Cell Cycle Checkpoints p16 and p21-Strong Predictors of Clinicopathologic Outcomes in High-Grade Osteosarcoma.

PURPOSE: In this study, we used a series of immunohistochemical measurements of 2 cell cycle regulators, p16 and p21, to evaluate their prognostic value, separately and in combination, for the disease outcomes. METHOD: A total of 101 patients with high-grade osteosarcoma were included in this study. Clinicopathologic data were collected, and immunohistochemistry for p16 and p21 was performed and interpreted by 3 independent pathologists. Statistical analysis was performed to assess the strength of each of these markers relative to disease outcome. RESULTS: Our results indicate that more than 90% expression (high) of p16 by immunohistochemistry on the initial biopsy has a strong predictive value for good histologic response to chemotherapy. The patients are also more likely to survive the past 5 years and less likely to develop metastasis than patients with less than 90% p16 (low) expression. The results for p21, on the other hand, show a unique pattern of relationship to the clinicopathologic outcomes of the disease. Patients with less than 1% (low) or more than 50% (high) expression of p21 by immunohistochemistry show a higher chance of metastasis, poor necrotic response to chemotherapy, and an overall decreased survival rate when compared with p21 expression between 1% and 50% (moderate). Our results also showed that the expression of p16 and combined p16 and p21 demonstrates a stronger predictive relationship to 5-year survival than tumor histologic necrosis and p21 alone. DISCUSSION: The results of this study, once proven to be reproducible by a larger number of patients, will be valuable in the initial assessment and risk stratification of the patients for treatment and possibly the clinical trials.

Toward an atlas of Salish Sea biodiversity: the flora and fauna of Galiano Island, British Columbia, Canada. Part I. Marine zoology.

Background: Based on records dating from 1859 to 2021, we provide an overview of the marine animal diversity reported for Galiano Island, British Columbia, Canada. More than 650 taxa are represented by 20,000 species occurrence records in this curated dataset, which includes dive records documented through the Pacific Marine Life Surveys, museum voucher specimens, ecological data and crowd-sourced observations from the BC Cetacean Sightings Network and iNaturalist. New information: We describe Galiano Island's marine animal diversity in relation to the Salish Sea's overall biodiversity and quantify the proportional contributions of different types of sampling effort to our current local knowledge. Overviews are provided for each taxonomic group in a format intended to be accessible to amateur naturalists interested in furthering research into the region's marine biodiversity. In summary, we find that the Pacific Marine Life Surveys, a regional community science diving initiative, account for 60% of novel records reported for Galiano Island. Voucher specimens account for 19% and crowd-sourced biodiversity data 18% of novel records, respectively, with the remaining 3% of reports coming from other sources. These findings shed light on the complementarity of different types of sampling effort and demonstrate the potential for community science to contribute to the global biodiversity research community. We present a biodiversity informatics framework that is designed to enable these practices by supporting collaboration among researchers and communities in the collection, curation and dissemination of biodiversity data.

Cerclage versus vaginal progesterone in low-risk pregnant women with a short cervix.

OBJECTIVE: To compare vaginal progesterone to cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, incidentally found sonographic cervical length of <15 mm, and no history of preterm birth. STUDY DESIGN: A retrospective cohort study was conducted on 68 women who delivered at the University of Kansas Health System with a singleton gestation found to have a cervical length <15 mm on transvaginal ultrasound and no history of preterm birth. Women treated with vaginal progesterone (n = 29) were compared to women who underwent cerclage placement (n = 39). The primary outcome was preterm birth at <34 weeks of gestation. Secondary outcomes include preterm birth at <37 and <28 weeks of gestation and neonatal morbidities. RESULTS: Of the 268 patients who had a cervical length of <15 mm on transvaginal ultrasound, 68 participants met inclusion criteria and were included in the final analysis. Twenty-nine participants received vaginal progesterone and 39 participants received cervical cerclage. The average cervical length at initiation of therapy was greater in the progesterone cohort versus cerclage cohort, respectively (10.5 vs. 8.0 mm, p < .01). All other baseline characteristics were similar between groups, including no difference in average gestational age at initiation of therapy (21.6 vs. 21.5 weeks, p = .87). Average latency after therapy did not differ between groups (100 vs. 92.7 days p = .43). The incidence of preterm birth at <37 weeks (OR = 1.49, 95% CI = 0.57-3.93), <34 weeks (OR = 1.47, 95% CI = 0.52-4.18), and <28 weeks (OR = 1.90, 95% CI = 0.45-8.07), did not differ significantly between groups. Additionally, no difference in neonatal morbidity was detected. CONCLUSION: At our institution, we found no difference between vaginal progesterone and cerclage in the average latency period or risk of preterm birth among women with an incidental short cervix of <15 mm and no history of preterm birth, despite the significantly shorter initial cervical length in the cerclage group. These findings suggest either vaginal progesterone or cerclage could be used to reduce the risk of preterm birth among this high-risk population.

