Postoperative radiotherapy delay in head and neck cancer patients undergoing major resection and free flap reconstruction.

BACKGROUND: Delays to postoperative radiotherapy (PORT) are frequent and associated with poorer oncologic outcomes in head and neck cancer (HNC) patients. Free flap patients have been suggested as the most at-risk group. Thus, PORT delivery experienced by HNC patients who required a free flap reconstruction was analysed, identifying reasons for the delays if any. METHODS: A retrospective analysis of a single tertiary unit's PORT delivery to HNC patients undergoing major resection followed by free flap reconstruction between 2017 and 2020. RESULTS: Eighty-seven patients were identified. Thirty-two patients received PORT within 6 weeks of their surgery date. Reasons for the delays could be categorised into surgery-derived, system-derived and patient-derived reasons. Five patients (5.74%) received PORT >6 weeks after their surgery due to surgical complications. No patients experienced surgical complications during their PORT. CONCLUSION: In our experience, surgical aspects of free flap reconstructions do not appear to overtly delay or interrupt PORT.

The Oxford Finger Nail Appearance Score - a new scoring system for fingernail deformity following paediatric finger tip trauma.

Fingernail deformity is common, yet current methods used to define cosmetic appearance following trauma are mainly descriptive. In order to quantify the cosmetic appearance of the fingernail, we developed the Oxford Fingernail Appearance Score using a three stage iterative process. The score has five cosmetic components marked as binary outcomes composed of nail shape, nail adherence, eponychial appearance, nail surface appearance and presence of a split. In the first stage, two assessors independently assessed 25 photographs of fingernails taken at a minimum of four months following paediatric nail bed repair and compared them to the corresponding contralateral uninjured finger. Following refinement in the score, ten different assessors scored a further 62 photographs of fingernails taken after paediatric nail bed repair. Assessors completed each of the five components, and the overall component score was calculated by statisticians post-hoc, taking the ideal appearance of each component as 1 ("identical to opposite" for nail shape, eponychium and surface, "complete" for adherence, "absent" for split) and all the non-ideal appearances as 0. Assessors effectively scored the photographs' integer values between 0 (least optimal appearance) and 5 (most optimal appearance). Refinements in the scoring system resulted in an improvement in a weighted kappa statistic of 0.36 (95% CI:0.09,0.68) in the initial score to 0.52 (95% CI: 0.42, 0.61). The Oxford Fingernail Appearance Score is a user-friendly and reliable scoring system which has application in a clinical trial setting.

Surgical intervention for paediatric infusion-related extravasation injury: a systematic review.

OBJECTIVES: This systematic review aims to assess the quality of literature supporting surgical interventions for paediatric extravasation injury and to determine whether there is sufficient evidence to support invasive techniques in children. METHODS: We performed a systematic review by searching Ovid MEDLINE and EMBASE as well as AMED, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and clinicaltrials.gov from inception to February 2019. Studies other than case reports were eligible for inclusion if the population was younger than 18 years old, if there was a surgical intervention aimed at treating extravasation injury and if they reported on outcomes. Study quality was graded according to the National Institutes of Health study quality assessment tools. RESULTS: 26 studies involving 728 children were included-one before-and-after study and 25 case series. Extravasation injuries were mainly confined to skin and subcutaneous tissues but severe complications were also encountered, including amputation (one toe and one below elbow). Of the surgical treatments described, the technique of multiple puncture wounds and instillation of saline and/or hyaluronidase was the most commonly used. However, there were no studies in which its effectiveness was tested against another treatment or a control and details of functional and aesthetic outcomes were generally lacking. CONCLUSION: Surgical management is commonly reported in the literature in cases where there is significant soft tissue injury but as there are no comparative studies, it is unclear whether this is optimal. Further observational and experimental research evaluating extravasation injuries, including a centralised extravasation register using a universal grading scheme and core outcome set with adequate follow-up, are required to provide evidence to guide clinician decision-making.

Implications for the Multi-Disciplinary Management of Children With Craniofrontonasal Syndrome.

