BACKGROUND:Tenofovir disoproxil-containing HIV pre-exposure prophylaxis (PrEP) is associated with a small risk of renal impairment. How this risk may differ in Aboriginal and Torres Strait Islander peoples (hereafter, respectfully, 'Indigenous') who have higher rates of chronic kidney disease and associated risk factors than non-Indigenous Australians, has yet to be described. METHODS:A retrospective longitudinal open cohort study of adults with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 commencing tenofovir disoproxil-containing PrEP as part of routine care was conducted. Client data were collected from 67 clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of Sexually Transmissible Infections and Blood Borne Viruses network between January 2012 and December 2019. The primary outcome was the rate of new renal impairment, defined as an eGFR of <60 mL/min/1.73 m2 or >25% decline of eGFR from baseline. RESULTS:Of the 8696 adults, 203 identified as Indigenous and were eligible for inclusion. The median age was 34 years (IQR 28-44), 96.8% were men who have sex with men and 90.1% resided in major cities. Indigenous clients were less likely to have a baseline eGFR 60-90 mL/min/1.73 m2 (15.8% vs 24.1%; P = 0.006). Over a median follow-up period of 1.7 years (IQR 1.1-2.4), rates of renal impairment were similar for Indigenous and non-Indigenous clients: 5.6 events/1000 person-years (95% CI 1.4-22.8) and 4.8 events/1000 person-years (95% CI 3.9-6.1) respectively (P = 0.83). CONCLUSIONS:Renal impairment was rare among Australians commencing PrEP as part of usual care. We observed no difference in the development of renal impairment among Indigenous and non-Indigenous Australians.

Background:Following reports of an outbreak of HIV infection among children in Larkana District, Pakistan, an international team investigated the extent and cause of the outbreak between April and June 2019. Aims:To investigate the incidence of HIV among children in Larkana District, Pakistan and describe the distribution of cases by time, place and person. Methods:Self-referred persons were tested for HIV using the national testing protocol. Local epidemiology of HIV was reviewed to generate hypotheses. An infection prevention and control (IPC) team conducted site visits and reviewed IPC practices. Results:Between 25 April and 27 June 2019, a total of 30 191 persons were tested for HIV in Larkana District, and 876 of them tested positive. Of those who tested positive, 719 (82%) were children aged <15 years. Traditional skin piercing procedures and transmission from high-risk populations to children were ruled out during the investigation. Informative interviews with parents or guardians of a convenience sample of 211 children aged <15 years showed that 99% of children had an injection or infusion for medical treatment within the past 12 months. Our investigation identified lack of HIV prevalence data for the general population including tuberculosis patients and those who attended antenatal care services. Conclusions:Investigations indicate that unsafe healthcare practices in formal and informal healthcare settings as the most likely cause of the 2019 outbreak of HIV infection in Larkana, Pakistan. Measures should be taken to improve IPC practices at the facility level, especially in pediatric and antenatal care clinics.

Abstract Background Lack of dependable morbidity and mortality data complicates efforts to measure the demographic or population-level impact of the global HIV/AIDS epidemic. Mortuary-based mortality surveillance can address gaps in vital statistics in low-resource settings by improving accuracy of measuring HIV-associated mortality and indicators of access to treatment services among decedents. This paper describes the process and considerations taken in conducting mortuary and hospital-based HIV mortality surveillance among decedents in Kenya. Main text We conducted HIV mortuary and hospital-based mortality surveillance at two of the largest mortuaries in Kisumu County, Kenya (April 16–July 12, 2019). Medical charts were reviewed for documentation of HIV status among eligible decedents. HIV testing was done on blood and oral fluid samples from decedents with undocumented HIV status and those whose medical records indicated HIV-negative test results > 3 months before death. A panel of experts established the cause of death according to the International Classification of Diseases, 10th Revision rules. Civil registry data for the year 2017 were abstracted and coded to corresponding ICD-10 codes. Of the 1004 decedents admitted to the two mortuaries during the study period, 49 (4.9%) were unavailable because they had been transferred to other facilities or dispatched for burial before enrolment. Of the 955 available decedents, 104 (10.9%) were ineligible for the study. Blood samples were collected from 659 (77.4%) decedents, and 654 (99.2%) were tested for HIV. Of the 564 decedents eligible for the OraQuick® validation sub-study, 154 were eligible for oral sample collection, and 132 (85.7%) matched pre- and post-embalming oral samples were collected and tested. Of the 851 eligible decedents, 241 (28.3%) had evidence of HIV infection: 119 had a diagnosis of HIV infection recorded in their patient files, and 122 had serological evidence of HIV infection. Conclusion This study shows that in low-resource settings, conducting hospital and mortuary-based surveillance is feasible and can be an alternative source of mortality data when civil registry data are inadequate.

