Greenville Memorial Hospital

PURPOSE: To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m(2) (49 patients) or 75 mg/m(2) (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. RESULTS: One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7. 1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P <.001), as was median survival (7.0 v 4.6 months; log-rank test, P =.047). The difference was more significant for docetaxel 75 mg/m(2) patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P =.010; 1-year survival, 37% v 11%; chi(2) test, P =.003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2), three of whom died, and in one patient treated with docetaxel 75 mg/m(2). Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. CONCLUSION: Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m(2), the benefits of docetaxel therapy outweigh the risks.

BACKGROUND: The incidence of the neonatal abstinence syndrome, a drug-withdrawal syndrome that most commonly occurs after in utero exposure to opioids, is known to have increased during the past decade. However, recent trends in the incidence of the syndrome and changes in demographic characteristics and hospital treatment of these infants have not been well characterized. METHODS: Using multiple cross-sectional analyses and a deidentified data set, we analyzed data from infants with the neonatal abstinence syndrome from 2004 through 2013 in 299 neonatal intensive care units (NICUs) across the United States. We evaluated trends in incidence and health care utilization and changes in infant and maternal clinical characteristics. RESULTS: Among 674,845 infants admitted to NICUs, we identified 10,327 with the neonatal abstinence syndrome. From 2004 through 2013, the rate of NICU admissions for the neonatal abstinence syndrome increased from 7 cases per 1000 admissions to 27 cases per 1000 admissions; the median length of stay increased from 13 days to 19 days (P<0.001 for both trends). The total percentage of NICU days nationwide that were attributed to the neonatal abstinence syndrome increased from 0.6% to 4.0% (P<0.001 for trend), with eight centers reporting that more than 20% of all NICU days were attributed to the care of these infants in 2013. Infants increasingly received pharmacotherapy (74% in 2004-2005 vs. 87% in 2012-2013, P<0.001 for trend), with morphine the most commonly used drug (49% in 2004 vs. 72% in 2013, P<0.001 for trend). CONCLUSIONS: From 2004 through 2013, the neonatal abstinence syndrome was responsible for a substantial and growing portion of resources dedicated to critically ill neonates in NICUs nationwide.

BACKGROUND: In ST-segment-elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. METHODS: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. RESULTS: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P=0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P=0.53). CONCLUSIONS: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.

