Publications by authors named "Faiz Anwer"

102 Publications

Prognostic Impact of Red Cell Distribution Width on the Development of Contrast Induced Nephropathy, Major Adverse Cardiac Events, and Mortality in Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention.

Curr Cardiol Rev 2021 Feb 4. Epub 2021 Feb 4.

Creighton University Medical Center, Omaha, Nebraska. United States.

Red cell distribution width (RDW) serves as an independent predictor towards the prognosis of coronary artery disease (CAD) in patients undergoing percutaneous coronary intervention (PCI). A systematic search of databases such as PubMed, Embase, Web of Science, and Cochrane library was performed on October 10th, 2019 to elaborate the relationship between RDW and in hospital and long term follow up all-cause and cardiovascular mortality, major adverse cardiac events (MACE) and development of contrast-induced nephropathy (CIN) in patients with CAD undergoing PCI. Twenty-one studies qualified this strict selection criteria (number of patients = 56,425): one study was prospective, and the rest were retrospective cohorts. Our analysis showed that patients undergoing PCI with high RDW had a significantly higher risk of in-hospital all-cause mortality (OR 2.41), long-term all-cause mortality (OR 2.44), cardiac mortality (OR 2.65), MACE (OR: 2.16) and odds of developing CIN (OR: 1.42) when compared to the patients with low RDW. Therefore, incorporating RDW in the predictive models for the development of CIN, MACE, and mortality can help in triage to improve the outcomes in coronary artery disease patients who undergo PCI.
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http://dx.doi.org/10.2174/1573403X17666210204154812DOI Listing
February 2021

Outcomes of surgical versus transcatheter aortic valve replacement in nonagenarians- a systematic review and meta-analysis.

J Community Hosp Intern Med Perspect 2021 Jan 26;11(1):128-134. Epub 2021 Jan 26.

Department of Cardiology, CHI Health Heart and Vascular Institute, Omaha, Nebraska.

: Since the approval of transcatheter aortic valve replacement (TAVR), nonagenarian group patients are being increasingly considered for TAVR. Therefore, we compared the clinical outcomes of surgical aortic valve replacement (SAVR) vs TAVR in nonagenarians with severe aortic stenosis. : A literature search was performed using MEDLINE, Embase, Web of Science, Cochrane, and Clinicaltrials.gov for studies reporting the comparative outcomes of TAVR versus SAVR in nonagenarians. The primary endpoint was short-term mortality. Secondary endpoints were post-operative incidences of stroke or transient ischemic attack (TIA), vascular complications, acute kidney injury (AKI), transfusion requirement, and length of hospital stay. : Four retrospective studies qualified for inclusion with a total of 8,389 patients (TAVR = 3,112, SAVR = 5,277). Short-term mortality was similar between the two groups [RR = 0.91 (95% CI: 0.76-1.10), p = 0.318]. The average length of hospital stay was shorter by 3 days in the TAVR group (p = 0.037). TAVR was associated with a significantly lower risk of AKI [RR = 0.72 (95% CI: 0.62-0.83), p < 0.001] and a lower risk of transfusion [RR = 0.71 (95% CI: 0.62-0.81), p < 0.001]. There was no difference in risk of stroke/TIA[RR = 1.01 (95% CI: 0.70-1.45), p = 0.957]. The risk of vascular complications was significantly higher in the TAVR group [RR = 3.39 (95% CI: 2.65-4.333), p < 0.001]. : In this high-risk population, TAVR compared to SAVR has similar short-term mortality benefit but has lower risks of perioperative complications and a higher number of patients being discharged to home.
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http://dx.doi.org/10.1080/20009666.2020.1843235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850375PMC
January 2021

A Single-Center Experience and Literature Review of Management Strategies for Infection in Hematopoietic Stem Cell Transplant Patients.

Infect Dis Clin Pract (Baltim Md) 2020 Jan;28(1):10-15

Department of Medicine, Division of Hematology and Oncology, University of Arizona, Tucson, AZ 85724.

Introduction: The aim of our study is to evaluate risk factors associated with the development of infection (CDI) in hematopoietic stem cell transplant (HSCT) patients, determine its incidence and report outcomes of CDI in our patient population.

Methods: We performed a retrospective review of medical records of adult HSCT recipients diagnosed between 2013 and 2016 at our center. Logistic regression models were used to determine the relationship between risk factors and the odds of CDI.

Results: The overall incidence of CDI in HSCT patients was 9.4%. The incidence of CDI was higher in allogeneic HSCT (20%) versus autologous HSCT (4.8%). No statistically significant differences in age, gender, cancer type, transplant type were found between those who developed CDI and those who did not. However, patients with CDI had a longer length of stay (25 days) and used more antibiotics (30 days prior to and during admission for HSCT) than non-CDI patients (19 days). Only two of 17 patients (11.8%) with CDI experienced recurrence among 180 patients after HSCT. No patient suffered from toxic megacolon or ileus and no patient underwent colectomy. There was no mortality associated with CDI at our center.

