Acute toxicities in proton therapy for head and neck cancer - A matched analysis of the DAHANCA 35 feasibility study.

Background and purpose: As preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy. Materials and methods: 62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months. Results: Baseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p < 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01-3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3-1.7, p < 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period. Conclusion: Proton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.

Radiation dose to multidisciplinary staff members during complex interventional procedures.

INTRODUCTION: Complex interventional radiology procedures involve extensive fluoroscopy and image acquisition while staff are in-room. Monitoring occupational radiation dose is crucial in optimization. The purpose was to determine radiation doses received by staff involved in complex interventional procedures performed in a dedicated vascular or neuro intervention room. METHODS: Individual real-time radiation dose for all staff involved in vascular and neuro-interventional procedures in adult patients was recorded over a one-year period using wireless electronic dosimeters attached to the apron thyroid shield. A reference dosimeter was attached to the C-arm near the tube housing to measure scattered, unshielded radiation. Radiology staff carried shoulder thermo-luminescent dosimeters with monthly read-out to monitor dose over time. RESULTS: Occupational radiation dose was measured in 99 interventional procedures. In many cases prostate artery embolization procedures exposed radiologists to high radiation doses with a median of 15.0 µSv and a very large spread, i.e. 0.2-152.5 µSv. In all procedures except uterine fibroid embolization radiographers were exposed to lower doses than those of radiologists, with endovascular aortic repair being the procedure with highest median exposure to assisting radiographers, i.e. 2.2 µSv ranging from 0.1 to 36.1 µSv. Median radiation dose for the reference dosimeter was 670 µGy while median staff dose for all procedures combined was 3.2 µGy. CONCLUSION: Radiation doses for multiple staff were determined and the ratio between staff dose and reference dosimeter indicated proper use of shielding in general. Some high-dose procedures may need further optimization for certain staff members, especially those not primarily employed in radiology. IMPLICATIONS FOR PRACTICE: The study provides benchmark doses that may be used widely in audits and in the ongoing effort to optimize radiation protection for staff in interventional radiology.

Considerations for study design in the DAHANCA 35 trial of protons versus photons for head and neck cancer.

Proton radiotherapy offers a dosimetric advantage compared to photon therapy in sparing normal tissue, but the clinical evidence for toxicity reductions in the treatment of head and neck cancer is limited. The Danish Head and Neck Cancer Group (DAHANCA) has initiated the DAHANCA 35 randomised trial to clarify the value of proton therapy (NCT04607694). The DAHANCA 35 trial is performed in an enriched population of patients selected by an anticipated benefit of proton therapy to reduce the risk of late dysphagia or xerostomia based on normal tissue complication probability (NTCP) modelling. We present our considerations on the trial design and a test of the selection procedure conducted before initiating the randomised study.

Colibactin mutational signatures in NTHL1 tumor syndrome and MUTYH associated polyposis patients.

Polyketide synthase (pks) island harboring Escherichia coli are, under the right circumstances, able to produce the genotoxin colibactin. Colibactin is a risk factor for the development of colorectal cancer and associated with mutational signatures SBS88 and ID18. This study explores colibactin-associated mutational signatures in biallelic NTHL1 and MUTYH patients. Targeted Next Generation Sequencing (NGS) was performed on colorectal adenomas and carcinomas of one biallelic NTHL and 12 biallelic MUTYH patients. Additional fecal metagenomics and genome sequencing followed by mutational signature analysis was conducted for the NTHL1 patient. Targeted NGS of the NTHL1 patient showed somatic APC variants fitting SBS88 which was confirmed using WGS. Furthermore, fecal metagenomics revealed pks genes. Also, in 1 out of 11 MUTYH patient a somatic variant was detected fitting SBS88. This report shows that colibactin may influence development of colorectal neoplasms in predisposed patients.

Introducing extended consultations for patients with severe mental illness in general practice: Results from the SOFIA feasibility study.

