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Is Deep Brain Stimulation Associated With Detrimental Effects on Cognitive Functions in Patients of Parkinson's Disease? A Systematic Review

Maheshwary, Ankush; Mohite, Divya; Omole, Janet A; Bhatti, Karandeep S; Khan, Safeera
Deep brain stimulation (DBS) is a rapidly evolving procedure with its application in multiple fields of neurology, but it is most prominent in Parkinson's disease (PD). Through electrode implantation in different areas of the brain, it brings a favorable change to the motor symptoms to the magnitude that none of the medications have been able to, but the effect on cognition of the patients is still unknown. We did a comprehensive search through PubMed and Cochrane databases and conducted a systematic review by following the PRISMA guidelines. Inclusion criteria were studies conducted only in PD patients, after the year 2008. The studies published in languages other than English were excluded. Thirteen studies, including randomized and non-randomized controlled trials, observational studies, and meta-analysis, were analyzed in detail. The results showed a declining trend in verbal fluency and attention domains of cognition, while other functions remained unchanged. The decline was significant but not enough to impact the quality index in patients. DBS is associated with worse performance in verbal fluency and attention, and there is a further need for studies focusing on these domains with long-term follow-up. The overall cognitive profile was not affected significantly.
PMCID:7486084
PMID: 32923280
ISSN: 2168-8184
CID: 5923072

Clinical, radiologic, and genetic characteristics of histone H3 K27M-mutant diffuse midline gliomas in adults

Schulte, Jessica D; Buerki, Robin A; Lapointe, Sarah; Molinaro, Annette M; Zhang, Yalan; Villanueva-Meyer, Javier E; Perry, Arie; Phillips, Joanna J; Tihan, Tarik; Bollen, Andrew W; Pekmezci, Melike; Butowski, Nicholas; Oberheim Bush, Nancy Ann; Taylor, Jennie W; Chang, Susan M; Theodosopoulos, Philip; Aghi, Manish K; Hervey-Jumper, Shawn L; Berger, Mitchel S; Solomon, David A; Clarke, Jennifer L
BACKGROUND:"Diffuse midline glioma (DMG), H3 K27M-mutant" is a new tumor entity established in the 2016 WHO classification of Tumors of the Central Nervous System that comprises a set of diffuse gliomas arising in midline structures and is molecularly defined by a K27M mutation in genes encoding the histone 3 variants H3.3 or H3.1. While this tumor entity is associated with poor prognosis in children, clinical experience in adults remains limited. METHODS:Patient demographics, radiologic and pathologic characteristics, treatment course, progression, and patient survival were collected for 60 adult patients with DMG, H3 K27M-mutant. A subset of tumors also underwent next-generation sequencing. Analysis of progression-free survival and overall survival was conducted using Kaplan-Meier modeling, and univariate and multivariate analysis. RESULTS:were frequently found. The overall survival of this adult cohort was 27.6 months, longer than historical averages for both H3 K27M-mutant DMG in children and IDH-wildtype glioblastoma in adults. CONCLUSIONS:Together, these findings indicate that H3 K27M-mutant DMG represents a heterogeneous disease with regard to outcomes, sites of origin, and molecular pathogenesis in adults versus children.
PMCID:7739048
PMID: 33354667
ISSN: 2632-2498
CID: 5920632

Diabetes Mellitus in the Middle-Aged and Elderly Population (>45 Years) and Its Association With Pancreatic Cancer: An Updated Review

