Brentuximab vedotin therapy followed by autologous peripheral stem cell transplantation as a viable treatment option for an older adult with transformed lymphoma: a case report and literature review.

This report presents a case involving a woman aged >65 years who had been diagnosed with marginal zone lymphoma 3 years prior. The patient was hospitalized with enlarged inguinal lymph nodes, and pathological examination revealed that the lymphoma had transformed into diffuse large B-cell lymphoma. After two cycles of brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (BV-R-CHP) chemotherapy, the patient achieved complete remission. This treatment was followed by autologous hematopoietic stem cell transplantation and lenalidomide maintenance therapy. At the last follow-up, the patient had been in continuous remission for 24 months. This case study suggests that the utilization of BV and R-CHP in conjunction can result in rapid remission, and it can be followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide. This treatment approach exhibits potential as a viable option for older individuals with transformed lymphoma.

Effect of Nrf2 on brain injury induced by hydraulic shock via regulation of mitophagy and apoptosis.

The specific protective mechanism of mitophagy and Nrf2 in brain injury has not been fully clarified. This study aimed to reveal the effect of Nrf2 on hydraulic shock brain injury in mice, and explore its possible mechanism. Twenty-four Nrf2 knockout (Nrf2-/-) and wild-type mice (WT) of C57BL/6J were randomly divided into two groups: control group (C) and brain injury group (TBI). Hematoxylin-eosin staining (HE) assay was used for the histomorphological observation. The apoptotic state of brain tissue was detected by TUNEL. Mechanical damage in vitro models of glial cells were prepared. The wild-type (WT) and Nrf2 knockout (KO) mice were constructed to investigate the changes of mitophagy and apoptosis-related indicators by Western blotting. The experimental results showed that 24 h after TBI, the tissue structure was highly porous, the cells were highly edema, the neuronal space increased significantly, the neuron degeneration, and the cell vacuolation was obvious. Meanwhile, the number of apoptotic cells and the apoptosis rate of glial cells increased significantly. After injury, the relative expression of Parkin, Pink, Beclin and LC-3II proteins were significantly decreased in all mice. The protein expressions of Caspase3 and Caspase12 were significantly increased. However, in the TBI group, KO mice were more impaired than WT mice. In conclusion, Nrf2 plays a protective role by promoting mitophagy to inhibit apoptosis in the process of brain injury caused by hydraulic shock in mice, which provides a new idea for the effective treatment of brain injury.

The Effect of Different Optic Nerve Sheath Diameter Measurements Using Ultrasound to Assess Intracranial Pressure in Patients With Acute Brain Injury.

BACKGROUND: Optic nerve sheath diameter (ONSD) is a promising, noninvasive invasive intracranial pressure (ICP) measurement method. This study aims to analyze the differences in ONSD between the left and right eyeballs and the differences in ultrasonic measurement between the transverse and sagittal planes. METHODS: Data from a total of 50 eligible patients with various types of brain injury who were admitted to our hospital from May 2019 to June 2021 were analyzed. An ONSD assessment was then performed using Philips B-mode ultrasound, measuring ONSD 3 mm posterior to the eyeballs. The left and right ONSDs in the transverse and sagittal planes were measured. Intraparenchymal fiber optic sensors and catheters were inserted into the ventricles and connected to an external pressure transducer to measure ICP. RESULTS: A total of 164 sonographic measurements of ONSD were performed in 50 patients with brain injury in a prospective observational study. Statistically significant differences were found in ONSD between the transverse and sagittal planes. The difference in the left ONSD between the transverse and sagittal planes was 0.007 ± 0.030 cm (P = 0.003). The Spearman rank correlation test showed that the correlation coefficient between ICP and left/right ONSD in the transverse/sagittal planes was 0.495 vs 0.546 and 0.559 vs 0.605, respectively. The results showed that the areas under the curve of ONSD in the transverse and sagittal planes were 0.843 and 0.805, respectively. Medcalc software was used to compare the areas under the receiver operator characteristic curve, and the results showed that ONSD in the sagittal plane is generally better than in the transverse plane (P = 0.0145). CONCLUSIONS: This study found that ONSD in the sagittal plane is superior to the transverse plane regarding the comprehensive efficacy of ICP, and unilateral measurement is sufficient.

