The immunologic outcomes and adverse events of COVID-19 vaccine booster dose in immunosuppressed people: A systematic review.

Introduction: This study examines the efficacy and safety of three COVID-19 booster vaccines including mRNA-based vaccines (BNT162b2 (BioNTech/Pfizer) and/or mRNA-1273 (Moderna)), Non-Replicating Viral-Vector vaccines (ChAdOx1 nCoV-19 vaccine (AstraZeneca) and/or Ad26. COV2.S (Johnson & Johnson)), and Protein Subunit vaccine (SpikoGen) in immunosuppressed patients. Methods: Relevant articles were systematically searched using medical subject heading (MeSH) and keywords "COVID-19" and "booster dose" or "booster vaccine" or ''fourth dose" in the online databases of PubMed, Embase, Scopus, and Web of Science. To identify eligible studies, a two-phase screening process was implemented. Initially, three researchers evaluated the studies based on the relevancy of the title and abstract. Results: A total of 58 studies met the inclusion criteria and were included in this review. The findings suggest that booster doses offer greater protection against the disease than the primary dose. The study also compared various vaccine types, revealing that viral vector and nucleic acid vaccines outperformed inactivated vaccines. Results indicated that individuals receiving booster doses experienced superior outcomes compared to those without boosters. Vaccination against COVID-19 emerged as the most effective preventive measure against infection and symptom severity. Elevated antibody levels post-booster dose vaccination in the population signaled robust immune responses, underscoring the benefits of supplementary vaccine doses. Conclusion: This systematic review highlights preliminary evidence supporting the immunologic outcomes and safety of COVID-19 vaccine boosters in enhancing immune responses against SARS-CoV-2. However, further research is needed to determine optimal timing intervals between primary vaccination series and boosters while considering global equity issues and variant-specific considerations.

The prognostic significance of insulin resistance in COVID-19: a review.

Objectives: Emerging publications indicate that diabetes predisposes patients with COVID-19 to more severe complications, which is partly attributed to inflammatory condition. In the current review, we reviewed recent published literature to provide evidence on the role of insulin resistance (IR) in diabetes, the association between diabetes and COVID-19 severity and mortality, the impact of COVID-19 infection on incident new-onset diabetes, mechanisms responsible for IR in COVID-19 patients, and the predictive value of different surrogates of IR in COVID-19. Method: The literature search performs to find out studies that have assessed the association between IR surrogates and morbidity and mortality in patients with COVID-19. Results: We showed that there is a bulk of evidence in support of the fact that diabetes is a potent risk factor for enhanced morbidity and mortality in COVID-19 patients. COVID-19 patients with diabetes are more prone to remarkable dysglycemia compared to those without diabetes, which is associated with an unfavourable prognosis. Furthermore, SARS-COV2 can make patients predispose to IR and diabetes via activating ISR, affecting RAAS signaling pathway, provoking inflammation, and changing the expression of PPARÉ£ and SREBP-1. Additionally, higher IR is associated with increased morbidity and mortality in COVID-19 patients and different surrogates of IR can be utilized as a prognostic biomarker for COVID-19 patients. Conclusion: Different surrogates of IR can be utilized as predictors of COVID-19 complications and death.

Evaluating the Relationship between Various Risk Factors and COVID-19 Incidence In People Living with HIV: A Cross-Sectional Study.

INTRODUCTION: People living with HIV (PLWH) are more susceptible to acquiring and having serious consequences from COVID-19. The objective of this study was to examine the correlation between COVID-19 infection and other risk factors in these patients. METHODS: This is a descriptive-analytical study recruiting 160 PLWH referred to the Behavioral Disease Counselling Centre of Imam Khomeini Hospital in Tehran in 2021. The patients were selected through convenient sampling. A checklist was used to collect the necessary data. Descriptive statistical tests, such as mean and standard deviation, were employed alongside inferential statistics, including chi-square, Fisher, independent t-tests, and logistic regression, all evaluated at a significance level of p<0.05 using the R software. RESULTS: The patients' average age was 43.15 ± 11.23. Forty-four women and 116 men were present. A notable association was observed between the incidence of COVID-19 and variables such as hepatitis C and the duration of time since HIV diagnosis (p<0.001). Moreover, a strong correlation was found between the amount of COVID-19 vaccination doses given to patients and their probability of acquiring the disease. The first vaccination dose was linked to a 5.45 percent increase in COVID-19 incidence in patients, whereas the second and third doses (t=2.95, t=7.57) reduced the risk of getting COVID-19. Furthermore, no discernible link (p>0.05) was found between the use of various antiretroviral medications and COVID-19 infection. CONCLUSION: This study finds that vaccine type doesn't impact COVID-19 outcomes in HIV-positive patients, but receiving more doses decreases the probability of occurrence of COVID-19, advocating for multiple vaccinations. However, PLWH, especially those non-compliant with antiretrovirals, need strict adherence to health protocols due to heightened vulnerability to viral illnesses.

