VZV myelitis with secondary HIV CSF escape.

A 52-year-old woman with HIV and recent antiretroviral therapy non-adherence presented with a 5-day history of widespread painful vesicular skin lesions. Direct fluorescent antibody testing of the skin lesions was positive for varicella zoster virus (VZV). On day 3, she developed profound right upper extremity weakness. MRI of the brain and cervical spine was suggestive of VZV myelitis. Lumbar puncture was positive for VZV PCR in the cerebrospinal fluid (CSF) and CSF HIV viral load was detected at 1030 copies/mL, indicating 'secondary' HIV CSF escape. She was treated with intravenous acyclovir for 4 weeks and subsequent oral therapy with famciclovir then valacyclovir for 6 weeks. She also received dexamethasone. The patient had an almost full recovery at 6 months. Myelitis is a rare complication of reactivated VZV infection that can have atypical presentation in immunocompromised patients. Such 'secondary' HIV CSF escape should be considered in immunosuppressed patients with concomitant central nervous system infection.

Preliminary In Vivo Evidence of Reduced Synaptic Density in Human Immunodeficiency Virus (HIV) Despite Antiretroviral Therapy.

BACKGROUND: Synaptic injury is a pathological hallmark of neurological impairment in people living with human immunodeficiency virus (HIV, PLWH), a common complication despite viral suppression with antiretroviral therapy (ART). Measurement of synaptic density in living humans may allow better understanding of HIV neuropathogenesis and provide a dynamic biomarker for therapeutic studies. We applied novel synaptic vesical protein 2A (SV2A) positron emission tomographic (PET) imaging to investigate synaptic density in the frontostriatalthalamic region in PLWH and HIV-uninfected participants. METHODS: In this cross-sectional pilot study,13 older male PLWH on ART underwent magnetic resonance imaging (MRI) and PET scanning with the SV2A ligand [11C]UCB-J with partial volume correction and had neurocognitive assessments. SV2A binding potential (BPND) in the frontostriatalthalamic circuit was compared to 13 age-matched HIV-uninfected participants and assessed with respect to neurocognitive performance in PLWH. RESULTS: PLWH had 14% lower frontostriatalthalamic SV2A synaptic density compared to HIV-uninfected (PLWH: mean [SD], 3.93 [0.80]; HIV-uninfected: 4.59 [0.43]; P = .02, effect size 1.02). Differences were observed in widespread additional regions in exploratory analyses. Higher frontostriatalthalamic SV2A BPND associated with better grooved pegboard performance, a measure of motor coordination, in PLWH (r = 0.61, P = .03). CONCLUSIONS: In a pilot study, SV2A PET imaging reveals reduced synaptic density in older male PLWH on ART compared to HIV-uninfected in the frontostriatalthalamic circuit and other cortical areas. Larger studies controlling for factors in addition to age are needed to determine whether differences are attributable to HIV or comorbidities in PLWH. SV2A imaging is a promising biomarker for studies of neuropathogenesis and therapeutic interventions in HIV.

Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection.

INTRODUCTION: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals. In this study we sought to determine if tracking smell sensitivity and loss using an at-home assessment could identify SARS-CoV-2 infection in HCW. METHODS AND FINDINGS: We performed a prospective cohort study tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, behavioral at-home assessment of olfaction with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and real-time quantitative polymerase chain reaction testing to identify SARS-CoV-2 infection. Our main measures were the prevalence of smell loss in SARS-CoV-2-positive HCW versus SARS-CoV-2-negative HCW, and timing of smell loss relative to SARS-CoV-2 test positivity. SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. HCW with SARS-CoV-2 infection were more likely to report smell loss than SARS-CoV-2-negative HCW on both the at-home assessment and the screening questionnaire (9/17, 53% vs 105/456, 23%, P < .01). 6/9 (67%) of SARS-CoV-2-positive HCW reporting smell loss reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among SARS-CoV-2-positive HCW who reported smell loss compared to those without smell loss (9/9, 100% vs 3/8, 38%, P < .01). CONCLUSIONS: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of SARS-CoV-2 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.

Challenging the concept of de novo acute myeloid leukemia: Environmental and occupational leukemogens hiding in our midst.