I. STATEMENT OF THE PROBLEM Evaluation of patients who have sustained blunt abdominal trauma (BAT) may pose a significant diagnostic challenge to the most seasoned trauma surgeon. Blunt trauma produces a spectrum of injury from minor, single-system injury to devastating, multisystem trauma. Trauma surgeons must have the ability to detect the presence of intra-abdominal injuries across this entire spectrum. Although a carefully performed physical examination remains the most important method to determine the need for exploratory laparotomy, there is little Level I evidence to support this tenet. In fact, several studies have highlighted the inaccuracies of the physical examination in BAT. 1,2 The effect of altered level of consciousness as a result of neurologic injury, alcohol, or drugs is another major confounding factor in assessing BAT. Because of the recognized inadequacies of physical examination, trauma surgeons have come to rely on a number of diagnostic adjuncts. Commonly used modalities include diagnostic peritoneal lavage (DPL) and computed tomographic (CT) scanning. Although not available universally, focused abdominal sonography for trauma (FAST) has recently been included in the diagnostic armamentarium. Diagnostic algorithms outlining appropriate use of each of these modalities individually have been established. Several factors influence the selection of diagnostic testing: type of hospital (i.e., trauma center vs. “nontrauma” hospital); access to a particular technology at the surgeon’s institution; and the surgeon’s individual experience with a given diagnostic modality. As facilities evolve, technologies mature, and surgeons gain new experience, it is important that any diagnostic strategy constructed be dynamic. The primary purpose of this study was to develop an evidence-based, systematic diagnostic approach to BAT using the three major diagnostic modalities: DPL, CT scanning, and FAST. This diagnostic regimen would be designed such that it could be reasonably applied by all general surgeons performing an initial evaluation of BAT. II. PROCESS A. Identification of References A MEDLINE search was performed using the key words “abdominal injuries” and the subheading “diagnosis.” This search was limited further to (1) clinical research, (2) published in English, and (3) publication dates January 1978 through February 1998. The initial search yielded 742 citations. Case reviews, review articles, meta-analyses, editorials, letters to the editor, technologic reports, pediatric series, and studies involving a significant number of penetrating abdominal injuries were excluded before formal review. Additional references, selected by the individual subcommittee members, were then included to compile the master reference list of 197 citations. B. Quality of the References Articles were distributed among subcommittee members for formal review. A review data sheet was completed for each article reviewed that summarized the main conclusions of the study and identified any deficiencies in the study. Furthermore, reviewers classified each reference by the methodology established by the Agency for Health Care Policy and Research of the U.S. Department of Health and Human Services as follows: Class I: Prospective, randomized, double-blinded study Class II: Prospective, randomized, nonblinded trial Class III: Retrospective series, meta-analysis After review by the subcommittee, references were excluded on the basis of poor design or invalid conclusions. An evidentiary table (Table 1) was constructed using the remaining 101 references: Class I, 20 references; Class II, 32 references; and Class III, 49 references. Recommendations were made on the basis of studies included in the evidentiary table (Table 1).Table 1: Euidentiary: Practice Management Guidelines for the Evaluation of Blunt Abdominal TraumaTable 1: ContinuedTable 1: ContinuedTable 1: ContinuedTable 1: ContinuedTable 1: ContinuedTable 1: ContinuedTable 1: ContinuedIII. RECOMMENDATIONS A. Level I 1. Exploratory laparotomy is indicated for patients with a positive DPL. 2. FAST may be considered as the initial diagnostic modality to exclude hemoperitoneum. B. Level II 1. When DPL is used, clinical decisions should be made on the basis of the presence of gross blood on initial aspiration (i.e., 10 mL) or microscopic analysis of lavage effluent. 2. Exploratory laparotomy is indicated in hemodynamically unstable patients with a positive FAST. In hemodynamically stable patients with a positive FAST, follow-up CT scan permits nonoperative management of select injuries. 3. Surveillance studies (i.e., DPL, CT scan, repeat FAST) should be considered in hemodynamically stable patients with indeterminate FAST results. 4. CT scanning is recommended for the evaluation of hemodynamically stable patients with equivocal findings on physical examination, associated neurologic injury, or multiple extra-abdominal injuries. Under these circumstances, patients with a negative CT scan should be admitted for observation. 5. CT scanning is the diagnostic modality of choice for nonoperative management of solid visceral injuries. 6. In hemodynamically stable patients, DPL and CT scanning are complementary diagnostic modalities. C. Level III 1. Objective diagnostic testing (i.e., FAST, DPL, CT scanning) is indicated for patients with abnormal mentation, equivocal findings on physical examination, multiple injuries, concomitant chest injury, or hematuria. 2. Patients with seat belt sign should be admitted for observation and serial physical examination. The presence of intraperitoneal fluid on FAST or CT scan in a patient with seat belt sign suggests the presence of an intra-abdominal injury that may require surgery. 3. CT scanning is indicated for the evaluation of suspected renal injuries. 4. In the patient at high risk for intra-abdominal injury (e.g., multiple orthopedic injuries, severe chest wall trauma, neurologic impairment), a follow-up CT scan should be considered after a negative FAST. 5. In hemodynamically stable patients with a positive DPL, follow-up CT scan should be considered, especially in the presence of pelvic fracture or suspected injuries to the genitourinary tract, diaphragm, or pancreas. IV. SCIENTIFIC FOUNDATION A. Diagnostic Peritoneal Lavage DPL was introduced by Root et al. in 1965 as a rapid and accurate method to identify the presence of intra-abdominal hemorrhage after trauma. 3 Subsequent studies have confirmed the efficacy of DPL in diagnosing abdominal hemorrhage as well as its superiority over physical examination alone. 4 The accuracy of DPL has been reported to be between 92% and 98%. 5–10 The high sensitivity of DPL is because of the significant false-positive rate of the technique. 11–13 Several authors have highlighted the importance of interpreting DPL results in the context of the overall clinical condition of the patient. A positive DPL does not necessarily mandate immediate laparotomy in the hemodynamically stable patient. 12,14–16 DPL has been shown to be more efficient than CT scanning in identifying patients that require surgical exploration. 17 The complication rate associated with DPL is quite low. 18 The incidence of complications is lower for open DPL compared with the closed technique. However, closed DPL can be performed more rapidly. 19–22 Studies designed to examine the ability of physicians to estimate the red blood cell (RBC) count in DPL fluid have demonstrated the poor sensitivity of visual inspection. 23–25 A positive DPL, on the basis of microscopic analysis of lavage fluid, has been defined as > 105 RBCs/mm3. It has been recommended that patients with RBC counts in the equivocal range (i.e., 25,000–75,000 RBCs/mm3) undergo additional diagnostic testing, such as CT scanning. 12 The false-positive rate for DPL is increased in patients with pelvic fractures. 26,27 To avoid sampling the retroperitoneal hematoma, a supraumbilical approach has been recommended, theoretically reducing the chances of a false-positive result. 28 The advantages of DPL for detection of hollow visceral injuries have been clearly demonstrated. 29,30 Two studies that advocate analysis of DPL fluid for amylase and alkaline phosphatase consistent with enteric injuries have been disputed. 