Gingival neurofibroma in a neurofibromatosis type 1 patient

Neurofibroma is a benign peripheral nerve sheath tumour. It is one of the most frequent tumours of neural origin and its presence is one of the clinical criteria for the diagnosis of type 1 neurofibromatosis (NF-I). Neurofibromatosis type 1 is an autosomal dominantly inherited disease due to an alteration in the long arm of chromosome 17. About 50% of NF-I patients have no family history of the disease. NF-I patients have skin lesions (cafe au lait spots and neurofibromas) as well as bone malformations and central nervous system tumours. Diagnosis is based on a series of clinical criteria. Gingival neurofibroma in NF-I is uncommon. Treatment of neurofibromas is surgical resection. The aim of this paper is to report a case of NF-I with gingival involvement and to review the literature.     

ASO Visual Abstract: Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Cancers with Peritoneal Metastasis—A 30-year Institutional Experience

Annals of Surgical Oncology -     

Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome

Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined. In order to establish how constitutive mutation of DNMT3A impacts blood development in TBRS we gathered clinical data and analyzed blood parameters in 18 individuals with TBRS. We also determined the distribution of major peripheral blood cell lineages by flow cytometric analyses. Our analyses revealed non-anemic macrocytosis, a relative decrease in lymphocytes and increase in neutrophils in TBRS individuals compared to unaffected controls. We were able to recapitulate these hematologic phenotypes in multiple murine models of TBRS and identified rare hematological and non-hematological malignancies associated with constitutive Dnmt3a mutation. We further show that loss of DNMT3A in TBRS is associated with an altered DNA methylation landscape in hematopoietic cells affecting regions critical to stem cell function and tumorigenesis. Overall, our data identify key hematopoietic effects driven by DNMT3A mutation with clinical implications for individuals with TBRS and DNMT3A-associated clonal hematopoiesis or malignancies.     

Expert opinion: defining response to omalizumab in patients with chronic spontaneous urticaria

Omalizumab (a recombinant, humanized anti-immunoglobulin-E anti-body) has been shown in three pivotal Phase III trials (ASTERIA I, II and GLACIAL) and real-world studies to be effective and well-tolerated for the treatment of chronic spontaneous urticaria (CSU), and is the only licensed third-line treatment for CSU. However, the definition of response to omalizumab treatment often differs between clinical trials, real-world studies, and daily practice of individual physicians globally. As such, a consensus definition of “complete”, “partial” and “non-response” to omalizumab is required in order to harmonize treatment management and compare data. Here, it is proposed that a disease measurement tool, for example, the 7-Day Urticaria Activity Score (UAS7) or Urticaria Control Test (UCT) is required for defining response. The addition of quality of life measurements is helpful to gain insight into a patient’s disease burden and its changes during treatment. A potential omalizumab treatment approach based on speed and pattern of response at 1-3 and 3-6 months is suggested. In cases where there is no response during the first 1-3 months, physicians should consider reassessing the original CSU diagnosis. Moreover, in patients showing partial response at 12 weeks, treatment with omalizumab should be continued in order to maximize the possibility of achieving symptom control. If patients have a UAS7>6 and/or UCT<12, then continued treatment is advised, dependent on physician judgement and patient expectations. In treatment responders, omalizumab treatment can be resumed at a later stage after discontinuation with the same degree of symptom control.     

Intraarterial urokinase for acute native arterial occlusion of the limbs

Since 1988, 49 limbs of 47 patients underwent intraarterial urokinase infusion for acute native artery occlusion. The time from the onset of ischemic symptoms ranged from 1 to 45 days (mean = 17.5). The arterial sectors involved were femoropopliteal in 32 cases, followed by aortoiliac in 13 cases, distal in three cases, and subclavian in one case. Treatment consisted of placing a catheter in the clot and the infusion of 4400 U/kg in 20′, followed by a series of 4400 U/kg weight/hour during 6 hours. Clinical evaluation, hemodinamic and coagulation parameters, and angiographical changes were assessed periodically. Infusion time ranged from 6 to 24 hours (mean = 13.2 hours). Improvement of ischemia was achieved in 43 (87.75%) patients. In five patients (12.25%) there was no improvement. Total immediate lysis was achieved in 35 cases (71.5%), and among them, 13 patients (26%) required no associated treatment, 16 (48%) underwent PTA, and four (12%) had surgery of underlying peripheral aneurysms revealed after thrombolysis. Partial lysis was achieved in 13 cases (26.5%), that was enough in four of them, but the remaining nine required further treatment (four PTA, and five arterial surgery). In one case no lysis was achieved, and arterial surgery was carried out. No mortality was recorded, and major complications included one upper gastrointestinal bleeding, and one cerebral hematoma. Late follow-up of successfully treated patients who did not require further surgery shows a cumulative patency rate of 81% at 24 months. (Ann Vasc Surg 1997; 11:565-573.)     

Fast Track: urgent care within a teaching hospital emergency department: can it work?

We performed a ten-week study to understand the feasibility of a fast track system within a teaching hospital setting. Our results show that 50% or fewer of patients entering an emergency department during evening and weekend day hours can be seen in Fast Track. Average turnaround time for all patients in the ED was 161 minutes. The average for all Fast Track patients was 94.5 minutes; if laboratory and/or radiographs were ordered the average was 121.5 minutes; with no laboratory/radiographs, 79.1 minutes. Urinalysis, strep screen, and complete blood count accounted for 80% of all laboratory work. Roentgenograms of the ankle, foot, and knee accounted for 80% of all radiographs. An evaluation questionnaire showed enhanced satisfaction with a reduction in the number of complaints from 79% to 22%. The Fast Track system failed when there was a predominance of acutely ill patients in the ED, as house officers were pulled to care for the acutely ill patients.