University of Virginia Medical Center

In Brief Study Design. Systematic review and modified Delphi technique. Objective. To use an evidence-based medicine process using the best available literature and expert opinion consensus to develop a comprehensive classification system to diagnose neoplastic spinal instability. Summary of Background Data. Spinal instability is poorly defined in the literature and presently there is a lack of guidelines available to aid in defining the degree of spinal instability in the setting of neoplastic spinal disease. The concept of spinal instability remains important in the clinical decision-making process for patients with spine tumors. Methods. We have integrated the evidence provided by systematic reviews through a modified Delphi technique to generate a consensus of best evidence and expert opinion to develop a classification system to define neoplastic spinal instability. Results. A comprehensive classification system based on patient symptoms and radiographic criteria of the spine was developed to aid in predicting spine stability of neoplastic lesions. The classification system includes global spinal location of the tumor, type and presence of pain, bone lesion quality, spinal alignment, extent of vertebral body collapse, and posterolateral spinal element involvement. Qualitative scores were assigned based on relative importance of particular factors gleaned from the literature and refined by expert consensus. Conclusion. The Spine Instability Neoplastic Score is a comprehensive classification system with content validity that can guide clinicians in identifying when patients with neoplastic disease of the spine may benefit from surgical consultation. It can also aid surgeons in assessing the key components of spinal instability due to neoplasia and may become a prognostic tool for surgical decision-making when put in context with other key elements such as neurologic symptoms, extent of disease, prognosis, patient health factors, oncologic subtype, and radiosensitivity of the tumor. Spinal instability is poorly defined especially in neoplastic disease. The SOSG has developed a comprehensive classification system to define neoplastic spinal instability (the Spine Instability Neoplastic Score). The Spine Instability Neoplastic Score will aid oncologists and primary care physicians in determining timing of referral to spine surgeons and will aid surgeons in assessing need for surgical stabilization.

The authors studied 538 patients who had sustained minor head trauma, which was defined as a history of unconsciousness of 20 minutes or less, a Glasgow Coma Scale score of 13 to 15, and hospitalization not exceeding 48 hours. Of these patients, 424 were evaluated 3 months after injury. The follow-up evaluation included a history of events since the accident, assessment of subjective complaints and objective measures such as employment status, a neurological examination, a psychosocial assessment designed for estimating life stress, and a neuropsychological test battery to measure higher cortical function. Of these 424 patients, 79% complained of persistent headaches, and 59% described problems with memory. Of the patients who had been gainfully employed before the accident, 34% were unemployed 3 months later. Comparisons were then made between the employed and the unemployed groups. Three explanations for the high rate of unemployment were examined. (a) Evidence of organic brain damage: Although the neurological examination was completely normal in nearly all patients, neuropsychological testing demonstrated some problems with attention, concentration, memory, or judgment in most of the 69 patients evaluated. (b) Psychological responses to the injury: Emotional stress caused by persistent symptoms seems to be a significant factor in the long term disability of these patients. (c) Litigation and compensation: These factors have a minimal role in determining outcome after minor head injury. In conclusion, the most striking observations of these studies are the high rates of morbidity and unemployment in patients 3 months after a seemingly insignificant head injury and the evidence that many of these patients may have, in fact, suffered organic brain damage. (Neurosurgery 9:221-228, 1981)