Conclusion: CDI has an incidence rate of 9.4% in HSCT recipients. Established risk factors including age, gender, cancer type, and transplant type were not identified as risk factors in our population. However, longer LOS and use of greater than four lines of antibiotics were observed among those with CDI compared to those without CDI.
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http://dx.doi.org/10.1097/ipc.0000000000000798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792527PMC
January 2020

COVID-19 and Its Psychological Impacts on Healthcare Staff - A Multi-Centric Comparative Cross-Sectional Study.

Cureus 2020 Nov 28;12(11):e11753. Epub 2020 Nov 28.

Oncology, Cleveland Clinic, Cleveland, USA.

Background Since the first case of coronavirus disease-19 (COVID-19) in Pakistan was reported in February 2020, the medical and paramedical staff has been working on the frontlines to deal with this disease. They have been facing significant strain and stress due to the pandemic, affecting their social, mental, and personal life. The purpose of this study is to investigate the psychological effects of the COVID-19 pandemic, etiology, personal coping mechanisms, and the strategies that are being adopted to reduce stress by the healthcare workers (HCWs) working in COVID-19 dedicated wards (group 2) and compare it with staff working in other departments but not in COVID-19 wards amid this pandemic (group 1) in various hospitals of Lahore, Pakistan. Methods The comparative cross-sectional study was designed which included doctors, nurses, and allied health professionals from various hospitals of Lahore, Pakistan. A questionnaire was designed which consisted of five sections, and 51 questions. A Chi-square test was used to compare the responses between these two groups. Results The study questionnaire was submitted by 200 participants, 100 responses for each group (see the Appendix). In group 1, HCWs not working in COVID-19 dedicated floors were afraid of getting infected, transmitting the infection to their families and concerned about using personal protective equipment (PPE) improperly. They reported a lack of concentration and tense muscles. The coping mechanisms of this group were exercise, strict precautions at work, and social distancing measures. While HCWs serving in COVID-19 dedicated wards were concerned and afraid of putting their families at risk by working in the high-risk environment; the major stresses in this group were: lack of knowledge about proper strategies for treatment, they faced insecurity due to physical and verbal violence by caretakers of COVID-19 patients, and lack of concentration. The coping mechanism was the support of their families and taking strict precautions, with self-isolation if required, to avoid any disease transmission to their families. The proposed strategies to be implemented included teaching skills for self-rescue as well as the implementation of policies at the administrative level to reduce working hours and frequent shift rotation. Conclusion The COVID-19 outbreak posed a great deal of mental stress among HCWs working on the COVID-19 floor as well as those serving in other departments of the hospital. The HCWs from group 1 were most afraid of getting infected and putting family members at risk, experienced tense muscles and lack of concentration, coped their stress by exercise and being more vigilant, and suggested the strategies of teaching skills for self-rescue and better community awareness. While the staff from the second group were most afraid of being the source of infection and violence from the caretakers of patients, experienced tense muscles, used family support, and strict isolation measures as coping mechanisms and suggested the strategies of self-rescue and increase in wages of directly exposed healthcare workers to deal with such pandemics in future in a better way.
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http://dx.doi.org/10.7759/cureus.11753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773302PMC
November 2020

Outcomes and factors impacting use of axicabtagene ciloleucel in patients with relapsed or refractory large B-cell lymphoma: results from an intention-to-treat analysis.

Leuk Lymphoma 2020 Dec 29:1-9. Epub 2020 Dec 29.

Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.

Data on real-world outcomes of axicabtagene ciloleucel (axi-cel) therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL) are limited. In this intent to treat (ITT) analysis, we reviewed records of 38 consecutive patients with R/R LBCL for whom axi-cel was intended. Twenty-seven (71%) patients received axi-cel and 11 (29%) did not. Patients in the non-axi-cel group had a higher hematopoietic cell transplantation comorbidity index (HCT-CI) (median 4 vs. 2,  = .04). Median overall survival for the ITT, axi-cel and non-axi-cel group was 10 (95% CI, 3.7 to 13), 13 (95% CI, 7.7 to N.R.) and 1 (95% CI, 0.4 to 3.7) month(s) respectively. Factors limiting axi-cel use were disease progression, sepsis, manufacturing failure and socioeconomic barrier in 6 (55%), 3 (27%), 1 (9%) and 1 (9%) patient(s) respectively. Additional strategies are needed to ensure all LBCL patients for whom chimeric antigen receptor (CAR) T-cell therapy is prescribed can receive this treatment.
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http://dx.doi.org/10.1080/10428194.2020.1864349DOI Listing
December 2020

Survival following relapse after allogeneic hematopoietic cell transplantation for acute leukemia and myelodysplastic syndromes in the contemporary era.

Hematol Oncol Stem Cell Ther 2020 Dec 5. Epub 2020 Dec 5.

Blood and Marrow Transplant Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address:

Objective/background: Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). No standard of care exists, and a wide range of treatments are used for post-alloHCT relapse. In the recent era, several novel therapies including targeted agents are available for acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS).

Methods: We reviewed outcomes after alloHCT relapse, with or without use of these newer agents for ALL, AML, and MDS. In total, 115 adults with relapsed or refractory ALL (n = 17), AML (n = 67), and MDS (n = 31) at median 5 (range, 1-64) months after their first alloHCT in 2010-2018 were included.

