-
Clinical Oral Investigations Jul 2024Orofacial clefts are complex congenital anomalies that call for comprehensive treatment based on a thorough assessment of the anatomy. This study aims to examine the...
OBJECTIVES
Orofacial clefts are complex congenital anomalies that call for comprehensive treatment based on a thorough assessment of the anatomy. This study aims to examine the effect of cleft type on craniofacial morphology using geometric morphometrics.
MATERIALS AND METHODS
We evaluated lateral cephalograms of 75 patients with bilateral cleft lip and palate, 63 patients with unilateral cleft lip and palate, and 76 patients with isolated cleft palate. Generalized Procrustes analysis was performed on 16 hard tissue landmark coordinates. Shape variability was studied with principal component analysis. In a risk model approach, the first nine principal components (PC) were used to examine the effect of cleft type.
RESULTS
We found statistically significant differences in the mean shape between cleft types. The difference is greatest between bilateral cleft lip and palate and isolated cleft palate (distance of means 0.026, P = 0.0011). Differences between cleft types are most pronounced for PC4 and PC5 (P = 0.0001), which together account for 10% of the total shape variation. PC4 and PC5 show shape differences in the ratio of the upper to the lower face, the posterior mandibular height, and the mandibular angle.
CONCLUSIONS
Cleft type has a statistically significant but weak effect on craniofacial morphological variability in patients with non-syndromic orofacial clefts, mainly in the vertical dimension.
CLINICAL RELEVANCE
Understanding the effects of clefts on craniofacial morphology is essential to providing patients with treatment tailored to their specific needs. This study contributes to the literature particularly due to our risk model approach in lieu of a prediction model.
Topics: Humans; Cleft Palate; Cleft Lip; Male; Cephalometry; Female; Adolescent; Anatomic Landmarks; Child; Principal Component Analysis
PubMed: 38954126
DOI: 10.1007/s00784-024-05796-y -
Cancer Immunology, Immunotherapy : CII Jul 2024Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of...
BACKGROUND
Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment.
MATERIALS AND METHODS
A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses.
RESULTS
A total of 571 patients with a median age of 61 years (range 17-85) were included in the analysis. With a median follow-up of 22.1 (1.0-89.0) months, 23.1% of patients were 2-year progression-free on treatment with nivolumab, hence they were categorized as long-term responders. Baseline characteristics, including age, gender, and histology, were similar between long- and short-term responders. Karnofsky Performance Status ≥ 80% was significantly associated with long-term response (p = 0.02), while bone metastases (p = 0.03), International mRCC Database Consortium intermediate-poor risk (p < 0.01) and Neutrophil-to-Lymphocyte Ratio ≥ 3.2 (p = 0.02) were associate with short-term responses. Long-term responders exhibited a median progression-free survival of 55.0 months versus 4.0 months of the short-term responders. The median OS was not reached in long-term responders while it was 17.0 months for short*term responders.
CONCLUSION
This retrospective analysis sheds light on factors associated with long-term response to nivolumab in mRCC. Understanding these clinical features will be essential for selecting patients who may mostly benefit from immunotherapy.
Topics: Humans; Nivolumab; Carcinoma, Renal Cell; Female; Male; Middle Aged; Aged; Adult; Kidney Neoplasms; Retrospective Studies; Aged, 80 and over; Young Adult; Adolescent; Antineoplastic Agents, Immunological; Follow-Up Studies
PubMed: 38954006
DOI: 10.1007/s00262-024-03741-2 -
Investigative Ophthalmology & Visual... Jul 2024To investigate the correlation between apparent diffusion coefficient (ADC) histograms and high-risk clinicopathologic features related to uveal melanoma (UM) prognosis.
PURPOSE
To investigate the correlation between apparent diffusion coefficient (ADC) histograms and high-risk clinicopathologic features related to uveal melanoma (UM) prognosis.
