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Objectives: Implementing enhanced recovery after surgery (ERAS) protocols and decreasing length of stay (LOS) have become a priority for major surgeries, including microvascular free tissue transfer (MVFTT) reconstruction of the head and neck. We describe an ERAS protocol with the goal to further reduce length of stay beyond national medians., Methods: Retrospective chart review between August 2016 and February 2023, including all patients who underwent MVFTT after oral cavity, skull base, salivary gland, and cutaneous ablative surgery. An ERAS protocol was implemented in March 2020., Results: A total of 383 patients were included. Approximately 59.8% underwent oral cavity MVFTT, 34.5% cutaneous and lateral skull base, and 5.8% maxillary and anterior skull base. A total of 209 (54.7%) patients had surgery prior to implementation of the ERAS protocol and 174 (45.3%) after. Median LOS decreased from 9 days (interquartile interval [IQR] 8-11) to 6 (IQR 5-7.5, p < 0.0001) following oral cavity MVFTT. For cutaneous and lateral skull base reconstruction, median LOS decreased from 6 days (IQR 5-8) to 3 (IQR 3-7, p < 0.0001). For anterior skull base and sinonasal MVFTT, median LOS decreased from 8 (IQR 7-9) to 5 days (IQR 4.5-7, p = 0.0005). Rate of discharge to skilled nursing or subacute rehabilitation facilities decreased (24% before ERAS, 9.2% after, p < 0.0001). Thirty-day readmission rate was similar before and after implementation (10.5% vs. 10.3, p = 0.954). Discharge to facility was associated with readmission (OR 2.34, 95% CI 1.12-4.89, p = 0.024)., Conclusion and Relevance: Implementation of the ERAS protocol was associated with decreased LOS. There was no increase in rate of readmission., Level of Evidence: NA Laryngoscope, 134:4527-4534, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: This study aims to evaluate the factors most associated with early and late complications following microvascular free tissue transfer (MVFTT) after mandibulectomy., Methods: A retrospective review of patients undergoing MVFTT after segmental mandibulectomy from September 2016 to February 2021 was performed across a single academic institution. Surgical variables were collected, including the location of the resultant mandibular defect (anterior vs posterior) and flap type (osseous or non-osseous). The primary outcome variables included postoperative complications (early, <90 days; and late, >90 days) and the patients' functional status (return to oral intake). Descriptive statistics, chi-square test, Fischer's exact test, and 2-sample t tests were used to analyze differences among variables., Results: We analyzed a cohort of 114 consecutive patients with mandibular defects, comprising 57 anterior and 57 posterior defects. Bony free flaps with hardware were used to reconstruct 98% of anterior defects compared to 58% of posterior defects ( P  < .001). All soft tissue only flaps did not utilize any hardware during the reconstruction. Anterior defects demonstrated more late complications requiring additional surgery (30% vs 9%, P  = .04). A secondary analysis of posterior mandibular reconstructions compared soft tissue only flaps and bony free flaps with hardware and showed equivalent rates of early (12% vs 13%, P  > .99) and late (9% vs 8%, P  > .99) complications requiring additional surgery while demonstrating a similar return to full oral competence (55% vs 46%, P  = .52) and recovery of a 100% oral diet (67% vs 54%, P  = .53)., Conclusion: Osseous free tissue transfer for segmental mandibular defects remains the gold standard in reconstruction. In our patient cohort, anterior mandibular defects are associated with greater late (>90 day) complications requiring additional surgery. Comparable outcomes may be achieved with soft tissue only versus osseous free flap reconstruction of posterior mandibular defects., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients with solid organ transplant (SOT) are at increased risk of developing aggressive cutaneous malignancies due to their immunosuppression, particularly cutaneous squamous cell carcinoma (cSCC)., Purpose: There is limited data regarding SOT patients with locally advanced cSCC requiring radical surgery and microvascular free tissue transfer (MVFTT). Our objectives were to characterize outcomes in SOT patients and compare them with a non-SOT cohort., Study Design: This is a retrospective cohort study of patients undergoing MVFTT for advanced cSCC of the head and neck between January 2016 and May 2020 at a tertiary referral center. Patients who underwent MVFTT as part of curative intent surgery for advanced cSCC during the study were considered for inclusion. Exclusion criteria included distant metastasis, palliative intent treatment, age less than 18 years, and lip primaries., Predictor: The predictor variable was SOT status. A cohort of non-SOT patients was matched to the SOT cohort based on age, smoking status, tumor stage, and defect size., Main Outcome Variables: The primary reconstructive outcome was the major surgical complications and secondary outcome measures included major medical complications and minor surgical complications. The primary oncologic outcome was overall survival and the secondary outcome was disease-specific survival. The primary predictor was transplant status., Covariates: Covariates included patient comorbidities, prior treatment, tumor stage, type of reconstruction, pathologic findings, and adjuvant therapy., Analysis: Continuous and categorical variables were compared using Student's T test and Fisher's exact test. Survival was calculated using the Kaplan-Meier method and differences in survival between groups were calculated using the log-rank test. Statistical significance was set a priori at P ≤ .05., Results: Fourteen SOT and 14 matched non-SOT patients met inclusion criteria. There was not a statistically significant difference in the rate of major surgical complications (7 vs 7%, P = .74) between the SOT and non-SOT cohorts. Rates of minor (21 vs 43%, P = .26) wound complications and medical complications (0 vs 14%, P = .24) were also similar between the SOT and non-SOT cohorts. Locoregional recurrences and distant metastasis were more common for SOT patients, though this was not statistically significant. Overall survival was significantly worse for SOT patients (21.7 vs 31.0 months, P = .04), though there was not a significant difference in disease-free survival (9.8 vs 31.0 months, P = .17)., Conclusions and Relevance: MVFTT in the management of SOT patients with locally advanced head and neck cSCC demonstrates similar complication rates with non-SOT patients. While survival and oncologic outcomes are worse in the SOT cohort, aggressive surgical intervention with MVFTT can be performed with comparable complication rates to patients without a history of SOT., (Copyright © 2023 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Dynamic contrast enhancement (DCE) imaging is a valuable sequence of multiparametric magnetic resonance imaging (mpMRI). A DCE sequence enhances the vasculature and complements T2-weighted (T2W) and Diffusion-weighted imaging (DWI), allowing early detection of prostate cancer. However, DCE assessment has remained primarily qualitative. The study proposes quantifying DCE characteristics (T1W sequences) using six time-dependent metrics computed on feature transformations (306 radiomic features) of abnormal image regions observed over time. We applied our methodology to prostate cancer patients with the DCE MRI images (n = 25) who underwent prostatectomy with confirmed pathological assessment of the disease using Gleason Score. Regions of abnormality were assessed on the T2W MRI, guided using the whole mount pathology. Preliminary analysis finds over six temporal DCE imaging features obtained on different transformations on the imaging regions showed significant differences compared to the indolent counterpart ( P ≤ 0.05, q ≤ 0.01). We find classifier models using logistic regression formed on DCE features after feature-based transformation (Centre of Mass) had an AUC of 0.89-0.94. While using mean feature-based transformation, the AUC was in the range of 0.71-0.76, estimated using the 0.632 bootstrap cross-validation method and after applying sample balancing using the synthetic minority oversampling technique (SMOTE). Our study finds, radiomic transformation of DCE images (T1 sequences) provides better signal standardization. Their temporal characteristics allow improved discrimination of aggressive disease., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To compare functional outcomes of total laryngectomy (TL) with microvascular free tissue transfer (MVFTT) reconstruction in the treatment of dysfunctional larynx (DL) versus salvage therapy for locally recurrent disease in patients with a history of laryngeal squamous cell carcinoma (SCC)., Methods: Retrospective review from a tertiary medical center between August 2015 and August 2022., Results: Sixty-nine patients underwent TL with MVFTT following primary laryngeal radiation or chemoradiation; 15 (22%) patients underwent functional laryngectomy (FL) and 54 (78%) underwent a salvage laryngectomy (SL). There were no total flap failures. Four (6%) patients developed a pharyngocutaneous fistula; one (7%) FL patient and 3 (6%) in the SL cohort. There was no significant difference in average hospital length of stay (LOS) between the cohorts (8.6 ± 3.0 days vs. 12.8 ± 10.1 days, p = 0.12). All patients (100%) in the FL cohort achieved a total oral diet compared to 41 (76%) in the SL cohort (p = 0.03). Two (13%) and 10 (19%) patients developed pharyngoesophageal stenosis in the FL and SL cohorts, respectively (p = 1.0). Nine (60%) and 23 (43%) patients in the FL and SL cohorts underwent tracheoesophageal puncture (TEP) placement, with 89% and 91% achieving fluency, respectively (p = 0.23)., Conclusion: Although the role of TL for the definitive treatment of laryngeal SCC has decreased over the past 30 years, organ-preservation protocols can impact speech, swallowing, and airway protection with life-threatening consequences. The use of elective FL with MVFTT for the treatment of DL results in similar or better functional outcomes compared to SL for recurrent disease., Level of Evidence: 3 Laryngoscope, 134:222-227, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: The objective of this study was to compare the rate of post-operative radiation therapy (PORT) initiation within 6 weeks for head and neck squamous cell carcinoma patients treated at a safety net, academic institutio between 2019 and 2021 versus those treated in 2022 after implementation of a new clinical pathway., Methods: A retrospective case-control study was performed at a single tertiary care, safety-net, academic institution. Patient demographics, tumor characteristics, dates of surgery, and other treatment dates were collected from the electronic medical record. The time from surgery to PORT was calculated. Patients who started radiation treatment within 42 days of surgery were regarded as having started PORT on time. The demographics, tumor characteristics, and rate of timely PORT for the two cohorts of patients were compared., Results: From 2018 to 2021, our rate of PORT initiation within 6 weeks of surgery was 12% ( n  = 57). In 2022, our rate of timely PORT was 88% ( n  = 16), p  < 0.5. Patient demographics and characteristics were similar with the exception of marital status and use of free-flap reconstruction. The 2022 cohort was more likely to be single ( p  < 0.5), and all patients underwent free-flap reconstruction in 2022 ( p  < 0.05)., Conclusion: Early referrals, frequent communication, and use of a secure registry were the key to the success found by our group despite the socioeconomic challenges of our underserved, safety-net hospital patient population. The changes made at our institution should serve as a template for other institutions seeking to improve the quality of care for their HNSCC patients., Competing Interests: The authors report no conflicts of interest for the existing work., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Habitat heterogeneity is a key driver of biodiversity of macroorganisms, yet how heterogeneity structures belowground microbial communities is not well understood. Importantly, belowground microbial communities may respond to any number of abiotic, biotic, and spatial drivers found in heterogeneous environments. Here, we examine potential drivers of prokaryotic and fungal communities in soils across the heterogenous landscape of the imperiled Florida scrub, a pyrogenic ecosystem where slight differences in elevation lead to large changes in water and nutrient availability and vegetation composition. We employ a comprehensive, large-scale sampling design to characterize the communities of prokaryotes and fungi associated with three habitat types and two soil depths (crust and subterranean) to evaluate (i) differences in microbial communities across these heterogeneous habitats, (ii) the relative roles of abiotic, biotic, and spatial drivers in shaping community structure, and (iii) the distribution of fungal guilds across these habitats. We sequenced soils from 40 complete replicates of habitat × soil depth combinations and sequenced the prokaryotic 16S and fungal internal transcribed spacer (ITS) regions using Illumina MiSeq. Habitat heterogeneity generated distinct communities of soil prokaryotes and fungi. Spatial distance played a role in structuring crust communities, whereas subterranean microbial communities were primarily structured by the shrub community, whose roots they presumably interacted with. This result helps to explain the unexpected transition we observed between arbuscular mycorrhiza-dominated soils at low-elevation habitats to ectomycorrhiza-dominated soils at high-elevation habitats. Our results challenge previous notions of environmental determinism of microbial communities and generate new hypotheses regarding symbiotic relationships across heterogeneous environments.