Results: Median follow-up was 19 (range, 6-80) months after relapse from alloHCT. Targeted agents were given to 29 (25%) patients. In multivariable analysis, use of targeted agent at any time point after relapse was not associated with survival. Matched unrelated (vs. matched sibling; hazard ratio [HR] 1.70; p = .027) or haploidentical donor grafts (vs. matched sibling; HR 2.69; p = .003), presence of grade II-IV acute graft-versus-host disease before relapse (HR 2.46; p < .001), and less than 12 months from HCT to relapse (<6 vs. > 12 months; HR 6.34; p < .001; 6-12 vs. > 12 months; HR 3.16; p = .005) were adverse prognostic factors for post-relapse survival.

Conclusion: Outcomes after alloHCT relapse remain poor regardless of the novel agent use. Innovative treatment strategies are needed to improve outcomes after relapse post-alloHCT.
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http://dx.doi.org/10.1016/j.hemonc.2020.11.006DOI Listing
December 2020

Cisplatin-Mediated Upregulation of APE2 Binding to MYH9 Provokes Mitochondrial Fragmentation and Acute Kidney Injury.

Cancer Res 2021 Feb 7;81(3):713-723. Epub 2020 Dec 7.

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.

Cisplatin chemotherapy is standard care for many cancers but is toxic to the kidneys. How this toxicity occurs is uncertain. In this study, we identified apurinic/apyrimidinic endonuclease 2 (APE2) as a critical molecule upregulated in the proximal tubule cells (PTC) following cisplatin-induced nuclear DNA and mitochondrial DNA damage in cisplatin-treated C57B6J mice. The APE2 transgenic mouse phenotype recapitulated the pathophysiological features of C-AKI (acute kidney injury, AKI) in the absence of cisplatin treatment. APE2 pulldown-MS analysis revealed that APE2 binds myosin heavy-Chain 9 (MYH9) protein in mitochondria after cisplatin treatment. Human MYH9-related disorder is caused by mutations in MYH9 that eventually lead to nephritis, macrothrombocytopenia, and deafness, a constellation of symptoms similar to the toxicity profile of cisplatin. Moreover, cisplatin-induced C-AKI was attenuated in APE2-knockout mice. Taken together, these findings suggest that cisplatin promotes AKI development by upregulating APE2, which leads to subsequent MYH9 dysfunction in PTC mitochondria due to an unrelated role of APE2 in DNA damage repair. This postulated mechanism and the availability of an engineered transgenic mouse model based on the mechanism of C-AKI provides an opportunity to identify novel targets for prophylactic treatment of this serious disease. SIGNIFICANCE: These results reveal and highlight an unexpected role of APE2 via its interaction with MYH9 and suggest that APE2 has the potential to prevent acute kidney injury in patients with cisplatin-treated cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/3/713/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869671PMC
February 2021

Fundamentals of Light Chain Cardiac Amyloidosis: A Focused Review.

Cardiovasc Hematol Disord Drug Targets 2020 ;20(4):274-283

University of Arizona, Tucson, Arizona, AZ 85721, United States.

The estimated prevalence of AL CA in the US is approximately 8-12 cases per million. Almost 30-50% diagnosed cases of AL amyloid in the US have multisystem involvement, including cardiac involvement. Even with the availability of advanced diagnostic testing and novel therapies, prognosis remains poor. It is overlooked as a cause of heart failure with preserved ejection fraction leading to a delay in diagnosis when management options are limited and associated with poor survival outcomes. Therefore, the education of physicians is needed to ensure that it would be highly considered as a differential diagnosis. The purpose of this manuscript is to review the advances in the diagnosis and management of cardiac amyloidosis with the aim of educating colleagues who provide care in the primary care setting. We have summarized the pathogenesis of amyloidosis, its association with plasma cell dyscrasias, novel diagnostic and surveillance approaches including echocardiography, cardiovascular magnetic resonance imaging, histopathologic techniques, systemic biomarkers, and advanced treatment approaches including supportive symptomatic management and standard of care chemotherapy targeting the amyloid deposits. Given the overall poor prognosis of amyloidosis, we have also discussed the role of palliative and hospice care.
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http://dx.doi.org/10.2174/1871529X20666201130110036DOI Listing
January 2020

Allogeneic hematopoietic stem cell transplantation in aplastic anemia: current indications and transplant strategies.

Blood Rev 2020 Oct 31:100772. Epub 2020 Oct 31.

Department of Hematology Oncology and Stem Cell Transplant, Quaid-e-Azam International Hospital, Islamabad 44000, Pakistan.

