Fatigue in children who have recently completed treatment for acute lymphoblastic leukemia: a longitudinal study.

BACKGROUND: This study examined fatigue in patients treated for childhood acute lymphoblastic leukemia (ALL) over a 2-year period (3- to 27-months post-treatment completion), from the perspective of children and parent caregivers, compared to a healthy comparison group. METHODS: Eighty-three patients (4-16 years at enrolment) and their parents, reported on the child's fatigue using the Pediatric Quality of Life Inventory- Multidimensional Fatigue Scale (PedsQL-MFS), at 3- 15- and 27-months post-treatment completion, and 53 healthy children and their parents reported on fatigue across the same timepoints. RESULTS: Parent proxy-reporting showed that parents of ALL patients reported more total fatigue than parents of the comparison group at all time points, with all subscales elevated (general, cognitive, and sleep/rest fatigue). In contrast, patient self-report of fatigue over this period differed from the comparison children for the general fatigue subscale only. Self-reported total fatigue was worse than the comparison group at the 27-month timepoint, with cognitive and sleep/rest fatigue symptoms contributing to this difference. Expected improvements in fatigue over time were not evident in either patient or parent report and no demographic risk factors were identified. Parents and children from both groups reported significantly more fatigue at all time points compared to commonly utilised normative population data. CONCLUSIONS: Patients treated for childhood ALL are impacted by fatigue symptoms in the post-treatment and early survivorship period. These findings highlight that patients in the 2-years following treatment require increased symptom surveillance and may benefit particularly from interventions that target cognitive and sleep/rest fatigue.

Acute generalized exanthematous pustulosis: European expert consensus for diagnosis and management.

Acute generalized exanthematous pustulosis (AGEP) is a rare, usually drug-induced, acute pustular rash. Despite the lack of strong data supporting the effectiveness of topical or systemic corticosteroids in this drug reaction, they are widely used. More generally, there is no consensus on the diagnostic modalities and the management of patients with AGEP. We aimed to provide European expert recommendations for the diagnosis and management or patients with AGEP. Members of the ToxiTEN group of the European Reference Network (ERN)-skin, all dermatologists and/or allergologists with expertise in drug reactions, elaborated these recommendations based on their own experience and on a review of the literature. Recommendations were separated into the following categories: professionals involved, assessment of the diagnosis of AGEP, management of the patient and allergological work-up after the acute phase. Consensus was obtained among experts for the list of professionals involved for the diagnosis and management of AGEP, including the minimum diagnostic work-up, the setting of management, the treatments, the modalities and the timing of allergological work-up and follow-up. European experts in drug allergies propose herein consensus on the diagnosis and management of patients with AGEP. A multidisciplinary approach is warranted, including dermatologists, allergologists and pharmacovigilance services.

Intake profile, milk production and energy balance of early lactation spring calving Holstein Friesian and Jersey x Holstein Friesian dairy cows in high utilisation pasture-based systems.

Early lactation is a critical period for dairy cows as energy requirements rapidly increase with the onset of lactation, however, early lactation dry matter intakes (DMI) in pasture-based systems are under-measured. The objectives of this study were 1) to measure and profile total DMI (TDMI) and animal performance of dairy cows during early lactation in a pasture-based system 2) to investigate early lactation energy balance in pasture-based systems and 3) to examine production efficiencies including TDMI and milk solids production per 100 kg bodyweight. Eighty spring-calving dairy cows were allocated to a grazing group as they calved over a 2 year period (2021 and 2022). Cows were offered a daily herbage allowance to achieve a post-grazing sward height of 4 cm with silage supplementation when necessary due to inclement weather. Total DMI was measured using the n-alkane technique over a 12 week period from 1st of February to the 23rd of April. Total DMI and daily milk yield were significantly affected by parity with both variables being greatest for third parity animals (17.7 kg DM and 26.3 kg/cow/day, respectively), lowest for first parity (13.2 kg DM and 19.6 kg/cow/day, respectively) and intermediate for second parity animals (16.8 kg DM and 24.1 kg/cow/day, respectively). Peak TDMI was reached on wk 10 for first parity animals (14.6 kg DM), wk 11 for second parity animals (19.3 kg DM) and wk 12 for third parity animals (19.9 kg DM). Parity also had a significant effect on UFL (feed units for milk) feed balance as first parity animals experienced a greater degree of negative energy balance (-3.2 UFL) compared with second and third parity animals (-2.3 UFL). Breed and parity had an effect on production efficiencies during the first 12 weeks of lactation as Jersey x Holstein Friesian cows had greater TDMI/100 kg bodyweight and milk solids/100 kg bodyweight compared with Holstein Friesian cows.