Objectives: Retrospective studies have shown that head and neck squamous cell carcinoma (HNSCC) patients taking metformin demonstrate superior survival compared to their counterparts. We sought to determine whether metformin combined with chemoradiation would improve HNSCC patient survival compared to historical controls., Materials and Methods: We conducted a Phase I/II prospective, single arm clinical trial in patients with newly diagnosed HNSCC (NCT02949700). Patients received platinum-based chemoradiation in combination with orally dosed metformin at one of 2 doses- 850 mg BID or 1500 mg BID administered during radiation, with a 2-week lead-in phase. Toxicity, disease response and survival metrics were ascertained throughout the study period., Results: A total of 25 patients were evaluable for toxicity and survival; 9 failed to reach the predetermined 70% compliance with the study drug. No dose limiting toxicities were identified in the Phase I component and there were no grade 4 adverse events likely related to metformin throughout the study. The primary outcome for the Phase II component was met with a response rate of 96%. Three-year overall survival was ∼70% in the per protocol p16 + cohort and 0% in the per protocol p16- cohort. Survival among participants with a ≥70% metformin compliance to <70% metformin compliance demonstrated a trend towards improvement in the ≥70% compliance cohort, though this did not reach significance., Conclusion: Metformin is well tolerated during concurrent chemoradiation for HNSCC. Its effectiveness as a chemo-radiosensitizer remains unclear and will require further study with randomized controlled clinical trials in this patient population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: We aimed to operationalize a head and neck microvascular free tissue transfer (MVFTT) program at a Veterans Affairs (VA) hospital with the emphasis on initiating radiotherapy within 6 weeks of surgery for cancer patients and minimizing readmissions., Study Design: Case series., Setting: Tertiary care VA hospital., Methods: A retrospective analysis was performed on consecutive head and neck MVFTT patients from May 1, 2017 and April 30, 2022. Demographics, patient and disease characteristics, per-operative data and postoperative outcomes were recorded from the electronic medical record. We sought to compare our rate of 30-day readmissions with those published in the literature., Results: One hundred and forty-one procedures were performed in the queried timeframe. Eighty-four percent (119) were performed after oncologic resections and 16% (22) were for nononcologic procedures. The rate of total flap loss was <1% and the rate of partial flap loss was 3.5%. For mucosal defects, the fistula rate was 2.3%. The rate of return to the OR for any reason within 30 days was 7.8%. The 30-day readmission rate was 6.4% while the rates reported in the literature range from 13% to 20%. One hundred and four patients required postoperative radiotherapy (PORT) and 76% started PORT within 42 days of surgery., Conclusion: Operationalizing a head and neck MVFTT program with a VA hospital is safe and allows for the successful delivery of multimodality treatment to cancer patients. These resources can be expanded for the care of head and neck cancer treatment sequelae, such as osteoradionecrosis, and other nononcologic patient needs., Competing Interests: Contents do not represent the views of the US Department of Veterans Affairs or the US Government. The authors report no conflicts of interest for the existing work., (© 2023 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Habitat specialization underpins biological processes from species distributions to speciation. However, organisms are often described as specialists or generalists based on a single niche axis, despite facing complex, multidimensional environments. Here, we analysed 236 environmental soil microbiomes across the United States and demonstrate that 90% of >1,200 prokaryotes followed one of two trajectories: specialization on all niche axes (multidimensional specialization) or generalization on all axes (multidimensional generalization). We then documented that this pervasive multidimensional specialization/generalization had many ecological and evolutionary consequences. First, multidimensional specialization and generalization are highly conserved with very few transitions between these two trajectories. Second, multidimensional generalists dominated communities because they were 73 times more abundant than specialists. Lastly, multidimensional specialists played important roles in community structure with ~220% more connections in microbiome networks. These results indicate that multidimensional generalization and specialization are evolutionarily stable with multidimensional generalists supporting larger populations and multidimensional specialists playing important roles within communities, probably stemming from their overrepresentation among pollutant detoxifiers and nutrient cyclers. Taken together, we demonstrate that the vast majority of soil prokaryotes are restricted to one of two multidimensional niche trajectories, multidimensional specialization or multidimensional generalization, which then has far-reaching consequences for evolutionary transitions, microbial dominance and community roles., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity., Methods: We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo-radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab., Results: Patients with HPV-associated tumors and nonsmokers demonstrated improved overall and disease-free survival along with locoregional and distant metastatic control regardless of chemotherapy regimen. Regardless of regimen selection, patients which received a cumulative cisplatin dose ≥200 mg/m 2 had a lower rate of distant metastasis. The HD regimen resulted in a greater fraction (75% vs. 50%) of patients receiving a cumulative cisplatin dose ≥200 mg/m 2 and a comparable measured toxicity burden compared to the LD regimen., Conclusions: Both HD and LD cisplatin regimens can be safely delivered to a Veteran OPSCC patient population which should allow for straightforward application of conclusions drawn from completed and active clinical trials testing cisplatin regimens., Level of Evidence: 4., Competing Interests: The authors have no relevant conflicts of interest to disclose., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Introduction: The incidence of ocular injury associated with maxillofacial trauma remains poorly defined, with reported rates ranging from 0.8% to 92%. Our study aims to more accurately characterize ocular injuries associated with midface fractures., Methods: We performed a retrospective review of 1677 patients from 2015 to 2020 with midface fractures at a Level I trauma center. Isolated nasal bone and frontal process of the maxilla fractures were excluded. Demographic information, mechanism of injury, need for surgery, and ophthalmologic findings were documented. Statistical analysis was conducted using SPSS., Results: 773 patients between the ages of 15 and 92 were identified. Trauma most commonly resulted from assault (63.8%). The association between the mechanism of injury and ocular injury was statistically significant (p = 0.003), with 78.6% of gunshot wounds and 44.3% of assault patients having an ocular injury. The Ophthalmology service evaluated 62.6% of cases preoperatively. Minor ocular injury occurred in 36% of patients, including 46.1% of isolated orbital floor, and 28.2% of zygomaticomaxillary complex fractures. Major ocular injury occurred in 10.5% of patients., Conclusions: Over 10% of patients with midface fractures were found to have major ocular injuries. Ophthalmologic exams should be performed for all patients with midface fractures to guide clinical decision making and prevent further intraoperative ocular insults., Level of Evidence: Level 4. This study represents a retrospective cohort study analyzing ocular injuries detected in patients presenting to a Level I trauma center with maxillofacial fractures between 2015 and 2020 Laryngoscope, 133:1624-1629, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Prostate cancer (PCa) identified incidentally (iPCa) after surgical treatment for symptomatic benign prostatic hyperplasia (BPH) causing lower urinary tract symptoms (LUTS) is considered low risk by the most current guidelines. Management protocols for iPCa are conservative and are identical to other prostate cancers classified as having favorable prognoses. The objectives of this paper are to discuss the incidence of iPCa stratified by BPH procedure, to highlight predictors of cancer progression, and to propose potential modifications to mainstream guidelines for the optimal management of iPCa. The correlation between the rate of iPCa detection and the method of BPH surgery is not clearly defined. Old age, small prostate volume, and high pre-operative prostate-specific antigen (PSA) are associated with an increased likelihood of detecting iPCa. PSA and tumor grade are strong predictors of cancer progression and can be used along with magnetic resonance imaging (MRI) and potential confirmatory biopsies to determine disease management. In instances that iPCa requires treatment, radical prostatectomy (RP), radiation therapy, and androgen deprivation therapy all have oncologic benefits but may be associated with increased risk after the BPH surgery. It is advised that patients with low to favorable intermediate-risk prostate cancer undergo post-operative PSA measurement and prostate MRI imaging before electing to choose between observation, surveillance without confirmatory biopsy, immediate confirmatory biopsy, or active treatment. Subdividing the binary T1a/b cancer staging into more categories with ranging percentages of malignant tissue would be a helpful first step in tailoring the management of iPCa., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Khan et al.)

