Etomoxir-carnitine, a novel pharmaco-metabolite of etomoxir, inhibits phospholipases A2 and mitochondrial respiration.

Mitochondrial fatty acid oxidation serves as an essential process for cellular survival, differentiation, proliferation, and energy metabolism. Numerous studies have utilized etomoxir (ETO) for the irreversible inhibition of carnitine palmitoylcarnitine transferase 1 (CPT1), which catalyzes the rate-limiting step for mitochondrial long-chain fatty acid ß-oxidation to examine the bioenergetic roles of mitochondrial fatty acid metabolism in many tissues in multiple diverse disease states. Herein, we demonstrate that intact mitochondria robustly metabolize ETO to etomoxir-carnitine (ETO-carnitine) prior to nearly complete ETO-mediated inhibition of CPT1. The novel pharmaco-metabolite, ETO-carnitine, was conclusively identified by accurate mass, fragmentation patterns, and isotopic fine structure. On the basis of these data, ETO-carnitine was successfully differentiated from isobaric structures (e.g., 3-hydroxy-C18:0 carnitine and 3-hydroxy-C18:1 carnitine). Mechanistically, generation of ETO-carnitine from mitochondria required exogenous Mg2+, ATP or ADP, CoASH, and L-carnitine, indicating that thioesterification by long-chain acyl-CoA synthetase to form ETO-CoA precedes its conversion to ETO-carnitine by CPT1. CPT1-dependent generation of ETO-carnitine was substantiated by an orthogonal approach using ST1326 (a CPT1 inhibitor), which effectively inhibits mitochondrial ETO-carnitine production. Surprisingly, purified ETO-carnitine potently inhibited calcium-independent PLA2γ and PLA2ß as well as mitochondrial respiration independent of CPT1. Robust production and release of ETO-carnitine from HepG2 cells incubated in the presence of ETO was also demonstrated. Collectively, this study identifies the chemical mechanism for the biosynthesis of a novel pharmaco-metabolite of ETO, ETO-carnitine, that is generated by CPT1 in mitochondria and likely impacts multiple downstream (non-CPT1 related) enzymes and processes in multiple subcellular compartments.

Role of Peroxiredoxin 1 Induced by Epstein-Barr Virus Infection in Nasopharyngeal Carcinoma.

BACKGROUND/AIM: Nasopharyngeal carcinoma (NPC), a common cancer in Southern China, is associated with Epstein-Barr Virus (EBV) infection. Although many therapies for NPC have been established, the definite role of EBV in NPC remains unclear. Therefore, this work focuses on LMP2A, a latent EBV gene, and investigates whether LMP2A is related to peroxiredoxin 1 (PRDX1) in EBV-positive NPC. MATERIALS AND METHODS: The mRNA and protein expression levels of LMP2A, PRDX1, and beta-catenin were compared in patient samples. To identify molecular mechanisms, EBV-negative NP69 and EBV-positive C666-1 NPC cell lines were used. After making an agar cell block for cell slides, the intensity of LMP2A expression was observed visually. To measure the level of reactive oxygen species, both fluorescence microscope and flow cytometry were used. To investigate the intracellular signaling molecular mechanisms with and without the LMP2A gene, reverse transcription polymerase chain reaction and western blotting were used. RESULTS: Both patient samples and cells of nasopharyngeal carcinoma infected with EBV had increased expression of LMP2A compared with controls, and high ROS levels were identified. Cell viability assay showed that LMP2A promoted cell growth by regulating gene expression. Furthermore, LMP2A induced the expression of PRDX1 and beta-catenin. LMP2A also increased the expression of both cyclin B1 and cyclin D1. CONCLUSION: In NPC cells, PRDX1 and beta-catenin were regulated through LMP2A expression, which reduced cell growth through cell cycle-related gene expression. This study suggests that LMP2A could be a target molecule for inhibiting cancer progression in NPC cells infected with EBV.

Treatment Outcomes of Proton Beam Therapy for Esophageal Squamous Cell Carcinoma at a Single Institute.

