Supporting cognitive catch-up: The effects of cluster-randomized psychosocial stimulation interventions on preterm low birthweight children in rural China.

Improved survival of preterm low birthweight (LBW) infants due to advances in neonatal care has brought issues such as postnatal development trajectories to the foreground. This study pools evidence from three cluster-randomized experiments evaluating community-based psychosocial stimulation programs conducted from 2014 to 2017 that included 3571 rural Chinese children aged 6-24 months (51.1% male, 96.2% Han Chinese). The risk of severe cognitive delay was found to be 26.5 percentage points higher for preterm LBW children than for their peers at age 2.5, with a prevalence rate of 48.3%. Results show that psychosocial stimulation interventions can improve child cognitive development at scale, with beneficial impacts on child cognition disproportionately larger for preterm LBW children, helping them to catch up developmentally.

Outcomes of subsequent antilymphoma therapies after second-line axicabtagene ciloleucel or standard of care in ZUMA-7.

ABSTRACT: The optimal management of patients with relapsed/refractory large B-cell lymphoma (LBCL) after disease progression or lack of response to second-line (2L) therapy remains unclear. Here, we report outcomes among patients who received subsequent antilymphoma therapy per investigator discretion separately by their randomized 2L arm in ZUMA-7, namely axicabtagene ciloleucel (axi-cel) vs standard of care (SOC). Progression-free survival (PFS) and overall survival (OS) were calculated from 3L therapy initiation. In the SOC arm, 127 of 179 randomized patients (71%) received 3L therapy. Median PFS among those who received 3L cellular immunotherapy (n = 68) vs those who did not (n = 59) was 6.3 vs 1.9 months, respectively; median OS was 16.3 vs 9.5 months, respectively. In the axi-cel arm, 84 of 180 randomized patients (47%) received 3L therapy. Median PFS among those who received 3L chemotherapy (n = 60) vs cellular immunotherapy (n = 8) was 1.7 vs 3.5 months, respectively; median OS was 8.1 months vs not reached, respectively. Of the 60 patients who received 3L chemotherapy, 10 underwent stem cell transplantation (SCT) after salvage chemotherapy. Median PFS was 11.5 vs 1.6 months, and median OS was 17.5 vs 7.2 months for those who did vs did not reach SCT, respectively. Eight patients received 3L cellular immunotherapy after 2L axi-cel. Of these, 6 patients received subsequent SCT in any line; all 6 were alive at data cutoff. These findings help inform subsequent treatment choices after 2L therapy failure for relapsed/refractory LBCL. The trial was registered at www.clinicaltrials.gov as #NCT03391466.

Subclinical Peripheral Neuropathy in Patients with Head and Neck Cancer: A Quantitative Sensory Testing (QST) Study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and chronic complication associated with cancer treatment. Prior investigations have demonstrated the presence of subclinical peripheral neuropathy in patients with colorectal cancer even before the patients had received chemotherapy. OBJECTIVE: To investigate subclinical peripheral neuropathy of the upper limbs in patients with squamous cell carcinoma (SCC) of the head and neck which developed before their exposure to neurotoxic anticancer agents. STUDY DESIGN: Retrospective analysis. METHODS: With the use of our quantitative sensory testing (QST) data bank, we retrospectively assessed the afferent fiber function of 25 patients with SCC of the head and neck before they had received chemotherapy (the patient group) and compared our findings with those from 23 healthy control patients. Skin temperature, sensorimotor function, sharpness detection, thermal detection, and touch detection (using both von Frey monofilaments and the Bumps detection test) were measured. RESULTS: Touch thresholds were statistically higher in the patient group than in the healthy volunteer group at the palm (mean [± SD], 0.54 g [± 0.07 g] and 0.27 g [± 0.05 g], respectively [P < 0.01]) and at the forearm (0.74 g [± 0.12 g] and 0.41 g [± 0.08 g] [P < 0.05]). There was also a clear deficit in touch sensation as indicated by a Bumps detection threshold in patients of 6.5 µm ± 0.8 µm and in controls of 3.7 µm ± 0.5 µm. This yields an elevation in threshold to 165% in the patients relative to that of the control volunteers. The grooved pegboard test showed delayed completion times for patients compared with controls, with differences of 18.65 seconds in the dominant hand and of 23.36 seconds in the nondominant hand. The sharpness detection thresholds did not differ between patients and volunteers. LIMITATIONS: Inadequacies in the original data acquisition and documentation of the QST and the medical records could not be addressed due to the retrospective nature of the study. In addition, based on available information, we did not find an objective parameter able to correlate the QST findings with pre-pain levels. CONCLUSION: Patients with SCC were found to have deficits in sensory function before undergoing treatment, suggesting that cancer itself alters peripheral nerve function and may contribute to the development of CIPN. These results confirm the sensitivity of the Bumps detection test and highlight its potential role in early detection of peripheral neuropathy, especially in cancer patients for whom chemotherapies associated with CIPN have been prescribed. KEY WORDS: Peripheral neuropathy, head and neck cancer, quantitative sensory testing.