Myeloid neoplasms like acute myeloid leukemia (AML) originate from genomic disruption, usually in a multi-step fashion. Hematopoietic stem/progenitor cell acquisition of abnormalities in vital cellular processes, when coupled with intrinsic factors such as germline predisposition or extrinsic factors such as the marrow microenvironment or environmental agents, can lead to requisite pre-leukemic clonal selection, expansion and evolution. Several of these entities have been invoked as "leukemogens." The known leukemogens are numerous and are found in the therapeutic, occupational and ambient environments, however they are often difficult to implicate for individual patients. Patients treated with particular chemotherapeutic agents or radiotherapy accept a calculated risk of therapy-related AML. Occupational exposures to benzene, dioxins, formaldehyde, electromagnetic and particle radiation have been associated with an increased risk of AML. Although regulatory agencies have established acceptable exposure limits in the workplace, accidental exposures and even ambient exposures to leukemogens are possible. It is plausible that inescapable exposure to non-anthropogenic ambient leukemogens may be responsible for many cases of non-inherited de novo AML. In this review, we discuss the current understanding of leukemogens as they relate to AML, assess to what extent the term "de novo" leukemia is meaningful, and describe the potential to identify and characterize new leukemogens.

Effect of recombinant human growth hormone on liver fat content in young adults with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in young adults with obesity. Obesity is associated with relative growth hormone (GH) deficiency, and data from animal studies and from humans with pituitary GH deficiency suggest a role for GH deficiency in the pathogenesis of NAFLD. The effects of GH on NAFLD in those with obesity are unknown, however, prompting this pilot study to assess effects of GH administration on measures of NAFLD in young adults. METHODS: Twenty-four men and women aged 18-29 years with BMI ≥ 30 kg/m2 , hepatic fat fraction (HFF) ≥ 5% on proton magnetic resonance spectroscopy (1 H-MRS) and insulin-like growth factor 1 (IGF-1) z-score ≤ 0 were randomized to treatment with recombinant human GH (rhGH) versus no treatment for 24 weeks. The primary endpoint was change in HFF. RESULTS: Compared to no treatment, the effect size of rhGH on absolute HFF over 24 weeks was -3.3% (95% confidence interval: -7.8%, 1.2%; p = .14). At 24 weeks, HFF < 5% was achieved in 5 of 9 individuals receiving rhGH versus 1 of 9 individuals receiving no treatment (p = .04). rhGH did not significantly reduce ALT, AST or GGT. Serum IGF-1 increased as expected with rhGH treatment, and there were no changes in fasting lipids, C-reactive protein, fasting glucose or 2-h glucose following an oral glucose tolerance test. CONCLUSION: Data from this pilot study suggest that rhGH treatment in young adults with obesity and NAFLD may have benefits to reduce liver fat content, although larger studies are needed to confirm this effect.

A clandestine culprit with critical consequences: Benzene and acute myeloid leukemia.

While most clinicians recognize adult therapy-related leukemias following cytotoxic chemotherapy and radiation, environmental regulatory agencies evaluate exposure to "safe levels" of leukemogenic compounds. Benzene represents the most notorious leukemogenic chemical. Used in the production of ubiquitous items such as plastics, lubricants, rubbers, dyes, and pesticides, benzene may be responsible for the higher risk of acute myeloid leukemia (AML) among automobile, janitorial, construction, and agricultural workers. It is possible that ambient benzene may contribute to many cases of "de novo" AML not arising out of germline predispositions. In this appraisal of the available literature, we evaluate and discuss the association between chronic, low-dose and ambient exposure to environmental benzene and the development of adult AML.

Tracking Smell Loss to Identify Healthcare Workers with SARS-CoV-2 Infection.

BACKGROUND: Healthcare workers (HCW) treating COVID-19 patients are at high risk for infection and may also spread infection through their contact with vulnerable patients. Smell loss has been associated with SARS-CoV-2 infection, but it is unknown whether monitoring for smell loss can be used to identify asymptomatic infection among high risk individuals, like HCW. METHODS: We performed a prospective cohort study, tracking 473 HCW across three months to determine if smell loss could predict SARS-CoV-2 infection in this high-risk group. HCW subjects completed a longitudinal, novel behavioral at-home assessment of smell function with household items, as well as detailed symptom surveys that included a parosmia screening questionnaire, and RT-qPCR testing to identify SARS-CoV-2 infection. RESULTS: SARS-CoV-2 was identified in 17 (3.6%) of 473 HCW. Among the 17 infected HCW, 53% reported smell loss, and were more likely to report smell loss than COVID-negative HCW on both the at-home assessment and the screening questionnaire (P < .01). 67% reported smell loss prior to having a positive SARS-CoV-2 test, and smell loss was reported a median of two days before testing positive. Neurological symptoms were reported more frequently among COVID-positive HCW who reported smell loss (P < .01). CONCLUSIONS: In this prospective study of HCW, self-reported changes in smell using two different measures were predictive of COVID-19 infection. Smell loss frequently preceded a positive test and was associated with neurological symptoms.

