Surgical Outcomes in Zenker Diverticula: A Multicenter, Prospective, Longitudinal Study.

OBJECTIVE: To compare improvement in patient-reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD). METHODOLOGY: Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10-item Eating Assessment Tool (EAT-10) pre- and post-procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t-test, Wilcoxon rank sum test or chi-square test, as appropriate. RESULTS: One hundred and forty-seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT-10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT-10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow-up was 86 and 97.5 days, respectively. CONCLUSION: Both endoscopic and open surgical management of ZD provide significant improvement in patient-reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:97-102, 2024.

Postoperative Care of Zenker Diverticula: Contemporary Perspective from the Prospective OUtcomes Cricopharyngeaus Hypertonicity (POUCH) Collaborative.

OBJECTIVES: The aim of the study was to identify trends in postoperative management of persons undergoing surgery for Zenker diverticula (ZD) by evaluating length of stay (LOS), diet on discharge, and imaging with or without surgical complication. METHODS: Prospectively enrolled adult patients with cricopharyngeal muscle dysfunction with diverticula undergoing surgery from August 1, 2017 to February 1, 2023 were included. Data were extracted from a multi-institutional REDCap database, summarizing means, medians, percentages, and frequencies. Fisher's exact or chi squared analyses were utilized, as appropriate, to compare subsets of data. Descriptive analysis assessed differences in clinical course and the relationship to postoperative management. RESULTS: There were 298 patients with a mean (standard deviation) age of 71.8 (11.2) years and 60% male. Endoscopic surgery was performed in 79.5% (237/298) of patients versus 20.5% (61/298) open surgery. Sixty patients (20.1%) received postoperative imaging, with four leaks identified. Complications were identified in 9.4% of cases (n = 29 complications in 28 patients), more commonly in open surgery. Most (81.2%) patients were discharged within 23 h. About half of patients (49%) were discharged from the hospital on a pureed/liquid diet; 36% had been advanced to a soft diet. In patients without complications, LOS was significantly longer following open cases (p = 0.002); postoperative diet was not different between open and endoscopic (p = 0.26). CONCLUSIONS: Overall, most patients are discharged within 23 h without imaging. However, LOS was affected by surgical approach. Postoperative complications are different in endoscopic versus open surgery. Complications with either approach were associated with prolonged LOS, need for imaging, and diet restriction. LEVEL OF EVIDENCE: Level III Laryngoscope, 134:2678-2683, 2024.

Comparison Between Custom Smartphone Acoustic Processing Algorithms and Praat in Healthy and Disordered Voices.

OBJECTIVE: The aim of this study was to understand the relationship between temporal and spectral-based acoustic measures derived using Praat and custom smartphone algorithms across patients with a wide range of vocal pathologies. METHODS: Voice samples were collected from 56 adults (11 vocally healthy, 45 dysphonic, aged 18-80 years) performing three speech tasks: (a) sustained vowel, (b) maximum phonation, and (c) the second and third sentences of the Rainbow passage. Data were analyzed to extract mean fundamental frequency (fo), maximum phonation time (MPT), and cepstral peak prominence (CPP) using Praat and our custom smartphone algorithms. Linear regression models were calculated with and without outliers to determine relationships. RESULTS: Statistically significant relationships were found between the smartphone algorithms and Praat for all three measures (r2 = 0.68-0.95, with outliers; r2 = 0.80-0.98, without outliers). An offset between CPP measures was found where Praat values were consistently lower than those computed by the smartphone app. Outlying data were identified and described, and findings indicated that speakers with high levels of clinician-perceived dysphonia resulted in smartphone algorithm errors. CONCLUSIONS: These results suggest that the proposed algorithms can provide measurements comparable to clinically derived values. However, clinicians should take caution when analyzing severely dysphonic voices as the current algorithms show reduced accuracy for measures of mean fo and MPT for these voice types.

Impact of naturalistic smartphone positioning on acoustic measures of voicea).