The impact of twice daily 3-nitroxypropanol supplementation on enteric methane emissions in grazing dairy cows.

Although 3-NOP has been proven to reduce enteric methane (CH4) by ∼30% in indoor systems of dairying when the additive is mixed throughout a total mixed ration (TMR), there has been very limited research to date in grazing systems in which the most convenient method of additive supplementation is at milking twice daily. To investigate the effect of twice daily 3-NOP supplementation on enteric CH4 emissions, a 12-week study was undertaken in which treatment cows (n = 26) were supplemented with 3-NOP (80 mg per kg dry matter intake; DMI) twice daily at morning and evening milking, while control cows (n = 26) received no additive supplementation. Enteric CH4, hydrogen (H2) and carbon dioxide (CO2) were measured using GreenFeed units, while milk production, body weight (BW), body condition score (BCS) and DMI were monitored to determine the effect of 3-NOP supplementation on productivity. There was no significant effect of 3-NOP supplementation on any of the aforementioned parameters with the exception of CH4 and H2 production, respectively. Cows supplemented with 3-NOP produced ∼36% more H2 (P < 0.001) across a 24-h period, with reductions in CH4 production of 28.5% recorded in the 3 h after additive consumption (P < 0.001), however, levels of CH4 production returned to that of the control group thereafter. When CH4 production was considered across the entire 24-h period, the cows offered 3-NOP produced ∼5% less CH4 than the control (P < 0.050). Future research should focus on methods to increase the efficacy of the additive throughout the day which would include the deployment of a slow-release form or an out of parlor feeding system that allows animals consume the product at additional time points.

What is a population-level approach to prevention, and how could we apply it to dementia risk reduction?

The World Health Organisation's 2022 'blueprint for dementia research' highlights the need for more research into population-level risk reduction. However, definitions of population-level prevention vary, and application to dementia is challenging because of its multi-factorial aetiology and a maturing prevention evidence base. This paper compares and contrasts key concepts of 'population-level prevention' from the literature, explores related theoretical models and policy frameworks, and applies this to dementia risk reduction. We reach a proposed definition of population-level risk reduction of dementia, which focusses on the need to change societal conditions such that the population is less likely to develop modifiable risk factors known to be associated with dementia, without the need for high-agency behaviour change by individuals. This definition, alongside identified policy frameworks, can inform synthesis of existing evidence and help to co-ordinate the generation of new evidence.

Risk factors for local atypical fibroxanthoma recurrence and progression to pleomorphic dermal sarcoma: A meta-analysis of individualized participant data.

BACKGROUND: Risk factors for local atypical fibroxanthoma (AFX) recurrence and progression to pleomorphic dermal sarcoma (PDS) have not previously been identified. OBJECTIVE: To identify risk factors and provide follow-up suggestions for local AFX recurrence and progression to PDS. METHODS AND MATERIALS: A literature search was performed in the PubMed, EMBASE, and Cochrane databases. The PRISMA and MOOSE guidelines were followed. The risks of local AFX recurrence and progression to PDS were presented as Kaplan-Meier plots and risk factors were presented as hazard ratios (HRs) calculated with univariate and multivariate Cox regression. RESULTS: Five hundred and ninety-eight patients with AFX from 14 studies were included. Age >74 years and male sex significantly increased the risk of local recurrence (HR: 7.31 [95% confidence interval [CI]: 1.78-30.0], p < 0.01 and HR: 2.89 [95% CI: 1.04-8.01], p < 0.05, respectively). There was no difference when comparing wide local excision and Mohs' micrographic surgery (p = 0.89). The risks of local AFX recurrence and progression to PDS after 2 years were <1%. CONCLUSION: A more intensive follow-up regimen could be considered in patients >74 years old and males due to the higher risk of local AFX recurrence.

