Dose Of Cyclophosphamide Research Articles

Evaluation of the Clinical Safety of the Low-Cost Warburg Therapy for the Treatment of Patients With Advanced Cancers.

Rising cancer care costs are becoming cost prohibitive for lower income people worldwide. We developed the Warburg protocol as a low-cost option for the treatment of cancer that was inspired. It was developed to exploit an Achilles heel which is a hallmark of cancer cells; the metabolic requirement for higher levels of glucose than normal cells. The purpose of this report is to assess the clinical safety and affordability of the Warburg therapy as an option for patients with advanced cancers. Between 2021 and 2023, 251 patients with advanced cancers received a total of 8542 treatments with the Warburg therapy. To restrict the supply of blood glucose to cancerous tumors, regular human insulin was administered (IV) sufficient to reduce blood glucose concentrations to hypoglycemic levels for 40-60 min. Subroutine doses of fluorouracil and cyclophosphamide were administered intravenously during this hypoglycemic period. Food or intravenous glucose was given as needed to return blood glucose to euglycemic levels after treatment. Patient symptoms, status, vitals, blood glucose, and hypoglycemic symptoms were monitored throughout treatment. Various blood parameters were measured before and after patients' course of treatment. There were no irreversible adverse reactions in advanced tumor patients of different ages and different cancer types after treatment. There was no significant fluctuation in blood glucose levels in diabetic and non-diabetic patients after treatment, and the weight, vital index and blood biochemical index of patients before and after multiple treatments exhibited little variation. Warburg therapy for the treatment of advanced tumors is clinically feasible, and safe for multiple treatments. It is inexpensive and widely applicable to different patient groups.

A neuropsychiatric systemic lupus erythematosus presenting with acute confusional state: a case report

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by variable clinical symptoms. It disproportionately affects African-American women and women from other ethnic groups. The complexity of SLE, stemming from its genetic and phenotypic diversity, poses challenges in diagnosis, treatment, and development of novel therapies. Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses a spectrum of neurological syndromes involving the central, peripheral, and autonomic nervous systems, as well as psychiatric syndromes diagnosed in SLE patients after ruling out other causes. Neuropsychiatric manifestations typically emerge in the later stages of SLE (10–75%). The acute onset of neuropsychiatric symptoms as the primary presentation of NPSLE is exceptionally rare and can be diagnostically elusive when other organs are unaffected. In this article, we present the case of a 53-year-old woman who was admitted to the hospital due to disorientation and an acute confusional state. Following the diagnosis of NPSLE, she received treatment consisting of three doses of pulse corticosteroids and one dose of cyclophosphamide. She exhibited a favorable clinical response, leading to partial resolution of her symptoms and subsequent discharge from the hospital. Practical Implications. Due to the rarity and diverse clinical presentations of NPSLE, particularly with the sudden onset of neuropsychiatric symptoms, there is a significant risk of delayed or incorrect diagnosis, which can lead to ineffective treatment. Therefore, maintaining a high index of clinical suspicion is paramount for achieving early and accurate diagnosis, which is crucial for initiating timely and effective treatment strategies.

GSTA1 gene polymorphisms are associated with cyclophosphamide effectiveness in lupus nephritis patients: A case-control study in Indonesia

Glutathione-S-transferase alpha-1 (GSTA1) is an enzyme with high conjugation activity against aldophosphamide, a metabolite of cyclophosphamide and promoter polymorphisms in GSTA1 may influence the cyclophosphamide effectiveness. The aim of this study was to evaluate the effectiveness and side effects of cyclophosphamide in lupus nephritis patients, using GSTA1 variants as predictors. A case-control study was conducted at Hasan Sadikin Hospital, Bandung, Indonesia, involving 100 lupus nephritis patients from February 2023 to January 2024. The PCR-Sanger sequencing was used to genotype five selected single nucleotide polymorphisms (SNPs) in the GSTA1 promoter: -52 A>G, -69 T>C, -513 A>G, -567 G>T, and -631 G>T. The endpoint was assessed after six doses of cyclophosphamide by evaluating renal function, disease activity and side effects. Results indicated that six doses of intravenous cyclophosphamide treatment improved renal function and disease activity in the patients, as evidenced by significant changes in serum creatinine (0.79 vs 0.69 mg/dL), dipstick proteinuria (3.00 vs 1.50), creatinine clearance (98.50 vs 109.50 mL/min), and Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (M-SLEDAI-2K) score (8.61 vs 6.95). The AG genotype at -513 A>G was associated with reduced cyclophosphamide effectiveness (odds ratio (OR): 0.19; 95%CI: 0.19–0.60; p=0.019). The GT genotype at -631 G>T independently increased the progression of anemia (OR: 2.41; 95%CI: 0.26–22.12; p=0.040). This study highlights that the presence of GSTA1 variants affected cyclophosphamide effectiveness in lupus nephritis patients, with heterozygous polymorphisms at -513 (AA to AG) and -631 (TT to GT) predicting reduced effectiveness of cyclophosphamide by enhancing GSTA1 promoter activity, while anemia further exacerbated lupus nephritis disease severity. GSTA1 polymorphism was not associated with the presence of alopecia, amenorrhea, gastrointestinal disorders, and leukopenia during cyclophosphamide therapy.

