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Article ; Online: Evaluating patient blood management practices using PBM metrics in a tertiary care center.

George, Ashna / Shastry, Shamee / Mohan, Ganesh / Belurkar, Sushma

Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine

2023 Volume 31, Issue 1, Page(s) 26–30

Abstract: Background: PBM metrics play a crucial role in assessing and monitoring the effectiveness of PBM programs in healthcare settings. The present study aimed to assess the indicators to achieve effective enforcement of PBM at a tertiary care referral ... ...

Abstract	Background: PBM metrics play a crucial role in assessing and monitoring the effectiveness of PBM programs in healthcare settings. The present study aimed to assess the indicators to achieve effective enforcement of PBM at a tertiary care referral hospital. Subjects and method: A prospective observational study was conducted on patients admitted for elective surgery at a tertiary care referral centre. PBM metrics were developed and assessed for various parameters, including documentation, patient evaluation, blood ordering schedule, and appropriateness. Experts in transfusion medicine and haematology checked content validity. Eleven different parameters were analysed, and a score was assigned based on the performance. The outcome was categorized as poor, satisfactory, or good. Results: The study included 612 patients meeting the inclusion criteria and recruited from Orthopaedics, General Surgery, OBG, Urology, and ENT departments. All departments completed pre-operative anaemia tests, with General Surgery and Orthopaedics conducting the most red cell transfusions. During the study, all of the blood units were used, and there was no waste. The C/T ratio was greater in the Departments of General Surgery, Urology, and Otorhinolaryngology. Pre-operative anaemia was found in 44.12% of patients, 44 patients had red cell transfusions, with 65% getting single-unit PRBC transfusions. All departments received a PBM score between 17-19, showing adequate PBM but with room for improvement. Conclusion: The current study utilized Patient Blood Management (PBM) metrics to critically assess the existing practices and identify the key gaps and areas for improvement in a tertiary care centre.
MeSH term(s)	Humans ; Anemia/diagnosis ; Anemia/therapy ; Blood Transfusion ; Erythrocyte Transfusion ; Hematology ; Tertiary Care Centers ; Prospective Studies
Language	English
Publishing date	2023-12-16
Publishing country	France
Document type	Observational Study ; Journal Article
ZDB-ID	1204698-x
ISSN	1953-8022 ; 1246-7820
ISSN (online)	1953-8022
ISSN	1246-7820
DOI	10.1016/j.tracli.2023.12.002
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Article ; Online: The KU-PARP14 axis differentially regulates DNA resection at stalled replication forks by MRE11 and EXO1

Ashna Dhoonmoon / Claudia M. Nicolae / George-Lucian Moldovan

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 18

Abstract: Protection of replication forks against nucleolytic degradation is crucial for genome stability. Here, Dhoonmoon et al identify PARP14 and the KU complex as essential regulators of fork degradation by MRE11 and EXO1 nucleases in BRCA-deficient cells. ...

Abstract	Protection of replication forks against nucleolytic degradation is crucial for genome stability. Here, Dhoonmoon et al identify PARP14 and the KU complex as essential regulators of fork degradation by MRE11 and EXO1 nucleases in BRCA-deficient cells.
Keywords	Science ; Q
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: The KU-PARP14 axis differentially regulates DNA resection at stalled replication forks by MRE11 and EXO1.

Dhoonmoon, Ashna / Nicolae, Claudia M / Moldovan, George-Lucian

Nature communications

2022 Volume 13, Issue 1, Page(s) 5063

Abstract: Suppression of nascent DNA degradation has emerged as an essential role of the BRCA pathway in genome protection. In BRCA-deficient cells, the MRE11 nuclease is responsible for both resection of reversed replication forks, and accumulation of single ... ...

