Development of a Pediatric Ebola Predictive Score, Sierra Leone1.

We compared children who were positive for Ebola virus disease (EVD) with those who were negative to derive a pediatric EVD predictor (PEP) score. We collected data on all children <13 years of age admitted to 11 Ebola holding units in Sierra Leone during August 2014-March 2015 and performed multivariable logistic regression. Among 1,054 children, 309 (29%) were EVD positive and 697 (66%) EVD negative, with 48 (5%) missing. Contact history, conjunctivitis, and age were the strongest positive predictors for EVD. The PEP score had an area under receiver operating characteristics curve of 0.80. A PEP score of 7/10 was 92% specific and 44% sensitive; 3/10 was 30% specific, 94% sensitive. The PEP score could correctly classify 79%-90% of children and could be used to facilitate triage into risk categories, depending on the sensitivity or specificity required.

Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds.

PURPOSE: 18F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. METHODS: Seventeen patients with proven cardiac amyloidosis underwent 18F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123I-serum amyloid P component (SAP). 18F-Florbetapir images were assessed for areas of increased tracer accumulation and time-uptake curves in terms of standardized uptake values (SUVmean) were produced. RESULTS: All 17 patients showed 18F-florbetapir uptake at one or more extracardiac sites. Uptake was seen in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123I-SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3 (18%), and in the kidney in 2 (12%) on the late half-body images. The 18F-florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100% sensitivity/sensitivity (in relation to 123I-SAP splenic uptake, the current standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of 66.7% and a specificity of 100% on the late half-body images. Intense lung uptake was seen in three patients, one of whom had lung interstitial infiltration suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging showed a stable appearance in all three patients suggesting no early impact of treatment response. CONCLUSION: 18F-Florbetapir PET/CT is a promising tool for the detection of extracardiac sites of amyloid deposition. The combination of uptake in the heart and uptake in the spleen on 18F-florbetapir PET/CT, a hallmark of AL, suggests that this tracer holds promise as a screening tool for AL.

Risk in the "Red Zone": Outcomes for Children Admitted to Ebola Holding Units in Sierra Leone Without Ebola Virus Disease.

We collected data on 1054 children admitted to Ebola Holding Units in Sierra Leone and describe outcomes of 697/1054 children testing negative for Ebola virus disease (EVD) and accompanying caregivers. Case-fatality was 9%; 3/630 (0.5%) children discharged testing negative were readmitted EVD-positive. Nosocomial EVD transmission risk may be lower than feared.

Ebola Virus Disease in Children, Sierra Leone, 2014-2015.

Little is known about potentially modifiable factors in Ebola virus disease in children. We undertook a retrospective cohort study of children <13 years old admitted to 11 Ebola holding units in the Western Area, Sierra Leone, during 2014-2015 to identify factors affecting outcome. Primary outcome was death or discharge after transfer to Ebola treatment centers. All 309 Ebola virus-positive children 2 days-12 years old were included; outcomes were available for 282 (91%). Case-fatality was 57%, and 55% of deaths occurred in Ebola holding units. Blood test results showed hypoglycemia and hepatic/renal dysfunction. Death occurred swiftly (median 3 days after admission) and was associated with younger age and diarrhea. Despite triangulation of information from multiple sources, data availability was limited, and we identified no modifiable factors substantially affecting death. In future Ebola virus disease epidemics, robust, rapid data collection is vital to determine effectiveness of interventions for children.

Hemodynamic effects of elevated cerebrospinal fluid pressure: alterations with adrenergic blockade.

The cardiovascular effects of elevated cerebrospinal fluid (CSF) pressure were studied in 18 dogs, 6 in a control group, 6 after alpha adrenergic blockade, and 6 after beta adrenergic blockade. Vascular pressures did not change until CSF pressure was increased from 100 mm Hg to 200 mm Hg. In the control group, the aortic, pulmonary arterial, wedge, and right atrial pressures increased significantly. Cardiac output, heart rate, and stroke volume increased but systemic and pulmonary vascular resistances did not change. In the alpha adrenergic blockade group, vascular pressures did not increase after elevation of CSF pressure. Cardiac output increased or did not change, stroke volume increased, systemic resistance decreased, and pumonary resistance did not change. In the beta adrenergic blockade group, the vascular pressures all increased significantly when CSF pressure was elevated, but cardiac output did not change. Systemic resistance increased and pulmonary resistance decreased. Central blood volume increased in all three groups when CSF pressure was 200 mm Hg. The data suggest that a large and distinct alpha and beta adrenergic stimulus occurred when CSF pressure was increased to 200 mm Hg.

