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Michael D Yu,1 Ji Kwan Park,2 Andrea L Kossler1 1Oculoplastic Surgery and Orbital Oncology Service, Byers Eye Institute, Stanford University, Palo Alto, CA, USA; 2Oculofacial Plastic and Orbital Surgery, Indianapolis, IN, USACorrespondence: Andrea L KosslerOculoplastic Surgery and Orbital Oncology Service, Byers Eye Institute, Stanford University, 2452 Watson Ct, Palo Alto, CA 94303, USATel +1 650-724-0105Email akossler@stanford.eduAbstract: Dry eye disease (DED) affects up to one-third of the global population. Traditional therapies, including topical lubricants, have been employed with variable success in the treatment of DED. Recently, neurostimulation of the lacrimal functional unit (LFU) has emerged as a promising alternative therapy for DED. In this review, we describe the neuroanatomical and pathophysiological considerations of DED and the LFU that make neurostimulation a viable therapeutic alternative. We further detail the various neurostimulatory approaches taken thus far—from implanted stimulators to external devices to chemical neurostimulation. Existing studies reveal the strengths of the neurostimulatory approach in increasing tear volume and improving dry eye symptoms, but further studies are needed to elucidate its true potential in treatment of DED.Keywords: oculoplastics, ocular surface, cornea, lacrimal gland, dry eye disease, tears, neurostimulation

Background/Objective: Nonislet cell tumor hypoglycemia (NICTH) is an uncommon cause of hypoglycemia due to a relative surplus of insulin-like growth factor 2 (IGF-2) or its precursor molecule. The diagnosis is confirmed by an elevated ratio of IGF-2 to insulin-like growth factor 1 (IGF-1). Myoepithelial carcinoma (MECA) is a rare and aggressive salivary gland cancer that has not been previously associated with NICTH. Case Report: A 63-year-old female with a past medical history of metastatic salivary MECA, type 2 diabetes mellitus previously on metformin, hypertension, and hypothyroidism presented to her oncologist for chemotherapy and was found to have a serum glucose of 30 mg/dL (reference: 65-99). She was admitted for further diagnostic work-up which revealed an insulin level of

Background/Objective: Extreme hypercortisolemia in an otherwise healthy patient can be due to familial dysalbuminemia, generalized glucocorticoid resistance, and estrogen-containing medications. I report a woman who appeared to have an exaggerated increase in the serum cortisol level following oral contraceptive treatment. Case Report: A 50-year-old woman presented with extreme morning hypercortisolemia—cortisol levels of 61 and 55 mcg/dL (4 and 3 months before presentation, respectively; normal range, 8-25 mcg/dL)—found during workup of mildly increased white cell counts. The morning cortisol level had been 10 mcg/dL after administration of 1-mg dexamethasone. The 24-hour urine free cortisol level had been normal and only slightly increased after correction by creatinine. The patient was anxious about the extremely high cortisol levels but otherwise felt well. She took norgestimate-ethinyl estradiol contraceptive (0.18/0.215/0.25 mg - 35 mcg). Physical examination showed a well-appearing, lean female. The thyroid-stimulating hormone, total thyroxine, free thyroxine, total triiodothyronine, free triiodothyronine, androstenedione, dehydroepiandrosterone sulfate, aldosterone, and renin levels were normal. Morning total cortisol and cortisol-binding globulin (CBG) were tested before and after she held the oral contraceptive for 2 months. The total cortisol and CBG levels decreased from 50 to 26 mcg/dL and from 6.4 to 3.8 mg/dL (normal range, 1.7-3.1 mg/dL), respectively. Discussion: Increases in the serum cortisol-binding proteins are a well-recognized cause for increases in the serum cortisol levels. Conclusion: This case suggests that modern oral contraceptives with low to moderate estrogen activity can cause extreme increases in the serum cortisol levels due to marked increases in the CBG levels.

Background: Cardiac surgery patients are at increased risk for venous thromboembolism (VTE). Prevention is the most critical strategy to reduce VTE-associated morbidity and death. However, there is a lack of data on the optimal approach to VTE prophylaxis in this population of high-risk patients. This study aimed to assess whether the standard dose of enoxaparin, the subcutaneous injection of 40 mg of enoxaparin daily, achieves adequate anti–factor Xa (aFXa) levels for VTE prophylaxis in patients after open heart surgery. Methods: All patients with open heart surgery with cardiopulmonary bypass from August to December 2022 who received at least 3 consecutive doses of subcutaneously administered enoxaparin were included in the study. Patients receiving therapeutic anticoagulation, patients who underwent cardiac transplantation or placement of ventricular assist device, and patients with renal insufficiency were excluded. Serum aFXa was measured 0.5 to 1 hour before the fourth dose to attain the steady-state trough levels. Results: Data were completed for 44 patients. The target aFXa level was between 0.10 and 0.20 IU/mL for the avoidance of both underanticoagulation (≤0.10 IU/mL) and overanticoagulation (>0.20 IU/mL). The mean was 0.049 IU/mL with SD of 0.026 IU/mL, which was statistically significantly lower than the lower end of the target aFXa values (0.10 IU/mL; t43 = −13; P < .001; d = −1.9; 99% CI, −0.059 to −0.043). Conclusions: The daily subcutaneous administration of 40 mg of enoxaparin leads to subprophylactic aFXa levels for most patients who undergo cardiac surgery. Further studies on the clinical relevance are warranted.

