Lohse, Christine M.

AbstractPurposeThe aim of this retrospective study was to summarize practice‐based evidence associated with long‐term outcomes (>20 years) in the management of edentulous patients. The patient population was managed with implant‐supported prostheses, following the original osseointegration protocol, provided over the period from 1983 to 1991 in the group prosthodontics practice at the Mayo Clinic. The data are an example of practice quality assurance monitoring and are used to refine care delivery when needed and to provide information regarding expected outcomes in a shared decision‐making interaction with prospective patients.Materials and MethodsTwo hundred and sixty four patients with at least one edentulous jaw were identified. Of these, 255 completed their care and follow‐up at the Mayo Clinic (209 mandible only, 35 maxilla only, 11 mandible and maxilla). Prosthodontic outcomes categorized as anticipated or unanticipated prosthetic and biologic events and the respective interventions required for each were recorded to assess follow‐up event dynamics for this care modality.ResultsThe mean duration of follow‐up for 190 of the 255 patients (65 died at a mean follow‐up of 12.6 years) was 13.0 years (median 13.6; range 0.3 to 28). At least one prosthetic event was experienced by 148 patients (58%), and 81 (32%) experienced at least one biologic event. Overall, patients experienced 3.8 times more prosthetic events than biologic events. Twenty‐four (9%) patients experienced 35 implant failures. Overall survival rates at 20 years were 86% for prostheses, 15% survived free of any event, and 92% experienced survival free of implant failure (95% confidence interval).ConclusionAnticipated and unanticipated prosthetic events occur throughout the life of the hybrid prosthesis. Prosthetic events significantly surpass (four times more) biologic events and occur significantly later in the follow‐up. For this patient group, 8.6% (22/255) had implant‐supported prostheses remade during follow‐up in this patient population. These findings support the recommendation that prosthodontic care for missing teeth be thought of in a “chronic condition” context, recognizing that long‐term outcome monitoring to provide realistic care expectations is important for demonstrating care value in oral health promotion.

Abstract Certain autoimmune bullous diseases ( AIBD ), including pemphigoid and pemphigus, confer increased infection risk. Infections have not been systematically studied in these conditions, however. Little is known about infection risk in these conditions, particularly dermatitis herpetiformis (DH). We aimed to characterize and compare infection patterns and risk factors in patients with pemphigoid, pemphigus, and DH. We retrospectively studied the medical records of Olmsted County, Minnesota, residents who had a diagnosis of AIBD between 1 January 1998 and 1 January 2011. Of 81 patients studied, 54 (67%) had pemphigoid, 11 (14%) had pemphigus and 16 (20%) had DH . Most patients studied developed at least one localized infection (72%) or one systemic infection (83%). Almost one‐third of patients (31%) developed infections requiring hospitalization or contributing to death. All patients taking systemic corticosteroids experienced a localized or systemic infection during the follow‐up period. Systemic infections were significantly less frequent in patients with DH than those with pemphigoid or pemphigus ( P = 0.03), as were systemic infections requiring hospitalization or contributing to death ( P = 0.002). Patients with DH were significantly less likely to require systemic corticosteroids ( P < 0.001) and significantly more likely to receive dapsone ( P = 0.002). The study design was retrospective and a limited number of patients met the inclusion criteria. Patients with AIBD frequently developed localized and systemic infections, a substantial portion of which contributed to hospitalization or death. Patients with DH experienced infections of lesser severity than patients with pemphigoid or pemphigus.

Health care reform focuses on primary care and development of Health Care Homes to improve patient-centered chronic illness care. This pilot study evaluated a community care team intervention that linked chronically ill older patients, support persons, and nurse care coordinators from a Health Care Home with community resources using an adaptation of the Wraparound process. A pragmatic clinical trial design was used. Patient-centered chronic illness care; physical, mental, and social health; service use; and study feasibility were evaluated. Differences between groups were compared using two-sample t, Wilcoxon rank sum, chi-square, or Fisher’s exact tests. At 3 months, the intervention group reported higher patient-centered chronic illness care (mean total Patient Assessment of Chronic Illness Care change scores were 0.39 for the intervention group and −0.11 for the control group, p = .03). Results indicate that the integrated community care team intervention is a promising strategy to support patient-centered chronic illness care.