The purpose of this retrospective study was to assess the genetic and phenotypic features of patients with craniofrontonasal syndrome (CFNS), and the implications of the condition for multidisciplinary management.The subjects were 25 female patients with a mutation of EFNB1, who presented to the Oxford Craniofacial Unit during a 38-year period. Medical records were reviewed for genetic and phenotypic information. Mean duration of follow-up was 12.6 years (range 0-30.7 years).This study examines neurodevelopment in constituent parts, with specific reference to speech, language, and cognition in relation to genotype. Three children had deletions extending beyond the EFNB1 gene; the 2 with available data presented with speech, language, or cognitive delay. The remaining 25 patients had intragenic mutations of EFNB1. Of these 25, those assessed in detail showed variable difficulties with speech and language development; 57% had receptive language difficulties (n = 4/7) and 88% had expressive language difficulties (n = 8/9). 55% presented with speech difficulties (n = 6/11). 2/3 patients with abnormal hearing had speech difficulties; 4/5 with normal hearing had normal speech development. Cognitive assessments indicated that IQ is variable; with full scale IQ ranging from 69 to 100.The complex, multifactorial presentation of patients with CFNS contributed to 41% (n = 7/17) of patients requiring additional educational support.Our results demonstrated significant multidisciplinary input is required, including Speech and Language Therapy, Plastic and Reconstructive Surgery, Genetics, Ear, Nose and Throat, Maxillofacial, Orthodontic, Orthopaedic, Clinical Psychology and Orthoptic teams. The results of this study reinforce the importance of multi-disciplinary long-term follow-up of children with CFNS.

Composite Grafts for Pediatric Fingertip Amputations: A Retrospective Case Series of 100 Patients.

BACKGROUND: Fingertip amputations are common. This study reports on the outcomes of composite grafts used for fingertip amputations in children, measuring graft take, predictors of graft take, complications, and patient-reported outcomes. METHODS: A retrospective case series of consecutive patients (≤ 16 years) undergoing composite grafts for fingertip amputations in a tertiary pediatric hospital, January 06 to December 16, was performed. Information was collected on amputations, graft take, and complications. Logistic regression was used to analyze factors predicting graft take (partial/complete or failure) including age; amputation level; mechanism and time delay to surgery. Patients were contacted via post or telephone to ask about functional and cosmetic outcomes and their perception of graft take. RESULTS: One hundred patients [57 (57%) males; mean age, 4.41 ± 3.98 years], presenting with 100 fingertip amputations, met the inclusion criteria. Amputation mechanism was crush in 75 (75%), avulsion in 13 (13%), and laceration in 12 (13%). Thirteen (13%) composite grafts survived completely, 46 (46%) partially, and 41 (41%) failed. Graft survival was higher in children under 4 years (P = 0.016). Seventeen (17%) grafts became infected, 9 (9%) required a reoperation, 9 (9%) had wound healing complications, and 4 (4%) patients developed psychological complications. Patient-reported survival was 33% higher than medical-reported survival. Cosmetic issues were the commonest complication reported by patients. Patients rated fingertips looking 3.5/5 normal, and that they were 4/5 satisfied with the appearance. Most patients were using their fingers normally by 2-6 months. CONCLUSIONS: Composite grafts for fingertip amputations mostly only partially survive, but morbidity is low, patient satisfaction is high, and acceptable cosmetic and functional outcomes are achieved.

Current margin practice and effect on re-excision rates following the publication of the SSO-ASTRO consensus and ABS consensus guidelines: a national prospective study of 2858 women undergoing breast-conserving therapy in the UK and Ireland.

INTRODUCTION: There is variation in margin policy for breast conserving therapy (BCT) in the UK and Ireland. In response to the Society of Surgical Oncology and American Society for Radiation Oncology (SSO-ASTRO) margin consensus ('no ink on tumour' for invasive and 2 mm for ductal carcinoma in situ [DCIS]) and the Association of Breast Surgery (ABS) consensus (1 mm for invasive and DCIS), we report on current margin practice and unit infrastructure in the UK and Ireland and describe how these factors impact on re-excision rates. METHODS: A trainee collaborative-led multicentre prospective study was conducted in the UK and Ireland between 1st February and 31st May 2016. Data were collected on consecutive BCT patients and on local infrastructure and policies. RESULTS: A total of 79 sites participated in the data collection (75% screening units; average 372 cancers annually, range 70-900). For DCIS, 53.2% of units accept 1 mm and 38% accept 2-mm margins. For invasive disease 77.2% accept 1 mm and 13.9% accept 'no ink on tumour'. A total of 2858 patients underwent BCT with a mean re-excision rate of 17.2% across units (range 0-41%). The re-excision rate would be reduced to 15% if all units applied SSO-ASTRO guidelines and to 14.8% if all units followed ABS guidelines. Of those who required re-operation, 65% had disease present at margin. CONCLUSION: There continues to be large variation in margin policy and re-excision rates across units. Altering margin policies to follow either SSO-ASTRO or ABS guidelines would result in a modest reduction in the national re-excision rate. Most re-excisions are for involved margins rather than close margins.

