No abstract

Standard (non-antimetabolite) combination chemotherapy administered past the first trimester, as early as 13 weeks gestation, was associated with few complications and expected maternal survival with lymphoma occurring during pregnancy.

We performed a multicenter, International analysis of solid organ transplant (SOT)-related primary central nervous system (PCNS) posttransplant lymphoproli-ferative disease (PTLD). Among 84 PCNS PTLD patients, median time of SOT-to-PTLD was 54 months, 79% had kidney SOT, histology was monomorphic in 83% and tumor was EBVþ in 94%. Further, 33% had deep brain involvement, 10% had CSF involvement, while none had ocular disease. Immunosuppression was reduced in 93%; additional first-line therapy included high-dose methotrexate (48%), high-dose cytarabine (33%), brain radiation (24%) and/or ritux-imab (44%). The overall response rate was 60%, while treatment-related mortality was 13%. With 42-month median follow-up, three-year progression-free survival (PFS) and overall survival (OS) were 32% and 43%, respectively. There was a trend on univariable analysis for improved PFS for patients who received rituximab and/or high-dose cytarabine. On multivariable Cox regression, poor performance status predicted inferior PFS (HR 2.61, 95% CI 1.32-5.17, p ¼ 0.006), while increased LDH portended inferior OS (HR 4.16, 95% CI 1.29-13.46, p ¼ 0.02). Moreover, lack of response to first-line therapy was the most dominant prognostic factor on multivariable analysis (HR 8.70, 95% CI 2.56-29.57, p ¼ 0.0005). Altogether, PCNS PTLD appears to represent a distinct clinicopathologic entity within the PTLD spectrum that is associated with renal SOT, occurs late, is monomorphic and retains EBV positivity.

Neuroactive steroids (NAS) are allosteric modulators of the γ-aminobutyric acid (GABA) system. NAS and GABA are implicated in depression. The peripartum period involves physiologic changes in NAS which may be associated with peripartum depression and anxiety. We measured peripartum plasma NAS and GABA in healthy comparison subjects (HCS) and those at-risk for postpartum depression (AR-PPD) due to current mild depressive or anxiety symptoms or a history of depression. We evaluated 56 peripartum medication-free subjects. We measured symptoms with the Hamilton Depression Rating Scale (HAM-D17), Hamilton Anxiety Rating Scale (HAM-A) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). Plasma NAS and GABA were quantified by liquid chromatography-mass spectrometry. We examined the associations between longitudinal changes in NAS, GABA and depressive and anxiety symptoms using generalized estimating equation methods. Peripartum GABA concentration was 1.9 ± 0.7 ng/mL (p=0.004) lower and progesterone and pregnanolone were 15.8 ± 7.5 (p=0.04) and 1.5 ± 0.7 ng/mL (p=0.03) higher in AR-PPD versus HCS, respectively. HAM-D17 was negatively associated with GABA (β=−0.14 ± 0.05, p=0.01) and positively associated with pregnanolone (β=0.16 ± 0.06, p=0.01). STAI-S was positively associated with pregnanolone (β=0.11 ± 0.04, p=0.004), allopregnanolone (β=0.13 ± 0.05, p=0.006) and pregnenolone (β=0.02 ± 0.01, p=0.04). HAM-A was negatively associated with GABA (β=−0.12 ± 0.04, p=0.004) and positively associated with pregnanolone (β=0.11 ± 0.05, p=0.05). Altered peripartum NAS and GABA profiles in AR-PPD women suggest that their interaction may play an important role in the pathophysiology of peripartum depression and anxiety.

Background The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancers. Objective Examine the association between screening colonoscopy and incident late-stage colorectal cancer (CRC) risk. Design Nested case-control study. Setting Four U.S. health plans Patients Average-risk adults with ≥5 years of enrollment in one of the health plans (n=1,039). Cases were 55–85 years old on their diagnosis date (reference date) of stage ≥IIB (late-stage) CRC during 2006–2008. We selected 1–2 controls for each case, matched on birth year, gender, health plan, and prior enrollment duration. Measurements Receipt of CRC screening between 3 months and up to 10 years before the reference date, ascertained through medical record audits. We compared cases and controls on receipt of screening colonoscopy or sigmoidoscopy using conditional logistic regressions that accounted for health history, socioeconomic status and other screening exposures. Results In analyses restricted to 471 eligible cases and their matched controls (n=509), 13 cases (2.8%) and 46 controls (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.30 (95% confidence interval [CI]: 0.15–0.59) for any late-stage CRC, 0.37 (CI: 0.16–0.82) for right colon cancers, and 0.26 (CI: 0.06–1.11) for left-sided colon/rectum cancers. Ninety-two cases (19.5%) and 173 controls (34.0%) underwent screening sigmoidoscopy, corresponding to an AOR of 0.51 (CI: 0.36–0.71) overall, 0.80 (CI: 0.52–1.25) for right colon late-stage cancers, and 0.26 (CI: 0.14–0.49) for left colon/rectum cancers. Limitations The small number of screening colonoscopies affected the precision of our estimates. Conclusions Screening with colonoscopy in average-risk persons was associated with reduced risk of diagnosis with incident late-stage CRC in both the right colon and left colon/rectum. For sigmoidoscopy, this association was observed for left-sided CRC, but the association for right colon late-stage cancer was not statistically significant. Primary Funding Source National Cancer Institute of the National Institutes of Health.