The study aims to assess the implementation of tobacco control policies in Mexico from 2003 through 2017 using the Tobacco Control Scale (TCS). The TCS is a research tool widely used in the European region. It facilitates assessment of tobacco control policy implementation based on six cost-effective interventions: tobacco taxes, smoke-free policies, advertising bans, public spending on the information campaign, health warnings, and smoking cessation treatment, reflecting results in a total score between 0 and 100. From 2003 through 2017, Mexico's total score improved from 24/100 to 55/100, with substantial progress in raising tobacco taxes, 11 subnational smoke-free laws, and with placement on cigarette packs of large health warnings with pictograms. Progress in tobacco control policies implemented in this period corresponds with a decrease in smoking prevalence across Mexico. This tool is useful for monitoring tobacco policy implementation in low- and middle-income countries and be used for advocacy purposes to enforce and improve tobacco control legislation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells (MuNI) and targeted transcriptomics. P16 was a dominant determinant of LRC, DFS and OS, but tobacco exposure, OP-TIL and MuNI risk features correlated with clinical outcomes independent of p16 status and the combination of p16, OP-TIL and MuNI generated a better stratification of OPSCC risk compared to individual parameters. Differential gene expression (DEG) analysis demonstrated overlap between MuNI and OP-TIL and identified genes involved in DNA repair, oxidative stress response and tumor immunity as the most prominent correlates with survival. Alteration of inflammatory/immune pathways correlated strongly with all risk features and oncologic outcomes. This suggests that development of OPSCC consists of an intersection between multiple required and permissive oncogenic and immunologic events which may be mechanistically linked. The strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status may provide opportunities for further biomarker development and precision oncology approaches incorporating immune checkpoint inhibitors for maximal anti-tumor efficacy., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Background: Patients on chronic pharmacologic immunosuppressive therapy are at increased risk of wound infection and complications after surgery. There is a paucity of data examining perioperative complications after microvascular free tissue transfer (MVFTT) reconstruction of the head and neck in this patient population., Methods: Retrospective cohort study performed at two tertiary referral centers between August 2016 and May 2020., Results: Nine hundred and seventy-nine patients underwent MVFTT during the study period; of these 47 (5%) patients were taking chronic immunosuppressive medications. The most common indications for immunosuppression were solid organ transplant and autoimmune disease. Fourteen (30%) patients had surgical complications within 30 days of surgery: 8 (17%) wound dehiscences, 6 (12%) hematomas, and 2 (4%) surgical site infections. There was one total and one partial flap failure with a 30-day reoperation rate of 4%., Conclusions: MVFTT of the head and neck appears to be safe in patients on chronic pharmacologic immunosuppression., (© 2022 Wiley Periodicals LLC.)

