Building blocks for a happy life: Longitudinal associations between early life income, mentorship and later well-being.

Longitudinal data from the Panel Study of Income Dynamics (PSID; N = 2996) were used to test hypotheses about the link between well-being and financial and social developmental resources. Results suggest that higher average family income from birth to age 18, and personal and professional mentoring received between 17 and 30, were positively associated with indicators of positive well-being and negatively related to negative indicators of well-being. Interactions between early life family income and mentoring during emerging adulthood were not significant predictors of any of the well-being outcomes. In all cases, the magnitudes of the coefficients became larger when simultaneously accounting for early life income, emerging adulthood mentoring, and their interactions-suggesting that financial and social resources in earlier life are independently linked to later life well-being. Findings highlight that mentoring received in emerging adulthood benefits downstream hedonic and eudemonic well-being, regardless of financial resources.

Hepatitis B virus reactivation in seronegative occult hepatitis B patient receiving ibrutinib therapy.

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment for several mature B-cell malignancies. Reactivation of hepatitis B virus (HBV) is a well-described complication in patients with chronic HBV infection or prior HBV exposure undergoing cytotoxic or immunosuppressive chemotherapy for hematologic malignancies. This phenomenon has been frequently reported with rituximab. However, published data on the risk of HBV reactivation induced by ibrutinib are scarce. Cases of HBV reactivation in hematologic patients receiving ibrutinib therapy have recently been described, but limited only to overt hepatitis B patients or seropositive occult hepatitis B patients. CASE PRESENTATION: We report the first case of HBV reactivation during ibrutinib treatment in an asymptomatic 82-year-old woman with seronegative occult hepatitis B patient (i.e., negative for HBsAg, anti-HBc and anti-HBs). Four months after ibrutinib treatment, her liver function test (LFT) was deranged, with seroconversion to HBsAg positivity. Serum hepatitis B virus DNA was quantified to be 1.92 × 108 IU/ml. Antiviral treatment was initiated, and viral load was gradually suppressed with improvement in LFT. CONCLUSIONS: Our case illustrated that in populations with a high incidence of HBV exposure, systematic screening for HBV exposure is essential prior to ibrutinib treatment, followed by serial monitoring of serologic and molecular markers of hepatitis B. There is a need for an international consensus to support the recommendation of antiviral prophylaxis against HBV reactivation in patients using ibrutinib.

In situ x-ray absorption investigations of a heterogenized molecular catalyst and its interaction with a carbon nanotube support.

A highly active heterogenized molecular CO2 reduction catalyst on a conductive carbon support is investigated to identify if its improved catalytic activity can be attributed to strong electronic interactions between catalyst and support. The molecular structure and electronic character of a [Re+1(tBu-bpy)(CO)3Cl] (tBu-bpy = 4,4'-tert-butyl-2,2'-bipyridine) catalyst deposited on multiwalled carbon nanotubes are characterized using Re L3-edge x-ray absorption spectroscopy under electrochemical conditions and compared to the homogeneous catalyst. The Re oxidation state is characterized from the near-edge absorption region, while structural changes of the catalyst are assessed from the extended x-ray absorption fine structure under reducing conditions. Chloride ligand dissociation and a Re-centered reduction are both observed under applied reducing potential. The results confirm weak coupling of [Re(tBu-bpy)(CO)3Cl] with the support, since the supported catalyst exhibits the same oxidation changes as the homogeneous case. However, these results do not preclude strong interactions between a reduced catalyst intermediate and the support, preliminarily investigated here using quantum mechanical calculations. Thus, our results suggest that complicated linkage schemes and strong electronic interactions with the initial catalyst species are not required to improve the activity of heterogenized molecular catalysts.

