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Vaccines Jun 2023Solid organ transplant (SOT) recipients are at increased risk of COVID-19 infection because of their suppressed immunity. The available data show that COVID-19 vaccines... (Review)
Review
Solid organ transplant (SOT) recipients are at increased risk of COVID-19 infection because of their suppressed immunity. The available data show that COVID-19 vaccines are less effective in SOT recipients. We aimed to assess the cellular and humoral immunogenicity with an increasing the number of doses of COVID-19 vaccines in SOT recipients and to identify factors affecting vaccine response in this population. A systematic review and meta-analysis were conducted to identify ongoing and completed studies of humoral and cellular immunity following COVID-19 vaccines in SOT recipients. The search retrieved 278 results with 45 duplicates, and 43 records did not match the inclusion criteria. After title and abstract screening, we retained 189 records, and 135 records were excluded. The reasons for exclusion involved studies with immunocompromised patients (non-transplant recipients), dialysis patients, and individuals who had already recovered from SARS-CoV-2 infection. After full-text reading, 55 observational studies and randomized clinical trials (RCTs) were included. The proportion of responders appeared higher after the third, fourth, and fifth doses. The risk factors for non-response included older age and the use of mycophenolate mofetil, corticosteroids, and other immunosuppressants. This systematic review and meta-analysis demonstrates the immunogenicity following different doses of COVID-19 vaccines among SOT patients. Due to the low immunogenicity of vaccines, additional strategies to improve vaccine response may be necessary.
PubMed: 37514982
DOI: 10.3390/vaccines11071166 -
Vaccines Jun 2023The humoral immune response and safety of the fourth dose of the coronavirus disease 2019 (COVID-19) vaccine in solid organ transplant (SOT) recipients need to be fully... (Review)
Review
The humoral immune response and safety of the fourth dose of the coronavirus disease 2019 (COVID-19) vaccine in solid organ transplant (SOT) recipients need to be fully elucidated. We conducted a systematic review and meta-analysis to assess the efficacy and safety associated with this additional dose of the COVID-19 vaccine in the SOT recipients. A comprehensive search was conducted to identify studies on SOT patients without prior natural SARS-CoV-2 infection who received the fourth dose of the COVID-19 vaccine. Serological antibody responses following vaccination were synthesized by a meta-analysis of proportions. The proportions for each outcome were integrated by using a random-effects model. Approximately 56-92% of the SOT patients developed a humoral immune response, and the pooled seroprevalence rate was 75% (95% confidence interval [CI], 62-82%) after administering the third vaccine dose. Following the fourth dose of vaccination, approximately 76-95% of the patients developed a humoral immune response. The pooled seroprevalence rate after the fourth dose was 85% (95% CI, 79-91%). Of the patients who initially tested seronegative after the second dose, approximately 22-76% of patients subsequently became seropositive after the third dose. The pooled seroconversion rate for the third dose was 47% (95% CI, 31-64%). Among the patients who were seronegative after the third dose, approximately 25-76% turned seropositive after the fourth dose. The pooled seroconversion rate after the fourth dose was 51% (95% CI, 40-63%). Safety data were reported in three studies, demonstrating that adverse effects following the fourth dose were generally mild, and patients with these adverse effects did not require hospitalization. No transplant rejection or serious adverse events were observed. A fourth dose of the COVID-19 vaccine in SOT recipients was associated with an improved humoral immune response, and the vaccine was considered relatively safe.
PubMed: 37514946
DOI: 10.3390/vaccines11071130 -
PloS One 2023Electrochemotherapy has gained international traction and commendation in national guidelines as an effective tool in the management of cutaneous malignancies not... (Review)
Review
Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: A systematic review and narrative synthesis.
BACKGROUND
Electrochemotherapy has gained international traction and commendation in national guidelines as an effective tool in the management of cutaneous malignancies not amenable to surgical resection. Despite this, no level 5 evidence exists comparing it to radiotherapy in the treatment of cutaneous malignancies. This systematic review aimed to examine the literature directly and indirectly comparing electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies.
