Citations

PURPOSE: To determine the toxicity and response rate in children treated with dexamethasone, etoposide, cisplatin, high-dose cytarabine, and l-asparaginase (DECAL) for recurrent non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease (HD). PATIENTS AND METHODS: Ninety-seven children with recurrent NHL (n = 68) or HD (n = 29) were enrolled. Treatment consisted of two cycles of DECAL, then bone marrow transplantation or up to four cycles of ifosfamide, mesna, and etoposide alternating with DECAL maintenance therapy. RESULTS: After two cycles of DECAL induction therapy, complete response (CR) or partial response (PR) was reported in 19 (65.5%; 10 CRs and nine PRs) of 29 patients with HD and 29 (41.6%; 23 CRs and six PRs) of 68 patients with NHL. When only 24 patients with HD and 58 patients with NHL who were assessable for response were considered, the response rates were 79.2% (19 of 24 patients) and 50.0% (29 of 58 patients), respectively. Five-year event-free survival was 26% ± 9% and 23% ± 5% in patients with HD and NHL, respectively. Five-year survival was 31% ± 14% and 30% ± 6%, respectively. Although median time to treatment failure was significantly longer in patients with HD (EFS, P = .002; survival, P = .011), this difference did not translate into a higher long-term survival. Grade 3 or 4 toxic effects were observed during induction in 70 (72%) of 97 patients and during maintenance in 45 (70%) of 64 courses of DECAL therapy. Pancytopenia and systemic infections in particular were frequently observed. Other toxic effects were uncommon. Although not a formal part of the therapy or the study design, 42 patients who responded to therapy who underwent bone marrow transplant did not show any benefit from this approach. CONCLUSION: DECAL is an effective and tolerable salvage regimen for treating patients with recurrent NHL and HD.

Background: Surgical indications for Scheuermann kyphosis are variable. We sought to evaluate the characteristics of patients undergoing operative versus nonoperative treatment of Scheuermann kyphosis to better understand current practices and the factors which contribute to the decision for surgical management. Methods: Multicenter prospective cohort study. We evaluated consecutive patients presenting with Scheuermann kyphosis. Patients underwent either surgical or nonoperative management according to surgeon and patient discretion. Preoperative patient-reported outcome measures (Scoliosis Research Society and Spinal Appearance Questionnaire scores), demographics, and radiographic characteristics were assessed. Results: Overall, 150 patients with Scheuermann kyphosis were enrolled, with 77 choosing nonoperative treatment and 73 treated operatively. Compared with the nonoperative cohort, patients treated operatively were older (16.3±2.0 vs. 15.1±2.2, P=0.0004), and had higher body mass index (26.3±7.2 vs. 22.7±6.5, P=0.003), had greater T2-T12 kyphosis (71±14 degrees vs. 61±12 degrees, P<0.001), increased pelvic incidence (46 vs. 41 degrees, P=0.03) and pelvic tilt (10 vs. 3 degrees, P=0.03). There was no detected difference in maximal sagittal Cobb angle in the operative versus nonoperative patients (73±11 vs. 70±12 degrees, P=0.11). Functionally, the operative patients had worse Scoliosis Research Society pain scores (3.7±0.9 vs. 4.1±0.7, P=0.0027) and appearance scores (2.9±0.7 vs. 3.4±0.8, P <0.0001). Conclusions: Patients undergoing surgical management of Scheuermann disease were more likely to have large body mass index and worse pain scores. Other factors beyond radiographic measurement likely contribute to the decision for surgical management of Scheuermann kyphosis. Level of Evidence: Level II.

Significance Antigen recognition by the immune system triggers rapid, specific, and protective responses, which are counterbalanced by inhibitory checkpoints to minimize potentially harmful immunity. The programmed death-1/ programmed death ligand-1 (PD-1/PD-L1) checkpoint is overreactive in cancer patients, curbing antitumor immunity. Whether a failing PD-1/PD-L1 checkpoint contributes to spontaneous autoimmune disease in humans is unknown. Here, we found that in patients with the autoimmune vasculitis giant cell arteritis, antigen-presenting cells provide insufficient negative signaling; unleashing highly activated T cells to infiltrate and damage the walls of large arteries. Thus, immunoinhibitory signals protect large arteries against inflammatory attack and checkpoint activation may be a suitable strategy to treat autoimmune vasculitis.