Spectrum of B-cell neoplasms associated with immunoglobulin G4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) has rarely been associated with lymphoid neoplasms, the spectrum of which remains unclear. B-cell lymphoid neoplasms (LN) associated with IgG4-RD diagnosed in a 4-year period were analysed. There were five men and three women at a median age of 76.5 (52-90) years; three with synchronous IgG4-RD and LN; three with IgG4-RD preceding LN by 2, 3, and 22 years; and two with LN preceding IgG4-RD by 2.5 and 7 years. All patients presented with disseminated lymphadenopathy. Monoclonal gammopathy of undetermined significance (MGUS)/smouldering multiple myeloma (SMM) was found in three patients, all with an IgGκ paraprotein. Levels of IgGκ and IgG4 correlated. Diffuse large B-cell lymphoma (DLBCL) was found in three patients, with one case showing co-existing lymphoma and IgG4-RD in the same lymph node biopsy. The remaining two cases were marginal zone lymphoma (MZL) developing in a lacrimal gland previously involved by IgG4-RD; and nodular lymphocyte predominant Hodgkin lymphoma (NLP-HL) diagnosed in a lymph node with concomitant IgG4-RD. Low-dose continuous prednisolone was given for MGUS/SMM, with both monoclonal IgGκ and IgG4 responding. Combination chemotherapy was given for DLBCL, with two patients achieving complete response and one patient dying from refractory lymphoma. The patient with MZL refused treatment, whereas the case of NLP-HL responded completely to chemotherapy. Our findings together with previous observations suggest that IgG4-RD has an increased risk of B-cell neoplasms. Patients with IgG4-RD presenting with lymphadenopathy require vigorous investigations to exclude lymphoid neoplasms.

Ruxolitinib in the management of steroid-resistant/-dependent acute and chronic graft-versus-host disease: results of routine practice in an academic centre.

Graft-versus-host disease (GVHD) is an important complication after allogeneic haematopoietic stem cell transplantation (HSCT). Corticosteroids are the standard first-line treatment. Steroid-resistant/-dependent (SR/D) acute and chronic GVHD (aGVHD, cGVHD) lead to significant morbidity/mortality. The JAK2 inhibitor ruxolitinib has recently been shown in clinical trials to be effective in SR/D aGVHD and cGVHD. We retrospectively analysed the efficacy and safety of ruxolitinib in a cohort of SR/D aGVHD and cGVHD patients treated in a non-trial setting. In the aGVHD cohort, there were 14 men and 12 women, median age at 38 (19-63) years. At day 28 post-ruxolitinib, the overall response rate (ORR) was 86% (complete response, CR, 36%; partial response, PR, 50%). Continued ruxolitinib beyond day 28 resulted in a final CR of 68%. However, 3/15 (20%) of CR patients developed cGVHD. In the cGVHD cohort, there were 16 men and 15 women, median age at 33 (21-64) years. The ORR, CR and PR rates changed with continued ruxolitinib treatment, being 86%, 17% and 69% at 1 month; 79%, 38% and 41% at 3 months; and 83%, 52% and 31% at 6 months. Five patients had overlap GVHD, four of whom achieved CR. Multivariate analysis showed that superior overall survival and failure-free survival were associated with CR at day 28 for aGVHD, and CR at 1 year for cGVHD. Ruxolitinib treatment was efficacious for SR/D aGVHD and cGVHD, and continued treatment for at least 6 months was needed to maximize benefit.

Eltrombopag as frontline treatment of aplastic anaemia in routine practice: implications on cost and efficacy.

The thrombopoietin mimetic eltrombopag (EPAG) is efficacious in clinical trials of newly diagnosed moderate (M), severe (S) and very severe (vS) aplastic anaemia (AA). Its use in routine practice and resource-constrained settings is not well described. Twenty-five men and 38 women at a median age of 54 (18-86) years with newly diagnosed AA treated consecutively in a 7-year period with EPAG (N = 6), EPAG/cyclosporine (CsA) (N = 33) and EPAG/CsA/anti-thymocyte globulin (ATG) (N = 24) were analyzed. Because EPAG was not reimbursed, peak doses ranged from 25 to 200 mg/day depending on affordability. EPAG/CsA-treated patients were older (median age: 61 years) with less severe AA (MAA, N = 15; SAA, N = 14; vSAA, N = 4), whereas EPAG/CsA/ATG-treated patients were younger (median age: 44 years) with more severe AA (MAA, N = 2; SAA, N = 12, vSAA, N = 10). The overall/trilineage response rates were 83%/50% for EPAG-treated patients; 79%/42% for EPAG/CsA-treated patients and 75%/63% for EPAG/CsA/ATG-treated patients. Adverse events included grade 1 liver derangement (N = 7) and grade 1 dyspepsia (N = 3). The 5-year overall survivals/failure-free survivals were 62%/80% for the entire cohort; 55%/75% for EPAG/CsA-treated patients and 82%/78% for EPAG/CsA/ATG-treated patients. EPAG showed robust efficacy in AA in routine practice. However, EPAG dosage and combinations remain to be optimized for AA of different severities.