MATERIALS & METHODS
The protocol for this review was registered on the PROSPERO International Prospective Register of Systematic Reviews with the protocol ID CRD42021285415. Searches of MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov databases were undertaken from database inception to 28 December 2021. Studies in humans comparing treatment with electrochemotherapy to radiotherapy and reporting tumour response with a minimum four week follow-up were eligible. Risk of bias was assessed using the ROBINS-I tool. Results are provided as a narrative synthesis.
RESULTS
Two case series with a total of 92 patients were identified as relevant to this study. Both case series examined patients with cutaneous squamous cell carcinoma. One case series examined elderly patients with predominantly head/neck lesions. The other examined younger patients with predominantly limb lesions who had cutaneous squamous cell carcinoma directly attributable to a rare skin condition.
CONCLUSION
There is little literature presenting comparative data for electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases. Included studies were marred by serious risk of bias particularly due to confounding. The inherent bias and heterogeneity of the included studies precluded synthesis of a consolidated comparison of clinical outcomes between the two therapies. Further research is required in this domain in the form of clinical trials and observational studies to inform guidelines for electrochemotherapy treatment.
Topics: Humans; Aged; Skin Neoplasms; Carcinoma, Squamous Cell; Electrochemotherapy
PubMed: 37440502
DOI: 10.1371/journal.pone.0288251 -
The Cochrane Database of Systematic... Jul 2023Pelvic organ prolapse (POP) is the descent of a woman's uterus, bladder, or rectum into the vagina. It affects 50% of women over 50 years old who have given birth to at... (Review)
Review
BACKGROUND
Pelvic organ prolapse (POP) is the descent of a woman's uterus, bladder, or rectum into the vagina. It affects 50% of women over 50 years old who have given birth to at least one child, and recognised risk factors are older age, higher number of births, and higher body mass index. This review assesses the effects of oestrogen therapy, alone or in combination with other treatments, on POP in postmenopausal women.
OBJECTIVES
To assess the benefits and harms of local and systemic oestrogen therapy in the management of pelvic organ prolapse symptoms in postmenopausal women, and to summarise the principal findings of relevant economic evaluations.
SEARCH METHODS
We searched the Cochrane Incontinence Specialised Register (up to 20 June 2022), which includes CENTRAL, MEDLINE, two trials registers, and handsearching of journals and conference proceedings. We also checked the reference lists of relevant articles for additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), quasi-RCTs, multi-arm RCTs, and cross-over RCTs that evaluated the effects of oestrogen therapy (alone or in combination with other treatments) versus placebo, no treatment, or other interventions in postmenopausal women with any grade of POP.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from the included trials using prespecified outcome measures and a piloted extraction form. The same review authors independently assessed the risk of bias of eligible trials using Cochrane's risk of bias tool. Had data allowed, we would have created summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We identified 14 studies including a total of 1002 women. In general, studies were at high risk of bias in terms of blinding of participants and personnel, and there were also some concerns about selective reporting. Owing to insufficient data for the outcomes of interest, we were unable to perform our planned subgroup analyses (systemic versus topical oestrogen, parous versus nulliparous women, women with versus without a uterus). No studies assessed the effects of oestrogen therapy alone versus no treatment, placebo, pelvic floor muscle training, devices such as vaginal pessaries, or surgery. However, we did identify three studies that assessed oestrogen therapy in conjunction with vaginal pessaries versus vaginal pessaries alone and 11 studies that assessed oestrogen therapy in conjunction with surgery versus surgery alone.
AUTHORS' CONCLUSIONS
There was insufficient evidence from RCTs to draw any solid conclusions on the benefits or harms of oestrogen therapy for managing POP symptoms in postmenopausal women. Topical oestrogen in conjunction with pessaries was associated with fewer adverse vaginal events compared with pessaries alone, and topical oestrogen in conjunction with surgery was associated with reduced postoperative urinary tract infections compared with surgery alone; however, these findings should be interpreted with caution, as the studies that contributed data varied substantially in their design. There is a need for larger studies on the effectiveness and cost-effectiveness of oestrogen therapy, used alone or in conjunction with pelvic floor muscle training, vaginal pessaries, or surgery, for the management of POP. These studies should measure outcomes in the medium and long term.