STUDY DESIGN: This retrospective, questionnaire-based investigation evaluated iliac crest bone graft (ICBG) site morbidity in patients having undergone a single-level anterior cervical discectomy and fusion (ACDF) procedure performed by a single surgeon (T.J.A.). OBJECTIVE: To evaluate acute and chronic problems associated with anterior ICBG donation, particularly long-term functional outcomes and impairments caused by graft donation. SUMMARY OF BACKGROUND DATA: Anterior cervical discectomy and fusion procedures frequently use autologous anterior ICBG to facilitate osseous union. Although autologous ICBG offers several advantages over alternative grafting materials, donor site morbidity can be significant. Acute and chronic complications of donor sites have been reported, yet there are currently no reports of long-term functional outcomes after autologous anterior ICBG donation after single-level ACDF. METHODS: A questionnaire was mailed to 187 consecutive patients who were retrospectively identified to have undergone autologous anterior ICBG harvest for single-level ACDF between 1994 and 1998. The questionnaire divided items into symptomatic (acute and chronic) and functional assessments. Patients answered yes, no, or not applicable; pain was assessed with a Visual Analogue Scale (VAS). RESULTS: Surveys were completed either by mail or follow-up telephone interview by 134 patients (71.6%). Average follow-up was 48 months (range, 24-72 months). Acute symptoms were reported at the following rates: ambulation difficulty, 50.7%; extended antibiotic usage, 7.5%; persistent drainage, 3.7%; wound dehiscence, 2.2%; and incision and drainage, 1.5%. The chronic symptom questionnaire demonstrated a high degree of satisfaction with the cosmetic result (92.5%). Pain at the donor site was reported by 26.1% of patients with a mean VAS score of 3.8 in 10, and 11.2% chronically use pain medication. Twenty-one patients (15.7%) reported abnormal sensations at the donor site, but only 5.2% reported discomfort with clothing. A unique functional assessment revealed current impairments at the following rates: ambulation, 12.7%; recreational activities, 11.9%; work activities, 9.7%; activities of daily living, 8.2%; sexual activity, 7.5%; and household chores, 6.7%. CONCLUSIONS: A large percentage of patients report chronic donor site pain after anterior ICBG donation, even when only a single-level ACDF procedure is performed. Moreover, long-term functional impairment can also be significant. Patients should be counseled regarding these potential problems, and alternative sources of graft material should be considered.

Acute elevation of intra-abdominal pressure above 30 mmHg caused oliguria in 11 postoperative patients. Operative re-exploration and decompression in seven patients resulted in immediate diuresis. Four patients who were not re-explored developed renal failure and died. If intra-abdominal pressure rises above 25 mmHg in the early postoperative period and is associated with oliguria and normal blood pressure and cardiac index, the patient should undergo re-exploration and decompression of the abdomen.

Smooth muscle cells (SMCs) possess remarkable phenotypic plasticity that allows rapid adaptation to fluctuating environmental cues, including during development and progression of vascular diseases such as atherosclerosis. Although much is known regarding factors and mechanisms that control SMC phenotypic plasticity in cultured cells, our knowledge of the mechanisms controlling SMC phenotypic switching in vivo is far from complete. Indeed, the lack of definitive SMC lineage-tracing studies in the context of atherosclerosis, and difficulties in identifying phenotypically modulated SMCs within lesions that have down-regulated typical SMC marker genes, and/or activated expression of markers of alternative cell types including macrophages, raise major questions regarding the contributions of SMCs at all stages of atherogenesis. The goal of this review is to rigorously evaluate the current state of our knowledge regarding possible phenotypes exhibited by SMCs within atherosclerotic lesions and the factors and mechanisms that may control these phenotypic transitions.

Peer Reviewed

PURPOSE: To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. METHODS: ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS: Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. RECOMMENDATIONS: Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non-small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy.Additional information is available at www.asco.org/neurooncology-guidelines.

Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of OO was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known OO were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO.