31–33 Similarly, the utility of the DPL white blood cell count has been questioned. 34–36 DPL is sensitive for mesenteric injury and, in fact, has been shown to be superior to CT scanning for the diagnosis of this injury. 37 Thus, DPL is a safe, rapid, and accurate method for determining the presence of intraperitoneal blood in victims of BAT. It is more accurate than CT scanning for the early diagnosis of hollow visceral and mesenteric injuries, but it does not reliably exclude significant injuries to retroperitoneal structures. False-positive results may occur in the presence of pelvis fractures. Hemodynamically stable patients with equivocal results are best managed by additional diagnostic testing to avoid unnecessary laparotomies. B. Computed Tomographic Scanning Routine use of CT scanning for the evaluation of BAT was not initially viewed with overwhelming enthusiasm. CT scanning requires a cooperative, hemodynamically stable patient. In addition, the patient must be transported out of the trauma resuscitation area to the radiographic suite. Specialized technicians and the availability of a radiologist for interpretation were also viewed as factors that limited the utility of CT scanning for trauma patients. CT scanners are now available in most trauma centers and, with the advent of helical scanners, scan time has been significantly reduced. As a result, CT scanning has become an accepted part of the traumatologist’s armamentarium. The accuracy of CT scanning in hemodynamically stable blunt trauma patients has been well established. Sensitivity between 92% and 97.6% and specificity as high as 98.7% have been reported in patients subjected to emergency CT scanning. 38,39 Most authors recommend admission and observation after a negative CT scan. 40,41 In a recent study of 2,774 patients, the authors concluded that the negative predictive value (99.63%) of CT scanning was sufficiently high to permit safe discharge of BAT patients after a negative CT scan. 42 CT scanning is notoriously inadequate for the diagnosis of mesenteric injuries and may also miss hollow visceral injuries. In patients at risk for mesenteric or hollow visceral injury, DPL is generally felt to be a more appropriate test. 37,43 A negative CT scan in such a patient cannot reliably exclude intra-abdominal injuries. CT scanning has the unique ability to detect clinically unsuspected injuries. In a series of 444 patients in whom CT scanning was performed to evaluate renal injuries, 525 concomitant abdominal and/or retroperitoneal injuries were diagnosed. Another advantage of CT scanning over other diagnostic modalities is its ability to evaluate the retroperitoneal structures. 40 Kane et al. performed CT scanning in 44 hemodynamically stable blunt trauma patients after DPL. In 16 patients, CT scan revealed significant intra-abdominal or retroperitoneal injuries not diagnosed by DPL. Moreover, the findings on CT scan resulted in a modification to the original treatment plan in 58% of the patients. 44 C. Focused Abdominal Sonography for Trauma In recent years, FAST has emerged as a useful diagnostic test in the evaluation of BAT. The advantages of the FAST examination have been clearly established. FAST is noninvasive, may be easily performed, and can be performed concurrently with resuscitation. In addition, the technology is portable and may be easily repeated if necessary. 45–48 In most cases, FAST may be completed within 3 or 4 minutes. 49–51 The test is especially useful for detecting intra-abdominal hemorrhage in the patient with multiple injuries or the pregnant patient. 52 A noted drawback to the FAST examination is the fact that a positive examination relies on the presence of free intraperitoneal fluid. In the hands of most operators, ultrasound will detect a minimum of 200 mL of fluid. 53 Injuries not associated with hemoperitoneum may not be detected by this modality. 49,54,55 Thus, ultrasound is not a reliable method for excluding hollow visceral injury. 47,49,56–58 In addition, the FAST examination cannot be used to reliably grade solid organ injuries. Therefore, in the hemodynamically stable patient, a follow-up CT scan should be obtained if nonoperative management is contemplated. 59 FAST compares favorably with more traditionally used diagnostic tests. In the hemodynamically stable patient with BAT, FAST offers a viable alternative to DPL. 60 DPL may also be used as a complementary examination in the hemodynamically stable patient in the presence of equivocal or negative ultrasound findings with strong clinical suspicion of visceral injury. 61,62 FAST has demonstrated utility in hemodynamically stable patients with BAT. 58,60,63 In addition, ultrasound has been shown to be more cost-effective when compared with DPL or CT scanning. 45,47,60 Overall, FAST has a sensitivity between 73% and 88% and a specificity between 98% and 100%, and is 96% to 98% accurate. 46,50,57,58,64,65 This level of accuracy is independent of the practitioner performing the study. Surgeons, emergency medicine physicians, ultrasound technicians, and radiologists have equivalent results. 46,53,64–66 D. Other Diagnostic Modalities As interest in laparoscopic procedures has increased among general surgeons, there has been speculation regarding the role of diagnostic laparoscopy (DL) in the evaluation of BAT. One of the potential benefits postulated is the reduction of nontherapeutic laparotomies. With modification of the technique to include smaller instruments, portable equipment, and local anesthesia, DL may be a useful tool in the initial evaluation of BAT. Although there are no randomized, controlled studies comparing DL to more commonly used modalities, experience at one institution using minilaparoscopy demonstrated a 25% incidence of positive findings on DL, which were successfully managed nonoperatively and would have resulted in nontherapeutic laparotomies. 67 Although its ultimate role remains unclear, another modality to be considered in the diagnostic evaluation of BAT is visceral angiography. This modality may have diagnostic value when used in conjunction with angiography of the pelvis or chest, or when other diagnostic studies are inconclusive. 68 V. SUMMARY Injury to intra-abdominal viscera must be excluded in all victims of BAT. Physical examination remains the initial step in diagnosis but has limited utility under select circumstances. Thus, various diagnostic modalities have evolved to assist the trauma surgeon in the identification of abdominal injuries. The specific tests are selected on the basis of the clinical stability of the patient, the ability to obtain a reliable physical examination, and the provider’s access to a particular modality. It is important to emphasize that many of the diagnostic tests used are complementary rather than exclusionary. On the basis of the above recommendations, a reasonable diagnostic approach to BAT is summarized in Figures 1 and 2. In hemodynamically stable patients with a reliable physical examination, clinical findings may be used to select patients who may be safely observed. In the absence of a reliable physical examination, the main diagnostic choice is between CT scanning or FAST (with CT scanning in a complementary role). Hemodynamically unstable patients may be initially evaluated with FAST or DPL.Fig. 1: Evaluation of BAT: unstable patient.Fig. 2: Evaluation of BAT: stable patient.VI. FUTURE INVESTIGATIONS Recent literature is replete with studies that emphasize the many advantages of ultrasound in the valuation of BAT. Although this technology is becoming more available to trauma surgeons, for a variety of reasons, it has not become universally available in all centers. Continued research addressing the utility of FAST, with emphasis on its advantages specific to resource use, is suggested. In addition, studies should be designed to more closely evaluate the feasibility of FAST as the sole diagnostic test in hemodynamically stable patients. Perhaps safe strategies for nonoperative management of solid visceral injuries could be developed that rely on FAST alone, such that the number of CT scans could be reduced.