Treatment options for newly diagnosed aplastic anemia (AA) patient includes upfront allogeneic hematopoietic stem cell transplant (HSCT) or immunosuppressive therapy (IST). With recent advances in supportive care, conditioning regimens and post-transplant immunosuppression the overall survival for HSCT approaches 70-90%. Transplant eligibility needs to be assessed considering age, comorbidities, donor availability and probability of response to immunosuppressive therapy (IST). Upfront HSCT should be offered to children and young adults with matched related donor (MRD). Upfront HSCT may also be offered to children and young adults with rapidly available matched unrelated donor (MUD) who require urgent HSCT. Bone marrow (BM) graft source and cyclosporine (CsA) plus methotrexate (MTX) as graft versus host disease (GVHD) prophylaxis are preferable when using anti-thymocyte globulin (ATG) based conditioning regimens. Alemtuzumab is an acceptable alternative to ATG and is used with CsA alone and with either BM or peripheral blood stem cells (PBSC). Cyclophosphamide (CY) plus ATG conditioning is preferable for patients receiving MRD transplant, while Fludarabine (Flu) based conditioning is reserved for older adults, those with risk factors of graft failure and those receiving MUD HSCT. For haploidentical transplant, use of low dose radiotherapy and post-transplant cyclophosphamide has resulted in a marked reduction in graft failure and GVHD.
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http://dx.doi.org/10.1016/j.blre.2020.100772DOI Listing
October 2020

Allogeneic hematopoietic stem cell transplant in rare hematologic disorders: a single center experience from Pakistan.

Bone Marrow Transplant 2020 Nov 12. Epub 2020 Nov 12.

Quaid-e-Azam International Hospital, Islamabad, Pakistan.

Management of rare hematological disorders pose unique diagnostic and therapeutic challenges due to unusual occurrence and limited treatment options. We retrospectively identified 45 patients receiving matched related donor transplant for rare hematological disorders from 2006 to 2019. Patients were divided into two groups (1) malignant and (2) non malignant. The malignant disorder group included four patients while the nonmalignant group included 41 patients divided into immune dysregulation (n = 23), bone marrow failure (n = 10), metabolic (n = 5), and bleeding diathesis (n = 3). Twenty-six (57.8%) patients received myeloablative conditioning (MAC) and 16 (35.6%) received reduced intensity conditioning (RIC), while 3 (6.6%) patients with severe combined immunodeficiency received stem cell infusion alone without conditioning. The cumulative incidence (CI) of grade II-IV acute GVHD (aGVHD) was 39.1% (n = 18) and chronic GVHD (cGVHD) 15.2% (n = 7). There was no primary graft failure while CI of secondary graft failure was 9%. Overall survival (OS) and disease-free survival (DFS) was 82.2% and 77.8% respectively. Group wise OS was 75% in the malignant group, 82.6% in the immune dysregulation group, 80% in patients with metabolic disorders and bone marrow failure, while 100% in patients with bleeding diathesis. This retrospective analysis shows that hematopoietic stem cell transplant can be a feasible treatment option for rare hematological disorders.
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http://dx.doi.org/10.1038/s41409-020-01126-4DOI Listing
November 2020

A Systematic Review of Transfusion-Transmissible Infections Among Blood Donors and Associated Safety Challenges in Pakistan.

J Blood Med 2020 2;11:405-420. Epub 2020 Nov 2.

Department of Hematology/Oncology, Cleveland Clinic, Taussig Cancer Center, Hematology-Oncology, BMT, Cleveland, OH, USA.

The blood transfusion (BT) system in Pakistan is fragmented, demand-driven and depends on weakly regulated transfusion practices. There is a considerable possibility that transfusion-transmissible infections (TTIs) are contributing to the current epidemic of hepatitis B virus (HBV) and hepatitis C virus (HCV) (affecting 7.4% of the general population) in the country. To study this issue, we conducted a systematic review to identify articles related to TTIs and transfusion safety in Pakistan from January 1, 2010 to January 31, 2020. A review of 33 articles met the final criteria for qualitative synthesis. Analysis of these studies showed a cumulative frequency of HBV 2.04%, HCV 2.44%, HIV 0.038%, syphilis 1.1% and malaria 0.11%. The frequency of coinfections among blood donors varied from 0.0099% to 0.35%. The highest number of coinfections were HCV and syphilis, followed by HCV and HBV infections. Syphilis and malaria were tested in only 38% and 46% of all the blood donations in one study. The rate of voluntary non-remunerated donations (VNRDs) was less than 13%, and male donors were 95% to 100% in these studies. There was a significant difference in the frequency of HBV and HCV in VNRDs (0.48%) as compared to replacement donors (RDs) (4.15%). In short, this review shows a high frequency of TTIs, especially HBV, HCV and syphilis in the blood donor population in Pakistan. There is a high dependency on RDs, minimal use of healthy voluntary blood donation practices, inadequate screening of high-risk donors, repeated collections of the blood from RDs, poor quality of screening methods and limited knowledge of donor health. Without standardized safe transfusion practices, there will be an ongoing increase in transmission of TTIs, especially HBV, HCV, syphilis, and HIV leading to a significant adverse public health impact.
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http://dx.doi.org/10.2147/JBM.S277541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646486PMC
November 2020

Advances in maintenance strategy in newly diagnosed multiple myeloma patients eligible for autologous transplantation.

Expert Rev Hematol 2020 12 26;13(12):1333-1347. Epub 2020 Oct 26.

Hematology Oncology Department, Stem Cell Transplantation Multiple Myeloma Program, Cleveland Clinic , Cleveland, Ohio, USA.

Introduction: Multiple myeloma (MM) lacks curative therapy. Therefore, researchers continue to conduct studies in an effort to improve progression-free survival (PFS) and overall survival (OS). Maintenance therapy (MT) after autologous stem cell transplant (ASCT) was extensively studied in the last decade and now considered a standard approach.

