bluuebunny/crossref_metadata_2025 huggingface dataset:
MPE beim mutierten NSCLC: Intrapleurale Applikation von Bevacizumab stellt effektive Therapie dar
Authors: Stanzel Franz
Published: July 2024

Background: Several studies have indicated that intrapleural infusion of bevacizumab is an effective treatment for non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). However, the impact of bevacizumab administered through an indwelling pleural catheter (IPC) on the prognosis of these patients is unknown. Methods: Consecutive advanced NSCLC patients with symptomatic MPE receiving an IPC alone or bevacizumab through an IPC were identified in a tertiary hospital. The patient characteristics and clinical outcomes were collected. Results: A total of 149 patients were included, and the median age was 60.3 years. Males and nonsmokers accounted for 48.3% and 65.8%, respectively. A total of 69.8% (104/149) of patients harbored actionable mutations, including 92 EGFR-activating mutations, 11 ALK fusions, and 1 ROS1 fusion. A total of 81.9% (122/149) of patients received IPC alone, and 18.1% (27/149) received bevacizumab through an IPC. The incidence of spontaneous pleurodesis during the first 6 months was greater in the bevacizumab-treated group than in the IPC-treated group in the subgroup with actionable mutations (64.3% vs. 46.9%, P = 0.28). The median overall survival (OS) in patients with actionable mutations treated with bevacizumab through an IPC was 42.2 months, which was significantly longer than the 26.7 months in patients who received an IPC alone (P = 0.045). However, the median OS did not differ between the two arms in the subgroup without actionable mutations (10.8 vs. 41.0 months, P = 0.24). No significant difference between the bevacizumab through an IPC group and the IPC group was detected in the number of participants who had adverse events, either in patients with actionable mutations (14.3% vs. 8.4%; P = 0.42) or in patients without actionable mutations (16.7% vs. 12.8%; P = 1.00).
Geriatric Assessment Scale for Optimal Management of Gastric Cancer in Older Adults Who Underwent Gastrectomy: A Systematic Review
Authors: Rodriguez-Arroyo Brenda , Caraballo Pedro , Pineda-Isaza Alejandro , Arias-Valderrama Oriana , Cleves Manuel A. , Zambrano Angela R.
Published: July 2024

Introduction: Stomach cancer is one of the most common causes of cancer worldwide, especially in the population over 65 years. The survival rate of the elderly is lower in comparison with young people, and they are underrepresented in clinical trials and research in general. The evaluation of Multidimensional Geriatric Assessment (MGA) would be key for assessing the prognosis of these patients and therefore having a more informed decision-making process when considering one of the most vulnerable populations. Methods: A search was performed in the OVID, Embase, and PubBMed databases. There was no restriction on publication time, language, or study design. Eligible studies were those that included geriatric patients with a diagnosis of nonmetastatic stomach cancer who receive oncospecific and surgical management, used Multidimensional/Comprehensive Geriatric Assessment (MGA), and which outcomes included at least overall survival, morbidity, and mortality. Results: Four studies were included, and the MGA battery was not implemented, but rather easily measurable scales such as nutritional status, functional status, cognitive and behavioral disorders, comorbidities, and polypharmacy. Some authors proposed that the assessment of overall survival is not explicit among the included studies; patients with gastric cancer and mild, moderate, severe, and total dependence had higher mortality than independent patients (39% [HR 1.39; 95% CI: 1.09–1.7], 68% [95% CI: 1.46–1.93], 187% [HR 2.87 95% CI: 2.47–3.34], and 234% [95% CI: 2.81–3.97]), respectively. The Zhou study showed an association between sarcopenia, assessed by imaging studies, and a longer hospital stay in days (16 [9] vs. 13 [6], p 0.004). The study by Pujara found that polypharmacy (OR 2.36 CI: 1.08–5.17) and weight loss greater than 10% in the past 6 months were associated with greater postoperative morbidity at 90 days (OR 2.36 CI: 1.08–5.17, OR 11.21 CI: 2.16–58.24). Conclusion: MGA was not broadly implemented. Geriatric assessment dependency appears to be a prognostic marker of survival in patients with gastric cancer. Sarcopenia appears to be an important prognostic marker for short- and long-term outcomes. Higher quality studies in this specific population are required to support the systematic use of this assessment for the choice of appropriate therapy according to the patient.
The Role of Enhanced Recovery after Surgery in Pancreaticoduodenectomy: A Systematic Review and Meta-Analysis
Authors: Liotiri Despoina , Diamantis Alexandros , Paraskeva Ismini , Brotis Alexandros , Symeonidis Dimitrios , Arnaoutoglou Eleni , Zacharoulis Dimitrios
Published: July 2024