PURPOSE: To evaluate the effectiveness of laser-assisted angioplasty for patients with critical limb ischemia (CLI) who were poor candidates for surgical revascularization. METHODS: A prospective registry at 14 sites in the US and Germany enrolled 145 patients with 155 critically ischemic limbs; the patients were poor candidates for bypass surgery owing to inadequate target vessel or saphenous vein, prohibitive cardiac disease, or significant comorbidities (ASA class 4). Additional comorbid risk factors included diabetes in 66%, hypertension in 83%, previous stroke in 21%, and myocardial infarction in 23%. Endovascular treatment included guidewire traversal and excimer laser angioplasty followed by balloon angioplasty with optional stenting. RESULTS: Occlusions were present in 92% of limbs. A mean of 2.7+/-1.4 lesions were treated per limb; the total median treatment length was 11 cm (mean 16.2, range 0.2-123). Stents were implanted in 45% of limbs. Procedural success, defined as <50% residual stenosis in all treated lesions, was seen in 86% of limbs. At 6-month follow-up, limb salvage was achieved in 110 (92%) of 119 surviving patients or 118 (93%) 127 limbs. CONCLUSION: Excimer laser-assisted angioplasty for CLI offers high technical success and limb salvage rates in patients unfit for traditional surgical revascularization.

OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory-based environment. BACKGROUND: Studies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons. METHODS: A total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report. RESULTS: The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses. CONCLUSIONS: The ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II-ADVISE II; NCT01740895).

BACKGROUND: Suture knots present several disadvantages in wound closure, because they are tedious to tie and place ischemic demands on tissue. Bulky knots may be a nidus for infection, and they may extrude through skin weeks after surgery. Needle manipulations during knot-tying predispose the surgeon to glove perforation. A barbed suture was developed that is self-anchoring, requiring no knots or slack management for wound closure. The elimination of knot tying may have advantages over conventional wound closure methods. METHODS: This prospective, randomized, controlled trial was designed to show that the use of barbed suture in dermal closure of the Pfannenstiel incision during nonemergent cesarean delivery surgery produces scar cosmesis at 5 weeks that is no worse than that observed with conventional closure using 3-0 polydioxanone suture. Cosmesis was assessed by review of postoperative photographs by a blinded, independent plastic surgeon using the modified Hollander cosmesis score. Secondary endpoints included infection, dehiscence, pain, closure time, and other adverse events. RESULTS: The study enrolled 195 patients, of whom 188 were eligible for analysis. Cosmesis scores did not significantly differ between the barbed suture group and the control group. Rates of infection, dehiscence, and other adverse events did not significantly differ between the two groups. Closure time and pain scores were comparable between the groups. CONCLUSIONS: The barbed suture represents an innovative option for wound closure. With a cosmesis and safety profile that is similar to that of conventional suture technique, it avoids the drawbacks inherent to suture knots.

Patients admitted to acute care frequently require intravenous access to effectively deliver medications and prescribed treatment. For patients with difficult intravenous access, those requiring multiple attempts, those who are obese, or have diabetes or other chronic conditions, determining the vascular access device (VAD) with the lowest risk that best meets the needs of the treatment plan can be confusing. Selection of a VAD should be based on specific indications for that device. In the clinical setting, requests for central venous access devices are frequently precipitated simply by failure to establish peripheral access. Selection of the most appropriate VAD is necessary to avoid the potentially serious complications of infection and/or thrombosis. An international panel of experts convened to establish a guide for indications and appropriate usage for VADs. This publication summarises the work and recommendations of the panel for the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC).

Insulin-like growth factor I (IGF-I) has been identified in human seminal plasma. This study was conducted to determine whether IGF-I is present in bovine seminal plasma, whether sperm cells express the IGF-I receptor (IGF-IR), and whether IGF-I affects sperm motility. Semen samples were collected from bulls by electroejaculation and maintained at 37 degrees C, and motility of sperm was assessed. After centrifugation to separate sperm cells from seminal plasma, the seminal plasma was submitted to a validated heterologous RIA for IGF-I. Significant concentrations of IGF-I (116.29 +/- 40.83 ng/ml expressed as mean +/- SD) were measured in bovine seminal plasma. Sperm cells were washed with buffer and subjected to either radioreceptor assay (RRA) or immunocytochemistry (IC). RRA revealed a single high affinity for the IGF-IR with a Kd of 0.83 nM as determined by the computer program LIGAND. IC, using three monoclonal antibodies, localized the IGF-IR to the acrosomal region of the sperm. Computer-assisted sperm-motion analysis was used to determine the effects of IGF-I and IGF-II on bovine sperm motility parameters. Both IGF-I and IGF-II increased sperm motility and straight-line velocity (p < 0.05) relative to the control. The presence of IGF-IR on sperm, the presence of IGF-I in semen, and the ability of IGF-I to stimulate sperm motility provide evidence that the IGF system may be involved in the fertilization process in the bovine species.

OBJECTIVE: Necrotizing enterocolitis (NEC) is associated with high morbidity and mortality among infants admitted for intensive care. The factors associated with mortality and catastrophic presentation remain poorly understood. Our objective was to describe the factors associated with mortality in infants with NEC and to quantify the degree to which catastrophic presentation contributes to mortality in infants with NEC. Catastrophic NEC was defined before data analysis as NEC that led to death within 7 days of diagnosis. STUDY DESIGN: We performed a retrospective review of the Pediatrix's Clinical Data Warehouse (1997 to 2009, n=560,227) to compare the demographic, therapeutic and outcome characteristics of infants who survived NEC vs those who died. Associations were tested by bivariate and multivariate analysis. RESULT: We compared the 5594 infants diagnosed with NEC and who were discharged home with 1505 infants diagnosed with NEC who died. In multivariate analysis, the factors associated with death (P<0.01 in analysis) were lower estimated gestational age, lower birth weight, treatment with assisted ventilation on the day of diagnosis of NEC, treatment with vasopressors at the time of diagnosis, and Black race. Patients who received only ampicillin and gentamicin on the day of diagnosis were less likely to die. Two-thirds of NEC deaths occurred quickly (<7 days from diagnosis), with a median time of death of one day from time of diagnosis. Infants who died within 7 days of diagnosis had a higher birth weight, more often were on vasopressors and high frequency ventilation at the time of diagnosis compared with patients who died at 7 or more days. Although mortality decreased with increasing gestational age, the proportion of deaths that occurred within 7 days was relatively consistent (65 to 75% of the patients who died) across all gestational ages. CONCLUSION: Mortality among infants who have NEC remains high and infants who die of NEC commonly (66%) die quickly. Most of the factors associated with mortality are related to immaturity, low birth weight and severity of illness.