Nature of the glomerular capillary injury in human membranous glomerulopathy.

A differential solute clearance technique was used to evaluate glomerular capillary wall function in 20 patients with membranous glomerulopathy and massive proteinuria. The clearance of inulin, the filtration fraction, and the fractional clearance of uncharged dextrans of a radius of 28-48 A were depressed significantly below control values in 20 healthy volunteers (P less than 0.01). In contrast, the fractional clearance of dextrans of radius greater than 50 A was elevated markedly. A theoretical model of solute transport that depicts the major portion of the glomerular capillary wall as an isoporous membrane and the minor portion as a nondiscriminatory shunt pathway revealed the calculated glomerular ultrafiltration coefficient to be five times lower and mean pore radius of the major membrane component to be 4 A smaller than control values. However, the fraction of filtrate volume permeating the shunt pathway was three- to fourfold above control values and correlated strongly in individual patients with the fractional clearance of albumin (r = 0.76) and of IgG (r = 0.80). Lowering renal plasma flow by 24% during indomethacin therapy in seven patients resulted in a 74% reduction in proteinuria accompanied by a corresponding diminution of filtrate formed through the shunt pathway. Morphometric analysis of glomerular ultrastructure revealed the magnitude of depression of the glomerular filtration rate and of urinary protein leakage to be related strongly to changes in the epithelial layer of the glomerular capillary wall, but not to the density of subepithelial immune deposits. We conclude that glomerular capillaries in membranous glomerulopathy are characterized by a loss of ultrafiltration capacity and of barrier size-selectivity, and that subepithelial immune deposits do not provide a structural basis for these functional alterations.

Pulmonary vascular morphology as an imaging biomarker in chronic thromboembolic pulmonary hypertension.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5-3.0] vs. 3.2 [3.0-3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30-0.41] vs. 0.23 [0.21-0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%-5.21%] vs. 4.63% [4.39%-4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.

Viraemia and Ebola virus secretion in survivors of Ebola virus disease in Sierra Leone: a cross-sectional cohort study.

BACKGROUND: In survivors of Ebola virus disease, clinical sequelae including uveitis, arthralgia, and fatigue are common and necessitate systematic follow-up. However, the infection risk to health-care providers is poorly defined. Here we report Ebola virus RT-PCR data for body site and fluid samples from a large cohort of Ebola virus survivors at clinic follow-up. METHODS: In this cross-sectional cohort study, consecutive survivors of Ebola virus disease attending Kerry Town survivor clinic (Freetown, Sierra Leone), who had been discharged from the Kerry Town Ebola treatment unit, were invited to participate. We collected and tested axillary, blood, conjunctival, forehead, mouth, rectal, semen, urine, and vaginal specimens for presence of Ebola virus using RT-PCR. We regarded samples to be positive for Ebola virus disease if the cycle threshold was 40 or lower. We collected demographic data from survivors of their age, sex, time since discharge from the treatment unit, and length of acute admission in the Ebola treatment unit using anonymised standard forms. FINDINGS: Between April 2, and June 16, 2015, of 151 survivors of Ebola virus disease invited to participate, 112 (74%) provided consent. The median age of participants was 21·5 years (IQR 14-31·5) with 34 (30%) participants younger than 16 years. 50 (45%) of 112 participants were male. We tested a total of 555 specimens: 103 from the axilla, 93 from blood, 92 from conjunctiva, 54 from forehead, 105 from mouth, 17 from the rectum, one from semen, 69 from urine, and 21 from the vagina. The median time from Ebola treatment unit discharge to specimen collection was 142 days (IQR 127-159). 15 participants had a total of 74 swabs taken less than 100 days from discharge. The semen sample from one participant tested positive for Ebola virus at 114 days after discharge from the treatment unit; specimens taken from the axilla, blood, conjunctiva, forehead, mouth, rectum, and urine of the same participant tested negative. All specimens from the other 111 participants tested negative. INTERPRETATION: Patients recovering from Ebola virus disease who do not meet the case definition for acute disease pose a low infection risk to health-care providers 6 weeks after clearance of viraemia. Personal protective equipment after this time might be limited to standard barrier precautions, unless contact with fluids from sanctuary sites is envisaged. FUNDING: Save the Children International, Public Health England.

Alpha-interferon in superficial bladder cancer: a Northern California Oncology Group Study.