Introduction: This study aimed to compare the safety and short-term outcomes of Enhanced Recovery After Surgery (ERAS) with standard care for patients undergoing pancreatoduodenectomy (PD) based on literature published following the first publication of ERAS guidelines for PD. Methods: Five medical databases were searched for studies that compared ERAS to standard care in adults undergoing PD. Data on postoperative complications, length of hospitalization, readmissions, and time to chemotherapy were analyzed using either a fixed- or random-effects model meta-analysis. Meta-regressions were conducted to investigate the role of operative technique, study origin, and study design. Results: Our analysis included 22 studies involving 4,043 patients. ERAS was associated with fewer complications (relative risk [RR]: 0.83; 0.75–0.91), particularly Clavien-Dindo (CD) grade 1 and 2 complications (RR: 0.82; 0.72–0.92), delayed gastric emptying (RR: 0.69; 0.52–0.93), and postoperative fistula (POPF) (RR: 0.76; 0.66–0.89), and a shorter time to chemotherapy (standardized mean difference [SMD]: −0.68; 95% CI: −0.88 to −0.48). ERAS did not affect the risk for CD grade 3 and 4 complications (RR: 1.00; 0.72–1.38), post-pancreatectomy hemorrhage (RR: 0.88; 0.67–1.14), length of stay (SMD: −0.56; 95% CI: −1.12 to 0.01), readmission (RR: 1.01; 0.84–1.21), and mortality (RR: 0.81; 0.54–1.22). The continent of origin was an effect moderator in the role of ERAS in CD grade 1 and 2 complications (p = 0.047) and POPF (p = 0.02). Conclusion: Implementing ERAS principles in PD improves surgical outcomes without compromising safety. ERAS may also accelerate time to chemotherapy, an essential issue for future research.
Lichen Planopilaris Trichoscopy in Caucasian Scalp: A Review
Authors: Orlando Gloria , Rapparini Luca , Bruni Francesca
Published: July 2024

Background: Lichen planopilaris (LPP) is a primary lymphocytic cicatricial alopecia characterized by several different patterns of permanent hair loss. Summary: Trichoscopy plays an essential role in the context of LPP, as recognizing the distinctive signs of the disease facilitates the diagnosis of all forms of lichenoid alopecia. Key Messages: This review aimed to recognizing the trichoscopic signs early on, enabling timely intervention, potentially preventing the disease from advancing to its permanent scarring stage.
Prognostic value of CAF marker expression in the intratumoral and marginal areas of soft tissue sarcoma
Authors: Umakoshi Michinobu , Kudo-Asabe Yukitsugu , Tsuchie Hiroyuki , Li Zhuo , Koyama Kei , Miyabe Ken , Yoshida Makoto , Nagasawa Hiroyuki , Nanjo Hiroshi , Okada Kyoji , Maeda Daichi , Miyakoshi Naohisa , Tanaka Masamitsu , Goto Akiteru
Published: July 2024

Introduction: The tumor microenvironment of sarcomas has not been studied in detail; in particular, little is known about cancer-associated fibroblasts (CAFs). Sarcoma cells are difficult to distinguish from CAFs, either histomorphologically or immunohistochemically.
Methods: We scored expression of individual CAF markers (fibroblast activating protein (FAP), CD10, and podoplanin) in the intratumoral and marginal areas of 133 sarcomas. We also examined the association between these markers, as well as the number of CD163-positive macrophages (i.e., tumor-associated macrophages), and clinical outcome. Results: In all cases, the log-rank test revealed that those with high marker scores and macrophage counts (except for marginal CD10+ CAFs) showed significantly worse disease-free survival (DFS). Grade 2/3 cases with high CAF scores (excluding the marginal FAP and CD10 scores) showed significantly worse DFS, whereas those with high intratumoral FAP/CD10 and marginal podoplanin scores showed significantly worse metastasis-free survival (MFS), and those with a high intratumoral CD10 score showed significantly worse local recurrence-free survival (LFS). Multivariate analysis identified intratumoral CD10/podoplanin scores and marginal FAP/podoplanin scores as independent prognostic factors for DFS, intratumoral FAP/CD10 and marginal FAP/podoplanin/CD163-positive macrophage scores as independent prognostic factors for MFS, and the intratumoral podoplanin score as an independent prognostic factor for LFS. There was a weak-to-moderate correlation between each score and CD163-positive macrophage counts. Conclusion: Patients with high CAF marker expression in the intratumoral and marginal areas have a poorer outcome.
Asthma bronchiale bei Kindern und Jugendlichen: Therapieadhärenz und Inhalationstechnik beeinflussen das klinische Outcome
Authors: Jorczyk Maximilian
Published: July 2024

Introduction: We aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroid-based maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma. Methods: Participants (6-14 years old) from the ARCA (Asthma Research in Children and Adolescents) cohort-a prospective, multicenter, observational study (NCT04480242)-were followed for a period from 6 months to 5 years via computer-assisted telephone interviews and a smartphone application. The Medication Intake Survey-Asthma (MIS-A) was administered to assess the implementation stage of adherence, and the Inhalation Technique Questionnaire (InTeQ) was used to assess the five key steps when using an inhaler. Symptom control was measured with the Asthma Control Questionnaire (ACQ), and HRQL was measured with the EQ-5D and the Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale (PROMIS-PAIS). Multilevel longitudinal mixed models were constructed separately with symptom control, exacerbation occurrence, EQ-5D, and PROMIS-PAIS as the dependent variables. Results: Of the 360 participants enrolled, 303 (1,203 interviews) were included in the symptom control and exacerbation analyses, 265 (732) in the EQ-5D, and 215 (617) in the PROMIS-PAIS. Around 60% of participants were male subjects, and most of them underwent maintenance treatment with inhaled corticosteroids plus long-acting β-agonists in a fixed dose (73.3%). Within-person variability was 83.6% for asthma control, 98.6% for exacerbations, 36.4% for EQ-5D, and 49.1% for PROMIS-PAIS. At the within-person level, patients with higher adherence had better symptom control (p = 0.002) and HRQoL over time (p = 0.016). Patients with a better inhalation technique reported worse HRQoL simultaneously (p = 0.012), but they showed better HRQoL in future assessments (p = 0.012). The frequency of reliever use was associated with symptom control (p < 0.001), exacerbation occurrence (p < 0.001), and HRQoL (p = 0.042); and boys were more likely to present better symptom control and HRQoL than girls.
Treatment Seeking Nitrous Oxide Users in Addiction Care: A Comparison with Cocaine Users on Clinical and Treatment Characteristics
Authors: Verboeket Sebastiaan O. , van den Bergh Judith , van Amsterdam Jan , Nabben Ton , van den Brink Wim , Goudriaan Anna E.
Published: July 2024