Areas Covered: This review evaluated the evidence and updates on various maintenance agents in newly diagnosed multiple myeloma (NDMM) after ASCT. Articles were searched on PubMed and Embase that were published in last 10 years. Both clinical trials and observational studies were evaluated.

Expert Opinion: Maintenance strategy after ASCT has consistent PFS benefit but lacks conclusive OS improvement. Lenalidomide is superior to thalidomide given reduced neurotoxicity. OS advantage is controversial for both due to inconsistent evidence. Lenalidomide may confer a PFS advantage even at lower doses due to toxicity with higher doses. Bortezomib-based maintenance has some evidence for OS benefit in high-risk MM (HRMM) and renal dysfunction. Ixazomib has preliminary promising results. Two or three drug combinations for MT are potentially safe and more effective, particularly in HRMM although data on this subject is still evolving. Efficacy of various MT regimens in terms of minimal residual disease status needs to be further investigated.
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http://dx.doi.org/10.1080/17474086.2020.1839886DOI Listing
December 2020

COVID-19 in Cancer Patients From New York City: A Comparative Single Center Retrospective Analysis.

Cancer Control 2020 Jan-Dec;27(1):1073274820960457

Tausig Cancer Center, Hematology/Oncology, Stem Cell Transplantation, 2569Cleveland Clinic, Cleveland, OH, USA.

In this retrospective study we analyze and compare clinical characteristics and outcomes of patients with and without cancer history who were infected with novel coronavirus disease 19 (COVID-19). Medical records were reviewed and a comparative analysis of 53 cancer and 135 non-cancer patients with COVID-19 were summarized. Results: The median age for COVID-19 patients with and without cancer was 71.5 and 61.6 years, respectively. Patients aged 60 years and above were 86.8% and 60.7% in cancer and non-cancer groups, respectively. A high proportion of cases were seen in African Americans 73.6% (with cancer) and 75.6% (without cancer) followed by Hispanic patients. Male and female patients had a high percentage of prostate (39.3%) and breast (32%) cancer respectively. Prostate cancer (18.9%) and myeloma (11.3%) were common among solid and hematological cancers respectively. Hypertension and smoking were prevalent among cancer (83% and 41.5%) compared to non-cancer (67.4% and 9.6%) patients. The common symptoms in cancer patients were dyspnea (64.2%) followed by fever and cough (50.9%) compared to fever (68.1%) and cough (66.7%) in non-cancer patients. Cancer patients had higher levels of lactic acidosis, C-reactive protein, lactate dehydrogenase, and alkaline phosphatase than non-cancer patients (p < 0.05). Conclusions: Rapid clinical deterioration was seen in cancer patients who were aged 60 years and above. Higher mortality was seen in this subgroup, especially when they had associated hypertension and elevated levels of CRP and LDH.
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http://dx.doi.org/10.1177/1073274820960457DOI Listing
October 2020

Role and mechanism of autophagy-regulating factors in tumorigenesis and drug resistance.

Asia Pac J Clin Oncol 2020 Sep 24. Epub 2020 Sep 24.

Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.

A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy-induced tumorigenesis and drug resistance including Beclin-1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF-2, MEG3, LAPTM4B, mTOR, BRAF and c-MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.
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http://dx.doi.org/10.1111/ajco.13449DOI Listing
September 2020

Prevalence of Transfusion Transmissible Infections in Beta-Thalassemia Major Patients in Pakistan: A Systematic Review.

Cureus 2020 Aug 27;12(8):e10070. Epub 2020 Aug 27.

Internal Medicine, MedStar Union Memorial Hospital, Baltimore, USA.

-thalassemia major (TM) is one of the most prevalent inherited hemoglobinopathies in Pakistan. It has one of the highest prevalence of transfusion-dependent TM patients globally, with an estimated greater than 100,000 active cases. Blood transfusions (BT) are essential in the management of severe TM; it is critical to have a safe BT to reduce the risk of transfusion transmissible infections (TTIs). Frequent blood transfusions in these patients increase their risk of acquiring TTIs compared to the general population. We performed a systematic literature search to identify studies related to the TTIs and transfusion-related infections in Pakistan from January 1, 2010, to January 31, 2020. The search was conducted using PubMed and PakMediNet, with initial search retrieved 981 studies. Among these, 166 studies met the inclusion criteria, and only 14 studies met the final criteria for qualitative synthesis. Analysis of 14 studies (n = 3786) showed the seroprevalence of hepatitis B virus (HBV) of 3.13% (0.66% to 7.4%) and hepatitis C virus (HCV) of 26% (5.56% to 68.2%). There were only two studies that reported HIV seroprevalence of 0% and 0.5% (n = 6). The rate of seropositivity for HBV and HCV was directly related to the number of transfusions, higher ferritin levels, and older age groups. There was an increase in the HCV rate with the increasing age of patients. Thalassemia patients, who were older than ten years of age, had an HCV rate of 22% compared to only 8.4% in patients younger than ten years of age. A comparison of HCV in healthy donors vs. thalassemia patients showed a rate of 1.9% vs. 13.1% for TM patients. The majority of the patients were males (51% to 88%). The seroprevalence of TTIs was higher in males than in females (73.4% vs. 26.6%). On average, a single TM patient is exposed to at least 17 different donors annually, requiring 1-2 transfusions every month. Our study highlights that the prevalence of transfusion-transmitted infections, especially HCV, is alarmingly higher (26%) in the TM population than in the general population. There is limited data regarding the prevalence of HIV, syphilis, and malaria in this population. This is mainly due to a fragmented system of blood transfusion, weak regulations, and lower rates of voluntary blood donations. These findings warrant better health measures to improve the blood donation system and specialized care for TM patients.
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http://dx.doi.org/10.7759/cureus.10070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455379PMC
August 2020

Evidence-based supportive care in multiple myeloma.