BACKGROUND: People with a severe mental illness (SMI) have shorter life expectancy and poorer quality of life compared to the general population. Most years lost are due to cardiovascular disease, respiratory disease, and various types of cancer. We co-designed an intervention to mitigate this health problem with key stakeholders in the area, which centred on an extended consultations for people with SMI in general practice. This study aimed to1) investigate general practitioners' (GPs) experience of the feasibility of introducing extended consultations for patients with SMI, 2) assess the clinical content of extended consultations and how these were experienced by patients, and 3) investigate the feasibility of identification, eligibility screening, and recruitment of patients with SMI. METHODS: The study was a one-armed feasibility study. We planned that seven general practices in northern Denmark would introduce extended consultations with their patients with SMI for 6 months. Patients with SMI were identified using practice medical records and screened for eligibility by the patients' GP. Data were collected using case report forms filled out by practice personnel and via qualitative methods, including observations of consultations, individual semi-structured interviews, a focus group with GPs, and informal conversations with patients and general practice staff. RESULTS: Five general practices employing seven GPs participated in the study, which was terminated 3 ½ month ahead of schedule due to the COVID-19 pandemic. General practices attempted to contact 57 patients with SMI. Of these, 38 patients (67%) attended an extended consultation, which led to changes in the somatic health care plan for 82% of patients. Conduct of the extended consultations varied between GPs and diverged from the intended conduct. Nonetheless, GPs found the extended consultations feasible and, in most cases, beneficial for the patient group. In interviews, most patients recounted the extended consultation as beneficial. DISCUSSION: Our findings suggest that it is feasible to introduce extended consultations for patients with SMI in general practice, which were also found to be well-suited for eliciting patients' values and preferences. Larger studies with a longer follow-up period could help to assess the long-term effects and the best implementation strategies of these consultations.

Effect of fumaric acid in combination with Asparagopsis taxiformis or nitrate on in vitro gas production, pH, and redox potential.

Reduction in enteric methane (CH4) emissions from cattle can be achieved through use of feed additives, which often results in increased emission of hydrogen (H2). The objective of this study was to investigate in vitro effects of a known hydrogen sink, fumaric acid, in combination with either of 2 methane inhibitors, the macroalga Asparagopsis taxiformis or nitrate, on CH4 and H2 production, feed degradability, pH, and redox potential. A corn silage (0.5 g; control) was incubated in buffered rumen fluid with the addition of 0.025 g of nitrate (Nit), 0.025 g of dried A. taxiformis (Asp), 0.025 g of nitrate + 0.025 g of fumaric acid (Nit+Fum), or 0.025 g of dried A. taxiformis + 0.025 g of fumaric acid (Asp+Fum). Accumulated gas production was determined using the AnkomRF system equipped with airtight gasbags. There were 9 replicates per treatment with 3 replicates per treatment stopped after 24, 36, and 48 h of incubation. The amount of undegraded feed was determined by filtration. Gas composition was determined by gas chromatography. Degradable dry matter, degradable organic matter, pH, redox potential, and gas production data were analyzed using a mixed model. Asp and Asp+Fum reduced CH4 production by 98% or greater at all incubation times, whereas Nit and Nit+Fum reduced CH4 production (mL of CH4/g of dry matter) by 52% to 63% compared with the control. Hydrogen was only detectable in gas from Asp and Asp+Fum treatments, with no difference in H2 production between the 2 treatments. The treatments had only minor effects on redox potential in the fermented rumen fluid, and pH was lowest for treatments including A. taxiformis. In conclusion, both A. taxiformis and nitrate reduced CH4 production. Fumaric acid in combination with A. taxiformis did not reduce H2 production, and treatments including nitrate did not result in any detectable levels of H2. Future dose-response in vitro studies will contribute to investigating the potential of fumaric acid as a hydrogen sink during CH4 mitigation.

Apparent treatment failure of praziquantel and pyrantel pamoate against anoplocephalid tapeworms.