Abstract	Suppression of nascent DNA degradation has emerged as an essential role of the BRCA pathway in genome protection. In BRCA-deficient cells, the MRE11 nuclease is responsible for both resection of reversed replication forks, and accumulation of single stranded DNA gaps behind forks. Here, we show that the mono-ADP-ribosyltransferase PARP14 is a critical co-factor of MRE11. PARP14 is recruited to nascent DNA upon replication stress in BRCA-deficient cells, and through its catalytic activity, mediates the engagement of MRE11. Loss or inhibition of PARP14 suppresses MRE11-mediated fork degradation and gap accumulation, and promotes genome stability and chemoresistance of BRCA-deficient cells. Moreover, we show that the KU complex binds reversed forks and protects them against EXO1-catalyzed degradation. KU recruits the PARP14-MRE11 complex, which initiates partial resection to release KU and allow long-range resection by EXO1. Our work identifies a multistep process of nascent DNA processing at stalled replication forks in BRCA-deficient cells.
MeSH term(s)	DNA ; DNA Replication ; DNA, Single-Stranded ; DNA-Binding Proteins ; Exodeoxyribonucleases ; MRE11 Homologue Protein
Chemical Substances	DNA, Single-Stranded ; DNA-Binding Proteins ; DNA (9007-49-2) ; Exodeoxyribonucleases (EC 3.1.-) ; MRE11 Homologue Protein (EC 3.1.-)
Language	English
Publishing date	2022-08-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-32756-5
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Article: A case report and review of literature on the role of automated red cell exchange in managing sickle cell crisis in India.

Rajendran, Vinu / Kalra, Archisha / George, Ashna / Chenna, Deepika / Mohan, Ganesh / Shastry, Shamee

Asian journal of transfusion science

2023 Volume 17, Issue 2, Page(s) 279–284

Abstract: Red cell exchanges (RCE) help in the treatment of complications of sickle cell anemia (SCA) by reducing the viscosity of blood and improving the oxygen-carrying capacity. We present a case of sickle cell crisis (SCC) managed with automated RCE and also ... ...

Abstract	Red cell exchanges (RCE) help in the treatment of complications of sickle cell anemia (SCA) by reducing the viscosity of blood and improving the oxygen-carrying capacity. We present a case of sickle cell crisis (SCC) managed with automated RCE and also reviewed the literature to assess the utilization and clinical efficiency of this therapy in India. A 19-year-old gentleman diagnosed with SCA presented with acute chest syndrome. Hemoglobin (Hb) was 8.8 g%, hematocrit (HCT) was 24%, and HbS was 90%. As there was worsening of symptoms with conventional management, the patient underwent two procedures of automated RCE. The clinical condition of the patient was improved, HbS was reduced to 16% and HCT was remained at 21% postprocedure. Articles on automated RCE in SCA conducted in India were reviewed and four articles were analyzed based on the search strategy. All the included articles concluded automated RCE as an effective procedure for complications of SCA. Common indication in India was SCA patients undergoing surgery as a prophylactic measure. Automated RCEs are promising as an acute treatment for indicated sickle cell complications. This therapy is underutilized in the Indian scenario, especially in patients with SCC.
Language	English
Publishing date	2023-05-11
Publishing country	India
Document type	Case Reports
ZDB-ID	2267310-6
ISSN	1998-3565 ; 0973-6247
ISSN (online)	1998-3565
ISSN	0973-6247
DOI	10.4103/ajts.ajts_138_22
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Article ; Online: Multi-step processing of replication stress-derived nascent strand DNA gaps by MRE11 and EXO1 nucleases.

Hale, Anastasia / Dhoonmoon, Ashna / Straka, Joshua / Nicolae, Claudia M / Moldovan, George-Lucian

Nature communications

2023 Volume 14, Issue 1, Page(s) 6265

Abstract: Accumulation of single stranded DNA (ssDNA) gaps in the nascent strand during DNA replication has been associated with cytotoxicity and hypersensitivity to genotoxic stress, particularly upon inactivation of the BRCA tumor suppressor pathway. However, ... ...

