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Cell Transplantation 2024Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell...
Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Lymphoproliferative Disorders; Male; Female; Adult; T-Lymphocytes; Transplantation, Homologous; Adolescent; Child; Middle Aged; Young Adult; Cyclophosphamide
PubMed: 38856035
DOI: 10.1177/09636897241259722 -
BMC Cancer Jun 2024Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous recombination repair deficiency (HRD). However, it is unclear which PARPi is optimal in mCRPC patients with HRD in 2nd -line setting.
METHOD
We conducted a systematic review of trials regarding PARPi- based therapies on mCRPC in 2nd -line setting and performed a Bayesian network meta-analysis (NMA). Radiographic progression-free survival (rPFS) was assessed as primary outcome. PSA response and adverse events (AEs) were evaluated as secondary outcomes. Subgroup analyses were performed according to specific genetic mutation.
RESULTS
Four RCTs comprised of 1024 patients (763 harbored homologous recombination repair (HRR) mutations) were identified for quantitative analysis. Regarding rPFS, olaparib monotherapy, rucaparib and cediranib plus olaparib showed significant improvement compared with ARAT. Olaparib plus cediranib had the highest surface under cumulative ranking curve (SUCRA) scores (87.5%) for rPFS, followed by rucaparib, olaparib and olaparib plus abiraterone acetate prednisone. For patients with BRCA 1/2 mutations, olaparib associated with the highest probability (98.1%) of improved rPFS. For patients with BRCA-2 mutations, olaparib and olaparib plus cediranib had similar efficacy. However, neither olaparib nor rucaparib showed significant superior effectiveness to androgen receptor-axis-targeted therapy (ARAT) in patients with ATM mutations. For safety, olaparib showed significantly lower ≥ 3 AE rate compared with cediranib plus olaparib (RR: 0.72, 95% CI: 0.51, 0.97), while olaparib plus cediranib was associated with the highest risk of all-grade AE.
CONCLUSION
PARPi-based therapy showed considerable efficacy for mCRPC patients with HRD in 2nd -line setting. However, patients should be treated accordingly based on their genetic background as well as the efficacy and safety of the selected regimen.
TRIAL REGISTRATION
CRD42023454079.
Topics: Humans; Poly(ADP-ribose) Polymerase Inhibitors; Bayes Theorem; Prostatic Neoplasms, Castration-Resistant; Mutation; Male; Phthalazines; Network Meta-Analysis; Piperazines; BRCA2 Protein; Recombinational DNA Repair; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic; Progression-Free Survival; Indoles; BRCA1 Protein; Treatment Outcome; Quinazolines
PubMed: 38851712
DOI: 10.1186/s12885-024-12388-2 -
Frontiers in Endocrinology 2024Subacute thyroiditis (SAT) is a self-limiting and inflammatory thyroid disease. Although SAT usually improves on its own within weeks, it needs treatment when patients... (Meta-Analysis)
Meta-Analysis Comparative Study
IMPORTANCE
Subacute thyroiditis (SAT) is a self-limiting and inflammatory thyroid disease. Although SAT usually improves on its own within weeks, it needs treatment when patients have pain, fever, and symptoms of thyrotoxicosis. Therapeutic drugs mainly include non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Currently, there is no systematic review or meta-analysis of the comparison of outcomes between NSAIDs and glucocorticoids for the treatment of SAT.
OBJECTIVES
To conduct a systematic review and meta-analysis on the outcomes in subacute thyroiditis patients treated with glucocorticoids or NSAIDs.
DATA SOURCES
Using the four electronic databases, including PubMed, Embase, Cochrane Library, Wanfang database and Web of Science. All publications until 21 June 2023 were searched. The reference lists of all selected articles were independently screened to identify additional studies left out in the initial search.
STUDY SELECTION
The literature comparing outcomes between glucocorticoids and non-steroidal anti-inflammatory drugs for patients with subacute thyroiditis will be included.
DATA EXTRACTION AND SYNTHESIS
Two independent investigators (Anqi Yuan and Jialu Wu) extracted the data following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (PRISMA) and then evaluated the quality of the eligible studies with the Newcastle-Ottawa Scale. Fixed-effects models for the meta-analyses were applied. Heterogeneity was assessed with the chi-squared (x²) test (Cochran's Q) and inconsistency index (I²). The robustness of the results was tested with the sensitivity analyses. The bias of publication was assessed with the Harbord test.
MAIN OUTCOMES AND MEASURES
The incidence of permanent hypothyroidism in SAT patients treated with corticosteroids or NSAIDs.