Background: COVID-19 infection is associated with a pro-coagulable state, thrombosis, and cardiovascular events. However, its impact on population-based rates of vascular events is less well understood. We studied temporal trends in hospitalizations for stroke and myocardial infarction in 3 Canadian provinces (Alberta, Ontario, and Nova Scotia) between 2014 and 2022. Methods: Linked administrative data from each province were used to identify admissions for ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, and myocardial infarction. Event rates per 100,000/quarter, standardized to the 2016 Canadian population, were calculated. We assessed changes from quarterly rates pre-pandemic (2014-2020), compared to rates in the pandemic period (2020-2022), using interrupted time-series analysis with a jump discontinuity at pandemic onset. Age group– and sex-stratified analyses also were performed. Results: We identified 162,497 strokes and 243,182 myocardial infarctions. At pandemic onset, no significant step change in strokesper 100,000/quarter was observed in any of the 3 provinces. During the pandemic, stroke rates were stable in Alberta and Ontario, but they increased in Nova Scotia (0.44 per 100,000/quarter, P = 0.004). At pandemic onset, a significant step decrease occurred in myocardial infarctions per 100,000/quarter in Alberta (4.72, P < 0.001) and Ontario (4.84, P < 0.001), but not in Nova Scotia. During the pandemic, myocardial infarctions per 100,000/quarter decreased in Alberta (–0.34, P = 0.01), but they remained stable in Ontario and Nova Scotia. No consistent patterns by age group or sex were noted. Conclusions: Hospitalization rates for stroke or myocardial infarction across 3 Canadian provinces did not increase substantially during the first 2 years of the pandemic. Continued surveillance is warranted as the virus becomes endemic. Résumé: Contexte: L’infection par la COVID-19 est associée à un état procoagulant, à la thrombose et à des événements cardiovasculaires. Son incidence sur les taux d'événements vasculaires dans la population est cependant moins bien comprise. Nous avons étudié les tendances temporelles des hospitalisations pour un accident vasculaire cérébral (AVC) et un infarctus du myocarde dans trois provinces canadiennes (Alberta, Ontario et Nouvelle-Écosse) entre 2014 et 2022. Méthodologie: Des données administratives couplées provenant de chaque province ont été utilisées pour recenser les hospitalisations pour un AVC ischémique, une hémorragie intracérébrale, une thrombose veineuse cérébrale et un infarctus du myocarde. Nous avons calculé les taux d’événements pour 100 000 admissions/trimestre, uniformisés pour correspondre à la population canadienne de 2016. Nous avons évalué les variations par rapport aux taux trimestriels d’avant la pandémie (2014-2020), comparativement aux taux pendant la pandémie (2020-2022), à l’aide d’une analyse de séries chronologiques interrompues avec discontinuité à saut fini au début de la pandémie. Des analyses stratifiées selon le groupe d’âge et le sexe ont également été réalisées. Résultats: Nous avons recensé 162 497 AVC et 243 182 infarctus du myocarde. Au début de la pandémie, aucune variation progressive significative au niveau des AVC pour 100 000 admissions/trimestre n’a été observée dans aucune des trois provinces. Pendant la pandémie, les taux d’AVC sont demeurés stables en Alberta et en Ontario, mais ont augmenté en Nouvelle-Écosse (0,44 pour 100 000 admissions/trimestre; p = 0,004). Au début de la pandémie, une diminution graduelle significative du taux d’infarctus du myocarde pour 100 000 admissions/trimestre a été observée en Alberta (4,72; p < 0,001) et en Ontario (4,84; p < 0,001), mais pas en Nouvelle-Écosse. Durant la pandémie, le taux d’infarctus du myocarde pour 100 000 admissions/trimestre a diminué en Alberta (–0,34; p = 0,01), mais est demeuré stable en Ontario et en Nouvelle-Écosse. Aucune tendance constante n’a été observée selon le groupe d’âge ou le sexe. Conclusions: Les taux d’hospitalisation pour un AVC ou un infarctus du myocarde n’ont pas augmenté de manière substantielle dans les trois provinces canadiennes durant les deux premières années de la pandémie. Une surveillance continue s’impose alors que le virus devient endémique.

IGFBP6, a member of the IGF binding protein (IGFBP) family, is a specific inhibitor of insulin-like growth factor II (IGF-II) and can inhibit the growth of malignant tumors overexpressing IGF-II. Type 2 diabetes (T2D) is a basic disorder of glucose metabolism that can be regulated by IGF-related pathways. We performed bioinformatics analysis of the TCGA database to explore the possible mechanism of IGFBP6 in breast cancer (BC) metabolism and prognosis and collected clinical samples from BC patients with and without T2D to compare and verify the prognostic effect of IGFBP6. In our study, the levels of IGFBP1–6 were positively correlated with overall survival (OS) in patients with breast cancer. IGFBP6 was upregulated in estrogen receptor (ER)-positive BC, and ER-positive and progesterone receptor (PR) positive patients had a higher expression level of IGFBP6 than ER-negative and PR-negative patients. IGFBP6 could be used as an independent prognostic factor in BC. The expression of IGFBP6 was decreased in BC tissue, and BC tissue from patients with T2D had lower IGFBP6 expression levels than BC tissue from patients without T2D. IGFBP6 is mainly involved in the PI3K–Akt and TGF-β signaling pathways and tumor microenvironment regulation. In terms of metabolism, the expression of IGFBP6 was negatively correlated with that of most glucose metabolism-related genes. IGFBP6 expression was mainly correlated with mutations in TP53, PIK3CA, CDH1, and MAP3K1. In addition, the upregulation of IGFBP6 in BC increased the drug sensitivity to docetaxel, paclitaxel and gemcitabine. Overall, these results indicated that high expression of IGFBP6 is associated with a good prognosis in BC patients, especially in those without T2D. It is not only involved in the maintenance of the tumor microenvironment in BC but also inhibits the energy metabolism of cancer cells through glucose metabolism-related pathways. These findings may provide a new perspective on IGFBP6 as a potential prognostic marker for BC.

ABSTRACT: Background: Facet arthroplasty, an alternative to lumbar fusion, offers stabilization and preserves range of motion. This subanalysis of the TOPS IDE trial (FDA #G160168) compared facet arthroplasty, using the TOPS device, with a standard single-level transforaminal lumbar interbody fusion (TLIF) in patients stratified by age (

Management of recurrent prostate cancer following radiotherapy and subsequent radical prostatectomy poses considerable challenges due to potential complications for patients. Focal therapies have emerged as a burgeoning approach in prostate cancer treatment. Research indicates that ablative therapies exhibit encouraging oncological efficacy while maintaining acceptable functional outcomes in salvage interventions. Here, we present a contemporary review of focal therapy treatment modalities as well as oncologic and functional outcomes.

Background: Colorectal cancer is a major cause of mortality among the prevalent malignant tumors of the gastrointestinal tract. Although chemotherapy is a standard treatment for colorectal cancer, its efficacy is limited by chemoresistance. Recent studies have investigated targeting tumor stem cells as a potential new therapeutic approach for addressing chemoresistance in colorectal cancer. Colorectal cancer frequently relapses, with tumor stem cells often representing one of the leading causes of treatment failure. Purpose: Understanding drug resistance in colorectal cancer stem cells is crucial for improving treatment outcomes. By focusing on developing targeted therapies that specifically address drug resistance in colorectal cancer stem cells, there is potential to make significant advancements in the treatment of colorectal cancer.This approach may lead to more effective and lasting outcomes in patients battling colorectal cancer. Research Design: In this review, a comprehensive overview of recent research on colorectal cancer stem cell treatment resistance is presented.Results: Elucidating the key underlying mechanisms. This review also highlights the potential benefits of targeted therapies in overcoming colorectal cancer resistance to treatment. Conclusions: CCSCs are key players in drug resistance of CRC, indicating their potential as targets for effective therapy. Elucidating their role in this process could aid in discovering tailored treatment strategies.The significance of signaling pathways, TME, and miRNA in regulating drug resistance in CCSCs is been highlighted.