Comparison of Omicron and Delta Variants of SARS-CoV-2: A Systematic Review of Current Evidence.

INTRODUCTION: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) caused the outbreak of coronavirus disease 2019 (COVID-19) in late 2019 in Wuhan, China. In early 2020, the disease spread rapidly around the world. Since the pandemic, SARS-CoV-2 has evolved dramatically into a wide variety of variants endowed with devastating properties. As of March 6, 2022, five SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, Delta, and Omicron strains have been identified. Due to the crucial importance of understanding the differences between the Omicron and Delta variants, this systematic review was conducted. METHODS: This systematic review investigated new variants of Omicron SARS-CoV-2 based on cur-rent studies. Online databases were searched for English articles as of January 03, 2023. Selection of publications was a two-step process of title/abstract and full-text assessment against eligibility crite-ria. The relevant data from the included articles were systematically collected and organized in a designed table for analysis. To ensure the quality of the review, the PRISMA checklist and Newcas-tle-Ottawa Scale (NOS) of quality assessment were utilized. RESULTS: The data extracted from 58 articles were analyzed, including 10003 pieces of evidence. Lower risk of hospitalization, ICU admission, and mortality after vaccination were reported in the Omicron variant compared to the Delta variant. Additionally, the Delta variant led to more severe clinical symptoms in comparison to the Omicron variant. CONCLUSION: The Omicron variant of SARS-CoV-2 results in less severe disease outcomes as com-pared to Delta. Nevertheless, it remains crucial to maintain ongoing monitoring, implement contain-ment measures, and adapt vaccination protocols to effectively address the evolving variants.

Estimating Hidden Population Size of COVID-19 Using Respondent- Driven Sampling Method - A Systematic Review.

INTRODUCTION: Currently, the ongoing COVID-19 pandemic is posing a challenge to health systems worldwide. Unfortunately, the true number of infections is underestimated due to the existence of a vast number of asymptomatic infected individual's proportion. Detecting the actual number of COVID-19-affected patients is critical in order to treat and prevent it. Sampling of such populations, so-called hidden or hard-to-reach populations, is not possible using conventional sampling methods. The objective of this research is to estimate the hidden population size of COVID-19 by using respondent-driven sampling methods. METHOD: This study is a systematic review. We have searched online databases of PubMed, Web of Science, Scopus, Embase, and Cochrane to identify English articles published from the beginning of December 2019 to December 2022 using purpose-related keywords. The complete texts of the final chosen articles were thoroughly reviewed, and the significant findings are condensed and presented in the table. RESULTS: Of the 7 included articles, all were conducted to estimate the actual extent of COVID- 19 prevalence in their region and provide a mathematical model to estimate the asymptomatic and undetected cases of COVID-19 amid the pandemic. Two studies stated that the prevalence of COVID-19 in their sample population was 2.6% and 2.4% in Sierra Leone and Austria, respectively. In addition, four studies stated that the actual numbers of infected cases in their sample population were significantly higher, ranging from two to 50 times higher than the recorded reports. CONCLUSIONS: In general, our study illustrates the efficacy of RDS sampling in the estimation of undetected asymptomatic cases with high cost-effectiveness due to its relatively trouble-free and low-cost methods of sampling the population. This method would be valuable in probable future epidemics.

Ocular manifestations of COVID-19: A systematic review of current evidence.