Purpose: High-risk oropharyngeal squamous cell carcinoma (OPSCC) associated with tobacco exposure remains difficult to treat due to high rates of locoregional recurrence similar to oral cavity squamous cell carcinoma (OCSCC). Current NCCN guidelines allow for surgical management of this disease, but oncologic and functional data in the modern era remain scarce. We sought to compare and contrast oncologic and functional considerations for surgical management of OPSCC and OCSCC in a cohort of Veterans., Materials and Methods: We conducted a retrospective review of patients treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2017 and 2020, treated using a homogenous, multi-modality algorithm., Results: OPSCC tumors presented with a higher rate of perineural invasion (p < 0.05) and extranodal extension (p = 0.02) compared to OCSCC tumors. Compliance with NCCN guidelines for adjuvant treatment were lower for OPSCC patients primarily due to a higher rate of previous irradiation; re-irradiation could be delivered in 75% of patients when recommended by NCCN guidelines. Total glossectomy was accompanied by concomitant total laryngectomy in 100% of OPSCC patients and 0% of OCSCC., Conclusion: Surgical resection and free flap reconstruction of high-risk OPSCC generates oncologic outcomes comparable to OCSCC with comparable complication rates but a lower overall functional status. Reconstruction focused on rapid healing allows for high-rates of re-irradiation and minimal treatment delays., Level of Evidence: level 4., (Published by Elsevier Inc.)

Abstract: Hernandez, DJ, Healy, S, Giacomini, ML, and Kwon, YS. Effect of rest interval duration on the volume completed during a high-intensity bench press exercise. J Strength Cond Res 35(11): 2981-2987, 2021-Between-set rest intervals (RIs) are one of the most important variables in resistance training; however, no known research has investigated the effects of RIs greater than 5 minutes during high-intensity strength training. The purpose of this research was to examine the effects of 3 different RIs on repetition sustainability and training volume (sets × reps × resistance) during a high-intensity bench press exercise. Fifteen resistance-trained male subjects (mean ± SD, age = 25.5 ± 4.5 years, and bench press 1 repetition maximum [1RM] ratio [1RM/body mass] = 1.39 ± 0.1) completed 3 experimental sessions, during which 4 sets of the bench press were performed with 85% of 1RM load. Subjects performed the bench press using 3 different RIs in a random counterbalanced design. Data were analyzed using both a one- and two-way analysis of variance with repeated measures. As sets progressed, repetitions were significantly different (p < 0.05) between all RIs, and only the 8-minute RI (p < 0.05) allowed for the complete sustainability of repetitions over 4 consecutive sets. Subjects attained the greatest training volume (p < 0.05) using an 8-minute RI between sets compared with a 2- or 5-minute RI. Similarly, a significantly greater training volume was achieved using the 5-minute RI compared with the 2-minute RI. Resistance-trained men, with the goal of greater volume during strength training, would benefit from longer RIs, specifically using an 8-minute RI between 4 consecutive sets of a bench press exercise., (Copyright © 2020 National Strength and Conditioning Association.)

Scapula tip free flaps (STFFs) have become an increasingly popular option for head and neck reconstruction. The aim of this study is to demonstrate the feasibility of using the STFF in a horizontal orientation to take advantage of the anatomy of the scapular tip bone to re-create a mandibular symphysis. Eight patients underwent oromandibular reconstruction with a horizontally oriented STFF between October 2016 and June 2020. Virtual surgical planning was used to design the bony reconstruction in 6 cases. Primary outcomes, including flap survival, complications, and return to oral diet, were collected. Cephalometric measurements were obtained to compare preoperative and postoperative mandibular projection and width. All flaps survived without compromise, and no fistulas developed postoperatively. Seven patients returned to taking an oral diet. Cephalometric analysis revealed comparable measurements between preoperative and postoperative mandibles and reconstructed mandibles, respectively. STFFs may be oriented horizontally to reconstruct large anterior mandibular defects with satisfactory results.