Background:. Botulinum toxin A (BTxA) has gained popularity as a nonsurgical aesthetic treatment for skin rejuvenation. However, previous studies on intradermal BTxA have shown inconsistent results. This systematic review and meta-analysis with trial sequential analysis aimed to assess the efficacy and safety of intradermal BTxA for facial rejuvenation. Methods:. Following PRISMA guidelines, a comprehensive search was conducted in various databases from January 2008 to March 2023. Outcome measures included sebum production, pore size, skin hydration, skin texture, erythema index, facial wrinkles, and facelift. Eligible studies included human-based clinical trials and prospective cohort studies published in English, focusing on healthy populations requiring facial rejuvenation. Two authors independently screened the titles and abstracts, followed by a full-text review to determine study eligibility. Data extraction and quality assessment were performed by two authors using predefined criteria. Results:. Ten studies met the inclusion criteria, including five randomized controlled trials and five prospective cohort studies with 153 participants. Studies revealed positive effects of intradermal BTxA on various outcome measures related to facial rejuvenation. These effects included improvements in sebum production, pore size, erythema index, facial wrinkles, skin texture and elasticity, and overall facelift but not skin hydration. All failed to reach the required information size in the trial sequential analysis. Conclusions:. Findings suggest positive outcomes in multiple attributes of skin quality and facial rejuvenation. However, more high-quality research is needed to establish definitive conclusions. These findings contribute to the evidence base for nonsurgical aesthetic treatments, emphasizing the importance of ongoing research in this field.

Summary:. A 26-year-old man was admitted to our hospital due to the replantation of the severed right upper arm and right thigh injury 6 days before. The patient received emergency treatment at a local hospital. He underwent amputation and replantation for the right upper arm and right thigh. After surgery, he experienced fever, limb swelling, and wound pain. At the time of admission to our hospital, the patient exhibited stable vital signs. An infection was found at the replanted wound, and the culture results showed Pseudomonas aeruginosa. After admission, the patient underwent symptomatic antiinflammatory treatment. In addition, he received fracture reduction and external fixation with a bracket, radial nerve exploration and release of the upper and lower limb external fixation with a bracket, upper femur osteotomy, and external fixation with a bracket. He also received reconstruction of elbow flexion functions with biceps femoris tendon transplantation; reconstruction of wrist joint fusion, finger extension function, and palm function; removal of the femoral external fixation with a bracket; and tibiofibular osteotomy and leg lengthening surgery. Moreover, the anterior tibial tendon was fixed to correct foot drop deformity, and the external fixation bracket was removed. Owing to these efforts, the patient achieved limb preservation with well-reconstructed functions.

Summary:. An 80-year-old female patient was admitted to the hospital due to recurrent lymphedema, ulcers, and lymphorrhea in the right lower limb for 7 years. The physical examination revealed changes after the Charles procedure below the right knee joint plane, with a 7 × 7 cm2 lymphorrhea area in the lower one-third plane of the anterior tibia area. Continuous lymphatic exudation and scattered ulcers could be seen. The dorsal artery of the foot could not be reached due to the thickening and fibrosis of the dorsal skin of the foot. The peripheral blood circulation was favorable. The glycated hemoglobin test revealed that blood sugar was not high and could be controlled. The color Doppler ultrasound of lower limb blood vessels revealed no obvious stenosis of arteries, with normal venous return. In addition, no varicose veins or deep venous thrombosis were observed. Based on these findings, the patient was diagnosed with primary lymphedema combined with lymphorrhea after the Charles procedure, complicated with diabetes. After admission, the patient underwent lymphaticovenous anastomosis on the right lower limb under general anesthesia. During the follow-up of 2 months after surgery, it was found that the lymphorrhea was alleviated, the ulcer basically healed, and the swelling on the right lower limb decreased. At the follow-up of 6 months after surgery, the lymphorrhea was eliminated and the ulcer was healed. There were 1-cm reduction in leg and back circumference and 10% volume reduction. The lymphedema quality-of-life score of this patient was 57 points after surgery.

Summary:. An 80-year-old male patient was admitted to the hospital due to swelling in the right lower limb with local blisters caused by a forced prone position for 9 hours after syncope. The patient got up in the middle of the night and fainted beside the bed due to a transient cerebral ischemia attack. The front of the right thigh and calf contacted the bed edge, presenting a forced prone position for 9 hours. The physical examination revealed swelling of the right lower limb, accompanied by local tension blisters, and the tension of the thigh and calf was increased. The patient had a history of diabetes, and no lower limb artery or vein thrombosis was found on B-ultrasound. Based on these findings, the patient was diagnosed with well leg compartment syndrome in the right thigh and calf. When the patient was admitted, the creatine phosphokinase level was 62,300 u/L, and the creatinine level was 2.66 mg/dL. Besides, the urea level of this patient was 11 mmol/L. He developed anuria with a high creatinine level, indicating acute kidney injury. Subsequently, temporary hemodialysis was performed for treatment. The patient underwent fasciotomy of the right thigh and calf, and the vacuum-assisted closure device was adopted for wound treatment. After 2 weeks of decompression, the wound was directly sutured under tension. After renal replacement therapy, the creatine phosphokinase level of this patient was 102 u/L, and the creatinine level was 95 mol/L, which tended to be normal.

Introduction With the advancements in cancer prevention and diagnosis, the proportion of newly diagnosed early-stage cervical cancers has increased. Adjuvant therapies based on high-risk postoperative histopathological factors significantly increase the morbidity of treatment complications and seriously affect patients’ quality of life. Objectives Our study aimed to establish a diagnostic nomogram for vaginal invasion (VI) among early-stage cervical cancer (CC) that can be used to reduce the occurrence of positive or close vaginal surgical margins. Methods We assembled the medical data of early-stage CC patients between January 2013 and December 2021 from the Fujian Cancer Hospital. Data on demographics, laboratory tests, MRI features, physical examination (PE), and pathological outcomes were collected. Univariate and multivariate logistic regression analyses were employed to estimate the diagnostic variables for VI in the training set. Finally, the statistically significant factors were used to construct an integrated nomogram. Results In this retrospective study, 540 CC patients were randomly divided into training and validation cohorts according to a 7:3 ratio. Multivariate logistic analyses showed that age [odds ratio (OR) = 2.41, 95% confidence interval (CI), 1.29-4.50, P = 0.006], prognostic nutritional index (OR = 0.18, 95% CI, 0.04-0.77, P = 0.021), histological type (OR = 0.28, 95% CI, 0.08-0.94, P = 0.039), and VI based on PE (OR = 3.12, 95% CI, 1.52-6.45, P = 0.002) were independent diagnostic factors of VI. The diagnostic nomogram had a robust ability to predict VI in the training [area under the receiver operating characteristic curve (AUC) = 0.76, 95% CI: 0.70-0.82] and validation (AUC = 0.70, 95% CI: 0.58-0.83) cohorts, and the calibration curves, decision curve analysis, and confusion matrix showed good prediction power. Conclusion Our diagnostic nomograms could help gynaecologists quantify individual preoperative VI risk, thereby optimizing treatment options, and minimizing the incidence of multimodality treatment-related complications and the economic burden.

