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A possible complication of total hip replacement surgery is nerve palsy, the temporary or permanent loss of sensation or loss the ability to move. This complication occurs in from 0.6 to 3.7 percent of patients who have total hip replacement procedures. Peripheral nerve injuries can occur as a result of nerve laceration, ischemia (decreased blood supply), mechanical injury such as compression or separation, or a combination of these circumstances. A review was undertaken of all patients who developed nerve palsy following total hip replacement during a 17-year period to determine long-term follow-up and prognosis and to identify patients at risk. There were 3,126 operations performed; the overall incidence of nerve palsy was 1.7 percent. The incidence of nerve palsy was significantly higher for patients with congenital dislocation of the hip (5.2 percent) and for patients who underwent revision procedures (3.2 percent) than for patients who had joint replacement for osteoarthritis (1.0 percent). The sciatic nerve (the body's largest nerve which passes from the lower spine down the back of the thigh) was involved in 80 percent of the neuropathies. Fifty-three extremities were reevaluated at follow-ups ranging from 1 to 16.5 years after surgery. Only 7 limbs recovered complete neurologic function; 18 limbs had mild weakness, sensory loss and/or mild dysesthesia (abnormal sensations such as numbness or tingling on the skin); and 15 limbs had more severe weakness. Six additional patients had limited walking ability, and seven patients had severely impaired motor function. All patients who had a nerve palsy had decreased walking ability. Patients younger than 48 years who had undergone primary hip replacement had the greatest disability. The degree of nerve injury influenced the prognosis of neurological recovery. All patients who maintained motor function or recovered some motor function during hospitalization made a good recovery. Patients with severe dysesthesia did not recover neurological function. (Consumer Summary produced by Reliance Medical Information, Inc.)

People who have had congenital dislocation of the hip frequently develop subsequent osteoarthrosis with dysplasia (abnormal tissue development) in the same area. Surgical correction using partial or total hip replacement is much more difficult in these patients than in patients whose only problem is osteoarthritis. Often the socket part of the hip is shallow, and this or other changes in the bony structure necessitate particular compensations in surgical hardware and techniques. The outcomes of 74 cemented total hip replacements, in which both ball and socket were replaced, in 55 patients (C group), and of 37 cemented surface replacements of the socket portion only in 32 patients (S group) were evaluated. Patients treated with surface rather than conventional replacements tended to have less severe dysplasia and require less extensive surgical reconstruction. Short-term outcomes in both groups were favorable, and patients reported pain relief and improved hip function. However, group C had more postsurgical complications such as infection, dislocation, and partial nerve paralysis. Infection may have been related to the greater degree of surgical intervention, while nerve dysfunction was related to surgically-induced leg lengthening. All older patients in the C group did well in the long-term, while durable long-term results were not achieved in younger patients in either group. Early surgical techniques and anatomic factors contributed to difficulties with the surface replacement surgery. The major failure necessitating additional surgery or treatment was aseptic (noninfected) loosening of the socket prosthesis. The results suggest that younger patients (under age 60) with osteoarthrosis following congenital hip dislocation should receive treatment other than total or surface hip replacement surgery. (Consumer Summary produced by Reliance Medical Information, Inc.)

Resection arthroplasty is often used as a salvage procedure when deep infection occurs following the insertion of a prosthesis during hip replacement surgery. This procedure is rarely indicated as a first or primary procedure. The results of 48 resected arthroplasties, performed on 43 patients, were analyzed. The indications for the procedure were: serious infection following total hip replacement, loosening of the hip prosthesis without sepsis or decay, and primary septic arthritis (bacterial infection of the joint). Sepsis was eliminated in 40 of the 43 patients using this procedure. The level of pain was markedly reduced for most patients; 35 percent of the patients achieved good pain relief. Following resection arthroplasty, the patients were generally inactive, but were able to be independent and walk a limited distance with support. In this study, women generally had less favorable outcomes than men. Patients who had resection arthroplasty due to sepsis following hip replacement also had poorer outcomes than the remainder of the study group. Regarding surgical technique, the authors suggest that as much of the femoral head as possible be left intact; better outcome and function were correlated with the amount of intact femoral bone. (Consumer Summary produced by Reliance Medical Information, Inc.)