Introduction: Over the past decade, frequent use of large quantities of nitrous oxide (N2O) has become more common in the Netherlands. Although N2O poses several negative health consequences for a subgroup of problematic N2O users, there is a lack of knowledge on what characterizes these intensive users. This study therefore aims to provide the demographic and substance use characteristics and experiences during treatment of treatment seeking problematic N2O users and to compare this with a matched group of treatment-seeking problematic cocaine users. Methods: A retrospective chart review was performed of patients who were referred for treatment of problematic N2O use at a large Dutch addiction care facility from January 2020 to September 2022, extracting demographics, pattern of use and follow-up data. Additionally, a subgroup of N2O users was propensity-score matched (1:1) with a subgroup of treatment seeking problematic cocaine users, both groups excluding users with substance use disorders or frequent use of substances other than N2O and cocaine, respectively. Results: 128 patients with a N2O use disorder were included in the total sample and a subgroup of 77 N2O-only users was propensity-score matched on age and sex to 77 cocaine-only users. N2O users were typically young (mean age 26.2 years), male (66.4%), unmarried (82.9%), with a low education level (59.0%) and born in the Netherlands (88.2%), with parents born in Morocco (45.3%). N2O was used intermittently (median 10 days/month, IQR 4.0–17.5 days) and often in very large quantities (median 5 kg [ca. 750 balloons] per average using day, IQR 2–10 kg). Compared to the patients with a cocaine use disorder, matched N2O users were lower educated, more often from Moroccan descent, and less likely to be alcohol or polysubstance users. Despite receiving similar treatments, N2O users were twice as likely to discontinue treatment before completion compared to cocaine users (63 vs. 35%, p = 0.004). Conclusion: Treatment-seeking problematic N2O users are demographically different from treatment-seeking problematic cocaine users and are much more likely to dropout from psychological treatment. Further research is needed into the needs and other factors of problematic N2O users that relate to poor treatment adherence in problematic N2O users.
Arteriovenous oscillometric plethysmography for fistula functional testing
Authors: Busch Veit , Streis Joachim , Müller Sandra , Mueller Niklas , Seibert Felix S. , Felderhoff Thomas , Westhoff Timm H.
Published: July 2024

The aim of the presented prospective observational study was to evaluate the effect of fistula flow on peripheral wave morphology and pulse wave velocity by means of the oscillometric Vicorder®-device with the purpose of fistula surveillance.
Methods:
Digitized and normalized curves of 53 haemodialysis patients at the fistula and non-fistula arm were analyzed. Slope parameters and the areas under the curve of characteristic sections of pulse waves as well as the power spectrum of the pulse waves and their first and second derivatives were computed. Furthermore, the amplitude of volumetric change (AMP) was assessed. Duplex-sonography served as a reference method.
Results:
In the comprehensive set of novel pulse wave parameters significant inter-arm differences were demonstrated and a significant delay of the systolic maximum at the fistula arm in comparison to the non-fistula arm (204 ± 3.4 versus 162 ± 5.3 ms, p<0.001) was proven. Unexpectedly, pulse wave velocity apparently did not differ between both arms (7.85 versus 8.05 m/sec at the fistula/non-fistula side, p=0.942). The inter-arm differences of the slope parameters were more pronounced in forearm than in upper arm fistulas. Finally, we showed that the inter-arm difference of AMP correlated with volume-flow (r= 0.326 with p=0.017).
Conclusion:
Pulse waves as assessed by oscillometric pulse wave analysis have distinct features at fistula and non-fistula arms. This is due to enhanced arteriovenous flow, i.e. in both the brachial artery and the fistula vein. The analysis of those alterations has the potential to assess fistula function.
Tumor-Intrinsic Perinuclear LOXL2: Prognostic Relevance and Relationship with YAP1 Activation Status in Oral Squamous Cell Carcinoma
Authors: Rodrigo Juan P. , Moreno-Bueno Gema , Lequerica-Fernández Paloma , Rodríguez-Santamarta Tania , Díaz Eva , Prieto-Fernández Llara , Álvarez-Teijeiro Saúl , García-Pedrero Juana M. , de Vicente Juan Carlos
Published: July 2024

Introduction: Lysyl oxidase-like 2 (LOXL2) expression and function is frequently altered in different cancers but scarcely explored in oral squamous cell carcinoma (OSCC). This prompted us to investigate the clinical relevance of LOXL2 expression pattern in OSCC and also a possible crosstalk with Hippo/YAP1 pathway signaling. Methods: Immunohistochemical analysis of LOXL2 protein expression was performed in 158 OSCC patient samples, together with Yes-associated protein 1 (YAP1) activation status. Correlations with clinicopathological parameters and patient survival were assessed. Results: Tumor cell-intrinsic LOXL2 expression showed two distinct expression patterns: diffuse cytoplasmic staining (64.6%) and heterogeneous perinuclear staining (35.4%). Remarkably, perinuclear LOXL2 staining was significantly associated with lymph node metastasis, advanced clinical stage and perineural invasion. Moreover, patients harboring tumors with perinuclear LOXL2 expression exhibited significantly poorer disease-specific survival (DSS) rates, and perinuclear LOXL2 positivity gradually increased in relation to YAP1 activation. Patients harboring tumors with concomitant perinuclear LOXL2 and fully active YAP1 exhibited the worst DSS. Multivariate Cox analysis further revealed combined perinuclear LOXL2 and fully active YAP1 as a significant independent predictor of poor DSS. Conclusion: Tumor-intrinsic perinuclear LOXL2 emerges as a clinically and biologically relevant feature associated with advanced disease, tumor aggressiveness, and poor prognosis in OSCC. Moreover, this study unprecedentedly uncovers a functional relationship between perinuclear LOXL2 and YAP1 activation with major prognostic implications. Notably, combined perinuclear LOXL2 and fully active YAP1 was revealed as independent predictor of poor prognosis. These findings encourage targeting oncogenic LOXL2 functions for personalized treatment regimens.
Serum Uric Acid Level May Be a Predictive Factor for BRAF V600E Mutation in Older Patients with Metastatic Colorectal Cancer: An Exploratory Analysis
Authors: Alkan Ali , Doğaner Gümran İlay , Tanrıverdi Özgür
Published: July 2024