Abstract	Accumulation of single stranded DNA (ssDNA) gaps in the nascent strand during DNA replication has been associated with cytotoxicity and hypersensitivity to genotoxic stress, particularly upon inactivation of the BRCA tumor suppressor pathway. However, how ssDNA gaps contribute to genotoxicity is not well understood. Here, we describe a multi-step nucleolytic processing of replication stress-induced ssDNA gaps which converts them into cytotoxic double stranded DNA breaks (DSBs). We show that ssDNA gaps are extended bidirectionally by MRE11 in the 3'-5' direction and by EXO1 in the 5'-3' direction, in a process which is suppressed by the BRCA pathway. Subsequently, the parental strand at the ssDNA gap is cleaved by the MRE11 endonuclease generating a double strand break. We also show that exposure to bisphenol A (BPA) and diethylhexyl phthalate (DEHP), which are widespread environmental contaminants due to their use in plastics manufacturing, causes nascent strand ssDNA gaps during replication. These gaps are processed through the same mechanism described above to generate DSBs. Our work sheds light on both the relevance of ssDNA gaps as major determinants of genomic instability, as well as the mechanism through which they are processed to generate genomic instability and cytotoxicity.
MeSH term(s)	Humans ; DNA Repair ; Exodeoxyribonucleases/metabolism ; Endonucleases/genetics ; Endonucleases/metabolism ; DNA/genetics ; Genomic Instability ; DNA Replication ; DNA, Single-Stranded/genetics ; DNA Repair Enzymes/metabolism
Chemical Substances	Exodeoxyribonucleases (EC 3.1.-) ; Endonucleases (EC 3.1.-) ; DNA (9007-49-2) ; DNA, Single-Stranded ; EXO1 protein, human (EC 3.1.-) ; DNA Repair Enzymes (EC 6.5.1.-)
Language	English
Publishing date	2023-10-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42011-0
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Article ; Online: Ischemic monomelic neuropathy

S Sheetal / S Athira Vijayan Remadevi / Ashna Sara Mathew / Alna Merin George

Current Medical Issues, Vol 20, Iss 4, Pp 257-

2022 Volume 258

Abstract: Ischemic monomelic neuropathy is a rare complication associated with arteriovenous fistula creation for hemodialysis. It is an acutely developing ischemic neuropathy involving multiple nerves of a single limb. The pathogenesis is thought to be decreased ... ...

Abstract	Ischemic monomelic neuropathy is a rare complication associated with arteriovenous fistula creation for hemodialysis. It is an acutely developing ischemic neuropathy involving multiple nerves of a single limb. The pathogenesis is thought to be decreased blood flow to the distal axons, due to the shunting of blood away from the distal limb. It is characterized by severe pain and muscle weakness along with multiple nerve distributions, confined to the limb. It is different from steal syndrome in that there is no muscle or skin necrosis. It is often a debilitating condition warranting immediate closure of the fistula. Hence, prompt recognition of this entity is essential. Hereby, we report the case of a 60-year-old male with chronic kidney disease, who underwent a brachiocephalic fistula creation in the left upper limb and developed features of ischemic monomelic neuropathy.
Keywords	brachiocephalic fistula ; hemodialysis ; ischemic monomelic neuropathy ; Medicine ; R
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clozapine and Ogilvie syndrome in Schizophrenia: Case report of a successful rechallenge.

Philip, Sharad / Jose, Ashna / Silvester, Lidiya / Shekhar, Avinash / George, Geo / Sudha, Midhun Dharan / Najeeb, Shamnad

Asian journal of psychiatry

2022 Volume 77, Page(s) 103249

MeSH term(s)	Antipsychotic Agents/adverse effects ; Clozapine/adverse effects ; Colonic Pseudo-Obstruction/drug therapy ; Colonic Pseudo-Obstruction/etiology ; Humans ; Schizophrenia/complications ; Schizophrenia/drug therapy
Chemical Substances	Antipsychotic Agents ; Clozapine (J60AR2IKIC)
Language	English
Publishing date	2022-09-05
Publishing country	Netherlands
Document type	Case Reports ; Letter
ZDB-ID	2456678-0
ISSN	1876-2026 ; 1876-2018
ISSN (online)	1876-2026
ISSN	1876-2018
DOI	10.1016/j.ajp.2022.103249
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Article ; Online: Lagging strand gap suppression connects BRCA-mediated fork protection to nucleosome assembly through PCNA-dependent CAF-1 recycling.