The range of injury severity that can be seen within the category of type II supracondylar humerus fractures (SCHFs) raises the question whether some could be treated nonoperatively. However, the clinical difficulty in using this approach lies in determining which type II SCHFs can be managed successfully without a surgical intervention.

Children with cerebral palsy CP have decreased strength, low bone mass, and an increased propensity to fracture. High-frequency, low-magnitude vibration might provide a noninvasive, nonpharmacologic, home–based treatment for these musculoskeletal deficits. The purpose of this study was to examine the effects of this intervention on bone and muscle in children with CP.

Matrix metalloproteinases (MMPs) play a well-defined role in later stages of tumor progression.  However, there has been evidence that they also contribute to earlier stages of malignant transformation.  The Wnt signaling transduction pathway plays a critical role in development and in the pathogenesis of many epithelial cancers.  Here we have used Wnt1-induced epithelial-mesenchymal transition (EMT) in C57MG murine mammary epithelial cells to study the role of MMPs in this early step of malignant progression.  Overexpression of Wnt1 in C57MG cells promoted EMT, the translocation of b-catenin from the cell membrane to the nucleus and its transcriptional activity, cell proliferation and cell motility.  Simultaneously, we observed an increased expression of stromelysin-1 (MMP-3) and a 5.5-fold increase in MMP-3 promoter activity in C57MG cells expressing Wnt1 compared with C57MG cells.  Treatment of Wnt-overexpressing cells with MMP inhibitor AG3340 decreased MMP-3 expression.  We also found evidence that MMP-3 and Wnt3a cooperate in enhancing the transcriptional activity of β-catenin in C57MG cells.  Consistently, the effects of Wnt1 on EMT, proliferation, and migration were inhibited by MMP inhibitors, or upon downregulation of MMP-3 by siRNA.  These results suggest that MMP-3 is both a direct transcriptional target and a necessary contributor of the Wnt/b-catenin signaling pathway.

Adenosine deaminase (ADA)–deficient severe combined immune deficiency (SCID) may be treated by allogeneic hematopoietic stem cell transplantation without prior cytoreductive conditioning, although the mechanism of immune reconstitution is unclear. We studied this process in a murine gene knockout model of ADA-deficient SCID. Newborn ADA-deficient pups received transplants of intravenous infusion of normal congenic bone marrow, without prior cytoreductive conditioning, which resulted in long-term survival, multisystem correction, and nearly normal lymphocyte numbers and mitogenic proliferative responses. Only 1% to 3% of lymphocytes and myeloid cells were of donor origin without a selective expansion of donor-derived lymphocytes; immune reconstitution was by endogenous, host-derived ADA-deficient lymphocytes. Preconditioning of neonates with 100 to 400 cGy of total body irradiation before normal donor marrow transplant increased the levels of engrafted donor cells in a radiation dose–dependent manner, but the chimerism levels were similar for lymphoid and myeloid cells. The absence of selective reconstitution by donor T lymphocytes in the ADA-deficient mice indicates that restoration of immune function occurred by rescue of endogenous ADA-deficient lymphocytes through cross-correction from the engrafted ADA-replete donor cells. Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy.

The Gillette Gait Index (GGI) is a summary measure incorporating 16 clinically important kinematic and temporal parameters. The purpose of this study was to compare GGI scores from computerized gait analysis versus qualitative visual assessments of overall gait to assess the validity of the GGI as a summary score for gait analysis.

The potential for brief periods of low‐magnitude, high‐frequency mechanical signals to enhance the musculoskeletal system was evaluated in young women with low BMD. Twelve months of this noninvasive signal, induced as whole body vibration for at least 2 minutes each day, increased bone and muscle mass in the axial skeleton and lower extremities compared with controls.Introduction:The incidence of osteoporosis, a disease that manifests in the elderly, may be reduced by increasing peak bone mass in the young. Preliminary data indicate that extremely low‐level mechanical signals are anabolic to bone tissue, and their ability to enhance bone and muscle mass in young women was investigated in this study.Materials and Methods:A 12‐month trial was conducted in 48 young women (15–20 years) with low BMD and a history of at least one skeletal fracture. One half of the subjects underwent brief (10 minutes requested), daily, low‐level whole body vibration (30 Hz, 0.3g); the remaining women served as controls. Quantitative CT performed at baseline and at the end of study was used to establish changes in muscle and bone mass in the weight‐bearing skeleton.Results:Using an intention‐to‐treat (ITT) analysis, cancellous bone in the lumbar vertebrae and cortical bone in the femoral midshaft of the experimental group increased by 2.1% (p= 0.025) and 3.4% (p< 0.001), respectively, compared with 0.1% (p= 0.74) and 1.1% (p= 0.14), in controls. Increases in cancellous and cortical bone were 2.0% (p= 0.06) and 2.3% (p= 0.04) greater, respectively, in the experimental group compared with controls. Cross‐sectional area of paraspinous musculature was 4.9% greater (p= 0.002) in the experimental group versus controls. When a per protocol analysis was considered, gains in both muscle and bone were strongly correlated to a threshold in compliance, where the benefit of the mechanical intervention compared with controls was realized once subjects used the device for at least 2 minute/day (n= 18), as reflected by a 3.9% increase in cancellous bone of the spine (p= 0.007), 2.9% increase in cortical bone of the femur (p= 0.009), and 7.2% increase in musculature of the spine (p= 0.001) compared with controls and low compliers (n= 30).Conclusions:Short bouts of extremely low‐level mechanical signals, several orders of magnitude below that associated with vigorous exercise, increased bone and muscle mass in the weight‐bearing skeleton of young adult females with low BMD. Should these musculoskeletal enhancements be preserved through adulthood, this intervention may prove to be a deterrent to osteoporosis in the elderly.

Neonates with ductal-dependent single-ventricle congenital heart disease palliated with a modified Blalock-Taussig shunt (mBTS) commonly have retrograde diastolic flow in the aorta, which may place them at increased risk of mesenteric ischemia. Recently, palliation with a right ventricle-to-pulmonary artery conduit, known as the Sano procedure, has been shown to eliminate retrograde diastolic flow, theoretically leading to better systemic perfusion.

Recently sling procedures have been shown to be effective in the treatment of all types of incontinence. In this study we evaluated the role of preoperative Valsalva leak point pressure (VLPP) in predicting the outcome of sling surgery.

We developed a preoperative model to risk stratify patients for prostate specific antigen (PSA) failure following radical prostatectomy (RP) and identify those at high risk who would be potential candidates for neoadjuvant clinical trials.

T stage stratification of organ confined renal tumors is based only on tumor size. Currently T1a and T1b are defined as tumors less or greater than 4 cm. However, to our knowledge the validity of this stratification has not been determined. We determined whether symptoms could add additional prognostic information when integrated with tumor size into the TNM classification.

Prostate specific antigen (PSA) density based on the surgical weight of the radical prostatectomy specimen has previously been shown to be an independent predictor of biochemical recurrence after radical prostatectomy. We determined whether preoperative PSA density calculated using transrectal ultrasound prostate volume was a better predictor of advanced pathological findings or biochemical recurrence after radical prostatectomy relative to PSA.

We outline the biology, prognosis and role of immunotherapy for renal cell carcinoma with gross venous tumor thrombus.

Upper pole tumors with direct extension into the adrenal gland are currently staged as pT3a tumors in the 1997 TNM staging system. To determine whether the clinical behavior of pT3a adrenal tumors differs from that of tumors with perinephric fat invasion (also stage pT3a) a retrospective analysis was performed.

A number of studies have failed to show significant differences in outcome following radical prostatectomy between men with palpable, clinically localized prostate cancer (cT2) and those whose tumors are not palpable (cT1c). We determined whether we could improve the prognostic value of the TNM staging system in men with cT1c and cT2 cancers by including information on whether prostate needle biopsy was unilaterally or bilaterally positive.

Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy.

p27 is an important cell cycle regulator, and decreased expression in radical prostatectomy specimens is associated with an increased risk of prostate specific antigen (PSA) failure. To our knowledge no prior study has shown that preoperative p27 status independently predicts recurrence after radical prostatectomy.