Fertility protective effects of Brillantaisia patula leaf extract against cyclophosphamide-induced ovarian damage in Wistar rats

BackgroundThe primary indication of infertility is the incapacity to conceive, and in females, the majority of instances of female infertility stem from ovulation disorders. This study evaluated the female fertility-enhancing effects and safety of aqueous leaf extract of Brillantaisia patula (ALEBP) in a cyclophosphamide (CYP) model of sterility in Wistar rats.MethodSixty-six female rats randomly allotted to six groups (n = 11) were administered with the appropriate regimen for 21 days and then mated with male rats. Group 1 (control) received distilled water. Groups 2–6 were treated with a single dose (200 mgkg− 1 body weight) of cyclophosphamide intraperitoneally and, in addition, received the same volume (0.5 mL) of distilled water, 18, 36, 72 mgkg− 1 body weight of ALEBP and 200 mg per body weight of vitamin C orally. Mating lasted 11 days; on day 20, the female Wistar rats were sacrificed. Data were analysed using One-way Analysis of Variance (ANOVA) followed by Dunett’s posthoc analysis, and GraphPad (at p < 0.05).ResultsResults herein showed that ALEBP significantly (p < 0.05) increased the diminution in activities/levels of glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity (TAC), cholesterol, alkaline phosphatase (ALP), acid phosphatase (ACP), estrogen (ES), and luteinising hormone (LH) induced by cyclophosphamide. ALEBP further reversed the increased level of malondialdehyde (MDA), tumour necrosis factor-α (TNFα), interleukin 8 (IL-8), and follicle-stimulating hormone (FSH) caused by cyclophosphamide (p < 0.05). In addition, ALEBP, while it significantly increased the cyclophosphamide-induced reduction in the number of implantations in each animal, the total number of viable fetuses, the total number of corpora lutea, and the fertility index, also significantly reduced the number of fetal resorptions in each animal and pre-implantation loss that was increased by cyclophosphamide. Moreover, the cyclophosphamide-induced degenerative and necrotic changes in the ovarian cells and uterus were reversed by ALEBP.ConclusionsConsidered as a whole, the aqueous leaf extract of Brillantaisia patula reversed oxidative stress and inflammatory side effects of cyclophosphamide, preserving ovarian function and fertility in the rats. This may suggest its exploration as a safe agent against toxic side effects of chemotherapy and fertility-related disorders of the uterus and ovary.

Oral cyclophosphamide monotherapy in advanced resistant ocular cicatricial pemphigoid