Getting out of a tight spot: an overview of ureteroenteric anastomotic strictures.

Radical cystectomy and urinary diversion is the gold-standard treatment for muscle-invasive and high-risk non-muscle-invasive bladder cancer. Ureteroenteric anastomotic stricture is a well-known complication of urinary diversion and is associated with serious sequelae that lead to total or partial loss of kidney function, infectious complications, and the need for additional procedures. Although the exact aetiology of benign ureteroenteric anastomotic strictures is unclear, they most likely occur secondary to ischaemia at the anastomotic region. Diagnosis can be achieved using retrograde contrast studies, CT scan or MAG3 renography. Open revision remains the gold-standard treatment for ureteroenteric anastomotic strictures; however, endourological techniques are being increasingly used and, in select patients, might be the optimal approach.

[Knowledge transfer and appropriation processes of nursing students and African settings of care: a multiple case study]. / Processus de transfert et d'appropriation des savoirs d'étudiantes en sciences infirmières et de milieux de soins Africains: une étude de cas multiples.

BACKGROUND: in this era of globalisation and international academic training, many nursing programs offer the possibility of intercultural placement to their students in their initial training. The rise of this phenomena is ubiquitous throughout all Canadian universities, leading to increased student mobility at the international level with increased placements being organised at the international level, on several continents. PURPOSE: this exploratory study aims at better understanding the processes of knowledge transfer and appropriation during international and intercultural placements in nursing in African countries. FRAMEWORK: the models of empowerment and the Cycle of knowledge to practice have guided this study. METHOD: a multiple case study has been conducted with six settings of care from two countries of Africa. Individual interviews were conducted with the nursing students (n = 11) and with the African nurses supervisors (n = 9), and group interviews with the local partners (n = 2). Direct and participant observations were also done by the nursing students while they were in Africa in the summer and by the two principal investigators when they spent a week in the settings of care, the following fall. RESULTS : advantages of this learning activity were noted, especially in regards to personal and professional growth of the nursing students and in regards to knowledge transfer to the host settings. DISCUSSION : four themes emerged and led to recommendations as to the importance of: 1) bidirectional communication, continuity of projects between cohorts of nurses, and support at distance and on site, 2) reinforcement of the emancipatory sociopolitical knowing 3) diversity of care and community sites and expositions, and 4) different phases of the Cycle of knowledge to practice.

Gyp5p and Gyl1p are involved in the control of polarized exocytosis in budding yeast.

We report here elements for functional characterization of two members of the Saccharomyces cerevisiae Ypt/Rab GTPase activating proteins family (GAP): Gyp5p, a potent GAP in vitro for Ypt1p and Sec4p, and the protein Ymr192wp/APP2 that we propose to rename Gyl1p (GYp like protein). Immunofluorescence experiments showed that Gyp5p and Gyl1p partly colocalize at the bud emergence site, at the bud tip and at the bud neck during cytokinesis. Subcellular fractionation and co-immunoprecipitation experiments showed that Gyp5p and Gyl1p co-fractionate with post-Golgi vesicles and plasma membrane, and belong to the same protein complexes in both localizations. We found by co-immunoprecipitation experiments that a fraction of Gyp5p interacts with Sec4p, a small GTPase involved in exocytosis, and that a fraction of Gyl1p associates at the plasma membrane with the Gyp5p/Sec4p complexes. We showed also that GYP5 genetically interacts with SEC2, which encodes the Sec4p exchange factor. Examination of the gyp5Deltagyl1Delta mutants grown at 13 degrees C revealed a slight growth defect, a secretion defect and an accumulation of secretory vesicles in the small-budded cells. These data suggest that Gyp5p and Gyl1p are involved in control of polarized exocytosis.

