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Pediatric Blood & Cancer Jan 2024Initially developed as immunosuppressive agents, mammalian target of rapamycin (mTOR) inhibitors are currently used widely in the management of vascular malformations... (Review)
Review
BACKGROUND AND OBJECTIVES
Initially developed as immunosuppressive agents, mammalian target of rapamycin (mTOR) inhibitors are currently used widely in the management of vascular malformations and tumors. The incidence of infectious complications in the vascular anomalies (VA) population is not well defined. The goal of this systematic review was to better define the types and severity of reported infectious complications in patients with VAs treated with mTOR inhibition.
METHODS
This was a systematic review conducted following PRISMA guidelines evaluating all research articles focused on infectious complications in patients with VAs treated with sirolimus or everolimus. Thirty articles including 1182 total patients and 316 infections (in 291 unique patients) were ultimately included.
RESULTS
The majority of infections were viral upper respiratory (n = 137, 54%), followed by pneumonia (n = 53, 20%), and cutaneous infections (n = 20, 8%). There were six total infection-related fatalities, which all occurred in patients younger than 2 years. Two cases of Pneumocystis jirovecii pneumonia (PJP) were reported. These were infants with kaposiform hemangioendothelioma (KHE) who were also treated with steroids and did not receive PJP prophylaxis. Almost one-third (n = 96, 32%) of infectious complications were graded 3-4 according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. Details of patient age, subtype of VA, and timing of infection were lacking from many reports.
CONCLUSIONS
Most infectious complications reported in patients with VA on mTOR inhibitors were viral respiratory infections and non-severe. Bacteremia, infectious fatalities, and PJP are exceedingly rare. Future studies are needed to clarify the spectrum of infectious risks in VA patients and to provide guidance for infection prevention.
Topics: Infant; Humans; Sirolimus; Immunosuppressive Agents; Everolimus; Pneumonia, Pneumocystis; Vascular Malformations; TOR Serine-Threonine Kinases
PubMed: 37933207
DOI: 10.1002/pbc.30758 -
The Cochrane Database of Systematic... Jul 2006Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10 to 20% during the initial infection and increases substantially with the need for mechanical ventilation. It was suggested that in these patients corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality.
OBJECTIVES
To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air).
SEARCH STRATEGY
We searched Medline (January 1980-December 2004), EMBASE (January 1985-December 2004) and The Cochrane Library (Issue 4, 2004) without language restrictions to identify randomised controlled trials that compared adjunctive corticosteroids to control in HIV-infected patients with PCP. We further reviewed the reference lists from previously published overviews, we searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts of the field, and searched reference lists of identified publications for citations of additional relevant articles.
SELECTION CRITERIA
Trials were considered eligible for this review if they compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, used random allocation, and reported mortality data. We excluded trials in patients with no or mild hypoxemia (arterial oxygen partial pressure >70 mmHg or an alveolar-arterial gradient <35 mmHg on room air) and trials with a follow-up of less than 30 days.
DATA COLLECTION AND ANALYSIS
Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups by using a random effects model.
MAIN RESULTS
Six studies were included in the review and meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval [CI], 0.32-0.98) at 1 month and 0.68 (95% CI, 0.50-0.94) at 3-4 months of follow-up. To prevent 1 death, numbers needed to treat are 9 patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.38 (95% CI, 0.20-0.73) in favour of adjunctive corticosteroids.
AUTHORS' CONCLUSIONS
The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but evidence from this review suggests a beneficial effect for patients with substantial hypoxemia.
Topics: AIDS-Related Opportunistic Infections; Adrenal Cortex Hormones; Chemotherapy, Adjuvant; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 16856118
DOI: 10.1002/14651858.CD006150 -
PloS One 2015To evaluate risk factors for death from acute lower respiratory infections (ALRI) in children in low- and middle-income countries. (Meta-Analysis)
Meta-Analysis Review
Risk factors for mortality from acute lower respiratory infections (ALRI) in children under five years of age in low and middle-income countries: a systematic review and meta-analysis of observational studies.
OBJECTIVE
To evaluate risk factors for death from acute lower respiratory infections (ALRI) in children in low- and middle-income countries.
DESIGN
Systematic review and meta-analysis.
STUDY SELECTION
Observational studies reporting on risk factors for death from ALRI in children below five years in low- and middle income countries.
DATA SOURCES
Medline, Embase, Global Health Library, Lilacs, and Web of Science to January 2014.
RISK OF BIAS ASSESSMENT
Quality In Prognosis Studies tool with minor adaptations to assess the risk of bias; funnel plots and Egger's test to evaluate publication bias.