Reirradiation in Conservative Salvage of Recurrent Soft-tissue Sarcoma: An Analysis of Treatment Efficacy and Toxicities.

OBJECTIVE: Compared with radical resection alone, perioperative radiation therapy (RT) combined with neurovascular preserving surgery is the standard for the management of virgin soft-tissue sarcomas. Yet, the optimal management of a local recurrence remains unclear. We report outcomes of patients with locally recurrent soft-tissue sarcoma treated with resection and reirradiation at the University of Florida. MATERIALS AND METHODS: We reviewed the records of patients treated with primary conservative surgery and radiation for soft-tissue sarcoma followed by salvage resection and reirradiation for a local recurrence at our institution. RESULTS: We analyzed 23 patients treated between 1976 and 2014 (median follow-up, 46 mo). Tumor sites included: proximal extremity, 11 patients; trunk, 6; distal extremity, 5; and head and neck, 1. All patients had conservative gross total resection of their recurrent tumor, without amputation. For reirradiation, 16 patients received external-beam RT alone, 6 received external-beam RT and brachytherapy, and 1 received brachytherapy alone. Two patients received chemotherapy. After retreatment, the 5-year overall survival, cause-specific survival, local control, and distant control rates were 39%, 42%, 46%, and 60%, respectively. Ten patients experienced local recurrences, 1 experienced regional recurrence, and 9 developed distant metastases. Retreatment-related complications ranged from delayed wound healing to limb amputation; 8 patients required amputation. Only 3 patients remained disease-free at last follow-up. No statistically significant associations were found between treatment factors (eg, RT dose) and local control. CONCLUSIONS: Achieving local control of recurrent soft-tissue sarcoma is challenging. Treatment with reoperation and reirradiation can lead to debilitating complications affecting function and quality of life.

Osteoradionecrosis in osseous free flap reconstruction: Risk factors and treatment.

OBJECTIVE: To determine the rate and risk factors for osteoradionecrosis (ORN) in osseous free flaps after postoperative radiation therapy (PORT). To describe the treatment of free flap ORN. METHODS: Seventy-four patients undergoing osseous free flap reconstruction were analyzed. Thirty-eight completed PORT. Patients were followed for ≥6 months. RESULTS: The rate of ORN was 34% overall; 0% with 50 to 59.9 Gy; 8% with 60 Gy; 40% with 66 Gy; 56% with 70 to 74.4 Gy. Mean time to ORN was 13.1 months. 0/28 patients without PORT developed free flap osteonecrosis. Multivariate analysis found the only factor predicting ORN: PORT >60 Gy, which increased the risk 21-fold. Treatment included PENTACLO, hyperbaric oxygen, and surgical debridement with 75% within 2 years. CONCLUSION: PORT >60 Gy is significantly associated with free flap ORN. As the dose of adjuvant RT increases beyond 60 Gy, the risk of ORN in free flaps rises. Consideration should be given to lower PORT doses or delaying free flap reconstruction when feasible.

The Utility of Lower Glycemic Targets for Treating Gestational Diabetes: A Retrospective Study.

OBJECTIVE: In vivo study of glucose homeostasis in pregnancy suggests normal glucose levels are lower than current glycemic targets used in gestational diabetes. After the HAPO study results, our institution began using glycemic targets of fasting 85 mg/dL and 2-hour postprandial of 110 mg/dL. We reviewed our results. METHODS: A retrospective cohort of GDM patients that delivered at KUMC from January 2007 to May 2017 was reviewed. All patients were diagnosed with the 2-step Carpenter-Coustan thresholds. High targets were compared with low targets. The primary outcome investigated was birthweight > 90% (large for gestational age, LGA). RESULTS: 604 patients were studied, and 34% were treated with low glycemic targets. Our unadjusted results showed that the low-target group had a lower incidence of LGA infants (24.0 vs. 31.8%), higher incidence of neonatal hypoglycemia (20.7 vs. 11.6%), and inductions (39.4 vs. 20.5%). After adjustment for demographic variables, only a higher risk of inductions remained (aOR 2.54 (1.44, 4.49)). CONCLUSION: Lower glycemic targets did not produce large reductions in fetal overgrowth, but they were associated with a higher rate of inductions. As there were no observed differences in maternal or neonatal outcomes otherwise, aiming for lower glycemic targets in GDM is likely not cost-effective.

