What Factors Are Associated With Local Metastatic Lesion Progression After Intramedullary Nail Stabilization?

BACKGROUND: Pathologic fracture of the long bones is a common complication of bone metastases. Intramedullary nail stabilization can be used prophylactically (for impending fractures) or therapeutically (for completed fractures) to preserve mobility and quality of life. However, local disease progression may occur after such treatment, and there is concern that surgical instrumentation and the intramedullary nail itself may seed tumor cells along the intramedullary tract, ultimately leading to loss of structural integrity of the construct. Identifying factors associated with local disease progression after intramedullary nail stabilization would help surgeons predict which patients may benefit from alternative surgical strategies. QUESTIONS/PURPOSES: (1) Among patients who underwent intramedullary nail stabilization for impending or completed pathologic fractures of the long bones, what is the risk of local progression, including progression of the existing lesion and development of a new lesion around the nail? (2) Among patients who experience local progression, what proportion undergo reoperation? (3) What patient characteristics and treatment factors are associated with postoperative local progression? (4) What is the difference in survival rates between patients who experienced local progression and those with stable local disease? METHODS: Between January 2013 and December 2019, 177 patients at our institution were treated with an intramedullary nail for an impending or completed pathologic fracture. We excluded patients who did not have a pathologic diagnosis of metastasis before fixation, who were younger than 18 years of age, who presented with a primary soft tissue mass that eroded into bone, and who experienced nonunion from radiation osteitis or an avulsion fracture rather than from metastasis. Overall, 122 patients met the criteria for our study. Three fellowship-trained orthopaedic oncology surgeons involved in the care of these patients treated an impending or pathologic fracture with an intramedullary nail when a long bone lesion either fractured or was deemed to be of at least 35% risk of fracture within 3 months, and in patients with an anticipated duration of overall survival of at least 6 weeks (fractured) or 3 months (impending) to yield palliative benefit during their lifetime. The most common primary malignancy was multiple myeloma (25% [31 of 122]), followed by lung carcinoma (16% [20 of 122]), breast carcinoma (15% [18 of 122]), and renal cell carcinoma (12% [15 of 122]). The most commonly involved bone was the femur (68% [83 of 122]), followed by the humerus (27% [33 of 122]) and the tibia (5% [6 of 122]). A competing risk analysis was used to determine the risk of progression in our patients at 1 month, 3 months, 6 months, and 12 months after surgery. A proportion of patients who ultimately underwent reoperation due to progression was calculated. A univariate analysis was performed to determine whether lesion progression was associated with various factors, including the age and sex of the patient, use of adjuvant therapies (radiation therapy at the site of the lesion, systemic therapy, and antiresorptive therapy), histologic tumor type, location of the lesion, and fracture type (impending or complete). Patient survival was assessed with a Kaplan-Meier curve. A p value < 0.05 was considered significant. RESULTS: The cumulative incidence of local tumor progression (with death as a competing risk) at 1 month, 3 months, 6 months, and 12 months after surgery was 1.9% (95% confidence interval 0.3% to 6.1%), 2.9% (95% CI 0.8% to 7.5%), 3.9% (95% CI 1.3% to 8.9%), and 4.9% (95% CI 1.8% to 10.3%), respectively. Of 122 patients, 6% (7) had disease progression around the intramedullary nail and 0.8% (1) had new lesions at the end of the intramedullary nail. Two percent (3 of 122) of patients ultimately underwent reoperation because of local progression. The only factors associated with progression were a primary tumor of renal cell carcinoma (odds ratio 5.1 [95% CI 0.69 to 29]; p = 0.03) and patient age (difference in mean age 7.7 years [95% CI 1.2 to 14]; p = 0.02). We found no associations between local disease progression and the presence of visceral metastases, other skeletal metastases, radiation therapy, systemic therapy, use of bisphosphonate or receptor activator of nuclear factor kappa-B ligand inhibitor, type of fracture, or the direction of nail insertion. There was no difference in survivorship curves between those with disease progression and those with stable local disease (= 0.36; p = 0.54). CONCLUSION: Our analysis suggests that for this population of patients with metastatic bone disease who have a fracture or impeding fracture and an anticipated survival of at least 6 weeks (completed fracture) or 3 months (impending fracture), the risk of experiencing local progression of tumor growth and reoperations after intramedullary nail stabilization seems to be low. Lesion progression was not associated with the duration of survival, although this conclusion is limited by the small number of patients in the current study and the competing risks of survival and local progression. Based on our data, patients who present with renal cell carcinoma should be cautioned against undergoing intramedullary nailing because of the risk of postoperative lesion progression. LEVEL OF EVIDENCE: Level III, therapeutic study.