Smartphone technology has been used for at-home health monitoring, but there are few available applications (apps) for tracking acoustic measures of voice for those with chronic voice problems. Current apps limit the user by restricting the range of smartphone positions to those that are unnatural and non-interactive. Therefore, we aimed to understand how more natural smartphone positions impacted the accuracy of acoustic measures in comparison to clinically acquired and derived measures. Fifty-six adults (11 vocally healthy, 45 voice disordered, aged 18-80 years) completed voice recordings while holding their smartphones in four different positions (e.g., as if reading from the phone, up to the ear, etc.) while a head-mounted high-quality microphone attached to a handheld acoustic recorder simultaneously captured voice recordings. Comparisons revealed that mean fundamental frequency (Hz), maximum phonation time (s), and cepstral peak prominence (CPP; dB) were not impacted by phone position; however, CPP was significantly lower on smartphone recordings than handheld recordings. Spectral measures (low-to-high spectral ratio, harmonics-to-noise ratio) were impacted by the phone position and the recording device. These results indicate that more natural phone positions can be used to capture specific voice measures, but not all are directly comparable to clinically derived values.

A Novel Instrument Holder to Improve Operative Efficiency in Endoscopic Laryngeal and Airway Surgery.

OBJECTIVE: Receiving instruments from surgical technicians during endoscopic laryngeal and airway microsurgery (ELAM) has challenges including repeated, expeditious handling of delicate instruments and passing them to the surgeon's hand opposite of where the surgical assistant is standing. Optimizing this interaction may reduce surgical errors and improve operative efficiency. METHODS: A proprietary ELAM instrument holder was attached to both sides of the operating room bed. The device consisted of an articulating arm with custom silicone inserts mounted on a tray (storing up to three endoscopic instruments). ELAM cases were randomized to be performed either with (device) or without the holder (control). Using custom software, instrument pass time (IPT), instrument drop rate (IDR), and communication errors (eg handing incorrect instruments) were manually recorded. Qualitative use metrics relating to overall device satisfaction were also obtained. RESULTS: Data were collected from 25 device and 23 control cases among three different laryngologists. Average IPT was nearly three times quicker for the device (0.80 s, n = 1175 passes) compared with controls (2.09 s, n = 1208 passes) [p < 0.001]. IPT interquartile range was five times higher for control (1.65 s) versus device cases (0.42 s). IDR was not significantly different [p = 0.48]; however, device cases had significantly lower communication errors compared to control cases [p = 0.01]. Surgeons and surgical assistants were similarly satisfied with the device on a 5-point Likert scale (mean: 4.2/5, standard deviation: 0.92). CONCLUSION: The proposed endoscopic instrument holder can improve ELAM operative workflow by reducing instrument passing time and variability without increasing IDR. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3492-3498, 2023.

Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11-Associated Recurrent Respiratory Papillomatosis.

OBJECTIVE: To evaluate the safety, immunogenicity, and efficacy of INO-3107, a DNA immunotherapy designed to elicit targeted T-cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433). METHODS: Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO-3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post-INO-3107 and cellular immune responses. RESULTS: An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO-3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO-3107 induced durable cellular responses against HPV-6 and HPV-11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential. CONCLUSION: The data suggest that INO-3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3087-3093, 2023.

The first randomized controlled trial in pediatric nephrology: the history of the International Study of Kidney Disease in Children (ISKDC).

The International Study of Kidney Disease in Children (ISKDC), begun in 1966, conducted the first international collaborative randomized blinded controlled trial in pediatric nephrology and one of the first in either pediatrics or nephrology. For this trial, the ISKDC developed the criteria, such as those for response and relapse, used today to describe the clinical course of the nephrotic syndrome, and the trial generated the nephropathologic terminology and criteria which largely remain the current standards. Over an approximately 20-year span, the ISKDC followed the natural history and evaluated the therapeutic effectiveness of therapies in over 500 children with the nephrotic syndrome from three continents. It published 14 peer-reviewed studies and several reports and commentaries, many of which helped create current standards of practice for therapy of childhood nephrotic syndrome and consequently remain highly cited today. The ISKDC continues to be an important model for subsequent collaborative studies and was the impetus for the development of regional and national pediatric nephrology societies leading to the recognition and growth of pediatric nephrology as a separate subspecialty. A higher resolution version of the Graphical abstract is available as Supplementary information.

