Relapse Rate Research Articles

Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission

In patients with relapsed DLBCL in complete remission (CR), autologous hematopoietic cell transplantation (auto-HCT) and CAR-T therapy are both effective, but it is unknown which modality provides superior outcomes. We compared the efficacy of auto-HCT vs. CAR-T in patients with DLBCL in a CR. A retrospective observational study comparing auto-HCT (2015–2021) vs. CAR-T (2018–2021) using the Center for International Blood & Marrow Transplant Research registry. Median follow-up was 49.7 months for the auto-HCT and 24.7 months for the CAR-T cohort. Patients ages 18 and 75 with a diagnosis of DLBCL were included if they received auto-HCT (n = 281) or commercial CAR-T (n = 79) while in a CR. Patients undergoing auto-HCT with only one prior therapy line and CAR-T patients with a previous history of auto-HCT treatment were excluded. Endpoints included Progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS). In univariate analysis, treatment with auto-HCT was associated with a higher rate of 2-year PFS (66.2% vs. 47.8%; p < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs. 48% ; p < 0.001), and a superior 2-year OS (78.9% vs. 65.6%; p = 0.037). In patients with early (within 12 months) treatment failure, auto-HCT was associated with a superior 2-year PFS (70.9% vs. 48.3% ; p < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs. 45.9% ; p < 0.001) and trend for higher 2-year OS (82.4% vs. 66.1% ; p = 0.076). In the multivariable analysis, treatment with auto-HCT was associated with a superior PFS (hazard ratio 1.83; p = 0.0011) and lower incidence of relapse (hazard ratio 2.18; p < 0.0001) compared to CAR-T. In patients with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with improved clinical outcomes compared to CAR-T. These data support the consideration of auto-HCT in select patients with LBCL achieving a CR in the relapsed setting.

Fludarabine, busulfan, and melphalan conditioning regimen in allogeneic hematopoietic stem cell transplantation for adult patients with myeloid malignancies: A multicenter retrospective study

AbstractRelapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo‐HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS‐IB‐1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow‐up was 507 days for survivors. The 2‐year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT‐CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05‐60.03, p = 0.045; HR = 3.64, 95%CI 1.40‐9.44, p = 0.008; respectively), while post‐transplantation cyclophosphamide based graft‐versus‐host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11‐0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.

Glioblastoma Multiforme miRNA based Comprehensive Study to Validate Phytochemicals for Effective Treatment against Deadly Tumour through In Silico Evaluation.

Glioblastoma Multiforme (GBM) is a prevalent and deadly type of primary astrocytoma, constituting over 60% of adult brain tumors, and has a poor prognosis, with a high relapse rate within 7 months of diagnosis. Despite surgical, radiotherapy, and chemotherapy treatments, GBM remains challenging due to resistance. MicroRNA (miRNAs) control gene expression at transcriptional and post-transcriptional levels by targeting their messenger RNA (mRNA), and also contribute to the development of various neoplasms, including GBM. The present study focuses on exploring the miRNAs-based pathogenesis of GBM and evaluating most potential plant-based therapeutic agents with in silico analysis. Gene chips were retrieved from the Gene Expression Omnibus (GEO) database, followed by the Robust- RankAggereg algorithm to determine the Differentially Expressed miRNAs (DEMs). The predicted targets were intersected with the GBM-associated genes, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the overlapping genes was performed. At the same time, five phytochemicals were selected for the Connectivity map (CMap), and the most efficient ones were those that had undergone molecular docking analysis to obtain the potential therapeutic agents. The hsa-miR-10b, hsa-miR-21, and hsa-miR-15b were obtained, and eight genes were found to be associated with glioma pathways; VSIG4, PROCR, PLAT, and ITGB2 were upregulated while, CAMK2B, PDE1A, GABRA1, and KCNJ6 were downregulated. The drugs Resveratrol and Quercetin were identified as the most prominent drugs. These miRNAs-based drugs can be used as a curative agent for the treatment of GBM. However, in vivo, experimental data, and clinical trials are necessary to provide an alternative to conventional GBM cancer chemotherapy.

