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INTRODUCTION: Surgery followed by pathology-guided adjuvant therapy is standard treatment for colon cancer. Data from the FOxTROT clinical trial showed potential benefit of a 6-wk neoadjuvant chemotherapy (NACT) in T3/T4 patients. The present study evaluated real-world outcomes of neoadjuvant therapy in a national cohort of patients with resectable colon cancer. METHODS: 169,120 patients with clinical stage I, II, or III colon cancer from the National Cancer Database registry were included. Patients were categorized as having received neoadjuvant therapy followed by surgery (NACT), surgery then adjuvant chemotherapy (AC), or surgery alone. Factors associated with treatment sequencing and outcomes were assessed. RESULTS: Of identified patients, 1.4% received NACT including 0.5% of stage I, 1.8% of stage II, and 3.0% of stage III. For stage I, 5-y overall survival (OS) was 74.7% after AC, 62.2% after NACT, and 76.4% after SA. For stage II, 5-y OS was 73.2% after AC, 66.8% after NACT, and 64.3% after SA. For stage III, 5-y OS was 67.3% after AC, 67.7% after NACT, and 42.4% after SA. Cox proportional-hazards model suggested NACT had worse outcomes versus AC in clinical stages I (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.39-1.85, P < 0.01) and II (HR = 1.37, 95% CI 1.23-1.52, P < 0.01). In stage III, there was no difference in OS between NACT and AC (HR = 1.1, 95% CI 0.99-1.22, P = 0.05). CONCLUSIONS: In a real-world national cohort of patients with resectable colon cancer, NACT had no OS benefit over AC. Future studies should examine which subset of patients might benefit from neoadjuvant approaches.
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Background: Pulmonary hypertension (PH) is a condition where the blood pressure increases in the pulmonary arteries, leading to reduced oxygen delivery to the body's tissues due to increased blood flow resistance. This condition can result in right ventricular hypertrophy, low cardiac output, and ischemia. In this study, the authors aim to investigate the impact of group II PH (GIIPH) on patients with congestive heart failure who were admitted with ST elevation myocardial infarction (STEMI) through a retrospective cohort study. Methods: Using the National Inpatient Sample (NIS) database from 2017 to 2020, a retrospective cross-sectional study of adult patients with a principal diagnosis of STEMI with a secondary diagnosis with or without GIIPH according to ICD-10 (International Classification of Disease, 10th edition) codes. Several demographics, including age, race, and gender, were analyzed. The primary endpoint was mortality, while the secondary endpoints included cardiogenic shock, mechanical intubation, length of stay in days, and patient charge in dollars. Multivariate logistic regression model analysis was used to adjust for confounders, with a P value less than 0.05 considered statistically significant. Results: The study included 26,925 patients admitted with a STEMI, 95 of whom had GIIPH. The mean age for patients with and without PH was 66.6 and 67.5 years, respectively. In the PH group, 37% were females compared to 34% in the non-PH group. The in-hospital mortality rate was higher in the PH group (31.6% vs. 9.6%, P<0.001, adjusted odds ratio (aOR) =3.33, P=0.02). The rates and adjusted odds of cardiogenic shock and mechanical ventilation were higher in the PH groups (aOR =1.15 and 2.14, respectively) but not statistically significant. Patients with PH had a longer length of stay and a higher total charge. Conclusions: GIIPH was associated with worse clinical and economic outcomes in heart failure patients admitted with STEMI.
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Discharging patients directly to home from the intensive care unit (ICU) is becoming a new trend. This review examines the feasibility, benefits, challenges, and considerations of directly discharging ICU patients. By analyzing available evidence and healthcare professionals' experiences, the review explores the potential impacts on patient outcomes and healthcare systems. The practice of direct discharge from the ICU presents both opportunities and complexities. While it can potentially reduce costs, enhance patient comfort, and mitigate complications linked to extended hospitalization, it necessitates meticulous patient selection and robust post-discharge support mechanisms. Implementing this strategy successfully mandates the availability of home-based care services and a careful assessment of the patient's readiness for the transition. Through critical evaluation of existing literature, this review underscores the significance of tailored patient selection criteria and comprehensive post-discharge support systems to ensure patient safety and optimal recovery. The insights provided contribute evidence-based recommendations for refining the direct discharge approach, fostering improved patient outcomes, heightened satisfaction, and streamlined healthcare processes. Ultimately, the review seeks to balance patient-centered care and effective resource utilization within ICU discharge strategies.