Abstract: PURPOSE: The purpose of the study was to study the efficacy of oral cyclophosphamide monotherapy in advanced resistant ocular cicatricial pemphigoid (OCP). MATERIALS AND METHODS: This retrospective case series examines patients diagnosed with advanced resistant OCP at a uveitis tertiary care center who were treated with oral cyclophosphamide therapy. RESULTS: Seventeen patients were included in this study. The average age of the participants was 74.3 ± 10.3 years, ranging from 60 to 99 years. The gender distribution was 8 females to 9 males. Oral cyclophosphamide-induced remission in 7 patients (41.1%) and was prematurely discontinued in 10 patients (58.9%), with 7 (63.7%) citing ineffectiveness and 3 (36.3%) experiencing side effects as reasons for discontinuation. The average therapy dose of cyclophosphamide administered was 116.1 ± 47.5 mg. The average duration required for the induction of remission was 150 ± 128 days. The overall therapy duration averaged 306 ± 189 days. Conducting univariate logistic regression with generalized estimating equations (GEEs) on variables did not reveal statistically significant differences between the two groups (responsive and nonresponsive to oral cyclophosphamide therapy), except for the maximum dose of oral cyclophosphamide therapy (P = 0.007). CONCLUSION: The prognosis of advanced OCP in patients is unlikely to be altered by the stepladder approach and step-up strategy. While oral cyclophosphamide can be efficacious for remission induction in resistant and aggressive OCP cases, a step-down strategy employing less potent agents with safer side effect profiles should be contemplated for subsequent treatment.

Immunomodulatory Potential of Melatonin in Immunosuppression: An in-vivo Study.

To assess the immunomodulatory effects of melatonin on the acquired immunity of immunosuppressed male Wistar rats by checking Interleukin 6 (IL-6) levels, total leucocyte counts (TLC), and differential leucocyte counts. Experimental study. Place and Duration of the Study: Animal laboratory, CMH Lahore Medical College, from June to October 2023. Fifty male Wistar rats, weighing 180g to 200g, were included in this study with 10 rats in each of the five groups namely cyclophosphamide (CP), CP + melatonin, CP + immunomodulator, melatonin-only, and control. A calculated dose of CP was administered intraperitoneally for 30 days (from 13/06/23 to 13/07/23) to each group except the control groups. After this, the experimental group was given melatonin CP + Melatonin for 7 days (from 14/07/23 to 20/07/23). CP + Immunomodulatory group was kept for comparison of immunomodulatory effects. Blood samples were drawn from all 5 groups. IL-6 was estimated through ELISA. Other parameters assessed were TLC and absolute differential leucocyte counts. Melatonin increased IL-6 levels significantly (p = 0.042) as well as the TLC levels (p <0.001) compared to the immuno-suppressed CP group. Melatonin was seen to have an upregulation of IL-6 levels in immunosuppression compared to the administration of immunomodulator preparation (p = 0.506) which was not as effective. Administration of melatonin significantly increased the TLC, neutrophil, lymphocyte, monocyte, and eosinophil count compared to known immunomodulators. Melatonin as a supplement may have some role in activating multiple immune response processes in immune-depressed states. It was also established that it allows quick recovery of cell components from immunosuppressed states. Melatonin, Immunomodulation, Rats, Interleukin-6, Acquired immunity, Cyclophosphamide.

Immunomodulatory Potential of Melatonin in Immunosuppression: An in-vivo Study.

To assess the immunomodulatory effects of melatonin on the acquired immunity of immunosuppressed male Wistar rats by checking Interleukin 6 (IL-6) levels, total leucocyte counts (TLC), and differential leucocyte counts. Experimental study. Place and Duration of the Study: Animal laboratory, CMH Lahore Medical College, from June to October 2023. Fifty male Wistar rats, weighing 180g to 200g, were included in this study with 10 rats in each of the five groups namely cyclophosphamide (CP), CP + melatonin, CP + immunomodulator, melatonin-only, and control. A calculated dose of CP was administered intraperitoneally for 30 days (from 13/06/23 to 13/07/23) to each group except the control groups. After this, the experimental group was given melatonin CP + Melatonin for 7 days (from 14/07/23 to 20/07/23). CP + Immunomodulatory group was kept for comparison of immunomodulatory effects. Blood samples were drawn from all 5 groups. IL-6 was estimated through ELISA. Other parameters assessed were TLC and absolute differential leucocyte counts. Melatonin increased IL-6 levels significantly (p = 0.042) as well as the TLC levels (p <0.001) compared to the immuno-suppressed CP group. Melatonin was seen to have an upregulation of IL-6 levels in immunosuppression compared to the administration of immunomodulator preparation (p = 0.506) which was not as effective. Administration of melatonin significantly increased the TLC, neutrophil, lymphocyte, monocyte, and eosinophil count compared to known immunomodulators. Melatonin as a supplement may have some role in activating multiple immune response processes in immune-depressed states. It was also established that it allows quick recovery of cell components from immunosuppressed states. Melatonin, Immunomodulation, Rats, Interleukin-6, Acquired immunity, Cyclophosphamide.