Thakar, Tanay / Dhoonmoon, Ashna / Straka, Joshua / Schleicher, Emily M / Nicolae, Claudia M / Moldovan, George-Lucian

Nature communications

2022 Volume 13, Issue 1, Page(s) 5323

Abstract: The inability to protect stalled replication forks from nucleolytic degradation drives genome instability and underlies chemosensitivity in BRCA-deficient tumors. An emerging hallmark of BRCA-deficiency is the inability to suppress replication-associated ...

Abstract	The inability to protect stalled replication forks from nucleolytic degradation drives genome instability and underlies chemosensitivity in BRCA-deficient tumors. An emerging hallmark of BRCA-deficiency is the inability to suppress replication-associated single-stranded DNA (ssDNA) gaps. Here, we report that lagging strand ssDNA gaps interfere with the ASF1-CAF-1 nucleosome assembly pathway, and drive fork degradation in BRCA-deficient cells. We show that CAF-1 function at replication forks is lost in BRCA-deficient cells, due to defects in its recycling during replication stress. This CAF-1 recycling defect is caused by lagging strand gaps which preclude PCNA unloading, causing sequestration of PCNA-CAF-1 complexes on chromatin. Importantly, correcting PCNA unloading defects in BRCA-deficient cells restores CAF-1-dependent fork stability. We further show that the activation of a HIRA-dependent compensatory histone deposition pathway restores fork stability to BRCA-deficient cells. We thus define lagging strand gap suppression and nucleosome assembly as critical enablers of BRCA-mediated fork stability.
MeSH term(s)	Chromatin Assembly Factor-1/genetics ; Chromatin Assembly and Disassembly ; DNA, Single-Stranded/genetics ; Nucleosomes ; Proliferating Cell Nuclear Antigen ; Recycling
Chemical Substances	Chromatin Assembly Factor-1 ; DNA, Single-Stranded ; Nucleosomes ; Proliferating Cell Nuclear Antigen
Language	English
Publishing date	2022-09-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-33028-y
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Article: Metastatic Carcinoma of the Breast Presenting as Gingival Swelling in the Maxilla: A Case Report.

Sadasivan, Arun / Rakul Nambiar, K / Mathew, Deepu George / Koshi, Elizabeth / Ramesh, Roshni / Benny, Ashna Mariya

Case reports in dentistry

2022 Volume 2022, Page(s) 2667415

Abstract: Background: Metastatic cancers in the oral cavity are usually very rare and are usually an indication of widespread malignancy. In some cases, oral metastasis was found to be the first presentation of distant site tumours. Even though oral metastatic ... ...

Abstract	Background: Metastatic cancers in the oral cavity are usually very rare and are usually an indication of widespread malignancy. In some cases, oral metastasis was found to be the first presentation of distant site tumours. Even though oral metastatic lesions may be found anywhere in the oral cavity, they commonly present in the posterior areas of the jaw bones. Among the soft tissues, the gingiva is the most common site. The presence of inflammation in the gingiva and the role of periodontal microbiota are suggested to play a role in the attraction of metastatic cells. The purpose of this case report is to present a rare case of metastatic breast carcinoma presenting as a gingival enlargement in the maxillary anterior region. Conclusion: This case report presents a metastatic oral lesion in the maxillary anterior region of the primary breast cancer site. The young age of patient and an uncommon site of metastatic lesion are the striking features of this case. We would like to highlight the importance of a thorough clinical, radiological, and histological evaluation of any gingival swelling as it could be a metastatic lesion. IHC staining helps in the diagnosis of the primary site of metastatic carcinomas. An early diagnosis and intervention could reduce the morbidity of the lesion and improve the survival rate.
Language	English
Publishing date	2022-09-19
Publishing country	Egypt
Document type	Case Reports
ZDB-ID	2627632-X
ISSN	2090-6455 ; 2090-6447
ISSN (online)	2090-6455
ISSN	2090-6447
DOI	10.1155/2022/2667415
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Article ; Online: Prescribing of disease modifying agents in older adults with multiple sclerosis.