Recently, proton beam therapy (PBT) has gathered attention for improving outcomes and reducing toxicities in various cancers; however, the evidence for esophageal squamous cell carcinoma (ESCC) is lacking. Our study retrospectively evaluated the outcomes of PBT for ESCC patients at a single institute. The patients treated with PBT between November 2015 and February 2022 were included in the study, excluding those with distant metastases or those that had undertaken prior treatment for esophageal cancer (EC). The 3 year overall survival (OS) and progression-free survival (PFS) rates were calculated based on stage grouping. The patterns of failure, salvage treatment outcomes, and toxicity profiles were analyzed. The median follow-up was 35.1 months, and 132 patients were analyzed. The 3 year OS and PFS rates for the stages I, II, and III disease cases were 81.0%, 62.9%, and 51.3%; and 70.6%, 71.8%, and 39.8%, respectively. Nineteen patients presented isolated local progression, ten patients underwent appropriate salvage procedures, and nine were successfully salvaged. One patient with isolated regional progression was also salvaged. No cases of grade ≥ 4 lymphopenia were observed. One patient had grade 4 pericardial effusion and esophageal fistula. For the patients with ESCC, PBT is an effective treatment in terms of the survival outcomes and toxicities.

Skin-Whitening Effect of a Callus Extract of Nelumbo nucifera Isolate Haman.

The sacred lotus (Nelumbo nucifera Gaertn. Isolate Haman, in the family Nelumbonaceae) used in this study originated from the Haman region of Korea, and lotus seeds dating back to the Goryeo Dynasty (650-760 years ago) were accidentally discovered. Lotus is known to possess antioxidant, anti-inflammatory, and soothing properties. Instead of using the lotus alone, we obtained extracts using Haman region lotus-derived callus (HLC), which allowed for a controlled, quantitative, and infinite supply. Based on the reported effects of the lotus, we formulated a hypothesis to investigate the skin-whitening effect of the HLC extract (HLCE). The HLCE was first obtained by extraction with distilled water and using 5% propanediol as a solvent and subsequently verified for the whitening effect (melanin content tests) using mammalian cells in vitro. Its efficacy at the molecular level was confirmed through real-time polymerase chain reaction (PCR) using melanin-related genes. Furthermore, clinical trials with 21 volunteers confirmed the significant whitening effect of cosmetics containing the HLCE. In conclusion, we found that the HLCE not only has anti-inflammatory, antioxidant, and skin-soothing properties but also plays an essential role in skin whitening. Therefore, we propose that the HLCE has the potential to become a new raw material for the cosmetic industry.

Definitive radiotherapy in patients with clinical T1N0M0 esophageal squamous cell carcinoma: A multicenter retrospective study (KROG 21-10).

PURPOSE: To assess the failure pattern and analyze the treatment scheme of definitive radiation therapy (RT) for T1N0M0 esophageal squamous cell carcinoma (ESCC). METHODS: We performed a multi-institutional retrospective analysis in T1N0M0 ESCC patients who underwent definitive RT from 2010 to 2019. Patterns of failure were demonstrated as in-, and out-field locoregional, and distant metastasis. In the analysis, freedom-from locoregional recurrence (FFLRR) and their association with clinicopathologic factors were evaluated. Propensity score matching in cT1b patients was done. RESULTS: 168 patients were included with a median follow-up of 34.0 months, and 26 cT1a, 116 cT1b disease. The rates of 3-year all and locoregional recurrence for cT1a were 30.5% and 24.1% and those for cT1b were 27.1% and 25.9%, respectively. Among 116 cT1b patients, 69 patients received elective nodal irradiation (ENI) and 47 received involved field irradiation (IFI). After propensity score matching, the 3-year FFLRR rate was 84.5%. There was no difference between ENI and IFI in FFLRR (P = 0.831) and OS (P = 0.525). The 3-year FFLRR was 83.8% (95% Confidence interval (CI), 61.8-93.8%) in IFI group and 85.3% (95% CI, 65.1-94.3%) in ENI group. In multivariate analysis, concurrent chemotherapy use was marginally associated with FFLRR (Hazard ratio, 0.16; P = 0.064). CONCLUSION: cT1a patients who cannot receive endoscopic resection showed similar failure rates as cT1b patients, questioning the staging accuracy and raised the need for thorough treatment like chemoradiotherapy. In cT1b patients, IFI with 50 to 60 Gy and concurrent chemotherapy could be reasonable.