Avacopan in the treatment of refractory scleritis secondary to granulomatosis with polyangiitis: A case report.

Avacopan is a novel C5a receptor inhibitor which was recently licensed for treatment of severe granulomatosis with polyangiitis (GPA) in the European Union and the United Kingdom. To the best of our knowledge, this is the first described case on initial ophthalmic outcomes in a patient with severe GPA and concurrent refractory scleritis treated with avacopan. We present a case of de novo scleritis in a 77-year-old male with a background of retinitis pigmentosa with Argus II implant in situ. Severe scleral inflammation occurred following a suture removal from the implant site. Remission was not maintained despite orbital floor injections and high dose oral prednisolone. The diagnostic work-up revealed GPA which quickly progressed to involve vital organs. In view of his systemic deterioration, he was started on avacopan alongside rituximab, cyclophosphamide and high dose oral prednisolone. Sustained remission of scleritis was noted after 7 months of treatment with avacopan and low dose oral prednisolone with no other maintenance immunosuppression. We observed a sustained benefit of avacopan in allowing for successful taper of systemic steroids. We report that avacopan used alongside other immunosuppressants may be a viable option in patients with GPA and concurrent refractory scleritis. Further studies are needed to establish the longer term impact of this agent on the control of scleral inflammation.

Geraniol alleviates cyclophosphamide-induced cardiotoxicity in mice

Objective: To explore the effect of geraniol on cyclophosphamide- induced cardiotoxicity. Methods: Mice were divided into five groups: the control group, the cyclophosphamide group (200 mg/kg cyclophosphamide, i.p. on day 7), the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14, along with a single dose of cyclophosphamide on day 7, and the geraniol alone group (200 mg/kg geraniol from day 1 to day 14). At the end of the study, animals were sacrificed, and blood and heart were collected and analyzed for biochemical, histopathological, and immunohistochemical changes. Results: Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers, malondialdehyde, and inflammatory and apoptotic markers, while increasing antioxidant activities in mice with cyclophosphamide-induced cardiotoxicity. Moreover, it remarkably alleviated histopathological aberrations in cardiac tissue. Conclusions: Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant, anti-inflammatory, and antiapoptotic effects.

TNF-α inhibitors in the management of refractory granulomatosis with polyangiitis: A report of two cases

Granulomatosis with polyangiitis (GPA) is a type of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) that causes granulomatous necrotizing inflammation of small blood vessels. The goal of AAV treatment is to create a long-term remission. For inducing remission, the European League Against Rheumatism recommends using glucocorticoids (GCs) in combination with either cyclophosphamide (CYC) or rituximab (RTX). Despite this, in 10-40% the disease is resistant to initial treatment. In this report, we present two cases of refractory GPA that successfully achieved long-term remission using tumor necrosis factor-α inhibitors. The first case is a 27-year-old woman with GPA with involvement of upper airway, breast and central nervous system with active disease despite treatment with high dose GCs, CYC and RTX, successfully treated with infliximab and the disease was in complete remission for 54 months. The second case is a 35-year-old man with GPA with arthritis, lung cavitary lesions and nephritis resistant to treatment with high dose GCs, CYC and RTX, treated with adalimumab and the disease was in complete remission for 40 months.

Long-term survival after unrelated donor marrow transplantation for aplastic anaemia after optimized conditioning regimen: a retrospective multicentre cohort study