Introduction: COVID-19 caused by SARS-CoV-2, commonly presents with symptoms such as fever and shortness of breath but can also affect other organs. There is growing evidence pointing to potential eye complications. In this article, we aim to systematically review the ocular manifestations of COVID-19. Methods: We conducted a systematic review to explore the ocular manifestations of COVID-19. We searched online databases including PubMed, Embase, Scopus, and Web of Science up to September 4, 2023. After a two-stage screening process and applying inclusion/exclusion criteria, eligible articles were advanced to the data extraction phase. The PRISMA checklist and Newcastle-Ottawa Scale (NOS) were used for quality and bias risk assessments. Results: We selected and extracted data from 42 articles. Most of the studies were cross-sectional (n = 33), with the highest number conducted in Turkey (n = 10). The most frequent ocular manifestation was conjunctivitis, reported in 24 articles, followed by photophobia, burning, chemosis, itching, and ocular pain. Most studies reported complete recovery from these manifestations; however, one study mentioned visual loss in two patients. Conclusion: In general, ocular manifestations of COVID-19 appear to resolve either spontaneously or with supportive treatments. For more severe cases, both medical treatment and surgery have been employed, with the outcomes suggesting that complete recoveries are attainable.

The effect of macronutrient and micronutrient supplements on COVID-19: an umbrella review.

BACKGROUND AND AIMS: A healthy diet play an important role in the prevention and even treatment of various diseases. Proper nutrition plays an important role in boosting of immune system. These include the consumption of macronutrients such as proteins, lipids, carbohydrates, and also micronutrients including vitamins. Here, we aimed to systematically review the effects of macronutrients and micronutrients on the prevention and treatment of COVID-19. METHODS: We searched the databases of PubMed, Scopus, Embase, and Web of Science on December 23, 2023. The records were downloaded into an EndNote file, the duplicates were removed, and the studies underwent a two-phase screening process based on their title/abstracts and full texts. The included articles were screened and underwent inclusion and exclusion criteria. We included the English systematic reviews and meta-analyses that concurred with the aim of our study. The selected articles were assessed by Cochrane's Risk of Bias in Systematic Reviews for the quality check. The data of the eligible studies were extracted in a pre-designed word table and were used for the qualitative synthesis. RESULTS: A total of 28 reviews were included in this study. Most studies have shown that micronutrients are effective in morbidity and mortality controlling in viral respiratory infections such as COVID-19 but some studies have shown that micronutrients are sometimes not effective in controlling severity. On the other hand, calcifediol was by far the most successful agent in reducing intensive care needs and mortality between studies. CONCLUSION: Individuals without malnutrition had a reduced risk of SARS-CoV-2 infection and severe disease. The administration of Vitamin D is effective in reducing the morbidity and mortality of COVID-19 patients. Patients with vitamin D deficiency were more prone to experience severe infection, and they were at higher risk of morbidities and mortality. Other micronutrients such as Vitamin A, Vitamin B, and Zinc also showed some benefits in patients with COVID-19. Vitamin C showed no efficacy in COVID-19 management even in intravenous form or in high doses.

The Upper-gastrointestinal Endoscopic Findings of People Living with HIV: A Systematic Review.

OBJECTIVE: This article aimed to analyze upper endoscopic findings in the HIV patient population to elucidate the upper-gastrointestinal complications related to HIV infection. Gastrointestinal (GI) disorders in individuals living with HIV/AIDS exhibit diverse and often nonspecific manifestations, imposing substantial morbidity and mortality burdens. Endoscopic evaluation with biopsies is essential in the diagnosis and management of these conditions. Delayed treatment due to undetected GI abnormalities during endoscopic examinations can lead to poorer health outcomes. METHODS: This systematic review has determined the findings of upper-GI endoscopy of HIV-infected patients. Online databases of PubMed, Web of Science, Jisc Library Hub Discover, and Library of Congress have been searched using relevant keyword combinations. We have retrieved all the pertinent papers and reports published in English and screened them against inclusion/exclusion criteria for data extraction in two steps. First, titles/abstracts have been evaluated and then full-text screening has been performed by independent researchers. This study has adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. RESULTS: In this review, 24 articles have been included in the final analysis. The study has focused on the characteristics of participants and the findings of endoscopic evaluations. The participants of the study have been HIV-positive patients, and the majority of them have undergone endoscopy due to gastrointestinal symptoms. The biopsy regions primarily targeted have been observed to be the esophagus, stomach, and duodenum. The most common result of the biopsy specimens has been chronic active gastritis. CONCLUSION: To improve clinical practice, this systematic review sought to provide an up-to-date reference for upper gastrointestinal endoscopic findings of HIV-infected persons. Our results are in line with earlier research showing how effective endoscopy is for determining a precise diagnosis and directing care. The majority of HIV patients with gastrointestinal symptoms have been found to have opportunistic infections and persistent active gastritis as well as mucosal abnormalities of the upper gastrointestinal tract. Studies have shown that endoscopic and histological assessment can aid in the early detection and management of issues involving the upper gastrointestinal tract.

