Citations

Abstract Human induced pluripotent stem cells (hiPSC) hold great promise in diagnostic and therapeutic applications. However, translation of hiPSC technology depends upon a means of assessing hiPSC quality that is quantitative, high-throughput, and can decipher malignant teratocarcinoma clones from normal cell lines. These attributes are lacking in current approaches such as detection of cell surface makers, RNA profiling, and/or teratoma formation assays. The latter remains the gold standard for assessing clone quality in hiPSCs, but is expensive, time-consuming, and incompatible with high-throughput platforms. Herein, we describe a novel method for determining hiPSC quality that exploits pluripotent cells’ documented hypersensitivity to the topoisomerase inhibitor etoposide (CAS No. 33419-42-0). Based on a study of 115 unique hiPSC clones, we established that a half maximal effective concentration (EC50) value of <300 nM following 24 hours of exposure to etoposide demonstrated a positive correlation with RNA profiles and colony morphology metrics associated with high quality hiPSC clones. Moreover, our etoposide sensitivity assay (ESA) detected differences associated with culture maintenance, and successfully distinguished malignant from normal pluripotent clones independent of cellular morphology. Overall, the ESA provides a simple, straightforward method to establish hiPSC quality in a quantitative and functional assay capable of being incorporated into a generalized method for establishing a quality control standard for all types of pluripotent stem cells.

BackgroundPatients who have granulomatosis with polyangiitis (GPA, syn. M. Wegener) often develop an external nose deformity which may have devastating psychological effects. Therefore, reconstruction of nasal deformities by rhinoplasty may become necessary to achieve a normal appearance.Objective of reviewThe aim of this systematic review was to investigate the efficacy and safety of surgical reconstruction in external nasal deformities and septal perforation in GPA patients.Search strategyA systematic literature search with defined search terms was performed for scientific articles archived in the MEDLINE‐Database up to 10 June 2016 (PubMed Advanced MEDLINE Search), describing management of cases or case series in GPA patients with saddle nose deformity and/or septal perforation.ResultsEleven of 614 publications met the criteria for this analysis including 41 GPA patients undergoing external nasal reconstruction and/or septal reconstruction with a median follow‐up of 2.6 years. Overall, saddle nose reconstruction in GPA patients is safe even if an increased rate of revision surgery has to be expected compared with individuals without GPA undergoing septorhinoplasty. Most implanted grafts were autografts of calvarial bone or costal cartilage. For septal perforation reconstruction, few studies were available. Therefore, based on the available data for surgical outcomes, it is impossible to make evidence‐based recommendations. All included GPA patients had minimal or no local disease at the time of reconstructive surgery. Therefore, the relationship between disease activity and its impact on surgical outcomes remains unanswered. The potential impact of immune‐modulating medications on increased complication rates and the impact of prophylactic antibiotics are unknown.ConclusionsThis study systematically reviews the efficacy and safety of surgical reconstruction of external nasal deformities in GPA patients for the first time. Saddle nose reconstruction in GPA patients with minimal or no local disease is a safe procedure despite an increased rate of revision surgery. Further research is required regarding the impact of antibiotic prophylaxis, immune‐modulating therapy, long‐term outcomes and functional outcomes measured with subjective and objective parameters.

Indeterminate dendritic cell neoplasm (IDCN) is an exceedingly rare and mostly cutaneous histiocytosis, frequently associated with other hematopoietic malignancies. We report 2 cases of multilesional cutaneous IDCN. A 55‐year‐old male with no associated malignancy and complete response to ultraviolet phototherapy; and a 72‐year‐old male with chronic myelomonocytic leukemia (CMML). Both cases showed histiocytoid cytology, positivity for CD1a and no expression of langerin or BRAFV600E. With our patients, the literature describes 79 cases of IDCNs, including 65 (82%) with only skin involvement, 7 cases (9%) with involvement of skin and a second site, 5 cases (6%) involving lymph nodes only, 1 splenic lesion and 1 systemic disease. Seventeen cases (22%) were associated with other hematopoietic malignancies, most commonly CMML (6 cases), follicular lymphoma (4 cases) and acute myeloid leukemia (3 cases). All IDCNs associated with myeloid malignancies were limited to the skin, while most cases associated with lymphoma were limited to lymph nodes. Reported responses of cutaneous lesions to ultraviolet phototherapy are encouraging, while systemic chemotherapy is appropriate for clinically aggressive cases and treatment of associated malignancies. Recognition of the clinico‐morphologic spectrum of IDCNs should prevent misdiagnoses and prompt investigation of possible associated neoplasms.