Sentinel lymph node biopsy for ocular adnexal melanoma.

BACKGROUND: We sought to update our prior report of findings on sentinel lymph node biopsy (SLNB) and predictors of a positive SLN in patients with conjunctival or eyelid melanoma. METHODS: We reviewed the records of all patients with ocular adnexal melanoma who underwent SLNB at one institution during 2000-2015. We determined rates of positive and false-negative findings on SLNB, primary tumour features correlated with positive findings and rate of nodal recurrence (false-negative event) after negative findings. RESULTS: The study included 51 patients, 31 with conjunctival and 20 with eyelid melanoma. These patients include 30 patients who underwent SLNB during 2000-2008, described in our previous report, and 21 additional patients who underwent SLNB during 2008-2015. There were 30 women and 21 men with median age at SLNB of 62 years (range, 24-83). The nodal basins most commonly sampled were intraparotid (27 patients) and level II (14 patients). Ten patients had positive SLNB findings. Compared to tumours with negative findings, tumours with positive findings had greater median thickness (3.5 mm versus 2.2 mm, p = 0.04), greater median number of mitotic figures (6 versus 2, p = 0.03) and greater incidence of ulceration (80% versus 26%, p = 0.003). Perineural and vascular invasion were not significantly associated with positive findings. There were three false-negative events. Three patients (6%) had temporary marginal mandibular weakness which resolved spontaneously. CONCLUSION: SLNB in patients with ocular adnexal melanoma is safe and identifies nodal micrometastasis in approximately 20% of cases. Histologic features associated with a positive SLN included greater tumour thickness, greater number of mitotic figures and ulceration.

Characterization of the metabolic actions of crude versus dispersed oil in salmon smolts via NMR-based metabolomics.

With maritime transport of crude oil from Alaska to California, there is significant potential for a catastrophic spill which could impact migrating salmon. Therefore, this study compared the lethal and sublethal metabolic actions of the water-accommodated fraction (WAF) and the chemically enhanced WAF (CEWAF, via Corexit 9500) of Prudhoe Bay crude oil in smolts of Chinook salmon (Onchorhyncus tshawytscha). After 96-h exposure to the CEWAF, the resulting LC50 was some 20 times higher (i.e., less toxic) than that of the WAF. Muscle and liver samples from surviving fish were collected and low-molecular weight metabolites were analyzed using one-dimensional (1)H and projections of two-dimensional (1)H J-resolved NMR. Principal component analysis (PCA), employed to analyze NMR spectra and identify most variance from the samples, revealed age-related metabolic changes in the fish within the replicated studies, but few consistent metabolic effects from the treatments. However, ANOVA results demonstrated that the dose-response metabolite patterns are both metabolite- and organ-dependent. In general, exposure to either WAF or CEWAF resulted in an increase of amino acids (i.e., valine, glutamine and glutamate) and a decrease of both organic osmolytes (i.e., glycerophosphorylcholine) and energetic substrates (i.e., succinate). The simultaneous increase of formate and decrease of glycerophosphorylcholine in the liver, or the decrease of glycerophosphorylcholine in muscle, may serve as sensitive sublethal biomarkers for WAF or CEWAF exposures, respectively. In conclusion, dispersant treatment significantly decreased the lethal potency of crude oil to salmon smolts, and the NMR-based metabolomics approach provided a sensitive means to characterize the sublethal metabolic actions.