Current Novel Targeted Therapeutic Strategies in Multiple Myeloma.

Multiple myeloma (MM) is a hematologic malignancy caused by the clonal expansion of immunoglobulin-producing plasma cells in the bone marrow and/or extramedullary sites. Common manifestations of MM include anemia, renal dysfunction, infection, bone pain, hypercalcemia, and fatigue. Despite numerous recent advancements in the MM treatment paradigm, current therapies demonstrate limited long-term effectiveness and eventual disease relapse remains exceedingly common. Myeloma cells often develop drug resistance through clonal evolution and alterations of cellular signaling pathways. Therefore, continued research of new targets in MM is crucial to circumvent cumulative drug resistance, overcome treatment-limiting toxicities, and improve outcomes in this incurable disease. This article provides a comprehensive overview of the landscape of novel treatments and emerging therapies for MM grouped by molecular target. Molecular targets outlined include BCMA, GPRC5D, FcRH5, CD38, SLAMF7, BCL-2, kinesin spindle protein, protein disulfide isomerase 1, peptidylprolyl isomerase A, Sec61 translocon, and cyclin-dependent kinase 6. Immunomodulatory drugs, NK cell therapy, and proteolysis-targeting chimera are described as well.

Beyond the kidney: extra-renal manifestations of monogenic nephrolithiasis and their significance.

BACKGROUND: The objective of this study was to explore the frequency of occurrence of extra-renal manifestations associated with monogenic nephrolithiasis. METHODS: A literature review was conducted to identify genes that are monogenic causes of nephrolithiasis. The Online Mendelian Inheritance in Man (OMIM) database was used to identify associated diseases and their properties. Disease phenotypes were ascertained using OMIM clinical synopses and sorted into 24 different phenotype categories as classified in OMIM. Disease phenotypes caused by the same gene were merged into a phenotypic profile of a gene (PPG) such that one PPG encompasses all related disease phenotypes for a specific gene. The total number of PPGs involving each phenotype category was measured, and the median phenotype category was determined. Phenotype categories were classified as overrepresented or underrepresented if the number of PPGs involving them was higher or lower than the median, respectively. Chi-square test was conducted to determine whether the number of PPGs affecting a given category significantly deviated from the median. RESULTS: Fifty-five genes were identified as monogenic causes of nephrolithiasis. A total of six significantly overrepresented and three significantly underrepresented phenotype categories were identified (p < 0.05). Four phenotypic categories (growth, neurological, skeletal, and abdomen/gastrointestinal) are significantly overrepresented after Bonferroni correction for multiple comparisons (p < 0.002). Among all phenotypes, impaired growth is the most common manifestation. CONCLUSION: Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal care in patients.

CD19-targeted chimeric antigen receptor T-cell therapy in patients with concurrent B-cell Non-Hodgkin lymphoma and rheumatic autoimmune diseases: a propensity score matching study.

Rheumatic autoimmune diseases not only involve the production of autoantibodies but also demonstrate T-cell dysfunction. In patients with concurrent B-cell non-Hodgkin lymphoma (NHL) and rheumatic autoimmune diseases, the safety and efficacy of CD19-targeted chimeric antigen receptor (CAR) T-cell therapy are unknown. Using an aggregated electronic health record database, patients with rheumatic autoimmune diseases (auto group) were compared to propensity score-matched patients without rheumatic autoimmune diseases (non-auto group). From 1/2019 to 1/2023, 58 (4.3%) of 1,363 patients who received CD19-targeted CAR T-cell therapy had concurrent rheumatic autoimmune diseases. Both groups had similar incidence, severity, and management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover, the two groups had similar time-to-next treatment or death (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.60 to 1.59, log-rank p = 0.91) and overall survival (HR 0.90, 95%CI 0.46 to 1.78, p = 0.76). Following CAR T-cell infusion, patients with rheumatic autoimmune diseases achieved decreased inflammatory markers, seronegative conversion of autoantibodies, as well as reduced use of steroids and disease-modifying anti-rheumatic drugs. In conclusion, the safety and efficacy of CAR T-cell therapy were not affected in patients with rheumatic autoimmune diseases. Moreover, they achieved better biochemical control of underlying rheumatic diseases.

High Entropy Nonlinear Dielectrics with Superior Thermally Stable Performance.