Abstract Recently, we have identified serum response factor (SRF) as a mediator of clinically relevant androgen receptor (AR) action in prostate cancer (PCa). Genes that rely on SRF for androgen-responsiveness represent a small fraction of androgen-regulated genes, but distinguish benign from malignant prostate and correlate with aggressive disease. Moreover, the SRF-AR expression signature is associated more strongly with biochemical recurrence than similarly sized sets of AREdriven AR target genes. Thus, understanding the mechanism(s) by which SRF conveys androgen effects to its target genes may provide novel opportunities to target clinically relevant androgen signaling. Here, we explore the role of the RhoA signaling axis, a well-known activating pathway upstream of SRF, in androgen activation of SRF action. PCa cells were treated with inhibitors of RhoA signaling or transfected with siRNAs targeting RhoA, the critical SRF cofactor MAL or control siRNAs in the presence or absence of the synthetic androgen R1881. Real-time RT-PCR and western blotting was done to assess effects on expression of SRF target genes. Cell fractionation experiments evaluated the cellular localization of AR, MAL and SRF. ChIP was performed to assess recruitment of MAL to SRF target genes. Wild-type, dominant-active and dominant-negative versions of RhoA were overexpressed to determine effects on androgen regulation of SRF target genes. Immunohistochemistry was done to evaluate RhoA expression in clinical PCa samples and a tissue microarray derived from a CWR22 PCa xenograft model that mimics progression from androgen-stimulated (AS) to castration-recurrent (CR) disease. Effects on AS and CR PCa cell biology were assessed using proliferation and migration assays. Here, we show that the small GTPase RhoA mediates androgen responsiveness of more than half of SRF target genes tested. Interference with expression of RhoA, activity of the RhoA effector RhoA-associated kinase (ROCK), and actin polymerization necessary for nuclear translocation of the SRF cofactor MAL, all prevented full androgen-regulation of SRF target genes. Androgen treatment increased the nuclear content of MAL and led to MAL recruitment to the promoter of the SRF target gene FHL2. Moreover, in clinical specimens RhoA expression was higher in PCa cells than benign prostate cells, and elevated RhoA expression levels were associated with aggressive disease features and decreased disease-free survival following radical prostatectomy. Overexpression of RhoA markedly increased the androgen responsiveness of select SRF target genes, in a manner that depends on its GTPase activity. Cell lines and a xenograft model that mimics the transition from AS to CR PCa indicate that RhoA levels are not altered during disease progression, suggesting that RhoA expression levels in the primary tumor determine disease aggressiveness. Silencing of RhoA, use of ROCK inhibitors or an inhibitor of SRF-MAL interaction blunted (androgen-regulated) cell viability and attenuated AS and CR PCa cell migration. Taken together, our work demonstrates that the RhoA signaling axis mediates clinically relevant AR action in PCa. In addition, these studies are the first to report on overexpression of RhoA in PCa and its association with aggressive disease and poor outcome. Note: This abstract was not presented at the conference because the presenter was unable to attend. Citation Format: Lucy Schmidt, Thomas Sebo, Donald Tindall, Hannelore Heemers, Kelly Duncan, Neelu Yadav, Kevin Regan, Christine Lohse, Elena Pop, Kristopher Attwood, Gregory Wilding, James Mohler. Androgen regulation of SRF target genes in prostate cancer cells is mediated in part by the small GTPase RhoA [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A8.

Objective To evaluate carbonic anhydrase IX ( CAIX ) expression as an independent prognostic marker for clear cell renal cell carcinoma ( ccRCC ). With recent smaller studies showing conflicting results, we aimed to update our initial analysis in 2007 with an additional 5‐year follow‐up. Patients and Methods We provided long‐term follow‐up of the same cohort used in our 2007 study (730 patients with unilateral, sporadic ccRCC treated surgically between 1990 and 1999). Associations of CAIX expression with RCC death and distant metastases were evaluated using C ox proportional hazards regression models. Results CAIX was expressed in 708 (97.0%) of the specimens; 163 tumours (22.3%) had low (≤85%) expression and 567 (77.7%) high (>85%) expression. There were 483 deaths and 265 RCC ‐specific deaths. The median follow‐up for the 247 patients still under observation was 13.8 years. Univariately, low CAIX expression was associated with an increased risk of RCC death vs high expression (hazard ratio 1.62; P < 0.001). Low CAIX expression was not statistically significantly associated with RCC death or distant metastases after adjusting for nuclear grade or coagulative tumour necrosis. Conclusion After additional long‐term follow‐up of our large cohort, our results continue to suggest that CAIX is not an independent prognostic marker for ccRCC .