Thirty-five patients with superficial transitional carcinoma of the bladder were treated intravesically with escalating doses of recombinant alpha-2-interferon administered weekly for 8 weeks. Of the 19 patients with high-grade intraepithelial neoplasia (17 carcinoma in situ [CIS], two severe dysplasia, all cytology positive), six (32%) had complete resolution of all histologic and cytologic evidence of disease (complete response). An additional three patients (16%) had complete resolution of CIS, but the interval appearance of a low-grade transitional cell neoplasm. Five (26%) had a partial response (complete resolution of all evidence of CIS on multiple bladder biopsies but persistently positive cytologic preparations). Sixteen patients with recurrent papillary tumors and extensive prior therapy were also treated. Four (25%) had a complete response. Twenty-three of the 35 patients had prior intravesical therapy. Seven of the 23 (30%) patients with prior intravesical chemotherapy or immunotherapy had a complete or partial response to interferon, while eight of the 12 patients (67%) without prior intravesical treatment responded. These responses were achieved with minimal local and systemic toxicity. Of the ten complete responders, five remain in continuous unmaintained remission for 18+ to 37+ months. Intracavitary alpha-2-interferon is an effective new treatment for some patients with bladder cancer.

Primary pulmonary hypertension: a look at the future.

Primary pulmonary hypertension is a well described but poorly understood illness. It is a disease of the small muscular pulmonary arteries in which proliferative lesions involving endothelial cells, smooth muscle cells and fibroblasts obstruct flow. Aggressive therapy with vasodilator drugs, especially calcium channel blockers, has improved the quality of life in a minority of patients; heart-lung transplantation is feasible for only a few. Rapid developments in the study of vascular biology in the last several years are likely to provide insight into the etiology and pathogenesis of primary pulmonary hypertension. The areas involved include the cell biology of pulmonary vascular endothelial and smooth muscle cells, studies of integrins, endothelial surface charge, angiogenesis and growth factors, endothelial-derived vasoactive substances, the effects of shear and the role of coagulation at the endothelial surface. The future looks bright for understanding and treating this difficult and cryptic illness.

T-lymphocyte populations following a period of high volume training in female soccer players.

PURPOSE: To investigate the T-lymphocyte response to a period of increased training volume in trained females compared to habitual activity in female controls. METHODS: Thirteen trained female (19.8 ± 1.9 yrs) soccer players were monitored during a two-week long high volume training period (increased by 39%) and thirteen female untrained (20.5 ± 2.2 yrs) controls were monitored during two-weeks of habitual activity. Blood lymphocytes, collected at rest, were isolated before and after the two-week period. Isolated lymphocytes were assessed for the cell surface expression of the co-receptor CD28, a marker of T-lymphocyte naivety, and CD57 a marker used to identify highly-differentiated T-lymphocytes. Co-expression of these markers was identified on helper CD4(+) and cytotoxic CD8(+) T-lymphocytes. In addition a further population of γδ(+) T-lymphocytes were identified. Plasma was used to determine Cytomegalovirus (CMV) serostatus. RESULTS: No difference was observed in the T-lymphocyte populations following the two-week period of increased volume training. At baseline the number of total CD3(+), cytotoxic CD8(+), naïve (CD8(+) CD28(+) CD57(-)), intermediate (CD8(+) CD28(+) CD57(+)) T-lymphocytes and the number and proportion of γδ(+) T-lymphocytes were greater in the trained compared to the untrained females (p<0.05). The proportion of CD4(+)T-lymphocytes was greater in the untrained compared to the trained (p<0.05), in turn the CD4(+):CD8(+) ratio was also greater in the untrained females (p<0.05). Inclusion of percentage body fat as a covariate removed the main effect of training status in all T-lymphocyte sub-populations, with the exception of the γδ(+) T-lymphocyte population. 8% of the untrained group was defined as positive for CMV whereas 23% of the trained group was positive for CMV. However, CMV was not a significant covariate in the analysis of T-lymphocyte proportions. CONCLUSION: The period of high volume training had no effect on T-lymphocyte populations in trained females. However, baseline training status differences were evident between groups. This indicates that long-term exercise training, as opposed to short-term changes in exercise volume, appears to elicit discernible changes in the composition of the blood T-lymphocyte pool.

Surreptitious diuretic ingestion and pseudo-Bartter's syndrome.

A patient with profound hypokalemia satisfied the criteria for Bartter's syndrome, including hyperreninemia, aldosteronism, normal blood pressure, and hyperplasia of the juxtaglomerular apparatus. Two screening tests of urine and one of plasma for diuretic agents gave negative results. A third urinary sample gave negative results for thiazide but positive for furosemide; the fourth and fifth samples gave negative results for furosemide but positive for thiazide. Urinary prostaglandin excretion was normal. We conclude that this apparent case of Bartter's syndrome was caused by long term surreptitious diuretic ingestion and suggest this may occur more frequently than is generally appreciated.