Anoplocephalid tapeworms are commonly occurring in grazing horses around the world. Two currently available anthelmintics have documented high efficacy against Anoplocephala perfoliata; praziquantel in various dosages ranging from 1.0 to 2.5 mg/kg and pyrantel pamoate administered at 13.2 mg base/kg. Anthelmintic resistance has not been reported in A. perfoliata, but anecdotal reports made during 2022 have suggested a possible loss of efficacy for both actives. This paper reports fecal egg count data from a Thoroughbred operation in Central Kentucky in 2023. Fifty-six yearlings were first dewormed with a combination of ivermectin (200 µg/kg) and praziquantel (1.5 mg/kg) and subsequently treated with pyrantel pamoate (13.2 mg base/kg). Fecal egg counts were determined at the day of treatment and again 14 days post-treatment. Two groups of mares (n = 39 and 45) were also treated with ivermectin/praziquantel and examined pre- and post-treatment. Low efficacy of ivermectin and pyrantel pamoate was demonstrated against strongylid parasites in the yearlings with mean Fecal Egg Count Reductions (FECRs) at 75.6% or below and upper 95% credible interval (CI) limits below 90% in all cases. Overall anti-cestodal FECR levels in the yearlings were 23.5% (95% CI: 11.2-48.0) for praziquantel and 50.9% (20.5-72.0) for pyrantel pamoate. Praziquantel eliminated anoplocephalid eggs from three of 17 yearlings, but another 5 yearlings went from negative to positive status following treatment. Pyrantel pamoate failed to eliminate anoplocephalid eggs from any of 14 treated tapeworm-positive yearlings. Nine of 84 mares tested positive for anoplocephalid eggs, and seven of these were still positive post praziquantel treatment. These findings sharply contrast data from historic field efficacy studies conducted for both actives and raise concern about anthelmintic resistance having possibly developed. This emphasizes the need for developing and refining antemortem methodologies for evaluating anti-cestodal treatment efficacy and for searching for possible alternative treatment options.

Evaluation of hop performance in children with anterior cruciate ligament reconstruction using healthy reference data: A cross-sectional study.

BACKGROUND: Hop performance evaluation in children after anterior cruciate ligament (ACL) reconstruction may benefit from comparison to healthy controls. Thus, the purpose was to investigate the hop performance in children one year after ACL reconstruction with a comparison to healthy controls. METHODS: Hop performance data from children with ACL reconstruction one year post-surgery and healthy children were compared. Four one-legged hop test data were analyzed: 1) single hop (SH), 2) 6 m timed hop (6 m-timed), 3) triple hop (TH), and 4) cross-over hop (COH). Outcomes were the best result (longest/fastest hop) from each leg and limb asymmetry. Differences in hop performance between-limbs (operated versus non-operated) and between-groups were estimated. RESULTS: 98 children with ACL reconstruction and 290 healthy children were included. Few statistically significant group differences were observed. Girls with ACL reconstruction outperformed healthy controls in two tests on the operated leg SH, COH) and in three tests on the non-operated leg (SH, TH, COH). However, the girls performed 4-5% worse on the operated leg when compared to the non-operated leg in all hop tests. No statistically significant between-group differences in the limb asymmetry were found. CONCLUSION: The hop performance in children with ACL reconstruction one year post-surgery was largely comparable to the level of healthy controls. Despite this, we cannot exclude that neuromuscular deficits exist among the children with ACL reconstruction. The inclusion of a healthy control group for evaluating hop performance evoked complex findings regarding the ACL reconstructed girls. Thus, they may represent a selected group.

Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis.

OBJECTIVE: Galectin-3 (Gal-3) has been suggested as a proinflammatory mediator in rheumatoid arthritis (RA). We aimed to study clinical and pathogenic aspects of Gal-3 in RA. METHOD: Plasma samples from healthy controls (n = 48) and patients with newly diagnosed, early RA were assayed for soluble Gal-3. In patients with chronic RA (n = 18), Gal-3 was measured in both plasma and synovial fluid. Synovial fluid mononuclear cells were used to purify fibroblast-like synoviocytes (FLSs) and osteoclasts. Monocultures of FLSs and autologous co-cultures of FLSs and peripheral blood mononuclear cells were established and co-incubated with a Gal-3 inhibitor. RESULTS: Patients with early and chronic RA had persistently increased plasma levels of Gal-3 compared with controls. However, changes in plasma Gal-3 at the level of individuals were associated with long-term disease activity. In seropositive early RA patients, all patients with decreasing plasma Gal-3 from 0 to 3 months had low disease activity after 2 years (p < 0.05). Gal-3 levels in synovial fluid were markedly elevated. In vitro, co-incubation with a Gal-3 inhibitor (GB1107, 10 µM) led to a significant reduction in both interleukin-1ß and tumour necrosis factor-α secretion from FLS monocultures (both p < 0.05) and decreased monocyte-derived osteoclastogenesis compared with controls (both p < 0.05). CONCLUSIONS: Our findings underscore the role of Gal-3 regarding disease activity and tissue destruction in RA. An initial decrease in plasma Gal-3 levels predicted decreased long-term disease activity. Correspondingly, a Gal-3 inhibitor decreased the activity of inflammatory FLSs and osteoclastogenesis in patients with RA.