This Perspective reviews recent efforts toward selfconsistent calculations of ground-state energies within the random phase approximation (RPA) in the (generalized) Kohn-Sham (KS) density functional theory context. Since the RPA correlation energy explicitly depends on the non-interacting KS potential, an additional condition to determine the energy as a functional of the density is necessary. This observation leads to the concept of functional selfconsistency (FSC), which requires that the KS density equals the interacting density defined as the functional derivative of the ground-state energy with respect to the external potential. While all existing selfconsistent RPA schemes violate FSC, the recent generalized KS semicanonical projected RPA (GKS-spRPA) method takes a step toward satisfying it. This leads to systematic improvements in densities, binding energy curves, reference state stability, and molecular properties compared to non-selfconsistent RPA as well as optimized effective potential RPA. GKS-spRPA orbital energies accurately approximate valence and core ionization potentials, and even electron affinities of non-valence bound anions. The computational cost and performance of GKS-spRPA are compared to those of related selfconsistent schemes, including GW and orbital optimization methods, and limitations are discussed. Large differences between KS and interacting densities observed in the absence of FSC and the well-rounded performance of GKS-spRPA suggest that the KS potential as a density functional should be defined via the FSC condition for explicitly potential-dependent density functionals.

Environmental stress is increasing worldwide, yet we lack a clear picture of how stress disrupts the stability of microbial communities and the ecosystem services they provide. Here, we present the first evidence that naturally-occurring microbiomes display network properties characteristic of unstable communities when under persistent stress. By assessing changes in diversity and structure of soil microbiomes along 40 replicate stress gradients (elevation/water availability gradients) in the Florida scrub ecosystem, we show that: (1) prokaryotic and fungal diversity decline in high stress, and (2) two network properties of stable microbial communities-modularity and negative:positive cohesion-have a clear negative relationship with environmental stress, explaining 51-78% of their variation. Interestingly, pathogenic taxa/functional guilds decreased in relative abundance along the stress gradient, while oligotrophs and mutualists increased, suggesting that the shift in negative:positive cohesion could result from decreasing negative:positive biotic interactions consistent with the predictions of the Stress Gradient Hypothesis. Given the crucial role microbiomes play in ecosystem functions, our results suggest that, by limiting the compartmentalization of microbial associations and creating communities dominated by positive associations, increasing stress in the Anthropocene could destabilize microbiomes and undermine their ecosystem services.

Background: Delays in treatment of head and neck squamous cell carcinoma (HNSCC) are known to increase disease recurrence, generating the need for additional salvage treatment, often with immunotherapy., Methods: Three treatment metrics were identified: time from diagnosis to treatment initiation (TTI), time from surgery to postoperative radiotherapy (surg → PORT), and total treatment package time (TPT). Financial toxicity was calculated using hazard ratios, pembrolizumab cost, and dosing data for a Veterans Health Administration (VHA) institutional cohort (n = 338) and a standardized cohort (n = 100)., Results: Estimated financial toxicity for the VHA cohort was $2 047 407, $316 545, and $1 114 101 for TTI, surg → PORT, and TPT, respectively. Estimated financial toxicity for the standardized patient cohort was $454 028, $544 576, and $1 879 628 for TTI, surg → PORT, and TPT, respectively., Conclusions: Failure to meet established HNSCC treatment metrics generates significant, yet avoidable, institutional financial toxicity which is particularly relevant to integrated single-payer systems such as the VHA in the modern immunotherapy era., (© 2020 Wiley Periodicals LLC.)

Objective: To characterize pharyngocutaneous fistula (PCF) rates and functional outcomes following microvascular free tissue transfer (MVFTT) reconstruction of salvage total laryngectomy (STL) with a review of two different flap inset techniques and a review of the literature., Methods: Retrospective review., Results: Review of the literature revealed 887 patients who underwent STL MVFTT from 14 references. Ninety-six STL MVFTTs were performed by the authors, with 36 (38%) patients undergoing multilayer fascial underlay (MLFU) closure and 60 (62%) a standard single layer closure (SLC). One (3%) PCF occurred in the MLFU group compared to 12 (20%) in the SLC cohort (P = .03). Postoperative gastrostomy (G)-tube dependence was lower following MLFU closure compared to SLC (25% vs. 57%, P < .01), whereas pharyngoesophageal stricture (PES) (28% vs. 38%), tracheoesophageal puncture (TEP) placement (42% vs. 42%), and TEP usage (87% vs. 88%) did not significantly differ (P > .05). Compared to pooled rates from the literature, patients who underwent a MLFU MVFTT inset technique demonstrated significantly lower PCF incidence (3% vs. 23%, P < .01) without significant differences in PES (28% vs 23%, P = .55), G-tube dependence (25% vs. 23%, P = .25), or TEP placement (42% vs. 59%, P = .09)., Conclusion: Despite MVFTT reconstruction after STL, G-tube dependence, PCF formation, and limitations of speaking rehabilitation (TEP) remain a significant issue. Modification of MVFTT inset may provide an opportunity to reduce PCF incidence without affecting other functional outcomes., Level of Evidence: 4 Laryngoscope, 131:E875-E881, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction  Standardized reconstruction protocols for large open anterior skull base defects with dural resection are not well described. Here we report the outcomes and technique of a multilayered reconstructive algorithm utilizing local tissue, dural graft matrix, and microvascular free tissue transfer (MVFTT) for reconstruction of these deformities. Design  This study is a retrospective review. Results  Eleven patients (82% males) met inclusion criteria, with five (45%) having concurrent orbital exenteration and eight (73%) requiring maxillectomy. All patients required dural resection with or without intracranial tumor resection, with the average dural defect being 36.0 ± 25.9 cm 2 . Dural graft matrices and pericranial flaps were used for primary reconstruction of the dural defects, which were then reinforced with free fascia or muscle overlay by means of MVFTT. Eight (73%) patients underwent anterolateral thigh MVFTT, with the radial forearm, fibula, and vastus lateralis comprising the remainder. Average total surgical time of tumor resection and reconstruction was 14.9 ± 3.8 hours, with median length of hospitalization being 10 days (IQR: 9.5, 14). Continuous cerebrospinal fluid drainage through a lumber drain was utilized in 10 (91%) patients perioperatively, with an average length of indwelling drain of 5 days. Postoperative complications occurred in two (18%) patients who developed asymptomatic pneumocephalus that resolved with high-flow oxygen therapy. Conclusion  A standardized multilayered closure technique of dural graft matrix, pericranial flap, and MVFTT overlay in the reconstruction of large open anterior craniofacial dural defects can assist the reconstructive team in approaching these complex deformities and may help prevent postoperative complications., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Objective: Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rapidly increasing, as are survival rates, in large part due to the human papillomavirus (HPV). Treatment intensity, however, has remained unchanged, making treatment-related toxicity (i.e., dysphagia) a critical problem for an increasing number of patients. The primary objective of this study was to determine whether pretreatment objective swallowing measures can predict percutaneous fluoroscopic guided gastrostomy tube (PFG) utilization during OPSCC treatment., Methods: Forty-one newly diagnosed OPSCC patients treated with radiation underwent evaluation of swallow function with modified barium swallow study (MBSS) prior to and at completion of radiation treatment using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST); a subset of patients were evaluated using the MD Anderson Dysphagia Inventory (MDADI)., Results: Patients were male (100%), primarily Caucasian (85.4%) and p16 positive (85.4%) with mean age of 65.7 years. PFG were placed in 70.7% patients (n = 29) and used by 63.4% (n = 26). Pre- and post-treatment DIGEST scores were associated with T-classification (t = -2.9, p = .001, t = -2.7, p = .01) and indicated deteriorating swallow function during treatment (mean change = 0.46 [t = -2.7, p = .01]). DIGEST and MDADI scores were generally not associated with patient PFG utilization. DIGEST and MDADI scores were significantly correlated prior to, but not following completion of treatment., Conclusion: Pre-treatment DIGEST and patient reported swallowing outcomes (MDADI) can be useful in identifying patients with unsafe and/or grossly inefficient swallowing function. However, objectively measured swallow function was not associated with PFG utilization. Development of PFG placement algorithms (reactive vs. prophylactic) therefore require additional inputs/metrics., Level of Evidence: 4 Laryngoscope, 130:2153-2159, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

