bluuebunny/crossref_metadata_2025 huggingface dataset:
Patienten-Arzt-Interaktion: Effektive Gesprächsführung bei fortgeschrittenen Krebserkrankungen
Authors: Witt Claudia M.
Published: October 2023

Importance: There are few robust evaluations of disease-specific question prompt sheets (QPS) in patient-physician communication among patients with advanced cancer. Objective: To compare the patient perception of helpfulness, global evaluation, and preference for the QPS vs a general information sheet (GIS), and to examine the effect of the QPS on participants’ anxiety, participants’ speaking time, number of questions asked, and length of the clinical encounter. Design: , setting, and participants: This controlled, double-blind randomized clinical trial was conducted at an outpatient palliative and supportive care clinic in a cancer center in the US. Eligible patients were 18 years or older, had a cancer diagnosis, and were undergoing their first outpatient consultation visit with a palliative care physician from September 1, 2017, to May 31, 2019. Data analysis used a modified intention-to-treat design. Data were analyzed from May 18 to June 27, 2022. Intervention: QPS, a 25-item list of questions developed by expert palliative care clinicians using a Delphi process and tested among ambulatory advanced cancer patients. The control was GIS, generic information material given routinely to patients seen at the supportive care clinic. Main outcomes and measures: The main outcome was patient perception of helpfulness. Secondary outcomes included global evaluation and preference of QPS compared with GIS immediately after the encounter. Results: A total of 130 patients (mean [SD] age, 58.6 [13.3] years; 79 [60.8%] female) were randomized to receive either QPS (67 patients [51.5%]) or GIS (63 patients [48.5%]). Patients considered QPS and GIS equally helpful, with no statistically significant difference (mean [SD] helpfulness score, 7.2 [2.3] points vs 7.1 [2.7] points; P = .79). The QPS group, compared with the GIS group, had a higher global positive view of the material (mean [SD] global perception score, 7.1 [1.3] vs 6.5 [1.7]; P = .03) and felt it prompted them more to generate new questions (mean [SD] rating, 7.0 [2.9] vs 5.3 [3.5]; P = .005). Of 47 patients asked their preference between the items, more participants preferred the QPS to the GIS in communicating with their physicians (24 patients [51.1%] vs 7 patients [14.9%]; P = .01) at the 4-week follow-up. No significant differences between the QPS and GIS groups were observed regarding participant anxiety, speaking time, number of questions asked, or consultation length (eg, mean [SD] anxiety rating, 2.3 [3.7] vs 1.6 [2.7]; P = .19). Conclusions: and relevance: In this randomized clinical trial, participants perceived both QPS and GIS as equally helpful, but they had a more positive global view of and preferred the QPS. QPS facilitated generation of new questions without increasing patient anxiety nor prolonging the consultation. The findings provide support for increased adoption and integration of QPS into routine oncologic care.
Long-Term 5-Year Response to Pembrolizumab, Bevacizumab, and Capecitabine Regimen in a Metastatic Colon Cancer Patient with MSI-High and KRAS Mutation: Case Report
Authors: Julka Pramod Kumar , Arya Deepika , Gupta Kush
Published: October 2023

With an estimated 1.88 million new cases and 0.92 million deaths in 2020, colorectal cancer accounts for nearly one-tenth of all new cancer and cancer-related deaths worldwide. Nearly half of the patients of colorectal cancer are diagnosed with metastatic or inoperable disease with a very dismal 5-year survival rate. Chemotherapy, targeted therapy, and immunotherapy have been used to treat metastatic disease, either alone or in combination. We present a case of recurrent metastatic colon carcinoma with KRAS exon 2 mutation and high microsatellite instability that was treated with a combination regimen of bevacizumab, capecitabine oral chemotherapy, and pembrolizumab immunotherapy. At nearly 5 years of treatment, the patient is alive with good performance status and improved quality of life owing to a favorable response to the molecular profiling-based treatment approach.
The Role of Hepatobiliary Scintigraphy as the Initial Investigative Modality for Significant Bile Leak following Laparoscopic Cholecystectomy
Authors: Bickel Amitai , Lagrissi Ron , Jerushalmi Jacqueline , Sbeit Wisam , Weiss Michael , Shiller Moshe , Ganam Samer , Kakiashvili Eli
Published: October 2023