METHODS
This retrospective study included 53 patients with UM who underwent diffusion-weighted imaging (DWI) between August 2015 and March 2024. Axial DWI was performed with a single-shot spin-echo echo-planar imaging sequence. ADC histogram parameters of ADCmean, ADC50%, interquartile range (IQR), skewness, kurtosis, and entropy were obtained from DWI. The relationships between histogram parameters and high-risk clinicopathological characteristics including tumor size, preoperative retinal detachment, histological subtypes, Ki-67 index, and chromosome status, were analyzed by Spearman correlation analysis, Mann-Whitney U test, or Kruskal-Wallis test.
RESULTS
A total of 53 patients (mean ± SD age, 55 ± 15 years; 22 men) were evaluated. The largest basal diameter (LBD) was correlated with kurtosis (r = 0.311, P = 0.024). Tumor prominence (TP) was correlated with entropy (r = 0.581, P < 0.001) and kurtosis (r = 0.273, P = 0.048). Additionally, significant correlations were identified between the Ki-67 index and ADCmean (r = -0.444, P = 0.005), ADC50% (r = -0.487, P = 0.002), and skewness (r = 0.394, P = 0.014). Finally, entropy was correlated with monosomy 3 (r = 0.541, P = 0.017).
CONCLUSIONS
The ADC histograms provided valuable insights into high-risk clinicopathologic features of UM and hold promise in the early prediction of UM prognosis.
Topics: Humans; Uveal Neoplasms; Male; Female; Middle Aged; Melanoma; Retrospective Studies; Prognosis; Diffusion Magnetic Resonance Imaging; Adult; Aged; Echo-Planar Imaging
PubMed: 38953846
DOI: 10.1167/iovs.65.8.3 -
MBio Jul 2024Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous . Under appropriate thermal conditions, mononuclear yeast forms alternate...
Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous . Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains and as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells . Multilateral yeast cells emerge in all three at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of . The ecological role of yeast forms in is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for or . We demonstrate that the dimorphic transition is common in species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.
PubMed: 38953355
DOI: 10.1128/mbio.00144-24 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2024Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid...
Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid nodules presenting a spoke-wheel blood flow pattern examined by ultrasound were collected,and the gray-scale ultrasound features of the nodules were recorded.The diagnostic performance of the Thyroid Imaging Reporting and Data System by American College of Radiology (ACR TI-RADS),Chinese Thyroid Imaging Reporting and Data System (C-TIRADS),and combined specific indicators for the thyroid nodules with a spoke-wheel blood flow pattern was evaluated by comparison with the pathological results,which was regarded as the gold standard.Results A total of 64 patients with thyroid nodules were finally included,including 47 patients with malignant nodules and 17 patients with benign nodules.In addition to the general ultrasound features,central scar mostly appeared in malignant nodules (=5.968,=0.015),while central coarse calcification was more common in benign nodules (=10.899,=0.001).After the combination of central scar and central gross calcification,the diagnostic performance of ACR TI-RADS and C-TIRADS was improved (both <0.001).Conclusions When the thyroid nodule shows a spoke-wheel blood flow pattern,one should be cautious of the possibility of malignancy.Combining central scar and central coarse calcification can improve the accuracy of ultrasonic diagnosis.
Topics: Humans; Thyroid Nodule; Middle Aged; Male; Female; Ultrasonography; Adult; Aged; Young Adult
PubMed: 38953260
DOI: 10.3881/j.issn.1000-503X.15894 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2024Objective To explore the relationship between the expression levels of microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in the colonic mucosal...
[Correlations Between the Expression of MicroRNA-155 and Suppressor of Cytokine Signaling 1 in Colonic Mucosal Tissue and Disease Severity in Patients With Ulcerative Colitis].