A Rare Case of Spontaneous Intrauterine Skull Fracture.

Skull fractures are rare in newborns and normally caused by maternal abdominal trauma or complicated deliveries. However, in rare cases, these fractures are found in neonates born after an uneventful pregnancy and delivery. We report a case of a primigravida who underwent cesarean delivery due to failure of descent and malpositioning of the fetal head. After birth, a right temporoparietal fracture and congenital muscular torticollis were diagnosed. The newborn's blood tests showed hypocalcemia and relative hypoparathyroidism. Both mother and newborn presented low vitamin D levels. Serial imaging control showed gradual resolution of the lesions, with the newborn being discharged at the 10th day of life with vitamin D supplementation. This is an interesting case because the combination of three conditions - maternal and fetal hypovitaminosis D, congenital torticollis and malposition of the cephalic pole during labor - may have synergistically contributed to a spontaneous intrauterine skull fracture.

As fraturas do crânio são raras em recém-nascidos, sendo mais comummente causadas por trauma abdominal ou como complicação do parto. Contudo, em casos mais raros, estas fraturas são encontradas isoladamente, sem associação a intercorrências da gravidez ou do parto. Apresentamos o caso de uma primigesta submetida a cesariana por ausência de descida da apresentação e mau posicionamento da mesma no canal de parto. Após o nascimento, foi diagnosticada fratura temporoparietal direita e torcicolo congénito. Analiticamente, o recém-nascido apresentava hipocalcemia e hipoparatiroidismo relativo. A díade mãe - recém-nascido apresentaram hipovitaminose D. Estudos imagiológicos seriados demonstraram resolução gradual das lesões, possibilitando a alta do recém-nascido ao 10º dia de vida com suplementação de vitamina D. Este caso é interessante porque se conjugam três condições ­ hipovitaminose D materna e fetal, torcicolo congénito e má orientação do polo cefálico ­ que, conjuntamente, podem ter contribuído para a ocorrência de fratura craniana intrauterina espontânea.

[Rickets and anaemia caused by coeliac disease in a three-year-old girl].

We present a case report of a three-year-old girl of Pakistani origin with coeliac disease. The first symptom was spontaneous fracture of the fibula. Vitamin D deficiency rickets and iron deficiency anaemia were demonstrated. An intestinal biopsy and elevated antibody levels confirmed the coeliac disease. Rickets is a known but rare presentation of coeliac disease, but this case report illustrates, how coeliac disease in children often presents with non-gastrointestinal symptoms. The importance of investigations for malabsorp-tion, if iron deficiency is not easily corrected with sufficient iron supplements, is underlined as well as the importance of screening for coeliac disease.

Pathologic fracture of the thoracic spine in a male master ultra-marathoner due to the combination of a vertebral hemangioma and osteopenia.

Vertebral hemangiomas are the most common benign vertebral neoplasms and are generally asymptomatic. In the present study, we report the case of a 52-year-old male master ultra-marathoner suffering from a pathologic fracture of the thoracic spine due to a vertebral hemangioma. A further examination in the athlete revealed an accompanying osteopenia, which was most likely due to a deficiency in both vitamin D and testosterone. The treatment of the fracture consisted of percutaneous vertebroplasty. Shortly after the operation the athlete was able to continue running. The most likely reason for the pathologic fracture of the vertebral body was the combination of the vertebral hemangioma and osteopenia. The further treatment consisted of supplementation of both vitamin D and testosterone. Athletes and physicians should be aware that male master ultra-marathoners older than 50 years might suffer from osteopenia, where a deficiency in vitamin D and testosterone could be contributing factors for osteopenia development in general.

Osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF) in an osteoporotic patient chronically treated with bisphosphonates.

The aim of the study is to report the rare association of two complications of long-term treatment of osteoporosis with bisphosphonates in the same Caucasian elderly patient. A female patient of Italian descent, age 87 years, consulted in February 2013. She had a history of osteoporosis and had taken alendronate weekly for 7 years (1999-2006). Due to low back pain, an orthopedist had indicated i.v. zoledronic acid, 5 mg/year for 3 years (2006-2008). She received occasional supplements of ergocalciferol. In 2009, she suffered a fall and sustained a subtrochanteric fracture of the left femur. She was operated on and recovered uneventfully. In 2012, she consulted a dentist due to loose teeth. She underwent the removal of a molar and was given a denture. She had discomfort when using the prosthesis, and developed an ulceration in the gum of the mandible, which exposed the bone and did not heal for 2 months. After radiologic studies, the diagnosis was osteonecrosis of the jaw. She improved after surgical debridement and local and systemic antibiotics. In early 2013, laboratory tests were normal except for a slight elevation of serum PTH and CTX-I. Calcitriol 0.25 mcg/day was prescribed; after 3 months serum calcium, phosphate, PTH, and CTX-I showed no variation. Two years later, she experienced acute low back pain after a fall; MRI showed recent crushing of D12, and chronic deformities of D11 and L1. Bone densitometry of her right hip (DXA) showed a T-score of -2.3 at the femoral neck. An X-ray film of the right femur showed diffuse thickening of both cortices. She was treated with nasal calcitonin and analgesics. After the back pain subsided, she was treated with s.c. denosumab. Although the association of ONJ and AFF was known in cancer patients treated with high doses of bisphosphonates, it is very rare in patients with osteoporosis receiving these drugs at usual doses. Only three cases have been reported, all in oriental women. This appears to be the first reported case in a Caucasian woman.

Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B.

In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved.

A case off the bell curve: customization of the dialysis prescription--a self-report.

BACKGROUND/AIMS: In a 35+-year dialysis patient, a series of spontaneous fractures and a history of severe somatic pains of unknown origin, superimposed on a history of generally adequate laboratory values, prompted an attempt at diagnosis of the cause of the condition. The patient was on a regimen of nocturnal home hemodialysis, a 4-night, 7-hour treatment. Physicians were divided on whether the cause might be neuropathic, muscular or osteopathic. METHODS: A bone biopsy was conducted to evaluate the integrity of the bones. RESULTS: The biopsy resulted in a diagnosis of osteomalacia - severe mineral depletion of the skeletal system. This was surprising because the hematologic laboratory values did not seem to indicate this. The calcium level in the dialysate was greatly increased, which was supplemented by moderate inclusion of sodium phosphate. CONCLUSION: The bones strengthened over time, resulting in no further fractures, an easing of general pain, and significantly improved mobility. The results demonstrate that customization of the dialysis prescription should be readily available for hemodialysis, whether treated in-center or at home.

Severe spinal deformity and multiple vertebral collapses in juvenile Cushing Syndrome: a case report.

Cushing's Syndrome (CS) is rare in adolescence but the pathological effects of excessive circulating glucocorticoids concentration on bone during the developmental age still represent a challenge for orthopedists. Only few reports describe the gravity of early developed damages of spine in young affected by CS. A 18-years-old woman suffering from Cushing's Disease presented after many years treatment of the primary disease referring severe back pain and worsening back deformity. Radiological investigations showed vertebral collapses a devastating thoraco-lumbar scoliosis of 80° Cobb. Lumbar dual X-ray absorptiometry Z-score values were very low and consistent with severe osteoporosis. The patient was treated with bracing, antiresorptive therapy, calcium and vitamin D supplementation, and followed-up with imaging investigations to screen for further fractures. The bone mineral density will be monitored until its normalization will allow to plane surgical treatment in case of progression of spinal deformity and collapses. Early diagnosis and treatment of hypercortisolism, periodical clinical and radiographic follow-up, and treatment for the bone damage are mandatory to prevent the devastating sequelae of secondary osteoporosis.