Radiation Treatment for Ewing Sarcoma Family of Tumors in Adult Patients: A Single Institution's Experience Over 40 Years.

PURPOSE/OBJECTIVES: To report prognostic factors and long-term outcomes in adults with Ewing sarcoma treated with definitive radiotherapy. MATERIALS AND METHODS: We reviewed patients 18 years old and above with nonmetastatic Ewing sarcoma treated with radiotherapy +/- chemotherapy or surgery. Outcomes were stratified by age (30 and above vs. younger than 30 y), soft tissue extension, tumor size (≥8.5 vs. <8.5 cm), tumor location, resection (yes vs. no), and treatment era (1970-1992 vs. 1993-2012). Toxicities were scored using the RTOG criteria. RESULTS: Fifty-five patients (21 women) were treated with radiotherapy. Average age at diagnosis: 26.7 years (38 patients below 30 vs. 17 patients 30 y and above). A total of 43 had soft tissue extension (78%). Median tumor size: 8.5 cm. Most tumors were in the pelvis (40%), followed by the lower (27%) and upper (24%) extremities. All but 1 patient received chemotherapy; 13 underwent resection. Median dose: 55 Gy. Median follow-up: 3.6 years; 17.5 years for living patients. The 5-year overall (OS) and cause-specific survival (CSS) rates were both 46%. OS and CSS rates were unaffected by age (P=0.97), tumor size (P=0.12), or tumor location (P=0.99). Soft tissue extension portended a significantly poorer prognosis for 5-year OS and CSS: 37% vs. 82% (with and without, respectively; P=0.04). Patients who underwent resection had improved 5-year OS and CSS: 77% vs. 37%, respectively (P=0.01). Patients treated after 1993 had improved 5-year OS: 58% vs. 37% (P=0.0264). CONCLUSIONS: Adult patients with Ewing sarcoma experience similar treatment outcomes regardless of age at diagnosis. Soft tissue extension represents a poor prognostic factor. Aggressive trimodality therapy achieved the highest OS and CSS.

Cesarean Delivery with External Negative Pressure Dressing System: A Retrospective Cohort Study.

Objective To determine whether the use of external negative pressure dressing system (ENPDS) can reduce the incidence of wound complications after cesarean delivery (CD) compared with traditional dressings. Methods Retrospective review of all patients undergoing CD between November 2011 and March 2013. Information was collected on demographics, body mass index (BMI), duration of labor, pre- and postnatal infections, incision and dressing type, and postoperative course. Comparisons were made between traditional dressing and an external negative pressure dressing system. Results Of 970 patients included in the study, wound complications occurred in 50 patients (5.2%). Comparisons of ENPDS ( n = 103) and traditional dressing ( n = 867) groups revealed higher wound complications for ENPDS with odds ratio (OR) 3.37 and confidence interval (CI) 1.68 to 6.39. ENPDS was more commonly used in patients with BMI > 30 and preexisting diabetes. After controlling for BMI and pregestational diabetes in logistic regression analysis, ENPDS was equivalent to traditional dressing for risk of wound complications with an adjusted OR 2.76 (CI 0.97 to 7.84), with a trend toward more wound complications with ENPDS. Wound separation also tended to be more common in ENPDS group versus traditional dressing with an adjusted OR 2.66 (CI 0.87 to 8.12), although this result did not reach significance. Conclusion ENPDS is equivalent to traditional dressing for preventing wound complications after controlling for the higher-risk population selected for its use. In particular, wound separation appears to occur more frequently in women treated with ENPDS versus traditional dressing and should be regarded as a potential hazard of the system.

Function Preservation After Conservative Resection and Radiotherapy for Soft-tissue Sarcoma of the Distal Extremity: Utility and Application of the Toronto Extremity Salvage Score (TESS).