Objective To explore the relationship between the expression levels of microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in the colonic mucosal tissue of patients with ulcerative colitis (UC) and the severity of the disease.Methods A total of 130 UC patients admitted to the Second Affiliated Hospital of Hebei North University from September 2021 to June 2023 were selected.According to the modified Mayo score system,the patients were assigned into an active stage group (=85) and a remission stage group (=45).According to the modified Truelove and Witts classification criteria,the UC patients at the active stage were assigned into a mild group (=35),a moderate group (=30),and a severe group (=20).A total of 90 healthy individuals who underwent colonoscopy for physical examination or those who had normal colonoscopy results after single polypectomy and excluded other diseases were selected as the control group.The colonic mucosal tissues of UC patients with obvious lesions and the colonic mucosal tissue 20 cm away from the anus of the control group were collected.The levels of miR-155 and SOCS1 mRNA in tissues were determined by fluorescence quantitative PCR,and the expression of SOCS1 protein in tissues was determined by immunohistochemistry.The correlations of the levels of miR-155 and SOCS1 mRNA in the colonic mucosal tissue with the modified Mayo score of UC patients were analyzed.The values of the levels of miR-155 and SOCS1 mRNA in predicting the occurrence of severe illness in the UC patients at the active stage were evaluated.Results Compared with the control group and the remission stage group,the active stage group showed up-regulated expression level of miR-155,down-regulated level of SOCS1 mRNA,and decreased positive rate of SOCS1 protein in the colonic mucosal tissue (all <0.001).The expression level of miR-155 and modified Mayo score in colonic mucosal tissues of UC patients at the active stage increased,while the mRNA level of SOCS1 was down-regulated as the disease evolved from being mild to severe (all <0.001).The modified Mayo score was positively correlated with the miR-155 level and negative correlated with the mRNA level of SOCS1 in colonic mucosal tissues of UC patients (all <0.001).The high miR-155 level (=2.762,95%=1.284-5.944,=0.009),low mRNA level of SOCS1 (=2.617,95%=1.302-5.258,=0.007),and modified Mayo score≥12 points (=3.232,95%=1.450-7.204,=0.004) were all risk factors for severe disease in the UC patients at the active stage.The area under curve of miR-155 combined with SOCS1 mRNA in predicting severe illness in the UC patients at the active stage was 0.920.Conclusions The expression levels of miR-155 and SOCS1 mRNA were correlated with the disease severity in the UC patients at the active stage.The combination of the two indicators demonstrates good performance in predicting the occurrence of severe illness in UC patients at the active stage.
Topics: Humans; MicroRNAs; Colitis, Ulcerative; Suppressor of Cytokine Signaling 1 Protein; Intestinal Mucosa; Severity of Illness Index; Colon; Female; Male; Middle Aged; Adult
PubMed: 38953257
DOI: 10.3881/j.issn.1000-503X.15863 -
Lung India : Official Organ of Indian... Jul 2024Modalities to improve tissue acquisition during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been investigated. Endobronchial...
BACKGROUND
Modalities to improve tissue acquisition during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been investigated. Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) is a modality to obtain larger histological samples by inserting a cryoprobe into the mediastinal lesion. We aimed to study the diagnostic yield and safety of EBUS-TMC.
METHODS
We performed a systematic search of the PubMed and Embase databases to extract the relevant studies. We then performed a meta-analysis to calculate the diagnostic yield of EBUS-TMC and compare it with EBUS-TBNA.
RESULTS
Following a systematic search, we identified 14 relevant studies (869 patients undergoing EBUS-TMC and EBUS-TBNA). We then performed a meta-analysis of the diagnostic yield of EBUS-TMC and EBUS-TBNA from studies wherein both procedures were performed. The pooled diagnostic yield of EBUS-TMC was 92% (95% confidence interval [CI], 89%-95%). The pooled diagnostic yield of EBUS-TBNA was 81% (95% CI, 77%-85%). The risk difference in yield was 11% (95% CI, 6%-15%, I2 = 0%) when EBUS-TMC and EBUS-TBNA were compared. The only complication reported commonly with EBUS-TMC was minor bleeding. The complication rate was comparable with EBUS-TBNA.
CONCLUSION
EBUS-TMC provides a greater diagnostic yield with a similar risk of adverse events compared to EBUS-TBNA. Future studies are required to clearly establish which patients are most likely to benefit from this modality.
PubMed: 38953193
DOI: 10.4103/lungindia.lungindia_606_23 -
Frontiers in Pharmacology 2024Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and...