Spontaneous supracondylar femoral fracture in an HIV patient in lotus position.

Bone disorders have been described in patients chronically infected with human immunodeficiency virus (HIV). A case of spontaneous supracondylar femoral fracture that occurred in a 58-year-old monk during meditation is reported. His AIDS disease was controlled with combination antiretroviral therapy. Vitamin D and calcium had been added 3yr before since osteoporosis was detected by dual-energy X-ray absorptiometry (DXA). At the time of the fracture, the patient was on treatment with 35mg every week of sodium risedronate, 1000mg of calcium, and 400IU of Vitamin D every day. Clinical use of DXA for HIV patients should be considered as a routine measure to help reducing risk for fractures.

3-year follow-up of 215 fracture patients from a prospective and consecutive osteoporosis screening program. Fracture patients care!

BACKGROUND AND PURPOSE: Fractures can be prevented if osteoporosis is identified and treated. Starting in 2002, we have been using a screening program in which patients between 50 and 75 years of age with a wrist, shoulder, vertebral, or hip fracture are assessed by DEXA of the hip and spine and if osteoporotic or osteopenic, they are encouraged to see a doctor of their own choice. The patients receive documents containing information, the results of DEXA, and a letter to present to their doctor with suggestions regarding blood tests and treatment. Here we report the 3-year follow-up regarding compliance to the recommended treatment. METHODS: A questionnaire was sent to fracture patients who participated in the initial screening study from November 2002 through November 2003. Questions included whether they had seen a doctor, whether treatment had been initiated, and their opinions about osteoporosis. RESULTS: 215 of the 236 patients answered the questionnaire, with a mean follow-up of 39 months. 76/87 of those with osteoporosis, 70/99 of those with osteopenia, and 11/29 of those with normal BMD had seen a doctor. Anti-resorptive treatment was prescribed to two-thirds of the osteoporotic patients, to one-sixth of the osteopenic patients, and to none of the patients with normal bone density. Calcium-vitamin D supplementation as monotherapy was given to one-third of the osteoporotic patients, to half of the osteopenic patients, and to half of the normal patients. Only a few osteoporotic patients, one-third of the osteopenic patients, and half of the normal patients received no treatment. Compliance to treatment was 80% over 3 years in those treated. Most patients felt that they could influence their skeletal health. INTERPRETATION: Screening of fracture patients for osteoporosis effectively identifies patients with low bone mineral density and the patient can be trusted to seek appropriate medical advice for treatment of osteoporosis. Based on the bone scan diagnosis, the treatment that these patients received reflects current treatment guidelines well.

Prevention and treatment of glucocorticoid-induced osteoporosis in daily dermatologic practice.

BACKGROUND: Systemic glucocorticoids (GCs) are often needed to treat dermatologic patients. The long-term use of GCs, however, is associated with potentially severe side-effects. GC-induced osteoporosis (GIO) is one of the most serious complications, but the risk of the occurrence of GIO seems to be generally underestimated. AIM: To provide an update of the recent advances in the prevention of GIO in dermatologic practice. METHODS: Review of the literature and several European and US guidelines up to August 2007. RESULTS: Data regarding the prevention and treatment of GIO are limited and guidelines for the prevention of GIO are not fully consistent. CONCLUSION: The prophylaxis of osteoporosis needs to be started early during treatment with GCs. Calcium and vitamin D supplements in all patients on systemic GCs and bisphosphonates in patients who take GCs for more than 3 months are practical and effective measures.

Trabecular bone structure obtained from multislice spiral computed tomography of the calcaneus predicts osteoporotic vertebral deformities.