Objectives Accurate survival predictions and early interventional therapy are crucial for people with clear cell renal cell carcinoma (ccRCC). Methods In this retrospective study, we identified differentially expressed immune-related (DE-IRGs) and oncogenic (DE-OGs) genes from The Cancer Genome Atlas (TCGA) dataset to construct a prognostic risk model using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. We compared the immunogenomic characterization between the high- and low-risk patients in the TCGA and the PUCH cohort, including the immune cell infiltration level, immune score, immune checkpoint, and T-effector cell- and interferon (IFN)-γ-related gene expression. Results A prognostic risk model was constructed based on 9 DE-IRGs and 3 DE-OGs and validated in the training and testing TCGA datasets. The high-risk group exhibited significantly poor overall survival compared with the low-risk group in the training ( P < 0.0001), testing ( P = 0.016), and total ( P < 0.0001) datasets. The prognostic risk model provided accurate predictive value for ccRCC prognosis in all datasets. Decision curve analysis revealed that the nomogram showed the best net benefit for the 1-, 3-, and 5-year risk predictions. Immunogenomic analyses of the TCGA and PUCH cohorts showed higher immune cell infiltration levels, immune scores, immune checkpoint, and T-effector cell- and IFN-γ-related cytotoxic gene expression in the high-risk group than in the low-risk group. Conclusion The 12-gene prognostic risk model can reliably predict overall survival outcomes and is strongly associated with the tumor immune microenvironment of ccRCC.

Purpose: Exosomes have been shown to play a role in most, if not all, steps of cancer progression. We still lack a comprehensive understanding of the bidirectional communication of exosomes between tumor cells and immune cells. This article aims to explore how exosomes can influence cancer growth and how they are affected by radiation therapy. Methods and Materials: We searched on PubMed and Web of Science on the impact of radiation on tumor derived exosomes and immune cell derived exosomes in tumor immune microenvironment. We screened all the related articles and summarized their main discoveries and important results. Results: This article reviewed the effects of tumor derived exosomes and immune cell-derived exosomes on TME and tumor progression after radiotherapy, suggesting the dual effects of exosomes which may refer to clinical practice. Moreover, we retrospected the clinical applications based on tumor derived exosomes, including liquid biopsy, radio-resistance and drug delivery, and discussed the challenges and prospects. Conclusions: Exosomes are important in cancer treatment, especially with radiation therapy. Learning more about them could lead to better treatments. However, there are still challenges to overcome. The review points out the need for more research in this area.

Summary:. A 50-year-old man was admitted to the hospital with a chief complaint of long-standing cold-induced numbness in the fingers for more than a year, accompanied by persistent hand pain and fingertip ulceration for 3 months. On physical examination, radial and ulnar artery pulsation was absent in both limbs, and pale skin color, low skin temperature, and limited finger range of motion were noted. Gangrene was detected in the fingertips of the left index and middle fingers, and the right middle and ring fingers. The patient was diagnosed with bilateral arterial occlusion and vibration white finger. Upon admission, the patient underwent an intervention surgery on the right side. Subsequently, transplantation of the descending branches of the left and right lateral femoral circumflex arteries was performed to restore blood flow in the bilateral radial arteries. Additionally, debridement was conducted without shortening after the surgical procedure, the patient received anticoagulation, anti-inflammatory, and symptomatic treatment. The bilateral finger skin temperature increased by 3 °C postoperatively, and the accompanying pain and numbness were alleviated. The wound healed 1 month after surgery, and no recurrence of pain or ulcer was reported during the 1-year follow-up period. Eventually, his hand function recovered, without any impact on the vascular donor site.

Background/Objective: To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy. Case Report: A 35-year-old woman with a history of Graves’ disease was referred for evaluation of hyperthyroidism in March 2020. She was started on methimazole and thyroid function normalized. The patient also had a history of a pituitary microadenoma and was previously treated with cabergoline which was stopped after 12 months as she became pregnant.In July 2020, the patient began to have polymenorrhea. Hyperprolactinemia was thought to be an unlikely cause as it most often causes hypogonadotropic hypogonadism with amenorrhea. A pelvic ultrasound demonstrated a bulky uterus with adenomyosis. Gynecology recommended treating adenomyosis by lowering her prolactin levels. She was started on cabergoline 0.25 mg weekly in October 2021. Within 2 months of initiation of cabergoline, she had resolution of symptoms and radiological resolution of adenomyosis. Discussion: Prolactin has been implicated in the pathogenesis of adenomyosis, endometriosis and leiomyomas suggesting that a decrease in prolactin levels may suppress these lesions. The pathogenesis of adenomyosis has been related to direct prolactin effects in the promotion of gland/cell proliferation and function. Conclusion: We conclude that prolonged elevation in prolactin may result in the development of adenomyosis and subsequent prolonged abnormal uterine bleeding. Dopamine agonists, like cabergoline, inhibit the synthesis and secretion of prolactin from the pituitary gland and may have a role in the management of adenomyosis in patients with hyperprolactinemia.

Purpose: Regional nodal irradiation (RNI) for breast cancer yields improvements in disease outcomes, yet comprehensive target coverage often increases cardiac radiation therapy (RT) dose. Volumetric modulated arc therapy (VMAT) may mitigate high-dose cardiac exposure, although it often increases the volume of low-dose exposure. The cardiac implications of this dosimetric configuration (in contrast to historic 3D conformal techniques) remain uncertain. Methods and Materials: Eligible patients receiving adjuvant RNI using VMAT for locoregional breast cancer were prospectively enrolled in an IRB-approved study. Echocardiograms were performed prior to RT, at the conclusion of RT, and 6 months following RT. Echocardiographic parameters were measured by a single reader and measures were compared pre- and post-RT via the signed-rank test. Changes in echocardiographic parameters over time were compared to mean and max heart doses via the Spearman correlation test. Results: Among 19 evaluable patients (median age 38 years), 89% (n = 17) received doxorubicin and 37% (n = 7) received trastuzumab/pertuzumab combination therapy. All patients received VMAT-based whole-breast/chest wall and RNI. The average mean heart dose was 456 cGy (range, 187-697 cGy) and the average max heart dose was 3001 cGy (1560-4793 cGy). Among salient echocardiographic parameters, no significant decrement in cardiac function was observed when comparing pre-RT to 6 months post-RT: mean left ventricular ejection fraction (LVEF) was 61.8% (SD 4.4%) pre-RT and 62.7% (SD 3.8%) 6 months post-RT (P = .493); mean global longitudinal strain (GLS) was –19.3% (SD 2.2%) pre-RT and –19.6% (SD 1.8%) 6 months post-RT (P = .627). No individual patient exhibited reduced LVEF or sustained decrement in GLS. No correlations were observed for changes in LVEF or GLS when compared to mean or maximum heart doses (P > .1 for all). Conclusions: VMAT for left-sided RNI yielded no significant early decrement in echocardiographic parameters of cardiac function, including LVEF and GLS, within this limited cohort. No patient exhibited significant LVEF changes, and none exhibited sustained decrements in GLS. VMAT may be a reasonable approach to cardiac avoidance in patients requiring RNI, including those receiving anthracyclines and HER2-directed therapy. Larger cohorts with longer follow-ups will be needed to validate these findings.