Killian Jamieson Diverticulum, the Great Mimicker: A Case Series and Contemporary Review.

OBJECTIVE: To assess barium esophagram (BAS) as a diagnostic marker for patients with Killian Jamieson diverticula (KJD). METHODS: Prospective, multicenter cohort study of individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative. Patient demographics, comorbidities, radiographic imaging reports, laryngoscopy findings, patient-reported outcome measures (PROM), and operative reporting were abstracted from a REDCap database and summarized using means, medians, percentages, frequencies. Paired t-tests and Wilcoxon Signed Rank test were used to test pre- to post-operative differences in RSI, EAT-10, and VHI-10 scores. Diagnostic test evaluation including sensitivity, specificity, positive, and negative predictive value with 95% confidence intervals were calculated comparing BAS findings to operative report. RESULTS: A total of 287 persons were enrolled; 13 (4%) patients were identified with confirmed KJD on operative reports. 100% underwent open transcervical excision. BAS has a 46.2% (95% confidence interval [CI]: 23.2, 70.9) sensitivity and 97.8% (95% CI: 95.3, 99.0) specificity in detecting a KJD and 50% (95% CI: 25.4, 74.6) positive predictive value but 97.4% (95%CI: 94.8, 98.7) negative predictive value. Preoperatively, patients reported mean (SD) RSI and EAT-10 of 19.4 (9) and 8.3 (7.5) accordingly. Postoperatively, patients reported mean (SD) RSI and EAT-10 as 5.4 (6.2) and 2.3 (3.3). Both changes in RSI and EAT-10 were statistically significant (p = 0.008, p = 0.03). CONCLUSION: KJD are rare and represent <5% of hypopharyngeal diverticula undergoing surgical intervention. Open transcervical surgery significantly improves symptoms of dysphagia. BAS has high specificity but low sensitivity in detecting KJD. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2110-2115, 2023.

Early-Stage Glottic Carcinoma in the United States: Demographics and Treatment Choice.

OBJECTIVE: Limited investigation of factors potentially contributing to treatment choice in early-stage glottic carcinoma (EGC) has been performed with large-scale data. The National Cancer Database (NCDB) represents >72% of all new cancer cases in the United States. We hypothesized that NCDB variables may lend insight into treatment decisions between surgery and radiation for EGC. METHODS: The NCDB was queried for all cases of T1-2  N0  M0 glottic carcinoma from 2004 to 2016. We used multivariable logistic regression analysis to examine factors associated with first-line treatment modality: radiation therapy (RT) versus surgery. All reported odds ratios (OR) were adjusted for age, gender, race, insurance, residence in a metropolitan area, region, and facility volume. RESULTS: 34,991 EGC patients received treatment: 6,687 (19%) surgery; 20,289 (58%) RT; and 8,015 (23%) surgery and RT. OR for receiving RT (vs. surgery alone) were >2 for: more advanced T stage cancers (OR 2.5 [95%CI: 2.3, 2.7]), treatment at non-academic facilities (OR 2.8, [95%CI: 2.6, 3.0]), and shorter travel distances to treatment centers (OR 2.2, [95%CI: 2.0, 2.4]). Surgery was more likely with treatment in the western US, higher income, private insurance, living in a metropolitan (vs. non-metropolitan) area, female gender, older age, and low facility volume. Hispanic ethnicity, education level, and race were not associated with treatment type in the multivariable model. CONCLUSION: Most patients in the NCDB receive first-line treatment with radiation for EGC, and this decision is associated with various tumor, patient, and treatment facility characteristics. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:901-907, 2023.

Cricopharyngeus Muscle Dysfunction and Hypopharyngeal Diverticula (e.g., Zenker): A Multicenter Study.

