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Article ; Online: Appraisal of International Guidelines for Cutaneous Melanoma Management using the AGREE II assessment tool.

Jacklin, C / Tan, M / Sravanam, S / Harrison, C J

2021 Volume 31, Page(s) 114–122

Abstract: Background: The evidence base behind new melanoma treatments is rapidly accumulating. This is not necessarily reflected in current guidance. A recent UK-based expert consensus statement, published in JPRAS, has called for updates to the widely accepted ... ...

Abstract	Background: The evidence base behind new melanoma treatments is rapidly accumulating. This is not necessarily reflected in current guidance. A recent UK-based expert consensus statement, published in JPRAS, has called for updates to the widely accepted 2015 National Institute for Health and Care Excellence (NICE) guideline for melanoma (NG14). We aimed to compare the quality of NG14 to all other melanoma guidelines published since. Methods: We conducted a systematic search of PubMed, Medline, and online clinical practice guideline databases to identify melanoma guidelines published between 29th July 2015 and 23rd August 2021 providing recommendations for adjuvant treatment, radiotherapy, surgical management, or follow-up care. Three authors independently assessed the quality of identified guidelines using the Appraisal of Guidelines for Research & Evaluation Instrument II (AGREE II) assessment tool, which measures six domains of guideline development. Inter-rater reliability was assessed by Kendall's coefficient of concordance (W). Results: Twenty-nine guidelines were included and appraised with excellent concordance (Kendall's W for overall guideline score 0.88, p<0.001). Overall, melanoma guidelines scored highly in the domains of 'Scope and purpose' and 'Clarity of presentation', but poorly in the 'Applicability' domain. The NICE guideline on melanoma (NG14) achieved the best overall scores. Conclusion: Melanoma treatment has advanced since NG14 was published, however, the NICE melanoma guideline is of higher quality than more recent alternatives. The planned update of NG14 in 2022 is in demand.
Language	English
Publishing date	2021-12-08
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2834721-3
ISSN	2352-5878 ; 2352-5878
ISSN (online)	2352-5878
ISSN	2352-5878
DOI	10.1016/j.jpra.2021.11.002
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Article ; Online: Twelve tips for teaching neuroanatomy, from the medical students' perspective.

Sravanam, Sanskrithi / Jacklin, Chloë / McNelis, Eoghan / Fung, Kwan Wai / Xu, Lucy

Medical teacher

2022 Volume 45, Issue 5, Page(s) 466–474

Abstract: Neuroanatomy is a complex and fascinating subject that is often a daunting prospect for medical students. In fact, the fear of learning neuroanatomy has gained its own name - "neurophobia." This widespread phenomenon among medical students poses a ... ...

Abstract	Neuroanatomy is a complex and fascinating subject that is often a daunting prospect for medical students. In fact, the fear of learning neuroanatomy has gained its own name - "neurophobia." This widespread phenomenon among medical students poses a challenge to medical teachers and educators. To tackle "neurophobia" by summarising tips for dynamic and engaging neuroanatomy teaching formulated based on our experiences as medical students and evidence-based techniques.Focusing on the anatomical, physiological, and clinical aspects of neurology and their integration, here we present 12 tips which are [1] Teach the basic structure before fine details, [2] Supplement teaching with annotated diagrams, [3] Use dissections for haptic learning, [4] Teach form and function together, [5] Group anatomy into systems, [6] Familiarise students with neuroimaging, [7] Teach from clinical cases, [8] Let the patient become the teacher, [9] Build from first principles, [10] Try working in reverse, [11] Let the student become the teacher, [12] Let the student become the examiner. These 12 tips can be used by teachers and students alike to provide a high-yield learning experience.
MeSH term(s)	Humans ; Neuroanatomy/education ; Students, Medical ; Curriculum ; Education, Medical, Undergraduate/methods ; Learning ; Teaching
Language	English
Publishing date	2022-07-22
Publishing country	England
Document type	Journal Article
ZDB-ID	424426-6
ISSN	1466-187X ; 0142-159X
ISSN (online)	1466-187X
ISSN	0142-159X
DOI	10.1080/0142159X.2022.2098097
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Article ; Online: Surgical and oncological score to estimate the survival benefit of resection and chemoradiotherapy in elderly (≥70 years) glioblastoma patients: A preliminary analysis.