The effects of irradiation on alaryngeal voice of totally laryngectomized patients.

The effects of radiation therapy on the ability of totally laryngectomized patients to produce voice and speech were examined using objective non-invasive methods. Moderate to severe losses were noted in patients producing voice with all types of alaryngeal modalities: tracheoesophageal, esophageal, and electrolaryngeal. Voice and speech losses were related to the impaired motility and vibratory capability of the esophageal wall and mucosa, to fibrosis of the submandibular region and to trismus. Tracheoesophageal and esophageal voice was recovered some weeks after completion of irradiation. No voice losses were observed in alaryngeal speakers who did not undergo voice restoration until after irradiation. All irradiated patients also showed various degrees of dysphagia during the treatment.

Neoplasms arising in congenital giant nevi: morphologic study of seven cases and a review of the literature.

Congenital giant nevi are complex cutaneous malformations composed of melanocytic and occasionally neural supportive elements. Malignant neoplasms arising in this setting are not uncommon, and their histologic appearances often differ significantly from the typical pattern of malignant melanoma. We report six patients with neoplasms arising in congenital giant nevi and one patient with a neoplasm arising in an extensive congenital blue nevus, and present a description of the neoplastic patterns encountered. These patterns include 1) poorly differentiated small round cell cancer, 2) malignant cellular blue nevus, 3) spindle-cell malignant tumor with lamellar cell (pseudomeissnerian) differentiation, 4) so-called minimal deviation melanoma, 5) heterologous malignant mesenchymal differentiation including rhabdomyosarcoma and liposarcoma, and 6) undifferentiated spindle cell cancer. We have reviewed the literature in order to address the question of frequency of malignant transformation in congenital giant nevi, the reported experience with the morphology of these cancers, and the histogenesis of these sometimes complex neoplasms as it is illuminated by our current understanding of the embryology of the neural crest.

Primary mucinous adenocarcinoma of the endometrium. A clinicopathologic and histochemical study.

Of 256 patients with carcinoma confined to the uterine corpus at the time of hysterectomy treated in the period 1959-1975 at Stanford University Hospital, 98 patients (38%) had neoplasms which demonstrated at least focal intracytoplasmic mucin. In 21 carcinomas (9%), intracytoplasmic mucin production was the dominant form of differentiation--a group which we designate primary mucinous carcinoma of the endometrium. Freedom from relapse and frequency of myometrial invasion were not statistically different for patients whose neoplasms contained intracytoplasmic mucin, regardless of the amount of mucin present, when compared with cases of nonmucin-containing carcinoma. Using histochemical methods, it was impossible reliably to distinguish between the intracytoplasmic mucin produced by carcinomas arising in endometrium and that produced by carcinomas primary in the endocervix. Differential biopsy and fractional curettage are stressed as useful tools in making this clinically important distinction. Since both benign mucinous metaplasia and mucinous carcinoma may arise in the endometrium, it is important to establish histopathologic criteria by which the malignant lesions may be recognized. The use of criteria illustrated in this paper (which include architectural complexity of proliferation, epithelial stratification, loss of epithelial polarity, and nuclear atypicality) resulted in the recognition of mucin producing proliferations which as a group manifest a 50% incidence of myometrial invasion.

Nonimmune hydrops fetalis in association with hemangioma of the umbilical cord.

Nonimmune hydrops fetalis is becoming the predominant form of fetal hydrops due to the declining frequency of Rh isoimmunization. Reported is the preterm delivery of a hydropic twin with umbilical cord and cutaneous hemangiomata. The unusual umbilical angiomatous malformation was associated with marked edema of the cord. This produced an ultrasonographic abnormality detected antenatally as a multicystic mass in close approximation to the fetal abdomen. The hydropic twin responded to aggressive neonatal management. It appears that hemangiomata of the umbilical cord may be causally related to fetal hydrops and may represent another entry in the differential diagnosis of this disorder.

Fungal colonization of tracheoesophageal voice prosthesis.

Laryngectomized patients fitted with tracheoesophageal (TE) puncture voice prosthesis may experience frequent failures in adequate production of neophonation. In some cases, these phonatory problems result from obstruction of the voice prosthesis with various deposits. The nature of these deposits was studied with mycologic techniques and by light and scanning electron microscopy. Candida albicans and other fungal species were identified.