RESULTS
Out of 10,655 papers retrieved, 77 studies from 39 countries (198,359 children) met the inclusion criteria. Host and disease characteristics more strongly associated with ALRI mortality were: diagnosis of very severe pneumonia as per WHO definition (odds ratio 9.42, 95% confidence interval 6.37‒13.92); age below two months (5.22, 1.70‒16.03); diagnosis of Pneumocystis Carinii (4.79, 2.67‒8.61), chronic underlying diseases (4.76, 3.27‒6.93); HIV/AIDS (4.68, 3.72‒5.90); and severe malnutrition (OR 4.27, 3.47‒5.25). Socio-economic and environmental factors significantly associated with increased odds of death from ALRI were: young maternal age (1.84, 1.03‒3.31); low maternal education (1.43, 1.13‒1.82); low socio-economic status (1.62, 1.32‒2.00); second-hand smoke exposure (1.52, 1.20 to 1.93); indoor air pollution (3.02, 2.11‒4.31). Immunisation (0.46, 0.36‒0.58) and good antenatal practices (0.50, 0.31‒0.81) were associated with decreased odds of death.
CONCLUSIONS
Host and disease characteristics as well as socio-economic and environmental determinants affect the risk of death from ALRI in children. Together with the prevention and treatment of chronic diseases, interventions to modify underlying risk factors such as poverty, lack of female education, and poor environmental conditions, should be considered among the strategies to reduce ALRI mortality in children in low- and middle-income countries.
Topics: Child, Preschool; Developing Countries; Environmental Exposure; Humans; Infant; Infant, Newborn; Observational Studies as Topic; Poverty; Respiratory Tract Infections; Risk Factors; Survival Analysis
PubMed: 25635911
DOI: 10.1371/journal.pone.0116380 -
Journal of Fungi (Basel, Switzerland) Feb 2021The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases...
Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis.
The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk.
PubMed: 33670864
DOI: 10.3390/jof7030176 -
The Cochrane Database of Systematic... Apr 2015Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10% to 20% during the initial infection and this increases substantially with the need for mechanical ventilation. It has been suggested that corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality in these patients.
OBJECTIVES
To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxaemia (arterial oxygen partial pressure < 70 mmHg or alveolar-arterial gradient > 35 mmHg on room air).
SEARCH METHODS
For the original review we searched The Cochrane Library (2004, Issue 4), MEDLINE (January 1980 to December 2004) and EMBASE (January 1985 to December 2004) without language restrictions. We further reviewed the reference lists from previously published overviews, searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts in the field and searched the reference lists of identified publications for citations of additional relevant articles.In this update of our review, we searched the above-mentioned databases in September 2010 and April 2014 for trials published since our original review. We also searched for ongoing trials in ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (ICTRP). We searched for conference abstracts via AEGIS.
SELECTION CRITERIA
Randomised controlled trials that compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, and reported mortality data. We excluded trials in patients with no or mild hypoxaemia (arterial oxygen partial pressure > 70 mmHg or an alveolar-arterial gradient < 35 mmHg on room air) and trials with a follow-up of less than 30 days.
DATA COLLECTION AND ANALYSIS
Two teams of review authors independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups using a random-effects model.In this update of our review, we used the GRADE methodology to assess evidence quality.
MAIN RESULTS
Of 2029 screened records, we included seven studies in the review and six in the meta-analysis. Risk of bias varied: the randomisation and allocation process was often not clearly described, five of seven studies were double-blind and there was almost no missing data. The quality of the evidence for mortality was high. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval (CI) 0.32 to 0.98) at one month and 0.59 (95% CI 0.41 to 0.85) at three to four months of follow-up. In adults, to prevent one death, numbers needed to treat are nine patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. The three largest trials provided moderate quality data on the need for mechanical ventilation, with a risk ratio of 0.38 (95% CI 0.20 to 0.73) in favour of adjunctive corticosteroids. One study was conducted in infants, suggesting a risk ratio for death in hospital of 0.81 (95% CI 0.51 to 1.29; moderate quality evidence).
AUTHORS' CONCLUSIONS
The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but the evidence from this review suggests a beneficial effect for adult patients with substantial hypoxaemia. There is insufficient evidence on the effect of adjunctive corticosteroids on survival in infants.
