Continuous low-dose everolimus shrinkage tuberous sclerosis complex-associated renal angiomyolipoma: a 48-month follow-up study

2018 ◽  
Vol 67 (3) ◽  
pp. 686-690 ◽  
Author(s):  
Chang-Ching Wei ◽  
Jeng-Daw Tsai ◽  
Ji-Nan Sheu ◽  
Sung-Lang Chen ◽  
Teng-Fu Tsao ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Low Dose ◽  
Benign Neoplasm ◽  
Volume Reduction ◽  
Response To Treatment ◽  
Renal Angiomyolipoma ◽  
Group I ◽  
Group Ii

Tuberous sclerosis complex (TSC) is a rare disease that causes multisystem benign neoplasm, induced by dysregulation of the mammalian target of the rapamycin pathway (mTOR). This study aimed to examine the effects of continuous low-dose everolimus, a potent and selective inhibitor of mTOR, on the treatment of TSC-associated renal angiomyolipoma (AML). Between July 2013 and August 2017, 11 patients with TSC-AML were enrolled for an everolimus therapy protocol. An oral everolimus dose starting at 2.5 mg daily was gradually increased to 5.0 mg daily. All patients were evaluated using MRI or CT scanning at baseline, 12, 24, 36 and 48 months after the start of treatment for measuring changes of renal AML mass volume. Everolimus therapy resulted in significant shrinkage of TSC-AML volume after 48 months follow-up. Serum levels of everolimus were subdivided into group I (<8 ng/mL, n=6) and group II (>8 ng/mL, n=5). The volume reduction rates were 10.6%–65.2% in group I and 42.5%–70.6% in group II. To evaluate the response to treatment, three of six (50%) were responders in group I, and all the patients in group II (5/5, 100%) were responders. The differences in AML volume reduction between the groups were statistically significant at 12 months (p=0.011), 24 months (p=0006), 36 months (p=0.014) and 48 months (p=0.05). These results suggest that continuous low-dose everolimus therapy (2.5–5 mg daily) might be effective in shrinking TSC-AML volume and minimizes adverse effects and subsequent reducing medical costs.

Does weekly versus daily low-dose of concurrent cisplatin have any effect on compliance and clinical outcomes in cases of locally advanced head and neck cancers?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17569-e17569
Author(s):  
Ayush Garg ◽  
Piyush Kumar ◽  
Arvind Kumar Chauhan ◽  
Pavan Kumar
Keyword(s):  
Statistical Difference ◽  
Low Dose ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Group I ◽  
Group Ii ◽  
Disease Free

e17569 Background: Concurrent Cisplatin with radiotherapy improves outcomes in locally advanced squamous cell carcinomas of the head neck.Cisplatin at 35mg/m2(weekly) raise compliance & hospitalization. There are only few reports on efficacy and toxicity of low dose Cisplatin (6mg/m2). Hence the purpose of this study was to evaluate the compliance and clinical outcomes between two concurrent cisplatin chemotherapy regimens & to see long term effects. Methods: Total 50 patients were included in study from Nov 2015 to Mar 2017 with 25 in each group. Radiotherapy given 70Gy/35# in 7weeks & Cisplatin at 35mg/m2 weekly (Group I) and 6mg/m2 daily (Group II). Assessment of toxicity was done by RTOG scoring criteria. WHO Response criterion was used to assess clinical response. Median follow up was 6 months. Results: Group I(80%) and Group II(84%)patients completed Radiotherapy. In Group I 48% patients received less than 6 cycles and Group II 40% received ≤25 cycles chemotherapy. Median OTT in Group I & II in was 51 & 52days. Neutropenia & Mucositis statistically insignificant between both groups.There was no statistical difference in complete response between the two groups. In Group I 40% patients developed Progressive disease on follow up as compared to 12% in Group II(p-0.02). After 1.5 years of follow up, Group I vs Group II 4 patients had complete response, 6 had recurrence & 11 vs 4 patients expired (p-0.03). At a median follow up of 6 months overall survival in Group I and II was 56% and 44%(p-0.39). While as median disease free survival in Group I & II was 6.6 & 11.9 months(p-0.14). Conclusions: Low dose daily Cisplatin offers ease of administration in the outpatient clinic, better tolerability and better quality of life.Group II patients were more compliant in terms of patients receiving chemotherapy or completing radiotherapy. At median follow up of 6 months there was no statistical difference in terms of overall and disease-free survival. The statistical difference was seen in terms of patients expired in Group I (44%) as compared to Group II (16%). Therefore, we need a larger number of patients for the use of low dose Cisplatin to be evaluated in future clinical trials.