A high configurational entropy, achieved through a proper design of compositions, can minimize the Gibbs free energy and stabilize the quasi-equilibrium phases in a solid-solution form. This leads to the development of high-entropy materials with unique structural characteristics and excellent performance, which otherwise could not be achieved through conventional pathways. This work develops a high-entropy nonlinear dielectric system, based on the expansion of lead magnesium niobate-lead titanate. A dense and uniform distribution of nano-polar regions is observed in the samples owing to the addition of Ba, Hf, and Zr ions, which lead to enhanced performance of nonlinear dielectrics. The fact that no structural phase transformation is detected up to 250 °C, and no noticeable change or a steep drop in structural and electrical characteristics is observed at high temperatures suggests a robust thermal stability of the dielectric systems developed. With these advantages, these materials hold vast potential for applications such as dielectric energy storage, dielectric tunability, and electrocaloric effect. Thus, this work offers a new high-entropy configuration with elemental modulation, with enhanced dielectric material features.

Risk stratification for worsening renal function and renal decline in heart failure patients with reduced ejection fraction after sacubitril/valsartan treatment.

BACKGROUND: In the real-world setting, data regarding renal decline following sacubitril/valsartan treatment are lacking. This study aimed to develop a scoring system to predict renal outcome in sacubitril/valsartan-treated patients. METHODS: Between 2017 and 2018, a total of 1505 heart failure patients with reduced ejection fraction (HFrEF) undergoing sacubitril/valsartan treatment were consecutively enrolled from 10 hospitals to serve as the derivation cohort. Another 1620 HFrEF patients receiving sacubitril/valsartan were included as the validation cohort. Worsening renal function (WRF) was defined as a serum creatinine increase of >0.3 mg/dL and/or >25 % at 8 months of sacubitril/valsartan treatment. The derivation cohort was used to identify independent predictive factors for WRF through multivariate analysis, which were then used to develop the risk score system. RESULTS: Among the 3125 HFrEF patients, 689 (22.0 %) patients had WRF at 8 months following sacubitril/valsartan treatment. In the derivation cohort, six prognostic factors (age, functional class, history of peripheral arterial disease, diabetes mellitus, gout or hyperuricemia, and serum albumin level) were independently associated with WRF, and were combined into a risk predicting score. This score showed accurate discrimination in the derivation and validation cohorts (Harrell's concordance indexes 0.74 and 0.71, 95 % confidence intervals 0.71-0.78 and 0.69-0.74, respectively). Patients with a higher risk score experienced a more rapid decline in renal function, poorer clinical outcomes, and a higher rate of discontinuation of sacubitril/valsartan treatment. CONCLUSIONS: This study developed a score for WRF after sacubitril/valsartan treatment, which may assist clinicians with risk stratification and therapeutic decision-making.

Novel compound heterozygote variants: c.4193_4206delinsG (p.Leu1398Argfs*25), c.793C > A (p.Pro265Thr), in the CPS1 gene (NM_001875.4) causing late onset carbamoyl phosphate synthetase 1 deficiency-Lessons learned.

Carbamoyl phosphate synthetase 1 (CPS1) deficiency is an autosomal recessive urea cycle disorder with varying presentations. Patients with a neonatal-onset phenotype are initially healthy but develop severe hyperammonemia days after birth and often have poor or lethal outcomes, while patients who present later in life may exhibit less severe clinical manifestations. CPS1 deficiency is rarely found on newborn screening because most states do not screen for this disease due to the technical difficulties. We report a case of an 11-year-old, previously healthy girl who presented with hyperammonemia and acute psychosis after eating large amounts of meat at summer camp. A diagnosis of carbamoyl phosphate synthetase type 1 deficiency was suspected by biochemical profiles and confirmed by molecular analysis. Subsequent follow up lab results revealed ammonia to be only 25-39 µmol/L shortly after glutamine reached levels as high as 770-1432 µmol/L with concurrent alanine elevations, highlighting the compensating mechanisms of the human body. Her initial hospital course also demonstrated the importance of continuous renal replacement therapy (CRRT) in avoiding rebound hyperammonemia and high glutamine and the benefits of intracranial pressure (ICP) monitoring, providing 3% hypertonic saline and temperature control to avoid fever in treating cerebral edema. Carglumic acid was not considered helpful in this case, with BUN levels ranging between 2 and 4 mg/dL after administration.

Clinical impacts of sacubitril/valsartan on patients eligible for cardiac resynchronization therapy.