RESULTS
Our study included a total of ten comparative cohort studies with 1337 participants. We found that the incidence of developing permanent hypothyroidism in the SAT patients who received glucocorticoids treatment was significantly lower than those who received NSAIDs treatment. (OR, 0.56; 95% CI, 0.36-0.88; P = 0.01). The risk of permanent hypothyroidism in patients who received prednisone at an average initial dose < 40 mg/d was significantly lower than that in patients who received NSAIDs (OR, 0.37; 95% CI, 0.14-0.94; P = 0.04). There was no significant difference in the occurrence of permanent hypothyroidism between SAT patients who received an average initial dose ≥ 40 mg/d of prednisone and those who received only NSAIDs (OR, 0.7; 95% CI, 0.14-3.53; P = 0.67). In addition, the recurrence rate was observably higher in those receiving glucocorticoids than in those receiving NSAIDs (OR, 1.98; 95% CI, 1.12-3.5; p = 0.02). The recurrence rate was significantly higher in patients with an average initial prednisone dose of < 40 mg/d than in the NSAIDs group. There was no significant difference in the recurrence rate between patients in the mean initial prednisone dose ≥ 40 mg/d group and those in the NSAIDs group.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, we compared the treatment outcomes of SAT patients between glucocorticoids and NSAIDs. Our results indicated that glucocorticoid treatment was associated with a lower incidence of permanent hypothyroidism than NSAID treatment. Patients treated with NSAIDs might have a lower recurrence rate. This finding might help to understand the outcome of the disease when choosing different drugs and help physicians to make appropriate decisions.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023427332.
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Thyroiditis, Subacute; Glucocorticoids; Treatment Outcome
PubMed: 38715797
DOI: 10.3389/fendo.2024.1384365 -
Frontiers in Oncology 2024This study aimed to evaluate the relative efficacy and safety of first-line treatment options for metastatic castration-resistant prostate cancer (mCRPC).
OBJECTIVE
This study aimed to evaluate the relative efficacy and safety of first-line treatment options for metastatic castration-resistant prostate cancer (mCRPC).
METHODS
We systematically searched electronic databases, including PubMed and Web of Science, for studies published from their inception to April 3rd, 2023. Inclusion criteria were: 1) Completed Phase III or IV randomized controlled trials (RCTs) registered on ClinicalTrials.gov; 2) Patients with a confirmed diagnosis of mCRPC who had not previously received chemotherapy or novel endocrine therapies. We conducted a network meta-analysis using R software (version 3.4.0). Network graphs and risk of bias graphs were generated using Stata 14.0 and RevMan 5.4, respectively. The primary outcome was overall survival (OS), and the secondary outcome was the incidence of severe adverse events (SAEs).
RESULTS
Seven RCTs encompassing 6,641 patients were included. The network meta-analysis revealed that both docetaxel+prednisone (DP) and cabazitaxel+prednisone (CP) significantly improved OS compared to abiraterone. Compared to placebo, DP showed comparable results to both cabazitaxel 20 mg/m+prednisone (C20P) and cabazitaxel 25 mg/m+prednisone (C25P) in terms of OS. For SAEs, both DP and C20P were superior to C25P, with no statistical difference between C20P and DP. The probability ranking plots indicated that C25P ranked highest for OS, while DP ranked highest for SAEs.
CONCLUSIONS
Based on our network meta-analysis, we recommend cabazitaxel 20 mg/m+prednisone (C20P) as the primary choice for first-line management of mCRPC, followed by DP. Enzalutamide and abiraterone are suggested as subsequent options. Radium-223 may be considered for patients presenting with bone metastases.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023443943.
PubMed: 38686197
DOI: 10.3389/fonc.2024.1378993 -
Journal of Neuromuscular Diseases 2024The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objective of this study was to describe predictors of loss of ambulation in Duchenne muscular dystrophy (DMD).
METHODS
This systematic review and meta-analysis included searches of MEDLINE ALL, Embase, and the Cochrane Database of Systematic Reviews from January 1, 2000, to December 31, 2022, for predictors of loss of ambulation in DMD. Search terms included "Duchenne muscular dystrophy" as a Medical Subject Heading or free text term, in combination with variations of the term "predictor". Risk of bias was assessed using the Newcastle-Ottawa Scale. We performed meta-analysis pooling of hazard ratios of the effects of glucocorticoids (vs. no glucocorticoid therapy) by fitting a common-effect inverse-variance model.
RESULTS
The bibliographic searches resulted in the inclusion of 45 studies of children and adults with DMD from 17 countries across Europe, Asia, and North America. Glucocorticoid therapy was associated with delayed loss of ambulation (overall meta-analysis HR deflazacort/prednisone/prednisolone: 0.44 [95% CI: 0.40-0.48]) (n = 25 studies). Earlier onset of first signs or symptoms, earlier loss of developmental milestones, lower baseline 6MWT (i.e.,<350 vs. ≥350 metres and <330 vs. ≥330 metres), and lower baseline NSAA were associated with earlier loss of ambulation (n = 5 studies). Deletion of exons 3-7, proximal mutations (upstream intron 44), single exon 45 deletions, and mutations amenable of skipping exon 8, exon 44, and exon 53, were associated with prolonged ambulation; distal mutations (intron 44 and downstream), deletion of exons 49-50, and mutations amenable of skipping exon 45, and exon 51 were associated with earlier loss of ambulation (n = 13 studies). Specific single-nucleotide polymorphisms in CD40 gene rs1883832, LTBP4 gene rs10880, SPP1 gene rs2835709 and rs11730582, and TCTEX1D1 gene rs1060575 (n = 7 studies), as well as race/ethnicity and level of family/patient deprivation (n = 3 studies), were associated with loss of ambulation. Treatment with ataluren (n = 2 studies) and eteplirsen (n = 3 studies) were associated with prolonged ambulation. Magnetic resonance biomarkers (MRI and MRS) were identified as significant predictors of loss of ambulation (n = 6 studies). In total, 33% of studies exhibited some risk of bias.