Prostate cancer is the most common malignancy of men in the United States. Small-cell carcinoma (SCC), which typically presents as an aggressive lung malignancy, is a rare diagnosis within the setting of prostate cancer pathology. Due to its limited prevalence, little information regarding the treatment and prognosis of this disease in large populations is available. To date our current knowledge base is largely limited to case reports and retrospective case reviews. The mainstay of treatment for this particular histology most often involves a multimodality approach utilizing chemotherapy in conjunction with radiation therapy, androgen deprivation therapy, or prostatectomy. Here we present the case of an elderly 89-year-old Caucasian male who was diagnosed with SCC of the prostate. Despite proceeding with a course of definitive radiotherapy, the patient experienced rapid progression of disease and ultimately elected to discontinue radiation therapy and receive hospice care.

ObjectiveTo determine if cholesterol is a risk factor for the development of lower urinary tract symptoms in asymptomatic men.MethodsA post‐hoc analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study was carried out in 2323 men with baseline International Prostate Symptom Score <8 and not taking benign prostatic hyperplasia or cholesterol medications. Cox proportion models were used to test the association between cholesterol, high‐density lipoprotein, low‐density lipoprotein and the cholesterol : high‐density lipoprotein ratio with incident lower urinary tract symptoms, defined as first report of medical treatment, surgery or two reports of an International Prostate Symptom Score >14.ResultsA total of 253 men (10.9%) developed incident lower urinary tract symptoms. On crude analysis, higher high‐density lipoprotein was associated with a decreased lower urinary tract symptoms risk (hazard ratio 0.89, P = 0.024), whereas total cholesterol and low‐density lipoprotein showed no association. After multivariable adjustment, the association between high‐density lipoprotein and incident lower urinary tract symptoms remained significant (hazard ratio 0.89, P = 0.044), whereas no association was observed for low‐density lipoprotein (P = 0.611). There was a trend for higher cholesterol to be linked with higher lower urinary tract symptoms risk, though this was not statistically significant (hazard ratio 1.04, P = 0.054). A higher cholesterol : high‐density lipoprotein ratio was associated with increased lower urinary tract symptoms risk on crude (hazard ratio 1.11, P = 0.016) and adjusted models (hazard ratio 1.12, P = 0.012).ConclusionsAmong asymptomatic men participating in the REDUCE study, higher cholesterol was associated with increased incident lower urinary tract symptoms risk, though the association was not significant. A higher cholesterol : high‐density lipoprotein ratio was associated with increased incident lower urinary tract symptoms, whereas higher high‐density lipoprotein was protective. These findings suggest dyslipidemia might play a role in lower urinary tract symptoms progression.

Early diagnosis of males with X-linked adrenoleukodystrophy (X-ALD) is essential for preventing loss of life due to adrenal insufficiency and for timely therapy of the childhood cerebral form of X-ALD with hematopoietic cell transplantation. This article describes X-ALD, the current therapies, the history of the development of the newborn screening test, the approval by the Secretary of Health and Human Services for the addition of X-ALD newborn screening to the recommended uniform panel of disorders screened as newborns (RUSP) and the successful implementation of X-ALD newborn screening in the state of New York beginning on 30 December 2013. Follow-up guidelines that have been established in New York are outlined. Based on the success of newborn screening in New York, and early results in Connecticut, where X-ALD newborn screening started in December 2015, and in California, where X-ALD newborn screening began in September 2016, we are confident and hopeful that X-ALD newborn screening will expand to include all US states and to countries that have established neonatal screening programs. The Minster of Health in the Netherlands has approved the addition of X-ALD to the newborn screening program with a start date expected in 2017. The states, such as Massachusetts, Illinois, Minnesota, New Jersey, Florida and Washington, that have legislative approval will commence screening as soon as budgetary resources, testing and follow-up procedures are in place.

Aims To examine the need for minimal diagnostic criteria for post-transplant lymphoproliferative disorders (PTLD) in children, we sought to determine the rate of incidental Epstein-Barr virus (EBV)-positivity in tissues from organ transplant recipients (OTR). Methods EBV in situ hybridisation (ISH) was done retrospectively on tissue from 34 paediatric autopsies of OTR and paediatric tonsillectomy specimens from non-OTR (96) and OTR (6). Patients with a history of PTLD were excluded from both data sets. Results EBV-positivity was found incidentally in 2/34 autopsy cases (5.9%). Median time from transplant to death for all patients was 12.8 months (range 0.1–153 months). Median time between transplant and death in EBV-positive cases was 34 months. EBV was positive in 26/102 tonsils (25%). Among tonsils from OTR, 4/6 (67%) were EBV-positive. Conclusions These findings reinforce the need for strict morphological and clinical criteria, other than EBV-positivity, when diagnosing PTLD in the paediatric population.

IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody–producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy–proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin–converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8–2.4) mg/dl, and proteinuria was 2.1 (0.6–5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose–deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.