Introduction: This study aimed to show the relationship between the serum uric acid level measured at diagnosis and the BRAF mutation status in the primary tumor tissue in patients with metastatic colorectal cancer. Methods: In this retrospective cross-sectional study, 264 patients (64% male) whose serum uric acid level was measured at the time of diagnosis and whose BRAF mutation status in the primary tumor was determined were included. Results: The BRAF mutation rate was 14% (n = 37). The median serum uric acid levels of all patients were 6.9 mg/dL (25%, 75% percentile range 3.7, 8.2). The serum uric acid level cut-off value was 6.6 mg/dL. Sensitivity and specificity for BRAF mutated patients were 84% and 27%, respectively. These rates were calculated as 85% and 70% in BRAF-mutated patients aged 65 and over. There was a significant correlation between BRAF mutation and high serum uric acid level, female gender, tumor located in the ascending colon, and multiple metastatic sites. The independent factors affecting BRAF mutation were age 65 and over, tumor in the ascending colon, and high serum uric acid level. Conclusion: As a result, we concluded that high serum uric acid level measured during diagnosis in metastatic colorectal cancer is an accessible and economical biomarker that can predict BRAF mutation in patients aged 65 and over.
A Non-Interventional, Multicenter Study to Characterize the Socio-Demographics, Clinical Characteristics, and Management of Generalized Pustular Psoriasis Patients in Spain: IMPULSE Study
Authors: Puig Lluís , Izu Belloso Rosa , Rivera-Díaz Raquel , Mollet Sánchez Jordi , Rodríguez Fernández-Freire Lourdes , Sahuquillo-Torralba Antonio , Ruiz-Villaverde Ricardo ,   on behalf of IMPULSE investigators group
Published: July 2024

Introduction: Generalized pustular psoriasis (GPP) is a chronic, rare, and potentially life-threatening skin condition characterized by flares comprising widespread sterile pustules and systemic inflammation. Both the rarity and heterogeneity of the disease have made GPP classification and standardization of clinical criteria challenging. Before the approval of spesolimab (IL-36R antibody) in 2022, there were no approved treatments in the USA or Europe for GPP flares. Treatment for GPP has amounted to off-label use of medicines approved to treat plaque psoriasis. Our aim was to describe the sociodemographics, clinical characteristics, and treatment patterns of patients with GPP in Spain. Methods: Non-interventional, descriptive, multi-center, retrospective chart review of patients diagnosed with GPP in Spain. Results: 56 patients (50% women) were included, with a mean (standard deviation, SD) age at diagnosis of 53.7 (20.5) and a mean (SD) time of follow-up of 3.7 (3.1) years. In 80% of patients, GPP diagnosis was associated with a flare and 67.3% had known risk factors for GPP (such as previous diagnosis or family history of plaque psoriasis, comorbidities, smoking or stress). Hypertension and plaque psoriasis were the most frequent comorbidities (44.6% each). The number of GPP flares per patient-year was 0.55 with (range 0–4) a mean (SD) body surface area involvement of 21.3% (19.1). The most frequent manifestations of GPP flares were pustules (88.5%), erythema (76.9%), and scaling (76.9%). Additionally, 65.4% of patients had plaque psoriasis, 53.8% had unspecified skin lesions, and 30.8% experienced pain. The treatments used for GPP flares were off-label conventional systemic drugs (75%), mostly corticosteroids, cyclosporine, and acitretin. In the periods between flares, off-label biologics were used in 56.5% of patients. During the study period, 9 patients (16.1%) had at least one complication and 5 of them required hospitalization. Conclusion: This is the first multicenter study in Spanish GPP patients. Most patients were in their fifties, with personal or family history of plaque psoriasis, stress, smoking and a wide range of comorbidities and complications. Even though the number of flares per patient/year was 0.55, there was variability between patients. Both off-label conventional systemics and off-label biologics were used for flare management without a clear treatment pattern.
Aortic Arch Calcification in Predicting Unfavorable Angiographic Outcomes for Patients with ST-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention
Authors: Köktürk Uğur , Önalan Orhan , Somuncu Mustafa Umut , Çakan Fahri , Güdül Naile Eriş , Erbay İlke , Avcı Ahmet
Published: July 2024