BACKGROUND: We describe severe and unexpected multisystem toxicity that occurred during a study of the antiviral nucleoside analogue fialuridine (1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil, or FIAU) as therapy for chronic hepatitis B virus infection. METHODS: Fifteen patients with chronic hepatitis B were randomly assigned to receive fialuridine at a dose of either 0.10 or 0.25 mg per kilogram of body weight per day for 24 weeks and were monitored every 1 to 2 weeks by means of a physical examination, blood tests, and testing for hepatitis B virus markers. RESULTS: During the 13th week lactic acidosis and liver failure suddenly developed in one patient. The study was terminated on an emergency basis, and all treatment with fialuridine was discontinued. Seven patients were found to have severe hepatotoxicity, with progressive lactic acidosis, worsening jaundice, and deteriorating hepatic synthetic function despite the discontinuation of fialuridine. Three other patients had mild hepatotoxicity. Several patients also had pancreatitis, neuropathy, or myopathy. Of the seven patients with severe hepatotoxicity, five died and two survived after liver transplantation. Histologic analysis of liver tissue revealed marked accumulation of microvesicular and macrovesicular fat, with minimal necrosis of hepatocytes or architectural changes. Electron microscopy showed abnormal mitochondria and the accumulation of fat in hepatocytes. CONCLUSIONS: In patients with chronic hepatitis B, treatment with fialuridine induced a severe toxic reaction characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. This toxic reaction was probably caused by widespread mitochondrial damage and may occur infrequently with other nucleoside analogues.

Leukocyte recruitment into inflammatory sites is initiated by a reversible transient adhesive contact with the endothelium called leukocyte rolling, which is thought to be mediated by the selectin family of adhesion molecules. Selectin-mediated rolling precedes inflammatory cell emigration, which is significantly impaired in both P- and L-selectin gene-deficient mice. We report here that approximately 13% of all leukocytes passing venules of the cremaster muscle of wild-type mice roll along the endothelium at < 20 min after surgical dissection. Rolling leukocyte flux fraction reaches a maximum of 28% at 40-60 min and returns to 13% at 80-120 min. In P-selectin-deficient mice, rolling is absent initially and reaches 5% at 80-120 min. Rolling flux fraction in L-selectin-deficient mice is similar to wild type initially and declines to 5% at 80-120 min. In both wild-type and L-selectin-deficient mice, initial leukocyte rolling (0-60 min) is completely blocked by the P-selectin monoclonal antibody (mAb) RB40.34, but unaffected by L-selectin mAb MEL-14. Conversely, rolling at later time points (60-120 min) is inhibited by mAb MEL-14 but not by mAb RB40.34. After treatment with tumor necrosis factor (TNF)-alpha for 2 h, approximately 24% of all passing leukocytes roll in cremaster venules of wild-type and P-selectin gene-deficient mice. Rolling in TNF-alpha-treated mice is unaffected by P-selectin mAb or E-selectin mAb 10E9.6. By contrast, rolling in TNF-alpha-treated P-selectin-deficient mice is completely blocked by L-selectin mAb. These data show that P-selectin is important during the initial induction of leukocyte rolling after tissue trauma. At later time points and in TNF-alpha-treated preparations, rolling is largely L-selectin dependent. Under the conditions tested, we are unable to find evidence for involvement of E-selectin in leukocyte rolling in mice.

Hypoglycemia can lead to various aversive symptomatic, affective, cognitive, physiological, and social consequences, which in turn can lead to the development of possible phobic avoidance behaviors associated with hypoglycemia. On the other hand, some patients may inappropriately deny or disregard warning signs of hypoglycemia. This study presents preliminary reliability and validity data on a psychometric instrument designed to quantify this fear: the hypoglycemic fear survey. The instrument was found to have internal consistency and test-retest stability, to covary with elevated glycosylated hemoglobin, and to be sensitive to a behavioral treatment program designed to increase awareness of hypoglycemia.

The effect of increased intra-abdominal pressure on cardiac output and renal function was investigated using anesthetized dogs into whom inflatable intraperitoneal bags were placed. Hemodynamic and renal function measurements were made at intra-abdominal pressures of 0, 20, and 40 mmHg. Renal blood flo and glomerular filtration rate decreased to les than 25% of normal when the intra-abdominal pressure was elevated to 20 mmHg. At 40 mmHg intra-abdominal pressure, three dogs became anuric, and the renal blood flow and glomerular filtration rate of the remaining dogs was 7% of normal, while cardiac output was reduced to 37% of normal. Expansion of the blood volume using Dextran-40 easily corrected the deficit in cardiac output, but renal blood flow and glomerular filtration rate remained less than 25% of normal. Renal vascular resistance increased 555% when the intra-abdominal pressure was elevated from 0 to 20 mmHg, an increase fifteen-fold that of systemic vascular resistance. This suggests that the impairment in renal function produced by increased intra-abdominal pressure is a local phenomenon caused by direct renal compression and is not related to cardiac output.

