Gamma knife surgery of vestibular schwannomas: volumetric dosimetry correlations to hearing loss suggest stria vascularis devascularization as the mechanism of early hearing loss.

OBJECTIVE: Determine which variables are correlated with early hearing changes after gamma knife surgery of vestibular schwannomas (VSs). STUDY DESIGN: Prospective clinical study of hearing outcomes, radiation dosimetry, conformity, and tumor size of all sporadic unilateral VS patients treated between June 2000 and July 2009. SETTING: Tertiary referral center. PATIENTS: : Fifty-nine VS patients with at least 6 months of follow-up data were studied. INTERVENTIONS: Audiometry and imaging were performed to determine auditory thresholds, speech discrimination, and tumor size. Radiation doses to 5 volumes were measured. MAIN OUTCOME MEASURES: Pretreatment and posttreatment comparisons were performed with regard to change in tumor size; radiation dose to specific volumes including the internal auditory canal, cochlea, basal turn of the cochlea, and modiolus; and conformity of the treatment. RESULTS: The mean follow-up was 63.76 months (standard deviation, ±29.02 mo; range, 9-109 mo). The median follow-up was 65.5 months. A statistically significant association between maximum radiation dose to the cochlea volume and 3-frequency pure-tone average in patients starting with 50 dB or lesser PTA3 was demonstrated using linear regression analysis. CONCLUSION: Longitudinal changes in hearing occur over time, with the largest changes seen in the first 12 months after treatment. With our study outcomes as basis, limiting the dose of radiation to the cochlea to no more than 4 Gy would likely reduce vascular injury to the stria vascularis and improve hearing outcomes. Shielding the cochlea during the treatment planning process would be one mechanism to accomplish this goal.

Outcome among patients with acute renal failure needing continuous renal replacement therapy: A single center study.

Outcome of acute renal failure (ARF) and use of continuous renal replacement therapy (CRRT) have shown a consistently high mortality. (1) Evaluate the short-term patient survival. (2) Evaluate dialysis-free survival. (3) Evaluate risk factors associated with overall survival and the continued need for intermittent dialysis. We identified adults (>/=18 years) needing CRRT, treated in the critical care units of Froedtert Medical and Lutheran Hospital from January 1, 2003 till December 31, 2005. Patients were divided into two major groups needing CRRT, end stage renal disease (ESRD) (chronic dialysis) and non-ESRD with ARF. Continuous renal replacement therapy was performed with an average of 2 L replacement fluid exchanges/h. Sigma stat software was used for analysis. Comparison was done for noncontinuous variables by chi-square and t test for categorical and continuous variables, respectively. A total of 110 (ESRD 24/non-ESRD 86) patients received CRRT during study period. Over all in-hospital mortality among non-ESRD patients was 63% vs. 46% for ESRD. Among non-ESRD patients who survived, 47% needed intermittent hemodialysis on intensive care unit discharge and 28% continued to need hemodialysis at last follow-up. Among non-ESRD patients alive at discharge, those who were dialysis dependent on last follow-up were older (64.5) than those who did not require dialysis on last follow-up (58.4) P=0.347. Non-ESRD patients who died were in the hospital for an average of 17.5 days compared with 29 days for those who were discharged from the hospital. Patients with ARF needing CRRT have high in-hospital mortality. A significant percentage of patients remained dialysis dependant on last follow-up.

The influence of surgery in MEN-1 syndrome: observations over 150 years.

BACKGROUND: Efficacy and timing of operative intervention in patients with multiple endocrine neoplasia type 1 (MEN-1) syndrome remains controversial. This report utilizes a novel approach to evaluate the influence of evolving operative interventions for patients with MEN-1 syndrome. METHODS: Six generations from a large MEN-1 family pedigree were studied. The number of operations for MEN-1 related pathology was recorded according to birth eras over 150 years. Length of life was a primary outcome measurement. RESULTS: Inheritance of the MEN-1 trait was near 50%. There were no instances of a skipped generation. Affected individuals born before 1900 died from gastrointestinal hemorrhage and without any surgical intervention. After 1900, there were increasing numbers of gastric, parathyroid, and pancreatic operations in successive eras. Death occurred >20 years earlier in MEN-1 individuals than unaffected family members in eras 1 and 2. Family members with MEN-1 lived longer in succeeding eras with increasing number of operative and pharmacologic interventions. CONCLUSION: MEN-1 family members invariably have pathologic changes in pituitary, parathyroid, and pancreatic islets when long lived, the "all-or-none" phenomenon. Patients are not cured with operative interventions, although they may live longer and without symptoms with a good quality of life. This model may allow better comparisons with other MEN-1 patients when evaluating outcomes of new medical and operative management schemes and long-term follow-up.

Gamma Knife surgery of vestibular schwannomas: longitudinal changes in vestibular function and measurement of the Dizziness Handicap Inventory.