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Social media has become omnipresent in society, especially given that it enables the rapid and widespread communication of news, events, and information. Social media platforms have become increasingly used by numerous surgical societies to promote meetings and surgical journals to increase the visibility of published content. In September 2020, Annals of Surgical Oncology (ASO) established its Social Media Committee (SMC), which has worked to steadily increase the visibility of published content on social media platforms, namely X (formerly known as Twitter). The purpose of this review is to highlight the 10 ASO original articles with the most engagement on X, based on total number of mentions, since the founding of the SMC. These articles encompass a wide variety of topics from various oncologic disciplines including hepatopancreatobiliary, breast, and gynecologic surgery.
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BACKGROUND: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival. METHODS: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS. RESULTS: Of 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien-Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post-NAT LNP rates were not different, and median LNR was 0.1, in AC and non-AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non-AC (24 vs. 20 months, respectively; p = 0.04). CONCLUSIONS: LNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC.
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BACKGROUND: Percutaneous endoscopic gastrostomy (P.E.G.) is recommended for stroke patients with dysphagia to sustain oral nutrition. OBJECTIVE: This study assesses the outcomes of stroke patients undergoing P.E.G. compared with those requiring nasogastric tube (N.G.T) or control group. METHODS: We performed a thorough search across five electronic databases to gather pertinent studies. Outcomes were analyzed using relative risk (R.R.) for categorical data and mean difference (M.D.) for continuous data, each with 95% confidence intervals (C.I.). The single-arm meta-analysis results were presented as proportions or mean changes, also with 95% C.I. RESULTS: We included 22 studies consisting of 996,567 patients. Our double-arm meta-analysis (924,134 patients) revealed no significant difference in post-hospitalization or in-hospital mortality between P.E.G. and control groups. However, P.E.G. patients showed a higher risk of aspiration pneumonia than control (R.R. = 11.72[3.75, 36.62], p < 0.00001). A comparison of P.E.G. and N.G.T. in three studies involving 691 patients indicated a non-significant difference in-hospital mortality risk (R.R. = 0.59, 95% C.I. [0.2, 1.72]). The single-arm analysis of stroke patients with P.E.G. identified a 19.8% in-hospital mortality, 13.6% rate of aspiration pneumonia, and 58% rate of pneumonia. CONCLUSION: Stroke patients undergoing P.E.G remain at high risk for aspiration pneumonia and with an in-hospital mortality suggesting the need for identifying the best candidates and timing for the procedure.
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The global spread and distribution of antibiotic resistance genes (ARGs) has received much attention whereas knowledge about the transmission of ARGs from one matrix to another is still insufficient. In this study, the paddy fields fertilized with chemical fertilizer, swine compost, and no fertilizer were investigated to assess the transfer of ARGs from soil to rice. Soil and plant samples were collected at day 0, 7, 30 and 79 representing various stages of paddy growth. High throughput qPCR was applied to quantify ARGs using a set of 144 primers. Gene copy number of ARGs measured in soil initially decreased and then increased in soil with no fertilizer and chemical fertilizer, indicating that crop planting and flooding conditions did influence the ARGs profiles in soil. Application of swine compost significantly enhanced the relative abundance and gene copy number of ARGs in paddy soil. Rice seedlings contained substantial amount of ARGs and their relative abundance continually decreased after transplant. Compared with initial stage, detection frequencies of ARGs increased in soil without swine compost at harvest time (day 79), indicating the transmission of ARGs from irrigation water to soil. Detection frequencies of ARGs increased in soil and rice root with swine compost at harvest time, indicating the transfer of ARGs from swine compost to soil and rice root. There was no significant difference in abundance and diversity of ARGs in rice grains with these three different fertilizations. The source of the ARGs in rice grain still needs further exploration.
