Thrombopoietin Receptor Agonists for Thrombocytopenia Secondary to HER2-Targeted Antibody Drug Conjugates.

Trastuzumab emtansine and trastuzumab deruxtecan are widely used in breast cancer and other solid tumor malignancies. Thrombocytopenia is a common adverse event associated with the use of these agents that can lead to a treatment delay, reduction in dose intensity, and discontinuation. The role of thrombopoietin receptor agonists (TPO-RA) remains unknown in this setting. We report a case series of 6 individuals with breast cancer that experienced dose-reductions and therapy delays due to thrombocytopenia secondary to trastuzumab emtansine or trastuzumab deruxtecan therapy and received intervention with TPO-RA. All 6 were able to resume therapy with TPO-RA support.

Predicting Hyperglycemia Among Patients Receiving Alpelisib Plus Fulvestrant for Metastatic Breast Cancer.

BACKGROUND: Hyperglycemia is recognized as a common adverse event for patients receiving alpelisib but has been little studied outside of clinical trials. We report the frequency of alpelisib-associated hyperglycemia in a real-world setting and evaluate proposed risk factors. PATIENTS AND METHODS: We retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with alpelisib plus fulvestrant between August 2019 and December 2021. Ordinal logistic regression evaluated 5 characteristics (diabetes, prediabetes, body mass index [BMI], age, and Asian ancestry) as independent risk factors for ALP-associated hyperglycemia grades 2-4. Risk of error from multiple hypothesis testing was controlled using the false discovery rate method. RESULTS: The study included n = 92 subjects, all but 1 female, mean age 59.9 (+11.9) years with 50% non-Hispanic White, 15% Hispanic/Latino, 13% Asian, 9% African/Black, and 13% other/unknown. In total 34% of patients had diabetes, 10% had pre-diabetes, and 56% had normoglycemia. Thirty-six percent were obese, 32% were overweight, 25% were normal weight, and 7% were lean. Frequency of grades 1-4 hyperglycemia in current subjects (64.1%) was similar to hyperglycemia reported in the SOLAR-1 trial (63.7%). Our subjects' risk of grades 2-4 hyperglycemia was independently increased by pre-existing diabetes (Odds ratio 3.75, 95% CI, 1.40-10.01), pre-diabetes (6.22, 1.12-34.47), Asian ancestry (7.10, 1.75-28.84), and each unit of BMI above 20 (1.17, 1.07-1.28). CONCLUSION: While receiving alpelisib, patients of Asian ancestry, as well as patients with pre-existing hyperglycemia and/or BMI above 20, should be closely monitored for hyperglycemia. The mechanism underlying the current association of alpelisib-associated hyperglycemia with Asian ancestry is independent of BMI and merits further study. The high incidence of hyperglycemia resulted in a change in practice to include consultation with a diabetes nurse educator or endocrinologist at the start of alpelisib.

Phase I Trial of Ipatasertib Plus Carboplatin, Carboplatin/Paclitaxel, or Capecitabine and Atezolizumab in Metastatic Triple-Negative Breast Cancer.

BACKGROUND: This trial evaluated the safety and efficacy of ipatasertib in combination with carboplatin, carboplatin/paclitaxel, or capecitabine/atezolizumab in patients with metastatic triple-negative breast cancer (mTNBC). METHODS: Eligibility criteria were mTNBC, RECIST 1.1 measurable disease, no prior use of platinum for metastatic disease (Arms A and B), and no prior exposure to immune checkpoint inhibitor (Arm C). Primary endpoints were safety and RP2D. Secondary endpoints were progression-free survival (PFS), response rate, and overall survival. RESULTS: RP2D for Arm A (n = 10) was ipatasertib 300 mg daily, carboplatin AUC2, and paclitaxel 80 mg m-2 days 1, 8, and 15 every 28 days. RP2D for Arm B (n = 12) was ipatasertib 400 mg daily and carboplatin AUC2 days 1, 8, and 15 every 28 days. RP2D for Arm C (n = 6) was likely ipatasertib 300 mg 21 days on 7 days off, capecitabine 750 mg m-2, twice a day, 7 days on 7 days off, and atezolizumab 840 mg days 1 and 15 every 28 days. The most common (≥10%) grade 3-4 AEs at RP2D for Arm A (N = 7 at RP2D) were neutropenia (29%), diarrhea (14%), oral mucositis (14%), and neuropathy (14%); Arm B had diarrhea (17%) and lymphopenia (25%); and Arm C had anemia, fatigue, cognitive disturbance, and maculopapular rash (17% each). Overall responses at RP2D were 29% Arm A, 25% Arm B, and 33% Arm C. PFS was 4.8, 3.9, and 8.2 months for patients on Arms A, B, and C, respectively. CONCLUSIONS: Continuous dosing of ipatasertib with chemotherapy was safe and well-tolerated. Further study is warranted in understanding the role of AKT inhibition in treatment of TNBCs. TRIAL REGISTRATION: NCT03853707.