Effect of Probiotic-Fortified Infant Formula on Infant Gut Health and Microbiota Modulation.

Compared to infant formula, breast milk is the best source of nutrition for infants; it not only improves the neonatal intestinal function, but also regulates the immune system and gut microbiota composition. However, probiotic-fortified infant formula may further enhance the infant gut environment by overcoming the limitations of traditional infant formula. We investigated the probiotic formula administration for one month by comparing 118 Korean infants into the following three groups: infants in each group fed with breast milk (50), probiotic formula (35), or placebo formula-fed group (33). Probiotic formula improved stool consistency and defecation frequency compared to placebo formula-fed group. The probiotic formula helped maintaining the level of secretory immunoglobulin A (sIgA), which had remarkably decreased over time in placebo formula-fed infants (compared to weeks 0 and 4). Moreover, probiotic formula decreased the acidity of stool and considerably increased the butyrate concentration. Furthermore, the fecal microbiota of each group was evaluated at weeks 0 and 4. The microbial composition was distinct between each groups, and the abundance of health-promoting bacteria increased in the probiotic formula compared to the placebo formula-fed group. In summary, supplementation of probiotic infant formula can help optimize the infant gut environment, microbial composition, and metabolic activity of the microbiota, mimicking those of breast milk.

Genetic deletion of skeletal muscle iPLA2γ results in mitochondrial dysfunction, muscle atrophy and alterations in whole-body energy metabolism.

Skeletal muscle is the major site of glucose utilization in mammals integrating serum glucose clearance with mitochondrial respiration. To mechanistically elucidate the roles of iPLA2γ in skeletal muscle mitochondria, we generated a skeletal muscle-specific calcium-independent phospholipase A2γ knockout (SKMiPLA2γKO) mouse. Genetic ablation of skeletal muscle iPLA2γ resulted in pronounced muscle weakness, muscle atrophy, and increased blood lactate resulting from defects in mitochondrial function impairing metabolic processing of pyruvate and resultant bioenergetic inefficiency. Mitochondria from SKMiPLA2γKO mice were dysmorphic displaying marked changes in size, shape, and interfibrillar juxtaposition. Mitochondrial respirometry demonstrated a marked impairment in respiratory efficiency with decreases in the mass and function of oxidative phosphorylation complexes and cytochrome c. Further, a pronounced decrease in mitochondrial membrane potential and remodeling of cardiolipin molecular species were prominent. Collectively, these alterations prevented body weight gain during high-fat feeding through enhanced glucose disposal without efficient capture of chemical energy thereby altering whole-body bioenergetics.

A novel classification of Kienbock's disease based on magnetic resonance imaging.

PURPOSE: We devised a classification system for Kienbock's disease using magnetic resonance imaging (MRI). Moreover, we compared it with the modified Lichtman classification and evaluated the inter-observer reliability. METHODS: Eighty-eight patients diagnosed with Kienbock's disease were included. All patients were classified using the modified Lichtman and MRI classifications. MRI staging was based on factors including partial marrow oedema, cortical integrity of the lunate, and dorsal subluxation of the scaphoid. The inter-observer reliability was evaluated. We also evaluated the presence of a displaced coronal fracture of the lunate and investigated its association with the presence of a dorsal subluxation of the scaphoid. RESULTS: Seven patients were categorized into stage I, 13 into II, 33 into IIIA, 33 into IIIB, and two into IV using the modified Lichtman classification. Six patients were categorized into stage I, 12 into II, 56 into IIIA, ten into IIIB, and four into IV using the MRI classification. The greatest shift between the stages was observed in stages IIIA and IIIB when the results of the two classification systems were compared. The inter-observer reliability of the MRI classification was greater than that of the modified Lichtman classification. Fifteen cases with a displaced coronal fracture of the lunate were identified, and a dorsal subluxation of the scaphoid was significantly more present in these patients. CONCLUSION: The MRI classification system is more reliable than is the modified Lichtman classification. MRI classification reflects carpal misalignment with higher fidelity and is more appropriate for classification into stages IIIA and IIIB.