Review of the prevalence, pathogenesis and management of OSA-COPD overlap.

PURPOSE: OSA-COPD overlap is an important and prevalent condition yet remains under-recognised among the vast majority of respiratory health professionals. Patients with OSA-COPD overlap experience more severe respiratory symptoms and worse quality of life, and the relative risk of exacerbations, hospitalisations, and mortality is higher than in either disease state alone. METHODS: Electronic databases PUBMED and Google Scholar were searched for studies and academic papers that discussed OSA-COPD overlap. Relevant papers that discussed prevalence, pathophysiology, microbiome studies, treatment regimens and outcomes were included in this paper. RESULTS: High-risk patients with either COPD or OSA should be screened for overlap syndrome as part of routine clinical practice. Screening questionnaires can identify high-risk patients with COPD who may benefit from formal polysomnography. Patients with OSA who are aged over 40 with a significant smoking history or environmental exposures have an increased pre-test probability of obstructive airway disease. The potential roles of gastro-oesophageal reflux disease and lung-gut microbiome are evolving and merit further investigation. A tailored approach to reach a timely diagnosis and thus optimisation of both conditions are key to management. CPAP is the primary therapy for OSA; however, patients with more advanced COPD, with daytime hypercapnia or severe nocturnal desaturations, may benefit from bilevel positive airway pressure. CONCLUSION: Increased awareness, access to timely investigations and initiation of therapy will improve overall outcomes in OSA-COPD overlap by reducing hospitalisations for exacerbations of COPD and improve mortality rates.

Ultrasound-guided foam sclerotherapy as a therapeutic modality in venous ulceration.

OBJECTIVES: The objective of this systematic review and meta-analysis was to evaluate rates of ulcer healing following ultrasound-guided foam sclerotherapy (UGFS). METHODS: The MEDLINE, CENTRAL and Embase databases were used to search for relevant studies using the terms ' (sclerotherapy AND ulcer) OR (vein AND ulcer) OR (sclerotherapy AND vein)'. Heterogeneity between studies was quantified using the I2 statistic. A random effects model was used to calculate risk ratios where substantial heterogeneity was found. RESULTS: The initial search yielded 8266 articles. 8 studies were included in the qualitative synthesis and 3 in the meta-analysis. Superior complete ulcer healing rates were noted in patients treated with foam sclerotherapy versus compression therapy alone (pooled OR 6.41, 95% CI = 0.3-148.2, p = 0.246, random effects method). A marked degree of heterogeneity was observed between studies (I2 = 81%). CONCLUSION: A prospective, trial is warranted in order to determine the true merits of UGFS in the setting of venous ulceration.

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Vulval acne: a case series describing clinical features and management.

Intermittent inflammation of the vulval pilosebaceous units is common and usually self-limiting, but some patients experience recurrent and more troublesome symptoms. There is a scarcity of information on this problem. We describe the clinical and histological features in these patients and the response to treatment. A retrospective, observational study of 16 patients with this phenomenon of recurrent, protracted folliculocentric inflammation of the vulval pilosebaceous unit was performed. Details on the clinical features, histology and response to treatment were collected. Mean age at presentation was 32 years (range 21-45). All patients reported recurrent painful papules and pustules on the labia majora and labia minora. Nine patients reported a cyclical pattern to the development of lesions, with premenstrual exacerbation being most common. Histological examination of these lesions showed a folliculocentric microabscess formation surrounded by an acute and chronic inflammatory cell infiltrate, with a focal foreign-body granulomatous reaction. All our patients responded well to tetracycline, antiandrogenic or retinoid therapy. We propose the term 'vulval acne' for this condition and propose a stepwise approach to its management. We hope to highlight this as a common but underreported entity.

