Incidence of radionecrosis in single-fraction radiosurgery compared with fractionated radiotherapy in the treatment of brain metastasis.

Introduction: Radiation-induced brain necrosis ["radionecrosis" (rn)] is a relatively uncommon but potentially severe adverse effect of stereotactic radiosurgery (srs) for brain metastasis. Although dose, volume, and hypofractionation have been suggested to affect rn rates, patient and treatment variability in this population make it difficult to clearly delineate the risk. We set out to establish the effect of fractionation on rn rates by reviewing patients receiving simultaneous multi-fraction and single-fraction treatment at our centre. Methods: Patients receiving simultaneous (within 1 month) 1-fraction (ssrs) and 3-fraction (fsrs) radiosurgery treatments during 2012-2015 were identified in our institution's database. Serial post-srs magnetic resonance imaging (mri) was reviewed to determine rn and local recurrence. The effect of maximum dose, volume, whole-brain radiotherapy (wbrt), and fractionation on rn development was assessed using logistic regression for paired data. Results are reported using odds ratios (ors) and corresponding 95% confidence intervals (cis). Results: Of 90 patients identified, 22 had at least a 6-month mri follow-up. Median follow-up was 320 days. The most common primary tumour type was non-small-cell lung cancer, followed by breast and rectal cancer. Radionecrosis developed in 16 patients [21 of 62 lesions (34%), with 4 being symptomatic (20%)]. Of the 21 lesions in which rn developed, 11 received 3 fractions, and 10 received 1 fraction. The or for the association between the incidence of rn and maximum dose was 1.0 (95% ci: 0.9 to 1.1); for fractionation it was 1.0 (95% ci: 0.3 to 3.6); for previous wbrt, it was 0.4 (95% ci: 0.2 to 1.2); and for a 10-unit increase in volume, it was 3.1 (95% ci: 1.0 to 9.6). Local recurrence developed in 8 patients (12%), 6 of whom belonged to the ssrs group. Conclusions: Our results indicate that patients receiving srs for multiple brain metastases experience a higher rate of rn than is reported in the literature and poorer survival despite having equivalent local control. Maximum dose did not appear to be associated with rn risk in our cohort, but volume was significantly associated with rn risk. Although fractionated treatment did not directly lower the rate of rn in this population, it might have played a role in reducing the magnitude of the rn risk in large-volume lesions. Further investigation will help to delineate optimal dose and fractionation so as to minimize rn while maintaining local control in this group.

Comparative survival in patients with brain metastases from non-small-cell lung cancer treated before and after implementation of radiosurgery.

INTRODUCTION: Survival after a diagnosis of brain metastasis in non-small-cell lung cancer (nsclc) is generally poor. We previously reported a median survival of approximately 4 months in a cohort of patients treated with whole-brain radiotherapy (wbrt). Since that time, we implemented a program of stereotactic radiosurgery (srs). In the present study, we examined survival and prognostic factors in a consecutive cohort of patients after the introduction of the srs program. METHODS: Data from a retrospective review of 167 nsclc patients with brain metastasis referred to a tertiary cancer centre during 2010-2012 were compared with data from a prior cohort of 91 patients treated during 2005-2007 ("pre-srs cohort"). RESULTS: Median overall survival from the date of diagnosis of brain metastasis (4.3 months in the srs cohort vs. 3.9 months in the pre-srs cohort, p = 0.74) was not significantly different in the cohorts. The result was similar when the no-treatment group was excluded from the srs cohort. Within the srs cohort only, significant differences is overall survival were observed between treatment groups (srs, wbrt plus srs, wbrt, and no treatment), with improved survival being observed on univariate and multivariate analysis for patients receiving srs compared with patients receiving wbrt alone (p < 0.001). CONCLUSIONS: No improvement in survival was observed for nsclc patients with brain metastases after the implementation of srs. Selected patients (younger age, female sex, good performance status, fewer brain metastases) treated with srs appeared to demonstrate improved survival. However, those observations might also reflect better patient selection for srs or a greater tendency to offer those patients systemic therapy in addition to srs.

