scholarly journals Sustained efficacy and safety of burosumab, a monoclonal antibody to FGF23, in children with X-linked hypophosphatemia

2021 ◽  
Author(s):  
Agnès Linglart ◽  
Erik A Imel ◽  
Michael P Whyte ◽  
Anthony A Portale ◽  
Wolfgang Högler ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Treatment Options ◽  
Dose Finding ◽  
Serum Phosphorus ◽  
Fasting Serum ◽  
Open Label ◽  
Treatment Groups ◽  
Clinical Consequences

Abstract Purpose In X-linked hypophosphatemia (XLH), excess FGF23 causes hypophosphatemia and low calcitriol, leading to musculoskeletal disease with clinical consequences. XLH treatment options include conventional oral phosphate with active vitamin D, or monotherapy with burosumab, a monoclonal antibody approved to treat children and adults with XLH. We have previously reported outcomes up to 64 weeks, and here, we report safety and efficacy follow-up results up to 160 weeks from an open-label, multicenter, randomized, dose-finding trial of burosumab for 5 to 12 year-old children with XLH. Methods After one week of conventional therapy washout, patients were randomized 1:1 to burosumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 64 weeks, with dosing titrated based on fasting serum phosphorus levels between baseline and Week 16. From Week 66 to Week 160, all patients received Q2W burosumab. Results Twenty-six children were randomized initially into each Q2W and Q4W group and all completed treatment to Week 160. In 41 children with open distal femoral and proximal tibial growth plates (from both treatment groups), total Rickets Severity Score significantly decreased by 0.9±0.1 (least squares mean±SE; p<0.0001) from baseline to Week 160. Fasting serum phosphorus increases were sustained by burosumab therapy throughout the study, with an overall population mean (SD) of 3.35 (0.39) mg/dL, within the pediatric normal range (3.2 to 6.1 mg/dL) at Week 160 (mean change from baseline p<0.0001). Most adverse events were mild to moderate in severity. Main conclusions In children with XLH, burosumab administration for 160 weeks improved phosphate homeostasis and rickets and was welltolerated. Long-term safety was consistent with the reported safety profile of burosumab.

Antiretroviral Treatment-Associated Labia Majora Lipohypertrophy: A Rare Case and Plastic Surgical Treatment Options

2017 ◽  
Vol 2 (1) ◽  
pp. 43
Author(s):  
Akmal Hisham ◽  
Devananthan Ilenghoven ◽  
Wan Syazli Wan Ahmad Kamal ◽  
Salina Ibrahim ◽  
Shah Jumaat Mohd Yussof
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Daily Living ◽  
Treatment Options ◽  
Hiv Positive ◽  
Highly Active ◽  
Labia Majora ◽  
The Face ◽  
Central Fat

The emergence of highly active antiretroviral therapy (HAART) has revolutionized the prognosis of HIV-infected patients. However, the extended use of HAART is associated with a disfiguring complication termed lipodystrophy, a disorder of body fat maldistribution causing peripheral fat loss (lipoatrophy) and central fat accumulation (lipohypertrophy). Lipoatrophy commonly affects the face, legs, buttocks and arm, whilst lipohypertrophy frequently favours the abdomen, breast and dorsocervical region. To our knowledge, we present only the second documented case in the literature of a labia majora lipohypertrophy in a HIV-positive patient receiving long-term HAART. The severity of labial abnormality caused significant physical and functional morbidities. Labiaplasty with dermolipectomy of the labia majora and excisional lipectomy of the mons pubis was successfully performed. At a 6-month follow-up, patient had no recurrence with resolution of symptoms and resumption of normal activities of daily living (ADL).

scholarly journals Rituximab-Containing Risk-Adapted Treatment Strategy in Nodular Lymphocyte Predominant Hodgkin Lymphoma: 7-Years Follow-Up

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1760
Author(s):  
Novella Pugliese ◽  
Marco Picardi ◽  
Roberta Della Pepa ◽  
Claudia Giordano ◽  
Francesco Muriano ◽  
...  
Keyword(s):  
Side Effects ◽  
Hodgkin Lymphoma ◽  
Prognostic Score ◽  
Single Agent ◽  
Response To Therapy ◽  
Baseline Risk ◽  
Historical Cohort ◽  
Treatment Groups

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.