Abstract Background Wireless motility capsule ( WMC ) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. Methods A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMC s on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. Key Results Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times ( GET ) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel ( SBTT ) and colon transit ( CTT ) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics ( P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT , and fewer gastric contractions ( P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores ( P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions ( P = .03). Diarrhea scores were higher with delayed SBTT and CTT ( P ≤ .04). Conclusions & Inferences Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.

Background Complication avoidance is paramount to the success of any surgical procedure. In the case of spine tumor surgery, the risk of complications is increased because of the primary disease process and the radiotherapy and chemotherapeutics used to treat the disease. If complications do occur, then life-saving adjuvant treatment must be delayed or withheld until the issue is resolved, potentially impacting overall disease control. Methods We reviewed the literature and our own best practices to provide recommendations on complication avoidance as well as the management of complications that may occur. Appropriate workup of suspected complications and treatment algorithms are also discussed. Results Appropriate patient selection and a multidisciplinary workup are imperative in the setting of spinal tumors. Intraoperative complications may be avoided by employing proper surgical technique and an understanding of the pathological changes in anatomy. Major postoperative issues include wound complications and spinal reconstruction failure. Preoperative surgical planning must include postoperative reconstruction. Patients undergoing spinal tumor resection should be closely monitored for local tumor recurrence, recurrence along the biopsy tract, and for distant metastatic disease. Any suspected recurrence should be closely watched, biopsied if necessary, and promptly treated. Conclusions Because patients with spinal tumors are normally treated with a multidisciplinary approach, emphasis should be placed on the recognition of surgical complications beyond the surgical setting.

Background Primary tumors are rare and those localized to a single location offer the potential for cure. To achieve this, early recognition of the primary tumor and proper workup and treatment are essential. Methods The authors reviewed the literature and best practices to provide recommendations on primary spine tumor treatment. Appropriate workup of primary spine tumors and treatment algorithms are also discussed. Results Patients suspected of a primary spine tumor should undergo fine-needle aspirate biopsy following consultation with the surgical team to ensure the biopsy tract is surgically resectable should the need arise. Once pathology is confirmed, metastatic workup should be performed to guide the level of treatment. If a localized lesion with poor radiation and chemotherapeutic response is diagnosed, then en bloc resection may be required for cure. If en bloc resection is not feasible or metastatic lesions are present, then radiation and medical oncology specialists must work in conjunction with the surgical team to determine the best treatment options. Conclusions Patients with suspected primary tumors of the spine should be treated in a multidisciplinary fashion from the outset. With thoughtful management, these lesions offer the opportunity for surgical cure.

Abstract Assessing tactile function among children with intellectual, motor, and communication impairments remains a clinical challenge. A case control design was used to test whether children with global developmental delays (GDD; n = 20) would be more/less reactive to a modified quantitative sensory test (mQST) compared to controls (n = 20). Reactivity was indexed by blinded behavioral coding across vocal, facial, and gross motor responses during the mQST. On average the children with GDD were significantly more reactive than controls to most tactile sensory modalities including light touch (p = .034), pin prick (p = .008), cool (p = .039), pressure (p = .037), and repeated von Frey (p = .003). The results suggest the mQST approach was feasible and highlights the GDD sample was more reactive than controls to a range of stimuli.