Protective and Promotive Factors in Migrant and Refugee Children Facing Violence: A Systematic Review.

Migrant and refugee children are at risk of experiencing various forms of violence before, during, or after migration. This study systematically identifies, reviews, and synthesizes evidence on protective and promotive factors that contribute to the resilience of migrant and refugee children facing violence. Of the 3,663 articles identified through search in five electronic databases and snowball technique, 31 quantitative or qualitative research studies met the inclusion criteria. To be included in the review, studies had to (1) have been published after 2013; (2) have been published in English; (3) include migrant or refugee children and/or adolescents aged 18 or below at the time of interview or migration; (4) mention some types of maltreatment, peer violence, or community violence faced by the children or adolescents; (5) examine the association between the hypothesized protective or promotive factors and indicators of adaptive functioning; and (6) include outcome measures that assessed adaptive functioning such as well-being or absence or low-levels of internalizing and externalizing problems. Quality assessment did not lead to the exclusion of any studies. Five levels of protective and promotive factors were identified: individual, family, school and peers, community, and spatial dimension, which converged to highlight the importance of regulatory, interpersonal, and meaning-making strengths for these children. Understanding and addressing these protective and promotive factors is crucial for promoting well-being and improving mental health outcomes in migrant and refugee children facing violence. The findings of this review have significant implications for designing intervention programs and public policies that support these children effectively.

Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: A multicenter, open-label, metabolic balance study.

BACKGROUND: Apraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide. METHODS: This was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-h fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks). RESULTS: PS volume decreased by -4702 mL/week (-52 %; p < 0.001) at week 52. Seven patients (78 %) achieved ≥1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253 g/day (p = 0.013). At 48 weeks, increases in wet weight absorption by 316 g/day (p = 0.039), energy absorption by 1134 kJ/day (p = 0.041) and carbohydrate absorption by 56.1 g/day (p = 0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7 cm (p = 0.012), duodenal wall thickness increased by 0.8 mm (p = 0.02) and motility in the proximal colon was reduced (p = 0.031). A total of 127 adverse events was reported, which were mostly mild to moderate. CONCLUSION: Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC. CLINICALTRIALS: gov, Number NCT04964986.

Extra-Limbic Seronegative Encephalitis Preceding Recurrent Hodgkin's Lymphoma and Gastric Diffuse Large B-Cell Lymphoma: A Case Report.

We describe a patient with extra-limbic seronegative encephalitis with relapsing progressive course as the harbinger of sequential Hodgkin's lymphoma and Diffuse Large B-Cell lymphoma. Diagnosis of probable paraneoplastic neurologic syndrome (PNS) was arrived at by exhaustive elimination of alternative causes and supportive tissue diagnosis. This case highlights the phenotypic variety of paraneoplastic neurologic syndromes associated with hematologic malignancies and the challenges in their recognition, diagnosis, and treatment. We discuss and apply the updated consensus diagnostic criteria for paraneoplastic syndromes to our case as a means of bolstering probability in cases of diagnostic uncertainty.

Clinicians' Use of Choice Framing in ICU Family Meetings.

OBJECTIVES: To quantify the frequency and patterns of clinicians' use of choice frames when discussing preference-sensitive care with surrogate decision-makers in the ICU. DESIGN: Secondary sequential content analysis. SETTING: One hundred one audio-recorded and transcribed conferences between surrogates and clinicians of incapacitated, critically ill adults from a prospective, multicenter cohort study. SUBJECTS: Surrogate decision-makers and clinicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four coders identified preference-sensitive decision episodes addressed in the meetings, including topics such as mechanical ventilation, renal replacement, and overall goals of care. Prior critical care literature provided specific topics identified as preference-sensitive specific to the critical care context. Coders then examined each decision episode for the types of choice frames used by clinicians. The choice frames were selected a priori based on decision science literature. In total, there were 202 decision episodes across the 101 transcripts, with 20.3% of the decision episodes discussing mechanical ventilation, 19.3% overall goals of care, 14.4% renal replacement therapy, 14.4% post-discharge care (i.e., discharge location such as a skilled nursing facility), and the remaining 32.1% other topics. Clinicians used default framing, in which an option is presented that will be carried out if another option is not actively chosen, more frequently than any other choice frame (127 or 62.9% of decision episodes). Clinicians presented a polar interrogative, or a "yes or no question" to accept or reject a specific care choice, in 43 (21.3%) decision episodes. Clinicians more frequently presented options emphasizing both potential losses and gains rather than either in isolation. CONCLUSIONS: Clinicians frequently use default framing and polar questions when discussing preference-sensitive choices with surrogate decision-makers, which are known to be powerful nudges. Future work should focus on designing interventions promoting the informed use of these and the other most common choice frames used by practicing clinicians.