J Community Hosp Intern Med Perspect 2020 Aug 2;10(4):313-317. Epub 2020 Aug 2.

Department of Medicine, Division of Hematology Oncology, Blood and Marrow Transplantation, University of Arizona, Tucson, AZ, USA.

Multiple myeloma (MM) is a hematological malignancy characterized by an abnormal clone of plasma cells in the bone marrow. MM and its therapy increase the risk of complications like anemia, osteolytic lesions, pain, infections, and renal abnormalities in MM patients. Supportive care for MM patients improves the quality of life. Treatment with bisphosphonates decreases skeletal-related events. Vertebroplasty and kyphoplasty are done in cases of vertebral compression fractures. Prophylactic antibiotics and antivirals can decrease infections related to morbidity. Plasmapheresis in patients with renal dysfunctions decreases dialysis dependency and improve quality of life.
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http://dx.doi.org/10.1080/20009666.2020.1771124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427456PMC
August 2020

Obstructive sleep apnea and peripheral vascular disease: a systematic review based on current literature.

J Community Hosp Intern Med Perspect 2020 Jun 14;10(3):188-193. Epub 2020 Jun 14.

Department of Internal Medicine, Cleveland Medical Center, Cleveland, OH, USA.

Introduction: Obstructive sleep apnea (OSA) is an established risk factor for poor cardiovascular outcomes and coronary artery disease, but its influence on the development of peripheral artery disease (PAD) is not well established. The aim of our study was to understand the mutual prevalence of OSA and PAD and any reported statistical association between the two conditions.

Methods: PubMed, Ovid Embase, Web of Science, Cochrane library and clinicaltrials.gov databases were systematically searched up to 29 November 2018. A total of 844 articles were identified and 744 articles were screened for relevance.

Results And Conclusion: Eleven prospective cohorts qualified for inclusion with = 63,642 ( = 28,062, = 35,494). All studies evaluated OSA severity primarily with apnea-hypopnea index (AHI) values. The overall prevalence of PAD was 20.5% ( = 13,068). Except for two studies, all studies reported an increased prevalence of OSA in patients with PAD. OSA severity was not found to have an association with poor ankle brachial index values or increasing daytime sleepiness as measured by Epworth sleepiness scale. Further prospective clinical trials are required to further delineate this finding.
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http://dx.doi.org/10.1080/20009666.2020.1764276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426973PMC
June 2020

Impact of acquired thrombocytopenia on cardiovascular outcomes in patients with coronary artery disease undergoing percutaneous coronary intervention: A systematic review and meta-analysis.

Cardiovasc Revasc Med 2020 Jul 24. Epub 2020 Jul 24.

Division of Cardiovascular Medicine, Creighton University Medical Center, Omaha, NE, USA.

Background: Acquired thrombocytopenia (aTP) is associated with a high frequency of bleeding and ischemic complications in patients undergoing percutaneous coronary intervention (PCI). Herein, we report a meta-analysis evaluating the adverse effects of aTP on cardiovascular outcomes and mortality post-PCI.

Methods: A literature search was performed using PubMed, Embase, Cochrane and, clinicaltrials.gov from the inception of these databases through October 2019. Patients were divided into two groups: 1) No Thrombocytopenia (nTP) and 2) Acquired Thrombocytopenia (aTP) after PCI. Primary endpoints were in-hospital, 30-day and all-cause mortality rates at the longest follow-up. The main summary estimate was random effects Risk ratio (RR) with 95% confidence intervals (CIs).

Results: Seven studies involving 57,247 participants were included. There was significantly increased in-hospital all-cause mortality (HR 10.73 [6.82-16.88]), MACE (HR 2.96 [2.24-3.94]), major bleeding (HR 4.78 [3.54-6.47]), and target vessel revascularization (TVR) (HR 7.53 [2.8-20.2]), in the aTP group compared to the nTP group. Similarly, aTP group had a statistically significant increased incidence of 30-day all-cause mortality (HR 6.08), MACE (HR 2.77), post-PCI MI (HR 1.98), TVR (HR 5.2), and major bleeding (HR 12.73). Outcomes at longest follow-up showed increased incidence of all-cause mortality (HR 3.98 [1.53-10.33]) and MACE (HR 1.24 [0.99-1.54]) in aTP group, while there was no significant difference for post-PCI MI (HR 0.94 [0.37-2.39]) and TVR (HR 0.96 [0.69-1.32]) between both groups.