No abstract

We performed a multicenter, International analysis of solid organ transplant (SOT)-related primary central nervous system (PCNS) posttransplant lymphoproliferative disease (PTLD). Among 84 PCNS PTLD patients, median time of SOT-to-PTLD was 54 months, 79% had kidney SOT, histology was monomorphic in 83% and tumor was EBVþ in 94%. Further, 33% had deep brain involvement, 10% had CSF involvement, while none had ocular disease. Immunosuppression was reduced in 93%; additional first-line therapy included high-dose methotrexate (48%), high-dose cytarabine (33%), brain radiation (24%) and/or rituximab (44%). The overall response rate was 60%, while treatment-related mortality was 13%. With 42-month median follow-up, three-year progression-free survival (PFS) and overall survival (OS) were 32% and 43%, respectively. There was a trend on univariable analysis for improved PFS for patients who received rituximab and/or high-dose cytarabine. On multivariable Cox regression, poor performance status predicted inferior PFS (HR 2.61, 95% CI 1.32-5.17, p ¼ 0.006), while increased LDH portended inferior OS (HR 4.16, 95% CI 1.29-13.46, p ¼ 0.02). Moreover, lack of response to first-line therapy was the most dominant prognostic factor on multivariable analysis (HR 8.70, 95% CI 2.56-29.57, p ¼ 0.0005). Altogether, PCNS PTLD appears to represent a distinct clinicopathologic entity within the PTLD spectrum that is associated with renal SOT, occurs late, is monomorphic and retains EBV positivity.

Postpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy ( 1 H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS. We examined between-group differences in RSFC and the relationship between cortical GABA+/Cr concentrations with RSFC. We investigated the relationship between NAS, RSFC and cortical GABA+/Cr concentrations. Within the default mode network (DMN) an area of the dorsomedial prefrontal cortex (DMPFC) had greater connectivity with the rest of the DMN in PPD (peak voxel: MNI coordinates (2, 58, 32), p = 0.002) and was correlated to depression scores (peak HAM-D17 voxel: MNI coordinates (0, 60, 34), p = 0.008). pgACC GABA+/Cr correlated positively with DMPFC RSFC in a region spanning the right anterior/posterior insula and right temporal pole (r = +0.661, p = 0.000). OCC GABA+/Cr correlated positively with regions spanning both amygdalae (right amygdala: r = +0.522, p = 0.000; left amygdala: r = +0.651, p = 0.000) as well as superior parietal areas. Plasma allopregnanolone was higher in PPD (p = 0.03) and positively correlated with intra DMPFC connectivity (r = +0.548, p = 0.000) but not GABA+/Cr. These results provide initial evidence that PPD is associated with altered DMN connectivity; cortical GABA+/Cr concentrations are associated with postpartum RSFC and allopregnanolone is associated with postpartum intra-DMPFC connectivity.Neuropsychopharmacology (2019) 44:546-554; https://doi.org/10.1038/s41386-018-0242-2 (DMN) [8] and salience networks (SN) [9] in PPD [10]. The DMN is a network of connected brain regions most active at rest and involved in monitoring of the external environment and internal mentation. Although studies differ, this network often includes the medial prefrontal cortex (MPFC), posterior cingulate cortex, precuneus and inferior parietal lobule [11]. The SN is a paralimbic-limbic network active both at rest and during taskrelated activity which integrates sensory, emotional and cognitive information to contribute to social behavior and self-awareness. The SN often includes the dorsal ACC, anterior insula, amygdala, ventral striatum, dorsomedial thalamus, hypothalamus and the substantia nigra/ventral tegmental area [12] Γ-aminobutyric acid (GABA) is believed to contribute to intrinsic functional connectivity of a network [13][14][15] and has been