Total Synthesis of Darobactin A.

The collaborative total synthesis of darobactin A, a recently isolated antibiotic that selectively targets Gram-negative bacteria, has been accomplished in a convergent fashion with a longest linear sequence of 16 steps from d-Garner's aldehyde and l-serine. Scalable routes toward three non-canonical amino acids were developed to enable the synthesis. The closure of the bismacrocycle was realized through sequential, halogen-selective Larock indole syntheses, where the proper order of cyclizations proved crucial for the formation of the desired atropisomer of the natural product.

Biocatalytic oxidation of alcohols using galactose oxidase and a manganese(III) activator for the synthesis of islatravir.

Galactose oxidase (GOase) is a Cu-dependent metalloenzyme that catalyzes the oxidation of alcohols to aldehydes. An evolved GOase variant was recently shown to catalyze a desymmetrizing oxidation as the first enzymatic step in the biocatalytic synthesis of islatravir. Horseradish peroxidase (HRP) is required to activate the GOase, introducing cost and protein burden to the process. Herein we describe that complexes of earth-abundant Mn(iii) (e.g. Mn(OAc)3) can be used at low loadings (2 mol%) as small molecule alternatives to HRP, providing similar yields and purity profiles. While an induction period is observed when using Mn(OAc)3 as the activator, employment of alternative Mn(iii) sources, such as Mn(acac)3 and K3[Mn(C2O4)3], eliminates the induction period and provides higher conversions to product. We demonstrate that use of the Mn(OAc)3 additive is also compatible with subsequent biocatalytic steps in the islatravir-forming cascade. Finally, to exhibit the wider utility of Mn(OAc)3, we show that Mn(OAc)3 functions as a suitable activator for several commercially available variants of GOase with a series of alcohol substrates.

Five-Step Enantioselective Synthesis of Islatravir via Asymmetric Ketone Alkynylation and an Ozonolysis Cascade.

A 5-step enantioselective synthesis of the potent anti-HIV nucleoside islatravir is reported. The highly efficient route was enabled by a novel enantioselective alkynylation of an α,ß-unsaturated ketone, a unique ozonolysis-dealkylation cascade in water, and an enzymatic aldol-glycosylation cascade.

Identifying eustachian tube dysfunction prior to hyperbaric oxygen therapy: Who is at risk for intolerance?

PURPOSE: Determine whether specific risk factors, symptoms and clinical examination findings are associated with hyperbaric oxygen therapy (HBOT) intolerance and subsequent tympanotomy tube placement. MATERIALS AND METHODS: A retrospective case series with chart review was conducted from 2007 to 2016 of patients undergoing HBOT clearance at a tertiary care university hospital in an urban city. Eighty-one (n=81) patient charts were reviewed for risk factors, symptoms and clinical examination findings related to HBOT eustachian tube dysfunction and middle ear barotrauma. Relative risk was calculated for each variable to determine risk for HBOT intolerance and need for tympanotomy tube placement. Risk factor, symptom, physical examination and HBOT complication-susceptibility scores were calculated for each patient. RESULTS: Mean risk factor, clinical and HBOT complication-susceptibility scores were significantly higher in patients who did not tolerate HBOT compared to patients who tolerated HBOT. Patients reporting a history of otitis media, tinnitus, and prior ear surgery were at a higher risk for HBOT intolerance. Patients reporting a history of pressure intolerance and prior ear surgery were more likely to undergo tympanotomy tube placement. Patients noted to have otologic findings prior to HBOT were at a higher risk for both HBOT intolerance and tympanotomy tube placement. CONCLUSIONS: A thorough otolaryngological evaluation can potentially predict and identify patients at risk for HBOT intolerance and tympanotomy tube placement.

Single-Electron Transmetalation via Photoredox/Nickel Dual Catalysis: Unlocking a New Paradigm for sp(3)-sp(2) Cross-Coupling.