Background: Despite advances in treatment, no-reflow, large thrombus burden (LTB), and myocardial blush grade (MBG) are associated with adverse cardiovascular outcomes in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). Aortic arch calcification (AAC) is associated with subclinical atherosclerosis and adverse cardiovascular events. We aimed to examine the relationship between AAC and unfavorable angiographic outcomes such as no-reflow, MBG, and LTB in STEMI patients undergoing PCI. Methods: A total of 269 consecutive patients who presented with STEMI and underwent primary PCI were included in the study prospectively. Patients were divided into 3 groups according to AAC degree: grade 0, grade 1, and grade 2/3. The relationship between AAC and the predictors of unfavorable angiographic outcomes, including LTB, no-reflow, and MBG, was specifically examined. Results: LTB, no-reflow, and MBG 0/1 were significantly higher in the grade 2/3 AAC group compared to the grade 0 and grade 1 groups (all p < 0.05). Moreover, grade 2/3 AAC was found to be an independent predictor for LTB, MBG 0/1, and no-reflow (p = 0.002, p = 0.005, p = 0.004, respectively). Patients were then classified according to thrombus burden, MBG, and no-reflow status. Grade 2/3 AAC was significantly higher than grade 0/1 AAC in the LTB, MBG 0/1, and no-reflow groups (all p < 0.05). Conclusion: AAC can be used as a reliable indicator in predicting no-reflow, MBG 0/1, and LTB in STEMI patients undergoing primary PCI.
Parental Influence on Intracerebral Hemorrhage Onset in Hereditary Dutch-Type Cerebral Amyloid Angiopathy
Authors: Rasing Ingeborg , Jellema Lisa , Voigt Sabine , Kaushik Kanishk , Koemans Emma A. , van Zwet Erik W. , van Etten Ellis S. , Greenberg Steven M. , van Walderveen Marianne A.A. , Terwindt Gisela M. , Wermer Marieke J.H.
Published: July 2024

Introduction: Dutch-type cerebral amyloid angiopathy (D-CAA) is an autosomal dominant hereditary form of CAA causing intracerebral hemorrhage (ICH) and cognitive decline. The age of onset of ICH in D-CAA mutation carriers is strikingly variable and ranges from late thirties up to 70 years. We investigated the presence of genetic anticipation and assessed the influence of parental age at onset and sex on age of ICH onset in offspring. Methods: We included (potential) D-CAA mutation carriers from our prospective D-CAA family database. Participants were sent a questionnaire by mail and asked for the onset age of symptomatic ICH and the onset age of symptomatic ICH of their affected first-degree relative(s), their siblings and affected parent. We used a Cox regression model with the age of onset of the parent as the covariate and the sex of the offspring as the factor. Next, we replaced the sex of the offspring with a factor with four levels: mother/daughter, mother/son, father/daughter, and father/son. We used a random effect per household. Results: A total of 66 respondents completed the questionnaire. Reported mean age of first symptomatic ICH was similar (both 52 years, p = 0.87) for D-CAA parents (n = 60) and their offspring (n = 100). Offspring with a mother with D-CAA seemed to have an earlier ICH onset (50 years, standard deviation [SD] ± 7) than offspring with a paternal inheritance (54 years, SD ± 6, p = 0.03). There was no association between onset of first ICH of the parent and offspring after adding sex of the offspring to the Cox regression model: hazard ratio 0.99, 95% CI: 0.94–1.03, p = 0.51. The interaction between parent’s sex and child’s sex was not significant (p = 0.70). The results with and without random effect were essentially identical. Conclusion: We found no indication for genetic anticipation in D-CAA in general, although maternal inheritance seemed to be associated with an earlier ICH onset.
Impaired microvascular reactivity in patients with chronic kidney disease submitted to kidney transplantation: a prospective observational study
Authors: Borges Paulo Sergio , Orange Flavia Augusta , Pontes Isabelle Albuquerque , Clough Geraldine F. , Alves João Guilherme Bezerra
Published: July 2024

Introduction: The effect of kidney transplantation on endothelial dysfunction and autonomic dysfunction in uremia remains controversial, and few studies have evaluated this question. Endothelial dysfunction and autonomic dysfunction, both, can be assessed non-invasively using laser Doppler flowmetry (LDF). This study evaluated cutaneous microvascular blood flow and reactivity using LDF in patients undergoing kidney transplantation. Methods: This prospective longitudinal cohort study involved forty patients with chronic kidney disease (CKD) undergoing kidney transplantation, compared with 40 patients without kidney disease. Using a laser Doppler flowmetry, post-occlusive reactive hyperemia (PORH) [resting flow, peak flow, ratio between peak and resting flow, hyperemic area, PORH index] and sympathetic constrictor response to inspiratory breath-hold [mean minimum inspiratory values] were evaluated. Results: Resting flow (RF) and sympathetic constrictor response to inspiratory breath-hold (mean minimum inspiratory values), were lower in the CKD group at one week and three months after transplantation (p<0.005). Mean minimum inspiratory values increase in the CDK group, three months after transplantation. Conclusion: Compared with controls with no CKD, in CKD patients undergoing kidney transplantation, microcirculation by laser Doppler flowmetry shows improvement after three months.
Albumin-Lymphocyte-Globulin-C-Reactive Protein Index as a Novel Prognostic Biomarker for Hepatocellular Carcinoma after Hepatectomy
Authors: Utsumi Masashi , Inagaki Masaru , Kitada Koji , Tokunaga Naoyuki , Yunoki Kosuke , Sakurai Yuya , Okabayashi Hiroki , Hamano Ryosuke , Miyaso Hideaki , Tsunemitsu Yosuke , Otsuka Shinya
Published: July 2024