Background:. As long-term, regular aesthetic botulinum neurotoxin A (BoNT-A) use becomes more commonplace, it is vital to understand real-world risk factors and impact of BoNT-A immunoresistance. The first Aesthetic Council on Ethical Use of Neurotoxin Delivery panel discussed issues relating to BoNT-A immunoresistance from the health care professionals’ (HCPs’) perspective. Understanding the implications of BoNT-A immunoresistance from the aesthetic patient’s viewpoint allows HCPs to better support patients throughout their aesthetic treatment journey. Methods:. A real-world consumer study surveyed 363 experienced aesthetic BoNT-A recipients across six Asia-Pacific territories. The survey mapped participants’ BoNT-A aesthetic treatment journey and characterized awareness and attitudes relating to BoNT-A immunoresistance and treatment implications. At the second Aesthetic Council on Ethical use of Neurotoxin Delivery meeting, panelists discussed survey findings and developed consensus statements relating to the impact of BoNT-A immunoresistance on the aesthetic treatment journey. Results:. Aesthetic BoNT-A patients’ depth of knowledge about BoNT-A immunoresistance remains low, and risk/benefit communications need to be more lay-friendly. The initial consultation is the most important touchpoint for HCPs to raise awareness of BoNT-A immunoresistance as a potential side effect considering increased risk with repeated high-dose treatments. HCPs should be cognizant of differences across BoNT-A formulations due to the presence of certain excipients and pharmacologically unnecessary components that can increase immunogenicity. Standardized screening for clinical signs of secondary nonresponse and a framework for diagnosing and managing immunoresistance-related secondary nonresponse were proposed. Conclusion:. These insights can help patients and HCPs make informed treatment decisions to achieve desired aesthetic outcomes while preserving future treatment options with BoNT-A.

We reported 5 patients with unilateral or bilateral tubal discontinuity between the ampulla and fimbria, occasionally detected through laparoscopy combined with hysteroscopy at the Reproductive Hospital Affiliated with Shandong University from 2017 to 2023. Three cases were observed to have this malformation on the left fallopian tube, 1 case on the right side, and 1 case bilaterally. None of these cases were combined with urological malformations. After surgery, there was 1 instance of postoperative delivery, 1 ongoing pregnancy, and 3 not yet conceived. The congenital ampulla and fimbria interruption of the fallopian tube may be independent of other significant deformities of reproductive or renal tracts. However, it can lead to hydrosalpinx and primary or secondary infertility. Surgical management options, such as salpingostomy, salpingectomy, and tubal ligation, have shown the potential to improve pregnancy outcomes.

This study aimed to assess the current status of gestational diabetes mellitus (GDM) diagnosis and management, and the demand for a digital healthcare system, in order to develop an optimal digital-based management model for GDM. An anonymous online survey was conducted targeting pregnant/postpartum women (Group W), internal medicine physicians (Group P), and obstetricians (group O) from September 6, 2022 to December 31, 2022. The survey assessed the women’s knowledge of GDM and gathered information about healthcare professionals’ (HCPs) current GDM management practices. All groups were asked about their acceptance of and demands for a digital healthcare system for GDM. Statistical comparisons between groups were conducted using the chi-square test or Fisher’s exact test where appropriate. A total of 168 participants were in Group W, 185 in Group P, and 256 in Group O. Participants from all groups recognized the need for a digital healthcare system for GDM (Group W: 95.8%, Group P: 85.9%, Group O: 60%). However, HCPs showed less willingness to integrate these systems into their clinics than pregnant/postpartum women. Essential features identified were recording blood glucose levels and insulin, along with automatic data linkage from self-monitoring devices. Group W showed a higher preference for lab test access, search functionality, and fetal weight assessment than groups P and O (all P

BACKGROUND: The diagnostic criteria and phenotypes in polycystic ovary syndrome are heterogeneous. Currently, it is unclear how to assess a patient's prognosis based on the onset time of menstruation disturbance. Evidence on this topic is scarce and has mainly focused on menstrual patterns. OBJECTIVE: This study aimed to assess the association between the onset time of menstrual disturbance and clinical features and in vitro fertilization pregnancy outcomes in patients with polycystic ovary syndrome. STUDY DESIGN: Our study was a secondary analysis of data collected as part of a randomized controlled trial conducted to compare live birth rates between fresh embryo transfer and frozen embryo transfer in 1508 individuals with polycystic ovary syndrome. Here, 1500 participants were classified into 2 groups according to the onset time of menstrual disturbance: immediately after menarche (early group) and after at least 1 year of regular menstruation (late group). We compared the prepregnancy clinical features, variables of ovarian stimulation, pregnancy outcomes after the initial cycle of embryo transfer, and perinatal and neonatal complications in the 2 groups. RESULTS: Compared with the late group, the early group had more antral follicles (32.00 [range, 27.25–39.50] vs 28.00 [range, 24.00–36.00]; P