Introduction: Currently, the rate of bile duct injury and leak following laparoscopic cholecystectomy (LC) is still higher than for open surgery. Diverse investigative algorithms were suggested for bile leak, shifting from hepatobiliary scintigraphy (HBS) toward invasive and more sophisticated means. We aimed to analyze the use of biliary scan as the initial modality to investigate significant bile leak in the drain following LC, attempting to avoid potential unnecessary invasive means when the scan demonstrate fair passage of nuclear substance to the intestine, without leak. Methods: We have conducted a prospective non-randomized study, mandating hepatobiliary scintigraphy first, for asymptomatic patients harboring drain in the gallbladder fossa, leaking more than 50 mL/day following LC. Analysis was done based on medical data from the surgical, gastroenterology, and the nuclear medicine departments. Results: Among 3,124 patients undergoing LC, significant bile leak in the drain was seen in 67 subjects, of whom we started with HBS in 50 patients, presenting our study group. In 27 of whom, biliary scan was the only investigative modality, showing fair passage of the nuclear isotope to the duodenum and absence of leak in the majority. The leak stopped spontaneously within a mean of 3.6 days, and convalescence as well as outpatient clinic follow-up was uneventful. In 23 patients, biliary scan that was interpreted as abnormal was followed by endoscopic retrograde cholangio-pancreatography (ERCP). However, ERCP did not demonstrate any bile leak in 13 subjects. In 17 patients, ERCP was used initially, without biliary scan, suggesting the possibility of avoiding invasive modalities in 7 patients. Conclusions: Based on a negative predictive value of 91%, we suggest that in cases of asymptomatic significant bile leak through a drain following LC, a normal HBS as the initial modality can safely decrease the rate of using invasive modalities.
Effectiveness Treatment of a BRAF-ZKSCAN5 Fusion Gene Melanoma Case with Dabrafenib/Trametinib
Authors: Kato Hiroshi , Kano Shinji , Yasui Yukiko , Nojiri Yuka , Yoshimitsu Maki , Nakamura Motoki , Morita Akimichi
Published: October 2023

The most important driver gene in malignant melanoma is the BRAF mutation, and molecularly targeted therapies targeting mutations, mainly V600E and V600k, are used in clinical practice. In this report, we treated a patient with malignant melanoma expressing a rare BRAF-ZKSCAN5 fusion gene with dabrafenib/trametinib. The patient was a 71-year-old female. She was diagnosed with malignant melanoma (pT4aN3M0, STAGE IIIC) of the abdomen with axillary lymph node metastasis. She underwent extended resection and axillary lymph node dissection and was treated with adjuvant therapy, but lung and mediastinal lymph node metastases developed. The patient was treated with immune checkpoint inhibitors for metastatic lesions and achieved complete remission, but relapsed and metastatic lesions appeared in the cervical lymph nodes. Next-generation sequencing revealed the BRAF-ZKSCAN5 fusion gene, and treatment with dabrafenib/trametinib was initiated. After 1 month of treatment, tumor growth stopped and the length of the tumor shrank by 22.2%, but she developed grade 3 adverse events of nausea, fatigue, and diarrhea and had difficulty exercising, forcing her to discontinue treatment after 6 weeks. The tumor continued to shrink during drug administration. This case report may provide insight into treatment options for cases in which the BRAF fusion gene was observed, which is expected to be detected in large numbers by next-generation sequencing in the future.
Large Retroperitoneal Teratoma Presenting with Unilateral Hydronephrosis in an Infant: A Case Report and Review of the Literature
Authors: Safaei Negar , Kamran Hooman , Anbardar Mohammad Hossein , Bordbar Mohammadreza , Zekavat Omid Reza , Forooghi Mehdi
Published: October 2023

Teratoma is a type of germ cell tumor layer that appears in the gonadal, sacrococcygeal, mediastinal, and retroperitoneal regions. Primary retroperitoneal teratoma is rare and asymptomatic but can present with symptoms due to a mass effect on neighboring organs. These tumors have to be considered in the differential diagnosis of a mass in the abdominal cavity of children to distinguish between Wilms’ tumor, neuroblastoma, and other intra-abdominal lesions. We presented an infant boy with protrusion of the left upper quadrant of the abdomen and a palpable abdominal mass that had progressively enlarged. An abdominal computed tomography scan revealed a large retroperitoneal cystic, solid mass on the left side of the abdominal cavity, causing pressure on the left ureter. Also, hydronephrosis of the left kidney was seen with a decreased enhancement of the left kidney due to obstruction uropathy. The mass was suspicious on imaging for a retroperitoneal teratoma. The patient underwent laparotomy, and excision of the huge retroperitoneal mass was done. The final diagnosis was an immature teratoma grade 3, and the patient was discharged in good condition. Retroperitoneal teratomas are rare tumors in infants. These tumors would be an incident diagnosis or diagnosed by the mass effect of giant tumors on other organs. They must be considered in the differential diagnosis of intra-abdominal tumors in children. Hydronephrosis and obstructive uropathy can be rare consequences of the mass effects of these tumors.
Transcirculation Approach for Matricidal Carotid Cavernous Aneurysm: Not a Good Choice – A Case Report of Unsuccessful Endovascular Treatment of Matricidal Carotid Cavernous Aneurysm
Authors: Svoboda Norbert , Malik Jozef , Charvat Frantisek , Netuka David
Published: October 2023

Matricidal carotid cavernous aneurysm (CCA) is a rare and dangerous condition. The treatment failure of the endovascular approach like flow diversion, coiling, or stent-coiling is relatively high with considerable morbidity and mortality. The transcirculation approach is an alternative treatment option, but in case of matricidal CCAs, the results are not well documented in the literature. The authors present a complicated case of an unsuccessful transcirculation approach for matricidal CCA finally treated with sacrifice of the parent artery and high-flow bypass.
Tele-Assessment of Oral Personal Narratives in Arabic- and Hebrew-Speaking Children Using the Global TALES Protocol
Authors: Ferman Sara , Kawar Khaloob
Published: October 2023