Topics: AIDS-Related Opportunistic Infections; Adrenal Cortex Hormones; Adult; Chemotherapy, Adjuvant; Humans; Hypoxia; Pneumocystis carinii; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 25835432
DOI: 10.1002/14651858.CD006150.pub2 -
Environmental Science and Pollution... May 2021Particulate matters (PMs) are significant components of air pollution in the urban environment. PMs with aerodynamic diameter less than 2.5 μm (PM) can penetrate to the... (Review)
Review
Particulate matters (PMs) are significant components of air pollution in the urban environment. PMs with aerodynamic diameter less than 2.5 μm (PM) can penetrate to the alveolar area and introduce numerous compounds to the pneumocystis that can initiate inflammatory response. There are several questions about this exposure as follows: does PM-induced inflammation lead to a specific disease? If yes, what is the form of the progressed disease? This systematic review was designed and conducted to respond to these questions. Four databases, including Web of Science, Scopus, PubMed, and Embase, were reviewed systematically to find the related articles. According to the included articles, the only available data on the inflammatory effects of PM comes from either in vitro or animal studies. Both types of studies have shown that the induced inflammation is type I and includes secretion of proinflammatory cytokines. The exposure duration of longer than 28 weeks was not observed in any of the reviewed studies. However, as there is not a specific antigenic component in the urban particulate matters and based on the available evidence, the antigen-presenting is not a common process in the inflammatory responses to PM. Therefore, neither signaling to repair cells such as fibroblasts nor over-secretion of extracellular matrix (ECM) proteins can occur following PM-induced inflammation. These pieces of evidence weaken the probability of the development of fibrotic diseases. On the other hand, permanent inflammation induces the destruction of ECM and alveolar walls by over-secretion of protease enzymes and therefore results in progressive obstructive effects.
Topics: Air Pollutants; Air Pollution; Animals; Dust; Lung; Lung Diseases, Obstructive; Particulate Matter; Pneumonia
PubMed: 33779901
DOI: 10.1007/s11356-021-13559-5 -
Sixteen-year history of rituximab therapy for 1085 pemphigus vulgaris patients: A systematic review.International Immunopharmacology Jan 2018Pemphigus vulgaris (PV) is a rare autoimmune disease due to the production of pathogenic autoantibodies directed against desmoglein 1 and 3, usually affecting both skin... (Review)
Review
Pemphigus vulgaris (PV) is a rare autoimmune disease due to the production of pathogenic autoantibodies directed against desmoglein 1 and 3, usually affecting both skin and mucous membranes. Recently, rituximab, a chimeric IgG1 monoclonal antibody which targets the CD20 molecules have been regarded as a promising treatment for PV. In this study, a systematic review was conducted to conclude on how and which PV patients could benefit from rituximab infusion. Search in PubMed results in 114 relevant studies, which met the criteria. Total of 1085 PV patients with different conditions, including unresponsive childhood/juvenile or adult PV patients, women of childbearing age, those with chronic infections with the risk of reactivation have been evaluated. Although the majority of these patients well responded to rituximab, some of them did not respond, and the paucity of patients experienced exacerbation of disease. In addition to the rituximab monotherapy or its combination with conventional therapies, different novel combination therapies of rituximab with immunoadsorption and/or IVIg have shown promising results. Moreover, using rituximab as the first-line treatment has emerged recently. Pneumocystis carinii pneumonia and septicemia were found as the two fatal and serious adverse events associated with rituximab. Moreover, development or reactivation of herpes simplex and herpes zoster and cytomegalovirus should be warned. Similar to the adults, those with childhood and juvenile PV could be successfully treated with rituximab. Although rituximab seems to trigger reactivation of chronic infections, such as viral hepatitis and HIV infection, no related report was found. Administration of rituximab in approximately ten months before conception also was found safe and effective for a successful pregnancy. In conclusion, rituximab is very effective in adult and childhood/juvenile PV. However, there is a risk of not responding, exacerbation of disease and development of fatal infections. Moreover, it seems to be a promising first-line treatment for refractory PV.
Topics: Antigens, CD20; Autoantibodies; Combined Modality Therapy; Desmoglein 1; Desmoglein 3; Drug-Related Side Effects and Adverse Reactions; Herpesviridae; Humans; Immunoglobulins, Intravenous; Immunotherapy; Mucous Membrane; Pemphigus; Rituximab; Skin; Virus Activation
PubMed: 29132070
DOI: 10.1016/j.intimp.2017.11.005 -
Frontiers in Endocrinology 2023Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical...
OBJECTIVE
Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical characteristics, risk factors, treatment, and prognosis of TMP-SMX-induced hypoglycemia.
METHODS
Case reports and series of TMP-SMX-induced hypoglycemia were systematically searched using Chinese and English databases. Primary patient and clinical information were extracted for analysis.
