Overview of trials on artificial intelligence algorithms in breast cancer screening - A roadmap for international evaluation and implementation.

Accumulating evidence from retrospective studies demonstrate at least non-inferior performance when using AI algorithms with different strategies versus double-reading in mammography screening. In addition, AI algorithms for mammography screening can reduce work load by moving to single human reading. Prospective trials are essential to avoid unintended adverse consequences before incorporation of AI algorithms into UK's National Health Service (NHS) Breast Screening Programme (BSP). A stakeholders' meeting was organized in Newnham College, Cambridge, UK to undertake a review of the current evidence to enable consensus discussion on next steps required before implementation into a screening programme. It was concluded that a multicentre multivendor testing platform study with opt-out consent is preferred. AI thresholds from different vendors should be determined while maintaining non-inferior screening performance results, particularly ensuring recall rates are not increased. Automatic recall of cases using an agreed high sensitivity AI score versus automatic rule out with a low AI score set at a high sensitivity could be used. A human reader should still be involved in decision making with AI-only recalls requiring human arbitration. Standalone AI algorithms used without prompting maintain unbiased screening reading performance, but reading with prompts should be tested prospectively and ideally provided for arbitration.

Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room.

OBJECTIVE: To determine whether a course of low-dose indomethacin therapy, when initiated within 24 hours of birth, would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room. DESIGN: Ninety infants, with birth weights of 600 to 1250 gm, were entered into a prospective, randomized, controlled trial to receive either indomethacin, 0.1 mg/kg per dose, or placebo less than 24 hours and again every 24 hours for six doses. Echocardiography was performed on day 1 before treatment and on day 7, 24 hours after treatment. A hemodynamically significant patent ductus arteriosus (PDA) was confirmed with an out-of-study echocardiogram, and the nonresponders were treated with standard indomethacin or ligation. RESULTS: Forty-three infants received indomethacin (birth weight, 915 +/- 209 gm; gestational age, 26.4 +/- 1.6 weeks; 25 boys), and 47 received placebo (birth weight, 879 +/- 202 gm; gestational age, 26.4 +/- 1.8 weeks; 22 boys) (P = not significant). Of 90 infants, 77 (86%) had a PDA by echocardiogram on the first day of life before study treatment; 84% of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93% in the placebo group. Nine of forty indomethacin-treated infants (21%) were study-dose nonresponders compared with 22 (47%) of 47 placebo-treated infants (p < 0.018). There were no significant differences between both groups in any of the long-term outcome variables, including intraventricular hemorrhage, duration of oxygen therapy, endotracheal intubation, duration of stay in neonatal intensive care unit, time to regain birth weight or reach full caloric intake, incidence of bronchopulmonary dysplasia, and survival. No significant differences were noted in the incidence of oliguria, elevated plasma creatinine concentration, thrombocytopenia, pulmonary hemorrhage, or necrotizing enterocolitis. CONCLUSION: The prophylactic use of low doses of indomethacin, when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room, decreases the incidence of left-to-right shunting at the level of the ductus arteriosus.

Activated clotting time tests with heparinase in the management of pediatric patients on cardiopulmonary bypass.

Routine ACT tests cannot distinguish between prolonged blood clotting due to heparin effect or acquired abnormalities of the coagulation system after a loading dose of heparin. The purpose of this study was to examine an ACT test that inactivates heparin with Heparinase allowing for ACT assessment with and without heparin effect (HR-ACT with/without Heparinase, HemoTec, Inc.). The HR-ACT values were compared with the standard OR procedure that employed the Hemochron ACT. Twenty pediatric patients undergoing cardiopulmonary bypass for repair of cardiac defects were examined. All comparative ACT values were obtained from the same blood sample. Five sampling times were examined: 1) A baseline ACT was obtained before heparin had been administered; 2) A pre bypass ACT after a single heparin dose; 3) On bypass; 4) A post protamine ACT at the conclusion of surgery; and 5) In the Intensive Care Unit (PICU), 1 hour post protamine. The HemoTec HR-ACT with Heparinase and HR-ACT tests differentiated clotting time results that reflected coagulation status without the heparin effect. It identified those patients on bypass who were less than 5 kg, with prolonged ACTs that were due in part to hemodilution despite efforts at hemoconcentration.