To investigate the role of indoor allergens in adult patients with acute asthma, we conducted a case-controlled study on patients presenting to an emergency room. One hundred and fourteen patients and 114 control subjects were enrolled over a 1-yr period in Wilmington, Delaware. Sera were assayed for total IgE, and for IgE antibodies to dust mites, cat dander, cockroach, grass pollen, and ragweed pollen. Dust was obtained from 186 homes and assayed for dust mite, cat, and cockroach allergens. IgE antibodies to mite, cat, and cockroach were each significantly associated with asthma, and this association was very strong among participants without medical insurance and among African Americans. Among 99 uninsured participants, sensitization to one of the indoor allergens (> 200 RAST units) was present in 28 of 57 asthmatics and in one of 42 control subjects (odds ratio, 39; confidence interval, 9.4 to 166). For cat and cockroach the combination of sensitization and presence of allergen in the house was significantly associated with asthma. Furthermore, there was a strong inverse relationship between IgE antibodies to cat and to cockroach, and the risk of this sensitization was in large part restricted to homes or areas with high levels of allergen. Thirty-eight percent of the asthmatics, but only 8% of the control subjects, were allergic to one of the three indoor allergens, and had high levels of the relevant allergen in their houses (odds ratio, 7.4; confidence interval, 3.3 to 16.5).(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the relation of carcinoembryonic antigen levels to time, site and extent of recurrence in 358 patients with colorectal cancer. The recurrence rate was higher in patients with Dukes' B and Dukes' C lesions who had preoperative levels higher than 5 ng per milliliter. There was a linear inverse correlation between preoperative levels and estimated mean time to recurrence in patients with Dukes' B and C lesions, ranging from 30 months for a level of 2 to 9.8 months for a level of 70 ng per milliliter. In patients with Dukes' C lesions the median time to recurrence was 13 months if preoperative levels were higher than 5 ng per milliliter, and 28 months if they were lower. Preoperative carcinoembryonic antigen levels in patients with resectable Dukes' B and C cancer provided an additional criterion for allocating these patients to groups at high or low risk for recurrence.

STUDY DESIGN: Retrospective review of prospective, multicenter database. OBJECTIVE: The aim of the study was to determine age-specific spino-pelvic parameters, to extrapolate age-specific Oswestry Disability Index (ODI) values from published Short Form (SF)-36 Physical Component Score (PCS) data, and to propose age-specific realignment thresholds for adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: The Scoliosis Research Society-Schwab classification offers a framework for defining alignment in patients with ASD. Although age-specific changes in spinal alignment and patient-reported outcomes have been established in the literature, their relationship in the setting of ASD operative realignment has not been reported. METHODS: ASD patients who received operative or nonoperative treatment were consecutively enrolled. Patients were stratified by age, consistent with published US-normative values (Norms) of the SF-36 PCS (<35, 35-44, 45-54, 55-64, 65-74, >75 y old). At baseline, relationships between between radiographic spino-pelvic parameters (lumbar-pelvic mismatch [PI-LL], pelvic tilt [PT], sagittal vertical axis [SVA], and T1 pelvic angle [TPA]), age, and PCS were established using linear regression analysis; normative PCS values were then used to establish age-specific targets. Correlation analysis with ODI and PCS was used to determine age-specific ideal alignment. RESULTS: Baseline analysis included 773 patients (53.7 y old, 54% operative, 83% female). There was a strong correlation between ODI and PCS (r = 0.814, P < 0.001), allowing for the extrapolation of US-normative ODI by age group. Linear regression analysis (all with r > 0.510, P < 0.001) combined with US-normative PCS values demonstrated that ideal spino-pelvic values increased with age, ranging from PT = 10.9 degrees, PI-LL = -10.5 degrees, and SVA = 4.1 mm for patients under 35 years to PT = 28.5 degrees, PI-LL = 16.7 degrees, and SVA = 78.1 mm for patients over 75 years. Clinically, older patients had greater compensation, more degenerative loss of lordosis, and were more pitched forward. CONCLUSION: This study demonstrated that sagittal spino-pelvic alignment varies with age. Thus, operative realignment targets should account for age, with younger patients requiring more rigorous alignment objectives.