Clinical surveillance compared with clinical and magnetic resonance imaging surveillance for brain metastasis: a feasibility survey.

INTRODUCTION: After stereotactic radiosurgery (srs) for brain metastases, patients are routinely monitored with magnetic resonance imaging (mri). The high rate of new brain metastases after srs treatment alone might not be as concerning with modern mri and target localization treatment. Intensive surveillance might induce anxiety, lowering the patient's quality of life (qol). The present work is the feasibility component of a prospective study evaluating the role of surveillance mri on qol in patients with limited (1-3) brain metastases. METHODS: Patients with limited brain metastases treated with srs alone, an Eastern Cooperative Oncology Group performance status of 2 or less, and documented stability in treated lesions, with no new lesions seen on mri at weeks 6-10 after srs, were eligible. All were asked about their interest in participating in the control (mri and clinical surveillance) or the experimental arm (symptom-directed mri and clinical surveillance). If 33% or more agreed to participate in the experimental arm, it would be considered feasible to conduct the prospective study. RESULTS: From November 2014 to July 2015, 45% of patients (10 of 22) agreed to participate in the experimental arm. Subgroup analyses found that the decision to participate has no statistically significant association with time of presentation (p = 0.696), display of symptoms (p = 0.840), age (p = 0.135), or number of lesions (p = 0.171). CONCLUSIONS: Results show that it is feasible to conduct the prospective cohort study. Because of the small sample size, we are limited in the conclusions able to be drawn in the subgroup analyses. However, the future study would allow for a better understanding of the attitudes of patients toward mri and its effect on qol.

Patch-Augmented Rotator Cuff Repair and Superior Capsule Reconstruction.

BACKGROUND: Massive rotator cuff tears in active patients with minimal glenohumeral arthritis remain a particular challenge for the treating surgeon. METHODS: A selective literature search was performed and personal surgical experiences are reported. RESULTS: For patients with irreparable rotator cuff tears, a reverse shoulder arthroplasty or a tendon transfer are often performed. However, both procedures have rather high complication rates and debatable long-term results, particularly in younger patients. Therefore, patch-augmented rotator cuff repair or superior capsule reconstruction (SCR) have been recently developed as arthroscopically applicable treatment options, with promising biomechanical and early clinical results. CONCLUSION: For younger patients with irreparable rotator cuff tears wishing to avoid tendon transfers or reverse total shoulder arthroplasty, both patch-augmentation and SCR represent treatment options that may delay the need for more invasive surgery.

The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population.

OBJECTIVE: To establish the prevalence of intrahepatic cholestasis of pregnancy (ICP) in a primarily Latina population in the United States. STUDY DESIGN: Over a period of 16 months, a convenience sample of subjects admitted to labor and delivery in the third trimester was enrolled. Each subject completed a questionnaire rating their severity of pruritus on a numeric scale of 1 to 10. Serum was analyzed via radioimmunoassay for total bile acid concentration. ICP was defined as pruritus score >4 and a total serum bile acid concentration of >or=20 micromol/l. Ethnicity was determined from hospital record demographic data. RESULTS: All invited participants enrolled in the study. Three hundred and forty subjects were enrolled. Three hundred and sixteen subjects (93%) were identified as Latina. The serum bile acid concentration range for the entire study population was 1 to 580 micromol/l with a mean of 10.4+/-34.9 micromol/l. Twenty-four (7.1%) subjects had a serum bile acid concentration >or=20 micromol/l. A pruritus score >4 was found in 19.7% (67/340). Of the 24 subjects with a bile acid concentration >or=20 micromol/l, 19 also had a pruritus score >4. Thus, the prevalence of ICP in this population was 5.6% (19/340). In subjects with ICP, the mean serum bile acid concentration was 89.5+/-124.0 micromol/l. When controlling for confounders, women with ICP were associated with higher rates of chorioamnionitis (P=0.043) and their fetuses had higher rates of thick meconium (P=0.053). CONCLUSIONS: The overall prevalence of ICP in this population was 5.6%, 10 to 100 times higher than previously reported data from the United States. Larger studies of perinatal morbidity examining the diagnostic criteria of cholestasis need to be conducted.

