Concurrent Histomonas meleagridis and Hemorrhagic Enteritis Virus Infection in a Turkey Flock with Recurrent History of Blackhead Disease.

Intestinal health is one of the key factors required for the growth and production of turkeys. Histomoniasis (blackhead disease), caused by a protozoan parasite, Histomonas meleagridis, is a reemerging threat to the turkey industry. Increased incidences of histomoniasis have been reported in recent years due to withdrawal of antihistomonas treatments. H. meleagridis affects ceca and causes cecal inflammation and necrosis. H. meleagridis migrates from ceca to the liver and causes liver necrosis, resulting in high mortalities. Ironically, field outbreaks of histomoniasis are not always associated with high mortalities, while low mortalities have also been documented. There are several exacerbating factors associated with high mortality rates in histomoniasis outbreaks, with concurrent infection being one of them. Recurrent histomoniasis outbreaks in a newly constructed barn were documented, and concurrent infection of H. meleagridis and hemorrhagic enteritis virus was confirmed. Currently, neither commercial vaccines nor prophylactic or therapeutic solutions are available to combat histomoniasis. However, there are treatments, vaccines, and solutions to minimize or prevent concurrent infections in turkeys. In addition to implementing biosecurity measures, measures to prevent concurrent infections are critical steps that the turkey industry can follow to reduce mortality rates and minimize the production and economic losses associated with histomoniasis outbreaks.

Infección simultánea por Histomonas meleagridis y el virus de la enteritis hemorrágica en una parvada de pavos con antecedentes recurrentes de enfermedad de la cabeza negra. La salud intestinal es uno de los factores clave necesarios para el crecimiento y producción de los pavos. La histomoniasis (enfermedad de la cabeza negra), causada por un parásito protozoario, Histomonas meleagridis, es una amenaza reemergente para la industria del pavo. En los últimos años se ha informado de un aumento de la incidencia de histomoniasis debido al retiro de los tratamientos con antihistomonas. Histomonas meleagridis afecta los ciegos y causa inflamación y necrosis cecal. Histomonas meleagridis migra desde los ciegos al hígado y causa necrosis hepática, lo que resulta en una alta mortalidad. Irónicamente, los brotes de histomoniasis en el campo no siempre se asocian con una mortalidad elevada, aunque también se han documentado mortalidades bajas. Hay varios factores exacerbantes asociados con altas tasas de mortalidad en los brotes de histomoniasis, siendo la infección concurrente uno de ellos. Se documentaron brotes recurrentes de histomoniasis en un alojamiento avícola recién construido y se confirmó la infección concurrente de H. meleagridis y el virus de la enteritis hemorrágica. Actualmente no se dis-pone de vacunas comerciales ni soluciones profilácticas o terapéuticas para combatir la histomoniasis. Sin embargo, existen tratamientos, vacunas y soluciones para minimizar o prevenir infecciones concurrentes en los pavos. Además de implementar medidas de bioseguridad, las medidas para prevenir infecciones concurrentes son pasos críticos que la industria del pavo puede seguir para reducir las tasas de mortalidad y minimizar las pérdidas económicas y de producción asociadas con los brotes de histomoniasis.

Umbilical cord gas analysis: clinical implications of a comprehensive, contemporary determination of normal ranges.