All plants host diverse microbial assemblages that shape plant health, productivity, and function. While some microbial effects are attributable to particular symbionts, interactions among plant-associated microbes can nonadditively affect plant fitness and traits in ways that cannot be predicted from pairwise interactions. Recent research into tripartite plant-microbe mutualisms has provided crucial insight into this nonadditivity and the mechanisms underlying plant interactions with multiple microbes. Here, we discuss how interactions among microbial mutualists affect plant performance, highlight consequences of biotic and abiotic context-dependency for nonadditive outcomes, and summarize burgeoning efforts to determine the molecular bases of how plants regulate establishment, resource exchange, and maintenance of tripartite interactions. We conclude with four goals for future tripartite studies that will advance our overall understanding of complex plant-microbial interactions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Multiple population studies have shown racial discrepancies in head and neck cancer treatment and outcomes. We sought to characterize the impact of race on clinical outcomes for patients with early glottic squamous cell carcinoma (SCC) in a tertiary institution which provides equivalent access to care., Methods: We retrospectively reviewed all early glottic (T1-T2) squamous cell carcinoma at a single institution, the Michael E. DeBakey Veterans' Administration Medical Center (MEDVAMC). Data collected included demographic information, primary and adjuvant treatment modalities, time to diagnosis, time to treatment, recurrences, recurrence treatment modality, secondary malignancies, recurrence-free survival (RFS), and overall survival (OS)., Results: One hundred seventeen patients with a primary diagnosis of T1-T2 glottic squamous cell carcinoma were included. Black and white patients demonstrated equivalent rates of recurrence, RFS, and OS. There was no significant difference in treatment delivery by race for all recorded parameters. T1b tumors were associated with an increased risk of recurrence which did not translate into a statistically significant decrease in RFS or OS. Surgical treatment was associated with increased recurrence but similar RFS and OS compared to radiation-based treatment. Secondary malignancies were common; 12% of patients were diagnosed with a second primary lung cancer during the study period., Conclusion: At our institution, race did not impact survival when access to care, treatment selection, and delivery are equivalent for early glottic SCC. Secondary lung cancer is a critical risk factor for mortality in this patient group and requires long-term surveillance and monitoring., Level of Evidence: 4 Laryngoscope, 130:1733-1739, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Advanced laryngeal squamous cell carcinoma remains associated with approximately 50% mortality at 5 years. Delivery of multimodality treatment remains critical to maximizing survival for this disease, but achieving this at a national level remains a difficult undertaking, particularly in under- and uninsured patients as well as minority patients. We sought to evaluate laryngeal cancer treatment delivery and clinical outcomes in a predominantly minority and underserved cohort of largely under- and uninsured patients in a county hospital., Study Design: Retrospective cohort study., Setting: Tertiary care county hospital in Houston, Texas., Subjects and Methods: Patients (N = 210) with a new diagnosis of laryngeal squamous cell carcinoma treated between 2005 and 2015 were included in a retrospective analysis of patient demographics, tumor and treatment characteristics, and oncologic outcomes., Results: The majority of patients presented with advanced disease (T4 = 43%, N>0 = 45%). Treatment selection was compliant with National Comprehensive Cancer Network guidelines in 81% of cases, but 76% of patients who required adjuvant radiotherapy were unable to start it within 6 weeks postsurgery. Overall survival and disease-free survival were 52% and 63% for the entire cohort, respectively. Supraglottic subsite and nodal metastases were significantly associated with decreased overall survival and disease-free survival. Race/ethnicity and insurance status were not associated with worse oncologic outcomes., Conclusion: Under- and uninsured patients often present with advanced laryngeal cancer. Oncologic outcomes in this cohort of patients is similar to that of other published series. Moreover, tumor characteristics rather than demographic variables drive oncologic outcomes for the predominantly minority and underserved patients seeking care in our tertiary care county hospital.