PURPOSE: To compare multislice computed tomography (MSCT)-derived parameters of the trabecular bone structure of the calcaneus with bone mineral density (BMD) in their ability to differentiate between donors with and without osteoporotic fractures of the spine and to optimize CT scan protocols. METHODS: Forty-two postmortem calcanei (81.2 +/- 10 years) were imaged with a 16-detector row MSCT system using 4 different scan protocols varying spatial resolution (12-24 lp/cm) and radiation dose. Structural parameters of trabecular bone were derived from these images, and BMDs of the calcanei were determined using dual x-ray absorptiometry. Vertebral deformities of the spine were radiographically classified using the Spinal Fracture Index. Diagnostic performance in differentiation between donors with and without vertebral fractures was assessed using receiver operating characteristic (ROC) analysis. RESULTS: There were significant case-control differences for many of the structural parameters measured (P < 0.05). The highest ROC values were found for apparent trabecular thickness using the high-resolution and high-dose protocols. Statistically significant correlations were found between most structure parameters and BMD (up to r = 0.85, P < 0.01). CONCLUSION: Structural parameters of trabecular bone as obtained from high-resolution MSCT images of the calcaneus can be used to differentiate between donors with and without osteoporotic vertebral fractures, using a high-resolution and high-dose CT protocol.

Quantitative ultrasound: use in the detection of fractures and in the assessment of bone composition.

Quantitative ultrasound (QUS) techniques have found widespread clinical use, but their specific role in clinical practice needs further refinement. This review discusses the ability of QUS approaches to predict the risk for prevalent vertebral fractures and the risk for future fractures. QUS approaches perform as well as central dual x-ray absorptiometry devices but with some disadvantages (at least for older QUS approaches) with regard to the predictive power for hip fractures. Technologic diversity of QUS approaches may lead to differences in performance. QUS also has the potential for assessing bone mineral density-independent aspects of bone composition that are relevant for bone strength. For measurements at the calcaneus, it is evident that bone microstructure is the key determinant of QUS variables obtained. However, in most cases, microstructure is so highly correlated with bone mineral density that no separate assessment can be performed in clinical practice. At cortical sites, a selective assessment of bone properties is easier. Technologies need to be adapted to this purpose because requirements differ significantly from those desired for optimum fracture risk assessment. More importantly, multiple partially independent QUS variables need to be defined to assess complementary aspects of bone tissue.

Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft.

OBJECTIVE: To discuss the case of a 79-year-old man who had a delayed posttraumatic vertebral collapse and an intravertebral vacuum cleft. The patient had been on long-term corticosteroid therapy. A discussion of Kummell's disease and the controversy surrounding the etiology of the condition is also presented. CLINICAL FEATURES: Six weeks before coming to the clinic, the patient remembered twisting, hearing a pop, and having severe low back pain. Two weeks after the incident, while hospitalized for bacterial cellulitis, he underwent lumbar spine radiography. The radiographs showed degenerative changes and remote (healed) compression fractures but did not demonstrate any deformity of L2. Four weeks later, he sought care for persistent low back pain. Radiographs revealed marked compression of the L2 vertebral body with an intravertebral vacuum phenomenon. INTERVENTION AND OUTCOME: The patient was referred to his geriatrician for evaluation as a candidate for vertebroplasty or other stabilization procedures. He required a moderately high dose (60 mg) of prednisone daily to combat the symptoms of myasthenia gravis; therefore, the prognosis appears unfavorable for this patient. CONCLUSION: Clinical research is needed to determine the definitive etiology and pathophysiology of Kummell's disease. This case demonstrates that the intravertebral vacuum is a dynamic entity, subject to changes in size and shape. Previous case reports have suggested that Kummell's disease only presents as a linear, horizontal cleft. This disease needs further investigation to determine the true correlation between radiographic signs and the underlying pathophysiology.

Fractal analysis of radiographic trabecular bone texture and bone mineral density: two complementary parameters related to osteoporotic fractures.