A total of 1,001 consecutive episodes of nosocomial pneumonia in 901 patients was identified by routine surveillance at the University of Virginia Medical Center between 1979 and 1983 (8.6 episodes/1,000 admissions). When only initial episodes were examined, 890 patients comprised the study sample. The overall case fatality rate was 30%. Stepwise logistic regression indicated that time from admission to pneumonia (p = 0.0006), age (p less than 0.0001), prior use of mechanical ventilation (p = 0.0032), and neoplastic disease (p = 0.0062) were associated with mortality. Multiple regression analysis indicated that the factors associated with increased length of hospitalization included posttracheostomy status (p = 0.0001), prior mechanical ventilation (p = 0.0001), immunosuppressive or leukopenic status (p = 0.0009), nasogastric intubation (p = 0.0003), and prior bacteremia (p = 0.0127). A sampled, individually matched cohort study (n = 74 pairs) was conducted to determine the proportion of mortality in cases that was attributable to infections (33%) and to determine excess hospital stay (seven days) among the patients with nosocomial pneumonia. Excess stay was statistically significant (p less than 0.0001), but proportional mortality was only marginally significant (p = 0.0892). Our findings suggest that nosocomial pneumonia accounts for approximately 33% of the crude mortality and contributes significantly to the economic burden associated with prolonged hospitalization.

STUDY DESIGN: Retrospective review of a multicenter database. OBJECTIVE: To determine the complication rates associated with surgical treatment of pediatric scoliosis and to assess variables associated with increased complication rates. SUMMARY OF BACKGROUND DATA: Wide variability is reported for complications associated with the operative treatment of pediatric scoliosis. Limited number of patients, surgeons, and diagnoses occur in most reports. The Scoliosis Research Society Morbidity and Mortality (M&M) database aggregates deidentified data, permitting determination of complication rates from large numbers of patients and surgeons. METHODS: Cases of pediatric scoliosis (age ≤18 years), entered into the Scoliosis Research Society M&M database between 2004 and 2007, were analyzed. Age, scoliosis type, type of instrumentation used, and complications were assessed. RESULTS: A total of 19,360 cases fulfilled inclusion criteria. Of these, complications occurred in 1971 (10.2%) cases. Overall complication rates differed significantly among idiopathic, congenital, and neuromuscular cases (P < 0.001). Neuromuscular scoliosis had the highest rate of complications (17.9%), followed by congenital scoliosis (10.6%) and idiopathic scoliosis (6.3%). Rates of neurologic deficit also differed significantly based on the etiology of scoliosis (P < 0.001), with the highest rate among congenital cases (2.0%), followed by neuromuscular types (1.1%) and idiopathic scoliosis (0.8%). Neur-omuscular scoliosis and congenital scoliosis had the highest rates of mortality (0.3% each), followed by idiopathic scoliosis (0.02%). Higher rates of new neurologic deficits were associated with revision procedures (P < 0.001) and with the use of corrective osteotomies (P < 0.001). The rates of new neurologic deficit were significantly higher for procedures using anterior screw-only constructs (2.0%) or wire-only constructs (1.7%), compared with pedicle screw-only constructs (0.7%) (P < 0.001). CONCLUSION: In this review of a large multicenter database of surgically treated pediatric scoliosis, neuromuscular scoliosis had the highest morbidity, but relatively high complication rates occurred in all groups. These data may be useful for preoperative counseling and surgical decision-making in the treatment of pediatric scoliosis.