Objective: To explore sociogeographical inequalities in the availability and distribution of ear, nose and throat specialists (ENTs) in 15 Latin American (LA) countries., Design: Ecological., Setting: Spanish and Portuguese-speaking countries of LA.The number of registered ENTs in 2017 was obtained from the National ENT Society in each country., Outcome Measures: The ENT rate/million population was calculated at the national and subnational (eg, state) level. Three measures were calculated to assess subnational distributive inequality of ENTs: (1) absolute and (2) relative index of dissimilarity; and (3) concentration index (using the Human Development Index as the equity stratifier). Finally, the ratio of ENTs/million population in the capital area compared with the rest of the country was calculated., Results: There was more than a 30-fold difference in the number of ENTs/million population across the included countries-from 61.0 in Argentina (95% CI 58.7 to 63.4) to 2.8 in Guatemala (95% CI 2.1 to 3.8). In all countries, ENTs were more prevalent in advantaged areas and in capital areas. To attain distributive equality, Paraguay would need to redistribute the greatest proportion of its ENT workforce (67.3%; 95% CI 57.8% to 75.6%) and Brazil the least (18.5%; 95% CI 17.6% to 19.5%)., Conclusions: There is high inequality in the number and distribution of ENTs between and within the 15 studied countries in LA. This evidence can be used to inform policies that improve access to ear and hearing services in the region, such as scale-up of training of ENTs and incentives to distribute specialists equally. These actions to reduce inequities, alongside addressing the social determinants of ear and hearing health, are essential to realise Universal Health Coverage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives/hypothesis: Intraoperative experience is an essential element of surgical training, but has the potential to impact patient outcomes. The purpose of this study was two-fold: 1) to evaluate the effect of resident involvement on morbidity and mortality following otolaryngology procedures and 2) to examine the influence of resident training level on the same outcomes., Study Design: Retrospective cohort study., Methods: This study reviewed 2,320,920 patients captured in the 2005 to 2012 National Surgical Quality Improvement Program databases to identify surgical otolaryngology cases. Outcomes of interest included surgical complications, medical complications, and mortality. Cases with and without resident involvement were propensity matched (caliper = 0.2) to account for nonrandomized assignment, and data were subject to multivariate logistic regression analyses., Results: Residents participated in 38.4% of the 20,307 cases identified. Cases with resident involvement demonstrated longer operative duration (178.8 minutes vs. 80.1 minutes, P < .001), increased surgical complexity (23.5 relative value units [RVU] vs. 12.4 RVU, P < .001) and greater overall morbidity burden. Logistic regression analyses of the matched cohort revealed that resident participation did not independently increase morbidity (odds ratio [OR] = 0.969, P = .751) or mortality (OR = 0.893, P = .758). A separate logistic regression analysis of the unmatched cohort using resident postgraduate year showed that training level did not confer differential risk to patients., Conclusions: Our data indicate that resident involvement does not increase the risk of morbidity or mortality, and that trainees are being assigned to appropriate cases for their level of experience. These findings suggest that the contemporary paradigm of graduate otolaryngology surgical education does not negatively impact patient outcomes., Level of Evidence: 2c Laryngoscope, 126:602-607, 2016., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Fundamentals of Laparoscopic Surgery (FLS) certification is required for general surgery. The recommended practice for learning FLS is to practice tasks one at a time until proficient (blocked practice). Learning theory suggests that interleaved practice, a method in which tasks are rotated rather than learned one at a time, may result in superior learning., Method: Residents were randomized into 1 of 2 groups: blocked practice or interleaved practice. We compared the performance of residents across groups over 20 trials of each of 4 FLS tasks (peg transfer, pattern cut, extracorporeal suture, and intracorporeal suture). Four weeks later, participants returned to the laboratory and completed 2 additional trials of each of the 4 tasks., Results: Performance on each of the tasks improved with increased practice. The interleaved group showed significantly better performance on the peg transfer task; trends favoring the interleaved group resulted for the other tasks. Standardized mean differences in favor of the interleaved group were substantial both at the end of practice and at follow-up (with the exception of the pattern cut)., Conclusion: Interleaved practice appears to have advantages over blocked practice in developing and retaining FLS skills. We encourage others to experiment with the method to confirm our findings., (Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Cellular angiofibromas (CAF) are rare, benign soft-tissue tumours. The diagnosis of CAF is important given the heavy resemblance to other tumours. Herein, we describe a case of a rapidly growing, very large (13.5 cm) CAF located in the deep pelvis of a middle-aged male who presented with difficulty voiding.

Purpose: We compared cuff sites and assessed anatomical and manometric differences between the transscrotal and perineal approaches to artificial urinary sphincter placement in fresh male cadavers., Materials and Methods: Artificial urinary sphincter implantation using perineal and transscrotal incisions was performed in 15 fresh male cadavers. The artificial urinary sphincter cuffs were placed as proximal as possible using each approach. After measuring urethral circumference at each cuff site, an appropriately sized cuff was placed at each location. The 61 to 70 cm H(2)O pressure reservoir and control pump were then connected to the cuffs. Retrograde leak point pressure was assessed sequentially across each cuff. The paired t test was used to compare urethral circumference and retrograde leak point pressure between the 2 approaches., Results: Mean urethral circumference using the perineal and transscrotal approaches was 5.38 (range 3.2 to 7.5) and 3.81 cm (range 3 to 4.5), respectively (p <0.0001, 95% CI of difference 0.99-2.13). Mean retrograde leak point pressure using the perineal and transscrotal approaches was 90.1 and 64.9 cm H(2)O, respectively (p = 0.0002, 95% CI of difference 13.7-33.5). On visual inspection of cuff sites, the perineal approach was more proximal on the urethra than the transscrotal approach., Conclusions: While the transscrotal approach to artificial urinary sphincter placement has the advantage of technical ease, the anatomical and manometric findings of this cadaver study suggest that the perineal approach offers a more proximal cuff location, more robust urethral size and more effective urethral coaptation than the transscrotal approach., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objective: The literature lacks knowledge about information preferences and decision-making in young prostate cancer patients. This study provides insight into information sources consulted and factors dictating treatment decision-making in young prostate cancer patients., Methods: Subjects were identified from pathology consult service of a National Center of Excellence. Questionnaires were mailed to 986 men, under 50 years of age, diagnosed with Gleason score 6 prostate cancer between 2001 and 2005., Results: Four hundred ninety-three men responded. The most common primary therapies were surgery 397 (81.4%), radiation 52 (10.7%), and active surveillance (AS) 26 (5.3%). Participants with at least some college education (P = 0.003) or annual income >$100,000 (P = 0.003) were more likely to consult three or more doctors. Amongst all treatments, "doctor's recommendation" was the most influential information source, although relatively less important in the AS group. Internet was the second most frequent information source. Participants with higher education (P = 0.0003) and higher income (P = 0.002) considered sexual function more important while making a treatment choice. Only 2% of the men preferred a passive role in the decision-making. Informed decision-making was preferred more by patients who chose radiation and AS while shared decision-making was preferred more by surgery patients (P < 0.05). The majority (89%) of the respondents did not regret their decision. No difference in satisfaction levels was found between different treatment modalities., Conclusions: This study provides insight into information sources consulted, such as the greater internet use, and various factors dictating treatment decision-making in young prostate cancer patients. There was an overall very high satisfaction rate regardless of the therapy chosen., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Protein absorption occurs as di- and tri-peptides via H(+)/peptide co-transporter-1 (PepT1)., Aim: The aim of this study is to identify mechanisms of ileal adaptation after massive proximal enterectomy., Hypothesis: Ileal adaptation in uptake of peptides is mediated through upregulation of PepT1 gene expression., Study Design: Rats underwent 70% jejunoileal resection. Total mucosal cellular levels of messenger RNA (mRNA) and protein and transporter-mediated uptake per centimeter of the di-peptide glycyl-sarcosine (Gly-Sar) were compared in remnant ileum 1 and 4 weeks postoperatively to control and to 1-week sham laparotomy rats. Histomorphology, food consumption, and weights of rats were monitored., Results: After 70% resection, although mRNA per cell for PepT1 decreased at 1 week (p = 0.002), expression of mRNA at 4 weeks and protein at 1 and 4 weeks in remnant ileum were unchanged (p > 0.1). Ileal Gly-Sar uptake (V (max)-nanomoles per centimeter per minute, i.e., number of transporters per centimeter) increased at 1 and 4 weeks compared to control and 1-week sham (p < 0.05 each); K (m) (i.e., transporter function) was unchanged. Villous heights (millimeters) in remnant ileum increased at 1- and 4-week time points over controls (0.45 and 0.57 vs 0.21, resp; p < 0.001)., Conclusions: Ileal adaptation to proximal resection for peptide absorption occurs through cellular proliferation (hyperplasia) and not through cellular upregulation of PepT1 mRNA or protein per enterocyte.