BACKGROUND: Umbilical cord gases are often used to assess the impact of labor and delivery on the fetus. However, no large series exists that reflects contemporary obstetrical practice or that analyzed blood gas ranges by route of delivery. Baseline, prelabor acid-base status in the human fetus is also poorly defined, rendering the assessment of blood gas changes during labor difficult. OBJECTIVE: This study aimed to define normal umbilical cord gas and lactate values, stratified by mode of delivery, in a large contemporary series in which universal umbilical cord gas evaluation was dictated by protocol. STUDY DESIGN: This was a retrospective cohort study. We analyzed the umbilical cord gas and lactate data of an unselected population of infants born between March 2012 and April 2022 at a large teaching hospital. These values were then analyzed by mode of delivery and, for cesarean deliveries, by indication for cesarean delivery and type of anesthesia. Umbilical cord gas values from infants delivered by elective cesarean delivey under general anesthesia without labor were considered representative of baseline, prelabor values. RESULTS: Data were available for 45,475 infants. The median arterial pH values and interquartile ranges for vaginal births, elective cesarean deliveries without labor, and cesarean deliveries performed for fetal heart rate concerns were 7.27 (0.09), 7.27 (0.06), and 7.25 (0.09), respectively. Arterial lactate values for these same 3 groups were 4.1 (2.5), 2.5 (1.2), and 4.0 (2.8) mmoles/L, respectively. Because of the very large sample size, most comparisons yielded differences that were statistically significant, but clinically irrelevant. Of all the infants, 14% had an arterial pH <7.20; a pH value of 7.1 represents 2 standard deviations from the mean. CONCLUSION: This large, population-based study of umbilical cord gas and lactate levels in an unselected population, stratified by delivery mode, represents a previously unavailable benchmark for the evaluation of umbilical cord gases. Arterial umbilical cord pH values for infants delivered by elective caesarean delivery without labor (median pH 7.28) reflect a lower prelabor fetal pH baseline than previously assumed. This finding, coupled with our determination that a 2 standard deviation below normal pH limit of 7.1, instead of the historic arbitrary pH of 7.2 threshold, helps to explain the poor positive predictive value of electronic fetal heart rate monitoring, a test designed to detect arterial pH levels that have fallen from an assumed baseline near pH 7.4 to an assumed potentially injurious pH level of <7.2. Uncomplicated labor, even when prolonged, does not generally lead to a clinically significant cumulative hypoxic stress to the human fetus. These findings, along with our determination that there is no difference in the acid-base status among infants delivered by cesarean delivery for fetal heart rate concerns, help to explain the failure of current approaches in labor and delivery management to reduce the rates of neonatal hypoxic-ischemic encephalopathy and cerebral palsy, conditions that almost always reflect developmental events rather than the effects of labor on the fetus.

Category II Intrapartum Fetal Heart Rate Patterns Unassociated With Recognized Sentinel Events: Castles in the Air.

The evolution of continuous electronic fetal heart rate (FHR) monitoring has presented the obstetrician with a critical clinical conundrum: basic science observations suggest that such monitoring might be associated with improved long-term neurologic outcomes, yet, after a half century of use and millions of cesarean deliveries based on FHR monitoring, evidence for such improvement remains absent. This dichotomy appears to be related to widespread misconceptions regarding the physiology underlying various FHR patterns and the developmental origins of cerebral palsy. These misconceptions are strengthened by a reliance on anecdotal experience and tradition in lieu of evidence-based medicine, the confusing "category II" FHR designation, medical-legal considerations, and our tendency to view fetal monitoring, as originally conceptualized, as a single, indivisible entity whose concepts must be accepted or rejected en bloc. Ill-defined and largely imaginary conditions such as "depletion of fetal reserve" are particularly harmful and their use in clinical medicine uniquely not evidence based. A solution to this self-inflicted injury to our specialty will require a concerted effort involving teachers, authors, and researchers.

Urologic morbidity associated with placenta accreta spectrum surgeries: single-center experience with a multidisciplinary team.

BACKGROUND: Hysterectomy for placenta accreta spectrum may be associated with urologic morbidity, including intentional or unintentional cystostomy, ureteral injury, and bladder fistula. Although previous retrospective studies have shown an association between placenta accreta spectrum and urologic morbidities, there is still a paucity of literature addressing these urologic complications. OBJECTIVE: We sought to report a systematic description of such morbidity and associated factors. STUDY DESIGN: This was a retrospective study of all histology-proven placenta accreta spectrum deliveries in an academic center between 2011 and 2020. Urologic morbidity was defined as the presence of at least one of the following: cystotomy, ureteral injury, or bladder fistula. Variables were reported as median (interquartile range) or number (percentage). Analyses were made using appropriate parametric and nonparametric tests. Multinomial regression analysis was performed to assess the association of adverse urologic events with the depth of placental invasion. RESULTS: In this study, 58 of 292 patients (19.9%) experienced urologic morbidity. Patients with urologic morbidity had a higher rate of placenta percreta (compared with placenta accreta and placenta increta) than those without such injuries. Preoperative ureteral stents were placed in 54 patients (93.1%) with and 146 patients (62.4%) without urologic injury (P=.003). After adjusting for confounding variables, multinomial regression analysis revealed that the odds of having adverse urologic events was 6.5 times higher in patients with placenta percreta than in patients with placenta accreta. CONCLUSION: Greater depth of invasion in placenta accreta spectrum was associated with more frequent and severe adverse urologic events. Whether stent placement confers any protective benefit requires further investigation.

Clinical Outcomes of a False-Positive Antenatal Diagnosis of Placenta Accreta Spectrum.

OBJECTIVE: Antenatal diagnosis of placenta accreta spectrum (PAS) is critical to reduce maternal morbidity. While clinical outcomes of women with PAS have been extensively described, little information is available regarding the women who undergo cesarean delivery with a presumptive PAS diagnosis that is not confirmed by histopathologic examination. We sought to examine resource utilization and clinical outcomes of this group of women with a false-positive diagnosis of PAS. STUDY DESIGN: This is a retrospective analysis of patients with prenatally diagnosed PAS cared for between 2015 and 2020 by our multidisciplinary PAS team. Maternal outcomes were examined. Univariate analysis was performed and a multivariate model was employed to compare outcomes between women with and without histopathologically confirmed PAS. RESULTS: A total of 162 patients delivered with the preoperative diagnosis of PAS. Of these, 146 (90%) underwent hysterectomy and had histopathologic confirmation of PAS. Thirteen women did not undergo the planned hysterectomy. Three women underwent hysterectomy but pathologic examination did not confirm PAS. In comparing women with and without pathologic confirmation of PAS, the false-positive PAS group delivered later in pregnancy (34 vs. 33 weeks of gestation, p = 0.015) and had more planned surgery (88 vs. 47%, p = 0.002). There was no difference in skin incision type or hysterotomy placement for delivery. No significant difference in either the estimated blood loss or blood components transfused was noted between groups. CONCLUSION: Careful intraoperative evaluation of women with preoperatively presumed PAS resulted in a 3/149 (2%) retrospectively unnecessary hysterectomy. Management of women with PAS in experienced centers benefits patients in terms of both resource utilization and avoidance of unnecessary maternal morbidity, understanding that our results are produced in a center of excellence for PAS. We also propose a management protocol to assist in the avoidance of unnecessary hysterectomy in women with the preoperative diagnosis of PAS. KEY POINTS: · Evaluation and delivery planning of patients with suspected placenta accreta spectrum in experienced centers provides acceptable outcomes.. · Under specific circumstances, delivery of placenta may be attempted if placenta accreta is suspected.. · Patients with suspected placenta accreta rarely undergo unindicated hysterectomy..

Relationship Between Umbilical Cord Gas Values and Neonatal Outcomes: Implications for Electronic Fetal Heart Rate Monitoring.