PURPOSE To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non–small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life. PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non–small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m2 (49 patients) or 75 mg/m2 (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks. RESULTS One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7.1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 v 6.7 weeks, respectively; P < .001), as was median survival (7.0 v 4.6 months; log-rank test, P = .047). The difference was more significant for docetaxel 75 mg/m2 patients, compared with corresponding best supportive care patients (7.5 v 4.6 months; log-rank test, P = .010; 1-year survival, 37% v 11%; χ2 test, P = .003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m2, three of whom died, and in one patient treated with docetaxel 75 mg/m2. Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups. CONCLUSION Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m2, the benefits of docetaxel therapy outweigh the risks.

Plants are proven sources of useful anti-tumor and chemopreventative compounds. Hence, identification of phytochemicals useful in dietary prevention and intervention of cancer is of paramount importance. The initial step in the formation of cancer is damage to the genome of a somatic cell producing a mutation in an oncogene or a tumor-suppressor gene. Fresh juices and organic solvent extracts from the fruits of strawberry, blueberry, and raspberry were evaluated for their ability to inhibit the production of mutations by the direct-acting mutagen methyl methanesulfonate and the metabolically activated carcinogen benzo[a]pyrene. Juice from strawberry, blueberry, and raspberry fruit significantly inhibited mutagenesis caused by both carcinogens. Ethanol extracts from freeze-dried fruits of strawberry cultivars (Sweet Charlie and Carlsbad) and blueberry cultivars (Tifblue and Premier) were also tested. Of these, the hydrolyzable tannin-containing fraction from Sweet Charlie strawberries was most effective at inhibiting mutations.

The authors conducted a double-blind, randomized, placebo-controlled trial to ascertain whether the use of fluconazole prophylaxis in 125 high-risk, critically ill patients would decrease the incidence of severe candida infection. Secondary objectives included assessing the impact of prophylaxis on mortality and length of hospital stay. Participants were randomly assigned to receive an 800-mg loading dose followed by 400 mg of fluconazole or placebo once daily for the length of their stay in the intensive care unit (ICU). Patients were monitored weekly by the study investigators via physical, hematologic, and microbiologic examinations. Twenty-five patients developed either clinically significant candida infection or severe inflammatory response syndrome (SIRS) within 7 days of discharge from the ICU. However, no significant difference in the incidence of candida infection or SIRS was observed between study groups. Mortality and length of stay were not significantly different between the two groups. Large-scale studies are needed before fluconazole prophylaxis can be recommended in this group of patients.

IMPORTANCE: Prophylactic vitamin A supplementation has been shown to reduce the incidence of chronic lung disease or death in extremely low-birth-weight infants. Beginning in 2010, a national shortage reduced the supply of vitamin A available. OBJECTIVE: To estimate the association between vitamin A supplementation and death or chronic lung disease in the context of the recent drug shortage. Intercenter variability in vitamin A use was assessed secondarily. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 7925 infants with birth weights between 401 and 1000 g who were cared for in US neonatal intensive care units managed by the Pediatrix Medical Group. Infants were discharged between January 1, 2010, and June 30, 2012, and data were collected from the Pediatrix Clinical Data Warehouse. Infants who had major congenital anomalies, died during the first 3 days of life, or had missing data were excluded from the analysis. EXPOSURES: Vitamin A supplementation. MAIN OUTCOMES AND MEASURES: The primary outcome was either death before hospital discharge or chronic lung disease, defined as receiving any respiratory support at 36 weeks' corrected gestational age. RESULTS: Of the 6210 eligible infants, 3011 (48.5%) experienced the primary outcome. Those who received vitamin A were more immature and more likely to receive mechanical ventilation during the first 3 days of life. During the study period, vitamin A supplementation significantly decreased (27.2% to 2.1%); however, the primary outcome was similar (48.4% to 49.5%; P = .40). Vitamin A was unrelated to death or chronic lung disease in unadjusted or multivariable analyses (relative risk [RR], 0.97; 95% CI, 0.91-1.03; P = .32) when demographic and clinical information were considered. After classifying centers by vitamin A use, the center of birth was significantly associated with the outcome, with birth in low- and medium-use centers related to a reduced likelihood of death or chronic lung disease. CONCLUSIONS AND RELEVANCE: The occurrence of death or chronic lung disease appears unaffected by the recent shortage of vitamin A. However, the center of birth appears to be an important risk factor for these infants' outcomes.