Fludarabine, busulfan, and melphalan conditioning regimen in allogeneic hematopoietic stem cell transplantation for adult patients with myeloid malignancies: A multicenter retrospective study

AbstractRelapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo‐HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS‐IB‐1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow‐up was 507 days for survivors. The 2‐year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT‐CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05‐60.03, p = 0.045; HR = 3.64, 95%CI 1.40‐9.44, p = 0.008; respectively), while post‐transplantation cyclophosphamide based graft‐versus‐host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11‐0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.

Effect of peptide-binding motif on survival of HLA-haploidentical transplantation with post-transplant cyclophosphamide.

Peptide-binding motif (PBM) model, a hierarchical clustering of HLA class I based on their binding specificity, was developed to predict immunopeptidome divergence. The effect of PBM mismatches on outcomes is unknown in HLA-haploidentical haematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy-haplo). We therefore conducted a retrospective study using national registry data in PTCy-haplo. Overall, 1352 patients were included in the study. PBM-A bidirectional mismatch was associated with an increased risk of overall mortality in multivariable analysis (hazard ratio, 1.26; 95% confidence interval, 1.06 to 1.50; p = 0.010). None of relapse, non-relapse mortality (NRM) and graft-versus-host disease showed significant differences according to PBM-A bidirectional mismatch status in the entire cohort. The impact of PBM-A bidirectional mismatch on overall survival (OS) was preserved within the HLA-A genotype bidirectional mismatch population, and their lower OS stemmed from higher relapse rate in this population. The worse OS due to high NRM with PBM-A bidirectional mismatch was prominent in lymphoid malignancies receiving reduced-intensity conditioning. The PBM model may predict outcomes more accurately than HLA genotype mismatches. In conclusion, this study demonstrated that the presence of PBM-A bidirectional mismatch elevated the risk of mortality of PTCy-haplo. Avoiding PBM-A bidirectional mismatch might achieve better outcomes in PTCy-haplo.

Multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes after autologous haematopoietic stem cell transplantation for acute myeloid leukaemia.

This retrospective study analysed 106 acute myeloid leukaemia (AML) patients undergoing autologous haematopoietic stem cell transplantation (ASCT) to assess the impact of multiple small-dose infusions of granulocyte-colony-stimulating factor (G-CSF)-mobilized haploidentical lymphocytes as post-ASCT maintenance therapy. Among them, 50 patients received lymphocyte maintenance therapy, 21 received alternative maintenance therapy, and 35 received no maintenance therapy. Patients receiving lymphocyte maintenance therapy demonstrated significantly higher overall survival (OS) and disease-free survival (DFS) compared to those without maintenance therapy, with 4-year OS and DFS rates notably elevated. While there were no significant differences in recurrence rates among the three groups, lymphocyte maintenance therapy showcased particular benefits for intermediate-risk AML patients, yielding significantly higher OS and DFS rates and lower relapse rates compared to alternative maintenance therapy and no maintenance therapy. The study suggests that multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes may offer promising outcomes for AML patients after ASCT, particularly for those classified as intermediate-risk. These findings underscore the potential efficacy of lymphocyte maintenance therapy in reducing disease relapse and improving long-term prognosis in this patient population.

Successful treatment with efgartigimod as an add-on therapy in acute attack of anti-AQP4 antibody-positive NMOSD: a case report.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune demyelinating disease characterized by recurrent myelitis and optic neuritis. It is associated with high rates of relapse and disability. The main treatment strategies for acute attacks include intravenous methylprednisolone pulse (IVMP) treatment and rescue treatment with plasma exchange (PLEX). Recently, the blockade of neonatal Fc receptor (FcRn)-IgG interaction has gained momentum as a therapeutic strategy. Efgartigimod, the first approved FcRn inhibitor for treating generalized myasthenia gravis, has shown impressive safety, efficacy, and tolerability, and is being regarded as "PLEX in a bottle". We report a 65-year-old female patient who was diagnosed with anti-AQP4 antibody positive NMOSD. Add-on treatment with efgartigimod to IVMP and intravenous immunoglobulin (IVIG) at the second acute relapse showed favorable results. This case suggests that efgartigimod is a potentially effective add-on therapy in acute attacks of AQP4-IgG-positive NMOSD.

