Comparing the efficacy of combined versus single immune cell adaptive therapy targeting colorectal cancer.

PURPOSE: Colorectal cancer (CRC) is the most frequent cancer with limited therapeutic achievements. Recently, adoptive cellular immunotherapy has been developed as an antitumor therapy. However, its efficacy has not been tested in CRC. This study investigated the ability of an immune cell cocktail of dendritic cells (DCs), T cells, and natural killer (NK) cells to overcome immunological hurdles and improve the therapeutic efficacy of cell therapy for CRC. METHODS: CRC lysate-pulsed monocyte-derived DCs (Mo-DCs), CRC antigen-specifically expanded T cells (CTL), and in vitro-expanded NK cells were cultured from patient peripheral blood mononuclear cells (PBMC). The ability of the combined immune cells to kill autologous tumor cells was investigated by co-culturing the combined immune cells with patient-derived tumor cells. RESULTS: The Mo-DCs produced expressed T cell co-stimulating molecules like CD80, CD86, human leukocyte antigen (HLA)-DR and HLA-ABC, at high levels and were capable of activating naive T cells. The expanded T cells were predominantly CD8 T cells with high levels of CD8 effector memory cells and low levels of regulatory T cells. The NK cells expressed high levels of activating receptors and were capable of killing other cancer cell lines (K562 and HT29). The immune cell cocktail demonstrated a higher ability to kill autologous tumor cells than single types. An in vivo preclinical study confirmed the safety of the combined immune cell adaptive therapy showing no therapy-related death or general toxicity symptoms. CONCLUSION: The results suggested that combined immune cell adaptive therapy could overcome the limited efficacy of cell immunotherapy.

Novel Screw Placement Method for Extremely Small Lumbar Pedicles in Scoliosis.

Study Design: Consecutive case series. Objective: To propose a screw placement method in patients with extremely small lumbar pedicles (ESLPs) (<2 mm) to maintain screw density and correction power, without relying on the O-arm navigation system. Summary of Background Data: In scoliosis surgery, ESLPs can hinder probe passage, resulting in exclusion or substitution of the pedicle screws with a hook. Screw density affects correction power, making it necessary to maximize the number of screw placements, especially in the lumbar curve. Limited studies provide technical guidelines for screw placement in patients with ESLPs, independent of the O-arm navigation system. Methods: We enrolled 19 patients who underwent scoliosis correction surgery using our novel screw placement method for ESLPs. Clinical, radiological, and surgical parameters were assessed. After posterior exposure of the spine, the C-arm fluoroscope was rotated to obtain a true posterior-anterior view and both pedicles were symmetrically visualized. An imaginary pedicle outline was presumed based on the elliptical or linear shadow from the pedicle. The screw entry point was established at a 2 (or 10) o'clock position in the presumed pedicle outline. After adjusting the gear-shift convergence, both cortices of the transverse process were penetrated and the tip was advanced towards the lateral vertebral body wall, where an extrapedicular screw was placed with tricortical fixation. Results: Out of 90 lumbar screws in 19 patients, 33 screws were inserted using our novel method, without correction loss or complications during an average follow-up period of 28.44 months, except radiological loosening of one screw. Conclusions: Our new extrapedicular screw placement method into the vertebral body provides an easy, accurate, and safe alternative for scoliosis patients with ESLPs without relying on the O-arm navigation system. Surgeons must consider utilizing this method to enhance correction power in scoliosis surgery, regardless of the small size of the lumbar pedicle.

Spatially Resolved Transcriptomes of CD30+-Transformed Mycosis Fungoides and Cutaneous Anaplastic Large-Cell Lymphoma.