The important role of transition metal-catalyzed cross-coupling in expanding the frontiers of accessible chemical territory is unquestionable. Despite empowering chemists with Herculean capabilities in complex molecule construction, contemporary protocols are not without their Achilles' heel: Csp(3)-Csp(2)/sp(3) coupling. The underlying challenge in sp(3) cross-couplings is 2-fold: (i) methods employing conventional, bench-stable precursors are universally reliant on extreme reaction conditions because of the high activation barrier of transmetalation; (ii) circumvention of this barrier invariably relies on use of more reactive precursors, thereby sacrificing functional group tolerance, operational simplicity, and broad applicability. Despite the ubiquity of this problem, the nature of the transmetalation step has remained unchanged from the seminal reports of Negishi, Suzuki, Kumada, and Stille, thus suggesting that the challenges in Csp(3)-Csp(2)/sp(3) coupling result from inherent mechanistic constraints in the traditional cross-coupling paradigm. Rather than submitting to the limitations of this conventional approach, we envisioned that a process rooted in single-electron reactivity could furnish the same key metalated intermediate posited in two-electron transmetalation, while demonstrating entirely complementary reactivity patterns. Inspired by literature reports on the susceptibility of organoboron reagents toward photochemical, single-electron oxidative fragmentation, realization of a conceptually novel open shell transmetalation framework was achieved in the facile coupling of benzylic trifluoroborates with aryl halides via cooperative visible-light activated photoredox and Ni cross-coupling catalysis. Following this seminal study, we disclosed a suite of protocols for the cross-coupling of secondary alkyl, α-alkoxy, α-amino, and α-trifluoromethylbenzyltrifluoroborates. Furthermore, the selective cross-coupling of Csp(3) organoboron moieties in the presence of Csp(2) organoboron motifs was also demonstrated, highlighting the nuances of this approach to transmetalation. Computational modeling of the reaction mechanism uncovered useful details about the intermediates and transition-state structures involved in the nickel catalytic cycle. Most notably, a unique dynamic kinetic resolution process, characterized by radical homolysis/recombination equilibrium of a Ni(III) intermediate, was discovered. This process was ultimately found to be responsible for stereoselectivity in an enantioselective variant of these cross-couplings. Prompted by the intrinsic limitations of organotrifluoroborates, we sought other radical feedstocks and quickly identified alkylbis(catecholato)silicates as viable radical precursors for Ni/photoredox dual catalysis. These hypervalent silicate species have several notable benefits, including more favorable redox potentials that allow extension to primary alkyl systems incorporating unprotected amines as well as compatibility with less expensive Ru-based photocatalysts. Additionally, these reagents exhibit an amenability to alkenyl halide cross-coupling while simultaneously expanding the aryl halide scope. In the process of exploring these reagents, we serendipitously discovered a method to effect thioetherification of aryl halides via a H atom transfer mechanism. This latter discovery emphasizes that this robust cross-coupling paradigm is "blind" to the origins of the radical, opening opportunities for a wealth of new discoveries. Taken together, our studies in the area of photoredox/nickel dual catalysis have validated single-electron transmetalation as a powerful platform for enabling conventionally challenging Csp(3)-Csp(2) cross-couplings. More broadly, these findings represent the power of rational design in catalysis and the strategic use of mechanistic knowledge and manipulation for the development of new synthetic methods.

Phenol Derivatives as Coupling Partners with Alkylsilicates in Photoredox/Nickel Dual Catalysis.

Photoredox/nickel dual catalysis via single electron transmetalation allows coupling of Csp(3)-Csp(2) hybridized centers under mild conditions. A procedure for the coupling of electron-deficient aryl triflates, -tosylates, and -mesylates with alkylbis(catecholato)silicates is presented. This method represents the first example of the use of phenol derivatives as electrophilic coupling partners in photoredox/nickel dual catalysis.

Mechanistic study of silver-catalyzed decarboxylative fluorination.