Anti-thymocyte globulin combined with post-transplantation cyclophosphamide reduce graft-versus-host disease in hematopoietic stem cell transplantation for pediatric leukemia

This retrospective analysis evaluated the use of anti-thymocyte globulin (ATG) with or without post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis in children with acute leukemia undergoing hematopoietic stem cell transplantation (HSCT). The study included 57 children, with 35 in the ATG-PTCy group and 22 in the ATG group. While overall incidence of acute and chronic GvHD did not differ significantly between groups, the ATG-PTCy group had lower rates of grade II-IV acute GvHD (p = 0.013) and moderate-to-severe chronic GvHD (p = 0.001) compared to the ATG group. Importantly, ATG-PTCy significantly improved GvHD/relapse-free survival (GRFS) compared to ATG (65.71% vs. 36.63%; p = 0.003). There were no differences in engraftment, infection rates, immune reconstitution, overall survival, leukemia-free survival, relapse rate, or non-relapse mortality between the two groups. Combining ATG with PTCy may reduce moderate-to-severe GvHD and improve GRFS in children undergoing HSCT for acute leukemia.

CCR5 Δ32 and CTLA-4 +49 A/G Gene Polymorphisms and Interferon-β Treatment Response in Croatian and Slovenian Multiple Sclerosis Patients.

The aim of the present study was to investigate the impact of CCR5 Δ32 and CTLA-4 polymorphisms on the response to IFN-β treatment in our cohort of MS patients from Croatia and Slovenia. Genomic DNA was obtained from 295 MS patients (230 female; 65 male) classified as responders (n = 173) and non-responders (n = 122) based on clinical criteria for treatment efficacy. Genotyping was performed via PCR/PCR-RFLP. No significant differences in the genotype/allele frequencies of CCR5Δ32 and CTLA-4 +49 A/G were detected between male responders and non-responders. A significantly higher prevalence (p = 0.039) of the CTLA-4 +49 AA genotype was found in female responders (42.1%) compared to non-responders (28.9%). Using multiple forward regression analysis, the CTLA-4 +49 AA genotype significantly predicted a positive response to IFN-β therapy in females (p = 0.011) and contributed to 4.5% of response variability. Furthermore, the combined presence of the CCR5Δ32 wtwt/CTLA-4 +49 AA genotype significantly predicted a positive response to treatment in females (p = 0.025). The age at disease onset, pretreatment relapse rate, and baseline EDSS score were not reliable predictors of treatment response in MS patients. Our results indicate that the presence of the CCR5Δ32 polymorphism was not associated with the response to IFN-β treatment, whereas the CTLA-4 +49 polymorphism showed a positive correlation with an optimal response in female patients.

Primary retroperitoneal lymph node dissection for metastatic non-seminomatous germ cell tumours: outcomes and adjuvant chemotherapy.

