Browsing by Subject "Recurrence"
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Item A Study of the Correlation of Incisive Biting Forces with Age, Sex and Anterior Occlusion(1971) Kotwal, Navroze Shavak; Standish, S. Miles; Chalian, Varoujan A.; Shanks, James C.This study was designed to prove or disprove the fact that incisive biting force can be correlated with the variables chosen which were age, sex and anterior occlusion (overjet, overbite and cuspid relation). The amount of linear contact made by the incisal edges of the upper and lower incisors was also included as one of the variables. One hundred and fifty individuals, 80 males and 70 females, between the ages of 10 and 25 were selected for this study. This was a cross sectional study in which four readings of the maximum biting ability were recorded for every individual just once during the study and an average of the four recordings was taken. An intra-oral force transducer using strain gages was employed to record incisive biting forces. The results indicated that age, sex and amount of linear contact were correlated with biting force when considered singly. When the variables were considered jointly through a stepwise regression analysis overbite also entered as a significant predictor of biting force in addition to the three mentioned variables. Multiple correlation coefficient R was 0.54 for the four entered variables (age squared, sex, overbite and linear contact squared) with biting force. The R squared value was 0.29 so that 29 percent of the variation in incisive biting force of this sample was due to these four variables. The correlated R-squared value indicates a large error of prediction and a low degree of precision in estimating biting force from these four variables. Therefore, a regression equation is not demonstrated.Item Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis(Springer Nature, 2022) Maakaron, Joseph E.; Zhang, Mei-Jie; Chen, Karen; Abhyankar, Sunil; Bhatt, Vijaya Raj; Chhabra, Saurabh; El Jurdi, Najla; Farag, Sherif S.; He, Fiona; Juckett, Mark; de Lima, Marcos; Majhail, Navneet; van der Poel, Marjolein; Saad, Ayman; Savani, Bipin; Ustun, Celalettin; Waller, Edmund K.; Litzow, Mark; Kebriaei, Partow; Hourigan, Christopher S.; Saber, Wael; Weisdorf, Daniel; Medicine, School of MedicineAcute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60-64; 65-69; 70+). With median follow-up of nearly 3 years, patients aged 60-64 had modestly, though significantly better OS, DFS and lower TRM than those either 65-69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.Item Antidepressant Treatment Duration in Pediatric Depressive and Anxiety Disorders: How Long is Long Enough?(Elsevier, 2018-02) Hathaway, Elizabeth E.; Walkup, John T.; Strawn, Jeffrey R.; Graduate Medical Education, IU School of MedicineAnxiety and depressive disorders are common in the pediatric primary care setting, and respond to both psychotherapeutic and psychopharmacologic treatment. However, there are limited data regarding the optimal treatment duration. This article systematically reviews guidelines and clinical trial data related to antidepressant treatment duration in pediatric patients with depressive and anxiety disorders. The extant literature suggests 9-12 months of antidepressant treatment for youth with major depressive disorder. For generalized, separation and social anxiety disorders, 6-9 months of antidepressant treatment may be sufficient, though many clinicians extend treatment to 12 months based on extrapolation of data from adults with anxiety disorders. Such extended treatment periods may decrease the risk of long-term morbidity and recurrence; however, the goal of treatment is ultimately remission, rather than duration of antidepressant pharmacotherapy. Moreover, while evidence-based guidelines represent a starting point, appropriate treatment duration varies and patient-specific response, psychological factors, and timing of discontinuation must be considered for individual pediatric patients.Item Comparison of Biomarker Expression between Proximal and Distal Colorectal Adenomas: The Tennessee-Indiana Adenoma Recurrence Study(Wiley, 2017-02) Su, Timothy; Washington, M. Kay; Ness, Reid M.; Rex, Douglas K.; Smalley, Walter E.; Ulbright, Thomas M.; Cai, Qiuyin; Zheng, Wei; Shrubsole, Martha J.; Medicine, School of MedicineIt is unclear if proximal and distal traditional adenomas present with differences in molecular events which contribute to cancer heterogeneity by tumor anatomical subsite. Participants from a colonoscopy-based study (n=380) were divided into