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BACKGROUND AND PURPOSE: Post thrombolytic intracerebral hemorrhage (ICH) is associated with higher rate of death or disability in acute ischemic stroke patients. We investigated the relationship between post thrombolytic ICH volume and change in volume and death or disability at 90 days in acute ischemic stroke patients. METHODS: We analyzed 110 patents recruited in the Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY) trial who received intravenous tissue plasminogen activator (tPA) followed by mechanical thrombectomy (if indicated) and 3K3A-APC or placebo. ICH volume was measured at Day 2 and Day 7 using susceptibility weighted sequence (SWI) on magnetic resonance imaging (MRI). We also calculated the post thrombolytic ICH volume change between Day 2 and Day 7. Outcomes were determined by using utility weighted modified Rankin scale (UW-mRs) at 90-days, Outcomes were determined by using utility weighted modified Rankin scale (UW-mRS) at 90 days. To minimize interpretation bias, outcome assessors were blinded to the treatment allocation and clinical data.We adjusted for age, gender, National Institute of Health Stroke Scale (NIHSS) score (<10,10-19 and ≥20), location of hemorrhage (single basal ganglia hemorrhage, single lobar, single cerebellum, and multiple sites) in multivariate regression analysis. RESULTS: A total of 88 (80%) of 110 patients had post thrombolytic ICH (mean volume 28.3 ml ± SD 62 ml). The strata of ICH volume were not associated with UW-mRs at 90 days: <20 cc (regression coefficient (RC)-0.05, p= 0.58), 20-39 cc (RC-0.22, p=0.17), or ≥40 cc (RC-0.34, p= 0.083) compared with no ICH after adjusting for potential confounders. Change in ICH mean volume 26.78 ml ±59.68, 52 had increase in volume) between Day 2 and day 7 was not associated with UW-mRS at 90 days (RC -67.71, p= 0.06). CONCLUSIONS: We did not observe any independent effect of post thrombolytic ICH volume on death or disability in acute ischemic stroke patients. Although further studies must be done, our data suggest that strategies to prevent ICH expansion such as antifibrinolytic medications and reduction in ICH volume such as surgical evacuation may not reduce death or disability in acute ischemic stroke patients with post thrombolytic ICH.
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This study investigates the perspectives of Canadian student and licenced pilots on general aviation pilot training and licencing practices. Employing a mixed-methods approach, this research critiques the reliance on flight hours as the sole competence metric and examines the alignment of existing practices with modern aviation's complexities. Findings reveal a divergence in opinions between novice and experienced pilots on flight hours' importance, with a consensus towards a competency-based evaluation model. The study identifies critical shortcomings in existing training practices, such as the challenge of integrating technology, fostering advanced skills, and efficiently utilising instructional resources. It suggests recommendations for regulatory enhancements, aiming to ensure training practices evolve in line with the changing requirements of aviation safety and technology. The conclusion calls for urgent reform, underlining the imperative for training adaptations that can prepare pilots to proficiently manage the complexities of contemporary airspace, thus safeguarding their proficiency and safety.
A survey conducted among Canadian student and licenced pilots to examine perspectives on general aviation pilot training and licencing practices uncovered critical shortcomings. The findings advocate for a strong preference for competency-based evaluations, urging reforms and regulatory improvements to ensure alignment with the evolving landscape of aviation safety and technological advancements.
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BACKGROUND: Clinical practice recommendations guide healthcare decisions. This study aims to evaluate the strength and quality of evidence supporting the American Heart Association (AHA)/American Stroke Association (ASA) guidelines for aneurysmal subarachnoid hemorrhage (aSAH) and spontaneous intracerebral hemorrhage (ICH). METHODS: We reviewed the current AHA/ASA guidelines for aSAH and spontaneous ICH and compared with previous guidelines. Guidelines were classified based on the Class of recommendation (COR) and Level of evidence (LOE). COR signifies recommendation strength (COR 1: Strong; COR 2a: Moderate; COR 2b: Weak; COR 3: No Benefit/Harm), while LOE denotes evidence quality (LOE A: High-Quality; LOE B-NR: Moderate-Quality, Not Randomized; LOE B-R: Moderate-Quality, Randomized; LOE C-EO: Expert Opinion; LOE C-LD: Limited Data). RESULTS: For aSAH, we identified 84 recommendations across 15 guideline categories. Of these, 31% were classified as COR I, 30% as COR 2a, 17% as COR 2b, and 18% as COR 3. In terms of LOE, 7% were based on LOE A, 10% on LOE B-R, 65% on LOE B-NR, 14% on LOE C-LD, and 5% on LOE C-EO. Compared to previous guidelines, there was a 46% decrease in LOE A, a 45% increase in LOE B, and an 11% decrease in LOE C. For spontaneous ICH, 124 guidelines were identified across 31 guideline categories. Of these, 28% were COR I, 32% COR 2b, and 9% COR 3. For LOE, 4% were based on LOE A, 35% on LOE B-NR, and 42% on LOE C-LD. Compared to previous guidelines, there was a 78% decrease in LOE A, an 82% increase in LOE B, and a 14% increase in LOE C. This analysis highlights that less than a third of AHA/ASA guidelines are classified as the highest class of recommendation, with less than 10% based on the highest LOE. CONCLUSION: Less than a third of AHA/ASA guidelines on aSAH and spontaneous ICH are classified as the highest class of recommendation with less than 10% based on highest LOE. There appears to be a decrease in proportion of guidelines based on highest LOE in most recent guidelines.