To compare the outcomes and treatment burden of primary retroperitoneal lymph node dissection (pRPLND) alone versus pRPLND + adjuvant chemotherapy (AC) in patients with pathological stage II (PSII) non-seminomatous germ cell tumours (NSGCT). Retrospective review of the Princess Margaret Cancer Center eTestes cancer database identified patients with PSII NSGCT after pRPLND between 1995 and 2020. The primary outcome was relapse-free survival (RFS). Secondary outcomes included disease-specific survival (DSS), burden of relapse treatment, and factors associated with relapse. A total of 109 PSII patients were included in the study. There were 96 patients treated with pRPLND alone and 13 treated with pRPLND + AC. The median follow-up was 61 months. The 5-year RFS was 72% for the pRPLND-only group vs 92% for the pRPLND + AC group (hazard ratio [HR] 4.372, 95% confidence interval [CI] 0.59-32.36; P = 0.11). Within the pRPLND-only group the 5-year RFS differed by pN stage (pN1 = 94% vs pN2/N3 = 67%, P = 0.03). Despite a higher relapse rate within the pRPLND-only group, the DSS was similar at 5 years (98% pRPLND only vs 100% pRPLND + AC, P = 0.48). Only 24 (25%) of the patients in the pRPLND-only group required any subsequent chemotherapy. Despite achieving similar survival, the cumulative post-RPLND treatment burden was less for the pRPLND-only group than the pRPLND+AC group overall (average 1.23 vs 2.46 cycles of chemotherapy per patient in group). The majority of patients with PSII NSGCT treated with pRPLND alone do not experience a recurrence or require chemotherapy. Despite a lower relapse risk when AC is given, no difference in survival was seen but higher chemotherapy burden was entertained. AC may constitute overtreatment for most patients with PSII NSGCT treated with pRPLND.

Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis

BackgroundManagement of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year.MethodsA retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed.ResultsAll groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy.ConclusionsOur data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO.Trial registrationNo registration, retrospective analysis.Graphical

The role of tobacco smoking in antineutrophil cytoplasmic antibody-associated vasculitis: a systematic review.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic pauci-immune necrotising vasculitides involving small vessels, characterised by the presence of specific ANCA autoantibodies directed to leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) and subdivided into three clinical entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The aetiology of AAV is unknown and many genetic, epigenetic and environmental factors have been reported to be involved in pathogenesis. Smoking is widely recognised as a risk factor for the development of many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. This systematic review will analyse known data about the role of smoking in the development, clinical presentation and outcome of AAV. Articles that examined interactions between tobacco smoking and AAV (GPA, MPA, EGPA) were included. All articles selected were in English. No limitation on publication date was established. Case reports were excluded. The systematic search was performed using PubMed/Medline and Cochrane Library databases. The search provided a total of 131 articles. Three studies were added, obtained from the review of the reference lists of articles. 70 were removed because they were duplicated or written in languages other than English. The title and abstract of 64 articles were screened. Of these, 30 were excluded as the title and/or abstract did not meet the inclusion criteria. Thus, 34 remained for full-text review, of which 8 were excluded. 26 articles were therefore included in this review. The role of smoking in AAV development is unclear. AAV patients current smoking appear appear to be younger and more frequently males, with a lower prevalence of EGPA and MPA than GPA. Ever smokers show higher relapse rate. Smoking seems to be associated with a higher risk of cardiovascular events during follow-up. Smokers incur an increased risk of infections. Finally, many data support smoking as a risk factor for end stage renal disease and mortality in AAV patients. Current data support the hypothesis that smoking influences prevalence, clinical phenotype and prognosis of ANCA-associated vasculitis. However, further studies are required to fully determine its role.

P-377 Understanding the interplay between multiple sclerosis patterns and ovarian reserve, which influences the other?