Trabecular bone microarchitecture and bone mineral density (BMD) are two main factors related to osteoporotic fractures. Currently, however, microarchitecture is not evaluated. We have developed and validated a trabecular bone texture analysis from radiographic images. The objective was to determine if the fractal analysis of texture was able to distinguish osteoporotic fracture groups from control groups, either in vertebrae, hip, or wrist fractures, and to determine if this indicator and BMD were independent and complementary. In this cross-sectional unicenter case-control population study in postmenopausal women, 107 fracture cases were enrolled and age-matched with 197 control cases. This population comprised 40 vertebral fractures (with 70 controls), 30 hip fractures (55 controls), and 37 wrist fractures (62 controls). Hip and lumbar spine BMD were measured by double-energy X-ray absorptiometry. Fractal analysis of texture was performed on calcaneus radiographs and the result was expressed as the H parameter (H = 2-fractal dimension). The H parameter showed a lower value (0.679 +/- 0.053 SD) in fracture cases versus control cases (0.696 +/- 0.030; p = 0.007), the statistical significance persisting after adjustment for age and for lumbar spine (LS) or hip BMD. This result was confirmed in vertebral fractures (p = 0.0001) and hip fractures (p = 0.003) but not wrist fractures (p = 0.07). We determined the threshold between high and low H values and then the odds ratios (OR) of fracture for low H for BMD < or = -2.5 SD in T score and for the combinations of both parameters. The OR of fracture for low H was 1.6 (95% CI, 1.1-2.6). For LS BMD < or = -2.5 SD the OR of 6.1 (3.4-10.8) shifted to 9.0 (4.0-20.4) when we added low H and for hip BMD it shifted from 5.6 (3.3-9.4) to 8.1 (4.0-16.8). In vertebral, hip, and wrist fracture cases the results were also significant. These data have shown that the fractal analysis of texture on calcaneus radiographs can distinguish osteoporotic fracture groups from control groups. This analysis and BMD provide independent and complementary information. These data suggest that we can improve the fracture risk evaluation by adding information related to microarchitecture, derived from analysis of conventional radiographic images.

Glomangiopericytoma causing oncogenic osteomalacia. A case report with immunohistochemical analysis.

A 47-year-old woman suffered from gait disturbance due to back pain and muscle weakness. Laboratory data showed serum hypophosphatemia, elevated alkaline phosphatase, and a normal level of ionized calcium. Radiological examinations revealed multiple pathologic fractures in the ribs and pubic rami. She had had no episode of familial or any other notable disorder, and so she was initially treated with medication for adult-onset osteomalacia. However, 19 years later (when she was 66 years old), she noticed a soft-tissue tumor in her buttock. The tumor was excised. The histological features were those of glomangiopericytoma characterized by both glomus tumor-like and hemangiopericytoma-like structures. After removal of the tumor, her symptoms disappeared immediately. Laboratory data normalized 8 months later. To our knowledge, this is the first report of oncogenic osteomalacia caused by glomangiopericytoma.

A 3-month-old baby with multiple fractures.

This case is presented to illustrate the radiographic and clinical findings of a condition of interest to orthopedic surgeons. The initial findings are noted on this page. The clinical and radiographic diagnoses are presented on the following pages.

[Generalized osteopathy with pathological fractures in a patient with long-term exposure to fluorine-containing plastics]. / Generalisierte Osteopathie mit pathologischen Frakturen bei einem Patienten mit Langzeitexposition gegenüber fluorhaltigen Kunststoffen.

In a 68-year-old man with a painful syndrome of the lower extremities which began at the age of 64 years, workup revealed a generalized osteopathy with sclerosis of the axial skeleton and osteopenia at the extremities associated with pathologic fractures. The occupational history showed exposure to several synthetics such as vinyl chloride, polyethylene, delrine and polyamides over 30 years. However, a presumptive connection between the skeletal disorder and the occupational exposure could not initially be substantiated. In a later analysis of the bone biopsies from 1991, a significant increase of fluorine in the tibia and fibula of the patient was detected and thus the diagnosis of industrial fluorosis established. The fluorine presumably originated from the workup of polytetrafluorethylene plates. A detailed analysis of the workplace is ongoing. The fluorosis may obviously appear as a variable skeletal disease. The clinical picture of fluorosis is incompletely described in most of the German textbooks. It calls for an extended description of the X-ray findings associated with fluorosis and a new definition of the disease.

Cone epiphysis of the knee and scurvy.

A rare case of metaphyseal cupping of the distal femur resulting from infantile scury in a child is reported. The radiological and surgical aspects of this case are of particular interest. MRI demonstrated central epiphysiodesis of the right knee, surgery achieved rupture of the epiphyseal plate and resulted in femoral lengthening. The child's limp disappeared as a result.