OBJECTIVE: To evaluate outcomes after conservative resection and radiotherapy (RT) for soft-tissue sarcoma (STS) of the distal extremity, with assessment of functional quality of life using the validated Toronto Extremity Salvage Score (TESS) questionnaire and Common Terminology Criteria for Adverse Events (CTCAE), v4.0. METHODS: Thirty-three patients with STS involving the hand/wrist (N=18) or foot/ankle (N=15) complex received adjuvant RT with conservative resection and were evaluated for local tumor control, survival, toxicities, and preservation of objective functional ability. Eight patients were treated with preoperative RT (median dose, 50.4 Gy) and 25 with postoperative RT (median dose, 61.8 Gy). Median follow-up was 11.5 years. Functional outcomes were measured using TESS; patients with amputations were excluded from the TESS analysis. Adverse events related to gait, limb edema, skin infection, wound complication, and wound dehiscence were assessed using the CTCAE. RESULTS: The 5- and 10-year local control rates were both 90%. The 10-year cause-specific, absolute, and distant metastasis-free survival rates were 97%, 87%, and 84%, respectively. Three patients had an amputation for reasons other than local recurrence or treatment complications and underwent amputation for patient preference. One third of the subjects (11/33 patients) were able to complete the TESS questionnaire; scores ranged from 88 to 100 (mean, 98.2). CTCAEv4 acute adverse events occurred in 2 cases: 1 patient had a grade 3 skin infection and 1 had a grade 2 wound complication of dehiscence. CONCLUSIONS: For management of distal extremity STS, the combination of adjuvant RT and conservative surgery achieves excellent local control and overall survival with few adverse events. In addition, through application of the TESS survey instrument, we have demonstrated that this treatment plan achieves robust functional preservation objectively and quantifiably.

Mutagenesis of lysines 156 and 159 in human immunodeficiency virus type 1 integrase (IN) reveals differential interactions between these residues and different IN inhibitors.

Human immunodeficiency virus (HIV) type I integrase (IN) active site, and viral DNA-binding residues K156 and K159 are predicted to interact both with strand transfer-selective IN inhibitors (STI), e.g. L-731,988, Elvitegravir (EVG), and the FDA-approved IN inhibitor, Raltegravir (RGV), and strand transfer non-selective inhibitors, e.g. dicaffeoyltartaric acids (DCTAs), e.g. L-chicoric acid (L-CA). To test posited roles for these two lysine residues in inhibitor action we assayed the potency of L-CA and several STI against a panel of K156 and K159 mutants. Mutagenesis of K156 conferred resistance to L-CA and mutagenesis of either K156 or K159 conferred resistance to STI indicating that the cationic charge at these two viral DNA-binding residues is important for inhibitor potency. IN K156N, a reported polymorphism associated with resistance to RGV, conferred resistance to L-CA and STI as well. To investigate the apparent preference L-CA exhibits for interactions with K156, we assayed the potency of several hybrid inhibitors containing combinations of DCTA and STI pharmacophores against recombinant IN K156A or K159A. Although K156A conferred resistance to diketo acid-branched bis-catechol hybrid inhibitors, neither K156A nor K159A conferred resistance to their monocatechol counterparts, suggesting that bis-catechol moieties direct DCTAs toward K156. In contrast, STI were more promiscuous in their interaction with K156 and K159. Taken together, the results of this study indicate that DCTAs interact with IN in a manner different than that of STI and suggest that DCTAs are an attractive candidate chemotype for development into drugs potent against STI-resistant IN.

Radiation therapy for hemangioendothelioma: the university of Florida experience.

OBJECTIVES: The benefit of radiotherapy (RT) for unresectable hemangioendotheliomas or patients with a high risk of local recurrence is unclear. This single-institution report describes the long-term effectiveness of RT for hemangioendothelioma. METHODS: From 1976 to 2009, 14 patients with nonmetastatic hemangioendothelioma were treated with RT at our institution. Median patient age was 45 years (range, 20 to 71 y). Nine patients had hemangioendothelioma of the extremities and 5 had spinal tumors. Eleven tumors originated from bone. Most tumors (n=12) were ≤5 cm in diameter. Nine patients had multifocal tumors. Four patients underwent surgery and postoperative RT, whereas 10 had RT alone. All 4 operative patients had microscopic negative margins. Median RT dose was 52.2 Gy (range, 45 to 60 Gy) for RT alone and 62.2 Gy (range, 60 to 64.8 Gy) for postoperative patients. Seven patients received 1.5-2 Gy once daily and 7 patients received 1.2 Gy twice daily. The median follow-up was 10.3 years (range, 0.1 to 28.0 y). RESULTS: The 10-year local control, cause-specific survival, and overall survival rates were 100%, 86%, and 73%, respectively. Two patients experienced a distant metastasis and died within 3 months of starting definitive RT. Three patients died of intercurrent illness at a median of 10.5 years after treatment. Nine patients had no evidence of disease at most recent follow-up. No patients experienced greater than grade 1 acute or late toxicity from RT. CONCLUSIONS: With no local recurrences and minimal risk of toxicity, our data suggest that RT can effectively manage this disease and radical surgery compromising function or cosmesis may be safely avoided with moderate-dose RT.