Almost all acquired severe aplastic anaemia is immune mediated and characterised by hypocellular bone marrow and ≥2 affected haematopoietic lineages. The optimal preparartive regimen for unrelated donor transplantation remains to be established. We aimed to study long-term outcomes after unrelated donor transplantation for severe aplastic anaemia with de-escalation of cyclophosphamide (Cy) dose in steps of 50mg/kg (150, 100, 50, 0mg/kg) in combination with total body irradiation (TBI) 2Gy, anti-thymocyte globulin (ATG) and fludarabine. Ninety-six patients with severe aplastic anaemia aged ≤65 years with adequate organ function enrolled on a trial of human leukocyte antigen (HLA)-matched or 1 HLA-locus mismatched unrelated donor marrow transplantation conducted between 02/2006 and 12/2013 in the United States (NCT00326417). Exclusion criteria were Karnofsky performance status of less than 60, clonal cytogenetic abnormalities and inherited marrow failure syndormes. The primary outcome was day-100 engraftment (achievement of absolute neutrophil recovery to at least 0.5×109/L without subsequent decline) and day-100 survival. The trial determined the lowest effective Cydose as 50mg/kg (n=38) for day-100 engraftment and survival. Cy dose 100mg/kg (n=41) was also acceptable. Accrual to Cy doses 150mg/kg (n=15) and 0mg/kg (n=3) was terminated early for toxicities. The current study is an extended follow up of patients enrolled on the trial (NCT00326477) and includes 76 of 96 patients alive ≥1 year after transplantation. There were 20 deaths in the first year after transplantation (Cy 0mg/kg [n=2], Cy 50mg/kg [n=1], Cy 100mg/kg [n=10], Cy 150mg/kg [n=7]). Patients were followed prospectively from transplantation and data reported using standardized data collection forms until death, loss to follow up or last contact through November 2023. The incidence of graft failure was calculated using the cumulative incidence estimator and the probability of survival using the Kaplan-Meier estimator. The median follow up of the cohort is 8.02 (IQR) 5.16-10.12) years. With Cy 50mg/kg, there was one graft failure and five deaths ≥1 year after transplantation. With Cy 100mg/kg there was only one late death and no graft failure. The 8-year probabilities of survival were 85.0% (95% CI 67.3-93.5) and 75.6% (95% CI 59.4-86.1) after Cy50mg/kg and 100mg/kg, respectively, P=0.31. With Cy 0mg/kg and 150mg/kg, there were no graft failures or death ≥1 year after transplantation. Regardless of Cy dose 12 of 15 patients aged ≥50 years died. Cy 50mg/kg or 100mg/kg with TBI 2Gy, ATG and fludarabine are effective conditioning regimens for unrelated donor marrow transplants for aplastic anaemia. Identification of an optimized transplantation approach for patients aged ≥50 years is needed. US National Institutes of Health.

Impact of dosing strategy on clinical outcomes of patients with lupus nephritis initially treated with lower-than-recommended-dose cyclophosphamide

AimCyclophosphamide is the mainstay treatment for patients with lupus nephritis (LN); it can be prescribed at lower doses than the recommended regimen to avoid side effects. We aimed to investigate the impact of cyclophosphamide dosing strategies on treatment outcomes of patients with LN initially treated with a lower-than-recommended dose. MethodsWe retrospectively reviewed patients with proliferative LN (class III, IV, or mixed) initially treated with lower-than-recommended-dose cyclophosphamide. Patients who received a titrated dose of cyclophosphamide ≥0.5 g/m2 were categorized into the titrate group, while those who received doses <0.5 g/m2 were categorized into the non-titrate group. The primary outcome was primary renal response (PRR) at 52 weeks. ResultsOf the 78 patients included, 47 were assigned to the titrate group and 31 to the non-titrate group. The titrate group had a higher proportion of PRR achievement (23 of 47 patients [48.9 %] vs. 7 of 31 patients [22.6 %] in the non-titrate group). After adjusting for potential confounders, a baseline urinary protein-to-creatinine ratio ≥3 g/g (OR, 0.3; 95 % CI, 0.1–0.9; P = 0.030), and titrating the dose of cyclophosphamide to ≥0.5 g/m2 (OR, 4.7; 95 % CI, 1.5–15.2; P = 0.010) were independent factors for PRR. Additionally, the titrate group had a lower rate of infection (8 of 47 patients [17.0 %] vs. 12 of 31 patients [38.7 %], respectively; OR, 0.3; 95 % CI, 0.1–0.9; P = 0.036) and death associated with LN (4 of 47 patients [8.5 %] vs. 8 of 31 patients [25.8 %], respectively; OR, 0.3; 95 % CI, 0.1–0.9; P = 0.047) compared with the non-titrate group. LN flare and the need for rescue therapy did not differ between the groups. ConclusionFor patients with LN initially treated with lower-than-recommended-dose cyclophosphamide, titration of the cyclophosphamide dose ≥0.5 g/m2 was beneficial on renal response, while reducing infection leading to hospitalization and LN-associated death.