Regional lymph node recurrence after stereotactic body radiation therapy for lung cancer: Patterns of recurrence, treatment approaches, and clinical outcomes (KROG 21-09).

PURPOSE: To present the multi-institutional data on patterns of recurrence, treatment approaches, and clinical outcomes for regional lymph node (LN) recurrence after stereotactic body radiation therapy (SBRT) for primary lung cancer. MATERIALS AND METHODS: The medical records of 114 patients who experienced regional LN recurrence as the first recurrence after lung SBRT were retrospectively reviewed. Patterns of recurrence were classified as local recurrence, regional recurrence, and distant metastasis. Clinical outcomes including progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: Half of the patients had regional LN recurrence only. The most common simultaneous recurrence was distant metastasis (38.6 %). Common sites of regional recurrence were ipsilateral hilar (47.2 %), ipsilateral upper mediastinal (40.6 %), and subcarinal (42.5 %) LN stations. 24 (21.1 %) patients underwent salvage radiation therapy (RT), and 44 (38.6 %) patients underwent palliative treatment. Better OS was observed in the salvage RT group (p = 0.025). The 1-year PFS and OS rates were 27.7 % and 55.2 %, respectively, with salvage RT, 14.0 % and 39.9 %, respectively, with palliative treatment, and 22.8 % and 26.8 %, respectively, with no additional treatment. Multivariate analysis showed that salvage RT (PFS, HR 0.463, p = 0.050; OS, HR 0.312, p = 0.002), palliative treatment (PFS, HR 0.436, p = 0.013; OS, HR 0.553, p = 0.050), and simultaneous distant metastasis (PFS, HR 2.335, p = 0.005; OS, HR 1.726, p = 0.054) affected clinical outcomes. CONCLUSION: Many cases of regional LN recurrence are confined to the locoregional area of patients, and appropriate treatment can improve the prognosis of these patients.

Relationship Between Hallux Valgus Recurrence and Sesamoid Position on Anteroposterior Standing Radiographs After Distal Chevron Metatarsal Osteotomy.

BACKGROUND: Recurrence of the hallux valgus deformity has various causes, and the incomplete reduction of sesamoids may be one of the important issues. However, we have seen several patients with postoperative lateral sesamoid displacement on anteroposterior (AP) standing radiographs who did not experience hallux valgus recurrence. Therefore, we hypothesized that lateral displacement of the sesamoid on AP standing radiographs does not cause hallux valgus recurrence. METHODS: The study included 269 feet (185 patients) with hallux valgus treated with distal chevron metatarsal osteotomy. Mean patient age was 64.26 (range, 15-80) years. Patients were followed up for an average of 33.85 (range, 12-228) months between April 2002 and December 2019. The patients were divided into 4 groups, according to the presence or absence of hallux valgus recurrence and sesamoid reduction. RESULTS: During outpatient follow-up, we discovered 99 feet (42.1%) in which hallux valgus did not recur despite lateral sesamoid displacement (grade IV-VII) on AP standing radiographs. Hallux valgus angle (HVA, 2.7 to 7.9 degrees), intermetatarsal angle (IMA, 4.6 to 6.2 degrees), and sesamoid grades (2.1 to 3.5) all deteriorated over time after surgery, and each indicator was statistically significantly altered, and changes in the 3 indicators had a statistically significant positive correlation. Changes in HVA and IMA between feet with and without sesamoid reduction on AP standing radiographs increased over time, with the differences in HVA (2.9 degrees) and IMA (0.9 degrees) being significant at final follow-up (P < .05 for each). Regardless of whether sesamoid reduction was achieved on AP standing radiographs, the final analysis showed that HVA and IMA in both groups worsened over time. Further, there were no differences between the 2 groups in the patterns of change over time. CONCLUSION: In our cohort, postoperative sesamoid position on AP standing radiographs was not associated with hallux valgus recurrence based on radiographic criteria. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Randomized, Multicenter, Phase 3 Study of Accelerated Fraction Radiation Therapy With Concomitant Boost to the Gross Tumor Volume Compared With Conventional Fractionation in Concurrent Chemoradiation in Patients With Unresectable Stage III Non-Small Cell Lung Cancer: The Korean Radiation Oncology Group 09-03 Trial.