OBJECTIVE: To evaluate the relationship between umbilical artery cord gas values and fetal tolerance of labor, as reflected by Apgar score. We hypothesized the existence of wide biological variability in fetal tolerance of metabolic acidemia, which, if present, would weaken one fundamental assumption underlying the use of electronic fetal heart rate (FHR) monitoring. METHODS: We conducted a retrospective cohort study of term, singleton, nonanomalous fetuses delivered in our institution between March 2012 and July 2020. Universally obtained umbilical cord gas values and Apgar scores were extracted. We calculated Spearman correlation coefficients and receiver operating characteristic curves for various levels of umbilical artery pH, base excess, and Apgar scores. RESULTS: We analyzed data from 29,787 deliveries. The statistical correlation between umbilical artery pH and base excess and both 1- and 5-minute Apgar scores was weak or nonexistent in all pH range subgroups (range 0.064-0.213). Receiver operating characteristic curve analysis suggested umbilical artery pH value of 7.22 yields the best discrimination for prediction of a severely depressed newborn (5-minute Apgar score less than 4), but sensitivity and specificity for this predictive value remains poor to moderate. CONCLUSION: The use of electronic FHR monitoring is predicated on a documented relationship between FHR patterns and umbilical artery pH, and an assumed correlation between pH and fetal outcomes, reflecting fetal tolerance of labor and delivery. Our data demonstrate a weak-to-absent correlation between metabolic acidemia and even short-term fetal condition, thus significantly weakening this latter assumption. No amount of future modification of FHR pattern interpretation to better predict newborn pH is likely to lead to improved newborn outcomes, given this weakness in a fundamental assumption on which FHR monitoring is based.

Diagnostic Imaging and Outcomes for Nonobstetric Surgery During Pregnancy.

A surgical disease occurring during pregnancy can present a diagnostic dilemma due to the desire to make a timely and accurate diagnosis within the constraints of limiting radiation exposure to the fetus. However, required diagnostic imaging should be pursued when indicated and attempts made to minimize the radiation dose by utilizing abdominal shielding and low-dose protocols when feasible. When surgery is indicated due to disease processes, treatment should not be altered or delayed due to pregnancy as the evidence for adverse pregnancy outcomes including early pregnancy loss and preterm delivery are overall of low quality due to substantial confounding by the disease process itself.

Can It Be Safe and Aesthetic? An Eight-year Retrospective Review of Mastopexy with Concurrent Breast Augmentation.

BACKGROUND: The safety of concurrently performing mastopexy and breast augmentation is controversial, due to the risk of breast tissue and nipple neurovascular compromise and overall potential high complications rates. This article describes a concurrent procedure of augmentation with implants and a "Tailor-Tack" mastopexy that consistently achieves an aesthetically pleasing breast with acceptable complication rates. METHODS: This is a retrospective chart review of all consecutive breast augmentations performed concurrently with mastopexy using the "Tailor-Tack" technique by the 2 senior authors (M.M. and O.T.) over an 8-year period. Independent variables were patient demographics, surgical approach, implant type, shape, size, duration of follow-up, and complications. Complications were categorized as "early" (ie, first 30 days) or "late" (ie, after 30 days). Potential early complications include hematoma, skin necrosis, infection, and nipple loss. Potential late complications include recurrent breast ptosis, poor shape of the nipple areolar complex, hypertrophic scarring, implant rupture, capsular contracture, decreased nipple sensation, implant extrusion, reoperation, and scar revisions. The key principle of the technique is to place the breast implant in the dual plane first, and then perform the tailor tacking of the skin for the mastopexy second. RESULTS: Fifty-six consecutive patients underwent augmentation and mastopexy over 8 years with this technique. The average age of the studied patients was 41.2 years. The average follow-up time period was 2.1 years (±8.9 months). Fifty-four patients (96.4%) had implants placed through the periareolar approach, 2 patients (3.6%) had implants placed via the inframammary approach. All implants were placed in a dual plane. Fifty-two patients (92.9%) received silicone implants and 4 patients (7.1%) received saline implants. Patient preference determined implant choice. All but 5 patients had textured implants. Average implant size was 277 cm3 (range 120-800 cm3). Ten patients had complications (17.9%). Complications included hypertrophic scarring in 5 (8.9%) patients; poor nipple-areola complex shape in 4 patients (7.1%); implant ruptures in 3 patients (5.4%); capsular contracture in 3 patients (5.4%); and recurrent ptosis in 2 patients (3.6%). There were no reported early complications such as nipple loss, breast skin necrosis, decreased nipple sensation, implant infections, or extrusions. However, 6 patients (10.7%) required return trips to the operating room for revisions, and 1 patient (1.8%) had a nipple areolar complex scar revised in the office, yielding a 12.5% surgical revision rate for the late complications. CONCLUSIONS: It is safe to concurrently perform mastopexy and breast augmentation. In our 8-year review, there were no early catastrophic complications such as skin loss, nipple loss, implant extrusion, or infection. The complications that occurred were the same complications known to occur with the independent performance of mastopexy alone or breast augmentation alone, and they occurred at rates comparable to or less than the national averages for those procedures when they are performed independently. The paramount principle for the success of this technique is to first adjust breast volume and then perform an intraoperatively determined skin resection to fit the new breast volume.