The silver-catalyzed fluorination of aliphatic carboxylic acids by Selectfluor in acetone/water provides access to fluorinated compounds under mild and straightforward reaction conditions. Although this reaction provides efficient access to fluorinated alkanes from a pool of starting materials that are ubiquitous in nature, little is known about the details of the reaction mechanism. We report spectroscopic and kinetic studies on the role of the individual reaction components in decarboxylative fluorination. The studies presented herein provide evidence that Ag(II) is the intermediate oxidant in the reaction. In the rate-limiting step of the reaction, Ag(I)-carboxylate is oxidized to Ag(II) by Selectfluor. Substrate inhibition of the process occurs through the formation of a silver-carboxylate. Water is critical for solubilizing reaction components and ligates to Ag(I) under the reaction conditions. The use of donor ligands on Ag(I) provides evidence of oxidation to Ag(II) by Selectfluor. The use of sodium persulfate as an additive in the reaction as well as NFSI as a fluorine source further supports the generation of a Ag(II) intermediate; this data will enable the development of a more efficient set of reaction conditions for the fluorination.

Improving Skin Paddle Reliability and Muscle Gliding in Free Functional Gracilis Transfers.

Free functional muscle transfer is an attractive option within reconstructive surgery when seeking to restore critical muscle function. The gracilis muscle has long been utilized for this purpose due to its expendability and consistent anatomy. Historically, survival of the skin overlying the distal one-third of the myocutaneous gracilis flap has been unpredictable. To address this, the myofasciocutaneous technique was developed, with prior studies demonstrating improved distal skin paddle viability with this approach; however, the mechanism is poorly defined. This study aimed to understand what factors contribute to survival benefit in myofasciocutaneous gracilis flaps. Using cadaveric dissections followed by latex dye injections, we discuss the creation of a deep fascial sheath that contains a rich vascular network and permits adhesion-free excursion at the recipient site. This study advances our understanding of the myofasciocutaneous gracilis flap and provides wider clinical applicability in free functional muscle transfer.

Outcomes of Biodegradable Temporizing Matrix for Soft Tissue Reconstruction of the Hand and Extremities.

Background: NovoSorb biodegradable temporizing matrix (BTM) is a novel, bilayer, synthetic skin substitute made of biodegradable polyurethane foam covered with a sealing membrane. BTM has demonstrated excellent outcomes in burn literature; however, few studies have been published for hand and extremity soft tissue reconstruction. Methods: All patients who underwent extremity reconstruction with BTM from 2018 to 2023 were reviewed. Demographics, presentations, and clinical outcomes were recorded. Results: A total of 86 cases from 54 patients (53.7% pediatric; age range: 0-81 years) were included. Common indications included trauma (36%), infection (18.6%), and malignancy (11.6%). BTM was placed over exposed tendon (38.4%), bone (19%), joints (12.8%), nerves (8.1%), and/or blood vessels (7%). BTM served as temporary wound coverage in 26 cases. Complications included hematoma (8.1%), infection (4.7%), and spontaneous delamination (4.7%). Wound closure was successfully obtained without flap use in 93.3%. Poor BTM take was associated with peripheral vascular disease, hypertension, immunosuppression, and BTM hematoma and infection (<0.05). Conclusion: This study contributes to the growing body of evidence favoring BTM use in challenging reconstructive cases. Although prospective comparative studies are forthcoming, BTM likely has broad applications in reconstructive surgery.

Uncovering the mechanism of the Ag(I)/persulfate-catalyzed cross-coupling reaction of arylboronic acids and heteroarenes.

The catalytic cross-coupling of arylboronic acids with pyridines through single-electron oxidation provides efficient access to substituted heterocycles. Despite the importance of this reaction, very little is known about its mechanism, and as a consequence, it is unclear whether the full scope of the transformation has been realized. Here we present kinetic and spectroscopic evidence showing a high degree of complexity in the reaction system. The mechanism derived from these studies shows the activation of Ag(I) for reduction of persulfate and an off-cycle protodeboronation by the pyridine substrate. These results provide key mechanistic insights that enable control of the off-cycle process, thus providing higher efficiency and yield.

Clinically Relevant Anatomical Variations in the Brachial Plexus.

Anatomical variation in the brachial plexus may result in a variety of clinically relevant patterns, including various neuralgias of the upper extremity and differing nerve territories. Some conditions can be debilitating in symptomatic patients, resulting in paresthesia, anesthesia, or weakness of the upper extremity. Others may simply result in cutaneous nerve territories that deviate from a traditional dermatome map. This study evaluated the frequency and anatomical presentations of a large number of clinically relevant brachial plexus nerve variations in a sample of human body donors. We identified a high frequency of various branching variants, of which clinicians, especially surgeons, should be aware. The medial pectoral nerves in 30% of the sample were found to originate from either the lateral cord, or both the medial and lateral cords of the brachial plexus rather than exclusively from the medial cord. The dual cord innervation pattern greatly increases the number of spinal cord levels traditionally believed to innervate the pectoralis minor muscle. The thoracodorsal nerve arose as a branch of the axillary nerve 17% of the time. The musculocutaneous nerve sent branches to the median nerve in 5% of specimens. The medial antebrachial cutaneous nerve shared a common trunk with the medial brachial cutaneous nerve in 5% of individuals and derived from the ulnar nerve in 3% of specimens.