Abstract Study question Is multiple sclerosis (MS) associated with diminished ovarian reserve in women? Does ovarian reserve influence multiple sclerosis progression patterns? Summary answer AntiMüllerian Hormone (AMH) is not diminished in MS patients compared to healthy matched controls. Ovarian reserve predicts multiple sclerosis patterns independently from chronological age. What is known already Population registries indicate increased childlessness in individuals with MS, but the influence of MS on ovarian reserve and the need for fertility preservation counseling are topics of ongoing debate. Notably, MS research highlights the concept of immunosenescence: with age the disease shifts from high relapse rates to disability accumulation and fewer relapses. It is uncertain whether ovarian aging, assessed through AMH, could serve as a marker of immunosenescence, offering more precise predictions of MS patterns compared to chronological age alone. Study design, size, duration This prospective observational study enrolled all female MS patients aged 18 to 50 presenting to the neurology service between June and November 2023, matching them in a 1:2 ratio with controls of similar age and BMI. The controls were healthy females, without known causes of female infertility. Exclusion criteria were: postmenopausal state, prior neoplasm requiring gonadotoxic therapy or prior hematopoietic stem cell transplantation. Participants/materials, setting, methods The study was conducted in an academic hospital, regional referral for neurology and fertility preservation. Detailed neurological and gynecological anamnesis was collected for 73 patients and 146 controls. AMH measurements were performed by the same laboratory with the Roche Elecsys AMH system. Multiple generalized linear models were carried out to explore the correlation between AMH and neurological data. All results were adjusted for age and use of hormonal contraception. Bonferroni corrected post-hoc analyses were performed. Main results and the role of chance Cases and controls were matched for age (33.6±6.1 vs. 34.4±4.5 years) and BMI (22.3±3.4 vs. 22.2±3.5 Kg/m2). The AMH values were not significantly different between cases and controls (2.7±3.5 vs. 2.7±1.6 ng/ml, p = 0.7) and showed no correlation with MS duration (p = 0.3) and disability measured with EDSS score (p = 0.9). Interestingly, higher AMH levels correlated with both having relapsed in the prior year (yes: 4.9±5.3 vs. no: 1.7±1.6 p = 0.008) and with the number of relapses in the 2 previous years (zero: 1.9±1.8, one: 2.3±2.9, more than 2: 5.8±6.2 ng/ml, p = 0.02). Consequently, patients with “No Evidence of Disease Activity”(NEDA) in the previous year showed lower AMH levels (1.68±1.3 vs. 4.1±4.7 ng/ml, p = 0.01), since absence of relapses is one of the components to define NEDA. In summary, patients with higher ovarian reserve showed a MS pattern typical of young age (higher relapse rates) independently from the actual chronological age. Limitations, reasons for caution The results should be confirmed by larger/multicenter datasets, powered to properly assess the possible influence of the different disease modifying therapies. Further research is warranted to understand the biological link behind the observed results. Wider implications of the findings Ovarian aging, measured through AMH, may provide a better indicator of a patient’s biological age than chronological age only. This may help neurologists in predicting MS patterns and treating it accordingly, providing a unique perspective on the mechanisms that link immunosenescence to the ovarian reserve reduction. Trial registration number Not Applicable

Evaluation of Micro-Needling Followed by Metformin Solution versus Micro-Needling Followed by Tranexamic Acid Solution in Treatment of Melasma: A Comparative Split Face Study

Abstract Background Melasma is a common acquired pigmentary disorder that manifests as symmetric hyperpigmented macules and patches on the face, more frequently affecting women of reproductive age. Various underling risk factors have been implicated in the etiology of melasma including; Genetic factors, pregnancy, oral contraceptives, endocrine dysfunction, hormone treatments, cosmetic contact sensitivity and exposure to ultraviolet (UV) light. Management of melasma is a frustrating experience both for the treating doctors and patients because of its recurrent and often recalcitrant nature. Numerous therapeutic modalities have been tried for this condition such as hydroquinone, kligman’s formula (hydroquinone + steroid + tretinoin), kojic acid, azelaic acid, arbutin, ascorbic acid, chemical peels, lasers, tranexamic acid, rucinol, oligopeptides, silymarin, orchid extracts, and various botanical extracts with variable success rates. Objectives Our aim was to assess and compare the therapeutic effects of topical metformin solution 30% with microneedling versus topical tranexamic acid (4mg\ml) solution with microneedling in treating patients with facial melasma. Patients and Methods This is a split-face study included 35 patients with facial melasma. The patients recruited from the Outpatient Dermatology Clinic at Ain Shams University Hospitals. Topical metformin 30% solution with microneedling sessions were done for the right side of the face (4sessions - two weeks apart), and topical tranexamic acid solution (4mg/ml) with microneedling on the left side of the face (4 sessions – two weeks apart). The patients were followed up for 3 months. The response of treatment was evaluated by Hemi MASI score and Antera 3D camera. Results Our study revealed that both microneedling followed by topical metformin solution and microneedling followed by topical TXA solution were efficient in treatment of facial melasma as shown by significant decrease in h-MASI score and average melanin level assessed by Antera camera. Although statistically insignificant, the percentage of change in h- MASI score was more evident with TXA treatment than metformin treatment. The side effects were limited and transient in the form of erythema, burning sensation, and xerosis. The main problem with either treatment was the high relapse rate. Conclusion Both metformin and tranexamic acid applied topically following microneedling sessions led to statistically significant improvement of melasma according to Hemi MASI scores. Topical metformin appears to be a promising therapeutic option in the treatment of melasma without serious adverse effects.