Coagulopathy in surgical management of placenta accreta spectrum.

BACKGROUND: One of the major complications of the placenta accreta spectrum (PAS) is the development of coagulopathy. The detection, prevention and prompt treatment of coagulopathy may be lifesaving. OBJECTIVE: Our objective was to study selected factors associated with coagulopathy in the management of PAS by a well-established multidisciplinary team. STUDY DESIGN: This is a retrospective review of all patients with pathologically proven PAS (including placenta accreta, increta or percreta) who underwent surgery by our multidisciplinary team between January 2011 and February 2017. Coagulopathy in this setting was defined as a platelet count of <100,000/mm3, international normalized ratio >1.5, and/or fibrinogen <300 mg/dL based on institutional protocols developed by our Division of Transfusion Medicine & Coagulation. The outcomes of those patients with and without coagulopathy were compared with appropriate adjustments. Receiver operating characteristics curves (ROCs) were constructed to assess the ability of select variables to discriminate between women with and without coagulopathy, and the area under the curves (AUCs) were calculated. RESULTS: Of 123 singleton patients with PAS, 37 (30.1%; 95%CI 22.1-39.0) developed coagulopathy and 86 (69.9%; 95%CI 61.0-77.9) did not. Baseline patient demographic characteristics did not differ significantly between these groups. Estimated blood loss (median and Inter-quartile range) was 2100cc (1800, 400) and 1400 (1000, 2500) in the presence and absence of coagulopathy, respectively (P < 0.01). The overall number of units of red blood cells (RBC) transfused was greatest in the coagulopathy group [3 (2, 9) vs. 1 (0, 4); P < 0.01]. Univariate regression analysis confirmed the association between coagulopathy and (i) the number of units of RBC's transfused, and (ii) the estimated blood loss. ROC curves showed that an estimated blood loss ≥ 1500 mL had the best discriminating power. Depth and/or severity of placental invasion were not associated with coagulopathy in patients with PAS. CONCLUSIONS: Coagulopathy in patients with PAS undergoing hysterectomy is strongly associated with blood loss and replacement. It may be prudent to establish protocols that aggressively monitor for, and treat, coagulopathy when EBL exceeds 1500 mL in such surgeries, prior to the development of clinical coagulopathy which if uncorrected may lead to massive blood loss.

Validation of the Siggaard-Andersen Acid-Base Nomogram for Hemoglobin F: Implications for Fetal Cord Blood Gas Analysis.

OBJECTIVE: The calculation of HCO3 and base excess in current blood gas analysis is based on the Siggaard-Andersen equation. One of the constants in this equation is dependent on the known buffering capacity of hemoglobin A. We sought to investigate differences in buffering capacity between adult hemoglobin A and fetal hemoglobin F as a potential explanation for the observed poor correlation between calculated base excess in umbilical cord blood and newborn outcomes. Such differences would influence a key constant in the Van Slyke/Siggaard-Andersen equation used to calculate HCO3 and base excess and could be an explanation of these observations. STUDY DESIGN: This was a prospective observational study. We analyzed umbilical cord blood bicarbonate levels both as calculated values from a traditional blood gas analyzer and as measured values in 20 women giving birth at term. Since the calculated value is dependent upon the concentration and known buffering capacity of hemoglobin A, significant differences in these two analyses would imply differences in the buffering capacity of hemoglobins A and F. RESULTS: The mean calculated HCO3 value was 25 mEq/L (25.3 ± 1.9) compared with a mean measured value of 25 mEq/L (24.6 ± 1.7) over a range of pH levels of 7.16 to 7.42. This difference was not significant (p = 0.07). CONCLUSION: The buffering capacity of hemoglobin F, for clinical purposes, is not different than that of hemoglobin A and is not an explanation for the recognized poor correlation between base excess and neonatal outcome.