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This review provides a comprehensive overview of the therapeutic and diagnostic implications of fluorescence imaging in neurosurgery. Fluorescence imaging has become a valuable intraoperative visualization and guidance tool, facilitating precise surgical interventions. The therapeutic role of fluorescence is examined, including its application in photodynamic therapy and tumor-targeted therapy. It also explores its diagnostic capabilities in tumor detection, margin assessment, and blood-brain barrier evaluation. Drawing from clinical and preclinical studies, the review underscores the growing evidence supporting the efficacy of fluorescence imaging in neurosurgical practice. Furthermore, it discusses current limitations and future directions, emphasizing the potential for emerging technologies to enhance the utility and accessibility of fluorescence imaging, ultimately improving patient outcomes in neurosurgery.
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BACKGROUND: Postoperative adverse events (AEs) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PC) treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. We conducted a preplanned secondary analysis of patients enrolled on the Alliance A021501 clinical trial to quantify perioperative AE rates. METHODS: The A021501 phase 2 trial randomized patients with BR-PC to receive 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX and hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (December 31, 2016 to May 31, 2019). Adverse events were assessed 90 days after pancreatectomy. RESULTS: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n = 32, Arm 1; n = 19, Arm 2) at 28 institutions. Five (10%) patients required reoperation within 90 days; 56% of patients (n = 27/48) experienced at least one grade 3 or higher AE (50% vs. 67%, p = 0.37). Ninety-day mortality was 2.0%. Readmission was less frequent in Arm 1 (16% vs. 42%, p = 0.05), but there were no differences between study arms in rates of reoperation (13% vs. 5%), pancreatic fistula or intra-abdominal abscess requiring drainage (9% vs. 16%), or wound infection (6% vs. 16%). Pancreatic fistula or intra-abdominal abscess requiring drainage was associated with receipt of adjuvant therapy (p = 0.012). No difference in overall survival was observed based on occurrence of postoperative AEs (hazard ratio = 1.1; 95% confidence interval 0.5-2.6). CONCLUSIONS: In this multicenter study, rates of postoperative AEs were consistent with those previously reported. Multimodality trials of preoperative therapy for BR-PC may be performed in the cooperative group setting with careful quality assurance and safety monitoring. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02839343.
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SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.
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BACKGROUND: Among heart transplantation (HT) recipients, the accuracy of serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) may be limited by fluctuations in muscle mass. Cystatin C (cysC) is less influenced by muscle mass, but its levels may increase with obesity and steroid use. Herein, we (1) longitudinally compared eGFRcysC and eGFRsCr among HT recipients; (2) investigated the association of body mass index (BMI), steroid use, and muscle mass with discrepancies between eGFRs; and (3) explored the implications of eGFRcysC use on valganciclovir (VGC) dosing. METHODS: cysC and sCr were measured in 294 blood samples obtained from 80 subjects. Intraindividual differences between eGFRs (eGFRdiffcysC-sCr) were calculated with negative values corresponding to eGFRsCr > eGFRcysC and positive values to eGFRcysC > eGFRsCr. In a patient subset (n = 21), pectoralis muscle measures were obtained. RESULTS: Marked differences between eGFRcysC and eGFRsCr were observed, particularly early post-HT (1-week post-HT, median eGFRdiffcysC-sCr -28 ml/min/1.73 m2). eGFRcysC demonstrated stability following a transient postoperative decline, while eGFRsCr decreased in the first year post-HT. Lower BMI and higher prednisone dose displayed a modest association with more negative eGFRdiffcysC-sCr values. Pectoralis muscle measures indicative of greater muscle mass and better tissue quality exhibited a stronger association with more positive eGFRdiffcysC-sCr values. The use of eGFRcysC would have led to VGC dose adjustment in 46% of samples, predominantly resulting in dose reduction. CONCLUSIONS: Among HT recipients, eGFRcysC and eGFRsCr markedly differ with implications for VGC dosing. The observed discrepancies may reflect changes in body composition and steroid use.