During the COVID-19 pandemic, public health agencies implemented an array of technologies and digital tools to support case investigation and contact tracing. Beginning in May 2020, the Association of State and Territorial Health Officials compiled information on digital tools used by its membership, which comprises 59 chief health officials from each of the 50 states, 5 US territories, 3 freely associated states, and the District of Columbia. This information was presented online through a publicly available technology and digital tools inventory. We describe the national landscape of digital tools implemented by public health agencies to support functions of the COVID-19 response from May 2020 through May 2021. We also discuss how public health officials and their informatics leadership referenced the information about the digital tools implemented by their peers to guide and refine their own implementation plans. We used a consensus-based approach through monthly discussions with partners to group digital tools into 5 categories: surveillance systems, case investigation, proximity technology/exposure notification, contact tracing, and symptom tracking/monitoring. The most commonly used tools included the National Electronic Disease Surveillance System Base System (NBS), Sara Alert, REDCap, and Maven. Some tools such as NBS, Sara Alert, REDCap, Salesforce, and Microsoft Dynamics were repurposed or adapted for >1 category. Having access to the publicly available technology and digital tools inventory provided public health officials and their informatics leadership with information on what tools other public health agencies were using and aided in decision making as they considered repurposing existing tools or adopting new ones.

Objective To assess and characterize the correlation between shoulder pathologies and sleep disturbances. Methods Participants enrolled into this case–control study were divided into two groups: patients with an established clinical diagnosis of active shoulder pathology (study group), and patients without any shoulder pathology (control group). All patients completed the Insomnia Severity Index (ISI) questionnaire, in addition to questions related to participant demographics, health status, medication, and other known insomnia risk factors. Results A total of 98 patients were included (46 in the study group and 52 controls). Mean ISI score was significantly higher (indicating more severe insomnia) in the study group versus control group (t[96] = –9.67), even after correcting for confounders (t[53.1] = –8.61). Additionally, in patients with shoulder pathology, those with comorbidities experienced more sleep disturbances than those without comorbidities (β = 0.36). Lastly, the shoulder pathology group was at a higher risk of having sleep disturbances compared with controls (relative risk 4.86, 95% confidence interval 2.24, 10.55). Conclusions Sleep disturbances are more common among patients with shoulder pathologies. Comorbidities and a shorter duration of pathology may predict more severe sleep disturbances.

Objectives:Health department personnel conduct daily active symptom monitoring for persons potentially exposed to SARS-CoV-2. This can be resource-intensive. Automation and digital tools can improve efficiency. We describe use of a digital tool, Sara Alert, for automated daily symptom monitoring across multiple public health jurisdictions.Methods:Eleven of the 20 U.S. public health jurisdictions using Sara Alert provided average daily activity data during June 29 to August 30, 2021. Data elements included demographics, communication preferences, timeliness of symptom monitoring initiation, responsiveness to daily messages, and reports of symptoms.Results:Participating jurisdictions served a U.S. population of over 22 million persons. Health department personnel used this digital tool to monitor more than 12,000 persons per day on average for COVID-19 symptoms. On average, monitoring began 3.9 days following last exposure and was conducted for an average of 5.7 days. Monitored persons were frequently < 18 years old (45%, 5,474/12,450) and preferred communication via text message (47%). Seventy-four percent of monitored persons responded to at least one daily automated symptom message.Conclusions:In our geographically diverse sample, we found that use of an automated digital tool might improve public health capacity for daily symptom monitoring, allowing staff to focus their time on interventions for persons most at risk or in need of support. Future work should include identifying jurisdictional successes and challenges implementing digital tools; the effectiveness of digital tools in identifying symptomatic individuals, ensuring appropriate isolation, and testing to disrupt transmission; and impact on public health staff efficiency and program costs.