Clinical phenotypes and therapeutic responses in cutaneous-predominant sarcoidosis: 6-year experience in a tertiary referral service.

BACKGROUND: There is a limited evidence base for the treatment of cutaneous sarcoidosis. OBJECTIVE: To describe treatment modalities and responses in patients with predominantly cutaneous sarcoidosis, in addition to clinical characteristics and prevalence of systemic disease. METHODS: Data were prospectively collected over a 6-year period. The Cutaneous Sarcoidosis Activity and Morphology Index was used to assess treatment effectiveness. RESULTS: In total, 47 patients with biopsy-confirmed cutaneous sarcoidosis were identified. Morphologically, the most common lesions were papules (49%) and plaques (42.6%). The most commonly affected sites were the head and neck (79%); 89.4% had systemic as well as cutaneous disease; 77% received systemic corticosteroid therapy, while 87% required further steroid-sparing treatment; 40% achieved clinical remission with hydroxychloroquine (HCQ) and 88% achieved clinical remission with methotrexate (MTX). OR of achieving remission on MTX compared with HCQ was 9.8 (95% CI 2.4-40.4, P = 0.001). MTX was superior to both azathioprine (AZA) (OR = 22; 95% CI 1.7-285.9; P = 0.02) and mycophenolate mofetil (MMF) (OR = 22; 95% CI 1.7-285.9; P = 0.02) in achieving remission. CONCLUSION: HCQ is effective and well-tolerated. MTX was associated with significantly increased probability of achieving clinical remission compared with AZA and MMF.

Cancer and breast cancer awareness interventions in an intellectual disability context: A review of the literature.

BACKGROUND: Women with an intellectual disability (ID) have a similar risk of developing breast cancer as women in the general population yet present with later stage breast cancers, which have poorer outcomes. AIM: To identify whether there is a need to develop a breast cancer awareness intervention for women with an ID. METHODS: Interventions aimed at increasing cancer awareness and breast cancer awareness for people with an ID were identified and critically appraised. RESULTS: Five interventions to increase cancer awareness or breast cancer awareness in people with an ID were identified. CONCLUSION: The review highlighted the paucity of theoretically underpinned breast cancer awareness interventions specifically aimed at women with an ID. Facilitating breast cancer awareness for women with an ID could potentially lead to earlier presentation of potential symptoms of breast cancer, earlier treatment, better prognosis and ultimately, improved survival. This article establishes that there is a need for an intervention underpinned by theory to increase breast cancer awareness in women with an ID.

Radial scars and complex sclerosing lesions on core needle biopsy of the breast: upgrade rates and long-term outcomes.

PURPOSE: Radial scars and complex sclerosing lesions of the breast are part of a group of "indeterminate" breast lesions, which are excised due to risk of coexistent carcinoma. The aim of this study was to assess rate of upgrade of these lesions to invasive and in situ carcinoma and to quantify the risk of development of subsequent cancer in women diagnosed with these lesions. METHODS: A retrospective review of a prospectively maintained breast screening database was performed. All patients with radial scar identified at either core biopsy or final excision biopsy between January 2006 and July 2012 were identified. Full pathological reports for both core biopsy and final excision biopsy were reviewed. Patient outcomes were followed for a mean of 117.1 months. RESULTS: Of 451 B3 biopsies performed at our screening unit, 95 (22%) were found to have a radial scar or complex sclerosing lesion (CSL) on core needle biopsy. Within this group, 77 had no atypia on CNB, with 7 (9%) upgraded to invasive/in situ carcinoma on final excision. Of nine with definite atypia on CNB, 3 (33%) were upgraded. In those patients without atypia or malignancy on final excision, 7.5% developed cancer during 10-year follow-up. CONCLUSION: Patients with radial scar with atypia have a higher risk of upgrade to malignancy. Further research is needed to identify which patients may safely avoid excision of radial scar. Patients with a diagnosis of radial scar on CNB are at increased subsequent risk of breast cancer and may benefit from additional screening.