Chinese Women's Acceptance of Intimate Partner Violence Against Women.

Few studies have empirically examined factors influencing attitudes toward acceptance of intimate partner violence (IPV), and no study has yet studied the topic in China. We empirically test the effects of attitudes toward gender roles and exposure to violence during childhood on the acceptance of IPV and the moderating effects of education and income on these relationships. Using survey data collected from 600 Chinese women from southern China, we found that education and income moderate the relationship between belief in gender equality and acceptance of IPV. The effect of exposure to parental physical violence on the acceptance of IPV is moderated by education.

A qualitative study on how intimate partner violence against women changes, escalates, and persists from pre- to postseparation.

Research has focused on intimate partner violence (IPV) against women either before or after separation, but little attention has been paid to the changes in and persistence of violent behaviors from one situation to the next. This study contributes to the literature by comparing the changes in types and frequencies of abusive behaviors of women's former husbands. This allows us to understand how mechanisms of power are enacted through IPV both before and after separation. We interviewed 19 women in the Midwestern United States who had experienced IPV by their former husbands and had subsequently divorced them. Data were analyzed using qualitative content analysis. The findings suggest that verbal abuse and using children were the most common forms of IPV both pre- and postseparation. Many preseparation behaviors were replaced by other forms of abuse; for example, physical abuse was not experienced after separation. Some forms of IPV, such as stalking and economic abuse, escalated after separation. This reveals that exerting control over women through nonphysical forms of IPV was more common after separation. In particular, using axial and selective coding approach, our findings present three composite narratives of women's experiences of the changes in, and the escalation and persistence of, the violence they faced. The three composite narratives show how abusive behaviors are situated within patriarchal notions of dominance, power, and control over women and their children. The implications of the findings are discussed in terms of healthcare services, advocacy-based victim assistance, school officials, and the courts.

Chinese Women's Financial Independence and Their Intimate Partner Violence Victimization Experiences.

China, as a traditional patriarchal society, provides an excellent context to examine whether and how increased financial independence of women may influence intimate partner violence. This study examines how financial independence influences Chinese women's victimization experiences of physical violence, psychological violence, controlling behavior, and sexual abuse. Data were collected from 600 married or divorced women aged between 20 and 60, who resided in a large metropolitan area in Southern China. Results indicated that while physical violence is reduced by women's financial independence, other forms of connective IPV against women are suggested as expressions of men's desire to keep financially independent women in place.

Telehealth for patients with diabetes.

ABSTRACT: New challenges like the COVID-19 pandemic have forced healthcare professionals to find alternative ways to manage the health of individuals living with diabetes. This article discusses the evolution of telehealth in diabetes management and cites a case study to examine the gaps and identify nursing strategies for implementation.

The Applicability of Social Structure and Social Learning Theory to Explain Intimate Partner Violence Perpetration Across National Contexts.

Intimate partner violence (IPV) affects men and women worldwide. However, a comprehensive examination of the etiology of IPV perpetration across national contexts is limited. Since Aker's Social Structure and Social Learning (SSSL) theory was developed as a general theory of crime, national differences in social structure should explain social learning, which in turn should explain IPV perpetration. Therefore, the current study tests the applicability of SSSL and the mediation effect of the social learning process on the connection between social structural factors and IPV perpetration. Data on IPV perpetration by both male and female college students in 30 nations were taken from the International Dating Violence Study. Structural-level indicators of gender equality for individual nations were taken from Global Gender Gap Index. Findings suggest that national-level gender equality is partially mediated by definitions favorable to breaking the law; a component of SSSL theory. However, other components of the social learning process, such as differential association, differential reinforcement, and imitation, were not found to have mediating effects. The findings only partially support SSSL theory that social learning variables mediate the effect of gender equality on IPV perpetration. Implications of the findings are discussed.