Mycosis fungoides with large-cell transformation (MF-LCT) occurs in a minor proportion of aggressive lesions, which express CD30 similar to primary cutaneous anaplastic large-cell lymphoma (pcALCL). We investigated the differences in spatially resolved transcriptome profiles of MF-LCT and pcALCL using CD30 morphology markers and 28 and 24 regions of interest (ROIs) in MF-LCT and pcALCL, respectively. Differentially expressed genes, pathway analysis, and immune-cell deconvolution by selective analysis of CD30-positive tumor cells and CD30-negative extratumoral areas were undertaken. In CD30-positive ROIs of MF-LCT, 190 differentially expressed genes were upregulated (29 were directly or indirectly associated with extracellular matrix remodeling), whereas 255 differentially expressed genes were downregulated, compared with those of pcALCL. Except for cornified envelope formation and keratinization, all six pathways enriched in CD30-positive ROIs of MF-LCT were associated with extracellular matrix remodeling. In CD30-positive ROIs in MF-LCT compared with those in pcALCL, immune-cell deconvolution revealed significantly increased fibroblasts and M2 macrophages (P = 0.012 and P = 0.023, respectively) but decreased M1 macrophages (P = 0.031). In CD30-negative ROIs in MF-LCT compared with those in pcALCL, memory B (P = 0.021), plasma (P = 0.023), and CD8 memory T (P = 0.001) cells significantly decreased, whereas regulatory T cells (P = 0.024) increased. Predomination of extracellular matrix remodeling pathways and immunosuppressive microenvironment in MF-LCT indicates pathophysiological differences between MF-LCT and pcALCL.

A rare case of secondary cutaneous lymphoplasmacytic lymphoma clinically presenting as acquired cutis laxa.

Lymphoplasmacytic lymphoma (LPL) is a rare variant of non-Hodgkin lymphoma, accounting for <1% of cases. Skin involvement in LPL is quite rare-accounting for approximately 5% of extramedullary disease-and includes a variety of clinical morphologies, such as erythematous-to-violaceous plaques, violaceous nodules or tumors, and ulceration at various anatomical sites. Herein, we report the case of a 45-year-old Korean woman who presented with generalized erythematous indurated plaques and pendulous skin growths, which were asymptomatic, with marked diffuse infiltration of lymphocytes and plasma cells in the dermis. Immunohistochemical studies revealed that the lymphoid cells expressed CD3, CD79a, and cytoplasmic IgG, but lacked CD10 and IgM. Moreover, kappa light chain restriction and monoclonal immunoglobulin heavy chain gene rearrangement were observed. Upon further workup, lymphoma involvement was reported in multiple lymph nodes, including those in the cervical and axillary regions. This case shows a unique form of cutaneous LPL clinically presenting as acquired cutis laxa, emphasizing the dermatologists' need to be vigilant for variant forms of this disease.

Fetal growth changes and prediction of selective fetal growth restriction following fetoscopic laser coagulation in twin-to-twin transfusion syndrome.

OBJECTIVE: To investigate fetal growth changes and predictive factors for selective fetal growth restriction (sFGR) in patients with twin-to-twin transfusion syndrome (TTTS) after fetoscopic laser coagulation (FLC). METHODS: This retrospective study included twin-pregnant women with fetal TTTS who underwent FLC at our institution between 2011 and 2020. Twin pairs who survived at least 28 days after FLC and at least 28 days after birth were included. A paired t-test was used to compare the mean discordance between the estimated fetal weights at the FLC and the birth weights. The predictive factors for sFGR after FLC were evaluated using univariate and multivariate logistic regression analyses. RESULTS: A total of 119 eligible pairs of patients who underwent FLC were analyzed. The weight percentile at birth significantly decreased after FLC in the recipients (53.7±30.4 percentile vs. 43.7±28.0 percentile; P<0.001), but increased in the donors (11.5±17.1 percentile vs. 20.7±22.8 percentile; P<0.001). Additionally, the mean weight discordance of twin pairs significantly decreased after FLC (23.9%±12.7% vs. 17.3%±15.7%; P<0.001). After FLC, Quintero stage ≥3, pre-FLC sFGR, abnormal cord insertion, and post-FLC abnormal umbilical artery Doppler (UAD) were all significantly higher in the sFGR group than the non-sFGR group. The prediction model using these variables indicated that the area under the receiver operating characteristic curve was 0.898. CONCLUSION: The recipient weight percentile decreased, whereas donor growth increased, resulting in reduced weight discordance after FLC. The Quintero stage, pre-FLC sFGR, and post-FLC abnormal UAD were useful predictors of sFGR after FLC in TTTS.

Hydride-Free Hydrogenation: Unraveling the Mechanism of Electrocatalytic Alkyne Semihydrogenation by Nickel-Bipyridine Complexes.