Modelling the Impact of Relapse and Weaning Off Immunity on Hepatitis B Virus Transmission Dynamics

In this study, we present a numerical simulation of the impact of relapse in patients with chronic HBV infection and weaning off immunity on vaccinated individuals within the transmission dynamics of Hepatitis B. The sensitivity analysis result establishes that relapse rate and weaning off immunity increase the value of the effective reproduction number when it is increased. Similarly, the result of the numerical simulation reveals that the combined effect of relapse and weaning off immunity increases the number of infected persons and thus, increases the spread of the Hepatitis B Virus. Also, relapse delays the quick response to the treatment regimen which consequently slows down the potential of recovery from the infection, whereas, weaning off immunity reduces the number of vaccinated individuals.

STAT: schema therapy for addiction treatment, a proposal for the integrative treatment of addictive disorders.

The nature and origins of addictions and of their adjunctive behaviors, as well as their chronicity, call for treatments that conceptualize and treat them as the long-term and complex processes that they are. Addictions are often comorbid with personality problems and with trauma histories. Patients suffering from these disorders often show poor engagement with treatment and high rates of relapse, possibly because available treatments have yet to address the patient suffering from addiction in a more integrated or holistic manner. In particular, comprehensive treatment models for addictive disorders - like treatments for personality disorders or trauma - are likely to require the integration of behavioral, cognitive, and emotion-focused interventions within a facilitative therapeutic relationship. However, most current treatment models, including ones which are highly effective in stabilization or behavioral change, lack one or more components of treatment that could sustain longer term recovery, wellness, and health for a higher percentage of patients. In this article, I propose approaching addictions and their treatment from the perspective of schema therapy, an integrative, developmental model with a strong track record of positive outcomes in addressing personality disorder symptoms and long-standing trauma histories, commonly comorbid with addictive disorders. In advancing this proposal, I begin by providing some background tying together addictions, attachment, and personality, suggesting they be treated simultaneously to achieve improved outcomes. Then, after briefly reviewing the leading approaches to the treatment of addictions, I introduce the idea that schema therapy is well-situated - both theoretically and practically - to address many of the shortcomings of existing treatment options. In particular, I note how addictive and co-occurring colluding behaviors are deeply intertwined with both early and continued frustration of core developmental needs. I illustrate how the addictive cycle is perpetuated through the process of schema reinforcement and through the operation of schema modes. I then demonstrate how these key terms (i.e., needs, schemas, and modes) inform the patient's assessment and case formulation, guiding treatment interventions from a strong therapeutic relationship that focuses on integrating recovery behavior change, healing dysfunctional schemas and modes, and preventing relapse.