The COVID Positive Pathway: a collaboration between public health agencies, primary care, and metropolitan hospitals in Melbourne.

OBJECTIVES: To assess the capacity of the COVID Positive Pathway, a collaborative model of care involving the Victorian public health unit, hospital services, primary care, community organisations, and the North Western Melbourne Primary Health Network, to support people with coronavirus disease 2019 (COVID-19) isolating at home. DESIGN, SETTING, PARTICIPANTS: Cohort study of adults in northwest Melbourne with COVID-19, 3 August - 31 December 2020. MAIN OUTCOME MEASURES: Demographic and clinical characteristics, and social and welfare needs of people cared for in the Pathway, by care tier level. RESULTS: Of 1392 people referred to the Pathway by the public health unit, 858 were eligible for enrolment, and 711 consented to participation; 647 (91%) remained in the Pathway until they had recovered and isolation was no longer required. A total of 575 participants (81%) received care in primary care, mostly from their usual general practitioners; 155 people (22%) received care from hospital outreach services, and 64 (9%) needed high tier care (hospitalisation). Assistance with food and other basic supplies was required by 239 people in the Pathway (34%). CONCLUSIONS: The COVID Positive Pathway is a feasible multidisciplinary, tiered model of care for people with COVID-19. About 80% of participants could be adequately supported by primary care and community organisations, allowing hospital services to be reserved for people with more severe illness or with risk factors for disease progression. The principles of this model could be applied to other health conditions if regulatory and funding barriers to information-sharing and care delivery by health care providers can be overcome.

The Earliest Food Deserts: Availability of Infant and Follow-on Formula, and Lactation Support Products among Stores in Black and Non-Hispanic White Zip Codes in Los Angeles County.

OBJECTIVES: This study investigates the availability, accessibility, and product depth of in-store infant feeding and galactagogues products in majority Black and majority white zip codes in Los Angeles County. METHODS: A cross-sectional study was conducted to determine racial/ethnic neighborhood differences in the availability of infant and follow-on formula and galactagogues products in 47 retail stores in 21 zip codes. Store-level data were collected in June 2019 and an observational tool for galactagogues products and infant/follow-on formula (availability, accessibility, product depth) was employed at each store. RESULTS: Most of the stores were grocery stores (87.2%). Stores in majority Black zip codes had less availability of infant formula ready-to-use (p = 0.001), less accessibility of follow-on powder (p = 0.028), and availability of galactagogues beverages (p = 0.036) versus majority white zip codes. Product depth (number of brands sold) of stores with one or more brands of the aforementioned products was consistently higher in majority white zip codes compared to majority Black zip codes. Stores in majority Black zip codes were most likely to have lower availability of infant formula and galactagogues products, an important part of the food environment for infant feeding options, in particular, for lactation support. CONCLUSIONS FOR PRACTICE: Most studies investigating the association of the food environment and health outcomes have focused only on solid foods. However, additional food products (e.g., liquids, powders) may be contributors to extensive disparities in infant mortality between Black and white infants and may lead to health disparities beyond infant stage (e.g., children, adolescents, and adults). Lastly, for breastfeeding inequities to decrease, pregnant and postpartum Black persons need equitable access and education on safe and quality galactagogues products.

The role of reactive oxygen species in the pathogenesis and treatment of retinal diseases.

Reactive oxygen species (ROS) normally play an important physiological role in health regulating cellular processes and signal transduction. The amount of ROS is usually kept in fine balance with the generation of ROS largely being offset by the body's antioxidants. A tipping of this balance has increasingly been recognised as a contributor to human disease. The retina, as a result of its cellular anatomy and physical location, is a potent generator of ROS that has been linked to several major retinal diseases. This review will provide a summary of the role of oxidative stress in the pathogenesis of diabetic retinopathy, age-related macular degeneration, myopia, retinal vein occlusion, retinitis pigmentosa and retinopathy of prematurity. Therapies aimed at controlling oxidative stress in these diseases are also examined.