OBJECTIVE: To describe demographics and imaging and compare findings and symptoms at presentation in a large cohort of persons with cricopharyngeus muscle dysfunction (CPMD) with and without hypopharyngeal diverticula. METHODOLOGY: Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeal Hypertonicity (POUCH) Collaborative. Patient survey, comorbidities, radiography, laryngoscopy findings, and patient-reported outcome measures (e.g., Eating Assessment Tool [EAT-10]) data were abstracted from a REDCap database and summarized using means, medians, percentages, and frequencies. Diagnostic categories were compared using analysis of variance. RESULTS: A total of 250 persons were included. The mean age (standard deviation [SD]) of the cohort was 69.0 (11.2). Forty-two percent identified as female. Zenker diverticula (ZD) was diagnosed in 85.2%, 9.2% with CPMD without diverticula, 4.4% with a Killian Jamieson diverticula (KJD), and 1.2% traction-type diverticula. There were no differences between diagnostic categories in regard to age, gender, and duration of symptoms (p = 0.25, 0.19, 0.45). The mean (SD) EAT-10 score for each group was 17.1 (10.1) for ZD, 20.2 (9.3) for CPMD, and 10.3 (9.4) for KJD. Patients with isolated CPMD had significantly greater EAT-10 scores compared to the other diagnostic groups (p = 0.03). CONCLUSION: ZD is the most common, followed by CPMD without diverticula, KJD, and traction-type. Patients with isolated obstructing CPMD may be more symptomatic than persons with ZD or KJD. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1349-1355, 2023.

Surgery and Adjuvant Therapy Improve Derkay Scores in Adult and Pediatric Respiratory Papillomatosis.

OBJECTIVES/HYPOTHESIS: Comparing Derkay anatomical score at time of procedure, disease characteristics, and mean treatment interval among adult and pediatric patients with recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Restrospective study. METHODS: Retrospective review of juvenile-onset (JO) and adult-onset (AO) RRP patients treated longitudinally at pediatric and adult institutions from 1999 to 2019. Patients were included if they had a tissue diagnosis of papilloma and had at least a 12-month follow-up. RESULTS: One hundred and twelve patients met inclusion criteria (68 JO-RRP and 44 AO-RRP). All patients were stratified into either potassium titanyl phosphate (KTP) (n = 42), CO2 (n = 21), or microdebrider (n = 49) treatment groups. The Derkay score improved between first and last procedure in the KTP group (mean difference, 3.5; P < .001), CO2 group (mean difference, 4.4; P < .001), and microdebrider group (mean difference, 4.1; P < .001), but overall improvement did not differ across groups (P = .73). Baseline mean to last mean Derkay score improved for nine patients during bevacizumab treatments (mean difference, 3.0; P = .01) but did not improve for these same patients during an interval prior to receiving bevacizumab treatments. Baseline mean to last mean Derkay score improved for 19 patients during cidofovir treatments (mean difference, 3.84; P < .001) but did not improve for these same patients during the interval prior to receiving cidofovir treatments. The AO-RRP population had more patients with dysplasia (50%) compared to JO-RRP population (10%) (P < .001). CONCLUSION: Various surgical modalities appear to be equally effective treatments for RRP. Adult and pediatric patients have decreased recurrent disease burden when receiving bevacizumab or cidofovir. AO-RRP patients have more concomitant dysplasia. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2420-2426, 2022.

Surgical Treatment of Acquired Velopharyngeal Insufficiency in Adults With Dysphagia and Dysphonia.