Placenta previa without morbidly adherent placenta: comparison of characteristics and outcomes between planned and emergent deliveries in a tertiary center.

OBJECTIVE: The objective of this study is to compare patient outcomes between planned and emergent cesarean deliveries for placenta previa without morbidly adherent placenta. STUDY DESIGN: All patients with confirmed, persistent placenta previa (without morbidly adherent placentation) who underwent the surgery between January 2010 and April 2016 were included in this retrospective study. Primary outcome was composite maternal morbidity defined as the presence of at least one of the followings: death, red blood cell (RBC) transfusion, hysterectomy, reoperation, hospital stay >7 d, ureteral injury, bowel injury, or cystotomy. RESULTS: Three hundred and four patients with placenta previa were identified during the study period, of whom 154 (50.65%) had an antenatal and 10 (3.28%) had an intraoperative diagnosis of morbidly adherent placenta. One hundred and forty patients met the inclusion criteria. Eighty (57.1%) underwent planned cesarean delivery (planned cesarean delivery (PCD) group), and 60 (42.8%) required emergent cesarean delivery due to uterine contractions and/or bleeding (emergent cesarean delivery (ECD) group). Baseline characteristics were similar between the two groups except for the gestational age at delivery (36.0 weeks (36.0, 37.0) in PCD versus 34.0 weeks (32.0, 36.0) in ECP, p < .001). Composite maternal morbidity was not significantly different between two groups: 11 (18.3%) in ECD and 10 (12.5%) in PCD (p = .35) Conclusions: In our referral tertiary centre, emergent and planned cesarean deliveries for placenta previa without morbidly adherent placenta have similar maternal outcomes. In patients without significant hemorrhage, delivery may be safely deferred until 36-37 weeks.

Nonobstetric Surgery During Pregnancy.

One percent to 2% of pregnant women undergo nonobstetric surgery during pregnancy. Historically, there has been a reluctance to operate on pregnant women based on concerns for teratogenesis, pregnancy loss, or preterm birth. However, a careful review of published data suggests four major flaws affecting much of the available literature. Many studies contain outcomes data from past years in which diagnostic testing, surgical technique, and perioperative maternal-fetal care were so different from current experience as to make these data of limited utility today. This issue is further compounded by a tendency to combine experience from vastly disparate types of surgery into a single report. In addition, reports in nonobstetric journals often focus on maternal outcomes and contain insufficient detail regarding perinatal outcomes to allow distinction between complications associated with surgical disease and those attributable to surgery itself. Finally, most series are either uncontrolled or use the general population of pregnant women as controls rather than women with surgical disease who are managed nonsurgically. Consideration of these factors as well as our own extensive experience suggests that when the risks of maternal hypotension or hypoxia are minimal, or can be adequately mitigated, indicated surgery during any trimester does not appear to subject either the mother or fetus to risks significantly beyond those associated with the disease itself or the complications of surgery in nonpregnant individuals. In some cases, reluctance to operate during pregnancy becomes a self-fulfilling prophecy in which delay in surgery contributes to adverse perinatal outcomes traditionally attributed to surgery itself.

Impact of contrast exposure from computed tomography angiography on acute kidney injury after neonatal cardiopulmonary bypass surgery.