Validity of a two-antibody testing algorithm for mismatch repair deficiency testing in cancer; a systematic literature review and meta-analysis.

Reflex mismatch repair immunohistochemistry (MMR IHC) testing for MLH1, PMS2, MSH2 and MSH6 is used to screen for Lynch syndrome. Recently MMR-deficiency (MMRd) has been approved as a pan-cancer predictive biomarker for checkpoint inhibitor therapy, leading to a vast increase in the use of MMR IHC in clinical practice. We explored whether immunohistochemical staining with PMS2 and MSH6 can be used as a reliable substitute. This two-antibody testing algorithm has the benefit of saving tissue, cutting costs and saving time. PubMed, Embase and Cochrane library were systematically searched for articles reporting on MMR IHC. The weighed percentage of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was analyzed using a random effects model meta-analysis in R. The search yielded 1704 unique citations, of which 131 studies were included, describing 9014 patients. A weighed percentage of 1.1% (95% CI 0.53-18.87, I = 87%) of cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone was observed. In the six articles with the main aim of investigating the two-antibody testing algorithm all MMRd cases were detected with the two-antibody testing algorithm, there were no cases with isolated MLH1 or MSH2 loss or combined MLH1/MSH2 loss alone. This high detection rate of MMRd of the two-antibody testing algorithm supports its use in clinical practice by specialized pathologists. Staining of all four antibodies should remain the standard in cases with equivocal results of the two-antibody testing algorithm. Finally, educational sessions in which staining pattern pitfalls are discussed will continue to be important.

A dermocosmetic formulation containing Vichy volcanic mineralizing water, Vitreoscilla filiformis extract, niacinamide, hyaluronic acid, and vitamin E regenerates and repairs acutely stressed skin.

The exposome has an impact on skin from life-long exposure. Acute short-term exposure to exposome stressors can also alter skin functions such as skin physical barrier and immune defenses, leading to skin dryness, sensitivity, flares of inflammatory skin conditions, or viral reactivations. Probiotics are defined as live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host. An extract produced by lysing Vitreoscilla filiformis (VfeV) cultured in Vichy volcanic mineralizing water (VVMW) has properties of probiotic fractions. In this review, we present in vivo and ex vivo studies with a dermocosmetic formulation containing 80% VVMW, 5% VfeV, 4% niacinamide (vitamin B3), 0.4% hyaluronic acid, and 0.2% vitamin E (M89PF) to evaluate the clinical efficacy in preventing and repairing stressed skin. Skin barrier benefits of M89PF were shown in studies after the skin was exposed to sudden thermal changes, after skin irritation by tape stripping, and in sleep-deprived women. M89PF significantly accelerated skin renewal compared to untreated skin. Skin antioxidant defense activity of M89PF was shown after exposure to stress from UVA plus cigarette smoke aggression. Skin microbiome recovery after acute stress from a harsh cleanser was significantly better in M89PF-treated skin compared to bare skin. Clinical benefits of M89PF on correcting clinical signs of stressed skin were shown in both Caucasian and Asian women exposed to a stressful lifestyle and various external (pollution, tobacco smoking, solar radiation) and internal (poor sleep, stressful work, unbalanced diet, and alcohol consumption) exposome factors. M89PF also showed depigmenting properties on dark spots in Asian women. Further clinical studies are now warranted to evaluate the efficacy of M89PF as adjuvant care to prevent and repair skin barrier disruption and reinforce skin defenses in skin exposed to acute stresses.

Peritoneal flap hernioplasty for repair of incisional hernias after orthotopic liver transplantation.