AIMS: Sacubitril/valsartan (SAC/VAL) has been used in patients with heart failure and reduced ejection fraction (HFrEF), and cardiac resynchronization therapy (CRT) could benefit the HFrEF patients with wide QRS durations. This study aimed to evaluate the clinical impacts of SAC/VAL on reverse cardiac remodelling in CRT-eligible and CRT-ineligible HFrEF patients with different QRS durations. METHODS AND RESULTS: The TAROT-HF study was a multicentre, observational study enrolling patients who initiated SAC/VAL from 10 hospitals since 2017. Patients with baseline left ventricular ejection fraction (LVEF) ≤ 35% were classified into two groups: (i) Group 1: CRT-eligible group, patients with left bundle branch block (LBBB) morphology plus QRS duration ≥130 ms or non-LBBB morphology plus QRS duration ≥150 ms; and (ii) Group 2: CRT-ineligible group. Propensity score matching was performed to adjust for confounders, and 1168 patients were analysed. Baseline characteristics were comparable between the two groups. The improvements in LVEF and left ventricular end-systolic volume index (LVESVi) were more significant in Group 2 than in Group 1 after 1 year SAC/VAL treatment (LVEF: 8.4% ± 11.3% vs. 4.5% ± 8.1%, P < 0.001; change percentages in LVESVi: -14.4% ± 25.9% vs. -9.6% ± 23.1%, P = 0.004). LVEF improving to ≥50% in Groups 1 and 2 constituted 5.2% and 20.2% after 1 year SAC/VAL treatment (P < 0.001). Multivariate analyses showed that wide QRS durations were negatively associated with the reverse cardiac remodelling in these HFrEF patients with SAC/VAL treatment. CONCLUSION: Despite SAC/VAL treatment, wide QRS durations are associated with lower degrees of left ventricular improvement than narrow ones in the HFrEF patients. Optimal intervention timing for the CRT-eligible patients requires further investigation.

Compound heterozygote variants: c.848A > G; p.Glu283Gly and c.890C > T; p.Ala297Val, of Isovaleric acid-CoA dehydrogenase (IVD) gene causing severe Isovaleric acidemia with hyperammonemia.

With the execution of expanded newborn screen (NBS) program nationwide, it is uncommon to see severe hyperammonemia associated with isovaleric acidemia (IVA). We present a seven-day-old boy with severe IVA complicated by hyperammonemia. This child was flagged by NBS at 4 days old, but confirmatory testing was delayed due to COVID19 pandemic and parental skepticism. His parents did not adhere to the leucine-restricted diet as recommended. On day 7, the patient presented to the ER with ammonia of 588 µg/dL. Ammonia subsequently rose to >1000 µg/dL. This child received carnitine, 1 dose of Ammonul (sodium benzoate and sodium phenylacetate), arginine, carglumic acid (Carbaglu) and CRRT. Plasma amino acid assay revealed a glutamine level of 256 µmol/L, which is below the lower limit of normal upon arrival to ER and PICU. The hyperammonemia was corrected in 15 h and with the continued use of carglumic acid for 3 days, there was no rebound of hyperammonemia. However, the patient suffered from bone marrow suppression associated with the organic acidemia and required frequent platelet transfusions, as well as G-CSF for neutropenia. The management of this patient provides supporting evidence of the many theoretic metabolic "facts" including why Ammonul is not helpful in organic acidemias.

Effects of Ivabradine on Patients with Depressed Left Ventricular Function after Cardiac Resynchronization Therapy.

Background: The potential synergistic effect of ivabradine and cardiac resynchronization therapy (CRT) in heart failure (HF) patients has rarely been studied. We aimed to evaluate the clinical benefits of ivabradine in patients with left ventricular dysfunction following CRT implantation. Methods: Two hundred and thirty-one patients receiving CRT were consecutively enrolled between January 2014 and December 2018 from two HF centers. A total of 123 patients had left ventricular ejection fraction (LVEF) < 40% and resting sinus heart rate (HR) ≥ 75 bpm after six months of CRT implantation. Among these patients, 45 were treated with ivabradine (Group 1), and 78 did not receive ivabradine treatment (Group 2). Results: Baseline characteristics and prescription rates of HF medications other than ivabradine were similar between the two groups. In Group 1, the mean HR decreased from 82.2 ± 11.4 bpm to 76.3 ± 10.5 bpm (p = 0.012), and the mean LVEF increased from 29.9 ± 6.5% to 38.8 ± 12.4% (p < 0.001). Atrial pacing percentage, biventricular pacing percentage, and burden of atrial fibrillation (AF) were not significantly different between the two groups during the study period. The patients' daily physical activity increased significantly in Group 1 compared to Group 2 (Δ daily activity 0.4 ± 0.7 hours/day vs. -0.1 ± 7.2 hours/day, p < 0.001). Conclusions: Ivabradine could effectively reduce HR and improve physical activity. It was safe to use and did not increase AF burden or affect biventricular pacing percentage in CRT recipients.