Hydrogenation reactions of carbon-carbon unsaturated bonds are central in synthetic chemistry. Efficient catalysis of these reactions classically recourses to heterogeneous or homogeneous transition-metal species. Whether thermal or electrochemical, C-C multiple bond catalytic hydrogenations commonly involve metal hydrides as key intermediates. Here, we report that the electrocatalytic alkyne semihydrogenation by molecular Ni bipyridine complexes proceeds without the mediation of a hydride intermediate. Through a combined experimental and theoretical investigation, we disclose a mechanism that primarily involves a nickelacyclopropene resting state upon alkyne binding to a low-valent Ni(0) species. A following sequence of protonation and electron transfer steps via Ni(II) and Ni(I) vinyl intermediates then leads to olefin release in an overall ECEC-type pattern as the most favored pathway. Our results also evidence that pathways involving hydride intermediates are strongly disfavored, which in turn promotes high semihydrogenation selectivity by avoiding competing hydrogen evolution. While bypassing catalytically competent hydrides, this type of mechanism still retains inner-metal-sphere characteristics with the formation of organometallic intermediates, often essential to control regio- or stereoselectivity. We think that this approach to electrocatalytic reductions of unsaturated organic groups can open new paradigms for hydrogenation or hydroelementation reactions.

Feasibility of fetoscopic laser coagulation in triplet pregnancy.

OBJECTIVE: To report the experiences of triplet pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser coagulation at a single center. METHODS: Herein, we conducted a retrospective analysis to investigate the management and perinatal outcomes of triplet pregnancies with TTTS treated at a single institution between 2017 and 2022. RESULTS: Seven of the 98 triplet pregnancies (7.1%) encountered were complicated by TTTS, and all were dichorionic triamniotic triplets. Of the seven triplet pregnancies complicated by TTTS, four were treated with fetoscopic laser coagulation at our center, at a median gestational age of 20 weeks. No procedure-related complications or maternal complications were observed. The survival rate was higher and perinatal outcomes were better in fetoscopic laser coagulation cases than in other management cases. Four donor and four recipient triplets survived, with a median gestational age of 33 weeks at delivery. Although there were no cases of poor neonatal outcomes, one case was diagnosed with white matter injury, suspected to be hypoxic-ischemic encephalopathy on postnatal investigation. CONCLUSION: Fetoscopic laser coagulation is a feasible treatment option for triplet TTTS, provided the attending specialists have extensive experience with this technique.

Performance of PRAME immunohistochemistry compared with that of c-Kit, c-Myc, or cyclin D1 for the diagnosis of acral melanocytic tumors.

The diagnostic role of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has not been thoroughly evaluated for acral melanocytic tumors. The objective of this study was to evaluate the utility of this modality for the diagnosis of acral melanocytic tumors compared with other potential markers. Melanocytic tumors were classified as either acral nevi, challenging melanocytic tumors (superficial atypical melanocytic proliferation of uncertain significance (SAMPUS)-favor benign (SAMPUS-FB), SAMPUS-favor malignant (SAMPUS-FM)) or acral melanomas. A total of 106 acral melanocytic tumors including acral nevi (n = 32), SAMPUS-FB (n = 17), SAMPUS-FM (n = 20), and acral melanomas (n = 37) were included. Diagnostic power, assessed using an area under the receiver operating characteristic curve (AUC) for distinguishing acral melanomas and acral nevi, was highest for PRAME (AUC = 0.997), followed by c-Myc (AUC = 0.755), cyclin D1 (AUC = 0.652), and c-Kit (AUC = 0.573). At a PRAME expression level ≥30% as a positive test for acral melanoma, the sensitivity and specificity of this marker for discriminating acral melanoma from acral nevus were 100% and 96.9%, respectively. PRAME immunohistochemistry also discriminated SAMPUS-FM from SAMPUS-FB with a sensitivity and specificity of 90.0% and 76.5%, respectively. In conclusion, PRAME immunohistochemistry can be used effectively to distinguish between various spectra of acral melanocytic neoplasms.

Anti-fatigue potential of Pinus koraiensis leaf extract in an acute exercise-treated mouse model.