Evaluation of Diagnostic Accuracy Following the Coadministration of Delta-Aminolevulinic Acid and Second Window Indocyanine Green in Rodent and Human Glioblastomas.

PURPOSE: Fluorescence-guided-surgery offers intraoperative visualization of neoplastic tissue. Delta-aminolevulinic acid (5-ALA), which targets enzymatic abnormality in neoplastic cells, is the only approved agent for fluorescence-guided neurosurgery. More recently, we described Second Window Indocyanine Green (SWIG) which targets neoplastic tissue through enhanced vascular permeability. We hypothesized that SWIG would demonstrate similar clinical utility in identification of high-grade gliomas compared with 5-ALA. PROCEDURES: Female C57/BL6 and nude/athymic mice underwent intracranial implantation of 300,000 GL261 and U87 cells, respectively. Tumor-bearing mice were euthanized after administration of 5-ALA (200 mg/kg intraperitoneal) and SWIG (5 mg/kg intravenous). Brain sections were imaged for protoporphyrin-IX and ICG fluorescence. Fluorescence and H&E images were registered using semi-automatic scripts for analysis. Human subjects with HGG were administered SWIG (2.5 mg/kg intravenous) and 5-ALA (20 mg/kg oral). Intraoperatively, tumors were imaged for ICG and protoporphyrin-IX fluorescence. RESULTS: In non-necrotic tumors, 5-ALA and SWIG demonstrated 90.2 % and 89.2 % tumor accuracy (p value = 0.52) in U87 tumors and 88.1 % and 87.7 % accuracy (p value = 0.83) in GL261 tumors. The most distinct difference between 5-ALA and SWIG distribution was seen in areas of tumor-associated necrosis, which often showed weak/no protoporphyrin-IX fluorescence, but strong SWIG fluorescence. In twenty biopsy specimens from four subjects with HGG, SWIG demonstrated 100 % accuracy, while 5-ALA demonstrated 75-85 % accuracy; there was 90 % concordance between SWIG and 5-ALA fluorescence. CONCLUSION: Our results provide the first direct comparison of the diagnostic utility of SWIG vs 5-ALA in both rodent and human HGG. Given the broader clinical utility of SWIG compared with 5-ALA, our data supports the use of SWIG in tumor surgery to improve the extent of safe resections. CLINICAL TRIAL: NCT02710240 (US National Library of Medicine Registry; https://www.clinicaltrials.gov/ct2/show/NCT02710240?id=NCT02710240&draw=2&rank=1 ).

Complication Rates During Endoscopic Microvascular Decompression Surgery Are Low With or Without Petrosal Vein Sacrifice.

OBJECTIVE: Endoscopic-microvascular decompression (E-MVD) is a well-described treatment for trigeminal neuralgia (TGN), but there has been debate on the safety of intraoperative sacrifice of the petrosal vein (PV) due to concern for subsequent venous insufficiency. Our objective was to investigate the risk of PV sacrifice during E-MVD in TGN and subsequent postoperative complications and pain outcomes. METHODS: 5 five-year review yielded 201 patients who underwent MVD for TGN. PV sacrifice, vascular compressive anatomy, and postoperative complications attributable to venous insufficiency were analyzed. Preoperative and postoperative pain outcomes were analyzed. RESULTS: PV was sacrificed in 118 of 201 (59%) of patients, with 43 of 201 (21%) patients undergoing partial sacrifice versus 75 of 201 (37%) with complete sacrifice. No cases of venous infarction, cerebellar swelling, or fatal complications were noted in either cohort. Non-neurologic complications occurred in 1.69% (2 of 118) of patients with PV sacrifice and 0% (0 of 83) of patients with PV preservation. Neurologic deficits (facial palsy, conductive hearing loss, gait instability, memory deficit) occurred in equal proportions in PV preservation and sacrifice groups (2.41% vs. 1.69%) Overall, 87.3% (145 of 166) patients reported their pain as "very much improved" or "much improved" at 1 month, and no difference between groups was identified. CONCLUSIONS: This study did not find higher complication rates in patients undergoing petrosal vein sacrifice during E-MVD for trigeminal neuralgia. In this series where petrosal vein was sacrificed only 59% of the time, it appears to be a safe technique, but larger studies will be needed to determine true incidence of complications after PV sacrifice.

