Treatment with Glucocorticoids or Calcineurin Inhibitors in Primary FSGS

Background and objectives

In primary FSGS, calcineurin inhibitors have primarily been studied in patients deemed resistant to glucocorticoid therapy. Few data are available about their use early in the treatment of FSGS. We sought to estimate the association between choice of therapy and ESRD in primary FSGS.

Design, setting, participants, & measurements

We used an inception cohort of patients diagnosed with primary FSGS by kidney biopsy between 1980 and 2012. Factors associated with initiation of therapy were identified using logistic regression. Time–dependent Cox models were performed to compare time to ESRD between different therapies.

Results

In total, 458 patients were studied (173 treated with glucocorticoids alone, 90 treated with calcineurin inhibitors with or without glucocorticoids, 12 treated with other agents, and 183 not treated with immunosuppressives). Tip lesion variant, absence of severe renal dysfunction (eGFR≥30 ml/min per 1.73 m²), and hypoalbuminemia were associated with a higher likelihood of exposure to any immunosuppressive therapy. Only tip lesion was associated with initiation of glucocorticoids alone over calcineurin inhibitors. With adjusted Cox regression, immunosuppressive therapy with glucocorticoids and/or calcineurin inhibitors was associated with better renal survival than no immunosuppression (hazard ratio, 0.49; 95% confidence interval, 0.28 to 0.86). Calcineurin inhibitors with or without glucocorticoids were not significantly associated with a lower likelihood of ESRD compared with glucocorticoids alone (hazard ratio, 0.42; 95% confidence interval, 0.15 to 1.18).

Conclusions

The use of immunosuppressive therapy with calcineurin inhibitors and/or glucocorticoids as part of the early immunosuppressive regimen in primary FSGS was associated with improved renal outcome, but the superiority of calcineurin inhibitors over glucocorticoids alone remained unproven.     

Telmisartan in the Treatment of Cohen-Rosenthal Diabetic Hypertensive Rats: The Benefit of PPAR-γ Agonism

The antihypertensive and hypoglycemic effects of telmisartan, which has dual angiotensin II antagonist-PPAR-γ agonist properties, was studied in Cohen-Rosenthal Diabetic Hypertensive rats (CRDH), a model in which hypertension, insulin resistance, and diabetes co-exist. CRDH, Cohen-diabetic rats (CDR), and SHR received telmisartan (3 mg/kg/day in drinking water) for five months. Telmisartan significantly lowered systolic and diastolic BP in SHR and CRDH, independent of body weight, and remained fairly constant in controls throughout the experiment. Blood glucose levels fell rapidly in the treated animals and remained steady in controls. Results indicate that telmisartan is a prototype of a new approach to treating coexisting diabetes and hypertension.     

Granulocytic sarcoma of the ileum treated by bone marrow transplantation

An 8-year-old boy with a granulocytic sarcoma of the proximal ileum metastatic to mesenteric lymph nodes was placed into complete remission with surgical excision of the primary tumor and conventional induction chemotherapy with daunorubicin and cytosine arabinoside. He was then treated with high dose cytosine arabinoside, fractionated total body irradiation, and allogeneic marrow transplantation from his 22-month-old brother who was completely matched at the major histocompatibility complex. Methotrexate was given following the transplant to prevent graft-versus-host disease (GVHD). His post-transplantation course was complicated by a transient autoimmune hemolytic anemia related to an ABO blood group incompatibility and hepatic fungal microabscesses which responded to Amphotericin therapy. Four years following the transplant the patient remains in complete remission. The prognosis for patients with granulocytic sarcoma has been poor although, perhaps, improved over the past decade. This is the first published case report of successful treatment of a granulocytic sarcoma of the ileum by allogeneic marrow transplantation.     

Suicide in Israel: 1985-1997

OBJECTIVE: To examine trends in suicide rates in Israel over a 13-year period. METHOD: All cases of autopsy-confirmed suicide in Israel from 1985 to 1997 were retrospectively reviewed. RESULTS: An overall annual increase in suicide rates, with rates in men 3 times higher than those in women, was observed. Suicide rates were highest in the second and third decades of life. Unlike Western countries where gunshot wounds are the most common method of suicide for men and poisoning is most common for women, asphyxiation by hanging was the most common method used by men in Israel, followed by firearm wounds and jumping from heights. In women, however, jumping from heights was the most common method, followed by hanging and poisoning. CONCLUSION: Increasing rates of suicide may be associated with waves of immigration to Israel, increased substance abuse and depression and the political and social climate. Further study to examine the precipitating factors is warranted.     

Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy.

PURPOSE: Current standard therapy for children and adolescents with Hodgkin's disease includes combination chemotherapy and low-dose involved-field radiation (LD-IFRT). Because radiation may be associated with adverse late effects, the Children's Cancer Group (CCG) investigated whether radiation could be omitted in patients achieving a complete response to initial chemotherapy without jeopardizing the excellent outcome obtained with combined-modality therapy. PATIENTS AND METHODS: Between January 1995 and December 1998, 829 eligible patients were enrolled onto CCG 5942. A total of 501 patients who achieved an initial complete response after risk-adapted combination chemotherapy were randomized to receive LD-IFRT or no further treatment. Event-free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate. RESULTS: The projected 3-year EFS from study entry for the entire cohort was 87% +/- 1.2%. Among patients who achieved a complete response to initial chemotherapy, 92% +/- 1.9% of those randomized to receive LD-IFRT were alive and disease free 3 years after randomization, versus 87% +/- 2.2% for patients randomized to receive no further therapy (stratified log-rank test; P =.057). With an "as-treated" analysis, 3-year EFS after randomization for the radiation cohort was 93% +/- 1.7% versus 85% +/- 2.3% for patients receiving no further therapy (stratified log-rank test; P =.0024). Three-year survival estimates for patients treated with and without LD-IFRT were 98% +/- 1.1% for patients who received radiation and 99% +/- 0.5% for patients who did not receive radiation. CONCLUSION: LD-IFRT after an initial complete response to risk-adapted chemotherapy improved EFS. At this time, there is no survival advantage for LD-IFRT, but follow-up remains short.     

The Eighth International Childhood Acute Lymphoblastic Leukemia Workshop ('Ponte di legno meeting') report: Vienna, Austria, April 27-28, 2005.

The International Acute Lymphoblastic Leukemia Working Group, the so-called 'Ponte di Legno Workshop' has led to substantial progress in international collaboration in leukemia research. On April 27-28, 2005, the 8th Meeting was held in Vienna, Austria, to continue the discussions about special common treatment elements in randomized clinical trials, ethical and clinical aspects of therapy. Furthermore, collaborative projects of clinical relevance with special emphasis on rare genetic subtypes of Childhood ALL were established. The following report summarizes the achievements and aspects of possible future cooperation.     

Statement by members of the Ponte di Legno group on the right of children with leukemia to have full access to essential treatment for acute lymphoblastic leukemia.

During the panel discussion in the Sixth International ChildhoodAcute Lymphoblastic Leukemia (ALL) meeting of the Ponte di LegnoWorking Group, held in San Diego in December 2003, it was apparentthat recent improvements in treatment have further paradoxicallywidened the gap of inequality between children living in resource-richcountries and those in low-income countries. The representativesfrom 15 leading study groups and institutions decided to issuea statement [1] to lobby international and national agenciesto provide the necessary drugs at affordable cost throughoutthe world for children with ALL or other highly curable cancer.We wish to draw a wider readership and support