Reconstruction and Simulation of Neocortical Microcircuitry.

We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm(3) containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies. PAPERCLIP: VIDEO ABSTRACT.

The biological role and future therapeutic uses of nitric oxide in extracorporeal membrane oxygenation, a narrative review.

BACKGROUND: Nitric oxide (NO) is a gas naturally produced by the human body that plays an important physiological role. Specifically, it binds guanylyl cyclase to induce smooth muscle relaxation. NO's other protective functions have been well documented, particularly its protective endothelial functions, effects on decreasing pulmonary vascular resistance, antiplatelet, and anticoagulation properties. The use of nitric oxide donors as vasodilators has been known since 1876. Inhaled nitric oxide has been used as a pulmonary vasodilator and to improve ventilation perfusion matching since the 1990s. It is currently approved by the United States Food and Drug Administration for neonates with hypoxic respiratory failure, however, it is used off-label for acute respiratory distress syndrome, acute bronchiolitis, and COVID-19. PURPOSE: In this article we review the currently understood biological action and therapeutic uses of NO through nitric oxide donors such as inhaled nitric oxide. We will then explore recent studies describing use of NO in cardiopulmonary bypass and extracorporeal membrane oxygenation and speculate on NO's future uses.

Balancing the Anteroposterior Diameters of the Nostril Lengths in Cleft Rhinoplasty.

BACKGROUND: Osteocartilaginous deformities in cleft rhinoplasties may be restored with numerous techniques. However, the anteroposterior (AP) diameter lengths of the nostrils may still be unequal and should also be addressed. A technique was designed to balance nostril AP diameter lengths and apical shapes. MATERIALS AND METHODS: Balance between AP nostril diameters was accomplished by reduction of the AP diameter of the nostril at the non-cleft side by medial crural reduction and augmentation of the AP diameter of the nostril at the cleft side by three-parted mini-flap reconstruction at the soft triangle. The cleft-side AP diameter length was divided by the non-cleft-side AP diameter length of the same preoperative, per-operative and 1-year postoperative base view photographs of each patient, and "nostril balancing ratio" was obtained. The more this ratio was near to "one," the more the AP nostril diameters were equal. RESULTS: Seventy-eight unilateral-cleft rhinoplasty were performed between January/2019 and May/2022. Forty-two of them required nostril AP diameter equalization. Twenty-nine patients were female, thirteen were male. Thirty-three of them were operated for a primary cleft rhinoplasty. Nine of them for secondary cleft rhinoplasty. Mean age was 28 years (22-39 years). Mean follow-up was 25 months (6-40 months). The preoperative, per-operative and postoperative mean "nostril balancing ratios" were 0.714 (0.621-0.813), 0.743 (0.721-0.752) and 0.971 (0.943-0.976), respectively. CONCLUSION: Balancing AP diameter symmetry with MCO at the non-cleft side and three-parted mini skin flap reconstruction at the cleft side may provide the satisfactory results. Three mini-flaps at the soft triangle may remold the nostril apex in an oval shape, which may result in a better shape symmetry. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Oncological outcomes of visibly complete transurethral resection prior to neoadjuvant chemotherapy for bladder cancer.

PURPOSE: To evaluate the potential oncologic benefit of a visibly complete transurethral resection of a bladder tumor (TURBT) prior to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). MATERIALS AND METHODS: We identified patients who received NAC and RC between 2011-2021. Records were reviewed to assess TURBT completeness. The primary outcome was pathologic downstaging (

Comparative clinical study with a novel technique for stabilization of the nasal tip projection and rotation: fixation of the septum and the strut graft through the septal cartilage autoextension.

PURPOSE: It is important to reinforce nasal tip support for long-term satisfactory results. Two workhorses of tip support are strut grafting and the tongue-in-groove technique. Tongue-in-groove causes retraction and stiffness; the strut causes loss of rotation and projection of tip. We introduced a novel technique that avoids these consequences. METHODS: Between February 2018-February 2019, 40 female underwent primary rhinoplasty. Mean age: 27 years (18-41 years). FOLLOW-UP: 1-2 years. In first group (20 patients), caudal septum was resected and strut was not fixated to caudal septum. In second group (20 patients), tongue-like extension (septal autoextension) was preserved at caudal septum and sutured to strut. Preoperative, peroperative, and postoperative images were compared. RESULTS: Tip projection ratio calculations, nasolabial angle measurements were evaluated by statistical analyses. The change in projection ratios between peroperative period and 1-year postoperative period of strut-only group was higher than septal autoextension group (p = 0.001). This result indicates that nasal tip projection loss in strut-only group was higher compared to septal autoextension group. The change in nasolabial angle measurements from peroperative period to 1-year postoperative period differed significantly between two groups (p = 0.001). Significant difference was observed between 1-year postoperative nasolabial angle measurements of two groups (p = 0.006); septal autoextension group measurements were higher than strut-only group. These results showed that fixation of strut graft to the septal autoextension provides better preservation of the nasolabial angle and stabilization of nasal tip projection. CONCLUSiON: Fixation of septum and strut graft through septal autoextension provides satisfactory stabilization of tip projection and rotation without stiffness or rigidity.