Direct sorting of the yeast uracil permease to the endosomal system is controlled by uracil binding and Rsp5p-dependent ubiquitylation.

The yeast uracil permease, Fur4p, is downregulated by uracil, which is toxic to cells with high permease activity. Uracil promotes cell surface Rsp5p-dependent ubiquitylation of the permease, signaling its endocytosis and further vacuolar degradation. We show here that uracil also triggers the direct routing of its cognate permease from the Golgi apparatus to the endosomal system for degradation, without passage via the plasma membrane. This early sorting was not observed for a variant permease with a much lower affinity for uracil, suggesting that uracil binding is the signal for the diverted pathway. The FUI1-encoded uridine permease is similarly sorted for early vacuolar degradation in cells exposed to a toxic level of uridine uptake. Membrane proteins destined for vacuolar degradation require sorting at the endosome level to the intraluminal vesicles of the multivesicular bodies. In cells with low levels of Rsp5p, Fur4p can be still diverted from the Golgi apparatus but does not reach the vacuolar lumen, being instead missorted to the vacuolar membrane. Correct luminal delivery is restored by the biosynthetic addition of a single ubiquitin, suggesting that the ubiquitylation of Fur4p serves as a specific signal for sorting to the luminal vesicles of the multivesicular bodies. A fused ubiquitin is also able to sort some Fur4p from the Golgi to the degradative pathway in the absence of added uracil but the low efficiency of this sorting indicates that ubiquitin does not itself act as a dominant signal for Golgi-to-endosome trafficking. Our results are consistent with a model in which the binding of intracellular uracil to the permease signals its sorting from the Golgi apparatus and subsequent ubiquitylation ensures its delivery to the vacuolar lumen.

Raft partitioning of the yeast uracil permease during trafficking along the endocytic pathway.

Lipid rafts, formed by the lateral association of sphingolipids and cholesterol in the external membrane leaflet, have been implicated in membrane traffic and cell signaling in mammalian cells. Yeast plasma membranes were also recently shown to contain lipid raft microdomains consisting of sphingolipids and ergosterol, and containing several plasma membrane proteins, including Gas1p, a GPI-anchored protein, and the [H+] ATPase Pma1p. In this study, we investigated whether lipid rafts were involved in the intracellular trafficking of a yeast transporter, uracil permease, which undergoes ubiquitin-dependent endocytosis. Regardless of its ubiquitination status, uracil permease was found to be associated with rafts in the plasma membrane. The expression of Fur4p in lcb1-100 cells, deficient in the first enzyme of sphingolipid synthesis, impaired the association of Fur4p with detergent-resistant fractions. When targeted to endocytic compartments, uracil permease appeared to be progressively transferred to detergent-soluble fractions, suggesting that the lipid environment might change between plasma membrane and endosomes. Consistent with this hypothesis, the wild-type form of the v-SNARE Snc1p, which is known to cycle between the plasma membrane and endosomal compartments, was recovered in both detergent-resistant and detergent-soluble fractions. In contrast, a variant Snc1p that accumulates at the plasma membrane was recovered exclusively in detergent-resistant fractions.

Casein kinase I controls a late step in the endocytic trafficking of yeast uracil permease.

The modification of yeast uracil permease by phosphorylation at the plasma membrane is a key mechanism for regulating transporter endocytosis. Uracil permease is phosphorylated at several serine residues within a well characterized PEST sequence. The phosphorylation of these residues facilitates the ubiquitination and internalization of the permease. Following endocytosis, the permease is targeted to the lysosome/vacuole for proteolysis. We have shown that in casein kinase 1 (CK1)-deficient cells, the permease is poorly phosphorylated, poorly ubiquitinated and that Yck activity may play a direct role in phosphorylating the permease. We show here that CK1-deficient cells accumulated permease that was subjected to endocytosis in an internal compartment on its way to the vacuole. Uracil permease, produced as a fusion protein with green fluorescent protein in CK1-deficient cells, was detected in dots adjacent to the vacuole. These dots probably correspond to the late endosome/prevacuolar compartment because they were partially colocalized with the Pep12p marker. This accumulation was abolished by mutations affecting the adaptor-related complex, AP-3. The CPY and ALP pathways to the vacuole were both unaffected in CK1-deficient cells. Our analysis provides the first evidence that CK1 is important for the delivery of proteins to the vacuole after endocytosis.