OBJECTIVE: Acute kidney injury (AKI) is a frequent complication after cardiopulmonary bypass (CBP) for cardiac surgery in neonates. It is unclear if exposure to computed tomography angiography (CTA) in the preoperative period increases the risk of AKI. We hypothesized a short interval between CTA and CPB surgery would be associated with higher rates of AKI in infants. DESIGN: In this single center retrospective review of patients between 2012 and 2015, neonates less than one month old were analyzed if they had CTA prior to cardiac surgery with CPB. Baseline, demographic, fluid balance, and laboratory data was analyzed. AKI was staged according to KDIGO criteria. RESULTS: Fifty-six neonates were analyzed. AKI developed in 42 (75%) of patients; severe AKI (KDIGO stages 2 and 3) occurred in 18 (32%). Patient characteristics were similar at baseline and at time of CTA between those with and without severe AKI. Patients with severe AKI had longer CPB time, lower postoperative urine output, higher peak serum creatinine, and longer hospital length of stay. When considering intervals between CTA and CPB surgery ≤1 day (n = 19), ≤3 days (n = 28), and >3 days (n = 28); there was no difference in AKI incidence nor postoperative outcomes among these three interval cohorts. CONCLUSION: Routine exposure to CTA and CPB surgery in close succession does not appear to increase the risk of AKI after neonatal cardiac surgery. Though other risks need to be weighed (eg, sedation, intubation, radiation exposure), this result may enable more liberal utilization of CTA for preoperative surgical planning of congenital heart operations in patients with unclear or complex anatomy.

InsR/IGF1R Pathway Mediates Resistance to EGFR Inhibitors in Glioblastoma.

PURPOSE: Aberrant activation of EGFR is a hallmark of glioblastoma. However, EGFR inhibitors exhibit at best modest efficacy in glioblastoma. This is in sharp contrast with the observations in EGFR-mutant lung cancer. We examined whether activation of functionally redundant receptor tyrosine kinases (RTKs) conferred resistance to EGFR inhibitors in glioblastoma. EXPERIMENTAL DESIGN: We collected a panel of patient-derived glioblastoma xenograft (PDX) lines that maintained expression of wild-type or mutant EGFR in serial xenotransplantation and tissue cultures. Using this physiologically relevant platform, we tested the abilities of several RTK ligands to protect glioblastoma cells against an EGFR inhibitor, gefitinib. Based on the screening results, we further developed a combination therapy cotargeting EGFR and insulin receptor (InsR)/insulin-like growth factor 1 receptor (IGF1R). RESULTS: Insulin and IGF1 induced significant protection against gefitinib in the majority of EGFR-dependent PDX lines with one exception that did not express InsR or IGF1R. Blockade of the InsR/IGF1R pathway synergistically improved sensitivity to gefitinib or dacomitinib. Gefitinib alone effectively attenuated EGFR activities and the downstream MEK/ERK pathway. However, repression of AKT and induction of apoptosis required concurrent inhibition of both EGFR and InsR/IGF1R. A combination of gefitinib and OSI-906, a dual InsR/IGF1R inhibitor, was more effective than either agent alone to treat subcutaneous glioblastoma xenograft tumors. CONCLUSIONS: Our results suggest that activation of the InsR/IGF1R pathway confers resistance to EGFR inhibitors in EGFR-dependent glioblastoma through AKT regulation. Concurrent blockade of these two pathways holds promise to treat EGFR-dependent glioblastoma.

A systematic approach to the identification and classification of near-miss events on labor and delivery in a large, national health care system.

We describe a systematic approach to the identification and classification of near-miss events on labor and delivery in a large, national health care system. Voluntary reports of near-miss events were prospectively collected during 2010 in 203,708 deliveries. These reports were analyzed according to frequency and potential severity. Near-miss events were reported in 0.69% of deliveries. Medication and patient identification errors were the most common near-miss events. However, existing barriers were found to be highly effective in preventing such errors from reaching the patient. Errors with the greatest potential for causing harm involved physician response and decision making. Fewer and less effective existing barriers between these errors and potential patient harm were identified. Use of a comprehensive system for identification of near-miss events on labor and delivery units have proven useful in allowing us to focus patient safety efforts on areas of greatest need.