Utility and duration of leuprolide stimulation testing in children.

Objective Basal (unstimulated) LH levels and leuprolide stimulation tests are used to define pubertal status of children presenting with signs of early puberty. The primary aims of this study were to (i) confirm utility of detectable basal LH levels in precluding the need for leuprolide stimulation testing, and, (ii) determine whether duration of testing could be abbreviated from usual 3 h test without compromising sensitivity. Methods We reviewed morning basal and leuprolide-stimulated LH levels in 105 children, aged 1-9 years (mean 6.9 years, SD 1.8) who were seen for concerns of precocious puberty and received a leuprolide stimulation test between June 2006 and March 2017. Results A pubertal basal LH level had high specificity and poor sensitivity for the following outcome measures: (1) peak stimulated LH≥5 mIU/mL (2) treatment with GnRHa; and (3) a composite outcome of (1) and/or (2). Following leuprolide stimulation, LH response was highest at 180 min in most children (n=78, 74.3%). Using a single cutoff of LH≥5 mIU/mL at any timepoint, 25% of children would have been misdiagnosed with an abbreviated 60 min test. A single sample at 180 min would have correctly identified 97% of patients. Conclusions A pubertal basal LH level is sufficient to distinguish children with precocious puberty without stimulation testing. However, prepubertal basal LH had relatively poor negative predictive value to refute CPP, necessitating clinical follow-up and/or a leuprolide stimulation test. For a cutoff of LH≥5 mIU/mL at any timepoint, test duration of 180 min maximizes sensitivity.

Diet Quality Is Low and Differs by Sex in People with HIV.

Background: People with HIV (PWH) are at risk for developing metabolic comorbidities driven, in part, by immune activation/inflammation. Little is known about diet quality, a potential modifiable factor in PWH. Objectives: This study aimed to explore diet quality in terms of conformance with US dietary guidelines by calculating Healthy Eating Index-2010 (HEI) scores among adults with and without HIV in Boston, MA, and determine associations with HEI and markers of immune activation/inflammation. Methods: One-hundred and three HIV-infected [50 women, 53 men; mean ± SD age: 47 ± 7 y; body mass index (BMI, in kg/m2): 26 ± 5] and 38 uninfected adults (17 women, 21 men; age: 46 ± 7 y; BMI: 28 ± 4) were included in this cross-sectional analysis. Participants who completed a 4-d food record from which HEI could be calculated were included. HEI was compared between participants with and without HIV, within HIV-infected participants stratified by sex, and by HIV serostatus and sex. In the HIV group, predictors of HEI were determined in multivariable modeling. Univariate associations with diet quality and inflammation/immune markers were assessed. Results: The HEI score was 51.3 in the HIV-infected participants and 57.3 in the HIV-uninfected participants (P = 0.052). In the comparison by HIV serostatus and sex, HIV-infected women had significantly lower HEI (49.2) compared with HIV-infected men (55.7) (P = 0.005) and HIV-uninfected men (61.8) (P = 0.002). Adjusting for potential confounding factors, sex remained an independent predictor of HEI in HIV (P = 0.02). In the HIV group, higher log HEI was associated with lower concentration of the immune activation marker sCD14 (P = 0.009). Conclusions: Diet quality tended to be lower in HIV-infected individuals compared with HIV-uninfected individuals and was lower among HIV-infected women compared with HIV-infected men, and HIV-uninfected men. There may also be an association with diet quality and sCD14 in PWH. Future prospective studies are needed to confirm these findings and determine whether improving diet quality is a useful strategy to reduce metabolic abnormalities in this population. This study was registered at clinicaltrials.gov as NCT00455793.