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The Journal of Dermatological Treatment May 2021Topical steroids have been previously associated with potential for hyperglycemia and glucosuria, and thought to have a relatively safe side effect profile. In prolonged... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Topical steroids have been previously associated with potential for hyperglycemia and glucosuria, and thought to have a relatively safe side effect profile. In prolonged use, there is the potential for steroids to be absorbed through the skin and eventually reach systemic circulation. We aimed to investigate the potential association between topical corticosteroid use and development of diabetes, we performed a systematic review and meta-analysis of available case-control data in the literature.
METHODS
Electronic database searches was performed to identify studies comparing the proportion of patients with diabetes in cases using topical corticosteroids compared to those without. The odds ratio (OR) was used as a summary statistic.
RESULTS
Four case-control studies were pooled for meta-analysis. Overall, we found a significant association between topical corticosteroid use and development of type 2 diabetes mellitus, even after adjustment for confounding factors (OR 1.24, 95% CI 1.15-1.34, I2 = 91%, < .00001). There was no potency-dependent effect noted, with no significant difference noted between the subgroups.
CONCLUSIONS
We demonstrate a potential association between topical corticosteroid use and risk of developing diabetes mellitus. This risk does not appear to be dependent on potency of the topical medication, but rather the cumulative dose and cumulative duration of use.
Topics: Administration, Topical; Adrenal Cortex Hormones; Databases, Factual; Diabetes Mellitus, Type 2; Humans; Odds Ratio; Steroids
PubMed: 31418613
DOI: 10.1080/09546634.2019.1657224 -
Cancers Oct 2021Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this... (Review)
Review
Despite the pivotal role of mitotane in adrenocortical carcinoma (ACC) management, data on the endocrine toxicities of this treatment are lacking. The aim of this systematic review is to collect the available evidence on the side effects of mitotane on the endocrine and metabolic systems in both children and adults affected by adrenal carcinoma. Sixteen articles on 493 patients were included. Among the adrenal insufficiency, which is an expected side effect of mitotane, 24.5% of patients increased glucocorticoid replacement therapy. Mineralocorticoid insufficiency usually occurred late in treatment in 36.8% of patients. Thyroid dysfunction is characterized by a decrease in FT4, which occurs within 3-6 months of treatment in 45.4% of patients, while TSH seems to not be a reliable marker. Dyslipidemia is characterized by an increase in both LDL-c and HDL-c (54.2%). Few studies have found evidence of hypertriglyceridemia. In males, gynecomastia and hypogonadism can occur after 3-6 months of treatment (38.4% and 35.6%, respectively), while in pre-menopausal women, mitotane can cause ovarian cysts and, less frequently, menstrual disorders. Most of these side effects appear to be reversible after mitotane discontinuation. We finally suggest an algorithm that could guide metabolic and endocrine safety assessments in patients treated with mitotane for ACC.
PubMed: 34638485
DOI: 10.3390/cancers13195001 -
Clinical Otolaryngology : Official... Jan 2024Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity... (Review)
Review
OBJECTIVES
Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients.
METHODS
Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales.
RESULTS
Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions.
CONCLUSIONS
Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.
Topics: Adult; Humans; Cisplatin; Antineoplastic Agents; Carboplatin; Ototoxicity; Hearing Loss; Neoplasms; Adrenal Cortex Hormones; Randomized Controlled Trials as Topic
PubMed: 37818931
DOI: 10.1111/coa.14106 -
Combinatorial Chemistry & High... 2024Anti-angiogenic agents could enhance tumor immunity response, and anti- angiogenesis plus immunotherapy has become a novel treatment option for advanced non-small cell... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anti-angiogenic agents could enhance tumor immunity response, and anti- angiogenesis plus immunotherapy has become a novel treatment option for advanced non-small cell lung cancer (NSCLC). The efficacy of this combination therapy remains controversial and obscure.
AIM
We conducted a meta-analysis to evaluate the clinical efficacy and safety of this therapeutic strategy in patients with advanced NSCLC and provide more guidance for treating NSCLC clinically.
METHODS
A systematic literature search was performed in PubMed, Embase, Web of Science, CNKI, and Wanfang databases to identify relevant studies published up to December 2021. The primary endpoint was the objective response rate (ORR). Second endpoints were progression-free survival (PFS), overall survival (OS), and grade ≥3 AEs adverse events (AEs). The sensitivity analysis was conducted to confirm the stability of the results. STATA 15.0 was utilized for all pooled analyses.