ObjectivesTo evaluate risk factors associated with iatrogenic splenectomy during nephrectomy and to assess outcomes among patients undergoing nephrectomy for renal tumors.MethodsOf 4323 patients who underwent nephrectomy at Mayo Clinic between 1992 and 2008, 33 (0.8%) had an iatrogenic/unplanned splenectomy. In a case–control study design, controls without splenectomy were matched 1:3 based on age, sex, surgical date, side of the renal tumor, surgical approach and surgeon. Perioperative features and survival were evaluated using conditional logistic and Cox regression.ResultsAmong the 33 iatrogenic splenectomy patients, the majority (94%) underwent radical, open and left‐sided nephrectomy. Primary tumor classification ≥T3 was the only clinicopathological risk factor significantly associated with splenectomy (odds ratio 3.4; P = 0.02). Compared with controls, patients with an iatrogenic splenectomy were more likely to have longer operative time (205 vs 171 min; P = 0.02), higher estimated blood loss (1.3 vs 0.3 L; P = 0.001), longer length of stay (median 7 vs 5 days; P = 0.03) and a higher likelihood for postoperative complications (odds ratio 5.3; P = 0.002). With a median of 9.8 years of follow up, splenectomy patients tended to have greater all‐cause mortality (hazard ratio 1.6; P = 0.07), although this difference approached statistical significance.ConclusionsIatrogenic splenectomy is a rare complication during nephrectomy and is associated with locally advanced tumors (≥pT3). It also carries prognostic significance for adverse perioperative outcomes and possibly diminished survival, although this warrants further study.

Objectives/HypothesisTo describe the natural history of primary inner ear schwannomas (PIES) and evaluate management outcomes and relationship between PIES location, clinical presentation, and time to diagnosis.Study DesignRetrospective chart review and systematic review of the literature.MethodsVestibular schwannoma confined to or arising from the inner ear were included. PIES classification was based on anatomic subsite(s) involved. Detailed clinical history and outcomes were recorded.ResultsIn a systematic review (1933–2011), including 14 patients from the authors' institution (1999–2009), a total of 72 studies comprising 234 patients were evaluated. Mean follow‐up was 32.8 ± 39.1 months (range, 0–183 months). The cochlea was the most commonly involved subsite (51%). Hearing loss was the most frequent presenting symptom (99%). Vertigo and abnormal balance were more common among tumors involving the vestibular system (P < .01). Average delay between symptom onset and diagnosis was 7.0 ± 8.0 years (median, 5 years; range, 0–40 years). Recent onset hearing loss was more likely to elicit an earlier diagnosis (P = .01). The majority of patients were observed without treatment (53%). Tumor progression was seen in 52% of patients.Conclusions PIES are rare tumors and most commonly involve the cochlea. Tumor location is often associated with clinical presentation and correlates with delay between symptom onset and diagnosis. A watch‐and‐scan approach is the management strategy of choice in the absence of intractable vertigo or extensive tumor growth. The majority of patients report stable or improved symptoms over time, regardless of treatment. Laryngoscope, 123:1957–1966, 2013

What's known on the subject? and What does the study add? There is great variability in the utilization of partial nephrectomy, but the causes of these variations are not well understood. The present study underscores the already observed phenomenon of surgical volume influencing surgical planning and outcomes, but it gets at why this might be so. We observe that high‐volume renal surgeons have different thresholds of ‘technical feasibility’. Objective To investigate why there continues to be wide variability in the application of partial nephrectomy ( PN ) for treating small renal masses despite guidelines in the US and E urope stating that a PN is a standard of care for a patient with a T 1 renal mass. Patients and Methods In June 2009, 764 surgeon‐members of the A merican U rologic A ssociation ( AUA ) participated in a survey evaluating the management of renal masses. Renal mass complexity was graded by nephrometry score ( NS ). Multivariable logistic regression models with generalized estimating equations were constructed to evaluate how tumour, surgeon and practice‐setting characteristics influence the use of PN . Results The survey response rate was 19%. Each urological surgeon responded to eight scenarios, providing 6112 evaluable cases. Tumour NS ranged from 4 to 10, and each unit increase in NS was associated with 59% increased likelihood of a surgeon offering RN on multivariable analysis (odds ratio [ OR ] = 1.59; 95% CI : 1.52–1.64). When holding patient and tumour characteristics constant, the following surgeon and practice‐setting characteristics significantly increased the odds of offering a PN: increasing renal case volume ( OR = 1.57; 95% CI : 1.27–1.95), academic practice ( OR = 1.80; 95% CI : 1.42–2.29), increasing PN % volume ( OR = 3.7; 95% CI : 2.46–5.55) and younger surgeon age (≤40 vs >50 years) ( OR = 1.64; 95% CI : 1.35–1.96). Conclusion The characteristics of a surgeon and the setting in which he or she practices influence the utilization of PN , the adherence to professional guidelines, and the threshold of tumour complexity at which a surgeon stops offering PN .