Low-dose pembrolizumab and nivolumab were efficacious and safe in relapsed and refractory classical Hodgkin lymphoma: Experience in a resource-constrained setting.

The efficacy and safety of low-dose anti-PD1 antibodies in relapsed/refractory classical Hodgkin lymphoma (cHL) require confirmation. Pembrolizumab (100 mg every 3 weeks, Q3W) or nivolumab (40 mg Q2W) were administered to patients with relapsed/refractory cHL. In the pembrolizumab cohort (N = 11), who had failed a median of three (1-6) therapies (brentuximab vedotin [BV]: 91%; autologous hematopoietic stem cell transplantation [auto-HSCT]: 18%), the overall response rate (ORR) by positron emission tomography-computed tomography was 100% (metabolic complete response [mCR]: 73%; partial response [PR]: 27%). Median cumulative dose for achieving best response was 400 (300-800) mg. Median progression-free survival (PFS) was 35 months. Median overall survival (OS) was not reached. Adverse events (AEs) of grade 1-2 were observed in three patients. In the nivolumab cohort (N = 6), who had failed a median of three (2-6) therapies (BV: 50%; auto-HSCT: 17%; allogeneic HSCT: 34%), the ORR was 100% (mCR: 67%; PR: 17%; indeterminate response: 17%). Median cumulative dose for achieving best response was 160 (160-360) mg. Median PFS was 33 months. Median OS was not reached. AEs of grade 1-2 were observed in four patients, two of whom had pre-existing autoimmune conditions. Five patients with Epstein-Barr virus (EBV) positive Reed-Sternberg cells underwent monitoring of plasma EBV DNA, which became negative in four mCR patients but remained positive in one PR patient who died ultimately from refractory lymphoma. Low-dose pembrolizumab and nivolumab were highly efficacious and safe in relapsed/refractory cHL. These observations have significant financial implications in resource-constrained settings.

Oral arsenic trioxide incorporation into frontline treatment with all-trans retinoic acid and chemotherapy in newly diagnosed acute promyelocytic leukemia: A 5-year prospective study.

BACKGROUND: Strategies using oral arsenic trioxide (As2 O3 ) are efficacious in relapsed acute promyelocytic leukemia (APL), but they have not been examined in newly diagnosed cases. METHODS: Sixty-two consecutive patients (24 men and 38 women) with a median age of 52 years (range, 22-85 years), 36% of whom had high-risk features, underwent induction with all-trans retinoic acid at 45 mg/m2 /d, oral As2 O3 at 10 mg/d, and ascorbic acid at 1 g/d (the all-trans retinoic acid-arsenic trioxide-ascorbic acid [AAA] regimen) for 6 weeks (with patients younger than 70 years additionally receiving daunorubicin at 50 mg/m2 /d × 3); they then underwent consolidation with 2 monthly cycles of daunorubicin (50 mg/m2 /d × 2) and cytarabine (100 mg/m2 /d × 5) and received AAA maintenance (2 weeks every 8 weeks) for 2 years. A contemporaneous cohort of 37 newly diagnosed patients (15 men and 22 women) with a median age of 51 years (range, 23-78 years), not consenting to oral As2 O3 induction but receiving similar induction, consolidation, and AAA maintenance, served as a comparator group; 46% of these patients had high-risk features. RESULTS: The oral As2 O3 induction cohort showed a complete remission (CR) rate of 100%. After a median of 37 months (range, 13-82 months), there were no relapses, so conventional risks (age, leukocyte and platelet counts, and Fms-like tyrosine kinase 3 [FLT3] mutations) were not relevant. The leukemia-free survival (LFS) and overall survival (OS) rates were 100% at 3 years and 94.1% at 5 years. The non-As2 O3 induction cohort showed a CR rate of 100%. After a median of 52 months (range, 14-77 months), there were 3 relapses (8%). Comparable patients in the oral As2 O3 induction and non-As2 O3 induction cohorts showed similar OS, but LFS was significantly superior in the oral As2 O3 induction cohort. CONCLUSIONS: The incorporation of oral As2 O3 into induction for newly diagnosed APL was safe and decreased relapses.