Kaleru, Thanmai; Vankeshwaram, Varun K; Maheshwary, Ankush; Mohite, Divya; Khan, Safeera
Diabetes mellitus (DM) and pancreatic cancer (PC) in the elderly are widely considered to be interrelated. New-onset diabetes (NOD) patients are considered a high-risk group for the development of PC within three years of diagnosis. We reviewed the literature to determine the pathophysiological association between DM and PC, which can help in the development of screening tests for early PC diagnosis in the elderly with NOD. We also studied the potential associations between them after pancreaticoduodenectomy (PD) or pancreatic resection. We collected studies published in the last five years in PubMed that are relevant to DM and PC in the elderly. We mainly focused on the pathophysiology and intracellular mechanisms involved between NOD and PC. We illustrated the clinical signs and immunological and metabolic biomarkers that can be used to diagnose early PC in the elderly with NOD. In the 34 studies we reviewed, five showed that long-term diabetes mellitus (LTDM) increases the risk of PC. Six studies showed that NOD in the elderly is an early sign of PC. Fourteen studies proposed that clinical signs and biomarker levels should be used to determine the high-risk risk group for PC among NOD patients. Six studies reported that NOD is associated with the worst outcomes postoperatively, and three studies showed that patients developed DM after pancreatic resection. LTDM is considered an independent risk factor for PC development in the elderly. NOD is a consequence and maybe the only early presenting sign of PC. Screening protocols and tests should be used in clinical practice to determine the proportion of NOD patients who should undergo further testing for early diagnosis of PC. DM and PC are also co-related postoperatively and patients should be monitored for impaired glucose levels, overall survival, and mortality.
PMCID:7388804
PMID: 32742851
ISSN: 2168-8184
CID: 5923062

NEURO-ONCOLOGY ADVANCES

Schulte, Jessica D.; Buerki, Robin A.; Lapointe, Sarah; Molinaro, Annette M.; Zhang, Yalan; Villanueva-Meyer, Javier E.; Perry, Arie; Phillips, Joanna J.; Tihan, Tarik; Bollen, Andrew W.; Pekmezci, Melike; Butowski, Nicholas; Bush, Nancy Ann Oberheim; Taylor, Jennie W.; Chang, Susan M.; Theodosopoulos, Philip; Aghi, Manish K.; Hervey-Jumper, Shawn L.; Berger, Mitchel S.; Solomon, David A.; Clarke, Jennifer L.
ISI:000905120600123
CID: 5920752

Autoimmune-Associated Vasculitis Presenting as Ischemic Stroke With Hemorrhagic Transformation: A Case Report and Literature Review [Case Report]

Uppal, Salil; Goel, Sandeep; Randhawa, Baljit; Maheshwary, Ankush
Autoimmune-associated vasculitis is related to conditions like granulomatosis with polyangiitis (GPA) and eosinophilic polyangiitis with granulomatosis (EGPA), among many others. An unlikely scenario is patients with the above conditions presenting with ischemic strokes before any renal or pulmonary pathology. These conditions are associated with increased antineutrophillic cytoplasmic antibodies (C-ANCA) levels in the blood, and its decline after treatment is directly proportional to the recovery of the patient. We present a case of a previously healthy 38-year-old male patient who presented with acute/subacute ischemic stroke with elevated C-ANCA levels; his MRI brain images revealed multiple posterior circulation infarcts with hemorrhagic transformation. With pulse steroid therapy, he had significant improvement in neurological functions. This case report highlights the importance of maintaining a high degree of suspicion and providing early treatment for autoimmune strokes in young patients with no clear etiology for such a presentation.
PMCID:7550030
PMID: 33062521
ISSN: 2168-8184
CID: 5923092

The influence of race and socioeconomic status on therapeutic clinical trial screening and enrollment

Morshed, Ramin A.; Reihl, Sheantel J.; Molinaro, Annette M.; Kakaizada, Sofia; Young, Jacob S.; Schulte, Jessica D.; Butowski, Nicholas; Taylor, Jennie; Bush, Nancy Ann; Aghi, Manish K.; Berger, Mitchel S.; Chang, Susan; Clarke, Jennifer; Hervey-Jumper, Shawn L.
ISI:000529598500002
ISSN: 0167-594x
CID: 5920742

Treatment-Emergent Adverse Events in Gene Therapy Trials for Inherited Retinal Diseases: A Narrative Review

Nuzbrokh, Yan; Kassotis, Alexis S; Ragi, Sara D; Jauregui, Ruben; Tsang, Stephen H
Patient safety is a primary priority in the conduction of retinal gene therapy trials. An understanding of risk factors and mitigation strategies for post-procedure complications is crucial for the optimization of gene therapy clinical trial protocols. In this review, we synthesize the literature on ocular delivery methods, vector platforms, and treatment-emergent adverse effects in recent gene therapy clinical trials for inherited retinal diseases.
PMCID:7708583
PMID: 32740739
ISSN: 2193-8245
CID: 5922752