Can optic nerve sheath diameter assessment be used as a non-invasive tool to dynamically monitor intracranial pressure?

This study aims to detect whether the optic nerve sheath diameter (ONSD) can be used to dynamically monitor intracranial pressure (ICP). Adult patients undergoing invasive ICP monitoring on the day of admission are included in this study. For each patient, the ONSD is first measured in the supine position and then in the 30° head-up position. Subsequently, a dynamic test is conducted on 16 patients. The ONSD is measured in the supine position once a day for three consecutive days starting on the day of admission. There is a strong correlation between the ONSD and ICP values in the supine position on admission (r = 0.799), and when patients are changed from the supine to the 30° head-up position, the ICP and ONSD values decrease correspondingly. However, the change in ICP is not strongly correlated with the change in ONSD (r = 0.358). In the dynamic test, a good agreement between the ICP and ONSD only exists in three patients (18.8%), and three patients have completely different profiles for ICP and ONSD. These results suggest that the changes in the ONSD and ICP values are not closely correlated after dynamic observation. Therefore, measurement of the ONSD may not be a suitable tool to dynamically monitor ICP.

Controlled Hemorrhage Sensitizes Angiotensin II-Elicited Hypertension through Activation of the Brain Renin-Angiotensin System Independently of Endoplasmic Reticulum Stress.

Hemorrhagic shock is associated with activation of renin-angiotensin system (RAS) and endoplasmic reticulum stress (ERS). Previous studies demonstrated that central RAS activation produced by various challenges sensitizes angiotensin (Ang) II-elicited hypertension and that ERS contributes to the development of neurogenic hypertension. The present study investigated whether controlled hemorrhage could sensitize Ang II-elicited hypertension and whether the brain RAS and ERS mediate this sensitization. Results showed that hemorrhaged (HEM) rats had a significantly enhanced hypertensive response to a slow-pressor infusion of Ang II when compared to sham HEM rats. Treatment with either angiotensin-converting enzyme (ACE) 1 inhibitor, captopril, or ACE2 activator, diminazene, abolished the HEM-induced sensitization of hypertension. Treatment with the ERS agonist, tunicamycin, in sham HEM rats also sensitized Ang II-elicited hypertension. However, blockade of ERS with 4-phenylbutyric acid in HEM rats did not alter HEM-elicited sensitization of hypertension. Either HEM or ERS activation produced a greater reduction in BP after ganglionic blockade, upregulated mRNA and protein expression of ACE1 in the hypothalamic paraventricular nucleus (PVN), and elevated plasma levels of Ang II but reduced mRNA expression of the Ang-(1-7) receptor, Mas-R, and did not alter plasma levels of Ang-(1-7). Treatment with captopril or diminazene, but not phenylbutyric acid, reversed these changes. No treatments had effects on PVN protein expression of the ERS marker glucose-regulated protein 78. The results indicate that controlled hemorrhage sensitizes Ang II-elicited hypertension by augmenting RAS prohypertensive actions and reducing RAS antihypertensive effects in the brain, which is independent of ERS mechanism.

Diagnostic accuracy and clinical utility of a new noninvasive index for hepatic steatosis in patients with hepatitis B virus infection.

The aim of the present study was to construct a cost-effective noninvasive diagnostic index for prediction of hepatic steatosis in patients with hepatitis B virus(HBV) infection. From January 2011 to January 2015, a total of 364 consecutive subjects who underwent liver biopsies were enrolled. The Receiver-operating characteristic(ROC) curves and Obuchowski measure were constructed to evaluate the diagnostic accuracy of the new index. The AUROCs of steatosis index of patients with HBV infection (SIHBV) in predicting of steatosis were 0.929 (95% confidence interval:0.889-0.970, P < 0.05) in the model group and 0.855 (0.794-0.917, P < 0.05) in the validation group respectively. Comparisons of AUROCs demonstrated that SIHBV was significantly superior to Korean Score, fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product(LAP), and fatty liver disease (FLD) index for prediction of hepatic steatosis in model group and validation group(all P < 0.01). Especially for patients with hepatic steatosis percentage of 5.0-9.9% and 10.0-19.9%, SIHBV had a sensitivity of 63.6% and 79.2%, whereas it were 29.1% and 45.8% for Ultrasonography (all P < 0.05). In conclusion, as a cost-effective, simple, noninvasive, and readily available method, SIHBV may act as a massive screening tool before further examinations such as MRI, CT, transient elastography, or liver biopsy, especially for developing countries.