BACKGROUND: Repair of incisional hernias following orthotopic liver transplantation (OLT) is a surgical challenge due to concurrent midline and transverse abdominal wall defects in the context of lifelong immunosuppression. The peritoneal flap hernioplasty addresses this problem by using flaps of the hernial sac to bridge the fascial gap and isolate the mesh from both the intraperitoneal contents and the subcutaneous space, exploiting the retro-rectus space medially and the avascular plane between the internal and external oblique muscles laterally. We report our short and long-term results of 26 consecutive liver transplant cases with incisional hernias undergoing repair with the peritoneal flap technique. METHODS: Post-OLT patients undergoing elective peritoneal flap hernioplasty for incisional hernias from Jan 1, 2010-Nov 1, 2017 were identified from the Lothian Surgical Audit system (LSA), a prospectively-maintained computer database of all surgical procedures in the Edinburgh region of south-east Scotland. Patient demographics and clinical data were obtained from the hospital case-notes. Follow-up data were obtained in Feb 2020. RESULTS: A total of 517 liver transplantations were performed during the inclusion period. Twenty-six of these (18 males, 69%) developed an incisional hernia and underwent a peritoneal flap repair. Median mesh size (Optilene Elastic, 48 g/m2, BBraun) was 900 cm2 (range 225-1500 cm2). The median time to repair following OLT was 33 months (range 12-70 months). Median follow-up was 54 months (range 24-115 months) and median postoperative stay was 5 days (range 3-11 days). Altogether, three patients (12%) presented with postoperative complications: 1 with hematoma (4%) and two with chronic pain (8%). No episodes of infection or symptomatic seroma were recorded. No recurrence was recorded within the follow-up period. CONCLUSION: Repair of incisional hernias in patients following liver transplantation with the Peritoneal Flap Hernioplasty is a safe procedure associated with few complications and a very low recurrence rate. We propose this technique for the reconstruction of incisional hernias following liver transplantation.

A feasibility study of "plan transformation": A novel workaround enabling patient transfer between different Varian machines.

PURPOSE: The objective of this work is to explore a methodology to enable plan transfers from Standard MLC (STD) to High Definition MLC (HD) Varian units without replanning. Using "Plan Transformation", we aim to utilize full departmental capacity to disperse patients from STD Varian units to HD units, when the former goes down for repair. METHODS: Our centre is equipped with four STD and two HD MLC Varian Truebeam units. Plan transformation is used to transfer patients from STD to HD units when needed. Static or manually segmented fields with Y jaws ≤ 21.6 cm are eligible for plan transformation. The MLC pattern for each field is exported out of Eclipse. An in-house program based on C# is used to convert those patterns from STD to HD. STD and HD MLCs are different in design but dosimetrically comparable for these type of plans. Still to avoid extra uncertainty, transformed plans are recalculated in Eclipse to enable the user to assess the quality of the process. RESULTS: On a given day, more than 25% of appointments on STD units were eligible for transformation. The majority of eligible plans were breast tangent and boost. The delivery and safety of plan transformation was examined directly on a Varian Truebeam linac. A gamma analysis comparison between measured and calculated transformed plans yields a pass-rate of 100% for 3%/3mm, identical to non-transformed plans. CONCLUSION: Plan transformation is feasible and saves time for planners as it takes less than a quarter the time required for a replan.

Clinically decisive (dis)agreement in multidisciplinary team assessment of esophageal squamous cell carcinoma; a prospective, national, multicenter study.

BACKGROUND: Decisions regarding tumor staging, operability, resectability, and treatment strategy in patients with esophageal cancer are made at multidisciplinary team (MDT) conferences. We aimed to assess interobserver agreement from four national MDT conferences and whether this would have a clinical impact. METHODS: A total of 20 patients with esophageal cancer were included across all four upper gastrointestinal (GI) cancer centers. Fully anonymized patient data were distributed among the MDT conferences which decided on TNM category, resectability, operability, curability, and treatment strategy blinded to each other's decisions. The interobserver agreement was expressed as both the raw observer agreement and with Krippendorff's α values. Finally, a case-by-case evaluation was performed to determine if disagreement would have had a clinical impact. RESULTS: A total of 80 MDT evaluations were available for analysis. A moderate to near-perfect observer agreement of 79.2%, 55.8%, and 82.5% for TNM category was observed, respectively. Substantial agreement for resectability and moderate agreement for curability were found. However, an only fair agreement was observed for the operability category. The treatment strategies had a slight agreement which corresponded to disagreement having a clinical impact in 12 patients. CONCLUSIONS: Esophageal cancer MDT conferences had an acceptable interobserver agreement on resectability and TM categories; however, the operability assessment had a high level of disagreement. Consequently, the agreement on treatment strategy was reduced with a potential clinical impact. In future MDT conferences, emphasis should be on prioritizing the relevant information being readily available (operability, T & M categories) to minimize the risk of disagreement in the assessments and treatment strategies, and thus, delayed or suboptimal treatment.

Geometric modelling of CORA-based levelling osteotomy in the dog.