RESULTS
A total of 34 patients were reported from 31 studies (16 males and 18 females). The patients had a median age of 64 years (range 0.4-91), and 75.8% had renal dysfunction. The median duration of a hypoglycemic episode was six days (range 1-20), and the median minimum glucose was 28.8 mg/dL (range 12-60). Thirty-two patients (97.0%) showed neuroglycopenic symptoms, with consciousness disturbance (30.3%) and seizure (24.2%), sweating (18.2%), confusion (15.2%), asthenia (12.1%) being the most common symptoms. Fifteen patients (44.1%) had elevated serum insulin levels, with a median of 31.8 μU/mL (range 3-115.3). C-peptide increased in 13 patients (38.2%), with a median of 7.7 ng/mL (range 2.2-20). Complete recovery from symptoms occurred in 88.2% of patients without sequelae. The duration of hypoglycemia symptoms was 8 hours to 47 days after the intervention. Interventions included discontinuation of TMP-SMX, intravenous glucose, glucagon, and octreotide.
CONCLUSION
Hypoglycemia is a rare and serious adverse effect of TMP-SMX. Physicians should be aware of this potential adverse effect, especially in patients with renal insufficiency, increased drug doses, and malnutrition.
Topics: Male; Female; Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Trimethoprim, Sulfamethoxazole Drug Combination; Risk Factors; Hypoglycemia; Renal Insufficiency; Glucose
PubMed: 36843590
DOI: 10.3389/fendo.2023.1059522 -
Rheumatology International Aug 2021The incidence of Pneumocystis jirovecii pneumonia (PJP) has increased over recent years in patients with systemic autoimmune rheumatic diseases (SARD). PJP prognosis is...
Is cotrimoxazole prophylaxis against Pneumocystis jirovecii pneumonia needed in patients with systemic autoimmune rheumatic diseases requiring immunosuppressive therapies?
The incidence of Pneumocystis jirovecii pneumonia (PJP) has increased over recent years in patients with systemic autoimmune rheumatic diseases (SARD). PJP prognosis is poor in those receiving immunosuppressive therapy and glucocorticoids in particular. Despite the effectiveness of cotrimoxazole against PJP, the risk of adverse effects remains significant, and no consensus has emerged regarding the need for PJP prophylaxis in SARD patients undergoing immunosuppressor therapies.Objective: To evaluate the efficacy and safety of cotrimoxazole prophylaxis against PJP in SARD adult patients receiving immunosuppressive therapies. Methods: We performed a systematic review, consulting MEDLINE, EMBASE, and Cochrane Library databases up to April 2020. Outcomes covered prevention of PJP, other infections, morbidity, mortality, and safety. The information obtained was summarized with a narrative review and results were tabulated. Of the 318 identified references, 8 were included. Two were randomized controlled trials and six observational studies. The quality of studies was moderate or low. Despite disparities in the cotrimoxazole prophylaxis regimens described, results were consistent in terms of efficacy, particularly with glucocorticoid doses > 20 mg/day. However, cotrimoxazole 400 mg/80 mg/day, prescribed three times/ week, or 200 mg/40 mg/day or in dose escalation, exhibited similar positive performances. Conversely, cotrimoxazole 400 mg/80 mg/day showed higher incidences of withdrawals and adverse effects. Cotrimoxazole prophylaxis against PJP exhibited efficacy in SARD, mainly in patients taking glucocorticoids ≥ 20 mg/day. All cotrimoxazole regimens exposed seemed equally efficacious, although, higher quality trials are needed. Adverse effects were observed 2 months after initiation, particularly with the 400 mg/80 mg/day regimen. Conversely, escalation dosing or 200 mg/40 mg/day regimens appeared better tolerated.
Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33656582
DOI: 10.1007/s00296-021-04808-4 -
Infectious Diseases & Clinical... Jun 2023This study aimed to identify opportunistic infections among human immunodeficiency virus (HIV) infected patients in Turkey. Therefore, we conducted a systematic... (Review)
Review
This study aimed to identify opportunistic infections among human immunodeficiency virus (HIV) infected patients in Turkey. Therefore, we conducted a systematic literature review of the studies published up to October 1, 2022, in the Pubmed, Web of Science (WoS), and ULAKBİM TR Dizin databases. We searched for medical subject headings (MeSH) terms of (HIV) OR (AIDS) OR (human immunodeficiency virus) AND (opportunistic infections) AND (Turkey). Fifty-five studies in Pubmed, 68 in WoS, and 212 in ULAKBİM TR Dizin were listed with these keywords. After removing duplicated studies, we included 22 original articles, two poster presentations, one short communication, one letter to the editor, and 17 case reports/series. Out of 1582 patients, we defined 788 patients (49.8%) as late presenters. In addition, we detected tuberculosis (286, 5.5%), candidal infections (207, 4%), and pneumonia (PCP) (113, 2.1%) as the most frequent opportunistic infections. According to our analysis, late presentation is a major problem in our country, and more screening and sensitization campaigns should be carried out to ensure early diagnosis and earlier care of patients.
PubMed: 38633009
DOI: 10.36519/idcm.2023.214