Pinus koraiensis leaf (PKL) extract exerts antihyperlipidemic, antidiabetic, and anticancer effects; however, its anti-fatigue properties have not been elucidated to date. In this study, the anti-fatigue properties of PKL were evaluated by assessing the endurance of mice by a weight-loaded forced swimming (WLFS) and rotarod (RR) tests. Subsequently, various behavioral, biochemical, and physiological parameters were measured. Treatment with PKL decreased hepatic and muscular glycogen levels in mice subjected to WLFS and RR test compared to those in acute exercise-treated (AET) mice. Additionally, plasma levels of stress-related biochemical factors (lactate, lactate dehydrogenase, aminotransferase, aspartate aminotransferase, and blood urea nitrogen) decreased significantly (P < 0.05), whereas the levels of superoxide dismutase and glutathione peroxidase increased. Furthermore, PKL potentially improved mental fatigue by decreasing corticosterone and increasing serotonin levels. PKL increased the expression of phosphorylated cyclic adenosine-3',5'-monophosphate response element-binding protein and brain-derived neurotrophic factor in the hippocampus. Collectively, the anti-fatigue effects of PKL could be explained by its antioxidant activity, mediating effects on glycogen synthesis, and control over stress. In conclusion, the findings of the present study suggest that PKL is a potential nutraceutical for improving exercise performance and alleviating fatigue.

CDI Exerts Anti-Tumor Effects by Blocking the FoxM1-DNA Interaction.

The Forkhead box protein M1 (FoxM1) is an appealing target for anti-cancer therapeutics as this cell proliferation-associated transcription factor is overexpressed in most human cancers. FoxM1 is involved in tumor invasion, angiogenesis, and metastasis. To discover novel inhibitors that disrupt the FoxM1-DNA interaction, we identified CDI, a small molecule that inhibits the FoxM1-DNA interaction. CDI was identified through an assay based on the time-resolved fluorescence energy transfer response of a labeled consensus oligonucleotide that was bound to a recombinant FoxM1-dsDNA binding domain (FoxM1-DBD) protein and exhibited potent inhibitory activity against FoxM1-DNA interaction. CDI suppressed cell proliferation and induced apoptosis in MDA-MB-231 cells obtained from a breast cancer patient. Furthermore, it decreased not only the mRNA and protein expression of FoxM1 but also that of downstream targets such as CDC25b. Additionally, global transcript profiling of MDA-MB-231 cells by RNA-Seq showed that CDI decreases the expression of FoxM1-regulated genes. The docking and MD simulation results indicated that CDI likely binds to the DNA interaction site of FoxM1-DBD and inhibits the function of FoxM1-DBD. These results of CDI being a possible effective inhibitor of FoxM1-DNA interaction will encourage its usage in pharmaceutical applications.

Berberine Induces Autophagic Cell Death by Inactivating the Akt/mTOR Signaling Pathway.

The incidence of skin cancer has been increasing over the past decades, and melanoma is considered highly malignant because of its high rate of metastasis. Plant-derived berberine, an isoquinoline quaternary alkaloid, has been reported to possess multiple pharmacological effects against various types of cancer cells. Therefore, we treated melanoma B16F10 cells with berberine to induce cell death and understand the cell death mechanisms. The berberine-treated cells showed decreased cell viability, according to berberine concentration. However, western blot analysis of apoptosis-related marker proteins showed that the expression of Bcl-2, an apoptosis inhibitory protein, and the Bcl-2/Bax ratio were increased. Therefore, by adding 3-methyladenine to the berberine-treated cells, we investigated whether the reduced cell viability was due to autophagic cell death. The results showed that 3-methyladenine restored the cell viability decreased by berberine, suggesting autophagy. To clarify autophagic cell death, we performed transmission electron microscopy analysis, which revealed the presence of autophagosomes and autolysosomes in the cells after treatment with berberine. Next, by analyzing the expression of autophagy-related proteins, we found an increase in the levels of light chain 3A-II and Atg12-Atg5 complex in the berberine-treated cells. We then assessed the involvement of the Akt/mTOR signaling pathway and found that berberine inhibited the expression of phosphorylated Akt and mTOR. Our data demonstrated that berberine induces autophagic cell death by inactivating the Akt/mTOR signaling pathway in melanoma cells and that berberine can be used as a possible target for the development of anti-melanoma drugs.

The Potential Anti-Photoaging Effect of Photodynamic Therapy Using Chlorin e6-Curcumin Conjugate in UVB-Irradiated Fibroblasts and Hairless Mice.