RESULTS
Eleven studies were eventually included in the meta-analysis, involving 533 patients with advanced NSCLC. The pooled ORR rate was 27% (95% CI 18% to 35%; I =84.2%; p<0.001), while the pooled median PFS and OS was 5.84 months (95% CI 4.66 to 7.03 months; I=78.4%; p<0.001) and 14.20 months (95% CI 11.08 to 17.32 months; I=82.2%; p=0.001), respectively. Most common grade ≥3 AEs included hypertension, hand-foot syndrome, diarrhea, adrenal insufficiency, hyponatremia, proteinuria, rash, thrombocytopenia, and fatigue.
CONCLUSION
Anti-angiogenesis combined with immunotherapy demonstrated satisfactory antitumor activity and an acceptable toxicity profile in patients with advanced NSCLC. The pooled results of our meta-analysis provided further evidence supporting the favorable efficacy and safety of this therapeutic strategy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Angiogenesis Inhibitors; Immunotherapy
PubMed: 37559541
DOI: 10.2174/1386207326666230808112656 -
The Lancet. Diabetes & Endocrinology Jan 2021Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We...
BACKGROUND
Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy.
METHODS
We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression.
FINDINGS
The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery).
INTERPRETATION
Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes.
FUNDING
US National Institutes of Health.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Cohort Studies; Female; Fetal Diseases; Humans; Incidence; Infant, Newborn; Infant, Newborn, Diseases; Male; Middle Aged; Pheochromocytoma; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Retrospective Studies; Young Adult
PubMed: 33248478
DOI: 10.1016/S2213-8587(20)30363-6 -
Pulmonary Medicine 2022The global prevalence of chronic obstructive pulmonary disease (COPD) is increasing, and the risk of lung cancer in these patients is high. The use of inhaled... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The global prevalence of chronic obstructive pulmonary disease (COPD) is increasing, and the risk of lung cancer in these patients is high. The use of inhaled corticosteroids (ICSs) in COPD patients could help to decrease potential lung cancer risk. We planned to conduct this systematic review and meta-analysis to determine the role of ICS in the risk of lung cancer among COPD patients.
METHODS
A comprehensive search of PubMed, Science Direct, Google Scholar, and Cochrane library and a manual search of the list of references were conducted. Studies with cohort, case-control, and randomized clinical trial designs for any ICS use reporting the incidence/hazard ratio (HR) of lung cancer were included. The random-effects model was used to pool hazard ratios. Subgroup analysis and metaregression analysis were employed. Funnel plot and Egger regression test were used to assess publication bias.
RESULTS
Combining the results of 14 observations, the pooled HR for cancer risk reduction was 0.69 (95% CI 0.59-0.79), value ≤ 0.001. The use of ICS in COPD patients showed a 31% reduction in the risk of lung cancer. Subgroup meta-analysis showed a significant reduction in the risk of lung cancer as well.
CONCLUSION
The use of ICS in COPD patients reduces the risk of lung cancer. The risk reduction was independent of smoking status and latency period. Future studies should focus on the optimum dose and controlling confounders like asthma.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Humans; Lung Neoplasms; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic
PubMed: 36046848
DOI: 10.1155/2022/9799858 -
The Journal of Clinical Endocrinology... Jul 2022We aimed to perform a systematic review and meta-analysis of all-cause and cause-specific mortality of patients with benign endogenous Cushing syndrome (CS). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to perform a systematic review and meta-analysis of all-cause and cause-specific mortality of patients with benign endogenous Cushing syndrome (CS).
METHODS
The protocol was registered in PROSPERO (CRD42017067530). PubMed, EMBASE, CINHAL, Web of Science, and Cochrane Central searches were undertaken from inception to January 2021. Outcomes were the standardized mortality ratio (SMR), proportion, and cause of deaths. The I2 test, subgroup analysis, and meta-regression were used to assess heterogeneity across studies.
RESULTS
SMR was reported in 14 articles including 3691 patients (13 Cushing disease [CD] and 7 adrenal CS [ACS] cohorts). Overall SMR was 3.0 (95% CI, 2.3-3.9; I2 = 80.5%) for all CS, 2.8 (95% CI, 2.1-3.7; I2 = 81.2%) for CD and 3.3 (95% CI, 0.5-6.6; I2 = 77.9%) for ACS. Proportion of deaths, reported in 87 articles including 19 181 CS patients (53 CD, 24 ACS, and 20 combined CS cohorts), was 0.05 (95% CI, 0.03-0.06) for all CS subtypes with meta-regression analysis revealing no differences between CS subtypes (P = .052). The proportion of deaths was 0.1 (10%) in articles published before 2000 and 0.03 (3%) in 2000 until the last search for CS (P < .001), CD (P < .001), and ACS (P = .01). The causes of death were atherosclerotic diseases and thromboembolism (43.4%), infection (12.7%), malignancy (10.6%), active disease (3.5%), adrenal insufficiency (3.0%), and suicide (2.2%). Despite improved outcomes in recent years, increased mortality from CS persists. The causes of death highlight the need to prevent and manage comorbidities in addition to treating hypercortisolism.