Introduction: This study evaluated the performance of the albumin-lymphocyte-globulin-C-reactive protein (CRP) (ALGC) index as a novel prognostic biomarker for hepatocellular carcinoma (HCC) after hepatectomy. Methods: Patients (n = 178) who underwent hepatectomy for HCC (July 2010–December 2021) were analyzed. The ALGC index was calculated as ([albumin × lymphocyte]/[CRP × globulin × 104]). Patients were divided into a low ALGC group (<1.82; n = 81) and a high ALGC group (≥1.82; n = 97). The association of the ALGC index with survival was assessed by univariate and multivariate analyses. Results: The median overall survival (OS) was 100 (range: 1–149) months with 1-, 3-, and 5-year OS rates of 91.6%, 81.2%, and 64.2%, respectively. In univariate analysis, ALGC index (<1.82), alpha-fetoprotein (≥25 ng/mL), tumor size (≥3.5 cm), microvascular invasion, and multiple tumors were associated with shorter OS. ALGC index (<1.82) (hazard ratio [95% confidence interval]) (2.48 [1.407–4.513]; p = 0.001) and multiple tumors (1.92 [1.070–3.356]; p = 0.029) were independent predictors of OS in multivariate analysis. Conclusion: ALGC index is a novel prognostic biomarker for HCC after hepatectomy. It may assist in treatment stratification and better management of patients with HCC.
Meta-Analysis of the Efficacy and Safety of Pembrolizumab in the Treatment of Advanced Gastric Cancer and Gastroesophageal Junction Cancer
Authors: Yang Jingyun , Luo Weisheng , Ma Xiaocong , Cui Yinhang , Xie Jiacheng , Pan Chengzhen , Chen Ziyao , Yang Shuang
Published: July 2024

Introduction: Pembrolizumab has been approved for the first-line treatment of patients with advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer. However, the results of several clinical trials are not entirely consistent, and the dominant population of first-line immunotherapy for advanced GC/GEJ still needs to be precisely determined. Purpose: The aim of this meta-analysis was to assess the efficacy and safety of pembrolizumab in the treatment of advanced GC/GEJ. Methods: We conducted computerized searches across multiple databases, including PubMed, Cochrane Library, Web of Science, and Embase. We established the inclusion criteria to comprise randomized clinical trials examining the efficacy of pembrolizumab in late-stage GC/GCJ cancer. We conducted a meta-analysis of outcome measures using STATA 14.0 software. Results: A total of six studies involving 1,448 cases were included in this analysis. The results of the meta-analysis indicate that, when compared to chemotherapy, patients in the pembrolizumab group experienced a significant reduction in the risk of mortality in terms of overall survival (OS) (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.65–0.79, p < 0.01). In terms of progression-free survival (PFS), pembrolizumab was associated with a similar PFS as compared to chemotherapy (HR = 0.88, 95% CI: 0.73–1.07, p = 0.206). Subgroup analyses based on PD-L1 expression levels indicated a significantly longer PFS with pembrolizumab in subgroups of patients with PD-L1 CPS ≥10 but not in those with PD-L1 CPS ≥1 and PD-L1 CPS ≥5. Subgroup analyses based on distinct geographical regions revealed a comparable effect of PFS in patients residing in Asia or the USA Subgroup analysis based on tumor sites consistently demonstrated a similar effect of PFS in patients with EC/GEJ tumors and GC patients. Conclusion: Our findings demonstrated that pembrolizumab led to a significant extension in OS and objective response rate, along with a favorable tolerability profile compared to chemotherapy. Furthermore, the observed survival benefits were particularly pronounced in subgroup patients with a CPS of ≥10. Given the potential limitations inherent in our study, it is imperative to underscore the necessity for further large-scale RCTs to corroborate our results.
Circ_0043314 Modulates Proliferation and Apoptosis of Ovarian Granulosa Cells in Polycystic Ovarian Syndrome via the MicroRNA-146b-3p/Apelin 13 Axis
Authors: Wang Wei , Tan Luni , Ge Liang , Gou Ruiqiang , Gou Li , Liu Lin , Zhang Lili , Ma Xiaoling
Published: July 2024

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. At present, the pathogenesis has not been clarified, and the clinical application of drugs and lifestyle intervention may not prevent disease progression. This study aimed to investigate how circ_0043314 regulates ovarian granulosa cell biological functions to provide a theoretical basis for the treatment of patients with PCOS. MicroRNA (miR)-146b-3p/Apelin 13 axis was used to investigate the mechanism by which circ_0043314 regulated ovarian granulosa cell proliferation and apoptosis in PCOS via miR-146b-3p/Apelin 13 axis. Participants/Materials, Methods: Ovarian tissues (cortical tissues) from 35 PCOS patients and 35 normal controls, as well as HEK293T and human ovarian granulosa cell line (KGN, COV434), were included in this study. We examined the expression levels of circ_0043314, miR-146b-3p, and Apelin 13 in PCOS tissues. Ovarian granulosa cells were transfected with corresponding plasmids to clarify the influence of circ_0043314, miR-146b-3p, or Apelin 13 on proliferation and apoptosis of ovarian granulosa cells through MTT and flow cytometry assays. Moreover, the relationships among circ_0043314, miR-146b-3p, and Apelin 13 were analyzed through dual-luciferase and RNA immunoprecipitation assays. Results: Circ_0043314 and Apelin 13 were highly expressed and miR-146b-3p was lowly expressed in ovarian tissues of PCOS compared with non-PCOS controls. Downregulation of circ_0043314 or upregulation of miR-146b-3p hindered ovarian granulosa cell proliferation and advanced its apoptosis. Downregulation of miR-146b-3p reversed the impacts of downregulation of circ_0043314, and overexpression of Apelin 13 counteracted the influences of upregulation of miR-146b-3p in ovarian granulosa cells. Mechanically, circ_0043314 could bind to miR-146b-3p, and miR-146b-3p directly targeted and modulated Apelin 13 expression. Limitations: This study was limited by the lack of animal experiments. Conclusion: Our data demonstrated that circ_0043314 enhances ovarian granulosa cell proliferation and suppresses its apoptosis via miR-146b-3p/Apelin 13 axis.
Lack of Nuclear Localization of the Creb3l1 Transcription Factor Causes Defects in Caudal Fin Bifurcation in Zebrafish Danio rerio
Authors: VanWinkle Peyton E. , Wynn Bridge , Lee Eunjoo , Nawara Tomasz J. , Thomas Holly , Parant John M. , Alvarez Cecilia , Serra Rosa , Sztul Elizabeth
Published: July 2024