Recent Advancements in the Diagnosis and Treatment of Congenital Hand Differences.

Congenital hand and upper limb differences include a wide spectrum of structural abnormalities that affect functional, appearance, and psychosocial domains of affected children. Ongoing advances in the understanding and treatment of these differences continue to shape management. Over the past 10 years, new developments have been made in areas of molecular genetics, noninvasive treatments, surgical techniques, and outcome measures in several commonly seen congenital hand differences. Applying these advances in knowledge and management of congenital hand differences will enable surgeons to achieve the best outcomes possible for these children.

Expanding Indications of the Medial Femoral Condyle Free Flap: Systematic Review in Head and Neck Reconstruction.

The medial femoral condyle free flap serves as an attractive reconstructive option for small- to intermediate-sized bony defects. It is commonly applied in the extremities with limited reports in the head and neck. Methods: A systematic review of the literature was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Seventeen articles met inclusion criteria, yielding 166 cases for analysis, with a majority of the cohort from a single study (n = 107; 64.4%). However, all included studies represented novel reconstructive sites and surgical indications. Flap components were described in 157 cases; periosteum was used only in four cases (2.5%), whereas all others are composed of cortical bone combined with periosteum, cancellous bone, and/or cartilage (97.5%). Additionally, a skin island was used in 43 cases (25.9%). Flap measurements were reported in 51 cases, averaging 4.5 ± 2.7 cm in length. Seven cases listed skin island dimensions, averaging 20.2 ± 12.8 cm2. The descending genicular artery was the primary pedicle employed (n = 162; 97.6%), while the superior medial genicular was used in the descending genicular artery's absence (n = 4; 2.4%). Descending genicular artery pedicle length from 15 reporting cases averaged 6.4 ± 1.2 cm. Successful reconstructions totaled 160 cases (96.4%). Recipient complications were seen in 16 cases (9.6%) with six constituting flap failures (3.6%). Donor site complications were minimal (n = 6; 3.6%); however, this included one major complication of femoral shaft fracture. Conclusion: The medial femoral condyle free flap is an effective reconstructive option for the head and neck due to its versatile nature, low complication profile at both recipient and donor site, ease of harvest, and two-team approach.

Learning Curve of Wrist-level Tendon Repairs Using a Novel Tendon Stapler versus Traditional Suture Methods.

Numerous effective techniques for primary tendon coaptations exist. However, these techniques are complex and require a substantial amount of training to become proficient. Recently, a novel tendon stapler device (TSD) was developed that could potentially diminish the discrepancies among surgeons of varying levels of training. We hypothesized that the TSD would be easier to learn and would demonstrate improved learning curve efficiencies across participants of differing tendon repair experience compared with traditional suture methods. Participants included a novice, intermediate, and expert in tendon repairs. Comparisons were performed on wrist-level flexors and extensors from human donor arms. The suture repairs were performed with a modified Kessler with a horizontal mattress and were performed in one session on two donor arms by each participant. In a second session, each participant performed the TSD repairs on the matched, contralateral donor arms. Scatterplots fitted with Loess curves, one-way analysis of variance, Tukey pairwise comparisons, two-sided independent samples t test, and Fisher exact test were used to analyze findings. Results of our study showed that TSD repair times did not vary significantly by experience level. Suture repairs reached a stable "learned" level around repair #30, whereas the TSD repairs showed a more efficient curve that stabilized around repair #23. The TSD required less educational time, demonstrated a more efficient learning curve, and showed less variability across participants and repair order. Overall, the TSD is easy to adopt and may carry positive implications for surgeons and patients.

HER2-targeted antibody-drug conjugates for breast cancer: ancestry and dose adjustment for thrombocytopenia.

