Multiple Adverse Drug Reactions to Calcineurin Inhibitors in a Renal Transplant Patient

Calcineurin inhibitors (CNIs) are typically used to prevent organ rejection and their use has significantly improved allograft and survival rates with a marked reduction in rejection rates. However, CNIs have been associated with various side effects including nephrotoxicity, hypertension, gingival hyperplasia, hypertrichosis, hepatotoxicity, hyperkalemia, and neurotoxicity. Significant intra-patient and interpatient pharmacokinetic variability and narrow therapeutic indices make the therapy complicated. Although CNIs are essential in preventing organ rejection, higher doses could lead to toxicity, which can reduce patient tolerability and negatively affect long-term allograft survival and patient mortality. As individual patients respond differently to comparable drug levels, attaining the optimal drug level range does not ensure lack of drug toxicity or complete immunosuppressant viability. One to two adverse effects are commonly observed in patients using CNIs. However, no case about CNI-induced gingival hyperplasia, hypertrichosis, tremors, facial nerve palsy, and blepharospasm after kidney transplantation in a single patient has been reported. Our report describes the unusual case of a patient presenting with CNI-induced multiple adverse reactions.

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Neoral: A Microemulsion Cyclosporine

Journal of Transplant Coordination ◽

10.1177/090591999600600103 ◽

1996 ◽

Vol 6 (1) ◽

pp. 5-8 ◽

Cited By ~ 1

Author(s):

David I Min

Keyword(s):

Therapeutic Range ◽

Survival Rates ◽

Drug Level ◽

Oral Solution ◽

Transplant Recipients ◽

Microemulsion Formulation ◽

Narrow Therapeutic Range ◽

Patient And Graft Survival ◽

Clinical Stability

Cyclosporine (Sandimmune), introduced in the 1980s, improved patient and graft survival rates primarily by decreasing the frequency and severity of early, acute rejection. Today, the challenge for coordinators and clinicians is to promote long-term clinical stability in transplant recipients. This requires maintaining the cyclosporine blood level within a relatively narrow therapeutic range to ensure adequate and stable immunosuppression, thus reducing the risk of rejection caused by a suboptimal drug level or drug-related toxicity because of a level above the therapeutic range. However, the clinical use of Sandimmune is complicated by low bioavailability and highly variable pharmacokinetics that provide management challenges and can affect clinical outcomes adversely. Neoral, a new oral microemulsion formulation (in capsules and oral solution) of cyclosporine, improves the bioavailability and pharmacokinetics of cyclosporine and reduces inter- and intraindividual pharmacokinetic variability with a safety profile comparable to that of Sandimmune.

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Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2015.61.3778 ◽

2016 ◽

Vol 34 (3) ◽

pp. 219-226 ◽

Cited By ~ 103

Author(s):

Randa Tao ◽

Sunil Krishnan ◽

Priya R. Bhosale ◽

Milind M. Javle ◽

Thomas A. Aloia ◽

...

Keyword(s):

Intrahepatic Cholangiocarcinoma ◽

Liver Tumors ◽

Survival Rates ◽

Continuous Variable ◽

Response Analysis ◽

Significant Treatment ◽

Term Survival ◽

Higher Doses

Purpose Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. Patients and Methods Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). Results Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. Conclusion Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection.

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Transapical versus Conventional Aortic Valve Replacement�A Propensity-Matched Comparison

The Heart Surgery Forum ◽

10.1532/hsf98.20111084 ◽

2012 ◽

Vol 15 (1) ◽

pp. 4 ◽

Cited By ~ 23

Author(s):

David M. Holzhey ◽

William Shi ◽

A. Rastan ◽

Michael A. Borger ◽

Martin H�nsig ◽

...

Keyword(s):