Introduction: Tele-assessment (TA) has the potential to enhance access to speech therapy. This preliminary study aimed to investigate the impact of assessment mode (face-to-face [FTF] vs. TA) on the microstructure level and chosen topics of personal narratives produced by Arabic-speaking and Hebrew-speaking school-age children living in Israel. We also investigated whether performance variations, if evident, could be attributed to the children’s language/culture. Methods: Eighty-nine 10-year-old children, 38 Arabic-speaking and 51 Hebrew-speaking, living in Israel, participated in this study. Forty participants were assigned to a TA group (via Zoom) and 49 to a FTF group. All participants were assessed using the Global TALES protocol, generating six personal narratives each. The narratives were analyzed regarding the following microstructural measures: total number of words, total number of utterances (TNU), number of different words, and mean length of utterance in words (MLU-W). Additionally, each narrative was categorized into a topic according to the Global TALES protocol. Results: The analysis revealed no significant main effect of assessment mode on any of the microstructure measures. However, a significant interaction effect between language/culture and assessment mode was found for TNU and MLU-W, with a significant main effect for TNU exclusively in the Arabic narratives, with the Arabic-speaking children producing more utterances through FTF compared to TA. Across language/culture groups, there was a significant effect of assessment mode on the chosen topic. Additionally, there were significantly higher scores in the Hebrew compared to the Arabic narratives in all microstructure measures, and language/culture also influenced the chosen topics. Conclusions: The results support the feasibility of TA mode for assessing personal narratives in school-aged children, using the Global TALES protocol. However, the results also suggest that TA results may be affected by the language/culture of the narrator. Finally, the findings highlight the potential influence of TA on the chosen topics of personal narratives, perhaps due to a decrease in the quality of communication in TA.
Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis
Authors: Aiba Takayuki , Hijiya Naoki , Akagi Tomonori , Tsukamoto Yoshiyuki , Hirashita Yuka , Kinoshita Keisuke , Uchida Tomohisa , Nakada Chisato , Kurogi Shusaku , Ueda Yoshitake , Shiroshita Hidefumi , Shiraishi Norio , Murakami Kazunari , Inomata Masafumi , Moriyama Masatsugu
Published: October 2023

Introduction: We have previously reported that overexpression of visinin-like protein 1 (VSNL1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis. Methods: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis, and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT-116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT-116 were identified using transcriptome and gene set enrichment analyses. Results: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT-116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT-116 cells. Conclusion: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.
Use of Sotrovimab for COVID-19 in a Patient with International Germ Cell Consensus Classification Poor Prognosis Testicular Germ Cell Tumor
Authors: Nagasaka Hirotaka , Takebe Shinichi , Yamamoto Shotaro , Kondo Takuya , Terao Hideyuki , Nakaigawa Noboru , Kishida Takeshi
Published: October 2023

A 35-year-old man was diagnosed with stage IIIC non-seminoma with paralysis of the lower half of his body due to 8th thoracic spine metastasis. The patient received bleomycin, etoposide, and cisplatin (BEP) therapy. On day 4 of the second course of BEP, the patient developed a fever and was diagnosed with coronavirus disease (COVID-19). COVID-19 was suspected to worsen because of cancer and chemotherapy-induced immunosuppression. However, the benefits of continuing BEP therapy outweighed these risks. After obtaining fully informed consent, BEP therapy was continued from day 5, while sotrovimab (anti-COVID-19 drug) was administered. The second course of BEP was completed without worsening severe COVID-19 or bleomycin-induced lung injury. The patient completed four courses of BEP, with normalization of tumor markers, partial response on imaging, and improvement in lower body paralysis. In this case, we successfully treated a patient with testicular germ cell tumor with chemotherapy while having COVID-19 without treatment delay. During the COVID-19 pandemic, concomitant chemotherapy and COVID-19 treatment are warranted because delaying treatment will decrease the efficacy of highly curative diseases such as germ cell tumors.
Etelcalcetide Inhibits the Progression of Left Atrial Volume Index Compared to Alfacalcidol in Hemodialysis Patients
Authors: Dörr Katharina , Reindl-Schwaighofer Roman , Lorenz Matthias , Marculescu Rodrig , Beitzke Dietrich , Hödlmoser Sebastian
Published: October 2023

