LTA4H Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis.

We conducted a prospective cohort study to determine the prevalence of leukotriene A4 hydrolase (LTA4H) polymorphisms in Zambian adults with tuberculous meningitis (TBM) and its association with mortality. We completed genotype testing on 101 definite cases of TBM and 119 consecutive non-TBM controls. The distribution of genotypes among TBM patients was as follows: C/C (0.83), C/T (0.14), T/T (0.03). There was no significant difference in genotype distribution between TBM and non-TBM patients. We found no relationship between LTA4H polymorphism and survival. Prospective studies are needed to determine the benefit of adjuvant steroids in TBM based upon population LTA4H genotype. ANN NEUROL 2021;90:994-998.

Occipital Headache Evaluation and Rates of Migraine Assessment, Diagnosis, and Treatment in Patients Receiving Greater Occipital Nerve Blocks in an Academic Pain Clinic.

OBJECTIVE: Diagnosis of patients with occipital headache can be challenging, as both primary and secondary causes must be considered. Our study assessed how often migraine is screened for, diagnosed, and treated in patients receiving greater occipital nerve blocks (GONBs) in a pain clinic. DESIGN: Institutional review board-approved, retrospective observational study. SETTING: Academic multidisciplinary pain clinic. SUBJECTS: One hundred forty-three consecutive patients who received GONBs. RESULTS: About 75% of patients had been evaluated by neurologists and about 25% by non-neurologist pain specialists only, and 62.2% of patients had photophobia, phonophobia, and nausea assessed. Compared with patients who had been evaluated by non-neurologists, patients who had been evaluated by a neurologist were more likely to have photophobia, phonophobia, and nausea assessed (75.9% vs 20.0%, odds ratio [OR] 12.6, 95% confidence interval [CI] 4.90 to 32.2); more likely to be diagnosed with migraine (48.1% vs 14.3%, OR 5.6, 95% CI 2.0 to 15); less likely to be diagnosed with occipital neuralgia (39.8% vs 65.7%, OR 0.3, 95% CI 0.2 to 0.8); and equally likely to be diagnosed with cervicogenic headache (21.3% vs 25.7%, OR 0.8, 95% CI 0.3 to 1.9). Among patients diagnosed with migraine, 82.5% received acute migraine treatment, 89.5% received preventive migraine treatment, and 52.6% were documented as receiving migraine lifestyle counseling. CONCLUSIONS: Of the patients in this study who had occipital headache and received GONBs, 62.2% were assessed for migraine, and most received appropriate acute, preventive, and lifestyle treatments when diagnosed. Patients seen by neurologists were significantly more likely to be screened for and diagnosed with migraine than were those evaluated by non-neurologist pain medicine specialists only. All clinicians should remain vigilant for migraine in patients with occipital headache.

Prospective Cohort Study on Performance of Cerebrospinal Fluid (CSF) Xpert MTB/RIF, CSF Lipoarabinomannan (LAM) Lateral Flow Assay (LFA), and Urine LAM LFA for Diagnosis of Tuberculous Meningitis in Zambia.

Tuberculous meningitis (TBM) is a devastating infection of the central nervous system lacking an adequate point-of-care diagnostic test. We conducted a prospective cohort study of 550 Zambian adults with suspected TBM to determine the diagnostic accuracy of cerebrospinal fluid (CSF) Xpert MTB/RIF, CSF lipoarabinomannan (LAM), urine LAM, CSF total protein, and CSF glucose compared with the gold standard of CSF culture. We categorized patients with a positive CSF tuberculosis (TB) culture as definite TBM. We also assessed inpatient and 1-year mortality on definite TBM patients when CSF Xpert MTB/RIF results were available in real time to treating physicians relative to a historical comparison cohort in whom Xpert results were not available in real time. Of the 550 patients, 474 (86.2%) were HIV-infected and 105/550 (19.1%) had definite TBM based on a positive CSF culture. The sensitivity/specificity of the diagnostic tests were CSF Xpert MTB/RIF, 52.9%/94.2%; CSF LAM, 21.9%/94.2%; urine LAM, 24.1%/76.1%; and CSF glucose <40 mg/dl, and total protein, >100 mg/dl, 66.3%/90%. A model including CSF Xpert MTB/RIF, CSF LAM, CSF glucose, and CSF total protein demonstrated an area under the receiver operating curve of 0.90. The inpatient and 1-year mortality for definite TBM was 43% and 57%, respectively. There was low sensitivity for the diagnosis of TBM across all diagnostics tests. CSF Xpert MTB/RIF and CSF LAM are highly specific for the diagnosis of TBM. Despite the use of Xpert MTB/RIF for diagnostic purpose in real time, TBM was still associated with a high mortality in Zambian patients.

THE RELATIONSHIP BETWEEN PITCHING VOLUME AND ARM SORENESS IN COLLEGIATE BASEBALL PITCHERS.