Evaluation of a rapid optical immunoassay-based test for group B streptococcus colonization in intrapartum patients.

OBJECTIVE: To compare an optical immunoassay (OIA) rapid diagnostic kit to standard culture for the diagnosis of vaginal colonization with group B streptococcus (GBS) and to assess the accuracy and reproducibility of the OIA results. METHOD: A total of 301 patients in labor were prospectively evaluated for GBS colonization with a test approved by the Food and Drug Administration (STREP B OIA kit, Biostar, Boulder, CO, USA) and by culture. The vagina was simultaneously sampled with two swabs. Rectal culture was obtained separately. RESULTS: By the criterion of a positive culture, the vagina was colonized by GBS in 33 of 301 (11%) patients; and the rectum in 42 of 301 (13.9%). The vagina or rectum or both were colonized by CBS in 54 of 301 (17.9%) of patients. The OIA had sensitivity, specificity, positive predictive value and negative predictive value of 63.6%, 86.3%, 37.5% and 94.8%, respectively. The OIA had a kappa statistic score of 0.59. CONCLUSION: The OIA is not an adequately sensitive rapid kit for reliable detection of GBS colonization of the vagina. The results of the OIA were only moderately accurate and reproducible.

Management of burn injuries during pregnancy.

Burns suffered during pregnancy is rare and can be a devastating injury. The presence of a fetus creates many special maternal physiological changes, and the burn wound places additional great stress on systems that are already highly modified. Most of the literature has come from developing countries, and most reports from developed countries have come before 1980 and do not reflect the current standard of care. We have compiled a retrospective review of eight patients burned during pregnancy. The total body surface area (TBSA) burned ranged from 1 to 85% in these patients, and all survived the injury. All patients gave birth to healthy children except the most severely burned patient, whose child suffers from cerebral palsy. Based on our experience as well as a review of the literature, management recommendations are proposed. These include: (1) early pregnancy test for all female patients of childbearing age, (2) prompt and aggressive fluid resuscitation, (3) early supplemental oxygen and low threshold for mechanical ventilatory support, (4) early delivery of the fetus if the pregnancy is in the third trimester, and (5) high suspicion for venous thrombosis and sepsis, with early and aggressive treatment.

Collegiate contingencies.

We discuss contemporary trends and developments that affect colleges and universities and describe several central contingencies that have given rise to, maintain, and operate in response to these trends and developments. We identify the differential impacts of these contingencies on faculty, students, and administrators in various types of higher education institutions. These contingencies are sources of conflict between and among these three groups within the academy that, we argue, cause significant instability in contemporary academe. We discuss prominent domains of this dis-equilibrium and propose several general interventions to address the sources of the instability.

Massive fetomaternal hemorrhage and fetal death: are they predictable?

OBJECTIVE: To report the incidence of massive fetomaternal hemorrhage (FMH) associated with fetal death and to test the hypothesis that FMH is more likely to occur in those with risk factors for FMH. STUDY DESIGN: All cases of fetal death of infants weighing > 500 gm between January 1, 1990 and December 31, 1994 were reviewed for evidence of massive FMH (> or = 2% fetal cells in the maternal circulation as measured by the Betke-Kleihauer test). Women with risk factors were compared with those without risk factors with respect to the occurrence of massive FMH. RESULTS: The prevalence of massive FMH was 14 of 319 (4.4%) cases, occurring in 4 of 102 (3.9%) of those with risk factors and 10 of 217 (4.6%) of patients without risk factors (p = 0.78). Otherwise unexplained fetal death was associated with massive FMH in 5 of 141 (3.5%). Major fetal anomalies were present in 5 of 14 (35.7%) cases of massive FMH. CONCLUSION: Clinical risk factors do not predict an increased likelihood of massive FMH. Massive FMH is associated with fetal anomalies. Betke-Kleihauer testing should be performed in all cases of fetal death, including those with anomalies regardless of the presence or absence of risk factors for FMH.