scholarly journals Efficacy of Low Dose Topiramate and Propranolol in Migraine Prophylaxis

2018 ◽  
Vol 9 (2) ◽  
pp. 49-54
Author(s):  
Muhammad Abdul Momen Khan ◽  
Jannatul Ferdous ◽  
AKM Golam Kabir ◽  
Md Mamnur Rashid ◽  
Md Enayet Ul Islam ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Low Dose ◽  
Migraine Prophylaxis ◽  
Drop Out ◽  
Group I ◽  
Significant Difference ◽  
Propranolol Group ◽  
Baseline Information ◽  
Group Ii

Background: Migraine, the second most common cause of headache that can significantly impair the lives of people. Various drugs are available for migraine prophylaxis but all of which have varying degrees of adverse effects that may significantly limit their use.Objectives: To observe whether low dose topiramate is more effective compared to propranolol in migraine prophylaxis.Methods: Total 120 patients the age range of 18 to 50 years were recruited as study population of migraine in the Out Patient Department (OPD) & Headache Clinic,BSMMU.60 patients were administered by Tab.Topiramate 50 mg/ day named as group-I and rest of 60 patients were administered by Tab. Propranolol 80 mg /day named as group-II. Out of them in total 96 patients had completed the study. 47 patients had completed study in group-I and 49 patients in group-II. During trial, three follow up visits were taken for both groups, 1st follow up after 4 weeks of baseline information, 2nd follow up after 4 weeks of treatment, 3rd follow up after 8 weeks of treatment. Efficacy of treatment was measured by frequency, duration and severity of headache as measured by the visual analogue scale (VAS).Results: The mean (SD) age of group-I (topiramate) and group-II (propranolol) group were found 29.72±9.58 years and 30.96±10.11 years respectively. Female sex was found predominant in both groups. At final follow up, there was statistically significant difference in mean (SD) value of frequency of migraine between topiramate and propranolol group (4.72±2.80 vs. 3.48±2.20; p=0.024]. Propranolol appeared statistically significant than topiramate [TPM 5.53±2.98 vs. PRO 4.36±1.55; p=0.047].Regarding severity of headache, better results also were observed in the propranolol group than topiramate (p< 0.05). Both drugs appeared significant in efficacy measurement (p<0.001). Patient drop out was more in the topiramate group than the propranolol group (21.68 % vs. 18.34%). Furthermore, in the topiramate group, patients complained of more adverse effects than propranolol group (23.4% vs. 14.3%), which was statistically significant.Conclusion: The present study suggests that low dose topiramate and propranolol are effective for migraine prophylaxis in reduction of frequency, severity and duration of migraine individually and propranolol appears more effective compared to that of topiramate.J Shaheed Suhrawardy Med Coll, December 2017, Vol.9(2); 49-54

scholarly journals Low-Dose Everolimus Maintenance Therapy for Renal Angiomyolipoma Associated With Tuberous Sclerosis Complex

2021 ◽  
Vol 8 ◽  
Author(s):  
Cong Luo ◽  
Wen-Rui Ye ◽  
Xiong-Bin Zu ◽  
Min-Feng Chen ◽  
Lin Qi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Tuberous Sclerosis ◽  
Induction Therapy ◽  
Tuberous Sclerosis Complex ◽  
Low Dose ◽  
Standard Dose ◽  
Gene Mutations ◽  
Renal Angiomyolipoma ◽  
Significance Level