PURPOSE: We designed the Korean Radiation Oncology Group 09-03 phase III clinical trial to compare accelerated hypofractionated radiation therapy (RT) using a concomitant boost to the gross tumor volume (GTV) with conventionally fractionated 60-Gy RT in patients with stage III unresectable non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: A conventionally fractionated RT group (arm 1; 124 patients) received a 2-Gy daily dose to a total cumulative dose of 44 Gy to the planning target volume (PTV) in 22 fractions and 60 Gy to the GTV in 30 fractions over 6 weeks. A hypofractionated RT group (arm 2; 142 patients) received a 1.8-Gy daily dose to the PTV with a synchronous boost of 0.6 Gy to the GTV, for total cumulative doses of 45 Gy to the PTV and 60 Gy to the GTV in 25 fractions over 5 weeks. All patients received concurrent weekly chemotherapy consisting of paclitaxel and cisplatin. RESULTS: The objective response rate of all patients was 86.5% (arm 1, 84.6%; arm 2, 88.1%; P = .612). The median overall survival was 26 months (arm 1, 26 months; arm 2, 27 months; P = .508). The median progression-free survival was 11 months (arm 1, 10 months; arm 2, 13 months; P = .295). The local tumor control rates at 2 and 5 years were 58.3% and 50.7%, respectively (arm 1, 62.4% and 51.0%, respectively; arm 2, 54.0% and 48.6%, respectively; P = .615). There were no significant between-group differences in the cumulative incidence of grade ≥3 radiation pneumonitis (P = .134) or radiation esophagitis (P = .539). CONCLUSIONS: This clinical trial did not confirm the superiority of accelerated 2.4-Gy hypofractionated RT compared with conventional 2-Gy fractionation in patients with unresectable stage III NSCLC undergoing concurrent chemoradiation therapy.

Predictive factors for favorable short-term response to interlaminar epidural block for cervical radiculopathy.

PURPOSE: We sought to identify clinical predictors of favorable short-term outcomes associated with cervical interlaminar epidural injection (CIEI). Previous studies investigating the predictive factors of CIEI efficacy have shown inconsistent results. Gaining information on the possible response determinants of CIEI is necessary for appropriate treatment selection and outcomes prediction in the treatment of cervical radiculopathy. METHODS: We analyzed the clinical data of 72 patients who received fluoroscopic-guided CIEI using the paramedian approach for cervical radiculopathy to identify the predictive factors for short-term outcomes of CIEI. Demographic characteristics, history of neck surgery, diagnosis, initial numeric rating score, duration of symptoms, Douleur Neuropathique 4 (DN4) questions, painDETECT questionnaire, neck disability index, and ventral epidural spread of contrast medium were assessed. Treatment success was defined as at least a 50% reduction in the numeric rating score after CIEI and was designated as a good response. RESULTS: The short-term success rate of CIEI for cervical radiculopathy was 55.56%. Multivariate logistic regression analysis established that spinal stenosis (odds ratio 0.183; P = 0.012), a longer duration of > 24 weeks of symptoms (odds ratio 0.206; P = 0.026), and combined positive results for the DN4 and painDETECT (odds ratio, 0.019; P = 0.008) decreased the odds ratio of a good response, 2-3 weeks after CIEI. CONCLUSIONS: CIEI provides a significant short-term outcome in patients with cervical radiculopathy. However, CIEI efficacy may be negatively affected in patients with spinal stenosis, the presence of a chronic state, and a possible neuropathic pain component.