OBJECTIVES:Exposure notification (EN) supplements traditional contact tracing by using proximity sensors in smartphones to record close contact between persons. This ledger is used to alert persons of potential SARS-CoV-2 exposure, so they can quarantine until their infection status is determined. We describe a model that estimates the impact of EN implementation on reducing the spread of SARS-CoV-2 and on the workload of public health officials, in combination with other key public health interventions such as traditional contact tracing, face mask wearing, and testing. METHODS:We created an agent-based model, Simulated Automated Exposure Notification (SimAEN), to explore the effectiveness of EN to slow the spread of SARS-CoV-2. We varied selected simulation variables, such as population adoption of EN and EN detector sensitivity configurations, to illustrate the potential effects of EN. We executed 20 simulations with SimAEN for each scenario and derived results for each simulation. RESULTS:When more sensitive versus more specific EN configurations were compared, the effective reproductive number, RE, was minimally affected (a decrease <0.03). For scenarios with increasing levels of EN adoption, an increasing number of additional infected persons were identified through EN, and total infection counts in the simulated population decreased; RE values for this scenario decreased with increasing EN adoption (a decrease of 0.1 to 0.2 depending on the scenario). CONCLUSIONS:Estimates from SimAEN can help public health officials determine which levels of EN adoption in combination with other public health interventions can maximize prevention of COVID-19 while minimizing unnecessary quarantine in their jurisdiction.

Background: Effective halting of outbreaks in skilled nursing facilities (SNFs) depends on the earliest recognition of cases. We assessed confirmed COVID-19 cases at an SNF impacted by COVID-19 in the United States to identify early indications of COVID-19 infection. Methods: We performed retrospective reviews of electronic health records for residents with laboratory-confirmed SARS-CoV-2 during February 28-March 16, 2020. Records were abstracted for comorbidities, signs and symptoms, and illness outcomes during the 2 weeks before and after the date of positive specimen collection. Relative risks (RRs) of hospitalization and death were calculated. Results: Of the 118 residents tested among approximately 130 residents from Facility A during February 28-March 16, 2020, 101 (86%) were found to test positive for SARS-CoV-2. At initial presentation, about two-thirds of SARS-CoV-2-positive residents had an abnormal vital sign or change in oxygen status. Most (90.2%) symptomatic residents had elevated temperature, change in mental status, lethargy, change in oxygen status, or cough; 9 (11.0%) did not have fever, cough, or shortness of breath during their clinical course. Those with change in oxygen status had an increased relative risk (RR) of 30-day mortality [51.1% vs 29.7%, RR 1.7, 95% confidence interval (CI) 1.0-3.0]. RR of hospitalization was higher for residents with underlying hepatic disease (1.6, 95% CI 1.1-2.2) or obesity (1.5, 95% CI 1.1-2.1); RR of death was not statistically significant. Conclusions and Implications: Our findings reinforce the critical role that monitoring of signs and symptoms can have in identifying COVID-19 cases early. SNFs should ensure they have a systematic approach for responding to abnormal vital signs and oxygen saturation and consider ensuring common signs and symptoms identified in Facility A are among those they monitor. Published by Elsevier Inc. on behalf of AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Background: From April to June 2019, 909 new HIV infections were identified in Larkana, Pakistan; 86% were children age <15 years. To identify the possible transmission links in this outbreak, a case-control study was conducted in June 2019. Methods: For cases, we selected a systematic random sample of 100 HIV positive children from the screening list. We chose two age and sex-matched controls from the neighborhood of each HIV+ case. All selected children were tested using the WHO approved rapid diagnosis test (RDT). We interviewed the parents of each selected child about previous exposures to parenteral treatment and compared exposures of case and control children using conditional logistic regression.Findings: The ages of the selected children ranged from one month to 10 years. Above 90% of both HIV+ and HIV- children had received outpatient healthcare from MBBS-qualified private physicians. 83% of HIV+ children compared to 46% of HIV- children had received healthcare from one private physician (adjusted odds ratio [aOR] = 29, 95% confidence interval [95% CI] = 10 to 79). Intravenous infusions during the last outpatient visit were more likely in case-children than control-children (aOR 57, 95% CI 2∙2 to > 1000), whereas no case-children and 17% of control-children had received only intramuscular injections (aOR 2 ∙ 2, 95% CI 0 to 41). Among case-children, 94% had been given infusions through a drip set compared to 85% of control-children (aOR = 7∙7, 95% CI 2∙3 to 26). Infusions had been administered with reused IV drip sets 70% of case-children compared to 8% of control-children (aOR = 197, 95% CI 16 to 2400).Interpretation: Private physicians reusing intravenous drip sets to treat outpatients seen in private practice were responsible for this HIV epidemic. Mapping and regulation of private practitioners was suggested.Funding: This investigation was funded using the operational budget of the Pakistan National Institute of Health, the Pakistan Field Epidemiology Program, the Sindh AIDS Control Program, the Sindh Ministry of Health, and the WHO Health Emergencies, WHO Country Office, Islamabad, Pakistan.Declaration of Interest: All authors declare no competing interests.Ethical Approval: This paper was approved by the Research Ethical Committee of the Health Services Sindh.