Zorman, Mark J / Webb, Philip / Nixon, Mickaela / Sravanam, Sanskrithi / Honeyman, Susan / Nandhabalan, Meera / Apostolopoulos, Vasileios / Stacey, Richard / Hobbs, Claire / Plaha, Puneet

Neuro-oncology advances

2022 Volume 4, Issue 1, Page(s) vdac007

Abstract: Background: Elderly patients with glioblastoma are perceived to face a poor prognosis with perceptions surrounding older age and a relative lack of randomized data contributing. This study evaluated survival prognosticators in elderly glioblastoma ... ...

Abstract	Background: Elderly patients with glioblastoma are perceived to face a poor prognosis with perceptions surrounding older age and a relative lack of randomized data contributing. This study evaluated survival prognosticators in elderly glioblastoma patients to more accurately guide their treatment. Methods: The records of 169 elderly (≥70 years) patients with a new diagnosis of glioblastoma who had undergone neurosurgical intervention were retrospectively examined for patient sex, age, performance status, comorbidities, MGMT promoter methylation, surgical intervention, and chemoradiation regime. The adjusted survival impact of these factors was determined using Cox proportional hazards model and used to devise a two-stage scoring system to estimate patient survival at the stage of surgical (Elderly Glioblastoma Surgical Score, EGSS) and oncological management (Elderly Glioblastoma Oncological Score, EGOS). Results: The median overall survival (mOS) of the cohort was 28.8 weeks. Gross-total and subtotal resection were associated with improved survival compared to biopsy alone (respective mOS 65.3 and 28.1 vs 15.7 weeks, Conclusions: Where appropriate and safe, elderly glioblastoma patients may benefit from surgical resection and combined chemoradiotherapy with Temozolomide. The proposed EGSS and EGOS scores take into account important prognostic factors to help guide which patients should receive such treatment.
Language	English
Publishing date	2022-01-28
Publishing country	England
Document type	Journal Article
ZDB-ID	3009682-0
ISSN	2632-2498 ; 2632-2498
ISSN (online)	2632-2498
ISSN	2632-2498
DOI	10.1093/noajnl/vdac007
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Article ; Online: Amplification of Replication Competent HIV-1 by Adoptive Transfer of Human Cells From Infected Humanized Mice.

Su, Hang / Sravanam, Sruthi / Gorantla, Santhi / Kaminski, Rafal / Khalili, Kamel / Poluektova, Larisa / Gendelman, Howard E / Dash, Prasanta K

Frontiers in cellular and infection microbiology

2020 Volume 10, Page(s) 38

Abstract: Detection of latent human immunodeficiency virus type 1 (HIV-1) in "putative" infectious reservoirs is required for determining treatment efficiency and for viral elimination strategies. Such tests require induction of replication competent provirus and ... ...

Abstract	Detection of latent human immunodeficiency virus type 1 (HIV-1) in "putative" infectious reservoirs is required for determining treatment efficiency and for viral elimination strategies. Such tests require induction of replication competent provirus and quantitative testing of viral load for validation. Recently, humanized mice were employed in the development of such tests by employing a murine viral outgrowth assay (mVOA). Here blood cells were recovered from virus infected antiretroviral therapy suppressed patients. These cells were adoptively transferred to uninfected humanized mice where replication competent virus was recovered. Prior reports supported the notion that an mVOA assay provides greater sensitivity than cell culture-based quantitative VOA tests for detection of latent virus. In the current study, the mVOA assays was adapted using donor human hematopoietic stem cells-reconstituted mice to affirm research into HIV-1 elimination. We simulated an antiretroviral therapy (ART)-treated virus-infected human by maintaining the infected humanized mice under suppressive treatment. This was operative prior to human cell adoptive transfers. Replication-competent HIV-1 was easily detected in recipient animals from donors with undetectable virus in plasma. Moreover, when the assay was used to investigate viral presence in tissue reservoirs, quantitative endpoints were determined in "putative" viral reservoirs not possible in human sample analyses. We conclude that adoptive transfer of cells between humanized mice is a sensitive and specific assay system for detection of replication competent latent HIV-1.
MeSH term(s)	Adoptive Transfer ; Animals ; CD4-Positive T-Lymphocytes ; HIV Infections/therapy ; HIV-1 ; Humans ; Mice ; Viral Load ; Virus Latency ; Virus Replication
Language	English
Publishing date	2020-02-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2020.00038
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Article ; Online: Traumatic Brain Injury-Related Pediatric Mortality and Morbidity in Low- and Middle-Income Countries: A Systematic Review.