Purpose: In the United States, brain metastases (BMs) affect 10% to 20% of patients with cancer, presenting a significant health care challenge and necessitating intricate, high-cost treatments. Few studies have explored the comprehensive care cost for BMs, and none have used real insurance claims data. Partnering with a northeastern health care insurer, we investigated the true costs of various brain-directed radiation methods, aiming to shed light on treatment expenses, modalities, and their efficacy. Methods and Materials: We analyzed medical claims from Highmark Health-insured patients in Pennsylvania, Delware, West Virginia, and New York diagnosed with BMs (ICD-10 code C79.31) and treated with radiation from January 1, 2020 to July 1, 2022. Costs for radiation techniques were grouped by specific current procedural terminology claim codes. We subdivided costs into technical and physician components and separated hospital from freestanding costs for some modalities. Results: From January 1, 2020 to July 1, 2022, 1048 Highmark Health members underwent treatment for BMs. Females (n = 592) significantly outnumbered males (n = 456), with an average age of 64.4 years. Each member had, on average, 5.309 claims costing $2015 per claim. Total cost totaled $10,697,749. Per-treatment analysis showed that hippocampal avoidance intensity modulated radiation therapy was the costliest treatment at $47,748, followed by stereotactic radiation therapy at $37,230, linear accelerator stereotactic radiosurgery (SRS) at $30,737, Gamma Knife SRS at $30,711, and whole-brain radiation therapy at $5225. Conclusions: Whole-brain radiation therapy was the least costly radiation technique. Similar per-treatment prices for Gamma Knife and linear accelerator SRS support their use in treating BMs. Stereotactic radiation therapy in general was costlier on a per-use basis than SRS, prompting further scrutiny on its frequent use. Hippocampal avoidance intensity modulated radiation therapy was the costliest radiation therapy on a per-use basis by a moderate amount, prompting further discussion about its comparative cost effectiveness against other radiation modalities. This study underscores the importance of multiple considerations in treating BMs, such as tumor control, survival, side effects, and costs.

BACKGROUND: Frozen embryo transfer resulted in a higher birthweight and an increased risk of macrosomia than fresh embryo transfer. However, the mechanism was still unclear. When the impact of frozen embryo transfer on fetal growth began was unknown. Crown-rump length at 11–13 weeks had been regarded as a good indicator of fetal growth in the first trimester and had been used for gestational age calculation in women with uncertain last menstrual periods. OBJECTIVE: To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, then fresh embryo transfer. The secondary objective was to investigate the potential correlation between crown-rump length and birthweight. STUDY DESIGN: This was a retrospective cohort study conducted at the Reproductive Medical Center of Shandong University. A total of 4949 patients who obtained singleton pregnancy after frozen embryo transfer and 1793 patients who got singleton pregnancy after fresh embryo transfer between January 1, 2017 and December 31, 2022 were included. The primary outcome was the crown-rump length measured via ultrasound at 11–13 weeks gestation. The secondary outcomes were perinatal outcomes, including birthweight and the risk of large for gestational age, small for gestational age, macrosomia, low birthweight, and premature delivery. Multivariable linear regression models were used to adjust for potential confounders of crown-rump length. RESULTS: A total of 6742 live singleton births after frozen embryo transfer or fresh embryo transfer were included in this study. In the univariable analysis, the frozen embryo transfer group had a larger crown-rump length (5.75±0.53 cm vs 5.57±0.48 cm, P

Hepatocellular carcinoma (HCC), partly because of its complexity and high heterogeneity, has a poor prognosis and an extremely high mortality rate. In this study, mRNA sequencing expression profiles and relevant clinical data of HCC patients were gathered from different public databases. Kaplan–Meier survival curves as well as ROC curves validated that OLA1|CLEC3B was an independent predictor with better predictive capability of HCC prognosis compared to OLA1 and CLEC3B separately. Further, the cell transfection experiment verified that knockdown of OLA1 inhibited cell proliferation, facilitated apoptosis, and improved sensitivity of HCC cells to gemcitabine. In this study, the prognostic model of HCC composed of OLA1/CLEC3B genes was constructed and verified, and the prediction ability was favorable. A higher level of OLA1 along with a lower level of CEC3B is a sign of poor prognosis in HCC. We revealed a novel gene pair OLA1|CLEC3B overexpressed in HCC patients, which may serve as a promising independent predictor of HCC survival and an approach for innovative diagnostic and therapeutic strategies.

Introduction: Opioid overprescribing may fuel the opioid epidemic and increase the risk of complications of opioid misuse. This study examined trends and determinants of chronic and heavy opioid use among elderly community dwellers in the U.S. Methods: Medicare Current Beneficiary Surveys data from 2006 to 2019 were used. Common opioid medications were identified in the prescription medication files (n=47,264). Patients with Chronic users were defined as those receiving 6 or more opioid prescriptions within a year or on medication for 3 or more months, and heavy users were those having an average daily dose of 90 or more morphine milligram equivalents or 3,780 morphine milligram equivalents or more per continuous treatment episode. Results: One in 6 elderly community dwellers ever used opioids during the study period. Chronic users were more likely to be women than men (68.9% vs 31.1%, p

Interventional ultrasound (IUS) is an important branch of modern minimally invasive medicine that has been widely applied in clinical practice due to its unique techniques and advantages. As a relatively emerging field, IUS has progressed towards standardization, precision, intelligence, and cutting-edge directions alone with more than 40 years of development, which is becoming increasingly important techniques in clinical medicine. This article will briefly review the development and advancement of IUS for diagnosis and treatment in China in the era of precision medicine from the aspects of artificial intelligence, virtual navigation, molecular imaging, and nanotechnology.

Objective: To investigate the feasibility and accuracy of artificial intelligence (AI) methods of facial deidentification in hospital-recorded epileptic seizure videos, for improved patient privacy protection while preserving clinically important features of seizure semiology. Patients and Methods: Videos of epileptic seizures displaying seizure-related involuntary facial changes were selected from recordings at Taipei Veterans General Hospital Epilepsy Unit (between August 1, 2020 and February 28, 2023), and a single representative video frame was prepared per seizure. We tested 3 AI transformation models: (1) morphing the original facial image with a different male face; (2) substitution with a female face; and (3) cartoonization. Facial deidentification and preservation of clinically relevant facial detail were calculated based on: (1) scoring by 5 independent expert clinicians and (2) objective computation. Results: According to the clinician scoring of 26 facial frames in 16 patients, the best compromise between deidentification and preservation of facial semiology was the cartoonization model. A male facial morphing model was superior to the cartoonization model for deidentification, but clinical detail was sacrificed. Objective similarity testing of video data reported deidentification scores in agreement with the clinicians’ scores; however, preservation of semiology gave mixed results likely due to inadequate existing comparative databases. Conclusion: Artificial intelligence-based face transformation of medical seizure videos is feasible and may be useful for patient privacy protection. In our study, the cartoonization approach provided the best compromise between deidentification and preservation of seizure semiology.