Introduction: Increased left atrial (LA) size is a risk factor for cardiovascular events and all-cause mortality. It is closely related to left ventricular hypertrophy and chronic volume overload, both of which are common in hemodialysis. Calcimimetic treatment with etelcalcetide (ETL) previously showed an inhibitory effect on left ventricular mass index (LVMI) progression in this population. Methods: This is a post hoc analysis of the EtECAR-HD trial, where 62 patients were randomized to ETL or alfacalcidol (ALFA) for 1 year. LA volume index (LAVI) was measured using cardiac magnetic resonance imaging. The aim of the study was to investigate whether ETL was associated with a change of LAVI. Results: Median baseline levels of LAVI were 40 mL/m2 (31, 54 IQR) in the ETL group and 36 mL/m2 (26, 46 IQR) in the ALFA group. In the ITT population, the change of LAVI was 5.0 mL/m2 [95% CI: −0.04, 10] lower under ETL, compared to ALFA (p = 0.052, R2adj = 0.259). In the PP population, the difference in LAVI changes widened to 5.8 [95% CI: 0.36, 11], p = 0.037, R2adj = 0.302). Secondary analysis showed that the study delta of LVMI was correlated with the LAVI delta (r = 0.387) and that an inclusion of LVMI delta in the ANCOVA model mediated the effect on LAVI delta to β = 3.3 [95% CI: −0.04, 10] (p = 0.2, R2adj = 0.323). The same could not be observed for parameters assessing the volume status. Conclusions: The analysis indicates that ETL could inhibit LAVI progression compared with ALFA. This effect was mediated by the change of LVMI.
The Evolution and Visual Prognosis of Glial Proliferation with Different Grades after Macular Hole Surgery: An Optical Coherence Tomography-Based Study
Authors: Qi Biying , Yu Yanping , Yang Xiaohan , Zhang Ke , Wu Xijin , Wang Xinbo , Feng Xiao , Jia Qinlang , Jin Zi-Bing , Liu Wu
Published: October 2023

Introduction: The glial proliferation after macular hole (MH) surgery was divided into two types previously: those replacing the entire intraretinal layer and those involving only the inner foveal layers. The evolution and prognosis of the former type were elaborated on in previous studies, but the latter one has received limited attention. Therefore, this study aims to investigate the evolution of glial proliferation with varying grades after MH surgery and its effects on foveal microstructure and best-corrected visual acuity (BCVA). Methods: In this retrospective research, we reviewed 202 eyes from 196 consecutive patients who underwent a successful idiopathic MHs repair. Based on optical coherence tomography images, glial proliferation was classified into three types: A-type, which replaced the entire intraretinal layer; B-type, located at the level of and above the external limiting membrane (ELM); and C-type, situated above the ELM. Results: Of the 67 eyes that attended the 1-, 4-, and 10-month follow-up, A-type, B-type, C-type, and no glial proliferation were identified in 27 (40.3%), 17 (25.4%), 20 (29.8%), and 3 eyes (4.5%), respectively, at 1 month. Within 10 months, the prevalence of A-type glial proliferation significantly decreased (p < 0.001), but the changes in B-type (p = 0.261), C-type (p = 0.151), and no glial proliferation (p = 0.492) were not significant. In 32 of the 67 eyes, the grade of glial proliferation gradually improved, with A-type transforming into B- or C-type in 19 of 27 eyes (70.4%), B-type into C-type or no glial proliferation in 11 out of 17 eyes (64.7%), and C-type gradually disappearing in 2 out of 20 eyes (10.0%). Among the eyes that attended at least one follow-up (1 M, 202 eyes; 4 M, 161 eyes; 10 M, 97 eyes), those with A-type glial proliferation showed the most defective outer retinal layers, worst BCVA, and thinnest central fovea compared with the other two types at all follow-up time points (p < 0.001). Eyes with C-type glial proliferation exhibited significantly better photoreceptor layer status and BCVA compared with those with B-type glial proliferation. A-type glial proliferation at 1 month, which showed significant association with BCVA at 10 months, could be accurately predicted by the minimum linear diameter with a cut-off >547.5 μm (p < 0.001). Conclusion: Within 10 months, A-type glial proliferation substantially resolves but the prevalence of B- and C-type remains unchanged. B-type glial proliferation hinders the restoration of photoreceptors and impairs visual recovery despite being located within the inner retina.
Objective Response and Progression-Free Survival Contribute to Prolong Overall Survival in Atezolizumab plus Bevacizumab Treatment for Unresectable Hepatocellular Carcinoma
Authors: Tajiri Kazuto , Tsukada Kenichiro , Tokimitsu Yoshiharu , Motofuji Yuchi , Kawai Kengo , Muraishi Nozomu , Murayama Aiko , Hayashi Yuka , Shimizu Yukihiro , Yasuda Ichiro
Published: October 2023

Introduction: Atezolizumab plus bevacizumab (Atez/Bev) is a standard treatment for unresectable hepatocellular carcinoma (HCC) due to its good antitumor and survival prolongation effects. Post-progression survival (PPS) has been reported to be a great contributor in the treatment with tyrosine kinase inhibitors for unresectable HCC. This study aimed to clarify the significance of progression-free survival (PFS) or PPS of Atez/Bev treatment for HCC. Methods: We analyzed the correlations of PFS and PPS with overall survival (OS) in studies of HCC patients treated with Atez/Bev and evaluated the contribution to OS in Atez/Bev treatment with patients at our institutions as clinical practice. Results: Analysis of 18 studies involving 3,752 patients treated with Atez/Bev found that PPS had a stronger correlation with OS (R2 = 0.872, p < 0.001) than did PFS (R2 = 0.605, p = 0.001). Analysis of 80 patients with unresectable HCC treated with Atez/Bev found that presence of antitumor responses during Atez/Bev was the most significant contributor to OS, and post-progression treatment after Atez/Bev also significantly contribute to OS. Conclusion: The presence of antitumor response with tumor shrinkage during Atez/Bev treatment contributes to good OS through its durable response. Atez/Bev treatment could be considered as first-line treatment for unresectable HCC. However, there is a need for optimal biomarkers for good antitumor response.
Desmoid Tumor after Sleeve Gastrectomy: Case Report and Literature Review
Authors: Medas Renato , Coelho Rosa , Bessa-Melo Renato , Pereira Pedro , Macedo Guilherme
Published: October 2023