In April 2019, local media reports alerted the Sindh AIDS Control Program (SACP) in Pakistan of 14 children aged <10 years with new diagnoses of HIV infection in Ratodero, a rural subdistrict of Larkana District in Sindh province* (1).The report of pediatric cases of HIV infection in these children, whose parents all had received negative HIV test results, was concerning given the low number of children living with HIV in Pakistan (4,200 in a population of 79 million children) and the low (<0.1%)HIV prevalence estimate in the general population.†, § Within 2 weeks, SACP, with assistance from the Pakistan Field Epidemiology and Laboratory Training Program (FELTP), established 18 health care and community testing sites throughout Larkana District to identify additional cases.Testing was limited to specimens from persons who visited these voluntary testing sites, regardless of symptoms, and did not include contact tracing of clients with positive test results for HIV infection or implementation of HIV testing at highrisk clinical entry points (e.g., emergency departments or infectious disease clinics).By May 18, 2019, among 16,856 persons tested, health officials identified 571 (3.4%) new cases of HIV infection, 463 (81%) of which were in children and adolescents aged ≤15 years, including 355 (62%) aged ≤5 years.¶ In late May 2019, Pakistan's Federal Health Ministry requested assistance from the World Health Organization (WHO).International partners including other United Nations agencies and CDC joined WHO to support SACP, FELTP, and other local partners in the outbreak investigation and response.Preliminary investigations (including patient interviews, site visits to clinics, hospitals, and blood banks, and review of surveillance data) identified unsafe injection practices at health care facilities, unsafe practices at blood banks, inadequate infection control measures, and improper management of medical waste as possible risk factors.The Expanded Programme on Immunization services in Pakistan, which includes immunizations against hepatitis B, tuberculosis, polio, and other childhood diseases,

Unsafe injection practices and injection drug use have been linked to multiple HIV outbreaks in Pakistan since 2003; however, few studies have systematically analyzed the causes of these outbreaks. We conducted a systematic review of published English-language literature indexed in bibliographic databases and search engines and a focused gray literature review to collate and analyze all reported HIV outbreaks in Pakistan during 2000-2019. Of 774 unique publications reviewed, we identified 25 eligible publications describing 7 outbreaks. More than half occurred during 2016-2019. The primary sources of transmission were iatrogenic transmission, affecting children, persons with chronic medical conditions, and the general population (4 outbreaks); injection drug use (2 outbreaks); and a combination of both (1 outbreak). In the absence of robust HIV testing and surveillance in Pakistan, timely and detailed outbreak reporting is important to understand the epidemiology of HIV in the country.