Ureaplasma urealyticum and chronic lung disease of prematurity: critical appraisal of the literature on causation.

A critical appraisal of four cohort studies examining the relationship between Ureaplasma urealyticum and chronic lung disease (CLD) of prematurity is presented. Three studies were concurrently conducted, but the fourth was conducted 4 years later when surfactant replacement was a widespread practice. Although infants were enrolled in all studies soon after birth before they had developed CLD, there were differences in patients population, the definition of colonization with U. urealyticum, neonatal management, and the definition of CLD of prematurity. Despite the differences, all four studies found an association between colonization and development of CLD of prematurity. A combined estimate of relative risk for the four studies was 1.91 (95% confidence interval, 1.54-2.37). When infants were categorized into groups by birth weight, the association was not observed in infants who weighed > 1,250 g. The association was also not observed in infants who weighed < 750 g, but the risk of CLD of prematurity in the uncolonized control group was already 82%. Because the cohort study design allows for the possibility that one or more additional factors associated with U. urealyticum may be the true cause(s) of CLD of prematurity, there is strong but not definitive evidence that U. urealyticum causes CLD of prematurity.

New prospective studies of the association of Ureaplasma urealyticum colonization and chronic lung disease.

This study examined the association between Ureaplasma urealyticum colonization and the development of chronic lung disease (CLD) in 93 premature infants who were treated with surfactant and who had birth weights < 1251 g. Nasopharyngeal and tracheal cultures for U. urealyticum were obtained at 2 +/- 1 and at 14 +/- 1 days after birth and were positive in 17 (18%) of 93 patients. Infants born vaginally were 4.5 times more likely to be colonized than were those born by cesarean section. Colonization with U. urealyticum was associated with 1.66 (95% confidence interval, 1.24-2.20, P = .024) times the risk of developing CLD and with a greater incidence of > or = 2+ polymorphonuclear leukocytes in the tracheal aspirate at 2 +/- 1 days of age compared with uncolonized infants (P = .025). We conclude that U. urealyticum colonization is associated with CLD even after surfactant treatment. The presence of U. urealyticum is also associated with inflammatory cells in the tracheal aspirate.

Cell-surface expression of immunoglobulin G receptors on the polymorphonuclear leukocytes and monocytes of extremely premature infants.

This study measured Fc gamma receptor (FcR) expression on polymorphonuclear leukocytes (PMN) and monocytes from extremely premature infants. Flow cytometry was used to quantitate FcRIII [cluster of differention (CD) 16], FcRII (CD32), FcRI (CD64), CD14, and CD67 proteins on the PMN surface. Sixty-four premature infants with a mean gestational age +/- SD of 26 +/- 2 wk (birth weight = 847 +/- 217 g), 12 infants born at term (gestational age = 38 +/- 1 wk), and 37 adults were studied. Premature infants' PMN expressed less FcRIII, measured as mean log channel fluorescence (MCF), than did term infants or adults (MCF = 4.7 +/- 1.4, 6.1 +/- 1.0, and 8.8 +/- 1.8, respectively, p < 0.050). Premature infants also had a lower proportion of FcRIII-positive PMN than term infants or adults (mean +/- SEM = 0.83 +/- 0.02 versus 0.92 +/- 0.04 and 0.96 +/- 0.01, respectively, p < 0.050). FcRIII expression on PMN was positively associated with cell isolation procedures (p = 0.004), birth weight (p = 0.004), and postnatal age (p = 0.032). Premature infants also had lower PMN expression of FcRII when compared with adults and term infants (MCF = 2.4 +/- 0.6 versus 3.0 +/- 0.7 and 3.1 +/- 0.3, p < 0.050). Both premature and term infants had fewer FcRII positive PMN than did adults (mean +/- SEM = 0.90 +/- 0.09 and 0.89 +/- 0.07 versus 0.99 +/- 0.00, p < 0.050). Premature infants' monocytes also expressed significantly less FcRIII (MCF = 2.4 +/- 0.6 versus 3.4 +/- 0.9, p = 0.047) and FcRII (2.1 +/- 0.5 versus 2.9 +/- 0.6, p = 0.01) compared with adults. We conclude that extremely premature infants have decreased expression of FcRIII and FcRII on both their PMN and monocytes when compared with adults. The decrease in PMN FcRIII expression appears related to birth weight and chronologic age.