Bandyopadhyay, Soham / Kawka, Michal / Marks, Katya / Richards, Georgia C / Taylor, Elliott H / Sravanam, Sanskrithi / Petrinic, Tatjana / Thango, Nqobile / Figaji, Anthony / Peter, Noel / Lakhoo, Kokila

World neurosurgery

2021 Volume 153, Page(s) 109–130.e23

Abstract: Background: The burden of pediatric traumatic brain injury (pTBI) in low- and middle-income countries (LMICs) is unknown. To fill this gap, we conducted a review that aimed to characterize the causes of pTBI in LMICs, and their reported associated ... ...

Abstract	Background: The burden of pediatric traumatic brain injury (pTBI) in low- and middle-income countries (LMICs) is unknown. To fill this gap, we conducted a review that aimed to characterize the causes of pTBI in LMICs, and their reported associated mortality and morbidity. Methods: A systematic review was conducted. MEDLINE, Embase, Global Health, and Global Index Medicus were searched from January 2000 to May 2020. Observational or experimental studies on pTBI of individuals aged between 0 and 16 years in LMICs were included. The causes of pTBI and morbidity data were descriptively analyzed, and case fatality rates were calculated. Prospero id: CRD42020171276. Results: A total of 136 studies were included. Fifty-seven studies were at high risk of bias. Of the remaining studies, 170,224 cases of pTBI were reported in 32 LMICs. The odds of having a pTBI were 1.8 times higher (95% confidence interval, 1.6-2.0) in males. The odds of a pTBI being mild were 4.4 times higher (95% confidence interval, 1.9-6.8) than a pTBI being moderate or severe. Road traffic accidents were the most common cause (n = 16,275/41,979; 39%) of pTBIs. On discharge, 24% of patients (n = 4385/17,930) had a reduction in their normal mental or physical function. The median case fatality rate was 7.3 (interquartile range, 2.1-7.7). Conclusions: Less than a quarter (n = 32) of all LMICs have published high-quality data on the volume and burden of pTBI. From the limited data available, young male children are at a high risk of pTBIs in LMICs, particularly after road traffic accidents.
MeSH term(s)	Adolescent ; Brain Injuries, Traumatic/epidemiology ; Child ; Child, Preschool ; Cost of Illness ; Developing Countries ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Morbidity ; Socioeconomic Factors
Language	English
Publishing date	2021-06-21
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2021.06.077
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Zs.A 1159: Show issues

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Article ; Online: Recovery of Latent HIV-1 from Brain Tissue by Adoptive Cell Transfer in Virally Suppressed Humanized Mice.

Su, Hang / Sravanam, Sruthi / Sillman, Brady / Waight, Emiko / Makarov, Edward / Mathews, Saumi / Poluektova, Larisa Y / Gorantla, Santhi / Gendelman, Howard E / Dash, Prasanta K

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2021 Volume 16, Issue 4, Page(s) 796–805

Abstract: Defining the latent human immunodeficiency virus type 1 (HIV-1) burden in the human brain during progressive infection is limited by sample access. Human hematopoietic stem cells (hu-HSCs)-reconstituted humanized mice provide an opportunity for this ... ...