Desmoid tumor is a rare mesenchymal neoplasm of unknown etiology. Despite rare, the diagnosis of desmoid tumors after bariatric surgery is increased over the last few years. We report a case of a 26-year-old male with complains of abdominal pain and postprandial fullness, diagnosed with a locally advanced large intra-abdominal mass (40 × 21 × 11.7 cm) centered in the mesentery, developed 3 years after sleeve gastrectomy. Percutaneous biopsy was suggestive of a mesenquimatous tumor and the patient underwent surgery. R0 surgical resection was achieved, despite intimal contact and common vascularization with a jejunal loop. Histopathology examination of the surgical specimen revealed fusiform to stellate cells with mild atypia, thin-walled vessels, and diffuse beta-catenin expression (negative for DOG-1, CD117, CD34, S100, desmin, and alpha-actin). The diagnosis of a desmoid tumor was made. The patient remained asymptomatic, and no recurrence occurred over a 4-year follow-up. With the increasing number of bariatric surgeries, owing to the alarming growing incidence of obesity and related conditions, it is expected that desmoid tumors reports will gradually increase over the next few years. Thus, both gastroenterologists and surgeons should be aware of the potential for desmoid tumor development shortly after surgery, to offer a prompt diagnosis and treatment.
Ube2L6 Promotes M1 Macrophage Polarization in High-Fat Diet-Fed Obese Mice via ISGylation of STAT1 to Trigger STAT1 Activation
Authors: Li Yunqian , Dong Xiao , He Wenqian , Quan Huibiao , Chen Kaining , Cen Chaoping , Wei Weiping
Published: October 2023

Introduction: In obesity-related type 2 diabetes mellitus (T2DM), M1 macrophages aggravate chronic inflammation and insulin resistance. ISG15-conjugation enzyme E2L6 (Ube2L6) has been demonstrated as a promoter of obesity and insulin resistance. This study investigated the function and mechanism of Ube2L6 in M1 macrophage polarization in obesity. Methods: Obesity was induced in Ube2L6AKO mice and age-matched Ube2L6flox/flox control mice by high-fat diet (HFD). Stromal vascular cells were isolated from the epididymal white adipose tissue of mice. Polarization induction was performed in mouse bone marrow-derived macrophages (BMDMs) by exposure to IFN-γ, lipopolysaccharide, or IL-4. F4/80 expression was assessed by immunohistochemistry staining. Expressions of M1/M2 macrophage markers and target molecules were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. Protein interaction was validated by co-immunoprecipitation (Co-IP) assay. The release of TNF-α and IL-10 was detected by ELISA. Results: The polarization of pro-inflammatory M1 macrophages together with an increase in macrophage infiltration was observed in HFD-fed mice, which could be restrained by Ube2L6 knockdown. Additionally, Ube2L6 deficiency triggered the repolarization of BMDMs from M1 to M2 phenotypes. Mechanistically, Ube2L6 promoted the expression and activation of signal transducer and activator of transcription 1 (STAT1) through interferon-stimulated gene 15 (ISG15)-mediated ISGlylation, resulting in M1 macrophage polarization. Conclusion: Ube2L6 exerts as an activator of STAT1 via post-translational modification of STAT1 by ISG15, thereby triggering M1 macrophage polarization in HFD-fed obese mice. Overall, targeting Ube2L6 may represent an effective therapeutic strategy for ameliorating obesity-related T2DM.
Novel Utility of Leucine-Rich Alpha-2-Glycoprotein as a Biomarker in Ulcerative Colitis: A Predictor of Endoscopic Remission Independent of Symptoms
Authors: Hayashi Tomoyuki , Kitamura Kazuya , Usami Masaaki , Miyazawa Masaki , Nishitani Masaki , Dejima Akihiro , Yamamoto Makoto , Kawase Shotaro , Funaki Masaya , Orita Noriaki , Nakagawa Hidetoshi , Morita Koki , Iida Noriho , Seki Akihiro , Nio Kouki , Kido Hidenori , Takayama Hideo , Takeuchi Yuta , Yamada Shinya , Takatori Hajime , Shimada Mari , Saito Hiroto , Yamamoto Daisuke , Toyama Tadashi , Yamashita Taro
Published: October 2023