Ventricular dysphonia: a profile of 40 cases.

Ventricular dysphonia is a poorly understood disorder involving ventricular fold participation during phonation. A population of ventricular dysphonia patients was evaluated using phonatory function studies such as laryngovideostroboscopy, advanced acoustic analysis, and electroglottography to identify shared epidemiologic characteristics and to discuss possible neuromuscular mechanisms and causes. Forty patients with ventricular dysphonia were studied and epidemiologic, acoustic, and histologic data were analyzed. In almost all cases, the authors found abnormalities affecting the glottis caused by a related medical condition. The abnormalities included true vocal cord (TVC) aperiodicity in 100% of the patients, TVC asymmetry in 65%, a laryngeal mass or foreign body (usually Teflon) in 35%, TVC erythema or edema in 32.5%, and TVC bowing in 22.5%. Ventricular dysphonia seems to be primarily a compensatory mechanism for glottic dysfunction. Therapy is based on identifying and correcting the underlying abnormalities. Laryngovideostroboscopy is a particularly important tool in examining chronic dysphonia.

Problems with tracheoesophageal fistula voice restoration in totally laryngectomized patients. A review of 95 cases.

OBJECTIVES: Tracheoesophageal fistula (TEF) construction, performed during or after total laryngectomy, is used for voice and speech restoration but has been associated with mild to severe complications. Our goal was to study the successes and complications in the application of this technique to restore voice function after laryngectomy in 95 consecutive patients. RESEARCH DESIGN: Retrospective cohort study with a mean follow-up time of 3.5 years. SETTING: Five medical facilities in northern California: the Veterans Affairs Medical Centers in San Francisco and Martinez, the Kaiser Permanente Medical Center in Oakland, and private practice offices in San Francisco and Pinole. PATIENTS: Ninety-five patients (90 men and five women) who had undergone total laryngectomy with subsequent or primary TEF construction. Patients' ages ranged from 35 to 80 years. INTERVENTIONS: Three- or two-layer closure was used, depending on whether TEF construction was done as a secondary or a primary procedure. Most patients underwent radiation therapy, and most used surface or intraoral electrolarynx devices before TEF construction. Insufflation tests were performed by clinicians, or self-insufflation tests were performed by the patient. Patients' voices were recorded and analyzed. In many cases, respiratory and pulmonary function studies were performed before and after total laryngectomy or TEF. Blom-Singer and Groningen voice prostheses were used. MAIN OUTCOME MEASURES: Voice restoration was considered successful when the patient was able to communicate effectively via the TEF. RESULTS: Approximately 92% of patients who underwent TEF construction and had voice prostheses placed were considered to be successfully rehabilitated. Complications ranged from mild to severe and included problems with predictive values obtained during insufflation, fistula retention, TEF angulation shifts, fungal colonization of the prosthesis, valve retention problems, difficulty with digital occlusion, pressure necrosis, postradiation necrosis, dysphagia, phonatory gagging, emesis, gastric distention, pouching, stenosis, infection, hypertrophy, shunt insufficiency, persistent spasm, myotomy, inadvertent fistula closure, and aspiration of the prosthesis. CONCLUSIONS: Acoustic measures indicate that speech produced with the TEF compares better with normal laryngeal speech than does esophageal or electronic speech. Thus, TEF should remain the preferred procedure to rehabilitate patients undergoing total laryngectomy.

Fine-needle aspiration in the diagnosis of salivary gland disorders in the community hospital setting.

From 1983 to 1988, 47 patients with salivary gland disorders were assessed with fine-needle aspiration (FNA) before surgery. The preoperative fine-needle diagnoses were then compared with the postoperative pathologic findings. In the same period, 63 patients from two other community hospitals who had been evaluated preoperatively with FNA were studied retrospectively. The overall sensitivity of FNA for salivary neoplasms was 80.6%. Fine-needle aspiration was more sensitive in identifying benign tumors (88.4%) than malignant neoplasms (58.3%) and was least sensitive in identifying nonneoplastic salivary diseases (35.3%). Pleomorphic adenomas were correctly identified preoperatively in 96.2% of cases, whereas for malignant neoplasms, the diagnostic accuracy was highest for mucoepidermoid carcinoma (50%). To demonstrate the strengths of FNA as a diagnostic tool, as well as to delineate its limitations, we present our 5-year experience. Our FNA results are similar to those reported by the major European and American referral centers. Because our medical centers are community based, our results may more accurately reflect those seen by otolaryngologists in private practice. To date, no evidence of tumor seeding along the FNA tract has been reported.