Comparison of ophthalmic artery Doppler with PlGF and sFlt-1/PlGF ratio at 35-37 weeks' gestation in prediction of imminent pre-eclampsia.

OBJECTIVE: To compare the predictive performance for delivery with pre-eclampsia (PE) at < 3 weeks and at any stage after assessment at 35 + 0 to 36 + 6 weeks' gestation of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio with that of a competing-risks model utilizing maternal risk factors, mean arterial pressure (MAP) and ophthalmic artery peak systolic velocity (PSV) ratio. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries and measurement of MAP, serum PlGF and serum sFlt-1. The performance of screening for delivery with PE at < 3 weeks and at any time after the examination was assessed using areas under the receiver-operating-characteristics curves and detection rates (DRs), at a 10% false-positive rate (FPR). McNemar's test was used to compare DRs, at a 10% FPR, between screening by PlGF concentration, the sFlt-1/PlGF concentration ratio and the competing-risks model utilizing maternal risk factors, MAP and ophthalmic artery PSV ratio. Model-based estimates of screening performance for different methods of screening were also produced. RESULTS: The study population of 2338 pregnancies contained 75 (3.2%) cases that developed PE, including 30 (1.3%) that delivered with PE at < 3 weeks from assessment, and 2263 cases unaffected by PE. The DR of PE at < 3 weeks from assessment, at a 10% FPR, of sFlt-1/PlGF ratio (70.0% (95% CI, 50.6-85.3%)) was superior to that of PlGF (50.0% (95% CI, 31.3-68.7%)) or PSV ratio (56.7% (95% CI, 37.4-74.5%)) but inferior to that of the combination of maternal risk factors, MAP multiples of the median (MoM) and PSV ratio delta (96.7% (95% CI, 82.8-99.9%)). Similarly, the DR of PE at any stage after assessment of sFlt-1/PlGF ratio (62.7% (95% CI, 50.7-73.6%)) was superior to that of PlGF (52.0% (95% CI, 40.2-63.7%)) or PSV ratio (41.3% (95% CI, 30.1-53.3%)) but inferior to that of the combination of maternal risk factors, MAP MoM and PSV ratio delta (78.7% (95% CI, 67.7-87.3%)). The empirical results for DR at a 10% FPR were consistent with the modeled results, both for delivery with PE at < 3 weeks and at any time after assessment. CONCLUSION: Ophthalmic artery Doppler in combination with maternal risk factors and blood pressure could potentially replace measurement of PlGF and sFlt-1/PlGF ratio in the prediction of imminent PE. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler in combination with other biomarkers in prediction of pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the potential value of maternal ophthalmic artery Doppler at 35-37 weeks' gestation in combination with the established biomarkers of pre-eclampsia (PE), including mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), in the prediction of subsequent development of PE. METHODS: This was a prospective observational study in women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries, and measurement of MAP, UtA-PI, serum PlGF and serum sFlt-1. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at any time and at < 3 weeks after assessment by a combination of maternal demographic characteristics and medical history with biomarkers. The area under the receiver-operating-characteristics curve and detection rate (DR) of delivery with PE, at a 10% false-positive rate (FPR), in screening by combinations of maternal factors with ophthalmic artery second to first peak of systolic velocity ratio (PSV ratio), MAP, UtA-PI, serum PlGF and serum sFlt-1 were determined. The modeled performance of screening for PE was also estimated. RESULTS: The study population of 2287 pregnancies contained 60 (2.6%) that developed PE, including 19 (0.8%) that delivered with PE at < 3 weeks after assessment. The PSV ratio improved the prediction of PE with delivery at any stage after assessment provided by maternal factors alone (from 25.4% to 50.6%), maternal factors and MAP (54.3% to 62.7%), maternal factors, MAP and PlGF (68.3% to 70.8%) and maternal factors, MAP, PlGF and sFlt-1 (75.7% to 76.7%), at a FPR of 10%. The PSV ratio also improved the prediction of PE with delivery at < 3 weeks after assessment provided by maternal factors alone (from 31.0% to 69.4%), maternal factors and MAP (74.1% to 83.4%), maternal factors, MAP and UtA-PI (77.1% to 85.0%) and maternal factors, MAP and PlGF (84.8% to 88.6%). The empirical results for DR at a 10% FPR were consistent with the modeled results. Screening by a combination of maternal factors with MAP and PSV ratio also detected 59.4% (95% CI, 58.6-82.5%) of cases of gestational hypertension with delivery at any stage after assessment, and 86.7% (95% CI, 82.4-100%) of those with delivery at < 3 weeks after assessment. CONCLUSION: Ophthalmic artery Doppler could potentially improve the performance of screening for PE at 35-37 weeks, especially imminent PE with delivery within 3 weeks after assessment, but further studies are needed to validate this finding. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of NADiA ProsVue PSA slope on secondary treatment decisions after radical prostatectomy.