Talwar, Ashna / Earla, Jagadeswara R / Hutton, George J / Aparasu, Rajender R

Multiple sclerosis and related disorders

2021 Volume 57, Page(s) 103308

Abstract: Background: The use of disease-modifying agents (DMAs) to treat Multiple Sclerosis (MS) in older adults is debated as the disease activity decreases with aging. However, limited data exist regarding prescribing patterns of DMAs among older adults with ... ...

Abstract	Background: The use of disease-modifying agents (DMAs) to treat Multiple Sclerosis (MS) in older adults is debated as the disease activity decreases with aging. However, limited data exist regarding prescribing patterns of DMAs among older adults with MS. Objective: To examine prescribing patterns of DMAs and the factors associated with DMA prescribing practices among older adults with MS using electronic medical records (EMR) data. Methods: A retrospective longitudinal cohort study was conducted using the TriNetX, a federated EMR network from the US, data from 2016 to 2019. The study included older adults (≥60 years) with MS diagnosis and at least one prescription record during the study period. Patients with DMA prescriptions were identified and further classified into injectable, oral, or infusion users based on their last DMA prescription. A multivariable logistic regression model was used to evaluate the factors associated with prescribing of DMAs. A multinomial logistic regression model was also used to determine the factors associated with prescribing a particular dosage form of DMA. Results: The study cohort consisted of 12,922 older adults with MS, with 2,455 (18.99%) receiving DMA prescriptions. The commonly prescribed DMAs were injectables (10.46%), followed by orals (6.06%) and infusions (2.40%). Multivariable logistic regression revealed that older adults between 60- to 64 years (Adjusted Odds Ratio [aOR]= 2.38) and 65-69 years (aOR=1.60) had higher odds of receiving DMA compared to older adults of 70 years and above. African Americans (aOR=1.71) had higher odds of receiving DMA prescriptions compared to Caucasians. The presence of symptoms (pain, fatigue, speech, walking difficulty) and use of symptomatic medication (anti-fatigue medication, bladder dysfunction medication, antispasmodics, antidepressants, and relapse medication) increased the odds of being prescribed DMAs. Multinomial logistic regression found that patients 60-64 years of age had higher odds of being prescribed infusion (aOR, 95% Confidence Interval [CI] =2.06, 1.35-3.15) and oral (65-69 years: aOR=1.60, 1.24-2.07) over injectable DMAs compared to the older adults aged 70 years and above.Older males (aOR=1.68, 95% CI: 1.23-2.30) were associated with increased odds of being prescribed infusion DMA over injectable DMA compared to females. The presence of comorbidities such as coagulopathy and peripheral vascular disorders decreased the odds of being prescribed oral DMA over injectable DMA. Patients with cerebellar symptoms had an increased likelihood of being prescribed with an infusion DMA over injectable DMA. Patients using drugs for treating relapses had higher odds of being prescribed an infusion DMA over an injectable DMA. In terms of healthcare utilization, older adults with outpatient visits had higher odds of being prescribed an infusion DMA over an injectable DMA, while older adults with inpatient visits had lower odds of being prescribed an infusion DMA over an injectable DMA. Conclusion: Nearly one in five older adults with MS are prescribed DMAs, with a majority receiving injectable DMAs. Several demographic and clinical factors were associated with DMA prescribing . This study fills the data gap regarding the utilization of DMAs in older adults with MS.
MeSH term(s)	Aged ; Cohort Studies ; Female ; Humans ; Longitudinal Studies ; Male ; Multiple Sclerosis/drug therapy ; Odds Ratio ; Retrospective Studies
Language	English
Publishing date	2021-10-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2021.103308
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