Introduction: Leucine-rich alpha-2-glycoprotein (LRG) is a potential biomarker for disease activity and reflects mucosal healing in patients with ulcerative colitis (UC). However, only a few studies have described a detailed sensitivity analysis of LRG in predicting mucosal healing in patients. This study aimed to evaluate the association between LRG and the endoscopic activity of UC and its predictability for mucosal healing and explore the utility and clinical application of LRG. Methods: The diagnostic accuracy of biomarkers, including LRG, in predicting the endoscopic activity of UC was evaluated. All consecutive patients who underwent total colonoscopy between April 2021 and September 2022 were included. The Mayo endoscopic subscore (MES) was used for assessing endoscopic activity. Furthermore, endoscopic remission was defined as an MES of ≤1. Clinical activity was evaluated based on stool frequency and bloody stool. Receiver operating characteristic curve analysis and binary logistic regression were performed to assess the diagnostic accuracy of the biomarkers. We evaluated LRG trends and treatment response in patients with MES ≥2 who underwent induction therapy. Results: This study comprised 214 patients. The proportions of endoscopically and clinically active patients were 33.6% and 49.1%, respectively. LRG had an area under the curve (AUC) of 0.856, with a higher diagnostic accuracy than other biomarkers, such as C-reactive protein, leukocyte, neutrophil, platelet, and albumin. The cutoff value for LRG was 15.6 μg/mL (sensitivity, 72.2%; specificity, 86.6%). Using the MES, patients with higher scores had higher LRG levels than those with lower scores. The cutoff value, AUC, sensitivity, and specificity varied with a higher AUC for left-sided colitis and pancolitis than for proctitis. Logistic regression analysis showed that LRG was an independent predictor of endoscopic remission using multivariate analysis, even with the factor of clinical activity. The change ratio of LRG pre- and post-treatment was statistically significant in the higher LRG group. Conclusion: LRG reflected endoscopic activity independently, regardless of clinical symptoms. An LRG below the cutoff value could indicate a significantly low probability of endoscopic activity in asymptomatic patients, and follow-up endoscopy (not for cancer screening) may be unnecessary. Furthermore, a higher LRG level might be more useful as an indicator of treatment efficacy.
Chemical and Biological Characterization of Mycobacterium tuberculosis-Specific ESAT6-Like Proteins and Their Potentials in the Prevention of Tuberculosis and Asthma
Authors: Mustafa Abu Salim
Published: October 2023

Early Secreted Antigenic Target 6 kDa (ESAT6) is a potent immunogenic protein secreted by the bacteria causing tuberculosis, i.e., Mycobacterium tuberculosis. Another highly immunogenic culture filtrate protein whose gene is linked to ESAT6/ESXA is known as CFP10/ESXB. Because of their high immunogenicity and specificity to M. tuberculosis, these proteins have been proposed as a vaccine to prevent tuberculosis and diagnose the active/latent disease. However, the same proteins cannot be used for prevention and diagnosis because immunized but healthy people will also show a positive response and be falsely reported as diseased. Therefore, in this review article, the search was made to identify if any other ESAT6-like proteins exist in the M. tuberculosis genome. The search identified 21 additional ESAT-like proteins, i.e., ESXC to ESXW. Immunological characterization has shown that some of them (especially ESXV) were able to induce immune responses in vitro with cells obtained from tuberculosis patients and healthy donors. When the protein ESXV was tested in different recombinant forms (expressed in Escherichia coli, mycobacterial vectors, and DNA plasmids) and injected in mice, immune responses were induced to multiple epitopes of the protein. Furthermore, immunization of mice with ESXV protected them from infection with M. tuberculosis. The same protein was also able to protect mice against the induction of asthma. These results suggest that ESXV has the potential to protect against two major diseases in the world, i.e., tuberculosis and asthma, and hence may be used as a common vaccine for both diseases.
Hippocampal Dynamic Functional Connectivity, HPA Axis Activity, and Personality Trait in Bipolar Disorder with Suicidal Attempt
Authors: Zhong Shuming , Chen Pan , Lai Shunkai , Zhang Yiliang , Chen Guanmao , He Jiali , Pan Youling , Tang Guixian , Wang Ying , Jia Yanbin
Published: October 2023

Introduction: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. Methods: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.
Relation between WHO Classification and Location- and Functionality-Based Classifications of Neuroendocrine Neoplasms of the Digestive Tract
Authors: Helderman Noah C. , Suerink Manon , Kilinç Gül , van den Berg José G. , Nielsen Maartje , Tesselaar Margot E.T.
Published: October 2023

Practice of neuroendocrine neoplasms (NENs) of the digestive tract, which comprise of a highly diverse group of tumors with a rising incidence, faces multiple biological, diagnostic, and therapeutic issues. Part of these issues is due to misuse and misinterpretation of the classification and terminology of NENs of the digestive tract, which make it increasingly challenging to evaluate and compare the literature. For instance, grade 3 neuroendocrine tumors (NETs) are frequently referred to as neuroendocrine carcinomas (NECs) and vice versa, while NECs are, by definition, high grade and therefore constitute a separate entity from NETs. Moreover, the term NET is regularly misused to describe NENs in general, and NETs are frequently referred to as benign, while they should always be considered malignancies as they do have metastatic potential. To prevent misconceptions in future NEN-related research, we reviewed the most recent terminology used to classify NENs of the digestive tract and created an overview that combines the classification of these NENs according to the World Health Organization (WHO) with location- and functionality-based classifications. This overview may help clinicians and researchers in understanding the current literature and could serve as a guide in the clinic as well as for writing future studies on NENs of the digestive tract. In this way, we aim for the universal use of terminology, thereby providing an efficient foundation for future NEN-related research.
Plasma MicroRNAs Related to Metabolic Syndrome in Mexican Women
Authors: Ramírez-Solano Marisol Adelina , Córdova Emilio J. , Orozco Lorena , Tejero María Elizabeth
Published: October 2023