Breast cancer in young black women.

BACKGROUND: Young age at breast cancer diagnosis is associated with negative prognostic outcomes, and breast cancer in black women often manifests at a young age. This study evaluated the effect of age on breast cancer management and outcomes in black women. METHODS: This was a retrospective cohort study of all black women treated for invasive breast cancer between 2005 and 2010 at a specialized tertiary-care cancer centre. Clinical and treatment characteristics were compared by age. Kaplan-Meier methodology was used to estimate overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 666 black women were identified. Median BMI was 30 (range 17-56) kg/m2 and median tumour size was 16 (1-155) mm. Most tumours were oestrogen receptor-positive (66·4 per cent). Women were stratified by age: less than 40 years (74, 11·1 per cent) versus 40 years or more (592, 88·9 per cent). Younger women were significantly more likely to have a mastectomy, axillary lymph node dissection and to receive chemotherapy, and were more likely to have lymphovascular invasion and positive lymph nodes, than older women. The 5-year OS rate was 88·0 (95 per cent c.i. 86·0 to 91·0) per cent and the 5-year DFS rate was 82·0 (79·0 to 85·0) per cent. There was no statistically significant difference in OS by age (P = 0·236). Although DFS was inferior in younger women on univariable analysis (71 versus 88 per cent; P < 0·001), no association was found with age on multivariable analysis. CONCLUSION: Young black women with breast cancer had more adverse pathological factors, received more aggressive treatment, and had worse DFS on univariable analysis. Young age at diagnosis was, however, not an independent predictor of outcome.

ANTECEDENTES: El diagnóstico de cáncer de mama a una edad joven se asocia con un pronóstico de resultados negativo, y en mujeres de raza negra, el cáncer de mama con frecuencia se manifiesta a edades tempranas. Este estudio analiza el efecto de la edad en el tratamiento y resultados del cáncer de mama en mujeres de raza negra. MÉTODOS: Estudio de cohortes retrospectivo de todas las mujeres de raza negra tratadas por cáncer de mama invasivo entre 2005-2010 en un centro oncológico terciario de alta especialización. Se compararon las características clínicas y del tratamiento en función de la edad. Se estimó la supervivencia global (overall survival, OS) y la supervivencia libre de enfermedad (disease-free survival, DFS) con el método de Kaplan-Meier y se utilizó la prueba de log-rank para las comparaciones entre grupos. RESULTADOS: Se identificaron un total de 666 mujeres de raza negra. La mediana del tamaño del tumor fue de 16 mm (rango 1-155 mm). La mayoría de los tumores fueron positivos para el receptor de estrógenos (66,4%); la mediana del índice de masa corporal (IMC) fue 30 kg/m2 (rango 17,2-56,5). Se estratificaron a las mujeres por su edad: < 40 años (n = 74; 11,1%) frente a ≥ 40 años (n = 592; 88,9%). La probabilidad de recibir una mastectomía, un vaciamiento ganglionar axilar y quimioterapia fue significativamente superior en las pacientes jóvenes y además fueron más propensas a presentar invasión linfovascular y ganglios linfáticos positivos en comparación con las mujeres mayores. Las OS y DFS a los 5 años fueron del 88,0% (i.c. del 95% 86-91%) y del 82% (i.c. del 95% 79-85%), respectivamente. No se observaron diferencias estadísticamente significativas en la OS (P = 0,236) en función de la edad. Aunque en el análisis univariado la DFS fue peor en las mujeres jóvenes (71% versus 88%, log-rank P < 0,001), en el análisis multivariable no se confirmó la asociación con la edad. CONCLUSIÓN: Las mujeres jóvenes de raza negra con cáncer de mama tuvieron más factores patológicos adversos, recibieron un tratamiento más agresivo y tuvieron una DFS peor en el análisis univariado. Sin embargo, la edad temprana en el momento del diagnóstico no fue un factor predictivo independiente del resultado.