BACKGROUND
Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis.
METHODS
We fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism.
RESULTS
In OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe's mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3.
CONCLUSION
This study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism.
PubMed: 38953111
DOI: 10.3389/fphar.2024.1406493 -
Research and Practice in Thrombosis and... May 2024Multiple guidelines recommend assessment of bleeding and venous thromboembolism (VTE) risk in adult medical inpatients to inform prevention strategies. There is no...
Validation of the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) risk scores for venous thromboembolism and bleeding in an independent population.
BACKGROUND
Multiple guidelines recommend assessment of bleeding and venous thromboembolism (VTE) risk in adult medical inpatients to inform prevention strategies. There is no agreed-upon method for VTE and bleeding risk assessment.
OBJECTIVES
To validate the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE and bleeding risk scores in an independent population.
METHODS
In this retrospective study, we calculated the IMPROVE VTE and bleeding risk scores in medical inpatients admitted between 2010 and 2019 at the University of Vermont Medical Center (UVMMC). Patients were followed for in-hospital bleeding events while hospitalized and VTE events while hospitalized and for 3 months after discharge. We assessed calibration of the risk models by comparing the observed incidence of events in the UVMMC and IMPROVE populations across the published risk categories. We also assessed performance of the IMPROVE risk factors after refitting the models in the UVMMC population. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC).
RESULTS
VTE occurred in 270 (1.1%) of 23,873 admissions, with 92 (34%) occurring during admission, and bleeding occurred in 712 (4.7%) of 15,240 admissions. When the IMPROVE-VTE risk factors were refitted to the UVMMC data, the AUC was 0.64. When the IMPROVE bleeding risk factors were refitted to the UVMMC data, the AUC was 0.67. The IMPROVE-VTE score tended to overestimate risk at higher scores, and the IMPROVE bleeding score underestimated risk at lower scores and overestimated risk at higher scores.
CONCLUSION
While the refitted IMPROVE VTE and bleeding risk scores had reasonable model fit, the scores were poorly calibrated and did not reliably identify or differentiate patients at risk for VTE and bleeding. Different methods are needed for risk assessment of medical inpatients for VTE and bleeding risk.
PubMed: 38953050
DOI: 10.1016/j.rpth.2024.102441 -
Open Medicine (Warsaw, Poland) 2024Renal cell carcinoma (RCC) with gene fusion caused by Xp11.2 translocations is a rare RCC subtype. This tumor is typically seen in children, comprising 20‒40% of...
BACKGROUND
Renal cell carcinoma (RCC) with gene fusion caused by Xp11.2 translocations is a rare RCC subtype. This tumor is typically seen in children, comprising 20‒40% of overall RCC cases compared to 1‒1.6% observed in adults. Xp11.2 RCC is associated with a poor prognosis due to both the progression of local lesions and early distant and lymphatic metastasis.
CASE PRESENTATION
A case of RCC with Xp11.2 RCC translocations and gene fusion was found in a pediatric patient, illustrating the catastrophic effects of ignoring the condition. The tumor developed from a local lesion to lymph metastasis (3.2-12 cm) within 4 years. Despite ongoing controversy, surgical resection remains the most common and productive approach. In this patient, renal retroperitoneal lymph node dissection and radical nephrectomy of the left kidney were performed via laparoscopic surgery. The RCC-associated Xp11.2 translocation/ gene fusions were identified by postoperative pathology. Microscopic analysis showed the presence of intravascular cancer thrombus, renal sinus invasion, and cancer necrosis. The pathological stages were confirmed as PT3aN1M0 with a negative margin. Follow-up at 5 months showed that the patient recovered without the use of any adjuvant treatments.
CONCLUSION
Our study highlights the natural course, diagnosis, and treatment of RCC-associated Xp11.2 translocation/TFE3 gene fusions, especially the necessity of early surgery. This case may be a helpful reference for urologists in the treatment of similar cases. It also serves as a precautionary signal for patients who neglect the renal neoplasm.
PubMed: 38953008
DOI: 10.1515/med-2024-0985