Obstructive Sleep Apnea and Non-alcoholic Fatty Liver Disease in Obese Patients Undergoing Bariatric Surgery.

BACKGROUND: Morbid obesity is associated with multiple comorbidities including obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD). It has been suggested that OSA may contribute to NAFLD pathogenesis due to intermittent nocturnal hypoxia. PURPOSE: The objective of this study was to assess the apnea-hypopnea index (AHI) and lower minimum oxygen saturation, markers of OSA, in patients undergoing bariatric surgery (BSx) with perioperative liver biopsy to detect NAFLD. METHODS: This was a single center cross-sectional study of 61 patients undergoing BSx who consented to have a perioperative wedged liver biopsy. Biochemical, clinical, anthropometric variables, and a sleep study test were performed prior to BSx. RESULTS: NAFLD was diagnosed in 49 (80.3%) patients; 12 had normal liver (NL). Those with NAFLD had significantly higher (p < 0.05) AST (42.6 vs 18.1 U/L) and ALT (35.0 vs 22.1 U/L) but similar clinical, anthropometric, and metabolic parameters to NL. There was a higher AHI (32.03 vs 14.35) and significantly lower minimum oxygen saturation (SaO2) (78.87 vs 85.63) in NAFLD compared with NL (p < 0.05). When assessing associations between OSA parameters and liver histology in NAFLD, AHI correlated significantly with lobular inflammation (p < 0.05). In a multivariate analysis, BMI was significantly correlated with lobular inflammation with mean SaO2 nearing significance. CONCLUSIONS: These results indicate that in a homogeneous bariatric population sample with similar characteristics, those with NAFLD had higher AHI and lower minimum SaO2 compared with NL. AHI correlated with liver inflammation suggesting a potential role for intermittent nocturnal hypoxia in the pathogenesis and progression of NAFLD.

Investigating association of perineural invasion on prostate biopsy with Gleason score upgrading at prostatectomy: A multi-institutional analysis.

BACKGROUND: The significance of perineural invasion (PNI) in prostate cancer (PC) is unclear. A recent report of patients with pT2N0R0 PC found that PNI at prostatectomy was independently associated with higher Gleason score and more diffuse prostatic disease. We aimed to test our hypothesis that PNI on prostate biopsy in pT2N0R0 patients is associated with increased Gleason score upgrading at prostatectomy. METHODS: We identified 2892 patients status post prostatectomy with pT2N0R0 PC from three institutions, diagnosed between 1 January 2008 and 31 December 2014. Multivariable logistic regression (MVA) was used to evaluate the association between prostate biopsy PNI status and surgical Gleason upgrading, while controlling for potential confounders. RESULTS: Of the 2892 patients identified, 14% had PNI on biopsy, of whom 21% had surgical Gleason upgrading, while 28% without PNI on biopsy had such upgrading (P < .01). On MVA, the odds ratio (OR) of surgical Gleason upgrading for patients with biopsy PNI relative to patients without biopsy PNI was 0.69 (P < .01). The variables associated with surgical Gleason upgrading were age ≤60 years (OR 1.22, P = .02) and preoperative PSA >4 ng/mL (OR 1.26, P = .02). CONCLUSIONS: In post-prostatectomy patients with favorable-risk PC, PNI on prostate biopsy was not associated with surgical Gleason score upgrading. This may be due to the association of PNI with more diffuse disease, leading to increased biopsy tumor yield and grading accuracy. These findings suggest that in this setting, biopsy PNI alone should not be a concern for more aggressive disease requiring pathologic confirmation or intervention. This may help guide treatment decision-making for men debating active surveillance, radiation, and surgery.

Near-Infrared Imaging with Second-Window Indocyanine Green in Newly Diagnosed High-Grade Gliomas Predicts Gadolinium Enhancement on Postoperative Magnetic Resonance Imaging.