subgroups based on the location of their most advanced adenoma: proximal, distal, or “equivalent both sides”. Eight biomarkers in the most advanced adenomas were evaluated by immunohistochemistry (Ki-67, COX-2, TGFβRII, EGFR, β-catenin, cyclin D1, c-Myc) or TUNEL (apoptosis). After an adjustment for pathological features, there were no significant differences between proximal and distal adenomas for any biomarker. Conversely, expression levels did vary by other features, such as their size, villous component, and synchronousness. Large adenomas had higher expression levels of Ki-67(P<0.001), TGFβRII (P<0.0001), c-Myc (P<0.001), and cyclin D1 (P<0.001) in comparison to small adenomas, and tubulovillous/villous adenomas also were more likely to have similar higher expression levels in comparison to tubular adenomas. Adenoma location is not a major determinant of the expression of these biomarkers outside of other pathological features. This study suggests similarly important roles of Wnt/β-catenin and TGF-β pathways in carcinogenesis in both the proximal and distal colorectum.Item Effect of Gap Geometry on Secondary Caries in Vitro(2009) Nassar, Hani M.; Cabezas, Carlos Gonzales, 1966-; Chu, Tien-Min Gabriel; Fontana, Margherita Ruth, 1966-; Gregory, Richard; Matis, Bruce; Cochran, MichaelObjective: To investigate the effect of the size of the space between the restoration and the dentinal wall of the tooth (i.e. the dentinal portion of the gap) on the development of secondary caries. Methods: Tooth-resin-matrix composite specimens were mounted on custom-made gap-model stages. Specimens were divided into four groups (n=10). Group 1 had a uniform gap size of 30μm throughout both enamel and dentin. Group 2 had a 30μm enamel gap size with a 530μm dentinal gap. Group 3 had 525μm gaps in both enamel and dentin. Group 4 had 525μm and 1025μm gaps in enamel and dentin, respectively. Specimens were attached to plastic Petri plates, gas-sterilized and then incubated in a microbial caries model with S. mutans TH16 in (1% sucrose tryptic soy broth for 1 h, 4 times/day, and with a buffer solution for the rest of the day). After 8 days of incubation, tooth specimens were sectioned and stained with a rhodamine B solution. Digital images were taken under a confocal microscope and analyzed for lesion size at the enamel outer lesion (EOL), enamel wall lesion (EWL), dentin wall lesion next to the DEJ (DWL-A) and dentin wall lesion at 750µm from the DEJ (DWL-B). Results: No difference in EOL size was found between the groups. DWL-A and -B were larger in group 3 than groups 1and 2. Larger DWL-B was found in group 3 than group 4. Group 4 had marginally significant larger EWL than groups 1 and 2 (p=0.0652 and p=0.0648, respectively). Also, group 4 had marginally significant (p=0.0607) larger DWL-B than group 1. Conclusions: Based on the results of this study, it can be concluded that the presence of additional space at the dentinal wall area did not affect secondary caries development as long as the enamel gap was small. However, with enamel gaps of ≈500 µm, the presence of the additional gap space at the dentinal wall led to the development of smaller dentinal wall lesions at the deeper parts of the simulated cavity. Also, in uniform gaps, the size of the interface was positively correlated with size of the dentinal wall lesions.Item Multifocal High-Grade Pancreatic Precursor Lesions: A Case Series and Management Recommendations(Mary Ann Liebert, 2019-04-29) Soufi, Mazhar; Yip-Schneider, Michele T.; Carr, Rosalie A.; Roch, Alexandra M.; Wu, Howard H.; Schmidt, Christian Max; Surgery, IU School of MedicineBackground: The risk of developing invasive cancer in the remnant pancreas after resection of multifocal high-grade pancreatic precursor lesions is not well known. We report three patients who were followed up after resection of multifocal high-grade pancreatic intraepithelial neoplasia (PanIN)-3 or intraductal papillary mucinous neoplasia (IPMN), two of whom eventually developed invasive carcinoma. Presentation: 1) 68-year-old woman who had a laparoscopic distal pancreatectomy for multifocal mixed-type IPMN, identified as high-grade on final pathology, with negative surgical margins. During semiannual monitoring, eight years from the first surgery, the patient developed suspicious features prompting surgical resection of the body with final pathology revealing invasive ductal adenocarcinoma in the setting of IPMN. 2) 48-year-old woman who had a distal pancreatectomy for severe acute/chronic symptomatic pancreatitis, with final pathology revealing multifocal high-grade PanIN-3, with negative surgical margins. Despite semiannual monitoring, two years from the first surgery, the patient developed pancreatic adenocarcinoma with liver metastasis. 