Aortic Valve ◽

Survival Rates ◽

Long Term Results ◽

Term Survival ◽

Kaplan Meier ◽

Risk Patients ◽

Short And Long Term ◽

Good Treatment Option ◽

Matched Comparison

Introduction: The goal of this study was to compare the short- and long-term outcomes after aortic valve (AV) surgery carried out via standard sternotomy/partial sternotomy versus transapical transcatheter AV implantation (taTAVI).Patients and Methods: All 336 patients who underwent taTAVI between 2006 and 2010 were compared with 4533 patients who underwent conventional AV replacement (AVR) operations between 2001 and 2010. Using propensity score matching, we identified and consecutively compared 2 very similar groups of 167 patients each. The focus was on periprocedural complications and long-term survival.Results: The 30-day mortality rate was 10.8% and 8.4% (P = .56) for the conventional AVR patients and the TAVI patients, respectively. The percentages of postoperative pacemaker implantations (15.0% versus 6.0%, P = .017) and cases of renal failure requiring dialysis (25.7% versus 12.6%, P = .004) were higher in the TAVI group. Kaplan-Meier curves diverged after half a year in favor of conventional surgery. The estimated 3-year survival rates were 53.5% � 5.7% (TAVI) and 66.7% � 0.2% (conventional AVR).Conclusion: Our study shows that even with all the latest successes in catheter-based AV implantation, the conventional surgical approach is still a very good treatment option with excellent long-term results, even for older, high-risk patients.

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Pulmonary Homografts for Aortic Valve Replacement: Long-term Comparison with Aortic Grafts

The Heart Surgery Forum ◽

10.1532/hsf98.20101162 ◽

2011 ◽

Vol 14 (4) ◽

pp. 237 ◽

Cited By ~ 3

Author(s):

Ferdinand Vogt ◽

Anke Kowert ◽

Andres Beiras-Fernandez ◽

Martin Oberhoffer ◽

Ingo Kaczmarek ◽

...

Keyword(s):

Aortic Valve ◽

Aortic Valve Replacement ◽

Valve Replacement ◽

Survival Rates ◽

Long Term Results ◽

Rank Test ◽

Aortic Graft ◽

Valve Prostheses ◽

Retrospective Comparative Study

Objective: The use of homografts for aortic valve replacement (AVR) is an alternative to mechanical or biological valve prostheses, especially in younger patients. This retrospective comparative study evaluated our single-center long-term results, with a focus on the different origins of the homografts.Methods: Since 1992, 366 adult patients have undergone AVR with homografts at our center. We compared 320 homografts of aortic origin and 46 homografts of pulmonary origin. The grafts were implanted via either a subcoronary technique or the root replacement technique. We performed a multivariate analysis to identify independent factors that influence survival. Freedom from reintervention and survival rates were calculated as cumulative events according to the Kaplan-Meier method, and differences were tested with the log-rank test.Results: Overall mortality within 1 year was 6.5% (21/320) in the aortic graft group and 17.4% (8/46) in the pulmonary graft group. In the pulmonary graft group, 4 patients died from valve-related complications, 1 patient died after additional heterotopic heart transplantation, and 1 patient who entered with a primary higher risk died from a prosthesis infection. Two patients died from non-valve-related causes. During the long-term follow-up, the 15-year survival rate was 79.9% for patients in the aortic graft group and 68.7% for patients in the pulmonary graft group (P = .049). The rate of freedom from reoperation was 77.7% in the aortic graft group and 57.4% in the pulmonary graft group (P < .001). The reasons for homograft explantation were graft infections (aortic graft group, 5.0%; pulmonary graft group, 6.5%) and degeneration (aortic graft group, 7.5%; pulmonary graft group, 32.6%).Conclusion: Our study demonstrated superior rates of survival and freedom from reintervention after AVR with aortic homografts. Implantation with a pulmonary graft was associated with a higher risk of redo surgery, owing to earlier degenerative alterations.

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Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

Orvosi Hetilap ◽

10.1556/650.2015.30260 ◽

2015 ◽

Vol 156 (45) ◽

pp. 1824-1833 ◽

Cited By ~ 1

Author(s):

Árpád Illés ◽

Ádám Jóna ◽

Zsófia Simon ◽

Miklós Udvardy ◽

Zsófia Miltényi

Keyword(s):

Stem Cell ◽

Hodgkin Lymphoma ◽

Treatment Options ◽

Survival Rates ◽

Relapse Free Survival ◽

Term Survival ◽

Free Survival ◽

Novel Treatment ◽

Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

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Nanostructured Lipid Carriers (NLCs) for drug delivery: Role of Liquid lipid (oil)

Current Drug Delivery ◽

10.2174/1567201817666200423083807 ◽

2020 ◽

Vol 17 ◽

Author(s):

Anisha D’Souza ◽

Ranjita Shegokar

Keyword(s):