OBJECTIVES: Velopharyngeal insufficiency (VPI) is a form of velopharyngeal dysfunction caused by abnormal or insufficient anatomy. This process is known to be associated with dysphagia and dysphonia but surgical interventions for these complex patients have not been well studied. The current study characterized a small cohort of adult patients with acquired VPI, dysphonia, and dysphagia, as well as associated surgical interventions. METHODS: A retrospective descriptive case series of 22 (N = 22) adult patients over a 6-year period with acquired VPI and varying degrees of dysphagia and dysphonia was described from a multi-disciplinary voice and swallowing clinic. Perceptual assessment, nasopharyngoscopy, fluoroscopic swallowing assessment, and patient reported outcomes were reviewed to characterize the cohort. RESULTS: VPI etiologies included: stroke (n = 4), head and neck cancer (n = 5), brainstem lesions (n = 5), trauma (n = 5), and other/unknown (n = 3). All 22 patients underwent nasopharyngoscopy and were categorized as having unilateral (n = 13), central (n = 4), or no (n = 5) velopharyngeal deficits. Seventeen patients (77.2%) underwent modified barium swallow studies, revealing that soft palate elevation scored least impaired among patients with no VPI, and most impaired among patients with unilateral VPI deficits. All 22 patients underwent some form of surgical intervention for VPI, with 14 (63.6%) of those patients requiring additional surgical revision. CONCLUSION: This series is one of the first to the authors' knowledge to characterize a cohort of individuals with VPI, dysphagia, and dysphonia and associated surgical interventions.

Vocal Fold Cyst Formation after Photoangiolytic KTP Laser Treatment of Early Glottic Cancer.

OBJECTIVE: The incidence of post-operative glottic cyst (POGC) formation in patients treated with transoral laser microsurgery with potassium-titanyl-phosphate laser (TLM-KTP) photoablation of early glottic carcinoma (EGC) has not previously been described. METHODS: A retrospective chart review was performed to identify all patients with early glottic cancer who underwent with single-modality TLM-KTP at our institution. Each patient received regular follow up with videostroboscopy for tumor surveillance. New glottic cysts seen on surveillance examinations were noted and their management was documented. RESULTS: A total of 33 patients met inclusion criteria. Eight patients (24%) developed POGC's within the original geographic perimeter of the cancerous vocal fold(s): 6 in the infraglottic region and 2 near the vocal process, at an average of 8 months after their initial cancer surgery. Of these 8 POGC's, 7 were at the periphery of the original tumor distribution and 1 was in the center of it. No POGC's were associated with any change in voice. Four of the 8 POGC's were phonosurgically excised, all without evidence of malignancy on pathology. The remaining 4 were monitored: 2 were stable for an average of 49 months of follow up; the remaining 2 resolved spontaneously by 7 and 31 months after first identification. CONCLUSIONS: POGC's are a frequent sequela of TLM-KTP for EGC. While these results suggest that they are unlikely to represent submucosal recurrences, surgeons should have a low threshold to biopsy if there is clinical concern for such and should counsel patients pre-operatively about the potential for their formation.

Subdiffusion and Many-Body Quantum Chaos with Kinetic Constraints.

We investigate the spectral and transport properties of many-body quantum systems with conserved charges and kinetic constraints. Using random unitary circuits, we compute ensemble-averaged spectral form factors and linear-response correlation functions, and find that their characteristic timescales are given by the inverse gap of an effective Hamiltonian-or equivalently, a transfer matrix describing a classical Markov process. Our approach allows us to connect directly the Thouless time, t_{Th}, determined by the spectral form factor, to transport properties and linear-response correlators. Using tensor network methods, we determine the dynamical exponent z for a number of constrained, conserving models. We find universality classes with diffusive, subdiffusive, quasilocalized, and localized dynamics, depending on the severity of the constraints. In particular, we show that quantum systems with "Fredkin" constraints exhibit anomalous transport with dynamical exponent z≃8/3.

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. STUDY DESIGN: Delphi method-based survey series. METHODS: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. RESULTS: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). CONCLUSION: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E1941-E1949, 2021.

Proteinuria Reduction and Kidney Survival in Focal Segmental Glomerulosclerosis.

RATIONALE & OBJECTIVE: Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival. STUDY DESIGN: Cohort analysis of clinical trial participants. SETTING & PARTICIPANTS: Patients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone. PREDICTORS: Reduction in proteinuria measured during 26 weeks after initiating treatment. OUTCOMES: Repeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization. ANALYTICAL APPROACH: Multivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome. RESULTS: 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90mL/min/1.73m2 per year increase in eGFR (95% CI, 2.01-5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to the composite outcome: the HR per 1-unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI, 0.12-0.44). LIMITATIONS: Limited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years. CONCLUSIONS: These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.