Estimating the Size of the Hidden Population of COVID-19.

INTRODUCTION: An asymptomatic population has the same infection as symptomatic individuals, so these individuals can unknowingly spread the virus. It is not possible to predict the rate of epidemic growth by considering only the identified isolated or hospitalized population. In this study, we want to estimate the size of the COVID-19 population, based on information derived from patients visiting medical centers. So, individuals who do not receive a formal diagnosis in those medical centers can be considered as hidden. METHODOLOGY: To estimate the Bayesian size of the hidden population of COVID-19 a respondentdriven sampling (RDS) method was used. Twenty-three people infected with COVID-19 seeds and who had positive PCR test results were selected as seeds. These participants were asked whether any of their friends and acquaintances who had COVID-19 did not visit a medical center or hid their illness. Access to other patients was gained through friendship and kinship, hence allowing the sampling process to proceed. RESULTS: Out of 23 selected seeds, only 15 seeds remained in the sample and the rest were excluded due to not participating in the further sampling process. After 5 waves, 50 people with COVID-19 who had hidden their disease and were not registered in the official statistics were included in the sample. It was estimated that 12,198 people were infected with COVID-19 in Khalkhal city in 2022. This estimate was much higher than recorded in the official COVID-19 statistics. CONCLUSIONS: The study findings indicate that the estimated 'true' numbers of COVID-19 patients in one town in Iran were significantly higher compared to the official numbers. The RDS method can help capture the potential size of infections in further pandemics or outbreaks globally.

Design, development and evaluation of a mobile-based self-care application for patients with COVID-19 not requiring hospitalization; a study of Northwest of Iran.

BACKGROUND: Given the effective role of a mobile applications in disease management, disease monitoring, and self-care in patients with COVID-19 disease, we aimed to design, development and evaluation of a self-care Mobile app for COVID-19 patients not requiring hospitalization. METHODS: The design, development and evaluation the usability of the self-care and education mobile app for patients with COVID-19 disease were conducted in two main phases at 2021 in Northwest of IRAN; (1) Determine the features and capabilities and (2) Design, development and evaluation of self-care mobile App. JAVA programming languages and Android Operating System were used and selected to design and development of a mobile app. There were 25 participants who conducted evaluations of the mobile app's usability and impact using the mobile health app usability a Questionnaire of User Interface Satisfaction was administered to assess the usability of the developed application. The results were analyzed via Excel 2013. RESULTS: The model of developing a mobile app as an Information System was the Waterfall model. The smartphone application based on a set of capabilities and features was designed and consists of two main parts: the login screen for user registration, and the main home menu. The user interface includes three main pages or activities; (a) Main Menu for quick access to all of the pages, (b) Symptom management and monitoring to monitor the signs and symptoms during the illness, and (c) Set Reminders and Alarms to notify patients. The users' mean score of the application usability was calculated as 7.91 out of 9 indicating a good level of satisfaction. CONCLUSION: This app can be a guideline and a useful tools for managing and monitoring symptoms, reminding medications, and implementing self-care instructions in outpatients. The authors suggest evaluating the efficacy and functionality test of mobile-based applications for COVID-19 in clinical trial studies.

Social stigma during COVID-19: A systematic review.