Cuboid nutcracker fracture in a 9-year-old child

2021 ◽  
Vol 14 (2) ◽  
pp. e240441
Author(s):  
Tannous Jorge Sassine ◽  
Bernardo Barcellos Terra ◽  
Vincenzo Giordano ◽  
Benno Ejnisman
Keyword(s):  
Direct Reduction ◽  
Treatment Options ◽  
Compression Fracture ◽  
Medium Term ◽  
Lateral Column ◽  
Cuboid Bone ◽  
Long Term Follow Up ◽  
Type Of Fracture

A 9-year-old girl presented to the emergency department reporting intense pain and inability to bear weight on her left foot after a classmate tripped over it. Imaging studies confirmed a fracture of the cuboid bone due to compression of the lateral column of the foot (also known as nutcracker fracture). The patient was treated surgically, with direct reduction of the compression fracture and definitive fixation with two Kirschner wires. Cuboid nutcracker fracture is rare in children and adolescents, and potential consequences can occur if it is not correctly diagnosed and adequately managed. Literature on this type of fracture is scarce, along with information on treatment options and results over medium-term and long-term follow-up. We describe this case and review the literature on this particular topic.

Open Surgical versus Minimally Invasive in Situ Femorodistal Bypass: Long-term Results

2003 ◽  
Vol 10 (1) ◽  
pp. 117-120 ◽  
Author(s):  
Nomdo S. Renken ◽  
Cees H.A. Wittens ◽  
Peter M.T. Pattynama ◽  
Nico A.J.J. Du Bois ◽  
Lukas C. van Dijk
Keyword(s):  
Minimally Invasive ◽  
Limb Salvage ◽  
Long Term Results ◽  
Open Technique ◽  
Treatment Groups ◽  
Closed Technique ◽  
Open Versus

Purpose: To compare long-term patency and limb survival rates for the classical in situ surgical bypass procedure versus a minimally invasive technique for femorodistal revascularization. Methods: From May 1992 to June 1994, a prospective multicenter study was undertaken at 4 centers to evaluate the open versus closed technique for femorodistal bypass grafting. Of 97 patients enrolled in the trial, 73 patients (49 men; mean age 71 years) were assigned to the long-term follow-up protocol and prospectively randomized to the open (n = 38) or closed (n = 35) procedure. The classical open technique is characterized by a long incision over the length of the bypass graft, while the minimally invasive procedure involves only two short incisions over each anastomosis site (the side branches are closed with a coaxial embolization catheter system). Graft patency was evaluated with duplex imaging periodically throughout the 4-year observation period. Results: There was no statistically significant difference between the treatment groups with respect to age, sex, hypertension, ischemic heart disease, or smoking. However, the open group had a significantly greater incidence of diabetes (p = 0.037). Over a median 4.7-year follow-up (range 0.3–6.4), 9 (12%) patients (3 open and 6 closed) were lost to follow-up: 2 died and 7 refused the duplex examination. No significant differences in 4-year patency, limb salvage, or survival was demonstrated between the open versus closed treatment groups; 4-year secondary patency was 62% versus 64%, respectively, and limb salvage was 72% versus 86%. Conclusions: The closed technique for femorodistal in situ bypass procedures yields favorable long-term outcomes compared to the traditional open technique.

Angiolymphoid Hyperplasia with Eosinophilia (Histiocytoid Hemangioma): Evaluation of Treatment Options

1993 ◽  
Vol 102 (4) ◽  
pp. 303-308 ◽  
Author(s):  
Mack L. Cheney ◽  
Samir Bhatt ◽  
Paul Googe ◽  
Patricia L. Hibberd
Keyword(s):  
Treatment Options ◽  
Clinical Problem ◽  
Radical Excision ◽  
Angiolymphoid Hyperplasia With Eosinophilia ◽  
Angiolymphoid Hyperplasia ◽  
Immunodeficiency Virus ◽  
Long Term Follow Up ◽  
Proliferative Lesion

Angiolymphoid hyperplasia with eosinophilia is an uncommon benign vascular proliferative lesion of unknown cause. In this report, a case is presented of a patient who was confirmed to be positive for human immunodeficiency virus and in whom the lesion had shown rapid accelerated growth. The case is used to illustrate a variety of therapeutic techniques and to evaluate the effectiveness of the various alternatives in the treatment of this unusual clinical problem. Long-term follow-up after radical excision of the tumor mass is presented.