Is Stem Cell Therapy the New Savior for Cerebral Palsy Patients? A Review

Vankeshwaram, Varun; Maheshwary, Ankush; Mohite, Divya; Omole, Janet A; Khan, Safeera
Cerebral Palsy (CP) is one of the foremost causes of childhood motor disability and disrupts the individual's development and ability to function. Several factors contribute to the development of CP such as preterm delivery, low birth weight, infection/inflammation, and additional pregnancy complications, both in preterm and term infants. As there is no specific treatment for CP, rehabilitation is the current option for the management of patients. The serious nature of this condition creates deficits that last a lifetime.  We collected studies that were published in the past 10 years, using PubMed as our main database. We chose studies that were relevant to CP and stem cell therapy. We mainly focused on various types of stem cells that can be used in treatment, mechanism of action (MOA) of stem cells, routes, dosage, and adverse effects, their efficacy, and safety in CP patients. Of all the 38 studies we reviewed, we found that five articles discussed the utilization of human umbilical cord blood [hUCB], four articles discussed autologous bone marrow stem cells, and one discussed allogeneic umbilical cord blood usage. One article discussed neural stem-like cells (NSLCs) derived from bone marrow and the remaining 27 articles were about CP and its treatment. We reviewed detailed information about the possible stem cell therapies and their benefits in patients with CP. We found that immune modulation is the major mechanism of action of stem cells, and among all the types of stem cells. Autologous umbilical cord mesenchymal stem cells appear to be safe and most effective in treatment compared to other stem cell treatments. Among all symptoms, motor symptoms are best corrected by stem cell therapy. Still, it did not show any marked improvement in treating other symptoms like speech defects, sensory or cognitive defects, or visual impairment.
PMCID:7535865
PMID: 33042660
ISSN: 2168-8184
CID: 5923082

Features of the Energy Spectrum of Cosmic Rays above 2.5×10^{18}  eV Using the Pierre Auger Observatory