Should We Use High-Flow Nasal Cannula in Patients Receiving Gastrointestinal Endoscopies? Critical Appraisals through Updated Meta-Analyses with Multiple Methodologies and Depiction of Certainty of Evidence.

(1) Background: High-flow nasal cannula (HFNC) therapy or conventional oxygen therapy (COT) are typically applied during gastrointestinal (GI) endoscopic sedation. (2) Methods: We conducted a rigorous systematic review enrolling randomized controlled trials (RCTs) from five databases. Risk of bias was assessed using Cochrane's RoB 2.0 tool; certainty of evidence (CoE) was assessed using GRADE framework. Meta-analysis was conducted using inverse-variance heterogeneity model and presented as relative risk (RR) with 95% confidence interval (CI). Trial sequential analysis was performed, and sensitivity analysis was conducted with Bayesian approach. (3) Results: Eight RCTs were included. Compared to COT, HFNC did not reduce the overall incidence of hypoxemia (RR 0.51; 95% CI 0.24-1.09; CoE: very low) but might reduce the incidence of hypoxemia in patients at moderate to high risk for hypoxemia (RR 0.54; 95% CI 0.31-0.96; and CoE: very low). HFNC might reduce the incidence of severe hypoxemia (RR 0.38; 95% CI 0.20-0.74; and CoE: low). HFNC might not affect the need of minor airway interventions (RR 0.31; 95% CI 0.08-1.22; and CoE: very low) and had no effect on procedure duration (CoE: very low); (4) Conclusions: During GI endoscopic sedation, HFNC might reduce the incidence of hypoxemia in patients at moderate to high risk for hypoxemia and prevent severe hypoxemia.

The Early Dynamic Change in Cardiac Enzymes and Renal Function Is Associated with Mortality in Patients with Fulminant Myocarditis on Extracorporeal Membrane Oxygenation: Analysis of a Single Center's Experience.

(1) Background: Fulminant myocarditis (FM) could result in hemodynamic derangement and fatal arrhythmia. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is used to maintain organ perfusion in FM patients complicating cardiogenic shock. The present study aims to assess the static and dynamic factors in association with mortality in FM patients on V-A ECMO (2) Methods: Twenty-eight patients were enrolled between 2013 to 2019 for analysis (3) Results: In-hospital survival rate was 78.5%. There was no statistical difference in demographics and baseline laboratory data between survivors and non-survivors. However, within 24 h after ECMO support, CK-MB increased by 96.8% among non-survivors, but decreased by 23.7% among survivors (p = 0.022). Troponin I increased by 378% among non-survivors and 1.7% among survivors (p = 0.032). Serum creatinine increased by 108% among non-survivors, but decreased by 8.5% among survivors (p = 0.005). The receiver operating characteristic curve suggested an increase in serum creatinine by 68% within 24 h after ECMO support was associated with increased mortality with an area under the curve of 0.91. (4) Conclusions: V-A ECMO is an excellent tool to support FM patients with cardiogenic shock. The early dynamic change of renal function and cardiac enzymes may be useful for outcome assessment.

Early-Onset Colorectal Cancer in Patients under 50 Years of Age: Demographics, Disease Characteristics, and Survival.