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Cytokines are key mediators of immune regulation, orchestrate communication between immune cells, and play a pivotal role in shaping the immune landscape during chronic infection and cancer. The therapeutic potential of IL-15/IL-15Rα and IL-12 has been explored individually in various immunotherapeutic strategies, though not as a combination. Therefore, we investigated whether the combination of IL-15/IL-15Rα and IL-12 treatment would enhance the potency and quality of either NK cells, SIV-specific CD8 T cells, or both, compared with single cytokine treatment. Our findings reveal that in vitro IL-15/IL-15Rα and IL-15/IL-15Rα plus IL-12 treatment results in an expansion of functional CD8 T cells and NK cells from uninfected and chronically infected macaques with simian/human immunodeficiency virus. Additionally, the cytokine combination significantly reduced CCR5 expression on total CD4 T cells, limiting the number of viral targets. This study supports the potential utilization of combined IL-15/IL-15Rα plus IL-12 treatment for chronic viral infections and cancer.
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â¢The use of quaternary ammonium compounds (QACs) as disinfectants has increased exponentially due to the COVID-19 pandemic.â¢There is, thus, a corresponding increase in human exposure to these compounds.â¢New studies reveal important human health concerns.â¢A re-evaluation of the use of these compounds is in order.â¢A change over to newer and safer products may bode well for the future.
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This study reports on the synthesis, characterization, and application of two acidic ionic liquids, namely, N-carboxymethylpyridinium acetate ([HO2CCH2Py][CH3CO2] or AIL1) and N-carboxyethylpyridinium acetate ([HO2C(CH2)2Py][CH3CO2] or AIL2), as both extractants and catalysts for the oxidative and extractive desulfurization (OEDS) of model fuel oils containing heteroaromatic sulfur compounds. The structural properties of the synthesized acidic ionic liquids (ILs) were confirmed by 1H NMR, 13C NMR, and FT-IR spectroscopic analysis. To optimize the performance of the acidic AILs in the desulfurization process, the effects of different parameters, such as H2O2 dosage, reaction time, and temperatures, were investigated. The experimental results showed that AIL1 has exceptionally high desulfurization-extraction rates, with values of 99.8%, 97.8%, and 95.4%, for DBT, BT, and 4,6-DMDBT, respectively, under the optimum conditions established. Under the same conditions, the desulfurization-extraction rates using AIL2 reached 91.6%, 87.3%, and 82.4%, respectively, for DBT, 4, 6-DMDBT, and BT. Both ionic liquids can be recycled up to 9 times without a significant decrease in their sulfur removal efficiencies. Furthermore, density functional theory (DFT) calculations were conducted to evaluate the electronic interaction energies (ΔIE) between the AILs with each of the sulfur-containing compounds and their putative oxidized products. The computational findings strongly supported the experimental outcomes.
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A patient with multiple comorbidities and an eight-year history of tracheostomy was being treated for tracheitis. At this point, she became incapable of using regular speaking valves, and multiple attempts to reintroduce the speaking valve failed. A Ferrer adjustable speaking valve (FASV) was designed with gradations of outflow closure, allowing air to go through the vocal cords for phonation. The FASV was offered to her through the compassionate use program at the FDA. At 20% initial closure, the patient was able to tolerate the valve and was advanced to 50% closure, at which point she could phonate partially. The use of the valve was terminated at the time of her transfer, 23 days after the initiation of use. This suggests the safety and possible efficacy of using an adjustable speaking valve earlier than regular valves, allowing patients to communicate earlier and further exercise their diaphragms.