Clean-Cut Smoothing of the Visible Cartilage Grafts by Sanding With a Scalpel.

The visibility of cartilage grafts underneath the skin is a complication of rhinoplasty particularly in patients with thin nasal skin. Preparing the graft with optimum dimensions, symmetry, and smoothness is crucial for the fine crafting of the cartilage to prevent visibility. The camouflage of the visible cartilage graft with a crushed cartilage, a resected cephalic portion of the lower lateral cartilage, fascia, connective and/or fatty tissues is another option for hiding the visibility. The nasal tip is the most common location where the graft visibility is of concern.The authors introduce the smoothing of the cartilage graft by sanding it with a scalpel. This technique safely provides perfection and precision of smoothing of the cartilage in very desired shape. It is possible to obtain 3D super clean-cut shining surface.The tangential sculpting of the cartilage graft with a scalpel carries the risk of over resection. However, the sanding with a scalpel moves forward so gentle that over resection is not possible.It is also possible to smooth non-visible structural grafts such as strut and spreader grafts to reduce surface irregularities.Additionally, the sand-dust caused by cartilage sanding is a 'cartilage pâté' which can be used for camouflage of minute irregularities of the nasal dorsum.

Bio-physically plausible visualization of highly scattering fluorescent neocortical models for in silico experimentation.

BACKGROUND: We present a visualization pipeline capable of accurate rendering of highly scattering fluorescent neocortical neuronal models. The pipeline is mainly developed to serve the computational neurobiology community. It allows the scientists to visualize the results of their virtual experiments that are performed in computer simulations, or in silico. The impact of the presented pipeline opens novel avenues for assisting the neuroscientists to build biologically accurate models of the brain. These models result from computer simulations of physical experiments that use fluorescence imaging to understand the structural and functional aspects of the brain. Due to the limited capabilities of the current visualization workflows to handle fluorescent volumetric datasets, we propose a physically-based optical model that can accurately simulate light interaction with fluorescent-tagged scattering media based on the basic principles of geometric optics and Monte Carlo path tracing. We also develop an automated and efficient framework for generating dense fluorescent tissue blocks from a neocortical column model that is composed of approximately 31000 neurons. RESULTS: Our pipeline is used to visualize a virtual fluorescent tissue block of 50 µm3 that is reconstructed from the somatosensory cortex of juvenile rat. The fluorescence optical model is qualitatively analyzed and validated against experimental emission spectra of different fluorescent dyes from the Alexa Fluor family. CONCLUSION: We discussed a scientific visualization pipeline for creating images of synthetic neocortical neuronal models that are tagged virtually with fluorescent labels on a physically-plausible basis. The pipeline is applied to analyze and validate simulation data generated from neuroscientific in silico experiments.

Physically-based in silico light sheet microscopy for visualizing fluorescent brain models.

BACKGROUND: We present a physically-based computational model of the light sheet fluorescence microscope (LSFM). Based on Monte Carlo ray tracing and geometric optics, our method simulates the operational aspects and image formation process of the LSFM. This simulated, in silico LSFM creates synthetic images of digital fluorescent specimens that can resemble those generated by a real LSFM, as opposed to established visualization methods producing visually-plausible images. We also propose an accurate fluorescence rendering model which takes into account the intrinsic characteristics of fluorescent dyes to simulate the light interaction with fluorescent biological specimen. RESULTS: We demonstrate first results of our visualization pipeline to a simplified brain tissue model reconstructed from the somatosensory cortex of a young rat. The modeling aspects of the LSFM units are qualitatively analysed, and the results of the fluorescence model were quantitatively validated against the fluorescence brightness equation and characteristic emission spectra of different fluorescent dyes. AMS SUBJECT CLASSIFICATION: Modelling and simulation.