PURPOSE: To report the 6-month outcomes from a prospective multicenter study investigating the use of cryoplasty (cold balloon angioplasty) to treat below-knee occlusive disease in patients with critical limb ischemia (CLI). METHODS: Between August 2004 and October 2005, 108 patients (77 men; mean age 73+/-12 years, range 41-101) with CLI involving 111 limbs were enrolled in a prospective multicenter trial (Below-the-Knee Chill Study), which was conducted at 16 institutions. The primary study endpoints were acute technical success, defined as the ability to achieve < or =50% residual stenosis and continuous inline flow to the foot, and absence of major (above or below-knee) amputation of the target limb 180 days post procedure. RESULTS: Acute technical success was achieved in 108 (97.3%) of the 111 limbs treated, with only 1 (0.9%) clinically significant dissection (> or =type C) and 2 residual stenoses >50%. During the 180-day follow-up, 15 (13.9%) of the initial 108 patients either withdrew or were lost to follow-up. Five (4.6%) deaths occurred, leaving 88 (81.5%) patients with 91 (82.0%) treated limbs available for 180-day assessment. The rate of freedom from major amputation at 180 days was 93.4%. Amputation-free survival was 89.3% at 180 days (5 deaths, 6 major amputations). Stratifying data by diabetics (n=71) versus non-diabetics (n=34), the 180-day death and amputation rates were 4.9% and 10.0%, respectively, for diabetics versus 6.7% and 0.0%, respectively, for non-diabetics. CONCLUSION: Cryoplasty therapy is a safe and effective method of treating infrapopliteal disease, providing excellent acute outcomes and a high rate of limb salvage in patients with CLI. Study outcomes support the use of cryoplasty therapy as a primary treatment option for patients with CLI secondary to below- knee disease.

This study compared sleep-awake patterns in clients following head injury with their sleep-awake patterns prior to head injury. Data were collected from 75 subjects who had experienced a minor head injury (MHI) with a disturbance in consciousness three months prior to filling out a questionnaire. The majority of the clients were males, 16 to 30 years old, who had been involved in a motor vehicle accident which resulted in MHI. Questions related to the sleep-awake patterns before and after head injury. Sleep-awake patterns following head injury differed from sleep-awake patterns prior to head injury in the following sleep indicators: sleep interruptions per week and per night increased significantly (p < .004, p < .001) as did the time needed to function at peak efficiency upon awakening (p < .001). The subjects reported significant increases (p < .02) in the number of times per month in which they were unable to return to sleep after an early morning awakening coupled with the difficulty in returning to sleep (p < .04). Overall, the clients reported significantly decreased sleep quality (p < .02) and increased complaints about sleep following head injury (p < .001). An increase in the time of consciousness disruption following head injury was related to the subjects having a tendency to sleep longer and to recall fewer, less vivid dreams. A decreased level of consciousness upon admission to the emergency department at time of injury correlated with the increased number of arousals during the sleep cycle and the reduced intensity of auditory stimulus needed to interrupt sleep. The anatomical site of the head injury and the duration of post-traumatic amnesia (PTA) were found to have no significant effect upon sleep-awake patterns following MHI.

Preventing the transmission of human immunodeficiency virus during surgical procedures requires attention to barrier techniques and to measures designed to prevent injury. Measures to prevent injury must focus on minimizing both the number of people at risk and the opportunities for injury to occur. Special rules are suggested to make surgical team movements more choreographed and deliberate to reduce the opportunities for collisions between hands and sharp instruments.

OBJECTIVE: As the population of patients with Fontan circulation surviving into adulthood increases, hepatic cirrhosis has grown to be a significant cause of morbidity and mortality. Early detection of advanced hepatic fibrosis is imperative for proper intervention and consideration for heart or combined heart/liver transplantation. Noninvasive biomarkers and elastography have been evaluated for their diagnostic utility with variable results in the Fontan population. DESIGN: The cohort included 14 patients age 26.4 SD 7.5 who underwent Fontan surgery. All patients were evaluated with FibroSURE, shear wave elastography (SWE), hepatic duplex sonography, and liver biopsy. Liver fibrosis on biopsy was evaluated according to the congestive hepatic fibrosis system. RESULTS: In our cohort, 100% of patients had fibrosis with 36% demonstrating advanced fibrosis. FibroSURE agreed with liver biopsy in only 5 out of 14 cases (36%): underestimating in 7 and overestimating in 2 individuals. SWE agreed with liver biopsy in 0% of cases: overestimating in 10 and underestimating in 4 cases. None of the duplex sonography indices predicted the presence or severity of liver fibrosis. CONCLUSION: This study demonstrates that children who have undergone a Fontan procedure universally develop some hepatic fibrosis and a significant number have advanced fibrosis by adulthood. The FibroSURE blood test, SWE, and hepatic duplex sonography were unable to accurately predict the presence or severity of hepatic fibrosis when compared with liver biopsy. Further studies are needed to investigate novel noninvasive methods and/or biomarkers that can adequately detect advanced hepatic fibrosis before the development of cirrhosis and hepatic decompensation.

