in the direction of a visible or approximated central mass. Rapid on-site evaluation of specimens was used. RESULTS: Superficial FNA was diagnostic in 11 patients (35.5%), whereas deeper FNA was diagnostic in 23 patients (74.2%, p = 0.002). Deeper FNA confirmed malignancy in all cases with diagnostic superficial FNA. We observed no pneumothoraces or major hemorrhage. All patients were ultimately diagnosed with malignancy (bronchogenic carcinoma, n = 30; lymphoma, n = 1). CONCLUSIONS: US-assisted FNA of drowned lung has an acceptable diagnostic yield and is safe.

The diagnostic yield and safety of ultrasound-assisted transthoracic biopsy of mediastinal masses.

BACKGROUND: Ultrasound (US)-assisted transthoracic biopsy offers a less invasive alternative to surgical biopsy in the setting of mediastinal masses. OBJECTIVES: The aim of this 1-year prospective study was to assess the diagnostic yield and safety of a novel single-session sequential approach of US-assisted transthoracic fine-needle aspirations (TTFNA) with rapid on-site evaluation (ROSE) followed by cutting needle biopsies (CNB) performed by physicians on patients with anterosuperior mediastinal masses. METHODS: US-assisted TTFNA with ROSE was performed on 45 consecutive patients (49.5 ± 27.7 years, 24 males), immediately followed by CNB where a provisional diagnosis of epithelial carcinoma or tuberculosis could not be established, provided a safety range could be assured. RESULTS: TTFNA alone was deemed adequate by means of ROSE in 27 (60%) patients. CNB could be performed in 17 of the remaining 18. The on-site diagnosis corresponded to the final diagnosis in 26/45 (57.8%). An accurate cytological diagnosis was made in 33 (73.3%), and was more likely to be diagnostic in epithelial carcinoma and tuberculosis (28/30) than all other pathologies (5/15, p < 0.001). CNB yielded a diagnosis in 15/17 (88.2%). Overall, 42/45 patients were diagnosed by the single-session approach (93.3%). The final diagnoses included 41 neoplasms, with small cell lung cancer (n = 13) the commonest diagnosis. We observed no pneumothorax or major haemorrhage. CONCLUSIONS: A single-session sequential approach of US-assisted TTFNA with ROSE followed by CNB, where indicated, has a high diagnostic yield for anterosuperior mediastinal masses, is safe and offers an alternative to surgical biopsy.

Sensitive and Feasible Specimen Collection and Testing Strategies for Diagnosing Tuberculosis in Young Children.

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.

Nicotinic Receptors in the Brainstem Ascending Arousal System in SIDS With Analysis of Pre-natal Exposures to Maternal Smoking and Alcohol in High-Risk Populations of the Safe Passage Study.

Pre-natal exposures to nicotine and alcohol are known risk factors for sudden infant death syndrome (SIDS), the leading cause of post-neonatal infant mortality. Here, we present data on nicotinic receptor binding, as determined by 125I-epibatidine receptor autoradiography, in the brainstems of infants dying of SIDS and of other known causes of death collected from the Safe Passage Study, a prospective, multicenter study with clinical sites in Cape Town, South Africa and 5 United States sites, including 2 American Indian Reservations. We examined 15 pons and medulla regions related to cardiovascular control and arousal in infants dying of SIDS (n = 12) and infants dying from known causes (n = 20, 10 pre-discharge from time of birth, 10 post-discharge). Overall, there was a developmental decrease in 125I-epibatidine binding with increasing postconceptional age in 5 medullary sites [raphe obscurus, gigantocellularis, paragigantocellularis, centralis, and dorsal accessory olive (p = 0.0002-0.03)], three of which are nuclei containing serotonin cells. Comparing SIDS with post-discharge known cause of death (post-KCOD) controls, we found significant decreased binding in SIDS in the nucleus pontis oralis (p = 0.02), a critical component of the cholinergic ascending arousal system of the rostral pons (post-KCOD, 12.1 ± 0.9 fmol/mg and SIDS, 9.1 ± 0.78 fmol/mg). In addition, we found an effect of maternal smoking in SIDS (n = 11) combined with post-KCOD controls (n = 8) on the raphe obscurus (p = 0.01), gigantocellularis (p = 0.02), and the paragigantocellularis (p = 0.002), three medullary sites found in this study to have decreased binding with age and found in previous studies to have abnormal indices of serotonin neurotransmission in SIDS infants. At these sites, 125I-epibatidine binding increased with increasing cigarettes per week. We found no effect of maternal drinking on 125I-epibatidine binding at any site measured. Taken together, these data support changes in nicotinic receptor binding related to development, cause of death, and exposure to maternal cigarette smoking. These data present new evidence in a prospective study supporting the roles of developmental factors, as well as adverse exposure on nicotinic receptors, in serotonergic nuclei of the rostral medulla-a finding that highlights the interwoven and complex relationship between acetylcholine (via nicotinic receptors) and serotonergic neurotransmission in the medulla.

The utilization of fine needle aspiration biopsy (FNAB) and flow cytometry (FC) in the diagnosis and classification of non-Hodgkin B-cell and T-cell lymphomas.

The subtypes of non-Hodgkin lymphomas may have similar morphology, but have a wide variation in origin, immunophenotype and biological features. Many ancillary investigations are available to help overcome these problems, including fine needle aspiration biopsy (FNAB) and flow cytometry (FC). FNAB coupled with FC can reliably distinguish between reactive and neoplastic lymphoid populations. It can be used in the diagnosis and classification of many lymphomas, obviating the need for surgical biopsy in a significant number of patients.