Topics: Female; Humans; Middle Aged; Estrogens; Pelvis; Pessaries; Postmenopause; Urinary Bladder
PubMed: 37431855
DOI: 10.1002/14651858.CD014592.pub2 -
World Journal of Diabetes Jun 2023Coronavirus disease 2019 (COVID-19) is one of the current global public health threats and vaccination is the most effective tool to reduce the spread and decrease the...
BACKGROUND
Coronavirus disease 2019 (COVID-19) is one of the current global public health threats and vaccination is the most effective tool to reduce the spread and decrease the severity of COVID-19. Diabetes is one of the important chronic diseases threatening human health and is a common comorbidity of COVID-19. What is the impact of diabetes on the immunization effect of COVID-19 vaccination? Conversely, does vaccination against COVID-19 exacerbate the severity of pre-existing diseases in patients with diabetes? There are limited and conflicting data on the interrelationship between diabetes and COVID-19 vaccination.
AIM
To explore the clinical factors and possible mechanisms underlying the interaction between COVID-19 vaccination and diabetes.
METHODS
We conducted a comprehensive search of PubMed, MEDLINE, EMBASE, and (https://www.referencecitationanalysis.com) online databases, and medRxiv and bioRxiv gray literature using the keywords "SARS-CoV-2", "COVID-19", "vaccine", "vaccination", "antibody", and "diabetes" individually or in combination, with a cut-off date of December 2, 2022. We followed inclusion and exclusion criteria and after excluding duplicate publications, studies with quantifiable evidence were included in the full-text review, plus three manually searched publications, resulting in 54 studies being included in this review.
RESULTS
A total of 54 studies were included, from 17 countries. There were no randomized controlled studies. The largest sample size was 350963. The youngest of the included samples was 5 years old and the oldest was 98 years old. The included population included the general population and also some special populations with pediatric diabetes, hemodialysis, solid organ transplantation, and autoimmune diseases. The earliest study began in November 2020. Thirty studies discussed the effect of diabetes on vaccination, with the majority indicating that diabetes reduces the response to COVID-19 vaccination. The other 24 studies were on the effect of vaccination on diabetes, which included 18 case reports/series. Most of the studies concluded that COVID-19 vaccination had a risk of causing elevated blood glucose. A total of 12 of the 54 included studies indicated a "no effect" relationship between diabetes and vaccination.
CONCLUSION
There is a complex relationship between vaccination and diabetes with a bidirectional effect. Vaccination may contribute to the risk of worsening blood glucose in diabetic patients and diabetic patients may have a lower antibody response after vaccination than the general population.
PubMed: 37383586
DOI: 10.4239/wjd.v14.i6.892 -
American Journal of Transplantation :... Nov 2023This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant... (Meta-Analysis)
Meta-Analysis
This study aimed to synthesize the available evidence on the immunogenicity, safety, and effectiveness of live-attenuated varicella vaccine in solid organ transplant recipients. Medline and EMBASE were searched using predefined search terms to identify relevant studies. The included articles reported varicella vaccine administration in the posttransplant period in children and adults. A pooled proportion of transplant recipients who seroconverted and who developed vaccine-strain varicella and varicella disease was generated. Eighteen articles (14 observational studies and 4 case reports) were included, reporting on 711 transplant recipients who received the varicella vaccine. The pooled proportion was 88.2% (95% confidence interval 78.0%-96.0%, 13 studies) for vaccinees who seroconverted, 0% (0%-1.2%, 13 studies) for vaccine-strain varicella, and 0.8% (0%-4.9%, 9 studies) for varicella disease. Most studies followed clinical guidelines for administering live-attenuated vaccines, with criteria that could include being at least 1 year posttransplant, 2 months postrejection episode, and on low-dose immunosuppressive medications. Varicella vaccination in transplant recipients was overall safe in the included studies, with few cases of vaccine-strain-induced varicella or vaccine failure, and although it was immunogenic, the proportion of recipients who seroconverted was lower than that seen in the general population. Our data support varicella vaccination in select pediatric solid organ transplant recipients.