INTRODUCTION: Incidence of early-onset colorectal cancer (EO-CRC) is increasing in younger demographics. This study analyzes disease-specific survival in individuals under 50 years of age. METHODS: Patients with colorectal malignancy were identified in the Surveillance Epidemiology and End Results (SEER) database from 2004 to 2015. Cases were categorized into typically screened (age 50-79 years) and non-typically screened (age 20-49 years) cohorts, as well as by decade. Kaplan-Meier curves and Cox proportional hazard models were used to study survival. RESULTS: A total of 240,772 patients with colorectal cancer were analyzed. Average annual percent change in incidence was -0.24% among typically screened patients and +1.12% among patients with EO-CRC. Patients with EO-CRC more frequently presented with distal tumors (70.6% vs. 57.6%, P < .001) and advanced tumor stage (61.3% vs. 48.6%, P < .001). Patients aged 50 and over had comparable 5 year disease-specific survival to younger patients (68.2% vs. 66.4%, P = .31); however, patients in the 3rd, 4th, and 8th decade of life had particularly low survival rates (59.0% vs. 65.8% vs. 65.8%, logrank P < .001). Patients aged 20-29 years had the most increased risk of cause-specific mortality on univariable Cox regression analysis [HR 1.43, 95% CI 1.31-1.56; P < .001], although this was not significant on multivariable analysis [HR 1.06, 95% CI 0.97-1.15; P = .201]. Male sex, older age, advanced stage, rectal and/or cecal primary, and earlier year of diagnosis were independently associated with increased mortality. CONCLUSION: Patients with EO-CRC are diagnosed at a later stage and have lower disease-specific survival than those in typically screened cohorts. Additional studies on tumor biology and surveillance strategies are needed to improve outcomes in this population.

Temporary coronary sinus pacing to improve ventricular dyssynchrony with cardiogenic shock: A case report.

BACKGROUND: Temporary transvenous pacing through the coronary sinus is a novel approach rarely used in treating unstable bradycardia. This modality could provide cardiac pacing while achieving better ventricular synchrony. We present a case who received cardiac pacing through the coronary sinus and provide a summary of evidence in the current literature. CASE SUMMARY: A 55-year-old woman with a history of advanced heart failure was admitted to the rehabilitation ward after a recent stroke. During hospitalization, she had paroxysmal atrial fibrillation with rapid ventricular response resulting from fluid overload. While atrial fibrillation was spontaneously reversed to sinus rhythm after diuresis, she developed multiple episodes of polymorphic ventricular tachycardia along with sinus bradycardia and prolonged QTc interval. She became hypotensive despite appropriate medical management. Pacing through her implantable cardioverter-defibrillator was attempted but worsened her hypotension. Ventricular dyssynchrony was suspected. Temporary transvenous atrial pacing through the coronary sinus was performed, which stabilized her blood pressure and improved end-organ perfusion. A permanent biventricular pacemaker was later implanted, and she was safely discharged to a nursing home. CONCLUSION: Temporary transvenous pacing through the coronary sinus, a novel approach to treat unstable bradycardia, may reduce ventricular dyssynchrony.

The Football Sign: An Alarming Feature on Supine Radiograph.

Football sign is a rare radiographic finding on abdominal x-ray that suggests massive pneumoperitoneum. Free air outlines the abdominal cavity and falciform ligament which creates the radiolucent oval contour of a football. Football sign is hardly reported in older children or adults. We present the first clear image of football sign caused by gastric perforation in an adult patient. A 57-year-old male with a history of hepatocellular carcinoma was diagnosed with an undrainable liver abscess and partial gastric outlet obstruction. He developed acute onset of severe abdominal pain afterward and abdominal plain film showed a large oval radiolucency over the central part of the abdomen without interruption by intestine, a classical finding of pneumoperitoneum also known as a "football sign". Emergent laparotomy revealed a 0.5 cm perforation hole at the anterior surface of the gastric antrum. Despite timely intervention, the patient died from progression of multiorgan failure. This case describes an alarming radiographic finding that rarely occurs in the adult population. Air could be identified on x-ray in this patient due to presence of massive ascites in his abdominal cavity. Recognizing radiographic patterns that suggest pneumoperitoneum on supine plain radiographs could expedite the diagnostic process and surgical intervention.

The Function-Preserving Frontalis Orbicularis Oculi Muscle Flap for the Correction of Severe Blepharoptosis With Poor Levator Function.