Diagnosing mycobacterial lymphadenitis in children using fine needle aspiration biopsy: cytomorphology, ZN staining and autofluorescence -- making more of less.

Although the incidence of TB has stabilized or declined in most world regions, it is increasing in Africa, Southeast Asia, and the Eastern Mediterranean, fuelled by the HIV pandemic. More than 4,000 people died daily from TB-related illnesses in 2005. TB is a major cause of childhood morbidity and mortality in these developing countries, and there is an urgent need for rapid and definitive modalities for mycobacterial diagnosis in children. This prospective study in Tygerberg Hospital, Cape Town, South Africa, evaluates the ability of fine needle aspiration biopsy (FNAB) to diagnose mycobacterial lymphadenitis in children, using cytomorphology, autofluorescence on Papanicolaou stained smears, Ziehl-Nielsen (ZN) staining and/or culture. FNABs were performed on 200 children, and 25 (12.5%) aspirates were inadequate. Cultures were positive in 79/175 (45%); Mycobacterium tuberculosis was identified in 61 and Mycobacterium bovis BCG in 18 cases. Using culture as the gold standard, the concordance of the different techniques was as follows: cytomorphology 70%, ZN staining 73%, and autofluorescence 68%. Using an alternative gold standard (culture positive and/or suggestive cytomorphology plus positive autofluorescence or ZN smear), the "true" diagnostic performance of the various techniques was as follows: cytomorphology-sensitivity 78%, specificity 91%, positive predictive value (PPV) 93%, ZN staining - sensitivity 62%%, specificity 97%, PPV 97%; autofluorescence-sensitivity 67%, specificity 97%, PPV 97%; and culture-sensitivity 75%, specificity 100%, and PPV 100%. FNAB was shown to provide a rapid and definitive diagnosis in the majority of cases of suspected tuberculous lymphadenitis in children, based on cytomorphology and identification of the organism.

Successful Introduction of Fine Needle Aspiration Biopsy for Diagnosis of Pediatric Lymphadenopathy.

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.

The Stillbirth Classification System for the Safe Passage Study.

Objective Describe the classification system for assigning the cause of stillbirth in the Safe Passage Study, an international, multi-institutional, prospective analysis conducted by the NIAAA/NICHD-funded Prenatal Alcohol in SIDS and Stillbirth (PASS) Research Network. The study mission is to determine the role of prenatal alcohol and/or cigarette smoke exposure in adverse pregnancy outcomes, including stillbirth, in a high-risk cohort of 12,000 maternal/fetal dyads. Methods The PASS Network classification system is based upon 5 "sites of origin" for cause of stillbirth, further subdivided into mechanism subcategories; both are employed to assign an ultimate cause of death. Each PASS stillbirth was assigned a cause of death and status of sporadic versus recurrent. Adjudication involved review of maternal and obstetrical records; fetal autopsy and placental findings; and required complete consensus in each case. Two published classification systems, ie, INCODE and ReCoDe, were used for comparison. Results Causes of stillbirth classified were fetal (26%), placental (53%), external (5%), and undetermined (16%). Nine cases (47%) had placental causes of death due to maternal disorders that carry recurrence risks. There was full agreement for cause of death across the 3 classification systems in 26% of cases and partial agreement among them in 42% of cases. Conclusions The proposed PASS schema employs a user-friendly classification that provides comparable information to previously published systems. Advantages include its simplicity, mechanistic formulations, tight clinicopathologic integration, provision for an undetermined category, and its wide applicability to perinatal mortality review boards with access to information routinely collected during clinicopathologic evaluations.

Tuberculous lymphadenitis as a cause of persistent cervical lymphadenopathy in children from a tuberculosis-endemic area.

BACKGROUND: Cervical lymphadenitis is the most common form of extrapulmonary tuberculosis in children, although its relative contribution as a cause of persistent cervical adenopathy is not well-documented. The aim of this study was to determine the relative contribution of tuberculous lymphadenitis as a cause of persistent cervical adenopathy in a tuberculosis-endemic setting and to document its clinical presentation at the primary health care level. METHODS: A prospective descriptive study was conducted from February 2003 through October 200 at 5 primary health care clinics in Cape Town, South Africa. The study included all children younger than 13 years presenting with persistent cervical adenopathy to the local primary health care clinic. RESULTS: A total of 158 children were evaluated of whom 35 (22.2%) were diagnosed with tuberculous lymphadenitis. Bacteriologic confirmation was achieved in 27 of 35 (77.1%) children; all 35 responded to standard antituberculosis treatment. The majority of those without tuberculous lymphadenitis (105 of 123, 85.4%) had a visible superficial lesion in the area drained by the affected nodes. In children with persistent lymphadenopathy > or =2 x 2 cm, tuberculosis lymphadenitis was diagnosed in 31 of 33 (93.9%); specificity was 98.4%, sensitivity was 88.6% and the positive predictive value was 93.4%. CONCLUSION: Children commonly present with persistent cervical adenopathy to the primary health care clinic. The use of a simple clinical algorithm provided an accurate diagnosis of tuberculous lymphadenitis in the study setting. Fine needle aspirations provided a rapid and definitive diagnosis in the majority of children and will have added diagnostic value in settings where alternative diagnoses are more likely.