The purpose of this study was to determine if a patient's reasons for undergoing a primary total hip arthroplasty (THA) changed at 1 year follow-up and, if the reasons did change, how does this change influence patient satisfaction with the procedure. Patients undergoing THA (101 patients) were evaluated with the McMaster Toronto Arthritis Patient Preference Disability (MACTAR) questionnaire and questions related to their expectations regarding the procedure. With the exception of pain and walking, most patients did not select the same preoperative and postoperative reasons for undergoing the procedure. In fact, 60% chose 2 new postoperative items. Patients whose expectations were not met were less likely to choose the same reasons for undergoing THA. Surgeons need to clarify patients' reasons for wanting a THA and attempt to identify new factors at follow-up that may influence patient satisfaction with the procedure. Copyright 2003, Elsevier Science (USA). All rights reserved.

Renal cell carcinoma (RCC) can present with a wide range of signs and symptoms. To our knowledge we report the first study to describe the frequency of paraneoplastic findings in a modern RCC series and assess the prognostic significance of each finding.

Outcome prediction for patients with renal cell carcinoma is based on a combination of factors. In this study a previously published clinical outcome algorithm based on 1997 T stage, Fuhrman grade and performance score is validated using an international database.

Biopsy Gleason score, serum prostate specific antigen (PSA) levels, and clinical stage are known to be independent predictors of adverse pathological features and biochemical failure after radical prostatectomy. We determine whether various prostate needle biopsy parameters were predictive of either adverse pathological findings or disease recurrence after radical prostatectomy.

Many young children present to pediatric orthopaedic surgeons with genu varum and mild beaking of the medial metaphysis on x-ray. Predicting whether these deformities will progress is challenging. In addition, there is no consensus as to whether these children should all be classified as having Blount disease. To avoid this latter problem, the authors included in this study all children presenting with bowed legs, regardless of diagnosis. With the aim of improving the ability to predict progression, the authors tested the hypothesis that patients with progression have more tibial than femoral varus. The authors reviewed 173 varus limbs of 98 patients younger than 4 years old. The authors determined the angular deformity in both femur and tibia by measuring the angles between their mechanical axes and the transverse axis of the knee, and determined the contribution of tibial deformity as a percentage of the total (DT). The metaphyseal–diaphyseal angles of the tibia (MDA) were also measured to compare the value of that test with the DT. There were 22 limbs with progressive and 141 limbs with resolving varus. Both the MDA and DT were significantly different between groups. Tibial varus was found to exceed femoral varus in all patients with progression and also in several patients whose deformity resolved spontaneously. Although more specific and more sensitive than the MDA, the DT is a good, but not perfect, predictor of progression. However, all patients in this series with both a DT >50 and an MDA of 16° or greater went on to progress. Using both of these tests together may therefore provide the surgeon with a reliable indicator of the children who would benefit from surgical correction.

We examined whether cytoreductive nephrectomy in patients with venous tumor thrombus and metastatic disease is associated with more complications than in those with thrombus without metastatic disease.

Previous studies have suggested that prostate specific antigen (PSA) density is a significant independent predictor of biochemical failure after primary therapy. We determined whether pathological PSA density using surgical weight of the radical prostatectomy specimen was an independent predictor of adverse pathological features or biochemical recurrence after radical prostatectomy. We also examined whether combining pathological PSA density with biopsy Gleason score improved risk stratification compared with serum PSA and biopsy Gleason score for predicting PSA recurrence after prostatectomy.

We tested the effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled trial.

An outcomes assessment of 14 elite college athletes who had undergone lumbar disc surgery was performed using the SF36, a validated questionnaire that assesses quality of life.

We compare the detection of metastatic disease by helical computerized tomography (CT), positron emission tomography (PET) with F-18 fluorodeoxyglucose and monoclonal antibody scan with 111indium capromab pendetide in patients with an elevated prostate specific antigen (PSA) after treatment for localized prostate cancer.

The natural history of Peyronie’s disease was evaluated in 97 men by means of a questionnaire. Disease duration ranged from 3 months to 8 years. Questions addressed pain, bending, ability for intercourse, over-all effect of the disease, psychological effects, treatments received and degree of disease progression. Approximately 40% of the patients found pain, bending, ability for intercourse and over-all effects to be unchanged during the course of the disease. Bending and ability for relations worsened in 40% of the patients during the same interval, while only 6% had worsening of pain. Of the patients 77% reported psychological effects due to Peyronie’s disease, which improved in 28%, did not change in 36% and worsened in 36%. Over-all, 13% of the patients believed the disease to be one of gradual resolution, 47% believed there had been little or no change and 40% believed that the disease pattern was one of gradual progression.