BACKGROUND: Thrombocytopenia is a common adverse event on HER2-targeted therapies, fam-trastuzumab deruxtecan (T-DXd) and ado-trastuzumab emtansine (T-DM1). A reported association of Asian ancestry with this event merits investigation to rule out potential confounding. METHODS: Subjects in this retrospective cohort were female patients with HER2 positive breast cancer, of Asian or non-Hispanic White ancestry, who initiated T-DM1 or T-DXd from January 2017 through October 2021. Follow-up closed in January 2022. Primary endpoint was dose adjustment for thrombocytopenia. Competing endpoints were discontinuation of drug for other toxicity, disease progression, or for completion of prescribed cycles. The association between Asian ancestry and thrombocytopenia-related dose adjustment was tested at p < 0.01 in a proportional hazards model for the sub-distributions of 4 (primary and competing) endpoints. Covariates examined as potential confounders were age, metastatic disease, specific HER2-targeted drug, and prior drug switching for toxicity. RESULTS: Among 181 subjects, 48 reported Asian ancestry. Incidence of dose adjustment for thrombocytopenia was higher in patients with Asian ancestry and among patients switched to T-DXd after experiencing thrombocytopenia on T-DM1. Independent of specific drug and prior drug switching, Asian ancestry was associated with dose adjustment for thrombocytopenia (hazards ratio 2.95, 95% confidence interval 1.41-6.18) but not with competing endpoints. Among participants of Asian ancestry, the ancestral origin was usually China or the Philippines (where Chinese ancestry is common). CONCLUSIONS: The association between Asian ancestry and thrombocytopenia on HER2-targeted therapy is independent of age, metastatic disease, drug, and history of similar toxicity. This association may have a genetic basis linked to Chinese ancestry.

Hyperglycemia and Glycemic Variability Associated with Glucocorticoids in Women without Pre-Existing Diabetes Undergoing Neoadjuvant or Adjuvant Taxane Chemotherapy for Early-Stage Breast Cancer.

Glucocorticoids, which are administered with chemotherapy, cause hyperglycemia. Glycemic variability among breast cancer patients without diabetes is not well known. A retrospective cohort study was conducted involving early-stage breast cancer patients without diabetes who received dexamethasone prior to neoadjuvant or adjuvant taxane chemotherapy between August 2017-December 2019. Random blood glucose levels were analyzed, and steroid-induced hyperglycemia (SIH) was defined as a random glucose level of >140 mg/dL. A multivariate proportional hazards model was used to identify the risk factors of SIH. Out of 100 patients, the median age was 53 years (IQR: 45-63.5). A total of 45% of patients were non-Hispanic White, 28% Hispanic, 19% Asian, and 5% African American. The incidence of SIH was 67%, and glycemic fluctuations were highest in those with glucose levels of >200 mg/dL. Non-Hispanic White patients represented a significant predictor for time to SIH, with a hazard ratio of 2.5 (95% CI: 1.04, 5.95, p = 0.039). SIH was transient in over 90% of the patients, and only seven patients remained hyperglycemic after glucocorticoid and chemotherapy completion. Pretaxane dexamethasone-induced hyperglycemia was observed in 67% of the patients, with the greatest glycemic lability in those patients with blood glucose levels of >200 mg/dL. The non-Hispanic White patients had a higher risk of developing SIH.

Inferiorly Based Alar Groove Flap for Correction of Alar Base Malposition and Nasal Stenosis.

When the external nasal valve (ENV) is excessively narrow or lacks support, nasal obstruction can develop causing decreased airflow. Although cartilage grafts may support a collapsed nasal ala, addressing severe nasal stenosis requires further intervention. Techniques to move flared ala inward are well-known; however, repositioning a medially displaced alar base is less commonly described. Our surgical team developed an inferiorly based alar groove flap to achieve lateral movement of a malpositioned alar base, with goals of widening the ENV and improving nasal symmetry and cosmesis. A retrospective chart review was performed on a series of five patients over a two-year period. Charts were reviewed for demographic data, medical and surgical history, functional airway complaints, and subjective aesthetic concerns. All patients presented with unilateral ENV collapse, alar base malposition, and nostril asymmetry. Our operative method consisted of repositioning the affected alar base laterally and inferiorly to alleviate nostril stenosis and using an alar rim graft to support the ENV. Postoperatively, all patients demonstrated immediate alleviation of subjective nasal obstruction and improvement in size of ENV aperture, nostril symmetry, and overall cosmesis. Four patients showed lasting postoperative results. One patient experienced restenosis by 4 months and required revision. Our inferiorly based alar groove flap provides a reproducible solution for repositioning a medially displaced alar base. This technique reliably corrects ENV stenosis, relieves airway obstruction, and improves nasal symmetry and cosmesis.