BACKGROUND: Excessive baseball pitch volume has been associated with increased risk of injury in adolescents. However, many collegiate athletes report non-time loss injuries over the course of the season. It is unknown how pitch volume throughout a collegiate baseball season affects arm soreness. PURPOSE: The primary purpose of this study was to determine the relationship between pitch volume and self-reported arm soreness. A secondary purpose was to determine the relationship between change in pitch volume and change in arm soreness over the course of the season for collegiate baseball pitchers. STUDY DESIGN: Prospective Cohort. METHODS: Seven collegiate baseball pitchers volunteered to participate in a yearlong prospective study. The seven pitchers reported daily pitch volume and level of soreness from the fall through spring collegiate baseball season during practices and games. The athletic trainer, a member of the research team, tracked athletic exposures and injuries for the entire season. Frequency counts of athletic exposures were categorized by game, practice, conditioning and injury status. Frequency counts of pitch volume was categorized by game, game bullpen, practice bullpen, flat ground, long toss and warm-up pitches. The pitch volume and soreness levels for each athlete were used to determine the relationship between these two variables using a Pearson correlation. RESULTS: The seven pitchers were involved with 1,256 athletic exposures and a total of 54,151 throws, averaging 7,735 throws per player for the entire season. The pitch volume and self-reported arm soreness for the entire season revealed a correlation of r = .72 (p = .004). The relationship between change in pitch volume and change in arm soreness was r = .635 (p = .001) over the season. CONCLUSION: There was a moderate significant correlation between arm soreness and pitch volume across the whole season. This relationship was maintained when evaluating weekly changes. LEVEL OF EVIDENCE: 4.

Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha.

Background: The mesenchymal phenotype in glioblastoma (GBM) and other cancers drives aggressiveness and treatment resistance, leading to therapeutic failure and recurrence of disease. Currently, there is no successful treatment option available against the mesenchymal phenotype. Methods: We classified patient-derived GBM stem cell lines into 3 subtypes: proneural, mesenchymal, and other/classical. Each subtype's response to the inhibition of diacylglycerol kinase alpha (DGKα) was compared both in vitro and in vivo. RhoA activation, liposome binding, immunoblot, and kinase assays were utilized to elucidate the novel link between DGKα and geranylgeranyltransferase I (GGTase I). Results: Here we show that inhibition of DGKα with a small-molecule inhibitor, ritanserin, or RNA interference preferentially targets the mesenchymal subtype of GBM. We show that the mesenchymal phenotype creates the sensitivity to DGKα inhibition; shifting GBM cells from the proneural to the mesenchymal subtype increases ritanserin activity, with similar effects in epithelial-mesenchymal transition models of lung and pancreatic carcinoma. This enhanced sensitivity of mesenchymal cancer cells to ritanserin is through inhibition of GGTase I and downstream mediators previously associated with the mesenchymal cancer phenotype, including RhoA and nuclear factor-kappaB. DGKα inhibition is synergistic with both radiation and imatinib, a drug preferentially affecting proneural GBM. Conclusions: Our findings demonstrate that a DGKα-GGTase I pathway can be targeted to combat the treatment-resistant mesenchymal cancer phenotype. Combining therapies with greater activity against each GBM subtype may represent a viable therapeutic option against GBM.

Talking with parents of high school football players about chronic traumatic encephalopathy: a concise summary.

Over the past decade, athletic-related chronic traumatic encephalopathy (CTE) has garnered a great deal of attention in the popular press and, more recently, in the scientific press. With increasing frequency, sports medicine practitioners and providers are faced with questions from the parents of high school football players about CTE and the risk posed to children who participate in this or other contact or collision sports. The purpose of this review was to summarize the research on CTE in an attempt to provide some evidence-based answers to frequently asked questions in clinics from parents. Addressed are (1) the definitions of CTE and its symptoms, (2) the evidence for CTE in football, (3) abnormal tau protein, (4) the use of neuroimaging in CTE diagnosis, (5) risk for CTE, (6) CTE diagnosis in youth, (7) CTE and its relationship to suicide, and (8) contact and collision sports as a risk factor for permanent brain injury or death.

Descriptive analysis of pitch volume in southeastern conference baseball pitchers.

BACKGROUND: Representative data on typical pitch volume for collegiate pitchers functioning in their specific roles is sparse and is needed for training specificity. OBJECTIVE: To report pitch volumes in Division I collegiate pitchers. The authors hypothesize that pitcher role will result in different pitch volumes. METHODS: Pitchers from twelve Division I collegiate baseball teams pitch volume during the 2009 baseball season was retrospectively reviewed through each team's website. The number of pitches and innings pitched for each pitcher were recorded. Pitchers were categorized based on their role as "Starter-only" (n=15), "Reliever-only" (n=76), or "Combined Starter/Reliever" (n=94) and compared using ANOVA. RESULTS: "Starter-only" pitchers threw the most pitches (97±10) and pitched the most innings (6.0±1.0) per appearance (p=<.001). "Combined Starter/Reliever" functioning as a starter threw significantly more pitches (68±19) and pitched more innings (4.0±1.3) per appearance compared to "Combined Starter/Reliever" functioning as a reliever and "Reliever-only" pitchers (p=<.001). The cumulative volume during a 13 week regular season revealed that "Starter-only" pitchers threw significantly more total pitches (1204±387) compared to "Combined Starter/Reliever" pitchers (613±182) who threw significantly more than "Reliever-only" pitchers (254±77) (P<.001). DISCUSSION: Pitcher's specific roles and representative volumes should be used to design training and rehabilitation programs. Comparison of this data to reported adolescent pitch volumes reveal that adolescent pitch volume per appearance approaches collegiate levels. CONCLUSIONS: Collegiate pitcher roles dictate their throwing volume. Starter-only pitchers (8%) throw the greatest cumulative number of pitches and should be trained differently than the majority of college pitchers (92%) who function primarily as a reliever or in combination starter/reliever roles that on average only requires approximately 40 pitches per appearance.