BACKGROUND: Selecting appropriate candidates for postprostatectomy radiotherapy is challenging, because adverse pathological features cannot accurately predict clinical recurrence. Biomarkers that identify residual disease activity may assist clinicians when counseling patients on the risks, benefits and costs of secondary treatment. NADiA ProsVue PSA slope results ≤2.0 pg ml(-1) month(-1) are predictive of a reduced risk of clinical recurrence; however, its clinical utility has not yet been studied. METHODS: We prospectively enrolled men treated by radical prostatectomy in a multicenter, institutional review board-approved clinical trial. At postsurgical follow-up, investigators (N=17) stratified men into low-, intermediate- or high-risk groups for prostate cancer recurrence based on clinicopathological findings and other factors. Investigators documented their initial treatment plan for each subject and serially collected three serum samples for ProsVue testing. After the ProsVue result was reported, investigators recorded whether or not the initial treatment plan was changed. The proportion of cases referred for secondary treatment before and after ProsVue was reported, and the significance of the difference determined. RESULTS: Complete assessments were reported for 225 men, 128 (56.9%) of whom were stratified into intermediate- and high-risk groups. Investigators reported that they would have referred 41/128 (32.0%) at-risk men for secondary treatment. However, after results were known, they referred only 15/128 (11.7%) men. The difference in proportions (-20.3%, 95% confidence interval (CI) -29.9 to -10.3%) is significant (P<0.0001). Odds of a referral was significantly reduced after results were reported (odds ratio 0.28, 95% CI 0.15-0.54, P<0.0001). CONCLUSIONS: Knowledge of a ProsVue result had significant impact on the final treatment plan. A ProsVue result ⩽2.0 pg ml(-1) month(-1) significantly reduced the proportion of men at risk of recurrence who otherwise would have been referred for secondary treatment.

Endometrial carcinoma: intraoperative evaluation of myometrial invasion. A prospective study.

AIM: The authors investigated the diagnostic value of intraoperative assessment of myometrial invasion in endometrial cancer patients. Following hysterectomy, the uterus was sectioned and macroscopically examined in order to assess the depth of myoinvasion, which was classified as <50% and >50%. In patients with macroscopic depth of invasion>30% and <50%, a frozen section of this area was carried out. The results of intraoperative evaluation were compared with the results of postoperative pathological examination. The agreement between methods was developed as generalized Kappa type statistic. Sensitivity, specificity, positive and negative predictive values for intraoperative only macro and macro/micro evaluation were calculated. METHODS: Seventy eight consecutive patients (median age 64 years, range 43-92; median Body Mass Index [BMI] 30.5, range 21.9-46.7) who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (THBSO) were included in the study. Following intraoperative macroscopic evaluation, frozen section was carried out in 15 (19%) patients. The median time to obtain the results was 16 min for macroscopic evaluation, and 29 min for the macro/micro assessment. RESULTS: Macroscopic only assessment correctly identified depth of myoinvasion in 91% of patients, while, when the frozen section was carried out, myoinvasion was correctly identified in 95% of patients. For macroscopic only and macro-micro assessment sensitivity and specificity were 76% and 98%, 86% and 98%, respectively. CONCLUSION: These data suggest that the frozen section may improve, the diagnostic value of macroscopic only intraoperative assessment of myometrial invasion in selected patients.

Excretion of sweat and urine pyridinoline crosslinks in healthy controls and subjects with established metabolic bone disease.

Convenient techniques for measuring rates of bone turnover have been developed in recent years with the advent of biochemical markers of bone metabolism. One recent of these techniques is a collection method and quantitative enzyme immunoassay for free pyridinoline crosslinks in human sweat. The concentrations of pyridinoline crosslinks in 5-day sweat collections and first morning void and 24-hour urine collections from healthy subjects and subjects with established metabolic bone disorders were determined. T-scores were higher in the sweat system than in the urine system by up to 10-fold in postmenopausal subjects, women with hyperparathyroidism, and subjects with postmenopausal osteoporosis. For subjects with postmenopausal osteoporosis, receiver-operating characteristic curve analysis yielded areas under the curve of 0.699, 0.629, and 0.520 for sweat pyridinoline, first morning void urine pyridinoline, and 24 hour urine pyridinoline respectively. The areas under the curve of the sweat and first morning void urine measurements were significantly greater (p<0.05) than the 24-hour pyridinoline measurements. Healthy postmenopausal subjects and subjects with postmenopausal osteoporosis were monitored before and during estrogen replacement therapy or alendronate therapy. Sweat pyridinoline values declined by 49.0 +/- 12.4% and 19.4 +/- 19.9% for estrogen and alendronate subjects respectively. We conclude that this non-invasive technique is a sensitive and specific measure of bone resorption and is appropriate as an adjunct to techniques such as bone density and may also be useful in monitoring of response to anti-resorptive therapies.