Monitoring and Treatment of Patients Undergoing Immunotherapy With Anti-CD20 Who are Exposed to HBV.

Reactivation of hepatitis B virus (HBV) is a potentially fatal complication of immunosuppressive therapy, and can occur in individuals who are hepatitis B surface antigen (HBsAg) negative but positive for hepatitis B core antibody (anti-HBc). While anti-HBc positivity indicates prior HBV exposure, it may also reflect clearance of HBsAg, but with viral persistence at low intrahepatic replicative and transcriptional levels.1 HBV reactivation can still occur during intense immunosuppression, including B cell-depleting therapy with anti-CD20 antibodies2 and hematopoietic stem cell transplantation.3 While prevention via antiviral prophylaxis is recommended, it remains uncertain, from a global perspective, if this is an ideal and cost-effective strategy. An alternative is regular HBV DNA monitoring.4 However, this approach is problematic in resource-constrained regions, where the logistics of sample collection, transportation, and molecular analysis in dedicated facilities poses challenges.5 We aimed to evaluate the effectiveness of simple monitoring strategies using routine liver biochemistry and serum HBsAg in preventing HBV-related complications during anti-CD20 therapy.

PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase.

Natural killer (NK)/T-cell lymphomas failing L-asparaginse regimens have no known salvage and are almost invariably fatal. Seven male patients with NK/T-cell lymphoma (median age, 49 years; range, 31-68 years) for whom a median of 2 (range, 1-5) regimens (including l-asparaginase regimens and allogeneic hematopoietic stem-cell transplantation [HSCT] in 2 cases) failed were treated with the anti-programmed death 1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic, and molecular (circulating Epstein-Barr virus [EBV] DNA) criteria. Two patients achieved complete response (CR) in all parameters. Three patients achieved clinical and radiologic CRs, with two having molecular remission (undetectable EBV DNA) but minimal EBV-encoded RNA-positive cells in lesions comprising predominantly CD3+CD4+ and CD3+CD8+ T cells (which ultimately disappeared, suggesting they represented pseudoprogression) and one having detectable EBV DNA despite morphologic CR. Two patients achieved partial response (PR). After a median of 7 (range, 2-13) cycles of pembrolizumab and a follow-up of a median of 6 (range, 2-10) months, all five CR patients were still in remission. The only adverse event was grade 2 skin graft-versus-host disease in one patient with previous allogeneic HSCT. Expression of the PD1 ligand was strong in 4 patients (3 achieving CR) and weak in 1 (achieving PR). PD1 blockade with pembrolizumab was a potent strategy for NK/T-cell lymphomas failing l-asparaginase regimens.

Long-term outcome of relapsed acute promyelocytic leukemia treated with oral arsenic trioxide-based reinduction and maintenance regimens: A 15-year prospective study.

BACKGROUND: For patients who have acute promyelocytic leukemia (APL) in second complete remission (CR2), optimal postremission strategies remain undefined. METHODS: The role of an oral arsenic trioxide (As2 O3 )-based regimen in the management of patients who had APL in CR2 was examined. RESULTS: Seventy-three patients with APL in first relapse (R1) were studied. Oral As2 O3 -based reinduction resulted uniformly in CR2, irrespective of previous As2 O3 exposure. All patients received oral As2 O3 -based maintenance in CR2. At a median follow-up of 94 months (range, 9-205 months), 43 patients (58.9%) were still in CR2, and 49 (67.1%) had finished the planned 2-year CR2 maintenance with all-trans retinoic acid, oral As2 O3 , and ascorbic acid. Reinduction and maintenance treatments were well tolerated. Grade 1 and 2 headache occurred in 20 patients (27.4%). Hepatotoxicity, all in the form of transaminitis, occurred in 35 patients (47.9%; grade 1 and 2, n = 26; grade 3 and 4, n = 9). Three patients had self-limiting QTc prolongation. The 10-year leukemia-free survival rate was 56.8%. Thirty patients developed R2. Oral As2 O3 -based reinduction led to CR3 in 27 patients (90%). Post-CR3 strategies included autologous hematopoietic stem cell transplantation and oral As2 O3 maintenance. At a post-CR3 follow-up of 30 months (range, 3-166 months), 11 patients were still in CR3. The 5-year and 10-year overall survival rates in the R1 cohort were 79.5% and 67.3%, respectively. Prior receipt of oral As2 O3 maintenance in CR1 was the only risk factor for inferior leukemia-free survival. Central nervous system involvement occurred in 15 patients, including 5 who remained alive. Relapse during oral As2 O3 therapy was the only significant risk factor for central nervous system involvement. CONCLUSIONS: For patients with relapsed APL, As2 O3 remained effective despite repeated As2 O3 exposures. Oral As2 O3 maintenance was an effective postremission strategy for CR2. Cancer 2018;124:2316-26. © 2018 American Cancer Society.

Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study.

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg-negative, anti-HBc-positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg-negative, anti-HBc-positive, of whom 62 were recruited and monitored for a median of 48 (4-104) weeks. The 2-year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8-100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft-versus-host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft-versus-host disease, compared with the remaining patient cohort, had a significantly lower 2-year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. CONCLUSION: HBsAg-negative, anti-HBc-positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft-versus-host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451-1461).

A Human Bite on the Scrotum: Case Report and Review of Management in the Emergency Department.

BACKGROUND: Human bites involving the genitalia rarely present to the emergency department (ED). They have the potential to cause life-threatening secondary infections as well as serious physical and functional damage. CASE REPORT: We report a case of an adult male who sustained a human bite to the scrotum, resulting in a ragged laceration on the anterior scrotum, with a devascularized flap and necrotic edges overlying the wound. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Human bites to the scrotum are rare and, hence, the experience of emergency physicians treating patients presenting with these injuries may be minimal. This puts patients at risk of underevaluation or suboptimal treatment. The rapid initiation of antibiotics in the ED and thorough wound debridement will prevent infections, aid healing, and lead to improved outcomes by preserving organ function and integrity. We therefore present a systematic approach to the management of patients with human bite to the scrotum in the ED.

Naturally Occurring Mentorship in a National Sample of First-Generation College Goers: A Promising Portal for Academic and Developmental Success.

Attending college is increasingly important to compete in this global world; however, young people whose parents did not attend college are significantly less likely to enroll in and finish college. Formal programs to support first-generation college goers are common, but not scalable to provide support to all young people who need it. Instead, mentoring that naturally occurs on these students' journeys into and out of college may be a more practical avenue for supporting their success. This study investigated the role community members, relatives, and educators play in first-generation college goers' educational outcomes. Data from 4,181 participants of the National Longitudinal Study of Adolescent and Adult Health were used to test differences in supports received between first-generation, continuing-generation, and non-college goers. Results demonstrated that mentorship in adolescence moderated the relationship between parental college attendance and educational attainment in adulthood. Next, findings suggested that first-generation students received less support for identity development from their mentors than continuing-generation students. This study has program implications for facilitating college attendance and fostering the development and success of first-generation students. Moreover, this project continues to concretize an emerging taxonomy of mentoring functions for youth and emerging adults.

Low-dose pembrolizumab for relapsed/refractory Hodgkin lymphoma: high efficacy with minimal toxicity.

Five patients with refractory/relapsed classical Hodgkin lymphoma (cHL), four having failed multiple lines of chemotherapy and brentuximab vedotin, were treated with low-dose pembrolizumab (median dose 100 mg, range: 100-200 mg, every 3 weeks). Complete response (CR) was achieved in four patients (80%), after a median cumulative dose of merely 495 (300-800) milligrams. Three CR patients have continued to receive pembrolizumab for a median of 16 (14-25) cycles, remaining in CR for a median of 18 (9-18) months. One CR patient underwent autologous hematopoietic stem cell transplantation and has remained in CR for 9 months. Partial response (PR) was achieved in one patient (20%), after a cumulative dose of 400 mg. The overall response rate was therefore 100% (CR: 80%; PR: 20%). Toxicity was virtually absent, with only grade 1 diarrhea and eczema each observed in one patient. Low-dose pembrolizumab was highly efficacious, achieving responses with minimal toxicity and at much lower costs.