Aab, A; Abreu, P; Aglietta, M; Albury, J M; Allekotte, I; Almela, A; Alvarez Castillo, J; Alvarez-Muñiz, J; Alves Batista, R; Anastasi, G A; Anchordoqui, L; Andrada, B; Andringa, S; Aramo, C; Araújo Ferreira, P R; Asorey, H; Assis, P; Avila, G; Badescu, A M; Bakalova, A; Balaceanu, A; Barbato, F; Barreira Luz, R J; Becker, K H; Bellido, J A; Berat, C; Bertaina, M E; Bertou, X; Biermann, P L; Bister, T; Biteau, J; Blanco, A; Blazek, J; Bleve, C; Boháčová, M; Boncioli, D; Bonifazi, C; Bonneau Arbeletche, L; Borodai, N; Botti, A M; Brack, J; Bretz, T; Briechle, F L; Buchholz, P; Bueno, A; Buitink, S; Buscemi, M; Caballero-Mora, K S; Caccianiga, L; Calcagni, L; Cancio, A; Canfora, F; Caracas, I; Carceller, J M; Caruso, R; Castellina, A; Catalani, F; Cataldi, G; Cazon, L; Cerda, M; Chinellato, J A; Choi, K; Chudoba, J; Chytka, L; Clay, R W; Cobos Cerutti, A C; Colalillo, R; Coleman, A; Coluccia, M R; Conceição, R; Condorelli, A; Consolati, G; Contreras, F; Convenga, F; Covault, C E; Dasso, S; Daumiller, K; Dawson, B R; Day, J A; de Almeida, R M; de Jesús, J; de Jong, S J; De Mauro, G; de Mello Neto, J R T; De Mitri, I; de Oliveira, J; de Oliveira Franco, D; de Souza, V; De Vito, E; Debatin, J; Del Río, M; Deligny, O; Dembinski, H; Dhital, N; Di Giulio, C; Di Matteo, A; Díaz Castro, M L; Dobrigkeit, C; D'Olivo, J C; Dorosti, Q; Dos Anjos, R C; Dova, M T; Ebr, J; Engel, R; Epicoco, I; Erdmann, M; Escobar, C O; Etchegoyen, A; Falcke, H; Farmer, J; Farrar, G; Fauth, A C; Fazzini, N; Feldbusch, F; Fenu, F; Fick, B; Figueira, J M; Filipčič, A; Fodran, T; Freire, M M; Fujii, T; Fuster, A; Galea, C; Galelli, C; García, B; Garcia Vegas, A L; Gemmeke, H; Gesualdi, F; Gherghel-Lascu, A; Ghia, P L; Giaccari, U; Giammarchi, M; Giller, M; Glombitza, J; Gobbi, F; Gollan, F; Golup, G; Gómez Berisso, M; Gómez Vitale, P F; Gongora, J P; González, N; Goos, I; Góra, D; Gorgi, A; Gottowik, M; Grubb, T D; Guarino, F; Guedes, G P; Guido, E; Hahn, S; Halliday, R; Hampel, M R; Hansen, P; Harari, D; Harvey, V M; Haungs, A; Hebbeker, T; Heck, D; Hill, G C; Hojvat, C; Hörandel, J R; Horvath, P; Hrabovský, M; Huege, T; Hulsman, J; Insolia, A; Isar, P G; Johnsen, J A; Jurysek, J; Kääpä, A; Kampert, K H; Keilhauer, B; Kemp, J; Klages, H O; Kleifges, M; Kleinfeller, J; Köpke, M; Kukec Mezek, G; Lago, B L; LaHurd, D; Lang, R G; Leigui de Oliveira, M A; Lenok, V; Letessier-Selvon, A; Lhenry-Yvon, I; Lo Presti, D; Lopes, L; López, R; Lorek, R; Luce, Q; Lucero, A; Machado Payeras, A; Malacari, M; Mancarella, G; Mandat, D; Manning, B C; Manshanden, J; Mantsch, P; Marafico, S; Mariazzi, A G; Mariş, I C; Marsella, G; Martello, D; Martinez, H; Martínez Bravo, O; Mastrodicasa, M; Mathes, H J; Matthews, J; Matthiae, G; Mayotte, E; Mazur, P O; Medina-Tanco, G; Melo, D; Menshikov, A; Merenda, K-D; Michal, S; Micheletti, M I; Miramonti, L; Mockler, D; Mollerach, S; Montanet, F; Morello, C; Mostafá, M; Müller, A L; Muller, M A; Mulrey, K; Mussa, R; Muzio, M; Namasaka, W M; Nellen, L; Nguyen, P H; Niculescu-Oglinzanu, M; Niechciol, M; Nitz, D; Nosek, D; Novotny, V; Nožka, L; Nucita, A; Núñez, L A; Palatka, M; Pallotta, J; Panetta, M P; Papenbreer, P; Parente, G; Parra, A; Pech, M; Pedreira, F; Pȩkala, J; Pelayo, R; Peña-Rodriguez, J; Perez Armand, J; Perlin, M; Perrone, L; Peters, C; Petrera, S; Pierog, T; Pimenta, M; Pirronello, V; Platino, M; Pont, B; Pothast, M; Privitera, P; Prouza, M; Puyleart, A; Querchfeld, S; Rautenberg, J; Ravignani, D; Reininghaus, M; Ridky, J; Riehn, F; Risse, M; Ristori, P; Rizi, V; Rodrigues de Carvalho, W; Rodriguez Fernandez, G; Rodriguez Rojo, J; Roncoroni, M J; Roth, M; Roulet, E; Rovero, A C; Ruehl, P; Saffi, S J; Saftoiu, A; Salamida, F; Salazar, H; Salina, G; Sanabria Gomez, J D; Sánchez, F; Santos, E M; Santos, E; Sarazin, F; Sarmento, R; Sarmiento-Cano, C; Sato, R; Savina, P; Schäfer, C; Scherini, V; Schieler, H; Schimassek, M; Schimp, M; Schlüter, F; Schmidt, D; Scholten, O; Schovánek, P; Schröder, F G; Schröder, S; Schulz, A; Sciutto, S J; Scornavacche, M; Shellard, R C; Sigl, G; Silli, G; Sima, O; Šmída, R; Sommers, P; Soriano, J F; Souchard, J; Squartini, R; Stadelmaier, M; Stanca, D; Stanič, S; Stasielak, J; Stassi, P; Streich, A; Suárez-Durán, M; Sudholz, T; Suomijärvi, T; Supanitsky, A D; Šupík, J; Szadkowski, Z; Taboada, A; Tapia, A; Timmermans, C; Tkachenko, O; Tobiska, P; Todero Peixoto, C J; Tomé, B; Torralba Elipe, G; Travaini, A; Travnicek, P; Trimarelli, C; Trini, M; Tueros, M; Ulrich, R; Unger, M; Urban, M; Vaclavek, L; Vacula, M; Valdés Galicia, J F; Valiño, I; Valore, L; van Vliet, A; Varela, E; Vargas Cárdenas, B; Vásquez-Ramírez, A; Veberič, D; Ventura, C; Vergara Quispe, I D; Verzi, V; Vicha, J; Villaseñor, L; Vink, J; Vorobiov, S; Wahlberg, H; Watson, A A; Weber, M; Weindl, A; Wiencke, L; Wilczyński, H; Winchen, T; Wirtz, M; Wittkowski, D; Wundheiler, B; Yushkov, A; Zapparrata, O; Zas, E; Zavrtanik, D; Zavrtanik, M; Zehrer, L; Zepeda, A; Ziolkowski, M; Zuccarello, F; ,
We report a measurement of the energy spectrum of cosmic rays above 2.5×10^{18}  eV based on 215 030 events. New results are presented: at about 1.3×10^{19}  eV, the spectral index changes from 2.51±0.03(stat)±0.05(syst) to 3.05±0.05(stat)±0.10(syst), evolving to 5.1±0.3(stat)±0.1(syst) beyond 5×10^{19}  eV, while no significant dependence of spectral features on the declination is seen in the accessible range. These features of the spectrum can be reproduced in models with energy-dependent mass composition. The energy density in cosmic rays above 5×10^{18}  eV is [5.66±0.03(stat)±1.40(syst)]×10^{53}  erg Mpc^{-3}.
PMID: 33016715
ISSN: 1079-7114
CID: 5910932