Topics: Cause of Death; Cushing Syndrome; Humans; Neoplasms
PubMed: 35486378
DOI: 10.1210/clinem/dgac265 -
Clinical Endocrinology Jan 2021Ganglioneuromas are very rare tumours of the sympathetic nervous system. Clinical and pathological knowledge is currently based on largely incomparable registries and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ganglioneuromas are very rare tumours of the sympathetic nervous system. Clinical and pathological knowledge is currently based on largely incomparable registries and case series that focus on paediatric or adrenal cases. To comprehensively characterize the full clinical spectrum across ages and locations, a meta-analysis was performed where amenable and complemented by systematic literature review of individual patient data (IPD).
DESIGN
Articles containing "ganglioneuroma" in English on humans, published from 1/1/1995-6/27/2018, were identified from PubMed. Aggregate data from 10 eligible patient series on 19 variables were considerably inhomogeneous, restricting meta-analysis to age and gender distribution. To determine basic disease characteristics across ages and locations, IPD were retrieved from case reports and small case series (PROSPERO CRD42018010247).
RESULTS
Individual patient data representing 364 cases revealed that 65.7% (60.6%-70.4%) were diagnosed in adults, more frequently in females (62%, 56.9%-66.9%). 24.5% (20.3%-39.1%) were discovered incidentally. Most often, ganglioneuromas developed in abdomen/pelvis (66.2, 32.1% adrenal). With age, the proportion of ganglioneuroma localizations with high post-surgical complication rate (35.6% head/neck and 16.3% thorax) decreased. Contrarily, the diagnosis of adrenal ganglioneuromas (<1% post-surgical complications) increased with age. Hormone production, hypertension or coincidence with another non-neuroblastic neural-crest-derived tumour component was more common for adrenal location. Recurrence and metastatic spread have not been reported for ganglioneuromas without secondary tumour component.
CONCLUSIONS
This work summarizes characteristics of the currently largest number of international GN patients across all ages. The data confirm a benign nature of GN, independent of age. Age-related differences in predominant tumour location, associated post-surgical complications and hormone production suggest case-centred management strategies.
Topics: Adrenal Gland Neoplasms; Adult; Child; Female; Ganglioneuroma; Humans; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Registries
PubMed: 32702779
DOI: 10.1111/cen.14297 -
The Kurume Medical Journal Jul 2023Immune checkpoint inhibitors (ICIs) including anti-CTLA-4, anti-PD-1, and anti-PD-L1 antibodies have been increasingly used for various malignancies. These ICIs activate...
BACKGROUND
Immune checkpoint inhibitors (ICIs) including anti-CTLA-4, anti-PD-1, and anti-PD-L1 antibodies have been increasingly used for various malignancies. These ICIs activate immune functions to treat malignant tumors; however, this causes characteristic complications called immune-related adverse events (irAE). In the gastrointestinal tract, ICIs cause adverse events such as diarrhea and enterocolitis, thus warranting treatment discontinuation. These irAEs require treatment that suppresses immunity; however, no treatment strategies based on approved guidelines have been reported. This review aimed to investigate the current treatment status for refractory cases of ICI-induced colitis in accordance with their diagnosis, therapy, and prognosis.
SUMMARY
We systematically reviewed studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist. Two investigators searched PubMed and Scopus in January 2019. We extracted data, including the number of ICI-treated patients developing colitis and diarrhea. The number of cases classified as severe per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) definitions and the progress of corticosteroid-treated and anti-TNF-α- antibody-treated cases (e.g., infliximab) were recorded. Details of further treatment were also recorded for cases that did not improve with antiTNF-α- antibody. Among patients receiving anti-CTLA-4 antibody, corticosteroids were administered to 14.6% of patients, and infliximab was administered to 5.7% of patients. Among patients receiving anti-PD-1/PD-L1 antibody, corticosteroids were administered to 2.37% of patients. For refractory cases unsuccessful with infliximab, the continuation of infliximab every 2 weeks, tacrolimus administration, prolonged corticosteroid treatment, colectomy, or vedolizumab administration were reported.