Objective: To assess the safety and efficacy of low-dose everolimus maintenance therapy for tuberous sclerosis complex-related renal angiomyolipoma (TSC-RAML) patients that had previously undergone standard-dose treatment for a minimum of 6 months.Materials and Methods: In total, 24 patients with a definitive TSC diagnosis were enrolled from April 2018 – April 2019 at Xiangya Hospital, Central South University. All patients underwent low-dose everolimus maintenance therapy following standard-dose everolimus induction therapy for a minimum of 6 months. Patients additionally underwent TSC1/TSC2 genetic testing, And they were followed-up at 3, 6, 12, 18, and 24 months. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria were used to monitor patient RAML responses, while adverse events (AEs) were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). P &lt; 0.05 was the significance level for all analyses, which were performed using SPSS 19.0.Results: TSC1/TSC2 gene mutations were present in all 24 patients, all of whom achieved a significant reduction in TSC-RAML volume within the initial 6-month induction therapy period, and exhibited volume stabilization during the low-dose maintenance therapy treatment period without any instances of TSC-RAML regrowth. Adverse events (AEs) were significantly less severe and less frequent over the course of maintenance therapy relative to standard therapy.Conclusions: Low-dose everolimus maintenance therapy represents an effective approach to achieving TSC-RAML control following a minimum of 6 months of full-dose induction therapy, and may be associated with decreases in everolimus-related AE frequency and severity.

1139 Everolimus for renal angiomyolipoma associated with tuberous sclerosis complex (TSC): EXIST-2 3-year follow-up

2014 ◽  
Vol 13 (1) ◽  
pp. e1139 ◽  
Author(s):  
J.J. Bissler ◽  
J.C. Kingswood ◽  
E. Radzikowska ◽  
B.A. Zonnenberg ◽  
M. Frost ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Renal Angiomyolipoma

Rare variant of genetically confirmed tuberous sclerosis complex presenting with bilateral renal angiomyolipoma in Wünderlich syndrome

2021 ◽  
Vol 14 (8) ◽  
pp. e243380
Author(s):  
Ramon Jr Bagaporo Larrazabal ◽  
Harold Henrison Chang Chiu ◽  
Dennis L Sacdalan
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Fluid Collection ◽  
Well Being ◽  
Renal Angiomyolipoma ◽  
Abdominal Ct ◽  
Once Daily ◽  
Mass Size ◽  
The Right

A 28-year-old woman came for non-traumatic right flank pain with hypotension and right flank mass. She had multiple hyperpigmented skin papules located on the centre area of her face, and angiomas on her toes. She was anaemic and had a blood transfusion on top of aggressive fluid resuscitation. Abdominal CT showed bilaterally enlarged kidneys and fluid collection in the right perirenal space (haemorrhage). The consideration was an angiomyolipoma in spontaneous perinephric haemorrhage. We considered tuberous sclerosis complex (TSC) and did genetic testing. Results revealed mutations in the TSC2 gene, consistent with the diagnosis of TSC. No immediate surgical plans were considered at that time. She opted to be discharged against medical advice and was scheduled for a close outpatient follow-up. The patient followed up after 2 weeks, already on sirolimus 2 mg once daily. She reported improved overall well-being and a decrease in the flank mass size.

scholarly journals Early but not late allograft nephrectomy reduces allosensitization after transplant failure

2013 ◽  
Vol 5 (6) ◽  
pp. 142
Author(s):  
Alp Sener ◽  
Anand K. Khakhar ◽  
Christopher Y. Nguan ◽  
Andrew A. House ◽  
Anthony M. Jevnikar ◽  
...  
Keyword(s):  
Graft Failure ◽  
Low Dose ◽  
Early Failure ◽  
Group I ◽  
Transplant Failure ◽  
Group Ii ◽  
Allograft Nephrectomy ◽  
The Impact ◽  
Reactive Antibody