Introduction: The metabolic syndrome (MetS) is a cluster of abnormalities related to cardiovascular disease (CVD). Circulating miRNAs (c-miRNAs) are non-coding RNAs associated with different phenotypes, some of them integrating the MetS. The aim of the study was to compare the c-miRNAs profile in plasma between women with MetS and controls and explore their possible association with dysregulation of metabolic pathways. Methods: The study was conducted in two phases. At the screening phase, miRNA composition in fasting plasma was compared between 8 participants with MetS and 10 healthy controls, using microarray technology. The validation phase included the analysis by qRT-PCR of 10 selected c-miRNAs in an independent sample (n = 29). Results: We found 21 c-miRNAs differentially expressed between cases and controls. The concentration in plasma of the c-miRNAs hsa-miR-1260a, hsa-miR-4514, and hsa-miR-4687-5p were also correlated with risk factors for CVD. Differences of hsa-miR-1260a between cases and controls were validated using qRT-PCR (fold-change = 7.0; p = 0.003). Conclusion: The signature of plasma c-miRNAs differed between women with MetS and controls. The identified miRNAs regulate pathways related to the MetS such as insulin resistance and adipokine activity. The role of c-miR-1260a in the MetS remains to be elucidated.
Clinicopathologic Characteristics of PANDAS in a Young Adult: A Case Report
Authors: Kulumani Mahadevan Lakshmi Shree , Murphy Melissa , Selenica Marina , Latimer Elizabeth , Harris Brent T.
Published: October 2023

Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is an acute onset or exacerbation of neuropsychiatric symptoms following a group A streptococcus infection. It is believed to be a result of autoimmune response to streptococcal infection, but there is insufficient evidence to fully support this theory. Although this disease is primarily thought to be a disease of childhood, it is reported to occur also in adults. PANDAS is a well-defined clinical entity, but the neuropathology of this condition has not been established yet. We describe the clinical course of a 26-year-old female diagnosed with PANDAS. She committed suicide and her brain was biobanked for further studies. We examined the banked tissue and performed special stains, immunohistochemical, and immunofluorescence analyses to characterize the neuropathology of this condition. Histology of the temporal lobes, hippocampus, and basal ganglia shows mild gliosis and Alzheimer’s type II astrocytes. Acute hypoxic ischemic changes were noted in hippocampus CA1 and CA2 areas. Immunostaining shows increased parenchymal/perivascular GFAP staining and many vessels with mild increases in CD3-, CD4-, and CD25-stained lymphocytes in the basal ganglia. The findings suggest that CD4- and CD25-positive T cells might have an important role in understanding the neuroinflammation and pathogenesis of this condition. The case represents the first neuropathological evaluation report for PANDAS.
Surgical Management of Gestational Trophoblastic Disease
Authors: Coopmans Leonoor , Larsson Agnes , Joneborg Ulrika , Lok Christianne , van Trommel Nienke
Published: October 2023

Background: Gestational trophoblastic disease (GTD) is a rare pregnancy-related condition consisting of premalignant and malignant forms arising from proliferation of trophoblastic cells. The malignant forms are collectively referred to as gestational trophoblastic neoplasia (GTN) and are highly sensitive to chemotherapy. However, surgical procedures remain indispensable in the diagnosis and treatment of GTD. Objectives: The aim of this review was to summarize surgical interventions in the treatment of GTD and GTN. We reviewed indications, efficacy, possible complications, and oncological outcomes of surgery. Methods: Three searches were performed in the databases of PubMed, Embase, and the Cochrane Library to create an up-to-date overview of existing literature on the following subjects: (1) the role of primary hysterectomy in GTD and GTN; (2) the role of second curettage in GTD and GTN; (3) fertility sparing surgery in GTN; (4) surgical management of metastases. Included articles originated from the time period 1952–2022. Articles written in English, Spanish, and French were included. Outcomes: Thirty-eight articles were found and selected. Surgical evacuation through suction curettage is most used and advised in the treatment of GTD. A second curettage could be beneficial in patients with low hCG levels and low FIGO scores. In women who have completed their families, primary hysterectomy might be considered as the risk of subsequent GTN is lower than after suction curettage. In case of the rare forms of GTN (epithelioid trophoblastic tumor or placental site trophoblastic tumor) surgical tumor resection remains the most important step in treatment. Data on fertility sparing surgery in GTN are scarce and this treatment should be considered experimental. Conclusion and Outlook: Surgery remains an important part of treatment of GTD and is sometimes indispensable to achieve curation. Further collection of evidence is needed to determine treatment steps.
Moderate Intensity Exercise Reduces Side Effects of Cancer Therapy and Maintains Cardiorespiratory Fitness in Male Breast Cancer Patients: Findings from the BRECA Male Crossover Study
Authors: Schultz Eva B. , Zubac Damir , Bloch Wilhelm , Baurecht Hansjörg , Rickert Jana , Baumann Freerk T.
Published: October 2023