Background/Objective: Clinical diagnosis of rare aggressive sellar malignancies requires a high index of suspicion. The objective was to report 2 patients with primary sellar atypical teratoid (AT)/rhabdoid tumor (RT) who presented with acute-onset headache and visual symptoms. Case Report: Patient 1 was a 45-year-old woman who presented with 3 weeks of headache and 1 week of eye pain and diplopia. Magnetic resonance imaging (MRI) identified a 2.2-cm sellar mass. Pituitary hormone testing showed elevated prolactin and suppressed luteinizing hormone, follicle-stimulating hormone, and estradiol levels. Patient 2 was a 32-year-old woman who presented with 1 month of headache and 1 week of diplopia. MRI showed a 2.1-cm sellar mass. Hormonal test results were reportedly unremarkable. Both patients did not have a significant medical history. They each underwent transsphenoidal resection. Surgical histology and molecular studies were consistent with primary sellar AT/RT. After surgery, patient 1 developed bilateral blindness and was lost to follow-up. Patient 2 developed hypopituitarism; her visual symptoms improved temporarily but recurred 2 weeks later. Pituitary MRI showed sellar recurrence. She underwent further debulking, but the tumor recurred promptly again. Despite radiation therapy, she died 4 months after the original presentation. Discussion: AT/RT appears to be the most aggressive sellar malignancy. Conclusion: Based on the 2 cases presented and the literature, I conclude that rapidly progressive headache with subsequent visual impairment in women with large sellar masses is almost pathognomonic of sellar AT/RT.

Background: Documented symptomatic progression of a paraganglioma (PGL) over many years is unusual. Our objective is to report a young man with such an occurrence. Case Report: A 27-year-old male presented with headache, sweating, and palpitation. He had a history of cyanotic congenital heart disease. Five years before presentation, he had 24-hour urine metanephrines 43 mcg/d (25-222), vanillylmandelic acid 3 mg/d (

ABSTRACT: Background: Lumbar spinal fusion surgery is a well-established treatment for various spinal disorders. However, one of its complications, pseudoarthrosis, poses a significant concern. This study aims to explore the incidence, time and predictive factors contributing to pseudoarthrosis in patients who have undergone lumbar fusion surgery over a 10-year period. Methods: Data for this research was sourced from the PearlDiver database where insurance claims of patients who underwent multilevel lumbar spinal fusion between 01/01/2010 and 10/31/2022 were examined for claims of pseudoarthrosis within the 10 years of their index procedure. A variety of demographic, comorbid, and surgical factors were assessed, including age, gender, Elixhauser Comorbidity Index (ECI), surgical approach, substance use disorders and history of spinal disorders. Statistical analyses, including chi-squared tests, multivariate analysis, and cox survival analysis were employed to determine significant associations. Results: Among the 76,337 patients included in this retrospective study, 2.70% were diagnosed with symptomatic lumbar pseudoarthrosis at an average of 7.38 years in a 10-year follow-up. Multivariate and Cox hazard analyses revealed that significant predictors of symptomatic pseudoarthrosis development following multilevel primary lumbar fusion include vitamin D deficiency, osteoarthritis, opioid and NSAID use, tobacco use, and a prior history of congenital spine disorders. Conclusions: In summary, this study revealed a 2.70% incidence of symptomatic lumbar pseudoarthrosis within 10 years of the index procedure. It highlighted several potential predictive factors, including comorbidities, surgical approaches, and substance use disorders, associated with the development of symptomatic pseudoarthrosis. Future research should focus on refining our understanding of these factors to improve patient outcomes and optimize healthcare resource allocation.

Purpose: To maximize the therapeutic ratio, it is important to identify adverse prognostic features in men with prostate cancer, especially among those with intermediate risk disease, which represents a heterogeneous group. These men may benefit from treatment intensification. Prior studies have shown pretreatment mpMRI may predict biochemical failure in patients with intermediate and/or high-risk prostate cancer undergoing conventionally fractionated external beam radiation therapy and/or brachytherapy. This study aims to evaluate pretreatment mpMRI findings as a marker for outcome in patients undergoing stereotactic body radiation therapy (SBRT). Methods and Materials: We identified all patients treated at our institution with linear accelerator based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) from November 2015 to March 2021. All patients underwent pretreatment Magnetic Resonance Imaging (MRI). Posttreatment Prostate Specific Imaging (PSA) measurements were typically obtained 4 months after SBRT, followed by every 3 to 6 months thereafter. A 2 sample t test was used to compare preoperative mpMRI features with clinical outcomes. Results: One hundred twenty-three men were included in the study. Pretreatment MRI variables including median diameter of the largest intraprostatic lesion, median number of prostate lesions, and median maximal PI-RADS score, were each predictive of PSA nadir and time to PSA nadir (P < .0001). When separated by ADT treatment, this association remained for patients who were not treated with ADT (P < .001). In patients who received ADT, the pretreatment MRI variables were each significantly associated with time to PSA nadir (P < .01) but not with PSA nadir (P > 0.30). With a median follow-up time of 15.9 months (IQR: 8.5-23.3), only 3 patients (2.4%) experienced biochemical recurrence as defined by the Phoenix criteria. Conclusions: Our experience shows the significant ability of mpMRI for predicting PSA outcome in prostate cancer patients treated with SBRT with or without ADT. Since PSA nadir has been shown to correlate with biochemical failure, this information may help radiation oncologists better counsel their patients regarding outcome after SBRT and can help inform future studies regarding who may benefit from treatment intensification with, for example, ADT and/or boosts to dominant intraprostatic lesions.

ABSTRACT: Background: Patients with long-term follow-up after cervical decompression and fusion have often been noted to have development of adjacent segment degeneration with a smaller subset of these patients progressing to adjacent segment disease (ASD), which results in the development of new symptomatic radiculopathy or myelopathy referable to a site either directly above or below a prior fused segment. The cause of ASD is multifactorial often involving natural age-related progression of spondylosis, accelerated progression following cervical decompression and fusion, operative technique, and patient-related factors. The effect of age at the time of index cervical decompression and fusion on the need for reoperation for ASD is not fully understood. This study aims to establish underlying risk factors for the development of symptomatic cervical ASD following cervical decompression and fusion requiring reoperation in patients of various age groups. Methods: A retrospective database review of patients aged 20 or greater with insurance claims of primary cervical decompression and fusion over the course of 11 years and 10 months (January 01, 2010–October 31, 2022) was conducted using an insurance claims database. The primary outcome was to evaluate the incidence of cervical ASD requiring reoperation amongst patients stratified by age at the time of their primary procedure. Secondary outcomes included an evaluation of various risk factors for ASD following cervical decompression and fusion including surgeon-controlled factors such as the number of levels fused and approach taken, patient cervical pathology including cervical disc disorder and cervical spondylosis, and underlying patient medical comorbidities including osteoporosis and vitamin D deficiency, and substance use. Results: A total of 60,292 patient records were analyzed, where the overall reoperation incidence for symptomatic ASD was 6.57%, peaking at 8.12% among those aged 30 to 39 and decreasing with age. Regression analysis revealed ages lower than 50 years as more predictive for the development of symptomatic ASD requiring reoperation. Multivariate regression analysis identified predictive factors for reoperation, including age, Elixhauser Comorbidity Index (ECI), multiple-level surgery, cervical spondylosis, cervical disc disorder, osteoporosis, and vitamin D deficiency. Notably, these factors had a variable impact across various age groups, as revealed by subgroup analysis. Conclusions: The incidence of reoperation secondary to symptomatic ASD is 6.57%, highest in those aged 30 to 39. The surgical approach had no significant impact on the need for reoperation, but multiple-level fusions posed a consistent risk in the development of symptomatic ASD requiring reoperation. Patient factors like degenerative disc disease, spondylosis, osteoporosis, and vitamin D deficiency were associated, urging further age-specific risk assessment and nonoperative intervention exploration.