Topics: Adult; Child; Humans; Chickenpox; Transplant Recipients; Chickenpox Vaccine; Viral Vaccines; Vaccines, Attenuated; Organ Transplantation
PubMed: 37321454
DOI: 10.1016/j.ajt.2023.06.008 -
Inflammatory Bowel Diseases Apr 2024Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients.
METHODS
Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy.
RESULTS
Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported.
CONCLUSION
Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.
Topics: Humans; Adalimumab; Biological Products; Inflammatory Bowel Diseases; Infliximab; Organ Transplantation; Ustekinumab
PubMed: 37300512
DOI: 10.1093/ibd/izad108 -
Transplantation and Cellular Therapy Jan 2024The safety and efficacy of chimeric antigen receptor (CAR) T cell therapy in solid organ transplant recipients is poorly understood, given the paucity of available data... (Meta-Analysis)
Meta-Analysis
The safety and efficacy of chimeric antigen receptor (CAR) T cell therapy in solid organ transplant recipients is poorly understood, given the paucity of available data in this patient population. There is a theoretical risk of compromising transplanted organ function with CAR T cell therapy; conversely, organ transplantation-related immunosuppression can alter the function of CAR T cells. Given the prevalence of post-transplantation lymphoproliferative disease, which often can be difficult to treat with conventional chemoimmunotherapy, understanding the risks and benefits of delivering lymphoma-directed CAR T cell therapy in solid organ transplant recipients is of utmost importance. We sought to determine the efficacy of CAR T cell therapy in solid organ transplant recipients as well as the associated adverse effects, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and compromised solid organ transplant function. We conducted a systematic review and meta-analysis of adult recipients of solid organ transplant who received CAR T cell therapy for non-Hodgkin lymphoma. Primary outcomes included efficacy, defined as overall response (OR), complete response (CR), progression-free survival, and overall survival, as well as rates of CRS and ICANS. Secondary outcomes included rates of transplanted organ loss, compromised organ function, and alterations to immunosuppressant regimens. After a systematic literature review and 2-reviewer screening process, we identified 10 studies suitable for descriptive analysis and 4 studies suitable for meta-analysis. Among all patients, 69% (24 of 35) achieved a response to CAR T cell therapy, and 52% (18 of 35) achieved a CR. CRS of any grade occurred in 83% (29 of 35), and CRS grade ≥3 occurred in 9% (3 of 35). Sixty percent of the patients (21 of 35) developed ICANS, and 34% (12 of 35) developed ICANS grade ≥3. The incidence of any grade 5 toxicity among all patients was 11% (4 of 35). Fourteen percent of the patients (5 of 35) experienced loss of the transplanted organ. Immunosuppressant therapy was held in 22 patients but eventually restarted in 68% of them (15 of 22). Among the studies included in the meta-analysis, the pooled OR rate was 70% (95% confidence interval [CI], 29.2% to 100%; I = 71%) and the pooled CR rate was 46% (95% CI, 25.4% to 67.8%; I = 29%). The rates of any grade CRS and grade ≥3 CRS were 88% (95% CI, 69% to 99%; I = 0%) and 5% (95% CI, 0% to 21%; I = 0%), respectively. The rates of any grade ICANS and ICANS grade ≥3 were 54% (95% CI, 9% to 96%; I = 68%) and 40% (95% CI, 3% to 85%; I = 63%), respectively. The efficacy of CAR T cell therapy in solid organ transplant recipients is comparable to that in the general population as reported in prior investigational studies, with an acceptable toxicity profile in terms of CRS, ICANS, and transplanted organ compromise. Further studies are needed to determine long-term effects on organ function, sustained response rates, and best practices peri-CAR T infusion period in this patient population.
Topics: Adult; Humans; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Lymphoma; Organ Transplantation; Adaptor Proteins, Signal Transducing; Antigens, CD19; Cytokine Release Syndrome; Immunosuppressive Agents; Cell- and Tissue-Based Therapy
PubMed: 37279856
DOI: 10.1016/j.jtct.2023.05.018 -
The Journal of Trauma and Acute Care... Sep 2023Observed variations in the management of pediatric solid organ injuries (SOIs) may be due to difficulty in finding and integrating recommendations from multiple clinical...