Background: From April to June 2019, a total of 909 new HIV infections were identified in Larkana, Pakistan; 86% was children younger than 15 years. To identify the possible transmission links in this outbreak, a case-control study was conducted in June 2019. Methods: For cases, we selected a systematic random sample of 100 HIV-positive children from the screening list. We chose 2 age-matched and sex-matched controls from the neighborhood of each HIV-positive case. All selected children were tested using the World Health Organization-approved rapid diagnosis test algorithm. We interviewed the parents of each selected child about previous exposures to parenteral treatment and compared exposures of case and control children using conditional logistic regression. Results: The ages of the selected children ranged from 1 month to 10 years. More than 90% of both HIV+ and HIV- children had received outpatient health care from MBBS-qualified private physicians. Eighty-three percent of HIV+ children versus 46% of HIV- children had received health care from one private physician [adjusted odds ratio (aOR) = 29, 95% confidence interval (95% CI): 10 to 79]. Intravenous infusions during the last outpatient visit were reported by 29% of case versus 7% of controls (aOR 57, 95% CI: 2.9 to >1000), whereas no case children and 17% of control children had received only intramuscular injections (aOR 0, 95% CI: 0 to 41). Among cases, 94% had been given infusions through a drip set compared with 85% of control children (aOR = 7.7, 95% CI: 2.3 to 26). Infusions had been administered with reused IV drip sets in 70% of cases compared with 8% of controls (aOR = 197, 95% CI: 16 to 2400). Discussion: Private physicians reusing intravenous drip sets to treat outpatients seen in private practice were responsible for this HIV epidemic. Mapping and regulation of private practitioners were suggested.

In the United States, outbreaks of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), were initially reported in densely populated urban areas (1); however, outbreaks have since been reported in rural communities (2,3). Rural residents might be at higher risk for severe COVID-19-associated illness because, on average, they are older, have higher prevalences of underlying medical conditions, and have more limited access to health care services.* In May, after a cluster of seven COVID-19 cases was identified in a rural Ohio Amish community, access to testing was increased. Among 30 additional residents tested by real-time reverse transcription-polymerase chain reaction (RT-PCR; TaqPath COVID-19 Combo Kit),† 23 (77%) received positive test results for SARS-CoV-2. Rapid and sustained transmission of SARS-CoV-2 was associated with multiple social gatherings. Informant interviews revealed that community members were concerned about having to follow critical mitigation strategies, including social distancing§ and mask wearing. To help reduce the ongoing transmission risk in a community, state and county health department staff members and community leaders need to work together to develop, deliver, and promote culturally responsive health education messages to prevent SARS-CoV-2 transmission and ensure that access to testing services is timely and convenient. Understanding the dynamics of close-knit communities is crucial to reducing SARS-CoV-2 transmission.

Introduction The US President’s Emergency Plan for AIDS Relief (PEPFAR) was launched to increase access to antiretroviral treatment (ART) among people living with HIV (PLHIV) and to prevent new HIV infections globally. As new infections have decreased in many PEPFAR-supported countries, PEPFAR is increasingly focusing on understanding and decreasing mortality among PLHIV, specifically by addressing advanced HIV disease (AHD) and its attendant opportunistic infections (OIs). Several developments in identifying AHD, in preventing, diagnosing, and treating selected OIs, and in PEPFAR’s support for mortality surveillance make this an opportune moment for PEPFAR to address HIV-related mortality. Discussion AHD upon diagnosis or re-engagement in HIV care is not uncommon, and it substantially increases risk of death from OIs. The World Health Organization provides evidence-based guidelines for a package of interventions for preventing, diagnosing, and treating common OIs, including tuberculosis (TB), cryptococcal meningitis, and severe bacterial infections. PEPFAR facilitates implementation of these guidelines. To identify PLHIV with low CD4, PEPFAR plans to support expanded access to CD4 testing, including a point-of-care assay that differentiates CD4 cell count as a binary of greater than or less than 200 cells/µL. To prevent AHD-related mortality, PEPFAR supports rapid ART initiation with integrase inhibitor–based regimens and implementation and documentation of TB preventive treatment. To diagnose selected OIs, PEPFAR is implementing urine lateral flow lipoarabinomannan use to identify TB among PLHIV who have a CD4 cell count < 200 cells/µL. To treat selected OIs, PEPFAR has focused on improving patient-centered care in TB/HIV co-infection services and scaling up implementation of new drug regimens for cryptococcal meningitis. To better understand mortality, PEPFAR has introduced an indicator, TX_ML, to routinely and systematically categorize outcomes, including deaths, among PLHIV on ART. Conclusions PEPFAR is increasing its efforts to identify AHD; to prevent, diagnose, and treat OIs; and to track mortality in its programs. These ongoing efforts, done in collaboration with other stakeholders, seek to decrease mortality among PLHIV.