Photodynamic therapy (PDT) has been used to treat cancers and non-malignant skin diseases. In this study, a chlorin e6-curcumin conjugate (Ce6-PEG-Cur), a combination of chlorin e6 (Ce6) and curcumin via a PEG linker, was used as a photosensitizer. The in vitro and in vivo effects of PDT using Ce6-PEG-Cur were analyzed in UVB-irradiated fibroblasts and hairless mice. The UVB-induced expression of MMPs was reduced in Hs68 fibroblast cells, and procollagen type Ⅰ expression was enhanced by Ce6-PEG-Cur-mediated PDT on a Western blotting gel. Moreover, UVB-induced collagen levels were restored upon application of Ce6-PEG-Cur-mediated PDT. Ce6-PEG-Cur-mediated PDT inhibited the expression of phosphorylated p38 in the MAPK signaling pathway, and it reduced the expression of phosphorylated NF-κB. In animal models, Ce6-PEG-Cur-mediated PDT inhibited the expression of MMPs, whereas procollagen type Ⅰ levels were enhanced in the dorsal skin of UVB-irradiated mice. Moreover, UVB-induced dorsal roughness was significantly reduced following Ce6-PEG-Cur-mediated PDT treatment. H&E staining and Masson's trichrome staining showed that the thickness of the epidermal region was reduced, and the density of collagen fibers increased. Taken together, Ce6-PEG-Cur-mediated PDT might delay and improve skin photoaging by ultraviolet light, suggesting its potential for use as a more effective photo-aging treatment.

Immunohistochemical Analysis of Postburn Scars following Treatment Using Dermal Substitutes.

BACKGROUND: Post-burn hypertrophic scars commonly occur after burns. Studies that compare dermal substitutes with other treatment methods are insufficient. The purpose was to analyze the histopathological differences in hypertrophic burn scars after Matriderm®+split-thickness skin graft (STSG) and compare with AlloDerm®+STSG, STSG, full-thickness skin graft (FTSG), and normal skin. METHODS: Samples of unburned, normal skin and deep 2nd or 3rd degree burns were obtained from patients who experienced a burn injury in the past to at least 6 months before biopsy, which was performed between 2011 and 2012. All subjects received >6 months of treatment before the biopsy. Intervention groups were normal (63), STSG (28), FTSG (6), Matriderm® (11), and AlloDerm® (18). Immunohistochemical analyses of elastin, collagen I, collagen III, cluster of differentiation 31 (CD31), smooth muscle actin (α-SMA), and laminin from scar and control tissues were performed and compared. RESULTS: α-SMA vascular quantity and vessel width, stromal CD31, and basement membrane laminin expression were not significantly different between normal and intervention groups. Matriderm® group showed no significant difference in elastin, collagen III, stromal CD31 and α-SMA, CD31 vessel width, stromal α-SMA, vessel quantity and width, and laminin length compared to the normal group, meaning they were not significantly different from the normal skin traits. CONCLUSION: Dermal substitutes may be an optimal alternative to address the cosmetic and functional limitations posed by other treatment methods.

Clinicopathological Factors Associated with the Prognosis and Chronicity of Lymphomatoid Papulosis: A Retrospective Cohort Study.

BACKGROUND: The clinical and pathological features of lymphomatoid papulosis (LYP) are diverse. The objective of this study is to evaluate the clinical and pathological features associated with the prognosis and clinical course of LYP. PATIENTS AND METHODS: The clinical and pathological features of LYP in a medical center database were retrospectively retrieved. RESULTS: Overall, 58 LYP patients were included in the study. The mean age at diagnosis was 39.1 years and the female-to-male ratio was 1:1.2. More than two-thirds (40/58, 69.0%) of the patients showed a chronic and recurrent disease course. A longer pre-diagnosis duration (odds ratio (OR), 1.01; 95% confidence interval (CI), 1.00-1.03) was significantly associated with secondary lymphoma development. Lower extremity involvement (OR, 10.40; 95% CI, 1.17-92.28) and the absence of eosinophils in the lesions (OR, 11.28; 95% CI, 1.01-126.24) were found to be significantly associated with the chronic and recurrent course of LYP. CONCLUSION: A longer pre-diagnosis duration is associated with secondary lymphoma, while a lower extremity involvement and the absence of lesional eosinophil infiltration are associated with the chronicity of LYP.