Risk factors responsible for the volume of hemorrhage in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a medical emergency with a high mortality and morbidity. There is a marked association of the ensuing neurological functional deficits following aSAH with the volume of hemorrhage. The volume of intracranial hemorrhage in aSAH is usually quantified by the revised Fisher grades. MATERIALS AND METHODS: A total of 155 patients who suffered from aSAH were evaluated for risk factors that led to an increased volume of intracranial hemorrhage. These included various demographic factors, the medical history, the preadmission blood pressure, and the aneurysm characteristics. RESULTS: The number of aneurysms was significantly related to poor revised Fisher grades (grade 3 or 4; P = 0.016). Thus, the presence of multiple aneurysms (2-4) was a significant risk factor responsible for a poor modified Fisher grade (odds ratio [OR] = 4.0, P = 0.004). Significantly higher risk of intracranial hemorrhage was also observed for aneurysms located on the the internal carotid artery (ICA), anterior communicating artery (ACOA), or middle cerebral artery (MCA) when compared with other sites (P < 0.001). Bleeding in ACOA was significantly associated with a poor Fisher's grade (OR = 4.3, P = 0.025). Additionally, the preadmission diastolic blood pressure (DBP) alone was significantly associated with a poor Fisher grade (P = 0.024). CONCLUSION: Preadmission DBP, multiple aneurysms, and aneurysms of the ACOA are associated with markedly increased volume of hemorrhage as evaluated by the revised Fisher grades. Thus, patients harboring an intracranial aneurysm having the above mentioned features should seek an early intervention in order to prevent the occurrence of aSAH.

Nomogram for hepatic steatosis: A simple and economical diagnostic tool for massive screening.

AIM: To establish a simple economical diagnostic tool for prediction of hepatic steatosis in patients with hepatitis B virus (HBV) infection. METHODS: From January 2006 to January 2015,a total of 1325 consecutive subjects who underwent liver biopsy were enrolled. According to the results of multivariate logistic regression analysis, a new nomogram was conducted. Then discrimination and calibration were conducted to assess the clinical diagnostic value of nomogram. RESULTS: The nomogram consisted of age, triglyceride (TG), low-density lipoprotein (LDL), uric acid (UA), haemoglobin (HGB). For prediction of hepatic steatosis, the AUROC of nomogram was 0.792 (95%CI: 0.758-0.826). With cut off value of 0.11, 699 (52.8%) of 1325 patients could be free from liver biopsy with a correct rate of 95.3% for diagnosis of hepatic steatosis. CONCLUSION: The nomogram for hepatic steatosis has a better clinical diagnostic value for prediction of hepatic steatosis in patients with HBV infection. From the perspective of cost-effectiveness and clinical practice, it is worth considering the use of the nomogram as a mass screening tool before further liver biopsy or imaging examinations.

Apolipoprotein E gene polymorphism and the risk of subarachnoid hemorrhage: a meta-analysis of case-control studies.

BACKGROUND: Studies investigating the association between the apolipoprotein E gene (APOE) polymorphism and the risk of subarachnoid hemorrhage (SAH) have reported inconsistent results. So we performed a meta-analysis to estimate the association between APOE polymorphism and SAH susceptibility. METHODS: Relevant studies published before 5 November 2015 were identified by searching PubMed, Embase, EBSCO, and ISI web of knowledge. The strength of relationship between the APOE gene and SAH susceptibility was assessed using odds ratio (OR) and corresponding 95 % confidence interval (95 % CI). RESULTS: A total number of six case-control studies including 638 SAH cases and 2,341 controls were identified. No association was found in dominant model or allele contrast genetic model (ε4 dominant model: OR = 1.06, 95 % CI = 0.91-1.25; ε3 dominant model: OR = 0.99, 95 % CI = 0.97-1.01; ε2 dominant model: OR = 0.99, 95 % CI = 0.78-1.25; ε4 versus ε3: OR = 1.14, 95 % CI = 0.96-1.35; ε4 versus ε2: OR = 1.07, 95 % CI = 0.90-1.28; ε3 versus ε2: OR = 1.00, 95 % CI = 0.96-1.04) for APOE polymorphism and SAH susceptibility. In the subgroup analyzed that was stratified by ethnicity, increased risk of SAH was found in Asian subjects when ε4 allele compared with ε3 allele (ε4 vs ε3, OR = 1.55, 95 % CI = 1.07-2.52). CONCLUSIONS: Our meta-analysis suggested that there is no association between APOE polymorphism and SAH risk for overall population. Due to several limitations in the present study, well-designed epidemiological studies with large sample size among different ethnicities should be performed in the future.