Objectives: Stigmatization was reported throughout the COVID pandemic for COVID-19 patients and close contacts. The aim of this systematic review was to comprehensively examine the prevalence and impact of stigmatization during COVID-19 pandemic. Methods: English articles were searched using online databases that included PubMed, Scopus, Embase, and Web of Science up to 24 August 2022. A two-step screening and selection process was followed utilizing an inclusion and exclusion criteria and then data was extracted from eligible articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed, and the risk of bias was assessed using the Newcastle-Ottawa Scale. Results: Seventy-six studies were eligible for inclusion. Twenty-two studies reported the prevalence of social stigma due to COVID-19 infection with social isolation being the most commonly reported stigma. There were 20 studies that reported the majority of participants experienced stigma due to COVID-19 infection, which was as high as 100% of participants in two studies. Participants in 16 studies reported blaming from others as the second most common type of stigma, with various other types reported such as psychological pressure, verbal violence, avoidance, and labeling. The most common effect of the stigma was anxiety followed by depression, and then reduction of socialization. Conclusion: Findings from the present review have identified that COVID-19-related stigma studies have generally focused on its prevalence, type, and outcome. Greater awareness of this topic may assist with improving public education during pandemics such as COVID-19 as well as access to support services for individuals impacted by stigmatization.

The relationship of hip fracture and thyroid disorders: a systematic review.

Introduction: Bone density regulation is considered one of the systems affected by thyroid hormones, leading to low bone density that can result in pathologic fractures, including hip fractures. This review aimed to update clinicians and researchers about the current data regarding the relationship between hip fractures and thyroid disorders. Methods: English papers were thoroughly searched in four main online databases of Scopus, Web of Science, PubMed, and Embase. Data extraction was done following two steps of screening/selection using distinct inclusion/exclusion criteria. This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and the Newcastle-Ottawa Scale (NOS) as bias assessment. Results: In total, 19 articles were included in the research. The risk of hip fractures in women with differentiated thyroid cancer (DTC) is higher than hip fractures caused by osteoporosis. Men with hyperthyroidism and subclinical hyperthyroidism are at higher risk for hip fracture. Also, a decrease in serum thyroid stimulating hormone (TSH) may be associated with an increased risk of hip fracture. Conclusion: Reaching a consensus conclusion regarding the association between subclinical thyroid dysfunction and hip fracture is not feasible due to the heterogenicity of evidence; however, there may be a higher risk of fracture in individuals with subclinical hyperthyroidism.

Current ART, determinants for virologic failure and implications for HIV drug resistance: an umbrella review.

OBJECTIVE: The purpose of this study is to investigate the incidence of determinants for virologic failure and to identify predisposing factors to enhance treatment efficacy. Tackling this global public health issue is the key to reducing the rate of virological failure and increasing the success of treatment for those living with HIV. METHODS: This umbrella review delves into various aspects of current anti-retroviral therapy (ART) which is the primary treatment for human immunodeficiency virus (HIV) infection. Comprehensive searches were conducted in online databases including PubMed, Embase, Scopus, and Web of Science, up to May 26, 2023. Following the screening and selection of relevant articles, eligible articles were included in the data extraction. This study adhered to the PRISMA guideline to report the results and employed the NIH quality and bias risk assessment tool to ensure the quality of included studies. RESULTS: In total, 40 review studies published from 2015 to 2023 were included. The bulk of these studies concurred on several major factors contributing to HIV drug resistance and virological failure. Key among these were medication adherence, baseline and therapeutic CD4 levels, the presence of co-infections, and the advanced clinical stage of the infection. CONCLUSION: The resistance to HIV drugs and instances of determinants for virologic failure have a profound impact on the life quality of those infected with HIV. Primary contributors to this scenario include insufficient adherence to treatment, decreased CD4 T-cell count, elevated viral levels, and certain treatment regimens. Implementing appropriate interventions could address these issues. Sub-Saharan Africa exhibits elevated rates of determinants for virologic failure, attributed to the delay in HIV testing and diagnosis, and late initiation of antiretroviral therapy (ART). It is essential to undertake further research aimed at enhancing the detection of resistance in HIV patients and mitigating viral failure by addressing these underlying causes.

Assessment of virtual education during the covid-19 pandemic from the perspective of faculty members and students: a cross-sectional descriptive study in northwest Iran.