Prior studies of radical prostatectomies have reported a small percentage of men with biochemical progression after radical prostatectomy showing organ-confined, Gleason Score 6. One might predict that this should virtually never occur. We identified 2551 (1983-2005) radical prostatectomies coded by the urologists at our institution as pathologically organ-confined, Gleason score 6 cancer with more than 1 year of follow-up. We re-examined histopathogically the serially sectioned and completely embedded radical prostatectomy specimens of 38 men who developed biochemical recurrence defined as a single prostate-specific antigen level of 0.2 ng/mL or greater. In 27 (71%) of 38 of cases, pathology re-review showed higher grade or stage than coded by the urologists. These included 10 cases of organ-confined with Gleason pattern 4 as either the primary or secondary pattern; 9 cases of organ-confined, Gleason score 6 with tertiary pattern 4 (in 4 cases, tertiary pattern 4 was described in the initial pathology report); 5 cases of Gleason score 7 plus extraprostatic extension; 1 case of Gleason score 6 with focal extraprostatic extension; and 2 cases with positive margins due to intraprostatic incision (listed in the initial pathology report). The remaining 11 cases were true organ-confined, Gleason score 6 tumors, but none of the patients developed systemic disease. Most prior reports of organ-confined, Gleason score 6 with progression are undergraded (upgrading with revision of Gleason system), understaged (difficulty recognizing focal extraprostatic extension), or suffer from situations with ambiguous staging (intraprostatic incision) or grading (tertiary pattern 4 or 2 + 4 = 6). Even for the rare true organ-confined, Gleason score 6 (no pattern 4) tumor with supposed biochemical progression, some may be false-positive progression based on low post-radical prostatectomy prostate-specific antigen levels and minute tumors that seem highly improbable to progress. With accurate pathologic evaluation, men with organ-confined, Gleason score 6 (no pattern 4) prostate cancer can be told that their risk of progression is very rare (0.4%).

Background: Protein is absorbed predominantly as di/tripeptides via H(+)/peptide cotransporter-1 (PEPT1). We demonstrated previously diurnal variations in expression and function of duodenal and jejunal but not ileal PEPT1; neural regulation of this pattern is unexplored., Hypothesis: Complete abdominal vagotomy abolishes diurnal variations in gene expression and transport function of PEPT1., Methods: Twenty-four rats maintained in a 12-h light/dark room [6AM-6PM] underwent abdominal vagotomy; 24 other rats were controls. Four weeks later, mucosal levels of mRNA and protein were measured at 9AM, 3PM, 9PM, and 3AM (n = 6 each) by quantitative real-time PCR and Western blots, respectively; transporter-mediated uptake of dipeptide (Gly-Sar) was measured by the everted-sleeve technique., Results: Diurnal variation in mRNA, as in controls, was retained post-vagotomy in duodenum and jejunum (peak at 3PM, p < 0.05) but not in ileum. Diurnal variations in expression of protein and Gly-Sar uptake, however, were absent post-vagotomy (p > 0.3). Similar to controls, maximal uptake was in jejunum after vagotomy (V (max), nmol/cm/min: jejunum vs. duodenum and ileum; 163 vs. 88 and 71 at 3AM; p < 0.04); K (m) remained unchanged., Conclusions: Vagal innervation appears to mediate in part diurnal variations in protein expression and transport function of PEPT1, but not diurnal variation in mRNA expression of PEPT1.

Renal cell carcinoma (RCC) comprises about 5% of pediatric renal neoplasms. It has been recognized as a second malignancy in multiple reports. It is generally symptomatic at diagnosis, and most children with RCC present with more locally advanced disease than do adults. Contemporary investigation of pediatric RCC has demonstrated that a large percentage of these tumors bear cytogenetic translocations involving the MiT family of transcription factors. Surgical therapy for these children resembles operative intervention for adult RCC, though debate continues about the precise role of lymph node dissection. There are no adequately powered studies to support conclusions about adjuvant or neoadjuvant chemotherapy for children with RCC. This may be ameliorated by a multi-institutional protocol which is enrolling patients.

Objectives: To develop a logistic regression-based model to predict prostate cancer biopsy at, and compare its performance to the risk calculator developed by the Prostate Cancer Prevention Trial (PCPT), which was based on age, race, prostate-specific antigen (PSA) level, a digital rectal examination (DRE), family history, and history of a previous negative biopsy, and to PSA level alone., Patients and Methods: We retrospectively analysed the data of 1280 men who had a biopsy while enrolled in a prospective, multicentre clinical trial. Of these, 1108 had all relevant clinical and pathological data available, and no previous diagnosis of prostate cancer. Using the PCPT risk calculator, we calculated the risks of prostate cancer and of high-grade disease (Gleason score > or =7) for each man. Receiver operating characteristic (ROC) curves for the risk calculator, PSA level and the novel regression-based model were compared., Results: Prostate cancer was detected in 394 (35.6%) men, and 155 (14.0%) had Gleason > or =7 disease. For cancer prediction, the area under the ROC curve (AUC) for the risk calculator was 66.7%, statistically greater than the AUC for PSA level of 61.9% (P < 0.001). For predicting high-grade disease, the AUCs were 74.1% and 70.7% for the risk calculator and PSA level, respectively (P = 0.024). The AUCs increased to 71.2% (P < 0.001) and 78.7% (P = 0.001) for detection and high-grade disease, respectively, with our novel regression-based models., Conclusions: ROC analyses show that the PCPT risk calculator modestly improves the performance of PSA level alone in predicting an individual's risk of prostate cancer or high-grade disease on biopsy. This predictive tool might be enhanced by including percentage free PSA and the number of biopsy cores.