CONCLUSION
Our synthesis of predictors of loss of ambulation in DMD contributes to the understanding the natural history of disease and informs the design of new trials of novel therapies targeting this heavily burdened patient population.
Topics: Muscular Dystrophy, Duchenne; Humans; Glucocorticoids; Walking; Pregnenediones; Latent TGF-beta Binding Proteins
PubMed: 38669554
DOI: 10.3233/JND-230220 -
The Journal of Allergy and Clinical... Apr 2024Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated...
BACKGROUND
Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear.
OBJECTIVE
To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids.
METHODS
We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach.
RESULTS
We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty).
CONCLUSIONS
Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more.
PubMed: 38642709
DOI: 10.1016/j.jaip.2024.04.016 -
Medicina (Kaunas, Lithuania) Feb 2024IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage...
IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Glomerulonephritis, IGA; Angiotensin Receptor Antagonists; Nephrologists; Antihypertensive Agents; Kidney Failure, Chronic; Steroids; Immunosuppressive Agents
PubMed: 38399561
DOI: 10.3390/medicina60020274 -
Cureus Dec 2023Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL... (Review)
Review
Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL remain underexplored, contributing to diagnostic complexities and a high mortality rate. This study endeavors to elucidate the salient clinical and investigative features of stroke linked to this condition. A systematic review was performed using the PubMed database from the incident to August 2023 including search categories for IVL and stroke. All studies, excluding review articles, were included in this study. There were 58 cases with a confirmed diagnosis of IVL associated with stroke, with a mean age of 62.9 ± 9.6 years (female 50%). Classical lateralizing stroke symptoms were noted in only 69% of cases. Other clinical syndromes included altered sensorium (31%), rapidly progressive cognitive impairment (23%), seizures (22%), and gait disturbances (19%). Common hematological abnormalities included elevated lactate dehydrogenase (LDH, 97%), erythrocyte sedimentation rate (ESR, 79%), C-reactive protein (CRP, 61%), interleukin-2, microglobulins, and cerebrospinal fluid (CSF) protein. CSF flow cytometry was not diagnostic, and cytology was mostly negative. The dynamic pattern for DWI/T2 lesions was predominant and primarily located in the subcortical regions. Diffuse background slowing (64%) was a major finding in the electroencephalogram. Seventy-one percent of cases died (n=45) mostly due to delayed diagnosis. Only 31% were treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone) chemotherapy, among whom 25% died. This study suggests that IVL-associated strokes carry a high mortality rate, largely due to challenges in timely diagnosis and therapy. Unlike classical stroke syndrome, key indicators to aid in early diagnosis include a clinical syndrome of multiple non-lateralizing neurological symptoms, dynamic MRI DWI/T2-lesions primarily located in subcortical regions, elevated serum LDH, ESR, CRP, interleukins, microglobulin, CSF protein, and CSF polymerase chain reaction analysis, apart from tissue examination. Larger studies should be performed to establish diagnostic and predictive scores.
PubMed: 38249220
DOI: 10.7759/cureus.50896 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Le Infezioni in Medicina 2023Listeriosis is a known cause of community acquired bacterial meningitis/meningoencephalitis. It occurs more frequently in neonates, older people and immunocompromised...
BACKGROUND
Listeriosis is a known cause of community acquired bacterial meningitis/meningoencephalitis. It occurs more frequently in neonates, older people and immunocompromised hosts. Rarely, brain abscesses can complicate the course of infection, which poses a difficulty in the management and elevates morbidity and mortality. Myasthenia gravis is an autoimmune disease that often requires immunosuppressive treatment, which increases the risk for invasive infections.
CASE DESCRIPTION
A 75-year-old myasthenic patient, treated with prednisone and pyridostigmine, was diagnosed with invasive listeriosis. He presented with muscle weakness, dyspnea, hemiparesis and altered mental status. Brain imaging revealed multiple abscesses and blood cultures were positive for . Despite combination antibiotic therapy, he died 6 weeks after admission.
SYSTEMATIC REVIEW
Ninety-six cases of brain abscesses from 1968 to 2023 were reviewed; the majority of the patients were men, 54 years-old on average, and had at least one risk factor for invasive listeriosis. The mortality exceeded 22%. Blood cultures and CSF/abscess cultures were positive in only 79.2% and 54.6%, respectively. The most common therapeutic approach was a combination regimen that included amoxicillin or ampicillin. Only 8 patients underwent surgery, of which one died.
CONCLUSION
This case highlights the importance of as a cause of brain abscesses in populations at risk, including myasthenic patients. The challenge of diagnosing and treating this condition is aggravated by the paucity of literature and the high mortality rate.
PubMed: 38075415
DOI: 10.53854/liim-3104-16