Umbilical arteriovenous PO2 and PCO2 differences and neonatal morbidity in term infants with severe acidosis.

OBJECTIVE: In term infants umbilical cord gas analysis is a poor predictor of immediate newborn complications associated with intrapartum asphyxia, unless the umbilical arterial pH is less than 7.00. We investigated whether umbilical arteriovenous blood gas differences may better predict asphyxia-related complications. STUDY DESIGN: The study population consisted of 82 term, nonanomalous, singleton, live-born infants with severe umbilical acidosis (pH < 7.00). Umbilical arteriovenous pH, PCO2, and PO2 differences were correlated with Apgar scores and the presence of seizures, hypoxic-ischemic encephalopathy, cardiopulmonary and renal dysfunction, and abnormal development in the neonatal period. RESULTS: Umbilical arteriovenous pH, PCO2, and PO2 differences were interrelated (p < 0.0001), but these parameters correlated only weakly with 1-minute and 5-minute Apgar scores. An arteriovenous PCO2 difference > 25 torr was a highly sensitive and specific parameter in identifying asphyxiated infants with seizures, hypoxic-ischemic encephalopathy, cardiopulmonary and renal dysfunction, and abnormal development in the neonatal period. Arteriovenous PO2 differences were less sensitive in the detection of neonatal morbidity than arteriovenous PCO2 differences. CONCLUSION: Umbilical cord blood arteriovenous PCO2 differences provide a new tool to predict neonatal morbidity and permanent neurologic injury in term infants with perinatal asphyxia.

Should the same glucose values be targeted for type 1 as for type 2 diabetics in pregnancy?

OBJECTIVE: Our purpose was to determine whether the same maternal glycemic control is necessary to achieve similar perinatal outcomes for type 1 as for type 2 diabetics. STUDY DESIGN: The subjects were all women with pregestational diabetes mellitus delivered of live-born singletons. Glycemic control was achieved with diet and insulin. Self-monitoring of blood glucose was performed before meals and at bedtime. Target glucose values were 60 to 90 mg/dl fasting and 60 to 105 mg/dl at other times. RESULTS: Of 60,628 deliveries, 46 type 1 and 113 type 2 diabetic women met inclusion criteria. Respective differences were found between type 1 and type 2 diabetics in average daily glucose levels (112 mg/dl vs 97 mg/dl, p < 0.001), percent of values within target ranges (35% vs 57%, p < 0.001), and mean amplitude of glycemic excursion (48.1 mg/dl vs 24.9 mg/dl, p < 0.001). At least one daily glucose value was < 50 mg/dl during 19% of observation days for type 1 vs 2% of observation days for type 2 pregnancies (p < 0.001). There were no statistically significant differences between type 1 and type 2 diabetic pregnancies in neonatal macrosomia (30% vs 34%), proportion of cesarean deliveries during labor for arrest disorders (67% vs 69%), shoulder dystocia (2% vs 6%), and neonatal hypoglycemia (18% vs 26%). CONCLUSIONS: Less stringent maternal glycemic control may permit comparable maternal and neonatal outcomes for type 1 compared with type 2 diabetics. Higher target values for type 1 diabetics may decrease the frequency of maternal hypoglycemic episodes.

Genital herpes during pregnancy: inability to distinguish primary and recurrent infections clinically.