Pediatric Heart Transplantation Over 36 Years and Contemporary Volume-Outcome Analysis of UNOS.

BACKGROUND: This study examines 36 years of national pediatric heart transplantation data to 1) identify trends in transplant volume, centers, and one-year graft survival, and 2) assess how center transplant volume impacts outcomes over a contemporary 11-year period. METHODS: We performed a retrospective review of pediatric patients (<18 years) undergoing heart transplantation from 1/1/1987 to 12/31/2022 using the United Network for Organ Sharing Database. Trend analyses included the whole cohort, while volume-outcome analyses included a contemporary cohort to account for the temporal changes observed in transplant survival. Highest volume centers were defined by the number of heart transplants performed per center per year. RESULTS: Over 36 years, 11,828 pediatric heart transplants were performed. Transplant volume steadily rose, the number of centers remained stable, and one-year graft survival has improved significantly. In the contemporary era (2012-2022), 89 centers conducted 4,959 pediatric heart transplants. The top 15% high-volume centers (13 centers) accounted for 48.3% (2,393) of transplants, with an average of 16.7±3.8 transplants per center annually, compared to 3.9±3.1 for lower volume centers. Despite transplanting higher risk patients, high-volume centers had similar postoperative outcomes and improved long-term survival. CONCLUSIONS: While the number of US pediatric heart transplant centers has remained stable, pediatric heart transplant volume is steadily increasing, as is one-year graft survival. In a contemporary cohort, the top 15th percentile highest volume centers accounted for 48.3% of US pediatric heart transplants and transplanted higher risk patients with similar postoperative outcomes and improved longitudinal survival.

Reconsidering FDA Guidelines: A Single-Center Experience of Prolonged Impella 5.5 Support.

OBJECTIVE: Impella 5.5 (Abiomed, Danvers, MA, USA) is approved by the US Food and Drug Administration (FDA) for mechanical circulatory support for ≤14 days. It is unknown whether prolonged support is associated with worse outcomes. We sought to review our single-center experience with Impella 5.5 and compare outcomes based on support duration. METHODS: We retrospectively reviewed adult patients (≥18 years old) supported with Impella 5.5 at our institution (May 2020 to April 2023). Patients on prolonged support (>14 days) were compared with those supported for ≤14 days. RESULTS: There were 31 patients supported with Impella 5.5 including 14 (45.2%) supported >14 days. Median support duration for those on prolonged support was 43.5 (interquartile range [IQR] 25 to 63.5) days versus 8 (IQR 6, 13) days for those who were not (P < 0.001). Overall, the device-related complication rate was 9.7% and did not differ between groups (P = 0.08). Overall, 30-day postimplant survival was 71% and did not differ by support duration (P = 0.2). In-hospital mortality was 32% and did not differ between cohorts (P > 0.99). Among those surviving to explant (n = 22), long-term strategy included bridge to durable ventricular assist device (18%, n = 4), cardiac transplant (55%, n = 12), and cardiac recovery (27%, n = 6). CONCLUSIONS: High-risk patients with cardiogenic shock may be supported with Impella 5.5 beyond the FDA-approved duration without increased risk of complications or mortality.

Intraoperative hypotension and postoperative acute kidney injury: A systematic review.

BACKGROUND: There is no consensus regarding safe intraoperative blood pressure thresholds that protect against postoperative acute kidney injury (AKI). This review aims to examine the existing literature to delineate safe intraoperative hypotension (IOH) parameters to prevent postoperative AKI. METHODS: PubMed, Cochrane Central, and Web of Science were systematically searched for articles published between 2015 and 2022 relating the effects of IOH on postoperative AKI. RESULTS: Our search yielded 19 articles. IOH risk thresholds ranged from <50 to <75 â€‹mmHg for mean arterial pressure (MAP) and from <70 to <100 â€‹mmHg for systolic blood pressure (SBP). MAP below 65 â€‹mmHg for over 5 â€‹min was the most cited threshold (N â€‹= â€‹13) consistently associated with increased postoperative AKI. Greater magnitude and duration of MAP and SBP below the thresholds were generally associated with a dose-dependent increase in postoperative AKI incidence. CONCLUSIONS: While a consistent definition for IOH remains elusive, the evidence suggests that MAP below 65 â€‹mmHg for over 5 â€‹min is strongly associated with postoperative AKI, with the risk increasing with the magnitude and duration of IOH.