Ameliorative Effect of Chitosan/Spirulina platensis Ethanolic Extract Nanoformulation against Cyclophosphamide-Induced Ovarian Toxicity: Role of PPAR-γ/Nrf-2/HO-1 and NF-kB/TNF-α Signaling Pathways.

Cyclophosphamide (CP) is an anticancer drug that causes infertility disorders. This study was designed to evaluate a nanoformulation of chitosan with an ethanolic extract from Spirulina platensis in terms of its protection against cyclophosphamide-induced ovarian toxicity. Nine groups of female Wistar rats were randomly assigned as follows: 1: control vehicle, 2: chitosan polymer, 3: telmisartan, 4: Spirulina platensis extract, 5: nanoformulation of the Spirulina platensis, and 6: single injection of CP; groups 7, 8, and 9 received the same treatments as those used in groups 3, 4, and 5, respectively, with a single dose of CP (200 mg/kg, I.P). The results displayed that the CP treatment decreased estradiol, progesterone, anti-mullerian hormone, and GSH content, and it downregulated PPAR-γ, Nrf-2, and HO-1 gene expression. In addition, the CP treatment caused an increase in the FSH, LH, and MDA levels. In the same manner, the protein expression of caspase-3, NF-kB, and TNF-α was upregulated in response to the CP treatment, while PPAR-γ was downregulated in comparison with the control. The rats treated with SPNPs exhibited a substantial reduction in the detrimental effects of oxidative stress and inflammation of the ovarian tissue. This study's conclusions showed that SPNPs counteracted the effects of CP, preventing the death of ovarian follicles and restoring the gonadotropin hormone balance and normal ovarian histological appearance.

Coenzyme Q10 ameliorates cyclophosphamide-induced chemobrain by repressing neuronal apoptosis and preserving hippocampal neurogenesis: Mechanistic roles of Wnt/ β-catenin signaling pathway

Deterioration in the neurocognitive function of cancer patients referred to as “Chemobrain” is a devastating obstacle associated with cyclophosphamide (CYP). CYP is an alkylating agent, clinically utilized as an efficient anticancer and immunosuppressant. Coenzyme Q10 (CoQ10) is a worthwhile micronutrient with diverse biological activities embracing antioxidant, anti-apoptotic, and neuroprotective effects. The current experiment was designed for investigating the neuroprotective capability of CoQ10 versus CYP-elicited chemobrain in rats besides elucidating the causal molecular mechanisms. Male Sprague Dawley rats received CoQ10 (10 mg/kg, orally, once daily, for 10 days) and/or a single dose of CYP (200 mg/kg i.p. on day 7). CoQ10 counteracted CYP-induced cognitive and motor dysfunction as demonstrated by the findings of neurobehavioral tests (passive avoidance, Y maze, locomotion, and rotarod tests). Histopathological analysis further affirmed the neuroprotective abilities of CoQ10. CoQ10 effectually diminished CYP-provoked oxidative injury by restoring the antioxidant activity of catalase (CAT) enzyme while reducing malondialdehyde (MDA) levels. Besides, CoQ10 efficiently repressed CYP-induced neuronal apoptosis by downregulating the expression of Bax and caspase-3 while upregulating the Bcl-2 expression. Moreover, CoQ10 hampered CYP-provoked upregulation in acetylcholinesterase (AChE) activity. Furthermore, CoQ10 considerably augmented hippocampal neurogenesis by elevating the expressions of brain-derived neurotrophic factor (BDNF) and Ki-67. These promising neuroprotective effects can be credited to upregulating Wnt/β-catenin pathway as evidenced by the elevated expressions of Wnt-3a, β-catenin, and Phoshpo-glycogen synthase kinase-3 β (p-GSK-3β). Collectively, these findings proved the neuroprotective capabilities of CoQ10 against CYP-induced chemobrain through combating oxidative injury, repressing intrinsic apoptosis, boosting neurogenesis, and eventually upregulating the Wnt/β-catenin pathway.