Introduction: Allosensitization is a significant obstacle to retransplantationfor patients with primary renal graft failure.Methods: We assessed the impact of allograft nephrectomy(Group I) and weaning of immunosuppression (Group II) on percentpanel reactive antibody (%PRA) at various time points after graftfailure in 132 patients with a median follow-up of 47 months. Ofthese, 68% had allograft nephrectomy while 32% were placed onthe waiting list and were either taken off immunosuppression, lefton prednisone or on low-dose immunosuppressive therapy.Results: When groups were stratified into early (<6 months) andlate (>6 months) graft failure, patients who had transplant nephrectomyfor early failure demonstrated a decline in %PRA from46% at time of graft failure to 27% at last follow-up (p = 0.02);conversely, %PRA continued to rise in Group II experiencing earlyallograft failure. Both Groups I and II patients with late graft failuremaintained elevated %PRA at last follow-up.Conclusion: Allograft nephrectomy may play a role in limitingallosensitization in patients with early but not late graft failures.RésuméIntroduction : L’allosensibilisation est un obstacle important à laretransplantation chez les patients présentant un échec primairede la greffe rénale.Méthodologie : Nous avons évalué l’impact d’une néphrectomiedu greffon (groupe I) et du sevrage de l’immunosuppression (groupeII) sur le taux d’immunisation (PRA pour panel reactive antibody) àdifférents points dans le temps après l’échec de la greffe chez 132patients; le suivi médian était de 47 mois. Sur les 132 patients, 68% ont subi une néphrectomie du greffon, tandis que 32 % ont étéplacés sur la liste d’attente, et on a soit mis fin à leur traitementd’immunosuppression, soit poursuivi leur traitement par prednisoneou par un agent immunosuppresseur à faible dose.Résultats : Lorsque les groupes ont été stratifiés en fonction del’échec précoce (< 6 mois) et tardif (> 6 mois) de la greffe, lespatients qui ont subi une néphrectomie du greffon en raison d’unéchec précoce ont montré une baisse du PRA, passant de 46 %au moment de l’échec de la greffe à 27 % lors du dernier suivi(p = 0,02); en revanche, le PRA a continué d’augmenter chez lespatients du groupe II qui ont présenté un échec précoce de la greffe.Dans les deux groupes, les patients ayant présenté un échec tardifde la greffe présentaient toujours un PRA élevé lors du dernier suivi.Conclusion : La néphrectomie du greffon peut contribuer à limiterl’allosensibilisation dans les cas d’échec précoce de la greffe, maispas dans les cas d’échec tardif.

scholarly journals Long-term Follow-up Assessing Renal Angiomyolipoma Treatment Patterns, Morbidity, and Mortality: An Observational Study in Tuberous Sclerosis Complex Patients in the Netherlands

2015 ◽  
Vol 66 (4) ◽  
pp. 638-645 ◽  
Author(s):  
Marinus J.C. Eijkemans ◽  
Willem van der Wal ◽  
Leida J. Reijnders ◽  
Kit C.B. Roes ◽  
Sahar Barjesteh van Waalwijk van Doorn-Khosrovani ◽  
...  
Keyword(s):  
The Netherlands ◽  
Observational Study ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Treatment Patterns ◽  
Renal Angiomyolipoma ◽  
Complex Patients ◽  
Long Term Follow Up

Comparative Assessment of Autogenous Cancellous Bone Graft and Bovine-Derived Demineralized Bone Matrix for Secondary Alveolar Bone Grafting in Patients With Unilateral Cleft Lip and Palate

2021 ◽  
pp. 105566562110251
Author(s):  
Vijay Kumar ◽  
Vidya Rattan ◽  
Sachin Rai ◽  
Satinder Pal Singh ◽  
Jai Kumar Mahajan
Keyword(s):  
Bone Graft ◽  
Iliac Crest ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Volumetric Analysis ◽  
Group I ◽  
Alveolar Bone Grafting ◽  
Group Ii ◽  
Demineralized Bone