Drug Delivery ◽

Essential Oils ◽

Drug Carrier ◽

Drug Loading ◽

Performance Criteria ◽

Long Term Stability ◽

Natural Oils ◽

Optimal Drug

: In recent years, SLNs and NLCs are among the popular drug delivery systems studied for delivery of lipophilic drugs. Both systems have demonstrated several beneficial properties as an ideal drug-carrier, optimal drug-loading and good long-term stability. NLCs are getting popular due to their stability advantages and possibility to load various oil components either as an active or as a matrix. This review screens types of oils used till date in combination with solid lipid to form NLCs. These oils are broadly classified in two categories: Natural oils and Essential oils. NLCs offer range advantages in drug delivery due to the formation of imperfect matrix owing to the presence of oil. The type and percentage of oil used determines optimal drug loading and stability. Literature shows that variety of oils is used in NLCs mainly as matrix, which is from natural origin, triglycerides class. On the other hand, essential oils not only serve as a matrix but as an active. In short, oil is the key ingredient in formation of NLCs, hence needs to be selected wisely as per the performance criteria expected.

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Herbal Medicine for Glioblastoma: Current and Future Prospects

Medicinal Chemistry ◽

10.2174/1573406416666200130100833 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1022-1043

Author(s):

Imran Khan ◽

Sadaf Mahfooz ◽

Mustafa A. Hatiboglu

Keyword(s):

Cell Proliferation ◽

Survival Rates ◽

Standard Of Care ◽

Natural Compounds ◽

Treatment Modalities ◽

Normal Brain ◽

The Central Nervous System ◽

Cycle Regulation ◽

Immense Potential

Background: Glioblastoma is one of the most aggressive and devastating tumours of the central nervous system with short survival time. Glioblastoma usually shows fast cell proliferation and invasion of normal brain tissue causing poor prognosis. The present standard of care in patients with glioblastoma includes surgery followed by radiotherapy and temozolomide (TMZ) based chemotherapy. Unfortunately, these approaches are not sufficient to lead a favorable prognosis and survival rates. As the current approaches do not provide a long-term benefit in those patients, new alternative treatments including natural compounds, have drawn attention. Due to their natural origin, they are associated with minimum cellular toxicity towards normal cells and it has become one of the most attractive approaches to treat tumours by natural compounds or phytochemicals. Objective: In the present review, the role of natural compounds or phytochemicals in the treatment of glioblastoma describing their efficacy on various aspects of glioblastoma pathophysiology such as cell proliferation, apoptosis, cell cycle regulation, cellular signaling pathways, chemoresistance and their role in combinatorial therapeutic approaches was described. Methods: Peer-reviewed literature was extracted using Pubmed, EMBASE Ovid and Google Scholar to be reviewed in the present article. Conclusion: Preclinical data available in the literature suggest that phytochemicals hold immense potential to be translated into treatment modalities. However, further clinical studies with conclusive results are required to implement phytochemicals in treatment modalities.

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Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis

Leukemia ◽

10.1038/s41375-020-01111-2 ◽

2021 ◽

Author(s):

Hagop M. Kantarjian ◽

Timothy P. Hughes ◽

Richard A. Larson ◽

Dong-Wook Kim ◽

Surapol Issaragrisil ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Survival Rates ◽

Chronic Phase ◽

Individual Treatment ◽

Molecular Response ◽

Newly Diagnosed ◽

Long Term Outcomes ◽

Treatment Free Remission

AbstractIn the ENESTnd study, with ≥10 years follow-up in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase, nilotinib demonstrated higher cumulative molecular response rates, lower rates of disease progression and CML-related death, and increased eligibility for treatment-free remission (TFR). Cumulative 10-year rates of MMR and MR4.5 were higher with nilotinib (300 mg twice daily [BID], 77.7% and 61.0%, respectively; 400 mg BID, 79.7% and 61.2%, respectively) than with imatinib (400 mg once daily [QD], 62.5% and 39.2%, respectively). Cumulative rates of TFR eligibility at 10 years were higher with nilotinib (300 mg BID, 48.6%; 400 mg BID, 47.3%) vs imatinib (29.7%). Estimated 10-year overall survival rates in nilotinib and imatinib arms were 87.6%, 90.3%, and 88.3%, respectively. Overall frequency of adverse events was similar with nilotinib and imatinib. By 10 years, higher cumulative rates of cardiovascular events were reported with nilotinib (300 mg BID, 16.5%; 400 mg BID, 23.5%) vs imatinib (3.6%), including in Framingham low-risk patients. Overall efficacy and safety results support the use of nilotinib 300 mg BID as frontline therapy for optimal long-term outcomes, especially in patients aiming for TFR. The benefit-risk profile in context of individual treatment goals should be carefully assessed.