Patient-Derived Tumor Xenograft Study with CDK4/6 Inhibitor Plus AKT Inhibitor for the Management of Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive malignancy with poor outcomes. To investigate novel therapeutic strategies, we characterized three new metastatic prostate cancer patient derived-tumor xenograft (PDTX) models and developed 3D spheroids from each to investigate molecular targeted therapy combinations including CDK4/6 inhibitors (CDK4/6i) with AKT inhibitors (ATKi). Metastatic prostate cancer tissue was collected and three PDTX models were established and characterized using whole-exome sequencing. PDTX 3D spheroids were developed from these three PDTXs to show resistance patterns and test novel molecular-targeted therapies. CDK4/6i's were combined with AKTi's to assess synergistic antitumor response to prove our hypothesis that blockade of AKT overcomes drug resistance to CDK4/6i. This combination was evaluated in PDTX three-dimensional (3D) spheroids and in vivo experiments with responses measured by tumor volumes, PSA, and Ga-68 PSMA-11 PET-CT imaging. We demonstrated CDK4/6i's with AKTi's possess synergistic antitumor activity in three mCRPC PDTX models. These models have multiple unique pathogenic and deleterious genomic alterations with resistance to single-agent CDK4/6i's. Despite this, combination therapy with AKTi's was able to overcome resistance mechanisms. The IHC and Western blot analysis confirmed on target effects, whereas tumor volume, serum PSA ELISA, and radionuclide imaging demonstrated response to therapy with statistically significant SUV differences seen with Ga-68 PSMA-11 PET-CT. These preclinical data demonstrating antitumor synergy by overcoming single-agent CDK 4/6i as well as AKTi drug resistance provide the rational for a clinical trial combining a CDK4/6i with an AKTi in patients with mCRPC whose tumor expresses wild-type retinoblastoma 1.

A New Prognostic Parameter Associated With Recurrence in Patients With Nasopharyngeal Cancer Treated With Chemoradiotherapy: The Ratio of the Hemoglobin-to-Red Cell Distribution Width.

INTRODUCTION: This study aims to investigate the prognostic significance of the pre-treatment hemoglobin-red blood cell distribution width (RDW) ratio (HRR) in terms of overall survival (OS) and disease-free survival (DFS) in patients with locally advanced nasopharyngeal cancer (LANC) treated with chemoradiotherapy. METHODS: Patients with LANC who attended the oncology clinic between October 2010 and June 2020 were retrospectively screened. HRR was calculated as hemoglobin (g/dL) divided by the RDW (%). Patients were assigned to either the low HRR group or the high HRR group. RESULTS: A total of 102 patients were included in the study. The cut-off value for HRR was taken as 0.97. Between the low and high HRR groups, mean age, Eastern Cooperative Oncology Group (ECOG) performance score, gamma-glutamyl transferase (GGT), albumin and lactate dehydrogenase (LDH) levels, weight loss at diagnosis, and recurrence and metastasis rate were significantly different. In the low HRR group, OS and DFS were 44.4 (95% CI: 4.9-83.8) and 15.7 months (95% CI: 0.1-36.2), respectively, but could not be reached in the high HRR group (p<0.001). In the multivariate analysis, low HRR was shown to be an independent factor in terms of both OS (p=0.004, hazard ratio (HR)=3.07, 95% CI: 1.444-6.529) and DFS (p<0.001, HR=3.94, 95% CI: 1.883-8.244). CONCLUSION: This is the first study showing that HRR is an independent prognostic marker for OS and DFS in patients with LANC treated with chemoradiotherapy. Thus, HRR can be used as an easily applicable, inexpensive marker in clinical practice in this patient group.

Eustachian Tube Dysfunction in Children with Adenoid Hypertrophy: The Effect of Intranasal Azelastine-Fluticasone Spray Treatment on Middle Ear Ventilation and Adenoid Tissue.