Introduction: The formation of normal bone and bone healing requires the cAMP-responsive element binding protein 3-like-1 (Creb3l1) transmembrane transcription factor, as deletion of the murine CREB3L1 results in osteopenic animals with limited capacity to repair bone after a fracture. Creb3l1 undergoes regulated intramembrane proteolysis (RIP) to release the N-terminal transcription activating (TA) fragment that enters the nucleus and regulates the expression of target genes. Methods: To expand our understanding of Creb3l1’s role in skeletal development and skeletal patterning, we aimed to generate animals expressing only the TA fragment of Creb3l1 lacking the transmembrane domain and thereby not regulated through RIP. However, the CRISPR/Cas9-mediated genome editing in zebrafish Danio rerio caused a frameshift mutation that added 56 random amino acids at the C-terminus of the TA fragment (TA+), making it unable to enter the nucleus. Thus, TA+ does not regulate transcription, and the creb3l1TA+/TA+ fish do not mediate creb3l1-dependent transcription. Results: We document that the creb3l1TA+/TA+ fish exhibit defects in the patterning of caudal fin lepidotrichia, with significantly distalized points of proximal bifurcation and decreased secondary bifurcations. Moreover, using the caudal fin amputation model, we show that creb3l1TA+/TA+ fish have decreased regeneration and that their regenerates replicate the distalization and bifurcation defects observed in intact fins of creb3l1TA+/TA+ animals. These defects correlate with altered expression of the shha and ptch2 components of the Sonic Hedgehog signaling pathway in creb3l1TA+/TA+ regenerates. Conclusion: Together, our results uncover a previously unknown intersection between Creb3l1 and the Sonic Hedgehog pathway and document a novel role of Creb3l1 in tissue patterning.
Determinants of the Utilization of Recognized Traditional and Complementary Medicine Service in Malaysia: A Secondary Analysis of a Cross-Sectional Population-Based Survey
Authors: Ng Suk Kuan , Nishino Kimihiro , Seman Zamtira , Inthaphatha Souphalak , Yamamoto Eiko
Published: July 2024

Introduction: The utilization of traditional and complementary medicine (T&CM) services has witnessed a global increase over the past decades. Currently, seven practice areas are recognized in Malaysia: traditional Malay medicine (TMM), traditional Chinese medicine (TCM), traditional Indian medicine, homeopathy, Islamic medical practice, chiropractic, and osteopathy. Many global studies have investigated the general determinants of T&CM service utilization. However, there has been no comprehensive study reporting specific determinants of recognized T&CM service utilization. This study aimed to examine the prevalence and specific determinants of recognized T&CM service utilization in Malaysia at a national level. Methods: This study is a secondary analysis of data from the National Health and Morbidity Survey (NHMS), a cross-sectional population-based survey conducted in Malaysia in 2015. A total of 6,207 respondents aged ≥18 years were included in this study. The associations of sociodemographic, health, and lifestyle factors with the utilization of the three T&CM service categories (TMM, TCM, and other T&CM) were examined using three separate logistic regression analyses. Results: The prevalence of recognized T&CM service utilization in the last 12 months was 19.3%, with 15.0% for TMM, 3.9% for TCM, and 1.5% for other T&CM. The determinants of TMM service utilization were female sex; age range of 18–29 years; married or widowed/divorced status; Malay, indigenous, or other ethnicities; high household income; and being overweight/obese. The determinants of TCM service utilization were the age range of 30–49 years, urban residential location, Chinese ethnicity, and adequate fruit and vegetable intake. No specific determinants were identified for other T&CM. Conclusion: This study provided novel evidence of a strong ethnocultural ownership toward traditional medicine. User profiles were distinctively different between varied T&CM services. Customized approaches to regulate, develop, and institutionalize specific T&CM services are crucial for fulfilling the unique needs of diverse communities.
Yoga as a Complementary Therapy for Cancer Patients: From Clinical Observations to Biochemical Mechanisms
Authors: Blockhuys Stéphanie , Wittung-Stafshede Pernilla
Published: July 2024

Background: Integrative oncology combines conventional and complementary, or integrative, therapies for a holistic treatment of cancer patients. Yoga is increasingly used as a complementary therapy for cancer patients, but there is no direct evidence for its effect on cancer pathophysiology like tumor response, or patient outcome like overall survival. Summary: In this narrative review, we present in detail published studies from randomized clinical trials on complementary yoga therapy for cancer patients, including details about the biochemical mechanisms involved. Medicinal hatha yoga with breathing, postures, meditation, and relaxation enhances the quality of life of cancer patients by providing both psychological and physiological health benefits, highlighting the interconnectedness of mind and body. Yoga therapy reduces stress levels improving heart rate variability, leading to changes in hormonal regulation (e.g., cortisol), reduced oxidative stress, and improved immune function with reduced inflammation. Still, the biochemical effects of yoga on the cancer disease itself are unrevealed. Key Messages: More clinical and basic research is needed for further establishment of yoga as complementary therapy in oncology.
Acoustic Character Governing Variation in Normal, Benign, and Malignant Voices
Authors: Liu Boquan , Lei Jianhan , Wischhoff Owen P. , Smereka Katerina A. , Jiang Jack J.
Published: July 2024