Long-term treatment outcomes for patients with synovial sarcoma: a 40-year experience at the University of Florida.

OBJECTIVES: The objective of the study was to evaluate our long-term outcomes and prognostic factors for patients treated for localized synovial sarcoma. METHODS: We retrospectively reviewed the medical records of 92 patients treated for nonmetastatic synovial sarcoma at the University of Florida from 1967 to 2007. Most patients were treated with limb-sparing surgery and radiation (63%), 27% received surgery alone and 10% received radiation only as definitive treatment. Among patients treated with surgery and radiation, 69% received preoperative radiation and 31% received postoperative radiation. RESULTS: Median follow-up of living patients was 12.5 years. Overall survival rates at 5 and 10 years were 61% and 56%, respectively. Progression-free survival rates were 56% and 53%, respectively. Local control (LC) rates at 5 and 10 years were 90% and 88%, respectively. Freedom from distant metastasis rates were 57% at 5 years and 55% at 10 years. The severe complication (requiring surgery) rate was 13%. Size >5 cm predicted worse overall survival, progression-free survival, and freedom from distant metastasis, but not LC. No other prognostic factor was significant on multivariate analysis. CONCLUSIONS: Selectively adding radiotherapy to surgery results in excellent LC for these patients. However, distant metastasis remains the principal factor limiting survival and seems directly related to primary tumor size at presentation.

Radiotherapy in the management of giant cell tumor of bone.

OBJECTIVES: To evaluate the long-term treatment outcomes for patients with giant cell tumor of bone (GCTB) treated with radiotherapy with or without surgical resection. METHODS: This retrospective review includes 34 patients with GCTB treated with megavoltage radiotherapy between January 1973 and January 2008 at the University of Florida. Patients' ages ranged from 16 to 85 years (median, 29). Tumor sizes ranges from 2.5 to 12 cm (median, 4.8 cm) in the maximum dimension. Twenty-one patients received radiation for gross disease, either de novo (22 patients) or recurrent (12 patients). Thirteen patients were treated with postoperative radiation after gross total resection. The median dose was 45 Gy in both the definitive and adjuvant settings. RESULTS: The median follow-up was 16.8 years. The 5- and 10-year local-control (LC) rates were 85% and 81%, respectively. Six patients developed an isolated local recurrence (2/13 treated postoperatively and 4/21 who were treated for gross disease). All 6 patients who developed a local recurrence were successfully salvaged with surgery; therefore, the ultimate LC rate was 100%. Both the 5- and 10-year freedom from distant metastasis rates were 91%. Three patients developed lung metastases, including 1 patient who experienced GCTB transformation into a high-grade sarcoma. The 5- and 10-year progression-free survival rates were both 78%. CONCLUSIONS: Moderate-dose radiotherapy for GCTB provides a long-term LC >80%, justifying its role as an alternative to morbid surgery.

External-beam radiotherapy for pediatric and young adult desmoid tumors.