The Diagnostic Accuracy and Clinical Utility of Three Noninvasive Models for Predicting Liver Fibrosis in Patients with HBV Infection.

AIM: To evaluate the diagnostic accuracy and clinical utility of the fibrosis index based on the four factors (FIB-4), aspartate aminotransferase -to-platelet ratio index (APRI), and aspartate aminotransferase-alanine aminotransferase ratio index (AAR) for predicting liver fibrosis in patients with HBV infection. METHODS: From January 2006 to December 2010,a total of 1543 consecutive chronic hepatitis B(CHB) patients who underwent liver biopsies were enrolled. FIB-4,APRI, and AAR were calculated.The areas under the receiver-operating characteristic curves (AUROCs) were calculated to assess the diagnostic accuracy of these models.The AUROCs of these models were compared by DeLong's test.For further comparisons in different studies,the AUROCs were adjusted to conduct Adjusted AUROCs(ADjAUROCs) according to the prevalence of fibrosis stages using the difference between advanced and nonadvanced fibrosis (DANA). RESULTS: For prediction of significant fibrosis,severe fibrosis,and cirrhosis,the AUROCs of FIB-4 were 0.646(ADjAUROC 0.717),0.670(ADjAUROC 0.741), and 0.715(ADjAUROC 0.786) respectively;whereas it were 0.656(ADjAUROC 0.727),0.653(ADjAUROC 0.724) and 0.639(ADjAUROC 0.710) for APRI, 0.498(ADjAUROC 0.569),0.548(ADjAUROC 0.619) and 0.573(ADjAUROC 0.644) for AAR. The further comparisons demonstrated that there were no significant differences of AUROCs between FIB-4 and APRI in predicting significant and severe fibrosis(P > 0.05),while FIB-4 was superior to APRI in predicting cirrhosis(P < 0.001). Further subgroup analysis demonstrated that the diagnostic accuracy of FIB-4 and APRI in patients with normal alanine aminotransferase(ALT) were higher than that in patients with elevated ALT. CONCLUSIONS: The results demonstrated that FIB-4 and APRI are useful for diagnosis of fibrosis. FIB-4 and APRI have similar diagnostic accuracy in predicting significant and severe fibrosis,while FIB-4 is superior to APRI in predicting cirrhosis. The clinical utility of FIB-4 and APRI for fibrosis need further external validation in a large population before it was used for prediction of fibrosis in patients with HBV infection.

Treatment of acutely ruptured wide-necked intracranial aneurysms using self-expanding stent.

OBJECTIVES: To evaluate the effectiveness and safety of self-expanding stent in treatment of acutely ruptured wide-necked intracranial aneurysms in the acute stage. METHOD: Treatment of 38 patients with self-expanding stent was retrospectively analyzed. RESULTS: From January 2009 to May 2014, a total of 38 patients with 44 acutely ruptured wide-necked intracranial aneurysms were embolized with self-expanding stents at our center. Immediate post-operative imaging demonstrated that the aneurysms were densely packed in 17 patients, subtotally embolized in 2 patients, and subtotally embolized with residual aneurysm necks in 19 patients. At discharge, the patients were assessed for prognosis and the results revealed nerve dysfunction in 3 patients (7.9%), coma in 6 patients (15.8%), hospital death in 1 case (2.6%). Twenty-eight (73.7%) patients were asymptomatic at discharge. Ten of the 38 patients were followed up by angiography for a period of 3.7 months on average, which showed complete occlusion in 9 patients (90%), remnant aneurysm necks in 1 patient (10%), and no recanalization was observed in all the followed-up patients. Stent related complications also were recorded. CONCLUSION: Stent-assisted coiling is effective in treating acutely ruptured wide-necked intracranial aneurysms. Angiographic investigation and clinical follow-up is needed for evaluation of long-term clinical outcomes.