PURPOSE: Intraoperative molecular imaging with tumor-targeting fluorophores offers real-time detection of neoplastic tissue. The second window indocyanine green (SWIG) technique relies on passive accumulation of indocyanine green (ICG), a near-infrared fluorophore, in neoplastic tissues. In this study, we explore the ability of SWIG to detect neoplastic tissue and to predict postoperative magnetic resonance imaging (MRI) findings intraoperatively. PROCEDURES: Retrospective data were collected from 36 patients with primary high-grade gliomas (HGG) enrolled as part of a larger trial between October 2014 and October 2018. Patients received systemic ICG infusions at 2.5-5 mg/kg 24 h preoperatively. Near-infrared fluorescence was recorded throughout the case and from biopsy specimens. The presence/location of residual SWIG signal after resection was compared to the presence/location of residual gadolinium enhancement on postoperative MRI. The extent of resection was not changed based on near-infrared imaging. RESULTS: All 36 lesions demonstrated strong near-infrared fluorescence (signal-to-background = 6.8 ± 2.2) and 100 % of tumors reaching the cortex were visualized before durotomy. In 78 biopsy specimens, near-infrared imaging demonstrated higher sensitivity and accuracy than white light for diagnosing neoplastic tissue intraoperatively. Furthermore, near-infrared imaging predicted gadolinium enhancement on postoperative MRI with 91 % accuracy, with visualization of residual enhancement as small as 0.3 cm3. Patients with no residual near-infrared signal after resection were significantly more likely to have complete resection on postoperative MRI (p value < 0.0001). CONCLUSIONS: Intraoperative imaging with SWIG demonstrates highly sensitive detection of HGG tissue in real time. Furthermore, post-resection near-infrared imaging correlates with postoperative MRI. Overall, our findings suggest that SWIG can provide surgeons with MRI-like results in real time, potentially increasing resection rates.

Near-infrared intraoperative molecular imaging with conventional neurosurgical microscope can be improved with narrow band "boost" excitation.

BACKGROUND: Intraoperative visualization of brain tumors with near-infrared (NIR)-fluorescent dyes is an emerging method for tumor margin approximation but are limited by existing fluorescence detection platforms. We previously showed that a dedicated NIR imaging platform outperformed a state-of-the-art neurosurgical microscope in fluorescence signal characteristics. This study examined whether conventional neurosurgical microscope NIR signal could be improved with the addition of a narrow wavelength excitation source. METHODS: Imaging was conducted with a broad-spectrum neurosurgical microscope and commercial near-infrared module. Addition of an 805-nm laser was used to "boost" NIR excitation of indocyanine green (ICG). In vitro quantification was performed on serial dilutions of ICG. Patients underwent tumor resection with delayed 24-h imaging of ICG infusion. NIR fluorescence of dura, cortex, or tumor was quantified from images prior to (pre-boost) and following added excitation with the laser (post-boost). Signal to background ratio (SBR) of pre- and post-boost was calculated as a readout of image enhancement. RESULTS: In vitro, excitation boost effected a 29% increase in mean SBR in six serial dilutions of ICG. Intraoperative boost was performed in 11 patients including meningioma, glioblastoma multiforme, and metastases. Increase in tumor fluorescence was pronounced under direct tumor visualization. Across all patients, boost excitation resulted in 35% mean improvement from pre-boost SBR (p < 0.001). CONCLUSION: Neurosurgical microscopes remain the preferred method of visualizing tumor during intracranial surgery. However, current modalities for NIR signal detection are suboptimal. We demonstrate that augmentation of a fluorescence microscope module with a focused excitation source is a simple mechanism of improving NIR tumor visualization. CLINICAL TRIAL REGISTRATION: NCT03262636.

Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials.

Fluorescence imaging is an emerging clinical technique for real-time intraoperative visualization of tumors and their boundaries. Though multiple fluorescent contrast agents are available in the basic sciences, few fluorescence agents are available for clinical use. Of the clinical fluorophores, delta aminolevulinic acid (5ALA) is unique for generating visible wavelength tumor-specific fluorescence. In 2017, 5ALA was FDA-approved for glioma surgery in the United States. Additionally, clinical studies suggest this agent may have utility in surgical subspecialties outside of neurosurgery. Data from dermatology, OB/GYN, urology, cardiothoracic surgery, and gastrointestinal surgery show 5ALA is helpful for intraoperative visualization of malignant tissues in multiple organ systems. This review summarizes data from English-language 5ALA clinical trials across surgical subspecialties. Imaging systems, routes of administration, dosing, efficacy, and related side effects are reviewed. We found that modified surgical microscopes and endoscopes are the preferred imaging devices. Systemic dosing across surgical specialties range between 5 and 30 mg/kg bodyweight. Multiple studies discussed potential for skin irritation with sun exposure, however this side effect is infrequently reported. Overall, 5ALA has shown high sensitivity for labeling malignant tissues and providing a means to visualize malignant tissue not apparent with standard operative light sources.