BACKGROUND: To report long-term outcomes following radiotherapy for desmoid tumors in children and young adults and identify variables impacting local-regional control and treatment complications. PROCEDURE: From 1978 to 2008, 30 patients <30 years old were treated with radiotherapy for a pathologically confirmed desmoid tumor. The median age at radiotherapy was 23.7 years old (range, 10.3-29.9). Fifteen patients underwent definitive radiotherapy, 14 received radiotherapy after gross total resection, and 1 received preoperative radiotherapy. Sixteen patients received 1.8 Gy once daily and 14 received 1.2 Gy twice daily. Variables analyzed for prognostic value included gender, age at diagnosis, primary or recurrent presentation, age at radiotherapy, tumor site, tumor size, extent of resection, fractionation schedule, and radiotherapy dose. RESULTS: The actuarial 15-year overall survival and local-regional control rates were 96% and 55%, respectively. Local-regional control in patients <18 years old at the time of radiotherapy was 20% versus 63% in those 18-30 years old (P = 0.08). Local-regional control rates for tumors receiving ≥ 55 Gy and < 55 Gy were 79% and 30%, respectively (P = 0.02). No other factors had a statistically significant association with local-regional control by univariate analysis. Twelve of 30 patients experienced grade 3-4 complications, including pathologic fractures, impaired range of motion, pain, and in-field skin cancers. CONCLUSIONS: The role of radiotherapy in managing young patients with desmoid tumors remains unclear. Younger patient age is associated with inferior local-regional control following RT. In children and young adults, doses ≥55 Gy were associated with improved tumor control, but also lead to increased risk of complications.

Definitive radiotherapy for unresectable pediatric and young adult nonrhabdomyosarcoma soft tissue sarcoma.

BACKGROUND: Few published articles describe outcomes following definitive radiation for unresectable pediatric and young adult nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). The purpose of this study is to evaluate the prognostic factors, outcomes, and complications in patients age 30 years or younger with NRSTS treated at the University of Florida from 1973 to 2002. PROCEDURE: Nineteen pediatric and young adult patients with NRSTS were treated with radiotherapy after biopsy. Thirteen patients had high-grade tumors. The median age at radiotherapy was 19.6 years; the median dose was 55.2 Gy. Twelve patients received chemotherapy. Prognostic factors for local recurrence, distant metastases, and survival were analyzed. RESULTS: Median follow-up was 2.6 years. The 5-year local-control rate was 40%. Nine out of 13 local failures occurred in the absence of metastatic disease. All patients with local failures died of their cancer, and 8 patients died without evidence of distant metastases. There was a trend toward improved local control with low/intermediate-grade tumors. Freedom from distant metastases at 5 years was 68%. Fourteen patients died of their disease. The 5-year overall survival was 37%. There was one grade 4 complication based on NCI Common Terminology Criteria for Adverse Events version 3. CONCLUSION: Young patients with unresectable NRSTS have a poor outcome thereby justifying current study efforts focused on treatment intensification. By demonstrating that all patients with local recurrence died of disease and more than half of these deaths occurred in the absence of distant spread, these results suggests that improved means of local control may translate into improvement in survival.

Anesthesia-related maternal mortality in the United States: 1979-2002.

OBJECTIVE: To examine 12 years of anesthesia-related maternal deaths from 1991 to 2002 and compare them with data from 1979 to 1990, to estimate trends in anesthesia-related maternal mortality over time, and to compare the risks of general and regional anesthesia during cesarean delivery. METHODS: The authors reviewed anesthesia-related maternal deaths that occurred from 1991 to 2002. Type of anesthesia involved, mode of delivery, and cause of death were determined. Pregnancy-related mortality ratios, defined as pregnancy-related deaths due to anesthesia per million live births were calculated. Case fatality rates were estimated by applying a national estimate of the proportion of regional and general anesthetics to the national cesarean delivery rate. RESULTS: Eighty-six pregnancy-related deaths were associated with complications of anesthesia, or 1.6% of total pregnancy-related deaths. Pregnancy-related mortality ratios for deaths related to anesthesia is 1.2 per million live births for 1991-2002, a decrease of 59% from 1979-1990. Deaths mostly occurred among younger women, but the percentage of deaths among women aged 35-39 years increased substantially. Delivery method could not be determined in 14%, but the remaining 86% were undergoing cesarean delivery. Case-fatality rates for general anesthesia were 16.8 per million in 1991-1996 and 6.5 per million in 1997-2002, and for regional anesthesia were 2.5 and 3.8 per million, respectively. The resulting risk ratio between the two techniques for 1997-2002 was 1.7 (confidence interval 0.6-4.6, P=.2). CONCLUSION: Anesthetic-related maternal mortality decreased nearly 60% when data from 1979-1990 were compared with data from 1991-2002. Although case-fatality rates for general anesthesia are falling, rates for regional anesthesia are rising. LEVEL OF EVIDENCE: II.