OBJECT: Gamma Knife surgery (GKS) is one of the methods available to treat vestibular schwannomas (VSs), in addition to microsurgical resection; however, clear information regarding balance function outcomes and the impact of treatment on patients' quality of life over time remains an important clinical need. The purpose of this study was to assess the longitudinal balance outcomes and Dizziness Handicap Inventory (DHI) following GKS for VSs. METHODS: This was a prospective clinical study of balance outcomes in all patients with VSs treated in the Acoustic Neuroma and Skull Base Surgery Program at a tertiary referral center by the senior author and the Gamma Knife team between June 2000 and May 2008. The main outcome measures included preoperative vestibular testing and postoperative caloric testing performed at 6-month intervals to determine vestibular function. The DHI questionnaires were administered retrospectively to assess the impact of GKS on self-perceived disability. RESULTS: Between June 2000 and May 2008, 55 sporadic VSs were treated. There was a >or= 60-month follow-up available in 27 of these patients, >or= 48 months in 32, >or= 36 months in 38, >or= 24 months in 43, >or= 12 months in 51, and >or= 6 months in 54 (1 patient was excluded from the analysis because the follow-up was < 6 months). Various patterns of changes in vestibular function were observed in either positive or negative directions. A significant difference in total DHI score was seen only in the elderly (> 65 years old) patients pre-GKS compared with post-GKS (t = 1.34, p = 0.05). CONCLUSIONS: Longitudinal changes in vestibular function occur over time, with the largest changes seen in the first 6 months after treatment. Potential for clinical intervention, such as vestibular rehabilitation therapy, exists during this interval; however, larger cohorts must be studied to determine the timing and efficacy of this intervention. The statistically significant improvement in the DHI score in the patient cohort > 65 years old treated with GKS suggests that this group may benefit from this option when considering the symptom of dizziness.

BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients.

BACKGROUND: BK virus nephritis (BKVN) has emerged as an important cause of renal transplant failure. Quantified analysis of its timing and clinical course is generally lacking. We have thus quantified the timing, risk factors, evolution of renal function, and transplant graft outcome in renal transplant recipients with BKVN from our center. METHODS: A total of 41 cases of BKVN were diagnosed in 1001 renal and renal/pancreas transplant recipients. There were 2 groups: group I (N= 16), with diagnosis based on renal biopsy alone from January 1996 to August 2001, and group II (N= 25), with diagnosis based on quantitative blood BKV-PCR and biopsy from September 2001 to December 2003. The demographics, the clinical course, immunosuppressive therapy, renal function, and graft outcome were quantified. Donor, recipient, and transplant risk variables were studied using a univariate analysis. Actuarial graft survival was calculated. An immunosuppressive scale created to evaluate the degree of immunosuppression in these patients and its reduction after the diagnosis of BKVN. RESULTS: The median time from transplant to BKVN diagnosis was 318 days (range 48-1356). The actuarial graft survival in patients with BKVN at 6 months, 1, 3, and 5 years was 97%, 90%, 58%, and 47%. The corresponding values for those without BKVN were 94%, 92%, 83%, and 76%, respectively, P < 0.001. Graft loss occurred in 46% of patients. The rate of decline of renal function in group II (N= 25) patients in the 4 months preceding BKVN was rapid (4.8 mL/min/month) and this declined to 0.7 mL/min/month at 3 months' post-BKVN diagnosis, P= 0.004. In those who recovered, the time to stabilization of renal function was a median of 112 days. The immunosuppressive scale score was 7 units at the time of diagnosis of BKVN and decreased to 3.5 units at 3 months' post-BKVN. Reduction in the dose of calcineurin inhibitors but not the overall reduction in dose of immunosuppression correlated with recovery of renal function in these patients. CONCLUSION: BKVN is a relatively late complication of renal transplantation. Despite reduction in immunosuppression, graft loss occurred in 46% of patients. There was a steep decline in renal function in months preceding the diagnosis of BKVN, and reduction in calcineurin inhibitor dose, but not overall immunosuppression, correlated with stabilization of renal function.

A murine model of invasive aspergillosis: variable benefit of interferon-gamma administration under in vitro and in vivo conditions.

BACKGROUND: Interferon-gamma modulates host defense in a number of infectious diseases. Previous studies have shown that systemic administration of interferon-gamma (IFN-gamma) can enhance survival in experimental invasive aspergillosis (IA). METHODS: Using a novel model of murine IA that is characterized by primary pulmonary infection, we investigated the role of IFN-gamma in the phagocytosis and killing of Aspergillus fumigatus by murine neutrophils and pulmonary alveolar macrophages in vitro and the impact of systemic and regional administration of IFN-gamma on the course of IA in glucocorticoid-treated mice. RESULTS: In vitro, IFN-gamma significantly enhanced phagocytosis and killing function of both neutrophils and alveolar macrophages from normal animals, but not cortisone-treated animals. In vivo, intravenous administration of IFN-gamma did not improve phagocyte recruitment, in vivo killing, or mortality from IA. Regional (intranasal) administration of IFN-gamma to the lungs enhanced recruitment of phagocytic cells to the lungs and improved in vivo killing, but did not alter (and actually worsened) mortality from IA. CONCLUSIONS: The in vitro and in vivo effects of IFN-gamma in IA are contingent on many variables, including the route of administration and the specific pathogenesis of infection.