Conclusions: Acquired Thrombocytopenia after PCI is associated with increased morbidity, mortality, adverse bleeding events and the need for in-hospital and 30-day TVR.
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http://dx.doi.org/10.1016/j.carrev.2020.07.014DOI Listing
July 2020

The Potential Vaccine Component for COVID-19: A Comprehensive Review of Global Vaccine Development Efforts.

Cureus 2020 Jun 27;12(6):e8871. Epub 2020 Jun 27.

Hematology and Oncology, Cleveland Clinic, Cleveland, USA.

The whole world is concerned about the pandemic of coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), due to fatality of this condition. This has become a public health emergency of international concern. No specific vaccine and medicine have proven effective in large-sized trials at this time. With the rapidly increasing number of positive cases and deaths, there is a dire need for effective treatments and an effective vaccine for prevention. An urgent unmet need led to the planning and opening of multiple drug development trials for treatment and vaccine development. In this article, we have summarized data on cell receptor interactions and data on prospects of new vaccines targeting the deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA), and viral minigenes. We have tabulated the available data on various clinical trials testing various aspects of COVID-19 vaccines.
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http://dx.doi.org/10.7759/cureus.8871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387075PMC
June 2020

Single-Agent Cyclosporine for Graft-versus-Host Disease Prophylaxis in Patients with Acquired Aplastic Anemia Receiving Fludarabine-Based Conditioning.

Biol Blood Marrow Transplant 2020 12 24;26(12):2245-2251. Epub 2020 Jul 24.

Department of Hematology Oncology and Stem Cell Transplant, Quaid-e-Azam International Hospital, Islamabad, Pakistan.

Cyclosporine (CsA) combined with short-course methotrexate is considered standard-of-care graft-versus-host disease (GVHD) prophylaxis for patients with severe aplastic anemia (AA) who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu)-based conditioning. We conducted a single-center retrospective analysis of patients with acquired AA (n = 106) undergoing MRD transplantation from July 2007 through January 2019. All patients received Flu-Cy-ATG conditioning and single-agent CsA as GVHD prophylaxis. Median age of the study cohort was 20 years (range, 3 to 52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range, 2.8 to 62). Graft source was bone marrow harvest in 71 (68%), combined bone marrow and peripheral blood stem cells in 34 (31%), and peripheral blood alone in 1 (1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% confidence interval [CI], 87.3% to 97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI, 84% to 96%). Cumulative incidence of primary graft failure at day 28 was 6.6% (95% CI, 4% to 8%) while secondary graft failure occurred at a median of 190 days (range, 90 to 415) at a cumulative incidence of 3.7% (95% CI, 2% to 5%). Cumulative incidence of grade II to IV acute GVHD at day 100 was 3.8% (95% CI, 1.4% to 9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI, 2.6% to 15%). Median follow-up post-transplant was 61 months (range, 6 to 144). Overall survival was 84.9%, disease-free survival was 80.2%, and GVHD-free relapse-free survival was 76.3%. This study indicates that single-agent cyclosporine is a feasible option for GVHD prophylaxis in MRD hematopoietic stem cell transplantation using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD.
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http://dx.doi.org/10.1016/j.bbmt.2020.07.026DOI Listing
December 2020

Risk of kidney toxicity with carfilzomib in multiple myeloma: a meta-analysis of randomized controlled trials.

Ann Hematol 2020 Jun 7;99(6):1265-1271. Epub 2020 May 7.

Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.

The incidence and relative risk of kidney toxicity with carfilzomib in multiple myeloma (MM) has been incompletely characterized. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing carfilzomib-based with non-carfilzomib-based regimens in MM to investigate the risk of kidney toxicity. Point estimates were pooled in the form of risk ratios (RR) with 95% confidence intervals (CI) using the random-effects model. We identified four RCTs with 2954 patients. The median duration of treatment ranged from 16.3 to 88 weeks in carfilzomib arms. The cumulative rate of kidney toxicities in the carfilzomib arms was 21.3% for all grades and 8.3% for grades 3-5 toxicities, with acute kidney injury being the predominantly reported event. Patients receiving a carfilzomib-based regimen had a significantly higher risk of total kidney toxicity compared with those in the control arms, with pooled RR of 1.79 (95% CI, 1.43-2.23, p < 0.001) and 2.29 (95% CI, 1.59-3.30; p < 0.001), for all grades and grades 3-5 toxicities, respectively. Despite adjustment for the duration of exposure in treatment arms, pooled incidence rate ratios (IRR) for kidney toxicity was significantly increased in the carfilzomib arm compared with control (pooled IRR of 1.28 for all grades and 1.66 for grades 3-5 toxicity). Subgroup analysis based on carfilzomib dose, infusion length, and treatment setting did not identify any significant subgroup effect. Kidney toxicity is an important adverse effect of carfilzomib-based regimens. Prospective studies should investigate patient-, disease-, and treatment-related risk factors for severe kidney toxicities and impact on long-term outcome.
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http://dx.doi.org/10.1007/s00277-020-04062-xDOI Listing
June 2020

Efficacy of Ibrutinib-Based Regimen in Chronic Lymphocytic Leukemia: A Systematic Review.

J Hematol 2019 Mar 30;8(1):1-10. Epub 2019 Mar 30.