Design, synthesis, and biological evaluation of novel hybrid dicaffeoyltartaric/diketo acid and tetrazole-substituted L-chicoric acid analogue inhibitors of human immunodeficiency virus type 1 integrase.

Fourteen analogues of the anti-HIV-1 integrase (IN) inhibitor L-chicoric acid (L-CA) were prepared. Their IC(50) values for 3'-end processing and strand transfer against recombinant HIV-1 IN were determined in vitro, and their cell toxicities and EC(50) against HIV-1 were measured in cells (ex vivo). Compounds 1-6 are catechol/ß-diketoacid hybrids, the majority of which exhibit submicromolar potency against 3'-end processing and strand transfer, though only with modest antiviral activities. Compounds 7-10 are L-CA/p-fluorobenzylpyrroloyl hybrids, several of which were more potent against strand transfer than 3'-end processing, a phenomenon previously attributed to the ß-diketo acid pharmacophore. Compounds 11-14 are tetrazole bioisosteres of L-CA and its analogues, whose in vitro potencies were comparable to L-CA but with enhanced antiviral potency. The trihydroxyphenyl analogue 14 was 30-fold more potent than L-CA at relatively nontoxic concentrations. These data indicate that L-CA analogues are attractive candidates for development into clinically relevant inhibitors of HIV-1 IN.

Percutaneous radionuclide ablation of axial aneurysmal bone cysts.

OBJECTIVE: The purpose of our study was to retrospectively examine the efficacy of intralesional injection of 32P chromic phosphate, a beta-emitting colloidal radiopharmaceutical, in the treatment of aneurysmal bone cysts of the axial skeleton. Five patients with large aneurysmal bone cysts were managed with injection of 32P chromic phosphate into their tumors under CT guidance. With only a single minor complication, all lesions were observed to ossify on follow-up CT, with an average follow up of 2 years. CONCLUSION: CT-guided injection of axial aneurysmal bone cysts with 32P chromic phosphate leads to excellent local lesion control. In addition, the morbidity associated with this procedure is lower than that associated with surgical or other nonsurgical treatments.

Perioperative analgesia for forequarter amputation in a child: a dual paravertebral approach.

We describe the management of postoperative pain for a 10-year-old girl who underwent forequarter amputation for osteosarcoma of the left humerus. Because the brachial plexus itself was divided and resected during surgery, and the main body part innervated by the nerves from this plexus (the entire upper limb including the scapula and clavicle) was removed, providing analgesia via a brachial plexus block alone would probably not have provided adequate coverage. Because the tissue not resected with this surgery was innervated via the cervical and brachial plexuses and some upper thoracic nerve roots, we elected to combine a perioperative high continuous cervical paravertebral block at the C5 level with a continuous thoracic paravertebral block at the T2 level for postoperative analgesia. Our patient experienced excellent postoperative analgesia and required no narcotics during the immediate postoperative period.

Cricoid pressure results in compression of the postcricoid hypopharynx: the esophageal position is irrelevant.

BACKGROUND: Sellick described cricoid pressure (CP) as pinching the esophagus between the cricoid ring and the cervical spine. A recent report noted that with the application of CP, the esophagus moved laterally more than 90% of the time, questioning the efficacy of this maneuver. We designed this study to accurately define the anatomy of the Sellick maneuver and to investigate its efficacy. METHODS: Twenty-four nonsedated adult volunteers underwent neck magnetic resonance imaging with and without CP. Measurements were made of the postcricoid hypopharynx, airway compression, and lateral displacement of the cricoid ring during the application of CP. The relevant anatomy was reviewed. RESULTS: The hypopharynx, not the esophagus, is what lies behind the cricoid ring and is compressed by CP. The distal hypopharynx, the portion of the alimentary canal at the cricoid level, was fixed with respect to the cricoid ring and not mobile. With CP, the mean anterioposterior diameter of the hypopharynx was reduced by 35% and the lumen likely obliterated, and this compression was maintained even when the cricoid ring was lateral to the vertebral body. CONCLUSIONS: The location and movement of the esophagus is irrelevant to the efficiency of the Sellick's maneuver (CP) in regard to prevention of gastric regurgitation into the pharynx. The hypopharynx and cricoid ring move together as an anatomic unit. This relationship is essential to the efficacy and reliability of Sellick's maneuver. The magnetic resonance images show that compression of the alimentary tract occurs with midline and lateral displacement of the cricoid cartilage relative to the underlying vertebral body.