BACKGROUND
Observed variations in the management of pediatric solid organ injuries (SOIs) may be due to difficulty in finding and integrating recommendations from multiple clinical practice guidelines (CPGs) with heterogeneous methodological approaches. We aimed to systematically review CPG recommendations for pediatric SOIs.
METHODS
We conducted a systematic review of CPGs including at least one recommendation targeting pediatric SOI populations, using Medical Analysis and Retrieval System Online, Excerpta Medica dataBASE, Web of Science, and websites of clinical organizations. Pairs of reviewers independently assessed eligibility, extracted data, and evaluated the quality of CPGs using the Appraisal of Guidelines Research and Evaluation II tool. We synthesized recommendations from moderate to high-quality CPGs using a recommendations matrix based on Grades of Recommendation, Assessment, Development, and Evaluation criteria.
RESULTS
We identified eight CPGs, including three rated moderate or high quality. Methodological weaknesses included lack of stakeholder involvement beyond surgeons, consideration of applicability (e.g., implementation tools), and clarity around the definition of pediatric populations. Five of the 15 recommendations from moderate to high-quality CPGs were based on moderate quality evidence or were rated as strong; these reflected nonoperative management and angioembolization for renal injuries and required length of stay for liver and spleen injuries.
CONCLUSION
We identified 15 recommendations on pediatric SOI management from 3 moderate or high-quality CPGs, but only one third were based on at least moderate-quality evidence or were rated as strong. Our results prompt the following recommendations for future CPG development or updates: (1) include all types of clinicians involved in the care of pediatric SOIs and patient and family representatives in the process, (2) develop clear definitions of the target population, and (3) provide advice and tools to promote implementation. Results also underline the urgent need for more rigorous research to support strong evidence-based recommendations in this population.
LEVEL OF EVIDENCE
Systematic Review/Meta-analysis; Level III.
Topics: Child; Humans; Wounds and Injuries; Pediatrics; Practice Guidelines as Topic
PubMed: 37272747
DOI: 10.1097/TA.0000000000004015 -
Journal of Pediatric Nursing 2023The transition from paediatric-centred to adult healthcare services in adolescent solid organ transplantation recipients is a period of increased risk and vulnerability,... (Review)
Review
PROBLEM
The transition from paediatric-centred to adult healthcare services in adolescent solid organ transplantation recipients is a period of increased risk and vulnerability, the issues related to healthcare transition have become key concerns to the healthcare community.
ELIGIBILITY CRITERIA
Qualitative studies of any design and qualitative components of mixed method studies that explored the experiences of healthcare transition among adolescent solid organ transplant recipients, parents, and healthcare professionals were included.
SAMPLE
Nine articles were finalised and included in the review.
METHODS
A systematic review of qualitative studies was conducted. Databases searched were Scopus, PsycINFO, EMBASE, Web of Science, PubMed, CINAHL and ProQuest Dissertations and Theses. Studies published between the inception of respective database and December 2022 inclusive were considered. A three-step inductive thematic synthesis method outlined by Thomas and Harden was used to form descriptive themes and the 10-item Joanna Briggs Institute Critical Appraisal Checklist was utilised to appraise the quality of included articles.
RESULTS
Two hundred and twenty studies were screened, and 9 studies published between 2013 and 2022 were included. Five analytical themes were generated: 'the struggle of being an adolescent with a transplant'; 'perceptions of transition'; 'the role of parents'; 'lack of transition readiness' and 'the need for better support'.
CONCLUSIONS
Adolescent solid organ transplant recipients, parents, and healthcare professionals faced multiple challenges in the healthcare transition.
IMPLICATIONS
Future interventions and health policies should provide targeted intervention strategies that address the barriers present in the healthcare transition to facilitate the optimization of the youth healthcare transition.
Topics: Adult; Humans; Child; Adolescent; Transition to Adult Care; Health Personnel; Parents; Qualitative Research; Delivery of Health Care; Organ Transplantation
PubMed: 37270387
DOI: 10.1016/j.pedn.2023.05.015