History in perspective: How Alzheimer's Disease came to be where it is?

Treatment of Alzheimer's Disease (AD) remains an unsolved issue despite the pronounced global attention it has received from researchers over the last four decades. Determining the primary cause of the disease is challenging due to its long prodromal phase and multifactorial etiology. Regardless, academic disagreements amongst the scientific community have helped in making significant advancements in underpinning the molecular basis of disease pathogenesis. Substantial development in fluid and imaging biomarkers for AD led to a sharp turn in defining the disease as a molecular construct, dispensing its clinical definition. With conceptual progress, revisions in the diagnostic criteria of AD were made, culminating into the research framework proposed by National Institute on Aging and Alzheimer's Association in 2018 which unified different stages of the disease continuum, giving a common language of AT(N)1 classification to researchers. With realization that dementia is the final stage of AD spectrum, its early diagnosis by means of cerebrospinal fluid biomarkers, Positron Emission Tomography and Magnetic Resonance Imaging of the brain holds crucial importance in discovering ways of halting the disease progression. This article maps the insights into the pathogenesis as well as the diagnostic criteria and tests for AD as these have evolved over time. A contextualized timeline of how the understanding of AD has matured with advancing knowledge allows future research to be directed and unexplored avenues to be prioritized.

Understanding COVID-19 vaccine acceptance in Pakistan: an echo of previous immunizations or prospect of change?

BACKGROUND: As countries ramp up their COVID-19 vaccination programs, attitudes of the population remain a determining player in the success of these plans. This study analyses the factors associated with intent to vaccinate against COVID-19 in the Pakistani population. METHODOLOGY: This cross-sectional, anonymous, online survey was carried out in April 2021. Participants' demographic details, experiences relating to COVID-19 and its vaccination, and their health beliefs were inquired and divided across Health Belief Model constructs. Multivariable regression was used to determine factors associated with a No/Not sure vs Yes response for vaccination intention. RESULTS: Of the 655 respondents, 62.0% were willing to get vaccinated. Significant predictors of a less likelihood of resisting vaccination included advanced age (AOR 0.25; 95% CI 0.07-0.88), fear of contracting COVID-19 (AOR 0.47; 95% CI 0.27-0.82), hope of preventing its spread (AOR 0.30; 95% CI 0.19-0.49), and community pressure (AOR 0.22; 95% CI 0.13-0.37). Concerns about vaccine reliability (AOR 2.75; 95% CI 1.67-4.53) and religious inhibitions (AOR 2.45; 95% CI 1.34-4.48) swayed people away from vaccination. CONCLUSION: Despite a reasonably good response of Pakistanis to vaccination, factors negatively influencing their intention need to be timely addressed to control this pandemic.

Outcomes with CD34-Selected Stem Cell Boost for Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) characterized by multilineage cytopenia in the absence of mixed donor chimerism (<95% donor), relapse, or severe graft-versus-host disease (GVHD). We present a systemic review and meta-analysis aimed at assessing the outcomes with CD34-selected stem cell boost (SCB) for PGF in adult allo-HSCT recipients. We screened a total of 1753 records identified from 4 databases (PubMed, Embase, Cochrane, and ClinicalTrials.gov) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the search terms "hematological malignancies," "hematopoietic stem cell transplantation," "CD34 antigen(s)," "graft failure," and "poor graft function," from the date of inception to January 2021. After excluding review, duplicate, and nonrelevant articles, we included 7 studies reporting outcomes following administration of CD34-selected SCB for PGF after allo-HSCT, including hematologic complete response (CR) and overall response rate (ORR), GVHD, and overall survival (OS). Quality evaluation was done using the National Institutes of Health quality assessment tool. Pooled analysis was done using the R 'meta' package, and proportions with 95% confidence intervals (CIs) were computed. The inter-study variance was calculated using the Der Simonian-Laird estimator. We identified 209 patients who received CD34-selected SCB for PGF after allo-HSCT. The median age was 49 years (range, 18 to 69 years), and 61% were men. Primary graft sources included peripheral blood stem cells (72%) and bone marrow (28%). Donor types were matched sibling (37%), matched unrelated (36%), mismatched unrelated (22%), and haploidentical donors (5%). The median time from allo-HSCT to SCB was 138 days (range, 113 to 450 days). The median SCB dose was 3.45 × 106 CD34 cells/kg (range, 3.1 to 4.9 × 106 cells/kg). CR and ORR were 72% (95% CI, 63% to 79%; I2 = 26%) and 80% (95% CI, 74% to 85%; I2 = 0%), respectively. After a median follow-up of 42 months (range, 30 to 77 months), the actuarial survival rate was 54% (95% CI, 47% to 61%; I2 = 0%). OS ranged from 80% at 1 year to 40% at 9 years. The incidences of acute and chronic GVHD after SCB were 17% (95% CI, 13% to 23%; I2 = 0%) and 18% (95% CI, 8% to 34%; I2 = 76%), respectively. Nonrelapse mortality was reported in 42 patients, with a pooled rate of 27% (95% CI, 17% to 40; I2 = 59%), and death due to relapse was reported in 25 patients, with a pooled rate of 17% (95% CI, 11% to 23%; I2 = 0%). Our data show that CD34-selected SCB improves outcomes after PGF post allo-HSCT with an acceptable toxicity profile. The literature lacks high-quality randomized evidence, and there remains an unmet need for prospective studies to address the optimal dosing and manipulation of SCB. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.