Centre of rotation of angulation (CORA)-based levelling osteotomy (CBLO) is a recent addition to surgical procedures for stabilization of the cranial cruciate ligament-deficient canine stifle joint. Careful identification of the CORA location preoperatively and use of this location intraoperatively are required to ensure accurate correction of the tibial plateau angle. Limited data are available regarding the magnitude and source of potential errors during planning and execution of CBLO. A geometric model enabling isolation of various error sources is described. Landmarks were derived from tibial radiographs (n = 50) by 5 observers and used to define proximal and distal anatomical axes for simulation of CBLO. Observer-specific CORA locations with mean landmark data were used to assess planning errors, and simulated malpositioning of the CORA at 10 mm from the ideal location was used to assess surgical errors. Planning errors result mainly from tibial plateau misidentification, with CORA locations dispersed up to ±10 mm proximodistally from ideal (95% confidence). Malpositioning of the CORA during surgery causes equal and opposite changes in tibial plateau angle (TPA) and anatomical-mechanical axis angles, and varying degrees of translation and limb length changes. The magnitude of these changes is dependent on initial TPA and limb length, with smaller dogs and steeper tibial plateaus resulting in larger errors. Optimal planning and execution are required to achieve the planned outcome of CBLO. The main source of error in our simulation is identification of the tibial plateau. While both pre- and intraoperative errors influenced TPA, based on our geometric model the effect in larger dogs may not be clinically significant. If distalisation of the CORA is required during surgery, compensation of the CORA angle to maintain the target TPA is possible.

Effectiveness of a formulation containing peptides and vitamin C in treating signs of facial ageing: three clinical studies.

OBJECTIVE: Vitamin C and peptides are widely used in cosmetic products but there is a paucity of clinical studies showing that the formulations are effective in treating signs of facial ageing. These 3 clinical studies evaluated the effectiveness of an anti-ageing formula containing natural vitamin C (10%), biopeptides (rice and lupin), hyaluronic acid, and Vichy volcanic mineralising water, in amber glass ampoules with no preservatives (Peptide-C ampoules). METHODS: Dansyl chloride fluorescence labelling compared cell turnover for Peptide-C ampoules vs untreated skin in 32 female subjects. Study 2, an open clinical study, evaluated the efficacy on wrinkles of Peptide-C ampoules by investigator clinical scoring based on Dynamical Atlas visual assessment (N = 40) and subject self-assessment questionnaires (N = 47). Study 3, an open clinical study, evaluated wrinkles by instrumental quantification with 3D fringe projection analysis (N = 40) and subject questionnaires (N = 51). RESULTS: The mean cell turnover was faster for skin treated with Peptide-C ampoules compared to untreated skin (17.1 days vs. 19.2 days; P < 0.0001). In study 2, after 28 days application of Peptide-C ampoules, clinical grading of crow's-feet wrinkles, forehead wrinkles and nasolabial folds decreased by 9%, 11% and 5%, respectively (all P < 0.05 vs baseline). Of 47 subjects, 77%, 64% and 79% indicated their skin seemed smoothed out, fine lines were less visible, and skin complexion was more radiant, respectively. In study 3, the number of wrinkles decreased by 11.5% after 29 days application of Peptide-C ampoules vs baseline (P < 0.05) and 65% of subjects responded the fine lines were less visible. CONCLUSION: This formulation of a combination of anti-ageing ingredients in ampoules, allowing a minimalist formula, showed significant results on improving facial wrinkles and radiance.