Abstract We identified characteristics of devices that caused needle-stick injuries in a university hospital over a 10-month period. Hospital employees who reported needle sticks were interviewed about the types of devices causing injury and the circumstances of the injuries. Of 326 injuries studied, disposable syringes accounted for 35 percent, intravenous tubing and needle assemblies for 26 percent, prefilled cartridge syringes for 12 percent, winged steel-needle intravenous sets for 7 percent, phlebotomy needles for 5 percent, intravenous catheter stylets for 2 percent, and other devices for 13 percent. When the data were corrected for the number of each type of device purchased, disposable syringes had the lowest rate of needle sticks (6.9 per 100,000 syringes purchased). Devices that required disassembly had rates of injury of up to 5.3 times the rate for disposable syringes. One third of the injuries were related to recapping. Competing hazards were often cited as reasons for recapping. They included the risk of disassembling a device with an uncapped, contaminated needle and the difficulty of safely carrying several uncapped items to a disposal box in a single trip. New designs could provide safer methods for covering contaminated needles. Devices should be designed so that the worker's hands remain behind the needle as it is covered, the needle should be covered before disassembly of the device, and the needle should remain covered after disposal. Such improvements could reduce the incentives for recapping needles and lower the risk of needle-stick injuries among health care workers. (N Engl J Med 1988;319:284–8.)

STUDY DESIGN: Prospective observational cohort study with matched and unmatched comparisons. Level II evidence. OBJECTIVE: The purpose of this study is to compare results of adult symptomatic lumbar scoliosis (ASLS) patients treated nonoperatively and operatively. This is an evidence-based prospective multicenter study to answer the question of whether nonoperative and operative treatment improves the quality of life (QOL) in these patients at 2-year follow-up. SUMMARY OF BACKGROUND DATA: Only 1 paper in the peer-reviewed published data directly addresses this question. That paper suggested that operative treatment was more beneficial than nonoperative care, but the limitations relate to historical context (all patients treated with Harrington implants) and the absence of validated patient-reported QOL (QOL) data. METHODS: This study assesses 160 consecutively enrolled patients (ages 40-80 years) with baseline and 2-year follow-up data from 5 centers. Lumbar scoliosis without prior surgical treatment was defined as a minimum Cobb angle of 30 degrees (mean: 54 degrees for patients in this study). All patients had either an Oswestry Disability Index (ODI) score of 20 or more (mean: 33) or Scoliosis Research Society (SRS) domain scores of 4 or less in pain, function, and self-image (mean: 3.2) at baseline. Pretreatment and 2-year follow-up data collected prospectively included basic radiographic parameters, complications and SRS QOL, ODI, and Numerical Rating Scale back and leg pain scores. RESULTS: At 2 years, follow-up on the operative patients was 95% and for the nonoperative patients it was 45%. The demographics for the nonoperative patients who were followed up for 2 years versus those who were lost to follow-up were identical. The operative cohort significantly improved in all QOL measures. The nonoperative cohort did not improve and nonsignificant decline in QOL scores was common. At minimum 2-year follow-up, operative patients outperformed nonoperative patients by all measures. CONCLUSION: It would appear from this study that common nonoperative treatments do not change the QOL in patients with ASLS at 2-year follow-up. However, operative treatment does significantly improve the QOL for this group of patients. Our conclusions are limited by the fact that we were only able to follow-up 45% of the nonoperative group to 2-year follow-up, in spite of extensive efforts on our part to accomplish such.

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95+/-9.4 ng/ml; mean+/-SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm(3)) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified.