OBJECTIVE Ideal timeframes for operating on traumatic stretch and blunt brachial plexus injuries remain a topic of debate. Whereas on the one hand spontaneous recovery might occur, on the other hand, long delays are believed to result in poorer functional outcomes. The goal of this review is to assess the optimal timeframe for surgical intervention for traumatic brachial plexus injuries. METHODS A systematic search was performed in January 2017 in PubMed and Embase databases according to the PRISMA guidelines. Search terms related to "brachial plexus injury" and "timing" were used. Obstetric plexus palsies were excluded. Qualitative synthesis was performed on all studies. Timing of operation and motor outcome were collected from individual patient data. Patients were categorized into 5 delay groups (0-3, 3-6, 6-9, 9-12, and > 12 months). Median delays were calculated for Medical Research Council (MRC) muscle grade ≥ 3 and ≥ 4 recoveries. RESULTS Forty-three studies were included after full-text screening. Most articles showed significantly better motor outcome with delays to surgery less than 6 months, with some studies specifying even shorter delays. Pain and quality of life scores were also significantly better with shorter delays. Nerve reconstructions performed after long time intervals, even more than 12 months, can still be useful. All papers reporting individual-level patient data described a combined total of 569 patients; 65.5% of all patients underwent operations within 6 months and 27.4% within 3 months. The highest percentage of ≥ MRC grade 3 (89.7%) was observed in the group operated on within 3 months. These percentages decreased with longer delays, with only 35.7% ≥ MRC grade 3 with delays > 12 months. A median delay of 4 months (IQR 3-6 months) was observed for a recovery of ≥ MRC grade 3, compared with a median delay of 7 months (IQR 5-11 months) for ≤ MRC grade 3 recovery. CONCLUSIONS The results of this systematic review show that in stretch and blunt injury of the brachial plexus, the optimal time to surgery is shorter than 6 months. In general, a 3-month delay appears to be appropriate because while recovery is better in those operated on earlier, this must be considered given the potential for spontaneous recovery.

Background and Purpose: Coronavirus disease 2019 (COVID-19) has been associated with an increased incidence of thrombotic events, including stroke. However, characteristics and outcomes of COVID-19 patients with stroke are not well known. Methods: We conducted a retrospective observational study of risk factors, stroke characteristics, and short-term outcomes in a large health system in New York City. We included consecutively admitted patients with acute cerebrovascular events from March 1, 2020 through April 30, 2020. Data were stratified by COVID-19 status, and demographic variables, medical comorbidities, stroke characteristics, imaging results, and in-hospital outcomes were examined. Among COVID-19-positive patients, we also summarized laboratory test results. Results: Of 277 patients with stroke, 105 (38.0%) were COVID-19-positive. Compared with COVID-19-negative patients, COVID-19-positive patients were more likely to have a cryptogenic (51.8% versus 22.3%, P <0.0001) stroke cause and were more likely to suffer ischemic stroke in the temporal ( P =0.02), parietal ( P =0.002), occipital ( P =0.002), and cerebellar ( P =0.028) regions. In COVID-19-positive patients, mean coagulation markers were slightly elevated (prothrombin time 15.4±3.6 seconds, partial thromboplastin time 38.6±24.5 seconds, and international normalized ratio 1.4±1.3). Outcomes were worse among COVID-19-positive patients, including longer length of stay ( P <0.0001), greater percentage requiring intensive care unit care ( P =0.017), and greater rate of neurological worsening during admission ( P <0.0001); additionally, more COVID-19-positive patients suffered in-hospital death (33% versus 12.9%, P <0.0001). Conclusions: Baseline characteristics in patients with stroke were similar comparing those with and without COVID-19. However, COVID-19-positive patients were more likely to experience stroke in a lobar location, more commonly had a cryptogenic cause, and had worse outcomes.

IntroductionThis review aims to summarize challenges in clinical management of concomitant gliomas and pregnancy and provides suggestions for this management based on current literature.MethodsPubMed and Embase databases were systematically searched for studies on glioma and pregnancy. Observational studies and articles describing expert opinions on clinical management were included. The strength of evidence was categorized as arguments from observational studies, consensus in expert opinions, or single expert opinions. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS).Results27 studies were selected, including 316 patients with newly diagnosed (n = 202) and known (n = 114) gliomas during pregnancy. The median sample size was 6 (range 1–65, interquartile range 1–9). Few recommendations originated from observational studies; the remaining arguments originated from consensus in expert opinions.ConclusionFindings from observational studies of adequate quality include (1) There is no known effect of pregnancy on survival in low-grade glioma patients; (2) Pregnancy can provoke clinical deterioration and tumor growth on MRI; (3) In stable women at term, there is no benefit of cesarean section over vaginal delivery, with respect to adverse events in mother or child. Unanswered questions include when pregnancy should be discouraged, what best monitoring schedule is for both mother and fetus, and if and how chemo- and radiation therapy can be safely administered during pregnancy. A multicenter individual patient level meta-analysis collecting granular information on clinical management and related outcomes is needed to provide scientific evidence for clinical decision-making in pregnant glioma patients.Electronic supplementary materialThe online version of this article (10.1007/s11060-018-2851-3) contains supplementary material, which is available to authorized users.

Background: In patients with one to three brain metastases who undergo resection, options for post-operative treatments include whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) of the resection cavity. In this meta-analysis, we sought to compare the efficacy of each post-operative radiation modality with respect to tumor recurrence and survival. Methods: Pubmed, Embase and Cochrane databases were searched through June 2016 for cohort studies reporting outcomes of SRS or WBRT after metastasis resection. Pooled effect estimates were calculated using fixed-effect and random-effect models for local recurrence, distant recurrence, and overall survival. Results: Eight retrospective cohort studies with 646 patients (238 with SRS versus 408 with WBRT) were included in the analysis. Comparing SRS to WBRT, the overall crude risk ratio using the fixed-effect model was 0.59 for local recurrence (95%-CI: 0.32-1.09, I

OBJECTIVELoss of pituitary function due to nonfunctional pituitary adenoma (NFPA) may be due to compression of the pituitary gland. It has been proposed that the size of the gland and relative perioperative gland expansion may relate to recovery of pituitary function, but the extent of this is unclear. This study aims to assess temporal changes in hormonal function after transsphenoidal resection of NFPA and the relationship between gland reexpansion and endocrine recovery.METHODSPatients who underwent endoscopic transsphenoidal surgery by a single surgeon for resection of a nonfunctional macroadenoma were selected for inclusion. Patients with prior pituitary surgery or radiosurgery were excluded. Patient characteristics and endocrine function were extracted by chart review. Volumetric segmentation of the pre- and postoperative (≥ 6 months) pituitary gland was performed using preoperative and long-term postoperative MR images. The relationship between endocrine function over time and clinical attributes, including gland volume, were examined.RESULTSOne hundred sixty eligible patients were identified, of whom 47.5% were female; 56.9% of patients had anterior pituitary hormone deficits preoperatively. The median tumor diameter and gland volume preoperatively were 22.5 mm (interquartile range [IQR] 18.0–28.8 mm) and 0.18 cm3 (IQR 0.13–0.28 cm3), respectively. In 55% of patients, endocrine function normalized or improved in their affected axes by median last clinical follow-up of 24.4 months (IQR 3.2–51.2 months). Older age, male sex, and larger tumor size were associated with likelihood of endocrine recovery. Median time to recovery of any axis was 12.2 months (IQR 2.5–23.9 months); hypothyroidism was the slowest axis to recover. Although the gland significantly reexpanded from preoperatively (0.18 cm3, IQR 0.13–0.28 cm3) to postoperatively (0.33 cm3, IQR 0.23–0.48 cm3; p < 0.001), there was no consistent association with improved endocrine function.CONCLUSIONSRecovery of endocrine function can occur several months and even years after surgery, with more than 50% of patients showing improved or normalized function. Tumor size, and not gland volume, was associated with preserved or recovered endocrine function.

Arsenic exposure increases risk for cancers and is teratogenic in animal models. Here we demonstrate that small ubiquitin-like modifier (SUMO)-and folate-dependent nuclear de novo thymidylate (dTMP) biosynthesis is a sensitive target of arsenic trioxide (As 2 O 3 ), leading to uracil misincorporation into DNA and genome instability. Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and serine hydroxymethyltransferase (SHMT) generate 5,10-methylenetetrahydrofolate for de novo dTMP biosynthesis and translocate to the nucleus during S-phase, where they form a multienzyme complex with thymidylate synthase (TYMS) and dihydrofolate reductase (DHFR), as well as the components of the DNA replication machinery. As 2 O 3 exposure increased MTHFD1 SUMOylation in cultured cells and in in vitro SUMOylation reactions, and increased MTHFD1 ubiquitination and MTHFD1 and SHMT1 degradation. As 2 O 3 inhibited de novo dTMP biosynthesis in a dose-dependent manner, increased uracil levels in nuclear DNA, and increased genome instability. These results demonstrate that MTHFD1 and SHMT1, which are key enzymes providing one-carbon units for dTMP biosynthesis in the form of 5,10-methylenetetrahydrofolate, are direct targets of As 2 O 3 -induced proteolytic degradation, providing a mechanism for arsenic in the etiology of cancer and developmental anomalies.MTHFD1 | arsenic trioxide | one-carbon metabolism | SUMO-1

PURPOSE Although the bulk of patient-generated health data are increasing exponentially, their use is impeded because most data come in unstructured format, namely as free-text clinical reports. A variety of natural language processing (NLP) methods have emerged to automate the processing of free text ranging from statistical to deep learning–based models; however, the optimal approach for medical text analysis remains to be determined. The aim of this study was to provide a head-to-head comparison of novel NLP techniques and inform future studies about their utility for automated medical text analysis. PATIENTS AND METHODS Magnetic resonance imaging reports of patients with brain metastases treated in two tertiary centers were retrieved and manually annotated using a binary classification (single metastasis v two or more metastases). Multiple bag-of-words and sequence-based NLP models were developed and compared after randomly splitting the annotated reports into training and test sets in an 80:20 ratio. RESULTS A total of 1,479 radiology reports of patients diagnosed with brain metastases were retrieved. The least absolute shrinkage and selection operator (LASSO) regression model demonstrated the best overall performance on the hold-out test set with an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89 to 0.94), accuracy of 83% (95% CI, 80% to 87%), calibration intercept of –0.06 (95% CI, –0.14 to 0.01), and calibration slope of 1.06 (95% CI, 0.95 to 1.17). CONCLUSION Among various NLP techniques, the bag-of-words approach combined with a LASSO regression model demonstrated the best overall performance in extracting binary outcomes from free-text clinical reports. This study provides a framework for the development of machine learning-based NLP models as well as a clinical vignette of patients diagnosed with brain metastases.

Brain metastases (BMs) have become increasingly prevalent and present unique considerations for patients, including neurocognitive sequelae and advanced disease burden. Therefore, assessing health-related quality of life (HRQoL) via patient-reported outcome measures (PROMs) is an important element of managing these patients. A systematic review of the literature was conducted with the aims of (1) assessing how PROMS used in BM patients were validated, (2) assessing PROM content, and (3) evaluating quality of PROM-results reporting. PROM validation and quality of reporting were assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) grading criteria and International Society of Quality of Life (ISOQOL)-recommended PROM-reporting standards, respectively. Forty-seven studies reporting on 5178 patients with a range of primacy cancer types were included. Eight different PROMs were applied, ranging from general to brain-specific questionnaires. Weaknesses in the validation of these PROMs were assessed by the COSMIN criteria. Many of these PROMs were not developed for BM patients and contained little information on cognitive symptoms. The overall quality of PROM reporting was insufficient based on the ISOQOL scale. Given the unique clinical considerations in BM patients, our results indicate the need for a standardized, validated questionnaire to assess HRQoL in this population. Additionally, there is room for quality improvement with regard to reporting of PROM-related results.