Ocrelizumab infusion experience in patients with relapsing and primary progressive multiple sclerosis: Results from the phase 3 randomized OPERA I, OPERA II, and ORATORIO studies.

BACKGROUND: Ocrelizumab is an infusible humanized monoclonal antibody that selectively depletes CD20+ B cells. Infusion-related reactions (IRRs) were summarized from the OPERA I, OPERA II, and ORATORIO trials for relapsing and primary progressive multiple sclerosis (MS). METHODS: OPERA I and OPERA II were identical, randomized, double-blind, active-controlled trials that enrolled patients with relapsing MS (RMS). Patients in the ocrelizumab group initially received two 300-mg intravenous (IV) infusions separated by 14 days (on Days 1 and 15); subsequent doses were administered as single 600-mg IV infusions. Ocrelizumab-treated patients also received subcutaneous (SC) placebo injections 3 times weekly. Patients in the active comparator group received SC injections of IFN ß-1a 3 times weekly, as well as placebo infusions on Days 1 and 15 and Weeks 24, 48, and 72. ORATORIO was a randomized, parallel-group, double-blind, placebo-controlled study that enrolled patients with primary progressive MS (PPMS). As in the OPERA studies, patients in the ocrelizumab group initially received two 300-mg infusions separated by 14 days; however, ORATORIO patients continued to receive this divided-dose regimen throughout the study. The ORATORIO control group received IV placebo. Prior to each infusion, all patients in the OPERA and ORATORIO studies were pretreated with 100 mg IV methylprednisolone; additional prophylactic treatment with analgesics, antipyretics, and/or an IV or oral antihistamine was optional. IRRs were defined as adverse events that occurred during or within 24 h of IV infusion of ocrelizumab or placebo. RESULTS: Safety analyses included 1651 patients with RMS from OPERA I and OPERA II (ocrelizumab, n = 825; IFN ß-1a, n = 826) and 725 patients with PPMS from ORATORIO (ocrelizumab, n = 486; placebo, n = 239). Across studies, IRRs were reported in 34.3% (vs 9.7% with IFN ß-1a) and 39.9% (vs 25.5% with placebo) of ocrelizumab-treated patients in the pooled OPERA and ORATORIO populations, respectively. The majority of IRRs were mild to moderate in the OPERA (ocrelizumab, 92.6%; IFN ß-1a, 98.8%) and ORATORIO (ocrelizumab, 96.9%; placebo, 93.4%) studies. IRRs most commonly occurred with the first infusion. Severe IRRs were reported in 2.4% of ocrelizumab-treated patients in the OPERA studies (vs 0.1% with IFN ß-1a) and 1.2% of ocrelizumab-treated patients in ORATORIO (vs 1.7% with placebo). Two serious IRRs occurred across the OPERA studies, both of which occurred with the initial infusion. The first event occurred in an IFN ß-1a-treated patient in association with the initial infusion of IV placebo and consisted of severe balance disorder, dizziness, flushing, and hypoesthesia. The second event was a life-threatening reaction (bronchospasm) that occurred in an ocrelizumab-treated patient 15 min after the infusion started. Frequently reported IRR symptoms included pruritus, rash, throat irritation, and flushing. Premedication use, particularly antihistamines, was associated with fewer IRRs. CONCLUSION: Findings from the OPERA I, OPERA II, and ORATORIO trials show that IRRs were the most frequently reported adverse events with ocrelizumab, were mostly mild to moderate in severity, were reduced with appropriate pretreatment, and decreased with subsequent dosing. IRRs that did occur were effectively managed through infusion rate adjustment and symptomatic treatment.