Interobserver Variability Prediction of Primary Gross Tumor in a Patient with Non-Small Cell Lung Cancer.

This research addresses the problem of interobserver variability (IOV), in which different oncologists manually delineate varying primary gross tumor volume (pGTV) contours, adding risk to targeted radiation treatments. Thus, a method of IOV reduction is urgently needed. Hypothesizing that the radiation oncologist's IOV may shrink with the aid of IOV maps, we propose IOV prediction network (IOV-Net), a deep-learning model that uses the fuzzy membership function to produce high-quality maps based on computed tomography (CT) images. To test the prediction accuracy, a ground-truth pGTV IOV map was created using the manual contour delineations of radiation therapy structures provided by five expert oncologists. Then, we tasked IOV-Net with producing a map of its own. The mean squared error (prediction vs. ground truth) and its standard deviation were 0.0038 and 0.0005, respectively. To test the clinical feasibility of our method, CT images were divided into two groups, and oncologists from our institution created manual contours with and without IOV map guidance. The Dice similarity coefficient and Jaccard index increased by ~6 and 7%, respectively, and the Hausdorff distance decreased by 2.5 mm, indicating a statistically significant IOV reduction (p < 0.05). Hence, IOV-net and its resultant IOV maps have the potential to improve radiation therapy efficacy worldwide.

Clinical Efficacy of Hypofractionated Proton Beam Therapy for Intrahepatic Cholangiocarcinoma.

Forty-seven patients with intrahepatic cholangiocarcinoma (IHCC) who received proton beam therapy (PBT) were analyzed to evaluate the clinical efficacy and safety of hypofractionated PBT in patients with inoperable or recurrent IHCC. The median prescribed dose of PBT was 63.3 GyE (range: 45-80 GyE) in 10 fractions, and the median duration of follow-up in all the patients was 18.3 months (range: 2.4-89.9 months). Disease progression occurred in 35 of the 47 (74.5%) patients; local, intrahepatic, and extrahepatic progression occurred in 5 (10.6%), 20 (42.6%), and 29 (61.7%) patients, respectively. The 2-year freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS) rates, and median time of OS were 86.9% (95% confidence interval [CI], 74.4-99.4%), 16.8% (95% CI, 4.3-29.3%), 42.7% (95% CI, 28.0-57.4%), and 21.9 months (95% CI, 16.2-28.3 months), respectively; grade ≥ 3 adverse events were observed in four (8.5%) patients. In selected patients with localized disease (no viable tumors outside of the PBT sites), the median time of OS was 33.8 months (95% CI, 5.4-62.3). These findings suggest that hypofractionated PBT is safe and could offer a high rate of FFLP and promising OS in patients with inoperable or recurrent IHCC.

Proton Beam Therapy for Treatment-Naïve Hepatocellular Carcinoma and Prognostic Significance of Albumin-Bilirubin (ALBI) Grade.

To evaluate the efficacy of proton beam therapy (PBT) as an initial treatment in treatment-naïve hepatocellular carcinoma (HCC) patients and to assess the prognostic significance of albumin-bilirubin (ALBI) grade, 46 treatment-naïve HCC patients treated with PBT were analyzed. The ALBI grade distribution was grade 1 in 11 (23.9%) patients, grade 2 in 34 (73.9%) patients, and grade 3 in 1 (2.2%) patient. The median duration of follow-up was 56.5 months (95% confidence interval [CI], 48.2−64.7). Among the 46 patients, disease progression was observed in 23 (50%) patients: local progression in 3 (6.5%) patients; intrahepatic progression in 22 (47.8%); and extrahepatic progression in 5 (10.9%). The 5-year freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were 92.7% (95% CI, 84.7−100.7), 43.3% (95% CI, 28.2−58.4), and 69.2% (95% CI, 54.9−83.5), respectively. In multivariate analysis, there were no independent factors for FFLP (p > 0.05 each), but tumor stage and ALBI grade were independent factors for PFS and OS (p < 0.05 each). PBT could result in comparable OS in treatment-naïve HCC patients to other recommended first-line treatments, and ALBI grade, in addition to tumor stage, could be useful for predicting OS.