OBJECTIVE: To determine if the signs and symptoms of genital herpes in pregnancy accurately identify primary genital herpes infections using serologic testing for final classification. METHODS: Twenty-three women with clinical signs and symptoms suggestive of primary genital herpes infections in the second and third trimesters of pregnancy were subsequently cultured and tested serologically (for herpes simplex virus type 1 and herpes simplex virus type 2 antibodies) and classified as having true primary (no herpes simplex virus type 1 or type 2 antibodies), nonprimary (heterologous herpes simplex virus antibodies present), or recurrent (homologous antibodies present) infections. RESULTS: Only one of 23 women with clinical illnesses consistent with primary genital herpes virus simplex infections had serologically-verified primary infection. This primary infection was caused by herpes simplex virus type 1. Three women had nonprimary type 2 infections, and 19 women had recurrent infections. Among culture-proven recurrent infections, 12 were caused by herpes simplex virus type 2 and three by herpes simplex virus type 1. Only one infant was born preterm, and no clinically significant perinatal morbidity was observed. CONCLUSION: Correct classification of gestational genital herpes infections can be accomplished only when clinical evaluation is correlated with viral isolation and serologic testing using a type-specific assay. Severe first episodes of genital herpes infections among women in the second and third trimesters of pregnancy are not usually primary infections and are not commonly associated with perinatal morbidity.

The effect of thigh-length support stockings on the hemodynamic response to ambulation in pregnancy.

OBJECTIVE: Our purpose was to determine the effect of thigh-length support stockings on hemodynamic response when pregnant subjects change from the sitting to the lateral recumbent position and then after standing with ambulation. STUDY DESIGN: Eighteen subjects in the late second and early third trimester of pregnancy acted as their own controls. The cardiovascular status of the subjects was assessed by a noninvasive technique--thoracic electrical bioimpedance before and after wearing support stockings for 1 week. Urine catecholamines were measured in 13 patients before and after wearing support stocking to assess the release of catecholamines. Samples were collected after the subjects had been in the lateral recumbent position 40 minutes and again 40 minutes later after standing with ambulation. RESULTS: Heart rate and mean arterial blood pressure decreased significantly when subjects changed from the sitting to the lateral recumbent position and then increased with ambulation. Wearing compression stockings significantly increased mean arterial pressure and afterload in all three positions. Position change from lateral recumbent to standing and ambulation marginally increased urinary dopamine levels (p = 0.097) and significantly increased norepinephrine levels (p = 0.006). CONCLUSIONS: There are significant hemodynamic changes in pregnant subjects when they change from the sitting position to the lateral recumbent position and then change to standing with ambulation. Support stocking have a significant mechanical effect: they significantly increase afterload and systemic vascular resistance by preventing pooling of blood in the lower extremities. There may also be a biochemical effect that results in less catecholamine release. These results suggest that compression stockings could play an important role in supporting the circulation during ambulation.

Amniotic fluid alpha fetoprotein (AFAFP) and maternal serum alpha fetoprotein (MSAFP) in abdominal pregnancies: correlation with extent and site of placental implantation and clinical implications.

The hypotheses are evaluated that in abdominal pregnancies 1) elevated MSAFP is due to an altered maternal-placental interface, and 2) differences in MSAFP levels may reflect placental location within the peritoneal cavity. A review of 1,193 ectopic pregnancies from 1983-1993 identified three cases of advanced abdominal pregnancy. All three had undergone second trimester genetic amniocentesis for amniotic fluid alpha fetoprotein (AFAFP) and karyotype. The clinical course was reviewed (including presentation and surgical findings). MSAFP was elevated in two of the three cases (3.63 and 4.88 MoM). AFAFP and fetal karyotype were normal in all three cases. Elevated MSAFP values were associated with more extensive visceral implantation, longer surgical operative time, greater blood loss and transfusion requirements. Abdominal pregnancies with elevated MSAFP appear to have more extensive placental involvement of the abdominal viscera; this would, in fact, account for the elevated MSAFP values given the normal AFAFP.

Apparent heparin resistance form elevated factor VIII in a patient with postoperative deep venous thrombosis. A case report.

BACKGROUND: During the puerperium, heparin levels, rather than the adjusted partial thromboplastin time test, can be used to identify heparin resistance and guide heparin therapy. CASE: A patient receiving heparin for deep venous thrombosis had artifactual resistance to heparin, with a short adjusted partial thromboplastin time due to elevation of factor VIII. Heparin assay revealed a heparin level above the therapeutic range. CONCLUSION: Direct measurement of heparin concentration and factor VIII activity should be performed when heparin resistance is suspected.