A total of 230 patients with localized prostate cancer underwent radical retropubic prostatectomy at UCLA (pathological stage T1–3 N0, M0). Classification into groups included 115 patients with organ confined disease (group 1), 82 with invasion into or through the capsule (group 2) and 33 with seminal vesicle involvement (group 3). Median followup was 48 months. The 10-year, cause-specific survival was 96%, 90% and 63%, and 5-year, clinical, disease-free survival was 91%, 79% and 58% for the 3 groups, respectively. Recent prostate specific antigen (PSA) levels were measured in most patients, even those operated upon many years ago. Of the patients 41 had detectable (0.4ng./ml. or greater) PSA levels without any other clinical evidence of progression and 15 with clinical evidence of progression had PSA levels in the detectable range at the time of clinical progression. When isolated detectable PSA was also considered an indicator of progression the 5-year and 10-year, disease-free rates were 61% and 41%, respectively.

Abstract:: Surface replacement is a bone-conserving alternative to total hip arthroplasty and is a significant development in the evolution of hip arthroplasty. Surface replacement with polyethylene bearings was largely abandoned, primarily because of component aseptic loosening caused by tissue reaction to high-volumetric polyethylene wear. For patients with osteonecrosis and collapse of the femoral head but with preservation of some acetabular articular cartilage, precision fit, hemisurface replacement of the femoral head only has emerged as the treatment of choice. The survivorship of our series of patients, performed in the 1981–84 era (average age, 32 years), has been 85% at 5 years, 67% at 10 years, and 42% at 16 years. In the absence of polyethylene, there has been no loosening. Revisions were for cartilage wear. The procedure is now much improved with instrumentation for non-trochanteric osteotomy approaches and off-the-shelf components in 1-mm increments. For arthritic hips, a new era of surface replacement has emerged. With metal-on-metal bearings, the volumetric wear has been reduced 20–100 times from those with polyethylene, and there is no penalty for the large ball size. The devices are now conservative on the acetabular as well as femoral side. Hybrid or all-cementless fixation is superior to earlier all-cemented devices. In those patients, the results with up to 4 years have been complication-free, with an absence of pain and a return to high functional levels, including participation in sports. Forty patients have received a Conserve Plus with interference fitting of the acetabular component with sintered beads to obtain fixation. Although the follow-up is short, surface replacement with the large ball size is extremely stable, and dislocation is rare.

This study was undertaken to assess the inter- and intraobserver variability associated with the assessment of acetabular index. Five readers (three senior orthopaedic residents and two pediatric orthopaedic attendings) read each of 24 films on three separate occasions (360 total readings). An independent observer who was blinded to the results of the study assessed whether the radiographs would result in a reproducible acetabular index. Variability was increased for the radiographs that were deemed poorly reproducible by the independent observer. Interobserver variability exceeded intraobserver variability. Variability was comparable for senior orthopaedic residents and attending pediatric orthopaedic surgeons. Even in the group with the least variability (intraobserver variability for reproducible radiographs), the 95% tolerance interval was 8.35°. The results of this study cast doubt on the reliability of the acetabular index based on a single reading.

Postoperative fever in the pediatric orthopaedic population remains a clinical concern even though prior studies concluded that fevers are a poor predictor of surgical complications. In this retrospective study of 177 patients, we established guidelines regarding the degree and time course of fever we should expect based on the perioperative conditions of magnitude of surgery, duration of surgery, need for intraoperative transfusion, estimated blood loss, age, and gender. To provide a more sensitive assessment of fever, we developed composite temperature curves for each patient and defined the area under these curves as the total febrile response (TFR). This allowed us to assess fever as a cumulative event, taking into account both its magnitude and duration. A multivariate model then determined that of the perioperative conditions studied, intraoperative transfusion status and estimated blood loss were most helpful in predicting a patient's TFR. The results of this study can be used as an additional tool for assessing postoperative progress and whether a fever is within the normal limits indicated by a patient's perioperative variables.