Abstract	Defining the latent human immunodeficiency virus type 1 (HIV-1) burden in the human brain during progressive infection is limited by sample access. Human hematopoietic stem cells (hu-HSCs)-reconstituted humanized mice provide an opportunity for this study. The model mimics, in measure, HIV-1 pathophysiology, transmission, treatment, and elimination in an infected human host. However, to date, brain HIV-1 latency in hu-HSC mice during suppressive antiretroviral therapy (ART) was not studied. To address this need, hu-HSC mice were administered long acting (LA) ART 14 days after HIV-1 infection was established. Animals were maintained under suppressive ART for 3 months, at which time HIV-1 infection was detected at low levels in brain tissue by droplet digital polymerase chain reaction (ddPCR) test on DNA. Notably, adoptive transfer of cells acquired from the hu-HSC mouse brains and placed into naive hu-HSC mice demonstrated viral recovery. These proof-of-concept results demonstrate replication-competent HIV-1 reservoir can be established in hu-HSC mouse brains that persists during long-term ART treatment. Hu-HSC mice-based mouse viral outgrowth assay (hu-MVOA) serves as a sensitive tool to interrogate latent HIV-1 brain reservoirs.
MeSH term(s)	Animals ; Mice ; Adoptive Transfer ; Brain ; CD4-Positive T-Lymphocytes ; Disease Models, Animal ; HIV Infections/drug therapy ; HIV-1 ; Viral Load ; Virus Latency ; Virus Replication ; Humans
Language	English
Publishing date	2021-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-021-10011-w
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Article ; Online: Immune Activations and Viral Tissue Compartmentalization During Progressive HIV-1 Infection of Humanized Mice.

Su, Hang / Cheng, Yan / Sravanam, Sruthi / Mathews, Saumi / Gorantla, Santhi / Poluektova, Larisa Y / Dash, Prasanta K / Gendelman, Howard E

Frontiers in immunology

2019 Volume 10, Page(s) 340

Abstract: Human immunodeficiency virus type one (HIV-1) tissue compartments are established soon after viral infection. However, the timing in which virus gains a permanent foothold in tissue and the cellular factors that control early viral-immune events are ... ...

Abstract	Human immunodeficiency virus type one (HIV-1) tissue compartments are established soon after viral infection. However, the timing in which virus gains a permanent foothold in tissue and the cellular factors that control early viral-immune events are incompletely understood. These are critical events in studies of HIV-1 pathogenesis and in the development of viral reservoirs after antiretroviral therapy. Moreover, factors affecting the permanence of viral-tissue interactions underlie barriers designed to eliminate HIV-1 infection. To this end we investigated the temporal and spatial viral and host factors during HIV-1 seeding of tissue compartments. Two humanized NOD.Cg-Prkdc
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/virology ; Disease Models, Animal ; Disease Progression ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Mice ; Mice, Transgenic ; Organ Specificity/immunology ; Viral Load ; Viral Proteins
Chemical Substances	Viral Proteins
Language	English
Publishing date	2019-02-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.00340
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Article ; Online: CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice.

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 19, Page(s) e2217887120

Abstract: Treatment of HIV- ... ...

Abstract	Treatment of HIV-1
MeSH term(s)	Mice ; Animals ; Humans ; Anti-Retroviral Agents/therapeutic use ; Gene Editing ; HIV Infections ; HIV Seropositivity ; Proviruses/genetics ; Receptors, CCR5
Chemical Substances	Anti-Retroviral Agents ; CCR5 protein, human ; Receptors, CCR5
Language	English
Publishing date	2023-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2217887120
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Zs.A 1148: Show issues

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Article ; Online: Creation of a long-acting rilpivirine prodrug nanoformulation.

Hilaire, James R / Bade, Aditya N / Sillman, Brady / Gautam, Nagsen / Herskovitz, Jonathan / Dyavar Shetty, Bhagya Laxmi / Wojtkiewicz, Melinda S / Szlachetka, Adam / Lamberty, Benjamin G / Sravanam, Sruthi / Fox, Howard S / Alnouti, Yazen / Dash, Prasanta K / McMillan, JoEllyn M / Edagwa, Benson J / Gendelman, Howard E

Journal of controlled release : official journal of the Controlled Release Society

2019 Volume 311-312, Page(s) 201–211

Abstract: Antiretroviral therapy requires lifelong daily dosing to attain viral suppression, restore immune function, and improve quality of life. As a treatment alternative, long-acting (LA) antiretrovirals can sustain therapeutic drug concentrations in blood for ...