BACKGROUND: Some children have persistent pain and instability following inversion injuries of the ankle. Radiographs may reveal a small osseous fragment distal to the lateral malleolus, suggesting an avulsion injury of the anterior talofibular ligament and/or calcaneofibular ligament. The avulsion injury may involve an os subfibulare, causing ligamentous laxity and chronic pain resulting from nonunion. This situation must be differentiated from an asymptomatic os subfibulare, which is a normal anatomic variant in 1% of children. The purpose of this study was to evaluate the intraoperative findings and long-term outcomes of patients treated operatively for symptomatic avulsion injuries or a symptomatic os subfibulare. METHODS: Twenty-three patients presented with chronic ankle pain and instability, tenderness anterior and distal to the lateral malleolus, and imaging studies (magnetic resonance imaging and/or stress radiographs) suspicious for avulsion injury of the anterior talofibular ligament and/or calcaneofibular ligament. After unsuccessful nonoperative treatment, all patients underwent excision of the osseous fragments, anatomic reconstruction of the anterior talofibular ligament with use of drill holes through the lateral malleolus, and a modified Broström procedure. RESULTS: The mean age of the patients was 10.4 years (range, eight to thirteen years) at the time of injury and 13.6 years (range, eight to seventeen years) at the time of surgery, representing a mean delay in diagnosis and treatment of 3.2 years. At a mean follow-up of 4.5 years (range, 2.1 to 13.2 years), the mean Foot and Ankle Outcome Score was 91.4 (range, 87 to 98) out of 100, with all but one patient returning to the preinjury recreational level. Only one patient had a long-term complication. CONCLUSIONS: In children with chronic pain and instability associated with an os subfibulare, surgical excision of the os subfibulare combined with reconstruction of the anterior talofibular ligament and a modified Broström procedure was effective in restoring ankle stability, eliminating pain, and permitting return to the preinjury functional level.

PURPOSE: To report the 12-month follow-up data from the prospective 16-center Below-the-Knee (BTK) Chill Trial, which examined the use of primary cryoplasty for BTK occlusive disease in patients with critical limb ischemia (CLI). METHODS: The trial included 108 patients (77 men; mean age 73 +/- 11 years, range 41-101) with CLI (Rutherford categories 4-6) involving 111 limbs with 115 target infrapopliteal lesions. Angiographic inclusion criteria were reference vessel diameter > or = 2.5 mm and < or = 5.0 mm and target lesion stenosis > or = 50%. The primary study endpoints were acute technical success (the ability to achieve < or = 50% residual stenosis and continuous inline flow to the foot) and absence of major amputation of the target limb at 6 months. Secondary endpoints were serious adverse events specifically related to use of primary cryoplasty and absence of major amputation of the target limb at 1, 3, and 12 months. RESULTS: Acute technical success was achieved in 108 (97.3%) of treated limbs, with only 1 clinically significant dissection (> or = type C) and 2 residual stenoses >50%; stent placement was required following cryoplasty in only 3 (2.7%) procedures. At 6 months and 1 year, major amputation was avoided in 93.4% (85/91) and 85.2% (69/81) of patients, respectively. Through 1 year, 21% (17/81) of patients underwent target limb revascularization. Rates of major amputation and death at 1 year were 0% for limbs of patients with initial Rutherford category 4; 11.4% and 0%, respectively, for initial category 5; and 40.0% and 31.8% for initial category 6. One-year rates of major amputation and death were 20.4% and 8.8%, respectively, for diabetics, versus 4.0% and 10.7% for non-diabetics. At 1 year, major amputation occurred in 16.7% (2/12) of limbs that were expected to be amputated at the time of treatment. CONCLUSION: Cryoplasty therapy is a safe and effective method of treating infrapopliteal disease, providing excellent results and a high rate of limb salvage in patients with CLI. Study outcomes through 1 year support the use of cryoplasty as a primary treatment option for patients with CLI secondary to BTK occlusive disease.