scholarly journals Chronic Health Conditions and Late Mortality Among Survivors of Childhood Acute Myeloid Leukemia: A Report from the Childhood Cancer Survivor Study (CCSS)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1315-1315
Author(s):  
Lucie M Turcotte ◽  
John A Whitton ◽  
Wendy M. Leisenring ◽  
Todd Gibson ◽  
Rebecca M Howell ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Health Conditions ◽  
Late Mortality ◽  
Treatment Groups ◽  
Childhood Acute Myeloid Leukemia ◽  
Health Related ◽  
Related Mortality

Introduction: Five-year survival following childhood acute myeloid leukemia (AML) has doubled over the last 4 decades due to advances in treatment and supportive care, including more widespread use of hematopoietic cell transplantation (HCT). The impact on long-term morbidity and mortality among survivors is unknown. Methods: Cumulative incidence and 95% confidence intervals (CI) for overall and cause-specific late (>5 years from diagnosis) mortality and CTCAE grades 3-5 chronic health conditions (CHC) were estimated among 5-year survivors of AML diagnosed <21 years of age between1970-99 in the CCSS. Comparisons were made by decade of diagnosis (1970s, 1980s, 1990s) and treatment (HCT vs. chemotherapy only [chemo-only]). Cox regression models estimated hazard ratios (HR) for health-related deaths and CHC based on treatment decade and HCT status. Results: Among 927 AML survivors (median age at diagnosis 7.1 years [range 1-21 years]; median age at last follow-up 29.4 years [range 8-60 years]; 16,069 person-years of follow-up; 37% treated with HCT [15% of 1970s survivors, 36% of 1980s survivors, 44% of 1990s survivors), the 20-year cumulative incidence of all-cause mortality was 6.7% (CI 4.2-9.2%) for chemo-only survivors and 13.5% (CI 9.2-17.8%) for HCT survivors. For chemo-only survivors, the highest incidence of health-related mortality were attributable to cardiac causes (1.5%, CI 0.5-2.6), relapse (0.9%, CI 0.1-1.8), and SMN (0.6%, CI 0.0-1.2), whereas for HCT survivors the highest health-related causes of death were relapse (6.5%, CI 3.7-9.2%), SMN (1.3%, CI 0-2.5%), and pulmonary causes (0.6%, CI 0-1.5%). When treatment groups were considered in multivariable Cox models, risk for late mortality was similar for chemo-only survivors from the 1990s compared to the 1970s (HR 0.4, CI 0.1-1.4), but risk was reduced for HCT survivors from the 1990s compared to the 1970s (HR 0.2, CI 0.1-0.4). The 20-year cumulative incidence of grade 3-5 CHCs among chemo-only survivors was 26.9% (CI 23.0-30.7%) compared to 46.8% (CI 40.9-52.7%) among HCT survivors, with the highest incidence occurring for cardiovascular CHC (chemo-only, 9.7%, CI 7.1-12.2%; HCT, 10.6%, CI 7.0-14.2%), pulmonary CHC (chemo-only, 1.0%, CI 0.1-1.9%; HCT, 2.9%, CI 1.0-4.8%) and SMN (chemo-only, 0.8%, CI 0.0-1.7%; HCT, 5.7%, CI 2.9-8.6%). Incidence of overall CHC decreased in more recent decades among HCT survivors (p=0.03, Figure); however, among chemo-only survivors, CHC incidence did not significantly change by decade (p=0.12). When treatment groups were considered in adjusted models, risk for CHC was similar for those treated in the 1990s compared to the 1970s among chemo-only survivors (HR 1.5, CI 1.0-2.3) and risk estimates among HCT survivors decreased over time but did not achieve statistical significance (HR 0.6, CI 0.3-1.1). Conclusions: AML survivors treated with HCT had a reduced risk of late mortality and serious CHC in more recent treatment eras. In contrast, treatment with chemo-only was not associated with differences in mortality and serious CHC risk over time. Five-year survivors treated with chemo-only had a significantly reduced risk of health-related mortality compared with HCT survivors across all treatment eras. While treatment intensification with HCT has improved the cure rates for AML in recent decades, there remains disparity in long-term outcomes among AML survivors treated with HCT vs. chemo-only. Disclosures No relevant conflicts of interest to declare.

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