Criteria for predicting the development of recurrent peripheral nerve sheas tumors

Peripheral nerve sheaths tumors (PNST) account for about 8 % of all nervous system cancers. The relapse rate ranges from 17.3 to 26.4 %, showing an upward trend. The causes and provoking factors for the development of relapses of PNST have not been fully studied. Purpose of the study: to establish criteria for predicting recurrence of PNST. Material and Methods. The study included 122 patients who were treated at the Department of Spine and Peripheral Nerve Surgery of A.I. Polenov Russian Research Neurosurgical Institute from 2009 to 2021. Among them, there were 87 (71.3 %) patients with primary PNST and 35 (28.7 %) patients with recurrent PNST. All patients underwent MRI and ENMG both before and after surgery. An immunohistochemical study of Ki67 and SO X10 markers was performed. Results. The majority of relapses occured within 1 year after surgery. In cases with radical removal of PNST, the risk of relapse was: 28.6 % for schwannomas 28.6 %, 37.1 % for neurofibromas and 34.3 % for MP NST 34.3 % (p≥0.05). The risk of developing relapse of PNST was 2.9 times higher in patients aged ≥49 years than in patients aged ≤48 years (p&lt;0.004). The larger the initial size of the tumor, the higher the risk of relapse in the late postoperative period. The risk of developing relapse of MP NST was 8.79 times higher in patients with tumor size of greater than 11.5 cm than in patients with smaller tumor size (p&lt;0.02). The of Ki67 level above 4.85 % in schwannomas and above 5.17 % in neurofibromas can predict relapse of PNST (p&lt;0.05). Loss of SO X10 protein expression was associated with an increase in histological anaplasia of the tumor, which causes a high risk of relapse and an unfavorable clinical course of the disease. Conclusion. Despite radical (total) resection of PNST, the risk of relapse remains high. The pathological type of tumor, its size, levels of SO X10 and Ki67 markers, patient’s age, degree of preoperative neurological deficit and extent of surgery are significant criteria for predicting the development of relapse of PNST.

Criteria for predicting the development of recurrent peripheral nerve sheas tumors

Peripheral nerve sheaths tumors (PNST) account for about 8 % of all nervous system cancers. The relapse rate ranges from 17.3 to 26.4 %, showing an upward trend. The causes and provoking factors for the development of relapses of PNST have not been fully studied. Purpose of the study: to establish criteria for predicting recurrence of PNST. Material and Methods. The study included 122 patients who were treated at the Department of Spine and Peripheral Nerve Surgery of A.I. Polenov Russian Research Neurosurgical Institute from 2009 to 2021. Among them, there were 87 (71.3 %) patients with primary PNST and 35 (28.7 %) patients with recurrent PNST. All patients underwent MRI and ENMG both before and after surgery. An immunohistochemical study of Ki67 and SO X10 markers was performed. Results. The majority of relapses occured within 1 year after surgery. In cases with radical removal of PNST, the risk of relapse was: 28.6 % for schwannomas 28.6 %, 37.1 % for neurofibromas and 34.3 % for MP NST 34.3 % (p≥0.05). The risk of developing relapse of PNST was 2.9 times higher in patients aged ≥49 years than in patients aged ≤48 years (p&lt;0.004). The larger the initial size of the tumor, the higher the risk of relapse in the late postoperative period. The risk of developing relapse of MP NST was 8.79 times higher in patients with tumor size of greater than 11.5 cm than in patients with smaller tumor size (p&lt;0.02). The of Ki67 level above 4.85 % in schwannomas and above 5.17 % in neurofibromas can predict relapse of PNST (p&lt;0.05). Loss of SO X10 protein expression was associated with an increase in histological anaplasia of the tumor, which causes a high risk of relapse and an unfavorable clinical course of the disease. Conclusion. Despite radical (total) resection of PNST, the risk of relapse remains high. The pathological type of tumor, its size, levels of SO X10 and Ki67 markers, patient’s age, degree of preoperative neurological deficit and extent of surgery are significant criteria for predicting the development of relapse of PNST.

The Core outcome Clubfoot (CoCo) study: relapse, with poorer clinical and quality of life outcomes, affects 37% of idiopathic clubfoot patients.