KTP Laser Treatment of Early Glottic Cancer: A Multi-Institutional Retrospective Study.

OBJECTIVES: The primary objectives were to report oncologic outcomes of transoral laser microsurgery with potassium-titanyl-phosphate (KTP) laser (TLM-KTP) ablation of early glottic cancer (EGC). The secondary objectives were to report vocal outcomes and to analyze factors that might influence outcomes. METHODS: A multi-institutional, retrospective analysis of consecutive patients treated for T1 or T2 glottic squamous cell carcinoma undergoing TLM-KTP ablation with at least 2 years of follow-up was performed. Patients with prior radiation or surgery for laryngeal disease were excluded. PRIMARY OUTCOME MEASURES INCLUDED: surgical failures requiring radiation or laryngectomy, disease-specific survival (DSS), and overall survival (OS). Secondary outcome measures included: pre- and postoperative Voice Handicap Index-10 (VHI-10) scores. The effects of smoking status, stage, and anterior commissure involvement on outcomes were analyzed. RESULTS: Overall 88 patients met inclusion criteria (83% male, 79.5% current or former smokers). Mean age was 68 (standard deviation (SD): 12). Mean follow-up was 39.5 months (SD: 15.3). Staging included 50 T1a, 21 T1b, and 20 T2 tumors, including three metachronous second primaries. Radiation and/or laryngectomy avoidance was achieved in 87/88 (98.9%) of patients, inclusive of 24 patients requiring KTP re-treatments. Two patients had biopsy-proven recurrence (2.3%), but only 21 of 24 re-treated patients received a formal biopsy. No patients died from laryngeal cancer. DSS and OS were 100% and 92.3%, respectively. The mean VHI-10 scores were 19.3 preoperatively, 3.8 at 6-months postop, and 3.8 at 2-years postop. Smokers had a longer interval to re-treatment (P = .03), patients with T2 lesions had a shorter interval to re-treatment (0.02), and patients with T2 lesions presented with worse initial VHI-10 scores (0.002). CONCLUSIONS: A multi-institutional, retrospective case series of TLM-KTP ablation of EGC demonstrated excellent oncologic outcomes when close surveillance and proactive re-treatments were utilized. Disease-specific survival, overall survival, and vocal function were excellent. Additional studies are necessary to further analyze the merits and risks of this treatment approach.

Atypical Laryngeal Infections: Localized Lesions from Unusual Organisms May Simulate Malignancy.

OBJECTIVE: The identification of rare sources of laryngeal infection in immunocompetent patients. Recovered organisms were Mycobacterium tuberculosis (laryngeal tuberculosis [LTB]), Mycobacterium fortuitum (laryngeal Mycobacterium fortuitum [LMF]), and Blastomyces dermatiditis (laryngeal blastomycosis [LB]). METHOD: Single institution retrospective case series of three patients over a 2.5-year period and review of the literature on laryngeal infections by three atypical organisms. RESULTS: Three patients presented with hoarseness and cough; one additionally had throat pain (LTB). Indirect laryngoscopy demonstrated diffuse laryngeal ulceration (LTB, LMF) and an exophytic, contiguous glottic mass (LB). Direct microlaryngoscopic biopsies and cultures established the diagnoses, including a frozen section in one case (LB), which prevented a simultaneously planned surgical resection. Appropriate antimicrobial therapy yielded dramatic laryngeal and corresponding vocal improvement, for which we provide unique photo and audio documentation. In the last 10 years, fewer than 500 cases of LTB have been reported in the English language medical literature, principally outside the United States. To date, there have been reports of only 34 LB and no cases of LMF. CONCLUSION: Atypical infections of the larynx may be localized and mimic laryngeal cancer on endoscopy. Tissue examination as well as microbiologic samples are diagnostic and complementary.

A brief history of rickets.

The review provides a historical perspective on the convergence of our understanding of the physiology and pathophysiology of bone, calcium, phosphorus, vitamin D, parathyroid hormone, and FGF-23 their impact on rickets.