Mental health problems among children with lupus nephritis

Aim of the workTo assess and compare depression, anxiety, and cognitive impairments in juvenile systemic erythematous lupus (JSLE) children with lupus nephritis (LN) during the induction and maintenance phases of treatment and to investigate the association with disease activity, damage and immunosuppressive medications. Patients and methodsThis study included 33 patients diagnosed as JSLE with LN. Attention and working memory were assessed by the working memory index Wechsler Intelligence Scale (WISC). Depression and anxiety were assessed by the Children Depression Inventory (CDI) and the Spence Children Anxiety Scale respectively. The SLE disease activity index 2000 (SLEDAI-2 K) was recorded. ResultsThe mean age of the children was 11.6 ± 2.2 years, 88 % were females and 12 % males with disease duration of 16.9 ± 9.2 months and age at onset of 10.2 ± 2.3 years. Mean anxiety scores were higher among patients during the induction phase than those during maintenance phase (62.1 ± 7.2 and 40.2 ± 8.8 respectively; p < 0.001). The depression score was higher in the induction (19 ± 5.5) than in the maintenance group (12.4 ± 5.6) (p = 0.002). Mean anxiety scores significantly correlated with SLEDAI-2 K and corticosteroids dose (r = 0.58 and r = 0.43, p = 0.0004 and p = 0.013 respectively) and a significant negative correlation with duration of corticosteroids and number of cyclophosphamide doses (r = 0.46 and r = 0.69, p = 0.008 and p = 0.0001 respectively). ConclusionDepression and anxiety levels were higher in children with LN during the induction phase of treatment than those in the maintenance phase. Mental health problems must be screened among children with LN and treating these problems can improve the medical and psychosocial outcomes.

Results of the JRS-I LRA0401 and LRB0402 Japan Rhabdomyosarcoma Study Group trials for low-risk embryonal rhabdomyosarcoma.

Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4g/m2. However, this dose may increase the risk of adverse events, including infertility, in some patients. The JRS-I LRA0401 and LRB0402 protocols aimed to reduce the cyclophosphamide dose to 9.6g/m2 and 17.6g/m2, respectively, without decreasing the FFS rates. Subgroup-A patients received eight cycles (24weeks) of vincristine, actinomycin D, and 1.2g/m2/cycle cyclophosphamide. Subgroup-B patients received eight cycles (24weeks) of vincristine, actinomycin D, and 2.2g/m2/cycle cyclophosphamide, followed by six cycles (24weeks) of vincristine and actinomycin D. Group II/III patients in both subgroups received radiotherapy. In subgroup A (n = 12), the 3-year FFS rate was 83% (95% confidence interval [CI], 48-96), and the 3-year overall survival (OS) rate was 100%. Only one isolated local recurrence was observed (8.3%). There were no unexpected grade-4 toxicities and no deaths. In subgroup B (n = 16), the 3-year FFS and OS rates were 88% (95% CI, 59-97) and 94% (95% CI, 63-99), respectively. There were no unexpected grade 4 toxicities and no deaths. Shorter duration therapy using vincristine, actinomycin D, and lower dose cyclophosphamide with or without radiotherapy for patients with low-risk subgroup A rhabdomyosarcoma (JRS-I LRA0401 protocol) and moderate reduction of cyclophosphamide dose for patients with low-risk subgroup B rhabdomyosarcoma (JRS-I LRB0402 protocol) did not compromise FFS.

In-depth analysis of transcriptomes in ovarian cortical follicles from children and adults reveals interfollicular heterogeneity

The ovarian cortical reserve of follicles is vital for fertility. Some medical treatments are toxic to follicles, leading to premature ovarian insufficiency. Ovarian tissue cryopreservation is an established method to preserve fertility in adults and even applied in prepuberty despite unproven efficacy. Here, we analyze transcriptomes of 120 cortical follicles from children and adults for detailed comparison. We discover heterogeneity with two main types of follicles in both age groups: one with expected oocyte-granulosa profiles and another with predicted role in signaling. Transcriptional changes during growth to the secondary stage are similar overall in children and adults, but variations related to extracellular matrix, theca cells, and miRNA profiles are found. Notably, cyclophosphamide dose correlates with interferon signaling in child follicles. Additionally, morphology alone is insufficient for follicle categorization suggesting a need for additional markers. Marker genes for early follicle activation are determined. These findings will help refine follicular classification and fertility preservation techniques across critical ages.

A Dedicated Nephrology Daycare Unit: A Step Toward a Patient-Centered Approach.