Summary:. Leg muscle hypertrophy is a unique physical symptom in East Asian women. Compared with traditional surgical treatment for calf muscle hypertrophy, botulinum toxin is widely favored by East Asian women because of its minimal trauma and significant effects. We describe the case of a 22-year-old woman with pulmonary embolism because of deep vein thrombosis, who presented with hypertrophy of bilateral calf muscles, and was administered 300 U of botulinum toxin A injection in July 2022. On the third day after the injection, she experienced swelling and pain in her left leg, which gradually worsened and made walking difficult. She underwent an ultrasound examination of lower limbs, which revealed several deep and shallow vein thrombi in the left lower limb. Computed tomography arterial imaging indicated multiple embolisms in pulmonary arteries. This study aimed to explore and analyze the causes of pulmonary embolism after botulinum toxin treatment for calf muscle hypertrophy by reviewing and analyzing the patient’s symptoms, diagnosis, and treatment process to provide management strategies for treatment and prevention of this disease.

MET protooncogene (MET) alterations are known driver oncogenes in NSCLC. Since the identification of MET as a potential therapeutic target, extensive clinical trials have been performed. As a result, MET-targeted therapies, including MET tyrosine kinase inhibitors, monoclonal antibodies, and MET antibody–drug conjugates now play important roles in the standard treatment of MET-altered NSCLC; they have considerably improved the outcomes of patients with tumors that harbor MET oncogenic drivers. Although clinical agents are currently available and numerous other options are in development, particular challenges in the field require attention. For example, the therapeutic efficacy of each drug remains unsatisfactory, and concomitantly, the resistance mechanisms are not fully understood. Thus, there is an urgent need for optimal drug sequencing and combinations, along with a thorough understanding of treatment resistance. In this review, we describe the current landscape of pertinent clinical trials focusing on MET-targeted strategies and discuss future developmental directions in this rapidly expanding field.

Objective As monotherapy such as topotecan has reached a plateau of effectiveness, new second-line treatments based on experience have been used in clinical application. This study compared the efficacy and safety of different second-line treatments for advanced small-cell lung cancer (SCLC). Methods A total of 380 patients with advanced SCLC were screened selectively in the retrospective study. Adverse events and patient responses were assessed using Common Terminology Criteria for Adverse Events v5.0 and Response Evaluation Criteria for Solid Tumors v1.1. The progression-free survival (PFS) was estimated using the Kaplan-Meier method or Cox survival regression model and compared using the log-rank test. Results In the platinum-resistant group, disease control rate (DCR) and median PFS (mPFS) were prolonged in the combination group versus single-agent group (DCR: 49.24% vs 24.39%, P = .004; mPFS: 3.73 vs 1.90 months, P

To investigate the predictive role of the neutrophil-platelet ratio (NPR) before intravenous thrombolysis (IVT) on hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS). AIS patients treated with IVT without endovascular therapy between June 2019 and February 2023 were included. Patients were divided into high NPR (>35) and low NPR (≤35) groups according to the optimal threshold NPR value for identifying high-risk patients before IVT. The baseline data and the incidence of HT and symptomatic intracranial hemorrhage (sICH) were compared between the two groups. The predictive role of the NPR and other related factors on HT after IVT was analyzed by multivariate logistic regression. A total of 247 patients were included, with an average age of 67.5 ± 12.4 years. Post-thrombolytic HT was observed in 18.6% of the patients, and post-thrombolytic sICH was observed in 1.2% of the patients. There were 69 patients in the high NPR group and 178 patients in the low NPR group. The incidence of HT in the high NPR group was significantly higher than that in the low NPR group (30.4% vs 16.3%, P 35 was positively correlated with HT (odds ratio (OR) = 3.236, 95% confidence interval (CI): 1.481-7.068, P = .003) and sICH (OR = 13.644, 95% CI: 2.392-77.833, P = .003). A high NPR (>35) before IVT may be a predictor of HT in AIS patients. This finding may help clinicians make clinical decisions before IVT in AIS patients.

Summary: Background: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. Methods: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human–AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. Findings: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969–0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738–0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497–0·554) and 0·799 (0·778–0·822), respectively. In the human–AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383–0·633) and 0·800 (0·700–0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345–0·411) and top-3 accuracy by 13·0% (0·545–0·616). Interpretation: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. Funding: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Since the 1990s, researchers have been seeking approaches for applying artificial intelligence (AI) to prenatal ultrasound. With the breakthrough of cloud computing technology and the development of deep learning technology, AI in prenatal ultrasound has already entered the clinical application stage in recent years. How does AI combine with clinical prenatal ultrasound? Is the clinical application of AI in prenatal ultrasound effective? What can we expect from AI in prenatal ultrasound? This review introduces the latest developments in this field and explores the challenges and opportunities brought by AI to prenatal ultrasound.

In 2023, the capabilities of text communication, language translation, image generation, and code writing demonstrated by ChatGPT and GPT-4 have received widespread attention in and out of China. With years of data and technology accumulation, many Chinese companies and research teams continue to make efforts in the field of large models, and their models cover many industries and have a number of characteristic functions. This paper will introduce the type and development trends of large models, and sort out the methods and characteristics of domestic large models. Finally, we will explain the advantages and disadvantages of the domestic models, and analyze the application prospect and challenges of them in the medical field.

Background/Objective: Large amount of protein wasting such as in nephrotic syndrome is a rare cause of high levothyroxine (LT4) replacement dose requirement. A case has been reported here that demonstrates that protein-losing enteropathy is a novel and yet unrecognized cause of high LT4 replacement dose requirement. Case Report: A 21-year-old man with congenital heart disease was found to have primary hypothyroidism and started LT4 replacement. His weight was approximately 60 kg. Nine months later, while he was taking LT4 100 μg daily, thyroid-stimulating hormone (TSH) level was >200 μIU/mL (normal range, 0.3-4.7 μIU/mL) and free thyroxine level was 0.3 ng/dL (normal range, 0.8-1.7 ng/dL). The patient had excellent medication compliance. LT4 dose was increased to 200 μg daily and then 200 and 300 μg every other day. Two months later, TSH level was 3.1 μIU/mL and free thyroxine level was 1.1 ng/dL. He did not exhibit malabsorption or proteinuria. His albumin levels had been low since the age of 18 years (mostly