BACKGROUND:The aim of this review was to summarize the data on HIV/AIDS epidemiology and affected populations in Ghana and to describe the United States President's Emergency Plan for Emergency Relief's (PEPFAR) response to the epidemic. DESIGN:We conducted a literature review focusing on PEPFAR's contribution to the HIV response in Ghana. Additionally, we summarized the epidemiology of HIV. We searched both peer-reviewed and grey literature. SETTING:Ghana. RESULTS:Overall, HIV prevalence in Ghana is 1.6% with regional variation. Key populations (KPs) are disproportionately affected by HIV in the country. FSW and their clients, and MSM, account for 28% of all new infections. PEPFAR provides technical assistance (TA) to Ghana to maximize the quality, coverage and impact of the national HIV/AIDS response. To ensure adequate supply of antiretrovirals (ARVs), in 2016-2017, PEPFAR invested $23.7 million as a onetime supplemental funding to support Ghana's ARV treatment program. In addition, the National AIDS Control Programme in collaboration with PEPFAR is implementing a scale up of viral load testing. PEPFAR is also implementing a comprehensive package of prevention services in five regions to help reach MSM and FSW and to expand HIV testing services for KPs. CONCLUSIONS:Ghana is making changes at both policy and program level in the fight against HIV/AIDS and is working towards achieving the UNAIDS' 90-90-90 targets. PEPFAR is providing TA to ensure these goals can be achieved. FUNDING:This manuscript has been supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC).

BackgroundMycoplasma genitaliumis increasingly seen as an emerging sexually transmitted pathogen, and has been likened toChlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determineM. genitaliumincidence, persistence, concordance between sexual partners and the risk of pelvic inflammatory disease (PID).MethodsWe searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies.ResultsWe screened 4634 records and included 18 studies; six (4201 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI 0.61 to 1.53, I20%). Median persistence ofM. genitaliumwas estimated from one to three months in four studies but 15 months in one study. In 10 studies measuringM. genitaliuminfection status in couples, 39%–50% of male or female sexual partners of infected participants also hadM. genitaliumdetected. In prospective studies, PID incidence was higher in women withM. genitaliumthan those without (risk ratio 1.73, 95% CI 0.92 to 3.28, I20%, two studies).DiscussionIncidence ofM. genitaliumin very highly developed countries is similar to that forC. trachomatis, but concordance might be lower. Taken together with other evidence about age distribution and antimicrobial resistance in the two infections,M. genitaliumis not the new chlamydia. Synthesised data about prevalence, incidence and persistence ofM. genitaliuminfection are inconsistent. These findings can be used for mathematical modelling to investigate the dynamics ofM. genitalium.Registration numbersCRD42015020420, CRD42015020405

Several studies detected abnormal mi-RNAs expression levels in childhood Acute Lymphoblastic Leukemia (ALL) with potential diagnostic value. We conducted a systematic search on certain microRNAs in childhood ALL. We included 17 studies with a total of 928 ALL children and 307 controls. Ten studies provided miRNAs expression levels and seven provided frequency data. Sensitivity and specificity of a single miRNA ranged from 46.55% to 100% and from 71.8% to 100%, respectively. The highest diagnostic odds ratio (DOR) was for the diagnostic panel (miR-128a and miR-223) reaching 546 [95% CI: 73.768–4041.282]. Also, miR-128a, miR-128b, miR-223, let-7b, miR-155 and miR-24 can be used as diagnostic discriminatory biomarkers between ALL and AML. Further large cohort studies are needed to confirm our results.

Graphical abstract shows a summary of ADSCs mechanisms in promoting wound healing. ADSCs: Adipose-derived stem cells, CXCR-4: CXC chemokine receptor type 4, ECM: Extracellular matrix, EGF: Epithelial growth factor, FGF: Fibroblast growth factor, HUVECs: Human umbilical vein endothelial cells, Mif: Macrophage migration inhibitor factor, PDGF: Platelet-derived growth factor, PI3K: Phosphoinositide 3-Kinase, SDF-1: Stromal-derived factor-1, TGF: Transforming growth factor, VEGF: Vascular endothelial growth factor, vWF: von Willebrand factor.