Background Nephrology services encompass a wide range of day-care procedures. Securing beds for day admissions can be challenging and may lead to significant delays in patient management. Objective This study aims to describe the impact of establishing a dedicated nephrology daycare unit at a tertiary care center. Methods Since January 2021, a dedicated nephrology daycare unit has been operational at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. This observational study retrospectively reviewed the admission records to the KAUH nephrology daycare unit from January 2021 to December 2023. Admissions with missing data were excluded from the analysis. The study outcomes included: 1. the number of patients served in the unit, 2. the scope of services provided, 3. the "time to completion" of immunosuppressive therapy administered in the unit, and 4. the rate of complications related to admission to the unit. Results There were 233 admissions for 157 patients. The scope of procedures included: 1. administration of immunosuppressive therapy (42 doses of cyclophosphamide, 70 doses of rituximab, three doses of methylprednisolone), 2. renal biopsies (25 procedures), 3. tunneled dialysis catheter procedures (40 procedures, both insertion and removal), 4. dialysis access angioplasty (three procedures), 5. IV iron therapy (45 admissions), and 6. other miscellaneous causes (five admissions). Ideal time to completion of cyclophosphamide therapy was achieved in 86% of patients, with the remaining 14% experiencing delays due to reasons other than bed availability. Time to completion of rituximab therapy was achieved without delay in 85% of patients, with a time interval of less than 21 days. There were no reported complications associated with admission to the unit. Conclusions Establishing a dedicated nephrology daycare unit facilitates the delivery of nephrology day-procedures and reduces delays in therapy.

Pharmacogenomic associations of cyclophosphamide pharmacokinetic candidate genes with 4hydroxycyclophosphamide formation in children with Cancer.

4-hydroxycyclophosphamide (4HCY) is the principal precursor to the cytotoxic metabolite of cyclophosphamide (CY), which is often used as first-line treatment of children with cancer. There is conflicting data regarding the relationship between CY efficacy, toxicity, and pharmacokinetics with the genes encoding proteins involved in 4HCY pharmacokinetics, specifically its formation and elimination. We evaluated germline pharmacogenetics in children with various malignancies receiving their first CY dose. Using linear regression, we analyzed the associations between two pharmacokinetic outcomes - how fast a child cleared CY (i.e., CY clearance) and the ratio of the 4HCY/CY exposure, specifically area under the plasma concentration-time curve (AUC), and 372 single nucleotide polymorphisms (SNP) in 14 drug-metabolizing transporters or enzymes involved in 4HCY formation or elimination. Age was associated with the ratio of 4HCY/CY AUC (P = 0.004); Chemotherapy regimen was associated with CY clearance (P = 0.003). No SNPs were associated with CY clearance or the ratio of 4HCY/CY AUC after controlling for a false discovery rate. Age and chemotherapy regimen, but not germline pharmacogenomics, were associated with CY clearance or the ratio of 4HCY/CY AUC. Other methods, such as metabolomics or lipidomics, should be explored.

Paraneoplastic glomerulonephritis and kidney infiltration by mantle cell lymphoma: A diagnostic challenge.

Mantle cell lymphoma (MCL) is a rare and aggressive type of lymphoma that can affect the kidneys. The disease can lead to kidney impairment, and glomerulonephritis (GN) is a rare but serious complication of MCL. We report a case of MCL with kidney interstitial infiltration and membranoproliferative glomerulonephritis with focal and segmental glomerulosclerosis. A 75-year-old man presented recurrent acute kidney failure and worsening of nephrotic syndrome. Kidney biopsy revealed membranoproliferative glomerulonephritis presented immunoglobulin and complement deposition, focal and segmental glomerulosclerosis of not otherwise specified type, and infiltration by mantle cell lymphoma. Bone marrow biopsy and PET/CT scan confirmed the diagnosis of mantle cell lymphoma. The patient was treated with R-CHOP21 chemotherapy with cyclophosphamide dose adjustment for nephroprotection. He achieved complete remission with normalization of hematological parameters, improvement of kidney function, and reduction of proteinuria and albuminuria. This case shows the importance of considering alternative diagnoses in patients with recurrent chronic kidney disease and worsening nephrotic syndrome. Early diagnosis and treatment of mantle cell lymphoma can lead to favorable outcomes.