A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice. METHODS: In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled. RESULTS: Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42. CONCLUSION: Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

Hyperpigmented mycosis fungoides: a retrospective and comparative analysis with other subtypes of mycosis fungoides.

In this study, the clinicopathologic features and survival outcomes of patients with hyperpigmented MF from a single tertiary referral center database were retrospectively evaluated. Hyperpigmented MF accounted for 10.9% (14/128) of all MF cases. The mean age at diagnosis was 46.9 years, and the female-to-male ratio was 1:1.3. Concurrent hypopigmented, ichthyosiform, and poikilodermatous lesions were detected in 21.4%, 14.3%, and 14.3% of the patients, respectively. Histopathologically, most patients (85.7%) showed interface change with pigment incontinence. Double negative (CD4- and CD8-) immunophenotypes were more frequent in patients with hyperpigmented MF (25%) than in those with other MF subtypes (9.8%). Most patients (85.7%) had early-stage disease at diagnosis. The survival outcomes did not differ significantly between hyperpigmented and other MF subtypes. In conclusion, hyperpigmented MF often accompanies other atypical MF variants and is frequently associated with atypical immunophenotypes. The outcomes of hyperpigmented MF are comparable to those of other MF subtypes.

Evaluation of Artificial Intelligence-Assisted Diagnosis of Skin Neoplasms: A Single-Center, Paralleled, Unmasked, Randomized Controlled Trial.

TRIAL DESIGN: This was a single-center, unmasked, paralleled, randomized controlled trial. METHODS: A randomized trial was conducted in a tertiary care institute in South Korea to validate whether artificial intelligence (AI) could augment the accuracy of nonexpert physicians in the real-world settings, which included diverse out-of-distribution conditions. Consecutive patients aged >19 years, having one or more skin lesions suspicious for skin cancer detected by either the patient or physician, were randomly allocated to four nondermatology trainees and four dermatology residents. The attending dermatologists examined the randomly allocated patients with (AI-assisted group) or without (unaided group) the real-time assistance of AI algorithm (https://b2020.modelderm.com#world; convolutional neural networks; unmasked design) after simple randomization of the patients. RESULTS: Using 576 consecutive cases (Fitzpatrick skin phototypes III or IV) with suspicious lesions out of the initial 603 recruitments, the accuracy of the AI-assisted group (n = 295, 53.9%) was found to be significantly higher than those of the unaided group (n = 281, 43.8%; P = 0.019). Whereas the augmentation was more significant from 54.7% (n = 150) to 30.7% (n = 138; P < 0.0001) in the nondermatology trainees who had the least experience in dermatology, it was not significant in the dermatology residents. The algorithm could help trainees in the AI-assisted group include more differential diagnoses than the unaided group (2.09 vs. 1.95 diagnoses; P = 0.0005). However, a 12.2% drop in Top-1 accuracy of the trainees was observed in cases in which all Top-3 predictions given by the algorithm were incorrect. CONCLUSIONS: The multiclass AI algorithm augmented the diagnostic accuracy of nonexpert physicians in dermatology.

Fetal cardiac parameters for predicting postnatal operation type of fetuses with tetralogy of Fallot.

BACKGROUND: To assess fetal cardiac parameters predictive of postnatal operation type in fetuses with tetralogy of Fallot (TOF). METHODS: Echocardiographic data obtained in the second and third trimesters were retrospectively reviewed for fetuses diagnosed with TOF between 2014 and 2018 at Asan Medical Center. The following fetal cardiac parameters were analyzed: 1) pulmonary valve annulus (PVA) z-score, 2) right pulmonary artery (RPA) z-score, 3) aortic valve annulus (AVA) z-score, 4) pulmonary valve peak systolic velocity (PV-PSV), 5) PVA/AVA ratio, and 6) RPA/descending aorta (DAo) ratio. These cardiac parameters were compared between a primary corrective surgery group and a palliative shunt operation followed by complete repair group. RESULTS: A total of 100 fetuses with TOF were included. Only one neonatal death occurred. Ninety patients underwent primary corrective surgery and 10 neonates underwent a multistage surgery. The PVA z-score, RPA z-score, and RPA/DAo ratio measured in the second trimester and the PVA z-score, RPA z-score, and PVA/AVA raio measured in the third trimester were significantly lower in the multistage surgery group, while the PV-PSV as measured in both trimesters were significantly higher in the multistage surgery group. CONCLUSION: Fetal cardiac parameters are useful for predicting the operation type necessary for neonates with TOF.