Effect of performing preoperative echocardiography in patients with cardiovascular risk on intraoperative anesthetic management and postoperative outcomes: A retrospective study.

Although echocardiography is widely used for preoperative cardiac risk evaluation, few studies have analyzed the effect of performing preoperative echocardiography on intraoperative anesthetic management and postoperative outcomes. We investigated the effect of performing echocardiography on intraoperative anesthetic management and postoperative outcomes in patients with cardiovascular risk. We retrospectively evaluated patients who had undergone major abdominal surgery and satisfied 2 or more of the following criteria: hypertension, diabetes mellitus, age ≥70 years, and previous cardiac disease. Patients were categorized into a group in which preoperative echocardiography was performed (echo) and a group in which it was not (non-echo). The primary outcomes were postoperative 30-day mortality and incidence of cardiovascular complications. Secondary outcomes were length of hospital stay, intraoperative incidence of hypotension, use of vasopressors, and findings on intraoperative invasive hemodynamic monitoring. There were no differences in 30-day mortality, incidence of postoperative cardiovascular complications, length of hospital stay, and intraoperative events between the groups. Only the incidence of cardiac output monitoring was lower in the echo group than in the non-echo group (59.6% vs 73.9%). Preoperative echocardiography does not affect postoperative outcomes, but it has the potential to affect intraoperative anesthetic management such as invasive hemodynamic monitoring during surgery.

Proton Beam Therapy versus Photon Radiotherapy for Stage I Non-Small Cell Lung Cancer.

Proton beam therapy (PBT) and photon radiotherapy for stage I non-small cell lung cancer (NSCLC) were compared in terms of clinical outcomes and dosimetry. Data were obtained from patients who underwent PBT or photon radiotherapy at two institutions-the only two facilities where PBT is available in the Republic of Korea. Multivariate Cox proportional hazards models and propensity score-matched analyses were used to compare local progression-free survival (PFS) and overall survival (OS). Survival and radiation exposure to the lungs were compared in the matched population. Of 289 patients included in the analyses, 112 and 177 underwent PBT and photon radiotherapy, respectively. With a median follow-up duration of 27 months, the 2-year local PFS and OS rates were 94.0% and 83.0%, respectively. In the multivariate analysis, a biologically effective dose (BED10, using α/ß = 10 Gy) of ≥125 cobalt gray equivalents was significantly associated with improved local PFS and OS. In the matched analyses, the local PFS and OS did not differ between groups. However, PBT showed significantly lower lung and heart radiation exposure in the mean dose, V5, and V10 than photon radiotherapy. PBT significantly reduced radiation exposure to the heart and lungs without worsening disease control in stage I NSCLC patients.

A Comparative Analysis of Photon versus Proton Beam Therapy in Neoadjuvant Concurrent Chemoradiotherapy for Intrathoracic Squamous Cell Carcinoma of the Esophagus at a Single Institute.

BACKGROUND: Proton beam therapy (PBT), as a neoadjuvant chemoradiotherapy (nCRT) modality, is expected to result in better outcomes than photon-based radiotherapy (RT) for esophageal cancer, particularly adenocarcinoma. This study reports the results of nCRT for locally advanced esophageal squamous cell carcinoma (ESCC) using both modalities. METHODS: We retrospectively reviewed the records of patients who underwent nCRT for ESCC between 2001 and 2020. A median of 41.4 Gy or cobalt gray equivalents of radiation was delivered using either photons or protons, with concurrent chemotherapy. Dosimetric and clinical parameters were compared between the two groups. RESULTS: Of the 31 patients, the lungs and heart of the proton group (n = 15) were exposed to significantly less radiation compared to the photon group (n = 16). No significant differences in short-term postoperative outcomes or lymphocyte count were observed between the groups, and there were no significant differences between the photon and proton groups in 2-year overall survival (67.8% vs. 68.6%, p = 0.867) or 2-year disease-free survival (33.3% vs. 34.5%, p = 0.749), with a median follow-up of 17 months. CONCLUSIONS: PBT provided a significant dosimetric benefit over photon-based RT during nCRT for ESCC; however, it did not improve clinical outcomes.