Lymphomatoid papulosis: an update and review.

Lymphomatoid papulosis (LyP) is a benign chronic often relapsing skin condition that belongs to the CD30-positive cutaneous lymphoproliferative disorders. LyP typically presents as crops of lesions with a tendency to self-resolve, and morphology can range from solitary to agminated or diffuse papules and plaques to nodules or tumours. The clinical-histological spectrum can range from borderline cases to overlap with primary cutaneous anaplastic cell lymphoma (pcALCL). Histology and immunophenotype commonly show overlap with other CD30-positive disorders and sometimes may be identical to pcALCL, making its diagnosis more difficult. Patients with LyP have an increased risk of developing a second neoplasm such as mycosis fungoides, pcALCL and/or Hodgkin lymphoma. Clinical correlation allows its proper classification and diagnosis, which is fundamental for treatment and prognosis. This review focuses on the clinical appearance, histopathological features, diagnosis, differential diagnosis and management of LyP.

Real-time optical redox imaging of cartilage metabolic response to mechanical loading.

OBJECTIVE: Metabolic dysregulation has recently been identified as a key feature of osteoarthritis. Mechanical overloading has been postulated as a primary cause of this metabolic response. Current methods of real-time metabolic activity analysis in cartilage are limited and challenging. However, optical redox imaging leverages the autofluorescence of co-enzymes NAD(P)H and FAD to provide dye-free real-time analysis of metabolic activity. This technique has not yet been applied to cartilage. This study aimed to assess the effects of a compressive load on cartilage using optical redox imaging. METHOD: Cartilage samples were excised from porcine femoral condyles. To validate this imaging modality in cartilage, glycolysis was inhibited via 2-deoxy-D-glucose (2DG) and oxidative phosphorylation was inhibited by rotenone. Optical redox images were collected pre- and post-inhibition. To assess the effects of mechanical loading, samples were subjected to a compressive load and imaged for approximately 30 min. Load and strain parameters were determined using high-speed camera images in Matlab. A range of loading magnitudes and rates were applied across samples. RESULTS: 2DG and rotenone demonstrated the expected inhibitory effects on fluorescence intensity in the channels corresponding to NAD(P)H and FAD, respectively. Mechanical loading induced an increase in NAD(P)H channel fluorescence which subsided by 30 min post-loading. Magnitude of loading parameters had mixed effects on metabolites. CONCLUSIONS: Optical redox imaging provides an opportunity to assess real-time metabolic activity in cartilage. This approach revealed a metabolic response to a single load and can be used to provide insight into the role of metabolism in mechanically-mediated cartilage degradation.

Malignant transformation of tailgut cysts is significantly higher than previously reported: systematic review of cases in the literature.

AIM: The best treatment for tailgut cysts has not been firmly established. We report a systematic review of the cases in the available literature in order to provide an evidence base for treatment. METHOD: A systematic search of articles wholly or partly in English was made of PubMed, Embase and Google Scholar; additional studies were discovered by searching reference lists and contacting authors directly. Search terms 'tailgut cyst', 'tail gut cyst', 'retrorectal hamartoma' and 'retrorectal tumour' were used for case reports or case series; no publication date restrictions were imposed. Only studies with histological confirmation of diagnosis and reporting the age and gender of patients were included. Papers were excluded by consensus between the first two authors. RESULTS: A total of 196 individual cases were analysed in detail including 51 cases of neoplasia. The overall rate of neoplastic transformation was 26.6%. Although the male:female cyst incidence ratio was 1:4, men over 18 had a significantly greater relative risk of neoplasm at 1.94 (P = 0.0055). Radiological evidence of nodular thickening of the cyst wall significantly increased the relative risk of the presence of cancer (P = 0.0023). CONCLUSIONS: Current orthodoxy that these are not dangerous embryological remnants is unfounded and may be false. The available data suggest the risk of malignant transformation is high and will apply to any residual tissue after excision. The same rationale behind total mesorectal excision in rectal cancer applies to tailgut cysts. Consequently they should be resected with similar oncological margins.