Introduction: There is growing evidence that aerobic exercise mitigates cancer therapy-related side effects and improves cardiorespiratory fitness (CRF). However, to the best of our knowledge, no exercise study has been conducted in male breast cancer (MBC) patients. The aim of this study was to investigate the feasibility and efficacy of different exercise intensities on CRF and self-reported questionnaire items in MBC patients. Methods: Twenty-two MBC patients (60 ± 9 years) participated in this randomized crossover study. After completion of medical treatment, MBC patients were randomly assigned to either moderate (40–50% of heart rate [HR] max. and self-perceived exertion: 11) or vigorous (70–80% of HR max. and self-perceived exertion: 15) exercise intensity during the first 3 months of the study. After a 1-month washout period, participants switched group assignments. Primary endpoints were CRF and questionnaire items. Results: We observed a dropout rate of 36% over 7 months, with the number of participants decreasing from 22 to 14. The results showed significant improvements in “Physical Function” (p = 0.037) and “Social Function” (p = 0.016) after moderate training. A non-significant improvement was also observed in “Breast Symptoms” (p = 0.095), but there was no change in “Fatigue” (p = 0.306). There were no differences observed in cardiovascular fitness (V̇O2 peak) between the treatment groups. Conclusion: This study emphasizes the effectiveness of exercise intervention for an exceedingly rare cancer, highlighting the vital role of moderate intensity aerobic exercise in mitigating treatment side effects. Despite minimal peak V̇O2 differences, both exercise protocols adequately sustain CRF. Future studies are imperative to design optimized, sex-specific rehabilitation strategies tailored to the unique requirements of MBC patients, advancing our understanding of this under explored realm.
Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib
Authors: Iavarone Massimo , Alimenti Eleonora , Tada Toshifumi , Shimose Shigeo , Suda Goki , Yoo Changhoon , Soldà Caterina , Piscaglia Fabio , Tosetti Giulia , Marra Fabio , Vivaldi Caterina , Conti Fabio , Schirripa Marta , Iwamoto Hideki , Sho Takuya , Lee So Heun , Rizzato Mario Domenico , Tonnini Matteo , Rimini Margherita , Campani Claudia , Masi Gianluca , Foschi Francesco , Bruccoleri Mariangela , Kawaguchi Takumi , Kumada Takashi , Hiraoka Atsushi , Atsukawa Masanori , Fukunishi Shinya , Ishikawa Toru , Tajiri Kazuto , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Hatanaka Takeshi , Kakizaki Satoru , Kawata Kazuhito , Tada Fujimasa , Ohama Hideko , Itokawa Norio , Okubo Tomomi , Arai Taeang , Imai Michitaka , Naganuma Atsushi , Casadei-Gardini Andrea , Lampertico Pietro
Published: October 2023

Introduction: Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib. Methods: In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy was available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence, and risk factors for the presence of EGV and high-risk EGV at baseline, as well as impact of EGV bleeding on patients’ survival. Results: 535 patients were enrolled in the study (median age: 72 years, 78% male, 63% viral etiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis [nPVT], 56% Barcelona Clinic Liver Cancer-C): 234 had EGV (44%), 70 (30%) were at high risk and 59 were on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high-risk EGV (hazard ratio: 6.94, 95% confidence interval [CI]: 2.23–21.57, p = 0.001). In these patients the 12-month risk was 17%. High-risk varices were independently associated with Child-Pugh B score (odds ratio [OR]: 2.12; 95% CI: 1.08–4.17, p = 0.03), nPVT (OR: 2.54; 95% CI: 1.40–4.61, p = 0.002), and platelets <150,000/μL (OR: 2.47; 95% CI: 1.35–4.50, p = 0.003). Conclusion: In hepatocellular carcinoma patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.
The Mediating Role of Affective States in Short-Term Effects of Activity Engagement on Working Memory in Older Age
Authors: Luo Minxia , Moulder Robert Glenn , Weber Elisa , Röcke Christina
Published: October 2023

Introduction: It has been shown that activity engagement is associated with cognitive ability in older age, but mechanisms behind the associations have rarely been examined. Following a recent study which showed short-term effects of activity engagement on working memory performance appearing 6 h later, this study examined the mediating role of affective states in this process. Methods: For 7 times per day over 2 weeks, 150 Swiss older adults (aged 65–91 years) reported their present (sociocognitive/passive leisure) activities and affective states (high-arousal positive, low-arousal positive, high-arousal negative, and low-arousal negative) and completed an ambulatory working memory task on a smartphone. Results: Multilevel vector autoregression models showed that passive leisure activities were associated with worse working memory performance 6 h later. Passive leisure activities were negatively associated with concurrent high-arousal positive affect (and high-arousal negative affect); high-arousal positive affect was negatively associated with working memory performance 6 h later. A Sobel test showed a significant mediation effect of high-arousal positive affect linking the time-lagged relationship between passive leisure activities and working memory. Additionally, sociocognitive activities were associated with better working memory performance 6 h later. Sociocognitive activities were associated with concurrent higher high- and low-arousal positive affect, which, however, were not associated with working memory performance 6 h later. Thus, a mediation related to sociocognitive activities was not found. Discussion: Passive leisure activities could influence working memory performance through high-arousal positive affect within a timeframe of several hours. Results are discussed in relation to an emotional, and possibly a neuroendocrine, pathway explaining the time-lagged effects of affective states on working memory performance.