Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma that frequently becomes chemoresistant over time. The distinct mechanisms of ibrutinib and lenalidomide provided a judicious rationale to explore the combination with anti-CD20 immunotherapy. In this phase 1b study (NCT02446236), patients (n = 25) with relapsed/refractory MCL received rituximab with escalating doses of lenalidomide (days 1-21) and ibrutinib 560 mg (days 1-28) of 28-day cycles. The MTD for lenalidomide was 20 mg; most common grade ≥3 adverse events were skin rashes (32%) and neutropenic fever (24%). The best ORR was 88%, CR rate was 83%, and median duration of response (DOR) was 36.92 months (95% CI 33.77, 51.37). Responses were seen even in refractory patients or with high-risk features (e.g. blastoid variant, TP53 mutation, Ki-67 > 30%). R2I was safe and tolerable in patients with R/R MCL.

A systematic review of psychological, clinical and psychosocial correlates of perceived food intolerance.

OBJECTIVE: Perceived food intolerance (PFI) is a distressing condition reported by 3% - 35% of individuals, whereas prevalence of food allergy is 0.9%-3%. The present paper aims to systematically review the evidence for psychological, clinical and psychosocial factors associated with PFI in order to advance the current understanding. METHODS: Articles published from 1970 until October 2020 were identified. Case-control, prospective cohort, cross-sectional and retrospective studies published in English that a) included a subject population of adults over 18 with PFI and b) examined psychological, clinical and/or psychosocial factors of PFI were reviewed against inclusion criteria. Methodological quality was assessed, data extracted, and a narrative synthesis conducted. RESULTS: Of 2864 abstracts identified, thirty-six articles met inclusion criteria. Evidence consistently found PFI is associated with female sex, and individuals with PFI often report physical health complaints including gastrointestinal and extraintestinal symptoms, and gastrointestinal and atopic conditions. Evidence for an association between psychological factors and PFI was inconsistent, although some suggested increased levels of common mental disorders and distress. Findings regarding psychosocial factors were mixed and sociodemographic data were infrequently collected. CONCLUSIONS: PFI is associated with female sex and gastrointestinal and extraintestinal complaints. Limited high-quality evidence supports the role of psychological factors associated with PFI. High-quality research using prospective and longitudinal designs with multivariate analyses is needed. Future research should explore modifiable psychological factors as potential targets for intervention and identify clinical and psychosocial risk factors of PFI to aid in formulating a biopsychosocial model of PFI.

IgA Monoclonal Gammopathy of Undetermined Significance and Complication of Streptococcus mitis Bacteremia.

This case presents a patient with bacteremia of an unusual organism with a history of monoclonal gammopathy of undetermined significance (MGUS). MGUS is typically thought to be asymptomatic until potential progression of the disease. This case reports a patient with a history of MGUS who does not show disease progression, however, may be showing symptoms, such as immunodeficiency. This case displays bacteremia with Streptococcus mitis within a two-week period of an invasive procedure. Recent studies parallel this case by showing MGUS patients may have two times the risk of infections compared to the unaffected population. This report brings up the question of taking prophylactic measures for this patient population to prevent future complications.

Use of Anti-Interleukin-6 Receptor Monoclonal Antibody in Drug-Induced Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a disorder that involves the activation of alveolar macrophages triggering the innate immune system. The parenchymal lung injury seen in ARDS is a result of many proinflammatory elevations including interleukin-6. There remains no effective standard of care of ARDS, and current treatments at this time currently do not target the immunological mechanisms or pathways involved. Treatments involving this pathway should be further investigated as targeted treatment. We discuss a case of a patient with multiple myeloma who was hospitalized with drug-induced ARDS who had a rapid response to an anti-interleukin-6 monoclonal antibody.

Feasibility of remotely supervised transcranial direct current stimulation and cognitive remediation: A systematic review.

With technological advancements and an aging population, there is growing interest in delivering interventions at home. Transcranial Direct Current Stimulation (tDCS) and Cognitive Remediation (CR) as well as Cognitive Training (CT) have been widely studied, but mainly in laboratories or hospitals. Thus, the objectives of this review are to examine feasibility and the interventions components to support the domiciliary administration of tDCS and CR. We performed a systematic search of electronic databases, websites and reference lists of included articles from the first date available until October 31, 2018. Articles included had to meet the following criteria: original work published in English using human subjects, majority of tDCS or CR intervention administered remotely. A total of 39 studies were identified (16 tDCS, 23 CR/CT, 5 using both tDCS & CT). Four studies were single case studies and two were multiple case studies. The remaining 33 studies had a range of 9-135 participants. Five tDCS and nine CR/CT studies were double blind randomized controlled trials. Most studies focused on schizophrenia (8/39) and multiple sclerosis (8/39). Literature examined suggests the feasibility of delivering tDCS or CR/CT remotely with the support of information and communication technologies.

White matter injury in term neonates with congenital heart diseases: Topology & comparison with preterm newborns.

BACKGROUND: Neonates with congenital heart disease (CHD) are at high risk of punctate white matter injury (WMI) and impaired brain development. We hypothesized that WMI in CHD neonates occurs in a characteristic distribution that shares topology with preterm WMI and that lower birth gestational age (GA) is associated with larger WMI volume. OBJECTIVE: (1) To quantitatively assess the volume and location of WMI in CHD neonates across three centres. (2) To compare the volume and spatial distribution of WMI between term CHD neonates and preterm neonates using lesion mapping. METHODS: In 216 term born CHD neonates from three prospective cohorts (mean birth GA: 39 weeks), WMI was identified in 86 neonates (UBC: 29; UCSF: 43; UCZ: 14) on pre- and/or post-operative T1 weighted MRI. WMI was manually segmented and volumes were calculated. A standard brain template was generated. Probabilistic WMI maps (total, pre- and post-operative) were developed in this common space. Using these maps, WMI in the term CHD neonates was compared with that in preterm neonates: 58 at early-in-life (mean postmenstrual age at scan 32.2 weeks); 41 at term-equivalent age (mean postmenstrual age at scan 40.1 weeks). RESULTS: The total WMI volumes of CHD neonates across centres did not differ (p = 0.068): UBC (median = 84.6 mm3, IQR = 26-174.7 mm3); UCSF (median = 104 mm3, IQR = 44-243 mm3); UCZ (median = 121 mm3, IQR = 68-200.8 mm3). The spatial distribution of WMI in CHD neonates showed strong concordance across centres with predilection for anterior and posterior rather than central lesions. Predominance of anterior lesions was apparent on the post-operative WMI map relative to the pre-operative map. Lower GA at birth predicted an increasing volume of WMI across the full cohort (41.1 mm3 increase of WMI per week decrease in gestational age; 95% CI 11.5-70.8; p = 0.007), when accounting for centre and heart lesion. While WMI in term CHD and preterm neonates occurs most commonly in the intermediate zone/outer subventricular zone there is a paucity of central lesions in the CHD neonates relative to preterms. CONCLUSIONS: WMI in term neonates with CHD occurs in a characteristic topology. The spatial distribution of WMI in term neonates with CHD reflects the expected maturation of pre-oligodendrocytes such that the central regions are less vulnerable than in the preterm neonates.