Intraoperative Molecular Imaging with Second Window Indocyanine Green Facilitates Confirmation of Contrast-Enhancing Tissue During Intracranial Stereotactic Needle Biopsy: A Case Series.

BACKGROUND: Stereotactic needle biopsy provides a minimally invasive option for the diagnosis of intracranial lesions but is limited by inconclusive diagnoses on frozen pathology. For rapid pathology, 5-aminovelunic acid and sodium fluorescein have previously demonstrated potential as diagnostic adjuvants. Stereotactic biopsy with near-infrared (NIR) fluorophores has not been reported. We identified 5 representative cases using NIR fluorescent dye indocyanine green (ICG) administered in a high dose, delayed manner. METHODS: Five patients underwent second window indocyanine green (SWIG)-guided stereotactic biopsy for diagnosis of suspected glioma or tumor recurrence. Up to 5 mg/kg ICG was administered approximately 24 hours prior to surgery. Biopsies were conducted in the standard fashion, targeting regions of suspected tumor using intraoperative frameless navigation. Samples were examined intraoperatively under standard visible light and for fluorescence using conventional NIR imaging platforms. Findings were correlated with frozen and final tumor pathology for all cases. RESULTS: A total of 10 biopsy specimens were obtained. Three did not fluoresce and did not demonstrate tumor on preliminary or final pathology, including a non-gadolinium-enhancing sample taken proximal to the final target. The remaining 7 fluoresced, of which 6 contained tumor and 1 contained necrosis. Fluorescence was also noted in a patient with radiation treatment effect. Overall fluorescence characteristics were highly concordant with preliminary and final diagnoses. CONCLUSIONS: SWIG provides rapid intraoperative confirmation of pathologic brain tissue by permeating neoplastic or inflammatory brain tissue via a mechanism similar to that of gadolinium enhancement. SWIG-guided stereotactic biopsy can improve surgical efficiency by enhancing confidence in acquisition of target tissue.

Dual inhibition of PI3K signaling and histone deacetylation halts proliferation and induces lethality in mantle cell lymphoma.

The dysregulation of PI3K signaling has been implicated as an underlying mechanism associated with resistance to Bruton's tyrosine kinase inhibition by ibrutinib in both chronic lymphocytic leukemia and mantle cell lymphoma (MCL). Ibrutinib resistance has become a major unmet clinical need, and the development of therapeutics to overcome ibrutinib resistance will greatly improve the poor outcomes of ibrutinib-exposed MCL patients. CUDC-907 inhibits both PI3K and HDAC functionality to exert synergistic or additive effects. Therefore, the activity of CUDC-907 was examined in MCL cell lines and patient primary cells, including ibrutinib-resistant MCL cells. The efficacy of CUDC-907 was further examined in an ibrutinib-resistant MCL patient-derived xenograft (PDX) mouse model. The molecular mechanisms by which CUDC-907 dually inhibits PI3K and histone deacetylation were assessed using reverse protein array, immunoblotting, and chromatin immunoprecipitation (ChIP) coupled with sequencing. We showed evidence that CUDC-907 treatment increased histone acetylation in MCL cells. We found that CUDC-907 caused decreased proliferation and increased apoptosis in MCL in vitro and in vivo MCL models. In addition, CUDC-907 was effective in inducing lethality in ibrutinib-resistant MCL cells. Lastly, CUDC-907 treatment increased histone acetylation in MCL cells. Overall, these studies suggest that CUDC-907 may be a promising therapeutic option for relapsed or resistant MCL.

Non-alcoholic fatty liver disease and obesity: the role of the gut bacteria.

Non-alcoholic fatty-liver disease (NAFLD) is now considered one of the leading causes of liver disease worldwide and is associated with metabolic syndrome and obesity. There are several factors contributing to the disease state. Recent research suggests that the intestinal microbiota (IM) and bacterial products may play a role through several mechanisms which include increased energy uptake, intestinal permeability and chronic inflammation. In addition to diet and exercise, treatment options targeting the IM are being investigated and include the use of pre-, pro- and synbiotics as well as the possibility of fecal microbial transfers. This literature review explores the relationship between NAFLD and the IM as well as highlight new IM treatment options that may become available in the near future.