Objective: Comparison between bovine-derived demineralized bone matrix (DMBM) and iliac crest graft over long term for secondary alveolar bone grafting (SABG) in patients with unilateral cleft lip and palate (UCLP) in terms of radiological and clinical outcomes. Design: Prospective, randomized, parallel groups, double-blind, controlled trial. Setting: Unit of Oral and Maxillofacial Surgery, Oral Health Science Centre, Postgraduate Institute of Medical Education & Research, Chandigarh. Participants: Twenty patients with UCLP. Interventions: Patients were allocated into group I (Iliac crest bone graft) and group II (DMBM) for SABG. Outcomes were assessed at 2 weeks, 6 months, and then after mean follow-up period of 63 months. Outcomes Measures: Volumetric analysis of the grafted bone in the alveolar cleft site was done through cone beam computed tomography using Cavalieri principle and modified assessment tool. Clinical assessment was performed in terms of pain, swelling, duration of hospital stay, cost of surgery, alar base symmetry, and donor site morbidity associated with iliac crest harvesting. Results: Volumetric analysis through Cavalieri principle revealed comparable bone uptake at follow-up of 6 months between group I (70%) and group II (69%). Modified assessment tool showed no significant difference between horizontal and vertical bone scores over short- and long-term follow-up. In group II, there was higher cost of surgery, but no donor site morbidity unlike group I. Conclusions: Demineralized bone matrix proved analogous to iliac crest bone graft as per volumetric analysis over shorter period. However, although statistically insignificant, net bone volume achieved was lower than the iliac crest graft at longer follow-up.

scholarly journals High-throughput screening of circRNAs reveals novel mechanisms of tuberous sclerosis complex-related renal angiomyolipoma

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Yang Zhao ◽  
Hao Guo ◽  
Wenda Wang ◽  
Guoyang Zheng ◽  
Zhan Wang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Regulatory Network ◽  
High Throughput Screening ◽  
Kidney Tissue ◽  
Cell Types ◽  
The Body ◽  
Differentially Expressed ◽  
Renal Angiomyolipoma

Abstract Objective Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by lesions throughout the body. Our previous study showed the abnormal up-regulation of miRNAs plays an important part in the pathogenesis of TSC-related renal angiomyolipoma (TSC-RAML). circRNAs were known as important regulators of miRNA, but little is known about the circRNAs in TSC-RAMLs. Methods Microarray chips and RNA sequencing were used to identify the circRNAs and mRNAs that were differently expressed between the TSC-RAML and normal kidney tissue. A competitive endogenous RNA (ceRNA) regulatory network was constructed to reveal the regulation of miRNAs and mRNAs by the circRNAs. The biological functions of circRNA and mRNA were analyzed by pathway analysis. Microenvironmental cell types were estimated with the MCP-counter package. Results We identified 491 differentially expressed circRNAs (DECs) and 212 differentially expressed genes (DEGs), and 6 DECs were further confirmed by q-PCR. A ceRNA regulatory network which included 6 DECs, 5 miRNAs, and 63 mRNAs was established. Lipid biosynthetic process was significantly up-regulated in TSC-RAML, and the humoral immune response and the leukocyte chemotaxis pathway were found to be down-regulated. Fibroblasts are enriched in TSC-RAML, and the up-regulation of circRNA_000799 and circRNA_025332 may be significantly correlated to the infiltration of the fibroblasts. Conclusion circRNAs may regulate the lipid metabolism of TSC-RAML by regulation of the miRNAs. Fibroblasts are enriched in TSC-RAMLs, and the population of fibroblast may be related to the alteration of circRNAs of TSC-RAML. Lipid metabolism in fibroblasts is a potential treatment target for TSC-RAML.

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