3) 55-year-old woman who had a Whipple procedure for symptomatic chronic pancreatitis, with multifocal PanIN-3 on final pathology. The patient underwent completion pancreatectomy due to symptomatology and her high-risk profile, with final pathology confirming multifocal PanIN-3. Conclusion: Multifocal high-grade dysplastic lesions of the pancreas might benefit from surgical resection.Item Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors and Poor Reliability of Causality Scoring: Report From INSPPIRE(Wiley, 2023) Morinville, Veronique D.; Husain, Sohail Z.; Wang, Fuchenchu; Cress, Gretchen A.; Abu-El-Haija, Maisam; Chugh, Ankur; Downs, Elissa; Ellery, Kate; Fishman, Douglas S.; Freeman, Alvin Jay; Gariepy, Cheryl E.; Giefer, Matthew; Gonska, Tanja; Liu, Quin; Maqbool, Asim; Mark, Jacob; Mcferron, Brian Arthur; Mehta, Megha; Nathan, Jaimie D.; Ng, Ken; Ooi, Chee Y.; Perito, Emily; Ruan, Wenly; Schwarzenberg, Sarah Jane; Sellers, Zachary M.; Serrano, Jose; Troendle, David M.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark; Uc, Aliye; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC); Pediatrics, School of MedicineObjectives: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children. Methods: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode. Results: Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in "probable" category and 19 ARP and 7 CP in "possible" category by Naranjo scores. Conclusions: Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as "definitive," raising questions about its reliability for DAP.Item Profiling molecular regulators of recurrence in chemorefractory triple-negative breast cancers(BioMed Central, 2019-08-05) Hancock, Bradley A.; Chen, Yu-Hsiang; Solzak, Jeffrey P.; Ahmad, Mufti N.; Wedge, David C.; Brinza, Dumitru; Scafe, Charles; Veitch, James; Gottimukkala, Rajesh; Short, Walt; Atale, Rutuja V.; Ivan, Mircea; Badve, Sunil S.; Schneider, Bryan P.; Lu, Xiongbin; Miller, Kathy D.; Radovich, Milan; Surgery, School of MedicineBACKGROUND: Approximately two thirds of patients with localized triple-negative breast cancer (TNBC) harbor residual disease (RD) after neoadjuvant chemotherapy (NAC) and have a high risk-of-recurrence. Targeted therapeutic development for TNBC is of primary significance as no targeted therapies are clinically indicated for this aggressive subset. In view of this, we conducted a comprehensive molecular analysis and correlated molecular features of chemorefractory RD tumors with recurrence for the purpose of guiding downstream therapeutic development. METHODS: We assembled DNA and RNA sequencing data from RD tumors as well as pre-operative biopsies, lymphocytic infiltrate, and survival data as part of a molecular correlative to a phase II post-neoadjuvant clinical trial. Matched somatic mutation, gene expression, and lymphocytic infiltrate were assessed before and after chemotherapy to understand how tumors evolve during chemotherapy. Kaplan-Meier survival analyses were conducted categorizing cancers with TP53 mutations by the degree of loss as well as by the copy number of a locus of 18q corresponding to the SMAD2, SMAD4, and SMAD7 genes. RESULTS: Analysis of matched somatic genomes pre-/post-NAC revealed chaotic acquisition of copy gains and losses including amplification of prominent oncogenes. In contrast, significant gains in deleterious point mutations and insertion/deletions were not observed. No trends between clonal evolution and recurrence were identified. Gene expression data from paired biopsies revealed enrichment of actionable regulators of stem cell-like behavior and depletion of immune signaling, which was corroborated by total lymphocytic infiltrate, but was not associated with recurrence. Novel characterization of TP53 mutation revealed prognostically relevant subgroups, which were linked to MYC-driven transcriptional amplification. Finally, somatic gains in 18q were associated with poor prognosis, likely driven by putative upregulation of TGFß signaling through the signal transducer SMAD2. CONCLUSIONS: We conclude TNBCs are dynamic during chemotherapy, demonstrating complex plasticity in subclonal diversity, stem-like qualities, and immune depletion, but somatic alterations of TP53/MYC and TGFß signaling in RD samples are prominent drivers of recurrence, representing high-yield targets for additional interrogation.Item Prospective, multicenter study of P4HB (Phasix™) mesh for hernia repair in cohort at risk for complications: 3-Year follow-up(Elsevier, 2021-01) Roth, John Scott; Anthone, Gary J.; Selzer, Don J.; Poulose, Benjamin K.; Pierce, Richard A.; Bittner, James G.; Hope, William W.; Dunn, Raymond M.; Martindale, Robert G.; Goldblatt, Matthew I.; Earle, David B.; Romanelli, John R.; Mancini, Gregory J.; Greenberg, Jacob A.; Linn, John G.; Parra-Davila, Eduardo; Sandler, Bryan J.; Deeken, Corey R.; Verbarg, Jasenka; Salluzzo, Jennifer L.; Voeller, Guy R.; Surgery, School of MedicineBackground: This study represents a prospective, multicenter, open-label study to assess the safety, performance, and outcomes of poly-4-hydroxybutyrate (P4HB, Phasix™) mesh for primary ventral, primary incisional, or multiply-recurrent hernia in subjects at risk for complications. This study reports 3-year clinical outcomes. Materials and methods: P4HB mesh was implanted in 121 patients via retrorectus or onlay technique. Physical exam and/or quality of life surveys were completed at 1, 3, 6,12, 18, 24, and 36 months, with 5-year (60-month) follow-up ongoing. Results: A total of n = 121 patients were implanted with P4HB mesh (n = 75 (62%) female) with a mean age of 54.7 ± 12.0 years and mean BMI of 32.2 ± 4.5 kg/m2 (±standard deviation). Comorbidities included: obesity (78.5%), active smokers (23.1%), COPD (28.1%), diabetes mellitus (33.1%), immunosuppression (8.3%), coronary artery disease (21.5%), chronic corticosteroid use (5.0%), hypo-albuminemia (2.5%), advanced age (5.0%), and renal insufficiency (0.8%). Hernias were repaired via retrorectus (n = 45, 37.2% with myofascial release (MR) or n = 43, 35.5% without MR), onlay (n = 8, 6.6% with MR or n = 24, 19.8% without MR), or not reported (n = 1, 0.8%). 82 patients (67.8%) completed 36-month follow-up. 17 patients (17.9% ± 0.4%) experienced hernia recurrence at 3 years, with n = 9 in the retrorectus group and n = 8 in the onlay group. SSI (n = 11) occurred in 9.3% ± 0.03% of patients. Conclusions: Long-term outcomes following ventral hernia repair with P4HB mesh demonstrate low recurrence rates at 3-year (36-month) postoperative time frame with no patients developing late mesh complications or requiring mesh removal. 5-year (60-month) follow-up is ongoing.Item A Prospective, Single Arm, Multi-Center Study Evaluating the Clinical Outcomes of Ventral Hernias Treated with OviTex® 1S Permanent Reinforced Tissue Matrix: The BRAVO Study 12-Month Analysis(MDPI, 2021-10-27) DeNoto, George, III.; Ceppa, Eugene P.; Pacella, Salvatore J.; Sawyer, Michael; Slayden, Geoffrey; Takata, Mark; Turma, Gary; Yunis, Jonathan; Surgery, School of MedicineBackground: Conflicting results from previous studies have led to dissent over whether surgical mesh is safe and effective in ventral hernia repair. A newer class of mesh known as a reinforced tissue matrix, combining a biologic scaffold and minimal polymer reinforcement, offers promise in reducing inflammatory response and increasing abdominal wall support. This study sought to assess the clinical utility of a reinforced tissue matrix (OviTex) in ventral hernia repair 12 months after implantation. Methods: This is a prospective, single-arm, multi-center study to evaluate the clinical performance of OviTex® 1S Permanent (OviTex) in the repair of primary or recurrent ventral hernias (VH) in consecutive patients (ClinicalTrials.gov/NCT03074474). The rate of surgical site occurrences (SSOs) was evaluated 90 days post-surgery as the primary endpoint. Hernia recurrence and the incidence of postoperative events were evaluated between three and 12 months as secondary endpoints. The incidence of other complications and patient-reported outcomes were also recorded. Results: Ninety-two (92) patients were enrolled in the study, of whom seventy-six (76) reached the 12-month follow-up. All patients were at least 18 years of age with a BMI of <40 kg/m2. Hernia defects were <20 × 20 cm, classified as class I–III according to the CDC wound classification system. Of the 76 patients who reached 12-month follow-up, twenty-six (34%) had previous VH repairs and thirteen (17%) had previous surgical infection. Sixty (79%) had factors known to increase the risk of recurrence. Twenty patients (26%) experienced SSOs, with ten (13%) requiring procedural intervention. Two of the 75 patients (2.7%) experienced a recurrence. Conclusions: The low rate of hernia recurrence and SSOs requiring intervention illustrates the potential that reinforced tissue matrices, and OviTex 1S, in particular, have to improve outcomes in VH repairs. Follow-up to 24 months is ongoing.