Introduction: Benign and malignant vocal fold lesions (VFLs) are growths that occur on the vocal folds. However, the treatments for these two types of lesions differ significantly. Therefore, it is imperative to use a multidisciplinary approach to properly recognize suspicious lesions. This study aimed to determine the important acoustic characteristics specific to benign and malignant VFLs. Methods: The acoustic model of voice quality was utilized to measure various acoustic parameters in 157 participants, including individuals with normal, benign, and malignant conditions. The study comprised 62 female and 95 male participants (43 ± 10 years). Voice samples were collected at the Shanghai Eye, Ear, Nose, and Throat Hospital of Fudan University between May 2020 and July 2021. The acoustic variables of the participants were analyzed using Principal Component Analysis (PCA) to present important acoustic characteristics that are specific to normal vocal folds, benign VFLs, and malignant VFLs. The similarities and differences in acoustic factors were also studied for benign conditions including Reinke’s edema, polyps, cysts, and leukoplakia. Results: Using the PCA method, the components that accounted for the variation in the data were identified, highlighting acoustic characteristics in the normal, benign, and malignant groups. The analysis indicated that coefficients of variation in root mean square energy were observed solely within the normal group. Coefficients of variation in pitch (F0) were found to be significant only in benign voices, while higher formant frequencies and their variability were identified as contributors to the acoustic variance within the malignant group. The presence of formant dispersion (FD) as a weighted factor in PCA was exclusively noted in individuals with Reinke’s edema. The amplitude ratio between subharmonics and harmonics (SHR) and its coefficients of variation were evident exclusively in the polyps group. In the case of voices with cysts, both pitch (F0) and coefficients of variation for FD were observed to contribute to variations. Additionally, higher formant frequencies and their coefficients of variation played a role in the acoustic variance among voices of patients with leukoplakia. Conclusion: Experimental evidence demonstrates the utility of the PCA method in the identification of vibrational alterations in the acoustic characteristics of voice affected by lesions. Furthermore, the PCA analysis has highlighted underlying acoustic differences between various conditions such as Reinke’s edema, polyps, cysts, and leukoplakia. These findings can be used in the future to develop an automated malignant voice analysis algorithm, which will facilitate timely intervention and management of vocal fold conditions.
Effect of Maternal Ursodeoxycholic Acid Treatment on Fetal Atrioventricular Conduction in Patients with Intrahepatic Cholestasis of Pregnancy
Authors: Eyisoy Ömer Gökhan , Demirci Oya , Taşdemir Ümit , Özdemir Mucize , Öcal Aydın , Kahramanoğlu Özge
Published: July 2024

Introduction: The aim of this study was, first, to investigate the difference in fetal atrioventricular conduction in patients with and without intrahepatic cholestasis of pregnancy (ICP) by measuring the fetal PR interval; second, to evaluate the altering effect of ursodeoxycholic acid (UDCA) treatment on the fetal PR interval in ICP patients. Methods: The study consisted of 42 ICP patients and 48 healthy pregnant women. Fetal echocardiography was performed to measure the mechanical PR interval. The fetal PR interval and the clinical characteristics were compared between the two groups. The effect of UDCA treatment on the fetal PR interval in ICP patients was evaluated. Results: In ICP patients, significantly longer fetal PR intervals were observed than in the control group (123.21 ± 8.54 vs. 115.13 ± 5.95 ms, p < 0.001). In the ICP group, there was a positive correlation between the fetal PR interval and maternal fasting total bile acid (TBA) levels (r = 0.514, p = 0.001). After 1 week of treatment with UDCA in patients with ICP, the PR interval was shorter than before, although the reduction was not statistically significant (120.98 ± 6.70 vs. 123.21 ± 8.54 ms, p = 0.095). In patients with severe ICP (TBA >40 mmol/L, n = 10), a significant reduction in the fetal PR interval was observed after treatment with UDCA (127.5 ms [IQR, 118.0–134.75] before vs. 122 ms [IQR, 109.5–126.5] after, p = 0.037). Conclusion: Fetal PR interval increased in ICP patients in correlation with maternal serum TBA concentration. Treatment with UDCA may have limited positive effects on the fetal AV conduction system. The beneficial effects of UDCA on the fetal PR interval may be more pronounced in patients with higher bile acid levels.
Transbronchial Cryoablation as Local Treatment for Central Airway Malignant Tumor
Authors: Hamakawa Masamitsu , Niwa Takashi , Fukuda Yasushi , Yokoyama Toshihide , Ishida Tadashi
Published: July 2024

Introduction: Transbronchial cryoablation has been performed for peripheral but not central airway malignant tumor. We demonstrate transbronchial cryoablation in 2 patients with central airway lesions. Case Presentation: Case 1 was an 86-year-old woman who developed intratracheal metastasis associated with postoperative recurrence of lung adenocarcinoma. The tumor was resected using a high-frequency electrosurgical snare and three transbronchial cryoablations. There was no tracheal recurrence in the 5 months after the third procedure. Case 2 was an 83-year-old man who developed intermediate bronchial metastasis associated with postoperative recurrence of lung squamous cell carcinoma. The tumor was resected using a high-frequency electrosurgical snare and one transbronchial cryoablation. There was no tumor recurrence in the bronchus intermedius for 12 months after treatment. In both cases, the only adverse event was minor bleeding. Conclusion: Transbronchial cryoablation deserves consideration as local treatment for central airway malignant tumors.