OBJECTIVES: Eustachian tube dysfunction (ETD) is frequent in children with adenoid hypertrophy (AH). Although the most common treatment of AH is surgical removal of adenoid tissue, numerous studies have reported the efficacy of intranasal steroids. The effects of the intranasal steroid and azelastine combination on AH and ETD have not been reported before. In this study, we tried to determine the effects of 3-month intranasal Azelastine-Fluticasone dipropionate combination (Aze-Flu) treatment in children with ETD and AH. MATERIALS AND METHODS: 100 children who had open mouth sleep, snoring, and sleep apnea and were diagnosed with AH and ETD participated in this study. The mean age was 7.73 ± 2.37 (4-14 years). The rates of adenoid tissue hypertrophy and choanal occlusion were evaluated using a rigid pediatric nasal endoscope and reassessed after 3 months of Aze-Flu nasal spray treatment. The function of the Eustachian tube (ET) was evaluated before and after medical treatment using the Eustachian tube score, the Eustachian dysfunction test-7 (ETS-7) and tubomanometry (TMM). RESULTS: The results were evaluated in 100 patients with AH and ETD. The adenoid tissue to choana rate was 82% before treatment and decreased to 37% after treatment. The ETS-7 test score was 6.36 before treatment and increased to 9.72 at the end of 3 months. Both the regression of the adenoid tissue and the improvement in the Eustachian function scores were statistically significant (p < 0.05). CONCLUSIONS: AH significantly increases the frequency of ETD. In this study, it was observed that Aze-Flu treatment was significantly effective in both regression of the adenoid tissue and Eustachian tube dysfunction. We believe that it can be applied as an initial therapy in children with AH and associated ETD.

Efficacy of Topical Azelastine and Fluticasone Dipropionate Combination in Children With Adenoid Hypertrophy.

OBJECTIVE: Adenoid hypertrophy (AH) is one of the common childhood diseases. Surgical and non-surgical treatment of AH in children is planned according to the severity of symptoms and associated complications. In recent years, treatment methods with intranasal sprays have been reported quite frequently in uncomplicated cases. We aim to evaluate the effectiveness of a new combination of azelastine - fluticasone (AZE-FLU) (137mcg azelastine and 50mcg fluticasone) nasal spray in children with uncomplicated AH. METHODS: Sixty-five children diagnosed with AH were included in the study. The mean age of the children was 7.42 ± 2.26 (4-13 years). The cohort consisted of 29 males and 36 females. All children were evaluated clinically and endoscopically. AZE-FLU nasal spray was applied to both nostrils twice a day for three months. Adenoid/choana ratio and symptom scores were evaluated before treatment and at the end of the 12th week. RESULTS: At the end of 24 weeks of AZE-FLU application, there was a statistically significant decrease in both adenoid/choana ratio and symptom scores. While the initial adenoid/choana (A/C) score was 3.57 ± 0.58, it decreased to 1.74 ± 0.61 following treatment. A dramatic decrease in total symptom scores was observed. The total symptom score average was 15.63 ± 1.28 before treatment, while it was 2.31 ± 1.4 after the treatment with the difference being statistically significant (P < .01). CONCLUSION: In this study, the effectiveness of AZE-FLU nasal spray on AH was investigated for the first time. This treatment provides an effective alternative to the surgical approach in children with uncomplicated adenoid hypertrophy. Using this protocol, 96% of patients were removed from the surgery list. LEVEL OF EVIDENCE: is IV.

Durable biventricular assist device support for 1212 days as a bridge to heart transplantation.

Experience with durable biventricular assist devices (BiVADs) as a bridge to heart transplantation (HTx) is limited, particularly in women. A 41-year-old woman with biventricular failure complicated by cardiogenic shock underwent durable concurrent BiVAD implantation and was supported for 1212 days as a bridge to HTx. During BiVAD support, she experienced bacteremia (day 1030 of support), appropriately managed with intravenous antibiotics. She is alive and well, 1479 days from BiVAD implantation and 267 days from orthotopic HTx. Strategies contributing to successful prolonged support include concurrent BiVAD implantation, aggressive cardiac rehabilitation, diet management for weight loss and frequent interval surveillance.

Statistical Mechanics Metrics in Pairing and Parsing In Silico and Phenotypic Data of a Novel Genetic NFκB1 (c.T638A) Variant.

(1) Background: Mutations in NFκB1, a transcriptional regulator of immunomodulating proteins, are a known cause of inborn errors of immunity. Our proband is a 22-year-old male with a diagnosis of common variable immunodeficiency (CVID), cytopenias with massive splenomegaly, and nodular regenerative hyperplasia of the liver. Genetic studies identified a novel, single-point mutation variant in NFκB1, c. T638A p. V213E. (2) Methods: Next-generation panel sequencing of the patient uncovered a novel single-point mutation in the NFκB1 gene that was modeled using the I-TASSER homology-modeling software, and molecular dynamics were assessed using the YASARA2 software (version 20.14.24). (3) Results: This variant replaces valine with glutamic acid at position 213 in the NFκB1 sequence. Molecular modeling and molecular dynamic studies showed altered dynamics in and around the rel homology domain, ankyrin regions, and death domain of the protein. We postulate that these changes alter overall protein function. (4) Conclusions: This case suggests the pathogenicity of a novel variant using protein-modeling techniques and molecular dynamic simulations.