Acquired aphasia in children after surgical resection of left-thalamic tumors.

Five children (three males, two females; four right-, one left-handed; age range 6 to 14 years) who developed aphasia after gross-total excision of left predominantly thalamic tumors are reported. Three patients had Broca aphasia, one had mixed transcortical aphasia, and one patient had conduction aphasia. In the months after surgery, three children improved while receiving radiation and/or chemotherapy, although none recovered completely. Two patients with malignant tumors developed worsening aphasia when the tumor recurred, and later died. Two of three patients tested had visuospatial difficulties in addition to language deficits. Attention and executive functioning were affected in three of three patients tested. Memory, verbal and/or visual functioning, were affected in four of four patients tested. Both patients who were tested showed transient right hemineglect. Two of two patients tested were probably apraxic. The wide range of deficits in these children highlights the importance of the thalamus and other subcortical structures in developing cognition.

A collection method and high-sensitivity enzyme immunoassay for sweat pyridinoline and deoxypyridinoline cross-links.

BACKGROUND: Collagen cross-link molecules such as pyridinoline (PYD), deoxypyridinoline (DPD), and N-terminal cross-linked peptides (NTX) have been measured in urine as indices of bone resorption. However, very little is known regarding the excretion of pyridinolines into other biological fluids. We report a collection device, normalizing analyte, and high-sensitivity immunoassay for quantitative analysis of free pyridinoline cross-links in sweat. METHODS: Flame atomic emission and ion-selective electrode techniques were used to measure potassium as a sweat volume marker. The Pyrilinks immunoassay for urine free pyridinolines was optimized to increase sensitivity for measurements in sweat. The precision, accuracy, and detection limit of this assay were characterized. To assess values and variability of sweat pyridinolines in human subjects, a nonocclusive skin patch was used to collect sweat samples from a reference group and from a mixed group experiencing accelerated bone resorption, postmenopausal women and men receiving gonadotropin-releasing hormone for prostate cancer. RESULTS: The immunoassay intra- and interassay variations were

[The use of recombinant interferon alfa-2b in the follow-up of patients laryngectomized for advanced stage carcinoma]. / Utilizzo dell'interferone alfa 2b ricombinante nel follow-up di pazienti laringectomizzati per carcinoma in stadio avanzato.

The AA. report the results of an experimental investigation on 60 subjects who underwent surgery for advanced stage carcinoma of the glottic larynx and treated with alpha 2b recombinant interferon at the dosage of 3,000,000 ul three times a week, before a six-months follow-up. The patients were examined also as to the respiratory functionality and the monitoring of some biological markers of cancers (CEA, TPA, Ca 125, Ca 15.3). The AA. support the satisfactory tolerability of alpha interferon which showed expected side effects; these effects were controlled by the symptomatic treatment, and their metabolic parameters as well as the ones related to the respiratory functionality kept always their valves in the average. The monitoring of biological markers, seems to support a real usefulness in the treatment with alpha interferon, even if a statistically meaningful record couldn't be noticed.

Prolactin secretion in chronic schizophrenia.

Basal prolactin secretion and its response to various stimuli have been studied in 20 chronic hebephrenic schizophrenics, 10 males and 10 females, aged 20-54 years. The duration of the disease varied between 4 and 30 years. Eight normal subjects from the hospital staff, four males and four females, matched for age, were used as controls. The patients had been off medication for 10 days in 17 cases, for 3 months in one case and for 1 year in two cases. The TRH stimulation test was done by giving 500 mug of TRH i.v., both to schizophrenics and controls. Schizophrenics and controls. Schizophrenics only were subjected to a 2-day therapy with chlorpromazine (4 mg/kg body weight per day orally), and therafter for 8 days to a combined therapy with chlorpromazine at the same dose plus 2-BRalpha-ergokryptine-mesilate (500 mg per day orally). Prolactin levels were assayed radioimmunologically in the basal condition, during the TRH stimulation test, after 2 days of chlorpromazine alone, and after 4 and 8 days of combined therapy with chlorpromazine plus 2-Br-alpha-ergokryptine-mesilate. The results obtained showed normal basal prolactin levels, significantly enhanced responses to TRH, normal increases after chlorpromazine alone, and substantial decreases after 2-Br-alpha-ergokryptine-mesilate. A possible relative catecholamine deficiency, related to the mental disease, is suggested to explain the results.