Contrast media and cutaneous reactions. Part 1. Immediate hypersensitivity reactions to contrast media and gadolinium deposition.

Contrast media (CM) are commonly used worldwide to enhance the quality of imaging, which is invaluable for diagnostic accuracy. Adverse reactions to CM are uncommon, but frequently involve cutaneous symptoms. This two-part article reviews adverse events secondary to CM that are relevant to the practising dermatologist. Part 1 will classify CM, address immediate hypersensitivity reactions and review the newly described condition, gadolinium deposition disease. Part 2 will cover the delayed hypersensitivity reactions of iodinated contrast medium including severe cutaneous adverse reactions and iododerma.

Contrast media and cutaneous reactions. Part 2: Delayed hypersensitivity reactions to iodinated contrast media.

Contrast media (CM) are an indispensable part of modern medical imaging. Adverse reactions to CM are uncommon, but frequently involve cutaneous symptoms. This two-part article reviews adverse events secondary to CM that are relevant to the practising dermatologist. Part 1 covers the classification of CM, immediate hypersensitivity reactions to CM and the newly described condition, gadolinium deposition disease. Given that there has only been two case reports to our knowledge of a delayed adverse reaction to gadolinium-based CM, this second part will focus on cutaneous delayed reactions caused by iodinated CM (ICM). Delayed hypersensitivity reactions to ICM commonly present as maculopapular exanthems, but more rarely, they can manifest as fixed drug eruptions, acute generalized exanthematous pustulosis, drug-related eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis, symmetrical drug-related intertriginous and flexural exanthema, graft-versus-host disease, vasculitis and iododerma. Delayed reactions to ICM may be underdiagnosed, as cutaneous symptoms may be attributed to oral medications, particularly if patients are on multiple drugs.

How herd best linear unbiased estimates affect the progress achievable from gains in additive and nonadditive genetic merit.

Sustainable dairy cow performance relies on coevolution in the development of breeding and management strategies. Tailoring breeding programs to herd performance metrics facilitates improved responses to breeding decisions. Although herd-level raw metrics on performance are useful, implicitly included within such statistics is the mean herd genetic merit. The objective of the present study was to quantify the expected response from selection decisions on additive and nonadditive merit by herd performance metrics independent of herd mean genetic merit. Performance traits considered in the present study were age at first calving, milk yield, calving to first service, number of services, calving interval, and survival. Herd-level best linear unbiased estimates (BLUE) for each performance trait were available on a maximum of 1,059 herds, stratified as best, average, and worst for each performance trait separately. The analyses performed included (1) the estimation of (co)variance for each trait in the 3 BLUE environments and (2) the regression of cow-level phenotypic performance on either the respective estimated breeding value (EBV) or the heterosis coefficient of the cow. A fundamental assumption of genetic evaluations is that 1 unit change in EBV equates to a 1 unit change in the respective phenotype; results from the present study, however, suggest that the realization of the change in phenotypic performance is largely dependent on the herd BLUE for that trait. Herds achieving more yield, on average, than expected from their mean genetic merit, had a 20% greater response to changes in EBV as well as 43% greater genetic standard deviation relative to herds within the worst BLUE for milk yield. Conversely, phenotypic performance in fertility traits (with the exception of calving to first service) tended to have a greater response to selection as well as a greater additive genetic standard deviation within the respective worst herd BLUE environments; this is suggested to be due to animals performing under more challenging environments leading to larger achievable gains. The attempts to exploit nonadditive genetic effects such as heterosis are often the basis of promoting cross-breeding, yet the results from the present study suggest that improvements in phenotypic performance is largely dependent on the environment. The largest gains due to heterotic effects tended to be within the most stressful (i.e., worst) BLUE environment for all traits, thus suggesting the heterosis effects can be beneficial in mitigating against poorer environments.