Acute kidney injury after hip fracture in organ transplant recipients.

BACKGROUND: This study aimed to investigate the incidence and risk factors of acute kidney injury (AKI) after hip fracture in organ transplant recipients. METHODS: In this single-center retrospective cohort study, 795 elderly patients who underwent hip fracture surgery were enrolled. AKI was defined according to Acute Kidney Injury Network criteria. Among the 795 patients, 23 underwent kidney transplantation (KT) and 20 underwent liver transplantation (LT). The incidence of AKI, dialysis requirement, and renal recovery rate were investigated. RESULTS: AKI occurred in 83 patients (10.5%), of whom 9 (39.1%), 3 (15%), and 71 (9.5%) were in the KT, LT, and nontransplantation groups, respectively. The incidence rates of AKI and severe AKI (17.4% vs. 1.4%) were significantly higher in the KT group than in the nontransplantation group (P = .001 for both). The renal recovery rate was significantly lower in the KT group than in the nontransplantation group (P = .033). The multivariate analysis revealed that male; body mass index; CKD; alkaline phosphatase; intraoperative hypotension; and history of KT were independent predictors of AKI development. CONCLUSIONS: AKI and severe AKI after hip fracture occurred more frequently in the KT recipients with lower renal recovery rates. Transplanted kidneys are more vulnerable to AKI after hip fracture.

Reliability and validity of the modified McGowan grade in patients with cubital tunnel syndrome.

INTRODUCTION: This study aimed to assess the reliability and validity of the modified McGowan grading system and to determine its ability to distinguish the severity of cubital tunnel syndrome (CuTS) between the different grades. MATERIALS AND METHODS: We prospectively enrolled 39 consecutive patients with CuTS from March 2018 to December 2020. Inter- and intra-observer reliability was assessed by two orthopaedic surgeons with a minimum 2-week interval using Cohen kappa coefficients. Validity was assessed by Spearman's correlation with objective clinical outcomes (grip strength, Semmes-Weinstein monofilament test [SWMT], static two-point discrimination [2PD], and motor conduction velocity [MCV]). In addition, the relationship between the grading system and patient-reported outcomes (Disabilities of the Arm, Shoulder and Hand score and Boston Questionnaire) was evaluated using Spearman's correlation. The ability to distinguish the severity between the different grades was assessed using the Kruskal-Wallis analysis. RESULTS: The inter-observer kappa value was 0.54 and intra-observer kappa value was 0.59, which imply a moderate reliability. The modified McGowan grade had a moderate correlation with objective clinical outcomes (grip strength [r = - 0.350, p = 0.029], SWMT [r = 0.552, p < 0.001], 2PD [r = 0.456, p = 0.004], and MCV [r = - 0.394, p = 0.021]). However, patient-reported outcomes did not correlate with this grading system. Kruskal-Wallis analysis revealed significant differences between grades in terms of SWMT, 2PD, grip strength, and Boston Questionnaire functional score (p = 0.006, 0.025, 0.014, and 0.043, respectively); however, these differences were statistically significant only for a limited number of parts. CONCLUSIONS: The modified McGowan grade has a moderate inter- and intra-observer reliability. This grading system moderately correlates with objective sensory-motor functions and MCV of patients with CuTS. However, the modified McGowan grade does not reflect the patient's perceived disabilities and has a weakness in distinguishing the severity of patients' conditions among the different grades.