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Comparison of clinicopathological features and long-term prognosis between mixed predominantly differentiated-type and pure differentiated-type early gastric cancer

BMC Cancer ◽

10.1186/s12885-021-07962-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yutaka Okagawa ◽

Tetsuya Sumiyoshi ◽

Hitoshi Kondo ◽

Yusuke Tomita ◽

Takeshi Uozumi ◽

...

Keyword(s):

Gastric Cancer ◽

Early Gastric Cancer ◽

Vascular Invasion ◽

Survival Rates ◽

Malignant Potential ◽

Clinicopathological Features ◽

Node Metastasis ◽

Group 5 ◽

Long Term Prognosis

Abstract Background Recent studies have shown that mixed predominantly differentiated-type (MD) early gastric cancer (EGC) might have more malignant potential than pure differentiated-type (PD) EGC. However, no study has analyzed all differentiated-type EGC cases treated endoscopically and surgically. This study aimed to compare the differences in clinicopathological features and long-term prognosis between MD- and PD-EGC. Methods We evaluated all patients with differentiated-type EGCs who were treated endoscopically and surgically in our hospital between January 2010 and October 2014. The clinicopathological features and long-term prognosis of MD-EGC were compared with those of PD-EGC. Results A total of 459 patients with 459 lesions were evaluated in this study; of them, 409 (89.1%) and 50 (10.9%) were classified into the PD and MD groups, respectively. Submucosal invasion was found in 96 (23.5%) patients of the PD group and in 33 (66.0%) patients of the MD group (p < 0.01). The rates of positive lymphatic and vascular invasion and ulceration were significantly higher in the MD group than in the PD group (p < 0.01). The proportion of patients with lymph node metastasis was also significantly higher in the MD group than in the PD group (5 (10%) vs 6 (1.5%), p < 0.01). The 5-year overall and EGC-specific survival rates in the PD group were 88.3 and 99.5%, respectively, while they were 94.0 and 98.0% in the MD group, respectively. Conclusions MD-EGC has more malignant potential than PD-EGC. However, the long-term prognosis of MD-EGC is good and is not significantly different from that of PD-EGC when treated appropriately.

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Management of Myositis-Associated Interstitial Lung Disease

Medicina ◽

10.3390/medicina57040347 ◽

2021 ◽

Vol 57 (4) ◽

pp. 347

Author(s):

Tomoyuki Fujisawa

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Current Knowledge ◽

Strong Predictor ◽

Calcineurin Inhibitors ◽

Pulmonary Involvement ◽

Trna Synthetase ◽

Evidence Based Guidelines ◽

Substantial Heterogeneity

Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases characterized by muscular involvement and extramuscular manifestations. Interstitial lung disease (ILD) has major pulmonary involvement and is associated with increased mortality in PM/DM/CADM. The management of PM-/DM-/CADM-associated ILD (PM/DM/CADM-ILD) requires careful evaluation of the disease severity and clinical subtype, including the ILD forms (acute/subacute or chronic), because of the substantial heterogeneity of their clinical courses. Recent studies have highlighted the importance of myositis-specific autoantibodies’ status, especially anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl tRNA synthetase (ARS) antibodies, in order to evaluate the clinical phenotypes and treatment of choice for PM/DM/CADM-ILD. Because the presence of the anti-MDA5 antibody is a strong predictor of a worse prognosis, combination treatment with glucocorticoids (GCs) and calcineurin inhibitors (CNIs; tacrolimus (TAC) or cyclosporin A (CsA)) is recommended for patients with anti-MDA5 antibody-positive DM/CADM-ILD. Rapidly progressive DM/CADM-ILD with the anti-MDA5 antibody is the most intractable condition, which requires immediate combined immunosuppressive therapy with GCs, CNIs, and intravenous cyclophosphamide. Additional salvage therapies (rituximab, tofacitinib, and plasma exchange) should be considered for patients with refractory ILD. Patients with anti-ARS antibody-positive ILD respond better to GC treatment, but with frequent recurrence; thus, GCs plus immunosuppressants (TAC, CsA, azathioprine, and mycophenolate mofetil) are often needed in order to achieve favorable long-term disease control. PM/DM/CADM-ILD management is still a therapeutic challenge for clinicians, as evidence-based guidelines do not exist to help with management decisions. A few prospective clinical trials have been recently reported regarding the treatment of PM/DM/CADM-ILD. Here, the current knowledge on the pharmacologic managements of PM/DM/CADM-ILD was mainly reviewed.

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