KEY MESSAGES
Treatment of ICI-induced colitis is important to avoid the need to discontinue cancer treatment. Many therapeutic agents for inflammatory bowel disease are reportedly effective in treating refractory ICI-induced colitis.
Topics: Humans; Immune Checkpoint Inhibitors; Infliximab; Tumor Necrosis Factor Inhibitors; Colitis; Neoplasms; Diarrhea; Adrenal Cortex Hormones
PubMed: 37100606
DOI: 10.2739/kurumemedj.MS682006 -
The Cochrane Database of Systematic... Aug 2021Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on... (Review)
Review
BACKGROUND
Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. So far, systemic corticosteroids are one of the few treatment options for COVID-19. Nonetheless, size of effect, certainty of the evidence, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated.
OBJECTIVES
To assess whether systemic corticosteroids are effective and safe in the treatment of people with COVID-19, and to keep up to date with the evolving evidence base using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 16 April 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19, irrespective of disease severity, participant age, gender or ethnicity. We included any type or dose of systemic corticosteroids. We included the following comparisons: systemic corticosteroids plus standard care versus standard care (plus/minus placebo), dose comparisons, timing comparisons (early versus late), different types of corticosteroids and systemic corticosteroids versus other active substances. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome or Middle East respiratory syndrome), corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality, ventilator-free days, new need for invasive mechanical ventilation, quality of life, serious adverse events, adverse events, and hospital-acquired infections.
MAIN RESULTS
We included 11 RCTs in 8075 participants, of whom 7041 (87%) originated from high-income countries. A total of 3072 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 2322). We also identified 42 ongoing studies and 16 studies reported as being completed or terminated in a study registry, but without results yet. Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo We included 10 RCTs (7989 participants), one of which did not report any of our pre-specified outcomes and thus our analysis included outcome data from nine studies. All-cause mortality (at longest follow-up available): systemic corticosteroids plus standard care probably reduce all-cause mortality slightly in people with COVID-19 compared to standard care alone (median 28 days: risk difference of 30 in 1000 participants fewer than the control group rate of 275 in 1000 participants; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.80 to 1.00; 9 RCTs, 7930 participants; moderate-certainty evidence). Ventilator-free days: corticosteroids may increase ventilator-free days (MD 2.6 days more than control group rate of 4 days, 95% CI 0.67 to 4.53; 1 RCT, 299 participants; low-certainty evidence). Ventilator-free days have inherent limitations as a composite endpoint and should be interpreted with caution. New need for invasive ventilation: the evidence is of very low certainty. Because of high risk of bias arising from deaths that occurred before ventilation we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics. Quality of life/neurological outcome: no data were available. Serious adverse events: we included data on two RCTs (678 participants) that evaluated systemic corticosteroids compared to standard care (plus/minus placebo); for adverse events and hospital-acquired infections, we included data on five RCTs (660 participants). Because of high risk of bias, heterogeneous definitions, and underreporting we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics (very low-certainty evidence). Different types, dosages or timing of systemic corticosteroids We identified one study that compared methylprednisolone with dexamethasone. The evidence for mortality and new need for invasive mechanical ventilation is very low certainty due to the small number of participants (n = 86). No data were available for the other outcomes. We did not identify comparisons of different dosages or timing. Outpatients with asymptomatic or mild disease Currently, there are no studies published in populations with asymptomatic infection or mild disease.
AUTHORS' CONCLUSIONS
Moderate-certainty evidence shows that systemic corticosteroids probably slightly reduce all-cause mortality in people hospitalised because of symptomatic COVID-19. Low-certainty evidence suggests that there may also be a reduction in ventilator-free days. Since we are unable to adjust for the impact of early death on subsequent endpoints, the findings for ventilation outcomes and harms have limited applicability to inform treatment decisions. Currently, there is no evidence for asymptomatic or mild disease (non-hospitalised participants). There is an urgent need for good-quality evidence for specific subgroups of disease severity, for which we propose level of respiratory support at randomisation. This applies to the comparison or subgroups of different types and doses of corticosteroids, too. Outcomes apart from mortality should be measured and analysed appropriately taking into account confounding through death if applicable. We identified 42 ongoing and 16 completed but not published RCTs in trials registries suggesting possible changes of effect estimates and certainty of the evidence in the future. Most ongoing studies target people who need respiratory support at baseline. With the living approach of this review, we will continue to update our search and include eligible trials and published data.
Topics: Adrenal Cortex Hormones; COVID-19; Humans; Immunization, Passive; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34396514
DOI: 10.1002/14651858.CD014963