Cardiovascular risk as a moderator of associations among anxiety sensitivity, distress tolerance, PTSD and depression symptoms among trauma-exposed firefighters

Ranney, Rachel M; Bing-Canar, Hanaan; Paltell, Katherine C; Tran, Jana K; Berenz, Erin C; Vujanovic, Anka A
BACKGROUND:Firefighters experience frequent and severe trauma exposure, which places them at elevated risk for posttraumatic stress disorder (PTSD) and major depression. Cardiovascular issues may exacerbate the effects of mental health risk factors, such as anxiety sensitivity (AS) and distress tolerance (DT), on PTSD and depression. The current study investigated cardiovascular risk as a moderator of associations between risk factors (AS and DT) and psychiatric symptoms (PTSD and depression) among firefighters. METHODS:Participants were 836 trauma-exposed active duty firefighters (93.90% men; with mean age 38 years, [SD = 9]). Participants endorsing at least one of three cardiovascular risk items-experiencing current high blood pressure, history of heart problems, and experiencing chest pains in the past 2 years-were considered high in cardiovascular risk. RESULTS:A structural equation model indicated that higher AS was associated with greater PTSD (β = 0.38, p < .01) and depression symptoms (β = 0.32, p < .01); lower DT was associated with greater PTSD (β = -0.18, p < .01) and depression symptoms (β = -0.31, p < .01). Multigroup analyses showed that cardiovascular risk moderated the association between 1) AS and PTSD symptoms, but not 2) AS and depression symptoms, 3) DT and PTSD symptoms, or 4) DT and depression symptoms. For those high in cardiovascular risk, higher AS was associated more strongly with greater PTSD symptoms (high cardiovascular risk group: β = 0.46, p < .01]; low cardiovascular risk group: β = 0.33, p < .01). CONCLUSIONS:High cardiovascular risk may contribute to PTSD symptoms among trauma-exposed firefighters with high AS. These results highlight the importance of considering physical and mental health vulnerabilities in first responder populations.
PMID: 33039951
ISSN: 1879-1360
CID: 5885802