Bowel Injury and Insidious Pneumoperitoneum after Lateral Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective review of prospectively collected cases. PURPOSE: To report bowel injury cases and determine the incidence and risk factors of insidious pneumoperitoneum after lateral lumbar interbody fusion (LLIF). OVERVIEW OF LITERATURE: Minimally invasive LLIF is considered a safe surgical approach with a low risk of complications. Visceral injury after LLIF is rare and, to our knowledge, no studies on pneumoperitoneum after LLIF have been performed. Bowel injury is a catastrophic complication, but the clinical signs may not be apparent. After we encountered two cases of bowel injury after LLIF, we decided to perform computed tomography of the abdomen and pelvis (APCT) after surgery for all patients who underwent LLIF. METHODS: A total of 90 patients underwent APCT within 48 hours of surgery. Medical records were reviewed to determine each patient's age, sex, body mass index, medical and surgical histories, characteristics of LLIF procedures, and subjective symptoms and abnormal findings in the physical examination related to acute abdomen after surgery. Various parameters were compared between patients with and without pneumoperitoneum. RESULTS: Bowel injuries were identified in the first two patients and five patients (5.5%) were diagnosed with pneumoperitoneum only on APCT. We found that the greater the number of fused segments, the higher the incidence of postoperative bowel injury and/or pneumoperitoneum. The incidence was significantly high when the L2-3 level was included in the LLIF surgery. CONCLUSIONS: Pneumoperitoneum after LLIF indicates damage to the peritoneum and the presence of bowel injury that may lead to peritonitis. However, it is difficult to distinguish pneumoperitoneum and/or bowel injury from general abdominal pain after surgery because patients may present with a wide range of symptoms. We recommend that APCT be routinely performed after LLIF surgery in order to promptly identify pneumoperitoneum and bowel injury.

Feasibility of fetal left modified myocardial performance index in twin anemia polycythemia sequence and perinatal outcomes after antenatal intervention.

OBJECTIVE: To evaluate the feasibility and clinical value of fetal left modified myocardial performance index (Mod-MPI) in assessment and management of prenatal twin anemia polycythemia sequence (TAPS). METHODS: We retrospectively reviewed fetuses with TAPS diagnosed prenatally between 2015 and 2019 at Asan Medical Center. Doppler ultrasound evaluation including the peak systolic velocity (PSV) of the middle cerebral artery (MCA) and fetal echocardiography including left Mod-MPI were evaluated and followed up after antenatal management. RESULTS: Among 10 cases of fetal twin pregnancies with prenatal TAPS, six were spontaneous and four were post-laser TAPS. Left Mod-MPI was abnormal in one or both twins of nine cases (90%) including all post-laser TAPS (n = 4) and 83.3% of spontaneous TAPS (n = 5). Three recipients, one donor and three former recipients/new donors had elevated left Mod-MPI values, and one donor, one recipient, two former donors/new recipients had decreased values. Antenatal intervention was performed in eight cases with intrauterine transfusion (n = 4), fetoscopic laser surgery (n = 2), radiofrequency ablation (n = 1), and intrauterine transfusion followed by radiofrequency ablation (n = 1). The remaining two cases were either delivered or managed expectantly. MCA-PSV and left Mod-MPI became normal on the follow-up scans in all cases except the delivered case. There were four fetal deaths: two occurred spontaneously and two were selectively terminated by radiofrequency ablation. Overall perinatal survival per fetus was 80% (16/20) and the median gestational age at delivery was 34.4 (range, 29.2-37.4) weeks. Neither postnatal death nor neurodevelopmental delay occurred during a median follow-up of 13 months (range, 0.25-60 months). CONCLUSION: Fetal left Mod-MPI was useful for assessment of compromised fetal cardiac function in cases with prenatal TAPS. Application of fetal left Mod-MPI in prenatal staging of TAPS might help evaluate the severity of TAPS and decide timely antenatal intervention.