OBJECTIF: La vitamine C et les peptides sont régulièrement utilisés dans les produits dermocosmétiques mais il existe peu d'études cliniques sur l'efficacité des formulations sur les signes du vieillissement cutané du visage. Trois études cliniques ont évalué l'efficacité d'une formule anti-âge contenant de la vitamine C naturelle (10%), des biopeptides (riz et lupin), de l'acide hyaluronique et de l'eau minéralisante volcanique de Vichy, dans un format d'ampoules en verre ambré, sans conservateur (ampoules Peptide-C). MÉTHODES: Une première étude a comparé par la technique de chlorure de Dansyl le renouvellement cellulaire avec la formulation ampoules Peptide-C et la peau non traitée chez 32 sujets féminins. La seconde étude, en ouvert, a évalué l'efficacité clinique sur les rides des ampoules Peptide-C en se reposant sur les Atlas Dynamiques (N=40) et les questionnaires d'auto-évaluation des sujets (N=47). La troisième étude, ouverte, a évalué les rides par quantification instrumentale avec l'analyse de projection de franges 3D (N=40) et les questionnaires d'autoévaluation des sujets (N=51). RÉSULTATS: Le renouvellement cellulaire était plus rapide pour la peau traitée avec des ampoules de Peptide-C comparées à la peau non traitée (17.1 jours contre 19.2 jours ; p<.0001). Dans l'étude 2, après 28 jours d'application des ampoules Peptide-C, l'évaluation clinique des rides de la patte d'oie, du front et des plis naso-labiaux a montré une amélioration de 9 %, 11 % et 5 %, respectivement (tous p<0,05 vs baseline). Sur 47 sujets, 77%, 64% et 79% ont indiqué que leur peau semblait respectivement lissée, que les ridules étaient moins visibles et que le teint de la peau était plus radieux. Dans l'étude 3, le nombre de rides a diminué de 11,5 % après 29 jours d'application des ampoules Peptide-C par rapport à la baseline (p<0,05) et 65 % des sujets ont répondu que les ridules étaient moins visibles. CONCLUSION: Cette combinaison d'ingrédients anti-âge dans un format d'ampoules, et une formulation minimaliste, a montré des résultats significatifs sur l'amélioration des rides faciales et de l'éclat du teint.

Postmastectomy Radiation Therapy Planning After Immediate Implant-based Reconstruction Using the European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice Consensus Guidelines for Target Volume Delineation.

AIMS: To evaluate how common radiation therapy techniques perform in the setting of the new European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) delineation recommendations for immediate breast reconstruction (IBR). MATERIALS AND METHODS: Seven Danish radiation therapy centres and six international European centres participated in this project. Two breast cancer cases (one left-sided and one right-sided) with a retropectoral implant were chosen for radiation therapy planning using deep-inspiration breath-hold. Target volumes were delineated according to ESTRO-ACROP delineation recommendations. The centres were asked to plan the cases using any radiation therapy technique according to the Danish Breast Cancer Group plan objectives. RESULTS: In total, 35 treatment plans were collected. Half of the submitted plans, for both the left-sided and the right-sided case, used the field-in-field (FiF) technique (nine for each), a quarter used volumetric arc radiation therapy (VMAT; five for right-sided, four for left-sided) and the remaining quarter was a mix of inverse intensity-modulated radiation therapy (IMRT), helicoidal therapy and hybrid (combined open fields and VMAT) techniques. Mean clinical target volume doses were in the range 99-102% of the prescribed dose. The median FiF mean heart dose (MHD) for right-sided radiation therapy was 1 Gy (range 0.8-3.7) and 5.2 Gy for left-sided radiation therapy (range 2.2-6.5). For right-sided radiation therapy, the median VMAT MHD was 3.42 Gy, for IMRT was 2.3 Gy and for helicoidal therapy was 5.1 Gy. For left-sided radiation therapy, the median VMAT MHD was 6.3 Gy, for IMRT was 7.8 Gy and for helicoidal therapy was 7.3 Gy. CONCLUSIONS: Different radiation therapy techniques could be used to plan radiation therapy in the setting of IBR. FiF provided good coverage with acceptable organ at risk doses. The best dose distribution results as a trade-off between the objectives of target volume coverage and high-dose organ at risk inclusion. The radiation therapy technique affects the interplay between these objectives.

Peritoneal flap hernioplasty for reconstruction of transverse incisional hernias.