There is a lack of high-quality research investigating outcomes of Ponseti-treated idiopathic clubfeet and correlation with relapse. This study assessed clinical and quality of life (QoL) outcomes using a standardized core outcome set (COS), comparing children with and without relapse. A total of 11 international centres participated in this institutional review board-approved observational study. Data including demographics, information regarding presentation, treatment, and details of subsequent relapse and management were collected between 1 June 2022 and 30 June 2023 from consecutive clinic patients who had a minimum five-year follow-up. The clubfoot COS incorporating 31 parameters was used. A regression model assessed relationships between baseline variables and outcomes (clinical/QoL). Overall, 293 patients (432 feet) with a median age of 89 months (interquartile range 72 to 113) were included. The relapse rate was 37%, with repeated relapse in 14%. Treatment considered a standard part of the Ponseti journey (recasting, repeat tenotomy, and tibialis anterior tendon transfer) was performed in 35% of cases, with soft-tissue release and osteotomies in 5% and 2% of cases, respectively. Predictors of relapse included duration of follow-up, higher initial Pirani score, and poor Evertor muscle activity. Relapse was associated with poorer outcomes. This is the first multicentre study using a standardized COS following clubfoot treatment. It distinguishes patients with and without relapse in terms of clinical outcomes and QoL, with poorer outcomes in the relapse group. This tool allows comparison of treatment methods and outcomes, facilitates information sharing, and sets family expectations. Predictors of relapse encourage us to create appropriate treatment pathways to reduce relapse and improve outcome.

The Clinical Effect and Safety of Dihuang Decoction in Henoch-Schönlein Purpura Compared With Different Traditional Programs: A Network Meta-Analysis.

This systematic review aims to evaluate the therapeutic efficacy of Dihuang decoction (DD), anti-inflammatory drugs (AIDs), blood circulation improvement drugs (BCIDs), and conventional therapy (CT) in the management of Henoch-Schönlein purpura (HSP)and to establish their comparative effectiveness rankings. Using the Population, Intervention, Comparison, Outcome, Study (PICOS) design framework, we developed a detailed search strategy. The literature search included databases such as PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, Weipu Journal Data, and the Chinese Biomedical Database, covering studies published up to June2024. We included randomized controlled trials that featured the DD as the experimental intervention, with three remaining treatments as comparators.Our analysis encompassed 63 studies with 5,435 participants, divided into 2,817 in the experimental group and 2,618 in the control group. The network meta-analysis suggested that theDD potentially surpasses AIDs, BCIDs, and CT in the management of HSP. This conclusion is supported by its superior SUCRA (Surface Under the Cumulative Ranking) scores across various measures, including the overall effective rate of medication, time to relief or disappearance of the rash, incidence of adverse reactions, time to relief or disappearance of abdominal pain, time to relief or disappearance of arthritic swelling or pain, IgA levels, and the relapse rate within six months (SUCRA scores: 100.0%, 88.3%, 79.8%, 94.4%, 99.9%, 88.3%, and 95.4%, respectively). In terms of overall effectiveness rate, the SUCRA efficacy rankings are as follows: DD > AIDs > AIDs+BCID > BCID > CT. Regarding rash relief and regression time, the SUCRA efficacy rankings are as follows: DD > CT > AIDs+BCID > AIDs. For the incidence rate of adverse reactions, the SUCRA efficacy rankings are as follows: DD > CT > AIDs > BCID > AIDs+BCID. For the relief and disappearance of abdominal pain, the SUCRA efficacy rankings are as follows: DD > CT > AIDs+BCID > AIDs. In terms of relief and disappearance of joint swelling and pain, the SUCRA efficacy rankings are as follows: DD > AIDs+BCID > AIDs. Regarding IgA changes, the SUCRA efficacy rankings are as follows: DD > CT > BCID > AIDs+BCID > AIDs. For the six-month recurrence rate, the SUCRA efficacy rankings are as follows: DD > AIDs > AIDs+BCID > CT. The DD appears to be a more effective alternative for treating HSP compared to AIDs, BCIDs, and CT.We hope that this study will provide better assistance to clinical practice.