We assessed health related quality of life in patients with advanced renal cell carcinoma treated with nephrectomy and tumor infiltrating lymphocyte therapy in combination with interleukin-2.

Early endocrine therapy after radical retropubic prostatectomy was compared to radical prostatectomy alone (nonearly endocrine therapy) for the treatment of carcinoma of the prostate with lymph node metastases. Our retrospective analysis demonstrated that the 2 cohorts were similar with respect to patient age, Gleason sum score, seminal vesicle invasion, lymph node involvement, tumor volume and pathological stage of the primary tumor. The cause-specific survival of the entire group was 84% at 60 months and 78% at 98 months. The cause-specific curves for the early and nonearly endocrine therapy group were not significantly different (p <0.194), although the estimated 9-year survival rates were 91 and 71%, respectively. Survival free of disease was significantly prolonged in the early endocrine therapy group (p <0.030), with a 9-year estimated rate free of disease of 67% versus 32% in the nonearly endocrine therapy group. Followup prostate specific antigen serum levels were analyzed and the value as a progression marker is discussed. These data suggest that a radical operation plus early endocrine therapy is effective palliation in selected patients with low volume lymph node metastases, patients.

In a prospective study we compared the ability of two quality assessment methods—the standard criteria list and the criteria map—to predict the appropriateness of the disposition decision for 421 patients with chest pain who presented to two emergency departments. To evaluate the quality of this decision, each patient was followed at home or in the hospital to determine whether an acute condition requiring hospital admission was present. Among the 169 discharged patients, the map scores of the eight with admissible disease were significantly higher than the score for those without admissible disease (p 0.02). For the 252 admitted patients, a similar relationship between map score and the admissible disease outcome was observed (p 0.0001). There was no significant relationship between list score and outcome among either the admitted or the discharged patients. Multivariate logistic analyses confirmed the importance of the map score as a predictor of admissible disease. The map score was superior to the list score and to demographic variables in its ability to correctly classify patients with and without admissible disease. The demonstrated relationship between map score and patient outcome enables the map to be used in a quality assurance system. An institution can ensure that physicians review an enriched sample of the inappropriate discharges and the unjustified admissions by selecting admitted patients with low map scores and discharged patients with high map scores.

Thirty-eight percent of patients with internal skeletal fixation had indications for removal other than uncomplicated healing. Plates were removed (p = 0.023) routinely, however, because intramedullary rods and staples were likely to be subcutaneous and painful (p = 0.02). Complications included incomplete removal of the device (1) and two postoperative fractures. Most complications had no known significant adverse effects on the patients. Operative time and blood loss were significantly increased when a tourniquet could not be used. We believe that the high percentage of other indications for metal removal and the low incidence of major complications support the practice of routine metal removal in this population.

We sought to quantify prostate tissue changes induced by finasteride and to identify a predictor of finasteride response in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled, double-blind clinical trial.

The relative effects of azathioprine (AZA) and prednisone (PRED) on natural killer (NK) activity and the antibody-dependent cellular cytotoxicity (ADCC) of K (killer) cells and the number of FcR and other lymphoid cells were examined in renal transplant recipients. In addition to both long-term (>6 months) and short-term (<6 months) transplant recipients receiving conventional AZA-PRED therapy, an important group of long-term recipients receiving PRED but not AZA was studied for the first time. Both NK activity and ADCC are profoundly reduced in the long-term AZA-PRED group but are normal in the long-term PRED-alone (no-AZA) group. The short-term AZA-PRED group exhibits NK and ADCC levels significantly lower than normal but not as low as those of the long-term AZA-PRED group. Patient groups with low NK and ADCC also have low circulating Fc receptor-bearing (FcR) cells. A single patient in the long-term AZA-PRED group was removed from AZA therapy, and approximately 3 months was required for the patient's suppressed NK and ADCC to return to normal. These findings indicate that AZA rather than PRED is the major drug important in suppressing ADCC and NK activity in renal transplant recipients. Several months are required for combination AZA-PRED therapy to reduce these cytotoxic activities. Similarly, several months are required for suppressed ADCC and NK activity to return to normal upon discontinuation of AZA.