BACKGROUND: Since the coronavirus outbreak, many countries have replaced traditional education with virtual education in order to prevent the disease spread, and also avoid stopping education. The aim of the present study was to assess the virtual education status at Khalkhal University of Medical Sciences during the covid-19 pandemic from the perspective of students and faculty members. METHODS: This is a descriptive-cross-sectional study that was conducted between December 2021and February 2022. The study population included faculty members and students who were selected by consensus. Data collection instruments included demographic information form and a virtual education assessment questionnaire. Data analysis was carried out using independent T-test, one sample T-test, Pearson Correlation, and ANOVA test in SPSS software. RESULTS: A total of 231 students and 22 faculty members of Khalkhal University of Medical Sciences participated in the present study. The response rate was 66.57%. The mean and standard deviation of assessment scores of students (3.3 ± 0.72) were lower than those of faculty members (3.94 ± 0.64), which showed a statistically significant difference (p < 0.01). User access to the virtual education system (3.8 ± 0.85) and lesson presentation (4.28 ± 0.71) obtained the highest scores from the perspective of students and faculty members, respectively. There was a statistically significant association between employment status and the assessment score of faculty members (p = 0.01), and the field of study (p < 0.01), the year of university entrance (p = 0.01), and the assessment score of students. CONCLUSION: The results showed a higher than mean assessment score in both groups of faculty members and students. There was a difference between faculty members and students in terms of virtual education scores in the parts that require the creation of better processes and more complete capabilities in the systems, which seems that more detailed planning and reforms will improve the process of virtual education.

The Effectiveness of Face Masks in Preventing COVID-19 Transmission: A Systematic Review.

INTRODUCTION: Since the beginning of the COVID-19 pandemic, face masks have been among the cornerstones of COVID-19 prevention. Therefore, evaluating their preventive effects against COVID-19 is crucial. This review aimed to systematically search for the systematic review articles that explored the role of various types of face masks in preventing COVID-19. METHODS: We browsed the keywords of this study in the online databases of Scopus, Web of Science, PubMed, and Cochrane on 10th January 2023 and retrieved all the relevant systematic review articles. The records were downloaded into an Endnote file, and the duplicates were removed. A two-step screening process consisting of title/abstract and full-text screenings was conducted to select the most relevant articles. To ensure the validity and reliability of the results, this study adhered to the PRISMA protocol. RESULTS: A total of 28 systematic reviews were included in this review. Most studies found that face masks are beneficial against viral respiratory infections, such as COVID-19. Different types of masks were evaluated in included studies. It appeared that mask efficacy depends on the material, layers, fitting on the face and user compliance. N 95 respirator had maximum efficacy, especially when used continuously. CONCLUSION: Face masks have a beneficial effect against COVID-19. Home masks are less protective than surgical masks or N95 personal breathing masks. Besides, the use of masks may elicit a false sense of security in people, which may lead to poor hand hygiene and violation of social distancing. Therefore, the necessary training should be provided to the public to increase awareness and encourage the right practice of using the mask, emphasizing the preventive effects of washing hands, social distancing, and using a face mask against COVID-19.

SARS-CoV-2 Infection and Severity in Patients with Hematologic Malignancies: A Systematic Review.

INTRODUCTION: Earlier reports described the possibility of higher SARS-CoV-2 infection and severity in patients with hematological malignancies. Given the importance and incidence of these malignancies, we aimed to systematically review SARS-CoV-2 infection and severity in patients with hematologic cancers. METHODS: We retrieved the relevant records by searching the keywords in online databases of PubMed, Web of Science, Cochrane, and Scopus on December 31st, 2021. A two-step screening; title/abstract and full-text screening, was employed to select the eligible studies. These eligible studies entered the final qualitative analysis. The study is adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure the reliability and validity of the results. RESULTS: Forty studies concerning different hematologic malignancies and the effect of COVID-19 infection on them were included in the final analysis. The findings showed that in general, the prevalence of SARS-CoV-2 infection and the severity of the disease are often higher in hematologic malignancies and the patients could experience higher morbidity and mortality compared to general populations. CONCLUSION: It appeared that individuals with hematologic malignancies are more vulnerable to COVID-19 infection and they experience more severe disease with higher mortality rates. The presence of other comorbidities could also deteriorate this situation. Further investigation is recommended to evaluate the outcome of COVID-19 infection in different subtypes of hematologic malignancies.