Surfer's toe: trauma-induced idiopathic acro-osteolysis in the toes of a 46-year-old surfer: a case report.

Acquired acro-osteolysis (AOL) is defined as the resorption of bone from the tufts or shafts of the terminal phalanges. Acquired acro-osteolysis can manifest as a primary osteolysis syndrome and also appears in a number of disease states including rheumatologic disorders, neuropathic diseases, the result of prolonged exposure to polyvinyl chloride, and in rare cases, as a response to repeated mechanical stress. In this report, a 46-year-old surfer was evaluated for AOL as a complication of sports-related repetitive trauma to the right second and third toes. Radiography showed the bony tips of his right second and third toes had been eroded away. Acquired acro-osteolysis in the surfer's toes resulted from increased blood flow initiated to repair microdamage caused by repeated trauma to the distal ends of his second and third right toes due to the habitual dragging of the affected toes across a surfboard. The always initial lytic phase of bone repair was magnified by the increased arterial input to warm the extremities after prolonged exposure to cold. At 6-years' follow-up, the use of a protective bandage while surfing has permitted full regeneration of the affected toes.

Use of intravenous sedation in periodontal practice: a national survey.

BACKGROUND: In the early 1990s, much of the periodontal profession perceived an upcoming shift in services performed by periodontists as many patients began to expect sedation for periodontal surgery. As a result, in 1993 the American Academy of Periodontology began encouraging postgraduate periodontal programs to train residents in the use of conscious sedation. The purpose of this study is to investigate trends in the training of intravenous (i.v.) sedation in residency and its use in periodontal practice. METHODS: An 18-question survey was mailed to a sample of 1596 active periodontists throughout the United States and Canada. Thirty-seven percent (596) of the surveys were returned. Twenty-two retired periodontists responded and were excluded from the analysis. The data from the remaining 574 surveys were analyzed with a statistical software package. RESULTS: Approximately half (49.8%) of the survey respondents offer i.v. sedation in their practices. Among respondents who completed residency prior to 1996, 42.6% offer i.v. sedation compared with 64.2% of respondents who completed residency in 1996 or later. The number of i.v. sedations performed in residency was moderately correlated with the number of i.v. sedations personally performed in periodontal practice (Spearman r = 0.5169, P <0.0001). The largest percentage of periodontists using i.v. sedation (74.0%) was reported from American Academy of Periodontology District 5 (south central United States), whereas District 7 (New Jersey and New York) reported the lowest usage (15.6%). CONCLUSIONS: Approximately half of all periodontists provide i.v. sedation, with more recent periodontal graduates more likely to personally offer and administer i.v. sedation services for their patients. Regional differences exist in the use and training of i.v. sedation.

Spanish as a primary language and its effect on breast cancer presentation.

PURPOSE: It is well documented that patients without health insurance tend to present at more advanced cancer stages than those with insurance. What has not been well documented is the effect that primary language has on cancer stage presentation. Given the significant number uninsured patients and patients not fluent in English who are treated at our institution, we sought to identify how these parameters affect cancer staging at presentation using breast cancer as a model. METHODS: We conducted a retrospective chart review over a 36-month period at an urban community hospital. Patients who received their initial surgical treatment at this facility were included. One hundred seventy patients were identified. Definitive breast cancer surgery, breast cancer stage, and type were recorded for all subjects. We analyzed patient demographics including ethnicity, primary language spoken, and insurance status. RESULTS: All patients were female. Patient populations were evenly distributed among three major ethnicities: 39% were African American, 36% were white, 23% were Hispanic, and 2% were listed as "other." Seventy percent of Hispanic patients noted that English was not their primary language. Ten percent of the white population presented at stage III or greater compared with 16% of African Americans and 22% of Hispanics. Twenty-seven percent of non-English-speaking Hispanics presented with advanced-stage disease. CONCLUSION: Non-English-speaking Hispanic patients presented at more advanced stages than their English-speaking counterparts. Health care reform must address the non-English-speaking Hispanic to effectively improve the health of all groups in the United States.