Abstract	Antiretroviral therapy requires lifelong daily dosing to attain viral suppression, restore immune function, and improve quality of life. As a treatment alternative, long-acting (LA) antiretrovirals can sustain therapeutic drug concentrations in blood for prolonged time periods. The success of recent clinical trials for LA parenteral cabotegravir and rilpivirine highlight the emergence of these new therapeutic options. Further optimization can improve dosing frequency, lower injection volumes, and facilitate drug-tissue distributions. To this end, we report the synthesis of a library of RPV prodrugs designed to sustain drug plasma concentrations and improved tissue biodistribution. The lead prodrug M3RPV was nanoformulated into the stable LA injectable NM3RPV. NM3RPV treatment led to RPV plasma concentrations above the protein-adjusted 90% inhibitory concentration for 25 weeks with substantial tissue depots after a single intramuscular injection in BALB/cJ mice. NM3RPV elicited 13- and 26-fold increases in the RPV apparent half-life and mean residence time compared to native drug formulation. Taken together, proof-of-concept is provided that nanoformulated RPV prodrugs can extend the apparent drug half-life and improve tissue biodistribution. These results warrant further development for human use.
MeSH term(s)	Animals ; Anti-HIV Agents/administration & dosage ; Anti-HIV Agents/pharmacokinetics ; Delayed-Action Preparations/administration & dosage ; Delayed-Action Preparations/pharmacokinetics ; HIV-1/drug effects ; Humans ; Macaca mulatta ; Macrophages/metabolism ; Male ; Mice, Inbred BALB C ; Nanoparticles/administration & dosage ; Prodrugs/administration & dosage ; Prodrugs/pharmacokinetics ; Rilpivirine/administration & dosage ; Rilpivirine/pharmacokinetics ; Tissue Distribution
Chemical Substances	Anti-HIV Agents ; Delayed-Action Preparations ; Prodrugs ; Rilpivirine (FI96A8X663)
Language	English
Publishing date	2019-09-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2019.09.001
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Zs.A 2055: Show issues

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Article ; Online: A year-long extended release nanoformulated cabotegravir prodrug.

Nature materials

2020 Volume 19, Issue 8, Page(s) 910–920

Abstract: Long-acting cabotegravir (CAB) extends antiretroviral drug administration from daily to monthly. However, dosing volumes, injection site reactions and health-care oversight are obstacles towards a broad usage. The creation of poloxamer-coated hydrophobic ...

Abstract	Long-acting cabotegravir (CAB) extends antiretroviral drug administration from daily to monthly. However, dosing volumes, injection site reactions and health-care oversight are obstacles towards a broad usage. The creation of poloxamer-coated hydrophobic and lipophilic CAB prodrugs with controlled hydrolysis and tissue penetrance can overcome these obstacles. To such ends, fatty acid ester CAB nanocrystal prodrugs with 14, 18 and 22 added carbon chains were encased in biocompatible surfactants named NMCAB, NM2CAB and NM3CAB and tested for drug release, activation, cytotoxicity, antiretroviral activities, pharmacokinetics and biodistribution. Pharmacokinetics studies, performed in mice and rhesus macaques, with the lead 18-carbon ester chain NM2CAB, showed plasma CAB levels above the protein-adjusted 90% inhibitory concentration for up to a year. NM2CAB, compared with NMCAB and NM3CAB, demonstrated a prolonged drug release, plasma circulation time and tissue drug concentrations after a single 45 mg per kg body weight intramuscular injection. These prodrug modifications could substantially improve CAB's effectiveness.
MeSH term(s)	Animals ; Anti-Retroviral Agents/metabolism ; Anti-Retroviral Agents/pharmacology ; Anti-Retroviral Agents/toxicity ; Biological Transport ; Delayed-Action Preparations ; Drug Compounding ; Drug Interactions ; Drug Stability ; Mice ; Nanostructures/chemistry ; Prodrugs/chemistry ; Prodrugs/metabolism ; Pyridones/metabolism ; Pyridones/pharmacology ; Pyridones/toxicity
Chemical Substances	Anti-Retroviral Agents ; Delayed-Action Preparations ; Prodrugs ; Pyridones ; cabotegravir (HMH0132Z1Q)
Language	English
Publishing date	2020-04-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2088679-2
ISSN	1476-4660 ; 1476-1122
ISSN (online)	1476-4660
ISSN	1476-1122
DOI	10.1038/s41563-020-0674-z
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