A Novel Approach for the Treatment of Sialolithiasis that Preserves Salivary Duct Anatomy.

OBJECTIVE: The sialendoscopy era in the treatment of salivary gland stones has reduced the use of classical surgical methods. However, the miniature ducts and tools may cause difficulties in removing large sialoliths. Therefore, invasive combined oral surgeries or gland resection may be considered. We searched for the most suitable method in order to stay in line with the minimally invasive approach that preserves the ductus anatomy, and that can reduce the surgical fears of patients. MATERIALS AND METHODS: The study included 84 cases (23 parotid and 61 submandibular) in whom stones were fragmented by pneumatic lithotripsy and removed between January 2015 and January 2020. The parotid cases comprised 7 females and 16 males, and the submandibular cases comprised 25 females and 36 males. Intraductal lithotripsy was performed using pneumatic lithotripter. This study has fourth level of evidence. RESULTS: Based on total number of cases (n = 84), success rate was 67/84 (79.7%) immediately after sialendoscopy, and overall success rate was 77/84 (91.6%). Based on number of stones treated (n = 111), our immediate success rate was 94/111 (84.6%), and overall success rate was 104/111 (93.7%). The success criteria were complete removal of the stone and fragments in a single sialendoscopy procedure and resolution of symptoms. CONCLUSIONS: We successfully treated salivary gland stones, including L3b stones, in our patient cohort with sialendoscopy combined with pneumatic lithotripsy. The lithotripsy method that we have adapted seems to be more useful and cost-effective compared to its alternatives. We were also able to preserve the ductus anatomy and relieve patients' concerns.Level of Evidence: Level IV.

Olfactory rehabilitation and olfactory bulb volume changes in patients after total laryngectomy: a prospective randomized study.

INTRODUCTION: After total laryngectomy, decreased olfactory function and olfactory bulb volume shrinkage have been reported to occur due to olfactory deprivation caused by nasal airflow interruption. There is evidence that the olfactory system can be modulated by repeated exposure to odors in a procedure called olfactory training. However, it is not known whether any recovery of the lost olfactory bulb volume is possible by eliminating olfactory deprivation via olfactory rehabilitation long after laryngectomy. OBJECTIVE: This study examined the recovery of olfactory function and the change in olfactory bulb volume via long-term olfactory rehabilitation after total laryngectomy. METHODS: Possible causes of olfactory dysfunction in the study participants were evaluated by collecting detailed anamnesis. As olfactory tests, orthonasal butanol threshold and odor discrimination tests were performed. Three-dimensional olfactory bulb volumes were calculated using manual segmentation on T2-weighted coronal magnetic resonance images. In olfactory rehabilitation, four different odors were applied to all patients orthonasally, using a larynx bypass technique for 30 min per day for 6 months. Olfactory tests were performed before the rehabilitation and after 6 months of rehabilitation, and olfactory bulb volume measurements were performed using magnetic resonance images. RESULTS: Eleven patients diagnosed with advanced laryngeal cancer who underwent total laryngectomy and postoperative radiotherapy with a follow-up of 5-10 years were included in the study. All patients were male, and the mean age was 58.18 ±â€¯4.17 years. In total laryngectomized patients, the olfactory bulb volumes measured on magnetic resonance images were 42.25 ±â€¯12.8 mm3 before and 55.5 ±â€¯11.22 mm3 after rehabilitation, and this increase was highly significant. Olfactory test scores were 2.3 ±â€¯1.27 before and 4.39 ±â€¯0.86 after rehabilitation, and this increase was also highly significant. CONCLUSION: As a result of the olfactory rehabilitation applied by providing orthonasal air flow, the olfactory function lost after total laryngectomy was improved considerably, and the olfactory bulb volume was significantly increased. The increase in olfactory bulb volume in total laryngectomy patients via olfactory rehabilitation to eliminate olfactory deprivation due to nasal airflow interruption was demonstrated for the first time in this prospective longitudinal study.