Department of Hematology Oncology, Cleveland Clinic, Cleveland, OH, USA.

Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive chronic lymphocytic leukemia (CLL) patients; however its role in del17 negative patients is less clear. We aim to evaluate the efficacy of ibrutinib-based regimens in CLL. Seven databases were searched in accordance with PRISMA statement guidelines using the following keywords: chronic lymphocytic leukemia, CLL, Bruton tyrosine kinase inhibitor, BTK inhibitor, ibrutinib, and PCI-32765. Data from only prospective clinical trials was included. In a phase 3 trial (n = 136), the overall response rate (ORR) with ibrutinib was 92% whereas 18% patients had a complete response (CR). Progression free survival (PFS) and overall survival (OS) at 2 years were 89% and 95% respectively. Phase 3 trial (n = 195) with single agent ibrutinib showed ORR of 63%. PFS at 6 months and OS at 12 months were 88% and 90% respectively. In a phase 2 trial of relapsed and/or refractory (R/R) or high risk treatment naive (TN) patients, combination of ibrutinib and rituximab (n = 104) achieved an ORR of 100% (CR 28%) as compared to ORR 98% (CR 21%) with ibrutinib monotherapy (n = 102) with no significant difference in PFS. Combination of ibrutinib and ublituximab (n = 64) had an ORR of 78% (CR 7%) in a phase 3 study. In del17p negative R/R patients, combination of bendamustine/rituximab (BR) and ibrutinib (n = 289) achieved an ORR of 83% (CR/CRi 10%) and the 18 month PFS was 79%. In a phase 2 trial treated with ibrutinib (n = 145), patients with del17p R/R disease achieved an ORR of 64% and the 24 month PFS and OS was 63% and 75% respectively. In TN del17p patients (n = 35), ORR was 97% (CR-0) and the 24 month PFS and OS were 82% and 84% respectively with single agent ibrutinib. Ibrutinib is the treatment of choice for patients with del17p mutation and has good efficacy in RR/TN patients without del17p mutation. Ibrutinib is being evaluated in combination with rituximab for del17p mutations. Future prospects include combination of ibrutinib with frontline chemotherapy and other novel agents for TN and RR del17p negative patients.
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http://dx.doi.org/10.14740/jh482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153674PMC
March 2019

Novel Targeted Therapies for Chronic Lymphocytic Leukemia in Elderly Patients: A Systematic Review.

Clin Lymphoma Myeloma Leuk 2020 07 27;20(7):e414-e426. Epub 2020 Feb 27.

Department of Hematology, Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH. Electronic address:

Chronic lymphocytic leukemia (CLL) typically affects older patients; administration of traditional cytotoxic therapies in old patients has very modest benefit with no survival improvement. With better understanding of CLL biology, trends are shifting towards the use of targeted therapies. The objective of this article is to review the safety and efficacy of various novel agents that specifically target the dysregulated pathways, with particular attention to elderly patients. Agents like B-cell receptor (BCR) inhibitors (Bruton's tyrosine kinase inhibitors [ibrutinib]), phosphatidylinositol 3-kinase inhibitors (idelalisib), spleen tyrosine kinase inhibitors (entospletinib), Bcl-2 inhibitors (venetoclax), immunomodulators (lenalidomide), and monoclonal antibodies (obinutuzumab, ofatumumab) have shown activity in CLL with a very favorable toxicity profile. Newer agents have improved clinical outcomes, and have tolerable toxicity profiles in elderly patients, resulting in the treatment with individualized therapy approach for CLL.
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http://dx.doi.org/10.1016/j.clml.2020.02.013DOI Listing
July 2020

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma.

Br J Haematol 2020 06 28;189(6):1074-1082. Epub 2020 Feb 28.

Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma (MM) is lacking in the current literature. We evaluated 258 patients with relapsed MM, diagnosed from 2008 to 2015, to investigate the prognostic impact of deep immunoparesis on post-relapse survival. On qualitative immunoparesis assessment, no, partial and full immunoparesis was present in 9%, 30% and 61% of patients, respectively. Quantitative immunoparesis was assessed by computing the average relative difference (ARD) between polyclonal immunoglobulin(s) and corresponding lower normal limit(s), with greater negative values indicating deeper immunoparesis. The median ARD was -39%, with an optimal cut-off of -50% for overall survival (OS) by recursive partitioning analysis. Deep immunoparesis (ARD ≤-50%) was associated with a higher tumour burden at first relapse compared to none/shallow [ARD >-50%] immunoparesis. The OS (P = 0·007) and progression-free survival (PFS; P < 0·001) differed significantly between the deep and none/shallow immunoparesis groups. Kaplan-Meier estimates for 3-year OS were 36% and 46%, and for 2-year PFS were 17% and 27%, respectively. On multivariable analysis (MVA) for PFS, both qualitative and quantitative immunoparesis retained negative prognostic impact independently. However, only quantitative immunoparesis was independently prognostic for OS on MVA. Depth of immunoparesis in relapsed MM is an important prognostic factor for post-relapse survival in the era of novel agents and continuous therapy.
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http://dx.doi.org/10.1111/bjh.16488DOI Listing
June 2020