BACKGROUND: Repair of transverse incisional hernias is a surgical challenge with current methods of abdominal wall reconstruction. The peritoneal flap hernioplasty addresses this problem using flaps of hernial sac to bridge the fascial gap and isolate the mesh from both the intraperitoneal contents and the subcutaneous space exploiting the retro-rectus space medially and the avascular plane between the internal and external oblique muscles laterally. The operative technique and long-term results of 80 consecutive cases with transverse incisional hernias undergoing repair with this method are reported. METHODS: Patients undergoing elective peritoneal flap hernioplasty repair for transverse incisional hernias from Jan. 1, 2010 to Dec. 31, 2014 were identified from the Lothian Surgical Audit system, a prospectively-maintained computer database of all surgical procedures in the Edinburgh region of south-east Scotland. Patient demographics and clinical data were obtained from the hospital case-notes. Follow-up data were obtained in May 2019 from hospital records and telephone interview. RESULTS: 80 patients, (n = 53 male, 66%) were identified. Mean follow-up was 83 months (range 55-114 months) and mean postoperative stay was 6.4 days (range 1-23 days). Eleven repairs (14%) were for recurrent hernia. Mean mesh size applied (Optilene Elastic, 48 g/m2, BBraun) was 747 cm2 (ranged 150-1500 cm2). Redundant skin excision was performed in 54% of cases. Altogether, seven patients (8.8%) presented with postoperative complications: five superficial wound infections (6.3%), one symptomatic seroma (1.3%) and one recurrence (1.3%) within the follow-up period. CONCLUSION: The peritoneal flap hernioplasty is associated with few complications and a very low recurrence rate. We propose this technique as the method of choice for reconstruction of transverse abdominal incisional hernias when primary fascial apposition is not possible.

Re-recurrence and pain 12 years after laparoscopic transabdominal preperitoneal (TAPP) or Lichtenstein's repair for a recurrent inguinal hernia: a multi-centre single-blinded randomised clinical trial.

BACKGROUND: Long-term clinical outcome after a recurrent inguinal hernia repair may be associated with the type of repair, that is, laparoscopic or open. The results from previous randomised controlled trials are inconclusive regarding the long-term risk of re-recurrence chronic pain. Accordingly, this trial compared laparoscopic transabdominal preperitoneal repair (TAPP) with Lichtenstein's repair. The primary outcome was repair for a re-recurrence. The secondary outcome was chronic pain. METHODS: Multi-centre single-blinded, randomised trial on TAPP vs Lichtenstein's repair in male patients operated for a recurrent inguinal hernia after a primary open inguinal hernia repair. Follow-up for repair for a re-recurrence was registered in the Danish Hernia Database. Prospective follow-up data were achieved by a structured questionnaire on pain-related functional impairment using the Activities Assessment Scale (AAS-pain). RESULT: A total of 360 patients were randomised, 297 were mailed the follow-up questionnaire (63 excluded) after median 12 years (range 9-15). A total of 265 patients responded to the questionnaire (response rate 89%). The cumulative rate of repair for re-recurrence after 12 years was 10% (95% confidence interval (CI) 5.3-15.1%) vs 10% (5.6-14.7%) after TAPP or Lichtenstein, respectively (p = 0.764). Moderate/severe AAS-pain was reported by 4% (95% CI 1-8%) vs 7% (95% CI 3-11%) patients after TAPP or Lichtenstein, respectively (p = 0.698) CONCLUSION: Long-term re-recurrence rate and incidence of chronic pain was surprisingly high respectless of surgical approach and neither TAPP nor Lichtenstein's procedure was superior to improve surgical results.

Short-term safety of preoperative administration of botulinum toxin A for the treatment of large ventral hernia with loss of domain.

PURPOSE: Preoperative intramuscular-administered botulinum toxin A (BTA) in the lateral abdominal muscles prior to abdominal wall reconstruction has been reported to produce a flaccid paralysis and improve the primary closure rate of large ventral hernias with loss of domain. Complications to this treatment remain sparsely described. The aim of the current study was to report safety and short-term outcome of abdominal wall reconstruction aided by BTA administration. METHODS: This was a retrospective two-center study including all patients undergoing abdominal wall reconstruction for ventral hernia aided by preoperative BTA administration to the lateral abdominal muscles. Data were retrieved from patient charts and included preoperative demographic and perioperative information as well as postoperative 30-day complications and readmissions. RESULTS: A total of 37 patients underwent BTA administration prior to hernia repair. The mean age and body mass index were 59.5 (SD 10.1) years and 31.1 (SD 5.2) kg/m2. The BTA injections were administered mean 31.6 days (SD 10.0) prior to the hernia repair. One (2.7%) patient reported pain as a complication immediately after the BTA administration. Subsequent to the hernia repair, six (16.2%) patients were readmitted within 30 days. Nine patients (24.3%) had wound complications and medical complications occurred in seven (18.9%) patients. CONCLUSIONS: We found early preoperative administration of BTA a safe adjunct to large ventral hernia repair, without adverse events related to the administration preoperative. Future studies should further highlight the efficacy of preoperative BTA for reconstruction of otherwise untreatable hernias.