BACKGROUND: Severe blepharoptosis with poor levator function (LF) has traditionally been managed with exogenous frontalis suspension but complications such as lagophthalmos, infection, and rejection are often reported. OBJECTIVES: The aim of this study was to design a function-preserving frontalis orbicularis oculi muscle (FOOM) flap to correct severe blepharoptosis with poor LF. The long-term surgical outcome of the technique was assessed. METHODS: This retrospective study included only adult patients with severe blepharoptosis and poor LF, all of whom had their surgery performed by the senior surgeon over a 6-year period. Clinical assessment of LF, palpebral fissure height (PFH), marginal reflex distance 1 (MRD1), duration of follow-up, and postoperative complications were recorded. RESULTS: A total of 34 patients and 59 eyelids were recorded during a mean follow-up period of 17.7 months. Postoperative evaluation yielded mean [standard deviation] improvements of PFH gain of 5.62 [1.61] mm (P < 0.001), and MRD1 and PFH increases of 4.03 [0.82] mm (P < 0.001) and 8.94 [0.81] mm (P < 0.001), respectively. All patients demonstrated normalization of orbicularis function: no lagophthalmos was observed at the 8-month postoperative follow-up. Recurrence of ptosis was recorded in 4 eyelids (6.78%). Revisions were performed in 2 eyelids (3.39%). No infection or granuloma was noted. CONCLUSIONS: The function-preserving FOOM flap is a useful vector for frontalis suspension. Not only does it effectively address lagophthalmos as well as other complications, but it provides aesthetically pleasing outcomes in patients with severe blepharoptosis and poor LF.

Activation of medial orbitofrontal cortex abolishes fear extinction and interferes with fear expression in rats.

Pavlovian fear conditioning and extinction procedures have long been used to study the regulation of learned fear. The amygdala is vital for the association of cues and fear expression, whereas the medial prefrontal cortex (mPFC) is critical for fear regulation after extinction. The medial orbitofrontal cortex (mOFC) has an extensive connection with the fear circuit. In human studies, emotional regulation disorders, such as obsessive-compulsive disorder and post-traumatic stress disorder, are often linked to an abnormality in the orbitofrontal cortex (OFC). Therefore, in a series of experiments, we examined whether abnormal mOFC activities interfere with the regulation of learned fear. The mOFC of rats was pharmacologically activated with N-methyl-D-aspartate (NMDA) during the acquisition, early consolidation, or retrieval phase of fear extinction. Under mOFC activation, there was a general initial suppression of the fear response followed by the development of nonspecific fear expression. Moreover, pre-extinction activation of the mOFC abolished extinction acquisition, causing an up-shift in the fear response during the retrieval test. Nonetheless, immediate post-extinction activation of the mOFC did not interfere with extinction consolidation. Overall, our results suggested that mOFC activation abolished fear extinction acquisition and interfered with fear expression.

Myotomy In Situ for Essential Blepharospasm Refractory to Botulinum Toxin.

BACKGROUND: Full myectomy is recommended for benign essential blepharospasm (BEB) refractory to botulinum toxin (BT) treatment, but long-term swelling, scar contracture, hollow appearance, and unnatural contour of the eyelids are common postoperative complications. We present myotomy in situ to minimize these adverse outcomes. METHODS: The redundant eyelid skin with its underlying muscle is resected first, and myotomy in situ is performed by completely cutting the residual orbicularis oculi muscles into multiple cubes and down to the subcutaneous layer, and then cutting the procerus and corrugator muscles down to the periosteum. Patient demographics, medical treatment history, BT injection history, blepharoptosis correction techniques, associated surgical procedures, and aesthetic outcomes were analyzed. Preoperative and postoperative BT injection dosage and frequency, as well as modified disability scores, were compared using paired Student t tests. RESULTS: Twenty-five patients underwent this technique. Their average ± SD age was 64.4 ± 8.9 years, with average postoperative follow-up occurring 17.0 ± 8.0 months. Associated diseases included blepharoptosis (88%) and apraxia of lid opening (44%). There were no postoperative hematoma, seroma, scar contracture, and depressed hollow eyelid contours. Preoperative to postoperative assessments revealed improvements in mean BT injection interval (10.4 ± 2.1 to 14.6 ± 2.9 weeks, P < 0.001), BT injection dosage (44.4 ± 13.3 to 28.1 ± 6.7 units, P < 0.001), and modified disability score (15.3 ± 3.0 to 2.8 ± 2.2, P < 0.001). All patients were highly satisfied with functional and aesthetic surgical outcomes (4.5 ± 0.6 on Likert scale). CONCLUSIONS: Myotomy in situ is effective for patients with BEB who are refractory to BT treatment, with therapeutic benefits similar to that of full myectomy with the ability to maintain favorable cosmetic results. Relative high incidence of blepharoptosis and apraxia of lid opening in patients with refractory BEB was reported. Simultaneous correction of the ptosis can further optimize outcomes.