Spontaneous, isolated intestinal perforations in neonates with birth weight less than 1,000 g not associated with necrotizing enterocolitis.

From January 1986 through December 1988, we have seen 7 cases of isolated intestinal perforation in 250 infants with birth weights less than 1,000 g (3% incidence) without histological or clinical evidence of necrotizing enterocolitis (NEC). Patients had a mean birth weight of 670 g, gestational age of 25.1 weeks, and sustained a perforation at a chronological age of 10.4 days. No infants had been fed. A definite, blue-discolored abdomen was the only consistent clinical sign (n = 7). Free intraperitoneal air on radiograms was rarely observed (n = 1). Abdominal ultrasounds (n = 3) and metrizamide contrast studies (n = 3) were not diagnostic. The presence of an umbilical artery catheter (7/7), falling hematocrit (6/7), thrombocytopenia (5/7), and a positive diagnostic paracentesis were most commonly found. In 6 of 7 patients, this perforation was associated with coagulase-negative staphylococcal sepsis. Surgical or histological diagnosis showed focal perforation in either the terminal ileum (n = 4) or the transverse and descending colon (n = 3). Survival was 3 of 7; 2 patients died of intracranial hemorrhage and 2 died of Candida sepsis. We conclude that (1) intestinal perforation can occur in the absence of NEC; (2) bluish discoloration of the abdomen is the most reliable clinical finding; and (3) perforation may be associated with coagulase-negative staphylococcal infection.

Rapid identification of respiratory syncytial virus infections by direct fluorescent antibody testing: reliability as a guide to patient cohorting.

This study compared the results of a commercially available, direct fluorescent antibody (DFA) test with viral culture in 880 specimens obtained from 690 patients by means of nasopharyngeal swabs. The two tests were congruent in 92.5% (814) of the specimens. The sensitivity of the DFA was 0.95, the specificity was 0.91, the positive predictive value was 0.82, and the negative predictive value was 0.98. Among 548 inpatients, there were 3 mixed infections (RSV and another virus), 8 RSV infections not identified by the DFA, and 35 positive DFA results not confirmed by cell culture. Use of the DFA test alone would have resulted in 502 (92%) correct patient-placement decisions. We conclude that the DFA test provides reliable evidence on which to base patient-placement decisions but that the error rate is too high to permit safe cohorting of high-risk patients, such as those with bronchopulmonary dysplasia.

Nonimmune binding of human immunoglobulin A to type II group B streptococci.

The binding of 125I-labeled human myeloma immunoglobulin A (IgA) to four type II strains and one nontypable strain of group B streptococci was measured after streptococcal chains were broken by brief sonication. Some IgA binding was observed with all strains, but specific binding (binding that was inhibited by excess unlabeled IgA, was dose dependent, and was saturable) occurred only with those strains possessing the trypsin-sensitive beta component of the c protein. Similar amounts of binding were observed with myeloma IgA and IgA1 purified from normal serum. Specific binding was more rapid at 25 degrees C than at 0 or 37 degrees C and reached a plateau in 6 to 8 h. Binding was drastically reduced (85 to 90%) when streptococci had been heated (90 degrees C for 1 h). Most radioactivity bound to group B streptococci could be displaced (greater than 60% in 3 days) by the addition of excess unlabeled IgA. The binding capacity of one strain (10(8) streptococci in 1 ml of buffer) was saturated by approximately 24 micrograms of IgA. When transformed for Scatchard analysis, these data indicated that there was a specific binding capacity of 16,000 molecules of monomeric serum IgA per single streptococcal cell. The dissociation constant for IgA binding was 19.3 nM. Since enzyme-linked immunosorbent assay studies showed that the myeloma IgA used for the studies described above was IgA1, our quantitative data apply only to the binding of this subclass to group B streptococci. However, an enzyme-linked immunosorbent-filtration assay showed that both IgA1 and IgA2 bound to a type II group B streptococcus bearing the c protein.