Association of Hepatitis B Core-Related Antigen With Hepatitis B Virus Reactivation in Occult Viral Carriers Undergoing High-Risk Immunosuppressive Therapy.

OBJECTIVES: Hepatitis B core-related antigen (HBcrAg) is a novel serum marker that correlates with intrahepatic hepatitis B virus (HBV) activity. Its association with HBV reactivation in hepatitis B surface antigen (HBsAg)-negative antibody to hepatitis B core antigen (anti-HBc)-positive patients undergoing high-risk immunosuppressive therapy is undefined. METHODS: HBcrAg was measured in HBsAg-negative, anti-HBc-positive Asian patients with undetectable HBV DNA, who participated in two prospective studies investigating HBV reactivation during rituximab-containing chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Patients were monitored every 4 weeks for up to 2 years, with entecavir started when HBV reactivation, defined as HBV DNA ≥10 IU ml-1, developed. RESULTS: One hundred and twenty-four HBsAg-negative, anti-HBc-positive patients (rituximab, N=62; allogeneic HSCT, N=62) with a median follow-up of 64 weeks (range: 4-104 weeks) were studied. HBV reactivation occurred in 31 patients, with a 2-year cumulative reactivation rate of 40.4%. Serum HBcrAg was detected in 43 (34.7%) patients. Baseline HBcrAg positivity was significantly associated with HBV reactivation (P=0.004, hazard ratio (HR): 2.94, 95% confidence interval (95% CI): 1.43-6.07). HBcrAg-positive patients had a significantly higher 2-year HBV reactivation rate than HBcrAg-negative patients (71.8 vs. 31%, P=0.002). In the rituximab cohort, the HRs for positive HBcrAg and negative antibody to HBsAg for HBV reactivation were 3.65 and 2.84, respectively (P=0.011, 95% CI: 1.35-9.86 and P=0.032, 95% CI: 1.10-7.37, respectively). CONCLUSIONS: Serum HBcrAg positivity is a significant risk factor of HBV reactivation in HBsAg-negative, anti-HBc-positive patients undergoing high-risk immunosuppressive therapy and can potentially have a role in identifying patients who will best benefit from prophylactic nucleoside analogue treatment.

Telmisartan increases systemic exposure to rosuvastatin after single and multiple doses, and in vitro studies show telmisartan inhibits ABCG2-mediated transport of rosuvastatin.

PURPOSE: The ATP-binding cassette transporter G2 (ABCG2) plays an important role in the disposition of rosuvastatin. Telmisartan, a selective angiotension-II type 1 (AT1) receptor blocker, inhibits the transport capacity of ABCG2, which may result in drug interactions. This study investigated the pharmacokinetic interaction between rosuvastatin and telmisartan and the potential mechanism. METHODS: In this two-phase fixed-order design study, healthy subjects received single doses of 10 mg rosuvastatin at baseline and after telmisartan 40 mg daily for 14 days. Patients with hyperlipidaemia who had been taking rosuvastatin 10 mg daily for at least 4 weeks were given telmisartan 40 mg daily for 14 days together with rosuvastatin. Plasma concentrations of rosuvastatin were measured over 24 h before and after telmisartan administration. In vitro experiments using a bidirectional transport assay were performed to investigate the involvement of ABCG2 in the interaction. RESULTS: Co-administration of telmisartan significantly increased the maximum plasma concentration (C max) and the area under the plasma concentration-time curve (AUC) of rosuvastatin by 71 and 26 %, respectively. The T max values were reduced after administration of telmisartan. There was no significant difference in the interaction of rosuvastatin with telmisartan between healthy volunteers and patients receiving long-term rosuvastatin therapy or among subjects with the different ABCG2 421 C>A genotypes. The in vitro experiment demonstrated that telmisartan inhibited ABCG2-mediated efflux of rosuvastatin. CONCLUSION: This study demonstrated that telmisartan significantly increased the systemic exposure to rosuvastatin after single and multiple doses.